Internal Medicine News

Doctors have urged caution in linking the weight loss drug tirzepatide to the death of a 58-year-old nurse from Scotland.

Susan McGowan, from North Lanarkshire, took two low-dose injections of tirzepatide (Mounjaro) over the course of about 2 weeks before her death in September. 

BBC News reported that multiple organ failure, septic shock, and pancreatitis were listed on her death certificate as the immediate cause of death, with “the use of prescribed tirzepatide” recorded as a contributing factor.

McGowan worked as a nurse at University Hospital Monklands in Airdrie. A family member said that, apart from carrying a “bit of extra weight,” she had been otherwise healthy and was not taking any other medication.

It is understood that McGowan had sought medical advice before purchasing a prescription for tirzepatide through a registered UK pharmacy. However, days after administering a second injection, she went to A&E at Monklands with severe stomach pain and sickness. She died on September 4.
 

Expert Insights

Commenting to the Science Media Centre (SMC), Amanda Adler, MD, PhD, professor of diabetic medicine and health policy at the University of Oxford, described the nurse’s death as “sad” but said that “whether or not it was related to tirzepatide may be difficult to prove.” While tirzepatide can be associated with uncommon problems such as acute pancreatitis, “one can develop acute pancreatitis for many other reasons as well,” she said. 

Naveed Sattar, MD, PhD, professor of metabolic medicine at the University of Glasgow, noted that data from multiple trials of tirzepatide, involving around 10,000 people living with diabetes or obesity, “do not suggest a higher risk of pancreatitis.” Furthermore, “the data seem to show acceptable safety thus far and a range of benefits including sizable average weight loss (near 20%), strong diabetes prevention, and considerable benefits in people living with sleep apnea,” he told the SMC.
 

Approved Based on Extensive Assessment

Tirzepatide, a GLP-1 receptor agonist, was approved for use as a weight loss aid in the United Kingdom in November last year by the Medicines and Healthcare products Regulatory Agency (MHRA). It lists nausea, diarrhea, and vomiting as the most common side effects, as well as hypoglycemia for patients with diabetes.

Available figures under the Yellow Card scheme up to 19 May 2024 show that there were 208 adverse drug reactions reported about tirzepatide this year, including 31 serious reactions and one suspected death of a man in his 60s.

In a statement, a spokesperson for the drug’s manufacturer, Eli Lilly, said, “Patient safety is Lilly’s top priority. We are committed to continually monitoring, evaluating, and reporting safety information for all Lilly medicines. 

“Mounjaro (tirzepatide) was approved based on extensive assessment of the benefits and risks of the medicine, and we provide information about the benefits and risks of all our medicines to regulators around the world to ensure the latest information is available for prescribers. If anyone is experiencing side effects when taking any Lilly medicine, they should talk to their doctor or other healthcare professional.” 

In October, the NHS submitted plans to the National Institute for Health and Care Excellence (NICE) for a phased rollout of tirzepatide in England that would initially prioritize patients with the greatest clinical need. The first phase would see the drug available to people with a body mass index of more than 40 kg/m² who also suffer from at least three of the main weight-related health problems: hypertension, dyslipidemia, obstructive sleep apnea, and cardiovascular disease.

“Our sincere sympathies are with the family of individual concerned,” said Alison Cave, MHRA Chief Safety Officer.

“Patient safety is our top priority and no medicine would be approved unless it met our expected standards of safety, quality, and effectiveness. Our role is to continually monitor the safety of medicines during their use, such as GLP-1 RAs. We have robust, safety monitoring and surveillance systems in place for all healthcare products.  

“New medicines, such as tirzepatide, are more intensively monitored to ensure that any new safety issues are identified promptly. We strongly encourage the reporting of all suspected reactions to newer medicines, which are denoted by an inverted Black Triangle symbol.

“On the basis of the current evidence the benefits of GLP-1 RAs outweigh the potential risks when used for the licensed indications. The decision to start, continue, or stop treatments should be made jointly by patients and their doctor, based on full consideration of the benefits and risks.” 

She encouraged patients and healthcare professionals to continue reporting suspected side effects to GLP-1 RAs, such as tirzepatide, through the Yellow Card Scheme. “When a safety issue is confirmed, we always act promptly to inform patients and healthcare professionals and take appropriate steps to mitigate any identified risk.”

The Department of Health and Social Care declined to comment. 

Adler disclosed being involved as an unpaid investigator on an Eli Lilly–funded trial for a different drug. Sattar has disclosed no relevant financial relationships.
 

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

Doctors have urged caution in linking the weight loss drug tirzepatide to the death of a 58-year-old nurse from Scotland.

Susan McGowan, from North Lanarkshire, took two low-dose injections of tirzepatide (Mounjaro) over the course of about 2 weeks before her death in September. 

BBC News reported that multiple organ failure, septic shock, and pancreatitis were listed on her death certificate as the immediate cause of death, with “the use of prescribed tirzepatide” recorded as a contributing factor.

McGowan worked as a nurse at University Hospital Monklands in Airdrie. A family member said that, apart from carrying a “bit of extra weight,” she had been otherwise healthy and was not taking any other medication.

It is understood that McGowan had sought medical advice before purchasing a prescription for tirzepatide through a registered UK pharmacy. However, days after administering a second injection, she went to A&E at Monklands with severe stomach pain and sickness. She died on September 4.
 

Expert Insights

Commenting to the Science Media Centre (SMC), Amanda Adler, MD, PhD, professor of diabetic medicine and health policy at the University of Oxford, described the nurse’s death as “sad” but said that “whether or not it was related to tirzepatide may be difficult to prove.” While tirzepatide can be associated with uncommon problems such as acute pancreatitis, “one can develop acute pancreatitis for many other reasons as well,” she said. 

Naveed Sattar, MD, PhD, professor of metabolic medicine at the University of Glasgow, noted that data from multiple trials of tirzepatide, involving around 10,000 people living with diabetes or obesity, “do not suggest a higher risk of pancreatitis.” Furthermore, “the data seem to show acceptable safety thus far and a range of benefits including sizable average weight loss (near 20%), strong diabetes prevention, and considerable benefits in people living with sleep apnea,” he told the SMC.
 

Approved Based on Extensive Assessment

Tirzepatide, a GLP-1 receptor agonist, was approved for use as a weight loss aid in the United Kingdom in November last year by the Medicines and Healthcare products Regulatory Agency (MHRA). It lists nausea, diarrhea, and vomiting as the most common side effects, as well as hypoglycemia for patients with diabetes.

Available figures under the Yellow Card scheme up to 19 May 2024 show that there were 208 adverse drug reactions reported about tirzepatide this year, including 31 serious reactions and one suspected death of a man in his 60s.

In a statement, a spokesperson for the drug’s manufacturer, Eli Lilly, said, “Patient safety is Lilly’s top priority. We are committed to continually monitoring, evaluating, and reporting safety information for all Lilly medicines. 

“Mounjaro (tirzepatide) was approved based on extensive assessment of the benefits and risks of the medicine, and we provide information about the benefits and risks of all our medicines to regulators around the world to ensure the latest information is available for prescribers. If anyone is experiencing side effects when taking any Lilly medicine, they should talk to their doctor or other healthcare professional.” 

In October, the NHS submitted plans to the National Institute for Health and Care Excellence (NICE) for a phased rollout of tirzepatide in England that would initially prioritize patients with the greatest clinical need. The first phase would see the drug available to people with a body mass index of more than 40 kg/m² who also suffer from at least three of the main weight-related health problems: hypertension, dyslipidemia, obstructive sleep apnea, and cardiovascular disease.

“Our sincere sympathies are with the family of individual concerned,” said Alison Cave, MHRA Chief Safety Officer.

“Patient safety is our top priority and no medicine would be approved unless it met our expected standards of safety, quality, and effectiveness. Our role is to continually monitor the safety of medicines during their use, such as GLP-1 RAs. We have robust, safety monitoring and surveillance systems in place for all healthcare products.  

“New medicines, such as tirzepatide, are more intensively monitored to ensure that any new safety issues are identified promptly. We strongly encourage the reporting of all suspected reactions to newer medicines, which are denoted by an inverted Black Triangle symbol.

“On the basis of the current evidence the benefits of GLP-1 RAs outweigh the potential risks when used for the licensed indications. The decision to start, continue, or stop treatments should be made jointly by patients and their doctor, based on full consideration of the benefits and risks.” 

She encouraged patients and healthcare professionals to continue reporting suspected side effects to GLP-1 RAs, such as tirzepatide, through the Yellow Card Scheme. “When a safety issue is confirmed, we always act promptly to inform patients and healthcare professionals and take appropriate steps to mitigate any identified risk.”

The Department of Health and Social Care declined to comment. 

Adler disclosed being involved as an unpaid investigator on an Eli Lilly–funded trial for a different drug. Sattar has disclosed no relevant financial relationships.
 

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

Doctors have urged caution in linking the weight loss drug tirzepatide to the death of a 58-year-old nurse from Scotland.

Susan McGowan, from North Lanarkshire, took two low-dose injections of tirzepatide (Mounjaro) over the course of about 2 weeks before her death in September. 

BBC News reported that multiple organ failure, septic shock, and pancreatitis were listed on her death certificate as the immediate cause of death, with “the use of prescribed tirzepatide” recorded as a contributing factor.

McGowan worked as a nurse at University Hospital Monklands in Airdrie. A family member said that, apart from carrying a “bit of extra weight,” she had been otherwise healthy and was not taking any other medication.

It is understood that McGowan had sought medical advice before purchasing a prescription for tirzepatide through a registered UK pharmacy. However, days after administering a second injection, she went to A&E at Monklands with severe stomach pain and sickness. She died on September 4.
 

Expert Insights

Commenting to the Science Media Centre (SMC), Amanda Adler, MD, PhD, professor of diabetic medicine and health policy at the University of Oxford, described the nurse’s death as “sad” but said that “whether or not it was related to tirzepatide may be difficult to prove.” While tirzepatide can be associated with uncommon problems such as acute pancreatitis, “one can develop acute pancreatitis for many other reasons as well,” she said. 

Naveed Sattar, MD, PhD, professor of metabolic medicine at the University of Glasgow, noted that data from multiple trials of tirzepatide, involving around 10,000 people living with diabetes or obesity, “do not suggest a higher risk of pancreatitis.” Furthermore, “the data seem to show acceptable safety thus far and a range of benefits including sizable average weight loss (near 20%), strong diabetes prevention, and considerable benefits in people living with sleep apnea,” he told the SMC.
 

Approved Based on Extensive Assessment

Tirzepatide, a GLP-1 receptor agonist, was approved for use as a weight loss aid in the United Kingdom in November last year by the Medicines and Healthcare products Regulatory Agency (MHRA). It lists nausea, diarrhea, and vomiting as the most common side effects, as well as hypoglycemia for patients with diabetes.

Available figures under the Yellow Card scheme up to 19 May 2024 show that there were 208 adverse drug reactions reported about tirzepatide this year, including 31 serious reactions and one suspected death of a man in his 60s.

In a statement, a spokesperson for the drug’s manufacturer, Eli Lilly, said, “Patient safety is Lilly’s top priority. We are committed to continually monitoring, evaluating, and reporting safety information for all Lilly medicines. 

“Mounjaro (tirzepatide) was approved based on extensive assessment of the benefits and risks of the medicine, and we provide information about the benefits and risks of all our medicines to regulators around the world to ensure the latest information is available for prescribers. If anyone is experiencing side effects when taking any Lilly medicine, they should talk to their doctor or other healthcare professional.” 

In October, the NHS submitted plans to the National Institute for Health and Care Excellence (NICE) for a phased rollout of tirzepatide in England that would initially prioritize patients with the greatest clinical need. The first phase would see the drug available to people with a body mass index of more than 40 kg/m² who also suffer from at least three of the main weight-related health problems: hypertension, dyslipidemia, obstructive sleep apnea, and cardiovascular disease.

“Our sincere sympathies are with the family of individual concerned,” said Alison Cave, MHRA Chief Safety Officer.

“Patient safety is our top priority and no medicine would be approved unless it met our expected standards of safety, quality, and effectiveness. Our role is to continually monitor the safety of medicines during their use, such as GLP-1 RAs. We have robust, safety monitoring and surveillance systems in place for all healthcare products.  

“New medicines, such as tirzepatide, are more intensively monitored to ensure that any new safety issues are identified promptly. We strongly encourage the reporting of all suspected reactions to newer medicines, which are denoted by an inverted Black Triangle symbol.

“On the basis of the current evidence the benefits of GLP-1 RAs outweigh the potential risks when used for the licensed indications. The decision to start, continue, or stop treatments should be made jointly by patients and their doctor, based on full consideration of the benefits and risks.” 

She encouraged patients and healthcare professionals to continue reporting suspected side effects to GLP-1 RAs, such as tirzepatide, through the Yellow Card Scheme. “When a safety issue is confirmed, we always act promptly to inform patients and healthcare professionals and take appropriate steps to mitigate any identified risk.”

The Department of Health and Social Care declined to comment. 

Adler disclosed being involved as an unpaid investigator on an Eli Lilly–funded trial for a different drug. Sattar has disclosed no relevant financial relationships.
 

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

TOPLINE:

Vitamin K supplementation significantly reduced the frequency, intensity, and duration of nocturnal leg cramps in older adults. No adverse events related to vitamin K were identified.

METHODOLOGY:

• Researchers conducted a multicenter, double-blind, placebo-controlled randomized clinical trial in China from September 2022 to December 2023.
• A total of 199 participants aged ≥ 65 years with at least two documented episodes of nocturnal leg cramps during a 2-week screening period were included.
• Participants were randomized in a 1:1 ratio to receive either 180 μg of vitamin K (menaquinone 7) or a placebo daily for 8 weeks.
• The primary outcome was the mean number of nocturnal leg cramps per week, while secondary outcomes were the duration and severity of muscle cramps.
• The ethics committees of Third People’s Hospital of Chengdu and Affiliated Hospital of North Sichuan Medical College approved the study, and all participants provided written informed consent.

TAKEAWAY:

• Vitamin K group experienced a significant reduction in the mean weekly frequency of cramps (mean difference, 2.60 [SD, 0.81] to 0.96 [SD, 1.41]) compared with the placebo group, which maintained a mean weekly frequency of 3.63 (SD, 2.20) (P < .001).
• The severity of nocturnal leg cramps decreased more in the vitamin K group (mean difference, −2.55 [SD, 2.12] points) than in the placebo group (mean difference, −1.24 [SD, 1.16] points).
• The duration of nocturnal leg cramps also decreased more in the vitamin K group (mean difference, −0.90 [SD, 0.88] minutes) than in the placebo group (mean difference, −0.32 [SD, 0.78] minutes).
• No adverse events related to vitamin K use were identified, indicating a good safety profile for the supplementation.

IN PRACTICE:

“Given the generally benign characteristics of NLCs, treatment modality must be both effective and safe, thus minimizing the risk of iatrogenic harm,” the study authors wrote.

SOURCE:

This study was led by Jing Tan, MD, the Third People’s Hospital of Chengdu in Chengdu, China. It was published online on October 28 in JAMA Internal Medicine.

LIMITATIONS: 

This study did not investigate the quality of life or sleep, which could have provided additional insights into the impact of vitamin K on nocturnal leg cramps. The relatively mild nature of nocturnal leg cramps experienced by the participants may limit the generalizability of the findings to populations with more severe symptoms.

DISCLOSURES:

This study was supported by grants from China Health Promotion Foundation and the Third People’s Hospital of Chengdu Scientific Research Project. Tan disclosed receiving personal fees from BeiGene, AbbVie, Pfizer, Xian Janssen Pharmaceutical, and Takeda Pharmaceutical outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Vitamin K supplementation significantly reduced the frequency, intensity, and duration of nocturnal leg cramps in older adults. No adverse events related to vitamin K were identified.

METHODOLOGY:

• Researchers conducted a multicenter, double-blind, placebo-controlled randomized clinical trial in China from September 2022 to December 2023.
• A total of 199 participants aged ≥ 65 years with at least two documented episodes of nocturnal leg cramps during a 2-week screening period were included.
• Participants were randomized in a 1:1 ratio to receive either 180 μg of vitamin K (menaquinone 7) or a placebo daily for 8 weeks.
• The primary outcome was the mean number of nocturnal leg cramps per week, while secondary outcomes were the duration and severity of muscle cramps.
• The ethics committees of Third People’s Hospital of Chengdu and Affiliated Hospital of North Sichuan Medical College approved the study, and all participants provided written informed consent.

TAKEAWAY:

• Vitamin K group experienced a significant reduction in the mean weekly frequency of cramps (mean difference, 2.60 [SD, 0.81] to 0.96 [SD, 1.41]) compared with the placebo group, which maintained a mean weekly frequency of 3.63 (SD, 2.20) (P < .001).
• The severity of nocturnal leg cramps decreased more in the vitamin K group (mean difference, −2.55 [SD, 2.12] points) than in the placebo group (mean difference, −1.24 [SD, 1.16] points).
• The duration of nocturnal leg cramps also decreased more in the vitamin K group (mean difference, −0.90 [SD, 0.88] minutes) than in the placebo group (mean difference, −0.32 [SD, 0.78] minutes).
• No adverse events related to vitamin K use were identified, indicating a good safety profile for the supplementation.

IN PRACTICE:

“Given the generally benign characteristics of NLCs, treatment modality must be both effective and safe, thus minimizing the risk of iatrogenic harm,” the study authors wrote.

SOURCE:

This study was led by Jing Tan, MD, the Third People’s Hospital of Chengdu in Chengdu, China. It was published online on October 28 in JAMA Internal Medicine.

LIMITATIONS: 

This study did not investigate the quality of life or sleep, which could have provided additional insights into the impact of vitamin K on nocturnal leg cramps. The relatively mild nature of nocturnal leg cramps experienced by the participants may limit the generalizability of the findings to populations with more severe symptoms.

DISCLOSURES:

This study was supported by grants from China Health Promotion Foundation and the Third People’s Hospital of Chengdu Scientific Research Project. Tan disclosed receiving personal fees from BeiGene, AbbVie, Pfizer, Xian Janssen Pharmaceutical, and Takeda Pharmaceutical outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Vitamin K supplementation significantly reduced the frequency, intensity, and duration of nocturnal leg cramps in older adults. No adverse events related to vitamin K were identified.

METHODOLOGY:

• Researchers conducted a multicenter, double-blind, placebo-controlled randomized clinical trial in China from September 2022 to December 2023.
• A total of 199 participants aged ≥ 65 years with at least two documented episodes of nocturnal leg cramps during a 2-week screening period were included.
• Participants were randomized in a 1:1 ratio to receive either 180 μg of vitamin K (menaquinone 7) or a placebo daily for 8 weeks.
• The primary outcome was the mean number of nocturnal leg cramps per week, while secondary outcomes were the duration and severity of muscle cramps.
• The ethics committees of Third People’s Hospital of Chengdu and Affiliated Hospital of North Sichuan Medical College approved the study, and all participants provided written informed consent.

TAKEAWAY:

• Vitamin K group experienced a significant reduction in the mean weekly frequency of cramps (mean difference, 2.60 [SD, 0.81] to 0.96 [SD, 1.41]) compared with the placebo group, which maintained a mean weekly frequency of 3.63 (SD, 2.20) (P < .001).
• The severity of nocturnal leg cramps decreased more in the vitamin K group (mean difference, −2.55 [SD, 2.12] points) than in the placebo group (mean difference, −1.24 [SD, 1.16] points).
• The duration of nocturnal leg cramps also decreased more in the vitamin K group (mean difference, −0.90 [SD, 0.88] minutes) than in the placebo group (mean difference, −0.32 [SD, 0.78] minutes).
• No adverse events related to vitamin K use were identified, indicating a good safety profile for the supplementation.

IN PRACTICE:

“Given the generally benign characteristics of NLCs, treatment modality must be both effective and safe, thus minimizing the risk of iatrogenic harm,” the study authors wrote.

SOURCE:

This study was led by Jing Tan, MD, the Third People’s Hospital of Chengdu in Chengdu, China. It was published online on October 28 in JAMA Internal Medicine.

LIMITATIONS: 

This study did not investigate the quality of life or sleep, which could have provided additional insights into the impact of vitamin K on nocturnal leg cramps. The relatively mild nature of nocturnal leg cramps experienced by the participants may limit the generalizability of the findings to populations with more severe symptoms.

DISCLOSURES:

This study was supported by grants from China Health Promotion Foundation and the Third People’s Hospital of Chengdu Scientific Research Project. Tan disclosed receiving personal fees from BeiGene, AbbVie, Pfizer, Xian Janssen Pharmaceutical, and Takeda Pharmaceutical outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Receiving radiotherapy after prostatectomy does negatively affect long-term health-related quality of life, including sexual function, urinary incontinence, and urinary irritation, but the timing of radiation after prostatectomy — within a year or over a year from surgery — does not appear to significantly affect patients’ quality of life over the long term, a recent analysis finds.

METHODOLOGY:

• Delaying radiotherapy after prostatectomy can help avoid overtreatment and mitigate genitourinary and erectile toxic effects. However, few studies have compared long-term patient-reported health-related quality-of-life outcomes on the basis of the timing of postprostatectomy radiotherapy.
• Researchers evaluated 1203 men (median age, 60.5 years; 92% were White and 6.8% were Black) with localized prostate cancer who underwent radical prostatectomy from the PROST-QA (2003-2006) and RP2 Consortium (2010-2013). Among these patients, 1082 underwent surgery only, 57 received early radiotherapy (within 12 months of surgery), and 64 underwent late radiotherapy (12 months or more after surgery).
• Patients who received early radiotherapy were more likely to receive androgen deprivation therapy than those who underwent late radiotherapy (40.4% vs 12.5%; P < .001).
• Primary outcome was health-related quality of life measured using the Expanded Prostate Cancer Index Composite at baseline, 2, 6, and 12 months, and annually after that. Health-related quality-of-life measures included sexual function, urinary incontinence, urinary irritation and/or obstruction, and bowel or rectal function.
• The median follow-up duration was 85.6 months.

TAKEAWAY:

• Postprostatectomy radiotherapy was associated with a significantly greater decline in health-related quality of life across all domains, including sexual function and urinary incontinence.
• Patients who received early radiation initially experienced worse urinary incontinence and sexual health, compared with patients in the late group, but the early group also had higher-risk disease and were more likely to receive concurrent androgen deprivation therapy.
• In the long term, the early radiotherapy group experienced more pronounced recovery of sexual function, urinary irritation, and urinary incontinence than the late radiotherapy group.
• Ultimately, patients in the early radiotherapy group had similar, potentially better, long-term health-related quality-of-life domain scores than those in the late group over the long term. For instance, the likelihood of being pad free increased for patients treated early with radiation, while it decreased for those treated late. In patients who received early radiation, the rate of freedom from pad use increased from 39% before radiation to 67% at the sixth follow-up visit after radiation, while it decreased from 73% to 48% in those who received late radiation.

IN PRACTICE:

“Long-term patient-reported sexual, incontinence, and urinary irritative outcomes did not significantly differ between early vs late postprostatectomy [radiotherapy],” the authors said. In fact, “men receiving early [radiation] experienced greater recovery of these toxicity domains and achieved similar, and possibly better, domain scores as those receiving late [radiation] at long-term follow-up.” Overall, “these results may help guide treatment counseling and support consideration of early [radiotherapy] after prostatectomy for men at particularly high risk of recurrence and metastasis.”

SOURCE:

The study, led by Sagar A. Patel, MD, MSc, Emory University in Atlanta, was published online in JAMA Network Open.

LIMITATIONS:

The early and late postprostatectomy radiotherapy groups were relatively small and underpowered to detect statistically significant differences between groups. The study has a nonrandomized design, which may introduce unaccounted for imbalances among the different groups. The study did not directly compare health-related quality of life between patients receiving adjuvant vs salvage radiotherapy.

DISCLOSURES:

This study received funding from National Institutes of Health grants and the Paul Calabresi Career Development Award for Clinical Oncology. Several authors reported receiving personal fees, grants, and having other ties with various sources. Additional disclosures are noted in the original article.

A version of this article appeared on Medscape.com.

TOPLINE:

Receiving radiotherapy after prostatectomy does negatively affect long-term health-related quality of life, including sexual function, urinary incontinence, and urinary irritation, but the timing of radiation after prostatectomy — within a year or over a year from surgery — does not appear to significantly affect patients’ quality of life over the long term, a recent analysis finds.

METHODOLOGY:

• Delaying radiotherapy after prostatectomy can help avoid overtreatment and mitigate genitourinary and erectile toxic effects. However, few studies have compared long-term patient-reported health-related quality-of-life outcomes on the basis of the timing of postprostatectomy radiotherapy.
• Researchers evaluated 1203 men (median age, 60.5 years; 92% were White and 6.8% were Black) with localized prostate cancer who underwent radical prostatectomy from the PROST-QA (2003-2006) and RP2 Consortium (2010-2013). Among these patients, 1082 underwent surgery only, 57 received early radiotherapy (within 12 months of surgery), and 64 underwent late radiotherapy (12 months or more after surgery).
• Patients who received early radiotherapy were more likely to receive androgen deprivation therapy than those who underwent late radiotherapy (40.4% vs 12.5%; P < .001).
• Primary outcome was health-related quality of life measured using the Expanded Prostate Cancer Index Composite at baseline, 2, 6, and 12 months, and annually after that. Health-related quality-of-life measures included sexual function, urinary incontinence, urinary irritation and/or obstruction, and bowel or rectal function.
• The median follow-up duration was 85.6 months.

TAKEAWAY:

• Postprostatectomy radiotherapy was associated with a significantly greater decline in health-related quality of life across all domains, including sexual function and urinary incontinence.
• Patients who received early radiation initially experienced worse urinary incontinence and sexual health, compared with patients in the late group, but the early group also had higher-risk disease and were more likely to receive concurrent androgen deprivation therapy.
• In the long term, the early radiotherapy group experienced more pronounced recovery of sexual function, urinary irritation, and urinary incontinence than the late radiotherapy group.
• Ultimately, patients in the early radiotherapy group had similar, potentially better, long-term health-related quality-of-life domain scores than those in the late group over the long term. For instance, the likelihood of being pad free increased for patients treated early with radiation, while it decreased for those treated late. In patients who received early radiation, the rate of freedom from pad use increased from 39% before radiation to 67% at the sixth follow-up visit after radiation, while it decreased from 73% to 48% in those who received late radiation.

IN PRACTICE:

“Long-term patient-reported sexual, incontinence, and urinary irritative outcomes did not significantly differ between early vs late postprostatectomy [radiotherapy],” the authors said. In fact, “men receiving early [radiation] experienced greater recovery of these toxicity domains and achieved similar, and possibly better, domain scores as those receiving late [radiation] at long-term follow-up.” Overall, “these results may help guide treatment counseling and support consideration of early [radiotherapy] after prostatectomy for men at particularly high risk of recurrence and metastasis.”

SOURCE:

The study, led by Sagar A. Patel, MD, MSc, Emory University in Atlanta, was published online in JAMA Network Open.

LIMITATIONS:

The early and late postprostatectomy radiotherapy groups were relatively small and underpowered to detect statistically significant differences between groups. The study has a nonrandomized design, which may introduce unaccounted for imbalances among the different groups. The study did not directly compare health-related quality of life between patients receiving adjuvant vs salvage radiotherapy.

DISCLOSURES:

This study received funding from National Institutes of Health grants and the Paul Calabresi Career Development Award for Clinical Oncology. Several authors reported receiving personal fees, grants, and having other ties with various sources. Additional disclosures are noted in the original article.

A version of this article appeared on Medscape.com.

TOPLINE:

Receiving radiotherapy after prostatectomy does negatively affect long-term health-related quality of life, including sexual function, urinary incontinence, and urinary irritation, but the timing of radiation after prostatectomy — within a year or over a year from surgery — does not appear to significantly affect patients’ quality of life over the long term, a recent analysis finds.

METHODOLOGY:

• Delaying radiotherapy after prostatectomy can help avoid overtreatment and mitigate genitourinary and erectile toxic effects. However, few studies have compared long-term patient-reported health-related quality-of-life outcomes on the basis of the timing of postprostatectomy radiotherapy.
• Researchers evaluated 1203 men (median age, 60.5 years; 92% were White and 6.8% were Black) with localized prostate cancer who underwent radical prostatectomy from the PROST-QA (2003-2006) and RP2 Consortium (2010-2013). Among these patients, 1082 underwent surgery only, 57 received early radiotherapy (within 12 months of surgery), and 64 underwent late radiotherapy (12 months or more after surgery).
• Patients who received early radiotherapy were more likely to receive androgen deprivation therapy than those who underwent late radiotherapy (40.4% vs 12.5%; P < .001).
• Primary outcome was health-related quality of life measured using the Expanded Prostate Cancer Index Composite at baseline, 2, 6, and 12 months, and annually after that. Health-related quality-of-life measures included sexual function, urinary incontinence, urinary irritation and/or obstruction, and bowel or rectal function.
• The median follow-up duration was 85.6 months.

TAKEAWAY:

• Postprostatectomy radiotherapy was associated with a significantly greater decline in health-related quality of life across all domains, including sexual function and urinary incontinence.
• Patients who received early radiation initially experienced worse urinary incontinence and sexual health, compared with patients in the late group, but the early group also had higher-risk disease and were more likely to receive concurrent androgen deprivation therapy.
• In the long term, the early radiotherapy group experienced more pronounced recovery of sexual function, urinary irritation, and urinary incontinence than the late radiotherapy group.
• Ultimately, patients in the early radiotherapy group had similar, potentially better, long-term health-related quality-of-life domain scores than those in the late group over the long term. For instance, the likelihood of being pad free increased for patients treated early with radiation, while it decreased for those treated late. In patients who received early radiation, the rate of freedom from pad use increased from 39% before radiation to 67% at the sixth follow-up visit after radiation, while it decreased from 73% to 48% in those who received late radiation.

IN PRACTICE:

“Long-term patient-reported sexual, incontinence, and urinary irritative outcomes did not significantly differ between early vs late postprostatectomy [radiotherapy],” the authors said. In fact, “men receiving early [radiation] experienced greater recovery of these toxicity domains and achieved similar, and possibly better, domain scores as those receiving late [radiation] at long-term follow-up.” Overall, “these results may help guide treatment counseling and support consideration of early [radiotherapy] after prostatectomy for men at particularly high risk of recurrence and metastasis.”

SOURCE:

The study, led by Sagar A. Patel, MD, MSc, Emory University in Atlanta, was published online in JAMA Network Open.

LIMITATIONS:

The early and late postprostatectomy radiotherapy groups were relatively small and underpowered to detect statistically significant differences between groups. The study has a nonrandomized design, which may introduce unaccounted for imbalances among the different groups. The study did not directly compare health-related quality of life between patients receiving adjuvant vs salvage radiotherapy.

DISCLOSURES:

This study received funding from National Institutes of Health grants and the Paul Calabresi Career Development Award for Clinical Oncology. Several authors reported receiving personal fees, grants, and having other ties with various sources. Additional disclosures are noted in the original article.

A version of this article appeared on Medscape.com.

TOPLINE:

Low-dose oral minoxidil (LDOM), used off-label to treat alopecia, does not significantly affect blood pressure (BP) in patients with alopecia, but is associated with a slight increase in heart rate and a 5% incidence of hypotensive symptoms.

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis of 16 studies, which involved 2387 patients with alopecia (60.7% women) who received minoxidil, a vasodilator originally developed as an antihypertensive, at doses of 5 mg or less per day.
• Outcomes included changes in mean arterial pressure, systolic BP, diastolic BP, and heart rate.
• Mean differences were calculated between pretreatment and posttreatment values.

TAKEAWAY:

• Hypotensive symptoms were reported in 5% patients, with no significant hypotensive episodes. About 1.8% patients experienced lightheadedness or syncope, 1.2% experienced dizziness, 0.9% had tachycardia, and 0.8% had palpitations.
• LDOM did not significantly alter systolic BP (mean difference, –0.13; 95% CI, –2.67 to 2.41), diastolic BP (mean difference, –1.25; 95% CI, –3.21 to 0.71), and mean arterial pressure (mean difference, –1.92; 95% CI, –4.00 to 0.17).
• LDOM led to a significant increase in heart rate (mean difference, 2.67 beats/min; 95% CI, 0.34-5.01), a difference the authors wrote would “likely not be clinically significant for most patients.”
• Hypertrichosis was the most common side effect (59.6%) and reason for stopping treatment (accounting for nearly 35% of discontinuations).

IN PRACTICE:

“LDOM appears to be a safe treatment for alopecia with no significant impact on blood pressure,” the authors wrote, noting that the study “addresses gaps in clinical knowledge involving LDOM.” Based on their results, they recommended that BP and heart rate “do not need to be closely monitored in patients without prior cardiovascular risk history.”

SOURCE:

The study was led by Matthew Chen, BS, Stony Brook Dermatology in New York. It was published online in The Journal of the American Academy of Dermatology.

LIMITATIONS:

The studies included had small sample sizes and retrospective designs, which may limit the reliability of the findings. Additional limitations include the absence of control groups, a potential recall bias in adverse effect reporting, and variability in dosing regimens and BP monitoring. 

DISCLOSURES:

The authors reported no external funding or conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Low-dose oral minoxidil (LDOM), used off-label to treat alopecia, does not significantly affect blood pressure (BP) in patients with alopecia, but is associated with a slight increase in heart rate and a 5% incidence of hypotensive symptoms.

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis of 16 studies, which involved 2387 patients with alopecia (60.7% women) who received minoxidil, a vasodilator originally developed as an antihypertensive, at doses of 5 mg or less per day.
• Outcomes included changes in mean arterial pressure, systolic BP, diastolic BP, and heart rate.
• Mean differences were calculated between pretreatment and posttreatment values.

TAKEAWAY:

• Hypotensive symptoms were reported in 5% patients, with no significant hypotensive episodes. About 1.8% patients experienced lightheadedness or syncope, 1.2% experienced dizziness, 0.9% had tachycardia, and 0.8% had palpitations.
• LDOM did not significantly alter systolic BP (mean difference, –0.13; 95% CI, –2.67 to 2.41), diastolic BP (mean difference, –1.25; 95% CI, –3.21 to 0.71), and mean arterial pressure (mean difference, –1.92; 95% CI, –4.00 to 0.17).
• LDOM led to a significant increase in heart rate (mean difference, 2.67 beats/min; 95% CI, 0.34-5.01), a difference the authors wrote would “likely not be clinically significant for most patients.”
• Hypertrichosis was the most common side effect (59.6%) and reason for stopping treatment (accounting for nearly 35% of discontinuations).

IN PRACTICE:

“LDOM appears to be a safe treatment for alopecia with no significant impact on blood pressure,” the authors wrote, noting that the study “addresses gaps in clinical knowledge involving LDOM.” Based on their results, they recommended that BP and heart rate “do not need to be closely monitored in patients without prior cardiovascular risk history.”

SOURCE:

The study was led by Matthew Chen, BS, Stony Brook Dermatology in New York. It was published online in The Journal of the American Academy of Dermatology.

LIMITATIONS:

The studies included had small sample sizes and retrospective designs, which may limit the reliability of the findings. Additional limitations include the absence of control groups, a potential recall bias in adverse effect reporting, and variability in dosing regimens and BP monitoring. 

DISCLOSURES:

The authors reported no external funding or conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Low-dose oral minoxidil (LDOM), used off-label to treat alopecia, does not significantly affect blood pressure (BP) in patients with alopecia, but is associated with a slight increase in heart rate and a 5% incidence of hypotensive symptoms.

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis of 16 studies, which involved 2387 patients with alopecia (60.7% women) who received minoxidil, a vasodilator originally developed as an antihypertensive, at doses of 5 mg or less per day.
• Outcomes included changes in mean arterial pressure, systolic BP, diastolic BP, and heart rate.
• Mean differences were calculated between pretreatment and posttreatment values.

TAKEAWAY:

• Hypotensive symptoms were reported in 5% patients, with no significant hypotensive episodes. About 1.8% patients experienced lightheadedness or syncope, 1.2% experienced dizziness, 0.9% had tachycardia, and 0.8% had palpitations.
• LDOM did not significantly alter systolic BP (mean difference, –0.13; 95% CI, –2.67 to 2.41), diastolic BP (mean difference, –1.25; 95% CI, –3.21 to 0.71), and mean arterial pressure (mean difference, –1.92; 95% CI, –4.00 to 0.17).
• LDOM led to a significant increase in heart rate (mean difference, 2.67 beats/min; 95% CI, 0.34-5.01), a difference the authors wrote would “likely not be clinically significant for most patients.”
• Hypertrichosis was the most common side effect (59.6%) and reason for stopping treatment (accounting for nearly 35% of discontinuations).

IN PRACTICE:

“LDOM appears to be a safe treatment for alopecia with no significant impact on blood pressure,” the authors wrote, noting that the study “addresses gaps in clinical knowledge involving LDOM.” Based on their results, they recommended that BP and heart rate “do not need to be closely monitored in patients without prior cardiovascular risk history.”

SOURCE:

The study was led by Matthew Chen, BS, Stony Brook Dermatology in New York. It was published online in The Journal of the American Academy of Dermatology.

LIMITATIONS:

The studies included had small sample sizes and retrospective designs, which may limit the reliability of the findings. Additional limitations include the absence of control groups, a potential recall bias in adverse effect reporting, and variability in dosing regimens and BP monitoring. 

DISCLOSURES:

The authors reported no external funding or conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

The search for a better biomarker than creatine for acute kidney injury (AKI) has been “long and elusive.” However, could researchers be on the right path now?

“The thinking is moving away from trying to find one biomarker that can be used for different types of kidney injury to a recognition that AKI is not just a single disease that a patient has or doesn’t have,” Rob D. Nerenz, PhD, an associate professor in the Department of Pathology and Laboratory Medicine at the Medical College of Wisconsin, Milwaukee, told this news organization. “It’s lots of different diseases that all affect the kidney in different ways.”

AKI is actually a “loose collection” of hepatorenal, cardiorenal, nephrotoxic, and sepsis-associated syndromes, as well as acute interstitial nephritis (AIN), he said. “So the question is not: ‘Is AKI present — yes or no?’ It’s: ‘What kind of AKI is present, and how do I treat it?’ ”
 

‘Mediocre Markers’

AKI affects about 10%-30% of hospitalized patients, according to Nerenz. It’s associated with an increased risk for adverse outcomes, including post-AKI chronic kidney disease and a mortality rate of approximately 24%.

Currently, AKI is defined by a rapid increase in serum creatinine, a decrease in urine output, or both.

“Those are mediocre markers,” Nerenz said, as serum creatinine is not very sensitive to acute change, and the increase is often detected after the therapeutic window of intervention has passed. In addition, “it only tells us that the kidneys are unhappy; it doesn’t say anything about the cause.”

Urine output is limited as a marker because many conditions affect it. “If you’re dehydrated, urine output is going to decrease,” he said. “And in some forms of AKI, urine output actually goes up.”

What’s needed, he said, is a more sensitive biomarker that’s detectable within a shorter timeframe of 2-6 hours following injury.

“Right now, we’re looking at 48 hours before a change becomes apparent, and that’s just too long. Plus, it should be kidney specific. One of the major limitations of the biomarkers that have been evaluated to this point is that, yes, they’re released by the kidney, but they’re also released by other tissue types within the body, and that hinders their effectiveness as a marker.”
 

Neutrophil Gelatinase-Associated Lipocalin (NGAL)

Although research on better biomarkers is ongoing, “there’s also a recognition that some of the protein markers that have been around for a while, if used appropriately, can provide value,” Nerenz said. These include, among others, NGAL.

NGAL works well in pediatric patients without other comorbidities, but it has been less useful in adult patients because it is also released by other cell types. However, recent research suggests it shows promise in patients with both cirrhosis and AKI.

There are three main causes of AKI in cirrhosis, Nerenz explained. The first is prerenal and can be primarily addressed through rehydration.

“When these patients come in, clinicians won’t do anything right away other than provide fluids. If creatinine improves over the 48-hour period of fluid replenishment, then the patient is sent home because there really isn’t extensive damage to the kidneys.”

If improvement isn’t seen after those 48 hours, then it could be one of two things: Hepatorenal syndrome or acute tubular necrosis. Patients with hepatorenal syndrome are candidates for terlipressin, which the Food and Drug Administration (FDA) approved for this indication in 2022 after it displayed notable efficacy in a double-blind study.

“You don’t want to give terlipressin to just anybody because if the issue is not a diminished blood supply to the kidney, it’s not going to help, and comes with some serious side effects, such as respiratory failure,” Nerenz explained. “Having a biomarker that can distinguish between hepatorenal syndrome and acute tubular necrosis really helps clinicians confidently identify which patients are good candidates for this drug. Right now, we’re flying blind to a certain extent, basically using clinical intuition.”

Currently, the determination of NGAL is FDA cleared only for pediatric use. One way hospitals have dealt with that is by making the test in their own labs, using appropriate reagents, validation, and so forth. These tests are then safe for use in adults but haven’t gone through the FDA approval process.

However, the FDA’s recent announcement stating that the agency should oversee lab-developed tests has made this situation unclear, Nerenz said.

“At this point, we don’t know if there’s still an opportunity to take the NGAL test (or any other cleared biomarker) and validate it for use in a different patient population. Many hospital labs simply don’t have the resources to take these tests through the whole FDA approval process.”
 

A New Biomarker for AIN?

Meanwhile, research is also moving forward on a better biomarker for AIN, which is also under the AKI umbrella.

“It’s important to diagnose AIN because it has a very specific treatment,” Dennis G. Moledina, MD, PhD, Yale School of Medicine in New Haven, Connecticut, told this news organization.

“AIN is caused by a bunch of different medications, such as proton pump inhibitors, cancer drugs, nonsteroidal anti-inflammatory drugs, and antibiotics, so when someone has this condition, you have to stop potentially life-saving medications and give unnecessary and potentially toxic immunosuppressive drugs, like prednisone,” he said. “If you get the diagnosis wrong, you’re stopping vital drugs and giving immunosuppression for no reason. And if you miss the diagnosis, AIN can lead to permanent chronic kidney disease.”

“Right now, the only way to diagnose AIN is to do a kidney biopsy, which is risky because it can often lead to significant bleeding,” he said. “Some people can’t undergo a biopsy because they’re on medications that increase the risk of bleeding, and they can’t be stopped.”

Furthermore, he noted, “the longer a patient takes a drug that’s causing AIN without getting a diagnosis, the less the chances of recovery because the longer you let this kidney inflammation go on, the more fibrosis and permanent damage develops. So it is important to diagnose it as early as possible, and that’s again why we have a real need for a noninvasive biomarker that can be tested rapidly.”

Moledina and colleagues have been working on identifying a suitable biomarker for close to 10 years, the latest example of which is their 2023 study validating urinary CXCL9 as just such a marker.

“We’re most excited about CXCL9 because it’s already used to diagnose some other diseases in plasma,” Moledina said. “We think that we can convince labs to test it in urine.”

In an accompanying editorial, Mark Canney, PhD, and colleagues at the University of Ottawa and The Ottawa Hospital in Ontario, Canada, wrote that the CXCL9 study findings “are exciting because they provide a road map of where diagnostics can get to for this common, yet poorly identified and treated, cause of kidney damage. The need for a different approach can be readily identified from the fact that clinicians’ gestalt for diagnosing AIN was almost tantamount to tossing a coin (AUC, 0.57). CXCL9 alone outperformed not only the clinician’s prebiopsy suspicion but also an existing diagnostic model and other candidate biomarkers both in the discovery and external validation cohorts.”

Like NGAL, CXCL9 will have to go through the FDA approval process before it can be used for AIN. Therefore, it may be a few years before it can become routinely available, Moledina said.

Nevertheless, Nerenz added, “I think the next steps for AKI are probably continuing on this path of context-dependent, selective biomarker use. I anticipate that we’ll see ongoing development in this space, just expanding to a wider variety of clinical scenarios.”

Nerenz declared receiving research funding from Abbott Labs for evaluation of an AKI biomarker. Moledina is a co-inventor on a pending patent, “Methods and Systems for Diagnosis of Acute Interstitial Nephritis”; a cofounder of the diagnostics company Predict AIN; and a consultant for Biohaven.

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

The search for a better biomarker than creatine for acute kidney injury (AKI) has been “long and elusive.” However, could researchers be on the right path now?

“The thinking is moving away from trying to find one biomarker that can be used for different types of kidney injury to a recognition that AKI is not just a single disease that a patient has or doesn’t have,” Rob D. Nerenz, PhD, an associate professor in the Department of Pathology and Laboratory Medicine at the Medical College of Wisconsin, Milwaukee, told this news organization. “It’s lots of different diseases that all affect the kidney in different ways.”

AKI is actually a “loose collection” of hepatorenal, cardiorenal, nephrotoxic, and sepsis-associated syndromes, as well as acute interstitial nephritis (AIN), he said. “So the question is not: ‘Is AKI present — yes or no?’ It’s: ‘What kind of AKI is present, and how do I treat it?’ ”
 

‘Mediocre Markers’

AKI affects about 10%-30% of hospitalized patients, according to Nerenz. It’s associated with an increased risk for adverse outcomes, including post-AKI chronic kidney disease and a mortality rate of approximately 24%.

Currently, AKI is defined by a rapid increase in serum creatinine, a decrease in urine output, or both.

“Those are mediocre markers,” Nerenz said, as serum creatinine is not very sensitive to acute change, and the increase is often detected after the therapeutic window of intervention has passed. In addition, “it only tells us that the kidneys are unhappy; it doesn’t say anything about the cause.”

Urine output is limited as a marker because many conditions affect it. “If you’re dehydrated, urine output is going to decrease,” he said. “And in some forms of AKI, urine output actually goes up.”

What’s needed, he said, is a more sensitive biomarker that’s detectable within a shorter timeframe of 2-6 hours following injury.

“Right now, we’re looking at 48 hours before a change becomes apparent, and that’s just too long. Plus, it should be kidney specific. One of the major limitations of the biomarkers that have been evaluated to this point is that, yes, they’re released by the kidney, but they’re also released by other tissue types within the body, and that hinders their effectiveness as a marker.”
 

Neutrophil Gelatinase-Associated Lipocalin (NGAL)

Although research on better biomarkers is ongoing, “there’s also a recognition that some of the protein markers that have been around for a while, if used appropriately, can provide value,” Nerenz said. These include, among others, NGAL.

NGAL works well in pediatric patients without other comorbidities, but it has been less useful in adult patients because it is also released by other cell types. However, recent research suggests it shows promise in patients with both cirrhosis and AKI.

There are three main causes of AKI in cirrhosis, Nerenz explained. The first is prerenal and can be primarily addressed through rehydration.

“When these patients come in, clinicians won’t do anything right away other than provide fluids. If creatinine improves over the 48-hour period of fluid replenishment, then the patient is sent home because there really isn’t extensive damage to the kidneys.”

If improvement isn’t seen after those 48 hours, then it could be one of two things: Hepatorenal syndrome or acute tubular necrosis. Patients with hepatorenal syndrome are candidates for terlipressin, which the Food and Drug Administration (FDA) approved for this indication in 2022 after it displayed notable efficacy in a double-blind study.

“You don’t want to give terlipressin to just anybody because if the issue is not a diminished blood supply to the kidney, it’s not going to help, and comes with some serious side effects, such as respiratory failure,” Nerenz explained. “Having a biomarker that can distinguish between hepatorenal syndrome and acute tubular necrosis really helps clinicians confidently identify which patients are good candidates for this drug. Right now, we’re flying blind to a certain extent, basically using clinical intuition.”

Currently, the determination of NGAL is FDA cleared only for pediatric use. One way hospitals have dealt with that is by making the test in their own labs, using appropriate reagents, validation, and so forth. These tests are then safe for use in adults but haven’t gone through the FDA approval process.

However, the FDA’s recent announcement stating that the agency should oversee lab-developed tests has made this situation unclear, Nerenz said.

“At this point, we don’t know if there’s still an opportunity to take the NGAL test (or any other cleared biomarker) and validate it for use in a different patient population. Many hospital labs simply don’t have the resources to take these tests through the whole FDA approval process.”
 

A New Biomarker for AIN?

Meanwhile, research is also moving forward on a better biomarker for AIN, which is also under the AKI umbrella.

“It’s important to diagnose AIN because it has a very specific treatment,” Dennis G. Moledina, MD, PhD, Yale School of Medicine in New Haven, Connecticut, told this news organization.

“AIN is caused by a bunch of different medications, such as proton pump inhibitors, cancer drugs, nonsteroidal anti-inflammatory drugs, and antibiotics, so when someone has this condition, you have to stop potentially life-saving medications and give unnecessary and potentially toxic immunosuppressive drugs, like prednisone,” he said. “If you get the diagnosis wrong, you’re stopping vital drugs and giving immunosuppression for no reason. And if you miss the diagnosis, AIN can lead to permanent chronic kidney disease.”

“Right now, the only way to diagnose AIN is to do a kidney biopsy, which is risky because it can often lead to significant bleeding,” he said. “Some people can’t undergo a biopsy because they’re on medications that increase the risk of bleeding, and they can’t be stopped.”

Furthermore, he noted, “the longer a patient takes a drug that’s causing AIN without getting a diagnosis, the less the chances of recovery because the longer you let this kidney inflammation go on, the more fibrosis and permanent damage develops. So it is important to diagnose it as early as possible, and that’s again why we have a real need for a noninvasive biomarker that can be tested rapidly.”

Moledina and colleagues have been working on identifying a suitable biomarker for close to 10 years, the latest example of which is their 2023 study validating urinary CXCL9 as just such a marker.

“We’re most excited about CXCL9 because it’s already used to diagnose some other diseases in plasma,” Moledina said. “We think that we can convince labs to test it in urine.”

In an accompanying editorial, Mark Canney, PhD, and colleagues at the University of Ottawa and The Ottawa Hospital in Ontario, Canada, wrote that the CXCL9 study findings “are exciting because they provide a road map of where diagnostics can get to for this common, yet poorly identified and treated, cause of kidney damage. The need for a different approach can be readily identified from the fact that clinicians’ gestalt for diagnosing AIN was almost tantamount to tossing a coin (AUC, 0.57). CXCL9 alone outperformed not only the clinician’s prebiopsy suspicion but also an existing diagnostic model and other candidate biomarkers both in the discovery and external validation cohorts.”

Like NGAL, CXCL9 will have to go through the FDA approval process before it can be used for AIN. Therefore, it may be a few years before it can become routinely available, Moledina said.

Nevertheless, Nerenz added, “I think the next steps for AKI are probably continuing on this path of context-dependent, selective biomarker use. I anticipate that we’ll see ongoing development in this space, just expanding to a wider variety of clinical scenarios.”

Nerenz declared receiving research funding from Abbott Labs for evaluation of an AKI biomarker. Moledina is a co-inventor on a pending patent, “Methods and Systems for Diagnosis of Acute Interstitial Nephritis”; a cofounder of the diagnostics company Predict AIN; and a consultant for Biohaven.

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

The search for a better biomarker than creatine for acute kidney injury (AKI) has been “long and elusive.” However, could researchers be on the right path now?

“The thinking is moving away from trying to find one biomarker that can be used for different types of kidney injury to a recognition that AKI is not just a single disease that a patient has or doesn’t have,” Rob D. Nerenz, PhD, an associate professor in the Department of Pathology and Laboratory Medicine at the Medical College of Wisconsin, Milwaukee, told this news organization. “It’s lots of different diseases that all affect the kidney in different ways.”

AKI is actually a “loose collection” of hepatorenal, cardiorenal, nephrotoxic, and sepsis-associated syndromes, as well as acute interstitial nephritis (AIN), he said. “So the question is not: ‘Is AKI present — yes or no?’ It’s: ‘What kind of AKI is present, and how do I treat it?’ ”
 

‘Mediocre Markers’

AKI affects about 10%-30% of hospitalized patients, according to Nerenz. It’s associated with an increased risk for adverse outcomes, including post-AKI chronic kidney disease and a mortality rate of approximately 24%.

Currently, AKI is defined by a rapid increase in serum creatinine, a decrease in urine output, or both.

“Those are mediocre markers,” Nerenz said, as serum creatinine is not very sensitive to acute change, and the increase is often detected after the therapeutic window of intervention has passed. In addition, “it only tells us that the kidneys are unhappy; it doesn’t say anything about the cause.”

Urine output is limited as a marker because many conditions affect it. “If you’re dehydrated, urine output is going to decrease,” he said. “And in some forms of AKI, urine output actually goes up.”

What’s needed, he said, is a more sensitive biomarker that’s detectable within a shorter timeframe of 2-6 hours following injury.

“Right now, we’re looking at 48 hours before a change becomes apparent, and that’s just too long. Plus, it should be kidney specific. One of the major limitations of the biomarkers that have been evaluated to this point is that, yes, they’re released by the kidney, but they’re also released by other tissue types within the body, and that hinders their effectiveness as a marker.”
 

Neutrophil Gelatinase-Associated Lipocalin (NGAL)

Although research on better biomarkers is ongoing, “there’s also a recognition that some of the protein markers that have been around for a while, if used appropriately, can provide value,” Nerenz said. These include, among others, NGAL.

NGAL works well in pediatric patients without other comorbidities, but it has been less useful in adult patients because it is also released by other cell types. However, recent research suggests it shows promise in patients with both cirrhosis and AKI.

There are three main causes of AKI in cirrhosis, Nerenz explained. The first is prerenal and can be primarily addressed through rehydration.

“When these patients come in, clinicians won’t do anything right away other than provide fluids. If creatinine improves over the 48-hour period of fluid replenishment, then the patient is sent home because there really isn’t extensive damage to the kidneys.”

If improvement isn’t seen after those 48 hours, then it could be one of two things: Hepatorenal syndrome or acute tubular necrosis. Patients with hepatorenal syndrome are candidates for terlipressin, which the Food and Drug Administration (FDA) approved for this indication in 2022 after it displayed notable efficacy in a double-blind study.

“You don’t want to give terlipressin to just anybody because if the issue is not a diminished blood supply to the kidney, it’s not going to help, and comes with some serious side effects, such as respiratory failure,” Nerenz explained. “Having a biomarker that can distinguish between hepatorenal syndrome and acute tubular necrosis really helps clinicians confidently identify which patients are good candidates for this drug. Right now, we’re flying blind to a certain extent, basically using clinical intuition.”

Currently, the determination of NGAL is FDA cleared only for pediatric use. One way hospitals have dealt with that is by making the test in their own labs, using appropriate reagents, validation, and so forth. These tests are then safe for use in adults but haven’t gone through the FDA approval process.

However, the FDA’s recent announcement stating that the agency should oversee lab-developed tests has made this situation unclear, Nerenz said.

“At this point, we don’t know if there’s still an opportunity to take the NGAL test (or any other cleared biomarker) and validate it for use in a different patient population. Many hospital labs simply don’t have the resources to take these tests through the whole FDA approval process.”
 

A New Biomarker for AIN?

Meanwhile, research is also moving forward on a better biomarker for AIN, which is also under the AKI umbrella.

“It’s important to diagnose AIN because it has a very specific treatment,” Dennis G. Moledina, MD, PhD, Yale School of Medicine in New Haven, Connecticut, told this news organization.

“AIN is caused by a bunch of different medications, such as proton pump inhibitors, cancer drugs, nonsteroidal anti-inflammatory drugs, and antibiotics, so when someone has this condition, you have to stop potentially life-saving medications and give unnecessary and potentially toxic immunosuppressive drugs, like prednisone,” he said. “If you get the diagnosis wrong, you’re stopping vital drugs and giving immunosuppression for no reason. And if you miss the diagnosis, AIN can lead to permanent chronic kidney disease.”

“Right now, the only way to diagnose AIN is to do a kidney biopsy, which is risky because it can often lead to significant bleeding,” he said. “Some people can’t undergo a biopsy because they’re on medications that increase the risk of bleeding, and they can’t be stopped.”

Furthermore, he noted, “the longer a patient takes a drug that’s causing AIN without getting a diagnosis, the less the chances of recovery because the longer you let this kidney inflammation go on, the more fibrosis and permanent damage develops. So it is important to diagnose it as early as possible, and that’s again why we have a real need for a noninvasive biomarker that can be tested rapidly.”

Moledina and colleagues have been working on identifying a suitable biomarker for close to 10 years, the latest example of which is their 2023 study validating urinary CXCL9 as just such a marker.

“We’re most excited about CXCL9 because it’s already used to diagnose some other diseases in plasma,” Moledina said. “We think that we can convince labs to test it in urine.”

In an accompanying editorial, Mark Canney, PhD, and colleagues at the University of Ottawa and The Ottawa Hospital in Ontario, Canada, wrote that the CXCL9 study findings “are exciting because they provide a road map of where diagnostics can get to for this common, yet poorly identified and treated, cause of kidney damage. The need for a different approach can be readily identified from the fact that clinicians’ gestalt for diagnosing AIN was almost tantamount to tossing a coin (AUC, 0.57). CXCL9 alone outperformed not only the clinician’s prebiopsy suspicion but also an existing diagnostic model and other candidate biomarkers both in the discovery and external validation cohorts.”

Like NGAL, CXCL9 will have to go through the FDA approval process before it can be used for AIN. Therefore, it may be a few years before it can become routinely available, Moledina said.

Nevertheless, Nerenz added, “I think the next steps for AKI are probably continuing on this path of context-dependent, selective biomarker use. I anticipate that we’ll see ongoing development in this space, just expanding to a wider variety of clinical scenarios.”

Nerenz declared receiving research funding from Abbott Labs for evaluation of an AKI biomarker. Moledina is a co-inventor on a pending patent, “Methods and Systems for Diagnosis of Acute Interstitial Nephritis”; a cofounder of the diagnostics company Predict AIN; and a consultant for Biohaven.

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

TOPLINE:

Heat waves are associated with an increase in heat-related emergency department visits, hospitalizations, and deaths among dually eligible individuals older than 65 years.

METHODOLOGY:

• The researchers conducted a retrospective time-series study using national Medicare and Medicaid data from 2016 to 2019 to assess the link between heat waves during warm months and adverse health events.
• A total of 5,448,499 dually eligible individuals (66% women; 20% aged ≥ 85 years) were included from 28,404 zip code areas across 50 states and Washington, DC.
• Heat waves were defined as three or more consecutive days of extreme heat with a maximum temperature of at least 90 °F and within the 97th percentile of daily maximum temperatures for each zip code.
• Primary outcomes were daily counts of heat-related emergency department visits and hospitalizations.
• Secondary outcomes were all-cause and heat-specific emergency department visits, all-cause and heat-specific hospitalizations, deaths, and long-term nursing facility placements within 3 months after a heat wave.

TAKEAWAY:

• Heat waves were associated with a 10% increase in heat-related emergency department visits (incidence rate ratio [IRR], 1.10; 95% CI, 1.08-1.12) and a 7% increase in heat-related hospitalizations (IRR, 1.07; 95% CI, 1.04-1.09).
• Mortality rates were 4% higher during heat wave days than during non–heat wave days (IRR, 1.04; 95% CI, 1.01-1.07).
• No significant difference was found in rates of long-term nursing facility placements or heat-related emergency department visits for nursing facility residents.
• All racial and ethnic groups showed higher incidence rates of heat-related emergency department visits during heat waves, especially among beneficiaries identified as Asian (IRR, 1.21; 95% CI, 1.12-1.29). Rates were higher among individuals residing in the Northwest, Ohio Valley, and the West.

IN PRACTICE:

“In healthcare settings, clinicians should incorporate routine heat wave risk assessments into clinical practice, especially in regions more susceptible to extreme heat, for all dual-eligible beneficiaries and other at-risk patients,” wrote Jose F. Figueroa, MD, MPH, of the Harvard T.H. Chan School of Public Health in Boston, in an invited commentary. “Beyond offering preventive advice, clinicians can adjust medications that may increase their patients’ susceptibility during heat waves, or they can refer patients to social workers and social service organizations to ensure that they are protected at home.”

SOURCE:

This study was led by Hyunjee Kim, PhD, of the Center for Health Systems Effectiveness at Oregon Health & Science University, Portland. It was published online in JAMA Health Forum.

LIMITATIONS:

This study relied on a claims database to identify adverse events, which may have led to omissions in coding, particularly for heat-related conditions if the diagnostic codes for heat-related symptoms had not been adopted. This study did not adjust for variations in air quality or green space, which could have confounded the association of interest. Indoor heat exposures or adaptive behaviors, such as air conditioning use, were not considered. The analysis could not compare the association of heat waves with adverse events between those with dual eligibility and those without dual eligibility.

DISCLOSURES:

This study was supported by the National Institute on Aging. One author reported receiving grants from the National Institutes of Health outside the submitted work. No other disclosures were reported.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Heat waves are associated with an increase in heat-related emergency department visits, hospitalizations, and deaths among dually eligible individuals older than 65 years.

METHODOLOGY:

• The researchers conducted a retrospective time-series study using national Medicare and Medicaid data from 2016 to 2019 to assess the link between heat waves during warm months and adverse health events.
• A total of 5,448,499 dually eligible individuals (66% women; 20% aged ≥ 85 years) were included from 28,404 zip code areas across 50 states and Washington, DC.
• Heat waves were defined as three or more consecutive days of extreme heat with a maximum temperature of at least 90 °F and within the 97th percentile of daily maximum temperatures for each zip code.
• Primary outcomes were daily counts of heat-related emergency department visits and hospitalizations.
• Secondary outcomes were all-cause and heat-specific emergency department visits, all-cause and heat-specific hospitalizations, deaths, and long-term nursing facility placements within 3 months after a heat wave.

TAKEAWAY:

• Heat waves were associated with a 10% increase in heat-related emergency department visits (incidence rate ratio [IRR], 1.10; 95% CI, 1.08-1.12) and a 7% increase in heat-related hospitalizations (IRR, 1.07; 95% CI, 1.04-1.09).
• Mortality rates were 4% higher during heat wave days than during non–heat wave days (IRR, 1.04; 95% CI, 1.01-1.07).
• No significant difference was found in rates of long-term nursing facility placements or heat-related emergency department visits for nursing facility residents.
• All racial and ethnic groups showed higher incidence rates of heat-related emergency department visits during heat waves, especially among beneficiaries identified as Asian (IRR, 1.21; 95% CI, 1.12-1.29). Rates were higher among individuals residing in the Northwest, Ohio Valley, and the West.

IN PRACTICE:

“In healthcare settings, clinicians should incorporate routine heat wave risk assessments into clinical practice, especially in regions more susceptible to extreme heat, for all dual-eligible beneficiaries and other at-risk patients,” wrote Jose F. Figueroa, MD, MPH, of the Harvard T.H. Chan School of Public Health in Boston, in an invited commentary. “Beyond offering preventive advice, clinicians can adjust medications that may increase their patients’ susceptibility during heat waves, or they can refer patients to social workers and social service organizations to ensure that they are protected at home.”

SOURCE:

This study was led by Hyunjee Kim, PhD, of the Center for Health Systems Effectiveness at Oregon Health & Science University, Portland. It was published online in JAMA Health Forum.

LIMITATIONS:

This study relied on a claims database to identify adverse events, which may have led to omissions in coding, particularly for heat-related conditions if the diagnostic codes for heat-related symptoms had not been adopted. This study did not adjust for variations in air quality or green space, which could have confounded the association of interest. Indoor heat exposures or adaptive behaviors, such as air conditioning use, were not considered. The analysis could not compare the association of heat waves with adverse events between those with dual eligibility and those without dual eligibility.

DISCLOSURES:

This study was supported by the National Institute on Aging. One author reported receiving grants from the National Institutes of Health outside the submitted work. No other disclosures were reported.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Heat waves are associated with an increase in heat-related emergency department visits, hospitalizations, and deaths among dually eligible individuals older than 65 years.

METHODOLOGY:

• The researchers conducted a retrospective time-series study using national Medicare and Medicaid data from 2016 to 2019 to assess the link between heat waves during warm months and adverse health events.
• A total of 5,448,499 dually eligible individuals (66% women; 20% aged ≥ 85 years) were included from 28,404 zip code areas across 50 states and Washington, DC.
• Heat waves were defined as three or more consecutive days of extreme heat with a maximum temperature of at least 90 °F and within the 97th percentile of daily maximum temperatures for each zip code.
• Primary outcomes were daily counts of heat-related emergency department visits and hospitalizations.
• Secondary outcomes were all-cause and heat-specific emergency department visits, all-cause and heat-specific hospitalizations, deaths, and long-term nursing facility placements within 3 months after a heat wave.

TAKEAWAY:

• Heat waves were associated with a 10% increase in heat-related emergency department visits (incidence rate ratio [IRR], 1.10; 95% CI, 1.08-1.12) and a 7% increase in heat-related hospitalizations (IRR, 1.07; 95% CI, 1.04-1.09).
• Mortality rates were 4% higher during heat wave days than during non–heat wave days (IRR, 1.04; 95% CI, 1.01-1.07).
• No significant difference was found in rates of long-term nursing facility placements or heat-related emergency department visits for nursing facility residents.
• All racial and ethnic groups showed higher incidence rates of heat-related emergency department visits during heat waves, especially among beneficiaries identified as Asian (IRR, 1.21; 95% CI, 1.12-1.29). Rates were higher among individuals residing in the Northwest, Ohio Valley, and the West.

IN PRACTICE:

“In healthcare settings, clinicians should incorporate routine heat wave risk assessments into clinical practice, especially in regions more susceptible to extreme heat, for all dual-eligible beneficiaries and other at-risk patients,” wrote Jose F. Figueroa, MD, MPH, of the Harvard T.H. Chan School of Public Health in Boston, in an invited commentary. “Beyond offering preventive advice, clinicians can adjust medications that may increase their patients’ susceptibility during heat waves, or they can refer patients to social workers and social service organizations to ensure that they are protected at home.”

SOURCE:

This study was led by Hyunjee Kim, PhD, of the Center for Health Systems Effectiveness at Oregon Health & Science University, Portland. It was published online in JAMA Health Forum.

LIMITATIONS:

This study relied on a claims database to identify adverse events, which may have led to omissions in coding, particularly for heat-related conditions if the diagnostic codes for heat-related symptoms had not been adopted. This study did not adjust for variations in air quality or green space, which could have confounded the association of interest. Indoor heat exposures or adaptive behaviors, such as air conditioning use, were not considered. The analysis could not compare the association of heat waves with adverse events between those with dual eligibility and those without dual eligibility.

DISCLOSURES:

This study was supported by the National Institute on Aging. One author reported receiving grants from the National Institutes of Health outside the submitted work. No other disclosures were reported.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

“Cortisol” has become a household word, popularized by social media and tagged in videos that garnered nearly 800 million views in 2023. This is linked to the also-trending term “moon face,” which TikTok influencers and others have suggested is caused by high cortisol levels and, conversely, can be reduced through stress reduction.

Although it’s true that cortisol is a hormone associated with stress, elevated stress levels are unlikely, by themselves, to cause the rounded facial features associated with “moon face.”

“When we hear the term ‘moon face,’ we’re typically referring to Cushing syndrome [CS] or treatment with prolonged high-dose glucocorticoids,” said Anat Ben-Shlomo, MD, co-director of the Multidisciplinary Adrenal Program, Pituitary Center, Division of Endocrinology, Diabetes and Metabolism at Cedars-Sinai Medical Center, Los Angeles. Medscape Medical News previously discussed moon face in an article detailing how to diagnose CS.

Ben-Shlomo noted that the labels “moon face” and “moon facies” should be avoided for their potentially derogatory, unprofessional-sounding connotations, and that the preferred terms are “rounded face” or “round plethoric face.”

There are several disorders that can be associated with facial roundness, not all of which relate to elevated cortisol.

“It’s important for clinicians to be able distinguish between presentations due to other pathophysiologies, identify the unique constellation of Cushing-associated signs and symptoms, engage in a differential diagnosis, and treat whatever the condition is appropriately,” Katherine Sherif, MD, professor and vice chair of academic affairs, Department of Medicine, Thomas Jefferson University, Philadelphia, said in an interview.
 

The Unique Presentation of CS

CS results from “prolonged elevation” in plasma cortisol levels caused by either exogenous steroid use or excess endogenous steroid production.

“The shape of the face isn’t the only feature associated with CS,” Ben-Shlomo said. “There’s central obesity, particularly in the neck, supraclavicular area, chest, and abdomen. You sometimes see a posterior cervical thoracic fat pad, colloquially — but unprofessionally — called a ‘cervical hump.’ Simultaneously, the arms and legs are getting thinner.” The development of a round, plethoric face is common in long-standing significant CS, and a reddening of the skin can appear.

Additional symptoms include hirsutism and acne. “These can also be seen in other conditions, such as PCOS [polycystic ovary syndrome] but, combined with the other facial features, are more suggestive of CS,” Ben-Shlomo said.

Deep, wide purple striae appear in the trunk, breast, upper arms, and thighs, but not in the face, Ben-Shlomo advised. These appear as the fragile, thinning under-skin breaks when the patient gains weight.

Additional metabolic issues that can occur comorbidly include insulin resistance and diabetes, hypertension, osteoporosis, dyslipidemia, ecchymoses, increased susceptibility to infections, mood changes, cognitive dysfunction, low libido, infertility, weakness of muscles in the shoulders and thighs, episodes of bleeding and/or clotting, and an increased risk for heart attacks and strokes, Ben-Shlomo said.

“Not everyone presents with full-blown disease, but if you see any of these symptoms, be suspicious of CS and conduct a biochemical evaluation.” Three screening tests to use as a starting point are recommended by the Pituitary Society’s updated Consensus on Diagnosis and Management of Cushing’s Disease. The tests should be repeated to account for intra-patient variability. If two or all three tests are positive, clinicians should be suspicious of CS and move to additional testing to identify the underlying cause, Ben-Shlomo said.
 

‘Subclinical’ CS

Ben-Shlomo highlighted a condition called minimal autonomous cortisol secretion (formerly “subclinical CS”). “This condition is found when a person has an adrenal nodule that produces cortisol in excess, however not to levels observed in CS. An abnormal finding on the overnight 1-mg low-dose dexamethasone suppression test (LDDST) will identify this disorder, showing mildly unsuppressed morning cortisol level, while all other tests will be within normal range.”

She described minimal autonomous cortisol secretion as a form of “smoldering CS,” which has become more commonly diagnosed. “The condition needs to be treated because the patient can develop insulin resistance, metabolic syndrome, and osteoporosis over time.”

Once a cause has been determined, the optimal course of action is to take a multidisciplinary approach because CS affects multiple systems.
 

‘Pseudo-Cushing Syndrome’

A variety of abnormalities of the hypothalamus-pituitary adrenal (HPA) axis can be associated with hypercortisolemia and a rounder facial appearance but aren’t actually CS, Ben-Shlomo said.

Often called “pseudo-Cushing syndrome,” these conditions have recently been renamed “non-neoplastic hypercortisolism” or “physiologic non-neoplastic endogenous hypercortisolism.” They share some clinical and biochemical features of CS, but the hypercortisolemia is usually secondary to other factors. They increase the secretion of hypothalamic corticotropin-releasing hormone, which stimulates adrenocorticotropic hormone (ACTH) and adrenal cortisol secretion.
 

Identifying PCOS

PCOS is often associated with central obesity, Sherif noted, but not all women with PCOS have overweight or a central distribution of fat.

“Ask about menstrual periods and whether they come monthly,” Sherif advised. “If women using hormonal contraception say they have a regular cycle, ask if their cycle was regular prior to starting contraception. So many women with PCOS are undiagnosed because they started contraception in their teens to ‘regulate their periods’ and never realized they had PCOS.”

Additional symptoms of PCOS and its impact are found in the figure below.

Medscape

• Irregular menstrual cycles
• Clinical hyperandrogenism or biochemical hyperandrogenism
• Polycystic ovarian morphology on transvaginal ultrasonography or high anti-mullerian hormone (applicable only if patient is ≥ 8 years from menarche)

If PCOS is suspected, further tests can be conducted to confirm or rule out the diagnosis.