Bianca Nogrady

Adding a MEK inhibitor to BRAF inhibitor treatment for metastatic melanoma is associated with a significant reduction in the risk of cutaneous squamous cell carcinoma and other cutaneous toxic effects, new data suggests.

A retrospective cohort study in 185 patients with unresectable stage IIIC and IV melanoma showed those treated with BRAF inhibitors dabrafenib or vemurafenib in combination with a MEK inhibitor had zero cases of cutaneous squamous cell carcinoma, verrucal keratosis or Grover disease but a 40% incidence of folliculitis, according to a paper published online July 22 in JAMA Dermatology.

In contrast, the rates of cutaneous squamous cell carcinoma were significantly higher among patients treated with either dabrafenib or vemurafenib alone (26.1% and 36.1%, respectively), as was the incidence of Grover disease (42.9% and 38.9%) and verrucal keratosis (66.4% and 72.2%).

“Recognition of the variety of cutaneous toxic effects associated with these different therapies, including the predisposing risk factors for their development, is important with the purpose of ensuring appropriate rapid intervention and thereby abrogating the need to delay or even withhold these essential treatments,” wrote Dr. Giuliana Carlos of Westmead Hospital, Sydney, and coauthors (JAMA Dermatology 2015, July 22 [doi:10.1001/jamadermatol.2015.1745]).

The study was supported by the Westmead Medical Research Foundation. Three authors reported travel support or consultancies with pharmaceutical companies, but there were no other conflicts of interest declared.

Adding a MEK inhibitor to BRAF inhibitor treatment for metastatic melanoma is associated with a significant reduction in the risk of cutaneous squamous cell carcinoma and other cutaneous toxic effects, new data suggests.

A retrospective cohort study in 185 patients with unresectable stage IIIC and IV melanoma showed those treated with BRAF inhibitors dabrafenib or vemurafenib in combination with a MEK inhibitor had zero cases of cutaneous squamous cell carcinoma, verrucal keratosis or Grover disease but a 40% incidence of folliculitis, according to a paper published online July 22 in JAMA Dermatology.

In contrast, the rates of cutaneous squamous cell carcinoma were significantly higher among patients treated with either dabrafenib or vemurafenib alone (26.1% and 36.1%, respectively), as was the incidence of Grover disease (42.9% and 38.9%) and verrucal keratosis (66.4% and 72.2%).

“Recognition of the variety of cutaneous toxic effects associated with these different therapies, including the predisposing risk factors for their development, is important with the purpose of ensuring appropriate rapid intervention and thereby abrogating the need to delay or even withhold these essential treatments,” wrote Dr. Giuliana Carlos of Westmead Hospital, Sydney, and coauthors (JAMA Dermatology 2015, July 22 [doi:10.1001/jamadermatol.2015.1745]).

The study was supported by the Westmead Medical Research Foundation. Three authors reported travel support or consultancies with pharmaceutical companies, but there were no other conflicts of interest declared.

Adding a MEK inhibitor to BRAF inhibitor treatment for metastatic melanoma is associated with a significant reduction in the risk of cutaneous squamous cell carcinoma and other cutaneous toxic effects, new data suggests.

A retrospective cohort study in 185 patients with unresectable stage IIIC and IV melanoma showed those treated with BRAF inhibitors dabrafenib or vemurafenib in combination with a MEK inhibitor had zero cases of cutaneous squamous cell carcinoma, verrucal keratosis or Grover disease but a 40% incidence of folliculitis, according to a paper published online July 22 in JAMA Dermatology.

In contrast, the rates of cutaneous squamous cell carcinoma were significantly higher among patients treated with either dabrafenib or vemurafenib alone (26.1% and 36.1%, respectively), as was the incidence of Grover disease (42.9% and 38.9%) and verrucal keratosis (66.4% and 72.2%).

“Recognition of the variety of cutaneous toxic effects associated with these different therapies, including the predisposing risk factors for their development, is important with the purpose of ensuring appropriate rapid intervention and thereby abrogating the need to delay or even withhold these essential treatments,” wrote Dr. Giuliana Carlos of Westmead Hospital, Sydney, and coauthors (JAMA Dermatology 2015, July 22 [doi:10.1001/jamadermatol.2015.1745]).

The study was supported by the Westmead Medical Research Foundation. Three authors reported travel support or consultancies with pharmaceutical companies, but there were no other conflicts of interest declared.

Patients treated with daclatasvir and sofosbuvir for hepatitis C who are coinfected with HIV have shown a significant virologic response, regardless of whether they had already been treated for their hepatitis C infection, according to data presented at the International AIDS Society Conference on HIV Pathogenesis, Treatment & Prevention.

The open-label ALLY-2 study – published simultaneously in the July 21 online edition of the New England Journal of Medicine – in 151 previously untreated patients with hepatitis C and HIV, and 52 previously treated patients, showed 12 weeks of treatment with NS5A inhibitor daclatasvir and sofosbuvir achieved a sustained virologic response in 96.4% of untreated patients and 97.7% of previously treated patients with HCV genotype 1, with no adverse effects on HIV-1 suppression.

Among previously untreated patients treated for 8 weeks, the response rate was 75.6%, and there were no study-drug discontinuations because of adverse events (N. Engl. J. Med. 2015 July 21 [doi:10.1056/NEJMoa1503153]).

“The lower efficacy observed after 8 weeks of treatment suggests that 12 weeks of therapy may be preferred for most patients with HIV-HCV coinfection,” wrote Dr. David L. Wyles of the University of California, San Diego, and his coauthors.

Bristol-Myers Squibb supported the study. Dr. Wyles reported serving as a scientific consultant to Bristol-Myers Squibb and Gilead Sciences. Some coauthors declared grants, personal fees, and speakers fees from pharmaceutical companies, including Bristol-Myers Squibb, and several authors are employees of Bristol-Myers Squibb.

Patients treated with daclatasvir and sofosbuvir for hepatitis C who are coinfected with HIV have shown a significant virologic response, regardless of whether they had already been treated for their hepatitis C infection, according to data presented at the International AIDS Society Conference on HIV Pathogenesis, Treatment & Prevention.

The open-label ALLY-2 study – published simultaneously in the July 21 online edition of the New England Journal of Medicine – in 151 previously untreated patients with hepatitis C and HIV, and 52 previously treated patients, showed 12 weeks of treatment with NS5A inhibitor daclatasvir and sofosbuvir achieved a sustained virologic response in 96.4% of untreated patients and 97.7% of previously treated patients with HCV genotype 1, with no adverse effects on HIV-1 suppression.

Among previously untreated patients treated for 8 weeks, the response rate was 75.6%, and there were no study-drug discontinuations because of adverse events (N. Engl. J. Med. 2015 July 21 [doi:10.1056/NEJMoa1503153]).

“The lower efficacy observed after 8 weeks of treatment suggests that 12 weeks of therapy may be preferred for most patients with HIV-HCV coinfection,” wrote Dr. David L. Wyles of the University of California, San Diego, and his coauthors.

Bristol-Myers Squibb supported the study. Dr. Wyles reported serving as a scientific consultant to Bristol-Myers Squibb and Gilead Sciences. Some coauthors declared grants, personal fees, and speakers fees from pharmaceutical companies, including Bristol-Myers Squibb, and several authors are employees of Bristol-Myers Squibb.

Patients treated with daclatasvir and sofosbuvir for hepatitis C who are coinfected with HIV have shown a significant virologic response, regardless of whether they had already been treated for their hepatitis C infection, according to data presented at the International AIDS Society Conference on HIV Pathogenesis, Treatment & Prevention.

The open-label ALLY-2 study – published simultaneously in the July 21 online edition of the New England Journal of Medicine – in 151 previously untreated patients with hepatitis C and HIV, and 52 previously treated patients, showed 12 weeks of treatment with NS5A inhibitor daclatasvir and sofosbuvir achieved a sustained virologic response in 96.4% of untreated patients and 97.7% of previously treated patients with HCV genotype 1, with no adverse effects on HIV-1 suppression.

Among previously untreated patients treated for 8 weeks, the response rate was 75.6%, and there were no study-drug discontinuations because of adverse events (N. Engl. J. Med. 2015 July 21 [doi:10.1056/NEJMoa1503153]).

“The lower efficacy observed after 8 weeks of treatment suggests that 12 weeks of therapy may be preferred for most patients with HIV-HCV coinfection,” wrote Dr. David L. Wyles of the University of California, San Diego, and his coauthors.

Bristol-Myers Squibb supported the study. Dr. Wyles reported serving as a scientific consultant to Bristol-Myers Squibb and Gilead Sciences. Some coauthors declared grants, personal fees, and speakers fees from pharmaceutical companies, including Bristol-Myers Squibb, and several authors are employees of Bristol-Myers Squibb.

Treatment with ledipasvir and sofosbuvir achieves sustained virologic response at 12 weeks in patients with hepatitis C who also are infected with HIV, according to the results of the open-label ION-4 study presented at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

The multicenter study in 335 patients – published simultaneously online July 21 by the New England Journal of Medicine – showed, overall, that 96% of patients had a sustained virologic response 12 weeks after the end of therapy, while the response rates were higher (100%) among individuals with HCV genotype 4 but lower in black patients.

“This association between black race and a decreased rate of virologic response was not observed in the 308 black patients who were monoinfected with HCV receiving ledipasvir-sofosbuvir across the phase III program,” wrote Dr. Susanna Naggie of the Duke Clinical Research Institute, Durham, N.C., and her coauthors.

Response rates were not influenced by previous treatments or the presence of cirrhosis, and while there were some adverse events such as headache, fatigue, and diarrhea, no patient had confirmed HIV-1 virologic rebound (N. Engl. J. Med. 2015 July 21 [doi:10.1056/NEJMoa1501315]).

The study was supported by Gilead Sciences. Some authors declared grants, support, advisory board positions, and consultancies from pharmaceutical companies, including Gilead Sciences, and several authors are employees of Gilead Sciences.

Treatment with ledipasvir and sofosbuvir achieves sustained virologic response at 12 weeks in patients with hepatitis C who also are infected with HIV, according to the results of the open-label ION-4 study presented at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

The multicenter study in 335 patients – published simultaneously online July 21 by the New England Journal of Medicine – showed, overall, that 96% of patients had a sustained virologic response 12 weeks after the end of therapy, while the response rates were higher (100%) among individuals with HCV genotype 4 but lower in black patients.

“This association between black race and a decreased rate of virologic response was not observed in the 308 black patients who were monoinfected with HCV receiving ledipasvir-sofosbuvir across the phase III program,” wrote Dr. Susanna Naggie of the Duke Clinical Research Institute, Durham, N.C., and her coauthors.

Response rates were not influenced by previous treatments or the presence of cirrhosis, and while there were some adverse events such as headache, fatigue, and diarrhea, no patient had confirmed HIV-1 virologic rebound (N. Engl. J. Med. 2015 July 21 [doi:10.1056/NEJMoa1501315]).

The study was supported by Gilead Sciences. Some authors declared grants, support, advisory board positions, and consultancies from pharmaceutical companies, including Gilead Sciences, and several authors are employees of Gilead Sciences.

Treatment with ledipasvir and sofosbuvir achieves sustained virologic response at 12 weeks in patients with hepatitis C who also are infected with HIV, according to the results of the open-label ION-4 study presented at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

The multicenter study in 335 patients – published simultaneously online July 21 by the New England Journal of Medicine – showed, overall, that 96% of patients had a sustained virologic response 12 weeks after the end of therapy, while the response rates were higher (100%) among individuals with HCV genotype 4 but lower in black patients.

“This association between black race and a decreased rate of virologic response was not observed in the 308 black patients who were monoinfected with HCV receiving ledipasvir-sofosbuvir across the phase III program,” wrote Dr. Susanna Naggie of the Duke Clinical Research Institute, Durham, N.C., and her coauthors.

Response rates were not influenced by previous treatments or the presence of cirrhosis, and while there were some adverse events such as headache, fatigue, and diarrhea, no patient had confirmed HIV-1 virologic rebound (N. Engl. J. Med. 2015 July 21 [doi:10.1056/NEJMoa1501315]).

The study was supported by Gilead Sciences. Some authors declared grants, support, advisory board positions, and consultancies from pharmaceutical companies, including Gilead Sciences, and several authors are employees of Gilead Sciences.

Childhood psychiatric disorders are associated with significant increases in the risk of adverse outcomes in adulthood, including dropping out of high school, addiction, suicidality, serious criminal activity, and housing problems, even after accounting for childhood hardship and adult psychiatric problems.

A prospective, population-based cohort study of 1,420 individuals aged 9-16 at enrollment showed those diagnosed with childhood psychiatric disorders, such as childhood depression or conduct disorder, were six times more likely to develop at least one adverse adult outcome, and nine times more likely to develop more than one, compared with those with no history of psychiatric illness.

Individuals without a diagnosis who had subthreshold psychiatric problems had a threefold increase in the risk of later problems, according to a study published online July 15 in JAMA Psychiatry.

“Our study suggests that recognizing subthreshold cases needs to be a public health priority and that intervention for these individuals may forestall future impairments, distress, and societal costs,” wrote William E. Copeland, Ph.D., of Duke University, Durham, N.C., and his coauthors (JAMA Psychiatry 2015 July 15 [doi:10.1001/jamapsychiatry.2015.0730]).

The National Institute of Mental Health, the National Institute on Drug Abuse, the Brain and Behavior Research Foundation, and the William T. Grant Foundation supported the study. No conflicts of interest were declared.

Childhood psychiatric disorders are associated with significant increases in the risk of adverse outcomes in adulthood, including dropping out of high school, addiction, suicidality, serious criminal activity, and housing problems, even after accounting for childhood hardship and adult psychiatric problems.

A prospective, population-based cohort study of 1,420 individuals aged 9-16 at enrollment showed those diagnosed with childhood psychiatric disorders, such as childhood depression or conduct disorder, were six times more likely to develop at least one adverse adult outcome, and nine times more likely to develop more than one, compared with those with no history of psychiatric illness.

Individuals without a diagnosis who had subthreshold psychiatric problems had a threefold increase in the risk of later problems, according to a study published online July 15 in JAMA Psychiatry.

“Our study suggests that recognizing subthreshold cases needs to be a public health priority and that intervention for these individuals may forestall future impairments, distress, and societal costs,” wrote William E. Copeland, Ph.D., of Duke University, Durham, N.C., and his coauthors (JAMA Psychiatry 2015 July 15 [doi:10.1001/jamapsychiatry.2015.0730]).

The National Institute of Mental Health, the National Institute on Drug Abuse, the Brain and Behavior Research Foundation, and the William T. Grant Foundation supported the study. No conflicts of interest were declared.

Childhood psychiatric disorders are associated with significant increases in the risk of adverse outcomes in adulthood, including dropping out of high school, addiction, suicidality, serious criminal activity, and housing problems, even after accounting for childhood hardship and adult psychiatric problems.

A prospective, population-based cohort study of 1,420 individuals aged 9-16 at enrollment showed those diagnosed with childhood psychiatric disorders, such as childhood depression or conduct disorder, were six times more likely to develop at least one adverse adult outcome, and nine times more likely to develop more than one, compared with those with no history of psychiatric illness.

Individuals without a diagnosis who had subthreshold psychiatric problems had a threefold increase in the risk of later problems, according to a study published online July 15 in JAMA Psychiatry.

“Our study suggests that recognizing subthreshold cases needs to be a public health priority and that intervention for these individuals may forestall future impairments, distress, and societal costs,” wrote William E. Copeland, Ph.D., of Duke University, Durham, N.C., and his coauthors (JAMA Psychiatry 2015 July 15 [doi:10.1001/jamapsychiatry.2015.0730]).

The National Institute of Mental Health, the National Institute on Drug Abuse, the Brain and Behavior Research Foundation, and the William T. Grant Foundation supported the study. No conflicts of interest were declared.

Here are 7 articles in the July issue of Clinician Reviews (accreditation valid until January 1, 2016):

1. BSR: Multiple Benefits Seen With Intensive Psoriatic Arthritis Therapy
Multiple joint and skin benefits can be achieved by intensively treating patients with psoriatic arthritis (PsA) until they achieve a set of minimal disease activity (MDA) criteria (see Table), an expert said at the British Society for Rheumatology annual conference.

To take the posttest, go to: http://bit.ly/1KaikxW

2. Subclinical Hyperthyroidism Linked to Higher Fracture Risk
Individuals with subclinical hyperthyroidism are at increased risk for hip and other fractures, according to the authors of a meta-analysis. The researchers examined data from 70,298 individuals—4,092 with subclinical hypothyroidism and 2,219 with subclinical hyperthyroidism—enrolled in 13 prospective cohort studies.

To take the posttest, go to: http://bit.ly/1H13j0t

3. Newer Oral Contraceptives Pose Higher VTE Risk
The risk for venous thromboembolism (VTE) is generally greater for women using oral contraceptives with newer types of progestogen hormones than for those taking older, second-generation birth control pills, study results showed.

To take the posttest, go to: http://bit.ly/1AKQert

4. Statins, Fibrates Lower Stroke Risk in Elderly
Both statin and fibrate therapies taken to improve lipid profiles decreased risk for stroke by 30% in a community-dwelling population of elderly people, according to a prospective European study published online in the British Medical Journal.

To take the posttest, go to: http://bit.ly/1FuyYCb

5. Cystic Fibrosis–related Diabetes Requires Different Approach
Cystic fibrosis–related diabetes (CFRD) is a unique disease that requires a different mindset on the part of the treating clinician.

To take the posttest, go to: http://bit.ly/1BKGZCm

6. CVD Risk Persists for 40 Years in Hodgkin Survivors
People who survive Hodgkin lymphoma in adolescence or young adulthood remain at very high risk for cardiovascular disease (CVD) for at least 40 years—the longest period for which they have been followed, according to the results of a retrospective cohort study of more than 2,500 patients.

To take the posttest, go to: http://bit.ly/1M5ymYG

7. Asymptomatic Carotid Stenosis and Central Sleep Apnea Linked
More than two-thirds of patients with asymptomatic carotid stenosis are likely to have sleep apnea, according to an observational study. The polysomnography results of 96 patients with ­asymptomatic extracranial carotid stenosis revealed that 69% had sleep apnea: 42% had obstructive sleep apnea (OSA) and 27%, central sleep apnea (CSA).

To take the posttest, go to: http://bit.ly/1SWGPmb

Here are 7 articles in the July issue of Clinician Reviews (accreditation valid until January 1, 2016):

1. BSR: Multiple Benefits Seen With Intensive Psoriatic Arthritis Therapy
Multiple joint and skin benefits can be achieved by intensively treating patients with psoriatic arthritis (PsA) until they achieve a set of minimal disease activity (MDA) criteria (see Table), an expert said at the British Society for Rheumatology annual conference.

To take the posttest, go to: http://bit.ly/1KaikxW

2. Subclinical Hyperthyroidism Linked to Higher Fracture Risk
Individuals with subclinical hyperthyroidism are at increased risk for hip and other fractures, according to the authors of a meta-analysis. The researchers examined data from 70,298 individuals—4,092 with subclinical hypothyroidism and 2,219 with subclinical hyperthyroidism—enrolled in 13 prospective cohort studies.

To take the posttest, go to: http://bit.ly/1H13j0t

3. Newer Oral Contraceptives Pose Higher VTE Risk
The risk for venous thromboembolism (VTE) is generally greater for women using oral contraceptives with newer types of progestogen hormones than for those taking older, second-generation birth control pills, study results showed.

To take the posttest, go to: http://bit.ly/1AKQert

4. Statins, Fibrates Lower Stroke Risk in Elderly
Both statin and fibrate therapies taken to improve lipid profiles decreased risk for stroke by 30% in a community-dwelling population of elderly people, according to a prospective European study published online in the British Medical Journal.

To take the posttest, go to: http://bit.ly/1FuyYCb

5. Cystic Fibrosis–related Diabetes Requires Different Approach
Cystic fibrosis–related diabetes (CFRD) is a unique disease that requires a different mindset on the part of the treating clinician.

To take the posttest, go to: http://bit.ly/1BKGZCm

6. CVD Risk Persists for 40 Years in Hodgkin Survivors
People who survive Hodgkin lymphoma in adolescence or young adulthood remain at very high risk for cardiovascular disease (CVD) for at least 40 years—the longest period for which they have been followed, according to the results of a retrospective cohort study of more than 2,500 patients.

To take the posttest, go to: http://bit.ly/1M5ymYG

7. Asymptomatic Carotid Stenosis and Central Sleep Apnea Linked
More than two-thirds of patients with asymptomatic carotid stenosis are likely to have sleep apnea, according to an observational study. The polysomnography results of 96 patients with ­asymptomatic extracranial carotid stenosis revealed that 69% had sleep apnea: 42% had obstructive sleep apnea (OSA) and 27%, central sleep apnea (CSA).

To take the posttest, go to: http://bit.ly/1SWGPmb

Here are 7 articles in the July issue of Clinician Reviews (accreditation valid until January 1, 2016):

1. BSR: Multiple Benefits Seen With Intensive Psoriatic Arthritis Therapy
Multiple joint and skin benefits can be achieved by intensively treating patients with psoriatic arthritis (PsA) until they achieve a set of minimal disease activity (MDA) criteria (see Table), an expert said at the British Society for Rheumatology annual conference.

To take the posttest, go to: http://bit.ly/1KaikxW

2. Subclinical Hyperthyroidism Linked to Higher Fracture Risk
Individuals with subclinical hyperthyroidism are at increased risk for hip and other fractures, according to the authors of a meta-analysis. The researchers examined data from 70,298 individuals—4,092 with subclinical hypothyroidism and 2,219 with subclinical hyperthyroidism—enrolled in 13 prospective cohort studies.

To take the posttest, go to: http://bit.ly/1H13j0t

3. Newer Oral Contraceptives Pose Higher VTE Risk
The risk for venous thromboembolism (VTE) is generally greater for women using oral contraceptives with newer types of progestogen hormones than for those taking older, second-generation birth control pills, study results showed.

To take the posttest, go to: http://bit.ly/1AKQert

4. Statins, Fibrates Lower Stroke Risk in Elderly
Both statin and fibrate therapies taken to improve lipid profiles decreased risk for stroke by 30% in a community-dwelling population of elderly people, according to a prospective European study published online in the British Medical Journal.

To take the posttest, go to: http://bit.ly/1FuyYCb

5. Cystic Fibrosis–related Diabetes Requires Different Approach
Cystic fibrosis–related diabetes (CFRD) is a unique disease that requires a different mindset on the part of the treating clinician.

To take the posttest, go to: http://bit.ly/1BKGZCm

6. CVD Risk Persists for 40 Years in Hodgkin Survivors
People who survive Hodgkin lymphoma in adolescence or young adulthood remain at very high risk for cardiovascular disease (CVD) for at least 40 years—the longest period for which they have been followed, according to the results of a retrospective cohort study of more than 2,500 patients.

To take the posttest, go to: http://bit.ly/1M5ymYG

7. Asymptomatic Carotid Stenosis and Central Sleep Apnea Linked
More than two-thirds of patients with asymptomatic carotid stenosis are likely to have sleep apnea, according to an observational study. The polysomnography results of 96 patients with ­asymptomatic extracranial carotid stenosis revealed that 69% had sleep apnea: 42% had obstructive sleep apnea (OSA) and 27%, central sleep apnea (CSA).

To take the posttest, go to: http://bit.ly/1SWGPmb

Whole exome sequencing of an infant who died at 5 months of severe protein-losing enteropathy has revealed a rare mutation in the plasmalemma vesicle–associated protein gene.

The infant, who was from consanguineous parents, presented at 8 days of age with secretory diarrhea, metabolic acidosis, lethargy, poor feeding, and severe hyponatremia causing seizures, then developed hematochezia a day later.

Laboratory tests showed undetectable albumin that did not respond to repeated infusions, but there was no evidence of proteinuria, according to a report published in the July issue of Cellular and Molecular Gastroenterology and Hepatology (doi:10.1016/j.jcmgh.2015.05.001).

“Over the next 2 months of life, he developed enteroviral and rhinoviral upper respiratory tract infections,” wrote Dr. Abdul Elkadri of the Hospital for Sick Children, Toronto, and colleagues.

“He persistently had severe anasarca and was found to have venous thrombosis in multiple locations.”

At 5 months, the infant developed sepsis, which resulted in multiorgan failure and death.

Researchers performed whole exome sequencing on samples obtained on two separate occasions during endoscopic investigation for severe protein-losing enteropathy, and used samples from patients with gastrointestinal symptoms but normal endoscopy and histology as controls.

Sequencing identified a homozygous nonsense mutation (1072C>T; p.Arg358*) in the plasmalemma vesicle–associated protein gene (PLVAP); an extremely rare mutation that has been identified only in one heterozygote individual from more than 121,000 sequenced.

“PLVAP is a cationic, integral membrane glycoprotein that is specifically expressed in endothelial cells,” the authors wrote.

“PLVAP forms homodimers and plays a critical role in the formation of the diaphragms of caveolae and fenestrae/transendothelial channels [and] PLVAP positive diaphragms of fenestrated capillaries are essential for the maintenance of blood composition.”

When the researchers examined the patient’s biopsies under electron microscope, they found a complete absence of the fenestrae and caveolae of endothelial cells of all the capillaries in the duodenum villi examined.

They also observed tissue edema, endothelial thickening, and extracellular lipid deposition that were previously reported in PLVAP knockout mice.

“These data suggested that the truncated mutant PLVAP was either not expressed or was incapable of forming diaphragms.”

The authors said this was the first human PLVAP mutation resulting in severe, fatal sieving hypoproteinemia and enteropathy.

“Deletion of fenestral diaphragms causes leakage of plasma proteins into the interstitium of organs provided with fenestrated capillaries (intestine, pancreas, adrenals) and from there into the peritoneal cavity and into the intestine lumen, but not in organs with continuous endothelium (heart, muscle, lung),” they wrote.

The patient also had severely depleted plasma proteins, which the authors suggested occurred because of the loss of fenestral diaphragms in the intestine.

Two broad categories of protein-losing enteropathies have previously been described – the mucosal injury observed with inflammatory bowel disease, and abnormalities of the lymphatic system observed in primary intestinal lymphangiectasia.

However, there has been growing interest in possible genetic causes of these severe intestinal conditions, and causative genetic defects have yet to be identified in many infants with severe intestinal disease, including protein-losing enteropathy.

“Further work in animals modeling the human PLVAP mutation should shed light on the molecular mechanism of PLVAP downregulation, as well as the molecular mechanisms resulting in epithelial barrier disruption prompting interventional strategies.”

No relevant conflicts of interest were declared.

Whole exome sequencing of an infant who died at 5 months of severe protein-losing enteropathy has revealed a rare mutation in the plasmalemma vesicle–associated protein gene.

The infant, who was from consanguineous parents, presented at 8 days of age with secretory diarrhea, metabolic acidosis, lethargy, poor feeding, and severe hyponatremia causing seizures, then developed hematochezia a day later.

Laboratory tests showed undetectable albumin that did not respond to repeated infusions, but there was no evidence of proteinuria, according to a report published in the July issue of Cellular and Molecular Gastroenterology and Hepatology (doi:10.1016/j.jcmgh.2015.05.001).

“Over the next 2 months of life, he developed enteroviral and rhinoviral upper respiratory tract infections,” wrote Dr. Abdul Elkadri of the Hospital for Sick Children, Toronto, and colleagues.

“He persistently had severe anasarca and was found to have venous thrombosis in multiple locations.”

At 5 months, the infant developed sepsis, which resulted in multiorgan failure and death.

Researchers performed whole exome sequencing on samples obtained on two separate occasions during endoscopic investigation for severe protein-losing enteropathy, and used samples from patients with gastrointestinal symptoms but normal endoscopy and histology as controls.

Sequencing identified a homozygous nonsense mutation (1072C>T; p.Arg358*) in the plasmalemma vesicle–associated protein gene (PLVAP); an extremely rare mutation that has been identified only in one heterozygote individual from more than 121,000 sequenced.

“PLVAP is a cationic, integral membrane glycoprotein that is specifically expressed in endothelial cells,” the authors wrote.

“PLVAP forms homodimers and plays a critical role in the formation of the diaphragms of caveolae and fenestrae/transendothelial channels [and] PLVAP positive diaphragms of fenestrated capillaries are essential for the maintenance of blood composition.”

When the researchers examined the patient’s biopsies under electron microscope, they found a complete absence of the fenestrae and caveolae of endothelial cells of all the capillaries in the duodenum villi examined.

They also observed tissue edema, endothelial thickening, and extracellular lipid deposition that were previously reported in PLVAP knockout mice.

“These data suggested that the truncated mutant PLVAP was either not expressed or was incapable of forming diaphragms.”

The authors said this was the first human PLVAP mutation resulting in severe, fatal sieving hypoproteinemia and enteropathy.

“Deletion of fenestral diaphragms causes leakage of plasma proteins into the interstitium of organs provided with fenestrated capillaries (intestine, pancreas, adrenals) and from there into the peritoneal cavity and into the intestine lumen, but not in organs with continuous endothelium (heart, muscle, lung),” they wrote.

The patient also had severely depleted plasma proteins, which the authors suggested occurred because of the loss of fenestral diaphragms in the intestine.

Two broad categories of protein-losing enteropathies have previously been described – the mucosal injury observed with inflammatory bowel disease, and abnormalities of the lymphatic system observed in primary intestinal lymphangiectasia.

However, there has been growing interest in possible genetic causes of these severe intestinal conditions, and causative genetic defects have yet to be identified in many infants with severe intestinal disease, including protein-losing enteropathy.

“Further work in animals modeling the human PLVAP mutation should shed light on the molecular mechanism of PLVAP downregulation, as well as the molecular mechanisms resulting in epithelial barrier disruption prompting interventional strategies.”

No relevant conflicts of interest were declared.

Whole exome sequencing of an infant who died at 5 months of severe protein-losing enteropathy has revealed a rare mutation in the plasmalemma vesicle–associated protein gene.

The infant, who was from consanguineous parents, presented at 8 days of age with secretory diarrhea, metabolic acidosis, lethargy, poor feeding, and severe hyponatremia causing seizures, then developed hematochezia a day later.

Laboratory tests showed undetectable albumin that did not respond to repeated infusions, but there was no evidence of proteinuria, according to a report published in the July issue of Cellular and Molecular Gastroenterology and Hepatology (doi:10.1016/j.jcmgh.2015.05.001).

“Over the next 2 months of life, he developed enteroviral and rhinoviral upper respiratory tract infections,” wrote Dr. Abdul Elkadri of the Hospital for Sick Children, Toronto, and colleagues.

“He persistently had severe anasarca and was found to have venous thrombosis in multiple locations.”

At 5 months, the infant developed sepsis, which resulted in multiorgan failure and death.

Researchers performed whole exome sequencing on samples obtained on two separate occasions during endoscopic investigation for severe protein-losing enteropathy, and used samples from patients with gastrointestinal symptoms but normal endoscopy and histology as controls.

Sequencing identified a homozygous nonsense mutation (1072C>T; p.Arg358*) in the plasmalemma vesicle–associated protein gene (PLVAP); an extremely rare mutation that has been identified only in one heterozygote individual from more than 121,000 sequenced.

“PLVAP is a cationic, integral membrane glycoprotein that is specifically expressed in endothelial cells,” the authors wrote.

“PLVAP forms homodimers and plays a critical role in the formation of the diaphragms of caveolae and fenestrae/transendothelial channels [and] PLVAP positive diaphragms of fenestrated capillaries are essential for the maintenance of blood composition.”

When the researchers examined the patient’s biopsies under electron microscope, they found a complete absence of the fenestrae and caveolae of endothelial cells of all the capillaries in the duodenum villi examined.

They also observed tissue edema, endothelial thickening, and extracellular lipid deposition that were previously reported in PLVAP knockout mice.

“These data suggested that the truncated mutant PLVAP was either not expressed or was incapable of forming diaphragms.”

The authors said this was the first human PLVAP mutation resulting in severe, fatal sieving hypoproteinemia and enteropathy.

“Deletion of fenestral diaphragms causes leakage of plasma proteins into the interstitium of organs provided with fenestrated capillaries (intestine, pancreas, adrenals) and from there into the peritoneal cavity and into the intestine lumen, but not in organs with continuous endothelium (heart, muscle, lung),” they wrote.

The patient also had severely depleted plasma proteins, which the authors suggested occurred because of the loss of fenestral diaphragms in the intestine.

Two broad categories of protein-losing enteropathies have previously been described – the mucosal injury observed with inflammatory bowel disease, and abnormalities of the lymphatic system observed in primary intestinal lymphangiectasia.

However, there has been growing interest in possible genetic causes of these severe intestinal conditions, and causative genetic defects have yet to be identified in many infants with severe intestinal disease, including protein-losing enteropathy.

“Further work in animals modeling the human PLVAP mutation should shed light on the molecular mechanism of PLVAP downregulation, as well as the molecular mechanisms resulting in epithelial barrier disruption prompting interventional strategies.”

No relevant conflicts of interest were declared.

Whole exome sequencing of an infant who died at 5 months of severe protein-losing enteropathy has revealed a rare mutation in the plasmalemma vesicle–associated protein gene.

The infant, who was from consanguineous parents, presented at 8 days of age with secretory diarrhea, metabolic acidosis, lethargy, poor feeding, and severe hyponatremia causing seizures, then developed hematochezia a day later.

Laboratory tests showed undetectable albumin that did not respond to repeated infusions, but there was no evidence of proteinuria, according to a report published online May 13 in Cellular and Molecular Gastroenterology and Hepatology (doi:10.1016/j.jcmgh.2015.05.001).

“Over the next 2 months of life, he developed enteroviral and rhinoviral upper respiratory tract infections,” wrote Dr. Abdul Elkadri of the Hospital for Sick Children, Toronto, and colleagues.

“He persistently had severe anasarca and was found to have venous thrombosis in multiple locations.”

At 5 months, the infant developed sepsis, which resulted in multiorgan failure and death.

Researchers performed whole exome sequencing on samples obtained on two separate occasions during endoscopic investigation for severe protein-losing enteropathy, and used samples from patients with gastrointestinal symptoms but normal endoscopy and histology as controls.

Sequencing identified a homozygous nonsense mutation (1072C>T; p.Arg358*) in the plasmalemma vesicle–associated protein gene (PLVAP); an extremely rare mutation that has only been identified in one heterozygote individual from more than 121,000 sequenced.

“PLVAP is a cationic, integral membrane glycoprotein that is specifically expressed in endothelial cells,” the authors wrote.

“PLVAP forms homodimers and plays a critical role in the formation of the diaphragms of caveolae and fenestrae/transendothelial channels [and] PLVAP positive diaphragms of fenestrated capillaries are essential for the maintenance of blood composition.”

When the researchers examined the patient’s biopsies under electron microscope, they found a complete absence of the fenestrae and caveolae of endothelial cells of all the capillaries in the duodenum villi examined.

They also observed tissue edema, endothelial thickening, and extracellular lipid deposition that were previously reported in PLVAP knockout mice.

“These data suggested that the truncated mutant PLVAP was either not expressed or was incapable of forming diaphragms.”

The authors said this was the first human PLVAP mutation resulting in severe, fatal sieving hypoproteinemia and enteropathy.

“Deletion of fenestral diaphragms causes leakage of plasma proteins into the interstitium of organs provided with fenestrated capillaries (intestine, pancreas, adrenals) and from there into the peritoneal cavity and into the intestine lumen, but not in organs with continuous endothelium (heart, muscle, lung),” they wrote.

The patient also had severely depleted plasma proteins, which the authors suggested occurred because of the loss of fenestral diaphragms in the intestine.

Two broad categories of protein-losing enteropathies have previously been described – the mucosal injury observed with inflammatory bowel disease, and abnormalities of the lymphatic system observed in primary intestinal lymphangiectasia.

However, there has been growing interest in possible genetic causes of these severe intestinal conditions, and causative genetic defects have yet to be identified in many infants with severe intestinal disease, including protein-losing enteropathy.

“Further work in animals modeling the human PLVAP mutation should shed light on the molecular mechanism of PLVAP downregulation, as well as the molecular mechanisms resulting in epithelial barrier disruption prompting interventional strategies.”

No conflicts of interest were declared.

Whole exome sequencing of an infant who died at 5 months of severe protein-losing enteropathy has revealed a rare mutation in the plasmalemma vesicle–associated protein gene.

The infant, who was from consanguineous parents, presented at 8 days of age with secretory diarrhea, metabolic acidosis, lethargy, poor feeding, and severe hyponatremia causing seizures, then developed hematochezia a day later.

Laboratory tests showed undetectable albumin that did not respond to repeated infusions, but there was no evidence of proteinuria, according to a report published online May 13 in Cellular and Molecular Gastroenterology and Hepatology (doi:10.1016/j.jcmgh.2015.05.001).

“Over the next 2 months of life, he developed enteroviral and rhinoviral upper respiratory tract infections,” wrote Dr. Abdul Elkadri of the Hospital for Sick Children, Toronto, and colleagues.

“He persistently had severe anasarca and was found to have venous thrombosis in multiple locations.”

At 5 months, the infant developed sepsis, which resulted in multiorgan failure and death.

Researchers performed whole exome sequencing on samples obtained on two separate occasions during endoscopic investigation for severe protein-losing enteropathy, and used samples from patients with gastrointestinal symptoms but normal endoscopy and histology as controls.

Sequencing identified a homozygous nonsense mutation (1072C>T; p.Arg358*) in the plasmalemma vesicle–associated protein gene (PLVAP); an extremely rare mutation that has only been identified in one heterozygote individual from more than 121,000 sequenced.

“PLVAP is a cationic, integral membrane glycoprotein that is specifically expressed in endothelial cells,” the authors wrote.

“PLVAP forms homodimers and plays a critical role in the formation of the diaphragms of caveolae and fenestrae/transendothelial channels [and] PLVAP positive diaphragms of fenestrated capillaries are essential for the maintenance of blood composition.”

When the researchers examined the patient’s biopsies under electron microscope, they found a complete absence of the fenestrae and caveolae of endothelial cells of all the capillaries in the duodenum villi examined.

They also observed tissue edema, endothelial thickening, and extracellular lipid deposition that were previously reported in PLVAP knockout mice.

“These data suggested that the truncated mutant PLVAP was either not expressed or was incapable of forming diaphragms.”

The authors said this was the first human PLVAP mutation resulting in severe, fatal sieving hypoproteinemia and enteropathy.

“Deletion of fenestral diaphragms causes leakage of plasma proteins into the interstitium of organs provided with fenestrated capillaries (intestine, pancreas, adrenals) and from there into the peritoneal cavity and into the intestine lumen, but not in organs with continuous endothelium (heart, muscle, lung),” they wrote.

The patient also had severely depleted plasma proteins, which the authors suggested occurred because of the loss of fenestral diaphragms in the intestine.

Two broad categories of protein-losing enteropathies have previously been described – the mucosal injury observed with inflammatory bowel disease, and abnormalities of the lymphatic system observed in primary intestinal lymphangiectasia.

However, there has been growing interest in possible genetic causes of these severe intestinal conditions, and causative genetic defects have yet to be identified in many infants with severe intestinal disease, including protein-losing enteropathy.

“Further work in animals modeling the human PLVAP mutation should shed light on the molecular mechanism of PLVAP downregulation, as well as the molecular mechanisms resulting in epithelial barrier disruption prompting interventional strategies.”

No conflicts of interest were declared.

Whole exome sequencing of an infant who died at 5 months of severe protein-losing enteropathy has revealed a rare mutation in the plasmalemma vesicle–associated protein gene.

The infant, who was from consanguineous parents, presented at 8 days of age with secretory diarrhea, metabolic acidosis, lethargy, poor feeding, and severe hyponatremia causing seizures, then developed hematochezia a day later.

Laboratory tests showed undetectable albumin that did not respond to repeated infusions, but there was no evidence of proteinuria, according to a report published online May 13 in Cellular and Molecular Gastroenterology and Hepatology (doi:10.1016/j.jcmgh.2015.05.001).

“Over the next 2 months of life, he developed enteroviral and rhinoviral upper respiratory tract infections,” wrote Dr. Abdul Elkadri of the Hospital for Sick Children, Toronto, and colleagues.

“He persistently had severe anasarca and was found to have venous thrombosis in multiple locations.”

At 5 months, the infant developed sepsis, which resulted in multiorgan failure and death.

Researchers performed whole exome sequencing on samples obtained on two separate occasions during endoscopic investigation for severe protein-losing enteropathy, and used samples from patients with gastrointestinal symptoms but normal endoscopy and histology as controls.

Sequencing identified a homozygous nonsense mutation (1072C>T; p.Arg358*) in the plasmalemma vesicle–associated protein gene (PLVAP); an extremely rare mutation that has only been identified in one heterozygote individual from more than 121,000 sequenced.

“PLVAP is a cationic, integral membrane glycoprotein that is specifically expressed in endothelial cells,” the authors wrote.

“PLVAP forms homodimers and plays a critical role in the formation of the diaphragms of caveolae and fenestrae/transendothelial channels [and] PLVAP positive diaphragms of fenestrated capillaries are essential for the maintenance of blood composition.”

When the researchers examined the patient’s biopsies under electron microscope, they found a complete absence of the fenestrae and caveolae of endothelial cells of all the capillaries in the duodenum villi examined.

They also observed tissue edema, endothelial thickening, and extracellular lipid deposition that were previously reported in PLVAP knockout mice.

“These data suggested that the truncated mutant PLVAP was either not expressed or was incapable of forming diaphragms.”

The authors said this was the first human PLVAP mutation resulting in severe, fatal sieving hypoproteinemia and enteropathy.

“Deletion of fenestral diaphragms causes leakage of plasma proteins into the interstitium of organs provided with fenestrated capillaries (intestine, pancreas, adrenals) and from there into the peritoneal cavity and into the intestine lumen, but not in organs with continuous endothelium (heart, muscle, lung),” they wrote.

The patient also had severely depleted plasma proteins, which the authors suggested occurred because of the loss of fenestral diaphragms in the intestine.

Two broad categories of protein-losing enteropathies have previously been described – the mucosal injury observed with inflammatory bowel disease, and abnormalities of the lymphatic system observed in primary intestinal lymphangiectasia.

However, there has been growing interest in possible genetic causes of these severe intestinal conditions, and causative genetic defects have yet to be identified in many infants with severe intestinal disease, including protein-losing enteropathy.

“Further work in animals modeling the human PLVAP mutation should shed light on the molecular mechanism of PLVAP downregulation, as well as the molecular mechanisms resulting in epithelial barrier disruption prompting interventional strategies.”

No conflicts of interest were declared.

Two studies of using fecal microbiota transplants to treat ulcerative colitis have had mixed results.

Researchers conducted a double-blind parallel study of 75 individuals with active ulcerative colitis; 38 received fecal microbiota transplants from healthy anonymous donors, and 37 received a placebo dose of water, once a week for 6 weeks.

While the trial was terminated early for reasons of futility, among the patients who completed treatment, the authors observed a 7-week remission rate of 24% among the patients who received the fecal transplants, compared with a 5% remission rate in the placebo group – a statistically significant difference – according to the study published in the July issue of Gastroenterology (doi:10.1053/j.gastro.2015.04.001).

“The benefit was relatively modest, but our endpoint for treatment success was more stringent than most trials in UC and remission rates seen with FMT [fecal microbiota transplants] were consistent with a similar endpoint for a novel biologic therapy,” wrote Dr. Paul Moayyedi of the Farncombe Family Digestive Health Research Institute, Ontario, and coauthors.

Seven of the nine patients who achieved remission – defined as a Mayo score ≤ 2 with an endoscopic Mayo score of 0 – after the fecal microbiota transplants were all treated with transplants from a single donor. “The efficacy of this approach may also be donor dependent and this may explain why some case series have shown promise, and others have had disappointing results,” the authors wrote.

Those who had ulcerative colitis for less than a year had a significantly higher rate of remission than those who had the disease for more than a year, while patients who received the transplants showed a greater microbial diversity in their stool, compared with their baseline, than did the patients in the control group.

A second study found no significant different in remission rates between patients who received donor fecal microbiota transplants and a control group who received autologous transplants.

In the double-blind randomized trial, 50 patients with moderately active ulcerative colitis were administered two transplants via nasoduodenal tube, 3 weeks apart, according to a paper published online March 30 in Gastroenterology.

Among the 37 patients who completed the study, 30.4% of those who received transplants from donors and 20% of controls met the primary endpoint of clinical remission (P = 0.51), according to the intention-to-treat analysis (Gastroenterology 2015 March 30 [doi:10.1053/j.gastro.2015.03.045]).

In the per-protocol analysis, the difference between the active and control group was slightly greater but still failed to reach statistical significance.

The authors suggested that low numbers may have contributed to the lack of effect of the donor fecal transplants, However the study did find that at 12 weeks, those who had received the donor fecal microbiota and responded to it had a microbiota similar to that of their healthy donors.

“Therefore we may assume that even though both treatment groups included responders, the subsequent effects on microbiota composition are different in the FMT-D (donor) and FMT-A (autologous) groups,” wrote Dr. Noortje G. Rossen of the Academic Medical Center, Amsterdam, and coauthors.

The first study was funded by Hamilton Academic Health Sciences Organization, and Crohn’s and Colitis Canada. Some authors declared honoraria, speaking engagements, advisory board positions, consultancies and research funding from a range of pharmaceutical companies.

The second study was supported by MLDS and NWO-Spinoza, and there were no conflicts of interest declared.

Two studies of using fecal microbiota transplants to treat ulcerative colitis have had mixed results.

Researchers conducted a double-blind parallel study of 75 individuals with active ulcerative colitis; 38 received fecal microbiota transplants from healthy anonymous donors, and 37 received a placebo dose of water, once a week for 6 weeks.

While the trial was terminated early for reasons of futility, among the patients who completed treatment, the authors observed a 7-week remission rate of 24% among the patients who received the fecal transplants, compared with a 5% remission rate in the placebo group – a statistically significant difference – according to the study published in the July issue of Gastroenterology (doi:10.1053/j.gastro.2015.04.001).

“The benefit was relatively modest, but our endpoint for treatment success was more stringent than most trials in UC and remission rates seen with FMT [fecal microbiota transplants] were consistent with a similar endpoint for a novel biologic therapy,” wrote Dr. Paul Moayyedi of the Farncombe Family Digestive Health Research Institute, Ontario, and coauthors.

Seven of the nine patients who achieved remission – defined as a Mayo score ≤ 2 with an endoscopic Mayo score of 0 – after the fecal microbiota transplants were all treated with transplants from a single donor. “The efficacy of this approach may also be donor dependent and this may explain why some case series have shown promise, and others have had disappointing results,” the authors wrote.

Those who had ulcerative colitis for less than a year had a significantly higher rate of remission than those who had the disease for more than a year, while patients who received the transplants showed a greater microbial diversity in their stool, compared with their baseline, than did the patients in the control group.

A second study found no significant different in remission rates between patients who received donor fecal microbiota transplants and a control group who received autologous transplants.

In the double-blind randomized trial, 50 patients with moderately active ulcerative colitis were administered two transplants via nasoduodenal tube, 3 weeks apart, according to a paper published online March 30 in Gastroenterology.

Among the 37 patients who completed the study, 30.4% of those who received transplants from donors and 20% of controls met the primary endpoint of clinical remission (P = 0.51), according to the intention-to-treat analysis (Gastroenterology 2015 March 30 [doi:10.1053/j.gastro.2015.03.045]).

In the per-protocol analysis, the difference between the active and control group was slightly greater but still failed to reach statistical significance.

The authors suggested that low numbers may have contributed to the lack of effect of the donor fecal transplants, However the study did find that at 12 weeks, those who had received the donor fecal microbiota and responded to it had a microbiota similar to that of their healthy donors.

“Therefore we may assume that even though both treatment groups included responders, the subsequent effects on microbiota composition are different in the FMT-D (donor) and FMT-A (autologous) groups,” wrote Dr. Noortje G. Rossen of the Academic Medical Center, Amsterdam, and coauthors.

The first study was funded by Hamilton Academic Health Sciences Organization, and Crohn’s and Colitis Canada. Some authors declared honoraria, speaking engagements, advisory board positions, consultancies and research funding from a range of pharmaceutical companies.

The second study was supported by MLDS and NWO-Spinoza, and there were no conflicts of interest declared.

Two studies of using fecal microbiota transplants to treat ulcerative colitis have had mixed results.

Researchers conducted a double-blind parallel study of 75 individuals with active ulcerative colitis; 38 received fecal microbiota transplants from healthy anonymous donors, and 37 received a placebo dose of water, once a week for 6 weeks.

While the trial was terminated early for reasons of futility, among the patients who completed treatment, the authors observed a 7-week remission rate of 24% among the patients who received the fecal transplants, compared with a 5% remission rate in the placebo group – a statistically significant difference – according to the study published in the July issue of Gastroenterology (doi:10.1053/j.gastro.2015.04.001).

“The benefit was relatively modest, but our endpoint for treatment success was more stringent than most trials in UC and remission rates seen with FMT [fecal microbiota transplants] were consistent with a similar endpoint for a novel biologic therapy,” wrote Dr. Paul Moayyedi of the Farncombe Family Digestive Health Research Institute, Ontario, and coauthors.

Seven of the nine patients who achieved remission – defined as a Mayo score ≤ 2 with an endoscopic Mayo score of 0 – after the fecal microbiota transplants were all treated with transplants from a single donor. “The efficacy of this approach may also be donor dependent and this may explain why some case series have shown promise, and others have had disappointing results,” the authors wrote.

Those who had ulcerative colitis for less than a year had a significantly higher rate of remission than those who had the disease for more than a year, while patients who received the transplants showed a greater microbial diversity in their stool, compared with their baseline, than did the patients in the control group.

A second study found no significant different in remission rates between patients who received donor fecal microbiota transplants and a control group who received autologous transplants.

In the double-blind randomized trial, 50 patients with moderately active ulcerative colitis were administered two transplants via nasoduodenal tube, 3 weeks apart, according to a paper published online March 30 in Gastroenterology.

Among the 37 patients who completed the study, 30.4% of those who received transplants from donors and 20% of controls met the primary endpoint of clinical remission (P = 0.51), according to the intention-to-treat analysis (Gastroenterology 2015 March 30 [doi:10.1053/j.gastro.2015.03.045]).

In the per-protocol analysis, the difference between the active and control group was slightly greater but still failed to reach statistical significance.

The authors suggested that low numbers may have contributed to the lack of effect of the donor fecal transplants, However the study did find that at 12 weeks, those who had received the donor fecal microbiota and responded to it had a microbiota similar to that of their healthy donors.

“Therefore we may assume that even though both treatment groups included responders, the subsequent effects on microbiota composition are different in the FMT-D (donor) and FMT-A (autologous) groups,” wrote Dr. Noortje G. Rossen of the Academic Medical Center, Amsterdam, and coauthors.

The first study was funded by Hamilton Academic Health Sciences Organization, and Crohn’s and Colitis Canada. Some authors declared honoraria, speaking engagements, advisory board positions, consultancies and research funding from a range of pharmaceutical companies.

The second study was supported by MLDS and NWO-Spinoza, and there were no conflicts of interest declared.

Two studies of using fecal microbiota transplants to treat ulcerative colitis have had mixed results.

Researchers conducted a double-blind parallel study of 75 individuals with active ulcerative colitis (UC); 38 received fecal microbiota transplants from healthy anonymous donors, and 37 received a placebo dose of water, once a week for 6 weeks.

While the trial was terminated early for reasons of futility, among the patients who completed treatment, the authors observed a 7-week remission rate of 24% among the patients who received the fecal transplants, compared with a 5% remission rate in the placebo group – a statistically significant difference – according to the study published in the July issue of Gastroenterology (doi:10.1053/j.gastro.2015.04.001).

“The benefit was relatively modest, but our endpoint for treatment success was more stringent than most trials in UC and remission rates seen with FMT [fecal microbiota transplants] were consistent with a similar endpoint for a novel biologic therapy,” wrote Dr. Paul Moayyedi of the Farncombe Family Digestive Health Research Institute, Ontario, and coauthors.

Seven of the nine patients who achieved remission – defined as a Mayo score ≤ 2 with an endoscopic Mayo score of 0 – after the FMTs were all treated with transplants from a single donor. “The efficacy of this approach may also be donor dependent and this may explain why some case series have shown promise, and others have had disappointing results,” the authors wrote.

Those who had UC for less than a year had a significantly higher rate of remission than those who had the disease for more than a year, while patients who received the transplants showed a greater microbial diversity in their stool, compared with baseline, than did the patients in the control group.

A second study found no significant different in remission rates between patients who received donor FMTs and a control group who received autologous transplants.

In the double-blind randomized trial, 50 patients with moderately active UC were administered two transplants via nasoduodenal tube, 3 weeks apart, according to the paper published in the July issue of Gastroenterology (doi:10.1053/j.gastro.2015.03.045).

Among the 37 patients who completed the study, 30.4% of those who received transplants from donors and 20% of controls met the primary endpoint of clinical remission (P = .51), according to the intention-to-treat analysis.

In the per-protocol analysis, the difference between the active and control group was slightly greater but still did not reach statistical significance.

The authors suggested that low numbers may have contributed to the lack of effect of the donor FMTs, but the study did find that, at 12 weeks, those who had received the donor FMTs and responded to it had a microbiota similar to that of their healthy donors.

“Therefore we may assume that even though both treatment groups included responders, the subsequent effects on microbiota composition are different in the FMT-D (donor) and FMT-A (autologous) groups,” wrote Dr. Noortje G. Rossen of the Academic Medical Center, Amsterdam, and coauthors.

The first study was funded by Hamilton Academic Health Sciences Organization, and Crohn’s and Colitis Canada. Some authors declared honoraria, speaking engagements, advisory board positions, consultancies, and research funding from pharmaceutical companies. The second study was supported by MLDS and NWO-Spinoza, and no conflicts of interest were declared.

Two studies of using fecal microbiota transplants to treat ulcerative colitis have had mixed results.

Researchers conducted a double-blind parallel study of 75 individuals with active ulcerative colitis (UC); 38 received fecal microbiota transplants from healthy anonymous donors, and 37 received a placebo dose of water, once a week for 6 weeks.

While the trial was terminated early for reasons of futility, among the patients who completed treatment, the authors observed a 7-week remission rate of 24% among the patients who received the fecal transplants, compared with a 5% remission rate in the placebo group – a statistically significant difference – according to the study published in the July issue of Gastroenterology (doi:10.1053/j.gastro.2015.04.001).

“The benefit was relatively modest, but our endpoint for treatment success was more stringent than most trials in UC and remission rates seen with FMT [fecal microbiota transplants] were consistent with a similar endpoint for a novel biologic therapy,” wrote Dr. Paul Moayyedi of the Farncombe Family Digestive Health Research Institute, Ontario, and coauthors.

Seven of the nine patients who achieved remission – defined as a Mayo score ≤ 2 with an endoscopic Mayo score of 0 – after the FMTs were all treated with transplants from a single donor. “The efficacy of this approach may also be donor dependent and this may explain why some case series have shown promise, and others have had disappointing results,” the authors wrote.

Those who had UC for less than a year had a significantly higher rate of remission than those who had the disease for more than a year, while patients who received the transplants showed a greater microbial diversity in their stool, compared with baseline, than did the patients in the control group.

A second study found no significant different in remission rates between patients who received donor FMTs and a control group who received autologous transplants.

In the double-blind randomized trial, 50 patients with moderately active UC were administered two transplants via nasoduodenal tube, 3 weeks apart, according to the paper published in the July issue of Gastroenterology (doi:10.1053/j.gastro.2015.03.045).

Among the 37 patients who completed the study, 30.4% of those who received transplants from donors and 20% of controls met the primary endpoint of clinical remission (P = .51), according to the intention-to-treat analysis.

In the per-protocol analysis, the difference between the active and control group was slightly greater but still did not reach statistical significance.

The authors suggested that low numbers may have contributed to the lack of effect of the donor FMTs, but the study did find that, at 12 weeks, those who had received the donor FMTs and responded to it had a microbiota similar to that of their healthy donors.

“Therefore we may assume that even though both treatment groups included responders, the subsequent effects on microbiota composition are different in the FMT-D (donor) and FMT-A (autologous) groups,” wrote Dr. Noortje G. Rossen of the Academic Medical Center, Amsterdam, and coauthors.

The first study was funded by Hamilton Academic Health Sciences Organization, and Crohn’s and Colitis Canada. Some authors declared honoraria, speaking engagements, advisory board positions, consultancies, and research funding from pharmaceutical companies. The second study was supported by MLDS and NWO-Spinoza, and no conflicts of interest were declared.

Two studies of using fecal microbiota transplants to treat ulcerative colitis have had mixed results.

Researchers conducted a double-blind parallel study of 75 individuals with active ulcerative colitis (UC); 38 received fecal microbiota transplants from healthy anonymous donors, and 37 received a placebo dose of water, once a week for 6 weeks.

While the trial was terminated early for reasons of futility, among the patients who completed treatment, the authors observed a 7-week remission rate of 24% among the patients who received the fecal transplants, compared with a 5% remission rate in the placebo group – a statistically significant difference – according to the study published in the July issue of Gastroenterology (doi:10.1053/j.gastro.2015.04.001).

“The benefit was relatively modest, but our endpoint for treatment success was more stringent than most trials in UC and remission rates seen with FMT [fecal microbiota transplants] were consistent with a similar endpoint for a novel biologic therapy,” wrote Dr. Paul Moayyedi of the Farncombe Family Digestive Health Research Institute, Ontario, and coauthors.

Seven of the nine patients who achieved remission – defined as a Mayo score ≤ 2 with an endoscopic Mayo score of 0 – after the FMTs were all treated with transplants from a single donor. “The efficacy of this approach may also be donor dependent and this may explain why some case series have shown promise, and others have had disappointing results,” the authors wrote.

Those who had UC for less than a year had a significantly higher rate of remission than those who had the disease for more than a year, while patients who received the transplants showed a greater microbial diversity in their stool, compared with baseline, than did the patients in the control group.

A second study found no significant different in remission rates between patients who received donor FMTs and a control group who received autologous transplants.

In the double-blind randomized trial, 50 patients with moderately active UC were administered two transplants via nasoduodenal tube, 3 weeks apart, according to the paper published in the July issue of Gastroenterology (doi:10.1053/j.gastro.2015.03.045).

Among the 37 patients who completed the study, 30.4% of those who received transplants from donors and 20% of controls met the primary endpoint of clinical remission (P = .51), according to the intention-to-treat analysis.

In the per-protocol analysis, the difference between the active and control group was slightly greater but still did not reach statistical significance.

The authors suggested that low numbers may have contributed to the lack of effect of the donor FMTs, but the study did find that, at 12 weeks, those who had received the donor FMTs and responded to it had a microbiota similar to that of their healthy donors.

“Therefore we may assume that even though both treatment groups included responders, the subsequent effects on microbiota composition are different in the FMT-D (donor) and FMT-A (autologous) groups,” wrote Dr. Noortje G. Rossen of the Academic Medical Center, Amsterdam, and coauthors.

The first study was funded by Hamilton Academic Health Sciences Organization, and Crohn’s and Colitis Canada. Some authors declared honoraria, speaking engagements, advisory board positions, consultancies, and research funding from pharmaceutical companies. The second study was supported by MLDS and NWO-Spinoza, and no conflicts of interest were declared.

Fewer than one in 10 elderly patients with a low ejection fraction after myocardial infarction who are eligible to receive an implantable cardioverter-defibrillator actually receive one within a year of their myocardial infarction, a study has found.

The retrospective observational study of 10,318 patients aged over 65 years who had experienced a myocardial infarction and had an ejection fraction of 35% or less showed only 8.1% received an implantable cardioverter-defibrillator (ICD) within a year of their MI, even though implantation within a year was associated with a 36% reduction in mortality at 2 years.

Those patients who did receive an ICD were more likely to have had a prior coronary artery bypass graft, had higher peak troponin levels, experienced in-hospital cardiogenic shock, or had a cardiology follow-up within 2 weeks of discharge, according to the paper published June 23 in JAMA.

“Individualized shared decision making, taking into context the patient’s quality of life, treatment goals, and preferences, is critical, because ICD therapy may shift death from a sudden event to a more gradual comorbid process,” wrote Dr. Sean D. Pokorney, of Duke University Medical Center, Durham, N.C., and co-authors (JAMA 2015;313:2433-40 [doi: 10.1001/jama.2015.6409]).

The study was supported by the Agency for Healthcare Research& Quality, and Boston Scientific. Some authors declared research grants, honoraria, advisory board positions, and consultancies with private industry.

Fewer than one in 10 elderly patients with a low ejection fraction after myocardial infarction who are eligible to receive an implantable cardioverter-defibrillator actually receive one within a year of their myocardial infarction, a study has found.

The retrospective observational study of 10,318 patients aged over 65 years who had experienced a myocardial infarction and had an ejection fraction of 35% or less showed only 8.1% received an implantable cardioverter-defibrillator (ICD) within a year of their MI, even though implantation within a year was associated with a 36% reduction in mortality at 2 years.

Those patients who did receive an ICD were more likely to have had a prior coronary artery bypass graft, had higher peak troponin levels, experienced in-hospital cardiogenic shock, or had a cardiology follow-up within 2 weeks of discharge, according to the paper published June 23 in JAMA.

“Individualized shared decision making, taking into context the patient’s quality of life, treatment goals, and preferences, is critical, because ICD therapy may shift death from a sudden event to a more gradual comorbid process,” wrote Dr. Sean D. Pokorney, of Duke University Medical Center, Durham, N.C., and co-authors (JAMA 2015;313:2433-40 [doi: 10.1001/jama.2015.6409]).

The study was supported by the Agency for Healthcare Research& Quality, and Boston Scientific. Some authors declared research grants, honoraria, advisory board positions, and consultancies with private industry.

Fewer than one in 10 elderly patients with a low ejection fraction after myocardial infarction who are eligible to receive an implantable cardioverter-defibrillator actually receive one within a year of their myocardial infarction, a study has found.

The retrospective observational study of 10,318 patients aged over 65 years who had experienced a myocardial infarction and had an ejection fraction of 35% or less showed only 8.1% received an implantable cardioverter-defibrillator (ICD) within a year of their MI, even though implantation within a year was associated with a 36% reduction in mortality at 2 years.

Those patients who did receive an ICD were more likely to have had a prior coronary artery bypass graft, had higher peak troponin levels, experienced in-hospital cardiogenic shock, or had a cardiology follow-up within 2 weeks of discharge, according to the paper published June 23 in JAMA.

“Individualized shared decision making, taking into context the patient’s quality of life, treatment goals, and preferences, is critical, because ICD therapy may shift death from a sudden event to a more gradual comorbid process,” wrote Dr. Sean D. Pokorney, of Duke University Medical Center, Durham, N.C., and co-authors (JAMA 2015;313:2433-40 [doi: 10.1001/jama.2015.6409]).

The study was supported by the Agency for Healthcare Research& Quality, and Boston Scientific. Some authors declared research grants, honoraria, advisory board positions, and consultancies with private industry.