tbuckley/cabot-search huggingface dataset:
PathoSPOT genomic epidemiology reveals under-the-radar nosocomial outbreaks
Authors: Ana Berbel Caban, Theodore R. Pak, Ajay Obla, Amy C. Dupper, Kieran I. Chacko, Lindsey Fox, Alexandra Mills, Brianne Ciferri, Irina Oussenko, Colleen Beckford, Marilyn Chung, Robert Sebra, Melissa Smith, Sarah Conolly, Gopi Patel, Andrew Kasarskis, Mitchell J. Sullivan, Deena R. Altman, Harm van Bakel
Journal: Genome Medicine (2020)

Abstract Background Whole-genome sequencing (WGS) is increasingly used to map the spread of bacterial and viral pathogens in nosocomial settings. A limiting factor for more widespread adoption of WGS for hospital infection prevention practices is the availability of standardized tools for genomic epidemiology. Methods We developed the Pathogen Sequencing Phylogenomic Outbreak Toolkit (PathoSPOT) to automate integration of genomic and medical record data for rapid detection and tracing of nosocomial outbreaks. To demonstrate its capabilities, we applied PathoSPOT to complete genome surveillance data of 197 MRSA bacteremia cases from two hospitals during a 2-year period. Results PathoSPOT identified 8 clonal clusters encompassing 33 patients (16.8% of cases), none of which had been recognized by standard practices. The largest cluster corresponded to a prolonged outbreak of a hospital-associated MRSA clone among 16 adults, spanning 9 wards over a period of 21 months. Analysis of precise timeline and location data with our toolkit suggested that an initial exposure event in a single ward led to infection and long-term colonization of multiple patients, followed by transmissions to other patients during recurrent hospitalizations. Conclusions We demonstrate that PathoSPOT genomic surveillance enables the detection of complex transmission chains that are not readily apparent from epidemiological data and that contribute significantly to morbidity and mortality, enabling more effective intervention strategies.
Eccentric Resistance Training Ameliorates Muscle Weakness in a Mouse Model of Idiopathic Inflammatory Myopathies
Authors: Koichi Himori, Yuki Ashida, Daisuke Tatebayashi, Masami Abe, Yuki Saito, Takako Chikenji, Håkan Westerblad, Daniel C. Andersson, Takashi Yamada
Journal: Arthritis & Rheumatology (2020)

High-force eccentric contractions (ECCs) have traditionally been excluded from rehabilitation programs that include patients with idiopathic inflammatory myopathies (IIMs) due to unverified fear of causing muscle damage and inflammation. In an IIM animal model that used mice with experimental autoimmune myositis (EAM), we undertook this study to investigate whether ECC training can safely and effectively be used to counteract muscle weakness in IIM.EAM was induced in BALB/c mice by immunization with 3 injections of myosin emulsified in Freund's complete adjuvant. Controls (n = 12) and mice with EAM (n = 12) were exposed to either an acute bout of 100 ECCs or 4 weeks of ECC training (20 ECCs every other day). To induce ECCs, plantar flexor muscles were electrically stimulated while the ankle was forcibly dorsiflexed.Less cell damage, as assessed by Evans blue dye uptake, was observed in the muscles of mice with EAM, compared to controls, after an acute bout of 100 ECCs (P < 0.05). Maximum Ca2+ -activated force was decreased in skinned gastrocnemius muscle fibers from mice with EAM, and this was accompanied by increased expression of endoplasmic reticulum (ER) stress proteins, including Gsp78 and Gsp94 (P < 0.05). ECC training prevented the decrease in force and the increase in ER stress proteins and also enhanced the expression and myofibrillar binding of small heat-shock proteins (HSPs) (P < 0.05), which can stabilize myofibrillar structure and function.ECC training protected against the reduction in myofibrillar force-generating capacity in an IIM mouse model, and this occurred via inhibition of ER stress responses and small HSP-mediated myofibrillar stabilization.
Does common cold coronavirus infection protect against severe SARS-CoV-2 disease?
Authors: David K. Meyerholz, Stanley Perlman
Journal: Journal of Clinical Investigation (2020)

The coronavirus disease 2019 (COVID-19) pandemic continues to cause morbidity and mortality. Since SARS coronavirus 2 (SARS-CoV-2) was identified as the cause for COVID-19, some have questioned whether exposure to seasonal common cold coronaviruses (CCCs) could provide tangible protection against SARS-CoV-2 infection or disease. In this issue of the JCI, Sagar et al. examined SARS-CoV-2 infections and outcomes of patients who had previously tested positive or negative for CCC infection (CCC+ or CCC–) by a comprehensive respiratory panel using PCR. No differences were seen between groups in terms of susceptibility to SARS-CoV-2 infection. However, hospitalized patients with a documented history of CCC infection had lower rates of intensive care unit (ICU) admissions and higher rates of survival than hospitalized CCC– patients. While these findings are associative and not causative, they highlight evidence suggesting that previous CCC infection may influence the disease course of SARS-CoV-2 infection.
Abstract 14495: Clinical Outcomes of Transcatheter Aortic Valve Replacement for De Novo Aortic Valve Insufficiency After Left Ventricular Assist Device Implantation
Authors: Yojiro Koda, Hidefumi Nishida, Ann Nguyen, Sara Kalantari, Bow Chung, Gene H Kim, Nitasha Sarswat, Bryan Smith, Jonathan Grinstein, David Onsager, Tae Song, Valluvan Jeevanandam, Takeyoshi Ota
Journal: Circulation (2020)

Objective: This study aimed to assess clinical outcomes of transcatheter aortic valve replacement (TAVR) for de novo aortic valve insufficiency (AI) after left ventricular assist device (LVAD) implantation. Methods: We defined de novo AI as a new-onset moderate AI or greater after the index LVAD implantation. Survival rate in patients with de novo AI was compared with ones without de novo AI, and clinical outcomes of TAVR in the patients with de novo AI were assessed. Results: Between 7.2008 - 1.2020, a total of 513 patients underwent LVAD implantation. Among them, 460 patients who had postoperative cardiac echography data available were included in this study. Sixty one patients (13%) developed de novo AI (dAI group) and 399 patients (87%) were not (non-dAI group). Overall survival in the dAI group was significantly lower than that in the non-dAI group (at 1 year: 54±7 vs. 73±2%, at 3 years: 30±8 vs. 51±3%,Log-Rank P=0.0004). In the dAI group, seven patients underwent TAVR for severe de novo AI of the native AVs. Calcification in the AVs measured by preoperative computed tomography (CT) was non-calcification in 4 patients, mild in 1 patient, and moderate in 2 patients. Based on measurements from CT, Valsalva sinus was 35 [32,36]mm (median[25%tile,75%tile]). All TAVR procedures were performed via a femoral artery approach. Sapien3 was implanted in 4 patients (23mm (N=1), 26mm (N=1), 29mm (N=2)). CoreValve was implanted in 3 patients (31mm (N=1), 31mmх2 (N=1), 34mm (N=1)). As an intraoperative complication, CoreValve migrated into the left ventricle in 1 patient. The degrees of postoperative residual AI were none or trace in 5 patients who were discharged in a good condition, and severe (perivalvular leakage (PVL)) in 2 patients who died during the admission. The 2 patients, who had severe postoperative PVL, did not have calcification in the AVs. Overall survival at 1 year in the 5 patients, who were discharged alive, was 100%, and freedom from moderate or greater AI was 100% at 6 months and 60% at 1 year. Conclusions: De novo AI negatively affected the survival rate in LVAD patients. TAVR treatment for de novo AI in LVAD patients might be a reasonable option. However, careful patient selection would be necessary.
Diacylglycerol kinase ζ limits IL-2-dependent control of PD-1 expression in tumor-infiltrating T lymphocytes
Authors: Javier Arranz-Nicolás, Miguel Martin-Salgado, Cristina Rodríguez-Rodríguez, Rosa Liébana, Maria C Moreno-Ortiz, Judith Leitner, Peter Steinberger, Antonia Ávila-Flores, Isabel Merida
Journal: Journal for ImmunoTherapy of Cancer (2020)

The inhibitory functions triggered by the programmed cell death-1 (PD-1) receptor following binding to its ligand (PD-L1) protect healthy organs from cytotoxic T cells, and neutralize antitumor T cell attack. Antibody-based therapies to block PD-1/PD-L1 interaction have yielded notable results, but most patients eventually develop resistance. This failure is attributed to CD8+ T cells achieving hyporesponsive states from which recovery is hardly feasible. Dysfunctional T cell phenotypes are favored by a sustained imbalance in the diacylglycerol (DAG)- and Ca2+-regulated transcriptional programs. In mice, DAG kinase ζ (DGKζ) facilitates DAG consumption, limiting T cell activation and cytotoxic T cell responses. DGKζ deficiency facilitates tumor rejection in mice without apparent adverse autoimmune effects. Despite its therapeutic potential, little is known about DGKζ function in human T cells, and no known inhibitors target this isoform. We used a human triple parameter reporter cell line to examine the consequences of DGKζ depletion on the transcriptional restriction imposed by PD-1 ligation. We studied the effect of DGKζ deficiency on PD-1 expression dynamics, as well as the impact of DGKζ absence on the in vivo growth of MC38 adenocarcinoma cells. We demonstrate that DGKζ depletion enhances DAG-regulated transcriptional programs, promoting interleukin-2 production and partially counteracting PD-1 inhibitory functions. DGKζ loss results in limited PD-1 expression and enhanced expansion of cytotoxic CD8+ T cell populations. This is observed even in immunosuppressive milieus, and correlates with the reduced ability of MC38 adenocarcinoma cells to form tumors in DGKζ-deficient mice. Our results, which define a role for DGKζ in the control of PD-1 expression, confirm DGKζ potential as a therapeutic target as well as a biomarker of CD8+ T cell dysfunctional states.
Consensus Statement for the Management and Treatment of Port-Wine Birthmarks in Sturge-Weber Syndrome
Authors: Sara Sabeti, Karen L. Ball, Craig Burkhart, Lawrence Eichenfield, Esteban Fernandez Faith, Ilona J. Frieden, Roy Geronemus, Deepti Gupta, Andrew C. Krakowski, Moise L. Levy, Denise Metry, J. Stuart Nelson, Megha M. Tollefson, Kristen M. Kelly
Journal: JAMA Dermatology (2020)

Sturge-Weber syndrome (SWS) is a neurocutaneous syndrome involving the skin, brain, and eyes. Consensus recommendations for management are lacking.
Use of Next Generation Sequencing and Single Nucleotide Polymorphism (SNP) Fingerprinting to Assess Post Transplant Engraftment Status
Authors: Abhinita S. Mohanty, Juan Camilo Gomez-Gelvez, Kseniya Petrova-Drus, Michael Zaidinski, Wei Wang, Jin Juan Yao, Caleb Ho, Ahmet Zehir, Maria E. Arcila
Journal: Blood (2017)
Abstract 339: Relationship Between Post-arrest Care Hemodynamics and Cerebral Oxygen Saturation in Comatose Survivors of Out-of-hospital Cardiac Arrest: Insights From the CAPITAL-RETURN Trial
Authors: Juan J Russo, Paul Boland, Simon Parlow, Jordan Bernick, Rebecca Mathew, Derek Y So, Benjamin M Hibbert, Christina Osborne, Sophie De Roock, Christopher Fordyce, Sean Van Diepen, Michel R Le May
Journal: Circulation (2020)

Introduction: Comatose survivors of OHCA develop a post cardiac arrest syndrome (PCAS) characterized by myocardial dysfunction and cerebrovascular dysregulation. Hemodynamic derangements related to PCAS can jeopardize cerebral oxygen delivery and therefore impair neurologic recovery. However, optimal hemodynamic targets to ensure adequate cerebral oxygen delivery following OHCA remain undefined. Accordingly, we examined the relationship between cardiac index (CI), mean arterial pressure (MAP), and regional cerebral oxygen saturation (rO 2 %) following OHCA. Methods: CAPITAL-RETURN was a prospective, single-center observational study examining hemodynamics in comatose survivors of OHCA undergoing targeted temperature management after an initial shockable rhythm. Between August 2016 and December 2017, comatose survivors of OHCA underwent continuous, blinded, non-invasive monitoring of CI and rO 2 % using bioimpedance (Cheetah Medical, Portland, OR, USA) and near-infrared spectroscopy (Covidien, Boulder, CO, USA), respectively, for 96 hours after intensive care unit admission. In the present study, we examined the relationship between CI, MAP, and rO 2 % using multivariable linear regression. Results: In 56 patients in this analysis, the mean CI and MAP during the first 96 hours of intensive care unit admission were 3.2±0.5 L/min/m 2 and 76±6 mmHg, respectively (Figure). The mean rO 2 % was 63±9% and increased over time (+0.1% per hour; p&lt;0.001). Higher CI was associated with improved rO 2 % (+3.2% per L/min/m2 increase in CI; p&lt;0.0001). There was no association between MAP and rO 2 % (p=0.42). After adjustment for MAP, the association between CI and rO 2 % remained significant (+3.1% per L/min/m2 increase in CI; p&lt;0.0001). Conclusion: In comatose survivors of OHCA with an initial shockable rhythm, a higher CI is associated with improved rO 2 %. Further studies are needed to determine whether CI targets improve rO2% and neurologic outcomes following OHCA.
Abstract 15861: The Role of Body Mass Index in Cryoballoon Ablation Outcomes for Paroxysmal Atrial Fibrillation
Authors: Abhishek Bose, Parag A Chevli, Zeba Hashmath, Ajay K Mishra, Gregory Berberian, ghasan ahmad, Jerzy Januszkiewicz, Qiying Dai, Douglas Laidlaw
Journal: Circulation (2020)

Introduction: Cryoballoon ablation (CBA) is recommended for patients with paroxysmal atrial fibrillation (AF) refractory to anti-arrhythmic drugs. However, only 70% of patients benefit from an initial CBA. Obesity is a known risk factor for development of AF but its role in predicting outcomes following CBA for paroxysmal AF remains unclear. Methods: We followed 103 patients (Age 60.6 ± 9.1, 29% women) with paroxysmal AF undergoing CBA for one year post procedure. Recurrence was assessed by documented atrial arrhythmias (AA) on EKG or any form of long-term cardiac rhythm monitoring. Using the body mass index (BMI) as a surrogate marker for obesity, we divided patients into five groups: normal &lt;24.9 kg/m 2 , overweight 25-29.9 kg/m 2 , class 1 obesity 30-34.9 kg/m 2 , class 2 obesity 35-39.9 kg/m 2 and class 3 obesity ≥40 kg/m 2 . A multivariable cox proportional hazard model was used to assess if BMI predicted risk of AA recurrence. Results: Among our study population, 7 (6.7%) had normal BMI and 34 were overweight (33%) while 17 (16.5%), 14 (13.5%) and 8 patients (7.7%) were categorized as class 1, 2 and 3 obesity respectively. After a one year follow up, 19 (18.4%) participants developed recurrence of AA. Baseline demographics were similar between the two groups except for a higher incidence of hypertension in the class 3 obesity group. On a multivariable model adjusted for baseline demographics and risk factors for AF, neither obesity nor overweight predicted recurrence of AA following CBA (Table, p=0.18). Similarly, on Kaplan-Meier analysis, BMI did not effect time to first recurrence of AA (Figure, p=0.07). Conclusion: Obesity is strongly associated with the risk of development of AF. However, in our study population increasing BMI had no influence on the recurrence of AA following CBA for paroxysmal AF.
Declining in-hospital mortality gap between systemic lupus erythematosus (SLE) and non-SLE hospitalisations: a national study
Authors: Jasvinder A Singh, John D Cleveland
Journal: Annals of the Rheumatic Diseases (2020)

Mortality in systemic lupus erythematosus (SLE) is twofold to threefold higher compared with the general population.1 Overall SLE mortality decreased over time,1 2 but in-hospital mortality has increased.3 We hypothesised an increase in in-hospital mortality rates in SLE and SLE–non-SLE mortality gap over time.

We included discharges from US National Inpatient Sample (NIS) from 1998 to 2014, the last year of the use of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). The NIS is a 20% stratified sample of hospital discharges. We identified primary SLE hospitalisations based on the presence of an ICD-9-CM code of 710.0x in the primary position; this diagnostic code has a sensitivity of 98% and specificity of 72%.4

We calculated the unadjusted, age-adjusted and age–sex-adjusted in-hospital mortality rates per 1000 primary SLE hospitalisations versus general non-SLE hospitalisations. We used the Cochran Armitage test to analyse mortality time trends.

The 241 130 primary SLE hospitalisations in 1998–2014 included predominantly black (34.3%), young (mean age, 36 years) and female (86.9%) patients. Deyo-Charlson Comorbidity Score was ≥2 for 47%; one-third were receiving Medicaid and 1.5% died in-hospital (table 1).

View this table:

Table 1 
Characteristics of hospitalisations in people with SLE in the USA from 1998 to 2014*



Unadjusted mortality in primary SLE hospitalisations wavered over time and decreased significantly from 17.9 per 1000 in 1998 to 9.5 in 2014, versus 28.1 per 1000 to 21.2 in non-SLE (45.2% vs 25.9% reduction; p<0.01 for both; figure 1); SLE hospitalisations occured in much younger people than non-SLE hospitalisations. Age, sex, race/ethnicity did not change over time, …
Abstract 16765: Sustained Total All-Region Perfusion During the Norwood Operation is Associated With Improved Post-Operative Recovery
Authors: James M Meza, Abigail Benkert, Neel Prabhu, Veerajalandhar Allareddy, Andrew McCrary, Nicholas D Andersen, Joseph W Turek
Journal: Circulation (2020)

Introduction: We developed a technique for Stage 1 “Norwood” reconstruction with continuous perfusion of the head, heart, and lower body at mild hypothermia, deemed Sustained Total All-Region (STAR) perfusion. Hypothesis: We hypothesized that STAR perfusion would shorten cardiopulmonary bypass and procedural times and expedite post-operative recovery, due to lack of cooling and re-warming and decreased total body ischemia. Methods: Between 2012-2019, 65 infants underwent Norwood reconstruction at our institution. Those who underwent prior pulmonary artery banding were excluded, yielding a cohort of 51 infants who underwent primary Norwood reconstruction. Outcomes for patients who underwent Norwood reconstruction using STAR perfusion (n=21) were compared to those who underwent Norwood reconstruction with conventional techniques using regional cerebral perfusion only (n=30). STAR perfusion was performed with innominate artery cannulation as well as olive tip cannulas inserted into the opened descending aorta and native aortic root to provide continuous perfusion of the head, heart, and lower body throughout the procedure (Figure), under mild hypothermia (32-34°C). Results: Norwood reconstruction with STAR perfusion was associated with shorter median CPB times vs. conventional perfusion techniques (161 vs. 226 mins,p&lt;0.0001) and elimination of myocardial ischemia (0 vs. 90 minutes cross-clamp time,p&lt;0.0001). Total operative time was reduced by over 3 hours (319 vs 514 mins,p&lt;0.0001), likely in part due to improved post-bypass coagulopathy. Improvements in post-operative recovery were noted with STAR perfusion, including more rapid normalization of serum lactate (19.3 vs. 26.5 hours, p=0.0009), lower peak serum lactate (8.6 vs.10 mmol/dL, p=0.04) and fewer days to chest closure (3 vs. 5 days, p=0.04). Survival to hospital discharge (95% vs 83%, p=0.38) was similar between groups. Conclusions: Norwood reconstruction with STAR perfusion is a safe technique that eliminates ischemic time to the heart and lower body and allows for the procedure to be performed at warmer temperatures. We found evidence of reduced CPB and operative times, as well as improved hemostasis, end-organ function, and post-operative recovery with this technique.
Abstract 15335: Hybrid Optical and CT Imaging Reveals Increased Matrix Metalloprotease Activity and Apoptosis Preceding Cardiac Failure in Progeroid Ercc1 Mice
Authors: Bibi S. van Thiel, Yanto Ridwan, Martine de Boer, Marion G.J. de Kleijnen, Nicole van Vliet, Paula M. van Heijningen, Wilbert P Vermeij, Jan H Danser, Roland Kanaar, Dirk J Duncker, Jan H.J. Hoeijmakers, Ingrid Van Der Pluijm, Jeroen Essers
Journal: Circulation (2019)

Background: Cardiovascular diseases are a leading cause of morbidity and mortality in the elderly population worldwide. Accumulation of unrepaired DNA damage over time is one of the driving forces ...
Genetically proxied interleukin-6 receptor inhibition: opposing associations with COVID-19 and pneumonia
Authors: Susanna C. Larsson, Stephen Burgess, Dipender Gill
Journal: European Respiratory Journal (2020)

<b>Respiratory disease is a main feature of severe COVID-19, and the potential of IL-6 receptor blockade to increase risk of pneumonia warrants vigilance and caution in its application to treat COVID-19</b>https://bit.ly/34Y8Ner
OP0097 Juvenile idiopathic arthritis (JIA) is associated with the D6S265 microsatellite polymorphisms on the high-risk DR8-DQ4 haplotype
Authors: A Smerdel, BA Lie, R Ploski, DE Undlien, B Flato, E Thorsby, O Forre
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Juvenile idiopathic arthritis (JIA) has been shown to be associated with at least four different alleles: HLA-A2, DR5 and DR6, and DP2. These associations are independent from each other, i.e. they are not caused by linkage disequilibrium between the markers. However, several studies have suggested that additional, unmapped, HLA-linked genes may participate in JIA. <h3>Objectives</h3> The purpose of this study was to look for additional genes involved in the susceptibility for JIA in the HLA complex using microsatellite polymorphisms. Since it is known that JIA is strongly associated with the DR8-DQ4 haplotype only DR8-DQ4 haplotype was included in the study, in order to exclude associations secondary to this high-risk haplotype. <h3>Methods</h3> We investigated 102, DRB1*08 positive, patients with JIA classified according to American Collage of Rheumatology criteria. As controls we selected 270, DRB1*08 positive, healthy individuals. We scanned 12 Mb of DNA covering the HLA complex using the following microsatellite polymorphisms, from centromeric to telomeric: D6S291, DQCar, D6S273, MIB, D6S265, D6S2223 and D6S2239. An EM algorythm was used to estimate haplotypes and only the distributions of microsatellite alleles on DR8-DQ4 haplotypes was compared between patients and controls. <h3>Results</h3> The microsatellite locus D6S265, which is located centromeric of HLA-A, showed a strong positive association with the disease for the *130 bp allele (OR = 30, p &lt; 1<sup>–6</sup>). In order to investigate whether this association could be explained by HLA-A2 the frequency of the HLA-A2 allele on DR8-DQ4-D6S265*130 haplotype was compared among patients and controls. However, the D6S265*130 allele still showed evidence for disease association (OR = 23, pp &lt; 1<sup>–5</sup>). <h3>Conclusion</h3> The observed association of D6S265*130 allele with JIA is not secondary to the association of this allele with the DR8-DQ4-A2 haplotype. It shows that D6S265*130 allele could be a marker for additional predisposing factor involved in JIA, and HLA-A2 cannot explain all associations to the JIA in HLA class I region.
Pain Severity and Management of Hidradenitis Suppurativa at US Emergency Department Visits
Authors: Matthew T. Taylor, Lauren A. V. Orenstein, John S. Barbieri
Journal: JAMA Dermatology (2020)

This repeated cross-sectional study compares pain severity and rates of prescriptions for opioids in emergency department visits for hidradenitis suppurative with those in visits for atopic dermatitis or psoriasis.