Itolizumab in combination with methotrexate modulates active rheumatoid arthritis: safety and efficacy from a phase 2, randomized,open-label,parallel-group,dose-ranging study

Clinical Rheumatology - The objective of this study was to assess the safety and efficacy of itolizumab with methotrexate in active rheumatoid arthritis (RA) patients who had inadequate response to...     

Gut microbiome in acute pancreatitis: A review based on current literature

The gut microbiome is a complex microbial community, recognized for its potential role in physiology, health, and disease. The available evidence supports the role of gut dysbiosis in pancreatic disorders, including acute pancreatitis (AP). In AP, the presence of gut barrier damage resulting in increased mucosal permeability may lead to translocation of intestinal bacteria, necrosis of pancreatic and peripancreatic tissue, and infection, often accompanied by multiple organ dysfunction syndrome. Preserving gut microbial homeostasis may reduce the systemic effects of AP. A growing body of evidence suggests the possible involvement of the gut microbiome in various pancreatic diseases, including AP. This review discusses the possible role of the gut microbiome in AP. It highlights AP treatment and supplementation with prebiotics, synbiotics, and probiotics to maintain gastrointestinal microbial balance and effectively reduce hospitalization, morbidity and mortality in an early phase. It also addresses novel therapeutic areas in the gut microbiome, personalized treatment, and provides a roadmap of human microbial contributions to AP that have potential clinical benefit.     

Abnormalities in motor cortical plasticity differentiate manifesting and nonmanifesting DYT1 carriers.

A mutation in the DYT1 gene causes dominantly inherited childhood-onset primary dystonia, but intriguingly, only 30 to 40% of those who carry the mutation ever develop symptoms. We have used the unique model provided by this group of patients to investigate the hypothesis that abnormalities in brain plasticity underlie the pathophysiology of primary dystonia. We recruited 8 DYT1 gene carriers with dystonia, 6 DYT1 gene carriers without dystonia, 6 patients with sporadic primary dystonia (torticollis), and 10 healthy control subjects. Groups were age-matched. We compared the effect in these groups of subjects of repetitive transcranial magnetic stimulation (rTMS) delivered to the motor cortex, by assessing changes in corticospinal excitability following rTMS. rTMS was given in the form of theta burst stimulation (TBS) using the inhibitory protocol "cTBS" (total of 300 pulses in 50-Hz bursts given every 5Hz). DYT1 gene carriers with dystonia and subjects with torticollis had a significantly prolonged response to rTMS in comparison with healthy subjects. In contrast, DYT1 gene carriers without dystonia had no significant response to rTMS. These data demonstrate an excessive response to an experimental "plasticity probing protocol" in subjects with dystonia, but a lack of response in genetically susceptible individuals who have not developed dystonia. These preliminary data suggest that the propensity to undergo plastic change may affect the development of symptoms in genetically susceptible individuals and that this may be an important mechanism in the pathogenesis of primary dystonia in general.     

A heterozygous effect for PINK1 mutations in Parkinson's disease?

OBJECTIVE: To investigate the significance of PINK1 mutations in sporadic Parkinson's disease (PD). METHODS: We determined the frequency of PINK1 mutations by direct sequencing in a large series of PD patients with apparently sporadic disease (n = 768). RESULTS: Twelve heterozygous mutations were identified, nine in PD patients and three in control subjects. INTERPRETATION: Given the difficulty in interpreting the pathogenic significance of the heterozygous mutations that have already been reported in parkin and DJ-1, we first determined the frequency of heterozygous PINK1 mutations in the general population by sequencing a large number of control subjects (n = 768), then subsequently assessed their functional significance by examining their effects on stress-induced alterations to the mitochondrial membrane potential (DeltaPsim). We demonstrate an enrichment of heterozygous mutations in sporadic PD patients compared with matched control subjects (1.2% in PD vs 0.4% in control subjects). Furthermore, we show that they adversely affect DeltaPsim in a similar way to the familial G309D mutation. Although it remains difficult to conclusively demonstrate the pathogenicity of heterozygous mutations, the results of this study and the previously reported subclinical nigrostriatal dysfunction in carriers of heterozygous PINK1 mutations suggest the possibility that these heterozygous mutations are a significant risk factor in the development of later onset PD.     

Patent Ductus Arteriosus Aneurysm: A Rare Cause of Dyspnea in an Adolescent Boy

We report a rare cause of dyspnea in an adolescent boy who presented with complaints of dyspnea on exertion since childhood without any cyanosis. Computed tomography angiography showed a large patent ductus arteriosus aneurysm that was seen compressing on the trachea and a left main bronchus with associated decreased left lung volume.     

Intravenous contrast enhanced computed tomography colonoscopy in children with suspected colonic polyps

Objective

The purpose of this study was to evaluate the diagnostic performance of intravenous contrast enhanced computed tomographic colonoscopy (IVCTC) in the diagnosis of clinically suspected colorectal polyps in children, using conventional colonoscopy (CC) as the gold standard.

Methods

This was a prospective study conducted between July 2008 and June 2010. 30 pediatric patients with history of rectal bleeding and clinically suspected to have colorectal polyps were enrolled. All of the patients underwent IVCTC followed by CC. 30 IVCTC and 31 CC were performed in 30 patients. The findings of IVCTC were compared with those of CC. Statistical analysis was performed to obtain diagnostic performance values of IVCTC on per polyp (sensitivity and positive predictive value) and per patient (sensitivity, specificity, positive predictive value and negative predictive value) basis.

Results

By IVCTC, 63 polyps were detected in 28 patients of which 53 polyps were eligible for inclusion in the statistical analysis. 60 polyps were detected by CC in 28 patients of which 50 polyps were eligible for inclusion in the statistical analysis. The per polyp sensitivity and positive predictive values were 94% and 88.6% respectively. The per patient sensitivity, specificity, positive predictive value, and negative predictive values were 96.4, 50, 96.4, and 50% respectively. Twenty polyps, in 10 patients, were visualized only after intravenous contrast administration of which 5 polyps, in 5 patients, were likely to have been missed in the absence of the intravenous contrast injection as these polyps were submerged in fluid. Four patients would have had a false negative CTC examination if the intravenous contrast had not been injected; while in another patient, the number of polyps would have been underestimated.

Conclusion

CTC is capable of serving as a safe and efficient non-invasive tool for evaluating children with clinically suspected colorectal polyps. Administration of intravenous contrast improves the sensitivity of polyp detection on CTC.     

Infant Deaths – Data Disparity and Use of Ante,Intra and Post-natal Services Utilization: An Experience from Tribal Areas of Gujarat

Background:

Infant death depends upon the care during the infancy and also upon the service utilization during antenatal and intra-natal periods and with its decline, it is necessary to find the under-reporting if any and identify the most appropriate agency for its reporting.

Objectives:

(1) To document disparities between different reporting systems about infant deaths and find out the under-reporting if any and identify the most appropriate agency and (2) To identify utilization of health services during ante, intra and post-natal period for all infant deaths.

Materials and Methods:

Study was conducted in 51 villages of 3 Primary Health Centers (PHCs) from a tribal dominated Taluka (block) of South Gujarat during September - November 2005. Information was gathered for 1 year (1 September 2004 to 31 August 2005) from 4 sources namely health care system, Integrated Child development services (ICDS) scheme, Civil Registration System (CRS) and Investigator himself (Gold standard). Data was collected in a designed verbal autopsy questionnaire by house to house survey and analyzed in Epi Info.

Results:

A total of 48 infant deaths were recorded by investigator against reported 2, 10 and 8 infant deaths by CRS, Health System and ICDS respectively. While profiling these 48 infant deaths it was found that only 29.2% mothers received full antenatal care (ANC) and 60.4% delivered at home (by untrained personnel). Not a single delivery was done at PHCs or its sub centers (SC). In 25% cases there was poor cord care. 39.6% mothers did not breastfeed and 35.4% gave pre-lacteal feeding.

Conclusions:

There was gross underreporting of infant mortality in all 3 agencies. The utilization of ANC and post natal care (PNC) services was poor in these death cases. Health system and ICDS need to be sensitized to work in coordination to provide quality ANC, INC and PNC to prevent such avoidable infant deaths.