Isotretinoin use contributed to abnormal lipid lab values in pediatric patients, but no secondary effects were observed, results from a single-center retrospective study demonstrated.

“Isotretinoin is a very effective treatment for severe acne,” Varsha Parthasarathy said at the annual meeting of the Society for Pediatric Dermatology. “However, initiating this medication requires a complex process of laboratory testing,” which includes human chorionic gonadotropin pregnancy testing, because isotretinoin is a teratogen, as well as lipid labs and liver function tests, she noted. “Importantly, triglycerides are measured due to an association in adults between isotretinoin and hypertriglyceridemia-associated pancreatitis. However, these findings in children are limited to case reports, as are findings of retinoid-induced hepatotoxicity.”

To identify the role of isotretinoin on changes in lipids, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), and to determine the impact on treatment course, Ms. Parthasarathy, a 4-year medical student at George Washington University, Washington, and colleagues retrospectively reviewed the charts of 130 patients aged 12-21 years who were cared for at Children’s National Hospital between January 2012 and October 2020. Nearly two-thirds (65%) were male, their average age was 16 years, and the mean time to obtain follow-up labs after starting isotretinoin was 3.25 months.

Between baseline and follow-up, the researchers observed increases in total cholesterol, triglycerides, and LDL (P less than .001 for all associations) and a decrease in HDL (P = .001), but there were no significant changes in AST or ALT levels. These findings were consistent with prior studies in adults examining the utility of these laboratory tests, most notably a 2016 study by Timothy J. Hansen, MD, and colleagues.

Among the 13 patients with elevated triglycerides at baseline, 9 (69%) were overweight or obese. Of the 20 patients with elevated triglycerides at follow-up, 11 patients (55%) were obese. At follow-up, 11 patients had levels of 200-500 mg/dL (grade I elevation), and 2 patients had levels of 501-1,000 mg/dL (grade II elevation). Isotretinoin was stopped in the latter two patients, who also had obesity as a risk factor for their hypertriglyceridemia.

“None of these patients had clinical sequelae from their hypertriglyceridemia, such as pancreatitis at baseline or follow-up,” Ms. Parthasarathy said. “However, since pancreatitis would be expected to be exceedingly rare, the sample size may be limited in identifying this adverse effect.”

She noted that while isotretinoin might cause a significant increase in lipid levels, the mean levels remained within normal limits at both baseline and follow-up. “Of the patients with elevated triglycerides at baseline and follow-up, obesity may have been a potential risk factor,” she said. “This could suggest a possible strategy for reduced testing in nonobese isotretinoin patients, which can be further explored in larger study populations.”

In addition, “there was a lack of significant change in AST and ALT in this study and adult studies, as well as minimal evidence for pediatric retinoid-induced hepatotoxicity, which raises the question of the necessity of baseline and follow-up comprehensive metabolic panel testing,” Ms. Parthasarathy added. “Clinicians must weigh the laboratory values with the costs of laboratory testing, including opportunity costs such as time, monetary costs, and the discomfort of testing for pediatric patients.”

The study’s senior author was A. Yasmine Kirkorian, MD, chief of dermatology at Children’s National Hospital, Washington. The researchers reported having no relevant financial disclosures.

[email protected]

Isotretinoin use contributed to abnormal lipid lab values in pediatric patients, but no secondary effects were observed, results from a single-center retrospective study demonstrated.

“Isotretinoin is a very effective treatment for severe acne,” Varsha Parthasarathy said at the annual meeting of the Society for Pediatric Dermatology. “However, initiating this medication requires a complex process of laboratory testing,” which includes human chorionic gonadotropin pregnancy testing, because isotretinoin is a teratogen, as well as lipid labs and liver function tests, she noted. “Importantly, triglycerides are measured due to an association in adults between isotretinoin and hypertriglyceridemia-associated pancreatitis. However, these findings in children are limited to case reports, as are findings of retinoid-induced hepatotoxicity.”

To identify the role of isotretinoin on changes in lipids, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), and to determine the impact on treatment course, Ms. Parthasarathy, a 4-year medical student at George Washington University, Washington, and colleagues retrospectively reviewed the charts of 130 patients aged 12-21 years who were cared for at Children’s National Hospital between January 2012 and October 2020. Nearly two-thirds (65%) were male, their average age was 16 years, and the mean time to obtain follow-up labs after starting isotretinoin was 3.25 months.

Between baseline and follow-up, the researchers observed increases in total cholesterol, triglycerides, and LDL (P less than .001 for all associations) and a decrease in HDL (P = .001), but there were no significant changes in AST or ALT levels. These findings were consistent with prior studies in adults examining the utility of these laboratory tests, most notably a 2016 study by Timothy J. Hansen, MD, and colleagues.

Among the 13 patients with elevated triglycerides at baseline, 9 (69%) were overweight or obese. Of the 20 patients with elevated triglycerides at follow-up, 11 patients (55%) were obese. At follow-up, 11 patients had levels of 200-500 mg/dL (grade I elevation), and 2 patients had levels of 501-1,000 mg/dL (grade II elevation). Isotretinoin was stopped in the latter two patients, who also had obesity as a risk factor for their hypertriglyceridemia.

“None of these patients had clinical sequelae from their hypertriglyceridemia, such as pancreatitis at baseline or follow-up,” Ms. Parthasarathy said. “However, since pancreatitis would be expected to be exceedingly rare, the sample size may be limited in identifying this adverse effect.”

She noted that while isotretinoin might cause a significant increase in lipid levels, the mean levels remained within normal limits at both baseline and follow-up. “Of the patients with elevated triglycerides at baseline and follow-up, obesity may have been a potential risk factor,” she said. “This could suggest a possible strategy for reduced testing in nonobese isotretinoin patients, which can be further explored in larger study populations.”

In addition, “there was a lack of significant change in AST and ALT in this study and adult studies, as well as minimal evidence for pediatric retinoid-induced hepatotoxicity, which raises the question of the necessity of baseline and follow-up comprehensive metabolic panel testing,” Ms. Parthasarathy added. “Clinicians must weigh the laboratory values with the costs of laboratory testing, including opportunity costs such as time, monetary costs, and the discomfort of testing for pediatric patients.”

The study’s senior author was A. Yasmine Kirkorian, MD, chief of dermatology at Children’s National Hospital, Washington. The researchers reported having no relevant financial disclosures.

[email protected]

Isotretinoin use contributed to abnormal lipid lab values in pediatric patients, but no secondary effects were observed, results from a single-center retrospective study demonstrated.

“Isotretinoin is a very effective treatment for severe acne,” Varsha Parthasarathy said at the annual meeting of the Society for Pediatric Dermatology. “However, initiating this medication requires a complex process of laboratory testing,” which includes human chorionic gonadotropin pregnancy testing, because isotretinoin is a teratogen, as well as lipid labs and liver function tests, she noted. “Importantly, triglycerides are measured due to an association in adults between isotretinoin and hypertriglyceridemia-associated pancreatitis. However, these findings in children are limited to case reports, as are findings of retinoid-induced hepatotoxicity.”

To identify the role of isotretinoin on changes in lipids, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), and to determine the impact on treatment course, Ms. Parthasarathy, a 4-year medical student at George Washington University, Washington, and colleagues retrospectively reviewed the charts of 130 patients aged 12-21 years who were cared for at Children’s National Hospital between January 2012 and October 2020. Nearly two-thirds (65%) were male, their average age was 16 years, and the mean time to obtain follow-up labs after starting isotretinoin was 3.25 months.

Between baseline and follow-up, the researchers observed increases in total cholesterol, triglycerides, and LDL (P less than .001 for all associations) and a decrease in HDL (P = .001), but there were no significant changes in AST or ALT levels. These findings were consistent with prior studies in adults examining the utility of these laboratory tests, most notably a 2016 study by Timothy J. Hansen, MD, and colleagues.

Among the 13 patients with elevated triglycerides at baseline, 9 (69%) were overweight or obese. Of the 20 patients with elevated triglycerides at follow-up, 11 patients (55%) were obese. At follow-up, 11 patients had levels of 200-500 mg/dL (grade I elevation), and 2 patients had levels of 501-1,000 mg/dL (grade II elevation). Isotretinoin was stopped in the latter two patients, who also had obesity as a risk factor for their hypertriglyceridemia.

“None of these patients had clinical sequelae from their hypertriglyceridemia, such as pancreatitis at baseline or follow-up,” Ms. Parthasarathy said. “However, since pancreatitis would be expected to be exceedingly rare, the sample size may be limited in identifying this adverse effect.”

She noted that while isotretinoin might cause a significant increase in lipid levels, the mean levels remained within normal limits at both baseline and follow-up. “Of the patients with elevated triglycerides at baseline and follow-up, obesity may have been a potential risk factor,” she said. “This could suggest a possible strategy for reduced testing in nonobese isotretinoin patients, which can be further explored in larger study populations.”

In addition, “there was a lack of significant change in AST and ALT in this study and adult studies, as well as minimal evidence for pediatric retinoid-induced hepatotoxicity, which raises the question of the necessity of baseline and follow-up comprehensive metabolic panel testing,” Ms. Parthasarathy added. “Clinicians must weigh the laboratory values with the costs of laboratory testing, including opportunity costs such as time, monetary costs, and the discomfort of testing for pediatric patients.”

The study’s senior author was A. Yasmine Kirkorian, MD, chief of dermatology at Children’s National Hospital, Washington. The researchers reported having no relevant financial disclosures.

[email protected]

The American Gastroenterological Association recently published a clinical practice update concerning endoscopic evaluation and management of early complications after bariatric/metabolic surgery.

The seven best practice advice statements, based on available evidence and expert opinion, range from a general call for high familiarity with available interventions to specific approaches for managing postoperative leaks.

According to lead author Vivek Kumbhari, MD, PhD, director of advanced endoscopy, department of gastroenterology and hepatology, Mayo Clinic, Jacksonville, Fla., and colleagues, the update was written in consideration of increasing rates of bariatric/metabolic surgery.

“Bariatric/metabolic surgery is unmatched with respect to its weight loss and metabolic benefits,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The selection criteria will continue to broaden, likely resulting in increasing numbers of less robust patients undergoing surgery (e.g., children, elderly, and those with significant cardiorespiratory comorbidities).”

Although the 90-day overall complication rate across all patients undergoing bariatric/metabolic surgery is only 4%, Dr. Kumbhari and colleagues noted that this rate is considerably higher, at 20.1%, among patients aged older than 65 years.

“As utilization escalates, so will the number of patients who suffer early complications,” they wrote.

The first three items of best practice advice describe who should be managing complications after bariatric/metabolic surgery, and how.

Foremost, Dr. Kumbhari and colleagues called for a multidisciplinary approach; they suggested that endoscopists should work closely with related specialists, such as bariatric/metabolic surgeons and interventional radiologists.

“Timely communication between the endoscopist, radiologist, surgeon, nutritionists, and inpatient medical team or primary care physician will result in efficient, effective care with prompt escalation and deescalation,” they wrote. “Daily communication is advised.”

The next two best practice advice statements encourage high familiarity with endoscopic treatments, postsurgical anatomy, interventional radiology, and surgical interventions, including risks and benefits of each approach.

“The endoscopist should ... have expertise in interventional endoscopy techniques, including but not limited to using concomitant fluoroscopy, stent deployment and retrieval, pneumatic balloon dilation, incisional therapies, endoscopic suturing, and managing percutaneous drains,” the investigators wrote. “Having the ability to perform a wide array of therapies will enhance the likelihood that the optimal endoscopic strategy will be employed, as opposed to simply performing a technique with which the endoscopist has experience.”

Following these best practices, Dr. Kumbhari and colleagues advised screening patients with postoperative complications for comorbidities, both medical in nature (such as infection) and psychological.

“Patients often have higher depression and anxiety scores, as well as a lower physical quality of life, and medical teams sometimes neglect the patient’s psychological state,” they wrote. “It is imperative that the multidisciplinary team recognize and acknowledge the patient’s psychological comorbidities and engage expertise to manage them.”

Next, the investigators advised that endoscopic intervention should be considered regardless of time interval since surgery, including the immediate postoperative period.

“Endoscopy is often indicated as the initial therapeutic modality, and it can safely be performed,” Dr. Kumbhari and colleagues wrote. “When endoscopy is performed, it is advised to use carbon dioxide for insufflation. Caution should be used when advancing the endoscope into the small bowel, as it is best to minimize pressure along the fresh staple lines. In cases in which the patient is critically ill or the interventional endoscopist does not have extensive experience with such a scenario, the endoscopy should be performed in the operating room with a surgeon present (preferably the surgeon who performed the operation).”

Dr. Kumbhari and colleagues discussed functional stenosis, which can precipitate and propagate leaks. They noted that “downstream stenosis is frequently seen at the level of the incisura angularis or in the proximal stomach when a sleeve gastrectomy is performed in a patient with a prior laparoscopic adjustable gastric band.”

To address stenosis, the update calls for “aggressive dilation” using a large pneumatic balloon, preferably with fluoroscopy to make sure the distal end of the balloon does not cross the pylorus. The investigators noted that endoscopic suturing may be needed if a tear involving the muscularis propria is encountered.

Lastly, the clinical practice update offers comprehensive guidance for managing staple-line leaks, which “most commonly occur along the staple line of the proximal stomach.”

As leaks are thought to stem from ischemia, “most leaks are not present upon completion of the operation, and they develop over the subsequent weeks, often in the setting of downstream stenosis,” the investigators wrote.

To guide management of staple-line leaks, the investigators presented a treatment algorithm that incorporates defect size, time since surgery, and presence or absence of stenosis.

For example, a defect smaller than 10 mm occurring within 6 weeks of surgery and lacking stenosis may be managed with a percutaneous drain and diversion. In contrast, a defect of similar size, also without stenosis, but occurring later than 6 weeks after the initial procedure, should be managed with endoscopic internal drainage or vacuum therapy.

“Clinicians should recognize that the goal for endoscopic management of staple-line leaks is often not necessarily initial closure of the leak site, but rather techniques to promote drainage of material from the perigastric collection into the gastric lumen such that the leak site closes by secondary intention,” wrote Dr. Kumbhari and colleagues.

The clinical practice update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. The investigators disclosed relationships with Boston Scientific, Medtronic, Apollo Endosurgery, and others.

The American Gastroenterological Association recently published a clinical practice update concerning endoscopic evaluation and management of early complications after bariatric/metabolic surgery.

The seven best practice advice statements, based on available evidence and expert opinion, range from a general call for high familiarity with available interventions to specific approaches for managing postoperative leaks.

According to lead author Vivek Kumbhari, MD, PhD, director of advanced endoscopy, department of gastroenterology and hepatology, Mayo Clinic, Jacksonville, Fla., and colleagues, the update was written in consideration of increasing rates of bariatric/metabolic surgery.

“Bariatric/metabolic surgery is unmatched with respect to its weight loss and metabolic benefits,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The selection criteria will continue to broaden, likely resulting in increasing numbers of less robust patients undergoing surgery (e.g., children, elderly, and those with significant cardiorespiratory comorbidities).”

Although the 90-day overall complication rate across all patients undergoing bariatric/metabolic surgery is only 4%, Dr. Kumbhari and colleagues noted that this rate is considerably higher, at 20.1%, among patients aged older than 65 years.

“As utilization escalates, so will the number of patients who suffer early complications,” they wrote.

The first three items of best practice advice describe who should be managing complications after bariatric/metabolic surgery, and how.

Foremost, Dr. Kumbhari and colleagues called for a multidisciplinary approach; they suggested that endoscopists should work closely with related specialists, such as bariatric/metabolic surgeons and interventional radiologists.

“Timely communication between the endoscopist, radiologist, surgeon, nutritionists, and inpatient medical team or primary care physician will result in efficient, effective care with prompt escalation and deescalation,” they wrote. “Daily communication is advised.”

The next two best practice advice statements encourage high familiarity with endoscopic treatments, postsurgical anatomy, interventional radiology, and surgical interventions, including risks and benefits of each approach.

“The endoscopist should ... have expertise in interventional endoscopy techniques, including but not limited to using concomitant fluoroscopy, stent deployment and retrieval, pneumatic balloon dilation, incisional therapies, endoscopic suturing, and managing percutaneous drains,” the investigators wrote. “Having the ability to perform a wide array of therapies will enhance the likelihood that the optimal endoscopic strategy will be employed, as opposed to simply performing a technique with which the endoscopist has experience.”

Following these best practices, Dr. Kumbhari and colleagues advised screening patients with postoperative complications for comorbidities, both medical in nature (such as infection) and psychological.

“Patients often have higher depression and anxiety scores, as well as a lower physical quality of life, and medical teams sometimes neglect the patient’s psychological state,” they wrote. “It is imperative that the multidisciplinary team recognize and acknowledge the patient’s psychological comorbidities and engage expertise to manage them.”

Next, the investigators advised that endoscopic intervention should be considered regardless of time interval since surgery, including the immediate postoperative period.

“Endoscopy is often indicated as the initial therapeutic modality, and it can safely be performed,” Dr. Kumbhari and colleagues wrote. “When endoscopy is performed, it is advised to use carbon dioxide for insufflation. Caution should be used when advancing the endoscope into the small bowel, as it is best to minimize pressure along the fresh staple lines. In cases in which the patient is critically ill or the interventional endoscopist does not have extensive experience with such a scenario, the endoscopy should be performed in the operating room with a surgeon present (preferably the surgeon who performed the operation).”

Dr. Kumbhari and colleagues discussed functional stenosis, which can precipitate and propagate leaks. They noted that “downstream stenosis is frequently seen at the level of the incisura angularis or in the proximal stomach when a sleeve gastrectomy is performed in a patient with a prior laparoscopic adjustable gastric band.”

To address stenosis, the update calls for “aggressive dilation” using a large pneumatic balloon, preferably with fluoroscopy to make sure the distal end of the balloon does not cross the pylorus. The investigators noted that endoscopic suturing may be needed if a tear involving the muscularis propria is encountered.

Lastly, the clinical practice update offers comprehensive guidance for managing staple-line leaks, which “most commonly occur along the staple line of the proximal stomach.”

As leaks are thought to stem from ischemia, “most leaks are not present upon completion of the operation, and they develop over the subsequent weeks, often in the setting of downstream stenosis,” the investigators wrote.

To guide management of staple-line leaks, the investigators presented a treatment algorithm that incorporates defect size, time since surgery, and presence or absence of stenosis.

For example, a defect smaller than 10 mm occurring within 6 weeks of surgery and lacking stenosis may be managed with a percutaneous drain and diversion. In contrast, a defect of similar size, also without stenosis, but occurring later than 6 weeks after the initial procedure, should be managed with endoscopic internal drainage or vacuum therapy.

“Clinicians should recognize that the goal for endoscopic management of staple-line leaks is often not necessarily initial closure of the leak site, but rather techniques to promote drainage of material from the perigastric collection into the gastric lumen such that the leak site closes by secondary intention,” wrote Dr. Kumbhari and colleagues.

The clinical practice update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. The investigators disclosed relationships with Boston Scientific, Medtronic, Apollo Endosurgery, and others.

The American Gastroenterological Association recently published a clinical practice update concerning endoscopic evaluation and management of early complications after bariatric/metabolic surgery.

The seven best practice advice statements, based on available evidence and expert opinion, range from a general call for high familiarity with available interventions to specific approaches for managing postoperative leaks.

According to lead author Vivek Kumbhari, MD, PhD, director of advanced endoscopy, department of gastroenterology and hepatology, Mayo Clinic, Jacksonville, Fla., and colleagues, the update was written in consideration of increasing rates of bariatric/metabolic surgery.

“Bariatric/metabolic surgery is unmatched with respect to its weight loss and metabolic benefits,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The selection criteria will continue to broaden, likely resulting in increasing numbers of less robust patients undergoing surgery (e.g., children, elderly, and those with significant cardiorespiratory comorbidities).”

Although the 90-day overall complication rate across all patients undergoing bariatric/metabolic surgery is only 4%, Dr. Kumbhari and colleagues noted that this rate is considerably higher, at 20.1%, among patients aged older than 65 years.

“As utilization escalates, so will the number of patients who suffer early complications,” they wrote.

The first three items of best practice advice describe who should be managing complications after bariatric/metabolic surgery, and how.

Foremost, Dr. Kumbhari and colleagues called for a multidisciplinary approach; they suggested that endoscopists should work closely with related specialists, such as bariatric/metabolic surgeons and interventional radiologists.

“Timely communication between the endoscopist, radiologist, surgeon, nutritionists, and inpatient medical team or primary care physician will result in efficient, effective care with prompt escalation and deescalation,” they wrote. “Daily communication is advised.”

The next two best practice advice statements encourage high familiarity with endoscopic treatments, postsurgical anatomy, interventional radiology, and surgical interventions, including risks and benefits of each approach.

“The endoscopist should ... have expertise in interventional endoscopy techniques, including but not limited to using concomitant fluoroscopy, stent deployment and retrieval, pneumatic balloon dilation, incisional therapies, endoscopic suturing, and managing percutaneous drains,” the investigators wrote. “Having the ability to perform a wide array of therapies will enhance the likelihood that the optimal endoscopic strategy will be employed, as opposed to simply performing a technique with which the endoscopist has experience.”

Following these best practices, Dr. Kumbhari and colleagues advised screening patients with postoperative complications for comorbidities, both medical in nature (such as infection) and psychological.

“Patients often have higher depression and anxiety scores, as well as a lower physical quality of life, and medical teams sometimes neglect the patient’s psychological state,” they wrote. “It is imperative that the multidisciplinary team recognize and acknowledge the patient’s psychological comorbidities and engage expertise to manage them.”

Next, the investigators advised that endoscopic intervention should be considered regardless of time interval since surgery, including the immediate postoperative period.

“Endoscopy is often indicated as the initial therapeutic modality, and it can safely be performed,” Dr. Kumbhari and colleagues wrote. “When endoscopy is performed, it is advised to use carbon dioxide for insufflation. Caution should be used when advancing the endoscope into the small bowel, as it is best to minimize pressure along the fresh staple lines. In cases in which the patient is critically ill or the interventional endoscopist does not have extensive experience with such a scenario, the endoscopy should be performed in the operating room with a surgeon present (preferably the surgeon who performed the operation).”

Dr. Kumbhari and colleagues discussed functional stenosis, which can precipitate and propagate leaks. They noted that “downstream stenosis is frequently seen at the level of the incisura angularis or in the proximal stomach when a sleeve gastrectomy is performed in a patient with a prior laparoscopic adjustable gastric band.”

To address stenosis, the update calls for “aggressive dilation” using a large pneumatic balloon, preferably with fluoroscopy to make sure the distal end of the balloon does not cross the pylorus. The investigators noted that endoscopic suturing may be needed if a tear involving the muscularis propria is encountered.

Lastly, the clinical practice update offers comprehensive guidance for managing staple-line leaks, which “most commonly occur along the staple line of the proximal stomach.”

As leaks are thought to stem from ischemia, “most leaks are not present upon completion of the operation, and they develop over the subsequent weeks, often in the setting of downstream stenosis,” the investigators wrote.

To guide management of staple-line leaks, the investigators presented a treatment algorithm that incorporates defect size, time since surgery, and presence or absence of stenosis.

For example, a defect smaller than 10 mm occurring within 6 weeks of surgery and lacking stenosis may be managed with a percutaneous drain and diversion. In contrast, a defect of similar size, also without stenosis, but occurring later than 6 weeks after the initial procedure, should be managed with endoscopic internal drainage or vacuum therapy.

“Clinicians should recognize that the goal for endoscopic management of staple-line leaks is often not necessarily initial closure of the leak site, but rather techniques to promote drainage of material from the perigastric collection into the gastric lumen such that the leak site closes by secondary intention,” wrote Dr. Kumbhari and colleagues.

The clinical practice update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. The investigators disclosed relationships with Boston Scientific, Medtronic, Apollo Endosurgery, and others.

A mechanistic link between red meat consumption and colorectal cancer (CRC) has been identified in the form of an alkylating mutational signature, according to investigators.

This is the first time a colorectal mutational signature has been associated with a component of diet, which demonstrates the value of large-scale molecular epidemiologic studies and suggests potential for early, precision dietary intervention, reported lead author Carino Gurjao, MSc, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, and colleagues.

“Red meat consumption has been consistently linked to the incidence of colorectal cancer,” the investigators wrote in Cancer Discovery. “The suggested mechanism is mutagenesis through alkylating damage induced by N-nitroso-compounds (NOCs), which are metabolic products of blood heme iron or meat nitrites/nitrates. Nevertheless, this mutational damage is yet to be observed directly in patients’ tumors.”

To this end, the investigators turned to three long-term, large-scale, prospective cohort studies: the Nurses’ Health Studies I and II, and the Health Professionals Follow-up Study. These databases include nearly 300,000 individuals with follow-up dating back as far as 1976. The investigators identified 900 cases of primary, untreated CRC with adequate tissue for analysis, then, for each case, performed whole exome sequencing on both tumor tissue and normal colorectal tissue.

This revealed an alkylating mutational signature previously undescribed in CRC that was significantly associated with consumption of red meat prior to diagnosis, but not other dietary or lifestyle factors. The signature occurred most frequently in tumors and normal crypts in the distal colon and rectum.

According to the investigators, the presence of the alkylating signature in normal colorectal crypts “suggests that mutational changes due to such damage may start to occur early in the path of colorectal carcinogenesis.”

Further analysis showed that tumors harboring common KRAS and PIK3CA driver mutations had the highest levels of alkylating damage, with higher levels predicting worse survival.

“These results ... further implicate the role of red meat in CRC initiation and progression,” the investigators concluded.
 

Early findings, important implications

Cosenior author Kana Wu, MD, PhD, principal research scientist in the department of nutrition at Harvard School of Public Health, Boston, noted that these are early findings, although they may pave the way toward new dietary recommendations and methods of food production.

“While more detailed analysis needs to be conducted, and our results need to be confirmed in other studies, this study is a promising first step to better understand the biological mechanisms underlying the role of red and processed meats in colorectal cancers,” Dr. Wu said in an interview. “It is important to gain more insight into the biological mechanisms so we can improve dietary guidelines for cancer prevention and guide food reformulation efforts to lower cancer risk.”

For now, Dr. Wu predicted that standing dietary recommendations will remain unchanged.

“This study will not alter current diet recommendations to limit intake of red and processed meats,” Dr. Wu said, referring to similar recommendations across several organizations, including the American Heart Association, the World Cancer Research Fund/American Institute for Cancer Research, and the American Cancer Society.

“For example,” Dr. Wu said, “the WCRF/AICR recommends limiting consumption of red and processed meat to ‘no more than moderate amounts [12-18 ounces per week] of red meat, such as beef, pork, and lamb, and [to] eat little, if any, processed meat.’”
 

Possible biomarker?

According to Patricia Thompson-Carino, PhD, deputy director of the Stony Brook (N.Y.) Cancer Center, the study provides convincing evidence linking red meat consumption with development of CRC.

“Higher frequency of the signature in the distal colon is compelling for its consistency with epidemiologic evidence,” Dr. Thompson-Carino said in an interview. “Combined with the observed worse survival in patients harboring the signature and association with oncogenic KRAS and PIK3CA driver mutations, this study significantly elevates the biological plausibility that red meat is a modifiable source of NOC mutagenicity and carcinogenesis in humans.”

The signature could be used as a biomarker to detect exposure to NOCs, and susceptibility to CRC, she added.

Still, Dr. Thompson-Carino suggested that more work is needed to fully elucidate underlying mechanisms of action, which are needed to accurately shape dietary guidance.

“Key to advancing red meat dietary recommendations will be understanding the relationships between the new mutation signature and the NOCs derived from red meat and their source, whether endogenous [for example, intestinal N-nitrosation] or exogenous [for example, chemical preservation or charring],” she said. The study was supported by the National Institutes of Health, the Stand Up To Cancer Colorectal Cancer Dream Team Translational Research Grant (coadministered by the American Association for Cancer Research), the Project P Fund, and others. The investigators, Dr. Wu, and Dr. Thompson-Carino reported no conflicts of interest related to this study.

A mechanistic link between red meat consumption and colorectal cancer (CRC) has been identified in the form of an alkylating mutational signature, according to investigators.

This is the first time a colorectal mutational signature has been associated with a component of diet, which demonstrates the value of large-scale molecular epidemiologic studies and suggests potential for early, precision dietary intervention, reported lead author Carino Gurjao, MSc, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, and colleagues.

“Red meat consumption has been consistently linked to the incidence of colorectal cancer,” the investigators wrote in Cancer Discovery. “The suggested mechanism is mutagenesis through alkylating damage induced by N-nitroso-compounds (NOCs), which are metabolic products of blood heme iron or meat nitrites/nitrates. Nevertheless, this mutational damage is yet to be observed directly in patients’ tumors.”

To this end, the investigators turned to three long-term, large-scale, prospective cohort studies: the Nurses’ Health Studies I and II, and the Health Professionals Follow-up Study. These databases include nearly 300,000 individuals with follow-up dating back as far as 1976. The investigators identified 900 cases of primary, untreated CRC with adequate tissue for analysis, then, for each case, performed whole exome sequencing on both tumor tissue and normal colorectal tissue.

This revealed an alkylating mutational signature previously undescribed in CRC that was significantly associated with consumption of red meat prior to diagnosis, but not other dietary or lifestyle factors. The signature occurred most frequently in tumors and normal crypts in the distal colon and rectum.

According to the investigators, the presence of the alkylating signature in normal colorectal crypts “suggests that mutational changes due to such damage may start to occur early in the path of colorectal carcinogenesis.”

Further analysis showed that tumors harboring common KRAS and PIK3CA driver mutations had the highest levels of alkylating damage, with higher levels predicting worse survival.

“These results ... further implicate the role of red meat in CRC initiation and progression,” the investigators concluded.
 

Early findings, important implications

Cosenior author Kana Wu, MD, PhD, principal research scientist in the department of nutrition at Harvard School of Public Health, Boston, noted that these are early findings, although they may pave the way toward new dietary recommendations and methods of food production.

“While more detailed analysis needs to be conducted, and our results need to be confirmed in other studies, this study is a promising first step to better understand the biological mechanisms underlying the role of red and processed meats in colorectal cancers,” Dr. Wu said in an interview. “It is important to gain more insight into the biological mechanisms so we can improve dietary guidelines for cancer prevention and guide food reformulation efforts to lower cancer risk.”

For now, Dr. Wu predicted that standing dietary recommendations will remain unchanged.

“This study will not alter current diet recommendations to limit intake of red and processed meats,” Dr. Wu said, referring to similar recommendations across several organizations, including the American Heart Association, the World Cancer Research Fund/American Institute for Cancer Research, and the American Cancer Society.

“For example,” Dr. Wu said, “the WCRF/AICR recommends limiting consumption of red and processed meat to ‘no more than moderate amounts [12-18 ounces per week] of red meat, such as beef, pork, and lamb, and [to] eat little, if any, processed meat.’”
 

Possible biomarker?

According to Patricia Thompson-Carino, PhD, deputy director of the Stony Brook (N.Y.) Cancer Center, the study provides convincing evidence linking red meat consumption with development of CRC.

“Higher frequency of the signature in the distal colon is compelling for its consistency with epidemiologic evidence,” Dr. Thompson-Carino said in an interview. “Combined with the observed worse survival in patients harboring the signature and association with oncogenic KRAS and PIK3CA driver mutations, this study significantly elevates the biological plausibility that red meat is a modifiable source of NOC mutagenicity and carcinogenesis in humans.”

The signature could be used as a biomarker to detect exposure to NOCs, and susceptibility to CRC, she added.

Still, Dr. Thompson-Carino suggested that more work is needed to fully elucidate underlying mechanisms of action, which are needed to accurately shape dietary guidance.

“Key to advancing red meat dietary recommendations will be understanding the relationships between the new mutation signature and the NOCs derived from red meat and their source, whether endogenous [for example, intestinal N-nitrosation] or exogenous [for example, chemical preservation or charring],” she said. The study was supported by the National Institutes of Health, the Stand Up To Cancer Colorectal Cancer Dream Team Translational Research Grant (coadministered by the American Association for Cancer Research), the Project P Fund, and others. The investigators, Dr. Wu, and Dr. Thompson-Carino reported no conflicts of interest related to this study.

A mechanistic link between red meat consumption and colorectal cancer (CRC) has been identified in the form of an alkylating mutational signature, according to investigators.

This is the first time a colorectal mutational signature has been associated with a component of diet, which demonstrates the value of large-scale molecular epidemiologic studies and suggests potential for early, precision dietary intervention, reported lead author Carino Gurjao, MSc, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, and colleagues.

“Red meat consumption has been consistently linked to the incidence of colorectal cancer,” the investigators wrote in Cancer Discovery. “The suggested mechanism is mutagenesis through alkylating damage induced by N-nitroso-compounds (NOCs), which are metabolic products of blood heme iron or meat nitrites/nitrates. Nevertheless, this mutational damage is yet to be observed directly in patients’ tumors.”

To this end, the investigators turned to three long-term, large-scale, prospective cohort studies: the Nurses’ Health Studies I and II, and the Health Professionals Follow-up Study. These databases include nearly 300,000 individuals with follow-up dating back as far as 1976. The investigators identified 900 cases of primary, untreated CRC with adequate tissue for analysis, then, for each case, performed whole exome sequencing on both tumor tissue and normal colorectal tissue.

This revealed an alkylating mutational signature previously undescribed in CRC that was significantly associated with consumption of red meat prior to diagnosis, but not other dietary or lifestyle factors. The signature occurred most frequently in tumors and normal crypts in the distal colon and rectum.

According to the investigators, the presence of the alkylating signature in normal colorectal crypts “suggests that mutational changes due to such damage may start to occur early in the path of colorectal carcinogenesis.”

Further analysis showed that tumors harboring common KRAS and PIK3CA driver mutations had the highest levels of alkylating damage, with higher levels predicting worse survival.

“These results ... further implicate the role of red meat in CRC initiation and progression,” the investigators concluded.
 

Early findings, important implications

Cosenior author Kana Wu, MD, PhD, principal research scientist in the department of nutrition at Harvard School of Public Health, Boston, noted that these are early findings, although they may pave the way toward new dietary recommendations and methods of food production.

“While more detailed analysis needs to be conducted, and our results need to be confirmed in other studies, this study is a promising first step to better understand the biological mechanisms underlying the role of red and processed meats in colorectal cancers,” Dr. Wu said in an interview. “It is important to gain more insight into the biological mechanisms so we can improve dietary guidelines for cancer prevention and guide food reformulation efforts to lower cancer risk.”

For now, Dr. Wu predicted that standing dietary recommendations will remain unchanged.

“This study will not alter current diet recommendations to limit intake of red and processed meats,” Dr. Wu said, referring to similar recommendations across several organizations, including the American Heart Association, the World Cancer Research Fund/American Institute for Cancer Research, and the American Cancer Society.

“For example,” Dr. Wu said, “the WCRF/AICR recommends limiting consumption of red and processed meat to ‘no more than moderate amounts [12-18 ounces per week] of red meat, such as beef, pork, and lamb, and [to] eat little, if any, processed meat.’”
 

Possible biomarker?

According to Patricia Thompson-Carino, PhD, deputy director of the Stony Brook (N.Y.) Cancer Center, the study provides convincing evidence linking red meat consumption with development of CRC.

“Higher frequency of the signature in the distal colon is compelling for its consistency with epidemiologic evidence,” Dr. Thompson-Carino said in an interview. “Combined with the observed worse survival in patients harboring the signature and association with oncogenic KRAS and PIK3CA driver mutations, this study significantly elevates the biological plausibility that red meat is a modifiable source of NOC mutagenicity and carcinogenesis in humans.”

The signature could be used as a biomarker to detect exposure to NOCs, and susceptibility to CRC, she added.

Still, Dr. Thompson-Carino suggested that more work is needed to fully elucidate underlying mechanisms of action, which are needed to accurately shape dietary guidance.

“Key to advancing red meat dietary recommendations will be understanding the relationships between the new mutation signature and the NOCs derived from red meat and their source, whether endogenous [for example, intestinal N-nitrosation] or exogenous [for example, chemical preservation or charring],” she said. The study was supported by the National Institutes of Health, the Stand Up To Cancer Colorectal Cancer Dream Team Translational Research Grant (coadministered by the American Association for Cancer Research), the Project P Fund, and others. The investigators, Dr. Wu, and Dr. Thompson-Carino reported no conflicts of interest related to this study.

SACRAMENTO (AP) – California is poised to approve reparations of up to $25,000 to some of the thousands of people – some as young as 13 – who were sterilized decades ago because the government deemed them unfit to have children.

The payments will make California at least the third state – following Virginia and North Carolina – to compensate victims of the so-called eugenics movement that peaked in the 1930s. Supporters of the movement believed sterilizing people with mental illnesses, physical disabilities, and other traits they deemed undesirable would improve the human race.

While California sterilized more than 20,000 people before its law was repealed in 1979, only a few hundred are still alive. The state has set aside $7.5 million for the reparations program, part of its $262.6 billion operating budget that is awaiting Gov. Gavin Newsom’s signature.

California’s proposal is unique because it also would pay women the state coerced to get sterilized while they were in prison, some as recently as 2010. First exposed by the Center for Investigative Reporting in 2013, a subsequent audit found California sterilized 144 women between 2005 and 2013 with little or no evidence that officials counseled them or offered alternative treatment.

While all of the women signed consent forms, officials in 39 cases did not do everything that was legally required to obtain their permission.

“We must address and face our horrific history,” said Lorena Garcia Zermeño, policy and communications coordinator for the advocacy group California Latinas for Reproductive Justice. “This isn’t something that just happened in the past.”

California’s forced sterilization program started in 1909, following similar laws in Indiana and Washington. It was by far the largest program, accounting for about a third of everyone sterilized in the United States under those laws.

California’s law was so prominent that it inspired similar practices in Nazi Germany, according to Paul Lombardo, a law professor at Georgia State University, Atlanta, and an expert on the eugenics movement.

“The promise of eugenics at the very earliest is: ‘We could do away with all the state institutions – prisons, hospitals, asylums, orphanages,’” Mr. Lombardo said. “People who were in them just wouldn’t be born after awhile if you sterilized all of their parents.”

In California, victims include Mary Franco, who was sterilized in 1934 when she was just 13. Paperwork described her as “feeble minded” because of “sexual deviance,” according to her niece, Stacy Cordova, who has researched her case.

Ms. Cordova said Franco actually was molested by a neighbor. She said her family put Ms. Franco in an institution to protect the family’s reputation.

Ms. Cordova said her late aunt loved children and wanted to have a family. She married briefly when she was about 17, but Ms. Cordova said the marriage was annulled when the man discovered Ms. Franco couldn’t have children. She lived a lonely life in a Mexican culture that revered big families, Ms. Cordova said.

“I don’t know if it is justice. Money doesn’t pay for what happened to them. But it’s great to know that this is being recognized,” said Ms. Cordova, who has advocated for the state to pay survivors. “For me, this is not about the money. This is about the memory.”

Relatives like Ms. Cordova aren’t eligible for the payments, only direct victims are.

Sterilizations in California prisons appear to date to 1999, when the state changed its policy for unknown reasons to include a sterilization procedure known as “tubal ligation” as part of inmates’ medical care. Over the next decade, women reported they were coerced into this procedure, with some not fully understanding the ramifications.

A state law passed in 2014 bans sterilizations for the purpose of birth control at state prisons and local jails. The law permits sterilizations that are “medically necessary,” such as removing cancer, and requires facilities to report each year how many people were sterilized and for what reason.

Questionable sterilizations also occurred in facilities run by local governments. In 2018, the Los Angeles County Board of Supervisors apologized after more than 200 women were sterilized at the Los Angeles–University of Southern California Medical Center between 1968 and 1974.

Those people are not eligible for reparations under California’s program. But advocates say they hope to include them in the future.

“It’s only the beginning,” said state Assemblywoman Wendy Carrillo, a Democrat from Los Angeles who has been advocating for reparations. “I can’t imagine the trauma, the depression, the stress of being incarcerated, being rehabilitated and trying to start your life again in society, wanting to start a family, only to find out that that choice was taken away from you.”

Of the people California sterilized under its old eugenics law, just a few hundred are still alive, according to research conducted by the Sterilization and Social Justice Lab. Including the inmates who were sterilized most recently, advocates estimate more than 600 people would be eligible for reparations.

But finding them will be difficult, with advocates predicting only about 25% of eligible people will ultimately apply for reparations and be paid.

California’s Victim Compensation Board will run the program, with $2 million used to find victims by advertising and poring through state records. The state also set aside $1 million for plaques to honor the victims, leaving $4.5 million for reparations.

A version of this article appeared on Medscape.com.

Associated Press © 2021 

SACRAMENTO (AP) – California is poised to approve reparations of up to $25,000 to some of the thousands of people – some as young as 13 – who were sterilized decades ago because the government deemed them unfit to have children.

The payments will make California at least the third state – following Virginia and North Carolina – to compensate victims of the so-called eugenics movement that peaked in the 1930s. Supporters of the movement believed sterilizing people with mental illnesses, physical disabilities, and other traits they deemed undesirable would improve the human race.

While California sterilized more than 20,000 people before its law was repealed in 1979, only a few hundred are still alive. The state has set aside $7.5 million for the reparations program, part of its $262.6 billion operating budget that is awaiting Gov. Gavin Newsom’s signature.

California’s proposal is unique because it also would pay women the state coerced to get sterilized while they were in prison, some as recently as 2010. First exposed by the Center for Investigative Reporting in 2013, a subsequent audit found California sterilized 144 women between 2005 and 2013 with little or no evidence that officials counseled them or offered alternative treatment.

While all of the women signed consent forms, officials in 39 cases did not do everything that was legally required to obtain their permission.

“We must address and face our horrific history,” said Lorena Garcia Zermeño, policy and communications coordinator for the advocacy group California Latinas for Reproductive Justice. “This isn’t something that just happened in the past.”

California’s forced sterilization program started in 1909, following similar laws in Indiana and Washington. It was by far the largest program, accounting for about a third of everyone sterilized in the United States under those laws.

California’s law was so prominent that it inspired similar practices in Nazi Germany, according to Paul Lombardo, a law professor at Georgia State University, Atlanta, and an expert on the eugenics movement.

“The promise of eugenics at the very earliest is: ‘We could do away with all the state institutions – prisons, hospitals, asylums, orphanages,’” Mr. Lombardo said. “People who were in them just wouldn’t be born after awhile if you sterilized all of their parents.”

In California, victims include Mary Franco, who was sterilized in 1934 when she was just 13. Paperwork described her as “feeble minded” because of “sexual deviance,” according to her niece, Stacy Cordova, who has researched her case.

Ms. Cordova said Franco actually was molested by a neighbor. She said her family put Ms. Franco in an institution to protect the family’s reputation.

Ms. Cordova said her late aunt loved children and wanted to have a family. She married briefly when she was about 17, but Ms. Cordova said the marriage was annulled when the man discovered Ms. Franco couldn’t have children. She lived a lonely life in a Mexican culture that revered big families, Ms. Cordova said.

“I don’t know if it is justice. Money doesn’t pay for what happened to them. But it’s great to know that this is being recognized,” said Ms. Cordova, who has advocated for the state to pay survivors. “For me, this is not about the money. This is about the memory.”

Relatives like Ms. Cordova aren’t eligible for the payments, only direct victims are.

Sterilizations in California prisons appear to date to 1999, when the state changed its policy for unknown reasons to include a sterilization procedure known as “tubal ligation” as part of inmates’ medical care. Over the next decade, women reported they were coerced into this procedure, with some not fully understanding the ramifications.

A state law passed in 2014 bans sterilizations for the purpose of birth control at state prisons and local jails. The law permits sterilizations that are “medically necessary,” such as removing cancer, and requires facilities to report each year how many people were sterilized and for what reason.

Questionable sterilizations also occurred in facilities run by local governments. In 2018, the Los Angeles County Board of Supervisors apologized after more than 200 women were sterilized at the Los Angeles–University of Southern California Medical Center between 1968 and 1974.

Those people are not eligible for reparations under California’s program. But advocates say they hope to include them in the future.

“It’s only the beginning,” said state Assemblywoman Wendy Carrillo, a Democrat from Los Angeles who has been advocating for reparations. “I can’t imagine the trauma, the depression, the stress of being incarcerated, being rehabilitated and trying to start your life again in society, wanting to start a family, only to find out that that choice was taken away from you.”

Of the people California sterilized under its old eugenics law, just a few hundred are still alive, according to research conducted by the Sterilization and Social Justice Lab. Including the inmates who were sterilized most recently, advocates estimate more than 600 people would be eligible for reparations.

But finding them will be difficult, with advocates predicting only about 25% of eligible people will ultimately apply for reparations and be paid.

California’s Victim Compensation Board will run the program, with $2 million used to find victims by advertising and poring through state records. The state also set aside $1 million for plaques to honor the victims, leaving $4.5 million for reparations.

A version of this article appeared on Medscape.com.

Associated Press © 2021 

SACRAMENTO (AP) – California is poised to approve reparations of up to $25,000 to some of the thousands of people – some as young as 13 – who were sterilized decades ago because the government deemed them unfit to have children.

The payments will make California at least the third state – following Virginia and North Carolina – to compensate victims of the so-called eugenics movement that peaked in the 1930s. Supporters of the movement believed sterilizing people with mental illnesses, physical disabilities, and other traits they deemed undesirable would improve the human race.

While California sterilized more than 20,000 people before its law was repealed in 1979, only a few hundred are still alive. The state has set aside $7.5 million for the reparations program, part of its $262.6 billion operating budget that is awaiting Gov. Gavin Newsom’s signature.

California’s proposal is unique because it also would pay women the state coerced to get sterilized while they were in prison, some as recently as 2010. First exposed by the Center for Investigative Reporting in 2013, a subsequent audit found California sterilized 144 women between 2005 and 2013 with little or no evidence that officials counseled them or offered alternative treatment.

While all of the women signed consent forms, officials in 39 cases did not do everything that was legally required to obtain their permission.

“We must address and face our horrific history,” said Lorena Garcia Zermeño, policy and communications coordinator for the advocacy group California Latinas for Reproductive Justice. “This isn’t something that just happened in the past.”

California’s forced sterilization program started in 1909, following similar laws in Indiana and Washington. It was by far the largest program, accounting for about a third of everyone sterilized in the United States under those laws.

California’s law was so prominent that it inspired similar practices in Nazi Germany, according to Paul Lombardo, a law professor at Georgia State University, Atlanta, and an expert on the eugenics movement.

“The promise of eugenics at the very earliest is: ‘We could do away with all the state institutions – prisons, hospitals, asylums, orphanages,’” Mr. Lombardo said. “People who were in them just wouldn’t be born after awhile if you sterilized all of their parents.”

In California, victims include Mary Franco, who was sterilized in 1934 when she was just 13. Paperwork described her as “feeble minded” because of “sexual deviance,” according to her niece, Stacy Cordova, who has researched her case.

Ms. Cordova said Franco actually was molested by a neighbor. She said her family put Ms. Franco in an institution to protect the family’s reputation.

Ms. Cordova said her late aunt loved children and wanted to have a family. She married briefly when she was about 17, but Ms. Cordova said the marriage was annulled when the man discovered Ms. Franco couldn’t have children. She lived a lonely life in a Mexican culture that revered big families, Ms. Cordova said.

“I don’t know if it is justice. Money doesn’t pay for what happened to them. But it’s great to know that this is being recognized,” said Ms. Cordova, who has advocated for the state to pay survivors. “For me, this is not about the money. This is about the memory.”

Relatives like Ms. Cordova aren’t eligible for the payments, only direct victims are.

Sterilizations in California prisons appear to date to 1999, when the state changed its policy for unknown reasons to include a sterilization procedure known as “tubal ligation” as part of inmates’ medical care. Over the next decade, women reported they were coerced into this procedure, with some not fully understanding the ramifications.

A state law passed in 2014 bans sterilizations for the purpose of birth control at state prisons and local jails. The law permits sterilizations that are “medically necessary,” such as removing cancer, and requires facilities to report each year how many people were sterilized and for what reason.

Questionable sterilizations also occurred in facilities run by local governments. In 2018, the Los Angeles County Board of Supervisors apologized after more than 200 women were sterilized at the Los Angeles–University of Southern California Medical Center between 1968 and 1974.

Those people are not eligible for reparations under California’s program. But advocates say they hope to include them in the future.

“It’s only the beginning,” said state Assemblywoman Wendy Carrillo, a Democrat from Los Angeles who has been advocating for reparations. “I can’t imagine the trauma, the depression, the stress of being incarcerated, being rehabilitated and trying to start your life again in society, wanting to start a family, only to find out that that choice was taken away from you.”

Of the people California sterilized under its old eugenics law, just a few hundred are still alive, according to research conducted by the Sterilization and Social Justice Lab. Including the inmates who were sterilized most recently, advocates estimate more than 600 people would be eligible for reparations.

But finding them will be difficult, with advocates predicting only about 25% of eligible people will ultimately apply for reparations and be paid.

California’s Victim Compensation Board will run the program, with $2 million used to find victims by advertising and poring through state records. The state also set aside $1 million for plaques to honor the victims, leaving $4.5 million for reparations.

A version of this article appeared on Medscape.com.

Associated Press © 2021 

Gastroenterology

May 2021
Understanding GI Twitter and its major contributors. Elfanagely Y et al. Gastroenterology. 2021 May;160(6):1917-21. doi: 10.1053/j.gastro.2021.01.232.

Long-term safety of fecal microbiota transplantation for recurrent Clostridioides difficile infection. Saha S et al. Gastroenterology. 2021 May;160(6):1961-9.e3. doi: 10.1053/j.gastro.2021.01.010.

How to incorporate health equity training into gastroenterology and hepatology fellowships. Lee-Allen J, Shah BJ. Gastroenterology. 2021 May;160(6):1924-8. doi: 10.1053/j.gastro.2021.03.018.

Functional dyspepsia and gastroparesis in tertiary care are interchangeable syndromes with common clinical and pathologic features. Pasricha PJ et al. Gastroenterology. 2021 May;160(6):2006-17. doi: 10.1053/j.gastro.2021.01.230.

June 2021
How to manage the large nonpedunculated colorectal polyp. Shahidi N, Bourke MJ. Gastroenterology. 2021 Jun;160(7):2239-43.e1. doi: 10.1053/j.gastro.2021.04.029.

Mortality, reoperation, and hospital stay within 90 days of primary and secondary antireflux surgery in a population-based multinational study. Yanes M et al. Gastroenterology. 2021 Jun;160(7):2283-90. doi: 10.1053/j.gastro.2021.02.022.

Endoscopic submucosal dissection in north america: A large prospective multicenter study. Draganov PV et al. Gastroenterology. 2021 Jun;160(7):2317-27.e2. doi: 10.1053/j.gastro.2021.02.036.

July 2021
Gluten degradation, pharmacokinetics, safety, and tolerability of TAK-062, an engineered enzyme to treat celiac disease. Pultz IG et al. Gastroenterology. 2021 Jul;161(1):81-93.e3. doi: 10.1053/j.gastro.2021.03.019.

Paternal exposure to immunosuppressive and/or biologic agents and birth outcomes in patients with immune-mediated inflammatory diseases. Meserve J et al. Gastroenterology. 2021 Jul;161(1):107-115.e3. doi: 10.1053/j.gastro.2021.03.020.

Ethnicity associations with food sensitization are mediated by gut microbiota development in the first year of life. Tun Hm et al. Gastroenterology. 2021 Jul;161(1):94-106. doi: 10.1053/j.gastro.2021.03.016.

How to incorporate bariatric training into your fellowship program. Jirapinyo P, Thompson CC. Gastroenterology. 2019 Jul;157(1):9-13. doi: 10.1053/j.gastro.2019.05.034.

CGH

May 2021
Intestinal failure: What all gastroenterologists should know. Jansson-Knodell CL et al. Clin Gastroenterol Hepatol. 2021 May;19(5):885-8. doi: 10.1016/j.cgh.2021.01.038.

When and how to use endoscopic tattooing in the colon: An international Delphi agreement. Medina-Prado L et al. Clin Gastroenterol Hepatol. 2021 May;19(5):1038-50. doi: 10.1016/j.cgh.2021.01.024.

Five-year outcomes of endoscopic sleeve gastroplasty for the treatment of obesity. Sharaiha RZ et al. Clin Gastroenterol Hepatol. 2021 May;19(5):1051-57.e2. doi: 10.1016/j.cgh.2020.09.055.

June 2021
GA Clinical Practice Update on management of bleeding gastric varices: Expert review. Henry Z et al. Clin Gastroenterol Hepatol. 2021 Jun;19(6):1098-107.e1. doi: 10.1016/j.cgh.2021.01.027.

Inter- and intra-individual variation, and limited prognostic utility, of serum alkaline phosphatase in a trial of patients with primary sclerosing cholangitis

Palak J. Trivedi PJ et al. Clin Gastroenterol Hepatol. 2021 Jun;19(6):1248-57. doi: 10.1016/j.cgh.2020.07.032.

Low-fat, high-fiber diet reduces markers of inflammation and dysbiosis and improves quality of life in patients with ulcerative colitis. Julia Fritsch J et al. Clin Gastroenterol Hepatol. 2021 Jun;19(6):1189-99.e30. doi: 10.1016/j.cgh.2020.05.026.

July 2021
Scoping out a better parental leave policy for gastroenterology fellows. Wegermann K. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1307-9. doi: 10.1016/j.cgh.2021.01.040.

An impetus for change: How COVID-19 will transform the delivery of GI health care. Leiman DA et al. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1310-1313. doi: 10.1016/j.cgh.2021.03.042.

Untangling nonerosive reflux disease from functional heartburn. Patel D et al. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1314-26. doi: 10.1016/j.cgh.2020.03.057.
 

AGA Clinical Practice Update on chemoprevention for colorectal neoplasia: Expert review. Liang PS et al. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1327-36. doi: 10.1016/j.cgh.2021.02.014.
 

CMGH

Drug inhibition of SARS-CoV-2 replication in human pluripotent stem cell–derived intestinal organoids. Krüger J et al. Cell Mol Gastroenterol Hepatol. 2021;11(4):935-48. doi: 10.1016/j.jcmgh.2020.11.003.
 

TIGE

Virtual interviews during the COVID-19 Pandemic: A survey of advanced endoscopy fellowship applicants and programs. Amrit K. Kamboj AK et al. Tech Innov Gastrointest Endosc. 2021;23(2):159-68. doi: 10.1016/j.tige.2021.02.001.

Triage of general gastrointestinal endoscopic procedures during the COVID-19 pandemic: Results from a national Delphi consensus panel. Feuerstein JD et al. Tech Innov Gastrointest Endosc. 2021;23(2):113-21. doi: 10.1016/j.tige.2020.12.005.

Development of a scoring system to predict a positive diagnosis on video capsule endoscopy for suspected small bowel bleeding. Marya NB et al. Tech Innov Gastrointest Endosc. 2021;22(4):178-84. doi: 10.1016/j.tige.2020.06.001.

Gastroenterology

May 2021
Understanding GI Twitter and its major contributors. Elfanagely Y et al. Gastroenterology. 2021 May;160(6):1917-21. doi: 10.1053/j.gastro.2021.01.232.

Long-term safety of fecal microbiota transplantation for recurrent Clostridioides difficile infection. Saha S et al. Gastroenterology. 2021 May;160(6):1961-9.e3. doi: 10.1053/j.gastro.2021.01.010.

How to incorporate health equity training into gastroenterology and hepatology fellowships. Lee-Allen J, Shah BJ. Gastroenterology. 2021 May;160(6):1924-8. doi: 10.1053/j.gastro.2021.03.018.

Functional dyspepsia and gastroparesis in tertiary care are interchangeable syndromes with common clinical and pathologic features. Pasricha PJ et al. Gastroenterology. 2021 May;160(6):2006-17. doi: 10.1053/j.gastro.2021.01.230.

June 2021
How to manage the large nonpedunculated colorectal polyp. Shahidi N, Bourke MJ. Gastroenterology. 2021 Jun;160(7):2239-43.e1. doi: 10.1053/j.gastro.2021.04.029.

Mortality, reoperation, and hospital stay within 90 days of primary and secondary antireflux surgery in a population-based multinational study. Yanes M et al. Gastroenterology. 2021 Jun;160(7):2283-90. doi: 10.1053/j.gastro.2021.02.022.

Endoscopic submucosal dissection in north america: A large prospective multicenter study. Draganov PV et al. Gastroenterology. 2021 Jun;160(7):2317-27.e2. doi: 10.1053/j.gastro.2021.02.036.

July 2021
Gluten degradation, pharmacokinetics, safety, and tolerability of TAK-062, an engineered enzyme to treat celiac disease. Pultz IG et al. Gastroenterology. 2021 Jul;161(1):81-93.e3. doi: 10.1053/j.gastro.2021.03.019.

Paternal exposure to immunosuppressive and/or biologic agents and birth outcomes in patients with immune-mediated inflammatory diseases. Meserve J et al. Gastroenterology. 2021 Jul;161(1):107-115.e3. doi: 10.1053/j.gastro.2021.03.020.

Ethnicity associations with food sensitization are mediated by gut microbiota development in the first year of life. Tun Hm et al. Gastroenterology. 2021 Jul;161(1):94-106. doi: 10.1053/j.gastro.2021.03.016.

How to incorporate bariatric training into your fellowship program. Jirapinyo P, Thompson CC. Gastroenterology. 2019 Jul;157(1):9-13. doi: 10.1053/j.gastro.2019.05.034.

CGH

May 2021
Intestinal failure: What all gastroenterologists should know. Jansson-Knodell CL et al. Clin Gastroenterol Hepatol. 2021 May;19(5):885-8. doi: 10.1016/j.cgh.2021.01.038.

When and how to use endoscopic tattooing in the colon: An international Delphi agreement. Medina-Prado L et al. Clin Gastroenterol Hepatol. 2021 May;19(5):1038-50. doi: 10.1016/j.cgh.2021.01.024.

Five-year outcomes of endoscopic sleeve gastroplasty for the treatment of obesity. Sharaiha RZ et al. Clin Gastroenterol Hepatol. 2021 May;19(5):1051-57.e2. doi: 10.1016/j.cgh.2020.09.055.

June 2021
GA Clinical Practice Update on management of bleeding gastric varices: Expert review. Henry Z et al. Clin Gastroenterol Hepatol. 2021 Jun;19(6):1098-107.e1. doi: 10.1016/j.cgh.2021.01.027.

Inter- and intra-individual variation, and limited prognostic utility, of serum alkaline phosphatase in a trial of patients with primary sclerosing cholangitis

Palak J. Trivedi PJ et al. Clin Gastroenterol Hepatol. 2021 Jun;19(6):1248-57. doi: 10.1016/j.cgh.2020.07.032.

Low-fat, high-fiber diet reduces markers of inflammation and dysbiosis and improves quality of life in patients with ulcerative colitis. Julia Fritsch J et al. Clin Gastroenterol Hepatol. 2021 Jun;19(6):1189-99.e30. doi: 10.1016/j.cgh.2020.05.026.

July 2021
Scoping out a better parental leave policy for gastroenterology fellows. Wegermann K. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1307-9. doi: 10.1016/j.cgh.2021.01.040.

An impetus for change: How COVID-19 will transform the delivery of GI health care. Leiman DA et al. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1310-1313. doi: 10.1016/j.cgh.2021.03.042.

Untangling nonerosive reflux disease from functional heartburn. Patel D et al. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1314-26. doi: 10.1016/j.cgh.2020.03.057.
 

AGA Clinical Practice Update on chemoprevention for colorectal neoplasia: Expert review. Liang PS et al. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1327-36. doi: 10.1016/j.cgh.2021.02.014.
 

CMGH

Drug inhibition of SARS-CoV-2 replication in human pluripotent stem cell–derived intestinal organoids. Krüger J et al. Cell Mol Gastroenterol Hepatol. 2021;11(4):935-48. doi: 10.1016/j.jcmgh.2020.11.003.
 

TIGE

Virtual interviews during the COVID-19 Pandemic: A survey of advanced endoscopy fellowship applicants and programs. Amrit K. Kamboj AK et al. Tech Innov Gastrointest Endosc. 2021;23(2):159-68. doi: 10.1016/j.tige.2021.02.001.

Triage of general gastrointestinal endoscopic procedures during the COVID-19 pandemic: Results from a national Delphi consensus panel. Feuerstein JD et al. Tech Innov Gastrointest Endosc. 2021;23(2):113-21. doi: 10.1016/j.tige.2020.12.005.

Development of a scoring system to predict a positive diagnosis on video capsule endoscopy for suspected small bowel bleeding. Marya NB et al. Tech Innov Gastrointest Endosc. 2021;22(4):178-84. doi: 10.1016/j.tige.2020.06.001.

Gastroenterology

May 2021
Understanding GI Twitter and its major contributors. Elfanagely Y et al. Gastroenterology. 2021 May;160(6):1917-21. doi: 10.1053/j.gastro.2021.01.232.

Long-term safety of fecal microbiota transplantation for recurrent Clostridioides difficile infection. Saha S et al. Gastroenterology. 2021 May;160(6):1961-9.e3. doi: 10.1053/j.gastro.2021.01.010.

How to incorporate health equity training into gastroenterology and hepatology fellowships. Lee-Allen J, Shah BJ. Gastroenterology. 2021 May;160(6):1924-8. doi: 10.1053/j.gastro.2021.03.018.

Functional dyspepsia and gastroparesis in tertiary care are interchangeable syndromes with common clinical and pathologic features. Pasricha PJ et al. Gastroenterology. 2021 May;160(6):2006-17. doi: 10.1053/j.gastro.2021.01.230.

June 2021
How to manage the large nonpedunculated colorectal polyp. Shahidi N, Bourke MJ. Gastroenterology. 2021 Jun;160(7):2239-43.e1. doi: 10.1053/j.gastro.2021.04.029.

Mortality, reoperation, and hospital stay within 90 days of primary and secondary antireflux surgery in a population-based multinational study. Yanes M et al. Gastroenterology. 2021 Jun;160(7):2283-90. doi: 10.1053/j.gastro.2021.02.022.

Endoscopic submucosal dissection in north america: A large prospective multicenter study. Draganov PV et al. Gastroenterology. 2021 Jun;160(7):2317-27.e2. doi: 10.1053/j.gastro.2021.02.036.

July 2021
Gluten degradation, pharmacokinetics, safety, and tolerability of TAK-062, an engineered enzyme to treat celiac disease. Pultz IG et al. Gastroenterology. 2021 Jul;161(1):81-93.e3. doi: 10.1053/j.gastro.2021.03.019.

Paternal exposure to immunosuppressive and/or biologic agents and birth outcomes in patients with immune-mediated inflammatory diseases. Meserve J et al. Gastroenterology. 2021 Jul;161(1):107-115.e3. doi: 10.1053/j.gastro.2021.03.020.

Ethnicity associations with food sensitization are mediated by gut microbiota development in the first year of life. Tun Hm et al. Gastroenterology. 2021 Jul;161(1):94-106. doi: 10.1053/j.gastro.2021.03.016.

How to incorporate bariatric training into your fellowship program. Jirapinyo P, Thompson CC. Gastroenterology. 2019 Jul;157(1):9-13. doi: 10.1053/j.gastro.2019.05.034.

CGH

May 2021
Intestinal failure: What all gastroenterologists should know. Jansson-Knodell CL et al. Clin Gastroenterol Hepatol. 2021 May;19(5):885-8. doi: 10.1016/j.cgh.2021.01.038.

When and how to use endoscopic tattooing in the colon: An international Delphi agreement. Medina-Prado L et al. Clin Gastroenterol Hepatol. 2021 May;19(5):1038-50. doi: 10.1016/j.cgh.2021.01.024.

Five-year outcomes of endoscopic sleeve gastroplasty for the treatment of obesity. Sharaiha RZ et al. Clin Gastroenterol Hepatol. 2021 May;19(5):1051-57.e2. doi: 10.1016/j.cgh.2020.09.055.

June 2021
GA Clinical Practice Update on management of bleeding gastric varices: Expert review. Henry Z et al. Clin Gastroenterol Hepatol. 2021 Jun;19(6):1098-107.e1. doi: 10.1016/j.cgh.2021.01.027.

Inter- and intra-individual variation, and limited prognostic utility, of serum alkaline phosphatase in a trial of patients with primary sclerosing cholangitis

Palak J. Trivedi PJ et al. Clin Gastroenterol Hepatol. 2021 Jun;19(6):1248-57. doi: 10.1016/j.cgh.2020.07.032.

Low-fat, high-fiber diet reduces markers of inflammation and dysbiosis and improves quality of life in patients with ulcerative colitis. Julia Fritsch J et al. Clin Gastroenterol Hepatol. 2021 Jun;19(6):1189-99.e30. doi: 10.1016/j.cgh.2020.05.026.

July 2021
Scoping out a better parental leave policy for gastroenterology fellows. Wegermann K. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1307-9. doi: 10.1016/j.cgh.2021.01.040.

An impetus for change: How COVID-19 will transform the delivery of GI health care. Leiman DA et al. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1310-1313. doi: 10.1016/j.cgh.2021.03.042.

Untangling nonerosive reflux disease from functional heartburn. Patel D et al. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1314-26. doi: 10.1016/j.cgh.2020.03.057.
 

AGA Clinical Practice Update on chemoprevention for colorectal neoplasia: Expert review. Liang PS et al. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1327-36. doi: 10.1016/j.cgh.2021.02.014.
 

CMGH

Drug inhibition of SARS-CoV-2 replication in human pluripotent stem cell–derived intestinal organoids. Krüger J et al. Cell Mol Gastroenterol Hepatol. 2021;11(4):935-48. doi: 10.1016/j.jcmgh.2020.11.003.
 

TIGE

Virtual interviews during the COVID-19 Pandemic: A survey of advanced endoscopy fellowship applicants and programs. Amrit K. Kamboj AK et al. Tech Innov Gastrointest Endosc. 2021;23(2):159-68. doi: 10.1016/j.tige.2021.02.001.

Triage of general gastrointestinal endoscopic procedures during the COVID-19 pandemic: Results from a national Delphi consensus panel. Feuerstein JD et al. Tech Innov Gastrointest Endosc. 2021;23(2):113-21. doi: 10.1016/j.tige.2020.12.005.

Development of a scoring system to predict a positive diagnosis on video capsule endoscopy for suspected small bowel bleeding. Marya NB et al. Tech Innov Gastrointest Endosc. 2021;22(4):178-84. doi: 10.1016/j.tige.2020.06.001.

The U.S. Food and Drug Administration has approved an updated label for the controversial Alzheimer’s drug aducanumab (Aduhelm), emphasizing that the drug should only be used in patients with the earliest stages of disease – the group studied in the clinical trials.

The FDA approved aducanumab in early June amid significant controversy and disregarding the recommendation by its own advisory panel not to approve the drug. The original prescribing information implied that the drug – which is administered intravenously and costs around $56,000 a year – could be used for treatment of any patient with Alzheimer’s disease.

The updated label now states that aducanumab should be initiated only in patients with mild cognitive impairment (MCI) or mild dementia stage of disease – the population in which treatment was initiated in the clinical trials leading to approval of the anti-amyloid drug.

The FDA granted accelerated approval of the drug based on data from clinical trials showing a reduction in amyloid beta plaques observed in patients with MCI or mild dementia stage of disease.

“Continued approval for the indication may be contingent upon verification of clinical benefit in confirmatory trial(s),” the label states. It emphasizes that there are no safety or effectiveness data on starting aducanumab treatment at earlier or later stages of the disease than were studied.

“Based on our ongoing conversations with prescribing physicians, FDA, and patient advocates, we submitted this label update with the goal to further clarify the patient population that was studied across the three Aduhelm clinical trials that supported approval,” Alfred Sandrock Jr., MD, PhD, Biogen’s head of research and development, said in a statement announcing the label update.   

“We are committed to continue to listen to the community’s needs as clinical practice adapts to this important, first-in-class treatment option,” said Dr. Sandrock.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved an updated label for the controversial Alzheimer’s drug aducanumab (Aduhelm), emphasizing that the drug should only be used in patients with the earliest stages of disease – the group studied in the clinical trials.

The FDA approved aducanumab in early June amid significant controversy and disregarding the recommendation by its own advisory panel not to approve the drug. The original prescribing information implied that the drug – which is administered intravenously and costs around $56,000 a year – could be used for treatment of any patient with Alzheimer’s disease.

The updated label now states that aducanumab should be initiated only in patients with mild cognitive impairment (MCI) or mild dementia stage of disease – the population in which treatment was initiated in the clinical trials leading to approval of the anti-amyloid drug.

The FDA granted accelerated approval of the drug based on data from clinical trials showing a reduction in amyloid beta plaques observed in patients with MCI or mild dementia stage of disease.

“Continued approval for the indication may be contingent upon verification of clinical benefit in confirmatory trial(s),” the label states. It emphasizes that there are no safety or effectiveness data on starting aducanumab treatment at earlier or later stages of the disease than were studied.

“Based on our ongoing conversations with prescribing physicians, FDA, and patient advocates, we submitted this label update with the goal to further clarify the patient population that was studied across the three Aduhelm clinical trials that supported approval,” Alfred Sandrock Jr., MD, PhD, Biogen’s head of research and development, said in a statement announcing the label update.   

“We are committed to continue to listen to the community’s needs as clinical practice adapts to this important, first-in-class treatment option,” said Dr. Sandrock.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved an updated label for the controversial Alzheimer’s drug aducanumab (Aduhelm), emphasizing that the drug should only be used in patients with the earliest stages of disease – the group studied in the clinical trials.

The FDA approved aducanumab in early June amid significant controversy and disregarding the recommendation by its own advisory panel not to approve the drug. The original prescribing information implied that the drug – which is administered intravenously and costs around $56,000 a year – could be used for treatment of any patient with Alzheimer’s disease.

The updated label now states that aducanumab should be initiated only in patients with mild cognitive impairment (MCI) or mild dementia stage of disease – the population in which treatment was initiated in the clinical trials leading to approval of the anti-amyloid drug.

The FDA granted accelerated approval of the drug based on data from clinical trials showing a reduction in amyloid beta plaques observed in patients with MCI or mild dementia stage of disease.

“Continued approval for the indication may be contingent upon verification of clinical benefit in confirmatory trial(s),” the label states. It emphasizes that there are no safety or effectiveness data on starting aducanumab treatment at earlier or later stages of the disease than were studied.

“Based on our ongoing conversations with prescribing physicians, FDA, and patient advocates, we submitted this label update with the goal to further clarify the patient population that was studied across the three Aduhelm clinical trials that supported approval,” Alfred Sandrock Jr., MD, PhD, Biogen’s head of research and development, said in a statement announcing the label update.   

“We are committed to continue to listen to the community’s needs as clinical practice adapts to this important, first-in-class treatment option,” said Dr. Sandrock.

A version of this article first appeared on Medscape.com.

Israeli officials are reporting a 30% decrease in the effectiveness of the Pfizer/BioNTech vaccine to prevent SARS-CoV-2 infection and mild to moderate cases of COVID-19. At the same time, protection against hospitalization and severe illness remains robust.

The country’s Ministry of Health data cited high levels of circulating Delta variant and a relaxation of public health measures in early June for the drop in the vaccine’s prevention of “breakthrough” cases from 94% to 64% in recent weeks.

However, it is important to consider the findings in context, experts cautioned.

“My overall take on this that the vaccine is highly protective against the endpoints that matter – hospitalization and severe disease,” Anna Durbin, MD, told this news organization.

“I was very pleasantly surprised with the very high efficacy against hospitalization and severe disease – even against the Delta variant,” added Dr. Durbin, professor of medicine at Johns Hopkins University, Baltimore.

Ali Mokdad, PhD, of the Institute for Health Metrics at the University of Washington, Seattle, agreed that the high degree of protection against severe outcomes should be the focus.

“That’s the whole idea. You want to defend against COVID-19. So even if someone is infected, they don’t end up in the hospital or in the morgue,” he said in an interview.

Compared with an earlier report, the efficacy of the Pfizer vaccine against hospitalization fell slightly from 98% to 93%.

“For me, the fact that there is increased infection from the Delta variant after the vaccines such as Pfizer is of course a concern. But the positive news is that there is 93% prevention against severe disease or mortality,” added Dr. Mokdad, who is also professor of global health at University of Washington.

In addition, the absolute numbers remain relatively small. The Ministry of Health data show that, of the 63 Israelis hospitalized with COVID-19 nationwide on July 3, 34 were in critical condition.
 

Unrealistic expectations?

People may have unrealistic expectations regarding breakthrough infections, Dr. Durbin said. “It seems that people are almost expecting ‘sterilizing immunity’ from these vaccines,” she said, explaining that would mean complete protection from infection.

Expectations may be high “because these vaccines have been so effective,” added Dr. Durbin, who is also affiliated with the Johns Hopkins Center for Global Health.

The higher the number of vaccinated residents, the more breakthrough cases will be reported, epidemiologist Katelyn Jetelina, PhD, MPH, assistant professor of epidemiology, human genetics, and environmental sciences at the University of Texas Science Center at Houston, wrote in her “Your Local Epidemiologist” blog.

This could apply to Israel, with an estimated 60% of adults in Israel fully vaccinated and 65% receiving at least one dose as of July 5, Our World in Data figures show.

How the updated figures were reported could be confusing, Dr. Jetelina said. Israel’s Health Minister Chezy Levy noted that “55% of the newly infected had been vaccinated” in a radio interview announcing the results.

“This language is important because it’s very different than ‘half of vaccinated people were infected,’ ” Dr. Jetelina noted.

Israel had a 7-day rolling average of 324 new confirmed COVID-19 cases as of July 5. Assuming 55% of these cases were among vaccinated people, that would mean 178 people experienced breakthrough infections.

In contrast, almost 6 million people in Israel are fully vaccinated. If 55% of them experienced breakthrough infections, the number would be much higher – more than 3 million.

Dr. Jetelina added that more details about the new Israel figures would be helpful, including the severity of COVID-19 among the vaccinated cases and breakdown of infections between adults and children.
 

Next steps

Israeli health officials are weighing the necessity of a third or booster dose of the vaccine. Whether they will reinstate public health measures to prevent spread of COVID-19 also remains unknown.

Going forward, Israel intends to study whether factors such as age, comorbidities, or time since immunization affect risk for breakthrough infections among people vaccinated against COVID-19.

“We want to prevent people from getting hospitalized, seriously ill, and of course, dying. It’s encouraging these vaccines will be able to have a high impact on those outcomes,” Dr. Durbin said. “We just need to get people vaccinated.”
 

A call for better global surveillance

A global surveillance system is a potential solution to track and respond to the growing threat of the Delta variant and other variants of concern, Scott P. Layne, MD, and Jeffery K. Taubenberger, MD, PhD, wrote in a July 7, 2021, editorial in Science Translational Medicine.

One goal, Dr. Layne said in an interview, is to highlight “the compelling need for a new global COVID-19 program of surveillance and offer a blueprint for building it.” A second aim is to promote global cooperation among key advisers and leaders in the G7, G20, and Asia-Pacific Economic Cooperation nations.

“It’s an uphill struggle with superpower discords, global warming, cybersecurity, and pandemics all competing for finite attention,” Dr. Layne said. “However, what other options do we have for taming the so-called forever virus?”

Dr. Mokdad and Dr. Jetelina had no relevant disclosures. Dr. Durban disclosed she was the site primary investigator for the phase 3 AstraZeneca vaccine trial and an investigator on the Pfizer COVID-19 vaccine trial.

A version of this article first appeared on Medscape.com.

Israeli officials are reporting a 30% decrease in the effectiveness of the Pfizer/BioNTech vaccine to prevent SARS-CoV-2 infection and mild to moderate cases of COVID-19. At the same time, protection against hospitalization and severe illness remains robust.

The country’s Ministry of Health data cited high levels of circulating Delta variant and a relaxation of public health measures in early June for the drop in the vaccine’s prevention of “breakthrough” cases from 94% to 64% in recent weeks.

However, it is important to consider the findings in context, experts cautioned.

“My overall take on this that the vaccine is highly protective against the endpoints that matter – hospitalization and severe disease,” Anna Durbin, MD, told this news organization.

“I was very pleasantly surprised with the very high efficacy against hospitalization and severe disease – even against the Delta variant,” added Dr. Durbin, professor of medicine at Johns Hopkins University, Baltimore.

Ali Mokdad, PhD, of the Institute for Health Metrics at the University of Washington, Seattle, agreed that the high degree of protection against severe outcomes should be the focus.

“That’s the whole idea. You want to defend against COVID-19. So even if someone is infected, they don’t end up in the hospital or in the morgue,” he said in an interview.

Compared with an earlier report, the efficacy of the Pfizer vaccine against hospitalization fell slightly from 98% to 93%.

“For me, the fact that there is increased infection from the Delta variant after the vaccines such as Pfizer is of course a concern. But the positive news is that there is 93% prevention against severe disease or mortality,” added Dr. Mokdad, who is also professor of global health at University of Washington.

In addition, the absolute numbers remain relatively small. The Ministry of Health data show that, of the 63 Israelis hospitalized with COVID-19 nationwide on July 3, 34 were in critical condition.
 

Unrealistic expectations?

People may have unrealistic expectations regarding breakthrough infections, Dr. Durbin said. “It seems that people are almost expecting ‘sterilizing immunity’ from these vaccines,” she said, explaining that would mean complete protection from infection.

Expectations may be high “because these vaccines have been so effective,” added Dr. Durbin, who is also affiliated with the Johns Hopkins Center for Global Health.

The higher the number of vaccinated residents, the more breakthrough cases will be reported, epidemiologist Katelyn Jetelina, PhD, MPH, assistant professor of epidemiology, human genetics, and environmental sciences at the University of Texas Science Center at Houston, wrote in her “Your Local Epidemiologist” blog.

This could apply to Israel, with an estimated 60% of adults in Israel fully vaccinated and 65% receiving at least one dose as of July 5, Our World in Data figures show.

How the updated figures were reported could be confusing, Dr. Jetelina said. Israel’s Health Minister Chezy Levy noted that “55% of the newly infected had been vaccinated” in a radio interview announcing the results.

“This language is important because it’s very different than ‘half of vaccinated people were infected,’ ” Dr. Jetelina noted.

Israel had a 7-day rolling average of 324 new confirmed COVID-19 cases as of July 5. Assuming 55% of these cases were among vaccinated people, that would mean 178 people experienced breakthrough infections.

In contrast, almost 6 million people in Israel are fully vaccinated. If 55% of them experienced breakthrough infections, the number would be much higher – more than 3 million.

Dr. Jetelina added that more details about the new Israel figures would be helpful, including the severity of COVID-19 among the vaccinated cases and breakdown of infections between adults and children.
 

Next steps

Israeli health officials are weighing the necessity of a third or booster dose of the vaccine. Whether they will reinstate public health measures to prevent spread of COVID-19 also remains unknown.

Going forward, Israel intends to study whether factors such as age, comorbidities, or time since immunization affect risk for breakthrough infections among people vaccinated against COVID-19.

“We want to prevent people from getting hospitalized, seriously ill, and of course, dying. It’s encouraging these vaccines will be able to have a high impact on those outcomes,” Dr. Durbin said. “We just need to get people vaccinated.”
 

A call for better global surveillance

A global surveillance system is a potential solution to track and respond to the growing threat of the Delta variant and other variants of concern, Scott P. Layne, MD, and Jeffery K. Taubenberger, MD, PhD, wrote in a July 7, 2021, editorial in Science Translational Medicine.

One goal, Dr. Layne said in an interview, is to highlight “the compelling need for a new global COVID-19 program of surveillance and offer a blueprint for building it.” A second aim is to promote global cooperation among key advisers and leaders in the G7, G20, and Asia-Pacific Economic Cooperation nations.

“It’s an uphill struggle with superpower discords, global warming, cybersecurity, and pandemics all competing for finite attention,” Dr. Layne said. “However, what other options do we have for taming the so-called forever virus?”

Dr. Mokdad and Dr. Jetelina had no relevant disclosures. Dr. Durban disclosed she was the site primary investigator for the phase 3 AstraZeneca vaccine trial and an investigator on the Pfizer COVID-19 vaccine trial.

A version of this article first appeared on Medscape.com.

Israeli officials are reporting a 30% decrease in the effectiveness of the Pfizer/BioNTech vaccine to prevent SARS-CoV-2 infection and mild to moderate cases of COVID-19. At the same time, protection against hospitalization and severe illness remains robust.

The country’s Ministry of Health data cited high levels of circulating Delta variant and a relaxation of public health measures in early June for the drop in the vaccine’s prevention of “breakthrough” cases from 94% to 64% in recent weeks.

However, it is important to consider the findings in context, experts cautioned.

“My overall take on this that the vaccine is highly protective against the endpoints that matter – hospitalization and severe disease,” Anna Durbin, MD, told this news organization.

“I was very pleasantly surprised with the very high efficacy against hospitalization and severe disease – even against the Delta variant,” added Dr. Durbin, professor of medicine at Johns Hopkins University, Baltimore.

Ali Mokdad, PhD, of the Institute for Health Metrics at the University of Washington, Seattle, agreed that the high degree of protection against severe outcomes should be the focus.

“That’s the whole idea. You want to defend against COVID-19. So even if someone is infected, they don’t end up in the hospital or in the morgue,” he said in an interview.

Compared with an earlier report, the efficacy of the Pfizer vaccine against hospitalization fell slightly from 98% to 93%.

“For me, the fact that there is increased infection from the Delta variant after the vaccines such as Pfizer is of course a concern. But the positive news is that there is 93% prevention against severe disease or mortality,” added Dr. Mokdad, who is also professor of global health at University of Washington.

In addition, the absolute numbers remain relatively small. The Ministry of Health data show that, of the 63 Israelis hospitalized with COVID-19 nationwide on July 3, 34 were in critical condition.
 

Unrealistic expectations?

People may have unrealistic expectations regarding breakthrough infections, Dr. Durbin said. “It seems that people are almost expecting ‘sterilizing immunity’ from these vaccines,” she said, explaining that would mean complete protection from infection.

Expectations may be high “because these vaccines have been so effective,” added Dr. Durbin, who is also affiliated with the Johns Hopkins Center for Global Health.

The higher the number of vaccinated residents, the more breakthrough cases will be reported, epidemiologist Katelyn Jetelina, PhD, MPH, assistant professor of epidemiology, human genetics, and environmental sciences at the University of Texas Science Center at Houston, wrote in her “Your Local Epidemiologist” blog.

This could apply to Israel, with an estimated 60% of adults in Israel fully vaccinated and 65% receiving at least one dose as of July 5, Our World in Data figures show.

How the updated figures were reported could be confusing, Dr. Jetelina said. Israel’s Health Minister Chezy Levy noted that “55% of the newly infected had been vaccinated” in a radio interview announcing the results.

“This language is important because it’s very different than ‘half of vaccinated people were infected,’ ” Dr. Jetelina noted.

Israel had a 7-day rolling average of 324 new confirmed COVID-19 cases as of July 5. Assuming 55% of these cases were among vaccinated people, that would mean 178 people experienced breakthrough infections.

In contrast, almost 6 million people in Israel are fully vaccinated. If 55% of them experienced breakthrough infections, the number would be much higher – more than 3 million.

Dr. Jetelina added that more details about the new Israel figures would be helpful, including the severity of COVID-19 among the vaccinated cases and breakdown of infections between adults and children.
 

Next steps

Israeli health officials are weighing the necessity of a third or booster dose of the vaccine. Whether they will reinstate public health measures to prevent spread of COVID-19 also remains unknown.

Going forward, Israel intends to study whether factors such as age, comorbidities, or time since immunization affect risk for breakthrough infections among people vaccinated against COVID-19.

“We want to prevent people from getting hospitalized, seriously ill, and of course, dying. It’s encouraging these vaccines will be able to have a high impact on those outcomes,” Dr. Durbin said. “We just need to get people vaccinated.”
 

A call for better global surveillance

A global surveillance system is a potential solution to track and respond to the growing threat of the Delta variant and other variants of concern, Scott P. Layne, MD, and Jeffery K. Taubenberger, MD, PhD, wrote in a July 7, 2021, editorial in Science Translational Medicine.

One goal, Dr. Layne said in an interview, is to highlight “the compelling need for a new global COVID-19 program of surveillance and offer a blueprint for building it.” A second aim is to promote global cooperation among key advisers and leaders in the G7, G20, and Asia-Pacific Economic Cooperation nations.

“It’s an uphill struggle with superpower discords, global warming, cybersecurity, and pandemics all competing for finite attention,” Dr. Layne said. “However, what other options do we have for taming the so-called forever virus?”

Dr. Mokdad and Dr. Jetelina had no relevant disclosures. Dr. Durban disclosed she was the site primary investigator for the phase 3 AstraZeneca vaccine trial and an investigator on the Pfizer COVID-19 vaccine trial.

A version of this article first appeared on Medscape.com.

With two sets of Clostridioides difficile recommendations being published within a month of each other, clinicians may find themselves trying to reconcile some of the conflicts between the two guidelines.

The first set, published June 1 by the American College of Gastroenterology, focuses on fecal microbiota transplantation (FMT) and the antibiotic vancomycin. The second, published June 24 by the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America, drives a shift in treatment for initial episodes and short-term recurrence from vancomycin to fidaxomicin and, in some cases, adding on the monoclonal antibody bezlotoxumab, both made by Merck.

The updates are timely because researchers are now recognizing that C. difficile can colonize people without causing symptoms, David Johnson, MD, professor of medicine and chief of gastroenterology at the Eastern Virginia School of Medicine, Norfolk, said in an interview. He was not involved in writing either set of guidelines. “C. diff infection was a hospital-type infection, but we’re now seeing it in up to approximately 35%-50% of patients coming from the community, so it’s a big concern.”

Although the guidelines agree on which treatments are effective, the recommendations give the options a different emphasis.

Infectious disease specialist Stuart Johnson, MD, professor of medicine at Loyola University Medical Center in Maywood, Ill., and a physician researcher at Edward Hines Jr. Veterans Affairs Hospital in Hines, Ill., is the first author in the IDSA/SHEA guidelines. He told this news organization that one reason the two sets of recommendations may diverge in emphasis for initial and recurrent C. difficile is that “everyone has a different way of looking at things.” Compared with infectious disease specialists like him, he said, gastroenterologists “for the most part see the world a little different and have their own bent on things.” 

The differences between the two guidelines relate to the first-line therapy for people with an initial or recurrent C. difficile episode. For an initial episode, the IDSA/SHEA authors conditionally recommend fidaxomicin as first preferred choice over vancomycin, with a moderate certainty of evidence. They noted that implementing this recommendation depends on “available resources,” a reference to the higher cost and difficulty of access associated with fidaxomicin.

Gastroenterologist Monika Fischer, MD, an associate professor of medicine at Indiana University, Indianapolis, is one of the authors of the ACG guidelines. She told this news organization that the cost difference between fidaxomicin and vancomycin is considerable and finds the choice to foreground fidaxomicin puzzling. “They did not reference any new data compared to those we have published.” Their recommendation may make sense in terms of efficacy, but real-world demands require attention to cost and reimbursement. “They themselves state this in their recommendations,” she noted. 

Dr. Fischer cited a ballpark of about $100 for a course of vancomycin, compared with about $3,000 for a course of fidaxomicin. The IDSA/SHEA guidelines do cite vancomycin as an acceptable alternative. According to Dr. Fischer, the ACG guidelines authors discussed fidaxomicin and concluded that there just wasn’t enough evidence to justify favoring this antibiotic over vancomycin, given the cost-benefit imbalance. The ACG guidelines call for a standard course of oral vancomycin for a first, nonsevere C. difficile episode, listing oral fidaxomicin or oral metronidazole as alternatives.

For a recurrence, the IDSA/SHEA authors also favor fidaxomicin in a conditional recommendation over a standard course of vancomycin. For multiple recurrences, a tapered and pulsed vancomycin regimen, vancomycin followed by rifaximin, or FMT are also options.

Dr. David Johnson said that these recommendations favoring fidaxomicin are “surprising,” and that lower costs of vancomycin outweigh the benefit of fidaxomicin, given more-or-less comparable data on cure rates.

In contrast, the ACG guidelines recommend that an initial recurrence be treated with a tapering dose of vancomycin, and call for FMT for patients who are eligible and who experience a second or more C. difficile recurrences after a round of pulsed vancomycin.

Dr. Stuart Johnson said that FMT carries its own special set of issues. “If you don’t have a donor program set up, you have to rely on a stool bank,” noting that one widely used stool bank “basically had to stop making the product because of the coronavirus.” Costs for FMT products have doubled in recent years, and because Food and Drug Administration approval of the therapy is lacking, insurance does not cover it.

Dr. David Johnson also said that he is not “terribly happy” about the ACG recommendation for vancomycin prophylaxis. “It may help, but it also can have off-target effects against colonic bacterial flora, so we would not agree with that recommendation.”

The IDSA/SHEA authors also conditionally recommend bezlotoxumab, on very low certainty of evidence, as a cotherapy with standard of care antibiotics for recurrence prevention in patients with an episode in the last 6 months, particularly for patients at high recurrence risk “where logistics is not an issue.” The FDA has warned that this monoclonal antibody should be used with great care in patients with heart failure and only when benefits outweigh risks.

The ACG guidelines conditionally recommend considering bezlotoxumab to prevent recurrence in patients with specific risk factors, including age over 65 years and severe presentation. The IDSA/SHEA guidelines expand this population to anyone with a recurrence within 6 months, Dr. Fischer pointed out.

The antibody treatment “does offer another 10% absolute reduction in recurrent C. diff disease,” said Dr. Stuart Johnson, which is a “helpful option and primarily for people who have had recurrent C. diff already.” In general, he said, for both drugs, “access is still something we have to work with.”

In a commentary on the ACG guidelines, Dr. David Johnson wrote that there is good evidence that bezlotoxumab prevents relapse, especially in patients with specific risk factors. The hitch is the $4,500 price tag for a 1,000-mg vial, with a recommended dose of 10 mg/kg.

Dr. Stuart Johnson agreed that the costs of the fidaxomicin and bezlotoxumab are important considerations. In addition, there are logistical issues with using the antibody because most hospitals don’t offer infusions, which pushes patients to infusion centers.

Regardless, he added, “we’re happy that we have new options.”

Dr. Fischer, Dr. Stuart Johnson, and Dr. David Johnson reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

With two sets of Clostridioides difficile recommendations being published within a month of each other, clinicians may find themselves trying to reconcile some of the conflicts between the two guidelines.

The first set, published June 1 by the American College of Gastroenterology, focuses on fecal microbiota transplantation (FMT) and the antibiotic vancomycin. The second, published June 24 by the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America, drives a shift in treatment for initial episodes and short-term recurrence from vancomycin to fidaxomicin and, in some cases, adding on the monoclonal antibody bezlotoxumab, both made by Merck.

The updates are timely because researchers are now recognizing that C. difficile can colonize people without causing symptoms, David Johnson, MD, professor of medicine and chief of gastroenterology at the Eastern Virginia School of Medicine, Norfolk, said in an interview. He was not involved in writing either set of guidelines. “C. diff infection was a hospital-type infection, but we’re now seeing it in up to approximately 35%-50% of patients coming from the community, so it’s a big concern.”

Although the guidelines agree on which treatments are effective, the recommendations give the options a different emphasis.

Infectious disease specialist Stuart Johnson, MD, professor of medicine at Loyola University Medical Center in Maywood, Ill., and a physician researcher at Edward Hines Jr. Veterans Affairs Hospital in Hines, Ill., is the first author in the IDSA/SHEA guidelines. He told this news organization that one reason the two sets of recommendations may diverge in emphasis for initial and recurrent C. difficile is that “everyone has a different way of looking at things.” Compared with infectious disease specialists like him, he said, gastroenterologists “for the most part see the world a little different and have their own bent on things.” 

The differences between the two guidelines relate to the first-line therapy for people with an initial or recurrent C. difficile episode. For an initial episode, the IDSA/SHEA authors conditionally recommend fidaxomicin as first preferred choice over vancomycin, with a moderate certainty of evidence. They noted that implementing this recommendation depends on “available resources,” a reference to the higher cost and difficulty of access associated with fidaxomicin.

Gastroenterologist Monika Fischer, MD, an associate professor of medicine at Indiana University, Indianapolis, is one of the authors of the ACG guidelines. She told this news organization that the cost difference between fidaxomicin and vancomycin is considerable and finds the choice to foreground fidaxomicin puzzling. “They did not reference any new data compared to those we have published.” Their recommendation may make sense in terms of efficacy, but real-world demands require attention to cost and reimbursement. “They themselves state this in their recommendations,” she noted. 

Dr. Fischer cited a ballpark of about $100 for a course of vancomycin, compared with about $3,000 for a course of fidaxomicin. The IDSA/SHEA guidelines do cite vancomycin as an acceptable alternative. According to Dr. Fischer, the ACG guidelines authors discussed fidaxomicin and concluded that there just wasn’t enough evidence to justify favoring this antibiotic over vancomycin, given the cost-benefit imbalance. The ACG guidelines call for a standard course of oral vancomycin for a first, nonsevere C. difficile episode, listing oral fidaxomicin or oral metronidazole as alternatives.

For a recurrence, the IDSA/SHEA authors also favor fidaxomicin in a conditional recommendation over a standard course of vancomycin. For multiple recurrences, a tapered and pulsed vancomycin regimen, vancomycin followed by rifaximin, or FMT are also options.

Dr. David Johnson said that these recommendations favoring fidaxomicin are “surprising,” and that lower costs of vancomycin outweigh the benefit of fidaxomicin, given more-or-less comparable data on cure rates.

In contrast, the ACG guidelines recommend that an initial recurrence be treated with a tapering dose of vancomycin, and call for FMT for patients who are eligible and who experience a second or more C. difficile recurrences after a round of pulsed vancomycin.

Dr. Stuart Johnson said that FMT carries its own special set of issues. “If you don’t have a donor program set up, you have to rely on a stool bank,” noting that one widely used stool bank “basically had to stop making the product because of the coronavirus.” Costs for FMT products have doubled in recent years, and because Food and Drug Administration approval of the therapy is lacking, insurance does not cover it.

Dr. David Johnson also said that he is not “terribly happy” about the ACG recommendation for vancomycin prophylaxis. “It may help, but it also can have off-target effects against colonic bacterial flora, so we would not agree with that recommendation.”

The IDSA/SHEA authors also conditionally recommend bezlotoxumab, on very low certainty of evidence, as a cotherapy with standard of care antibiotics for recurrence prevention in patients with an episode in the last 6 months, particularly for patients at high recurrence risk “where logistics is not an issue.” The FDA has warned that this monoclonal antibody should be used with great care in patients with heart failure and only when benefits outweigh risks.

The ACG guidelines conditionally recommend considering bezlotoxumab to prevent recurrence in patients with specific risk factors, including age over 65 years and severe presentation. The IDSA/SHEA guidelines expand this population to anyone with a recurrence within 6 months, Dr. Fischer pointed out.

The antibody treatment “does offer another 10% absolute reduction in recurrent C. diff disease,” said Dr. Stuart Johnson, which is a “helpful option and primarily for people who have had recurrent C. diff already.” In general, he said, for both drugs, “access is still something we have to work with.”

In a commentary on the ACG guidelines, Dr. David Johnson wrote that there is good evidence that bezlotoxumab prevents relapse, especially in patients with specific risk factors. The hitch is the $4,500 price tag for a 1,000-mg vial, with a recommended dose of 10 mg/kg.

Dr. Stuart Johnson agreed that the costs of the fidaxomicin and bezlotoxumab are important considerations. In addition, there are logistical issues with using the antibody because most hospitals don’t offer infusions, which pushes patients to infusion centers.

Regardless, he added, “we’re happy that we have new options.”

Dr. Fischer, Dr. Stuart Johnson, and Dr. David Johnson reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

With two sets of Clostridioides difficile recommendations being published within a month of each other, clinicians may find themselves trying to reconcile some of the conflicts between the two guidelines.

The first set, published June 1 by the American College of Gastroenterology, focuses on fecal microbiota transplantation (FMT) and the antibiotic vancomycin. The second, published June 24 by the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America, drives a shift in treatment for initial episodes and short-term recurrence from vancomycin to fidaxomicin and, in some cases, adding on the monoclonal antibody bezlotoxumab, both made by Merck.

The updates are timely because researchers are now recognizing that C. difficile can colonize people without causing symptoms, David Johnson, MD, professor of medicine and chief of gastroenterology at the Eastern Virginia School of Medicine, Norfolk, said in an interview. He was not involved in writing either set of guidelines. “C. diff infection was a hospital-type infection, but we’re now seeing it in up to approximately 35%-50% of patients coming from the community, so it’s a big concern.”

Although the guidelines agree on which treatments are effective, the recommendations give the options a different emphasis.

Infectious disease specialist Stuart Johnson, MD, professor of medicine at Loyola University Medical Center in Maywood, Ill., and a physician researcher at Edward Hines Jr. Veterans Affairs Hospital in Hines, Ill., is the first author in the IDSA/SHEA guidelines. He told this news organization that one reason the two sets of recommendations may diverge in emphasis for initial and recurrent C. difficile is that “everyone has a different way of looking at things.” Compared with infectious disease specialists like him, he said, gastroenterologists “for the most part see the world a little different and have their own bent on things.” 

The differences between the two guidelines relate to the first-line therapy for people with an initial or recurrent C. difficile episode. For an initial episode, the IDSA/SHEA authors conditionally recommend fidaxomicin as first preferred choice over vancomycin, with a moderate certainty of evidence. They noted that implementing this recommendation depends on “available resources,” a reference to the higher cost and difficulty of access associated with fidaxomicin.

Gastroenterologist Monika Fischer, MD, an associate professor of medicine at Indiana University, Indianapolis, is one of the authors of the ACG guidelines. She told this news organization that the cost difference between fidaxomicin and vancomycin is considerable and finds the choice to foreground fidaxomicin puzzling. “They did not reference any new data compared to those we have published.” Their recommendation may make sense in terms of efficacy, but real-world demands require attention to cost and reimbursement. “They themselves state this in their recommendations,” she noted. 

Dr. Fischer cited a ballpark of about $100 for a course of vancomycin, compared with about $3,000 for a course of fidaxomicin. The IDSA/SHEA guidelines do cite vancomycin as an acceptable alternative. According to Dr. Fischer, the ACG guidelines authors discussed fidaxomicin and concluded that there just wasn’t enough evidence to justify favoring this antibiotic over vancomycin, given the cost-benefit imbalance. The ACG guidelines call for a standard course of oral vancomycin for a first, nonsevere C. difficile episode, listing oral fidaxomicin or oral metronidazole as alternatives.

For a recurrence, the IDSA/SHEA authors also favor fidaxomicin in a conditional recommendation over a standard course of vancomycin. For multiple recurrences, a tapered and pulsed vancomycin regimen, vancomycin followed by rifaximin, or FMT are also options.

Dr. David Johnson said that these recommendations favoring fidaxomicin are “surprising,” and that lower costs of vancomycin outweigh the benefit of fidaxomicin, given more-or-less comparable data on cure rates.

In contrast, the ACG guidelines recommend that an initial recurrence be treated with a tapering dose of vancomycin, and call for FMT for patients who are eligible and who experience a second or more C. difficile recurrences after a round of pulsed vancomycin.

Dr. Stuart Johnson said that FMT carries its own special set of issues. “If you don’t have a donor program set up, you have to rely on a stool bank,” noting that one widely used stool bank “basically had to stop making the product because of the coronavirus.” Costs for FMT products have doubled in recent years, and because Food and Drug Administration approval of the therapy is lacking, insurance does not cover it.

Dr. David Johnson also said that he is not “terribly happy” about the ACG recommendation for vancomycin prophylaxis. “It may help, but it also can have off-target effects against colonic bacterial flora, so we would not agree with that recommendation.”

The IDSA/SHEA authors also conditionally recommend bezlotoxumab, on very low certainty of evidence, as a cotherapy with standard of care antibiotics for recurrence prevention in patients with an episode in the last 6 months, particularly for patients at high recurrence risk “where logistics is not an issue.” The FDA has warned that this monoclonal antibody should be used with great care in patients with heart failure and only when benefits outweigh risks.

The ACG guidelines conditionally recommend considering bezlotoxumab to prevent recurrence in patients with specific risk factors, including age over 65 years and severe presentation. The IDSA/SHEA guidelines expand this population to anyone with a recurrence within 6 months, Dr. Fischer pointed out.

The antibody treatment “does offer another 10% absolute reduction in recurrent C. diff disease,” said Dr. Stuart Johnson, which is a “helpful option and primarily for people who have had recurrent C. diff already.” In general, he said, for both drugs, “access is still something we have to work with.”

In a commentary on the ACG guidelines, Dr. David Johnson wrote that there is good evidence that bezlotoxumab prevents relapse, especially in patients with specific risk factors. The hitch is the $4,500 price tag for a 1,000-mg vial, with a recommended dose of 10 mg/kg.

Dr. Stuart Johnson agreed that the costs of the fidaxomicin and bezlotoxumab are important considerations. In addition, there are logistical issues with using the antibody because most hospitals don’t offer infusions, which pushes patients to infusion centers.

Regardless, he added, “we’re happy that we have new options.”

Dr. Fischer, Dr. Stuart Johnson, and Dr. David Johnson reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Although adolescents with acne received different cumulative doses of isotretinoin based on their body mass index, there were no differences in acne clearance, relapse, and most side effects between normal-weight, overweight, and obese individuals, a retrospective cohort study found.

“Oral isotretinoin is among the most effective treatments for acne and is indicated for the treatment of severe acne or when first-line regimens have failed,” Maggie Tallmadge said at the annual meeting of the Society for Pediatric Dermatology. In adolescents with acne, isotretinoin is prescribed at a dose of 0.5-1 mg/kg per day “with the goal of reaching a cumulative dose of 120-150 mg/kg and clinical clearance with durable remission,” she said. “Most providers do not prescribe a daily dose over 80 mg due to perceived increased risk of side effects, including xerosis, cheilitis, liver dysfunction, and acne flare. However, many adolescents weigh over 80 kg and are therefore effectively underdosed, prolonging treatment time and possibly increasing the risk of side effects due to prolonged therapy.”

To evaluate differences in treatment courses among normal-weight, overweight, and obese adolescents, and the efficacy and safety of treatment, Ms. Tallmadge, a third-year medical student at the Medical College of Wisconsin, Milwaukee, and colleagues completed a retrospective chart review of 550 dermatology patients at Children’s Wisconsin, also in Milwaukee, who completed at least 2 months of isotretinoin treatment for acne when they were between the ages of 10 and 24, from November 2012 to January 2020. They collected data on age, weight, height, daily dose, cumulative dose, time to acne clearance, side effects, and acne recurrence after treatment, and classified patients as normal weight, overweight, or obese based on their body mass index for age percentile.

Of the 550 patients, 367 (67%) were normal weight, 101 (18%) were overweight, and 82 (15%) were obese. The median age of those in the normal-weight and overweight groups was 16, and was 15 in the obese group.

There was were significant differences in the median cumulative dose in each weight group: 143.7 mg/kg for normal-weight patients, 138.2 mg/kg for overweight patients, and 140.6 mg/kg for obese patients (P < .001).

“Despite achieving different cumulative doses, there was no difference in acne clearance, relapse, and most side effects among the three [body mass index] cohorts,” Ms. Tallmadge said. “Thus, it appears that current treatment strategies may be appropriate for overweight and obese adolescents.”

The proportion of patients with acne clearance did not differ significantly among the three groups of patients: 62% who were in the normal weight range, 60% who were overweight, and 59% who were obese had clearance of facial acne with treatment (P = .84).

Of patients whose treatment course was completed by the time of data collection, the proportion with acne recurrences was similar between the three groups: 25% of normal-weight patients, 27% of overweight patients, and 35% of obese patients (P > .05). Of patients whose treatment course was completed by the time of data collection, there was no significant differences in acne recurrence: 25% of normal-weight patients, 27% of overweight patients, and 35% of obese patients.

However, the proportion of patients reporting headaches differed significantly between the groups: 29% of normal-weight patients, compared with 40% of both overweight and obese patients (P = .035). The researchers also observed a significant positive correlation between increased BMI and increased triglyceride and ALT levels during treatment (P < .001 for both associations), yet no elevations required clinical action.

Funding for the study was provided by the MCW Medical Student Summer Research Program and the American Acne & Rosacea Society.

[email protected]

Although adolescents with acne received different cumulative doses of isotretinoin based on their body mass index, there were no differences in acne clearance, relapse, and most side effects between normal-weight, overweight, and obese individuals, a retrospective cohort study found.

“Oral isotretinoin is among the most effective treatments for acne and is indicated for the treatment of severe acne or when first-line regimens have failed,” Maggie Tallmadge said at the annual meeting of the Society for Pediatric Dermatology. In adolescents with acne, isotretinoin is prescribed at a dose of 0.5-1 mg/kg per day “with the goal of reaching a cumulative dose of 120-150 mg/kg and clinical clearance with durable remission,” she said. “Most providers do not prescribe a daily dose over 80 mg due to perceived increased risk of side effects, including xerosis, cheilitis, liver dysfunction, and acne flare. However, many adolescents weigh over 80 kg and are therefore effectively underdosed, prolonging treatment time and possibly increasing the risk of side effects due to prolonged therapy.”

To evaluate differences in treatment courses among normal-weight, overweight, and obese adolescents, and the efficacy and safety of treatment, Ms. Tallmadge, a third-year medical student at the Medical College of Wisconsin, Milwaukee, and colleagues completed a retrospective chart review of 550 dermatology patients at Children’s Wisconsin, also in Milwaukee, who completed at least 2 months of isotretinoin treatment for acne when they were between the ages of 10 and 24, from November 2012 to January 2020. They collected data on age, weight, height, daily dose, cumulative dose, time to acne clearance, side effects, and acne recurrence after treatment, and classified patients as normal weight, overweight, or obese based on their body mass index for age percentile.

Of the 550 patients, 367 (67%) were normal weight, 101 (18%) were overweight, and 82 (15%) were obese. The median age of those in the normal-weight and overweight groups was 16, and was 15 in the obese group.

There was were significant differences in the median cumulative dose in each weight group: 143.7 mg/kg for normal-weight patients, 138.2 mg/kg for overweight patients, and 140.6 mg/kg for obese patients (P < .001).

“Despite achieving different cumulative doses, there was no difference in acne clearance, relapse, and most side effects among the three [body mass index] cohorts,” Ms. Tallmadge said. “Thus, it appears that current treatment strategies may be appropriate for overweight and obese adolescents.”

The proportion of patients with acne clearance did not differ significantly among the three groups of patients: 62% who were in the normal weight range, 60% who were overweight, and 59% who were obese had clearance of facial acne with treatment (P = .84).

Of patients whose treatment course was completed by the time of data collection, the proportion with acne recurrences was similar between the three groups: 25% of normal-weight patients, 27% of overweight patients, and 35% of obese patients (P > .05). Of patients whose treatment course was completed by the time of data collection, there was no significant differences in acne recurrence: 25% of normal-weight patients, 27% of overweight patients, and 35% of obese patients.

However, the proportion of patients reporting headaches differed significantly between the groups: 29% of normal-weight patients, compared with 40% of both overweight and obese patients (P = .035). The researchers also observed a significant positive correlation between increased BMI and increased triglyceride and ALT levels during treatment (P < .001 for both associations), yet no elevations required clinical action.

Funding for the study was provided by the MCW Medical Student Summer Research Program and the American Acne & Rosacea Society.

[email protected]

Although adolescents with acne received different cumulative doses of isotretinoin based on their body mass index, there were no differences in acne clearance, relapse, and most side effects between normal-weight, overweight, and obese individuals, a retrospective cohort study found.

“Oral isotretinoin is among the most effective treatments for acne and is indicated for the treatment of severe acne or when first-line regimens have failed,” Maggie Tallmadge said at the annual meeting of the Society for Pediatric Dermatology. In adolescents with acne, isotretinoin is prescribed at a dose of 0.5-1 mg/kg per day “with the goal of reaching a cumulative dose of 120-150 mg/kg and clinical clearance with durable remission,” she said. “Most providers do not prescribe a daily dose over 80 mg due to perceived increased risk of side effects, including xerosis, cheilitis, liver dysfunction, and acne flare. However, many adolescents weigh over 80 kg and are therefore effectively underdosed, prolonging treatment time and possibly increasing the risk of side effects due to prolonged therapy.”

To evaluate differences in treatment courses among normal-weight, overweight, and obese adolescents, and the efficacy and safety of treatment, Ms. Tallmadge, a third-year medical student at the Medical College of Wisconsin, Milwaukee, and colleagues completed a retrospective chart review of 550 dermatology patients at Children’s Wisconsin, also in Milwaukee, who completed at least 2 months of isotretinoin treatment for acne when they were between the ages of 10 and 24, from November 2012 to January 2020. They collected data on age, weight, height, daily dose, cumulative dose, time to acne clearance, side effects, and acne recurrence after treatment, and classified patients as normal weight, overweight, or obese based on their body mass index for age percentile.

Of the 550 patients, 367 (67%) were normal weight, 101 (18%) were overweight, and 82 (15%) were obese. The median age of those in the normal-weight and overweight groups was 16, and was 15 in the obese group.

There was were significant differences in the median cumulative dose in each weight group: 143.7 mg/kg for normal-weight patients, 138.2 mg/kg for overweight patients, and 140.6 mg/kg for obese patients (P < .001).

“Despite achieving different cumulative doses, there was no difference in acne clearance, relapse, and most side effects among the three [body mass index] cohorts,” Ms. Tallmadge said. “Thus, it appears that current treatment strategies may be appropriate for overweight and obese adolescents.”

The proportion of patients with acne clearance did not differ significantly among the three groups of patients: 62% who were in the normal weight range, 60% who were overweight, and 59% who were obese had clearance of facial acne with treatment (P = .84).

Of patients whose treatment course was completed by the time of data collection, the proportion with acne recurrences was similar between the three groups: 25% of normal-weight patients, 27% of overweight patients, and 35% of obese patients (P > .05). Of patients whose treatment course was completed by the time of data collection, there was no significant differences in acne recurrence: 25% of normal-weight patients, 27% of overweight patients, and 35% of obese patients.

However, the proportion of patients reporting headaches differed significantly between the groups: 29% of normal-weight patients, compared with 40% of both overweight and obese patients (P = .035). The researchers also observed a significant positive correlation between increased BMI and increased triglyceride and ALT levels during treatment (P < .001 for both associations), yet no elevations required clinical action.

Funding for the study was provided by the MCW Medical Student Summer Research Program and the American Acne & Rosacea Society.

[email protected]

People whose immune systems are compromised by therapy or disease may benefit from additional doses of vaccines against SARS-CoV-2, researchers say.

In a study involving 101 people with solid-organ transplants, there was a significant boost in antibodies after the patients received third doses of the Pfizer vaccine, said Nassim Kamar, MD, PhD, professor of nephrology at Toulouse University Hospital, France.

None of the transplant patients had antibodies against the virus before their first dose of the vaccine, and only 4% produced antibodies after the first dose. That proportion rose to 40% after the second dose and to 68% after the third dose.

The effect is so strong that Dr. Kamar and colleagues at Toulouse University Hospital routinely administer three doses of mRNA vaccines to patients with solid-organ transplant without testing them for antibodies.

“When we observed that the second dose was not sufficient to have an immune response, the Francophone Society of Transplantation asked the National Health Authority to allow the third dose,” he told this news organization.

That agency on April 11 approved third doses of mRNA vaccines not only for people with solid-organ transplants but also for those with recent bone marrow transplants, those undergoing dialysis, and those with autoimmune diseases who were receiving strong immunosuppressive treatment, such as anti-CD20 or antimetabolites. Contrary to their procedure for people with solid-organ transplants, clinicians at Toulouse University Hospital test these patients for antibodies and administer third doses of vaccine only to those who test negative or have very low titers.

The researchers’ findings, published on June 23 as a letter to the editor of The New England Journal of Medicine, come as other researchers document more and more categories of patients whose responses to the vaccines typically fall short.

A study at the University of Pittsburgh that was published as a preprint on MedRxiv compared people with various health conditions to healthy health care workers. People with HIV who were taking antivirals against that virus responded almost as well as did the health care workers, said John Mellors, MD, chief of infectious diseases at the university. But people whose immune systems were compromised for other reasons fared less well.

“The areas of concern are hematological malignancy and solid-organ transplants, with the most nonresponsive groups being those who have had lung transplantation,” he said in an interview.

For patients with liver disease, mixed news came from the International Liver Congress (ILC) 2021 annual meeting.

In a study involving patients with liver disease who had received the Pfizer vaccine at Hadassah University Medical Center in Jerusalem, antibody titers were lower in patients who had received liver transplants or who had advanced liver fibrosis, as reported by this news organization.

A multicenter study in China that was presented at the ILC meeting and that was also published in the Journal of Hepatology, provided a more optimistic picture. Among patients with nonalcoholic fatty liver disease who were immunized against SARS-CoV-2 with the Sinopharm vaccine, 95.5% had neutralizing antibodies; the median neutralizing antibody titer was 32.

In the Toulouse University Hospital study, for the 40 patients who were seropositive after the second dose, antibody titers increased from 36 before the third dose to 2,676 a month after the third dose, a statistically significant result (P < .001).

For patients whose immune systems are compromised for reasons other than having received a transplant, clinicians at Toulouse University Hospital use a titer of 14 as the threshold below which they administer a third dose of mRNA vaccines. But Dr. Kamar acknowledged that the threshold is arbitrary and that the assays for antibodies with different vaccines in different populations can’t be compared head to head.

“We can’t tell you simply on the basis of the amount of antibody in your laboratory report how protected you are,” agreed William Schaffner, MD, professor of infectious diseases at Vanderbilt University, Nashville, Tenn., who is a spokesperson for the Infectious Diseases Society of America.

Not enough research has been done to establish that relationship, and results vary from one laboratory to another, he said.

That doesn’t mean that antibody tests don’t help, Dr. Schaffner said. On the basis of views of other experts he has consulted, Dr. Schaffner recommends that people who are immunocompromised undergo an antibody test. If the test is positive – meaning they have some antibodies to SARS-CoV-2, however low the titers – patients can take fewer precautions than before they were vaccinated.

But they should still be more cautious than people with healthy immune systems, he said. “Would I be going to large indoor gatherings without a mask? No. Would I be outside without a mask? Yes. Would I gather with three other people who are vaccinated to play a game of bridge? Yes. You have to titrate things a little and use some common sense,” he added.

If the results are negative, such patients may still be protected. Much research remains to be done on T-cell immunity, a second line of defense against the virus. And the current assays often produce false negative results. But to be on the safe side, people with this result should assume that their vaccine is not protecting them, Dr. Schaffner said.

That suggestion contradicts the Food and Drug Administration, which issued a recommendation on May 19 against using antibody tests to check the effectiveness of SARS-CoV-2 vaccination.

The studies so far suggest that vaccines are safe for people whose immune systems are compromised, Dr. Schaffner and Dr. Kamar agreed. Dr. Kamar is aware of only two case reports of transplant patients rejecting their transplants after vaccination. One of these was his own patient, and the rejection occurred after her second dose. She has not needed dialysis, although her kidney function was impaired.

But the FDA has not approved additional doses of SARS-CoV-2 vaccine to treat patients who are immunocompromised, and Dr. Kamar has not heard of any other national regulatory agencies that have.

In the United States, it may be difficult for anyone to obtain a third dose of vaccine outside of a clinical trial, Dr. Schaffner said, because vaccinators are likely to check databases and deny vaccination to anyone who has already received the recommended number.

Dr. Kamar, Dr. Mellors, and Dr. Schaffner have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People whose immune systems are compromised by therapy or disease may benefit from additional doses of vaccines against SARS-CoV-2, researchers say.

In a study involving 101 people with solid-organ transplants, there was a significant boost in antibodies after the patients received third doses of the Pfizer vaccine, said Nassim Kamar, MD, PhD, professor of nephrology at Toulouse University Hospital, France.

None of the transplant patients had antibodies against the virus before their first dose of the vaccine, and only 4% produced antibodies after the first dose. That proportion rose to 40% after the second dose and to 68% after the third dose.

The effect is so strong that Dr. Kamar and colleagues at Toulouse University Hospital routinely administer three doses of mRNA vaccines to patients with solid-organ transplant without testing them for antibodies.

“When we observed that the second dose was not sufficient to have an immune response, the Francophone Society of Transplantation asked the National Health Authority to allow the third dose,” he told this news organization.

That agency on April 11 approved third doses of mRNA vaccines not only for people with solid-organ transplants but also for those with recent bone marrow transplants, those undergoing dialysis, and those with autoimmune diseases who were receiving strong immunosuppressive treatment, such as anti-CD20 or antimetabolites. Contrary to their procedure for people with solid-organ transplants, clinicians at Toulouse University Hospital test these patients for antibodies and administer third doses of vaccine only to those who test negative or have very low titers.

The researchers’ findings, published on June 23 as a letter to the editor of The New England Journal of Medicine, come as other researchers document more and more categories of patients whose responses to the vaccines typically fall short.

A study at the University of Pittsburgh that was published as a preprint on MedRxiv compared people with various health conditions to healthy health care workers. People with HIV who were taking antivirals against that virus responded almost as well as did the health care workers, said John Mellors, MD, chief of infectious diseases at the university. But people whose immune systems were compromised for other reasons fared less well.

“The areas of concern are hematological malignancy and solid-organ transplants, with the most nonresponsive groups being those who have had lung transplantation,” he said in an interview.

For patients with liver disease, mixed news came from the International Liver Congress (ILC) 2021 annual meeting.

In a study involving patients with liver disease who had received the Pfizer vaccine at Hadassah University Medical Center in Jerusalem, antibody titers were lower in patients who had received liver transplants or who had advanced liver fibrosis, as reported by this news organization.

A multicenter study in China that was presented at the ILC meeting and that was also published in the Journal of Hepatology, provided a more optimistic picture. Among patients with nonalcoholic fatty liver disease who were immunized against SARS-CoV-2 with the Sinopharm vaccine, 95.5% had neutralizing antibodies; the median neutralizing antibody titer was 32.

In the Toulouse University Hospital study, for the 40 patients who were seropositive after the second dose, antibody titers increased from 36 before the third dose to 2,676 a month after the third dose, a statistically significant result (P < .001).

For patients whose immune systems are compromised for reasons other than having received a transplant, clinicians at Toulouse University Hospital use a titer of 14 as the threshold below which they administer a third dose of mRNA vaccines. But Dr. Kamar acknowledged that the threshold is arbitrary and that the assays for antibodies with different vaccines in different populations can’t be compared head to head.

“We can’t tell you simply on the basis of the amount of antibody in your laboratory report how protected you are,” agreed William Schaffner, MD, professor of infectious diseases at Vanderbilt University, Nashville, Tenn., who is a spokesperson for the Infectious Diseases Society of America.

Not enough research has been done to establish that relationship, and results vary from one laboratory to another, he said.

That doesn’t mean that antibody tests don’t help, Dr. Schaffner said. On the basis of views of other experts he has consulted, Dr. Schaffner recommends that people who are immunocompromised undergo an antibody test. If the test is positive – meaning they have some antibodies to SARS-CoV-2, however low the titers – patients can take fewer precautions than before they were vaccinated.

But they should still be more cautious than people with healthy immune systems, he said. “Would I be going to large indoor gatherings without a mask? No. Would I be outside without a mask? Yes. Would I gather with three other people who are vaccinated to play a game of bridge? Yes. You have to titrate things a little and use some common sense,” he added.

If the results are negative, such patients may still be protected. Much research remains to be done on T-cell immunity, a second line of defense against the virus. And the current assays often produce false negative results. But to be on the safe side, people with this result should assume that their vaccine is not protecting them, Dr. Schaffner said.

That suggestion contradicts the Food and Drug Administration, which issued a recommendation on May 19 against using antibody tests to check the effectiveness of SARS-CoV-2 vaccination.

The studies so far suggest that vaccines are safe for people whose immune systems are compromised, Dr. Schaffner and Dr. Kamar agreed. Dr. Kamar is aware of only two case reports of transplant patients rejecting their transplants after vaccination. One of these was his own patient, and the rejection occurred after her second dose. She has not needed dialysis, although her kidney function was impaired.

But the FDA has not approved additional doses of SARS-CoV-2 vaccine to treat patients who are immunocompromised, and Dr. Kamar has not heard of any other national regulatory agencies that have.

In the United States, it may be difficult for anyone to obtain a third dose of vaccine outside of a clinical trial, Dr. Schaffner said, because vaccinators are likely to check databases and deny vaccination to anyone who has already received the recommended number.

Dr. Kamar, Dr. Mellors, and Dr. Schaffner have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People whose immune systems are compromised by therapy or disease may benefit from additional doses of vaccines against SARS-CoV-2, researchers say.

In a study involving 101 people with solid-organ transplants, there was a significant boost in antibodies after the patients received third doses of the Pfizer vaccine, said Nassim Kamar, MD, PhD, professor of nephrology at Toulouse University Hospital, France.

None of the transplant patients had antibodies against the virus before their first dose of the vaccine, and only 4% produced antibodies after the first dose. That proportion rose to 40% after the second dose and to 68% after the third dose.

The effect is so strong that Dr. Kamar and colleagues at Toulouse University Hospital routinely administer three doses of mRNA vaccines to patients with solid-organ transplant without testing them for antibodies.

“When we observed that the second dose was not sufficient to have an immune response, the Francophone Society of Transplantation asked the National Health Authority to allow the third dose,” he told this news organization.

That agency on April 11 approved third doses of mRNA vaccines not only for people with solid-organ transplants but also for those with recent bone marrow transplants, those undergoing dialysis, and those with autoimmune diseases who were receiving strong immunosuppressive treatment, such as anti-CD20 or antimetabolites. Contrary to their procedure for people with solid-organ transplants, clinicians at Toulouse University Hospital test these patients for antibodies and administer third doses of vaccine only to those who test negative or have very low titers.

The researchers’ findings, published on June 23 as a letter to the editor of The New England Journal of Medicine, come as other researchers document more and more categories of patients whose responses to the vaccines typically fall short.

A study at the University of Pittsburgh that was published as a preprint on MedRxiv compared people with various health conditions to healthy health care workers. People with HIV who were taking antivirals against that virus responded almost as well as did the health care workers, said John Mellors, MD, chief of infectious diseases at the university. But people whose immune systems were compromised for other reasons fared less well.

“The areas of concern are hematological malignancy and solid-organ transplants, with the most nonresponsive groups being those who have had lung transplantation,” he said in an interview.

For patients with liver disease, mixed news came from the International Liver Congress (ILC) 2021 annual meeting.

In a study involving patients with liver disease who had received the Pfizer vaccine at Hadassah University Medical Center in Jerusalem, antibody titers were lower in patients who had received liver transplants or who had advanced liver fibrosis, as reported by this news organization.

A multicenter study in China that was presented at the ILC meeting and that was also published in the Journal of Hepatology, provided a more optimistic picture. Among patients with nonalcoholic fatty liver disease who were immunized against SARS-CoV-2 with the Sinopharm vaccine, 95.5% had neutralizing antibodies; the median neutralizing antibody titer was 32.

In the Toulouse University Hospital study, for the 40 patients who were seropositive after the second dose, antibody titers increased from 36 before the third dose to 2,676 a month after the third dose, a statistically significant result (P < .001).

For patients whose immune systems are compromised for reasons other than having received a transplant, clinicians at Toulouse University Hospital use a titer of 14 as the threshold below which they administer a third dose of mRNA vaccines. But Dr. Kamar acknowledged that the threshold is arbitrary and that the assays for antibodies with different vaccines in different populations can’t be compared head to head.

“We can’t tell you simply on the basis of the amount of antibody in your laboratory report how protected you are,” agreed William Schaffner, MD, professor of infectious diseases at Vanderbilt University, Nashville, Tenn., who is a spokesperson for the Infectious Diseases Society of America.

Not enough research has been done to establish that relationship, and results vary from one laboratory to another, he said.

That doesn’t mean that antibody tests don’t help, Dr. Schaffner said. On the basis of views of other experts he has consulted, Dr. Schaffner recommends that people who are immunocompromised undergo an antibody test. If the test is positive – meaning they have some antibodies to SARS-CoV-2, however low the titers – patients can take fewer precautions than before they were vaccinated.

But they should still be more cautious than people with healthy immune systems, he said. “Would I be going to large indoor gatherings without a mask? No. Would I be outside without a mask? Yes. Would I gather with three other people who are vaccinated to play a game of bridge? Yes. You have to titrate things a little and use some common sense,” he added.

If the results are negative, such patients may still be protected. Much research remains to be done on T-cell immunity, a second line of defense against the virus. And the current assays often produce false negative results. But to be on the safe side, people with this result should assume that their vaccine is not protecting them, Dr. Schaffner said.

That suggestion contradicts the Food and Drug Administration, which issued a recommendation on May 19 against using antibody tests to check the effectiveness of SARS-CoV-2 vaccination.

The studies so far suggest that vaccines are safe for people whose immune systems are compromised, Dr. Schaffner and Dr. Kamar agreed. Dr. Kamar is aware of only two case reports of transplant patients rejecting their transplants after vaccination. One of these was his own patient, and the rejection occurred after her second dose. She has not needed dialysis, although her kidney function was impaired.

But the FDA has not approved additional doses of SARS-CoV-2 vaccine to treat patients who are immunocompromised, and Dr. Kamar has not heard of any other national regulatory agencies that have.

In the United States, it may be difficult for anyone to obtain a third dose of vaccine outside of a clinical trial, Dr. Schaffner said, because vaccinators are likely to check databases and deny vaccination to anyone who has already received the recommended number.

Dr. Kamar, Dr. Mellors, and Dr. Schaffner have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.