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AI Tools Could Change Pulmonological Imaging and Prognosis
MADRID — Artificial intelligence (AI) can enhance endobronchial ultrasound (EBUS) image processing and new techniques such as cryoEBUS to achieve significant diagnostic and prognostic breakthroughs in interventional pulmonology and general pulmonology.
Pulmonologists are witnessing a surge in new technologies for endoscopy and pulmonology in general. Some, such as AI, robotic bronchoscopy, radiomics, or improvements in electromagnetic bronchial navigation, are minimally invasive diagnostic techniques that significantly enhance the characterization of lung lesions, said Virginia Pajares, MD, a member of the Catalan Society of Pulmonology and coordinator of the Bronchoscopy Unit at Hospital de Sant Pau in Barcelona, Spain. She spoke at the XLI Pneumological Day of the Catalan Society of Pulmonology in Vilanova i la Geltrú, Spain.
Regarding AI, pulmonologists “already have platforms that enable the calculation of the malignancy risk of lung lesions and mediastinal adenopathies. In addition, some devices that allow for an initial radiological assessment of lung nodules are starting to be used,” said Dr. Pajares.
Radiomics: Histology and Markers
“At an endoscopic level, some studies have confirmed the ability of AI applied to imaging to differentiate between benign and malignant lesions, although currently the studies are limited and in the initial stages,” said Dr. Pajares. “AI in interventional pulmonology will be highly beneficial in image interpretation and patient assessment for those who require more invasive diagnostic techniques or for follow-up.”
Regarding the application of AI in medicine, “we lack knowledge and require specific training, especially concerning the learning curve of different technologies, such as electromagnetic navigation, cryoEBUS, or robotic bronchoscopy, which require significant training efforts,” said Dr. Pajares. “The use of AI without a specific goal, that is, creating a mathematical algorithm and feeding it with clinical patient data without control and validation, can lead to inaccurate conclusions. Additionally, we need to determine how to input patient data into these systems to avoid ethical issues, and, of course, legislation on this matter is essential.”
Electromagnetic Navigation
Bronchial electromagnetic navigation is a bronchoscopic technique that allows access to peripheral lung lesions. “It involves virtual route planning using the patient’s chest CT scan and subsequently performing bronchoscopy with navigation using a dirigible electromagnetic probe that allows access to the lesion,” Dr. Pajares explained. “Currently, we have navigators that can incorporate imaging techniques (fluoroscopy or cone-beam CT) to immediately correct discrepancies observed during navigation.”
These new technologies enable a greater number of precise diagnoses and may bring greater patient safety. Studies like NAVIGATE, which was published in 2022 by Folch and colleagues, confirm the diagnostic possibilities and performance of electromagnetic navigation.
In this prospective study, which followed patients for 24 months, the indications are broad. “Its most common use is as a diagnostic technique for peripheral lung nodules and for marking lung lesions for surgical resection or marking for radiotherapy field fiducial placement,” said Dr. Pajares. “Results are also beginning to be published on the treatment of lung lesions using electromagnetic navigation ablation, demonstrating its safety and efficacy in this area.”
Nonsolid Imaging
The challenges in navigation include “improving the diagnosis of lung lesions that are nonsolid, known as ground glass opacities, and verifying it as an additional treatment option for lung nodules in patients who are not candidates for surgical resection,” said Dr. Pajares.
Tess Kramer, PhD, of Amsterdam University Medical Center, Amsterdam, the Netherlands, advocates for the combined use of different technologies to have a beneficial impact on patients’ clinical outcomes.
Robotic bronchoscopy has been implemented in the United States for several years, enhancing the precision of lung nodule diagnosis. However, “currently, there are no clear differences in the diagnostic performance of robotic bronchoscopy compared with navigation in general. Soon, there will be studies to assess in which type of nodules one technique may be more cost-effective.” No centers in Spain have this technology yet, “although some are already evaluating the acquisition of robotic bronchoscopy; it’s only a matter of time,” said Dr. Pajares.
Improvements in echobronchoscopy technology include high-quality image processors and smaller device calibers with greater angulation to diagnose lesions and hard-to-reach adenopathies. From an imaging perspective, AI, combined with the creation of risk calculators, could enable the prediction of lymph node malignancy.
Moreover, the use of small-caliber cryoprobes (1.1 mm) for obtaining samples of adenopathies (cryoEBUS) has enhanced diagnosis by enabling larger tissue samples. Current studies are being conducted to confirm the utility of cryoEBUS in pathologies requiring extensive molecular and immunohistochemical studies for diagnosing lymphoproliferative syndromes or neoplasms.
In a different context, liquid biopsy, a recent laboratory technology unrelated to bronchoscopy, allows the analysis of blood/pleural fluid samples that were extracted using the aforementioned technologies to locate tumor cells and differentiate between malignancy and benignity.
The Challenge of Pneumonitis
Samantha Aso, MD, a pulmonologist, member of the Catalan Society of Pulmonology, and specialist at the Lung Unit of Bellvitge University Hospital in Barcelona, Spain, discussed the challenge of managing pneumonitis in oncology patients.
Pneumonitis is an inflammation of the lungs that can be secondary to treatments, such as oncological therapy, which is the leading cause in 15%-50% of cases. Most oncological treatments can result in this process, including chemotherapy, chest radiotherapy, targeted therapies, conjugated monoclonal antibodies, and monotherapy.
To date, there is no known idiosyncratic cause of this process, except for autoimmune diseases. Pulmonary fibrosis is believed to be a risk factor. “Patients with interstitial lung disease and pulmonary fibrosis have been found to have a higher mortality risk due to pneumonitis. Consequently, cancer treatment cannot be administered to these patients,” said Dr. Aso.
Pulmonologists face the challenge of managing pneumonitis secondary to monotherapy, which currently is treated with cortisone. Patients respond well to this medication, but after corticosteroid withdrawal, reinflammation may occur. “In pneumonitis patients, oncological treatment (monotherapy) should be suspended while pulmonologists manage the pneumonitis with corticosteroids. However, we are uncertain about how rapidly or slowly to reduce the dosage. We cannot taper these doses as quickly as desired because reinflammation may occur, and to date, there are no alternative treatments apart from corticosteroids,” said Dr. Aso.
She noted that excellent survival results are achieved with monotherapy, but further research is required on the safety of antineoplastic drugs as a secondary endpoint. “Suspending oncological treatment due to pneumonitis means that patients are not receiving adequate cancer treatment, which has a significant psychological impact that also needs to be addressed,” Dr. Aso concluded.
Dr. Pajares and Dr. Aso declared no relevant financial relationships.
This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
MADRID — Artificial intelligence (AI) can enhance endobronchial ultrasound (EBUS) image processing and new techniques such as cryoEBUS to achieve significant diagnostic and prognostic breakthroughs in interventional pulmonology and general pulmonology.
Pulmonologists are witnessing a surge in new technologies for endoscopy and pulmonology in general. Some, such as AI, robotic bronchoscopy, radiomics, or improvements in electromagnetic bronchial navigation, are minimally invasive diagnostic techniques that significantly enhance the characterization of lung lesions, said Virginia Pajares, MD, a member of the Catalan Society of Pulmonology and coordinator of the Bronchoscopy Unit at Hospital de Sant Pau in Barcelona, Spain. She spoke at the XLI Pneumological Day of the Catalan Society of Pulmonology in Vilanova i la Geltrú, Spain.
Regarding AI, pulmonologists “already have platforms that enable the calculation of the malignancy risk of lung lesions and mediastinal adenopathies. In addition, some devices that allow for an initial radiological assessment of lung nodules are starting to be used,” said Dr. Pajares.
Radiomics: Histology and Markers
“At an endoscopic level, some studies have confirmed the ability of AI applied to imaging to differentiate between benign and malignant lesions, although currently the studies are limited and in the initial stages,” said Dr. Pajares. “AI in interventional pulmonology will be highly beneficial in image interpretation and patient assessment for those who require more invasive diagnostic techniques or for follow-up.”
Regarding the application of AI in medicine, “we lack knowledge and require specific training, especially concerning the learning curve of different technologies, such as electromagnetic navigation, cryoEBUS, or robotic bronchoscopy, which require significant training efforts,” said Dr. Pajares. “The use of AI without a specific goal, that is, creating a mathematical algorithm and feeding it with clinical patient data without control and validation, can lead to inaccurate conclusions. Additionally, we need to determine how to input patient data into these systems to avoid ethical issues, and, of course, legislation on this matter is essential.”
Electromagnetic Navigation
Bronchial electromagnetic navigation is a bronchoscopic technique that allows access to peripheral lung lesions. “It involves virtual route planning using the patient’s chest CT scan and subsequently performing bronchoscopy with navigation using a dirigible electromagnetic probe that allows access to the lesion,” Dr. Pajares explained. “Currently, we have navigators that can incorporate imaging techniques (fluoroscopy or cone-beam CT) to immediately correct discrepancies observed during navigation.”
These new technologies enable a greater number of precise diagnoses and may bring greater patient safety. Studies like NAVIGATE, which was published in 2022 by Folch and colleagues, confirm the diagnostic possibilities and performance of electromagnetic navigation.
In this prospective study, which followed patients for 24 months, the indications are broad. “Its most common use is as a diagnostic technique for peripheral lung nodules and for marking lung lesions for surgical resection or marking for radiotherapy field fiducial placement,” said Dr. Pajares. “Results are also beginning to be published on the treatment of lung lesions using electromagnetic navigation ablation, demonstrating its safety and efficacy in this area.”
Nonsolid Imaging
The challenges in navigation include “improving the diagnosis of lung lesions that are nonsolid, known as ground glass opacities, and verifying it as an additional treatment option for lung nodules in patients who are not candidates for surgical resection,” said Dr. Pajares.
Tess Kramer, PhD, of Amsterdam University Medical Center, Amsterdam, the Netherlands, advocates for the combined use of different technologies to have a beneficial impact on patients’ clinical outcomes.
Robotic bronchoscopy has been implemented in the United States for several years, enhancing the precision of lung nodule diagnosis. However, “currently, there are no clear differences in the diagnostic performance of robotic bronchoscopy compared with navigation in general. Soon, there will be studies to assess in which type of nodules one technique may be more cost-effective.” No centers in Spain have this technology yet, “although some are already evaluating the acquisition of robotic bronchoscopy; it’s only a matter of time,” said Dr. Pajares.
Improvements in echobronchoscopy technology include high-quality image processors and smaller device calibers with greater angulation to diagnose lesions and hard-to-reach adenopathies. From an imaging perspective, AI, combined with the creation of risk calculators, could enable the prediction of lymph node malignancy.
Moreover, the use of small-caliber cryoprobes (1.1 mm) for obtaining samples of adenopathies (cryoEBUS) has enhanced diagnosis by enabling larger tissue samples. Current studies are being conducted to confirm the utility of cryoEBUS in pathologies requiring extensive molecular and immunohistochemical studies for diagnosing lymphoproliferative syndromes or neoplasms.
In a different context, liquid biopsy, a recent laboratory technology unrelated to bronchoscopy, allows the analysis of blood/pleural fluid samples that were extracted using the aforementioned technologies to locate tumor cells and differentiate between malignancy and benignity.
The Challenge of Pneumonitis
Samantha Aso, MD, a pulmonologist, member of the Catalan Society of Pulmonology, and specialist at the Lung Unit of Bellvitge University Hospital in Barcelona, Spain, discussed the challenge of managing pneumonitis in oncology patients.
Pneumonitis is an inflammation of the lungs that can be secondary to treatments, such as oncological therapy, which is the leading cause in 15%-50% of cases. Most oncological treatments can result in this process, including chemotherapy, chest radiotherapy, targeted therapies, conjugated monoclonal antibodies, and monotherapy.
To date, there is no known idiosyncratic cause of this process, except for autoimmune diseases. Pulmonary fibrosis is believed to be a risk factor. “Patients with interstitial lung disease and pulmonary fibrosis have been found to have a higher mortality risk due to pneumonitis. Consequently, cancer treatment cannot be administered to these patients,” said Dr. Aso.
Pulmonologists face the challenge of managing pneumonitis secondary to monotherapy, which currently is treated with cortisone. Patients respond well to this medication, but after corticosteroid withdrawal, reinflammation may occur. “In pneumonitis patients, oncological treatment (monotherapy) should be suspended while pulmonologists manage the pneumonitis with corticosteroids. However, we are uncertain about how rapidly or slowly to reduce the dosage. We cannot taper these doses as quickly as desired because reinflammation may occur, and to date, there are no alternative treatments apart from corticosteroids,” said Dr. Aso.
She noted that excellent survival results are achieved with monotherapy, but further research is required on the safety of antineoplastic drugs as a secondary endpoint. “Suspending oncological treatment due to pneumonitis means that patients are not receiving adequate cancer treatment, which has a significant psychological impact that also needs to be addressed,” Dr. Aso concluded.
Dr. Pajares and Dr. Aso declared no relevant financial relationships.
This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
MADRID — Artificial intelligence (AI) can enhance endobronchial ultrasound (EBUS) image processing and new techniques such as cryoEBUS to achieve significant diagnostic and prognostic breakthroughs in interventional pulmonology and general pulmonology.
Pulmonologists are witnessing a surge in new technologies for endoscopy and pulmonology in general. Some, such as AI, robotic bronchoscopy, radiomics, or improvements in electromagnetic bronchial navigation, are minimally invasive diagnostic techniques that significantly enhance the characterization of lung lesions, said Virginia Pajares, MD, a member of the Catalan Society of Pulmonology and coordinator of the Bronchoscopy Unit at Hospital de Sant Pau in Barcelona, Spain. She spoke at the XLI Pneumological Day of the Catalan Society of Pulmonology in Vilanova i la Geltrú, Spain.
Regarding AI, pulmonologists “already have platforms that enable the calculation of the malignancy risk of lung lesions and mediastinal adenopathies. In addition, some devices that allow for an initial radiological assessment of lung nodules are starting to be used,” said Dr. Pajares.
Radiomics: Histology and Markers
“At an endoscopic level, some studies have confirmed the ability of AI applied to imaging to differentiate between benign and malignant lesions, although currently the studies are limited and in the initial stages,” said Dr. Pajares. “AI in interventional pulmonology will be highly beneficial in image interpretation and patient assessment for those who require more invasive diagnostic techniques or for follow-up.”
Regarding the application of AI in medicine, “we lack knowledge and require specific training, especially concerning the learning curve of different technologies, such as electromagnetic navigation, cryoEBUS, or robotic bronchoscopy, which require significant training efforts,” said Dr. Pajares. “The use of AI without a specific goal, that is, creating a mathematical algorithm and feeding it with clinical patient data without control and validation, can lead to inaccurate conclusions. Additionally, we need to determine how to input patient data into these systems to avoid ethical issues, and, of course, legislation on this matter is essential.”
Electromagnetic Navigation
Bronchial electromagnetic navigation is a bronchoscopic technique that allows access to peripheral lung lesions. “It involves virtual route planning using the patient’s chest CT scan and subsequently performing bronchoscopy with navigation using a dirigible electromagnetic probe that allows access to the lesion,” Dr. Pajares explained. “Currently, we have navigators that can incorporate imaging techniques (fluoroscopy or cone-beam CT) to immediately correct discrepancies observed during navigation.”
These new technologies enable a greater number of precise diagnoses and may bring greater patient safety. Studies like NAVIGATE, which was published in 2022 by Folch and colleagues, confirm the diagnostic possibilities and performance of electromagnetic navigation.
In this prospective study, which followed patients for 24 months, the indications are broad. “Its most common use is as a diagnostic technique for peripheral lung nodules and for marking lung lesions for surgical resection or marking for radiotherapy field fiducial placement,” said Dr. Pajares. “Results are also beginning to be published on the treatment of lung lesions using electromagnetic navigation ablation, demonstrating its safety and efficacy in this area.”
Nonsolid Imaging
The challenges in navigation include “improving the diagnosis of lung lesions that are nonsolid, known as ground glass opacities, and verifying it as an additional treatment option for lung nodules in patients who are not candidates for surgical resection,” said Dr. Pajares.
Tess Kramer, PhD, of Amsterdam University Medical Center, Amsterdam, the Netherlands, advocates for the combined use of different technologies to have a beneficial impact on patients’ clinical outcomes.
Robotic bronchoscopy has been implemented in the United States for several years, enhancing the precision of lung nodule diagnosis. However, “currently, there are no clear differences in the diagnostic performance of robotic bronchoscopy compared with navigation in general. Soon, there will be studies to assess in which type of nodules one technique may be more cost-effective.” No centers in Spain have this technology yet, “although some are already evaluating the acquisition of robotic bronchoscopy; it’s only a matter of time,” said Dr. Pajares.
Improvements in echobronchoscopy technology include high-quality image processors and smaller device calibers with greater angulation to diagnose lesions and hard-to-reach adenopathies. From an imaging perspective, AI, combined with the creation of risk calculators, could enable the prediction of lymph node malignancy.
Moreover, the use of small-caliber cryoprobes (1.1 mm) for obtaining samples of adenopathies (cryoEBUS) has enhanced diagnosis by enabling larger tissue samples. Current studies are being conducted to confirm the utility of cryoEBUS in pathologies requiring extensive molecular and immunohistochemical studies for diagnosing lymphoproliferative syndromes or neoplasms.
In a different context, liquid biopsy, a recent laboratory technology unrelated to bronchoscopy, allows the analysis of blood/pleural fluid samples that were extracted using the aforementioned technologies to locate tumor cells and differentiate between malignancy and benignity.
The Challenge of Pneumonitis
Samantha Aso, MD, a pulmonologist, member of the Catalan Society of Pulmonology, and specialist at the Lung Unit of Bellvitge University Hospital in Barcelona, Spain, discussed the challenge of managing pneumonitis in oncology patients.
Pneumonitis is an inflammation of the lungs that can be secondary to treatments, such as oncological therapy, which is the leading cause in 15%-50% of cases. Most oncological treatments can result in this process, including chemotherapy, chest radiotherapy, targeted therapies, conjugated monoclonal antibodies, and monotherapy.
To date, there is no known idiosyncratic cause of this process, except for autoimmune diseases. Pulmonary fibrosis is believed to be a risk factor. “Patients with interstitial lung disease and pulmonary fibrosis have been found to have a higher mortality risk due to pneumonitis. Consequently, cancer treatment cannot be administered to these patients,” said Dr. Aso.
Pulmonologists face the challenge of managing pneumonitis secondary to monotherapy, which currently is treated with cortisone. Patients respond well to this medication, but after corticosteroid withdrawal, reinflammation may occur. “In pneumonitis patients, oncological treatment (monotherapy) should be suspended while pulmonologists manage the pneumonitis with corticosteroids. However, we are uncertain about how rapidly or slowly to reduce the dosage. We cannot taper these doses as quickly as desired because reinflammation may occur, and to date, there are no alternative treatments apart from corticosteroids,” said Dr. Aso.
She noted that excellent survival results are achieved with monotherapy, but further research is required on the safety of antineoplastic drugs as a secondary endpoint. “Suspending oncological treatment due to pneumonitis means that patients are not receiving adequate cancer treatment, which has a significant psychological impact that also needs to be addressed,” Dr. Aso concluded.
Dr. Pajares and Dr. Aso declared no relevant financial relationships.
This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Artificial sweeteners no help for weight loss: Review
It also shows evidence that these products are not beneficial for controlling excess weight.
Francisco Gómez-Delgado, MD, PhD, and Pablo Pérez-Martínez, MD, PhD, are members of the Spanish Society of Arteriosclerosis and of the Spanish Society of Internal Medicine. They have coordinated an updated review of the leading scientific evidence surrounding artificial sweeteners: evidence showing that far from positively affecting our health, they have “negative effects for the cardiometabolic system.”
The paper, published in Current Opinion in Cardiology, delves into the consumption of these sweeteners and their negative influence on the development of obesity and of several of the most important cardiometabolic risk factors (hypertension, dyslipidemia, and diabetes).
Globalization and the increase in consumption of ultraprocessed foods have led to a need for greater knowledge on the health impacts of certain nutrients such as artificial sweeteners (nutritive and nonnutritive). This review aims to analyze their role and their effect on cardiometabolic and cardiovascular disease risk.
Cardiovascular risk
The detrimental effects of a high-calorie, high-sugar diet have been well established. For this reason, health authorities recommend limiting sugar consumption. The recommendation has led the food industry to develop different artificial sweeteners with specific properties, such as flavor and stability (nutritive artificial sweeteners), and others aimed at limiting sugar in the diet (nonnutritive artificial sweeteners). Recent evidence explores the influence of these two types of artificial sweeteners on cardiovascular disease risk through risk factors such as obesity and type 2 diabetes, among others.
Initially, the consumption of artificial sweeteners was presented as an alternative for reducing calorie intake in the diet as an option for people with excess weight and obesity. However, as this paper explains, the consumption of these artificial sweeteners favors weight gain because of neuroendocrine mechanisms related to satiety that are abnormally activated when artificial sweeteners are consumed.
Weight gain
On the other hand, evidence shows that consuming artificial sweeteners does not encourage weight loss. “Quite the contrary,” Dr. Pérez-Martínez, scientific director at the Maimonides Biomedical Research Institute and internist at the University Hospital Reina Sofia, both in Córdoba, told this news organization. “There is evidence showing weight gain resulting from the effect that artificial sweetener consumption has at the neurohormonal level by altering the mechanisms involved in regulating the feeling of satiety.”
However, on the basis of current evidence, sugar cannot be claimed to be less harmful. “What we do know is that in both cases, we should reduce or remove them from our diets and replace them with other healthier alternatives for weight management, such as eating plant-based products or being physically active.”
Confronting ignorance
Nonetheless, these recommendations are conditional, “because the weight of the evidence is not extremely high, since there have not been a whole lot of studies. All nutritional studies must be viewed with caution,” Manuel Anguita, MD, PhD, said in an interview. Dr. Anguita is department head of clinical cardiology at the University Hospital Reina Sofia in Córdoba and past president of the Spanish Society of Cardiology.
“It’s something that should be included within the medical record when you’re assessing cardiovascular risk. In addition to identifying patients who use artificial sweeteners, it’s especially important to emphasize that it’s not an appropriate recommendation for weight management.” Healthier measures include moderate exercise and the Mediterranean diet.
Explaining why this research is valuable, he said, “It’s generally useful because there’s ignorance not only in the population but among physicians as well [about] these negative effects of sweeteners.”
Diabetes and metabolic syndrome
Artificial sweeteners cause significant disruptions in the endocrine system, leading our metabolism to function abnormally. The review revealed that consuming artificial sweeteners raises the risk for type 2 diabetes by between 18% and 24% and raises the risk for metabolic syndrome by up to 44%.
Dr. Gómez-Delgado, an internal medicine specialist at the University Hospital of Jaen in Spain and first author of the study, discussed the deleterious effects of sweeteners on metabolism. “On one hand, neurohormonal disorders impact appetite, and the feeling of satiety is abnormally delayed.” On the other hand, “they induce excessive insulin secretion in the pancreas,” which in the long run, encourages metabolic disorders that lead to diabetes. Ultimately, this process produces what we know as “dysbiosis, since our microbiota is unable to process these artificial sweeteners.” Dysbiosis triggers specific pathophysiologic processes that negatively affect cardiometabolic and cardiovascular systems.
No differences
Regarding the type of sweetener, Dr. Gómez-Delgado noted that currently available studies assess the consumption of special dietary products that, in most cases, include various types of artificial sweeteners. “So, it’s not possible to define specific differences between them as to how they impact our health.” Additional studies are needed to confirm this effect at the cardiometabolic level and to analyze the different types of artificial sweeteners individually.
“There’s enough evidence to confirm that consuming artificial sweeteners negatively interferes with our metabolism – especially glucose metabolism – and increases the risk of developing diabetes,” said Dr. Gómez-Delgado.
High-sodium drinks
When it comes to the influence of artificial sweeteners on hypertension, “there is no single explanation. The World Health Organization already discussed this issue 4-5 years ago, not only due to their carcinogenic risk, but also due to this cardiovascular risk in terms of a lack of control of obesity, diabetes, and hypertension,” said Dr. Anguita.
Another important point “is that this is not in reference to the sweeteners themselves, but to soft drinks containing those components, which is where we have more studies,” he added. There are two factors explaining this increase in hypertension, which poses a problem at the population level, with medium- to long-term follow-up. “The sugary beverages that we mentioned have a higher sodium content. That is, the sweeteners add this element, which is a factor that’s directly linked to the increase in blood pressure levels.” Another factor that can influence blood pressure is “the increase in insulin secretion that has been described as resulting from sweeteners. In the medium and long term, this is associated with increased blood pressure levels.”
Cardiovascular risk factor?
Are artificial sweeteners considered to be a new cardiovascular risk factor? “What they really do is increase the incidence of the other classic risk factors,” including obesity, said Dr. Anguita. It has been shown that artificial sweeteners don’t reduce obesity when used continuously. Nonetheless, “there is still not enough evidence to view it in the same light as the classic risk factors,” added Dr. Anguita. However, it is a factor that can clearly worsen the control of the other factors. Therefore, “it’s appropriate to sound an alarm and explain that it’s not the best way to lose weight; there are many other healthier choices.”
“We need more robust evidence to take a clear position on the use of this type of sweetener and its detrimental effect on health. Meanwhile, it would be ideal to limit their consumption or even avoid adding artificial sweeteners to coffee or teas,” added Dr. Pérez-Martínez.
Regulate consumption
Dr. Pérez-Martínez mentioned that the measures proposed to regulate the consumption of artificial sweeteners and to modify the current legislation must involve “minimizing the consumption of these special dietary products as much as possible and even avoiding adding these artificial sweeteners to the foods that we consume; for example, to coffee and tea.” On the other hand, “we must provide consumers with information that is as clear and simple as possible regarding the composition of the food they consume and how it impacts their health.”
However, “we need more evidence to be able to take a clear position on what type of sweeteners we can consume in our diet and also to what extent we should limit their presence in the foods we consume,” said Dr. Pérez-Martínez.
Last, “most of the evidence is from short-term observational studies that assess frequencies and patterns of consumption of foods containing these artificial sweeteners.” Of course, “we need studies that specifically analyze their effects at the metabolic level as well as longer-term studies where the nutritional follow-up of participants is more accurate and rigorous, especially when it comes to the consumption of this type of food,” concluded Dr. Gómez-Delgado.
This article was translated from the Medscape Spanish Edition. A version appeared on Medscape.com.
It also shows evidence that these products are not beneficial for controlling excess weight.
Francisco Gómez-Delgado, MD, PhD, and Pablo Pérez-Martínez, MD, PhD, are members of the Spanish Society of Arteriosclerosis and of the Spanish Society of Internal Medicine. They have coordinated an updated review of the leading scientific evidence surrounding artificial sweeteners: evidence showing that far from positively affecting our health, they have “negative effects for the cardiometabolic system.”
The paper, published in Current Opinion in Cardiology, delves into the consumption of these sweeteners and their negative influence on the development of obesity and of several of the most important cardiometabolic risk factors (hypertension, dyslipidemia, and diabetes).
Globalization and the increase in consumption of ultraprocessed foods have led to a need for greater knowledge on the health impacts of certain nutrients such as artificial sweeteners (nutritive and nonnutritive). This review aims to analyze their role and their effect on cardiometabolic and cardiovascular disease risk.
Cardiovascular risk
The detrimental effects of a high-calorie, high-sugar diet have been well established. For this reason, health authorities recommend limiting sugar consumption. The recommendation has led the food industry to develop different artificial sweeteners with specific properties, such as flavor and stability (nutritive artificial sweeteners), and others aimed at limiting sugar in the diet (nonnutritive artificial sweeteners). Recent evidence explores the influence of these two types of artificial sweeteners on cardiovascular disease risk through risk factors such as obesity and type 2 diabetes, among others.
Initially, the consumption of artificial sweeteners was presented as an alternative for reducing calorie intake in the diet as an option for people with excess weight and obesity. However, as this paper explains, the consumption of these artificial sweeteners favors weight gain because of neuroendocrine mechanisms related to satiety that are abnormally activated when artificial sweeteners are consumed.
Weight gain
On the other hand, evidence shows that consuming artificial sweeteners does not encourage weight loss. “Quite the contrary,” Dr. Pérez-Martínez, scientific director at the Maimonides Biomedical Research Institute and internist at the University Hospital Reina Sofia, both in Córdoba, told this news organization. “There is evidence showing weight gain resulting from the effect that artificial sweetener consumption has at the neurohormonal level by altering the mechanisms involved in regulating the feeling of satiety.”
However, on the basis of current evidence, sugar cannot be claimed to be less harmful. “What we do know is that in both cases, we should reduce or remove them from our diets and replace them with other healthier alternatives for weight management, such as eating plant-based products or being physically active.”
Confronting ignorance
Nonetheless, these recommendations are conditional, “because the weight of the evidence is not extremely high, since there have not been a whole lot of studies. All nutritional studies must be viewed with caution,” Manuel Anguita, MD, PhD, said in an interview. Dr. Anguita is department head of clinical cardiology at the University Hospital Reina Sofia in Córdoba and past president of the Spanish Society of Cardiology.
“It’s something that should be included within the medical record when you’re assessing cardiovascular risk. In addition to identifying patients who use artificial sweeteners, it’s especially important to emphasize that it’s not an appropriate recommendation for weight management.” Healthier measures include moderate exercise and the Mediterranean diet.
Explaining why this research is valuable, he said, “It’s generally useful because there’s ignorance not only in the population but among physicians as well [about] these negative effects of sweeteners.”
Diabetes and metabolic syndrome
Artificial sweeteners cause significant disruptions in the endocrine system, leading our metabolism to function abnormally. The review revealed that consuming artificial sweeteners raises the risk for type 2 diabetes by between 18% and 24% and raises the risk for metabolic syndrome by up to 44%.
Dr. Gómez-Delgado, an internal medicine specialist at the University Hospital of Jaen in Spain and first author of the study, discussed the deleterious effects of sweeteners on metabolism. “On one hand, neurohormonal disorders impact appetite, and the feeling of satiety is abnormally delayed.” On the other hand, “they induce excessive insulin secretion in the pancreas,” which in the long run, encourages metabolic disorders that lead to diabetes. Ultimately, this process produces what we know as “dysbiosis, since our microbiota is unable to process these artificial sweeteners.” Dysbiosis triggers specific pathophysiologic processes that negatively affect cardiometabolic and cardiovascular systems.
No differences
Regarding the type of sweetener, Dr. Gómez-Delgado noted that currently available studies assess the consumption of special dietary products that, in most cases, include various types of artificial sweeteners. “So, it’s not possible to define specific differences between them as to how they impact our health.” Additional studies are needed to confirm this effect at the cardiometabolic level and to analyze the different types of artificial sweeteners individually.
“There’s enough evidence to confirm that consuming artificial sweeteners negatively interferes with our metabolism – especially glucose metabolism – and increases the risk of developing diabetes,” said Dr. Gómez-Delgado.
High-sodium drinks
When it comes to the influence of artificial sweeteners on hypertension, “there is no single explanation. The World Health Organization already discussed this issue 4-5 years ago, not only due to their carcinogenic risk, but also due to this cardiovascular risk in terms of a lack of control of obesity, diabetes, and hypertension,” said Dr. Anguita.
Another important point “is that this is not in reference to the sweeteners themselves, but to soft drinks containing those components, which is where we have more studies,” he added. There are two factors explaining this increase in hypertension, which poses a problem at the population level, with medium- to long-term follow-up. “The sugary beverages that we mentioned have a higher sodium content. That is, the sweeteners add this element, which is a factor that’s directly linked to the increase in blood pressure levels.” Another factor that can influence blood pressure is “the increase in insulin secretion that has been described as resulting from sweeteners. In the medium and long term, this is associated with increased blood pressure levels.”
Cardiovascular risk factor?
Are artificial sweeteners considered to be a new cardiovascular risk factor? “What they really do is increase the incidence of the other classic risk factors,” including obesity, said Dr. Anguita. It has been shown that artificial sweeteners don’t reduce obesity when used continuously. Nonetheless, “there is still not enough evidence to view it in the same light as the classic risk factors,” added Dr. Anguita. However, it is a factor that can clearly worsen the control of the other factors. Therefore, “it’s appropriate to sound an alarm and explain that it’s not the best way to lose weight; there are many other healthier choices.”
“We need more robust evidence to take a clear position on the use of this type of sweetener and its detrimental effect on health. Meanwhile, it would be ideal to limit their consumption or even avoid adding artificial sweeteners to coffee or teas,” added Dr. Pérez-Martínez.
Regulate consumption
Dr. Pérez-Martínez mentioned that the measures proposed to regulate the consumption of artificial sweeteners and to modify the current legislation must involve “minimizing the consumption of these special dietary products as much as possible and even avoiding adding these artificial sweeteners to the foods that we consume; for example, to coffee and tea.” On the other hand, “we must provide consumers with information that is as clear and simple as possible regarding the composition of the food they consume and how it impacts their health.”
However, “we need more evidence to be able to take a clear position on what type of sweeteners we can consume in our diet and also to what extent we should limit their presence in the foods we consume,” said Dr. Pérez-Martínez.
Last, “most of the evidence is from short-term observational studies that assess frequencies and patterns of consumption of foods containing these artificial sweeteners.” Of course, “we need studies that specifically analyze their effects at the metabolic level as well as longer-term studies where the nutritional follow-up of participants is more accurate and rigorous, especially when it comes to the consumption of this type of food,” concluded Dr. Gómez-Delgado.
This article was translated from the Medscape Spanish Edition. A version appeared on Medscape.com.
It also shows evidence that these products are not beneficial for controlling excess weight.
Francisco Gómez-Delgado, MD, PhD, and Pablo Pérez-Martínez, MD, PhD, are members of the Spanish Society of Arteriosclerosis and of the Spanish Society of Internal Medicine. They have coordinated an updated review of the leading scientific evidence surrounding artificial sweeteners: evidence showing that far from positively affecting our health, they have “negative effects for the cardiometabolic system.”
The paper, published in Current Opinion in Cardiology, delves into the consumption of these sweeteners and their negative influence on the development of obesity and of several of the most important cardiometabolic risk factors (hypertension, dyslipidemia, and diabetes).
Globalization and the increase in consumption of ultraprocessed foods have led to a need for greater knowledge on the health impacts of certain nutrients such as artificial sweeteners (nutritive and nonnutritive). This review aims to analyze their role and their effect on cardiometabolic and cardiovascular disease risk.
Cardiovascular risk
The detrimental effects of a high-calorie, high-sugar diet have been well established. For this reason, health authorities recommend limiting sugar consumption. The recommendation has led the food industry to develop different artificial sweeteners with specific properties, such as flavor and stability (nutritive artificial sweeteners), and others aimed at limiting sugar in the diet (nonnutritive artificial sweeteners). Recent evidence explores the influence of these two types of artificial sweeteners on cardiovascular disease risk through risk factors such as obesity and type 2 diabetes, among others.
Initially, the consumption of artificial sweeteners was presented as an alternative for reducing calorie intake in the diet as an option for people with excess weight and obesity. However, as this paper explains, the consumption of these artificial sweeteners favors weight gain because of neuroendocrine mechanisms related to satiety that are abnormally activated when artificial sweeteners are consumed.
Weight gain
On the other hand, evidence shows that consuming artificial sweeteners does not encourage weight loss. “Quite the contrary,” Dr. Pérez-Martínez, scientific director at the Maimonides Biomedical Research Institute and internist at the University Hospital Reina Sofia, both in Córdoba, told this news organization. “There is evidence showing weight gain resulting from the effect that artificial sweetener consumption has at the neurohormonal level by altering the mechanisms involved in regulating the feeling of satiety.”
However, on the basis of current evidence, sugar cannot be claimed to be less harmful. “What we do know is that in both cases, we should reduce or remove them from our diets and replace them with other healthier alternatives for weight management, such as eating plant-based products or being physically active.”
Confronting ignorance
Nonetheless, these recommendations are conditional, “because the weight of the evidence is not extremely high, since there have not been a whole lot of studies. All nutritional studies must be viewed with caution,” Manuel Anguita, MD, PhD, said in an interview. Dr. Anguita is department head of clinical cardiology at the University Hospital Reina Sofia in Córdoba and past president of the Spanish Society of Cardiology.
“It’s something that should be included within the medical record when you’re assessing cardiovascular risk. In addition to identifying patients who use artificial sweeteners, it’s especially important to emphasize that it’s not an appropriate recommendation for weight management.” Healthier measures include moderate exercise and the Mediterranean diet.
Explaining why this research is valuable, he said, “It’s generally useful because there’s ignorance not only in the population but among physicians as well [about] these negative effects of sweeteners.”
Diabetes and metabolic syndrome
Artificial sweeteners cause significant disruptions in the endocrine system, leading our metabolism to function abnormally. The review revealed that consuming artificial sweeteners raises the risk for type 2 diabetes by between 18% and 24% and raises the risk for metabolic syndrome by up to 44%.
Dr. Gómez-Delgado, an internal medicine specialist at the University Hospital of Jaen in Spain and first author of the study, discussed the deleterious effects of sweeteners on metabolism. “On one hand, neurohormonal disorders impact appetite, and the feeling of satiety is abnormally delayed.” On the other hand, “they induce excessive insulin secretion in the pancreas,” which in the long run, encourages metabolic disorders that lead to diabetes. Ultimately, this process produces what we know as “dysbiosis, since our microbiota is unable to process these artificial sweeteners.” Dysbiosis triggers specific pathophysiologic processes that negatively affect cardiometabolic and cardiovascular systems.
No differences
Regarding the type of sweetener, Dr. Gómez-Delgado noted that currently available studies assess the consumption of special dietary products that, in most cases, include various types of artificial sweeteners. “So, it’s not possible to define specific differences between them as to how they impact our health.” Additional studies are needed to confirm this effect at the cardiometabolic level and to analyze the different types of artificial sweeteners individually.
“There’s enough evidence to confirm that consuming artificial sweeteners negatively interferes with our metabolism – especially glucose metabolism – and increases the risk of developing diabetes,” said Dr. Gómez-Delgado.
High-sodium drinks
When it comes to the influence of artificial sweeteners on hypertension, “there is no single explanation. The World Health Organization already discussed this issue 4-5 years ago, not only due to their carcinogenic risk, but also due to this cardiovascular risk in terms of a lack of control of obesity, diabetes, and hypertension,” said Dr. Anguita.
Another important point “is that this is not in reference to the sweeteners themselves, but to soft drinks containing those components, which is where we have more studies,” he added. There are two factors explaining this increase in hypertension, which poses a problem at the population level, with medium- to long-term follow-up. “The sugary beverages that we mentioned have a higher sodium content. That is, the sweeteners add this element, which is a factor that’s directly linked to the increase in blood pressure levels.” Another factor that can influence blood pressure is “the increase in insulin secretion that has been described as resulting from sweeteners. In the medium and long term, this is associated with increased blood pressure levels.”
Cardiovascular risk factor?
Are artificial sweeteners considered to be a new cardiovascular risk factor? “What they really do is increase the incidence of the other classic risk factors,” including obesity, said Dr. Anguita. It has been shown that artificial sweeteners don’t reduce obesity when used continuously. Nonetheless, “there is still not enough evidence to view it in the same light as the classic risk factors,” added Dr. Anguita. However, it is a factor that can clearly worsen the control of the other factors. Therefore, “it’s appropriate to sound an alarm and explain that it’s not the best way to lose weight; there are many other healthier choices.”
“We need more robust evidence to take a clear position on the use of this type of sweetener and its detrimental effect on health. Meanwhile, it would be ideal to limit their consumption or even avoid adding artificial sweeteners to coffee or teas,” added Dr. Pérez-Martínez.
Regulate consumption
Dr. Pérez-Martínez mentioned that the measures proposed to regulate the consumption of artificial sweeteners and to modify the current legislation must involve “minimizing the consumption of these special dietary products as much as possible and even avoiding adding these artificial sweeteners to the foods that we consume; for example, to coffee and tea.” On the other hand, “we must provide consumers with information that is as clear and simple as possible regarding the composition of the food they consume and how it impacts their health.”
However, “we need more evidence to be able to take a clear position on what type of sweeteners we can consume in our diet and also to what extent we should limit their presence in the foods we consume,” said Dr. Pérez-Martínez.
Last, “most of the evidence is from short-term observational studies that assess frequencies and patterns of consumption of foods containing these artificial sweeteners.” Of course, “we need studies that specifically analyze their effects at the metabolic level as well as longer-term studies where the nutritional follow-up of participants is more accurate and rigorous, especially when it comes to the consumption of this type of food,” concluded Dr. Gómez-Delgado.
This article was translated from the Medscape Spanish Edition. A version appeared on Medscape.com.
FROM CURRENT OPINION IN CARDIOLOGY
Experts call for early screening for chronic kidney disease
MADRID – A late diagnosis of chronic kidney disease is cause for concern. Scientific societies are therefore advocating for screening at younger ages to reverse this trend and slow the progression of the disease. Nearly all patients seen in primary care are candidates for screening because of their risk factors for kidney disease.
During the 29th National Conference of General and Family Medicine of the Spanish Society for General and Family Physicians, Teresa Benedito, MD, family doctor and member of the society’s cardiovascular group, and Roberto Alcázar, MD, nephrologist at the Infanta Leonor University Hospital, Madrid, presented a clinical case encountered in primary care. They used this case to frame a strong argument for the importance of early screening for chronic kidney disease, and they discussed how to properly manage such screening.
The presentation followed the guidelines in the SEMG publication regarding the management and referral of patients with type 2 diabetes. Dr. Benedito explained that the first thing to ask oneself during a patient visit is “whether they present risk factors for kidney disease. If so, we can’t let them leave before we do a kidney screening.” She then listed the factors in question: age older than 60 years, African heritage, family history of chronic kidney disease, decreased kidney mass, weight loss at birth, hypertension, diabetes, smoking, obesity, and low socioeconomic status.
For his part, Dr. Alcázar mentioned how these factors are similar to cardiovascular risk factors, because “the kidneys are a ball of vessels with double capillarization for purifying blood. They’re the organs with the most arteries per unit of weight, so anything that can damage the arteries can damage the kidneys.”
Candidates for screening
“Chronic kidney disease develops in 15% of the adult population in Spain. So, it’s worth asking how many patients have been diagnosed and who should we should be screening.” To the factors listed above, Dr. Alcázar added treatment with nephrotoxic drugs (including nonsteroidal anti-inflammatory drugs) for patients with obstructive urinary tract disease, and a history of acute kidney injury for patients with chronic autoimmune disease or neoplasms. “Thus, nearly all patients seen in primary care would need to be screened.”
Another fundamental question raised was whether patients should be screened before age 60 years. “As a nephrologist, I feel that we have been diagnosing chronic kidney disease late, even though we’ve been doing everything by the book,” said Dr. Alcázar. In his opinion, “the answer to whether we should be screening earlier ... is yes, for two reasons: first, because it’s cost-effective, and second, because it’s very inexpensive.”
Dr. Benedito explained in detail the process for diagnosing this disease. She began by defining the disease as changes in kidney structure and function that last longer than 3 months. These changes are identified by use of two criteria: glomerular filtration rate less than 60 mL/min and kidney injury or lesions with or without reduced filtration rate (renal biopsy, albumin/creatinine ratio greater than 30 mg/g, proteinuria, alterations in urinary sediment or in imaging tests). Thus, “if one of these two criteria persists for more than 3 months, the diagnosis is chronic kidney disease. Also, high creatinine levels are not diagnostic for the disease,” she emphasized.
Two related parameters
Glomerular filtration and albuminuria “are highly relevant, because screening for chronic kidney disease is based on these two parameters,” said Dr. Benedito. Glomerular filtration rate varies with age, sex, ethnicity, and body mass. It is useful for identifying the stage of the disease and for monitoring disease progression. Albuminuria, on the other hand, is an indication of the severity of the disease. It’s an early marker for kidney injury and systemic disease and is more sensitive than proteinuria. Therefore, “this factor, together with glomerular filtration rate, allows us to detect, classify, and monitor the progression of chronic kidney disease.”
On this point, Dr. Alcázar emphasized the importance of trends, since variation in glomerular filtration depends on serum creatinine, which can vary by nearly 9%. He explained that glomerular filtration rate is related to the number of nephrons remaining. A glomerular filtration rate of less than 60 mL/min implies that more than half of the nephrons in each kidney have been lost. Albuminuria informs about structural damage (that is, the condition of the remaining nephrons). It’s therefore essential to test for both parameters. “We need to be actively monitoring and then making our decisions based on trends and not on isolated results. We need to be aware of albuminuria when we make our decisions,” said Dr. Alcázar. Some studies have shown the importance of testing for albuminuria whenever creatinine level is assessed. “We need to buy into this. If we don’t do this, we’ll only ever have half the information we need.”
Reducing late diagnosis
According to the IBERICAN study, 14% of patients seen in primary care in Spain have chronic kidney disease. “This statistic should make us stop and think, own our responsibility, and ask ourselves why this screening isn’t taking place [earlier],” said Dr. Benedito. She added, “We need to head off this trend toward late diagnosis. As the disease progresses, it significantly increases cardiovascular risk and leads to higher mortality, going on dialysis, transplants, et cetera.”
Dr. Alcázar noted that 80% of nephrology cases that are referred to him come from primary care. He explained the need to understand that “these patients have a sevenfold greater risk of suffering a serious cardiovascular event within the next year than people without kidney problems.” Most of these patients will experience an event, even if they don’t undergo dialysis (stage 3 and those near stage 4).
Correct staging
Also fundamental is having a detailed understanding of how staging is performed. Dr. Benedito explained that a chart that pairs glomerular filtration rate (six categories) with the level of albuminuria (three categories) should be used during the visit. For example, a case might be classified as G3a-A2. However, the simplified form of the chart may prove more practical. It classifies chronic kidney disease as being associated with mild, moderate, and severe risk, using different colors to aid comprehension.
Dr. Alcázar noted that the latest guidelines from the European Society of Hypertension for 2023 include albuminuria as an important parameter. The guidelines indicate that for a patient with moderate or severe risk, it is not necessary to calculate their score. “It’s considered high cardiovascular risk, and steps would need to be taken for intervention.”
He then listed the tools available for reversing albuminuria. The process begins by reducing salt consumption and involves the use of medications (angiotensin-converting enzyme inhibitors/angiotensin II receptor antagonists, aldosterone receptor antagonists, glucagon-like peptide-1 analogues, and sodium-glucose cotransporter-2 inhibitors, which slow kidney damage regardless of other measures) and strict management of cardiovascular risk factors (smoking, weight management, blood glucose, hypertension, and moderate physical activity).
Reducing cardiovascular risk
Dr. Alcázar highlighted important factors to keep in mind when managing each of the cardiovascular risk factors. For hypertension, the aim is to achieve levels less than 130/80 mm Hg, although recommendations vary, depending on the guidelines consulted. “KDIGO (Kidney Disease: Improving Global Outcomes) 2021 states that there is no evidence for monitoring diastolic blood pressure, only systolic blood pressure. If we measure it according to the standardized form, SBP should be less than 120 mm Hg, and if not, we would fall back on readings of 130/80 mm Hg.”
For lipid control (specifically, low-density lipoprotein cholesterol), the staging chart indicates that for patients at mild risk, levels should be less than 100 mg/dL; for those at moderate risk, less than 70 mg/dL; and for those at severe risk, less than 55 mg/dL. Hypertriglyceridemia “should only be treated with fibrates if it comes in over 1,000 mg/dL. Also, care must be taken, because these drugs interfere with creatinine excretion, increasing it,” said Dr. Alcázar.
Guidelines from the KDIGO and the American Diabetes Association state that anyone with diabetes and chronic kidney disease should receive a sodium-glucose cotransporter-2 inhibitor if their glomerular filtration rate exceeds 20 mL/min, “which may contradict slightly what it says on the label. Also, if they have hypertension, they should take an angiotensin-converting enzyme inhibitor,” said Dr. Alcázar. He added that “oral antidiabetics, including metformin, must be adjusted based on renal function if glomerular filtration rate is under 30 mL/min.”
Act immediately
When asked whether the course of chronic kidney disease can be changed, Dr. Alcázar responded with an emphatic yes and added that cardiovascular risk can also be substantially reduced. “As nephrologists, we don’t have access to patients in early stages. But family doctors do. Hence the importance of early screening, because going on dialysis at age 60 isn’t the same as at 80.” Currently, “scientific societies are encouraging authorities to screen for chronic kidney disease at earlier ages.”
Regarding drug-based therapy, Dr. Alcázar said that “empagliflozin is not currently indicated for chronic kidney disease in adults.” This sodium-glucose cotransporter-2 inhibitor delays kidney disease and reduces morbidity. Both benefits were highlighted in two recent studies (DAPA-CKD and CREDENCE). Published in January, EMPA-KIDNEY presents a new twist on nephroprotection for patients with chronic kidney disease (diabetic or not) whose glomerular filtration rates are between 20 and 40 mL/min without albuminuria or whose glomerular filtration rates are between 45 and 90 mL/min with albuminuria. For more than 6,000 patients, empagliflozin was observed “to clearly reduce kidney disease progression, cardiovascular mortality and all-cause mortality, and the need to go on dialysis,” stated Dr. Alcázar.
What professionals expect
Dr. Benedito also explained the criteria for referral to a specialist: glomerular filtration rate less than 30 mL/min (unless the patient is older than 80 years and does not have progressively worsening renal function), albumin/creatinine ratio greater than 300 mg/g, acute worsening of renal function, progressive worsening of renal function of greater than 5 mL/min/yr, chronic kidney disease, hypertension treated with triple therapy (including a diuretic) at maximum doses, anemia of less than 10 g/dL, and nonurologic hematuria, especially in combination with albuminuria.
Dr. Benedito explained what nephrologists expect from family doctors in the management of chronic kidney disease: “screening for early detection, identifying and treating risk factors for chronic kidney disease, detecting progression and complications, adjusting drugs based on glomerular filtration rate, and ensuring that our patients are benefiting from sodium-glucose cotransporter-2 inhibitors. These are among the most important steps to be taken.”
Dr. Alcázar mentioned what family doctors expect from nephrologists: “two-way communication, accessibility, coordination of actions to be taken, and using shared and mutually agreed-upon protocols.”
This article was translated from the Medscape Spanish Edition and a version appeared on Medscape.com.
MADRID – A late diagnosis of chronic kidney disease is cause for concern. Scientific societies are therefore advocating for screening at younger ages to reverse this trend and slow the progression of the disease. Nearly all patients seen in primary care are candidates for screening because of their risk factors for kidney disease.
During the 29th National Conference of General and Family Medicine of the Spanish Society for General and Family Physicians, Teresa Benedito, MD, family doctor and member of the society’s cardiovascular group, and Roberto Alcázar, MD, nephrologist at the Infanta Leonor University Hospital, Madrid, presented a clinical case encountered in primary care. They used this case to frame a strong argument for the importance of early screening for chronic kidney disease, and they discussed how to properly manage such screening.
The presentation followed the guidelines in the SEMG publication regarding the management and referral of patients with type 2 diabetes. Dr. Benedito explained that the first thing to ask oneself during a patient visit is “whether they present risk factors for kidney disease. If so, we can’t let them leave before we do a kidney screening.” She then listed the factors in question: age older than 60 years, African heritage, family history of chronic kidney disease, decreased kidney mass, weight loss at birth, hypertension, diabetes, smoking, obesity, and low socioeconomic status.
For his part, Dr. Alcázar mentioned how these factors are similar to cardiovascular risk factors, because “the kidneys are a ball of vessels with double capillarization for purifying blood. They’re the organs with the most arteries per unit of weight, so anything that can damage the arteries can damage the kidneys.”
Candidates for screening
“Chronic kidney disease develops in 15% of the adult population in Spain. So, it’s worth asking how many patients have been diagnosed and who should we should be screening.” To the factors listed above, Dr. Alcázar added treatment with nephrotoxic drugs (including nonsteroidal anti-inflammatory drugs) for patients with obstructive urinary tract disease, and a history of acute kidney injury for patients with chronic autoimmune disease or neoplasms. “Thus, nearly all patients seen in primary care would need to be screened.”
Another fundamental question raised was whether patients should be screened before age 60 years. “As a nephrologist, I feel that we have been diagnosing chronic kidney disease late, even though we’ve been doing everything by the book,” said Dr. Alcázar. In his opinion, “the answer to whether we should be screening earlier ... is yes, for two reasons: first, because it’s cost-effective, and second, because it’s very inexpensive.”
Dr. Benedito explained in detail the process for diagnosing this disease. She began by defining the disease as changes in kidney structure and function that last longer than 3 months. These changes are identified by use of two criteria: glomerular filtration rate less than 60 mL/min and kidney injury or lesions with or without reduced filtration rate (renal biopsy, albumin/creatinine ratio greater than 30 mg/g, proteinuria, alterations in urinary sediment or in imaging tests). Thus, “if one of these two criteria persists for more than 3 months, the diagnosis is chronic kidney disease. Also, high creatinine levels are not diagnostic for the disease,” she emphasized.
Two related parameters
Glomerular filtration and albuminuria “are highly relevant, because screening for chronic kidney disease is based on these two parameters,” said Dr. Benedito. Glomerular filtration rate varies with age, sex, ethnicity, and body mass. It is useful for identifying the stage of the disease and for monitoring disease progression. Albuminuria, on the other hand, is an indication of the severity of the disease. It’s an early marker for kidney injury and systemic disease and is more sensitive than proteinuria. Therefore, “this factor, together with glomerular filtration rate, allows us to detect, classify, and monitor the progression of chronic kidney disease.”
On this point, Dr. Alcázar emphasized the importance of trends, since variation in glomerular filtration depends on serum creatinine, which can vary by nearly 9%. He explained that glomerular filtration rate is related to the number of nephrons remaining. A glomerular filtration rate of less than 60 mL/min implies that more than half of the nephrons in each kidney have been lost. Albuminuria informs about structural damage (that is, the condition of the remaining nephrons). It’s therefore essential to test for both parameters. “We need to be actively monitoring and then making our decisions based on trends and not on isolated results. We need to be aware of albuminuria when we make our decisions,” said Dr. Alcázar. Some studies have shown the importance of testing for albuminuria whenever creatinine level is assessed. “We need to buy into this. If we don’t do this, we’ll only ever have half the information we need.”
Reducing late diagnosis
According to the IBERICAN study, 14% of patients seen in primary care in Spain have chronic kidney disease. “This statistic should make us stop and think, own our responsibility, and ask ourselves why this screening isn’t taking place [earlier],” said Dr. Benedito. She added, “We need to head off this trend toward late diagnosis. As the disease progresses, it significantly increases cardiovascular risk and leads to higher mortality, going on dialysis, transplants, et cetera.”
Dr. Alcázar noted that 80% of nephrology cases that are referred to him come from primary care. He explained the need to understand that “these patients have a sevenfold greater risk of suffering a serious cardiovascular event within the next year than people without kidney problems.” Most of these patients will experience an event, even if they don’t undergo dialysis (stage 3 and those near stage 4).
Correct staging
Also fundamental is having a detailed understanding of how staging is performed. Dr. Benedito explained that a chart that pairs glomerular filtration rate (six categories) with the level of albuminuria (three categories) should be used during the visit. For example, a case might be classified as G3a-A2. However, the simplified form of the chart may prove more practical. It classifies chronic kidney disease as being associated with mild, moderate, and severe risk, using different colors to aid comprehension.
Dr. Alcázar noted that the latest guidelines from the European Society of Hypertension for 2023 include albuminuria as an important parameter. The guidelines indicate that for a patient with moderate or severe risk, it is not necessary to calculate their score. “It’s considered high cardiovascular risk, and steps would need to be taken for intervention.”
He then listed the tools available for reversing albuminuria. The process begins by reducing salt consumption and involves the use of medications (angiotensin-converting enzyme inhibitors/angiotensin II receptor antagonists, aldosterone receptor antagonists, glucagon-like peptide-1 analogues, and sodium-glucose cotransporter-2 inhibitors, which slow kidney damage regardless of other measures) and strict management of cardiovascular risk factors (smoking, weight management, blood glucose, hypertension, and moderate physical activity).
Reducing cardiovascular risk
Dr. Alcázar highlighted important factors to keep in mind when managing each of the cardiovascular risk factors. For hypertension, the aim is to achieve levels less than 130/80 mm Hg, although recommendations vary, depending on the guidelines consulted. “KDIGO (Kidney Disease: Improving Global Outcomes) 2021 states that there is no evidence for monitoring diastolic blood pressure, only systolic blood pressure. If we measure it according to the standardized form, SBP should be less than 120 mm Hg, and if not, we would fall back on readings of 130/80 mm Hg.”
For lipid control (specifically, low-density lipoprotein cholesterol), the staging chart indicates that for patients at mild risk, levels should be less than 100 mg/dL; for those at moderate risk, less than 70 mg/dL; and for those at severe risk, less than 55 mg/dL. Hypertriglyceridemia “should only be treated with fibrates if it comes in over 1,000 mg/dL. Also, care must be taken, because these drugs interfere with creatinine excretion, increasing it,” said Dr. Alcázar.
Guidelines from the KDIGO and the American Diabetes Association state that anyone with diabetes and chronic kidney disease should receive a sodium-glucose cotransporter-2 inhibitor if their glomerular filtration rate exceeds 20 mL/min, “which may contradict slightly what it says on the label. Also, if they have hypertension, they should take an angiotensin-converting enzyme inhibitor,” said Dr. Alcázar. He added that “oral antidiabetics, including metformin, must be adjusted based on renal function if glomerular filtration rate is under 30 mL/min.”
Act immediately
When asked whether the course of chronic kidney disease can be changed, Dr. Alcázar responded with an emphatic yes and added that cardiovascular risk can also be substantially reduced. “As nephrologists, we don’t have access to patients in early stages. But family doctors do. Hence the importance of early screening, because going on dialysis at age 60 isn’t the same as at 80.” Currently, “scientific societies are encouraging authorities to screen for chronic kidney disease at earlier ages.”
Regarding drug-based therapy, Dr. Alcázar said that “empagliflozin is not currently indicated for chronic kidney disease in adults.” This sodium-glucose cotransporter-2 inhibitor delays kidney disease and reduces morbidity. Both benefits were highlighted in two recent studies (DAPA-CKD and CREDENCE). Published in January, EMPA-KIDNEY presents a new twist on nephroprotection for patients with chronic kidney disease (diabetic or not) whose glomerular filtration rates are between 20 and 40 mL/min without albuminuria or whose glomerular filtration rates are between 45 and 90 mL/min with albuminuria. For more than 6,000 patients, empagliflozin was observed “to clearly reduce kidney disease progression, cardiovascular mortality and all-cause mortality, and the need to go on dialysis,” stated Dr. Alcázar.
What professionals expect
Dr. Benedito also explained the criteria for referral to a specialist: glomerular filtration rate less than 30 mL/min (unless the patient is older than 80 years and does not have progressively worsening renal function), albumin/creatinine ratio greater than 300 mg/g, acute worsening of renal function, progressive worsening of renal function of greater than 5 mL/min/yr, chronic kidney disease, hypertension treated with triple therapy (including a diuretic) at maximum doses, anemia of less than 10 g/dL, and nonurologic hematuria, especially in combination with albuminuria.
Dr. Benedito explained what nephrologists expect from family doctors in the management of chronic kidney disease: “screening for early detection, identifying and treating risk factors for chronic kidney disease, detecting progression and complications, adjusting drugs based on glomerular filtration rate, and ensuring that our patients are benefiting from sodium-glucose cotransporter-2 inhibitors. These are among the most important steps to be taken.”
Dr. Alcázar mentioned what family doctors expect from nephrologists: “two-way communication, accessibility, coordination of actions to be taken, and using shared and mutually agreed-upon protocols.”
This article was translated from the Medscape Spanish Edition and a version appeared on Medscape.com.
MADRID – A late diagnosis of chronic kidney disease is cause for concern. Scientific societies are therefore advocating for screening at younger ages to reverse this trend and slow the progression of the disease. Nearly all patients seen in primary care are candidates for screening because of their risk factors for kidney disease.
During the 29th National Conference of General and Family Medicine of the Spanish Society for General and Family Physicians, Teresa Benedito, MD, family doctor and member of the society’s cardiovascular group, and Roberto Alcázar, MD, nephrologist at the Infanta Leonor University Hospital, Madrid, presented a clinical case encountered in primary care. They used this case to frame a strong argument for the importance of early screening for chronic kidney disease, and they discussed how to properly manage such screening.
The presentation followed the guidelines in the SEMG publication regarding the management and referral of patients with type 2 diabetes. Dr. Benedito explained that the first thing to ask oneself during a patient visit is “whether they present risk factors for kidney disease. If so, we can’t let them leave before we do a kidney screening.” She then listed the factors in question: age older than 60 years, African heritage, family history of chronic kidney disease, decreased kidney mass, weight loss at birth, hypertension, diabetes, smoking, obesity, and low socioeconomic status.
For his part, Dr. Alcázar mentioned how these factors are similar to cardiovascular risk factors, because “the kidneys are a ball of vessels with double capillarization for purifying blood. They’re the organs with the most arteries per unit of weight, so anything that can damage the arteries can damage the kidneys.”
Candidates for screening
“Chronic kidney disease develops in 15% of the adult population in Spain. So, it’s worth asking how many patients have been diagnosed and who should we should be screening.” To the factors listed above, Dr. Alcázar added treatment with nephrotoxic drugs (including nonsteroidal anti-inflammatory drugs) for patients with obstructive urinary tract disease, and a history of acute kidney injury for patients with chronic autoimmune disease or neoplasms. “Thus, nearly all patients seen in primary care would need to be screened.”
Another fundamental question raised was whether patients should be screened before age 60 years. “As a nephrologist, I feel that we have been diagnosing chronic kidney disease late, even though we’ve been doing everything by the book,” said Dr. Alcázar. In his opinion, “the answer to whether we should be screening earlier ... is yes, for two reasons: first, because it’s cost-effective, and second, because it’s very inexpensive.”
Dr. Benedito explained in detail the process for diagnosing this disease. She began by defining the disease as changes in kidney structure and function that last longer than 3 months. These changes are identified by use of two criteria: glomerular filtration rate less than 60 mL/min and kidney injury or lesions with or without reduced filtration rate (renal biopsy, albumin/creatinine ratio greater than 30 mg/g, proteinuria, alterations in urinary sediment or in imaging tests). Thus, “if one of these two criteria persists for more than 3 months, the diagnosis is chronic kidney disease. Also, high creatinine levels are not diagnostic for the disease,” she emphasized.
Two related parameters
Glomerular filtration and albuminuria “are highly relevant, because screening for chronic kidney disease is based on these two parameters,” said Dr. Benedito. Glomerular filtration rate varies with age, sex, ethnicity, and body mass. It is useful for identifying the stage of the disease and for monitoring disease progression. Albuminuria, on the other hand, is an indication of the severity of the disease. It’s an early marker for kidney injury and systemic disease and is more sensitive than proteinuria. Therefore, “this factor, together with glomerular filtration rate, allows us to detect, classify, and monitor the progression of chronic kidney disease.”
On this point, Dr. Alcázar emphasized the importance of trends, since variation in glomerular filtration depends on serum creatinine, which can vary by nearly 9%. He explained that glomerular filtration rate is related to the number of nephrons remaining. A glomerular filtration rate of less than 60 mL/min implies that more than half of the nephrons in each kidney have been lost. Albuminuria informs about structural damage (that is, the condition of the remaining nephrons). It’s therefore essential to test for both parameters. “We need to be actively monitoring and then making our decisions based on trends and not on isolated results. We need to be aware of albuminuria when we make our decisions,” said Dr. Alcázar. Some studies have shown the importance of testing for albuminuria whenever creatinine level is assessed. “We need to buy into this. If we don’t do this, we’ll only ever have half the information we need.”
Reducing late diagnosis
According to the IBERICAN study, 14% of patients seen in primary care in Spain have chronic kidney disease. “This statistic should make us stop and think, own our responsibility, and ask ourselves why this screening isn’t taking place [earlier],” said Dr. Benedito. She added, “We need to head off this trend toward late diagnosis. As the disease progresses, it significantly increases cardiovascular risk and leads to higher mortality, going on dialysis, transplants, et cetera.”
Dr. Alcázar noted that 80% of nephrology cases that are referred to him come from primary care. He explained the need to understand that “these patients have a sevenfold greater risk of suffering a serious cardiovascular event within the next year than people without kidney problems.” Most of these patients will experience an event, even if they don’t undergo dialysis (stage 3 and those near stage 4).
Correct staging
Also fundamental is having a detailed understanding of how staging is performed. Dr. Benedito explained that a chart that pairs glomerular filtration rate (six categories) with the level of albuminuria (three categories) should be used during the visit. For example, a case might be classified as G3a-A2. However, the simplified form of the chart may prove more practical. It classifies chronic kidney disease as being associated with mild, moderate, and severe risk, using different colors to aid comprehension.
Dr. Alcázar noted that the latest guidelines from the European Society of Hypertension for 2023 include albuminuria as an important parameter. The guidelines indicate that for a patient with moderate or severe risk, it is not necessary to calculate their score. “It’s considered high cardiovascular risk, and steps would need to be taken for intervention.”
He then listed the tools available for reversing albuminuria. The process begins by reducing salt consumption and involves the use of medications (angiotensin-converting enzyme inhibitors/angiotensin II receptor antagonists, aldosterone receptor antagonists, glucagon-like peptide-1 analogues, and sodium-glucose cotransporter-2 inhibitors, which slow kidney damage regardless of other measures) and strict management of cardiovascular risk factors (smoking, weight management, blood glucose, hypertension, and moderate physical activity).
Reducing cardiovascular risk
Dr. Alcázar highlighted important factors to keep in mind when managing each of the cardiovascular risk factors. For hypertension, the aim is to achieve levels less than 130/80 mm Hg, although recommendations vary, depending on the guidelines consulted. “KDIGO (Kidney Disease: Improving Global Outcomes) 2021 states that there is no evidence for monitoring diastolic blood pressure, only systolic blood pressure. If we measure it according to the standardized form, SBP should be less than 120 mm Hg, and if not, we would fall back on readings of 130/80 mm Hg.”
For lipid control (specifically, low-density lipoprotein cholesterol), the staging chart indicates that for patients at mild risk, levels should be less than 100 mg/dL; for those at moderate risk, less than 70 mg/dL; and for those at severe risk, less than 55 mg/dL. Hypertriglyceridemia “should only be treated with fibrates if it comes in over 1,000 mg/dL. Also, care must be taken, because these drugs interfere with creatinine excretion, increasing it,” said Dr. Alcázar.
Guidelines from the KDIGO and the American Diabetes Association state that anyone with diabetes and chronic kidney disease should receive a sodium-glucose cotransporter-2 inhibitor if their glomerular filtration rate exceeds 20 mL/min, “which may contradict slightly what it says on the label. Also, if they have hypertension, they should take an angiotensin-converting enzyme inhibitor,” said Dr. Alcázar. He added that “oral antidiabetics, including metformin, must be adjusted based on renal function if glomerular filtration rate is under 30 mL/min.”
Act immediately
When asked whether the course of chronic kidney disease can be changed, Dr. Alcázar responded with an emphatic yes and added that cardiovascular risk can also be substantially reduced. “As nephrologists, we don’t have access to patients in early stages. But family doctors do. Hence the importance of early screening, because going on dialysis at age 60 isn’t the same as at 80.” Currently, “scientific societies are encouraging authorities to screen for chronic kidney disease at earlier ages.”
Regarding drug-based therapy, Dr. Alcázar said that “empagliflozin is not currently indicated for chronic kidney disease in adults.” This sodium-glucose cotransporter-2 inhibitor delays kidney disease and reduces morbidity. Both benefits were highlighted in two recent studies (DAPA-CKD and CREDENCE). Published in January, EMPA-KIDNEY presents a new twist on nephroprotection for patients with chronic kidney disease (diabetic or not) whose glomerular filtration rates are between 20 and 40 mL/min without albuminuria or whose glomerular filtration rates are between 45 and 90 mL/min with albuminuria. For more than 6,000 patients, empagliflozin was observed “to clearly reduce kidney disease progression, cardiovascular mortality and all-cause mortality, and the need to go on dialysis,” stated Dr. Alcázar.
What professionals expect
Dr. Benedito also explained the criteria for referral to a specialist: glomerular filtration rate less than 30 mL/min (unless the patient is older than 80 years and does not have progressively worsening renal function), albumin/creatinine ratio greater than 300 mg/g, acute worsening of renal function, progressive worsening of renal function of greater than 5 mL/min/yr, chronic kidney disease, hypertension treated with triple therapy (including a diuretic) at maximum doses, anemia of less than 10 g/dL, and nonurologic hematuria, especially in combination with albuminuria.
Dr. Benedito explained what nephrologists expect from family doctors in the management of chronic kidney disease: “screening for early detection, identifying and treating risk factors for chronic kidney disease, detecting progression and complications, adjusting drugs based on glomerular filtration rate, and ensuring that our patients are benefiting from sodium-glucose cotransporter-2 inhibitors. These are among the most important steps to be taken.”
Dr. Alcázar mentioned what family doctors expect from nephrologists: “two-way communication, accessibility, coordination of actions to be taken, and using shared and mutually agreed-upon protocols.”
This article was translated from the Medscape Spanish Edition and a version appeared on Medscape.com.
The metaverse is the dermatologist’s ally
MADRID – There are endless possibilities within the dermoverse (a term coined by joining “dermatology” and “metaverse”), from a robot office assistant to the brand new world it offers for virtual training and simulation.
A group of dermatologists expert in new technologies came together at the 50th National Congress of the Spanish Academy for Dermatology and Venereology to discuss the metaverse: that sum of all virtual spaces that bridges physical and digital reality, where users interact through their avatars and where these experts are discovering new opportunities for treating their patients. The metaverse and AI offer a massive opportunity for improving telehealth visits, immersive surgical planning, or virtual training using 3-D skin models. These are just a few examples of what this technology may eventually provide.
“The possibilities offered by the metaverse in the field of dermatology could be endless,” explained Miriam Fernández-Parrado, MD, dermatologist at Navarre Hospital, Pamplona, Spain. To her, “the metaverse could mean a step forward in teledermatology, which has come of age as a result of the pandemic.” These past few years have shown that it’s possible to perform some screenings online. This, in turn, has produced significant time and cost savings, along with greater efficacy in initial screening and early detection of serious diseases.
The overall percentage of cases that are potentially treatable in absentia is estimated to exceed 70%. “This isn’t a matter of replacing in-person visits but of finding a quality alternative that, far from dehumanizing the doctor-patient relationship, helps to satisfy the growing need for this relationship,” said Dr. Fernández-Parrado.
Always on duty
Julián Conejo-Mir, MD, PhD, professor and head of dermatology at the Virgen del Rocío Hospital in Seville, Spain, told this news organization that AI will help with day-to-day interactions with patients. It’s already a reality. “But to say that with a simple photo, we can address 70% of dermatology cases without being physically present with our patients – I don’t think that will become a reality in the next 20 years.”
Currently, algorithms can identify tumors with high success rates (80%-90%) using photographs and dermoscopic images; rates increase significantly when both kinds of images are available. These high success rates are possible because tumor morphology is stationary. “However, for inflammatory conditions, accurate diagnosis generally doesn’t exceed 60%, since these are conditions in which morphology can change a lot from one day to the next and can vary significantly, depending on their anatomic location or the patient’s age.”
Maybe once metaclinics, with 3-D virtual reality, have been established and clinicians can see the patient in real time from their offices, the rate of accurate diagnosis will reach 70%, especially with patients who have limited mobility or who live at a distance from the hospital. “But that’s still 10-15 years away, since more powerful computers are needed, most likely quantum computers,” cautioned Dr. Conejo-Mir.
The patient’s ally
In clinical practice, facilitating access to the dermoverse may help reduce pain and divert the patient’s attention, especially during in-person visits that require bothersome or uncomfortable interventions. “This is especially effective in pediatric dermatology, since settings of immersive virtual reality may contribute to relaxation among children,” explained Dr. Fernández-Parrado. She also sees potential applications among patients who need surgery. The metaverse would allow them to preview a simulation of their operation before undergoing it, thus reducing their anxiety and allaying their fears about these procedures.
Two lines are being pursued: automated diagnosis for telehealth consultations, which are primarily for tumors, and robotic office assistants.
“We have been using the first one in clinical practice, and we can achieve a success rate of 85%-90%.” The second one is much more complex, “and we’re having a hard time moving it forward within our research team, since it doesn’t involve only one algorithm. Instead, it requires five algorithms working together simultaneously (chatbot, automatic writing, image analysis, selecting the most appropriate treatment, ability to make recommendations, and even an additional one involving feelings),” explained Dr. Conejo-Mir.
A wise consultant
Dr. Conejo-Mir offered examples of how this might work in the near future. “In under 5 years, you’ll be able to sit in front of a computer or your smartphone, talk to an avatar that we’re able to select (sex, appearance, age, kind/serious), show the avatar your lesions, and it will tell us a basic diagnostic impression and even the treatment.”
With virtual learning, physicians can also gather knowledge or take refresher courses, using skin models in augmented reality with tumors and other skin lesions, or using immersive simulation courses that aid learning. Digital models that replicate the anatomy and elasticity of the skin or other characteristics unique to the patient can be used to reach decisions regarding surgeries and to practice interventions before entering the operating room, explained Dr. Fernández-Parrado.
Optimal virtual training
Virtual reality and simulation will doubtless play a major role in this promising field of using these devices for training purposes. “There will be virtual dermatology clinics or metaclinics, where you can do everything with virtual simulated patients, from gaining experience in interviews or health histories (even with patients who are difficult to deal with), to taking biopsies and performing interventions,” said Dr. Conejo-Mir.
A recent study titled “How the World Sees the Metaverse and Extended Reality” gathered data from 29 countries regarding the next 10 years. One of the greatest benefits of this technology is expected in health resources (59%), even more than in the trading of digital assets. While it is difficult to predict when the dermoverse will be in operation, Dr. Fernández-Parrado says she’s a techno-optimist. Together with Dr. Héctor Perandones, MD, a dermatologist at the University Healthcare Complex in León, Spain, and coauthor with Dr. Fernández-Parrado of the article, “A New Universe in Dermatology: From Metaverse to Dermoverse,” she’s convinced that “if we can imagine it, we can create it.”
A differential diagnostician
Over the past 10 years, AI has become a major ally of dermatology, providing new techniques that simplify the diagnosis and treatment of patients. There are many applications for which it adds tremendous value in dermatology: establishing precise differential diagnoses for common diseases, such as psoriasis, atopic dermatitis, or acne; eveloping personalized therapeutic protocols; and predicting medium- and long-term outcomes.
Furthermore, in onco-dermatology, AI has helped to automate the diagnosis of skin tumors by making it possible to differentiate between melanocytic and nonmelanocytic lesions. This distinction promotes early diagnosis and helps produce screening systems that are capable of prioritizing cases on the basis of their seriousness.
When asked whether any group has published any promising tools with good preliminary results, Dr. Conejo-Mir stated that his group has produced three articles that have been published in top-ranking journals. In these articles, “we explain our experience with artificial intelligence in Mohs surgery, in automated diagnosis, and for calculating the thickness of melanomas.” The eight-person research team, which comprises dermatologists and software engineers, has been working together in this area for the past 4 years.
Aesthetic dermatology
Unlike other specialists, dermatologists have 4-D vision when it comes to aesthetics, since they are also skin experts. AI plays a major role in aesthetic dermatology. It supports this specialty by providing a greater analytic capacity and by evaluating the procedure and technique to be used. “It’s going to help us think and make decisions. It has taken great strides in aesthetic dermatology, especially when it comes to techniques and products. There have been products like collagen, hyaluronic acid, then thread lifts ... Also, different techniques have been developed, like Botox, for example. Before, Botox was given following one method. Now, there are other methods,” explained Dr. Conejo-Mir.
He explained, “We have analyzed the facial image to detect wrinkles, spots, enlarged pores, et cetera, to see whether there are any lesions, and, depending on what the machine says you have, it provides you with a personalized treatment. It tells you the pattern of care that the patient should follow. It also tells you what you’re going to do, whether or not there is any problem, depending on the location and on what the person is like, et cetera. Then, for follow-up, you’re given an AI program that tells you if you’re doing well or not. Lastly, it gives you product recommendations.
“We are among the specialties that are going through the most change,” said Dr. Conejo-Mir.
An intrusive technology?
AI will be a tremendous help in decision-making, to the point where “in 4 or 5 years, it will become indispensable, just like the loupe in years past, and then the dermatoscope.” However, the machine will have to depend on human beings. “They won’t replace us, but they will become unavoidable assistants in our day-to-day medical practice.”
Questions have arisen regarding the potential dangers of these new technologies, like that of reducing the number of dermatologists within the population, and whether they might encourage intrusiveness. Dr. Conejo-Mir made no bones about it. “AI will never cut back the number of specialists. That is false. When AI supports us in teledermatology, even currently on our team, it spits out information, but the one making the decision is the practitioner, not the machine.”
AI is a tool but is not in itself something that treats patients. It is akin to the dermatoscope. Dermatologists use these tools every day, and they help arrive at diagnoses in difficult cases, but they are not a replacement for humans. “At least for the next 50 years, then we’ll see. In 2050 is when they say AI will surpass humans in its intelligence and reasoning capacity,” said Dr. Conejo-Mir.
Dr. Conejo-Mir has disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish Edition. A version of this article appeared on Medscape.com.
MADRID – There are endless possibilities within the dermoverse (a term coined by joining “dermatology” and “metaverse”), from a robot office assistant to the brand new world it offers for virtual training and simulation.
A group of dermatologists expert in new technologies came together at the 50th National Congress of the Spanish Academy for Dermatology and Venereology to discuss the metaverse: that sum of all virtual spaces that bridges physical and digital reality, where users interact through their avatars and where these experts are discovering new opportunities for treating their patients. The metaverse and AI offer a massive opportunity for improving telehealth visits, immersive surgical planning, or virtual training using 3-D skin models. These are just a few examples of what this technology may eventually provide.
“The possibilities offered by the metaverse in the field of dermatology could be endless,” explained Miriam Fernández-Parrado, MD, dermatologist at Navarre Hospital, Pamplona, Spain. To her, “the metaverse could mean a step forward in teledermatology, which has come of age as a result of the pandemic.” These past few years have shown that it’s possible to perform some screenings online. This, in turn, has produced significant time and cost savings, along with greater efficacy in initial screening and early detection of serious diseases.
The overall percentage of cases that are potentially treatable in absentia is estimated to exceed 70%. “This isn’t a matter of replacing in-person visits but of finding a quality alternative that, far from dehumanizing the doctor-patient relationship, helps to satisfy the growing need for this relationship,” said Dr. Fernández-Parrado.
Always on duty
Julián Conejo-Mir, MD, PhD, professor and head of dermatology at the Virgen del Rocío Hospital in Seville, Spain, told this news organization that AI will help with day-to-day interactions with patients. It’s already a reality. “But to say that with a simple photo, we can address 70% of dermatology cases without being physically present with our patients – I don’t think that will become a reality in the next 20 years.”
Currently, algorithms can identify tumors with high success rates (80%-90%) using photographs and dermoscopic images; rates increase significantly when both kinds of images are available. These high success rates are possible because tumor morphology is stationary. “However, for inflammatory conditions, accurate diagnosis generally doesn’t exceed 60%, since these are conditions in which morphology can change a lot from one day to the next and can vary significantly, depending on their anatomic location or the patient’s age.”
Maybe once metaclinics, with 3-D virtual reality, have been established and clinicians can see the patient in real time from their offices, the rate of accurate diagnosis will reach 70%, especially with patients who have limited mobility or who live at a distance from the hospital. “But that’s still 10-15 years away, since more powerful computers are needed, most likely quantum computers,” cautioned Dr. Conejo-Mir.
The patient’s ally
In clinical practice, facilitating access to the dermoverse may help reduce pain and divert the patient’s attention, especially during in-person visits that require bothersome or uncomfortable interventions. “This is especially effective in pediatric dermatology, since settings of immersive virtual reality may contribute to relaxation among children,” explained Dr. Fernández-Parrado. She also sees potential applications among patients who need surgery. The metaverse would allow them to preview a simulation of their operation before undergoing it, thus reducing their anxiety and allaying their fears about these procedures.
Two lines are being pursued: automated diagnosis for telehealth consultations, which are primarily for tumors, and robotic office assistants.
“We have been using the first one in clinical practice, and we can achieve a success rate of 85%-90%.” The second one is much more complex, “and we’re having a hard time moving it forward within our research team, since it doesn’t involve only one algorithm. Instead, it requires five algorithms working together simultaneously (chatbot, automatic writing, image analysis, selecting the most appropriate treatment, ability to make recommendations, and even an additional one involving feelings),” explained Dr. Conejo-Mir.
A wise consultant
Dr. Conejo-Mir offered examples of how this might work in the near future. “In under 5 years, you’ll be able to sit in front of a computer or your smartphone, talk to an avatar that we’re able to select (sex, appearance, age, kind/serious), show the avatar your lesions, and it will tell us a basic diagnostic impression and even the treatment.”
With virtual learning, physicians can also gather knowledge or take refresher courses, using skin models in augmented reality with tumors and other skin lesions, or using immersive simulation courses that aid learning. Digital models that replicate the anatomy and elasticity of the skin or other characteristics unique to the patient can be used to reach decisions regarding surgeries and to practice interventions before entering the operating room, explained Dr. Fernández-Parrado.
Optimal virtual training
Virtual reality and simulation will doubtless play a major role in this promising field of using these devices for training purposes. “There will be virtual dermatology clinics or metaclinics, where you can do everything with virtual simulated patients, from gaining experience in interviews or health histories (even with patients who are difficult to deal with), to taking biopsies and performing interventions,” said Dr. Conejo-Mir.
A recent study titled “How the World Sees the Metaverse and Extended Reality” gathered data from 29 countries regarding the next 10 years. One of the greatest benefits of this technology is expected in health resources (59%), even more than in the trading of digital assets. While it is difficult to predict when the dermoverse will be in operation, Dr. Fernández-Parrado says she’s a techno-optimist. Together with Dr. Héctor Perandones, MD, a dermatologist at the University Healthcare Complex in León, Spain, and coauthor with Dr. Fernández-Parrado of the article, “A New Universe in Dermatology: From Metaverse to Dermoverse,” she’s convinced that “if we can imagine it, we can create it.”
A differential diagnostician
Over the past 10 years, AI has become a major ally of dermatology, providing new techniques that simplify the diagnosis and treatment of patients. There are many applications for which it adds tremendous value in dermatology: establishing precise differential diagnoses for common diseases, such as psoriasis, atopic dermatitis, or acne; eveloping personalized therapeutic protocols; and predicting medium- and long-term outcomes.
Furthermore, in onco-dermatology, AI has helped to automate the diagnosis of skin tumors by making it possible to differentiate between melanocytic and nonmelanocytic lesions. This distinction promotes early diagnosis and helps produce screening systems that are capable of prioritizing cases on the basis of their seriousness.
When asked whether any group has published any promising tools with good preliminary results, Dr. Conejo-Mir stated that his group has produced three articles that have been published in top-ranking journals. In these articles, “we explain our experience with artificial intelligence in Mohs surgery, in automated diagnosis, and for calculating the thickness of melanomas.” The eight-person research team, which comprises dermatologists and software engineers, has been working together in this area for the past 4 years.
Aesthetic dermatology
Unlike other specialists, dermatologists have 4-D vision when it comes to aesthetics, since they are also skin experts. AI plays a major role in aesthetic dermatology. It supports this specialty by providing a greater analytic capacity and by evaluating the procedure and technique to be used. “It’s going to help us think and make decisions. It has taken great strides in aesthetic dermatology, especially when it comes to techniques and products. There have been products like collagen, hyaluronic acid, then thread lifts ... Also, different techniques have been developed, like Botox, for example. Before, Botox was given following one method. Now, there are other methods,” explained Dr. Conejo-Mir.
He explained, “We have analyzed the facial image to detect wrinkles, spots, enlarged pores, et cetera, to see whether there are any lesions, and, depending on what the machine says you have, it provides you with a personalized treatment. It tells you the pattern of care that the patient should follow. It also tells you what you’re going to do, whether or not there is any problem, depending on the location and on what the person is like, et cetera. Then, for follow-up, you’re given an AI program that tells you if you’re doing well or not. Lastly, it gives you product recommendations.
“We are among the specialties that are going through the most change,” said Dr. Conejo-Mir.
An intrusive technology?
AI will be a tremendous help in decision-making, to the point where “in 4 or 5 years, it will become indispensable, just like the loupe in years past, and then the dermatoscope.” However, the machine will have to depend on human beings. “They won’t replace us, but they will become unavoidable assistants in our day-to-day medical practice.”
Questions have arisen regarding the potential dangers of these new technologies, like that of reducing the number of dermatologists within the population, and whether they might encourage intrusiveness. Dr. Conejo-Mir made no bones about it. “AI will never cut back the number of specialists. That is false. When AI supports us in teledermatology, even currently on our team, it spits out information, but the one making the decision is the practitioner, not the machine.”
AI is a tool but is not in itself something that treats patients. It is akin to the dermatoscope. Dermatologists use these tools every day, and they help arrive at diagnoses in difficult cases, but they are not a replacement for humans. “At least for the next 50 years, then we’ll see. In 2050 is when they say AI will surpass humans in its intelligence and reasoning capacity,” said Dr. Conejo-Mir.
Dr. Conejo-Mir has disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish Edition. A version of this article appeared on Medscape.com.
MADRID – There are endless possibilities within the dermoverse (a term coined by joining “dermatology” and “metaverse”), from a robot office assistant to the brand new world it offers for virtual training and simulation.
A group of dermatologists expert in new technologies came together at the 50th National Congress of the Spanish Academy for Dermatology and Venereology to discuss the metaverse: that sum of all virtual spaces that bridges physical and digital reality, where users interact through their avatars and where these experts are discovering new opportunities for treating their patients. The metaverse and AI offer a massive opportunity for improving telehealth visits, immersive surgical planning, or virtual training using 3-D skin models. These are just a few examples of what this technology may eventually provide.
“The possibilities offered by the metaverse in the field of dermatology could be endless,” explained Miriam Fernández-Parrado, MD, dermatologist at Navarre Hospital, Pamplona, Spain. To her, “the metaverse could mean a step forward in teledermatology, which has come of age as a result of the pandemic.” These past few years have shown that it’s possible to perform some screenings online. This, in turn, has produced significant time and cost savings, along with greater efficacy in initial screening and early detection of serious diseases.
The overall percentage of cases that are potentially treatable in absentia is estimated to exceed 70%. “This isn’t a matter of replacing in-person visits but of finding a quality alternative that, far from dehumanizing the doctor-patient relationship, helps to satisfy the growing need for this relationship,” said Dr. Fernández-Parrado.
Always on duty
Julián Conejo-Mir, MD, PhD, professor and head of dermatology at the Virgen del Rocío Hospital in Seville, Spain, told this news organization that AI will help with day-to-day interactions with patients. It’s already a reality. “But to say that with a simple photo, we can address 70% of dermatology cases without being physically present with our patients – I don’t think that will become a reality in the next 20 years.”
Currently, algorithms can identify tumors with high success rates (80%-90%) using photographs and dermoscopic images; rates increase significantly when both kinds of images are available. These high success rates are possible because tumor morphology is stationary. “However, for inflammatory conditions, accurate diagnosis generally doesn’t exceed 60%, since these are conditions in which morphology can change a lot from one day to the next and can vary significantly, depending on their anatomic location or the patient’s age.”
Maybe once metaclinics, with 3-D virtual reality, have been established and clinicians can see the patient in real time from their offices, the rate of accurate diagnosis will reach 70%, especially with patients who have limited mobility or who live at a distance from the hospital. “But that’s still 10-15 years away, since more powerful computers are needed, most likely quantum computers,” cautioned Dr. Conejo-Mir.
The patient’s ally
In clinical practice, facilitating access to the dermoverse may help reduce pain and divert the patient’s attention, especially during in-person visits that require bothersome or uncomfortable interventions. “This is especially effective in pediatric dermatology, since settings of immersive virtual reality may contribute to relaxation among children,” explained Dr. Fernández-Parrado. She also sees potential applications among patients who need surgery. The metaverse would allow them to preview a simulation of their operation before undergoing it, thus reducing their anxiety and allaying their fears about these procedures.
Two lines are being pursued: automated diagnosis for telehealth consultations, which are primarily for tumors, and robotic office assistants.
“We have been using the first one in clinical practice, and we can achieve a success rate of 85%-90%.” The second one is much more complex, “and we’re having a hard time moving it forward within our research team, since it doesn’t involve only one algorithm. Instead, it requires five algorithms working together simultaneously (chatbot, automatic writing, image analysis, selecting the most appropriate treatment, ability to make recommendations, and even an additional one involving feelings),” explained Dr. Conejo-Mir.
A wise consultant
Dr. Conejo-Mir offered examples of how this might work in the near future. “In under 5 years, you’ll be able to sit in front of a computer or your smartphone, talk to an avatar that we’re able to select (sex, appearance, age, kind/serious), show the avatar your lesions, and it will tell us a basic diagnostic impression and even the treatment.”
With virtual learning, physicians can also gather knowledge or take refresher courses, using skin models in augmented reality with tumors and other skin lesions, or using immersive simulation courses that aid learning. Digital models that replicate the anatomy and elasticity of the skin or other characteristics unique to the patient can be used to reach decisions regarding surgeries and to practice interventions before entering the operating room, explained Dr. Fernández-Parrado.
Optimal virtual training
Virtual reality and simulation will doubtless play a major role in this promising field of using these devices for training purposes. “There will be virtual dermatology clinics or metaclinics, where you can do everything with virtual simulated patients, from gaining experience in interviews or health histories (even with patients who are difficult to deal with), to taking biopsies and performing interventions,” said Dr. Conejo-Mir.
A recent study titled “How the World Sees the Metaverse and Extended Reality” gathered data from 29 countries regarding the next 10 years. One of the greatest benefits of this technology is expected in health resources (59%), even more than in the trading of digital assets. While it is difficult to predict when the dermoverse will be in operation, Dr. Fernández-Parrado says she’s a techno-optimist. Together with Dr. Héctor Perandones, MD, a dermatologist at the University Healthcare Complex in León, Spain, and coauthor with Dr. Fernández-Parrado of the article, “A New Universe in Dermatology: From Metaverse to Dermoverse,” she’s convinced that “if we can imagine it, we can create it.”
A differential diagnostician
Over the past 10 years, AI has become a major ally of dermatology, providing new techniques that simplify the diagnosis and treatment of patients. There are many applications for which it adds tremendous value in dermatology: establishing precise differential diagnoses for common diseases, such as psoriasis, atopic dermatitis, or acne; eveloping personalized therapeutic protocols; and predicting medium- and long-term outcomes.
Furthermore, in onco-dermatology, AI has helped to automate the diagnosis of skin tumors by making it possible to differentiate between melanocytic and nonmelanocytic lesions. This distinction promotes early diagnosis and helps produce screening systems that are capable of prioritizing cases on the basis of their seriousness.
When asked whether any group has published any promising tools with good preliminary results, Dr. Conejo-Mir stated that his group has produced three articles that have been published in top-ranking journals. In these articles, “we explain our experience with artificial intelligence in Mohs surgery, in automated diagnosis, and for calculating the thickness of melanomas.” The eight-person research team, which comprises dermatologists and software engineers, has been working together in this area for the past 4 years.
Aesthetic dermatology
Unlike other specialists, dermatologists have 4-D vision when it comes to aesthetics, since they are also skin experts. AI plays a major role in aesthetic dermatology. It supports this specialty by providing a greater analytic capacity and by evaluating the procedure and technique to be used. “It’s going to help us think and make decisions. It has taken great strides in aesthetic dermatology, especially when it comes to techniques and products. There have been products like collagen, hyaluronic acid, then thread lifts ... Also, different techniques have been developed, like Botox, for example. Before, Botox was given following one method. Now, there are other methods,” explained Dr. Conejo-Mir.
He explained, “We have analyzed the facial image to detect wrinkles, spots, enlarged pores, et cetera, to see whether there are any lesions, and, depending on what the machine says you have, it provides you with a personalized treatment. It tells you the pattern of care that the patient should follow. It also tells you what you’re going to do, whether or not there is any problem, depending on the location and on what the person is like, et cetera. Then, for follow-up, you’re given an AI program that tells you if you’re doing well or not. Lastly, it gives you product recommendations.
“We are among the specialties that are going through the most change,” said Dr. Conejo-Mir.
An intrusive technology?
AI will be a tremendous help in decision-making, to the point where “in 4 or 5 years, it will become indispensable, just like the loupe in years past, and then the dermatoscope.” However, the machine will have to depend on human beings. “They won’t replace us, but they will become unavoidable assistants in our day-to-day medical practice.”
Questions have arisen regarding the potential dangers of these new technologies, like that of reducing the number of dermatologists within the population, and whether they might encourage intrusiveness. Dr. Conejo-Mir made no bones about it. “AI will never cut back the number of specialists. That is false. When AI supports us in teledermatology, even currently on our team, it spits out information, but the one making the decision is the practitioner, not the machine.”
AI is a tool but is not in itself something that treats patients. It is akin to the dermatoscope. Dermatologists use these tools every day, and they help arrive at diagnoses in difficult cases, but they are not a replacement for humans. “At least for the next 50 years, then we’ll see. In 2050 is when they say AI will surpass humans in its intelligence and reasoning capacity,” said Dr. Conejo-Mir.
Dr. Conejo-Mir has disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish Edition. A version of this article appeared on Medscape.com.
Scientific advances and dietary measures to slow down aging
These findings are closer than ever to being applied in older adults. Currently, diet is the most accessible form of intervention, but it is appropriate to clarify current myths and realities.
An article published in Cell in 2013 summarized for the first time the molecular indicators of aging in mammals. The article had a great impact and served as a knowledge map about aging. Now the authors have updated and extended this knowledge in the same journal.
A barometer of interest in the topic is that approximately 300,000 articles on aging have been published since 2013, which is as many as were published during the previous century. In addition, almost 80 experiments have been conducted with mammals, including humans, that confirm that interventions in the aging process can prevent, delay, and even avoid age-related diseases such as cancer.
María A. Blasco, MD, scientific director of the National Cancer Research Center, an international leader in telomere research and coauthor of the study, noted on the institution’s website, “The spectacular advances in recent years to increase the longevity of model organisms, including in mammals, indicate that it will be important to develop rational strategies to intervene in human aging.”
Eighty experimental interventions
The new article verifies the conclusions of the analysis carried out a decade ago. “Now there is much more investment, and we are closer to applying basic knowledge to new ways of treating diseases,” said Dr. Blasco. The researchers identified nine indicators of aging – molecular signatures that mark the progress of the process and on which it was possible to act to prolong life.
They also point to four primary causes of aging: genomic instability, shortening of telomeres, epigenetic alterations, and imbalance between protein synthesis and degradation. These are strongly interconnected processes. Aging results from their joint action, which is why there are multiple ways to act on the physiologic process of aging. The new study includes a table with almost 80 recent experimental interventions with mammals (mostly mice) that suggest that it is possible to prolong life or treat age-associated diseases. Some of those studies concern humans; others investigate how to delay aging through diet. “Acting on the diet is one of the most accessible ways to intervene in human aging,” according to the researchers.
Nutrient sensors
Dietary interventions are related to a key indicator of aging: the dysregulation of the nutrient sensing mechanism. This mechanism is the sophisticated network of molecular signals that alert all mammals that food is available.
“Nutrient sensors are therapeutic targets for potential anti-longevity drugs, but health benefits and lifespan extension could also be achieved through dietary interventions. However, the results obtained in this line in our species are still unclear: Clinical trials based on dietary restriction in humans become complicated due to poor compliance, although they suggest positive effects on immunity and inflammation,” wrote the researchers.
Diet and disease
Javier Gómez Pavón, MD, head of geriatrics at Red Cross Hospital in Madrid and member of the leadership team of the Spanish Society of Geriatrics and Gerontology, told this news organization, “Currently, the evidence we have indicates that certain types of diet in population cohort studies are associated with a lower incidence and prevalence of certain diseases.”
Dr. Gómez mentioned contrasting examples. “The Mediterranean diet has been shown in different studies to be associated with a lower cardiovascular risk (stroke, ischemic heart disease, dyslipidemia) and a lower risk of cognitive impairment, especially due to its vascular component.”
Eating nuts (e.g., almonds, walnuts) is associated with a less dyslipidemia. A diet rich in fiber is also associated with less colonic digestive pathology, such as constipation and especially colon cancer. In addition, a diet low in fatty meats and rich in fruits and vegetables is associated with less prostate, breast, and colon disease. A diet with adequate protein intake is related to better muscle mass at all ages, and a diet rich in calcium products, such as nuts and dairy products, is linked to better bone mass and less osteoporosis and its consequences.
“At the moment, there is no study that links any type of diet with greater longevity, although in view of these data, it seems logical that a Mediterranean diet rich in fruits, vegetables, vegetables with proteins of animal origin, preferably fish or white meat, avoiding excess red meat and its calcium component in the form of nuts and dairy products would be associated with better disease-free aging,” said Dr. Gómez.
Aging indicators
The article expands the aging indicators from 9 to 12 (genomic instability, telomere wear, epigenetic alterations, loss of proteostasis, inactivated macroautophagy, dysregulation of nutrient sensing, mitochondrial dysfunction, cellular senescence, depletion of hematopoietic progenitor cells, alteration of intercellular communication, chronic inflammation, and imbalances in the microbiome), which are measurable processes that change with the aging of the organism and which, when manipulated experimentally, induce an acceleration or, on the contrary, an interruption, even a regression, of aging.
“Each of these indicators should be considered an entry point for future exploration of the aging process, as well as for the development of new antiaging drugs,” the researchers concluded.
A decade ago, it was recognized that telomere shortening was at the origin of age-related diseases, said Dr. Blasco. “It is now emphasized that the generation of mouse models with short telomeres has shown that telomeric wasting is at the origin of prevalent age-associated diseases, such as pulmonary and renal fibrosis.”
The recent study reviews new interventions to delay aging and age-related diseases that act on telomeres. “For example, the activation of telomerase through a gene therapy strategy has shown therapeutic effects in mouse models of pulmonary fibrosis and aplastic anemia,” Dr. Blasco added.
Food fact and fiction
Since diet is currently the most easily accessible element to slow down aging, Dr. Gómez refutes the most widespread myths that are circulating about food and longevity. First, regarding dairy products, it is said that yogurt is not useful for the elderly, since the elderly do not have adequate enzymes to digest yogurt and that it is only for children or young people who are growing. “It is not true. Dairy products are not important for their proteins but for their calcium and vitamin D content. [These are] fundamental elements at all ages, but especially in aging, where there is bone loss secondary to aging itself and an increased risk of osteoporosis and associated fractures. Especially in the elderly, the tragic hip fracture is associated with high morbidity and mortality.”
Another myth is that it is not good to eat fruit with meals. “Due to its rich content in antioxidants and vitamins, it is a fundamental food of the Mediterranean diet. Antioxidants of any type (nuts, vegetables, fruits, etc.) are undoubtedly the most important components against pathological aging (stroke, myocardial infarction, dementia, etc.). It may be true that they can be more easily digested if they are eaten outside of meals, but the important thing is that they be eaten whenever.”
Sugars and meat
“Regarding the ‘fact’ that the sugars in legumes and bread are harmful, it is not true. In addition to sugar, legumes contain fiber and other very important antioxidants, just like bread. The difference is the amount, as in all food. On the contrary, refined sugars, such as pastries, sugary drinks, etc., should be avoided, since they are directly related to cardiovascular disease and obesity,” added Dr. Gómez.
“As for the popular saying, ‘Do not even try meat,’ it is not sound, since red meat and fish, including oily fish, are rich in protein and vitamin B as well as iron and, therefore, are necessary.
“As always, it is the amount that should be limited, especially red meat, not so much oily fish. I would recommend reducing red meat and replacing it with white meat, since the former are rich in saturated fats that produce more cholesterol,” added Dr. Gómez.
Another phrase that circulates around is that wine is food. “Careful. Wine in small quantities, a glass at lunch and dinner, is beneficial due to its antioxidant power, but at more than these amounts, the negative power of alcohol predominates over its benefits,” concluded Dr. Gómez.
Dr. Gómez has disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.
These findings are closer than ever to being applied in older adults. Currently, diet is the most accessible form of intervention, but it is appropriate to clarify current myths and realities.
An article published in Cell in 2013 summarized for the first time the molecular indicators of aging in mammals. The article had a great impact and served as a knowledge map about aging. Now the authors have updated and extended this knowledge in the same journal.
A barometer of interest in the topic is that approximately 300,000 articles on aging have been published since 2013, which is as many as were published during the previous century. In addition, almost 80 experiments have been conducted with mammals, including humans, that confirm that interventions in the aging process can prevent, delay, and even avoid age-related diseases such as cancer.
María A. Blasco, MD, scientific director of the National Cancer Research Center, an international leader in telomere research and coauthor of the study, noted on the institution’s website, “The spectacular advances in recent years to increase the longevity of model organisms, including in mammals, indicate that it will be important to develop rational strategies to intervene in human aging.”
Eighty experimental interventions
The new article verifies the conclusions of the analysis carried out a decade ago. “Now there is much more investment, and we are closer to applying basic knowledge to new ways of treating diseases,” said Dr. Blasco. The researchers identified nine indicators of aging – molecular signatures that mark the progress of the process and on which it was possible to act to prolong life.
They also point to four primary causes of aging: genomic instability, shortening of telomeres, epigenetic alterations, and imbalance between protein synthesis and degradation. These are strongly interconnected processes. Aging results from their joint action, which is why there are multiple ways to act on the physiologic process of aging. The new study includes a table with almost 80 recent experimental interventions with mammals (mostly mice) that suggest that it is possible to prolong life or treat age-associated diseases. Some of those studies concern humans; others investigate how to delay aging through diet. “Acting on the diet is one of the most accessible ways to intervene in human aging,” according to the researchers.
Nutrient sensors
Dietary interventions are related to a key indicator of aging: the dysregulation of the nutrient sensing mechanism. This mechanism is the sophisticated network of molecular signals that alert all mammals that food is available.
“Nutrient sensors are therapeutic targets for potential anti-longevity drugs, but health benefits and lifespan extension could also be achieved through dietary interventions. However, the results obtained in this line in our species are still unclear: Clinical trials based on dietary restriction in humans become complicated due to poor compliance, although they suggest positive effects on immunity and inflammation,” wrote the researchers.
Diet and disease
Javier Gómez Pavón, MD, head of geriatrics at Red Cross Hospital in Madrid and member of the leadership team of the Spanish Society of Geriatrics and Gerontology, told this news organization, “Currently, the evidence we have indicates that certain types of diet in population cohort studies are associated with a lower incidence and prevalence of certain diseases.”
Dr. Gómez mentioned contrasting examples. “The Mediterranean diet has been shown in different studies to be associated with a lower cardiovascular risk (stroke, ischemic heart disease, dyslipidemia) and a lower risk of cognitive impairment, especially due to its vascular component.”
Eating nuts (e.g., almonds, walnuts) is associated with a less dyslipidemia. A diet rich in fiber is also associated with less colonic digestive pathology, such as constipation and especially colon cancer. In addition, a diet low in fatty meats and rich in fruits and vegetables is associated with less prostate, breast, and colon disease. A diet with adequate protein intake is related to better muscle mass at all ages, and a diet rich in calcium products, such as nuts and dairy products, is linked to better bone mass and less osteoporosis and its consequences.
“At the moment, there is no study that links any type of diet with greater longevity, although in view of these data, it seems logical that a Mediterranean diet rich in fruits, vegetables, vegetables with proteins of animal origin, preferably fish or white meat, avoiding excess red meat and its calcium component in the form of nuts and dairy products would be associated with better disease-free aging,” said Dr. Gómez.
Aging indicators
The article expands the aging indicators from 9 to 12 (genomic instability, telomere wear, epigenetic alterations, loss of proteostasis, inactivated macroautophagy, dysregulation of nutrient sensing, mitochondrial dysfunction, cellular senescence, depletion of hematopoietic progenitor cells, alteration of intercellular communication, chronic inflammation, and imbalances in the microbiome), which are measurable processes that change with the aging of the organism and which, when manipulated experimentally, induce an acceleration or, on the contrary, an interruption, even a regression, of aging.
“Each of these indicators should be considered an entry point for future exploration of the aging process, as well as for the development of new antiaging drugs,” the researchers concluded.
A decade ago, it was recognized that telomere shortening was at the origin of age-related diseases, said Dr. Blasco. “It is now emphasized that the generation of mouse models with short telomeres has shown that telomeric wasting is at the origin of prevalent age-associated diseases, such as pulmonary and renal fibrosis.”
The recent study reviews new interventions to delay aging and age-related diseases that act on telomeres. “For example, the activation of telomerase through a gene therapy strategy has shown therapeutic effects in mouse models of pulmonary fibrosis and aplastic anemia,” Dr. Blasco added.
Food fact and fiction
Since diet is currently the most easily accessible element to slow down aging, Dr. Gómez refutes the most widespread myths that are circulating about food and longevity. First, regarding dairy products, it is said that yogurt is not useful for the elderly, since the elderly do not have adequate enzymes to digest yogurt and that it is only for children or young people who are growing. “It is not true. Dairy products are not important for their proteins but for their calcium and vitamin D content. [These are] fundamental elements at all ages, but especially in aging, where there is bone loss secondary to aging itself and an increased risk of osteoporosis and associated fractures. Especially in the elderly, the tragic hip fracture is associated with high morbidity and mortality.”
Another myth is that it is not good to eat fruit with meals. “Due to its rich content in antioxidants and vitamins, it is a fundamental food of the Mediterranean diet. Antioxidants of any type (nuts, vegetables, fruits, etc.) are undoubtedly the most important components against pathological aging (stroke, myocardial infarction, dementia, etc.). It may be true that they can be more easily digested if they are eaten outside of meals, but the important thing is that they be eaten whenever.”
Sugars and meat
“Regarding the ‘fact’ that the sugars in legumes and bread are harmful, it is not true. In addition to sugar, legumes contain fiber and other very important antioxidants, just like bread. The difference is the amount, as in all food. On the contrary, refined sugars, such as pastries, sugary drinks, etc., should be avoided, since they are directly related to cardiovascular disease and obesity,” added Dr. Gómez.
“As for the popular saying, ‘Do not even try meat,’ it is not sound, since red meat and fish, including oily fish, are rich in protein and vitamin B as well as iron and, therefore, are necessary.
“As always, it is the amount that should be limited, especially red meat, not so much oily fish. I would recommend reducing red meat and replacing it with white meat, since the former are rich in saturated fats that produce more cholesterol,” added Dr. Gómez.
Another phrase that circulates around is that wine is food. “Careful. Wine in small quantities, a glass at lunch and dinner, is beneficial due to its antioxidant power, but at more than these amounts, the negative power of alcohol predominates over its benefits,” concluded Dr. Gómez.
Dr. Gómez has disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.
These findings are closer than ever to being applied in older adults. Currently, diet is the most accessible form of intervention, but it is appropriate to clarify current myths and realities.
An article published in Cell in 2013 summarized for the first time the molecular indicators of aging in mammals. The article had a great impact and served as a knowledge map about aging. Now the authors have updated and extended this knowledge in the same journal.
A barometer of interest in the topic is that approximately 300,000 articles on aging have been published since 2013, which is as many as were published during the previous century. In addition, almost 80 experiments have been conducted with mammals, including humans, that confirm that interventions in the aging process can prevent, delay, and even avoid age-related diseases such as cancer.
María A. Blasco, MD, scientific director of the National Cancer Research Center, an international leader in telomere research and coauthor of the study, noted on the institution’s website, “The spectacular advances in recent years to increase the longevity of model organisms, including in mammals, indicate that it will be important to develop rational strategies to intervene in human aging.”
Eighty experimental interventions
The new article verifies the conclusions of the analysis carried out a decade ago. “Now there is much more investment, and we are closer to applying basic knowledge to new ways of treating diseases,” said Dr. Blasco. The researchers identified nine indicators of aging – molecular signatures that mark the progress of the process and on which it was possible to act to prolong life.
They also point to four primary causes of aging: genomic instability, shortening of telomeres, epigenetic alterations, and imbalance between protein synthesis and degradation. These are strongly interconnected processes. Aging results from their joint action, which is why there are multiple ways to act on the physiologic process of aging. The new study includes a table with almost 80 recent experimental interventions with mammals (mostly mice) that suggest that it is possible to prolong life or treat age-associated diseases. Some of those studies concern humans; others investigate how to delay aging through diet. “Acting on the diet is one of the most accessible ways to intervene in human aging,” according to the researchers.
Nutrient sensors
Dietary interventions are related to a key indicator of aging: the dysregulation of the nutrient sensing mechanism. This mechanism is the sophisticated network of molecular signals that alert all mammals that food is available.
“Nutrient sensors are therapeutic targets for potential anti-longevity drugs, but health benefits and lifespan extension could also be achieved through dietary interventions. However, the results obtained in this line in our species are still unclear: Clinical trials based on dietary restriction in humans become complicated due to poor compliance, although they suggest positive effects on immunity and inflammation,” wrote the researchers.
Diet and disease
Javier Gómez Pavón, MD, head of geriatrics at Red Cross Hospital in Madrid and member of the leadership team of the Spanish Society of Geriatrics and Gerontology, told this news organization, “Currently, the evidence we have indicates that certain types of diet in population cohort studies are associated with a lower incidence and prevalence of certain diseases.”
Dr. Gómez mentioned contrasting examples. “The Mediterranean diet has been shown in different studies to be associated with a lower cardiovascular risk (stroke, ischemic heart disease, dyslipidemia) and a lower risk of cognitive impairment, especially due to its vascular component.”
Eating nuts (e.g., almonds, walnuts) is associated with a less dyslipidemia. A diet rich in fiber is also associated with less colonic digestive pathology, such as constipation and especially colon cancer. In addition, a diet low in fatty meats and rich in fruits and vegetables is associated with less prostate, breast, and colon disease. A diet with adequate protein intake is related to better muscle mass at all ages, and a diet rich in calcium products, such as nuts and dairy products, is linked to better bone mass and less osteoporosis and its consequences.
“At the moment, there is no study that links any type of diet with greater longevity, although in view of these data, it seems logical that a Mediterranean diet rich in fruits, vegetables, vegetables with proteins of animal origin, preferably fish or white meat, avoiding excess red meat and its calcium component in the form of nuts and dairy products would be associated with better disease-free aging,” said Dr. Gómez.
Aging indicators
The article expands the aging indicators from 9 to 12 (genomic instability, telomere wear, epigenetic alterations, loss of proteostasis, inactivated macroautophagy, dysregulation of nutrient sensing, mitochondrial dysfunction, cellular senescence, depletion of hematopoietic progenitor cells, alteration of intercellular communication, chronic inflammation, and imbalances in the microbiome), which are measurable processes that change with the aging of the organism and which, when manipulated experimentally, induce an acceleration or, on the contrary, an interruption, even a regression, of aging.
“Each of these indicators should be considered an entry point for future exploration of the aging process, as well as for the development of new antiaging drugs,” the researchers concluded.
A decade ago, it was recognized that telomere shortening was at the origin of age-related diseases, said Dr. Blasco. “It is now emphasized that the generation of mouse models with short telomeres has shown that telomeric wasting is at the origin of prevalent age-associated diseases, such as pulmonary and renal fibrosis.”
The recent study reviews new interventions to delay aging and age-related diseases that act on telomeres. “For example, the activation of telomerase through a gene therapy strategy has shown therapeutic effects in mouse models of pulmonary fibrosis and aplastic anemia,” Dr. Blasco added.
Food fact and fiction
Since diet is currently the most easily accessible element to slow down aging, Dr. Gómez refutes the most widespread myths that are circulating about food and longevity. First, regarding dairy products, it is said that yogurt is not useful for the elderly, since the elderly do not have adequate enzymes to digest yogurt and that it is only for children or young people who are growing. “It is not true. Dairy products are not important for their proteins but for their calcium and vitamin D content. [These are] fundamental elements at all ages, but especially in aging, where there is bone loss secondary to aging itself and an increased risk of osteoporosis and associated fractures. Especially in the elderly, the tragic hip fracture is associated with high morbidity and mortality.”
Another myth is that it is not good to eat fruit with meals. “Due to its rich content in antioxidants and vitamins, it is a fundamental food of the Mediterranean diet. Antioxidants of any type (nuts, vegetables, fruits, etc.) are undoubtedly the most important components against pathological aging (stroke, myocardial infarction, dementia, etc.). It may be true that they can be more easily digested if they are eaten outside of meals, but the important thing is that they be eaten whenever.”
Sugars and meat
“Regarding the ‘fact’ that the sugars in legumes and bread are harmful, it is not true. In addition to sugar, legumes contain fiber and other very important antioxidants, just like bread. The difference is the amount, as in all food. On the contrary, refined sugars, such as pastries, sugary drinks, etc., should be avoided, since they are directly related to cardiovascular disease and obesity,” added Dr. Gómez.
“As for the popular saying, ‘Do not even try meat,’ it is not sound, since red meat and fish, including oily fish, are rich in protein and vitamin B as well as iron and, therefore, are necessary.
“As always, it is the amount that should be limited, especially red meat, not so much oily fish. I would recommend reducing red meat and replacing it with white meat, since the former are rich in saturated fats that produce more cholesterol,” added Dr. Gómez.
Another phrase that circulates around is that wine is food. “Careful. Wine in small quantities, a glass at lunch and dinner, is beneficial due to its antioxidant power, but at more than these amounts, the negative power of alcohol predominates over its benefits,” concluded Dr. Gómez.
Dr. Gómez has disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.
FROM CELL
Hormone changes: The star of every stage in women’s sleep
MADRID – Because of the hormone changes that occur throughout their lives, women experience sleep problems that differ significantly from those experienced by men. Indeed, 75%-84% of pregnant women don’t sleep well during the third trimester, and up to 80% of women in menopause have symptoms that prevent them from getting a good night’s rest. For those seeking a precision medicine approach, the challenge is to identify the relationship between the different sex-related phenotypes and the sleep conditions.
Irene Cano, MD, PhD, is the coordinator of the sleep department at the Spanish Society of Pulmonology and Thoracic Surgery. She spoke with this news organization about the significant impact of hormones on sleep disorders in women.
“Reproductive hormones like estrogen and progesterone play a meaningful role in brain functions – not only those linked to the regulation of reproduction but also other physiological processes related to the regulation of circadian rhythms, cognitive performance, mood, and sleep. In addition, other hormones – for example, prolactin, growth hormone, cortisol, and melatonin – have sex-dependent effects on sleep,” Dr. Cano said.
Girls start puberty at a younger age than boys. As girls enter adolescence, they go to bed later and waking up earlier. So, girls are getting less than the 10 hours of sleep that they should be getting at this stage of life. The result is sleep debt, which gives rise to various problems: poor academic performance, ADHD, obesity, and metabolic problems, to name a few. As Ariadna Farré, RN, a sleep unit nurse, noted at SEPAR’s Joint Winter Meeting, “schools would have to start morning classes later to get adolescents to perform well academically. As the situation is now, half of the kids are falling asleep at their desks.”
Influencing sleep quality
Dr. Cano explained the issue as follows: “In adolescence, along with changes in young women’s hormone levels, we begin to see differences between the sexes. The changes in levels of estrogens and progesterone are what’s responsible for the changes that, to some extent, cause those disturbances in the quality of our sleep and in the stages of our sleep.”
Thus, sleep can be affected by the changes in hormone level that occur during a menstrual cycle. Estrogens, which increase during the follicular phase, are associated with REM sleep, while progesterone, which increases during the luteal phase, increases non-REM sleep. “In the 3-6 days prior to menstruation, it’s quite common for a woman to report difficulties falling asleep and staying asleep, in connection with a decline in the percentage of time she spends in REM sleep, in the context of premenstrual syndrome. In addition,” Dr. Cano pointed out, “menstrual bleeding, that loss of blood, is associated with a drop in iron levels, making it more likely that the woman will experience restless legs syndrome.”
Cardiovascular system
This news organization also spoke with Milagros Merino, MD, PhD, president of the Spanish Sleep Society. “The consequences that lack of sleep have on the cardiovascular system – we’re essentially talking about certain arrhythmias, high blood pressure, thrombosis in some cases, stroke, and heart attack. Lack of sleep also gives rise to endocrine and metabolic issues, like overweight and being at a greater risk of developing diabetes. And as for mental health, we see, among other things, attention and memory problems, emotional lability, and irascibility. Numerous studies have confirmed all of this.”
Sleep apnea also deserves mention, Dr. Merino added. “Although this disorder is more common in men, we’re seeing it more and more now in women, along with the cardiovascular issues that it brings about.”
Another cardiovascular risk factor is insomnia, said Dr. Merino. “This sleep disorder is more prevalent in women. As hormones constantly change, the ways women sleep constantly change, from one stage of life to the next. They sleep one way in childhood, another way in adolescence, and yet another way in menopause.”
Sleep in pregnancy
During pregnancy, hormone changes are much more pronounced. During the first trimester, progesterone levels increase, making the woman drowsy. On top of that, her sleep is interrupted by more frequent visits to the bathroom as well as greater general discomfort.
In the second trimester, sleep interruptions persist but are not as bad as they were during the first 3 months. In the third trimester, 75%-84% of pregnant women find it difficult to sleep because of aches and pains, the need to urinate during the night, cramps, and heartburn.
“Major physical changes are happening. When the bladder gets compressed, the woman has to get up and go to the bathroom. There’s an interruption in her sleep,” Ms. Farré explained. In addition, as the pregnancy progresses, the woman gains weight and her body mass index (BMI) increases, which can bring on obstructive sleep apnea, high blood pressure, preeclampsia, and diabetes, if not closely monitored.
Other factors include concomitant treatments, such as contraceptives, and the stages of life, such as pregnancy and lactation. “When a woman of childbearing age has restless legs syndrome, more often than not, this means that she has an iron deficiency that needs to be treated with oral iron supplements,” said Dr. Merino. “However, there are few medications that can be given to a pregnant woman – and RLS is relatively common during pregnancy. So, we have to turn to oral or intravenous iron supplements. Yet another matter is narcolepsy. In these cases, all medications have to be stopped during pregnancy and lactation, as they can be harmful to the baby.”
Sleep apnea
While one in five menopausal women are asymptomatic, the others experience mild to severe symptoms of apnea that frequently interrupt their sleep. In this stage of life, which begins around age 50 years, the hormones that had provided protection against sleep disruptions start to decrease. As a result, there is a rise in sleep problems, especially insomnia, breathing-related sleep disorders (for example, apnea), and restless legs syndrome.
The prevalence of breathing-related sleep disorders during menopause is attributable to weight gain, the drop in levels of estrogens, and the redistribution of adipose tissue in the body. Other factors also increase a woman’s risk of experiencing apnea. They range from stress, depression, and other psychological and psychiatric conditions to health status, medication use, and simply the fact of getting older. “Sleep apnea is more common in men than in premenopausal women. The numbers even out, though, when we compare men against menopausal women,” Dr. Cano noted.
In women, symptoms of sleep apnea are frequently attributed to menopause. There is some overlap: insomnia, headache, irritability, low mood, decreased libido, fatigue during the day, and feeling sleepy. Only much later is the woman’s condition correctly diagnosed as sleep apnea. So, even though presenting with the same complaints, a man will be diagnosed with sleep apnea sooner than a woman will – in some cases, around 10 years sooner.
“On the other hand, we’d always thought that, in menopause, insomnia was characterized by awakenings occurring throughout the second half of the night. But perhaps what happens more often is that women are regularly waking up repeatedly over the course of the entire night, as opposed to experiencing a wakefulness that starts early and lasts throughout the night or having a problem falling asleep to begin with,” said Dr. Merino. “The good news is that hormone replacement therapy can get things back to the way they were. And getting better sleep will help to overcome insomnia.”
Socioeconomic status
Insomnia is the most common sleep disorder. It affects 10%-20% of people, mostly women. “The fact that sleep problems are more prevalent in women can be explained by the fact that among women, there is a higher incidence of conditions that disrupt sleep, such as depression,” said Dr. Cano.
“Insomnia is much more common in adult women than adult men. And at menopause, women find that the insomnia only gets worse,” Dr. Merino added. “But around that same age, 50 years old, what we start to see more frequently in men is REM sleep behavior disorder, a type of parasomnia that’s a risk marker of degenerative nerve diseases.”
Dr. Cano emphasized one finding that, though basic, is not well known. “After adjusting for socioeconomic characteristics, the difference between the sexes in reporting sleep problems is cut in half. This suggests that an important factor that explains why there are differences in sleep problems between the sexes is that women’s socioeconomic status is generally lower than men’s.
“As for sleep apnea in particular,” Dr. Cano continued, “the kinds of symptoms that women have can be different from the classic ones seen in men – snoring, pauses in breathing, and daytime sleepiness; women are being underdiagnosed, and when they are diagnosed, that’s happening at a later age and at a higher BMI.”
So, it’s alarming that, as reported by SEPAR, 90% of women with obstructive sleep apnea are not being diagnosed.
Precision medicine approach
“The majority of research studies on sleep apnea have focused on men – given the prevalence of cases – and the results have been extrapolated to women. This is why there’s still a lot of work to be done in terms of better defining the characteristics specific to each sleep disorder and how they relate to each sex,” said Dr. Cano. “Being able to identify the relationship between the different sex-related phenotypes and each condition will allow us to take a precision medicine approach tailored to a patient’s particular characteristics.”
As Dr. Merino put it: “The approach to sleep disorders is always personalized. The patient’s sex, in and of itself, doesn’t have that great of an impact on this approach. What does have a great impact are women’s life stages. There are some subtle differences here and there, such as types of continuous positive airway pressure machines. The ones that are designed for women have masks that are better suited to their facial features, which differ from men’s.”
A precision medicine approach can be taken to treat any sleep disorder. For insomnia, the approach allows healthcare professionals to employ an appropriate cognitive-behavioral therapy plan or to determine which drugs would be more effective – all on the basis of symptoms and the characteristics of the particular case. Regarding sleep apnea, Dr. Cano explained, “taking into account the different anatomical characteristics or the higher prevalence of positional apnea will also allow us to offer different therapeutic alternatives to continuous positive airway pressure, such as mandibular advancement devices or positional therapy devices.”
Women should be encouraged to develop good sleep habits. These include taking circadian rhythms into account and aligning lifestyles accordingly. It also means going to bed earlier than the men in the household. For menopausal women, recommended sleep habits range from keeping their bedroom at an ideal temperature, following a diet rich in vegetables to avoid becoming overweight, and exercising daily. While this advice may be more applicable to teenagers, adults can benefit from it as well: Electronic devices should be turned off well before bedtime. Whether from a phone screen, a tablet screen, or a TV screen, the light emitted can keep one awake, which can be harmful to one’s health.
Dr. Cano and Dr. Merino disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com. This article was translated from the Medscape Spanish edition.
MADRID – Because of the hormone changes that occur throughout their lives, women experience sleep problems that differ significantly from those experienced by men. Indeed, 75%-84% of pregnant women don’t sleep well during the third trimester, and up to 80% of women in menopause have symptoms that prevent them from getting a good night’s rest. For those seeking a precision medicine approach, the challenge is to identify the relationship between the different sex-related phenotypes and the sleep conditions.
Irene Cano, MD, PhD, is the coordinator of the sleep department at the Spanish Society of Pulmonology and Thoracic Surgery. She spoke with this news organization about the significant impact of hormones on sleep disorders in women.
“Reproductive hormones like estrogen and progesterone play a meaningful role in brain functions – not only those linked to the regulation of reproduction but also other physiological processes related to the regulation of circadian rhythms, cognitive performance, mood, and sleep. In addition, other hormones – for example, prolactin, growth hormone, cortisol, and melatonin – have sex-dependent effects on sleep,” Dr. Cano said.
Girls start puberty at a younger age than boys. As girls enter adolescence, they go to bed later and waking up earlier. So, girls are getting less than the 10 hours of sleep that they should be getting at this stage of life. The result is sleep debt, which gives rise to various problems: poor academic performance, ADHD, obesity, and metabolic problems, to name a few. As Ariadna Farré, RN, a sleep unit nurse, noted at SEPAR’s Joint Winter Meeting, “schools would have to start morning classes later to get adolescents to perform well academically. As the situation is now, half of the kids are falling asleep at their desks.”
Influencing sleep quality
Dr. Cano explained the issue as follows: “In adolescence, along with changes in young women’s hormone levels, we begin to see differences between the sexes. The changes in levels of estrogens and progesterone are what’s responsible for the changes that, to some extent, cause those disturbances in the quality of our sleep and in the stages of our sleep.”
Thus, sleep can be affected by the changes in hormone level that occur during a menstrual cycle. Estrogens, which increase during the follicular phase, are associated with REM sleep, while progesterone, which increases during the luteal phase, increases non-REM sleep. “In the 3-6 days prior to menstruation, it’s quite common for a woman to report difficulties falling asleep and staying asleep, in connection with a decline in the percentage of time she spends in REM sleep, in the context of premenstrual syndrome. In addition,” Dr. Cano pointed out, “menstrual bleeding, that loss of blood, is associated with a drop in iron levels, making it more likely that the woman will experience restless legs syndrome.”
Cardiovascular system
This news organization also spoke with Milagros Merino, MD, PhD, president of the Spanish Sleep Society. “The consequences that lack of sleep have on the cardiovascular system – we’re essentially talking about certain arrhythmias, high blood pressure, thrombosis in some cases, stroke, and heart attack. Lack of sleep also gives rise to endocrine and metabolic issues, like overweight and being at a greater risk of developing diabetes. And as for mental health, we see, among other things, attention and memory problems, emotional lability, and irascibility. Numerous studies have confirmed all of this.”
Sleep apnea also deserves mention, Dr. Merino added. “Although this disorder is more common in men, we’re seeing it more and more now in women, along with the cardiovascular issues that it brings about.”
Another cardiovascular risk factor is insomnia, said Dr. Merino. “This sleep disorder is more prevalent in women. As hormones constantly change, the ways women sleep constantly change, from one stage of life to the next. They sleep one way in childhood, another way in adolescence, and yet another way in menopause.”
Sleep in pregnancy
During pregnancy, hormone changes are much more pronounced. During the first trimester, progesterone levels increase, making the woman drowsy. On top of that, her sleep is interrupted by more frequent visits to the bathroom as well as greater general discomfort.
In the second trimester, sleep interruptions persist but are not as bad as they were during the first 3 months. In the third trimester, 75%-84% of pregnant women find it difficult to sleep because of aches and pains, the need to urinate during the night, cramps, and heartburn.
“Major physical changes are happening. When the bladder gets compressed, the woman has to get up and go to the bathroom. There’s an interruption in her sleep,” Ms. Farré explained. In addition, as the pregnancy progresses, the woman gains weight and her body mass index (BMI) increases, which can bring on obstructive sleep apnea, high blood pressure, preeclampsia, and diabetes, if not closely monitored.
Other factors include concomitant treatments, such as contraceptives, and the stages of life, such as pregnancy and lactation. “When a woman of childbearing age has restless legs syndrome, more often than not, this means that she has an iron deficiency that needs to be treated with oral iron supplements,” said Dr. Merino. “However, there are few medications that can be given to a pregnant woman – and RLS is relatively common during pregnancy. So, we have to turn to oral or intravenous iron supplements. Yet another matter is narcolepsy. In these cases, all medications have to be stopped during pregnancy and lactation, as they can be harmful to the baby.”
Sleep apnea
While one in five menopausal women are asymptomatic, the others experience mild to severe symptoms of apnea that frequently interrupt their sleep. In this stage of life, which begins around age 50 years, the hormones that had provided protection against sleep disruptions start to decrease. As a result, there is a rise in sleep problems, especially insomnia, breathing-related sleep disorders (for example, apnea), and restless legs syndrome.
The prevalence of breathing-related sleep disorders during menopause is attributable to weight gain, the drop in levels of estrogens, and the redistribution of adipose tissue in the body. Other factors also increase a woman’s risk of experiencing apnea. They range from stress, depression, and other psychological and psychiatric conditions to health status, medication use, and simply the fact of getting older. “Sleep apnea is more common in men than in premenopausal women. The numbers even out, though, when we compare men against menopausal women,” Dr. Cano noted.
In women, symptoms of sleep apnea are frequently attributed to menopause. There is some overlap: insomnia, headache, irritability, low mood, decreased libido, fatigue during the day, and feeling sleepy. Only much later is the woman’s condition correctly diagnosed as sleep apnea. So, even though presenting with the same complaints, a man will be diagnosed with sleep apnea sooner than a woman will – in some cases, around 10 years sooner.
“On the other hand, we’d always thought that, in menopause, insomnia was characterized by awakenings occurring throughout the second half of the night. But perhaps what happens more often is that women are regularly waking up repeatedly over the course of the entire night, as opposed to experiencing a wakefulness that starts early and lasts throughout the night or having a problem falling asleep to begin with,” said Dr. Merino. “The good news is that hormone replacement therapy can get things back to the way they were. And getting better sleep will help to overcome insomnia.”
Socioeconomic status
Insomnia is the most common sleep disorder. It affects 10%-20% of people, mostly women. “The fact that sleep problems are more prevalent in women can be explained by the fact that among women, there is a higher incidence of conditions that disrupt sleep, such as depression,” said Dr. Cano.
“Insomnia is much more common in adult women than adult men. And at menopause, women find that the insomnia only gets worse,” Dr. Merino added. “But around that same age, 50 years old, what we start to see more frequently in men is REM sleep behavior disorder, a type of parasomnia that’s a risk marker of degenerative nerve diseases.”
Dr. Cano emphasized one finding that, though basic, is not well known. “After adjusting for socioeconomic characteristics, the difference between the sexes in reporting sleep problems is cut in half. This suggests that an important factor that explains why there are differences in sleep problems between the sexes is that women’s socioeconomic status is generally lower than men’s.
“As for sleep apnea in particular,” Dr. Cano continued, “the kinds of symptoms that women have can be different from the classic ones seen in men – snoring, pauses in breathing, and daytime sleepiness; women are being underdiagnosed, and when they are diagnosed, that’s happening at a later age and at a higher BMI.”
So, it’s alarming that, as reported by SEPAR, 90% of women with obstructive sleep apnea are not being diagnosed.
Precision medicine approach
“The majority of research studies on sleep apnea have focused on men – given the prevalence of cases – and the results have been extrapolated to women. This is why there’s still a lot of work to be done in terms of better defining the characteristics specific to each sleep disorder and how they relate to each sex,” said Dr. Cano. “Being able to identify the relationship between the different sex-related phenotypes and each condition will allow us to take a precision medicine approach tailored to a patient’s particular characteristics.”
As Dr. Merino put it: “The approach to sleep disorders is always personalized. The patient’s sex, in and of itself, doesn’t have that great of an impact on this approach. What does have a great impact are women’s life stages. There are some subtle differences here and there, such as types of continuous positive airway pressure machines. The ones that are designed for women have masks that are better suited to their facial features, which differ from men’s.”
A precision medicine approach can be taken to treat any sleep disorder. For insomnia, the approach allows healthcare professionals to employ an appropriate cognitive-behavioral therapy plan or to determine which drugs would be more effective – all on the basis of symptoms and the characteristics of the particular case. Regarding sleep apnea, Dr. Cano explained, “taking into account the different anatomical characteristics or the higher prevalence of positional apnea will also allow us to offer different therapeutic alternatives to continuous positive airway pressure, such as mandibular advancement devices or positional therapy devices.”
Women should be encouraged to develop good sleep habits. These include taking circadian rhythms into account and aligning lifestyles accordingly. It also means going to bed earlier than the men in the household. For menopausal women, recommended sleep habits range from keeping their bedroom at an ideal temperature, following a diet rich in vegetables to avoid becoming overweight, and exercising daily. While this advice may be more applicable to teenagers, adults can benefit from it as well: Electronic devices should be turned off well before bedtime. Whether from a phone screen, a tablet screen, or a TV screen, the light emitted can keep one awake, which can be harmful to one’s health.
Dr. Cano and Dr. Merino disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com. This article was translated from the Medscape Spanish edition.
MADRID – Because of the hormone changes that occur throughout their lives, women experience sleep problems that differ significantly from those experienced by men. Indeed, 75%-84% of pregnant women don’t sleep well during the third trimester, and up to 80% of women in menopause have symptoms that prevent them from getting a good night’s rest. For those seeking a precision medicine approach, the challenge is to identify the relationship between the different sex-related phenotypes and the sleep conditions.
Irene Cano, MD, PhD, is the coordinator of the sleep department at the Spanish Society of Pulmonology and Thoracic Surgery. She spoke with this news organization about the significant impact of hormones on sleep disorders in women.
“Reproductive hormones like estrogen and progesterone play a meaningful role in brain functions – not only those linked to the regulation of reproduction but also other physiological processes related to the regulation of circadian rhythms, cognitive performance, mood, and sleep. In addition, other hormones – for example, prolactin, growth hormone, cortisol, and melatonin – have sex-dependent effects on sleep,” Dr. Cano said.
Girls start puberty at a younger age than boys. As girls enter adolescence, they go to bed later and waking up earlier. So, girls are getting less than the 10 hours of sleep that they should be getting at this stage of life. The result is sleep debt, which gives rise to various problems: poor academic performance, ADHD, obesity, and metabolic problems, to name a few. As Ariadna Farré, RN, a sleep unit nurse, noted at SEPAR’s Joint Winter Meeting, “schools would have to start morning classes later to get adolescents to perform well academically. As the situation is now, half of the kids are falling asleep at their desks.”
Influencing sleep quality
Dr. Cano explained the issue as follows: “In adolescence, along with changes in young women’s hormone levels, we begin to see differences between the sexes. The changes in levels of estrogens and progesterone are what’s responsible for the changes that, to some extent, cause those disturbances in the quality of our sleep and in the stages of our sleep.”
Thus, sleep can be affected by the changes in hormone level that occur during a menstrual cycle. Estrogens, which increase during the follicular phase, are associated with REM sleep, while progesterone, which increases during the luteal phase, increases non-REM sleep. “In the 3-6 days prior to menstruation, it’s quite common for a woman to report difficulties falling asleep and staying asleep, in connection with a decline in the percentage of time she spends in REM sleep, in the context of premenstrual syndrome. In addition,” Dr. Cano pointed out, “menstrual bleeding, that loss of blood, is associated with a drop in iron levels, making it more likely that the woman will experience restless legs syndrome.”
Cardiovascular system
This news organization also spoke with Milagros Merino, MD, PhD, president of the Spanish Sleep Society. “The consequences that lack of sleep have on the cardiovascular system – we’re essentially talking about certain arrhythmias, high blood pressure, thrombosis in some cases, stroke, and heart attack. Lack of sleep also gives rise to endocrine and metabolic issues, like overweight and being at a greater risk of developing diabetes. And as for mental health, we see, among other things, attention and memory problems, emotional lability, and irascibility. Numerous studies have confirmed all of this.”
Sleep apnea also deserves mention, Dr. Merino added. “Although this disorder is more common in men, we’re seeing it more and more now in women, along with the cardiovascular issues that it brings about.”
Another cardiovascular risk factor is insomnia, said Dr. Merino. “This sleep disorder is more prevalent in women. As hormones constantly change, the ways women sleep constantly change, from one stage of life to the next. They sleep one way in childhood, another way in adolescence, and yet another way in menopause.”
Sleep in pregnancy
During pregnancy, hormone changes are much more pronounced. During the first trimester, progesterone levels increase, making the woman drowsy. On top of that, her sleep is interrupted by more frequent visits to the bathroom as well as greater general discomfort.
In the second trimester, sleep interruptions persist but are not as bad as they were during the first 3 months. In the third trimester, 75%-84% of pregnant women find it difficult to sleep because of aches and pains, the need to urinate during the night, cramps, and heartburn.
“Major physical changes are happening. When the bladder gets compressed, the woman has to get up and go to the bathroom. There’s an interruption in her sleep,” Ms. Farré explained. In addition, as the pregnancy progresses, the woman gains weight and her body mass index (BMI) increases, which can bring on obstructive sleep apnea, high blood pressure, preeclampsia, and diabetes, if not closely monitored.
Other factors include concomitant treatments, such as contraceptives, and the stages of life, such as pregnancy and lactation. “When a woman of childbearing age has restless legs syndrome, more often than not, this means that she has an iron deficiency that needs to be treated with oral iron supplements,” said Dr. Merino. “However, there are few medications that can be given to a pregnant woman – and RLS is relatively common during pregnancy. So, we have to turn to oral or intravenous iron supplements. Yet another matter is narcolepsy. In these cases, all medications have to be stopped during pregnancy and lactation, as they can be harmful to the baby.”
Sleep apnea
While one in five menopausal women are asymptomatic, the others experience mild to severe symptoms of apnea that frequently interrupt their sleep. In this stage of life, which begins around age 50 years, the hormones that had provided protection against sleep disruptions start to decrease. As a result, there is a rise in sleep problems, especially insomnia, breathing-related sleep disorders (for example, apnea), and restless legs syndrome.
The prevalence of breathing-related sleep disorders during menopause is attributable to weight gain, the drop in levels of estrogens, and the redistribution of adipose tissue in the body. Other factors also increase a woman’s risk of experiencing apnea. They range from stress, depression, and other psychological and psychiatric conditions to health status, medication use, and simply the fact of getting older. “Sleep apnea is more common in men than in premenopausal women. The numbers even out, though, when we compare men against menopausal women,” Dr. Cano noted.
In women, symptoms of sleep apnea are frequently attributed to menopause. There is some overlap: insomnia, headache, irritability, low mood, decreased libido, fatigue during the day, and feeling sleepy. Only much later is the woman’s condition correctly diagnosed as sleep apnea. So, even though presenting with the same complaints, a man will be diagnosed with sleep apnea sooner than a woman will – in some cases, around 10 years sooner.
“On the other hand, we’d always thought that, in menopause, insomnia was characterized by awakenings occurring throughout the second half of the night. But perhaps what happens more often is that women are regularly waking up repeatedly over the course of the entire night, as opposed to experiencing a wakefulness that starts early and lasts throughout the night or having a problem falling asleep to begin with,” said Dr. Merino. “The good news is that hormone replacement therapy can get things back to the way they were. And getting better sleep will help to overcome insomnia.”
Socioeconomic status
Insomnia is the most common sleep disorder. It affects 10%-20% of people, mostly women. “The fact that sleep problems are more prevalent in women can be explained by the fact that among women, there is a higher incidence of conditions that disrupt sleep, such as depression,” said Dr. Cano.
“Insomnia is much more common in adult women than adult men. And at menopause, women find that the insomnia only gets worse,” Dr. Merino added. “But around that same age, 50 years old, what we start to see more frequently in men is REM sleep behavior disorder, a type of parasomnia that’s a risk marker of degenerative nerve diseases.”
Dr. Cano emphasized one finding that, though basic, is not well known. “After adjusting for socioeconomic characteristics, the difference between the sexes in reporting sleep problems is cut in half. This suggests that an important factor that explains why there are differences in sleep problems between the sexes is that women’s socioeconomic status is generally lower than men’s.
“As for sleep apnea in particular,” Dr. Cano continued, “the kinds of symptoms that women have can be different from the classic ones seen in men – snoring, pauses in breathing, and daytime sleepiness; women are being underdiagnosed, and when they are diagnosed, that’s happening at a later age and at a higher BMI.”
So, it’s alarming that, as reported by SEPAR, 90% of women with obstructive sleep apnea are not being diagnosed.
Precision medicine approach
“The majority of research studies on sleep apnea have focused on men – given the prevalence of cases – and the results have been extrapolated to women. This is why there’s still a lot of work to be done in terms of better defining the characteristics specific to each sleep disorder and how they relate to each sex,” said Dr. Cano. “Being able to identify the relationship between the different sex-related phenotypes and each condition will allow us to take a precision medicine approach tailored to a patient’s particular characteristics.”
As Dr. Merino put it: “The approach to sleep disorders is always personalized. The patient’s sex, in and of itself, doesn’t have that great of an impact on this approach. What does have a great impact are women’s life stages. There are some subtle differences here and there, such as types of continuous positive airway pressure machines. The ones that are designed for women have masks that are better suited to their facial features, which differ from men’s.”
A precision medicine approach can be taken to treat any sleep disorder. For insomnia, the approach allows healthcare professionals to employ an appropriate cognitive-behavioral therapy plan or to determine which drugs would be more effective – all on the basis of symptoms and the characteristics of the particular case. Regarding sleep apnea, Dr. Cano explained, “taking into account the different anatomical characteristics or the higher prevalence of positional apnea will also allow us to offer different therapeutic alternatives to continuous positive airway pressure, such as mandibular advancement devices or positional therapy devices.”
Women should be encouraged to develop good sleep habits. These include taking circadian rhythms into account and aligning lifestyles accordingly. It also means going to bed earlier than the men in the household. For menopausal women, recommended sleep habits range from keeping their bedroom at an ideal temperature, following a diet rich in vegetables to avoid becoming overweight, and exercising daily. While this advice may be more applicable to teenagers, adults can benefit from it as well: Electronic devices should be turned off well before bedtime. Whether from a phone screen, a tablet screen, or a TV screen, the light emitted can keep one awake, which can be harmful to one’s health.
Dr. Cano and Dr. Merino disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com. This article was translated from the Medscape Spanish edition.
AML’s seasonal peak suggests viral or environmental etiology
Most diagnoses of acute myeloid leukemia (AML) are made during January. This finding strongly implies that seasonal factors, such as infectious agents or environmental triggers, influence the development or proliferation of the disease, which points to prevention opportunities. This was the conclusion of an international study led by a team from the Jiménez Díaz Foundation University Hospital Health Research Institute (IIS-FJD) in Madrid, in collaboration with colleagues from the University of Bristol, England. Their work was published in the British Journal of Haematology.
The study’s aim was to investigate the potential seasonal and long-term trends in AML diagnosis in an overall population and in subgroups according to sex and age. To do so, the researchers examined 26,472 cases of AML diagnosed in Spain between 2004 and 2015. They found seasonality in the diagnosis of this type of leukemia. This “could point to there being an underlying seasonal etiology at play,” noted one of the main authors of the study, Juan Manuel Alonso, MD, a physician in the IIS-FJD’s department of hematology and hemotherapy.
“The environmental triggers involved could be radiation, pollution, allergens, or infectious agents like viruses. We’re leaning toward viruses, because there are already distinct solid tumor and hematologic cancers that are caused by them and because, in the winter months, there’s an increased incidence of cancers due to viral infections,” Dr. Alonso said in an interview. “The etiological mechanism should be different from that exerted by chronic viral pressure, because here we’re dealing with an acute and aggressive disease that probably needs a short incubation period.”
Various hypotheses
In an interview, David Martínez, MD, a hematologist at La Fe University Hospital in Valencia, Spain, described the research as “an extremely well done and much-discussed study on AML, a disease that appears to be diagnosed more frequently at a certain time of year – namely, January.
“There’s no clear explanation for this finding,” Dr. Martínez said. “Several possible reasons have been put forward and are being talked about. The one that seems to hold the most water is the hypothesis that infectious agents and environmental factors may have a greater influence. This is because the idea that they’re involved in neoplastic diseases is nothing new. In fact, there are a lot of publications and a good amount of scientific evidence that link viral infections and environmental factors with the development of oncologic diseases.”
AML is a rare disease yet is responsible for many cancer-related deaths. Mutations that cause AML can occur due to an inherited mutant gene or exposure to certain carcinogens, such as chemotherapy, radiotherapy, ionizing radiation, tobacco, and benzene. These findings are broadly similar to those of a large U.S.-based study by Calip et al., who found a peak of adult AML diagnoses during December and January from 1992 to 2008. Previous smaller studies have provided conflicting evidence, likely due to lower power or to the use of less advanced statistical approaches.
Seasonal factors involved?
Demonstration of seasonal variation in the occurrence of AML would, firstly, provide supportive evidence of etiology by seasonal factors, such as infectious agents or environmental factors, and, secondly, focus research onto the etiologic role of such factors.
The current study used population-based data on cases of AML occurring in Spain from a nationwide hospital discharge registry for the years 2004 to 2015. “This is, to our knowledge, the largest study aimed at investigating the potential seasonal and long-term trends in AML incidence in an overall population and in subgroups according to sex and age while employing novel statistical models with serial dependence for discrete-valued time series,” wrote the researchers.
They extracted information from the register of each case about the date of admission, discharge date, the anonymous identifier for each patient, International Classification of Diseases (ICD)–9 codes, sex, and date of birth, from which they derived age groups as described for the at-risk population. For patients hospitalized on more than one occasion, only the record corresponding to their first diagnosis of AML was selected.
AML cases per month were standardized to months of equal length.
Age/sex-standardized monthly incidence rates of AML were calculated using the census of Spanish population in 2010 as a “standard” population. Age-standardized and sex-standardized monthly incidence rates of AML were calculated.
Nine separate time-series decompositions were performed as an initial exploratory analysis on the monthly incidence rates of AML using data for all cases and data for each sex and age group. Nine separate Poisson generalized linear autoregressive moving average (GLARMA) models were fitted to evaluate the temporal dynamics in AML incidence using data for all cases, and data for each sex and age group.
Long-term trend
A total of 26,472 patients with a first diagnosis of active AML were hospitalized in Spain and registered at the country’s Minimum Basic Data Set (CMBD) during 2004-2015. In the end, there were 26,475 patients in the study population; a greater proportion of cases were male (56.0%), and the median age at diagnosis was 67 years.
Seasonal and trend decomposition using Loess decomposition of the incidence rates observed in the overall population exhibited seasonal fluctuation with a peak in January. A slight upward trend was apparent from visual inspection with an upturn in early 2005 and a downturn at the end of 2013. As for the differences by sex groups and age groups, Dr. Alonso said, “For both sexes and in age groups 5-19, 20-49, and 50-64 years, we found that the results were identical to those found in the overall population.”
The final model included an upward linear long-term trend, as well as the variables monthly seasonality and December 2015. The estimated monthly long-term trend implies that the monthly incidence rates of AML diagnoses annually increased by 0.4% (95% confidence interval [CI], 0.2%-0.6%; P = .0011), given that the other covariates are held constant.
January displayed the highest incidence rate of AML, with a minimum average difference of 7%, when compared with February (95% CI, 2%-12%; P = .0143) and a maximum average difference of 16%, compared with November (95% CI, 11%-21%; P < .0001) and August (95% CI, 10%-21%; P < .0001).
The incidence rate of AML for December 2015 was 0.43 (95% CI, 0.34-0.54; P < .0001) times the average incidence rate for the rest of the study period.
Potential role of viruses
“We have to keep in mind that infectious agents (viral infections) and environmental factors (allergens) don’t disappear in the warmer months,” Dr. Martínez added. “There are just other viruses and different factors. We don’t know the role or the weight that each one of the factors has, either individually or specifically, in the development of AML. In addition, we know that AML is a very heterogeneous disease and that various factors, including genetic ones, can be involved in its etiopathogenesis.”
With respect to the stem cell theory in this leukemia, Dr. Alonso emphasized that, “in theory, the virus could fit into it with no problem. That said, any other environmental agent could also produce the described phenomenon where the rapid proliferation of quiescent leukemic stem cells is stimulated, thereby hastening the diagnosis.”
“Should the etiological factor be found,” Dr. Martínez noted, “we can try to reduce exposure and thereby decrease the incidence of AML. On the other hand, discovering how the environmental factor stimulates the proliferation of quiescent leukemic [stem] cells could enhance our knowledge about the regulation of that.”
As to whether there is evidence for the involvement of infections in other hematologic malignancies, Dr. Martínez reported, “This has already been seen. And this study shows other examples (Epstein-Barr virus and human T-cell lymphotropic virus type 1 with lymphomas), and there could also be Helicobacter pylori and lymphomas.”
Outside of hematology, human papillomavirus has been associated with cervical cancer, tobacco with lung cancer, sun with skin cancer, and diet with the development of some solid neoplasms.
“The study speaks about the concept of a latency period. To accept the idea that a factor or virus that’s more prevalent in winter produces, on its own, AML in a few weeks or months means accepting the idea of a very short latency period – something that’s not usually the case. For that, another explanation is given: An abnormal immune response or that a seasonal infectious agent can be capable of promoting leukemogenesis. These are also hypotheses to be explored in the future,” suggested Dr. Martínez.
New research network
Several potential limitations of this study should be considered. One limitation is that AML cases were obtained from the CMBD registry as defined by ICD-9, and no other AML classifications were available. Another limitation is that information on the date of onset of clinical symptoms was not available for analysis. In addition, a further limitation related to the source of their data may have led the researchers to underestimate the incidence rates of AML in older patients, as only hospitalized patients were captured in their study.
As for continuing the research, the results make it necessary to carry out complementary epidemiologic studies that will examine the association between seasonal risk factors and the increased diagnosis of AML during winter months.
To go forward, the first step would be to secure funding. For this purpose, a network is being put together featuring collaborators from other world-renowned research groups that are at the top of their respective disciplines. Through this network, they hope to be able to apply together for public research grants from countries in Europe and elsewhere as well as to establish collaborations with various companies in the private sector.
“This could open up new therapeutic avenues in the future, as we could try to force leukemic stem cells to divide, thereby reducing the resistance that the standard treatments usually demonstrate,” Dr. Alonso concluded.
Dr. Alonso received research funding from Incyte, Pfizer International, and Astellas Pharma outside the present work. Dr. Martínez disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish edition. A version of the article appeared on Medscape.com.
Most diagnoses of acute myeloid leukemia (AML) are made during January. This finding strongly implies that seasonal factors, such as infectious agents or environmental triggers, influence the development or proliferation of the disease, which points to prevention opportunities. This was the conclusion of an international study led by a team from the Jiménez Díaz Foundation University Hospital Health Research Institute (IIS-FJD) in Madrid, in collaboration with colleagues from the University of Bristol, England. Their work was published in the British Journal of Haematology.
The study’s aim was to investigate the potential seasonal and long-term trends in AML diagnosis in an overall population and in subgroups according to sex and age. To do so, the researchers examined 26,472 cases of AML diagnosed in Spain between 2004 and 2015. They found seasonality in the diagnosis of this type of leukemia. This “could point to there being an underlying seasonal etiology at play,” noted one of the main authors of the study, Juan Manuel Alonso, MD, a physician in the IIS-FJD’s department of hematology and hemotherapy.
“The environmental triggers involved could be radiation, pollution, allergens, or infectious agents like viruses. We’re leaning toward viruses, because there are already distinct solid tumor and hematologic cancers that are caused by them and because, in the winter months, there’s an increased incidence of cancers due to viral infections,” Dr. Alonso said in an interview. “The etiological mechanism should be different from that exerted by chronic viral pressure, because here we’re dealing with an acute and aggressive disease that probably needs a short incubation period.”
Various hypotheses
In an interview, David Martínez, MD, a hematologist at La Fe University Hospital in Valencia, Spain, described the research as “an extremely well done and much-discussed study on AML, a disease that appears to be diagnosed more frequently at a certain time of year – namely, January.
“There’s no clear explanation for this finding,” Dr. Martínez said. “Several possible reasons have been put forward and are being talked about. The one that seems to hold the most water is the hypothesis that infectious agents and environmental factors may have a greater influence. This is because the idea that they’re involved in neoplastic diseases is nothing new. In fact, there are a lot of publications and a good amount of scientific evidence that link viral infections and environmental factors with the development of oncologic diseases.”
AML is a rare disease yet is responsible for many cancer-related deaths. Mutations that cause AML can occur due to an inherited mutant gene or exposure to certain carcinogens, such as chemotherapy, radiotherapy, ionizing radiation, tobacco, and benzene. These findings are broadly similar to those of a large U.S.-based study by Calip et al., who found a peak of adult AML diagnoses during December and January from 1992 to 2008. Previous smaller studies have provided conflicting evidence, likely due to lower power or to the use of less advanced statistical approaches.
Seasonal factors involved?
Demonstration of seasonal variation in the occurrence of AML would, firstly, provide supportive evidence of etiology by seasonal factors, such as infectious agents or environmental factors, and, secondly, focus research onto the etiologic role of such factors.
The current study used population-based data on cases of AML occurring in Spain from a nationwide hospital discharge registry for the years 2004 to 2015. “This is, to our knowledge, the largest study aimed at investigating the potential seasonal and long-term trends in AML incidence in an overall population and in subgroups according to sex and age while employing novel statistical models with serial dependence for discrete-valued time series,” wrote the researchers.
They extracted information from the register of each case about the date of admission, discharge date, the anonymous identifier for each patient, International Classification of Diseases (ICD)–9 codes, sex, and date of birth, from which they derived age groups as described for the at-risk population. For patients hospitalized on more than one occasion, only the record corresponding to their first diagnosis of AML was selected.
AML cases per month were standardized to months of equal length.
Age/sex-standardized monthly incidence rates of AML were calculated using the census of Spanish population in 2010 as a “standard” population. Age-standardized and sex-standardized monthly incidence rates of AML were calculated.
Nine separate time-series decompositions were performed as an initial exploratory analysis on the monthly incidence rates of AML using data for all cases and data for each sex and age group. Nine separate Poisson generalized linear autoregressive moving average (GLARMA) models were fitted to evaluate the temporal dynamics in AML incidence using data for all cases, and data for each sex and age group.
Long-term trend
A total of 26,472 patients with a first diagnosis of active AML were hospitalized in Spain and registered at the country’s Minimum Basic Data Set (CMBD) during 2004-2015. In the end, there were 26,475 patients in the study population; a greater proportion of cases were male (56.0%), and the median age at diagnosis was 67 years.
Seasonal and trend decomposition using Loess decomposition of the incidence rates observed in the overall population exhibited seasonal fluctuation with a peak in January. A slight upward trend was apparent from visual inspection with an upturn in early 2005 and a downturn at the end of 2013. As for the differences by sex groups and age groups, Dr. Alonso said, “For both sexes and in age groups 5-19, 20-49, and 50-64 years, we found that the results were identical to those found in the overall population.”
The final model included an upward linear long-term trend, as well as the variables monthly seasonality and December 2015. The estimated monthly long-term trend implies that the monthly incidence rates of AML diagnoses annually increased by 0.4% (95% confidence interval [CI], 0.2%-0.6%; P = .0011), given that the other covariates are held constant.
January displayed the highest incidence rate of AML, with a minimum average difference of 7%, when compared with February (95% CI, 2%-12%; P = .0143) and a maximum average difference of 16%, compared with November (95% CI, 11%-21%; P < .0001) and August (95% CI, 10%-21%; P < .0001).
The incidence rate of AML for December 2015 was 0.43 (95% CI, 0.34-0.54; P < .0001) times the average incidence rate for the rest of the study period.
Potential role of viruses
“We have to keep in mind that infectious agents (viral infections) and environmental factors (allergens) don’t disappear in the warmer months,” Dr. Martínez added. “There are just other viruses and different factors. We don’t know the role or the weight that each one of the factors has, either individually or specifically, in the development of AML. In addition, we know that AML is a very heterogeneous disease and that various factors, including genetic ones, can be involved in its etiopathogenesis.”
With respect to the stem cell theory in this leukemia, Dr. Alonso emphasized that, “in theory, the virus could fit into it with no problem. That said, any other environmental agent could also produce the described phenomenon where the rapid proliferation of quiescent leukemic stem cells is stimulated, thereby hastening the diagnosis.”
“Should the etiological factor be found,” Dr. Martínez noted, “we can try to reduce exposure and thereby decrease the incidence of AML. On the other hand, discovering how the environmental factor stimulates the proliferation of quiescent leukemic [stem] cells could enhance our knowledge about the regulation of that.”
As to whether there is evidence for the involvement of infections in other hematologic malignancies, Dr. Martínez reported, “This has already been seen. And this study shows other examples (Epstein-Barr virus and human T-cell lymphotropic virus type 1 with lymphomas), and there could also be Helicobacter pylori and lymphomas.”
Outside of hematology, human papillomavirus has been associated with cervical cancer, tobacco with lung cancer, sun with skin cancer, and diet with the development of some solid neoplasms.
“The study speaks about the concept of a latency period. To accept the idea that a factor or virus that’s more prevalent in winter produces, on its own, AML in a few weeks or months means accepting the idea of a very short latency period – something that’s not usually the case. For that, another explanation is given: An abnormal immune response or that a seasonal infectious agent can be capable of promoting leukemogenesis. These are also hypotheses to be explored in the future,” suggested Dr. Martínez.
New research network
Several potential limitations of this study should be considered. One limitation is that AML cases were obtained from the CMBD registry as defined by ICD-9, and no other AML classifications were available. Another limitation is that information on the date of onset of clinical symptoms was not available for analysis. In addition, a further limitation related to the source of their data may have led the researchers to underestimate the incidence rates of AML in older patients, as only hospitalized patients were captured in their study.
As for continuing the research, the results make it necessary to carry out complementary epidemiologic studies that will examine the association between seasonal risk factors and the increased diagnosis of AML during winter months.
To go forward, the first step would be to secure funding. For this purpose, a network is being put together featuring collaborators from other world-renowned research groups that are at the top of their respective disciplines. Through this network, they hope to be able to apply together for public research grants from countries in Europe and elsewhere as well as to establish collaborations with various companies in the private sector.
“This could open up new therapeutic avenues in the future, as we could try to force leukemic stem cells to divide, thereby reducing the resistance that the standard treatments usually demonstrate,” Dr. Alonso concluded.
Dr. Alonso received research funding from Incyte, Pfizer International, and Astellas Pharma outside the present work. Dr. Martínez disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish edition. A version of the article appeared on Medscape.com.
Most diagnoses of acute myeloid leukemia (AML) are made during January. This finding strongly implies that seasonal factors, such as infectious agents or environmental triggers, influence the development or proliferation of the disease, which points to prevention opportunities. This was the conclusion of an international study led by a team from the Jiménez Díaz Foundation University Hospital Health Research Institute (IIS-FJD) in Madrid, in collaboration with colleagues from the University of Bristol, England. Their work was published in the British Journal of Haematology.
The study’s aim was to investigate the potential seasonal and long-term trends in AML diagnosis in an overall population and in subgroups according to sex and age. To do so, the researchers examined 26,472 cases of AML diagnosed in Spain between 2004 and 2015. They found seasonality in the diagnosis of this type of leukemia. This “could point to there being an underlying seasonal etiology at play,” noted one of the main authors of the study, Juan Manuel Alonso, MD, a physician in the IIS-FJD’s department of hematology and hemotherapy.
“The environmental triggers involved could be radiation, pollution, allergens, or infectious agents like viruses. We’re leaning toward viruses, because there are already distinct solid tumor and hematologic cancers that are caused by them and because, in the winter months, there’s an increased incidence of cancers due to viral infections,” Dr. Alonso said in an interview. “The etiological mechanism should be different from that exerted by chronic viral pressure, because here we’re dealing with an acute and aggressive disease that probably needs a short incubation period.”
Various hypotheses
In an interview, David Martínez, MD, a hematologist at La Fe University Hospital in Valencia, Spain, described the research as “an extremely well done and much-discussed study on AML, a disease that appears to be diagnosed more frequently at a certain time of year – namely, January.
“There’s no clear explanation for this finding,” Dr. Martínez said. “Several possible reasons have been put forward and are being talked about. The one that seems to hold the most water is the hypothesis that infectious agents and environmental factors may have a greater influence. This is because the idea that they’re involved in neoplastic diseases is nothing new. In fact, there are a lot of publications and a good amount of scientific evidence that link viral infections and environmental factors with the development of oncologic diseases.”
AML is a rare disease yet is responsible for many cancer-related deaths. Mutations that cause AML can occur due to an inherited mutant gene or exposure to certain carcinogens, such as chemotherapy, radiotherapy, ionizing radiation, tobacco, and benzene. These findings are broadly similar to those of a large U.S.-based study by Calip et al., who found a peak of adult AML diagnoses during December and January from 1992 to 2008. Previous smaller studies have provided conflicting evidence, likely due to lower power or to the use of less advanced statistical approaches.
Seasonal factors involved?
Demonstration of seasonal variation in the occurrence of AML would, firstly, provide supportive evidence of etiology by seasonal factors, such as infectious agents or environmental factors, and, secondly, focus research onto the etiologic role of such factors.
The current study used population-based data on cases of AML occurring in Spain from a nationwide hospital discharge registry for the years 2004 to 2015. “This is, to our knowledge, the largest study aimed at investigating the potential seasonal and long-term trends in AML incidence in an overall population and in subgroups according to sex and age while employing novel statistical models with serial dependence for discrete-valued time series,” wrote the researchers.
They extracted information from the register of each case about the date of admission, discharge date, the anonymous identifier for each patient, International Classification of Diseases (ICD)–9 codes, sex, and date of birth, from which they derived age groups as described for the at-risk population. For patients hospitalized on more than one occasion, only the record corresponding to their first diagnosis of AML was selected.
AML cases per month were standardized to months of equal length.
Age/sex-standardized monthly incidence rates of AML were calculated using the census of Spanish population in 2010 as a “standard” population. Age-standardized and sex-standardized monthly incidence rates of AML were calculated.
Nine separate time-series decompositions were performed as an initial exploratory analysis on the monthly incidence rates of AML using data for all cases and data for each sex and age group. Nine separate Poisson generalized linear autoregressive moving average (GLARMA) models were fitted to evaluate the temporal dynamics in AML incidence using data for all cases, and data for each sex and age group.
Long-term trend
A total of 26,472 patients with a first diagnosis of active AML were hospitalized in Spain and registered at the country’s Minimum Basic Data Set (CMBD) during 2004-2015. In the end, there were 26,475 patients in the study population; a greater proportion of cases were male (56.0%), and the median age at diagnosis was 67 years.
Seasonal and trend decomposition using Loess decomposition of the incidence rates observed in the overall population exhibited seasonal fluctuation with a peak in January. A slight upward trend was apparent from visual inspection with an upturn in early 2005 and a downturn at the end of 2013. As for the differences by sex groups and age groups, Dr. Alonso said, “For both sexes and in age groups 5-19, 20-49, and 50-64 years, we found that the results were identical to those found in the overall population.”
The final model included an upward linear long-term trend, as well as the variables monthly seasonality and December 2015. The estimated monthly long-term trend implies that the monthly incidence rates of AML diagnoses annually increased by 0.4% (95% confidence interval [CI], 0.2%-0.6%; P = .0011), given that the other covariates are held constant.
January displayed the highest incidence rate of AML, with a minimum average difference of 7%, when compared with February (95% CI, 2%-12%; P = .0143) and a maximum average difference of 16%, compared with November (95% CI, 11%-21%; P < .0001) and August (95% CI, 10%-21%; P < .0001).
The incidence rate of AML for December 2015 was 0.43 (95% CI, 0.34-0.54; P < .0001) times the average incidence rate for the rest of the study period.
Potential role of viruses
“We have to keep in mind that infectious agents (viral infections) and environmental factors (allergens) don’t disappear in the warmer months,” Dr. Martínez added. “There are just other viruses and different factors. We don’t know the role or the weight that each one of the factors has, either individually or specifically, in the development of AML. In addition, we know that AML is a very heterogeneous disease and that various factors, including genetic ones, can be involved in its etiopathogenesis.”
With respect to the stem cell theory in this leukemia, Dr. Alonso emphasized that, “in theory, the virus could fit into it with no problem. That said, any other environmental agent could also produce the described phenomenon where the rapid proliferation of quiescent leukemic stem cells is stimulated, thereby hastening the diagnosis.”
“Should the etiological factor be found,” Dr. Martínez noted, “we can try to reduce exposure and thereby decrease the incidence of AML. On the other hand, discovering how the environmental factor stimulates the proliferation of quiescent leukemic [stem] cells could enhance our knowledge about the regulation of that.”
As to whether there is evidence for the involvement of infections in other hematologic malignancies, Dr. Martínez reported, “This has already been seen. And this study shows other examples (Epstein-Barr virus and human T-cell lymphotropic virus type 1 with lymphomas), and there could also be Helicobacter pylori and lymphomas.”
Outside of hematology, human papillomavirus has been associated with cervical cancer, tobacco with lung cancer, sun with skin cancer, and diet with the development of some solid neoplasms.
“The study speaks about the concept of a latency period. To accept the idea that a factor or virus that’s more prevalent in winter produces, on its own, AML in a few weeks or months means accepting the idea of a very short latency period – something that’s not usually the case. For that, another explanation is given: An abnormal immune response or that a seasonal infectious agent can be capable of promoting leukemogenesis. These are also hypotheses to be explored in the future,” suggested Dr. Martínez.
New research network
Several potential limitations of this study should be considered. One limitation is that AML cases were obtained from the CMBD registry as defined by ICD-9, and no other AML classifications were available. Another limitation is that information on the date of onset of clinical symptoms was not available for analysis. In addition, a further limitation related to the source of their data may have led the researchers to underestimate the incidence rates of AML in older patients, as only hospitalized patients were captured in their study.
As for continuing the research, the results make it necessary to carry out complementary epidemiologic studies that will examine the association between seasonal risk factors and the increased diagnosis of AML during winter months.
To go forward, the first step would be to secure funding. For this purpose, a network is being put together featuring collaborators from other world-renowned research groups that are at the top of their respective disciplines. Through this network, they hope to be able to apply together for public research grants from countries in Europe and elsewhere as well as to establish collaborations with various companies in the private sector.
“This could open up new therapeutic avenues in the future, as we could try to force leukemic stem cells to divide, thereby reducing the resistance that the standard treatments usually demonstrate,” Dr. Alonso concluded.
Dr. Alonso received research funding from Incyte, Pfizer International, and Astellas Pharma outside the present work. Dr. Martínez disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish edition. A version of the article appeared on Medscape.com.
FROM THE BRITISH JOURNAL OF HEMATOLOGY
About 19% of COVID-19 headaches become chronic
Approximately one in five patients who presented with headache during the acute phase of COVID-19 developed chronic daily headache, according to a study published in Cephalalgia. The greater the headache’s intensity during the acute phase, the greater the likelihood that it would persist.
The research, carried out by members of the Headache Study Group of the Spanish Society of Neurology, evaluated the evolution of headache in more than 900 Spanish patients. Because they found that headache intensity during the acute phase was associated with a more prolonged duration of headache, the team stressed the importance of promptly evaluating patients who have had COVID-19 and who then experience persistent headache.
Long-term evolution unknown
Headache is a common symptom of COVID-19, but its long-term evolution remains unknown. The objective of this study was to evaluate the long-term duration of headache in patients who presented with this symptom during the acute phase of the disease.
Recruitment for this multicenter study took place in March and April 2020. The 905 patients who were enrolled came from six level 3 hospitals in Spain. All completed 9 months of neurologic follow-up.
Their median age was 51 years, 66.5% were women, and more than half (52.7%) had a history of primary headache. About half of the patients required hospitalization (50.5%); the rest were treated as outpatients. The most common headache phenotype was holocranial (67.8%) of severe intensity (50.6%).
Persistent headache common
In the 96.6% cases for which data were available, the median duration of headache was 14 days. The headache persisted at 1 month in 31.1% of patients, at 2 months in 21.5%, at 3 months in 19%, at 6 months in 16.8%, and at 9 months in 16.0%.
“The median duration of COVID-19 headache is around 2 weeks,” David García Azorín, MD, PhD, a member of the Spanish Society of Neurology and one of the coauthors of the study, said in an interview. “However, almost 20% of patients experience it for longer than that. When still present at 2 months, the headache is more likely to follow a chronic daily pattern.” Dr. García Azorín is a neurologist and clinical researcher at the headache unit of the Hospital Clínico Universitario in Valladolid, Spain.
“So, if the headache isn’t letting up, it’s important to make the most of that window of opportunity and provide treatment in that period of 6-12 weeks,” he continued. “To do this, the best option is to carry out preventive treatment so that the patient will have a better chance of recovering.”
Study participants whose headache persisted at 9 months were older and were mostly women. They were less likely to have had pneumonia or to have experienced stabbing pain, photophobia, or phonophobia. They reported that the headache got worse when they engaged in physical activity but less frequently manifested as a throbbing headache.
Secondary tension headaches
On the other hand, Jaime Rodríguez Vico, MD, head of the headache unit at the Jiménez Díaz Foundation Hospital in Madrid, said in an interview that, according to his case studies, the most striking characteristics of post–COVID-19 headaches “in general are secondary, with similarities to tension headaches that patients are able to differentiate from other clinical types of headache. In patients with migraine, very often we see that we’re dealing with a trigger. In other words, more migraines – and more intense ones at that – are brought about.”
He added: “Generally, post–COVID-19 headache usually lasts 1-2 weeks, but we have cases of it lasting several months and even over a year with persistent daily headache. These more persistent cases are probably connected to another type of pathology that makes them more susceptible to becoming chronic, something that occurs in another type of primary headache known as new daily persistent headache.”
Primary headache exacerbation
Dr. García Azorín pointed out that it’s not uncommon that among people who already have primary headache, their condition worsens after they become infected with SARS-CoV-2. However, many people differentiate the headache associated with the infection from their usual headache because after becoming infected, their headache is predominantly frontal, oppressive, and chronic.
“Having a prior history of headache is one of the factors that can increase the likelihood that a headache experienced while suffering from COVID-19 will become chronic,” he noted.
This study also found that, more often than not, patients with persistent headache at 9 months had migraine-like pain.
As for headaches in these patients beyond 9 months, “based on our research, the evolution is quite variable,” said Dr. Rodríguez Vico. “Our unit’s numbers are skewed due to the high number of migraine cases that we follow, and therefore our high volume of migraine patients who’ve gotten worse. The same thing happens with COVID-19 vaccines. Migraine is a polygenic disorder with multiple variants and a pathophysiology that we are just beginning to describe. This is why one patient is completely different from another. It’s a real challenge.”
Infections are a common cause of acute and chronic headache. The persistence of a headache after an infection may be caused by the infection becoming chronic, as happens in some types of chronic meningitis, such as tuberculous meningitis. It may also be caused by the persistence of a certain response and activation of the immune system or to the uncovering or worsening of a primary headache coincident with the infection, added Dr. García Azorín.
“Likewise, there are other people who have a biological predisposition to headache as a multifactorial disorder and polygenic disorder, such that a particular stimulus – from trauma or an infection to alcohol consumption – can cause them to develop a headache very similar to a migraine,” he said.
Providing prognosis and treatment
Certain factors can give an idea of how long the headache might last. The study’s univariate analysis showed that age, female sex, headache intensity, pressure-like quality, the presence of photophobia/phonophobia, and worsening with physical activity were associated with headache of longer duration. But in the multivariate analysis, only headache intensity during the acute phase remained statistically significant (hazard ratio, 0.655; 95% confidence interval, 0.582-0.737; P < .001).
When asked whether they planned to continue the study, Dr. García Azorín commented, “The main questions that have arisen from this study have been, above all: ‘Why does this headache happen?’ and ‘How can it be treated or avoided?’ To answer them, we’re looking into pain: which factors could predispose a person to it and which changes may be associated with its presence.”
In addition, different treatments that may improve patient outcomes are being evaluated, because to date, treatment has been empirical and based on the predominant pain phenotype.
In any case, most doctors currently treat post–COVID-19 headache on the basis of how similar the symptoms are to those of other primary headaches. “Given the impact that headache has on patients’ quality of life, there’s a pressing need for controlled studies on possible treatments and their effectiveness,” noted Patricia Pozo Rosich, MD, PhD, one of the coauthors of the study.
“We at the Spanish Society of Neurology truly believe that if these patients were to have this symptom correctly addressed from the start, they could avoid many of the problems that arise in the situation becoming chronic,” she concluded.
Dr. García Azorín and Dr. Rodríguez Vico disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Approximately one in five patients who presented with headache during the acute phase of COVID-19 developed chronic daily headache, according to a study published in Cephalalgia. The greater the headache’s intensity during the acute phase, the greater the likelihood that it would persist.
The research, carried out by members of the Headache Study Group of the Spanish Society of Neurology, evaluated the evolution of headache in more than 900 Spanish patients. Because they found that headache intensity during the acute phase was associated with a more prolonged duration of headache, the team stressed the importance of promptly evaluating patients who have had COVID-19 and who then experience persistent headache.
Long-term evolution unknown
Headache is a common symptom of COVID-19, but its long-term evolution remains unknown. The objective of this study was to evaluate the long-term duration of headache in patients who presented with this symptom during the acute phase of the disease.
Recruitment for this multicenter study took place in March and April 2020. The 905 patients who were enrolled came from six level 3 hospitals in Spain. All completed 9 months of neurologic follow-up.
Their median age was 51 years, 66.5% were women, and more than half (52.7%) had a history of primary headache. About half of the patients required hospitalization (50.5%); the rest were treated as outpatients. The most common headache phenotype was holocranial (67.8%) of severe intensity (50.6%).
Persistent headache common
In the 96.6% cases for which data were available, the median duration of headache was 14 days. The headache persisted at 1 month in 31.1% of patients, at 2 months in 21.5%, at 3 months in 19%, at 6 months in 16.8%, and at 9 months in 16.0%.
“The median duration of COVID-19 headache is around 2 weeks,” David García Azorín, MD, PhD, a member of the Spanish Society of Neurology and one of the coauthors of the study, said in an interview. “However, almost 20% of patients experience it for longer than that. When still present at 2 months, the headache is more likely to follow a chronic daily pattern.” Dr. García Azorín is a neurologist and clinical researcher at the headache unit of the Hospital Clínico Universitario in Valladolid, Spain.
“So, if the headache isn’t letting up, it’s important to make the most of that window of opportunity and provide treatment in that period of 6-12 weeks,” he continued. “To do this, the best option is to carry out preventive treatment so that the patient will have a better chance of recovering.”
Study participants whose headache persisted at 9 months were older and were mostly women. They were less likely to have had pneumonia or to have experienced stabbing pain, photophobia, or phonophobia. They reported that the headache got worse when they engaged in physical activity but less frequently manifested as a throbbing headache.
Secondary tension headaches
On the other hand, Jaime Rodríguez Vico, MD, head of the headache unit at the Jiménez Díaz Foundation Hospital in Madrid, said in an interview that, according to his case studies, the most striking characteristics of post–COVID-19 headaches “in general are secondary, with similarities to tension headaches that patients are able to differentiate from other clinical types of headache. In patients with migraine, very often we see that we’re dealing with a trigger. In other words, more migraines – and more intense ones at that – are brought about.”
He added: “Generally, post–COVID-19 headache usually lasts 1-2 weeks, but we have cases of it lasting several months and even over a year with persistent daily headache. These more persistent cases are probably connected to another type of pathology that makes them more susceptible to becoming chronic, something that occurs in another type of primary headache known as new daily persistent headache.”
Primary headache exacerbation
Dr. García Azorín pointed out that it’s not uncommon that among people who already have primary headache, their condition worsens after they become infected with SARS-CoV-2. However, many people differentiate the headache associated with the infection from their usual headache because after becoming infected, their headache is predominantly frontal, oppressive, and chronic.
“Having a prior history of headache is one of the factors that can increase the likelihood that a headache experienced while suffering from COVID-19 will become chronic,” he noted.
This study also found that, more often than not, patients with persistent headache at 9 months had migraine-like pain.
As for headaches in these patients beyond 9 months, “based on our research, the evolution is quite variable,” said Dr. Rodríguez Vico. “Our unit’s numbers are skewed due to the high number of migraine cases that we follow, and therefore our high volume of migraine patients who’ve gotten worse. The same thing happens with COVID-19 vaccines. Migraine is a polygenic disorder with multiple variants and a pathophysiology that we are just beginning to describe. This is why one patient is completely different from another. It’s a real challenge.”
Infections are a common cause of acute and chronic headache. The persistence of a headache after an infection may be caused by the infection becoming chronic, as happens in some types of chronic meningitis, such as tuberculous meningitis. It may also be caused by the persistence of a certain response and activation of the immune system or to the uncovering or worsening of a primary headache coincident with the infection, added Dr. García Azorín.
“Likewise, there are other people who have a biological predisposition to headache as a multifactorial disorder and polygenic disorder, such that a particular stimulus – from trauma or an infection to alcohol consumption – can cause them to develop a headache very similar to a migraine,” he said.
Providing prognosis and treatment
Certain factors can give an idea of how long the headache might last. The study’s univariate analysis showed that age, female sex, headache intensity, pressure-like quality, the presence of photophobia/phonophobia, and worsening with physical activity were associated with headache of longer duration. But in the multivariate analysis, only headache intensity during the acute phase remained statistically significant (hazard ratio, 0.655; 95% confidence interval, 0.582-0.737; P < .001).
When asked whether they planned to continue the study, Dr. García Azorín commented, “The main questions that have arisen from this study have been, above all: ‘Why does this headache happen?’ and ‘How can it be treated or avoided?’ To answer them, we’re looking into pain: which factors could predispose a person to it and which changes may be associated with its presence.”
In addition, different treatments that may improve patient outcomes are being evaluated, because to date, treatment has been empirical and based on the predominant pain phenotype.
In any case, most doctors currently treat post–COVID-19 headache on the basis of how similar the symptoms are to those of other primary headaches. “Given the impact that headache has on patients’ quality of life, there’s a pressing need for controlled studies on possible treatments and their effectiveness,” noted Patricia Pozo Rosich, MD, PhD, one of the coauthors of the study.
“We at the Spanish Society of Neurology truly believe that if these patients were to have this symptom correctly addressed from the start, they could avoid many of the problems that arise in the situation becoming chronic,” she concluded.
Dr. García Azorín and Dr. Rodríguez Vico disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Approximately one in five patients who presented with headache during the acute phase of COVID-19 developed chronic daily headache, according to a study published in Cephalalgia. The greater the headache’s intensity during the acute phase, the greater the likelihood that it would persist.
The research, carried out by members of the Headache Study Group of the Spanish Society of Neurology, evaluated the evolution of headache in more than 900 Spanish patients. Because they found that headache intensity during the acute phase was associated with a more prolonged duration of headache, the team stressed the importance of promptly evaluating patients who have had COVID-19 and who then experience persistent headache.
Long-term evolution unknown
Headache is a common symptom of COVID-19, but its long-term evolution remains unknown. The objective of this study was to evaluate the long-term duration of headache in patients who presented with this symptom during the acute phase of the disease.
Recruitment for this multicenter study took place in March and April 2020. The 905 patients who were enrolled came from six level 3 hospitals in Spain. All completed 9 months of neurologic follow-up.
Their median age was 51 years, 66.5% were women, and more than half (52.7%) had a history of primary headache. About half of the patients required hospitalization (50.5%); the rest were treated as outpatients. The most common headache phenotype was holocranial (67.8%) of severe intensity (50.6%).
Persistent headache common
In the 96.6% cases for which data were available, the median duration of headache was 14 days. The headache persisted at 1 month in 31.1% of patients, at 2 months in 21.5%, at 3 months in 19%, at 6 months in 16.8%, and at 9 months in 16.0%.
“The median duration of COVID-19 headache is around 2 weeks,” David García Azorín, MD, PhD, a member of the Spanish Society of Neurology and one of the coauthors of the study, said in an interview. “However, almost 20% of patients experience it for longer than that. When still present at 2 months, the headache is more likely to follow a chronic daily pattern.” Dr. García Azorín is a neurologist and clinical researcher at the headache unit of the Hospital Clínico Universitario in Valladolid, Spain.
“So, if the headache isn’t letting up, it’s important to make the most of that window of opportunity and provide treatment in that period of 6-12 weeks,” he continued. “To do this, the best option is to carry out preventive treatment so that the patient will have a better chance of recovering.”
Study participants whose headache persisted at 9 months were older and were mostly women. They were less likely to have had pneumonia or to have experienced stabbing pain, photophobia, or phonophobia. They reported that the headache got worse when they engaged in physical activity but less frequently manifested as a throbbing headache.
Secondary tension headaches
On the other hand, Jaime Rodríguez Vico, MD, head of the headache unit at the Jiménez Díaz Foundation Hospital in Madrid, said in an interview that, according to his case studies, the most striking characteristics of post–COVID-19 headaches “in general are secondary, with similarities to tension headaches that patients are able to differentiate from other clinical types of headache. In patients with migraine, very often we see that we’re dealing with a trigger. In other words, more migraines – and more intense ones at that – are brought about.”
He added: “Generally, post–COVID-19 headache usually lasts 1-2 weeks, but we have cases of it lasting several months and even over a year with persistent daily headache. These more persistent cases are probably connected to another type of pathology that makes them more susceptible to becoming chronic, something that occurs in another type of primary headache known as new daily persistent headache.”
Primary headache exacerbation
Dr. García Azorín pointed out that it’s not uncommon that among people who already have primary headache, their condition worsens after they become infected with SARS-CoV-2. However, many people differentiate the headache associated with the infection from their usual headache because after becoming infected, their headache is predominantly frontal, oppressive, and chronic.
“Having a prior history of headache is one of the factors that can increase the likelihood that a headache experienced while suffering from COVID-19 will become chronic,” he noted.
This study also found that, more often than not, patients with persistent headache at 9 months had migraine-like pain.
As for headaches in these patients beyond 9 months, “based on our research, the evolution is quite variable,” said Dr. Rodríguez Vico. “Our unit’s numbers are skewed due to the high number of migraine cases that we follow, and therefore our high volume of migraine patients who’ve gotten worse. The same thing happens with COVID-19 vaccines. Migraine is a polygenic disorder with multiple variants and a pathophysiology that we are just beginning to describe. This is why one patient is completely different from another. It’s a real challenge.”
Infections are a common cause of acute and chronic headache. The persistence of a headache after an infection may be caused by the infection becoming chronic, as happens in some types of chronic meningitis, such as tuberculous meningitis. It may also be caused by the persistence of a certain response and activation of the immune system or to the uncovering or worsening of a primary headache coincident with the infection, added Dr. García Azorín.
“Likewise, there are other people who have a biological predisposition to headache as a multifactorial disorder and polygenic disorder, such that a particular stimulus – from trauma or an infection to alcohol consumption – can cause them to develop a headache very similar to a migraine,” he said.
Providing prognosis and treatment
Certain factors can give an idea of how long the headache might last. The study’s univariate analysis showed that age, female sex, headache intensity, pressure-like quality, the presence of photophobia/phonophobia, and worsening with physical activity were associated with headache of longer duration. But in the multivariate analysis, only headache intensity during the acute phase remained statistically significant (hazard ratio, 0.655; 95% confidence interval, 0.582-0.737; P < .001).
When asked whether they planned to continue the study, Dr. García Azorín commented, “The main questions that have arisen from this study have been, above all: ‘Why does this headache happen?’ and ‘How can it be treated or avoided?’ To answer them, we’re looking into pain: which factors could predispose a person to it and which changes may be associated with its presence.”
In addition, different treatments that may improve patient outcomes are being evaluated, because to date, treatment has been empirical and based on the predominant pain phenotype.
In any case, most doctors currently treat post–COVID-19 headache on the basis of how similar the symptoms are to those of other primary headaches. “Given the impact that headache has on patients’ quality of life, there’s a pressing need for controlled studies on possible treatments and their effectiveness,” noted Patricia Pozo Rosich, MD, PhD, one of the coauthors of the study.
“We at the Spanish Society of Neurology truly believe that if these patients were to have this symptom correctly addressed from the start, they could avoid many of the problems that arise in the situation becoming chronic,” she concluded.
Dr. García Azorín and Dr. Rodríguez Vico disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CEPHALALGIA