Etiological profile of diarrhea in solid organ transplant recipients at a tertiary care center in Southern India.

BACKGROUND: Diarrhea is one of the common gastrointestinal (GI) adverse events after solid organ transplantation. Diarrhea may be caused by infectious or non-infectious etiology. The infectious etiology of diarrhea varies according to the location and duration of diarrhea. Non-infectious etiologies include drugs, inflammatory bowel disease, neoplasia. The objective of this study was to evaluate the etiological profile of diarrhea in solid organ transplant recipients presenting to a tertiary care center in Southern India. METHODS: This was a retrospective analysis of prospectively collected data of all solid organ transplantation recipients referred to the Department of Medical Gastroenterology for evaluation of diarrhea from April 2012 till May 2014. All patients had stool evaluated by wet mount examination, modified acid fast (AFB) stain, trichrome stain, culture, and Clostridium difficile toxin assay. EDTA plasma was collected for quantitative Cytomegalovirus (CMV) detection by real-time PCR. If the diarrhea was acute (<2 wk), and no etiological agent was identified, empirical antibiotic therapy was instituted and followed up. If persistent or chronic diarrhea (>2-4 wk), endoscopic evaluation (upper GI endoscopy and/or colonoscopy with biopsies), depending on the clinical type of diarrhea was done. If no specific etiological diagnosis was established after endoscopic evaluation, breath test for SIBO and celiac serology were done. If no specific etiology was identified after the above investigations, dose of immunosuppressive drugs was reduced. If diarrhea responded to dose reduction, it was considered to be drug related. RESULTS: Fifty-eight episodes of diarrhea occurred in 55 solid organ transplant recipients during the study period. Renal transplant recipients constituted the majority (70%). Most (79%) of patients included in the study had their transplant > 6 mo ago. Infective diarrhea was the etiology in 46%, drug-related diarrhea in 29.3%. No specific etiology was identified in 22.4% of patients. Parasites accounted for 69% of all infective diarrhea. Stool evaluation was the main investigation in establishing diagnosis in acute diarrhea. Endoscopic evaluation was required in two thirds of patients to establish diagnosis in chronic diarrhea. CONCLUSION: GI infections and drug-related diarrhea were the common causes of diarrhea in solid organ transplant recipients. Parasites were the most common infectious etiology of diarrhea. Step-wise evaluation was able to identify the etiology in ~ 77% of patients. Overall, 98% of diarrheal episodes resolved.

TLR5 Polymorphisms rs2072493, rs5744174, and rs5744168 Are Not Genetic Risk Factors for Chronic Helicobacter pylori Infection in Indian Tamils.

The incidence of Helicobacter pylori (H. pylori) infection and gastric cancer is on the rise in India, and the genetic factors influencing the increased susceptibility in Indian population remain obscure. Toll-like receptors (TLRs) play a major role in innate immune system and genetic polymorphisms affecting their function were reported to enhance the risk for H. pylori infection. Seventy-seven patients (n = 77) diagnosed with H. pylori infection and 230 healthy subjects were recruited in this study. The rs2072493, rs5744174, and rs5744168 polymorphisms within TLR5 gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Tetra-ARMS PCR genotyping techniques. Present study revealed that these studied polymorphisms are less frequent in south Indian Tamils and thus failed to confer a significant risk to develop chronic H. pylori infections. The distribution of ancestral allele of rs2072493 polymorphism conferred resistance to develop chronic H. pylori infection in our population (p = 0.024; OR  =  0.53; 95% CI: 0.3-0.91). The lesser incidence of polymorphic alleles suggests that the TLR5 gene is under genetic selection pressure to withstand the prevailing endemic infections among south Indian Tamils.

Comparative Proteomic Analysis Reveals Novel Biomarkers for Gastric Cancer in South Indian Tamil Population.

BACKGROUND: Gastric Cancer (GC) remains a major global health problem due to a poor understanding of its progression at the molecular level and a lack of early detection or diagnosis. Early detection is highly crucial for improving prognosis. The incidence of GC is very high in countries, like India, due to the limitations among the established biomarkers for GC owing to poor sensitivity and specificity. OBJECTIVE: This study aimed to identify the novel biomarkers from serum samples obtained from GC patients compared to healthy subjects. METHODS: Serum samples from GC patients were analyzed by two-Dimensional Gel Electrophoresis (2DGE) coupled with tandem Mass Spectrometry (MS), including both Matrix-Assisted Laser Desorption/Ionization-Time of Flight (MALDI-ToF) and Liquid Chromatography-MS (LC-MS/MS) analysis. Identified proteins were further analyzed by gene ontology and protein interaction studies. RESULTS: A total of 73 protein spots were detected in 2DGE image analysis. Among them, seven differentially-expressed proteins were identified using MS analyses, including serotransferrin/ transferrin, albumin, ceruloplasmin, C-reactive protein (CRP), fibrinogen γ-chain (FGG), and two unreported novel proteins, immunoglobulin kappa constant (IgκC) region and Homo sapiens zinc finger protein 28 (ZNF28) homolog. Among these proteins, serotransferrin, albumin, ceruloplasmin, FGG, and ZNF28 were down-regulated in GC samples (p<0.05), while IgκC region and CRP were up-regulated significantly. CONCLUSION: Most of the differentially expressed proteins were involved in angiogenesis, plasminogen-activating cascade, and blood coagulation pathways which are known to play a critical role in gastric tumorigenesis. Our current results provide a panel of candidate biomarkers for GC with novel biomarkers which have not been reported earlier.

Patulous upper esophageal sphincter - an unusual endoscopic finding.

The upper esophageal sphincter (UES) has various important functions, such as protection of the airway from aspiration and conduct of bolus into esophagus, which are controlled by complex neuronal mechanisms. The functions will be affected when there is malfunction of the UES due to various etiologies. Here we present an 80-year-old male with non-progressive dysphagia and patulous UES incidentally found on esophagoduodenoscopy. There are no documented cases of idiopathic patulous UES in literature. Endoscopists must be aware of this rare condition while evaluating a patient presenting with oropharyngeal dysphagia.

A simplified technique of esophageal self-expandable metallic stent placement without fluoroscopic and endoscopic guidance for treating esophageal carcinoma.

BACKGROUND/AIMS: Self-expandable metallic stent (SEMS) placement with fluoroscopic guidance is a commonly used technique to relieve obstruction in patients with esophageal carcinoma. However, it has disadvantages such as radiation exposure. SEMS placement with endoscopic guidance also has the disadvantages of causing discomfort to patients as the endoscope and SEMS assembly are simultaneously used and it needs two experts for the procedure to be performed. To overcome these disadvantages, a simplified technique for SEMS placement was developed that does not require fluoroscopic or endoscopic guidance. Our objective was to compare the efficacy and safety of this simplified technique with the conventional SEMS placement method. MATERIALS AND METHODS: This is a retrospective study including patients with esophageal carcinoma who underwent SEMS placement for the palliation of dysphagia. RESULTS: Sixty-two patients were placed on stents for the palliation for esophageal carcinoma, with 46 patients in the conventional technique group (group A) and 16 in the simplified technique group (group B). The duration of the procedure was considerably lesser in group B than in group A (2 min 53 s vs. 15 min 4 s, p=0.001). The technical success rate achieved in groups A and B were 97.82% and 100%, respectively. SEMS placement required two experts in the conventional technique whereas the simplified technique required only one expert. CONCLUSION: The advantages of the simplified technique are as follows: technical ease, cost-effectiveness, no exposure to radiation, requirement of minimal manpower, and less time-consuming; these advantages make it the technique day-care procedure.

Genetic variants of TLR4 and TLR9 are risk factors for chronic Helicobacter pylori infection in South Indian Tamils.

Toll like receptors (TLRs) are a class of molecular pattern recognition receptors, elicits a strong inflammatory immune response against pathogens. Helicobacter pylori (H. pylori), a gram negative flagellate colonizes the human stomach, is responsible for the development of chronic gastritis and gastric carcinoma. The higher incidence of H. pylori infection and gastric cancer in South Indian Tamils demands a genetic study to unravel the influence of TLR4 and TLR9 polymorphisms associated with chronic H. pylori infection. In this study, 230 healthy individuals and 77 patients diagnosed with H. pylori infection were screened for TLR4 (rs1927914, rs4986790, rs4986791) and TLR9 (rs352140, rs34399053, rs150459369) polymorphisms by PCR-RFLP and ARMS-PCR. We observed that the individuals harboring heterozygous and homozygous polymorphic variants of TLR4 conferred a significant risk to develop chronic H. pylori infection and peptic ulcer disease [rs4986790 AG, p=0.001, OR-2.7, 95%CI: 1.5-5.03; GG, p=0.0006, OR-9.8, 95%CI: 2.4-39.4; rs4986791CT, p=0.0001, OR-7.2, 95%CI: 3.7-7.2; TT, p=0.0001, OR-7.9, 95%CI: 2.6-23.7]. Also, the heterozygous variant of TLR9 rs352140, favoured the persistence of the H. pylori infection [p=0.037, OR-1.87, 95%CI: 1.07-3.29]. Thus our findings suggest that TLR4 rs4986790, rs4986791 and TLR9 rs352140 polymorphisms are potential genetic risk factors influencing the disease susceptibility and clinical manifestation of chronic H. pylori infection in Indian Tamils.