Percutaneous tricuspid valvotomy for pacemaker lead-induced tricuspid stenosis

AbstractPermanent pacemaker lead-induced tricuspid regurgitation is extremely uncommon. We report a patient with severe tricuspid stenosis detected 10 years after permanent single chamber pacemaker implantation in surgically corrected congenital heart disease. The loop at the level of the tricuspid valve may have caused endothelial injury and eventually led to stenosis. Percutaneous balloon valvotomy for such stenosis has not been reported from India

Changes in the source and transport mechanism of terrigenous input to the Indian sector of southern ocean during the late quaternary and its palaeoceanographic implications

Changes in the terrigenous sediment source and transport mechanisms during the late Quaternary have been investigated using four sediment cores within the Indian sector of Southern Ocean, using the magnetic susceptibility (MS) and sedimentological records. Sediments deposited during the Holocene and other interglacial periods were characterised by low MS, low sand content, reduced ice-rafted detritus (IRD) input and increased illite possibly transported via hydrographic advection from the south. The glacial intervals are characterised by high MS, high sand content, increased IRD input and reduced illite clays, derived from both local as well as Antarctic sources. Significant reduction in clay fraction and illite content during glacials suggests that the erosive and transporting capabilities of the deep and bottom waters could have reduced compared to the interglacial times. The changes in terrigenous influx to this region were significantly influenced by the rhythmic glacial–interglacial fluctuations in bottom circulation and the position of the Polar Front

Reversal of gastrointestinal carcinoma-induced immunosuppression and induction of antitumoural immunity by a combination of cyclophosphamide and gene transfer of IL-12

Immunotherapy-based strategies for gastrointestinal carcinomas (GIC) have been exploited so far, but these approaches have to face strong mechanisms of immune escape induced by tumours. We previously demonstrated that sub-therapeutic doses of an adenovirus expressing IL-12 genes (AdIL-12) mediated a potent antitumour effect against subcutaneous (s.c.) colorectal carcinomas (CRC) in mice pre-treated with low doses of cyclophosphamide (Cy). In our study we used this combination to assess its impact on the immunosuppressive microenvironment. In s.c. CRC model we demonstrated that non-responder mice failed to decrease Tregs in tumour, spleen and peripheral blood. Reconstitution of Tregs into tumour-bearing mice treated with combined therapy abolished the antitumoural effect. In addition, Cy + AdIL-12 modified Tregs functionality by inhibiting the in vitro secretion of IL-10 and TGF-β and their ability to inhibit dendritic cells activation. Combined treatment decreased the number of myeloid-derived suppressor cells (MDSCs) in comparison to non-treated mice and, interestingly, administration of Tregs restored splenic MDSCs population. Furthermore, combined therapy potently generated specific cytotoxic IFN-γ-secreting CD4+ T cells able to eradicate established CRC tumours after adoptive transfer. Finally, we evaluated the combination on disseminated CRC and pancreatic carcinoma (PC). Cy + AdIL-12 were able to eradicate liver metastatic CRC (47%) and PC tumour nodules (40%) and to prolong animal survival. The results of this study support the hypothesis that Cy + AdIL-12 might be a valid immunotherapeutic strategy for advanced GIC.Fil: Malvicini, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Ingolotti, Mariana. Universidad Austral; ArgentinaFil: Piccioni, Flavia Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: García, Mariana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Bayo Fina, Juan Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Atorrasagasti, María Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Aquino, Jorge Benjamin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Espinoza, Jaime A.. Universidad Adolfo Ibañez; Chile. Universidad de La Frontera; ChileFil: Gidekel, Manuel. Universidad Adolfo Ibañez; ChileFil: Scharovsky, Olga Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Matar, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Mazzolini Rizzo, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentin

A cluster randomized, controlled trial of breast and cervix cancer screening in Mumbai, India: methodology and interim results after three rounds of screening

Cervix and Breast cancers are the most common cancers among women worldwide and extract a large toll in developing countries. In May 1998, supported by a grant from the NCI (US), the Tata Memorial Hospital, Mumbai, India, started a cluster-randomized, controlled, screening-trial for cervix and breast cancer using trained primary health workers to provide health-education, visual-inspection of cervix (with 4% acetic acid-VIA) and clinical breast examination (CBE) in the screening arm, and only health education in the control arm. Four rounds of screening at 2-year intervals will be followed by 8 years of monitoring for incidence and mortality from cervix and breast cancers. The methodology and interim results after three rounds of screening are presented here. Good randomization was achieved between the screening (n = 75360) and control arms (n = 76178). In the screening arm we see: High screening participation rates; Low attrition; Good compliance to diagnostic confirmation; Significant downstaging; Excellent treatment completion rate; Improving case fatality ratios. The ever-screened and never-screened participants in the screening arm show significant differences with reference to the variables religion, language, age, education, occupation, income and health-seeking behavior for gynecological and breast-related complaints. During the same period, in the control arm we see excellent participation rate for health education; Low attrition and a good number of symptomatic referrals for both cervix and breast

Estimation of reactive inorganic iodine fluxes in the Indian and Southern Ocean marine boundary layer

Iodine chemistry has noteworthy impacts on the oxidising capacity of the marine boundary layer (MBL) through the depletion of ozone (O3) and changes to HOx (OH=HO2) and NOx (NO=NO2) ratios. Hitherto, studies have shown that the reaction of atmospheric O3 with surface seawater iodide (I-) contributes to the flux of iodine species into the MBL mainly as hypoiodous acid (HOI) and molecular iodine (I2). Here, we present the first concomitant observations of iodine oxide (IO), O3 in the gas phase, and sea surface iodide concentrations. The results from three field campaigns in the Indian Ocean and the Southern Ocean during 2015 2017 are used to compute reactive iodine fluxes in the MBL. Observations of atmospheric IO by multi-axis differential optical absorption spectroscopy (MAX-DOAS) show active iodine chemistry in this environment, with IO values up to 1 pptv (parts per trillion by volume) below latitudes of 40° S. In order to compute the sea-to-air iodine flux supporting this chemistry, we compare previously established global sea surface iodide parameterisations with new regionspecific parameterisations based on the new iodide observations. This study shows that regional changes in salinity and sea surface temperature play a role in surface seawater iodide estimation. Sea air fluxes of HOI and I2, calculated from the atmospheric ozone and seawater iodide concentrations (observed and predicted), failed to adequately explain the detected IO in this region. This discrepancy highlights the need to measure direct fluxes of inorganic and organic iodine species in the marine environment. Amongst other potential drivers of reactive iodine chemistry investigated, chlorophyll a showed a significant correlation with atmospheric IO (R D 0:7 above the 99 % significance level) to the north of the polar front. This correlation might be indicative of a biogenic control on iodine sources in this region

Extrahepatic Anomalies in Infants With Biliary Atresia: Results of a Large Prospective North American Multicenter Study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100275/1/hep26512.pd

Total Serum Bilirubin within 3 Months of Hepatoportoenterostomy Predicts Short-Term Outcomes in Biliary Atresia

OBJECTIVES: To prospectively assess the value of serum total bilirubin (TB) within 3 months of hepatoportoenterostomy (HPE) in infants with biliary atresia as a biomarker predictive of clinical sequelae of liver disease in the first 2 years of life. STUDY DESIGN: Infants with biliary atresia undergoing HPE between June 2004 and January 2011 were enrolled in a prospective, multicenter study. Complications were monitored until 2 years of age or the earliest of liver transplantation (LT), death, or study withdrawal. TB below 2 mg/dL (34.2 μM) at any time in the first 3 months (TB <2.0, all others TB ≥ 2) after HPE was examined as a biomarker, using Kaplan-Meier survival and logistic regression. RESULTS: Fifty percent (68/137) of infants had TB < 2.0 in the first 3 months after HPE. Transplant-free survival at 2 years was significantly higher in the TB < 2.0 group vs TB ≥ 2 (86% vs 20%, P < .0001). Infants with TB ≥ 2 had diminished weight gain (P < .0001), greater probability of developing ascites (OR 6.4, 95% CI 2.9-14.1, P < .0001), hypoalbuminemia (OR 7.6, 95% CI 3.2-17.7, P < .0001), coagulopathy (OR 10.8, 95% CI 3.1-38.2, P = .0002), LT (OR 12.4, 95% CI 5.3-28.7, P < .0001), or LT or death (OR 16.8, 95% CI 7.2-39.2, P < .0001). CONCLUSIONS: Infants whose TB does not fall below 2.0 mg/dL within 3 months of HPE were at high risk for early disease progression, suggesting they should be considered for LT in a timely fashion. Interventions increasing the likelihood of achieving TB <2.0 mg/dL within 3 months of HPE may enhance early outcomes

The GYMSSA trial: a prospective randomized trial comparing gastrectomy, metastasectomy plus systemic therapy versus systemic therapy alone

<p>Abstract</p> <p>Background</p> <p>The standard of care for metastatic gastric cancer (MGC) is systemic chemotherapy which leads to a median survival of 6-15 months. Survival beyond 3 years is rare. For selected groups of patients with limited MGC, retrospective studies have shown improved overall survival following gastrectomy and metastasectomies including peritoneal stripping with continuous hyperthermic peritoneal perfusion (CHPP), liver resection, and pulmonary resection. Median survival after liver resection for MGC is up to 34 months, with a five year survival rate of 24.5%. Similarly, reported median survival after pulmonary resection of MGC is 21 months with long term survival of greater than 5 years a possibility. Several case reports and small studies have documented evidence of long-term survival in select individuals who undergo CHPP for MGC.</p> <p>Design</p> <p>The GYMSSA trial is a prospective randomized trial for patients with MGC. It is designed to compare two therapeutic approaches: gastrectomy with metastasectomy plus systemic chemotherapy (GYMS) versus systemic chemotherapy alone (SA). Systemic therapy will be composed of the FOLFOXIRI regimen. The aim of the study is to evaluate overall survival and potential selection criteria to determine those patients who may benefit from surgery plus systemic therapy. The study will be conducted by the Surgery Branch at the National Cancer Institute (NCI), National Institutes of Health (NIH) in Bethesda, Maryland. Surgeries and followup will be done at the NCI, and chemotherapy will be given by either the local oncologist or the medical oncology branch at NCI.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov ID. NCT00941655</p

Human breast cancer-derived soluble factors facilitate CCL19-induced chemotaxis of human dendritic cells

Breast cancer remains as a challenging disease with high mortality in women. Increasing evidence points the importance of understanding a crosstalk between breast cancers and immune cells, but little is known about the effect of breast cancer-derived factors on the migratory properties of dendritic cells (DCs) and their consequent capability in inducing T cell immune responses. Utilizing a unique 3D microfluidic device, we here showed that breast cancers (MCF-7, MDA-MB-231, MDA-MB-436 and SK-BR-3)-derived soluble factors increase the migration of DCs toward CCL19. The enhanced migration of DCs was mainly mediated via the highly activated JNK/c-Jun signaling pathway, increasing their directional persistence, while the velocity of DCs was not influenced, particularly when they were co-cultured with triple negative breast cancer cells (TNBCs or MDA-MB-231 and MDA-MB-436). The DCs up-regulated inflammatory cytokines IL-1?? and IL-6 and induced T cells more proliferative and resistant against activation-induced cell death (AICD), which secret high levels of inflammatory cytokines IL-1??, IL-6 and IFN-??. This study demonstrated new possible evasion strategy of TNBCs utilizing their soluble factors that exploit the directionality of DCs toward chemokine responses, leading to the building of inflammatory milieu which may support their own growth.ope