A prospective, multicentre, observational study of patients with chronic cholestatic liver diseases receiving Udiliv® in India: Splendid study

Background: Data on clinical spectrum and etiology of chronic cholestatic liver disease (CCLD) in Indian patients is limited. This prospective, observational real-world study aimed to profile patients with CCLD being recommended Udiliv®, determine reasons for recommendation along with its safety and effectiveness.Methods: CCLD patients (18-65 years) scheduled to receive Udiliv® as part of routine clinical practice were enrolled. Healthcare utilizations, clinical manifestations (jaundice, pruritus, fatigue) and liver biochemistry were assessed over 12 weeks. Reasons for recommending Udiliv® were recorded at the initiation of therapy.Results: The intent-to-treat analysis population included 248 patients. The mean (±SD) age was 44.1(11.8) years and 78.23% were males. Majority (89.1%) were classified as intrahepatic cholestasis (IHC). Most common etiologies of IHC were alcoholic liver disease (ALD) (39.92%) and viral hepatitis (24.60%) followed by non-alcoholic fatty liver disease (NAFLD) (22.18%), which is less well known. Udiliv®, 300 mg twice daily was preferred dose due to known efficacy (73.39%), as standard of care (62.5%) and good tolerability (45.56%). There was reduction in healthcare visits, inpatient hospitalization and days off work, within 4 weeks of treatment initiation (P<0.0001). There was improvement in clinical presentation (P<0.0001) and reduction in biochemical markers over 12 weeks. The treatment was well-tolerated.Conclusions: NAFLD, a less perceived etiology for CCLD, was found to be a significant contributor to CCLD. Physicians recommend Udiliv® due to its known efficacy and tolerability. Udiliv® reduced CCLD disease burden and was found to be an effective and well-tolerated treatment option

Prevalence of functional constipation and constipation-predominant irritable bowel syndrome in Indian patients with constipation

Background: Evaluate prevalence of functional constipation (FC) and irritable bowel syndrome-constipation (IBS-C) in Indian constipated patients and assess their demographic/socio-economic/clinical characteristics.Methods: Patients (≥18 years) who visited their general physician with symptoms of constipation (Rome III criteria for FC or IBS-C as per physician assessment) and willing to participate were enrolled in this prospective, clinical-epidemiological study. Demographic, socioeconomic status, lifestyle and dietary habits, comorbid conditions, treatment history, concomitant medications, stool form (Bristol stool form scale), severity of constipation (constipation scoring system [CSS]), constipation-related symptoms (patient assessment of constipation symptoms [PAC-SYM]) and quality of life (patient assessment of constipation-quality of life questionnaire [PAC-QoL]) were recorded.Results: Out of 925 constipated patients, 75.6% were diagnosed with FC against 24.4% with IBS-C (P < 0.0001). Patients of both subtypes had high average scores of PAC-SYM (FC: 27.1 ± 6; IBS-C: 30.1 ± 4.9) and CSS (FC: 8.4 ± 3.1; IBS-C: 11.2 ± 3), leading to high PAC-QoL score (FC: 38.1 ± 16.8; IBS-C: 42.2 ± 13.6). Hypertension (16%) and diabetes (10%) in patients with FC while acid peptic disorders (21.7%) amongst IBS-C patients were the most common comorbid conditions observed. Laxatives were the most common medication used; osmotic (32.6% versus 40.7%) and bulk laxatives (22.8% versus 37.4%) were the commonest laxatives. However, about 1/5th patients of FC were using home remedies.Conclusions: There was a higher prevalence of FC over IBS-C in Indian constipated patients; both subtypes had high frequency and severity of constipation-related symptoms and poor QoL

Placental inflammation in spontaneous preterm birth and neonatal outcomes

Background: Preterm birth (PTB) can be classified as spontaneous or indicated. The complications of PTB can affect all systems and result in chronic physical and mental disabilities. Objective: The objective of the study was to assess the incidence of placental inflammation in PTB with and without preterm premature rupture of membranes (pPROM) and its effects on various neonatal outcomes. Materials and Methods: This prospective observational study was conducted in a tertiary hospital where all preterm neonates born by spontaneous onset vaginal delivery and cesarean section were included in the study. Neonates born to mothers having significant uterine anomalies, multiple gestations, and those with any major congenital anomalies were excluded from the study. Placentas were assessed for evidence of inflammation on histopathological examination. Correlation of placental inflammation with neonatal morbidity and mortality was also assessed. Results: The incidence of placental inflammation in spontaneous onset preterm births (sPTB) was found to be 29%. Most placentas showed Stage 1 chorioamnionitis (47%). Three placentas had evidence of fetal inflammatory response, of which one had early funisitis (Stage 1) and two had intermediate funisitis (Stage 2). Of the nine neonates who had features of sepsis (definite or probable), 4 (44.4%) had evidence of placental inflammation. No significant association was found between placental inflammation and other secondary outcomes such as duration of neonatal intensive care unit stay, neonatal mortality, requirement of phototherapy, and need for continuous positive airway pressure support. Conclusions: Placental inflammation was seen in almost one-third of cases of sPTB, of which 78% were without pPROM. Hence, sPTB irrespective of pPROM should be considered as indirect marker of ongoing inflammation

The effects of exogenous growth factors on matrix metalloproteinase secretion by human brain tumour cells

Matrix metalloproteinases (MMPs) are a growing family of zinc-dependent endopeptidases that are capable of degrading various components of the extracellular matrix. These enzymes have been implicated in a variety of physiological and pathological conditions including embryogenesis and tumour invasion. The synthesis of many MMPs is thought to be regulated by growth factors, cytokines and hormones. In this study, we investigated the effects of five exogenous growth factors known to be expressed by gliomas [epidermal growth factor (EGF), basic growth factor (bFGF), transforming growth factor beta (TGF-β1,2) and vascular endothelial growth factor (VEGF)] on MMP-2 and MMP-9 expression in an ependymoma, two grade III astrocytomas, a grade III oligoastrocytoma and a benign meningioma. Zymogram analysis revealed that the effects of the growth factors depended upon the cell lines used in the study. Growth factors generally up-regulated MMP-2 and MMP-9 expression in the gliomas but were least effective in the meningioma; the effect being most prominent with TGF-β1 and TGF-β2 in all the cell lines. It is hypothesized that paracrine growth factor interplay may be crucial in the regulation of MMP expression by glioma invasion of the normal brain. © 2000 Cancer Research Campaig

Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma

MMPs (matrix metalloproteinases), ADAMs (a disintegrin and metalloproteinase) and TIMPs (tissue inhibitors of metalloproteinases) are implicated in invasion and angiogenesis: both are tissue remodeling processes involving regulated proteolysis of the extracellular matrix, growth factors and their receptors. The expression of these three groups and their correlations with clinical behaviour has been reported in gliomas but a similar comprehensive study in meningiomas is lacking. In the present study, we aimed to evaluate the patterns of expression of 23 MMPs, 4 TIMPs, 8 ADAMs, selective growth factors and their receptors in 17 benign meningiomas using a quantitative real-time polymerase chain reaction (qPCR). Results indicated very high gene expression of 13 proteases, inhibitors and growth factors studied: MMP2 and MMP14, TIMP-1, -2 and -3, ADAM9, 10, 12, 15 and 17, EGF-R, EMMPRIN and VEGF-A, in almost every meningioma. Expression pattern analysis showed several positive correlations between MMPs, ADAMs, TIMPs and growth factors. Furthermore, our findings suggest that expression of MMP14, ADAM9, 10, 12, 15 and 17, TIMP-2, EGF-R and EMMPRIN reflects histological subtype of meningioma such that fibroblastic subtype had the highest mRNA expression, transitional subtype was intermediate and meningothelial type had the lowest expression. In conclusion, this is the first comprehensive study characterizing gene expression of ADAMs in meningiomas. These neoplasms, although by histological definition benign, have invasive potential. Taken together, the selected elevated gene expression pattern may serve to identify targets for therapeutic intervention or indicators of biological progression and recurrence

Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma

MMPs (matrix metalloproteinases), ADAMs (a disintegrin and metalloproteinase) and TIMPs (tissue inhibitors of metalloproteinases) are implicated in invasion and angiogenesis: both are tissue remodeling processes involving regulated proteolysis of the extracellular matrix, growth factors and their receptors. The expression of these three groups and their correlations with clinical behaviour has been reported in gliomas but a similar comprehensive study in meningiomas is lacking. In the present study, we aimed to evaluate the patterns of expression of 23 MMPs, 4 TIMPs, 8 ADAMs, selective growth factors and their receptors in 17 benign meningiomas using a quantitative real-time polymerase chain reaction (qPCR). Results indicated very high gene expression of 13 proteases, inhibitors and growth factors studied: MMP2 and MMP14, TIMP-1, -2 and -3, ADAM9, 10, 12, 15 and 17, EGF-R, EMMPRIN and VEGF-A, in almost every meningioma. Expression pattern analysis showed several positive correlations between MMPs, ADAMs, TIMPs and growth factors. Furthermore, our findings suggest that expression of MMP14, ADAM9, 10, 12, 15 and 17, TIMP-2, EGF-R and EMMPRIN reflects histological subtype of meningioma such that fibroblastic subtype had the highest mRNA expression, transitional subtype was intermediate and meningothelial type had the lowest expression. In conclusion, this is the first comprehensive study characterizing gene expression of ADAMs in meningiomas. These neoplasms, although by histological definition benign, have invasive potential. Taken together, the selected elevated gene expression pattern may serve to identify targets for therapeutic intervention or indicators of biological progression and recurrence

Systematic review and meta-analysis on trimodal therapy versus radical cystectomy for muscle-invasive bladder cancer: Does the current quality of evidence justify definitive conclusions?

OBJECTIVES To systematically review and meta-analyze the current literature in a methodologically rigorous and transparent manner for quantitative evidence on survival outcomes among patients diagnosed with muscle-invasive bladder cancer that were treated by either trimodal therapy or radical cystectomy. MATERIALS AND METHODS MEDLINE, EMBASE, CENTRAL were systematically searched for comparative observational studies reporting disease-specific survival and/or overall survival on adult patients diagnosed with localized muscle-invasive bladder cancer that were exposed to either trimodal therapy or radical cystectomy. Studies qualified for meta-analysis (random effects model) if they were not at critical risk of bias (RoB). RESULTS The literature search identified 12 eligible studies. Three (all rated as "moderate RoB") out of 6 studies reporting on disease-specific survival qualified for quantitative analysis and yielded a pooled hazard ratio (trimodal therapy versus radical cystectomy) of 1.39 (95% confidence interval: 1.03-1.88). Four (mainly rated as "serious RoB") out of 12 studies were included in the meta-analysis of overall survival and estimated a hazard ratio of 1.39 (1.20-1.59). CONCLUSION Pooled results were significant in favor of radical cystectomy. The conclusion is mainly driven by large population-based studies that are at high RoB. Hence, the certainty of these treatment estimates can be considered very low and further research will likely have an important impact on these estimates. At present, the ultimate decision between trimodal therapy and radical cystectomy should be left to the patient based on individual preferences and on the recommendation of a multidisciplinary provider team experienced with both approaches