Multi-lead cephalic venous access and long-term performance of high-voltage leads.

BACKGROUND: Cardiac resynchronization therapy-defibrillator (CRT-D) implantation via the cephalic vein is feasible and safe. Recent evidence has suggested a higher implantable cardioverter-defibrillator (ICD) lead failure in multi-lead defibrillator therapy via the cephalic route. We evaluated the relationship between CRT-D implantation via the cephalic and ICD lead failure. METHODS: Data was collected from three CRT-D implanting centers between October 2008 and September 2017. In total 633 patients were included. Patient and lead characteristics with ICD lead failure were recorded. Comparison of "cephalic" (ICD lead via cephalic) versus "non-cephalic" (ICD lead via non-cephalic route) cohorts was performed. Kaplan-Meier survival and a Cox-regression analysis were applied to assess variables associated with lead failure. RESULTS: The cephalic and non-cephalic cohorts were equally male (81.9% vs. 78%; p = .26), similar in age (69.7 ± 11.5 vs. 68.7 ± 11.9; p = .33) and body mass index (BMI) (27.7 ± 5.1 vs. 27.1 ± 5.7; p = .33). Most ICD leads were implanted via the cephalic vein (73.5%) and patients had a mean of 2.9 ± 0.28 leads implanted via this route. The rate of ICD lead failure was low and statistically similar between both groups (0.36%/year vs. 0.13%/year; p = .12). Female gender was more common in the lead failure cohort than non-failure (55.6% vs. 17.9%, respectively; p = .004) as was hypertension (88.9% vs. 54.2%, respectively, p = .038). On multivariate Cox-regression, female sex (p = .008; HR, 7.12 [1.7-30.2]), and BMI (p = .047; HR, 1.12 [1.001-1.24]) were significantly associated with ICD lead failure. CONCLUSION: CRT-D implantation via the cephalic route is not significantly associated with premature ICD lead failure. Female gender and BMI are predictors of lead failure

Predictive value of S100-B and copeptin for outcomes following seizure: the BISTRO International Cohort Study.

OBJECTIVE: To evaluate the performance of S100-B protein and copeptin, in addition to clinical variables, in predicting outcomes of patients attending the emergency department (ED) following a seizure. METHODS: We prospectively included adult patients presented with an acute seizure, in four EDs in France and the United Kingdom. Participants were followed up for 28 days. The primary endpoint was a composite of seizure recurrence, all-cause mortality, hospitalization or rehospitalisation, or return visit in the ED within seven days. RESULTS: Among the 389 participants included in the analysis, 156 (40%) experienced the primary endpoint within seven days and 195 (54%) at 28 days. Mean levels of both S100-B (0.11 μg/l [95% CI 0.07-0.20] vs 0.09 μg/l [0.07-0.14]) and copeptin (23 pmol/l [9-104] vs 17 pmol/l [8-43]) were higher in participants meeting the primary endpoint. However, both biomarkers were poorly predictive of the primary outcome with a respective area under the receiving operator characteristic curve of 0.57 [0.51-0.64] and 0.59 [0.54-0.64]. Multivariable logistic regression analysis identified higher age (odds ratio [OR] 1.3 per decade [1.1-1.5]), provoked seizure (OR 4.93 [2.5-9.8]), complex partial seizure (OR 4.09 [1.8-9.1]) and first seizure (OR 1.83 [1.1-3.0]) as independent predictors of the primary outcome. A second regression analysis including the biomarkers showed no additional predictive benefit (S100-B OR 3.89 [0.80-18.9] copeptin OR 1 [1.00-1.00]). CONCLUSION: The plasma biomarkers S100-B and copeptin did not improve prediction of poor outcome following seizure. Higher age, a first seizure, a provoked seizure and a partial complex seizure are independently associated with adverse outcomes

Regression of devil facial tumour disease following immunotherapy in immunised Tasmanian devils

Devil facial tumour disease (DFTD) is a transmissible cancer devastating the Tasmanian devil (Sarcophilus harrisii) population. The cancer cell is the 'infectious' agent transmitted as an allograft by biting. Animals usually die within a few months with no evidence of antibody or immune cell responses against the DFTD allograft. This lack of anti-tumour immunity is attributed to an absence of cell surface major histocompatibility complex (MHC)-I molecule expression. While the endangerment of the devil population precludes experimentation on large experimental groups, those examined in our study indicated that immunisation and immunotherapy with DFTD cells expressing surface MHC-I corresponded with effective anti-tumour responses. Tumour engraftment did not occur in one of the five immunised Tasmanian devils, and regression followed therapy of experimentally induced DFTD tumours in three Tasmanian devils. Regression correlated with immune cell infiltration and antibody responses against DFTD cells. These data support the concept that immunisation of devils with DFTD cancer cells can successfully induce humoral responses against DFTD and trigger immune-mediated regression of established tumours. Our findings support the feasibility of a protective DFTD vaccine and ultimately the preservation of the species.Research support was provided by the Australian Research Council (ARC Linkage grant #LP0989727, ARC Discovery grant #DP130100715), University of Tasmania Foundation through funds raised by the Save the Tasmanian Devil Appeal. J.M.M. acknowledges fellowship support (APP1105754) and L.M.C. Program Grant funding (APP1054925) from NHMRC. J.M.M. and L.M.C. acknowledge NHMRC IRIISS (9000220) and Victorian Government Operational Infrastructure Support. Y.C. and K.B. are supported by the Australian Research Council (ARC Discovery grant #DP140103260). K.B. is funded by an ARC Future Fellowship. J.K. is supported by a Wellcome Trust programme Grant (089305)

Growth factors in multiple myeloma: a comprehensive analysis of their expression in tumor cells and bone marrow environment using Affymetrix microarrays

<p>Abstract</p> <p>Background</p> <p>Multiple myeloma (MM) is characterized by a strong dependence of the tumor cells on their microenvironment, which produces growth factors supporting survival and proliferation of myeloma cells (MMC). In the past few years, many myeloma growth factors (MGF) have been described in the literature. However, their relative importance and the nature of the cells producing MGF remain unidentified for many of them.</p> <p>Methods</p> <p>We have analysed the expression of 51 MGF and 36 MGF receptors (MGFR) using Affymetrix microarrays throughout normal plasma cell differentiation, in MMC and in cells from the bone marrow (BM) microenvironment (CD14, CD3, polymorphonuclear neutrophils, stromal cells and osteoclasts).</p> <p>Results</p> <p>4/51 MGF and 9/36 MGF-receptors genes were significantly overexpressed in plasmablasts (PPC) and BM plasma cell (BMPC) compared to B cells whereas 11 MGF and 11 MGFR genes were overexpressed in BMPC compared to PPC. 3 MGF genes (AREG, NRG3, Wnt5A) and none of the receptors were significantly overexpressed in MMC versus BMPC. Furthermore, 3/51 MGF genes were overexpressed in MMC compared to the the BM microenvironment whereas 22/51 MGF genes were overexpressed in one environment subpopulation compared to MMC.</p> <p>Conclusions</p> <p>Two major messages arise from this analysis 1) The majority of MGF genes is expressed by the bone marrow environment. 2) Several MGF and their receptors are overexpressed throughout normal plasma cell differentiation. This study provides an extensive and comparative analysis of MGF expression in plasma cell differentiation and in MM and gives new insights in the understanding of intercellular communication signals in MM.</p

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]