Increased levels of carnitine and acylcarnitines are associated with increased dysbiosis and disease activity in pediatric inflammatory bowel disease (IBD), according to investigators.

These findings improve our understanding of IBD pathogenesis and disease course, and could prove valuable in biomarker research, reported lead author Gary D. Wu, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

In health, carnitine and acylcarnitines aid in fatty acid transport, the investigators wrote in September in Cellular and Molecular Gastroenterology and Hepatology. Acylcarnitines are also involved in metabolic signaling, and in the absence of sufficient short-chain fatty acids may serve as an alternative energy source for the intestinal epithelium.

“Recently, we and others have shown that fecal acylcarnitines are increased in patients with IBD, especially during dysbiosis,” they noted. “However, the mechanism(s) responsible for the increase of fecal acylcarnitines in IBD and their biological function have not been elucidated.”

The present study aimed to address this knowledge gap by characterizing both carnitine and acylcarnitines in pediatric IBD.

First, the investigators confirmed that both carnitine and acylcarnitines were elevated in fecal samples from pediatric patients with IBD.

Next, they analyzed fecal samples from subjects in the Food and Resulting Microbiota and Metabolome (FARMM) study, which compared microbiota recovery after gut purge and antibiotics among participants eating an omnivorous diet, a vegan diet, or an exclusive enteral nutrition (EEN) diet lacking in fiber. After the antibiotics, levels of fecal carnitine and acylcarnitines increased significantly in all groups, suggesting that microbiota were consuming these molecules.

To clarify the relationship between inflammation and levels of carnitine and acylcarnitines in the absence of microbiota, Dr. Wu and colleagues employed a germ-free mouse model with dextran sodium sulfate (DSS)–induced colitis. Levels of both molecule types were significantly increased in bile and plasma of mice with colitis versus those that were not exposed to DSS.

“Because the gut microbiota consumes both carnitine and acylcarnitines, these results are consistent with the notion that the increase of these metabolites in the feces of patients with IBD is driven by increased biliary delivery of acylcarnitines to the lumen combined with the reduced number and function of mitochondria in the colonic epithelium as previously reported,” the investigators wrote.

Further experiments with plated cultures and mice revealed that various bacterial species consumed carnitine and acylcarnitines in distinct patterns. Enterobacteriaceae demonstrated a notable proclivity for consumption in vitro and within the murine gut.

“As a high-dimensional analytic feature, the pattern of fecal acylcarnitines, perhaps together with bacterial taxonomy, may have utility as a biomarker for the presence or prognosis of IBD,” Dr. Wu and colleagues concluded. “In addition, based on currently available information about the impact of carnitine on the biology of Enterobacteriaceae, acylcarnitines also may have an important functional effect on the biology of the gut microbiota that is relevant to the pathogenesis or course of disease in patients with IBD.”

The study was supported by the Crohn’s and Colitis Foundation, the PennCHOP Microbiome Program, the Penn Center for Nutritional Science and Medicine, and others. The investigators disclosed no conflicts of interest.

Increased levels of carnitine and acylcarnitines are associated with increased dysbiosis and disease activity in pediatric inflammatory bowel disease (IBD), according to investigators.

These findings improve our understanding of IBD pathogenesis and disease course, and could prove valuable in biomarker research, reported lead author Gary D. Wu, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

In health, carnitine and acylcarnitines aid in fatty acid transport, the investigators wrote in September in Cellular and Molecular Gastroenterology and Hepatology. Acylcarnitines are also involved in metabolic signaling, and in the absence of sufficient short-chain fatty acids may serve as an alternative energy source for the intestinal epithelium.

“Recently, we and others have shown that fecal acylcarnitines are increased in patients with IBD, especially during dysbiosis,” they noted. “However, the mechanism(s) responsible for the increase of fecal acylcarnitines in IBD and their biological function have not been elucidated.”

The present study aimed to address this knowledge gap by characterizing both carnitine and acylcarnitines in pediatric IBD.

First, the investigators confirmed that both carnitine and acylcarnitines were elevated in fecal samples from pediatric patients with IBD.

Next, they analyzed fecal samples from subjects in the Food and Resulting Microbiota and Metabolome (FARMM) study, which compared microbiota recovery after gut purge and antibiotics among participants eating an omnivorous diet, a vegan diet, or an exclusive enteral nutrition (EEN) diet lacking in fiber. After the antibiotics, levels of fecal carnitine and acylcarnitines increased significantly in all groups, suggesting that microbiota were consuming these molecules.

To clarify the relationship between inflammation and levels of carnitine and acylcarnitines in the absence of microbiota, Dr. Wu and colleagues employed a germ-free mouse model with dextran sodium sulfate (DSS)–induced colitis. Levels of both molecule types were significantly increased in bile and plasma of mice with colitis versus those that were not exposed to DSS.

“Because the gut microbiota consumes both carnitine and acylcarnitines, these results are consistent with the notion that the increase of these metabolites in the feces of patients with IBD is driven by increased biliary delivery of acylcarnitines to the lumen combined with the reduced number and function of mitochondria in the colonic epithelium as previously reported,” the investigators wrote.

Further experiments with plated cultures and mice revealed that various bacterial species consumed carnitine and acylcarnitines in distinct patterns. Enterobacteriaceae demonstrated a notable proclivity for consumption in vitro and within the murine gut.

“As a high-dimensional analytic feature, the pattern of fecal acylcarnitines, perhaps together with bacterial taxonomy, may have utility as a biomarker for the presence or prognosis of IBD,” Dr. Wu and colleagues concluded. “In addition, based on currently available information about the impact of carnitine on the biology of Enterobacteriaceae, acylcarnitines also may have an important functional effect on the biology of the gut microbiota that is relevant to the pathogenesis or course of disease in patients with IBD.”

The study was supported by the Crohn’s and Colitis Foundation, the PennCHOP Microbiome Program, the Penn Center for Nutritional Science and Medicine, and others. The investigators disclosed no conflicts of interest.

Increased levels of carnitine and acylcarnitines are associated with increased dysbiosis and disease activity in pediatric inflammatory bowel disease (IBD), according to investigators.

These findings improve our understanding of IBD pathogenesis and disease course, and could prove valuable in biomarker research, reported lead author Gary D. Wu, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

In health, carnitine and acylcarnitines aid in fatty acid transport, the investigators wrote in September in Cellular and Molecular Gastroenterology and Hepatology. Acylcarnitines are also involved in metabolic signaling, and in the absence of sufficient short-chain fatty acids may serve as an alternative energy source for the intestinal epithelium.

“Recently, we and others have shown that fecal acylcarnitines are increased in patients with IBD, especially during dysbiosis,” they noted. “However, the mechanism(s) responsible for the increase of fecal acylcarnitines in IBD and their biological function have not been elucidated.”

The present study aimed to address this knowledge gap by characterizing both carnitine and acylcarnitines in pediatric IBD.

First, the investigators confirmed that both carnitine and acylcarnitines were elevated in fecal samples from pediatric patients with IBD.

Next, they analyzed fecal samples from subjects in the Food and Resulting Microbiota and Metabolome (FARMM) study, which compared microbiota recovery after gut purge and antibiotics among participants eating an omnivorous diet, a vegan diet, or an exclusive enteral nutrition (EEN) diet lacking in fiber. After the antibiotics, levels of fecal carnitine and acylcarnitines increased significantly in all groups, suggesting that microbiota were consuming these molecules.

To clarify the relationship between inflammation and levels of carnitine and acylcarnitines in the absence of microbiota, Dr. Wu and colleagues employed a germ-free mouse model with dextran sodium sulfate (DSS)–induced colitis. Levels of both molecule types were significantly increased in bile and plasma of mice with colitis versus those that were not exposed to DSS.

“Because the gut microbiota consumes both carnitine and acylcarnitines, these results are consistent with the notion that the increase of these metabolites in the feces of patients with IBD is driven by increased biliary delivery of acylcarnitines to the lumen combined with the reduced number and function of mitochondria in the colonic epithelium as previously reported,” the investigators wrote.

Further experiments with plated cultures and mice revealed that various bacterial species consumed carnitine and acylcarnitines in distinct patterns. Enterobacteriaceae demonstrated a notable proclivity for consumption in vitro and within the murine gut.

“As a high-dimensional analytic feature, the pattern of fecal acylcarnitines, perhaps together with bacterial taxonomy, may have utility as a biomarker for the presence or prognosis of IBD,” Dr. Wu and colleagues concluded. “In addition, based on currently available information about the impact of carnitine on the biology of Enterobacteriaceae, acylcarnitines also may have an important functional effect on the biology of the gut microbiota that is relevant to the pathogenesis or course of disease in patients with IBD.”

The study was supported by the Crohn’s and Colitis Foundation, the PennCHOP Microbiome Program, the Penn Center for Nutritional Science and Medicine, and others. The investigators disclosed no conflicts of interest.

American Gastroenterological Association (AGA) has released a new Clinical Practice Update (CPU) guiding the use of vasoactive drugs and intravenous albumin in patients with cirrhosis.

The publication, authored by Vincent Wai-Sun Wong, MBChB, MD, and colleagues, includes 12 best-practice-advice statements concerning 3 common clinical scenarios: variceal hemorrhage, ascites and spontaneous bacterial peritonitis, and acute kidney injury and hepatorenal syndrome.

These complications of liver decompensation “are manifestations of portal hypertension with a [consequent] vasodilatory–hyperdynamic circulatory state, resulting in progressive decreases in effective arterial blood volume and renal perfusion,” the update authors wrote in November in Gastroenterology. “Because a potent vasoconstrictor, terlipressin, was recently approved by the United States Food and Drug Administration and because recent trials have explored use of intravenous albumin in other settings, it was considered that a best practice update would be relevant regarding the use of vasoactive drugs and intravenous albumin in these 3 specific scenarios.”
 

Variceal Hemorrhage

Comprising 70% of all upper GI hemorrhage in patients with cirrhosis, and carrying a 6-week mortality rate as high as 43%, Dr. Wong and colleagues advise immediate initiation of vasoactive drugs upon suspision of variceal hemorrhage, ideally before therapeutic and/or diagnostic endoscopy.

“The goals of management of acute variceal hemorrhage include initial hemostasis, preventing early rebleeding, and reducing in-hospital and 6-week mortality,” they wrote, noting that vasoactive drugs are effective at stopping bleeding in up to 8 out of 10 cases.

In patients with acute variceal hemorrhage undergoing endoscopic hemostasis, vasoactive agents should be continued for 2-5 days to prevent early rebleeding, according to the second best-practice-advice statement.

The third statement suggests octreotide as the drug of choice for variceal hemorrhage due to its favorable safety profile.

“Nowadays, vasopressin is no longer advised in patients with acute variceal hemorrhage because of a high risk of cardiovascular adverse events,” the update authors noted.
 

Ascites and Spontaneous Bacterial Peritonitis

In cases requiring large-volume (greater than 5 L) paracentesis, intravenous albumin should be administered at time of fluid removal, according to the update. In these patients, albumin reduces the risk of post-paracentesis circulatory dysfunction (defined as an increase in plasma renin activity), thereby reducing the risk of acute kidney injury.

Intravenous albumin should also be considered in patients with spontaneous bacterial peritonitis as this can overcome associated vasodilatation and decreased effective arterial blood volume, which may lead to acute kidney injury if untreated. In contrast, because of a demonstrated lack of efficacy, albumin is not advised in infections other than spontaneous bacterial peritonitis, unless associated with acute kidney injury.

Long-term albumin administration should be avoided in patients with cirrhosis and uncomplicated ascites, whether they are hospitalized or not, as evidence is lacking to support a consistent beneficial effect.

The update also advises against vasoconstrictors in patients with uncomplicated ascites, bacterial peritonitis, and after large-volume paracentesis, again due to a lack of supporting evidence.
 

Acute Kidney Injury and Hepatorenal Syndrome

In hospitalized patients with cirrhosis and ascites presenting with acute kidney injury, Dr. Wong and colleagues called albumin “the volume expander of choice in hospitalized patients with cirrhosis and ascites presenting with acute kidney injury,” however, the authors caution the dose of albumin “should be tailored to the volume status of the patient.”

The update authors suggested that terlipressin and norepinephrine are suitable options for patients with cirrhosis and the hepatorenal syndrome; however, they suggest terlipressin above the others based on available evidence and suggested concomitant albumin administration as it may further improve renal blood flow by filling the central circulation.

Terlipressin also has the advantage (over norepinephrine) of being administrable via a peripheral line without the need for intensive care unit monitoring, the update authors wrote. The agent is contraindicated in patients with hypoxia or with coronary, peripheral, or mesenteric ischemia, and it should be used with caution in patients with ACLF grade 3, according to the publication. Risks of terlipressin may also outweigh benefits in patients with a serum creatine greater than 5 mg/dL and those listed for transplant with a MELD score of 35 or higher.

The Clinical Practice Update was commissioned and supported by AGA. The authors disclosed relationships with Advanz, Boehringer Ingelheim, 89bio, and others.

American Gastroenterological Association (AGA) has released a new Clinical Practice Update (CPU) guiding the use of vasoactive drugs and intravenous albumin in patients with cirrhosis.

The publication, authored by Vincent Wai-Sun Wong, MBChB, MD, and colleagues, includes 12 best-practice-advice statements concerning 3 common clinical scenarios: variceal hemorrhage, ascites and spontaneous bacterial peritonitis, and acute kidney injury and hepatorenal syndrome.

These complications of liver decompensation “are manifestations of portal hypertension with a [consequent] vasodilatory–hyperdynamic circulatory state, resulting in progressive decreases in effective arterial blood volume and renal perfusion,” the update authors wrote in November in Gastroenterology. “Because a potent vasoconstrictor, terlipressin, was recently approved by the United States Food and Drug Administration and because recent trials have explored use of intravenous albumin in other settings, it was considered that a best practice update would be relevant regarding the use of vasoactive drugs and intravenous albumin in these 3 specific scenarios.”
 

Variceal Hemorrhage

Comprising 70% of all upper GI hemorrhage in patients with cirrhosis, and carrying a 6-week mortality rate as high as 43%, Dr. Wong and colleagues advise immediate initiation of vasoactive drugs upon suspision of variceal hemorrhage, ideally before therapeutic and/or diagnostic endoscopy.

“The goals of management of acute variceal hemorrhage include initial hemostasis, preventing early rebleeding, and reducing in-hospital and 6-week mortality,” they wrote, noting that vasoactive drugs are effective at stopping bleeding in up to 8 out of 10 cases.

In patients with acute variceal hemorrhage undergoing endoscopic hemostasis, vasoactive agents should be continued for 2-5 days to prevent early rebleeding, according to the second best-practice-advice statement.

The third statement suggests octreotide as the drug of choice for variceal hemorrhage due to its favorable safety profile.

“Nowadays, vasopressin is no longer advised in patients with acute variceal hemorrhage because of a high risk of cardiovascular adverse events,” the update authors noted.
 

Ascites and Spontaneous Bacterial Peritonitis

In cases requiring large-volume (greater than 5 L) paracentesis, intravenous albumin should be administered at time of fluid removal, according to the update. In these patients, albumin reduces the risk of post-paracentesis circulatory dysfunction (defined as an increase in plasma renin activity), thereby reducing the risk of acute kidney injury.

Intravenous albumin should also be considered in patients with spontaneous bacterial peritonitis as this can overcome associated vasodilatation and decreased effective arterial blood volume, which may lead to acute kidney injury if untreated. In contrast, because of a demonstrated lack of efficacy, albumin is not advised in infections other than spontaneous bacterial peritonitis, unless associated with acute kidney injury.

Long-term albumin administration should be avoided in patients with cirrhosis and uncomplicated ascites, whether they are hospitalized or not, as evidence is lacking to support a consistent beneficial effect.

The update also advises against vasoconstrictors in patients with uncomplicated ascites, bacterial peritonitis, and after large-volume paracentesis, again due to a lack of supporting evidence.
 

Acute Kidney Injury and Hepatorenal Syndrome

In hospitalized patients with cirrhosis and ascites presenting with acute kidney injury, Dr. Wong and colleagues called albumin “the volume expander of choice in hospitalized patients with cirrhosis and ascites presenting with acute kidney injury,” however, the authors caution the dose of albumin “should be tailored to the volume status of the patient.”

The update authors suggested that terlipressin and norepinephrine are suitable options for patients with cirrhosis and the hepatorenal syndrome; however, they suggest terlipressin above the others based on available evidence and suggested concomitant albumin administration as it may further improve renal blood flow by filling the central circulation.

Terlipressin also has the advantage (over norepinephrine) of being administrable via a peripheral line without the need for intensive care unit monitoring, the update authors wrote. The agent is contraindicated in patients with hypoxia or with coronary, peripheral, or mesenteric ischemia, and it should be used with caution in patients with ACLF grade 3, according to the publication. Risks of terlipressin may also outweigh benefits in patients with a serum creatine greater than 5 mg/dL and those listed for transplant with a MELD score of 35 or higher.

The Clinical Practice Update was commissioned and supported by AGA. The authors disclosed relationships with Advanz, Boehringer Ingelheim, 89bio, and others.

American Gastroenterological Association (AGA) has released a new Clinical Practice Update (CPU) guiding the use of vasoactive drugs and intravenous albumin in patients with cirrhosis.

The publication, authored by Vincent Wai-Sun Wong, MBChB, MD, and colleagues, includes 12 best-practice-advice statements concerning 3 common clinical scenarios: variceal hemorrhage, ascites and spontaneous bacterial peritonitis, and acute kidney injury and hepatorenal syndrome.

These complications of liver decompensation “are manifestations of portal hypertension with a [consequent] vasodilatory–hyperdynamic circulatory state, resulting in progressive decreases in effective arterial blood volume and renal perfusion,” the update authors wrote in November in Gastroenterology. “Because a potent vasoconstrictor, terlipressin, was recently approved by the United States Food and Drug Administration and because recent trials have explored use of intravenous albumin in other settings, it was considered that a best practice update would be relevant regarding the use of vasoactive drugs and intravenous albumin in these 3 specific scenarios.”
 

Variceal Hemorrhage

Comprising 70% of all upper GI hemorrhage in patients with cirrhosis, and carrying a 6-week mortality rate as high as 43%, Dr. Wong and colleagues advise immediate initiation of vasoactive drugs upon suspision of variceal hemorrhage, ideally before therapeutic and/or diagnostic endoscopy.

“The goals of management of acute variceal hemorrhage include initial hemostasis, preventing early rebleeding, and reducing in-hospital and 6-week mortality,” they wrote, noting that vasoactive drugs are effective at stopping bleeding in up to 8 out of 10 cases.

In patients with acute variceal hemorrhage undergoing endoscopic hemostasis, vasoactive agents should be continued for 2-5 days to prevent early rebleeding, according to the second best-practice-advice statement.

The third statement suggests octreotide as the drug of choice for variceal hemorrhage due to its favorable safety profile.

“Nowadays, vasopressin is no longer advised in patients with acute variceal hemorrhage because of a high risk of cardiovascular adverse events,” the update authors noted.
 

Ascites and Spontaneous Bacterial Peritonitis

In cases requiring large-volume (greater than 5 L) paracentesis, intravenous albumin should be administered at time of fluid removal, according to the update. In these patients, albumin reduces the risk of post-paracentesis circulatory dysfunction (defined as an increase in plasma renin activity), thereby reducing the risk of acute kidney injury.

Intravenous albumin should also be considered in patients with spontaneous bacterial peritonitis as this can overcome associated vasodilatation and decreased effective arterial blood volume, which may lead to acute kidney injury if untreated. In contrast, because of a demonstrated lack of efficacy, albumin is not advised in infections other than spontaneous bacterial peritonitis, unless associated with acute kidney injury.

Long-term albumin administration should be avoided in patients with cirrhosis and uncomplicated ascites, whether they are hospitalized or not, as evidence is lacking to support a consistent beneficial effect.

The update also advises against vasoconstrictors in patients with uncomplicated ascites, bacterial peritonitis, and after large-volume paracentesis, again due to a lack of supporting evidence.
 

Acute Kidney Injury and Hepatorenal Syndrome

In hospitalized patients with cirrhosis and ascites presenting with acute kidney injury, Dr. Wong and colleagues called albumin “the volume expander of choice in hospitalized patients with cirrhosis and ascites presenting with acute kidney injury,” however, the authors caution the dose of albumin “should be tailored to the volume status of the patient.”

The update authors suggested that terlipressin and norepinephrine are suitable options for patients with cirrhosis and the hepatorenal syndrome; however, they suggest terlipressin above the others based on available evidence and suggested concomitant albumin administration as it may further improve renal blood flow by filling the central circulation.

Terlipressin also has the advantage (over norepinephrine) of being administrable via a peripheral line without the need for intensive care unit monitoring, the update authors wrote. The agent is contraindicated in patients with hypoxia or with coronary, peripheral, or mesenteric ischemia, and it should be used with caution in patients with ACLF grade 3, according to the publication. Risks of terlipressin may also outweigh benefits in patients with a serum creatine greater than 5 mg/dL and those listed for transplant with a MELD score of 35 or higher.

The Clinical Practice Update was commissioned and supported by AGA. The authors disclosed relationships with Advanz, Boehringer Ingelheim, 89bio, and others.

HAMBURG, Germany — The human microbiome comprises 39 to 44 billion microbes. That is ten times more than the number of cells in our body. Hendrik Poeck, MD, managing senior physician of internal medicine at the University Hospital Regensburg, illustrated this point at the annual meeting of the German Society for Hematology and Medical Oncology. If the gut microbiome falls out of balance, then “intestinal dysbiosis potentially poses a risk for the pathogenesis of local and systemic diseases,” explained Dr. Poeck.

Cancers and their therapies can also be influenced in this way. “Microbial diversity affects whether a tumor grows, whether it leads to inflammation, immune escape mechanisms or genomic instability, or whether therapeutic resistances develop,” said Dr. Poeck.

Microbial diversity could be beneficial for cancer therapy, too. The composition of the microbiome varies significantly from host to host and can mutate. These properties make it a target for precision microbiotics, which involves using the gut microbiome as a biomarker to predict various physical reactions and to develop individualized diets.

Microbiome and Pathogenesis

The body’s microbiome fulfills a barrier function, especially where the body is exposed to an external environment: at the epidermis and the internal mucous membranes, in the gastrointestinal tract, and in the lungs, chest, and urogenital system.

Association studies on humans and experimental manipulations on mouse models of cancer showed that certain microorganisms can have either protective or harmful effects on cancer development, on the progression of a malignant disease, and on the response to therapy.

A Master Regulator?

Disruptions of the microbial system in the gut, as occur during antibiotic therapy, can have significant effects on a patient’s response to immunotherapy. Taking antibiotics shortly before or after starting therapy with immune checkpoint inhibitors (ICIs) significantly affected both overall survival (OS) and progression-free survival (PFS), as reported in a recent review and meta-analysis, for example.

Proton pump inhibitors also affect the gut microbiome and reduce the response to immunotherapy; this effect was demonstrated by an analysis of data from more than 2700 cancer patients that was recently presented at the annual meeting of the European Society for Medical Oncology (ESMO).

The extent to which the gut microbiome influences the efficacy of an ICI or predicts said efficacy was examined in a retrospective analysis published in Science in 2018, which Dr. Poeck presented. Resistance to ICI correlated with the relative frequency of the bacteria Akkermansia muciniphila in the gut of patients with cancer. In mouse models, the researchers restored the efficacy of the PD-1 blockade through a stool transplant.

Predicting Immunotherapy Response

If A muciniphila is present, can the composition of the microbiome act as a predictor for an effective ICI therapy?

Laurence Zitvogel, MD, PhD, and her working group at the National Institute of Health and Medical Research in Villejuif, France, performed a prospective study in 338 patients with non–small cell lung cancer and examined the prognostic significance of the fecal bacteria A muciniphila (Akk). The “Akkerman status” (low Akk vs high Akk) in a patient’s stool correlated with an increased objective response rate and a longer OS, independently of PD-L1 expression, antibiotics, and performance status. The OS for low Akk was 13.4 months, vs 18.8 months for high Akk in first-line treatment.

These results are promising, said Dr. Poeck. But there is no one-size-fits-all solution. No conclusions can be drawn from one bacterium on the efficacy of therapies in humans, since “the entirety of the bacteria is decisive,” said Dr. Poeck. In addition to the gut microbiome, the composition of gut metabolites influences the response to immunotherapies, as shown in a study with ICI.

Therapeutic Interventions

One possible therapeutic intervention to restore the gut microbiome is fecal microbiota transplantation (FMT). In a phase 1 study presented by Dr. Poeck, FMT was effective in the treatment of 20 patients with melanoma with ICI in an advanced and treatment-naive stage. Seven days after the patients received FMT, the first cycle with anti-PD-1 immunotherapy was initiated, with a total administration of three to four cycles. After 12 weeks, most patients were in complete or partial remission, as evidenced on imaging.

However, FMT also carries some risks. Two cases of sepsis with multiresistant Escherichia coli occurred, as well as other serious infections. Since then, there has been an FDA condition for extended screening of the donor stool, said Dr. Poeck. Nevertheless, this intervention is promising. A search of the keywords “FMT in cancer/transplant setting” reveals 46 currently clinical studies on clinicaltrials.gov.

Nutritional Interventions

Dr. Poeck advises caution about over-the-counter products. These products usually contain only a few species, such as Lactobacillus and Bifidobacterium. “Over-the-counter probiotics can even delay the reconstitution of the microbiome after antibiotics,” said Dr. Poeck, according to a study. In some studies, the response rates were significantly lower after probiotic intake or led to controversial results, according to Dr. Poeck.

In contrast, Dr. Poeck said prebiotics (that is, a fiber-rich diet with indigestible carbohydrates) were promising. During digestion, prebiotics are split into short-chain fatty acids by bacterial enzymes and promote the growth of certain microbiota.

In this way, just 20 g of extremely fiber-rich food had a significant effect on PFS in 128 patients with melanoma undergoing anti-PD-1 immunotherapy. With 20 g of fiber-rich food per day, the PFS was stable over 60 months. The most significant benefit was observed in patients with a sufficient fiber intake who were not taking probiotics.

What to Recommend?

In summary, Dr. Poeck said that it is important to “budget” well, particularly with antibiotic administration, and to strive for calculated therapy with as narrow a spectrum as possible. For patients who experience complications such as cytokine release syndrome as a reaction to cell therapy, delaying the use of antibiotics is important. However, it is often difficult to differentiate this syndrome from neutropenic fever. The aim should be to avoid high-risk antibiotics, if clinically justifiable. Patients should avoid taking antibiotics for 30 days before starting immunotherapy.

Regarding nutritional interventions, Dr. Poeck referred to the recent Onkopedia recommendation for nutrition after cancer and the 10 nutritional rules of the German Nutrition Society. According to Dr. Poeck, the important aspects of these recommendations are a fiber-rich diet (> 20 g/d) from various plant products and avoiding artificial sweeteners and flavorings, as well as ultraprocessed (convenience) foods. In addition, meat should be consumed only in moderation, and as little processed meat as possible should be consumed. In addition, regular (aerobic and anaerobic) physical activity is important.

“Looking ahead into the future,” said Dr. Poeck, “we need a uniform and functional understanding and we need a randomized prediction for diagnosis.”


This article was translated from the Medscape German edition.

A version of this article appeared on Medscape.com.

HAMBURG, Germany — The human microbiome comprises 39 to 44 billion microbes. That is ten times more than the number of cells in our body. Hendrik Poeck, MD, managing senior physician of internal medicine at the University Hospital Regensburg, illustrated this point at the annual meeting of the German Society for Hematology and Medical Oncology. If the gut microbiome falls out of balance, then “intestinal dysbiosis potentially poses a risk for the pathogenesis of local and systemic diseases,” explained Dr. Poeck.

Cancers and their therapies can also be influenced in this way. “Microbial diversity affects whether a tumor grows, whether it leads to inflammation, immune escape mechanisms or genomic instability, or whether therapeutic resistances develop,” said Dr. Poeck.

Microbial diversity could be beneficial for cancer therapy, too. The composition of the microbiome varies significantly from host to host and can mutate. These properties make it a target for precision microbiotics, which involves using the gut microbiome as a biomarker to predict various physical reactions and to develop individualized diets.

Microbiome and Pathogenesis

The body’s microbiome fulfills a barrier function, especially where the body is exposed to an external environment: at the epidermis and the internal mucous membranes, in the gastrointestinal tract, and in the lungs, chest, and urogenital system.

Association studies on humans and experimental manipulations on mouse models of cancer showed that certain microorganisms can have either protective or harmful effects on cancer development, on the progression of a malignant disease, and on the response to therapy.

A Master Regulator?

Disruptions of the microbial system in the gut, as occur during antibiotic therapy, can have significant effects on a patient’s response to immunotherapy. Taking antibiotics shortly before or after starting therapy with immune checkpoint inhibitors (ICIs) significantly affected both overall survival (OS) and progression-free survival (PFS), as reported in a recent review and meta-analysis, for example.

Proton pump inhibitors also affect the gut microbiome and reduce the response to immunotherapy; this effect was demonstrated by an analysis of data from more than 2700 cancer patients that was recently presented at the annual meeting of the European Society for Medical Oncology (ESMO).

The extent to which the gut microbiome influences the efficacy of an ICI or predicts said efficacy was examined in a retrospective analysis published in Science in 2018, which Dr. Poeck presented. Resistance to ICI correlated with the relative frequency of the bacteria Akkermansia muciniphila in the gut of patients with cancer. In mouse models, the researchers restored the efficacy of the PD-1 blockade through a stool transplant.

Predicting Immunotherapy Response

If A muciniphila is present, can the composition of the microbiome act as a predictor for an effective ICI therapy?

Laurence Zitvogel, MD, PhD, and her working group at the National Institute of Health and Medical Research in Villejuif, France, performed a prospective study in 338 patients with non–small cell lung cancer and examined the prognostic significance of the fecal bacteria A muciniphila (Akk). The “Akkerman status” (low Akk vs high Akk) in a patient’s stool correlated with an increased objective response rate and a longer OS, independently of PD-L1 expression, antibiotics, and performance status. The OS for low Akk was 13.4 months, vs 18.8 months for high Akk in first-line treatment.

These results are promising, said Dr. Poeck. But there is no one-size-fits-all solution. No conclusions can be drawn from one bacterium on the efficacy of therapies in humans, since “the entirety of the bacteria is decisive,” said Dr. Poeck. In addition to the gut microbiome, the composition of gut metabolites influences the response to immunotherapies, as shown in a study with ICI.

Therapeutic Interventions

One possible therapeutic intervention to restore the gut microbiome is fecal microbiota transplantation (FMT). In a phase 1 study presented by Dr. Poeck, FMT was effective in the treatment of 20 patients with melanoma with ICI in an advanced and treatment-naive stage. Seven days after the patients received FMT, the first cycle with anti-PD-1 immunotherapy was initiated, with a total administration of three to four cycles. After 12 weeks, most patients were in complete or partial remission, as evidenced on imaging.

However, FMT also carries some risks. Two cases of sepsis with multiresistant Escherichia coli occurred, as well as other serious infections. Since then, there has been an FDA condition for extended screening of the donor stool, said Dr. Poeck. Nevertheless, this intervention is promising. A search of the keywords “FMT in cancer/transplant setting” reveals 46 currently clinical studies on clinicaltrials.gov.

Nutritional Interventions

Dr. Poeck advises caution about over-the-counter products. These products usually contain only a few species, such as Lactobacillus and Bifidobacterium. “Over-the-counter probiotics can even delay the reconstitution of the microbiome after antibiotics,” said Dr. Poeck, according to a study. In some studies, the response rates were significantly lower after probiotic intake or led to controversial results, according to Dr. Poeck.

In contrast, Dr. Poeck said prebiotics (that is, a fiber-rich diet with indigestible carbohydrates) were promising. During digestion, prebiotics are split into short-chain fatty acids by bacterial enzymes and promote the growth of certain microbiota.

In this way, just 20 g of extremely fiber-rich food had a significant effect on PFS in 128 patients with melanoma undergoing anti-PD-1 immunotherapy. With 20 g of fiber-rich food per day, the PFS was stable over 60 months. The most significant benefit was observed in patients with a sufficient fiber intake who were not taking probiotics.

What to Recommend?

In summary, Dr. Poeck said that it is important to “budget” well, particularly with antibiotic administration, and to strive for calculated therapy with as narrow a spectrum as possible. For patients who experience complications such as cytokine release syndrome as a reaction to cell therapy, delaying the use of antibiotics is important. However, it is often difficult to differentiate this syndrome from neutropenic fever. The aim should be to avoid high-risk antibiotics, if clinically justifiable. Patients should avoid taking antibiotics for 30 days before starting immunotherapy.

Regarding nutritional interventions, Dr. Poeck referred to the recent Onkopedia recommendation for nutrition after cancer and the 10 nutritional rules of the German Nutrition Society. According to Dr. Poeck, the important aspects of these recommendations are a fiber-rich diet (> 20 g/d) from various plant products and avoiding artificial sweeteners and flavorings, as well as ultraprocessed (convenience) foods. In addition, meat should be consumed only in moderation, and as little processed meat as possible should be consumed. In addition, regular (aerobic and anaerobic) physical activity is important.

“Looking ahead into the future,” said Dr. Poeck, “we need a uniform and functional understanding and we need a randomized prediction for diagnosis.”


This article was translated from the Medscape German edition.

A version of this article appeared on Medscape.com.

HAMBURG, Germany — The human microbiome comprises 39 to 44 billion microbes. That is ten times more than the number of cells in our body. Hendrik Poeck, MD, managing senior physician of internal medicine at the University Hospital Regensburg, illustrated this point at the annual meeting of the German Society for Hematology and Medical Oncology. If the gut microbiome falls out of balance, then “intestinal dysbiosis potentially poses a risk for the pathogenesis of local and systemic diseases,” explained Dr. Poeck.

Cancers and their therapies can also be influenced in this way. “Microbial diversity affects whether a tumor grows, whether it leads to inflammation, immune escape mechanisms or genomic instability, or whether therapeutic resistances develop,” said Dr. Poeck.

Microbial diversity could be beneficial for cancer therapy, too. The composition of the microbiome varies significantly from host to host and can mutate. These properties make it a target for precision microbiotics, which involves using the gut microbiome as a biomarker to predict various physical reactions and to develop individualized diets.

Microbiome and Pathogenesis

The body’s microbiome fulfills a barrier function, especially where the body is exposed to an external environment: at the epidermis and the internal mucous membranes, in the gastrointestinal tract, and in the lungs, chest, and urogenital system.

Association studies on humans and experimental manipulations on mouse models of cancer showed that certain microorganisms can have either protective or harmful effects on cancer development, on the progression of a malignant disease, and on the response to therapy.

A Master Regulator?

Disruptions of the microbial system in the gut, as occur during antibiotic therapy, can have significant effects on a patient’s response to immunotherapy. Taking antibiotics shortly before or after starting therapy with immune checkpoint inhibitors (ICIs) significantly affected both overall survival (OS) and progression-free survival (PFS), as reported in a recent review and meta-analysis, for example.

Proton pump inhibitors also affect the gut microbiome and reduce the response to immunotherapy; this effect was demonstrated by an analysis of data from more than 2700 cancer patients that was recently presented at the annual meeting of the European Society for Medical Oncology (ESMO).

The extent to which the gut microbiome influences the efficacy of an ICI or predicts said efficacy was examined in a retrospective analysis published in Science in 2018, which Dr. Poeck presented. Resistance to ICI correlated with the relative frequency of the bacteria Akkermansia muciniphila in the gut of patients with cancer. In mouse models, the researchers restored the efficacy of the PD-1 blockade through a stool transplant.

Predicting Immunotherapy Response

If A muciniphila is present, can the composition of the microbiome act as a predictor for an effective ICI therapy?

Laurence Zitvogel, MD, PhD, and her working group at the National Institute of Health and Medical Research in Villejuif, France, performed a prospective study in 338 patients with non–small cell lung cancer and examined the prognostic significance of the fecal bacteria A muciniphila (Akk). The “Akkerman status” (low Akk vs high Akk) in a patient’s stool correlated with an increased objective response rate and a longer OS, independently of PD-L1 expression, antibiotics, and performance status. The OS for low Akk was 13.4 months, vs 18.8 months for high Akk in first-line treatment.

These results are promising, said Dr. Poeck. But there is no one-size-fits-all solution. No conclusions can be drawn from one bacterium on the efficacy of therapies in humans, since “the entirety of the bacteria is decisive,” said Dr. Poeck. In addition to the gut microbiome, the composition of gut metabolites influences the response to immunotherapies, as shown in a study with ICI.

Therapeutic Interventions

One possible therapeutic intervention to restore the gut microbiome is fecal microbiota transplantation (FMT). In a phase 1 study presented by Dr. Poeck, FMT was effective in the treatment of 20 patients with melanoma with ICI in an advanced and treatment-naive stage. Seven days after the patients received FMT, the first cycle with anti-PD-1 immunotherapy was initiated, with a total administration of three to four cycles. After 12 weeks, most patients were in complete or partial remission, as evidenced on imaging.

However, FMT also carries some risks. Two cases of sepsis with multiresistant Escherichia coli occurred, as well as other serious infections. Since then, there has been an FDA condition for extended screening of the donor stool, said Dr. Poeck. Nevertheless, this intervention is promising. A search of the keywords “FMT in cancer/transplant setting” reveals 46 currently clinical studies on clinicaltrials.gov.

Nutritional Interventions

Dr. Poeck advises caution about over-the-counter products. These products usually contain only a few species, such as Lactobacillus and Bifidobacterium. “Over-the-counter probiotics can even delay the reconstitution of the microbiome after antibiotics,” said Dr. Poeck, according to a study. In some studies, the response rates were significantly lower after probiotic intake or led to controversial results, according to Dr. Poeck.

In contrast, Dr. Poeck said prebiotics (that is, a fiber-rich diet with indigestible carbohydrates) were promising. During digestion, prebiotics are split into short-chain fatty acids by bacterial enzymes and promote the growth of certain microbiota.

In this way, just 20 g of extremely fiber-rich food had a significant effect on PFS in 128 patients with melanoma undergoing anti-PD-1 immunotherapy. With 20 g of fiber-rich food per day, the PFS was stable over 60 months. The most significant benefit was observed in patients with a sufficient fiber intake who were not taking probiotics.

What to Recommend?

In summary, Dr. Poeck said that it is important to “budget” well, particularly with antibiotic administration, and to strive for calculated therapy with as narrow a spectrum as possible. For patients who experience complications such as cytokine release syndrome as a reaction to cell therapy, delaying the use of antibiotics is important. However, it is often difficult to differentiate this syndrome from neutropenic fever. The aim should be to avoid high-risk antibiotics, if clinically justifiable. Patients should avoid taking antibiotics for 30 days before starting immunotherapy.

Regarding nutritional interventions, Dr. Poeck referred to the recent Onkopedia recommendation for nutrition after cancer and the 10 nutritional rules of the German Nutrition Society. According to Dr. Poeck, the important aspects of these recommendations are a fiber-rich diet (> 20 g/d) from various plant products and avoiding artificial sweeteners and flavorings, as well as ultraprocessed (convenience) foods. In addition, meat should be consumed only in moderation, and as little processed meat as possible should be consumed. In addition, regular (aerobic and anaerobic) physical activity is important.

“Looking ahead into the future,” said Dr. Poeck, “we need a uniform and functional understanding and we need a randomized prediction for diagnosis.”


This article was translated from the Medscape German edition.

A version of this article appeared on Medscape.com.

TOPLINE:

Changes in statin prescribing guidelines in 2013 had little effect on statin use for patients who are at risk for atherosclerotic cardiovascular disease (ASCVD), according to a study published Dec. 5 in the Annals of Internal Medicine. 

METHODOLOGY:

• Statins lower cholesterol and can reduce the risk for heart and circulatory disease.
• In 2013, the American College of Cardiology and the American Heart Association (ACC/AHA) expanded indications for which clinicians could prescribe statins to adults for primary prevention, including risk scores for ASCVD above a certain threshold. 
• Researchers studied trends in statin use between 1999 and 2018 using National Health and Nutrition Examination Survey data for 21,961 adults older than 20 years who did not have ASCVD. 
• They analyzed data from before and after implementation of the 2013 guidelines.

TAKEAWAY:

• Statin usage increased since 1999 but peaked at 35% in 2013 despite the expanded ACC/AHA guidelines.
• No changes in usage were observed for the proportion of adults who were newly eligible for statins. 
• Statin use among patients with diabetes increased by 31.1 percentage points between 1999 and 2014 but then remained stagnant from 2014 to 2018.
• Statin use among those with ASCVD risk of more than 20% increased by 23.1 percentage points between 1999 and 2013 but did not increase between 2013 and 2018.

IN PRACTICE:

“Although the ACC/AHA guidelines expanded indications for primary prevention, they also increased decision-making complexity, requiring new multistep risk calculation… Many clinicians do not routinely use cardiovascular risk calculators because of a lack of time, input availability, or buy-in. Electronic health record tools that calculate ASCVD risks show promise, but they are not routinely implemented and do not address other barriers, such as competing patient priorities and limited time for shared decision-making.“

SOURCE:

The study was led by Timothy S. Anderson, MD, MAS, Division of General Internal Medicine, at the University of Pittsburgh. The research was funded by the National Institute on Aging of the National Institutes of Health.

LIMITATIONS:

Data on whether patients had previously been offered and declined statins were not available. Risk score data for baseline ASCVD, which affects risk classification, were also not available.

DISCLOSURES:

The authors report no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Changes in statin prescribing guidelines in 2013 had little effect on statin use for patients who are at risk for atherosclerotic cardiovascular disease (ASCVD), according to a study published Dec. 5 in the Annals of Internal Medicine. 

METHODOLOGY:

• Statins lower cholesterol and can reduce the risk for heart and circulatory disease.
• In 2013, the American College of Cardiology and the American Heart Association (ACC/AHA) expanded indications for which clinicians could prescribe statins to adults for primary prevention, including risk scores for ASCVD above a certain threshold. 
• Researchers studied trends in statin use between 1999 and 2018 using National Health and Nutrition Examination Survey data for 21,961 adults older than 20 years who did not have ASCVD. 
• They analyzed data from before and after implementation of the 2013 guidelines.

TAKEAWAY:

• Statin usage increased since 1999 but peaked at 35% in 2013 despite the expanded ACC/AHA guidelines.
• No changes in usage were observed for the proportion of adults who were newly eligible for statins. 
• Statin use among patients with diabetes increased by 31.1 percentage points between 1999 and 2014 but then remained stagnant from 2014 to 2018.
• Statin use among those with ASCVD risk of more than 20% increased by 23.1 percentage points between 1999 and 2013 but did not increase between 2013 and 2018.

IN PRACTICE:

“Although the ACC/AHA guidelines expanded indications for primary prevention, they also increased decision-making complexity, requiring new multistep risk calculation… Many clinicians do not routinely use cardiovascular risk calculators because of a lack of time, input availability, or buy-in. Electronic health record tools that calculate ASCVD risks show promise, but they are not routinely implemented and do not address other barriers, such as competing patient priorities and limited time for shared decision-making.“

SOURCE:

The study was led by Timothy S. Anderson, MD, MAS, Division of General Internal Medicine, at the University of Pittsburgh. The research was funded by the National Institute on Aging of the National Institutes of Health.

LIMITATIONS:

Data on whether patients had previously been offered and declined statins were not available. Risk score data for baseline ASCVD, which affects risk classification, were also not available.

DISCLOSURES:

The authors report no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Changes in statin prescribing guidelines in 2013 had little effect on statin use for patients who are at risk for atherosclerotic cardiovascular disease (ASCVD), according to a study published Dec. 5 in the Annals of Internal Medicine. 

METHODOLOGY:

• Statins lower cholesterol and can reduce the risk for heart and circulatory disease.
• In 2013, the American College of Cardiology and the American Heart Association (ACC/AHA) expanded indications for which clinicians could prescribe statins to adults for primary prevention, including risk scores for ASCVD above a certain threshold. 
• Researchers studied trends in statin use between 1999 and 2018 using National Health and Nutrition Examination Survey data for 21,961 adults older than 20 years who did not have ASCVD. 
• They analyzed data from before and after implementation of the 2013 guidelines.

TAKEAWAY:

• Statin usage increased since 1999 but peaked at 35% in 2013 despite the expanded ACC/AHA guidelines.
• No changes in usage were observed for the proportion of adults who were newly eligible for statins. 
• Statin use among patients with diabetes increased by 31.1 percentage points between 1999 and 2014 but then remained stagnant from 2014 to 2018.
• Statin use among those with ASCVD risk of more than 20% increased by 23.1 percentage points between 1999 and 2013 but did not increase between 2013 and 2018.

IN PRACTICE:

“Although the ACC/AHA guidelines expanded indications for primary prevention, they also increased decision-making complexity, requiring new multistep risk calculation… Many clinicians do not routinely use cardiovascular risk calculators because of a lack of time, input availability, or buy-in. Electronic health record tools that calculate ASCVD risks show promise, but they are not routinely implemented and do not address other barriers, such as competing patient priorities and limited time for shared decision-making.“

SOURCE:

The study was led by Timothy S. Anderson, MD, MAS, Division of General Internal Medicine, at the University of Pittsburgh. The research was funded by the National Institute on Aging of the National Institutes of Health.

LIMITATIONS:

Data on whether patients had previously been offered and declined statins were not available. Risk score data for baseline ASCVD, which affects risk classification, were also not available.

DISCLOSURES:

The authors report no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Commercial health insurance does not necessarily protect cancer patients from potentially devastating out-of-pocket costs.

METHODOLOGY:

• Out-of-pocket costs contribute to financial toxicity in cancer, but little is known about how they vary across various tumor types and stages over time.
• To find out, investigators reviewed claims data for 7494 US patients diagnosed with stage I-IV breast, cervical, colorectal, lung, ovarian, or prostate cancer from 2016 to 2020.
• They assessed cumulative out-of-pocket (OOP) costs — defined as copayments, deductibles, and coinsurance — in the first 3 years following diagnosis.
• Subjects had private, commercial health insurance through United Healthcare.

TAKEAWAY:

• By the end of 3 years, average cumulative OOP costs ranged from $16,673 for stage I prostate cancer to $35,253 for stage IV lung cancer.
• Across all cancer types, average OOP costs in the first year ranged from $2,754 for stage I anal cancer to $25,876 for stage IV vaginal cancer.
• However, the upper limits of OOP costs exceeded $100,000 across many tumors and stages in the first year, reaching a high of $450,374 for stage I breast cancer and far exceeding $200,000 for stage II-IV colorectal and lung cancer.
• OOP costs were generally highest during the first year of treatment and for cancers diagnosed at later stages.

IN PRACTICE:

“OOP costs may present an extreme economic stressor on patients diagnosed with cancer,” leading to emotional distress, reduced treatment adherence, and poor outcomes. “Even cancer patients with insurance coverage [are] not protected.” Future research is “needed to help clarify the type of patient most burdened by OOP costs” as well as ways to reduce them, including promoting “diagnosis at an earlier stage and increas[ing] access to health plans that minimize patient cost sharing.”

SOURCE:

The work was led by November McGarvey of BluePath Solutions, Los Angeles, and published in the Journal of Medical Economics.

LIMITATIONS:

The study did not include additional OOP costs, such as transportation. It also did not assess the long-term impacts of cancer-related out-of-pocket spending. Details on health plan types and features were limited, and the results are limited to patients with commercial health insurance.

DISCLOSURES:

The work was funded by Grail. The investigators are employees of Grail or BluePath Solutions.

TOPLINE:

Commercial health insurance does not necessarily protect cancer patients from potentially devastating out-of-pocket costs.

METHODOLOGY:

• Out-of-pocket costs contribute to financial toxicity in cancer, but little is known about how they vary across various tumor types and stages over time.
• To find out, investigators reviewed claims data for 7494 US patients diagnosed with stage I-IV breast, cervical, colorectal, lung, ovarian, or prostate cancer from 2016 to 2020.
• They assessed cumulative out-of-pocket (OOP) costs — defined as copayments, deductibles, and coinsurance — in the first 3 years following diagnosis.
• Subjects had private, commercial health insurance through United Healthcare.

TAKEAWAY:

• By the end of 3 years, average cumulative OOP costs ranged from $16,673 for stage I prostate cancer to $35,253 for stage IV lung cancer.
• Across all cancer types, average OOP costs in the first year ranged from $2,754 for stage I anal cancer to $25,876 for stage IV vaginal cancer.
• However, the upper limits of OOP costs exceeded $100,000 across many tumors and stages in the first year, reaching a high of $450,374 for stage I breast cancer and far exceeding $200,000 for stage II-IV colorectal and lung cancer.
• OOP costs were generally highest during the first year of treatment and for cancers diagnosed at later stages.

IN PRACTICE:

“OOP costs may present an extreme economic stressor on patients diagnosed with cancer,” leading to emotional distress, reduced treatment adherence, and poor outcomes. “Even cancer patients with insurance coverage [are] not protected.” Future research is “needed to help clarify the type of patient most burdened by OOP costs” as well as ways to reduce them, including promoting “diagnosis at an earlier stage and increas[ing] access to health plans that minimize patient cost sharing.”

SOURCE:

The work was led by November McGarvey of BluePath Solutions, Los Angeles, and published in the Journal of Medical Economics.

LIMITATIONS:

The study did not include additional OOP costs, such as transportation. It also did not assess the long-term impacts of cancer-related out-of-pocket spending. Details on health plan types and features were limited, and the results are limited to patients with commercial health insurance.

DISCLOSURES:

The work was funded by Grail. The investigators are employees of Grail or BluePath Solutions.

TOPLINE:

Commercial health insurance does not necessarily protect cancer patients from potentially devastating out-of-pocket costs.

METHODOLOGY:

• Out-of-pocket costs contribute to financial toxicity in cancer, but little is known about how they vary across various tumor types and stages over time.
• To find out, investigators reviewed claims data for 7494 US patients diagnosed with stage I-IV breast, cervical, colorectal, lung, ovarian, or prostate cancer from 2016 to 2020.
• They assessed cumulative out-of-pocket (OOP) costs — defined as copayments, deductibles, and coinsurance — in the first 3 years following diagnosis.
• Subjects had private, commercial health insurance through United Healthcare.

TAKEAWAY:

• By the end of 3 years, average cumulative OOP costs ranged from $16,673 for stage I prostate cancer to $35,253 for stage IV lung cancer.
• Across all cancer types, average OOP costs in the first year ranged from $2,754 for stage I anal cancer to $25,876 for stage IV vaginal cancer.
• However, the upper limits of OOP costs exceeded $100,000 across many tumors and stages in the first year, reaching a high of $450,374 for stage I breast cancer and far exceeding $200,000 for stage II-IV colorectal and lung cancer.
• OOP costs were generally highest during the first year of treatment and for cancers diagnosed at later stages.

IN PRACTICE:

“OOP costs may present an extreme economic stressor on patients diagnosed with cancer,” leading to emotional distress, reduced treatment adherence, and poor outcomes. “Even cancer patients with insurance coverage [are] not protected.” Future research is “needed to help clarify the type of patient most burdened by OOP costs” as well as ways to reduce them, including promoting “diagnosis at an earlier stage and increas[ing] access to health plans that minimize patient cost sharing.”

SOURCE:

The work was led by November McGarvey of BluePath Solutions, Los Angeles, and published in the Journal of Medical Economics.

LIMITATIONS:

The study did not include additional OOP costs, such as transportation. It also did not assess the long-term impacts of cancer-related out-of-pocket spending. Details on health plan types and features were limited, and the results are limited to patients with commercial health insurance.

DISCLOSURES:

The work was funded by Grail. The investigators are employees of Grail or BluePath Solutions.

Early diagnosis improves lung cancer survival. Yet in the general population, only 17% of cases are diagnosed at an early stage. Among veterans, that rises to more than 30%.

Despite the impact lung cancer screening (LCS) has on improving survival, screening rates in the US remain low. In November 2017, the US Department of Veterans Affairs (VA) issued a memorandum providing recommendations for LCS with low-dose computer tomography (CT) scans at VA facilities. The memorandum was updated July 2022. While the Office of the Inspector General (OIG) called the memoranda “guidelines,” it also stipulated to VA facilities that they may “only” perform LCS when they meet all 10 mandatory elements:  

• Standardized, evidence-based criteria for eligibility, frequency, and duration of LCS
• Processes to facilitate the identification of patients who meet VA LCS eligibility criteria
• Patient education materials and shared decision making for patients regarding participation in an LCS program
• Clinical LCS coordinator(s) to coordinate the care and management of patients in the program
• Access to an effective, evidence-based smoking cessation program
• An LCS program oversight board responsible for oversight of the program’s conduct and management
• Access to a multidisciplinary lung nodule management board with clinical expertise in lung nodule management and diagnostic pathways
• Access to a tumor board with expertise in lung cancer treatment
• Optimized radiology CT protocols and standardized procedure names, along with standardized reporting methodology/codes and lung nodule management guidelines
• A patient management tool/registry to rigorously track and manage patients to ensure high levels of adherence to LCS management guidelines

However, in a recent investigation, the OIG found that facility staff involved in LCS reported that VA LCS guideline requirements “presented barriers to broader adoption of LCS” and did not ensure consistent implementation.

One problem, the OIG found, was the limited use of LCS at VA facilities. Just over half of the surveyed VA facilities reported having an established LCS program consistent with VA guidelines for LCS in 2022. There were also barriers to implementing LCS program requirements, such as the absence of an LCS coordinator, the lack of adequate staffing, the absence of a patient registry, and the lack of a multidisciplinary board.

Another problem was the inconsistent implementation of screening. Facilities with LCS programs reported varied use of program elements, including inconsistent use of an LCS coordinator to manage patients in the program.

The OIG also found that regardless of whether facilities had established an adherent LCS program, they varied in how they identified screening-eligible patients. The VA National Center for LCS recommends the use of clinical reminders as the preferred method to identify patients—but it is not required and not all facilities use it. The clinical reminder, the OIG report points out, can capture accurate smoking history information within the electronic health record to support identifying patients meeting LCS criteria.

The facilities also varied in their methods for interpreting low-dose CT scans. Ten sites, for instance, reported not using an established system for the classification of the results. The OIG notes that this could lead to inaccurate interpretation of the low-dose CT scan results and increase the risk for patient harm and health care costs.

The OIG made the following 3 recommendations to the Under Secretary for Health: (1) Review the operational memorandum for lung cancer screening implementation and assess whether LCS rates could be enhanced by allowing a facility to conduct LCS while developing all mandated elements; (2) Review the operational memorandum for LCS implementation and assess whether LCS rates could be enhanced by reevaluating, prioritizing, and clarifying the mandated elements; and (3) Consider mandating eligible patients be offered LCS consistent with other required cancer screenings in the VA.

The Under Secretary for Health concurred with the recommendations and provided an acceptable action plan. The OIG will follow up on the planned actions until they are completed.

Early diagnosis improves lung cancer survival. Yet in the general population, only 17% of cases are diagnosed at an early stage. Among veterans, that rises to more than 30%.

Despite the impact lung cancer screening (LCS) has on improving survival, screening rates in the US remain low. In November 2017, the US Department of Veterans Affairs (VA) issued a memorandum providing recommendations for LCS with low-dose computer tomography (CT) scans at VA facilities. The memorandum was updated July 2022. While the Office of the Inspector General (OIG) called the memoranda “guidelines,” it also stipulated to VA facilities that they may “only” perform LCS when they meet all 10 mandatory elements:  

• Standardized, evidence-based criteria for eligibility, frequency, and duration of LCS
• Processes to facilitate the identification of patients who meet VA LCS eligibility criteria
• Patient education materials and shared decision making for patients regarding participation in an LCS program
• Clinical LCS coordinator(s) to coordinate the care and management of patients in the program
• Access to an effective, evidence-based smoking cessation program
• An LCS program oversight board responsible for oversight of the program’s conduct and management
• Access to a multidisciplinary lung nodule management board with clinical expertise in lung nodule management and diagnostic pathways
• Access to a tumor board with expertise in lung cancer treatment
• Optimized radiology CT protocols and standardized procedure names, along with standardized reporting methodology/codes and lung nodule management guidelines
• A patient management tool/registry to rigorously track and manage patients to ensure high levels of adherence to LCS management guidelines

However, in a recent investigation, the OIG found that facility staff involved in LCS reported that VA LCS guideline requirements “presented barriers to broader adoption of LCS” and did not ensure consistent implementation.

One problem, the OIG found, was the limited use of LCS at VA facilities. Just over half of the surveyed VA facilities reported having an established LCS program consistent with VA guidelines for LCS in 2022. There were also barriers to implementing LCS program requirements, such as the absence of an LCS coordinator, the lack of adequate staffing, the absence of a patient registry, and the lack of a multidisciplinary board.

Another problem was the inconsistent implementation of screening. Facilities with LCS programs reported varied use of program elements, including inconsistent use of an LCS coordinator to manage patients in the program.

The OIG also found that regardless of whether facilities had established an adherent LCS program, they varied in how they identified screening-eligible patients. The VA National Center for LCS recommends the use of clinical reminders as the preferred method to identify patients—but it is not required and not all facilities use it. The clinical reminder, the OIG report points out, can capture accurate smoking history information within the electronic health record to support identifying patients meeting LCS criteria.

The facilities also varied in their methods for interpreting low-dose CT scans. Ten sites, for instance, reported not using an established system for the classification of the results. The OIG notes that this could lead to inaccurate interpretation of the low-dose CT scan results and increase the risk for patient harm and health care costs.

The OIG made the following 3 recommendations to the Under Secretary for Health: (1) Review the operational memorandum for lung cancer screening implementation and assess whether LCS rates could be enhanced by allowing a facility to conduct LCS while developing all mandated elements; (2) Review the operational memorandum for LCS implementation and assess whether LCS rates could be enhanced by reevaluating, prioritizing, and clarifying the mandated elements; and (3) Consider mandating eligible patients be offered LCS consistent with other required cancer screenings in the VA.

The Under Secretary for Health concurred with the recommendations and provided an acceptable action plan. The OIG will follow up on the planned actions until they are completed.

Early diagnosis improves lung cancer survival. Yet in the general population, only 17% of cases are diagnosed at an early stage. Among veterans, that rises to more than 30%.

Despite the impact lung cancer screening (LCS) has on improving survival, screening rates in the US remain low. In November 2017, the US Department of Veterans Affairs (VA) issued a memorandum providing recommendations for LCS with low-dose computer tomography (CT) scans at VA facilities. The memorandum was updated July 2022. While the Office of the Inspector General (OIG) called the memoranda “guidelines,” it also stipulated to VA facilities that they may “only” perform LCS when they meet all 10 mandatory elements:  

• Standardized, evidence-based criteria for eligibility, frequency, and duration of LCS
• Processes to facilitate the identification of patients who meet VA LCS eligibility criteria
• Patient education materials and shared decision making for patients regarding participation in an LCS program
• Clinical LCS coordinator(s) to coordinate the care and management of patients in the program
• Access to an effective, evidence-based smoking cessation program
• An LCS program oversight board responsible for oversight of the program’s conduct and management
• Access to a multidisciplinary lung nodule management board with clinical expertise in lung nodule management and diagnostic pathways
• Access to a tumor board with expertise in lung cancer treatment
• Optimized radiology CT protocols and standardized procedure names, along with standardized reporting methodology/codes and lung nodule management guidelines
• A patient management tool/registry to rigorously track and manage patients to ensure high levels of adherence to LCS management guidelines

However, in a recent investigation, the OIG found that facility staff involved in LCS reported that VA LCS guideline requirements “presented barriers to broader adoption of LCS” and did not ensure consistent implementation.

One problem, the OIG found, was the limited use of LCS at VA facilities. Just over half of the surveyed VA facilities reported having an established LCS program consistent with VA guidelines for LCS in 2022. There were also barriers to implementing LCS program requirements, such as the absence of an LCS coordinator, the lack of adequate staffing, the absence of a patient registry, and the lack of a multidisciplinary board.

Another problem was the inconsistent implementation of screening. Facilities with LCS programs reported varied use of program elements, including inconsistent use of an LCS coordinator to manage patients in the program.

The OIG also found that regardless of whether facilities had established an adherent LCS program, they varied in how they identified screening-eligible patients. The VA National Center for LCS recommends the use of clinical reminders as the preferred method to identify patients—but it is not required and not all facilities use it. The clinical reminder, the OIG report points out, can capture accurate smoking history information within the electronic health record to support identifying patients meeting LCS criteria.

The facilities also varied in their methods for interpreting low-dose CT scans. Ten sites, for instance, reported not using an established system for the classification of the results. The OIG notes that this could lead to inaccurate interpretation of the low-dose CT scan results and increase the risk for patient harm and health care costs.

The OIG made the following 3 recommendations to the Under Secretary for Health: (1) Review the operational memorandum for lung cancer screening implementation and assess whether LCS rates could be enhanced by allowing a facility to conduct LCS while developing all mandated elements; (2) Review the operational memorandum for LCS implementation and assess whether LCS rates could be enhanced by reevaluating, prioritizing, and clarifying the mandated elements; and (3) Consider mandating eligible patients be offered LCS consistent with other required cancer screenings in the VA.

The Under Secretary for Health concurred with the recommendations and provided an acceptable action plan. The OIG will follow up on the planned actions until they are completed.

TOPLINE:

Patients with psoriasis had a 1.77-fold increased risk of having obstructive sleep apnea, in a study comparing patients with psoriasis with controls.

METHODOLOGY:

• Prior studies have established a link between psoriasis and obstructive sleep apnea (OSA), but some have suggested that confounders may drive the association.
• Using a case-control design, researchers analyzed data from 156,707 participants in the National Institutes of Health’s : 5140 with psoriasis and 151,567 controls.
• They used Pearson’s x 2 test to compare the prevalence of OSA among cases and controls, logistic regression to calculate odds ratios (ORs) in multivariable analysis, and two-sided t-tests to evaluate the significance between continuous variables.

TAKEAWAY:

• Compared with controls, patients with psoriasis were older (a mean of 62.4 vs 57.3 years, respectively), more likely to be White (86.1% vs 70.6%), reported higher annual household incomes (59.9% vs 52.6%), and were more likely to smoke (48.2% vs 43.4%).
• The rate of OSA was significantly higher among patients with psoriasis compared with controls (29.3% vs 17.1%; P < .001).
• On unadjusted multivariable logistic regression controlling for age, gender, and race, psoriasis was significantly associated with OSA (OR, 1.77, 95% CI, 1.66 - 1.89; P < .001).
• Psoriasis was also significantly associated with OSA in the adjusted model controlling for age, gender, race, BMI, and smoking status (OR, 1.66, 95% CI, 1.55 - 1.77; P < .001) and in the adjusted model controlling for age, gender, race, BMI, smoking status, type 2 diabetes, congestive heart failure, hypertension, history of myocardial infarction, angina, and peripheral artery disease (OR, 1.45, 95% CI, 1.35 - 1.55; P <.001).

IN PRACTICE:

“This study further substantiates the association between psoriasis and OSA, reinforcing the importance of evaluation for OSA when clinically appropriate given that both psoriasis and OSA contribute to adverse health outcomes,” the authors conclude.

SOURCE:

Corresponding author Jeffrey M. Cohen, MD, of the Department of Dermatology at Yale University, New Haven, Connecticut, led the research. The study was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

Study limitations included the use of electronic health record data, a potential lack of generalizability to the US population, and reliance on survey data for certain variables such as income and smoking status.

DISCLOSURES:

The All of Us Research Program is supported by the National Institutes of Health. Cohen disclosed that he serves on a data safety and monitoring board for Advarra.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with psoriasis had a 1.77-fold increased risk of having obstructive sleep apnea, in a study comparing patients with psoriasis with controls.

METHODOLOGY:

• Prior studies have established a link between psoriasis and obstructive sleep apnea (OSA), but some have suggested that confounders may drive the association.
• Using a case-control design, researchers analyzed data from 156,707 participants in the National Institutes of Health’s : 5140 with psoriasis and 151,567 controls.
• They used Pearson’s x 2 test to compare the prevalence of OSA among cases and controls, logistic regression to calculate odds ratios (ORs) in multivariable analysis, and two-sided t-tests to evaluate the significance between continuous variables.

TAKEAWAY:

• Compared with controls, patients with psoriasis were older (a mean of 62.4 vs 57.3 years, respectively), more likely to be White (86.1% vs 70.6%), reported higher annual household incomes (59.9% vs 52.6%), and were more likely to smoke (48.2% vs 43.4%).
• The rate of OSA was significantly higher among patients with psoriasis compared with controls (29.3% vs 17.1%; P < .001).
• On unadjusted multivariable logistic regression controlling for age, gender, and race, psoriasis was significantly associated with OSA (OR, 1.77, 95% CI, 1.66 - 1.89; P < .001).
• Psoriasis was also significantly associated with OSA in the adjusted model controlling for age, gender, race, BMI, and smoking status (OR, 1.66, 95% CI, 1.55 - 1.77; P < .001) and in the adjusted model controlling for age, gender, race, BMI, smoking status, type 2 diabetes, congestive heart failure, hypertension, history of myocardial infarction, angina, and peripheral artery disease (OR, 1.45, 95% CI, 1.35 - 1.55; P <.001).

IN PRACTICE:

“This study further substantiates the association between psoriasis and OSA, reinforcing the importance of evaluation for OSA when clinically appropriate given that both psoriasis and OSA contribute to adverse health outcomes,” the authors conclude.

SOURCE:

Corresponding author Jeffrey M. Cohen, MD, of the Department of Dermatology at Yale University, New Haven, Connecticut, led the research. The study was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

Study limitations included the use of electronic health record data, a potential lack of generalizability to the US population, and reliance on survey data for certain variables such as income and smoking status.

DISCLOSURES:

The All of Us Research Program is supported by the National Institutes of Health. Cohen disclosed that he serves on a data safety and monitoring board for Advarra.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with psoriasis had a 1.77-fold increased risk of having obstructive sleep apnea, in a study comparing patients with psoriasis with controls.

METHODOLOGY:

• Prior studies have established a link between psoriasis and obstructive sleep apnea (OSA), but some have suggested that confounders may drive the association.
• Using a case-control design, researchers analyzed data from 156,707 participants in the National Institutes of Health’s : 5140 with psoriasis and 151,567 controls.
• They used Pearson’s x 2 test to compare the prevalence of OSA among cases and controls, logistic regression to calculate odds ratios (ORs) in multivariable analysis, and two-sided t-tests to evaluate the significance between continuous variables.

TAKEAWAY:

• Compared with controls, patients with psoriasis were older (a mean of 62.4 vs 57.3 years, respectively), more likely to be White (86.1% vs 70.6%), reported higher annual household incomes (59.9% vs 52.6%), and were more likely to smoke (48.2% vs 43.4%).
• The rate of OSA was significantly higher among patients with psoriasis compared with controls (29.3% vs 17.1%; P < .001).
• On unadjusted multivariable logistic regression controlling for age, gender, and race, psoriasis was significantly associated with OSA (OR, 1.77, 95% CI, 1.66 - 1.89; P < .001).
• Psoriasis was also significantly associated with OSA in the adjusted model controlling for age, gender, race, BMI, and smoking status (OR, 1.66, 95% CI, 1.55 - 1.77; P < .001) and in the adjusted model controlling for age, gender, race, BMI, smoking status, type 2 diabetes, congestive heart failure, hypertension, history of myocardial infarction, angina, and peripheral artery disease (OR, 1.45, 95% CI, 1.35 - 1.55; P <.001).

IN PRACTICE:

“This study further substantiates the association between psoriasis and OSA, reinforcing the importance of evaluation for OSA when clinically appropriate given that both psoriasis and OSA contribute to adverse health outcomes,” the authors conclude.

SOURCE:

Corresponding author Jeffrey M. Cohen, MD, of the Department of Dermatology at Yale University, New Haven, Connecticut, led the research. The study was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

Study limitations included the use of electronic health record data, a potential lack of generalizability to the US population, and reliance on survey data for certain variables such as income and smoking status.

DISCLOSURES:

The All of Us Research Program is supported by the National Institutes of Health. Cohen disclosed that he serves on a data safety and monitoring board for Advarra.

A version of this article appeared on Medscape.com.

Family members of veterans exposed to contaminated drinking water at Marine Corps Base Camp Lejeune, Jacksonville, North Carolina, from August 1, 1953, to December 31, 1987, are now eligible for reimbursement of health care costs associated with Parkinson disease (PD) under the Camp Lejeune Family Member Program, the US Department of Veterans Affairs (VA) has announced.

That brings the number of illnesses or conditions those family members can be reimbursed for to 16: esophageal, lung, breast, bladder, and kidney cancer, leukemia, multiple myeloma, renal toxicity, miscarriage, hepatic steatosis, female infertility, myelodysplastic syndromes, scleroderma, neurobehavioral effects, non-Hodgkin lymphoma, and Parkinson disease.

A recent JAMA study of 340,489 service members found that the risk of PD is 70% higher for veterans stationed at Camp Lejeune (n = 279) compared with veterans stationed at Camp Pendleton, California (n = 151).

The researchers say water supplies at Camp Lejeune were contaminated with several volatile organic compounds. They suggest that the risk of PD may be related to trichloroethylene exposure (TCE), a volatile organic compound widely used as a cleaning agent, in the manufacturing of some refrigerants, and found in paints and other products. In January, the US Environmental Protection Agency issued a revised risk determination saying that TCE presents an unreasonable risk to the health of workers, occupational nonusers (workers nearby but not in direct contact with this chemical), consumers, and bystanders.

Levels at Camp Lejeune were highest for TCE, with monthly median values greater than 70-fold the permissible amount.

Camp Lejeune veterans also had a significantly increased risk of prodromal PD diagnoses, including tremor, anxiety, and erectile dysfunction, and higher cumulative prodromal risk scores. No excess risk was found for other forms of neurodegenerative parkinsonism.

The PACT Act allows veterans and their families to file lawsuits for harm caused by exposure to contaminated water at Camp Lejeune. “Veterans and their families deserve no-cost health care for the conditions they developed due to the contaminated water at Camp Lejeune,” said VA’s Under Secretary for Health, Dr. Shereef Elnahal, MD. “We’re proud to add Parkinson disease to the list of conditions that are covered for veteran family members, and we implore anyone who may be living with this disease—or any of the other conditions covered by VA’s Camp Lejeune Family Member Program—to apply for assistance today.”

Family members of veterans exposed to contaminated drinking water at Marine Corps Base Camp Lejeune, Jacksonville, North Carolina, from August 1, 1953, to December 31, 1987, are now eligible for reimbursement of health care costs associated with Parkinson disease (PD) under the Camp Lejeune Family Member Program, the US Department of Veterans Affairs (VA) has announced.

That brings the number of illnesses or conditions those family members can be reimbursed for to 16: esophageal, lung, breast, bladder, and kidney cancer, leukemia, multiple myeloma, renal toxicity, miscarriage, hepatic steatosis, female infertility, myelodysplastic syndromes, scleroderma, neurobehavioral effects, non-Hodgkin lymphoma, and Parkinson disease.

A recent JAMA study of 340,489 service members found that the risk of PD is 70% higher for veterans stationed at Camp Lejeune (n = 279) compared with veterans stationed at Camp Pendleton, California (n = 151).

The researchers say water supplies at Camp Lejeune were contaminated with several volatile organic compounds. They suggest that the risk of PD may be related to trichloroethylene exposure (TCE), a volatile organic compound widely used as a cleaning agent, in the manufacturing of some refrigerants, and found in paints and other products. In January, the US Environmental Protection Agency issued a revised risk determination saying that TCE presents an unreasonable risk to the health of workers, occupational nonusers (workers nearby but not in direct contact with this chemical), consumers, and bystanders.

Levels at Camp Lejeune were highest for TCE, with monthly median values greater than 70-fold the permissible amount.

Camp Lejeune veterans also had a significantly increased risk of prodromal PD diagnoses, including tremor, anxiety, and erectile dysfunction, and higher cumulative prodromal risk scores. No excess risk was found for other forms of neurodegenerative parkinsonism.

The PACT Act allows veterans and their families to file lawsuits for harm caused by exposure to contaminated water at Camp Lejeune. “Veterans and their families deserve no-cost health care for the conditions they developed due to the contaminated water at Camp Lejeune,” said VA’s Under Secretary for Health, Dr. Shereef Elnahal, MD. “We’re proud to add Parkinson disease to the list of conditions that are covered for veteran family members, and we implore anyone who may be living with this disease—or any of the other conditions covered by VA’s Camp Lejeune Family Member Program—to apply for assistance today.”

Family members of veterans exposed to contaminated drinking water at Marine Corps Base Camp Lejeune, Jacksonville, North Carolina, from August 1, 1953, to December 31, 1987, are now eligible for reimbursement of health care costs associated with Parkinson disease (PD) under the Camp Lejeune Family Member Program, the US Department of Veterans Affairs (VA) has announced.

That brings the number of illnesses or conditions those family members can be reimbursed for to 16: esophageal, lung, breast, bladder, and kidney cancer, leukemia, multiple myeloma, renal toxicity, miscarriage, hepatic steatosis, female infertility, myelodysplastic syndromes, scleroderma, neurobehavioral effects, non-Hodgkin lymphoma, and Parkinson disease.

A recent JAMA study of 340,489 service members found that the risk of PD is 70% higher for veterans stationed at Camp Lejeune (n = 279) compared with veterans stationed at Camp Pendleton, California (n = 151).

The researchers say water supplies at Camp Lejeune were contaminated with several volatile organic compounds. They suggest that the risk of PD may be related to trichloroethylene exposure (TCE), a volatile organic compound widely used as a cleaning agent, in the manufacturing of some refrigerants, and found in paints and other products. In January, the US Environmental Protection Agency issued a revised risk determination saying that TCE presents an unreasonable risk to the health of workers, occupational nonusers (workers nearby but not in direct contact with this chemical), consumers, and bystanders.

Levels at Camp Lejeune were highest for TCE, with monthly median values greater than 70-fold the permissible amount.

Camp Lejeune veterans also had a significantly increased risk of prodromal PD diagnoses, including tremor, anxiety, and erectile dysfunction, and higher cumulative prodromal risk scores. No excess risk was found for other forms of neurodegenerative parkinsonism.

The PACT Act allows veterans and their families to file lawsuits for harm caused by exposure to contaminated water at Camp Lejeune. “Veterans and their families deserve no-cost health care for the conditions they developed due to the contaminated water at Camp Lejeune,” said VA’s Under Secretary for Health, Dr. Shereef Elnahal, MD. “We’re proud to add Parkinson disease to the list of conditions that are covered for veteran family members, and we implore anyone who may be living with this disease—or any of the other conditions covered by VA’s Camp Lejeune Family Member Program—to apply for assistance today.”

TOPLINE:

Reducing the urine albumin-to-creatinine ratio (UACR) significantly reduces kidney risk in people with type 2 diabetes, per new research in the Annals of Internal Medicine.

METHODOLOGY:

• Post hoc retrospective analysis of two phase 3 double-blind trials of finerenone in people with type 2 diabetes and chronic kidney disease
• Quantify the long-term health effects of reducing UACR within 4 months of taking finerenone by examining the records of 12,512 participants with an equal chance of receiving finerenone or placebo
• Isolate the impact of UACR reduction on kidney function and cardiovascular function by tracking health indicators related to the kidneys and the heart in participants for up to 4 years

TAKEAWAY:

• Over half of participants who received finerenone had reduced UACR by at least 30% from the baseline of 514 mg/g at the 4-month point after starting treatment, and the median UACR reduction in this group was 33%.
• By 4 months, a little over a quarter of participants who received the placebo had reduced their UACR levels by at least 30%, and the median UACR reduction in this group was 2.6%.
• A UACR reduction of at least 30% reduced kidney risk by 64%, as measured by reductions in kidney failure, sufficient glomerular filtration, and death from kidney disease.
• A UACR reduction of at least 30% reduced cardiovascular risk by 26%, as measured by fewer incidences of cardiovascular death, nonfatal infarction or stroke, and hospitalization for heart failure.

IN PRACTICE:

“Achieving early UACR reduction can lead to tangible benefits for kidney and cardiovascular health,” the authors note.

SOURCE:

The study was published in the Annals of Internal Medicine; the lead author is Rajiv Agarwal, MD, MS.

LIMITATIONS:

The study pertains only to finerenone, so the findings cannot be extrapolated to other drugs with different mechanisms of action.

DISCLOSURES:

Bayer AG Pharmaceuticals, which manufactures finerenone, was the primary funder of the study. The US National Institutes of Health and Veterans Administration also provided funding. Some study authors are full-time employees of Bayer AG. Many authors report consulting relationships with various pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Reducing the urine albumin-to-creatinine ratio (UACR) significantly reduces kidney risk in people with type 2 diabetes, per new research in the Annals of Internal Medicine.

METHODOLOGY:

• Post hoc retrospective analysis of two phase 3 double-blind trials of finerenone in people with type 2 diabetes and chronic kidney disease
• Quantify the long-term health effects of reducing UACR within 4 months of taking finerenone by examining the records of 12,512 participants with an equal chance of receiving finerenone or placebo
• Isolate the impact of UACR reduction on kidney function and cardiovascular function by tracking health indicators related to the kidneys and the heart in participants for up to 4 years

TAKEAWAY:

• Over half of participants who received finerenone had reduced UACR by at least 30% from the baseline of 514 mg/g at the 4-month point after starting treatment, and the median UACR reduction in this group was 33%.
• By 4 months, a little over a quarter of participants who received the placebo had reduced their UACR levels by at least 30%, and the median UACR reduction in this group was 2.6%.
• A UACR reduction of at least 30% reduced kidney risk by 64%, as measured by reductions in kidney failure, sufficient glomerular filtration, and death from kidney disease.
• A UACR reduction of at least 30% reduced cardiovascular risk by 26%, as measured by fewer incidences of cardiovascular death, nonfatal infarction or stroke, and hospitalization for heart failure.

IN PRACTICE:

“Achieving early UACR reduction can lead to tangible benefits for kidney and cardiovascular health,” the authors note.

SOURCE:

The study was published in the Annals of Internal Medicine; the lead author is Rajiv Agarwal, MD, MS.

LIMITATIONS:

The study pertains only to finerenone, so the findings cannot be extrapolated to other drugs with different mechanisms of action.

DISCLOSURES:

Bayer AG Pharmaceuticals, which manufactures finerenone, was the primary funder of the study. The US National Institutes of Health and Veterans Administration also provided funding. Some study authors are full-time employees of Bayer AG. Many authors report consulting relationships with various pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Reducing the urine albumin-to-creatinine ratio (UACR) significantly reduces kidney risk in people with type 2 diabetes, per new research in the Annals of Internal Medicine.

METHODOLOGY:

• Post hoc retrospective analysis of two phase 3 double-blind trials of finerenone in people with type 2 diabetes and chronic kidney disease
• Quantify the long-term health effects of reducing UACR within 4 months of taking finerenone by examining the records of 12,512 participants with an equal chance of receiving finerenone or placebo
• Isolate the impact of UACR reduction on kidney function and cardiovascular function by tracking health indicators related to the kidneys and the heart in participants for up to 4 years

TAKEAWAY:

• Over half of participants who received finerenone had reduced UACR by at least 30% from the baseline of 514 mg/g at the 4-month point after starting treatment, and the median UACR reduction in this group was 33%.
• By 4 months, a little over a quarter of participants who received the placebo had reduced their UACR levels by at least 30%, and the median UACR reduction in this group was 2.6%.
• A UACR reduction of at least 30% reduced kidney risk by 64%, as measured by reductions in kidney failure, sufficient glomerular filtration, and death from kidney disease.
• A UACR reduction of at least 30% reduced cardiovascular risk by 26%, as measured by fewer incidences of cardiovascular death, nonfatal infarction or stroke, and hospitalization for heart failure.

IN PRACTICE:

“Achieving early UACR reduction can lead to tangible benefits for kidney and cardiovascular health,” the authors note.

SOURCE:

The study was published in the Annals of Internal Medicine; the lead author is Rajiv Agarwal, MD, MS.

LIMITATIONS:

The study pertains only to finerenone, so the findings cannot be extrapolated to other drugs with different mechanisms of action.

DISCLOSURES:

Bayer AG Pharmaceuticals, which manufactures finerenone, was the primary funder of the study. The US National Institutes of Health and Veterans Administration also provided funding. Some study authors are full-time employees of Bayer AG. Many authors report consulting relationships with various pharmaceutical companies.

A version of this article appeared on Medscape.com.

NEW YORK — New treatments for acne, including the recent FDA approval of a topical gel that combines an antibiotic, a retinoid, and an antimicrobial agent, and reports on the safe use of lasers in people with darker skin types, were presented at the annual Mount Sinai Winter Symposium – Advances in Medical and Surgical Dermatology.

Also highlighted were recommendations regarding antibiotic stewardship and consideration of a treatment’s beneficial effects beyond 12 weeks.

“Patients want clear skin and many don’t care how they get there. I see patients who have been on minocycline [a broad-spectrum antibiotic] for 2 years; this is really not the best way to treat our patients,” said Joshua Zeichner, MD, associate professor of dermatology at the Icahn School of Medicine at Mount Sinai Hospital, New York, who reviewed the current state of acne treatments at the meeting.

Patients often do not care about the risk of developing antibiotic resistance, he noted, citing a survey (funded by Almirall and presented at a previous conference), which found that less than 10% of adult patients or caregivers of patients being treated for acne were moderately or extremely worried about antibiotics compared with more than 65% of the clinicians. But despite their concerns, nearly 60% of clinicians surveyed reported prescribing broad-spectrum antibiotics “most” or “all of the time,” he said.

Dr. Zeichner said that patients’ short-term wishes overriding dermatologists’ own concerns can lead to antibiotic resistance, with a negative impact on patients’ microbiomes. He encouraged prescribers to incorporate sarecycline and other narrow spectrum antibiotics into their practice as part of antibiotic stewardship. These drugs have less of an impact on the gut microbiome than broad spectrum antibiotics, while targeting the patient’s acne.

Dr. Zeichner noted that “acne is more than a 12-week disease,” but manufacturers of acne treatments can only market information based on what is in the product labeling, which usually includes 12-week results. Yet, for many acne treatments, “as you continue treating over time, you’re seeing much better improvements,” he said.

As an example, he referred to data from an unpublished phase 4 Galderma study. Patients aged 17-35 years with acne and scarring who were treated with trifarotene cream demonstrated about a 52% rate of success in acne clearance as measured by the Investigator Global Assessment (IGA) at 24 weeks, up from 31.4% at 12 weeks, highlighting the need to consider long-term data, which is helpful for patients to know, he said.

Dr. Zeichner noted that many patients and their caregivers are enthusiastic about the idea of treatment that does not involve pharmaceuticals and that these options, while not “silver bullets,” are available and advancing.

These include light-based devices. He referred to a 7-week, open label efficacy and safety study of a photo-pneumatic device with broadband light (Strata Skin Sciences). This device uses thermal heat to target and destroy Cutibacterium acnes and reduce sebum production and has a vacuum feature that removes occlusive material from the pilosebaceous unit, which he said “leads directly to a reduction in acne lesions.”

Of note is the fact that the device’ filters out visible wavelength light, which minimizes absorption by melanin in the epidermis that can damage darker skin, making the treatment safe for most skin types. In the study of patients with mild to moderate facial acne, aged 12-40 years, treatment resulted in significant reductions in mean inflammatory and noninflammatory lesion counts, and mean IGA score at day 49 compared with baseline.

Similarly, Dr. Zeichner presented a 2022 study demonstrating the use of higher spectrum lasers (a 1726-nm [nanometer] laser) to shrink sebaceous glands and reduce sebum production to treat acne. In addition, lasers that operate at such a high frequency do not cause hyperpigmentation in individuals with darker skin types, he said.

Dr. Zeichner disclosed that he is an advisor, consultant, or speaker for AbbVie, Allergan, Arcutis, Beiersdorf, Dermavant, Galderma, Kenvue, L’Oreal, Ortho, Pfizer, Regeneron, UCB, and Sun.

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

NEW YORK — New treatments for acne, including the recent FDA approval of a topical gel that combines an antibiotic, a retinoid, and an antimicrobial agent, and reports on the safe use of lasers in people with darker skin types, were presented at the annual Mount Sinai Winter Symposium – Advances in Medical and Surgical Dermatology.

Also highlighted were recommendations regarding antibiotic stewardship and consideration of a treatment’s beneficial effects beyond 12 weeks.

“Patients want clear skin and many don’t care how they get there. I see patients who have been on minocycline [a broad-spectrum antibiotic] for 2 years; this is really not the best way to treat our patients,” said Joshua Zeichner, MD, associate professor of dermatology at the Icahn School of Medicine at Mount Sinai Hospital, New York, who reviewed the current state of acne treatments at the meeting.

Patients often do not care about the risk of developing antibiotic resistance, he noted, citing a survey (funded by Almirall and presented at a previous conference), which found that less than 10% of adult patients or caregivers of patients being treated for acne were moderately or extremely worried about antibiotics compared with more than 65% of the clinicians. But despite their concerns, nearly 60% of clinicians surveyed reported prescribing broad-spectrum antibiotics “most” or “all of the time,” he said.

Dr. Zeichner said that patients’ short-term wishes overriding dermatologists’ own concerns can lead to antibiotic resistance, with a negative impact on patients’ microbiomes. He encouraged prescribers to incorporate sarecycline and other narrow spectrum antibiotics into their practice as part of antibiotic stewardship. These drugs have less of an impact on the gut microbiome than broad spectrum antibiotics, while targeting the patient’s acne.

Dr. Zeichner noted that “acne is more than a 12-week disease,” but manufacturers of acne treatments can only market information based on what is in the product labeling, which usually includes 12-week results. Yet, for many acne treatments, “as you continue treating over time, you’re seeing much better improvements,” he said.

As an example, he referred to data from an unpublished phase 4 Galderma study. Patients aged 17-35 years with acne and scarring who were treated with trifarotene cream demonstrated about a 52% rate of success in acne clearance as measured by the Investigator Global Assessment (IGA) at 24 weeks, up from 31.4% at 12 weeks, highlighting the need to consider long-term data, which is helpful for patients to know, he said.

Dr. Zeichner noted that many patients and their caregivers are enthusiastic about the idea of treatment that does not involve pharmaceuticals and that these options, while not “silver bullets,” are available and advancing.

These include light-based devices. He referred to a 7-week, open label efficacy and safety study of a photo-pneumatic device with broadband light (Strata Skin Sciences). This device uses thermal heat to target and destroy Cutibacterium acnes and reduce sebum production and has a vacuum feature that removes occlusive material from the pilosebaceous unit, which he said “leads directly to a reduction in acne lesions.”

Of note is the fact that the device’ filters out visible wavelength light, which minimizes absorption by melanin in the epidermis that can damage darker skin, making the treatment safe for most skin types. In the study of patients with mild to moderate facial acne, aged 12-40 years, treatment resulted in significant reductions in mean inflammatory and noninflammatory lesion counts, and mean IGA score at day 49 compared with baseline.

Similarly, Dr. Zeichner presented a 2022 study demonstrating the use of higher spectrum lasers (a 1726-nm [nanometer] laser) to shrink sebaceous glands and reduce sebum production to treat acne. In addition, lasers that operate at such a high frequency do not cause hyperpigmentation in individuals with darker skin types, he said.

Dr. Zeichner disclosed that he is an advisor, consultant, or speaker for AbbVie, Allergan, Arcutis, Beiersdorf, Dermavant, Galderma, Kenvue, L’Oreal, Ortho, Pfizer, Regeneron, UCB, and Sun.

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

NEW YORK — New treatments for acne, including the recent FDA approval of a topical gel that combines an antibiotic, a retinoid, and an antimicrobial agent, and reports on the safe use of lasers in people with darker skin types, were presented at the annual Mount Sinai Winter Symposium – Advances in Medical and Surgical Dermatology.

Also highlighted were recommendations regarding antibiotic stewardship and consideration of a treatment’s beneficial effects beyond 12 weeks.

“Patients want clear skin and many don’t care how they get there. I see patients who have been on minocycline [a broad-spectrum antibiotic] for 2 years; this is really not the best way to treat our patients,” said Joshua Zeichner, MD, associate professor of dermatology at the Icahn School of Medicine at Mount Sinai Hospital, New York, who reviewed the current state of acne treatments at the meeting.

Patients often do not care about the risk of developing antibiotic resistance, he noted, citing a survey (funded by Almirall and presented at a previous conference), which found that less than 10% of adult patients or caregivers of patients being treated for acne were moderately or extremely worried about antibiotics compared with more than 65% of the clinicians. But despite their concerns, nearly 60% of clinicians surveyed reported prescribing broad-spectrum antibiotics “most” or “all of the time,” he said.

Dr. Zeichner said that patients’ short-term wishes overriding dermatologists’ own concerns can lead to antibiotic resistance, with a negative impact on patients’ microbiomes. He encouraged prescribers to incorporate sarecycline and other narrow spectrum antibiotics into their practice as part of antibiotic stewardship. These drugs have less of an impact on the gut microbiome than broad spectrum antibiotics, while targeting the patient’s acne.

Dr. Zeichner noted that “acne is more than a 12-week disease,” but manufacturers of acne treatments can only market information based on what is in the product labeling, which usually includes 12-week results. Yet, for many acne treatments, “as you continue treating over time, you’re seeing much better improvements,” he said.

As an example, he referred to data from an unpublished phase 4 Galderma study. Patients aged 17-35 years with acne and scarring who were treated with trifarotene cream demonstrated about a 52% rate of success in acne clearance as measured by the Investigator Global Assessment (IGA) at 24 weeks, up from 31.4% at 12 weeks, highlighting the need to consider long-term data, which is helpful for patients to know, he said.

Dr. Zeichner noted that many patients and their caregivers are enthusiastic about the idea of treatment that does not involve pharmaceuticals and that these options, while not “silver bullets,” are available and advancing.

These include light-based devices. He referred to a 7-week, open label efficacy and safety study of a photo-pneumatic device with broadband light (Strata Skin Sciences). This device uses thermal heat to target and destroy Cutibacterium acnes and reduce sebum production and has a vacuum feature that removes occlusive material from the pilosebaceous unit, which he said “leads directly to a reduction in acne lesions.”

Of note is the fact that the device’ filters out visible wavelength light, which minimizes absorption by melanin in the epidermis that can damage darker skin, making the treatment safe for most skin types. In the study of patients with mild to moderate facial acne, aged 12-40 years, treatment resulted in significant reductions in mean inflammatory and noninflammatory lesion counts, and mean IGA score at day 49 compared with baseline.

Similarly, Dr. Zeichner presented a 2022 study demonstrating the use of higher spectrum lasers (a 1726-nm [nanometer] laser) to shrink sebaceous glands and reduce sebum production to treat acne. In addition, lasers that operate at such a high frequency do not cause hyperpigmentation in individuals with darker skin types, he said.

Dr. Zeichner disclosed that he is an advisor, consultant, or speaker for AbbVie, Allergan, Arcutis, Beiersdorf, Dermavant, Galderma, Kenvue, L’Oreal, Ortho, Pfizer, Regeneron, UCB, and Sun.

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