tbuckley/cabot-search huggingface dataset:
Hypoplastic Left Heart Stage I
Authors: Dietmar Schranz, Anoosh Esmaeili, Roland Schrewe, Gunter Kerst, Hakan Akintuerk
Journal: Circulation (2020)

Endoluminal pulmonary banding and duct stenting are the basis for nonsurgical, transcatheter stage I in newborns with hypoplastic left heart syndrome (HLHS).We report a novel, nonsurgical palliation for newborns with HLHS and variants. 1 The aim of our transcatheter approach is to replace the Norwood and open-chest hybrid procedures, 2 as well as complex neonatal biventricular repairs, to enable comprehensive stage II or biventricular repair with a lower overall risk by postponing surgeries to later infancy.Following institutional guidelines, this compassionate percutaneous transcatheter approach was performed with written parental consent and was approved by our ethics committee.Spontaneously breathing, sedated newborns received an endoluminal pulmonary artery (PA) branch banding with US Food and Drug Administration-approved, CE-marked Medtronic Micro Vascular Plug (MVP) devices, manually modified to a pulmonary flow restrictor (PFR), as previously described. 3After bilateral PFR placement, the arterial duct was stented, as is routine in the Giessen hybrid approach. 4Briefly, after local anesthesia, the femoral vein and artery were punctured, and 4F sheaths were placed.Heparin was administered intravenously in a single dose of 100 U/kg, followed by 50 U/kg after placement of PFRs.On the basis of angiographically determined diameters of the left and right PAs, custom-made MVPs were chosen: MVP-5Q for a vessel size up to 5 mm, 7Q for up to 7 mm, and 9Q for up to 9 mm.Cineangiograms were performed in 20° to 25° cranial and 25° to 30° left oblique or 25° to 30° right oblique planes.Contrast medium was injected manually through a 4F Terumo Cobra shaped catheter positioned within pulmonary branches.The same diagnostic catheter was used for PFR placement.The thin polytetrafluoroethylenecovered, nitinol-framed, self-expandable MVPs were manually converted from a plug device to a flow restrictor.Considering that the MVP-5Q consists of 7 and the 7Q and 9Q consist of 10 covered segments, the covering of 1 or 2 segments was carefully removed by scalpel, generating perforations of ≈3 to 4.5 mm (Figure).After loading of the modified MVP within the Cobra 4F (0.038-in) catheter, the PFRs were placed within the PA branches under fluoroscopy guidance.After bilateral PFR placement, the arterial duct was stented with a Formula balloonexpandable stent (COOK, Copenhagen, Denmark) for treating a narrowed duct and a self-expandable Sinus-Superflex-DS stent (OptiMed, Karlsruhe, Germany) for stenting a wide-open arterial duct.Follow-up drug treatment consisted of continuous infusion of heparin (400 U•kg -1 •d -1 ) for 2 days, followed by oral clopidogrel (0.2 mg•kg -1 •d -1 ) and acetylsalicylic acid (1-2 mg•kg -1 •d -1 ) together with low-dose bisoprolol/lisinopril/ spironolactone.
Genomic Risk Score impact on susceptibility to systemic sclerosis
Authors: Lara Bossini-Castillo, Gonzalo Villanueva-Martin, Martin Kerick, Marialbert Acosta-Herrera, Elena López-Isac, Carmen P Simeón, Norberto Ortego-Centeno, Shervin Assassi, Nicolas Hunzelmann, Armando Gabrielli, J K de Vries-Bouwstra, Yannick Allanore, Carmen Fonseca, Christopher P Denton, Timothy RDJ Radstake, Marta Eugenia Alarcón-Riquelme, Lorenzo Beretta, Maureen D Mayes, Javier Martin
Journal: Annals of the Rheumatic Diseases (2020)

Genomic Risk Scores (GRS) successfully demonstrated the ability of genetics to identify those individuals at high risk for complex traits including immune-mediated inflammatory diseases (IMIDs). We aimed to test the performance of GRS in the prediction of risk for systemic sclerosis (SSc) for the first time.Allelic effects were obtained from the largest SSc Genome-Wide Association Study (GWAS) to date (9 095 SSc and 17 584 healthy controls with European ancestry). The best-fitting GRS was identified under the additive model in an independent cohort that comprised 400 patients with SSc and 571 controls. Additionally, GRS for clinical subtypes (limited cutaneous SSc and diffuse cutaneous SSc) and serological subtypes (anti-topoisomerase positive (ATA+) and anti-centromere positive (ACA+)) were generated. We combined the estimated GRS with demographic and immunological parameters in a multivariate generalised linear model.The best-fitting SSc GRS included 33 single nucleotide polymorphisms (SNPs) and discriminated between patients with SSc and controls (area under the receiver operating characteristic (ROC) curve (AUC)=0.673). Moreover, the GRS differentiated between SSc and other IMIDs, such as rheumatoid arthritis and Sjögren's syndrome. Finally, the combination of GRS with age and immune cell counts significantly increased the performance of the model (AUC=0.787). While the SSc GRS was not able to discriminate between ATA+ and ACA+ patients (AUC<0.5), the serological subtype GRS, which was based on the allelic effects observed for the comparison between ACA+ and ATA+ patients, reached an AUC=0.693.GRS was successfully implemented in SSc. The model discriminated between patients with SSc and controls or other IMIDs, confirming the potential of GRS to support early and differential diagnosis for SSc.
Clinical Outcome–Related Mutational Signatures Identified by Integrative Genomic Analysis in Nasopharyngeal Carcinoma
Authors: Wei Dai, Dittman Lai-Shun Chung, Larry Ka-Yue Chow, Valen Zhuoyou Yu, Lisa Chan Lei, Merrin Man-Long Leong, Candy King-Chi Chan, Josephine Mun-Yee Ko, Maria Li Lung
Journal: Clinical Cancer Research (2020)

Investigation of biological mechanisms underlying genetic alterations in cancer can assist the understanding of etiology and identify the potential prognostic biomarkers.We performed an integrative genomic analysis for a total of 731 nasopharyngeal carcinoma cases from five independent nasopharyngeal carcinoma cohorts to identify the genetic events associated with clinical outcomes.In addition to the known mutational signatures associated with aging, APOBEC and mismatch repair (MMR), a new signature for homologous recombination deficiency (BRCAness) was discovered in 64 of 216 (29.6%) cases in the discovery set including three cohorts. This signature appeared more frequently in the recurrent and metastatic tumors and significantly correlated with shorter overall survival (OS) in the primary tumors. Independent prognostic value of MMR and BRCAness signatures was revealed by multivariable Cox analysis after adjustment for clinical parameters and stratification by studies. The cases with both signatures had much worse clinical outcome than those without these signatures [hazard ratio (HR), 12.4; P = 0.002]. This correlation was confirmed in the validation set (HR, 8.9; P = 0.003). The BRCAness signature is highly associated with BRCA2 pathogenic germline or somatic alterations (7.8% vs. 0%; P = 0.002). Targeted sequencing results from a prospective nasopharyngeal carcinoma cohort (N = 402) showed that the cases carrying BRCA2 germline rare variants are more likely to have poor OS and progression-free survival.Our study highlights importance of defects of DNA repair machinery in nasopharyngeal carcinoma pathogenesis and their prognostic values for clinical implications. These signatures will be useful for patient stratification to evaluate conventional and new treatment for precision medicine in nasopharyngeal carcinoma.
THE GUILLAIN-BARRÉ SYNDROME
Authors: Lalitha Sivaswamy
Journal: JAMA (1966)

Key Points Guillain-Barré syndrome (GBS) is a group of acquired, immune-mediated conditions affecting peripheral nerves and nerve roots.Guillain-Barré syndrome is the most common cause of acute flaccid paralysis in childhood.The most common age-group affected by GBS is 4 through 8 years.One-half to two-thirds of cases manifest as a postinfectious illness 1 to 3 weeks after infection.Most evidence linking GBS to vaccines is temporal and causality has not been established clearly.Diagnosis is primarily based on a constellation of typical symptoms, neurologic signs, and paraclinical findings with exclusion of relevant differential.Laboratory and electrophysiological testing are important to establish diagnosis.Consensus on the basis of case series and retrospective analysis indicates that intravenous immunoglobulin can reduce duration of hospitalization and time to ambulation.
Abstract IA09: Tumor cell oxidative metabolism as a barrier to antitumor immunity in melanoma
Authors: Greg M. Delgoffe
Journal: Cancer Research (2020)

Abstract The treatment of melanoma has been fundamentally changed by immunotherapies like blockade of coinhibitory “checkpoint” molecules like CTLA-4 and PD-1. However, despite these remarkable successes, even within T cell-inflamed, high-mutational-burden tumors, response rates remain low, likely due to additional immune inhibitory mechanisms present in the tumor microenvironment. It is now generally appreciated that the tumor microenvironment is characterized by a distinct metabolic landscape, having low oxygen tension, depleted levels of essential nutrients, and buildup of toxic byproducts. We sought to determine whether this metabolic landscape was variable from patient to patient and how this landscape affected antitumor immunity and thus response to immunotherapy. Using extracellular metabolic flux analysis, we profiled the metabolic derangement of patient-derived cell lines as well as direct ex vivo patient tumor samples, revealing striking heterogeneity not only in the degree of metabolic derangement but also in the type of metabolism a tumor cell was dependent on. Analysis of the tumor infiltrate revealed that a tumor’s preference for oxidative metabolism was associated with immune dysfunction, suggesting that the ability to generate hypoxic regions in vivo is a key aspect of immune resistance. We confirmed this finding in vivo using a novel model of melanoma in which individual metabolic pathways can be selectively targeted in a single-cell derived line: loss of oxidative metabolism in tumor cells sensitizes animals to PD-1 blockade immunotherapy, while loss of glycolytic metabolism has no appreciable effect on antitumor immunity. Analysis of melanoma patient biopsy samples prior to initiation of immunotherapy revealed that increased tumor oxidative metabolism and intratumoral hypoxia was associated with poorer responses to checkpoint blockade. Our data highlight the use of tumor microenvironment hypoxia as a potential predictor of immunotherapy resistance and shed light on the use of modulators of tumor cell oxidation as a means to improve responses to checkpoint blockade. Citation Format: Greg M. Delgoffe. Tumor cell oxidative metabolism as a barrier to antitumor immunity in melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr IA09.
Cancer metastasis linked to macrophage size, shape, and metabolism
Authors: Peter J. Murray
Journal: The Journal of Experimental Medicine (2020)

Using macrophage morphology in human colorectal cancer liver metastasis, Donadon et al. in this issue of JEM (https://doi.org/10.1084/jem.20191847) provide a window into lipid metabolism and foamy macrophages, which accrue in numerous pathological states and here are shown to have clinical application.
CD47/SIRPα blocking peptide identification and synergistic effect with irradiation for cancer immunotherapy
Authors: Hongfei Wang, Yixuan Sun, Xiuman Zhou, Chunxia Chen, Ling Jiao, Wanqiong Li, Shanshan Gou, Yanying Li, Jiangfeng Du, Guanyu Chen, Wenjie Zhai, Yahong Wu, Yuanming Qi, Yanfeng Gao
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Immunotherapy has achieved remarkable advances via a variety of strategies against tumor cells that evade immune surveillance. As important innate immune cells, macrophages play important roles in maintaining homeostasis, preventing pathogen invasion, resisting tumor cells and promoting adaptive immune response. CD47 is found to be overexpressed on tumor cells and act as a don’t eat me’ signal, which contributes to immune evasion. Macrophages mediated phagocytosis via blockade CD47/SIRPα (signal regulatory protein alpha) interaction was proved to induce effective antitumor immune response. Methods A novel peptide pep-20, specifically targeting CD47 and blocking CD47/SIRPα interaction, was identified via high-throughput phage display library bio-panning. The capability to enhance the macrophage-mediated phagocytosis activities and antitumor effects of pep-20 were investigated. The mechanism of pep-20 to induce T-cell response was explored by ex vivo analysis and confirmed via macrophage depleting strategy. The structure-activity relationship and D-amino acid substitution of pep-20 were also studied. The antitumor effects and mechanism of a proteolysis resistant D-amino acid derivate pep-20-D12 combined with irradiation (IR) were also investigated. Results Pep-20 showed remarkable enhancement of macrophage-mediated phagocytosis to both solid and hematologic tumor cells in vitro, and inhibited tumor growth in immune-competent tumor-bearing mice. Furthermore, pep-20 promoted macrophages to mobilize the antitumor T-cell response with minimal toxicity. Furthermore, systemic administration of the derivate pep-20-D12 showed robust synergistic antitumor efficacy in combination with IR. Conclusion In summary, these results demonstrated that CD47/SIRPα blocking peptides, pep-20 and its derivate, could serve as promising candidates to promote macrophages-mediated phagocytosis and immune response in cancer immunotherapy.
Response by Siedlinski et al to Letters Regarding Article, “White Blood Cells and Blood Pressure: A Mendelian Randomization Study”
Authors: Mateusz Siedlinski, Michael V. Holmes, Tomasz J. Guzik
Journal: Circulation (2020)

between lymphocyte count and coronary heart disease 5 in more detail (ie, with use of BP as a potential mediator).This would address a question of great relevance and further characterize a network of causal relationships between the above traits and vascular disease.
Association of Early-Life Mental Health With Biomarkers in Midlife and Premature Mortality
Authors: George B. Ploubidis, G. David Batty, Praveetha Patalay, David Bann, Alissa Goodman
Journal: JAMA Psychiatry (2020)

Early-life mental health is known to be associated with socioeconomic adversity and psychological distress in adulthood, but less is known about potential associations with biomarkers and mortality.To investigate the association between early-life mental health trajectories with biomarkers in midlife and premature mortality.This study used data from the British National Child Development Study, a population-based birth cohort. The initial sample of 17 415 individuals consisted of all infants born in Great Britain in a single week in 1958. Analysis began Feburary 2017 and ended May 2020.Biomarkers collected at age 44 to 45 years were fibrinogen, C-reactive protein, glycated hemoglobin, high- and low-density lipoprotein cholesterol, forced expiratory volume, blood pressure, and waist-to-hip ratio. Information on all-cause mortality was available up to age 58 years and cause-specific mortality up to age 50 years.Biomarkers were analyzed from 9377 participants (age, 44-45 years, 4712 female [50.3%]) and mortality data from 15 067 participants (age, 58 years; 7379 female [49.0%]). A 4-group longitudinal typology of early-life conduct problems and affective symptoms was identified: (1) stable low, (2) teacher-identified adolescent onset, (3) moderate, and (4) stable high. Compared with the stable-low group, the stable-high (B, 2.308; 95% CI, 0.213-4.404) and teacher-identified adolescent-onset (B, 2.114; 95% CI, 0.725-3.503) groups had less favorable levels of fibrinogen in middle age. Effect modification was observed by sex (P < .005) such that compared with the stable-low group, differences in high-density lipoprotein and abdominal obesity were only observed in female individuals. The stable-high and teacher-identified adolescent-onset groups had elevated risk for all-cause mortality (hazard ratio, 1.878; 95% CI, 1.501-2.350 and hazard ratio, 1.412; 95% CI, 1.174-1.698). Psychopathology-associated mortality was higher in both groups but unintentional injuries-associated mortality only in the stable-high group.Experiencing affective symptoms and conduct problems in childhood and adolescence is associated with less favorable levels of biomarkers 28 years later and elevated risk of premature mortality. These findings, if causal and generalizable to younger cohorts, may imply that effective interventions on early-life mental health have the potential to shift the distribution of risk and improve population health.
The in-hospital burden of dermatomyositis on patients with acute myocardial infarction: A nationwide cross-sectional analysis from 2004 to 2015
Authors: Alvaro J Ramos-Rodriguez, Karina J Cancel-Artau, Alejandro Lemor, Osward Y Carrasquillo, Mario Lozano-Franco, Marely Santiago-Vazquez, Julian Barrera-Llaurador, Rafael F Martin-Garcia
Journal: Journal of the American Academy of Dermatology (2020)
Role of serum biomarkers in cancer patients receiving cardiotoxic cancer therapies: a position statement from the <scp>Cardio‐Oncology Study Group</scp> of the <scp>Heart Failure Association</scp> and the <scp>Cardio‐Oncology Council of the European Society of Cardiology</scp>
Authors: Radek Pudil, Christian Mueller, Jelena Čelutkienė, Peter A. Henriksen, Dan Lenihan, Susan Dent, Ana Barac, Susanna Stanway, Javid Moslehi, Thomas M. Suter, Bonnie Ky, Martin Štěrba, Daniela Cardinale, Alain Cohen‐Solal, Carlo Gabriele Tocchetti, Dimitrios Farmakis, Jutta Bergler‐Klein, Markus S. Anker, Stephan Von Haehling, Yury Belenkov, Zaza Iakobishvili, Christoph Maack, Fortunato Ciardiello, Frank Ruschitzka, Andrew J.S. Coats, Petar Seferovic, Mitja Lainscak, Massimo F. Piepoli, Ovidiu Chioncel, Jereon Bax, Jean‐Sebastien Hulot, Hadi Skouri, Eva Simona Hägler‐Laube, Riccardo Asteggiano, Teresa Lopez Fernandez, Rudolf A. de Boer, Alexander R. Lyon
Journal: European Journal of Heart Failure (2020)
Association of Bioprosthetic Aortic Valve Leaflet Calcification on Hemodynamic and Clinical Outcomes
Authors: Bin Zhang, Erwan Salaun, Nancy Côté, Yongjian Wu, Haifa Mahjoub, Patrick Mathieu, Abdellaziz Dahou, Anne-Sophie Zenses, Marine Clisson, Philippe Pibarot, Marie-Annick Clavel
Journal: Journal of the American College of Cardiology (2020)
Expanding the screening toolbox to promote athlete health: how the US Olympic &amp; Paralympic Committee screened for health problems in 940 elite athletes
Authors: Dustin Nabhan, Melie Lewis, David Taylor, Roald Bahr
Journal: British Journal of Sports Medicine (2020)

Aim To assess the value of including validated screening tools for allergies, anxiety, depression, sleep apnoea and sleep quality into an electronic patient health history questionnaire. Methods In this descriptive study, we reviewed electronic medical records of Olympic and Paralympic athletes who completed health screenings, which included validated screens for allergies (Allergy Questionnaire for Athletes), anxiety (General Anxiety Disorder-2), depression (Patient Health Questionaire-2), sleep apnoea (Berlin Questionnaire) and sleep quality (Pittsburgh Sleep Quality Index), using established criteria for a positive screen. We report the prevalence of positive tests and the associations between positive screening tools. Results A total of 683 Olympic and 257 Paralympic athletes (462 male, 478 female) completed the health history between May and September of 2019. At least one positive screen was reported by 37% of athletes training for the Olympics and 48% of athletes training for the Paralympics. More than 20% of all athletes screened positive for allergies and poor sleep quality. Athletes training for the Paralympics had a significantly higher percentage of positive screens for anxiety, depression, poor sleep quality and sleep apnoea risk. Females had significantly more positive screens for allergy and poor sleep quality. Conclusions The addition of standardised screening tools to an electronic health history resulted in the identification of potential mental health, sleep and allergy problems in both Olympic and Paralympic athletes. Strong associations between mental health and sleep disorders suggest these problems should be considered together in health screening programmes.
Autonomic dysreflexia in spinal cord injury
Authors: Helen Cowan, Celine Lakra, Manish Desai
Journal: BMJ (2020)

### What you need to know

Autonomic dysreflexia is a potentially life threatening complication of spinal cord injury. It carries a mortality rate of 22%1 and increases the risk of stroke by 300% to 400%.2 Clinicians working in emergency or urgent care may not see patients with this condition often, but when they do, prompt recognition and treatment are required. This practice pointer gives a brief overview of autonomic dysreflexia and how to identify it.

Autonomic dysreflexia is the product of dysregulation of the autonomic system, leading to an uncoordinated response to a noxious stimulus below the level of a spinal cord injury,2 usually in individuals with a spinal cord injury above the level of T6 (fig 1). It is three times more prevalent in those with complete spinal cord injury than in those with incomplete injury (91% versus 27%, respectively).3 Autonomic dysreflexia is clinically defined as an acute episode of systolic blood pressure elevated 25 mm Hg or above the patient’s normal measurements. …
COVID-19 reminds us strongly of the necessity of physical activity: step on!
Authors: Maarten H Moen
Journal: British Journal of Sports Medicine (2020)

You see, it’s that easy!’, I was thinking. I looked down at my iPhone and discovered that cycling 30 min twice a day added 6000 steps to my daily count. I badly needed those steps to improve my daily average to what I perceived as reasonable. Often, and especially after a busy day of work, my step count was not something to be proud of. During the COVID-19 lockdown period, several of my friends complained about gaining extra CoronaWeight. I wondered why that was. Were they eating more? Or was their eating unchanged compared to normal life, and were they just moving less? The odds were high that their daily activity, and hence their step count, had plummeted.

It turns out they are not alone. An article in Nature from 2017 investigated step count in a global study. 1 The authors did so using phone data from 68 million days in 717 527 people. The daily step-count worldwide was, on average, 4961 steps. Positive exceptions were Hong Kong and Ukraine, with 6880 and 6107 steps, respectively. Poorer examples were present as well, with Indonesia at 3513, and the Saudi Arabia totalling 3807.

JAMA published a paper in March 2020, that, with the Nature article still fresh in mind, is both powerful and worrying.2 In this paper, several thousand Americans, older than 40, were followed up for 10 years after their activity was measured between 2003 and 2006. It turned out that better …
Characteristics of anti-CD19 CAR T cell infusion products associated with efficacy and toxicity in patients with large B cell lymphomas
Authors: Qing Deng, Guangchun Han, Nahum Puebla-Osorio, Man Chun John Ma, Paolo Strati, Beth Chasen, Enyu Dai, Minghao Dang, Neeraj Jain, Haopeng Yang, Yuanxin Wang, Shaojun Zhang, Ruiping Wang, Runzhe Chen, Jordan Showell, Sreejoyee Ghosh, Sridevi Patchva, Qi Zhang, Ryan Sun, Frederick Hagemeister, Luis Fayad, Felipe Samaniego, Hans C. Lee, Loretta J. Nastoupil, Nathan Fowler, R. Eric Davis, Jason Westin, Sattva S. Neelapu, Linghua Wang, Michael R. Green
Journal: Nature Medicine (2020)