Defining Metrics for Short Term Success After LVAD Implant: An Analysis of the Society of Thoracic Surgeons Intermacs Registry

Purpose: While clinical trials evaluating left ventricular assist device (LVAD) technology typically use composite outcomes to assess efficacy, composite outcomes including patient reported outcomes (PROs) have not been utilized as benchmarks for LVAD implant center performance improvement initiatives or quality ranking. The objective of the study was to assess the feasibility of generating a patient composite outcome measure including PROs from a real world registry. Methods: Short term (ST, 180 days) adverse events (AEs) and mortality were tallied for Intermacs patients undergoing LVAD implant between 1/2012 and 12/2019. ST postoperative events included mortality on first device and frequencies of stroke, reoperation (device malfunction/other), right heart failure (RHF), prolonged respiratory failure, and/or dialysis on first device. Logistic regression was used to generate odds ratios for mortality for each AE. Separately, the EuroQOL visual analog scale (VAS) was assessed at baseline and 180 days in ST survivors. Results: Of 20,115 patients, 37% suffered at least one event, most commonly death, reoperation and stroke (Table, column A). Stroke, prolonged respiratory failure, and dialysis attributed the most to ST mortality (Table, column B). Of the 16725 patients alive at 180 days, 43% completed a VAS with 82.0% showing VAS improvement. Renal failure and RHF contributed most to failure to improve VAS (Figure). Conclusion: Assessment of a ST composite outcome metric after LVAD implant from a real world data source is feasible but limited by incomplete PRO reporting. ST adverse events display differential effects on mortality and PROs that can be used in development of global rank outcome scores. While reoperation is common, stroke, prolonged respiratory failure and renal failure conferred highest risks of ST deaths within Intermacs. Assessment of PROs should become a priority for LVAD centers to allow the field to generate a complete assessment of patient-centered outcomes

Outcomes in patients with gunshot wounds to the brain.

Introduction:Gunshot wounds to the brain (GSWB) confer high lethality and uncertain recovery. It is unclear which patients benefit from aggressive resuscitation, and furthermore whether patients with GSWB undergoing cardiopulmonary resuscitation (CPR) have potential for survival or organ donation. Therefore, we sought to determine the rates of survival and organ donation, as well as identify factors associated with both outcomes in patients with GSWB undergoing CPR. Methods:We performed a retrospective, multicenter study at 25 US trauma centers including dates between June 1, 2011 and December 31, 2017. Patients were included if they suffered isolated GSWB and required CPR at a referring hospital, in the field, or in the trauma resuscitation room. Patients were excluded for significant torso or extremity injuries, or if pregnant. Binomial regression models were used to determine predictors of survival/organ donation. Results:825 patients met study criteria; the majority were male (87.6%) with a mean age of 36.5 years. Most (67%) underwent CPR in the field and 2.1% (n=17) survived to discharge. Of the non-survivors, 17.5% (n=141) were considered eligible donors, with a donation rate of 58.9% (n=83) in this group. Regression models found several predictors of survival. Hormone replacement was predictive of both survival and organ donation. Conclusion:We found that GSWB requiring CPR during trauma resuscitation was associated with a 2.1% survival rate and overall organ donation rate of 10.3%. Several factors appear to be favorably associated with survival, although predictions are uncertain due to the low number of survivors in this patient population. Hormone replacement was predictive of both survival and organ donation. These results are a starting point for determining appropriate treatment algorithms for this devastating clinical condition. Level of evidence:Level II

HRS/EHRA/APHRS/LAHRS/ACC/AHA worldwide practice update for telehealth and arrhythmia monitoring during and after a pandemic

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), started in the city of Wuhan late in 2019. Within a few months, the disease spread toward all parts of the world and was declared a pandemic on March 11, 2020. The current health care dilemma worldwide is how to sustain the capacity for quality services not only for those suffering from COVID-19 but also for non-COVID-19 patients, all while protecting physicians, nurses, and other allied health care workers

Crowd-sourced amputee gait data : a feasibility study using YouTube videos of unilateral trans-femoral gait

Collecting large datasets of amputee gait data is notoriously difficult. Additionally, collecting data on less prevalent amputations or on gait activities other than level walking and running on hard surfaces is rarely attempted. However, with the wealth of user-generated content on the Internet, the scope for collecting amputee gait data from alternative sources other than traditional gait labs is intriguing. Here we investigate the potential of YouTube videos to provide gait data on amputee walking. We use an example dataset of trans-femoral amputees level walking at self-selected speeds to collect temporal gait parameters and calculate gait asymmetry. We compare our YouTube data with typical literature values, and show that our methodology produces results that are highly comparable to data collected in a traditional manner. The similarity between the results of our novel methodology and literature values lends confidence to our technique. Nevertheless, clear challenges with the collection and interpretation of crowd-sourced gait data remain, including long term access to datasets, and a lack of validity and reliability studies in this area

ESNOQ, Proteomic Quantification of Endogenous S-Nitrosation

S-nitrosation is a post-translational protein modification and is one of the most important mechanisms of NO signaling. Endogenous S-nitrosothiol (SNO) quantification is a challenge for detailed functional studies. Here we developed an ESNOQ (Endogenous SNO Quantification) method which combines the stable isotope labeling by amino acids in cell culture (SILAC) technique with the detergent-free biotin-switch assay and LC-MS/MS. After confirming the accuracy of quantification in this method, we obtained an endogenous S-nitrosation proteome for LPS/IFN-γ induced RAW264.7 cells. 27 S-nitrosated protein targets were confirmed and using our method we were able to obtain quantitative information on the level of S-nitrosation on each modified Cys. With this quantitative information, over 15 more S-nitrosated targets were identified than in previous studies. Based on the quantification results, we found that the S-nitrosation levels of different cysteines varied within one protein, providing direct evidence for differences in the sensitivity of cysteine residues to reactive nitrosative stress and that S-nitrosation is a site-specific modification. Gene ontology clustering shows that S-nitrosation targets in the LPS/IFN-γ induced RAW264.7 cell model were functionally enriched in protein translation and glycolysis, suggesting that S-nitrosation may function by regulating multiple pathways. The ESNOQ method described here thus provides a solution for quantification of multiple endogenous S-nitrosation events, and makes it possible to elucidate the network of relationships between endogenous S-nitrosation targets involved in different cellular processes

Targeting of B and T lymphocyte associated (BTLA) prevents graft-versus-host disease without global immunosuppression

One-time treatment with an antibody against BTLA provides long-term protection against graft-versus-host disease without affecting effector T cell responses to tumors or pathogens

The -786T>C promoter polymorphism of the NOS3 gene is associated with prostate cancer progression

<p>Abstract</p> <p>Background</p> <p>There is no biological or epidemiological data on the association between <it>NOS3 </it>promoter polymorphisms and prostate cancer. The polymorphisms in the promoter region of <it>NOS3 </it>gene may be responsible for variations in the plasma NO, which may promote cancer progression by providing a selective growth advantage to tumor cells by angiogenic stimulus and by direct DNA damage.</p> <p>Methods</p> <p>This study aimed evaluating the <it>NOS3 </it>promoter polymorphisms by PCR-SSCP and sequencing, associating genotypes and haplotypes with <it>NOS3 </it>expression levels through semi-quantitative RT-PCR, and with <it>PCA</it>3 mRNA detection, a specific tumor biomarker, in the peripheral blood of pre-surgical samples from 177 patients; 83 PCa and 94 BPH.</p> <p>Results</p> <p>Three novel SNPs were identified -764A>G, -714G>T and -649G>A in the <it>NOS3 </it>gene promoter region, which together with the -786T>C generated four haplotypes (N, T, C, A). <it>NOS3 </it>gene expression levels were affected by the -786T>C polymorphism, and there was a 2-fold increase in <it>NOS3 </it>levels favored by the incorporation of each C allele. <it>NOS3 </it>levels higher than 80% of the constitutive gene expression level (<it>B2M</it>) presented a 4-fold increase in PCa occurrence.</p> <p>Conclusion</p> <p>The -786T>C polymorphism was the most important promoter alteration of the <it>NOS3 </it>gene that may affect the PCa progression, but not its occurrence, and the incorporation of the C allele is associated with increased levels of <it>NOS3 </it>transcripts. The <it>NOS3 </it>transcript levels presented a bimodal behavior in tumor development and may be used as a biomarker together with the <it>PCA3 </it>marker for molecular staging of the prostate cancer.</p

Higher fungal diversity is correlated with lower CO2 emissions from dead wood in a natural forest

Wood decomposition releases almost as much CO2 to the atmosphere as does fossil-fuel combustion, so the factors regulating wood decomposition can affect global carbon cycling. We used metabarcoding to estimate the fungal species diversities of naturally colonized decomposing wood in subtropical China and, for the first time, compared them to concurrent measures of CO2 emissions. Wood hosting more diverse fungal communities emitted less CO2, with Shannon diversity explaining 26 to 44% of emissions variation. Community analysis supports a ‘pure diversity’ effect of fungi on decomposition rates and thus suggests that interference competition is an underlying mechanism. Our findings extend the results of published experiments using low-diversity, laboratory-inoculated wood to a high-diversity, natural system. We hypothesize that high levels of saprotrophic fungal biodiversity could be providing globally important ecosystem services by maintaining dead-wood habitats and by slowing the atmospheric contribution of CO2 from the world’s stock of decomposing wood. However, large-scale surveys and controlled experimental tests in natural settings will be needed to test this hypothesis