A randomized double-blind, placebo-controlled trial to evaluate the safety and efficacy of live Bifidobacterium longum CECT 7347 (ES1) and heat-treated Bifidobacterium longum CECT 7347 (HT-ES1) in participants with diarrhea-predominant irritable bowel syndrome.

To determine the efficacy of the probiotic Bifidobacterium longum CECT 7347 (ES1) and postbiotic heat-treated Bifidobacterium longum CECT 7347 (HT-ES1) in improving symptom severity in adults with diarrhea-predominant irritable bowel syndrome (IBS-D), a randomised, double-blind, placebo-controlled trial with 200 participants split into three groups was carried out. Two capsules of either ES1, HT-ES1 or placebo were administered orally, once daily, for 84 days (12 weeks). The primary outcome was change in total IBS-Symptom Severity Scale (IBS-SSS) score from baseline, compared to placebo. Secondary outcome measures were stool consistency, quality of life, abdominal pain severity and anxiety scores. Safety parameters and adverse events were also monitored. The change in IBS-SSS scores from baseline compared to placebo, reached significance in the ES1 and HT-ES1 group, on Days 28, 56 and 84. The decrease in mean IBS-SSS score from baseline to Day 84 was: ES1 (-173.70 [±75.60]) vs placebo (-60.44 [±65.5]) (p < .0001) and HT-ES1 (-177.60 [±79.32]) vs placebo (-60.44 [±65.5]) (p < .0001). Secondary outcomes included changes in IBS-QoL, APS-NRS, stool consistency and STAI-S and STAI-T scores, with changes from baseline to Day 84 being significant in ES1 and HT-ES1 groups, compared to the placebo group. Both ES1 and HT-ES1 were effective in reducing IBS-D symptom severity, as evaluated by measures such as IBS-SSS, IBS-QoL, APS-NRS, stool consistency, and STAI, in comparison to the placebo. These results are both statistically significant and clinically meaningful, representing, to the best of the authors' knowledge, the first positive results observed for either a probiotic or postbiotic from the same strain, in this particular population.

What is already known on this topicIBS is a chronic functional gastrointestinal disorder characterized by abdominal pain, bloating and abnormalities in stool frequency or form. The gut microbiota of people living with IBS differs markedly to the microbiota of healthy individuals. Gut microbiota may play a key role in IBS aetiology and IBS symptoms may be alleviated by modulating the gut microbiota. Several proposed ways to modulate gut health include normalizing the gut microbiota, preventing the overgrowth of pathogenic bacteria, modulating visceral afferent pathways, and enhancing intestinal barrier function. However, significant heterogeneity between studies, study quality and population, study design and concerns about sample size have limited national and supranational bodies from recommending probiotics for IBS. Further well-powered, randomized, repeatable and controlled trials are warranted.What this study addsThe results of this study substantially contribute to the IBS research field, firstly by providing clinically meaningful and statistically significant results from a rigorous, well designed randomized, placebo-controlled trial and secondly, by exploring the use of postbiotics in IBS, an area of research still in its infancy. Probiotic (ES1) and postbiotic (HT-ES1) supplementation significantly reduced IBS symptom severity scores compared to placebo. This study met primary and secondary outcomes and strongly suggest that ES1 and HT-ES1 could be beneficial in the management of IBS.How this study might affect research, practice, or policyThis study adds to the current evidence base, supporting the use of probiotic/postbiotics for IBS. This research could be used to inform health professionals about using probiotics in IBS and help improve the quality of life and wellbeing for people living with the condition.

Efficacy of different methods for detecting the onset of ovarian cyclicity in post-partum Murrah buffaloes.

This study was designed to investigate the sensitivity and specificity of three methods for detecting the onset of cyclicity in post-partum Murrah buffaloes. The methods investigated were visual signs, transrectal ultrasonography, and serum progesterone (P4) assay. For this study, 102 post-partum Murrah buffalo cows were grouped for monitoring their ovarian activity. The first group of buffaloes was between 26 and 35 days post-partum. Thereafter, the buffalo cows that calved were grouped after every 10 days for the study sample. Thus, the study animals were adjudged between 26 and 35, 36-45, 46-55, 56-65, 66-75, 76-85, and 86-95 days post-partum with an average of 30, 40, 50, 60, 70, 80, and 90 days post-partum, respectively. Visual estrus signs were monitored twice daily, and simultaneously, ultrasound examination was carried out at 10 days interval for accessing the presence of corpus luteum (CL). Serum P4 was estimated in the animals which were adjudged cyclic by ultrasound examination, and the assay was repeated after 10 days. The buffalo cows in estrus were inseminated artificially, and pregnancy status was assessed after 30 days post-insemination. In this study, the sensitivity and specificity of visual observation were low (39.37 and 70.73%, respectively) when compared to P4 assay (98.80 and 96.47%) and ultrasound examination (single, 97.59 and 97.59%; double, 100 and 100%), respectively. Furthermore, the sensitivity and specificity of single and double ultrasound examination and P4 assay were comparable. In conclusion, this study reports that single and double ultrasound examination and P4 assay are more efficient than visual observation in detecting the onset of ovarian cyclicity in post-partum Murrah buffaloes.

Suppressed heat shock protein response in the kidney of exercise-trained diabetic rats.

Impaired expression of heat shock proteins (HSPs) and increased oxidative stress may contribute to the pathophysiology of diabetes by disrupted tissue protection. Acute exercise induces oxidative stress, whereas exercise training up-regulates endogenous antioxidant defenses and HSP expression. Although diabetic nephropathy is a major contributor to diabetic morbidity, information regarding the effect of HSPs on kidney protection is limited. This study evaluated the effects of eight-week exercise training on kidney HSP expression and markers of oxidative stress at rest and after acute exercise in rats with or without streptozotocin-induced diabetes. Induction of diabetes increased DNA-binding activity of heat shock factor-1, but decreased the expression of HSP72, HSP60, and HSP90. The inflammatory markers IL-6 and TNF-alpha were increased in the kidney tissue of diabetic animals. Both exercise training and acute exercise increased HSP72 and HSP90 protein levels only in non-diabetic rats. On the other hand, exercise training appeared to reverse the diabetes-induced histological changes together with decreased expression of TGF-beta as a key inducer of glomerulosclerosis, and decreased levels of IL-6 and TNF-alpha. Notably, HSP72 and TGF-beta were negatively correlated. In conclusion, impaired HSP defense seems to contribute to kidney injury vulnerability in diabetes and exercise training does not up-regulate kidney HSP expression despite the improvements in histopathological and inflammatory markers.

Clostridium difficile infection after restorative proctocolectomy and ileal pouch anal anastomosis for ulcerative colitis.

AIM: Clostridium difficile infection (CDI) of the ileal pouch following restorative proctocolectomy (RPC) is becoming increasingly recognized. We aimed to understand better (i) the associated risk factors, (ii) treatment practices and (iii) the pouch diversion and failure rate in patients who developed CDI of the pouch after RPC for ulcerative colitis (UC). METHOD: Patients who tested positive for C. difficile of the pouch between 2007 and 2010 were included in the analysis. Data collected included patient demographics, time from RPC to documented CDI, the treatment of CDI and rate of excision of the pouch. RESULTS: Of 2785 patients recorded in the hospital CDI database, 15 had had an RPC with ileal pouch anal anastomosis. The median age was 44 years and the median interval from RPC to first documented episode of CDI was 3 years. Thirteen (81%) patients had had multiple episodes of pouchitis before and after CDI infection, and all were symptomatic at the time of testing for CDI. Within 30 days of the diagnosis of CDI, six (40%) patients were taking immunosuppressive medication, seven (47%) were taking a proton pump inhibitor and 12 (80%) had received antibiotics. Five patients required hospitalization for CDI and four had severe infections characterized by a serum creatinine more than 1.5 times baseline (n = 3) and a white cell count above 15 000 (n = 1). Six patients who underwent endoscopy had severe inflammation of the pouch including the presence of a pseudomembrane in one case. Ten patients were treated with metronidazole alone and five with vancomycin. Two patients had recurrent CDI of the pouch during a median follow-up period of 2.9 years and one had CDI refractory to medical management. This patient required diversion of the pouch with an ileostomy for refractory CDI but no patient required excision of the pouch. CONCLUSION: All 15 patients developing CDI of the pouch were successfully treated with antibiotics and only one required surgery in the form of an ileostomy.

An unusual cause of hemoperitoneum: case report with review of literature.

Spontaneous hemoperitoneum (SH) is a rare entity which can be life-threatening. Gastrointestinal neurofibromas are rare. Occasionally, such lesions may be the initial sign of NF1 in patients without any other clinical manifestations of the disease. The clinical presentations of isolated neurofibromatous lesions of the intestines are variable. In asymptomatic patient no treatment may be required and patient may be kept on follow up. Occasionally, they manifest with complications such as intestinal bleeding, obstruction or perforation. Surgery is the treatment of choice in symptomatic intestinal neurofibroma. We present the case of a 55 year-old male with acute abdomen due to rupture of isolated neurofibroma as one of the cause of SH. This case represents a rare presentation of isolated intestinal neurofibromatosis in a patient without systemic manifestations and highlights the need for high index of suspicion to exclude neurofibromatosis type 1 or multiple endocrine neoplasia type 2b.

Systematic review: colitis associated with anti-CTLA-4 therapy.

BACKGROUND: Cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) has an important role in T-cell regulation, proliferation and tolerance. Anti-CTLA-4 agents, such as ipilimumab and tremelimumab, have been shown to prolong overall survival in patients with metastatic melanoma, and their use is being investigated in the treatment of other malignancies. Their novel immunostimulatory mechanism, however, predisposes patients to immune-related adverse effects, of which gastrointestinal effects such as diarrhoea and colitis are the most common. AIMS: To discuss the existing literature and summarise the epidemiology, pathogenesis and clinical features of anti-CTLA-4-associated colitis, and to present a management algorithm for it. METHODS: We searched PubMed for studies published through October 2014 using the terms 'anti-CTLA,' 'ipilimumab,' 'tremelimumab,' 'colitis,' 'gastrointestinal,' 'immune-related adverse effect,' 'immunotherapy,' 'melanoma,' and 'diarrhoea.' RESULTS: Watery diarrhoea is commonly associated with anti-CTLA-4 therapy (27-54%), and symptoms occur within a few days to weeks of therapy. Diffuse acute and chronic colitis are the most common findings on endoscopy (8-22%). Concomitant infectious causes of diarrhoea must be evaluated. Most cases may be successfully managed with discontinuation of anti-CTLA-4 and conservative therapy. Those with persistent grade 2 and grade 3/4 diarrhoea should undergo endoscopic evaluation and require corticosteroid therapy. Corticosteroid-resistant cases may respond to anti-tumour necrosis factor-alpha therapy such as infliximab. Surgery is reserved for patients with bowel perforation or failure of medical therapy. CONCLUSION: Given the increasing use of anti-CTLA-4 therapy, clinicians must be aware of related adverse events and their management.

Acute small intestinal obstruction-an unusual complication of capsule endoscopy.

We report a case of endoscopic capsule impaction causing acute small intestinal obstruction in a patient with Crohn's disease (CD), having obscure gastrointestinal bleeding. A 57-year old female presented with features of acute small bowel obstruction 2 days after capsule endoscopy elsewhere for the evaluation of intermittent bleeding per rectum and iron deficiency anemia. Patient underwent an exploratory laparotomy with right hemicolectomy for the diseased ileocecal region which mimicked malignancy. The capsule was found to be impacted in the strictured lumen of the terminal ileum. Post operative histopathological examination revealed it to be Crohn's disease.

Adrenal tumors: An experience of 10 years in a single surgical unit.

INTRODUCTION: Most of the adrenal masses are discovered incidentally by imaging techniques for reasons unrelated to adrenal diseases. Treatment is based on various factors such as, nature of adrenal mass, age of presentation, size of tumor, and the functional status of tumor. We report a series of 14 consecutive cases of adrenal tumors treated in a single surgical unit in our hospital. AIM: The aim of this study was to evaluate the clinical profile and outcome of treatment of adrenal tumors treated in a surgical unit. MATERIALS AND METHODS: It is a retrospective study data of 14 cases of adrenal tumors treated in a single surgical unit in University Hospital over 10 years have been analyzed. Various parameters such as gender, age, size of tumor, functional status, histopathology, type of management, and outcome have been reviewed. RESULTS: A total of 14 patients with adrenal masses were seen over a 10 year period (1997-2006). All were referred cases, either from endocrinology or medicine wards. There were seven female and seven male patients. Mean age of patients was 48.6 years (range 14-60 years). Mean size of tumor was 8.0 cm (5.9 cm for benign tumors and 9.7 cm for malignant tumors). There were six cases of adrenal carcinoma, four cases of adrenal myelolipoma, two cases of pheochromocytoma, and one each case of adrenal hyperplasia and histoplasmosis. There were only two functional tumors. All, except two malignant cases were treated operatively. A total of 5 year survival was 100% in benign cases and 27% in malignant tumors. CONCLUSION: Adrenal tumors need to be assessed for their functional status and malignant potential prior to treatment. Surgical excision is usually curative for benign lesion. Among malignant tumors the benefits of surgery depend on local extent and metastatic status of tumors.

Detection rate and outcome of colonic serrated epithelial changes in patients with ulcerative colitis or Crohn's colitis.

BACKGROUND: Chronic ulcerative colitis (CUC) and colonic Crohn's disease (CD) increase colorectal neoplasia (CRN) risk. While sessile serrated polyp (SSP) is a known cancer precursor, serrated epithelial changes (SEC) are of uncertain prevalence and neoplastic risk. AIM: To assess the serrated lesion detection rates in CUC and CD and documented incidence of subsequent CRN in a retrospective, single-centre cohort study. METHODS: Patients were identified by a central diagnostic index and pathology review confirmed SEC, SSP, CUC and CD diagnoses from 2006-12. Matched controls were identified from among all CUC and CD patients having colonoscopy during the second half of the time period. All were followed for incident CRN, estimated by the Kaplan-Meier method. RESULTS: Between 2006 and 2012, 79 SEC and 10 SSP cases were identified. Detection rates were estimated to be 10/1000 and 2/1000 patients, for SEC and SSP respectively, among 4208 unique CUC or CD patients having colonoscopy from 2010-12. With only 10 cases, SSP patients were not further analysed. Cumulative incidence of subsequent CRN at 1 and 3 years was 12% (95% CI, 0-30%) and 30% (3-57%), respectively, in SEC patients compared to 4% (0-12%) and 9% (0-23%), respectively, in CUC or CD controls (P = 0.047, log-rank). However, this statistical difference was not significant after patients were stratified for history of prior or synchronous dysplasia (P = 0.09). CONCLUSIONS: Serrated epithelial changes and sessile serrated polyps are uncommonly detected by colonoscopy in chronic ulcerative colitis and Crohn's disease patients. Histology with changes of serrated epithelium may be associated with risk of subsequent colorectal neoplasia, however further studies are needed to explore this relationship.

Pro-apoptotic miRNA-128-2 modulates ABCA1, ABCG1 and RXRα expression and cholesterol homeostasis.

Aberrant regulation of cholesterol homeostasis is associated with obesity as well as multiple types of cancer. However, the mechanism behind these is largely missing. Here, we show that microRNA (miRNA)-128-2 is not only a pro-apoptotic microRNA but it also alters the expression of genes involved in cellular cholesterol homeostasis. Cholesterol efflux via ATP-binding cassette transporters (ABCA1 and ABCG1) is a mechanism for cells to eliminate excess cholesterol and prevent cellular cholesterol accumulation. The regulation of these pathways is complex with transcriptional regulation by sterol-regulatory element-binding protein (SREBP) and liver X receptor/retinoid X receptor (RXR) transcription factors but poorly understood at the post-transcriptional levels. MiR-128-2 increases the expression of SREBP2 and decreases the expression of SREBP1 in HepG2, MCF7 and HEK293T cells independent of sirtuin 1 (SIRT1) status. MiR-128-2 inhibits the expression of ABCA1, ABCG1 and RXRα directly through a miR-128-2-binding site within their respective 3'untranslated regions. The administration of miR-128-2 leads to decline in the protein and mRNA levels of ABCA1, ABCG1 and RXRα. Conversely, anti-miRNA treatment leads to increased ABCA1, ABCG1 and RXRα expression. The inverse correlation between miR-128-2 and its targets viz. ABCA1 and ABCG1 was also established during high-fat diet in different mice tissues. Our data show that cholesterol efflux is attenuated by miR-128-2 overexpression and, conversely, stimulated by miR-128-2 silencing. Further, we also observed the induction of ER stress response by miR-128-2. In this study, we provide the first evidence of miR-128-2 to be a new regulator of cholesterol homeostasis. Our study shows dual role of miR-128-2, as a pro-apoptotic molecule as well as a regulator of cholesterol homeostasis.

Skin tumorigenic potential of benzanthrone: prevention by ascorbic acid.

Benzanthrone (BA) exposed occupational workers have been found to exhibit toxicological manifestations in the skin, thus it is quite likely that long term exposure may lead to skin tumorigenicity. Thus, attempts were made to elucidate the tumor initiating and promoting potentials of pure (PBA) and commercial benzanthrone (CBA). Additionally, the preventive role of ascorbic acid (AsA) was also assessed. PBA showed tumor initiating activity while CBA demonstrated tumor initiating as well as promoting activities in two-stage mouse skin tumor protocol. Further, prior treatment of AsA to PBA and CBA followed by twice weekly application of 12-o-tetradecanoyl phorbal myristate acetate (TPA) resulted into delayed onset of tumor formation and similarly single application of 7,12-dimethylbenz [α] anthracene (DMBA) followed by twice weekly application of AsA and CBA showed an increase in the latency period. Thus, AsA showed a protective effect against CBA promoted skin tumor. Furthermore, the topical application of CBA significantly increased the levels of xenobiotic enzymes. The animals topically treated with AsA along with topical application of CBA, restored all the impairment observed in enzyme activities. Thus, this study suggested that AsA can be useful in preventing PBA and CBA induced skin tumorigenicity.

Anterior neck lipoma with anterior mediastinal extention - a rare case report.

Lipomas are the most common benign mesenchymal tumour. Thirteen percent of lipomas are seen in head and neck region. Anterior neck lipoma is a rare one. Anterior neck lipoma with mediastinal extension is extremely rare. We are presenting a case of 52 years old male reported to Central Referral Hospital, Sikkim Manipal Institute of Medical Sciences, Gangtok, Sikkim with complains of swelling in left side of neck for last 18 months along with occasional history of dyspnoea. Physical examination, ultrasound, computed tomography and fine needle aspiration cytology are in favor of lipoma. Due to its location up to the anterior mediastinum, the surgery could not be done in this hospital and patient was referred to higher center having cardiothoracic surgical back up.

Pulmonary coccidiomycosis in New Delhi, India.

Coccidioidomycosis is an endemic disease of the western hemisphere. In cases occurring in non-endemic areas, eliciting a history of exposure as well as a high index of suspicion is imperative for timely and accurate diagnosis. In this case, a 65-year-old male presented to our hospital with fever, dry cough and malaise, and on X-ray chest, was found to have a lower lobe consolidation left lung with nodular lesions in both lungs and necrotic mediastinal lymphadenopathy. He lived in Arizona, USA, for 6 months before admission. Pulmonary coccidioidomycosis was confirmed by the isolation of Coccidioides spp. in pure culture from both broncho-alveolar lavage and lung biopsy specimens. The identity of the isolate was confirmed as C. posadasii by gene sequencing. The patient improved after being treated with fluconazole.

Anaesthesia for robotic gynaecological surgery.

Robotic surgery is gaining widespread popularity due to advantages such as reduced blood loss, reduced postoperative pain, shorter hospital stay and better visualisation of fine structures. Robots are being used in urological, cardiac, thoracic, orthopaedic, gynaecological and general surgery. Robotic surgery received US Food and Drug Administration approval for use in gynaecological surgery in 2005. The various gynaecological robotic operations being performed are myomectomy, total and supracervical hysterectomy, ovarian cystectomy, sacral colpopexy, tubal reanastomosis, lymph node dissection, surgery of retroperitoneal ectopic pregnancy, Moskowitz procedure and endometriosis surgery. The anaesthetic considerations include difficult access to the patient intraoperatively, steep Trendelenburg position, long surgical duration and the impact of pneumoperitoneum. We highlight the complications encountered in these surgeries and methods to prevent these complications. Robotic gynaecological surgery can be safely performed after considering the physiological effects of the steep Trendelenburg position and of pneumoperitoneum. The benefits of the surgical procedure should be weighed against the risks in patients with underlying cardiorespiratory problems.

A case of 'an upside down stomach'.

Neonatal paraesophageal hernia with intrathoracic gastric volvulus is very rare in the newborn period. We report a case of a 2-day-old term neonate who presented with an antenatal diagnosis of paraesophageal hernia. We discuss the diagnosis and management with classical radiological features including an antenatal diagnosis of this extremely rare surgical cause of neonatal nonbilious emesis.