Peripheral Vascular Disorders

TOPLINE:

Rituximab and cyclophosphamide are equally effective in achieving remission or low disease activity rates in childhood-onset antineutrophil cytoplasmic antibody–associated vasculitis (AAV), and those who received rituximab required a significantly lower steroid dose than those who received cyclophosphamide or a combination therapy.

METHODOLOGY:

• Researchers evaluated the efficacy of rituximab, cyclophosphamide, or a combination of both in pediatric patients diagnosed with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis.
• A total of 104 patients (median age at diagnosis, 14 years; 67% girls) were included from A Registry of Childhood Vasculitis; the majority had a diagnosis of GPA (81%) and renal involvement (87%). Overall, induction therapy involved rituximab for 43%, cyclophosphamide for 46%, and a combination of both for 11% patients.
• The primary endpoint was the rate of achieving remission (Pediatric Vasculitis Activity Score [PVAS] of 0) or low disease activity (PVAS ≤ 2) at the post-induction visit (4-6 months after diagnosis).
• The secondary endpoints were the degree of disease-related damage at 12- and 24-month visits and rates of drug-related hospitalization occurring between the diagnosis and post-induction visits.

TAKEAWAY:

• At the post-induction visit, 63% patients achieved remission or low disease activity, with the rates being similar between patients who received rituximab and those who received cyclophosphamide (64% vs 62%).
• Patients treated with rituximab required a significantly lower median steroid dose (0.13 mg/kg per day) than those treated with cyclophosphamide (0.3 mg/kg per day) or the combination therapy (0.3 mg/kg per day; P < .001) at the post-induction visit.
• Overall, 61% and 56% patients receiving rituximab and cyclophosphamide, respectively, had disease-related damage measure on the Pediatric Vasculitis Damage Index at the 12-month visit; however, the degree of damage was low.
• The percentage of patients requiring hospitalization was higher in the rituximab group than in the cyclophosphamide group (22% vs 10%), primarily stemming from drug- or infection-related causes (11% vs 2%).

IN PRACTICE:

“The results of this study may assist with current clinical decision-making with regard to the choice of induction medications in childhood-onset AAV and will complement the ongoing [Childhood Arthritis and Rheumatology Research Alliance] prospective [consensus treatment plans] study,” the authors wrote.

SOURCE:

This study was led by Samuel J. Gagne, MD, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center in Pennsylvania, and was published online in Arthritis Care & Research.

LIMITATIONS:

Study limitations included the inconsistencies in glucocorticoid dosing, which may have affected remission rates. Moreover, data on the adverse events not requiring hospitalization and long-term adverse events were not captured.

DISCLOSURES:

This study received funding through a Nationwide Children’s Hospital intramural grant award. The authors reported no potential 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:

Rituximab and cyclophosphamide are equally effective in achieving remission or low disease activity rates in childhood-onset antineutrophil cytoplasmic antibody–associated vasculitis (AAV), and those who received rituximab required a significantly lower steroid dose than those who received cyclophosphamide or a combination therapy.

METHODOLOGY:

• Researchers evaluated the efficacy of rituximab, cyclophosphamide, or a combination of both in pediatric patients diagnosed with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis.
• A total of 104 patients (median age at diagnosis, 14 years; 67% girls) were included from A Registry of Childhood Vasculitis; the majority had a diagnosis of GPA (81%) and renal involvement (87%). Overall, induction therapy involved rituximab for 43%, cyclophosphamide for 46%, and a combination of both for 11% patients.
• The primary endpoint was the rate of achieving remission (Pediatric Vasculitis Activity Score [PVAS] of 0) or low disease activity (PVAS ≤ 2) at the post-induction visit (4-6 months after diagnosis).
• The secondary endpoints were the degree of disease-related damage at 12- and 24-month visits and rates of drug-related hospitalization occurring between the diagnosis and post-induction visits.

TAKEAWAY:

• At the post-induction visit, 63% patients achieved remission or low disease activity, with the rates being similar between patients who received rituximab and those who received cyclophosphamide (64% vs 62%).
• Patients treated with rituximab required a significantly lower median steroid dose (0.13 mg/kg per day) than those treated with cyclophosphamide (0.3 mg/kg per day) or the combination therapy (0.3 mg/kg per day; P < .001) at the post-induction visit.
• Overall, 61% and 56% patients receiving rituximab and cyclophosphamide, respectively, had disease-related damage measure on the Pediatric Vasculitis Damage Index at the 12-month visit; however, the degree of damage was low.
• The percentage of patients requiring hospitalization was higher in the rituximab group than in the cyclophosphamide group (22% vs 10%), primarily stemming from drug- or infection-related causes (11% vs 2%).

IN PRACTICE:

“The results of this study may assist with current clinical decision-making with regard to the choice of induction medications in childhood-onset AAV and will complement the ongoing [Childhood Arthritis and Rheumatology Research Alliance] prospective [consensus treatment plans] study,” the authors wrote.

SOURCE:

This study was led by Samuel J. Gagne, MD, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center in Pennsylvania, and was published online in Arthritis Care & Research.

LIMITATIONS:

Study limitations included the inconsistencies in glucocorticoid dosing, which may have affected remission rates. Moreover, data on the adverse events not requiring hospitalization and long-term adverse events were not captured.

DISCLOSURES:

This study received funding through a Nationwide Children’s Hospital intramural grant award. The authors reported no potential 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:

Rituximab and cyclophosphamide are equally effective in achieving remission or low disease activity rates in childhood-onset antineutrophil cytoplasmic antibody–associated vasculitis (AAV), and those who received rituximab required a significantly lower steroid dose than those who received cyclophosphamide or a combination therapy.

METHODOLOGY:

• Researchers evaluated the efficacy of rituximab, cyclophosphamide, or a combination of both in pediatric patients diagnosed with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis.
• A total of 104 patients (median age at diagnosis, 14 years; 67% girls) were included from A Registry of Childhood Vasculitis; the majority had a diagnosis of GPA (81%) and renal involvement (87%). Overall, induction therapy involved rituximab for 43%, cyclophosphamide for 46%, and a combination of both for 11% patients.
• The primary endpoint was the rate of achieving remission (Pediatric Vasculitis Activity Score [PVAS] of 0) or low disease activity (PVAS ≤ 2) at the post-induction visit (4-6 months after diagnosis).
• The secondary endpoints were the degree of disease-related damage at 12- and 24-month visits and rates of drug-related hospitalization occurring between the diagnosis and post-induction visits.

TAKEAWAY:

• At the post-induction visit, 63% patients achieved remission or low disease activity, with the rates being similar between patients who received rituximab and those who received cyclophosphamide (64% vs 62%).
• Patients treated with rituximab required a significantly lower median steroid dose (0.13 mg/kg per day) than those treated with cyclophosphamide (0.3 mg/kg per day) or the combination therapy (0.3 mg/kg per day; P < .001) at the post-induction visit.
• Overall, 61% and 56% patients receiving rituximab and cyclophosphamide, respectively, had disease-related damage measure on the Pediatric Vasculitis Damage Index at the 12-month visit; however, the degree of damage was low.
• The percentage of patients requiring hospitalization was higher in the rituximab group than in the cyclophosphamide group (22% vs 10%), primarily stemming from drug- or infection-related causes (11% vs 2%).

IN PRACTICE:

“The results of this study may assist with current clinical decision-making with regard to the choice of induction medications in childhood-onset AAV and will complement the ongoing [Childhood Arthritis and Rheumatology Research Alliance] prospective [consensus treatment plans] study,” the authors wrote.

SOURCE:

This study was led by Samuel J. Gagne, MD, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center in Pennsylvania, and was published online in Arthritis Care & Research.

LIMITATIONS:

Study limitations included the inconsistencies in glucocorticoid dosing, which may have affected remission rates. Moreover, data on the adverse events not requiring hospitalization and long-term adverse events were not captured.

DISCLOSURES:

This study received funding through a Nationwide Children’s Hospital intramural grant award. The authors reported no potential 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.

“Petechial rash often prompts further investigation into hematological, dermatological, or vasculitis causes. However, if the above investigations are negative and skin biopsy has not revealed a cause, there is a Renaissance-era diagnosis that is often overlooked but is easily investigated and treated,” wrote Andrew Dermawan, MD, and colleagues from Sir Charles Gairdner Hospital in Nedlands, Australia, in BMJ Case Reports. The diagnosis they highlight is scurvy, a disease that has faded from common medical concern but is reemerging, partly because of the rise in bariatric surgery.

Diagnosing Scurvy in the 2020s

In their article, Dermawan and colleagues present the case of a 50-year-old man with a bilateral petechial rash on his lower limbs, without any history of trauma. The patient, who exhibited no infectious symptoms, also had gross hematuria, microcytic anemia, mild neutropenia, and lymphopenia. Tests for autoimmune and hematological diseases were negative, as were abdominal and leg CT scans, ruling out abdominal hemorrhage and vasculitis. Additionally, a skin biopsy showed no causative findings.

The doctors noted that the patient had undergone sleeve gastrectomy, prompting them to inquire about his diet. They discovered that, because of financial difficulties, his diet primarily consisted of processed foods with little to no fruits or vegetables, and he had stopped taking supplements recommended by his gastroenterologist. Further tests revealed a vitamin D deficiency and a severe deficiency in vitamin C. With the diagnosis of scurvy confirmed, the doctors treated the patient with 1000 mg of ascorbic acid daily, along with cholecalciferol, folic acid, and a multivitamin complex, leading to a complete resolution of his symptoms.
 

Risk Factors Then and Now

Scurvy can present with a range of symptoms, including petechiae, perifollicular hemorrhage, ecchymosis, gingivitis, edema, anemia, delayed wound healing, malaise, weakness, joint swelling, arthralgia, anorexia, neuropathy, and vasomotor instability. It can cause mucosal and gastric hemorrhages, and if left untreated, it can lead to fatal bleeding.

Historically known as “sailors’ disease,” scurvy plagued men on long voyages who lacked access to fresh fruits or vegetables and thus did not get enough vitamin C. In 1747, James Lind, a British physician in the Royal Navy, demonstrated that the consumption of oranges and lemons could combat scurvy.

Today’s risk factors for scurvy include malnutrition, gastrointestinal disorders (eg, chronic inflammatory bowel diseases), alcohol and tobacco use, eating disorders, psychiatric illnesses, dialysis, and the use of medications that reduce the absorption of ascorbic acid (such as corticosteroids and proton pump inhibitors).

Scurvy remains more common among individuals with unfavorable socioeconomic conditions. The authors of the study emphasize how the rising cost of living — specifically in Australia but applicable elsewhere — is changing eating habits, leading to a high consumption of low-cost, nutritionally poor foods.

Poverty has always been a risk factor for scurvy, but today there may be an additional cause: bariatric surgery. Patients undergoing these procedures are at a risk for deficiencies in fat-soluble vitamins A, D, E, and K, and if their diet is inadequate, they may also experience a vitamin C deficiency. Awareness of this can facilitate the timely diagnosis of scurvy in these patients.

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

“Petechial rash often prompts further investigation into hematological, dermatological, or vasculitis causes. However, if the above investigations are negative and skin biopsy has not revealed a cause, there is a Renaissance-era diagnosis that is often overlooked but is easily investigated and treated,” wrote Andrew Dermawan, MD, and colleagues from Sir Charles Gairdner Hospital in Nedlands, Australia, in BMJ Case Reports. The diagnosis they highlight is scurvy, a disease that has faded from common medical concern but is reemerging, partly because of the rise in bariatric surgery.

Diagnosing Scurvy in the 2020s

In their article, Dermawan and colleagues present the case of a 50-year-old man with a bilateral petechial rash on his lower limbs, without any history of trauma. The patient, who exhibited no infectious symptoms, also had gross hematuria, microcytic anemia, mild neutropenia, and lymphopenia. Tests for autoimmune and hematological diseases were negative, as were abdominal and leg CT scans, ruling out abdominal hemorrhage and vasculitis. Additionally, a skin biopsy showed no causative findings.

The doctors noted that the patient had undergone sleeve gastrectomy, prompting them to inquire about his diet. They discovered that, because of financial difficulties, his diet primarily consisted of processed foods with little to no fruits or vegetables, and he had stopped taking supplements recommended by his gastroenterologist. Further tests revealed a vitamin D deficiency and a severe deficiency in vitamin C. With the diagnosis of scurvy confirmed, the doctors treated the patient with 1000 mg of ascorbic acid daily, along with cholecalciferol, folic acid, and a multivitamin complex, leading to a complete resolution of his symptoms.
 

Risk Factors Then and Now

Scurvy can present with a range of symptoms, including petechiae, perifollicular hemorrhage, ecchymosis, gingivitis, edema, anemia, delayed wound healing, malaise, weakness, joint swelling, arthralgia, anorexia, neuropathy, and vasomotor instability. It can cause mucosal and gastric hemorrhages, and if left untreated, it can lead to fatal bleeding.

Historically known as “sailors’ disease,” scurvy plagued men on long voyages who lacked access to fresh fruits or vegetables and thus did not get enough vitamin C. In 1747, James Lind, a British physician in the Royal Navy, demonstrated that the consumption of oranges and lemons could combat scurvy.

Today’s risk factors for scurvy include malnutrition, gastrointestinal disorders (eg, chronic inflammatory bowel diseases), alcohol and tobacco use, eating disorders, psychiatric illnesses, dialysis, and the use of medications that reduce the absorption of ascorbic acid (such as corticosteroids and proton pump inhibitors).

Scurvy remains more common among individuals with unfavorable socioeconomic conditions. The authors of the study emphasize how the rising cost of living — specifically in Australia but applicable elsewhere — is changing eating habits, leading to a high consumption of low-cost, nutritionally poor foods.

Poverty has always been a risk factor for scurvy, but today there may be an additional cause: bariatric surgery. Patients undergoing these procedures are at a risk for deficiencies in fat-soluble vitamins A, D, E, and K, and if their diet is inadequate, they may also experience a vitamin C deficiency. Awareness of this can facilitate the timely diagnosis of scurvy in these patients.

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

“Petechial rash often prompts further investigation into hematological, dermatological, or vasculitis causes. However, if the above investigations are negative and skin biopsy has not revealed a cause, there is a Renaissance-era diagnosis that is often overlooked but is easily investigated and treated,” wrote Andrew Dermawan, MD, and colleagues from Sir Charles Gairdner Hospital in Nedlands, Australia, in BMJ Case Reports. The diagnosis they highlight is scurvy, a disease that has faded from common medical concern but is reemerging, partly because of the rise in bariatric surgery.

Diagnosing Scurvy in the 2020s

In their article, Dermawan and colleagues present the case of a 50-year-old man with a bilateral petechial rash on his lower limbs, without any history of trauma. The patient, who exhibited no infectious symptoms, also had gross hematuria, microcytic anemia, mild neutropenia, and lymphopenia. Tests for autoimmune and hematological diseases were negative, as were abdominal and leg CT scans, ruling out abdominal hemorrhage and vasculitis. Additionally, a skin biopsy showed no causative findings.

The doctors noted that the patient had undergone sleeve gastrectomy, prompting them to inquire about his diet. They discovered that, because of financial difficulties, his diet primarily consisted of processed foods with little to no fruits or vegetables, and he had stopped taking supplements recommended by his gastroenterologist. Further tests revealed a vitamin D deficiency and a severe deficiency in vitamin C. With the diagnosis of scurvy confirmed, the doctors treated the patient with 1000 mg of ascorbic acid daily, along with cholecalciferol, folic acid, and a multivitamin complex, leading to a complete resolution of his symptoms.
 

Risk Factors Then and Now

Scurvy can present with a range of symptoms, including petechiae, perifollicular hemorrhage, ecchymosis, gingivitis, edema, anemia, delayed wound healing, malaise, weakness, joint swelling, arthralgia, anorexia, neuropathy, and vasomotor instability. It can cause mucosal and gastric hemorrhages, and if left untreated, it can lead to fatal bleeding.

Historically known as “sailors’ disease,” scurvy plagued men on long voyages who lacked access to fresh fruits or vegetables and thus did not get enough vitamin C. In 1747, James Lind, a British physician in the Royal Navy, demonstrated that the consumption of oranges and lemons could combat scurvy.

Today’s risk factors for scurvy include malnutrition, gastrointestinal disorders (eg, chronic inflammatory bowel diseases), alcohol and tobacco use, eating disorders, psychiatric illnesses, dialysis, and the use of medications that reduce the absorption of ascorbic acid (such as corticosteroids and proton pump inhibitors).

Scurvy remains more common among individuals with unfavorable socioeconomic conditions. The authors of the study emphasize how the rising cost of living — specifically in Australia but applicable elsewhere — is changing eating habits, leading to a high consumption of low-cost, nutritionally poor foods.

Poverty has always been a risk factor for scurvy, but today there may be an additional cause: bariatric surgery. Patients undergoing these procedures are at a risk for deficiencies in fat-soluble vitamins A, D, E, and K, and if their diet is inadequate, they may also experience a vitamin C deficiency. Awareness of this can facilitate the timely diagnosis of scurvy in these patients.

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

TOPLINE:

There is no significant association between the use of proton pump inhibitors (PPIs) and risk for cardiovascular events, a meta-analysis shows. However, patients with gastroesophageal reflux disease (GERD) do experience a slight increase in cardiovascular events with PPI use.

METHODOLOGY:

• PPIs are commonly used gastric acid suppressants; however, they have pleiotropic effects, some of which have been hypothesized to augment cardiovascular disorders.
• Researchers conducted a meta-analysis of randomized clinical trials with at least 100 patients and treatment durations > 30 days, which compared groups receiving PPIs to those on placebo or other active treatments.
• The primary outcome was a composite of nonfatal myocardial infarctions, nonfatal strokes, fatal cardiovascular adverse events, coronary revascularizations, and hospitalizations for unstable angina.

TAKEAWAY:

• Researchers included data from 52 placebo-controlled trials, with 14,988 patients and 8323 patients randomized to receive a PPI or placebo, respectively; the mean treatment duration was 0.45 person-years for those treated with PPIs and 0.32 person-years for those treated with placebo.
• Among placebo-controlled trials, 24 were conducted in patients with GERD.
• Researchers also included 61 active-controlled trials that compared PPIs with histamine-2 receptor antagonists (51 trials) or other active treatments.
• The incidence rate ratio for the primary outcome was 0.72 when comparing PPI to placebo, indicating no significant association between PPI and cardiovascular events.
• Among patients with GERD, cardiovascular events occurred only in those treated with PPIs, leading to approximately one excess cardiovascular event per 100 person-years of PPI treatment relative to placebo.
• Researchers found no association between PPI treatment and the risk for cardiovascular events in trials comparing PPIs with other active treatments.

IN PRACTICE:

“We found no association of cardiovascular events with PPI treatment,” the authors wrote. “Cardiovascular events appeared more frequent with PPI treatment in GERD trials, but results from this subgroup should be interpreted with the limitations of the analysis in mind.”

SOURCE:

The study, led by Andrew D. Mosholder, MD, MPH, Division of Epidemiology, US Food and Drug Administration Center for Drug Evaluation and Research, Silver Spring, Maryland, was published online in The American Journal of Gastroenterology.

LIMITATIONS:

This study lacked individual patient data, which precluded a time-to-event analysis or an analysis accounting for patient characteristics such as age or sex. The mean duration of PPI treatment in these trials was a few months, limiting the assessment of cardiovascular risk with extended use. The risk estimates were influenced the most by data on omeprazole and esomeprazole.

DISCLOSURES:

This study did not receive any funding. The authors declared no conflicts of interests.

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:

There is no significant association between the use of proton pump inhibitors (PPIs) and risk for cardiovascular events, a meta-analysis shows. However, patients with gastroesophageal reflux disease (GERD) do experience a slight increase in cardiovascular events with PPI use.

METHODOLOGY:

• PPIs are commonly used gastric acid suppressants; however, they have pleiotropic effects, some of which have been hypothesized to augment cardiovascular disorders.
• Researchers conducted a meta-analysis of randomized clinical trials with at least 100 patients and treatment durations > 30 days, which compared groups receiving PPIs to those on placebo or other active treatments.
• The primary outcome was a composite of nonfatal myocardial infarctions, nonfatal strokes, fatal cardiovascular adverse events, coronary revascularizations, and hospitalizations for unstable angina.

TAKEAWAY:

• Researchers included data from 52 placebo-controlled trials, with 14,988 patients and 8323 patients randomized to receive a PPI or placebo, respectively; the mean treatment duration was 0.45 person-years for those treated with PPIs and 0.32 person-years for those treated with placebo.
• Among placebo-controlled trials, 24 were conducted in patients with GERD.
• Researchers also included 61 active-controlled trials that compared PPIs with histamine-2 receptor antagonists (51 trials) or other active treatments.
• The incidence rate ratio for the primary outcome was 0.72 when comparing PPI to placebo, indicating no significant association between PPI and cardiovascular events.
• Among patients with GERD, cardiovascular events occurred only in those treated with PPIs, leading to approximately one excess cardiovascular event per 100 person-years of PPI treatment relative to placebo.
• Researchers found no association between PPI treatment and the risk for cardiovascular events in trials comparing PPIs with other active treatments.

IN PRACTICE:

“We found no association of cardiovascular events with PPI treatment,” the authors wrote. “Cardiovascular events appeared more frequent with PPI treatment in GERD trials, but results from this subgroup should be interpreted with the limitations of the analysis in mind.”

SOURCE:

The study, led by Andrew D. Mosholder, MD, MPH, Division of Epidemiology, US Food and Drug Administration Center for Drug Evaluation and Research, Silver Spring, Maryland, was published online in The American Journal of Gastroenterology.

LIMITATIONS:

This study lacked individual patient data, which precluded a time-to-event analysis or an analysis accounting for patient characteristics such as age or sex. The mean duration of PPI treatment in these trials was a few months, limiting the assessment of cardiovascular risk with extended use. The risk estimates were influenced the most by data on omeprazole and esomeprazole.

DISCLOSURES:

This study did not receive any funding. The authors declared no conflicts of interests.

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:

There is no significant association between the use of proton pump inhibitors (PPIs) and risk for cardiovascular events, a meta-analysis shows. However, patients with gastroesophageal reflux disease (GERD) do experience a slight increase in cardiovascular events with PPI use.

METHODOLOGY:

• PPIs are commonly used gastric acid suppressants; however, they have pleiotropic effects, some of which have been hypothesized to augment cardiovascular disorders.
• Researchers conducted a meta-analysis of randomized clinical trials with at least 100 patients and treatment durations > 30 days, which compared groups receiving PPIs to those on placebo or other active treatments.
• The primary outcome was a composite of nonfatal myocardial infarctions, nonfatal strokes, fatal cardiovascular adverse events, coronary revascularizations, and hospitalizations for unstable angina.

TAKEAWAY:

• Researchers included data from 52 placebo-controlled trials, with 14,988 patients and 8323 patients randomized to receive a PPI or placebo, respectively; the mean treatment duration was 0.45 person-years for those treated with PPIs and 0.32 person-years for those treated with placebo.
• Among placebo-controlled trials, 24 were conducted in patients with GERD.
• Researchers also included 61 active-controlled trials that compared PPIs with histamine-2 receptor antagonists (51 trials) or other active treatments.
• The incidence rate ratio for the primary outcome was 0.72 when comparing PPI to placebo, indicating no significant association between PPI and cardiovascular events.
• Among patients with GERD, cardiovascular events occurred only in those treated with PPIs, leading to approximately one excess cardiovascular event per 100 person-years of PPI treatment relative to placebo.
• Researchers found no association between PPI treatment and the risk for cardiovascular events in trials comparing PPIs with other active treatments.

IN PRACTICE:

“We found no association of cardiovascular events with PPI treatment,” the authors wrote. “Cardiovascular events appeared more frequent with PPI treatment in GERD trials, but results from this subgroup should be interpreted with the limitations of the analysis in mind.”

SOURCE:

The study, led by Andrew D. Mosholder, MD, MPH, Division of Epidemiology, US Food and Drug Administration Center for Drug Evaluation and Research, Silver Spring, Maryland, was published online in The American Journal of Gastroenterology.

LIMITATIONS:

This study lacked individual patient data, which precluded a time-to-event analysis or an analysis accounting for patient characteristics such as age or sex. The mean duration of PPI treatment in these trials was a few months, limiting the assessment of cardiovascular risk with extended use. The risk estimates were influenced the most by data on omeprazole and esomeprazole.

DISCLOSURES:

This study did not receive any funding. The authors declared no conflicts of interests.

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.

A new scanner can provide three-dimensional (3D) photoacoustic images of millimeter-scale veins and arteries in seconds.

The scanner, developed by researchers at University College London (UCL) in England, could help clinicians better visualize and track microvascular changes for a wide range of diseases, including cancer, rheumatoid arthritis (RA), and peripheral vascular disease (PVD).

In exploratory case studies, researchers demonstrated how the scanner visualized vessels with a corkscrew-like structure in patients with suspected PVD and mapped new blood vessel formation driven by inflammation in patients with RA.

The case studies “illustrate potential areas of application that warrant future, more comprehensive clinical studies,” the authors wrote. “Moreover, they demonstrate the feasibility of using the scanner on a real-world patient cohort where imaging is more challenging due to frailty, comorbidity, or pain that may limit their ability to tolerate prolonged scan times.”

The work was published online in Nature Biomedical Engineering.
 

Improving Photoacoustic Imaging

PAT works using the photoacoustic effect, a phenomenon where sound waves are generated when light is absorbed by a material. When pulsed light from a laser is directed at tissue, some of that light is absorbed and causes an increase in heat in the targeted area. This localized heat also increases pressure, which generates ultrasound waves that can be detected by specialized sensors.

While previous PAT scanners translated these sound waves to electric signals directly to generate imaging, UCL engineers developed a sensor in the early 2000s that can detect these ultrasound waves using light. The result was much clearer, 3D images.

“That was great, but the problem was it was very slow, and it would take 5 minutes to get an image,” explained Paul Beard, PhD, professor of biomedical photoacoustics at UCL and senior author of the study. “That’s fine if you’re imaging a dead mouse or an anesthetized mouse, but not so useful for human imaging,” he continued, where motion would blur the image.

In this new paper, Beard and colleagues outlined how they cut scanning times to an order of seconds (or fraction of a second) rather than minutes. While previous iterations could detect only acoustic waves from one point at a time, this new scanner can detect waves from multiple points simultaneously. The scanner can visualize veins and arteries up to 15 mm deep in human tissue and can also provide dynamic, 3D images of “time-varying tissue perfusion and other hemodynamic events,” the authors wrote.

With these types of scanners, there is always a trade-off between imaging quality and imaging speed, explained Srivalleesha Mallidi, PhD, an assistant professor of biomedical engineering at Tufts University in Medford, Massachusetts. She was not involved with the work.

“With the resolution that [the authors] are providing and the depth at which they are seeing the signals, it is one of the fastest systems,” she said.
 

Clinical Utility

Beard and colleagues also tested the scanner to visualize blood vessels in participants with RA, suspected PVD, and skin inflammation. The scanning images “illustrated how vascular abnormalities such as increased vessel tortuosity, which has previously been linked to PVD, and the neovascularization associated with inflammation can be visualized and quantified,” the authors wrote.

The next step, Beard noted, is testing whether these characteristics can be used as a marker for the progression of disease.

Nehal Mehta, MD, a cardiologist and professor of medicine at the George Washington University, Washington, DC, agreed that more longitudinal research is needed to understand how the abnormalities captured in these images can inform detection and diagnosis of various diseases.

“You don’t know whether these images look bad because of reverse causation — the disease is doing this — or true causation — that this is actually detecting the root cause of the disease,” he explained. “Until we have a bank of normal and abnormal scans, we don’t know what any of these things mean.”

Though still some time away from entering the clinic, Mehta likened the technology to the introduction of optical coherence tomography in the 1980s. Before being adapted for clinical use, researchers first needed to visualize differences between normal coronary vasculature and myocardial infarction.

“I think this is an amazingly strong first proof of concept,” Mehta said. “This technology is showing a true promise in the field imaging.”

The work was funded by grants from Cancer Research UK, the Engineering & Physical Sciences Research Council, Wellcome Trust, the European Research Council, and the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre. Beard and two coauthors are shareholders of DeepColor Imaging to which the intellectual property associated with the new scanner has been licensed, but the company was not involved in any of this research. Mallidi and Mehta had no relevant disclosures.

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

A new scanner can provide three-dimensional (3D) photoacoustic images of millimeter-scale veins and arteries in seconds.

The scanner, developed by researchers at University College London (UCL) in England, could help clinicians better visualize and track microvascular changes for a wide range of diseases, including cancer, rheumatoid arthritis (RA), and peripheral vascular disease (PVD).

In exploratory case studies, researchers demonstrated how the scanner visualized vessels with a corkscrew-like structure in patients with suspected PVD and mapped new blood vessel formation driven by inflammation in patients with RA.

The case studies “illustrate potential areas of application that warrant future, more comprehensive clinical studies,” the authors wrote. “Moreover, they demonstrate the feasibility of using the scanner on a real-world patient cohort where imaging is more challenging due to frailty, comorbidity, or pain that may limit their ability to tolerate prolonged scan times.”

The work was published online in Nature Biomedical Engineering.
 

Improving Photoacoustic Imaging

PAT works using the photoacoustic effect, a phenomenon where sound waves are generated when light is absorbed by a material. When pulsed light from a laser is directed at tissue, some of that light is absorbed and causes an increase in heat in the targeted area. This localized heat also increases pressure, which generates ultrasound waves that can be detected by specialized sensors.

While previous PAT scanners translated these sound waves to electric signals directly to generate imaging, UCL engineers developed a sensor in the early 2000s that can detect these ultrasound waves using light. The result was much clearer, 3D images.

“That was great, but the problem was it was very slow, and it would take 5 minutes to get an image,” explained Paul Beard, PhD, professor of biomedical photoacoustics at UCL and senior author of the study. “That’s fine if you’re imaging a dead mouse or an anesthetized mouse, but not so useful for human imaging,” he continued, where motion would blur the image.

In this new paper, Beard and colleagues outlined how they cut scanning times to an order of seconds (or fraction of a second) rather than minutes. While previous iterations could detect only acoustic waves from one point at a time, this new scanner can detect waves from multiple points simultaneously. The scanner can visualize veins and arteries up to 15 mm deep in human tissue and can also provide dynamic, 3D images of “time-varying tissue perfusion and other hemodynamic events,” the authors wrote.

With these types of scanners, there is always a trade-off between imaging quality and imaging speed, explained Srivalleesha Mallidi, PhD, an assistant professor of biomedical engineering at Tufts University in Medford, Massachusetts. She was not involved with the work.

“With the resolution that [the authors] are providing and the depth at which they are seeing the signals, it is one of the fastest systems,” she said.
 

Clinical Utility

Beard and colleagues also tested the scanner to visualize blood vessels in participants with RA, suspected PVD, and skin inflammation. The scanning images “illustrated how vascular abnormalities such as increased vessel tortuosity, which has previously been linked to PVD, and the neovascularization associated with inflammation can be visualized and quantified,” the authors wrote.

The next step, Beard noted, is testing whether these characteristics can be used as a marker for the progression of disease.

Nehal Mehta, MD, a cardiologist and professor of medicine at the George Washington University, Washington, DC, agreed that more longitudinal research is needed to understand how the abnormalities captured in these images can inform detection and diagnosis of various diseases.

“You don’t know whether these images look bad because of reverse causation — the disease is doing this — or true causation — that this is actually detecting the root cause of the disease,” he explained. “Until we have a bank of normal and abnormal scans, we don’t know what any of these things mean.”

Though still some time away from entering the clinic, Mehta likened the technology to the introduction of optical coherence tomography in the 1980s. Before being adapted for clinical use, researchers first needed to visualize differences between normal coronary vasculature and myocardial infarction.

“I think this is an amazingly strong first proof of concept,” Mehta said. “This technology is showing a true promise in the field imaging.”

The work was funded by grants from Cancer Research UK, the Engineering & Physical Sciences Research Council, Wellcome Trust, the European Research Council, and the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre. Beard and two coauthors are shareholders of DeepColor Imaging to which the intellectual property associated with the new scanner has been licensed, but the company was not involved in any of this research. Mallidi and Mehta had no relevant disclosures.

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

A new scanner can provide three-dimensional (3D) photoacoustic images of millimeter-scale veins and arteries in seconds.

The scanner, developed by researchers at University College London (UCL) in England, could help clinicians better visualize and track microvascular changes for a wide range of diseases, including cancer, rheumatoid arthritis (RA), and peripheral vascular disease (PVD).

In exploratory case studies, researchers demonstrated how the scanner visualized vessels with a corkscrew-like structure in patients with suspected PVD and mapped new blood vessel formation driven by inflammation in patients with RA.

The case studies “illustrate potential areas of application that warrant future, more comprehensive clinical studies,” the authors wrote. “Moreover, they demonstrate the feasibility of using the scanner on a real-world patient cohort where imaging is more challenging due to frailty, comorbidity, or pain that may limit their ability to tolerate prolonged scan times.”

The work was published online in Nature Biomedical Engineering.
 

Improving Photoacoustic Imaging

PAT works using the photoacoustic effect, a phenomenon where sound waves are generated when light is absorbed by a material. When pulsed light from a laser is directed at tissue, some of that light is absorbed and causes an increase in heat in the targeted area. This localized heat also increases pressure, which generates ultrasound waves that can be detected by specialized sensors.

While previous PAT scanners translated these sound waves to electric signals directly to generate imaging, UCL engineers developed a sensor in the early 2000s that can detect these ultrasound waves using light. The result was much clearer, 3D images.

“That was great, but the problem was it was very slow, and it would take 5 minutes to get an image,” explained Paul Beard, PhD, professor of biomedical photoacoustics at UCL and senior author of the study. “That’s fine if you’re imaging a dead mouse or an anesthetized mouse, but not so useful for human imaging,” he continued, where motion would blur the image.

In this new paper, Beard and colleagues outlined how they cut scanning times to an order of seconds (or fraction of a second) rather than minutes. While previous iterations could detect only acoustic waves from one point at a time, this new scanner can detect waves from multiple points simultaneously. The scanner can visualize veins and arteries up to 15 mm deep in human tissue and can also provide dynamic, 3D images of “time-varying tissue perfusion and other hemodynamic events,” the authors wrote.

With these types of scanners, there is always a trade-off between imaging quality and imaging speed, explained Srivalleesha Mallidi, PhD, an assistant professor of biomedical engineering at Tufts University in Medford, Massachusetts. She was not involved with the work.

“With the resolution that [the authors] are providing and the depth at which they are seeing the signals, it is one of the fastest systems,” she said.
 

Clinical Utility

Beard and colleagues also tested the scanner to visualize blood vessels in participants with RA, suspected PVD, and skin inflammation. The scanning images “illustrated how vascular abnormalities such as increased vessel tortuosity, which has previously been linked to PVD, and the neovascularization associated with inflammation can be visualized and quantified,” the authors wrote.

The next step, Beard noted, is testing whether these characteristics can be used as a marker for the progression of disease.

Nehal Mehta, MD, a cardiologist and professor of medicine at the George Washington University, Washington, DC, agreed that more longitudinal research is needed to understand how the abnormalities captured in these images can inform detection and diagnosis of various diseases.

“You don’t know whether these images look bad because of reverse causation — the disease is doing this — or true causation — that this is actually detecting the root cause of the disease,” he explained. “Until we have a bank of normal and abnormal scans, we don’t know what any of these things mean.”

Though still some time away from entering the clinic, Mehta likened the technology to the introduction of optical coherence tomography in the 1980s. Before being adapted for clinical use, researchers first needed to visualize differences between normal coronary vasculature and myocardial infarction.

“I think this is an amazingly strong first proof of concept,” Mehta said. “This technology is showing a true promise in the field imaging.”

The work was funded by grants from Cancer Research UK, the Engineering & Physical Sciences Research Council, Wellcome Trust, the European Research Council, and the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre. Beard and two coauthors are shareholders of DeepColor Imaging to which the intellectual property associated with the new scanner has been licensed, but the company was not involved in any of this research. Mallidi and Mehta had no relevant disclosures.

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

Edema in the feet and legs is a common complaint in our practices. It can cause pain, weakness, heaviness, discomfort, limited movement, and a negative body image. Medications can contribute to edema, either alone or in combination with other health issues.

Edema is also associated with advanced age, female sex, obesity, diabetes, hypertension, pain, lack of physical activity, and mobility limitations. These factors often necessitate medication prescriptions, which can aggravate the problem. Therefore, it is important to know how to treat or prevent medication-induced edema.

There are four main causes of edema, and all can facilitate medication-induced edema.

• Increased capillary pressure. Conditions such as heart failure, renal dysfunction, venous insufficiency, deep vein thrombosis, and cirrhosis can increase capillary pressure, leading to edema.
• Decreased oncotic pressure. Hypoalbuminemia, a primary cause of reduced colloid oncotic pressure, can result from nephrotic syndrome, diabetic nephropathy, lupus nephropathy, amyloidosis, nephropathies, cirrhosis, chronic liver disease, and malabsorption or malnutrition.
• Increased capillary permeability. Vascular injury, often associated with diabetes, can increase capillary permeability and contribute to edema.
• Impaired lymphatic drainage. Lymphatic obstruction is common in patients with lymphedema, tumors, inflammation, fibrosis, certain infections, surgery, and congenital anomalies. Conditions such as thyroid disorders can also cause an increase in interstitial albumin and other proteins without a corresponding increase in lymphatic flow, leading to lymphedema.

Medications That Can Cause Edema

• Calcium channel blockers (CCBs). Drugs such as nifedipine and amlodipine can increase hydrostatic pressure by causing selective vasodilation of precapillary vessels, leading to increased intracapillary pressures. Newer lipophilic CCBs (eg, levamlodipine) exhibit lower rates of edema. Reducing the dose is often effective. Diuretics are not very effective for vasodilation-induced edema. Combining CCBs with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), which induce postcapillary dilation and normalize intracapillary pressure, may reduce fluid leakage into the interstitial space. This combination may be more beneficial than high-dose CCB monotherapy.
• Thiazolidinedione (eg, pioglitazone). These increase vascular permeability and hydrostatic pressure. They work by stimulating the peroxisome proliferator–activated gamma receptor, increasing vascular endothelial permeability, vascular endothelial growth factor secretion, and renal retention of sodium and fluids. Because of other adverse effects, their use is now limited.
• Agents for neuropathic pain (gabapentin and pregabalin). These drugs can induce selective vasodilation of arterioles through a mechanism similar to that of CCBs, causing increased intracapillary pressures. Edema usually begins within the first month of treatment or dose increase and often regresses after dose reduction or drug discontinuation.
• Antiparkinsonian dopamine agonists. These increase hydrostatic pressure by reducing sympathetic tone and dilating arterioles through alpha-2 adrenergic receptor activity.
• New antipsychotics. Drugs like clozapine, iloperidone, lurasidone, olanzapine, quetiapine, risperidone, and ziprasidone can increase hydrostatic pressure through antagonistic effects on alpha-1 adrenergic receptors, causing vasodilation.
• Nitrates. These drugs increase hydrostatic pressure by causing preferential venous dilation, leading to increased venous pooling.
• Nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs can increase hydrostatic pressure by inhibiting vasodilation of afferent renal arterioles, decreasing the glomerular filtration rate, and stimulating the renin-angiotensin-aldosterone system, which leads to sodium and water retention. These adverse effects warrant cautious use of these agents.
• ACE inhibitors. Drugs such as enalapril and ramipril can increase vascular permeability. They reduce the metabolism and accumulation of bradykinin, which increases vascular permeability and fluid leakage. These effects are rare and are usually related to allergic responses.
• Insulin. Insulin decreases capillary oncotic pressure and increases vascular permeability. Rapid correction of hyperglycemia can cause a loss of oncotic pressure, while chronic hyperglycemia can damage vascular membranes, increasing permeability. These effects are generally benign and can be managed with careful dose titration, sodium restriction, or diuretics.
• Steroids. Steroids with mineralocorticoid activity can increase renal sodium and water retention, leading to increased blood volume. Fludrocortisone has the highest mineralocorticoid activity, while dexamethasone and methylprednisolone have negligible activity.

Implications

Understanding how these medications cause edema is important for effective management. For example, in the case of those causing edema due to reduced oncotic pressure, like insulin, slow dose titrations can help adapt to osmolarity changes. For drugs causing edema due to increased hydrostatic pressure, diuretics are more effective in acute management.

The key takeaways from this review are:

• Awareness of drug-induced edema. Many drugs besides CCBs can cause edema.
• Combination therapy. Combining ACE inhibitors or ARBs with CCBs can prevent or reduce CCB-induced edema.
• Edema management strategies. Strategies to manage or prevent edema should include dose reductions or replacement of the problematic medication, especially in severe or refractory cases.

Dr. Wajngarten, professor of cardiology, University of São Paulo, Brazil, has disclosed no relevant financial relationships.

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

Edema in the feet and legs is a common complaint in our practices. It can cause pain, weakness, heaviness, discomfort, limited movement, and a negative body image. Medications can contribute to edema, either alone or in combination with other health issues.

Edema is also associated with advanced age, female sex, obesity, diabetes, hypertension, pain, lack of physical activity, and mobility limitations. These factors often necessitate medication prescriptions, which can aggravate the problem. Therefore, it is important to know how to treat or prevent medication-induced edema.

There are four main causes of edema, and all can facilitate medication-induced edema.

• Increased capillary pressure. Conditions such as heart failure, renal dysfunction, venous insufficiency, deep vein thrombosis, and cirrhosis can increase capillary pressure, leading to edema.
• Decreased oncotic pressure. Hypoalbuminemia, a primary cause of reduced colloid oncotic pressure, can result from nephrotic syndrome, diabetic nephropathy, lupus nephropathy, amyloidosis, nephropathies, cirrhosis, chronic liver disease, and malabsorption or malnutrition.
• Increased capillary permeability. Vascular injury, often associated with diabetes, can increase capillary permeability and contribute to edema.
• Impaired lymphatic drainage. Lymphatic obstruction is common in patients with lymphedema, tumors, inflammation, fibrosis, certain infections, surgery, and congenital anomalies. Conditions such as thyroid disorders can also cause an increase in interstitial albumin and other proteins without a corresponding increase in lymphatic flow, leading to lymphedema.

Medications That Can Cause Edema

• Calcium channel blockers (CCBs). Drugs such as nifedipine and amlodipine can increase hydrostatic pressure by causing selective vasodilation of precapillary vessels, leading to increased intracapillary pressures. Newer lipophilic CCBs (eg, levamlodipine) exhibit lower rates of edema. Reducing the dose is often effective. Diuretics are not very effective for vasodilation-induced edema. Combining CCBs with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), which induce postcapillary dilation and normalize intracapillary pressure, may reduce fluid leakage into the interstitial space. This combination may be more beneficial than high-dose CCB monotherapy.
• Thiazolidinedione (eg, pioglitazone). These increase vascular permeability and hydrostatic pressure. They work by stimulating the peroxisome proliferator–activated gamma receptor, increasing vascular endothelial permeability, vascular endothelial growth factor secretion, and renal retention of sodium and fluids. Because of other adverse effects, their use is now limited.
• Agents for neuropathic pain (gabapentin and pregabalin). These drugs can induce selective vasodilation of arterioles through a mechanism similar to that of CCBs, causing increased intracapillary pressures. Edema usually begins within the first month of treatment or dose increase and often regresses after dose reduction or drug discontinuation.
• Antiparkinsonian dopamine agonists. These increase hydrostatic pressure by reducing sympathetic tone and dilating arterioles through alpha-2 adrenergic receptor activity.
• New antipsychotics. Drugs like clozapine, iloperidone, lurasidone, olanzapine, quetiapine, risperidone, and ziprasidone can increase hydrostatic pressure through antagonistic effects on alpha-1 adrenergic receptors, causing vasodilation.
• Nitrates. These drugs increase hydrostatic pressure by causing preferential venous dilation, leading to increased venous pooling.
• Nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs can increase hydrostatic pressure by inhibiting vasodilation of afferent renal arterioles, decreasing the glomerular filtration rate, and stimulating the renin-angiotensin-aldosterone system, which leads to sodium and water retention. These adverse effects warrant cautious use of these agents.
• ACE inhibitors. Drugs such as enalapril and ramipril can increase vascular permeability. They reduce the metabolism and accumulation of bradykinin, which increases vascular permeability and fluid leakage. These effects are rare and are usually related to allergic responses.
• Insulin. Insulin decreases capillary oncotic pressure and increases vascular permeability. Rapid correction of hyperglycemia can cause a loss of oncotic pressure, while chronic hyperglycemia can damage vascular membranes, increasing permeability. These effects are generally benign and can be managed with careful dose titration, sodium restriction, or diuretics.
• Steroids. Steroids with mineralocorticoid activity can increase renal sodium and water retention, leading to increased blood volume. Fludrocortisone has the highest mineralocorticoid activity, while dexamethasone and methylprednisolone have negligible activity.

Implications

Understanding how these medications cause edema is important for effective management. For example, in the case of those causing edema due to reduced oncotic pressure, like insulin, slow dose titrations can help adapt to osmolarity changes. For drugs causing edema due to increased hydrostatic pressure, diuretics are more effective in acute management.

The key takeaways from this review are:

• Awareness of drug-induced edema. Many drugs besides CCBs can cause edema.
• Combination therapy. Combining ACE inhibitors or ARBs with CCBs can prevent or reduce CCB-induced edema.
• Edema management strategies. Strategies to manage or prevent edema should include dose reductions or replacement of the problematic medication, especially in severe or refractory cases.

Dr. Wajngarten, professor of cardiology, University of São Paulo, Brazil, has disclosed no relevant financial relationships.

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

Edema in the feet and legs is a common complaint in our practices. It can cause pain, weakness, heaviness, discomfort, limited movement, and a negative body image. Medications can contribute to edema, either alone or in combination with other health issues.

Edema is also associated with advanced age, female sex, obesity, diabetes, hypertension, pain, lack of physical activity, and mobility limitations. These factors often necessitate medication prescriptions, which can aggravate the problem. Therefore, it is important to know how to treat or prevent medication-induced edema.

There are four main causes of edema, and all can facilitate medication-induced edema.

• Increased capillary pressure. Conditions such as heart failure, renal dysfunction, venous insufficiency, deep vein thrombosis, and cirrhosis can increase capillary pressure, leading to edema.
• Decreased oncotic pressure. Hypoalbuminemia, a primary cause of reduced colloid oncotic pressure, can result from nephrotic syndrome, diabetic nephropathy, lupus nephropathy, amyloidosis, nephropathies, cirrhosis, chronic liver disease, and malabsorption or malnutrition.
• Increased capillary permeability. Vascular injury, often associated with diabetes, can increase capillary permeability and contribute to edema.
• Impaired lymphatic drainage. Lymphatic obstruction is common in patients with lymphedema, tumors, inflammation, fibrosis, certain infections, surgery, and congenital anomalies. Conditions such as thyroid disorders can also cause an increase in interstitial albumin and other proteins without a corresponding increase in lymphatic flow, leading to lymphedema.

Medications That Can Cause Edema

• Calcium channel blockers (CCBs). Drugs such as nifedipine and amlodipine can increase hydrostatic pressure by causing selective vasodilation of precapillary vessels, leading to increased intracapillary pressures. Newer lipophilic CCBs (eg, levamlodipine) exhibit lower rates of edema. Reducing the dose is often effective. Diuretics are not very effective for vasodilation-induced edema. Combining CCBs with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), which induce postcapillary dilation and normalize intracapillary pressure, may reduce fluid leakage into the interstitial space. This combination may be more beneficial than high-dose CCB monotherapy.
• Thiazolidinedione (eg, pioglitazone). These increase vascular permeability and hydrostatic pressure. They work by stimulating the peroxisome proliferator–activated gamma receptor, increasing vascular endothelial permeability, vascular endothelial growth factor secretion, and renal retention of sodium and fluids. Because of other adverse effects, their use is now limited.
• Agents for neuropathic pain (gabapentin and pregabalin). These drugs can induce selective vasodilation of arterioles through a mechanism similar to that of CCBs, causing increased intracapillary pressures. Edema usually begins within the first month of treatment or dose increase and often regresses after dose reduction or drug discontinuation.
• Antiparkinsonian dopamine agonists. These increase hydrostatic pressure by reducing sympathetic tone and dilating arterioles through alpha-2 adrenergic receptor activity.
• New antipsychotics. Drugs like clozapine, iloperidone, lurasidone, olanzapine, quetiapine, risperidone, and ziprasidone can increase hydrostatic pressure through antagonistic effects on alpha-1 adrenergic receptors, causing vasodilation.
• Nitrates. These drugs increase hydrostatic pressure by causing preferential venous dilation, leading to increased venous pooling.
• Nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs can increase hydrostatic pressure by inhibiting vasodilation of afferent renal arterioles, decreasing the glomerular filtration rate, and stimulating the renin-angiotensin-aldosterone system, which leads to sodium and water retention. These adverse effects warrant cautious use of these agents.
• ACE inhibitors. Drugs such as enalapril and ramipril can increase vascular permeability. They reduce the metabolism and accumulation of bradykinin, which increases vascular permeability and fluid leakage. These effects are rare and are usually related to allergic responses.
• Insulin. Insulin decreases capillary oncotic pressure and increases vascular permeability. Rapid correction of hyperglycemia can cause a loss of oncotic pressure, while chronic hyperglycemia can damage vascular membranes, increasing permeability. These effects are generally benign and can be managed with careful dose titration, sodium restriction, or diuretics.
• Steroids. Steroids with mineralocorticoid activity can increase renal sodium and water retention, leading to increased blood volume. Fludrocortisone has the highest mineralocorticoid activity, while dexamethasone and methylprednisolone have negligible activity.

Implications

Understanding how these medications cause edema is important for effective management. For example, in the case of those causing edema due to reduced oncotic pressure, like insulin, slow dose titrations can help adapt to osmolarity changes. For drugs causing edema due to increased hydrostatic pressure, diuretics are more effective in acute management.

The key takeaways from this review are:

• Awareness of drug-induced edema. Many drugs besides CCBs can cause edema.
• Combination therapy. Combining ACE inhibitors or ARBs with CCBs can prevent or reduce CCB-induced edema.
• Edema management strategies. Strategies to manage or prevent edema should include dose reductions or replacement of the problematic medication, especially in severe or refractory cases.

Dr. Wajngarten, professor of cardiology, University of São Paulo, Brazil, has disclosed no relevant financial relationships.

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

Approximately half of adults with idiopathic pulmonary arterial hypertension (IPAH) had nonplexiform vasculopathy characterized in part by severe pulmonary microvascular remodeling, based on data from 50 individuals.

The clinical phenotype of IPAH was historically described as a rapidly progressive rare disease in young women and characterized by plexiform lesions, wrote Esther J. Nossent, MD, of Amsterdam University Medical Centers, Amsterdam, the Netherlands, and colleagues. However, the patient population with IPAH has become older and predominantly men, and the nature of vascular phenotypes and histologic patterns in patients with contemporary IPAH has not been well studied, the researchers said.

In a cross-sectional study published in CHEST, the researchers reviewed lung histology data from 50 adults with IPAH that had been assessed by two experienced pathologists. The mean age of the patients was 52 years and 58% were women. Based on a histopathologic evaluation, 24 patients had nonplexiform vasculopathy (48%) and 26 had plexiform vasculopathy (52%). Notably, microvascular remodeling involving arterioles and venules was substantial in patients with nonplexiform vasculopathy but mild or absent in those with plexiform vasculopathy, the researchers wrote.

The researchers also compared the clinical characteristics of patients with plexiform vs nonplexiform vasculopathy. Hemodynamic parameters were similar in both patient groups. However, those with nonplexiform vasculopathy were significantly older than those with plexiform vasculopathy (60 years vs 44 years), were more likely to be men (67% vs 20%), and had a lower diffusing capacity of the lungs for carbon monoxide (DLCO) at diagnosis (all P < .001). Patients with nonplexiform vasculopathy also were significantly more likely than those with plexiform vasculopathy to have a history of smoking (P = .03). Genetic testing revealed no mutations in established PAH genes in the nonplexiform group.

Low DLCO has been associated with worse outcomes regardless of hemodynamic response, the researchers noted. In the current study, “a DLCO of < 45% almost perfectly identified patients with nonplexiform vasculopathy with prominent pulmonary microvascular disease,” they said.

The findings were limited by several factors, including the small study population and the higher frequency of surgical lung biopsies in the nonplexiform group vs the plexiform group, which is not part of the general workup of patients with IPAH, the researchers noted.

More research is needed to better define the subgroup of patients with IPAH with nonplexiform vasculopathy and to identify the causes, biological features, and treatment approaches for these patients, they said. However, the results suggest that differences between patients with IPAH with plexiform vasculopathy and those with nonplexiform vasculopathy could ultimately inform targeted treatment strategies.

“Recognizing these clinical phenotypes allows revisiting current datasets to understand better the potential future clinical consequences of the vascular phenotypes for treatment response and clinical outcome,” the researchers concluded.
 

Findings May Inform More Targeted Therapy

“Any investigation that adds substantive insight into a complex disease that can translate into a better understanding of clinical patient phenotypes and eventually into improved treatments and patient outcomes has relevance at any time,” Paul Forfia, MD, professor of medicine at the Lewis Katz School of Medicine at Temple University, Philadelphia, said in an interview.

“There is focus on the antiproliferative forms of pulmonary arterial hypertension–specific therapy, and the results of the current study may have implications to these therapies,” said Dr. Forfia, who was not involved in the current study.

“In the current study, the investigators show that 48% of patients that were traditionally categorized as IPAH had a vascular phenotype that is not considered ‘typical’ or classic for IPAH,” Dr. Forfia told this news organization. “These findings highlight a significant heterogeneity of the pulmonary vascular phenotype within IPAH, which raises the question of whether the nonplexiform patient would be less responsive to the novel, antiproliferative forms of therapy,” he said.

The new findings are quite interesting but not surprising, Dr. Forfia said. “The World Symposia diagnostic groupings for pulmonary hypertension are a very important and necessary form of categorization and differentiation amongst forms of PH [pulmonary hypertension], and these groupings make a best attempt based on available evidence to separate patients of varying PH pathophysiology, both in terms of diagnosis and in how PH patients are treated,” he explained.

“However, clinical experts in PH have known that subphenotypes of PH pathophysiology exist within group I PAH, as well as in PH related to left heart disease (group 2), chronic respiratory disease (group 3), and chronic thromboembolic disease (group 4),” he said.

Findings from the current study reinforce the importance of clinical and physiological phenotyping of each patient, which can help in terms of therapy selection and in managing expectations in response to therapy, Dr. Forfia added.

“Perhaps the most evident and important clinical implication from the current study is to remind clinicians treating patients with PH that heterogeneity exists within the vascular phenotype and clinical makeup of patients even within the same type of PAH,” Dr. Forfia said. “With this insight, clinicians are more informed and thus more apt to consider nuances in the diagnosis, treatment, and expectations for treatment response within PAH,” he said.

Dr. Forfia also highlighted the potential implications of the association between cigarette smoking and the nonplexiform vascular phenotype. “This association was present in the absence of radiographic evidence of emphysema and raises the provocative notion that cigarette smoking may lead to pulmonary vascular abnormalities, perhaps even PAH, in patients without a diagnosis of emphysema,” he said.

“An important limitation from the current study is that the vascular phenotypes observed within their cohort of IPAH patients were obtained from histopathology specimens at the time of autopsy, explant at the time of lung transplantation, and surgical lung biopsy spanning over a 22-year period,” Dr. Forfia noted. Additional research is needed to explore how vascular phenotypic differences can be appreciated in the absence of histopathology and how these differences could impact therapy selection and patient outcomes, he said.

The study received no outside funding. Dr. Nossent disclosed receiving speaker fees from Janssen, MSD, and United Therapeutics/Ferrer and consulting fees from Janssen and United Therapeutics/Ferrer. Dr. Forfia had no financial conflicts to disclose.

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

Approximately half of adults with idiopathic pulmonary arterial hypertension (IPAH) had nonplexiform vasculopathy characterized in part by severe pulmonary microvascular remodeling, based on data from 50 individuals.

The clinical phenotype of IPAH was historically described as a rapidly progressive rare disease in young women and characterized by plexiform lesions, wrote Esther J. Nossent, MD, of Amsterdam University Medical Centers, Amsterdam, the Netherlands, and colleagues. However, the patient population with IPAH has become older and predominantly men, and the nature of vascular phenotypes and histologic patterns in patients with contemporary IPAH has not been well studied, the researchers said.

In a cross-sectional study published in CHEST, the researchers reviewed lung histology data from 50 adults with IPAH that had been assessed by two experienced pathologists. The mean age of the patients was 52 years and 58% were women. Based on a histopathologic evaluation, 24 patients had nonplexiform vasculopathy (48%) and 26 had plexiform vasculopathy (52%). Notably, microvascular remodeling involving arterioles and venules was substantial in patients with nonplexiform vasculopathy but mild or absent in those with plexiform vasculopathy, the researchers wrote.

The researchers also compared the clinical characteristics of patients with plexiform vs nonplexiform vasculopathy. Hemodynamic parameters were similar in both patient groups. However, those with nonplexiform vasculopathy were significantly older than those with plexiform vasculopathy (60 years vs 44 years), were more likely to be men (67% vs 20%), and had a lower diffusing capacity of the lungs for carbon monoxide (DLCO) at diagnosis (all P < .001). Patients with nonplexiform vasculopathy also were significantly more likely than those with plexiform vasculopathy to have a history of smoking (P = .03). Genetic testing revealed no mutations in established PAH genes in the nonplexiform group.

Low DLCO has been associated with worse outcomes regardless of hemodynamic response, the researchers noted. In the current study, “a DLCO of < 45% almost perfectly identified patients with nonplexiform vasculopathy with prominent pulmonary microvascular disease,” they said.

The findings were limited by several factors, including the small study population and the higher frequency of surgical lung biopsies in the nonplexiform group vs the plexiform group, which is not part of the general workup of patients with IPAH, the researchers noted.

More research is needed to better define the subgroup of patients with IPAH with nonplexiform vasculopathy and to identify the causes, biological features, and treatment approaches for these patients, they said. However, the results suggest that differences between patients with IPAH with plexiform vasculopathy and those with nonplexiform vasculopathy could ultimately inform targeted treatment strategies.

“Recognizing these clinical phenotypes allows revisiting current datasets to understand better the potential future clinical consequences of the vascular phenotypes for treatment response and clinical outcome,” the researchers concluded.
 

Findings May Inform More Targeted Therapy

“Any investigation that adds substantive insight into a complex disease that can translate into a better understanding of clinical patient phenotypes and eventually into improved treatments and patient outcomes has relevance at any time,” Paul Forfia, MD, professor of medicine at the Lewis Katz School of Medicine at Temple University, Philadelphia, said in an interview.

“There is focus on the antiproliferative forms of pulmonary arterial hypertension–specific therapy, and the results of the current study may have implications to these therapies,” said Dr. Forfia, who was not involved in the current study.

“In the current study, the investigators show that 48% of patients that were traditionally categorized as IPAH had a vascular phenotype that is not considered ‘typical’ or classic for IPAH,” Dr. Forfia told this news organization. “These findings highlight a significant heterogeneity of the pulmonary vascular phenotype within IPAH, which raises the question of whether the nonplexiform patient would be less responsive to the novel, antiproliferative forms of therapy,” he said.

The new findings are quite interesting but not surprising, Dr. Forfia said. “The World Symposia diagnostic groupings for pulmonary hypertension are a very important and necessary form of categorization and differentiation amongst forms of PH [pulmonary hypertension], and these groupings make a best attempt based on available evidence to separate patients of varying PH pathophysiology, both in terms of diagnosis and in how PH patients are treated,” he explained.

“However, clinical experts in PH have known that subphenotypes of PH pathophysiology exist within group I PAH, as well as in PH related to left heart disease (group 2), chronic respiratory disease (group 3), and chronic thromboembolic disease (group 4),” he said.

Findings from the current study reinforce the importance of clinical and physiological phenotyping of each patient, which can help in terms of therapy selection and in managing expectations in response to therapy, Dr. Forfia added.

“Perhaps the most evident and important clinical implication from the current study is to remind clinicians treating patients with PH that heterogeneity exists within the vascular phenotype and clinical makeup of patients even within the same type of PAH,” Dr. Forfia said. “With this insight, clinicians are more informed and thus more apt to consider nuances in the diagnosis, treatment, and expectations for treatment response within PAH,” he said.

Dr. Forfia also highlighted the potential implications of the association between cigarette smoking and the nonplexiform vascular phenotype. “This association was present in the absence of radiographic evidence of emphysema and raises the provocative notion that cigarette smoking may lead to pulmonary vascular abnormalities, perhaps even PAH, in patients without a diagnosis of emphysema,” he said.

“An important limitation from the current study is that the vascular phenotypes observed within their cohort of IPAH patients were obtained from histopathology specimens at the time of autopsy, explant at the time of lung transplantation, and surgical lung biopsy spanning over a 22-year period,” Dr. Forfia noted. Additional research is needed to explore how vascular phenotypic differences can be appreciated in the absence of histopathology and how these differences could impact therapy selection and patient outcomes, he said.

The study received no outside funding. Dr. Nossent disclosed receiving speaker fees from Janssen, MSD, and United Therapeutics/Ferrer and consulting fees from Janssen and United Therapeutics/Ferrer. Dr. Forfia had no financial conflicts to disclose.

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

Approximately half of adults with idiopathic pulmonary arterial hypertension (IPAH) had nonplexiform vasculopathy characterized in part by severe pulmonary microvascular remodeling, based on data from 50 individuals.

The clinical phenotype of IPAH was historically described as a rapidly progressive rare disease in young women and characterized by plexiform lesions, wrote Esther J. Nossent, MD, of Amsterdam University Medical Centers, Amsterdam, the Netherlands, and colleagues. However, the patient population with IPAH has become older and predominantly men, and the nature of vascular phenotypes and histologic patterns in patients with contemporary IPAH has not been well studied, the researchers said.

In a cross-sectional study published in CHEST, the researchers reviewed lung histology data from 50 adults with IPAH that had been assessed by two experienced pathologists. The mean age of the patients was 52 years and 58% were women. Based on a histopathologic evaluation, 24 patients had nonplexiform vasculopathy (48%) and 26 had plexiform vasculopathy (52%). Notably, microvascular remodeling involving arterioles and venules was substantial in patients with nonplexiform vasculopathy but mild or absent in those with plexiform vasculopathy, the researchers wrote.

The researchers also compared the clinical characteristics of patients with plexiform vs nonplexiform vasculopathy. Hemodynamic parameters were similar in both patient groups. However, those with nonplexiform vasculopathy were significantly older than those with plexiform vasculopathy (60 years vs 44 years), were more likely to be men (67% vs 20%), and had a lower diffusing capacity of the lungs for carbon monoxide (DLCO) at diagnosis (all P < .001). Patients with nonplexiform vasculopathy also were significantly more likely than those with plexiform vasculopathy to have a history of smoking (P = .03). Genetic testing revealed no mutations in established PAH genes in the nonplexiform group.

Low DLCO has been associated with worse outcomes regardless of hemodynamic response, the researchers noted. In the current study, “a DLCO of < 45% almost perfectly identified patients with nonplexiform vasculopathy with prominent pulmonary microvascular disease,” they said.

The findings were limited by several factors, including the small study population and the higher frequency of surgical lung biopsies in the nonplexiform group vs the plexiform group, which is not part of the general workup of patients with IPAH, the researchers noted.

More research is needed to better define the subgroup of patients with IPAH with nonplexiform vasculopathy and to identify the causes, biological features, and treatment approaches for these patients, they said. However, the results suggest that differences between patients with IPAH with plexiform vasculopathy and those with nonplexiform vasculopathy could ultimately inform targeted treatment strategies.

“Recognizing these clinical phenotypes allows revisiting current datasets to understand better the potential future clinical consequences of the vascular phenotypes for treatment response and clinical outcome,” the researchers concluded.
 

Findings May Inform More Targeted Therapy

“Any investigation that adds substantive insight into a complex disease that can translate into a better understanding of clinical patient phenotypes and eventually into improved treatments and patient outcomes has relevance at any time,” Paul Forfia, MD, professor of medicine at the Lewis Katz School of Medicine at Temple University, Philadelphia, said in an interview.

“There is focus on the antiproliferative forms of pulmonary arterial hypertension–specific therapy, and the results of the current study may have implications to these therapies,” said Dr. Forfia, who was not involved in the current study.

“In the current study, the investigators show that 48% of patients that were traditionally categorized as IPAH had a vascular phenotype that is not considered ‘typical’ or classic for IPAH,” Dr. Forfia told this news organization. “These findings highlight a significant heterogeneity of the pulmonary vascular phenotype within IPAH, which raises the question of whether the nonplexiform patient would be less responsive to the novel, antiproliferative forms of therapy,” he said.

The new findings are quite interesting but not surprising, Dr. Forfia said. “The World Symposia diagnostic groupings for pulmonary hypertension are a very important and necessary form of categorization and differentiation amongst forms of PH [pulmonary hypertension], and these groupings make a best attempt based on available evidence to separate patients of varying PH pathophysiology, both in terms of diagnosis and in how PH patients are treated,” he explained.

“However, clinical experts in PH have known that subphenotypes of PH pathophysiology exist within group I PAH, as well as in PH related to left heart disease (group 2), chronic respiratory disease (group 3), and chronic thromboembolic disease (group 4),” he said.

Findings from the current study reinforce the importance of clinical and physiological phenotyping of each patient, which can help in terms of therapy selection and in managing expectations in response to therapy, Dr. Forfia added.

“Perhaps the most evident and important clinical implication from the current study is to remind clinicians treating patients with PH that heterogeneity exists within the vascular phenotype and clinical makeup of patients even within the same type of PAH,” Dr. Forfia said. “With this insight, clinicians are more informed and thus more apt to consider nuances in the diagnosis, treatment, and expectations for treatment response within PAH,” he said.

Dr. Forfia also highlighted the potential implications of the association between cigarette smoking and the nonplexiform vascular phenotype. “This association was present in the absence of radiographic evidence of emphysema and raises the provocative notion that cigarette smoking may lead to pulmonary vascular abnormalities, perhaps even PAH, in patients without a diagnosis of emphysema,” he said.

“An important limitation from the current study is that the vascular phenotypes observed within their cohort of IPAH patients were obtained from histopathology specimens at the time of autopsy, explant at the time of lung transplantation, and surgical lung biopsy spanning over a 22-year period,” Dr. Forfia noted. Additional research is needed to explore how vascular phenotypic differences can be appreciated in the absence of histopathology and how these differences could impact therapy selection and patient outcomes, he said.

The study received no outside funding. Dr. Nossent disclosed receiving speaker fees from Janssen, MSD, and United Therapeutics/Ferrer and consulting fees from Janssen and United Therapeutics/Ferrer. Dr. Forfia had no financial conflicts to disclose.

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

On World Brain Day (July 22, 2024), the German Society of Neurology (DGN) and the German Brain Foundation pointed out that too much sugar can harm the brain. The current results of the Global Burden of Diseases study shows that stroke and dementia are among the top 10 causes of death. A healthy, active lifestyle with sufficient exercise and sleep, along with the avoidance of harmful substances like alcohol, nicotine, or excessive sugar, protects the brain.

“Of course, the dose makes the poison as the brain, being the body’s powerhouse, needs glucose to function,” said Frank Erbguth, MD, PhD, president of the German Brain Foundation, in a press release from DGN and the German Brain Foundation. “However, with a permanent increase in blood sugar levels due to too many, too lavish meals and constant snacking on the side, we overload the system and fuel the development of neurologic diseases, particularly dementia and stroke.”

The per capita consumption of sugar was 33.2 kg in 2021/2022, which is almost twice the recommended amount. The German Nutrition Society recommends that no more than 10% of energy come from sugar. With a goal of 2000 kilocalories, that’s 50 g per day, or 18 kg per year. This total includes not only added sugar but also naturally occurring sugar, such as in fruits, honey, or juices.
 

What’s the Mechanism?

High blood sugar levels damage brain blood vessels and promote deposits on the vessel walls, thus reducing blood flow and nutrient supply to brain cells. This process can cause various limitations, as well as vascular dementia.

In Germany, around 250,000 people are diagnosed with dementia annually, and 15%-25% have vascular dementia. That proportion represents between 40,000 and 60,000 new cases each year.

In addition, glycosaminoglycans, which are complex sugar molecules, can directly impair cognition. They affect the function of synapses between nerve cells and, thus, affect neuronal plasticity. Experimental data presented at the 2023 American Chemical Society Congress have shown this phenomenon.

Twenty years ago, a study provided evidence that a diet high in fat and sugar disrupts neuronal plasticity and can impair the function of the hippocampus in the long term. A recent meta-analysis confirms these findings: Although mental performance improves at 2-12 hours after sugar consumption, sustained sugar intake can permanently damage cognitive function.

Diabetes mellitus can indirectly cause brain damage. Since the 1990s, it has been known that patients with type 2 diabetes have a significantly higher risk for dementia. It is suspected that glucose metabolism is also disrupted in neurons, thus contributing to the development of Alzheimer’s disease. Insulin also plays a role in the formation of Alzheimer’s plaques.

The Max Planck Institute for Metabolism Research demonstrated in 2023 that regular consumption of high-sugar and high-fat foods can change the brain. This leads to an increased craving for high-sugar and high-fat foods, which in turn promotes the development of obesity and type 2 diabetes.
 

Reduce Sugar Consumption

DGN and the German Brain Foundation advise minimizing sugar consumption. This process is often challenging, as even a small dose of sugar can trigger the gut to send signals to the brain via the vagus nerve, thus causing a strong craving for more sugar. “This could be the reason why some people quickly eat a whole chocolate bar after just one piece,” said Dr. Erbguth. In addition, dopamine, a “feel-good hormone,” is released in the brain when consuming sugar, thus leading to a desire for more.

“It is wise to break free from this cycle by largely avoiding sugar,” said Peter Berlit, MD, secretary general and spokesperson for DGN. “The effort is worth it, as 40% of all dementia cases and 90% of all strokes are preventable, with many of them linked to industrial sugar,” said Dr. Berlit. DGN and the German Brain Foundation support the call for a tax on particularly sugary beverages. They also pointed out that foods like yogurt or tomato ketchup contain sugar, and alcohol can also significantly raise blood sugar levels.

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

On World Brain Day (July 22, 2024), the German Society of Neurology (DGN) and the German Brain Foundation pointed out that too much sugar can harm the brain. The current results of the Global Burden of Diseases study shows that stroke and dementia are among the top 10 causes of death. A healthy, active lifestyle with sufficient exercise and sleep, along with the avoidance of harmful substances like alcohol, nicotine, or excessive sugar, protects the brain.

“Of course, the dose makes the poison as the brain, being the body’s powerhouse, needs glucose to function,” said Frank Erbguth, MD, PhD, president of the German Brain Foundation, in a press release from DGN and the German Brain Foundation. “However, with a permanent increase in blood sugar levels due to too many, too lavish meals and constant snacking on the side, we overload the system and fuel the development of neurologic diseases, particularly dementia and stroke.”

The per capita consumption of sugar was 33.2 kg in 2021/2022, which is almost twice the recommended amount. The German Nutrition Society recommends that no more than 10% of energy come from sugar. With a goal of 2000 kilocalories, that’s 50 g per day, or 18 kg per year. This total includes not only added sugar but also naturally occurring sugar, such as in fruits, honey, or juices.
 

What’s the Mechanism?

High blood sugar levels damage brain blood vessels and promote deposits on the vessel walls, thus reducing blood flow and nutrient supply to brain cells. This process can cause various limitations, as well as vascular dementia.

In Germany, around 250,000 people are diagnosed with dementia annually, and 15%-25% have vascular dementia. That proportion represents between 40,000 and 60,000 new cases each year.

In addition, glycosaminoglycans, which are complex sugar molecules, can directly impair cognition. They affect the function of synapses between nerve cells and, thus, affect neuronal plasticity. Experimental data presented at the 2023 American Chemical Society Congress have shown this phenomenon.

Twenty years ago, a study provided evidence that a diet high in fat and sugar disrupts neuronal plasticity and can impair the function of the hippocampus in the long term. A recent meta-analysis confirms these findings: Although mental performance improves at 2-12 hours after sugar consumption, sustained sugar intake can permanently damage cognitive function.

Diabetes mellitus can indirectly cause brain damage. Since the 1990s, it has been known that patients with type 2 diabetes have a significantly higher risk for dementia. It is suspected that glucose metabolism is also disrupted in neurons, thus contributing to the development of Alzheimer’s disease. Insulin also plays a role in the formation of Alzheimer’s plaques.

The Max Planck Institute for Metabolism Research demonstrated in 2023 that regular consumption of high-sugar and high-fat foods can change the brain. This leads to an increased craving for high-sugar and high-fat foods, which in turn promotes the development of obesity and type 2 diabetes.
 

Reduce Sugar Consumption

DGN and the German Brain Foundation advise minimizing sugar consumption. This process is often challenging, as even a small dose of sugar can trigger the gut to send signals to the brain via the vagus nerve, thus causing a strong craving for more sugar. “This could be the reason why some people quickly eat a whole chocolate bar after just one piece,” said Dr. Erbguth. In addition, dopamine, a “feel-good hormone,” is released in the brain when consuming sugar, thus leading to a desire for more.

“It is wise to break free from this cycle by largely avoiding sugar,” said Peter Berlit, MD, secretary general and spokesperson for DGN. “The effort is worth it, as 40% of all dementia cases and 90% of all strokes are preventable, with many of them linked to industrial sugar,” said Dr. Berlit. DGN and the German Brain Foundation support the call for a tax on particularly sugary beverages. They also pointed out that foods like yogurt or tomato ketchup contain sugar, and alcohol can also significantly raise blood sugar levels.

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

On World Brain Day (July 22, 2024), the German Society of Neurology (DGN) and the German Brain Foundation pointed out that too much sugar can harm the brain. The current results of the Global Burden of Diseases study shows that stroke and dementia are among the top 10 causes of death. A healthy, active lifestyle with sufficient exercise and sleep, along with the avoidance of harmful substances like alcohol, nicotine, or excessive sugar, protects the brain.

“Of course, the dose makes the poison as the brain, being the body’s powerhouse, needs glucose to function,” said Frank Erbguth, MD, PhD, president of the German Brain Foundation, in a press release from DGN and the German Brain Foundation. “However, with a permanent increase in blood sugar levels due to too many, too lavish meals and constant snacking on the side, we overload the system and fuel the development of neurologic diseases, particularly dementia and stroke.”

The per capita consumption of sugar was 33.2 kg in 2021/2022, which is almost twice the recommended amount. The German Nutrition Society recommends that no more than 10% of energy come from sugar. With a goal of 2000 kilocalories, that’s 50 g per day, or 18 kg per year. This total includes not only added sugar but also naturally occurring sugar, such as in fruits, honey, or juices.
 

What’s the Mechanism?

High blood sugar levels damage brain blood vessels and promote deposits on the vessel walls, thus reducing blood flow and nutrient supply to brain cells. This process can cause various limitations, as well as vascular dementia.

In Germany, around 250,000 people are diagnosed with dementia annually, and 15%-25% have vascular dementia. That proportion represents between 40,000 and 60,000 new cases each year.

In addition, glycosaminoglycans, which are complex sugar molecules, can directly impair cognition. They affect the function of synapses between nerve cells and, thus, affect neuronal plasticity. Experimental data presented at the 2023 American Chemical Society Congress have shown this phenomenon.

Twenty years ago, a study provided evidence that a diet high in fat and sugar disrupts neuronal plasticity and can impair the function of the hippocampus in the long term. A recent meta-analysis confirms these findings: Although mental performance improves at 2-12 hours after sugar consumption, sustained sugar intake can permanently damage cognitive function.

Diabetes mellitus can indirectly cause brain damage. Since the 1990s, it has been known that patients with type 2 diabetes have a significantly higher risk for dementia. It is suspected that glucose metabolism is also disrupted in neurons, thus contributing to the development of Alzheimer’s disease. Insulin also plays a role in the formation of Alzheimer’s plaques.

The Max Planck Institute for Metabolism Research demonstrated in 2023 that regular consumption of high-sugar and high-fat foods can change the brain. This leads to an increased craving for high-sugar and high-fat foods, which in turn promotes the development of obesity and type 2 diabetes.
 

Reduce Sugar Consumption

DGN and the German Brain Foundation advise minimizing sugar consumption. This process is often challenging, as even a small dose of sugar can trigger the gut to send signals to the brain via the vagus nerve, thus causing a strong craving for more sugar. “This could be the reason why some people quickly eat a whole chocolate bar after just one piece,” said Dr. Erbguth. In addition, dopamine, a “feel-good hormone,” is released in the brain when consuming sugar, thus leading to a desire for more.

“It is wise to break free from this cycle by largely avoiding sugar,” said Peter Berlit, MD, secretary general and spokesperson for DGN. “The effort is worth it, as 40% of all dementia cases and 90% of all strokes are preventable, with many of them linked to industrial sugar,” said Dr. Berlit. DGN and the German Brain Foundation support the call for a tax on particularly sugary beverages. They also pointed out that foods like yogurt or tomato ketchup contain sugar, and alcohol can also significantly raise blood sugar levels.

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

TOPLINE:

Arterial stiffness increases the risk for developing glaucoma, a new study found.

METHODOLOGY:

• To study the link between arterial stiffness and glaucoma, the researchers evaluated 4713 individuals (mean age, 66 years; 58% men) without the eye condition at baseline between April 2011 and November 2012.
• They assessed arterial stiffness by measuring aortic pulse wave velocity, estimated carotid-femoral pulse wave velocity, and aortic pulse pressure.
• The primary outcome was incident glaucoma, identified from prescriptions for eye drops or hospital records.

TAKEAWAY:

• Overall, 301 people in the study developed glaucoma over a mean follow-up period of 10.5 years.
• For every standard deviation increase in aortic pulse wave velocity, participants had a 32% higher risk for developing glaucoma (standardized hazard ratio [sHR], 1.32; 95% CI, 1.10-1.60), while estimated carotid-femoral pulse wave velocity was associated with a 37% higher risk (sHR, 1.37; 95% CI, 1.11-1.70).
• Incident glaucoma increased across all quartiles of arterial stiffness, with the highest risk observed in the fourth quartile for aortic pulse wave velocity (HR, 2.41; 95% CI, 1.36-4.26), estimated carotid-femoral pulse wave velocity (HR, 2.29; 95% CI, 1.27-4.13), and aortic pulse pressure (HR, 1.76; 95% CI, 1.10-2.82).
• The cumulative incidence of glaucoma rose with increases in arterial stiffness. This trend was statistically significant for both aortic and estimated pulse wave velocity (P < .0001) and aortic pulse pressure (P = .02).

IN PRACTICE:

“Arterial stiffness…which can be easily and accurately measured, could be used as a tool in clinical practice [as part of routine blood pressure measurement] to help identify people at risk of glaucoma and as a therapeutic target to prevent glaucoma progression,” the authors wrote.

SOURCE:

This study was led by Angela L. Beros, MPH, of the School of Population Health at the University of Auckland, Auckland, New Zealand, and published online in the American Journal of Ophthalmology.

LIMITATIONS:

The cohort study did not clinically assess for glaucoma, potentially leading to the inclusion of individuals with the condition. Not all participants with incident glaucoma, particularly those unaware of their diagnosis, may have been identified. Intraocular pressure and central corneal thickness, which are common risk factors for glaucoma, were not included in the multivariate analysis.

DISCLOSURES:

The study did not receive any funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Arterial stiffness increases the risk for developing glaucoma, a new study found.

METHODOLOGY:

• To study the link between arterial stiffness and glaucoma, the researchers evaluated 4713 individuals (mean age, 66 years; 58% men) without the eye condition at baseline between April 2011 and November 2012.
• They assessed arterial stiffness by measuring aortic pulse wave velocity, estimated carotid-femoral pulse wave velocity, and aortic pulse pressure.
• The primary outcome was incident glaucoma, identified from prescriptions for eye drops or hospital records.

TAKEAWAY:

• Overall, 301 people in the study developed glaucoma over a mean follow-up period of 10.5 years.
• For every standard deviation increase in aortic pulse wave velocity, participants had a 32% higher risk for developing glaucoma (standardized hazard ratio [sHR], 1.32; 95% CI, 1.10-1.60), while estimated carotid-femoral pulse wave velocity was associated with a 37% higher risk (sHR, 1.37; 95% CI, 1.11-1.70).
• Incident glaucoma increased across all quartiles of arterial stiffness, with the highest risk observed in the fourth quartile for aortic pulse wave velocity (HR, 2.41; 95% CI, 1.36-4.26), estimated carotid-femoral pulse wave velocity (HR, 2.29; 95% CI, 1.27-4.13), and aortic pulse pressure (HR, 1.76; 95% CI, 1.10-2.82).
• The cumulative incidence of glaucoma rose with increases in arterial stiffness. This trend was statistically significant for both aortic and estimated pulse wave velocity (P < .0001) and aortic pulse pressure (P = .02).

IN PRACTICE:

“Arterial stiffness…which can be easily and accurately measured, could be used as a tool in clinical practice [as part of routine blood pressure measurement] to help identify people at risk of glaucoma and as a therapeutic target to prevent glaucoma progression,” the authors wrote.

SOURCE:

This study was led by Angela L. Beros, MPH, of the School of Population Health at the University of Auckland, Auckland, New Zealand, and published online in the American Journal of Ophthalmology.

LIMITATIONS:

The cohort study did not clinically assess for glaucoma, potentially leading to the inclusion of individuals with the condition. Not all participants with incident glaucoma, particularly those unaware of their diagnosis, may have been identified. Intraocular pressure and central corneal thickness, which are common risk factors for glaucoma, were not included in the multivariate analysis.

DISCLOSURES:

The study did not receive any funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Arterial stiffness increases the risk for developing glaucoma, a new study found.

METHODOLOGY:

• To study the link between arterial stiffness and glaucoma, the researchers evaluated 4713 individuals (mean age, 66 years; 58% men) without the eye condition at baseline between April 2011 and November 2012.
• They assessed arterial stiffness by measuring aortic pulse wave velocity, estimated carotid-femoral pulse wave velocity, and aortic pulse pressure.
• The primary outcome was incident glaucoma, identified from prescriptions for eye drops or hospital records.

TAKEAWAY:

• Overall, 301 people in the study developed glaucoma over a mean follow-up period of 10.5 years.
• For every standard deviation increase in aortic pulse wave velocity, participants had a 32% higher risk for developing glaucoma (standardized hazard ratio [sHR], 1.32; 95% CI, 1.10-1.60), while estimated carotid-femoral pulse wave velocity was associated with a 37% higher risk (sHR, 1.37; 95% CI, 1.11-1.70).
• Incident glaucoma increased across all quartiles of arterial stiffness, with the highest risk observed in the fourth quartile for aortic pulse wave velocity (HR, 2.41; 95% CI, 1.36-4.26), estimated carotid-femoral pulse wave velocity (HR, 2.29; 95% CI, 1.27-4.13), and aortic pulse pressure (HR, 1.76; 95% CI, 1.10-2.82).
• The cumulative incidence of glaucoma rose with increases in arterial stiffness. This trend was statistically significant for both aortic and estimated pulse wave velocity (P < .0001) and aortic pulse pressure (P = .02).

IN PRACTICE:

“Arterial stiffness…which can be easily and accurately measured, could be used as a tool in clinical practice [as part of routine blood pressure measurement] to help identify people at risk of glaucoma and as a therapeutic target to prevent glaucoma progression,” the authors wrote.

SOURCE:

This study was led by Angela L. Beros, MPH, of the School of Population Health at the University of Auckland, Auckland, New Zealand, and published online in the American Journal of Ophthalmology.

LIMITATIONS:

The cohort study did not clinically assess for glaucoma, potentially leading to the inclusion of individuals with the condition. Not all participants with incident glaucoma, particularly those unaware of their diagnosis, may have been identified. Intraocular pressure and central corneal thickness, which are common risk factors for glaucoma, were not included in the multivariate analysis.

DISCLOSURES:

The study did not receive any funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Compared with supervised treadmill workouts at a gym, which is considered first-line therapy for walking impairment in lower extremity peripheral artery disease (PAD), exercising at home significantly improves 6-minute walking (6MW) distance, but not maximal treadmill walking distance, results of a new meta-analysis show.

METHODOLOGY:

• The analysis included five randomized clinical trials with a total of 719 participants, mean age 68.6 years, all led by researchers at Northwestern University, Chicago, that compared either supervised treadmill or home-based walking exercise with a nonexercise control group in people with PAD (defined as Ankle Brachial Index ≤ 0.90).
• All trials measured 6-minute walk (6MW) distance (walking as far as possible in 6 minutes), treadmill walking performance, and outcomes from the Walking Impairment Questionnaire (WIQ), which includes distance, walking speed, and stair-climbing domains, at baseline and at 6 months.
• Supervised treadmill exercise interventions included three individualized exercise sessions per week with an exercise physiologist at an exercise center, and home-based exercises involved walking near home 5 days per week, both for up to 50 minutes per session.

TAKEAWAY:

• After adjusting for study, age, sex, race, smoking, history of myocardial infarction, heart failure, and baseline 6MW distance, the study found both exercise interventions were better than nonexercise controls for 6MW distance.
• Compared with supervised treadmill exercise, home-based walking was associated with significantly improved mean 6MW distance (31.8 m vs. 55.6 m; adjusted between-group difference: −23.8 m; 95% confidence interval, −44.0 to −3.6; P = .021), and significantly improved WIQ walking speed score.
• However, home-based walking was associated with significantly less improvement in maximal treadmill walking distance, compared with supervised treadmill exercise (adjusted between-group difference: 132.5 m; 95% CI, 72.1-192.9; P < .001).

IN PRACTICE:

Home-based walking exercise “circumvents” barriers to accessing supervised exercise such as having to travel to a facility, said the authors, who noted the new data “demonstrated a large and consistent effect of home-based walking exercise on improved 6MW distance and also significantly improved the WIQ walking speed score, compared with supervised treadmill exercise.”

SOURCE:

The study was conducted by Neela D. Thangada, MD, Northwestern University, Chicago, and colleagues. It was published online in JAMA Network Open.

LIMITATIONS:

Data were combined from different randomized clinical trials that were led by one investigative team, and reported comparisons were not prespecified. Comparisons between supervised and home-based exercise lacked statistical power for the WIQ distance and stair-climbing measures.

DISCLOSURES:

The study was sponsored by the National Center for Research Resources and the National Heart, Lung, and Blood Institute of the National Institutes of Health. Dr. Thangada reports no relevant financial relationships. Disclosures for study coauthors can be found with the original article.

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

TOPLINE:

Compared with supervised treadmill workouts at a gym, which is considered first-line therapy for walking impairment in lower extremity peripheral artery disease (PAD), exercising at home significantly improves 6-minute walking (6MW) distance, but not maximal treadmill walking distance, results of a new meta-analysis show.

METHODOLOGY:

• The analysis included five randomized clinical trials with a total of 719 participants, mean age 68.6 years, all led by researchers at Northwestern University, Chicago, that compared either supervised treadmill or home-based walking exercise with a nonexercise control group in people with PAD (defined as Ankle Brachial Index ≤ 0.90).
• All trials measured 6-minute walk (6MW) distance (walking as far as possible in 6 minutes), treadmill walking performance, and outcomes from the Walking Impairment Questionnaire (WIQ), which includes distance, walking speed, and stair-climbing domains, at baseline and at 6 months.
• Supervised treadmill exercise interventions included three individualized exercise sessions per week with an exercise physiologist at an exercise center, and home-based exercises involved walking near home 5 days per week, both for up to 50 minutes per session.

TAKEAWAY:

• After adjusting for study, age, sex, race, smoking, history of myocardial infarction, heart failure, and baseline 6MW distance, the study found both exercise interventions were better than nonexercise controls for 6MW distance.
• Compared with supervised treadmill exercise, home-based walking was associated with significantly improved mean 6MW distance (31.8 m vs. 55.6 m; adjusted between-group difference: −23.8 m; 95% confidence interval, −44.0 to −3.6; P = .021), and significantly improved WIQ walking speed score.
• However, home-based walking was associated with significantly less improvement in maximal treadmill walking distance, compared with supervised treadmill exercise (adjusted between-group difference: 132.5 m; 95% CI, 72.1-192.9; P < .001).

IN PRACTICE:

Home-based walking exercise “circumvents” barriers to accessing supervised exercise such as having to travel to a facility, said the authors, who noted the new data “demonstrated a large and consistent effect of home-based walking exercise on improved 6MW distance and also significantly improved the WIQ walking speed score, compared with supervised treadmill exercise.”

SOURCE:

The study was conducted by Neela D. Thangada, MD, Northwestern University, Chicago, and colleagues. It was published online in JAMA Network Open.

LIMITATIONS:

Data were combined from different randomized clinical trials that were led by one investigative team, and reported comparisons were not prespecified. Comparisons between supervised and home-based exercise lacked statistical power for the WIQ distance and stair-climbing measures.

DISCLOSURES:

The study was sponsored by the National Center for Research Resources and the National Heart, Lung, and Blood Institute of the National Institutes of Health. Dr. Thangada reports no relevant financial relationships. Disclosures for study coauthors can be found with the original article.

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

TOPLINE:

Compared with supervised treadmill workouts at a gym, which is considered first-line therapy for walking impairment in lower extremity peripheral artery disease (PAD), exercising at home significantly improves 6-minute walking (6MW) distance, but not maximal treadmill walking distance, results of a new meta-analysis show.

METHODOLOGY:

• The analysis included five randomized clinical trials with a total of 719 participants, mean age 68.6 years, all led by researchers at Northwestern University, Chicago, that compared either supervised treadmill or home-based walking exercise with a nonexercise control group in people with PAD (defined as Ankle Brachial Index ≤ 0.90).
• All trials measured 6-minute walk (6MW) distance (walking as far as possible in 6 minutes), treadmill walking performance, and outcomes from the Walking Impairment Questionnaire (WIQ), which includes distance, walking speed, and stair-climbing domains, at baseline and at 6 months.
• Supervised treadmill exercise interventions included three individualized exercise sessions per week with an exercise physiologist at an exercise center, and home-based exercises involved walking near home 5 days per week, both for up to 50 minutes per session.

TAKEAWAY:

• After adjusting for study, age, sex, race, smoking, history of myocardial infarction, heart failure, and baseline 6MW distance, the study found both exercise interventions were better than nonexercise controls for 6MW distance.
• Compared with supervised treadmill exercise, home-based walking was associated with significantly improved mean 6MW distance (31.8 m vs. 55.6 m; adjusted between-group difference: −23.8 m; 95% confidence interval, −44.0 to −3.6; P = .021), and significantly improved WIQ walking speed score.
• However, home-based walking was associated with significantly less improvement in maximal treadmill walking distance, compared with supervised treadmill exercise (adjusted between-group difference: 132.5 m; 95% CI, 72.1-192.9; P < .001).

IN PRACTICE:

Home-based walking exercise “circumvents” barriers to accessing supervised exercise such as having to travel to a facility, said the authors, who noted the new data “demonstrated a large and consistent effect of home-based walking exercise on improved 6MW distance and also significantly improved the WIQ walking speed score, compared with supervised treadmill exercise.”

SOURCE:

The study was conducted by Neela D. Thangada, MD, Northwestern University, Chicago, and colleagues. It was published online in JAMA Network Open.

LIMITATIONS:

Data were combined from different randomized clinical trials that were led by one investigative team, and reported comparisons were not prespecified. Comparisons between supervised and home-based exercise lacked statistical power for the WIQ distance and stair-climbing measures.

DISCLOSURES:

The study was sponsored by the National Center for Research Resources and the National Heart, Lung, and Blood Institute of the National Institutes of Health. Dr. Thangada reports no relevant financial relationships. Disclosures for study coauthors can be found with the original article.

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