Differentiating Crohn’s disease (CD) and intestinal tuberculosis (ITB) has remained a dilemma for most of the clinicians in the developing world, which are endemic for ITB, and where the disease burden of inflammatory bowel disease is on the rise. Although, there are certain clinical (diarrhea/hematochezia/perianal disease common in CD; fever/night sweats common in ITB), endoscopic (longitudinal/aphthous ulcers common in CD; transverse ulcers/patulous ileocaecal valve common in ITB), histologic (caseating/confluent/large granuloma common in ITB; microgranuloma common in CD), microbiologic (positive stain/culture for acid fast-bacillus in ITB), radiologic (long segment involvement/comb sign/skip lesions common in CD; necrotic lymph node/contiguous ileocaecal involvement common in ITB), and serologic differences between CD and ITB, the only exclusive features are caseation necrosis on biopsy, positive smear for acid-fast bacillus (AFB) and/or AFB culture, and necrotic lymph node on cross-sectional imaging in ITB. However, these exclusive features are limited by poor sensitivity, and this has led to the development of multiple multi-parametric predictive models. These models are also limited by complex formulae, small sample size and lack of validation across other populations. Several new parameters have come up including the latest Bayesian meta-analysis, enumeration of peripheral blood T-regulatory cells, and updated computed tomography based predictive score. However, therapeutic anti-tubercular therapy (ATT) trial, and subsequent clinical and endoscopic response to ATT is still required in a significant proportion of patients to establish the diagnosis. Therapeutic ATT trial is associated with a delay in the diagnosis of CD, and there is a need for better modalities for improved differentiation and reduction in the need for ATT trial.

ObjectivePharmacological treatment of non-alcoholic fatty liver disease (NAFLD) is still evolving. Probiotics could be a promising treatment option, but their effectiveness needs to be established. The present study aimed to evaluate the efficacy of a high potency multistrain probiotic in adult patients with NAFLD.MethodsThirty-nine liver biopsy-proven patients with NAFLD were randomised in a double-blind fashion to either lifestyle modifications plus an oral multistrain probiotic (675 billion bacteria daily, n=19) or identical placebo (n=20) for 1 year. Lifestyle modifications included regular exercise for all and control of overweight/obesity (with additional dietary restrictions), hypertension and hyperlipidaemia in those with these risk factors. Primary objective of the study was the histological improvement in NAFLD activity score (NAS) and its components and secondary objectives were improvement in alanine transaminase (ALT) and cytokine profile.ResultsThirty (76.9%) out of 39 patients with NAFLD completed the study with 1 year of follow-up. A repeat liver biopsy at 1 year could be done in 10 patients (52.6%) in probiotic group and five patients (25%) in placebo group. In comparison to baseline, hepatocyte ballooning (p=0.036), lobular inflammation (p=0.003) and NAS score (p=0.007) improved significantly at 1 year in the probiotic group. When compared with placebo, the NAS score improved significantly in the probiotic group (p=0.004), along with improvements in hepatocyte ballooning (p=0.05) and hepatic fibrosis (p=0.018). A significant improvement in levels of ALT (p=0.046), leptin (p=0.006), tumour necrosis factor-α (p=0.016) and endotoxins (p=0.017) was observed in probiotic group in comparison to placebo at 1 year. No significant adverse events were reported in the study.ConclusionPatients with NAFLD managed with lifestyle modifications and multistrain probiotic showed significant improvement in liver histology, ALT and cytokines.Trial registration numberThe clinical trial is registered with CLINICAL TRIAL REGISTRYINDIA (CTRI); http://ctri.nic.in, No. CTRI/2008/091/000074

Chronic exposure of the oral mucosa to carcinogens in tobacco is linked to inflammation and development of oral premalignant lesions (OPLs) with high risk of progression to cancer; there is currently no clinical methodology to identify high-risk lesions. We hypothesized that identification of differentially expressed proteins in OPLs in relation to normal oral tissues using proteomic approach will reveal changes in multiple cellular pathways and aid in biomarker discovery. Isobaric mass tags (iTRAQ)-labeled oral dysplasias and normal tissues were compared against pooled normal control by online liquid chromatography and tandem mass spectrometry. Verification of biomarkers was carried out in an independent set of samples by immunohistochemistry, immunoblotting, and RT-PCR. We identified 459 nonredundant proteins in OPLs, including structural proteins, signaling components, enzymes, receptors, transcription factors, and chaperones. A panel of three best-performing biomarkers identified by iTRAQ analysis and verified by immunohistochemistrystratifin (SFN), YWHAZ, and hnRNPKachieved a sensitivity of 0.83, 0.91, specificity of 0.74, 0.95, and predictive value of 0.87 and 0.96, respectively, in discriminating dysplasias from normal tissues, thereby confirming their utility as potential OPL biomarkers. Pathway analysis revealed direct interactions between all the three biomarkers and their involvement in two major networks involved in inflammation, signaling, proliferation, regulation of gene expression, and cancer. In conclusion, our work on determining the OPL proteome unraveled novel networks linking inflammation and development of epithelial dysplasia and their key regulatory proteins may serve as novel chemopreventive/therapeutic targets for early intervention. Additionally, we identified and verified a panel of OPL biomarkers that hold promise for large-scale validation for ultimate clinical use.

Oral leukoplakia is a heterogeneous lesion with risk of cancer development; there are no biomarkers to predict its potential of malignant transformation. Tissue proteomic analysis of oral leukoplakia using iTRAQ labeling liquid chromatography–mass spectrometry showed overexpression of heterogeneous ribonucleoprotein K (hnRNP K), a transformation‐related RNA‐binding protein, in leukoplakia in comparison with normal tissue. Herein, we investigated the clinical significance of hnRNP K in identification of oral leukoplakic lesions in early stages and as a prognostic marker in head‐and‐neck/oral squamous cell carcinomas (HNOSCCs). Immunohistochemical analysis of hnRNP K was performed in 100 HNOSCCs, 199 leukoplakias and 55 nonmalignant tissues and correlated with clinicopathologic parameters and disease prognosis over 6 years for HNOSCCs. hnRNP K nuclear expression increased from normal tissues to leukoplakia, and frank malignancy (p < 0.001). Cytoplasmic hnRNP K increased significantly from leukoplakia to HNOSCCs (p < 0.001) and was associated with poor prognosis of HNOSCCs (p = 0.011) by Kaplan–Meier analysis. The most important finding of our follow‐up study is that cytoplasmic hnRNP K is an independent predictor of disease recurrence in HNOSCC patients. In conclusion, nuclear hnRNP K may serve as a potential marker for early diagnosis, whereas its cytoplasmic accumulation can help to identify a subgroup of HNOSCC patients with poor prognosis, suggesting its putative utility in clinical management of HNOSCC. © 2009 UICC