Mongersen: A SENSE-ible approach to Crohn’s Disease

Mongersen, an Oral SMAD7 Antisense Oligonucleotide, and Crohn’s Disease — NEJM.

Crohn’s disease is often difficult to treat and that explains a plethora of therapeutic modalities including a large number of biologics in use presently. A new paper in NEJM has reported gratifying results with the use of mongersen, an oral antisense oligonucleotide which degrades SMAD7 messenger RNA. SMAD7 is responsible for blocking TGF- beta signaling. This approach hopes to restore the TGF-beta signaling and reduce proinflammatory cytokines. While the reduction in the Crohn’s Disease activity scores were impressive, the patients recruited seemed to have a low baseline CRP. Also endoscopic remission was not sought. Even with caveats, the new drug represents an advancement and offers hope for patients with Crohn’s Disease.

Preventing HBV reactivation in patients planned for chemotherapy

In a recently published randomized trial conducted in China patients with untreated diffuse large B-cell lymphoma receiving chemotherapy treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, the patients received either Entecavir or Lamuvidine. HBV hepatitis and HBV reactivation were much less with the use of Entecavir. For further details please visit http://jama.jamanetwork.com/article.aspx?articleid=2040216&resultClick=3

Colonic Control of Abdominal Bulge

A remarkable paper which has appeared early online at GUT  reports that the use of colonic propionate stimulates release of anorexogens like PYY and GLP-1. Use of colonic propionate over long term in overweight individuals reduces weight gain, intra-abdominal fat accretion and the fat content in liver. The findings, if reproducible, will enable newer armamentarium in the the fight to control the epidemic of obesity and its complications like the NAFLD  Read the paper at  http://gut.bmj.com/cgi/content/long/gutjnl-2014-307913v1

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Nasoenteric feeding in Acute Pancreatitis

Nasojejunal and nasogastric feedings are commonly utilized to initiate early enteral feedings in  severe acute pancreatitis. Early enteral feedings have demonstrable benefit vis-a-vis reduction in local complications. The Dutch Pancreatitis group conducted a randomised trial comparing early initiation of nasoenteric feeding and on demand nasoenteric feeding (initially oral feeding was provided, if it failed then nasoenteric) in predicted severe acute pancreatitis. They found no benefit of early enteral feeding in SAP vis-a-vis mortality and rate of infection. The paper is available at http://www.nejm.org/doi/full/10.1056/NEJMoa1404393

Not Al(bumin) the way

Albumin, long recognised to have benefit in preventing hepatorenal syndrome in patients with cirrhosis related Spontaneous Bacterial Peritonitis, was evaluated in a randomised trial for benefit in cirrhotics with non-SBP infections. The trial reported no benefit in mortality  at 3 months duration although after adjustment for confounders albumin therapy appeared to improve survival….So no clear benefit of albumin in non-SBP infection until a better trial provides more conclusive evidence. Read the results at http://www.journal-of-hepatology.eu/article/S0168-8278(12)00439-4/abstract

Alas ! Not with the drugs.

Inspite of a great push by pharma majors to push up the sales of Anti-HBV oral drugs and promote them for all with detectable virus in the blood recent research published at http://gut.bmj.com/content/63/12/1943.abstract in GUT indicates that drugs do not seem to yield benefits vis-a-vis HCC prevention when compared to inactive carriers. Therefore, as of today the drugs should not be prescribed solely for HCC prevention. Some workers have suggested recently that immunotolerant HBV patients should be treated for preventing HCC. The evidence, unfortunately, is still awaited…..

Mucoprotection in Ulcerative colitis.

A European group has reported results of a placebo controlled trial on use of a modified release formulation of phosphatidylcholine (LT-02) in patients with mesalazine-refractory ulcerative colitis. PC is a componenet of colonic mucus. A signifiant drop in severity of Ulcerative colitis was reported with 3.2 gm dose of LT-02. The drug had an ecellent safety profile an as expected no effect on extra-intestinal manifestations. http://www.nature.com/ajg/journal/v109/n7/full/ajg2014104a.html?WT.ec_id=AJG-201407

Beta-Blockers: No longer the Aspirin for Gastroenterologists

Non selective beta blockers have use in reducing variceal bleed in patients with chronic liver disease and may have benefits beyond bleed prevention. However, emerging evidence indicates that NSBB must not be given blindly to all patients with risk for variceal bleeding. A new report in Gastroenterology indicates that in Spontaneous Bacterial Peritonitis, risk of Hepatorenal syndrome increases with use of NSBBs. 

Hold back the tome !

Ten percent patients report abdominal pain after cholecystectomy and in around 10% of patients with postcholecystectomy pain, sphincter of Oddi dysfunction is implicated as a cause. In the recently published EPISOD trial, patients with adominal pain for > 3 months after the surgery and otherwise negative workup (with normal CBD and liver enzymes) were randomized to receive a sham procedure or biliary sphincterotomy stratified on basis of sphincter pressures. Those with pancreatic sphincteric hypertension also received pancreatic sphincterotomy in a 1:1 design. The results demonstrate that irrespective of the manometry findings, sphincterotomy was no better than a sham procedure for relief of abdominal pain. The results are important with a caveat that they are applicable only to patients with Type III SOD. Those with elevated liver/pancreatic enzymes and/or ductal dilatation may still be considered for the procedure. 

http://jama.jamanetwork.com/article.aspx?articleid=1874513 

HCV Guidelines: Time to call it a day

Recently AP & T has published UK guidelines for HCV therapy and the guidelines highlight the problem of plenty with the HCV research. The guidelines are out of date the day they become available. This UK guideline also recommends interferon based therapy for HCV-1 which probably is out of date when one looks at recent data published in NEJM. Please see the previous post for that data. Anyways it is far better to go to http://www.hcvguidelines.org/for the latest on HCV

http://onlinelibrary.wiley.com/doi/10.1111/apt.12764/abstract