tbuckley/cabot-search huggingface dataset:
Management of a Immunotherapy Unit During the COVID-19 Outbreak: Building a Resilient Health Care System.
Authors: Inmaculada Sanchez-Machin, Ruperto Gonzalez Perez, Paloma Poza Guedes, Cristina Alava Cruz, Elena Mederos Luis, Victor Matheu
Journal: Journal of Allergy and Clinical Immunology (2021)

Immunotherapy Units (IU) went through an unexpected transformation in order to get re-organized during the COVID pandemic. The aim of the present work is to share our experience in the IU through this rapid conversion during the outbreak. The current investigation was carried out at the IU located serving the Allergy Department in a public Tertiary-care referral Hospital, regularly managing an average of 320 in-patients/month. Standard scheduled regimes included hymenoptera venom subcutaneous immunotherapy (SCIT), cluster or specific SCIT schedules for respiratory conditions and subjects with documented previous SCIT adverse reactions. During the enforced COVID-19 confinement, only hymenoptera SCIT was maintained in the IU, while all SCIT-associated respiratory disease was postponed. Telehealth, including telephone e-mail consultations and previously developed electronic consultations, enabled the virtual management of the IU. The number of re-scheduled SCIT was over 100 subjects per month. During confinement, a total of 65 starting and 176 maintenance SCIT doses were re-scheduled reaching 494 starts and 332 maintenance SCIT doses, with a median of 23 telephone and 16 mail resolved user's questions per week. A full re-allocation of human resources, spaces and operation hours have been achieved, regardless of the increase in the absolute number of SCIT adverse reactions during this period. In our experience, telemedicine greatly aided in the transition to the re-organization of the IU, favoring further work in this direction. The unexpected COVID-19 outbreak resulted in no increase of AIT-associated adverse reactions in the IU despite the associated greater work pressure related to this period.
Use of high dose cyproterone acetate and risk of intracranial meningioma in women: cohort study
Authors: Alain Weill, Pierre Nguyen, Moujahed Labidi, Benjamin Cadier, Thibault Passeri, Lise Duranteau, Anne-Laure Bernat, Isabelle Yoldjian, Sylvie Fontanel, Sébastien Froelich, Joël Coste
Journal: BMJ (2021)

To assess the risk of meningioma associated with use of high dose cyproterone acetate, a progestogen indicated for clinical hyperandrogenism.Observational cohort study.Data from SNDS, the French administrative healthcare database, between 2007 and 2015.253 777 girls and women aged 7-70 years living in France who started cyproterone acetate between 2007 and 2014. Participants had at least one reimbursement for high dose cyproterone acetate and no history of meningioma or benign brain tumour, or long term disease status. Participants were considered to be exposed when they had received a cumulative dose of at least 3 g during the first six months (139 222 participants) and very slightly exposed (control group) when they had received a cumulative dose of less than 3 g (114 555 participants). 10 876 transgender participants (male to female) were included in an additional analysis.Surgery (resection or decompression) or radiotherapy for one or more intracranial meningiomas.Overall, 69 meningiomas in the exposed group (during 289 544 person years of follow-up) and 20 meningiomas in the control group (during 439 949 person years of follow-up) were treated by surgery or radiotherapy. The incidence of meningioma in the two groups was 23.8 and 4.5 per 100 000 person years, respectively (crude relative risk 5.2, 95% confidence interval 3.2 to 8.6; adjusted hazard ratio 6.6, 95% confidence interval 4.0 to 11.1). The adjusted hazard ratio for a cumulative dose of cyproterone acetate of more than 60 g was 21.7 (10.8 to 43.5). After discontinuation of cyproterone acetate for one year, the risk of meningioma in the exposed group was 1.8-fold higher (1.0 to 3.2) than in the control group. In a complementary analysis, 463 women with meningioma were observed among 123 997 already using cyproterone acetate in 2006 (risk of 383 per 100 000 person years in the group with the highest exposure in terms of cumulative dose). Meningiomas located in the anterior skull base and middle skull base, particularly the medial third of the middle skull base, involving the spheno-orbital region, appeared to be specific to cyproterone acetate. An additional analysis of transgender participants showed a high risk of meningioma (three per 14 460 person years; 20.7 per 100 000 person years).A strong dose-effect relation was observed between use of cyproterone acetate and risk of intracranial meningiomas. A noticeable reduction in risk was observed after discontinuation of treatment.
Impact of Facility Surgical Volume on Survival in Patients With Cancer
Authors: Kelsey C. Stoltzfus, Biyi Shen, Leila Tchelebi, Daniel M. Trifiletti, Niraj J. Gusani, Vonn Walter, Ming Wang, Nicholas G. Zaorsky
Journal: Journal of the National Comprehensive Cancer Network (2021)

Increased facility surgical treatment volume is sometimes associated with improved survival in patients with cancer; however, published studies evaluating volume are heterogeneous and disparate in their patient inclusion and definition of volume. The purpose of this work was to evaluate uniformly the impact of surgical facility volume on survival in patients with cancer.The National Cancer Database was searched for patients diagnosed in 2004 through 2013 with the 12 cancers most commonly treated surgically. Facilities were stratified by 4 categories using the overall population (low, intermediate, high, and very high), each including 25% of patients, and then stratified by each individual disease site. Five-year postsurgery survival was estimated using both the Kaplan-Meier method and corresponding log-rank tests for group comparisons. Cox proportional hazard models were used to evaluate the effects of facility volume on 5-year postsurgery survival further, adjusted for multiple covariates.A total of 3,923,618 patients who underwent surgery were included from 1,139 facilities. Of these, 40.4% had breast cancer, 12.8% prostate cancer, and 10.0% colon cancer. Most patients were female (65.0%), White (86.4%), and privately insured (51.6%) with stage 0-III disease (64.8%). For all cancers, the risk of death for patients undergoing surgery at very high-volume facilities was 88% of that for those treated at low-volume facilities. Hazard ratios (HRs) were greatest (very high vs low volume) for cancer of the prostate (HR, 0.66; 95% CI, 0.63-0.69), pancreas (HR, 0.75; 95% CI, 0.71-0.78), and esophagus (HR, 0.78; 95% CI, 0.73-0.83), and for melanoma (HR, 0.81; 95% CI, 0.78-0.84); differences were smallest for uterine and non-small cell lung cancers. Overall survival differences were greatest for cancers of the brain, pancreas, and esophagus.Patients treated surgically at higher-volume facilities consistently had improved overall survival compared with those treated at low-volume centers, although the magnitude of difference was cancer-specific.
miR-31 Displays Subtype Specificity in Lung Cancer
Authors: Mackenzie L. Davenport, John B. Echols, Austin D. Silva, Joshua C. Anderson, Philip Owens, Clayton Yates, Qing Wei, Shuko Harada, Douglas R. Hurst, Mick D. Edmonds
Journal: Cancer Research (2021)

Abstract miRNA rarely possess pan-oncogenic or tumor-suppressive properties. Most miRNAs function under tissue-specific contexts, acting as either tumor suppressors in one tissue, promoting oncogenesis in another, or having no apparent role in the regulation of processes associated with the hallmarks of cancer. What has been less clear is the role of miRNAs within cell types of the same tissue and the ability within each cell type to contribute to oncogenesis. In this study, we characterize the role of one such tissue-specific miRNA, miR-31, recently identified as the most oncogenic miRNA in lung adenocarcinoma, across the histologic spectrum of human lung cancer. Compared with normal lung tissue, miR-31 was overexpressed in patient lung adenocarcinoma, squamous cell carcinoma, and large-cell neuroendocrine carcinoma, but not small-cell carcinoma or carcinoids. miR-31 promoted tumor growth in mice of xenografted human adenocarcinoma and squamous cell carcinoma cell lines, but not in large- or small-cell carcinoma lines. While miR-31 did not promote primary tumor growth of large- and small-cell carcinoma, it did promote spontaneous metastasis. Mechanistically, miR-31 altered distinct cellular signaling programs within each histologic subtype, resulting in distinct phenotypic differences. This is the first report distinguishing diverse functional roles for this miRNA across the spectrum of lung cancers and suggests that miR-31 has broad clinical value in human lung malignancy. Significance: These findings demonstrate the oncogenic properties of miR-31 in specific subtypes of lung cancer and highlight it as a potential therapeutic target in these subtypes.
Abstract 15407: Initial Shunt Type Does Not Impact Echocardiographic Indices in Transplant-Free Survivors After Single Right Ventricle Palliations During Early Childhood—The SVR Trial at 6 Years
Authors: Peter C Frommelt, Chenwei Hu, Felicia Trachtenberg, Jeanne M Baffa, Richard J Boruta, Shahryar Chowdhury, James F Cnota, Andreea Dragulescu, Jami C Levine, Jimmy Lu, Laura Mercer-Rosa, Thomas A Miller, Amee Shah, Gary Stapleton, Jessica Stelter, Timothy C Slesnick, Pierre Wong, Jane W Newburger
Journal: Circulation (2017)

Introduction: Current data from single center studies are conflicting regarding the impact of shunt type on longitudinal right ventricular (RV) function after Norwood. The Pediatric Heart Network S...
Abstract 16018: Plasma Extracellular Vesicles MicroRNAs Serve as Potential Mediators for Atherosclerotic Cardiovascular Disease in HIV Patients
Authors: Andrea da Fonseca Ferreira, Chunming Dong, Conrad Macon, Lukun Zhang, Jian Qin Wei, Bernard Degnan, Derek Dykxhoorn, Dushyantha Jayaweera, Liyong Wang
Journal: Circulation (2019)

Introduction: HIV+ individuals have acquired long life spans due to the development of antiretroviral therapy. However, atherosclerotic cardiovascular disease (CVD) occurs prematurely in this popul...
The Heterogeneous Landscape and Early Evolution of Pathogen-Associated CpG Dinucleotides in SARS-CoV-2
Authors: Andrea Di Gioacchino, Petr Šulc, Anastassia V Komarova, Benjamin D Greenbaum, Rémi Monasson, Simona Cocco
Journal: Molecular Biology and Evolution (2021)

Abstract COVID-19 can lead to acute respiratory syndrome, which can be due to dysregulated immune signaling. We analyze the distribution of CpG dinucleotides, a pathogen-associated molecular pattern, in the SARS-CoV-2 genome. We characterize CpG content by a CpG force that accounts for statistical constraints acting on the genome at the nucleotidic and amino acid levels. The CpG force, as the CpG content, is overall low compared with other pathogenic betacoronaviruses; however, it widely fluctuates along the genome, with a particularly low value, comparable with the circulating seasonal HKU1, in the spike coding region and a greater value, comparable with SARS and MERS, in the highly expressed nucleocapside coding region (N ORF), whose transcripts are relatively abundant in the cytoplasm of infected cells and present in the 3′UTRs of all subgenomic RNA. This dual nature of CpG content could confer to SARS-CoV-2 the ability to avoid triggering pattern recognition receptors upon entry, while eliciting a stronger response during replication. We then investigate the evolution of synonymous mutations since the outbreak of the COVID-19 pandemic, finding a signature of CpG loss in regions with a greater CpG force. Sequence motifs preceding the CpG-loss-associated loci in the N ORF match recently identified binding patterns of the zinc finger antiviral protein. Using a model of the viral gene evolution under human host pressure, we find that synonymous mutations seem driven in the SARS-CoV-2 genome, and particularly in the N ORF, by the viral codon bias, the transition–transversion bias, and the pressure to lower CpG content.
Prognostic Value of Day 14 Bone Marrow Biopsy (d14BM) in Acute Myeloid Leukemia (AML)
Authors: Marcos Lemos, Fatima Costa, Catia L Gaspar, Margarida Fevereiro, Nuno Almeida, Leonor Sarmento, Luis P Monteiro, Ana Tome, Aida B. Sousa
Journal: Blood (2017)
Two novel variants in signal transduction and activator of transcription 1 (STAT1) coiled-coil region cause STAT1 gain of function in an infant presenting with Pneumocystis jiroveci pneumonia (PJP) and CMV viremia
Authors: Tina Banzon, Sandra Burchett, Andrew Wehrman, Pui Lee, Craig Platt
Journal: Journal of Allergy and Clinical Immunology (2021)
Patient participation groups could provide huge voluntary support to the NHS
Authors: Joan Woolard
Journal: BMJ (2021)

NHS England has announced more plans for reorganising the NHS.1

Patient participation groups were the idea of a doctor in 1972 to support the work of medical practices in much the same way as parent teacher associations support schools. They were slow to take off, and even though about 75% of general practitioners now sign a contractual agreement to have them, many people don’t know they exist. The reason for this apparent reluctance to participate might be that the fittest patients to run these voluntary groups are …
Detection of Recurrent Genetic Mutations in Intravascular Large B-Cell Lymphoma By Comprehensive Genetic Analyses Using Peripheral Blood Circulating Cell-Free DNA
Authors: Akihiro Tomita, Kazuyuki Shimada, Kenichi Yoshida, Yasuhiro Suzuki, Chisako Iriyama, Masashi Sanada, Masaaki Yuge, Yusuke Takagi, Shigeru Kusumoto, Yasufumi Masaki, Takahiko Ito, Yuichiro Inagaki, Akinao Okamoto, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Seishi Ogawa, Hitoshi Kiyoi
Journal: Blood (2017)
Pregnancy in Familial Chylomicronemia syndrome: Plasmapheresis as Therapeutic Approach
Authors: Leskovar Dunja, Šabić Marina, Perica Dražen, Šućur Nediljko, Godan Hauptman Ana, Merćep Iveta, Borovečki Fran, Jelaković Bojan, Reiner Željko, Pećin Ivan
Journal: Metabolism (2021)
Puberty blockers do not alleviate negative thoughts in children with gender dysphoria, finds study
Authors: Clare Dyer
Journal: BMJ (2021)

Puberty blockers used to treat children aged 12 to 15 who have severe and persistent gender dysphoria had no significant effect on their psychological function, thoughts of self-harm, or body image, a study has found.1

However, as expected, the children experienced reduced growth in height and bone strength by the time they finished their treatment at age 16.

The findings, from a study of 44 children treated by the Gender Identity Development Service (GIDS) run by the Tavistock and Portman NHS Foundation Trust in London, have emerged as the trust prepares to appeal against a High Court ruling that led NHS England to pause referrals of under 16s for puberty blockers.2

The appeal, expected to be heard on …
Comparative analysis of the role of mast cells in murine asthma models using Kit‐sufficient mast cell‐deficient animals
Authors: Lea Pohlmeier, Sanchaita Sriwal Sonar, Hans‐Reimer Rodewald, Manfred Kopf, Luigi Tortola
Journal: Allergy (2021)

Abstract Background Asthma is a frequent chronic disease that can potentially severely affect the respiratory capacity and well‐being of patients. Mast cells (MCs) are regarded as major players in human asthma due to their capacity to release crucial inflammatory mediators following allergen exposure. However, unambiguous characterization of their role in animal models has long been hindered by the unavailability of specific MC‐deficient models lacking confounding MC‐unrelated effects. This study aims to examine the role of MCs in Kit ‐sufficient MC‐deficient Cpa3 Cre /+ mice. Methods We used a variety of models of acute and chronic asthma employing distinct routes and regimes of sensitization. These sensitizations were done via the peritoneal cavity, the skin, or the lung. Additionally, different allergens, i.e. ovalbumin and house dust mite extract, were used. Results Our results show that the absence of MCs had no impact on the severity of allergic airway inflammation in any of the tested mouse models, as measured by leukocyte infiltration in the airways, cytokine expression, antibody production, airway hyper‐responsiveness and mucus production. Conclusion This indicates that MCs do not play a major role in murine allergic airway inflammation.
Prospective validation of Canadian TIA Score and comparison with ABCD2 and ABCD2i for subsequent stroke risk after transient ischaemic attack: multicentre prospective cohort study
Authors: Jeffrey J Perry, Marco L A Sivilotti, Marcel Émond, Ian G Stiell, Grant Stotts, Jacques Lee, Andrew Worster, Judy Morris, Ka Wai Cheung, Albert Y Jin, Wieslaw J Oczkowski, Demetrios J Sahlas, Heather E Murray, Ariane Mackey, Steve Verreault, Marie-Christine Camden, Samuel Yip, Philip Teal, David J Gladstone, Mark I Boulos, Nicolas Chagnon, Elizabeth Shouldice, Clare Atzema, Tarik Slaoui, Jeanne Teitlebaum, Kasim E Abdulaziz, Marie-Joe Nemnom, George A Wells, Mukul Sharma
Journal: BMJ (2021)

Abstract Objective To validate the previously derived Canadian TIA Score to stratify subsequent stroke risk in a new cohort of emergency department patients with transient ischaemic attack. Design Prospective cohort study. Setting 13 Canadian emergency departments over five years. Participants 7607 consecutively enrolled adult patients attending the emergency department with transient ischaemic attack or minor stroke. Main outcome measures The primary outcome was subsequent stroke or carotid endarterectomy/carotid artery stenting within seven days. The secondary outcome was subsequent stroke within seven days (with or without carotid endarterectomy/carotid artery stenting). Telephone follow-up used the validated Questionnaire for Verifying Stroke Free Status at seven and 90 days. All outcomes were adjudicated by panels of three stroke experts, blinded to the index emergency department visit. Results Of the 7607 patients, 108 (1.4%) had a subsequent stroke within seven days, 83 (1.1%) had carotid endarterectomy/carotid artery stenting within seven days, and nine had both. The Canadian TIA Score stratified the risk of stroke, carotid endarterectomy/carotid artery stenting, or both within seven days as low (risk ≤0.5%; interval likelihood ratio 0.20, 95% confidence interval 0.09 to 0.44), medium (risk 2.3%; interval likelihood ratio 0.94, 0.85 to 1.04), and high (risk 5.9% interval likelihood ratio 2.56, 2.02 to 3.25) more accurately (area under the curve 0.70, 95% confidence interval 0.66 to 0.73) than did the ABCD2 (0.60, 0.55 to 0.64) or ABCD2i (0.64, 0.59 to 0.68). Results were similar for subsequent stroke regardless of carotid endarterectomy/carotid artery stenting within seven days. Conclusion The Canadian TIA Score stratifies patients’ seven day risk for stroke, with or without carotid endarterectomy/carotid artery stenting, and is now ready for clinical use. Incorporating this validated risk estimate into management plans should improve early decision making at the index emergency visit regarding benefits of hospital admission, timing of investigations, and prioritisation of specialist referral.
The BNT162b2 (BioNTech/Pfizer) vaccine had 95% efficacy against COVID-19 ≥7 days after the 2nd dose
Authors: Zain Chagla
Journal: Annals of Internal Medicine (2021)

Source CitationPolack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383:2603-15. https://pubmed.ncbi.nlm.nih.gov/33301246/AbstractClinical Impact RatingsGIM/FP/GP: Emergency Med: Hospitalists: Infectious Disease:
Cholesterol-associated lysosomal disorder triggers cell death of hematological malignancy: Dynamic analysis on cytotoxic effects of LW-218
Authors: Po Hu, Hui Li, Wenzhuo Sun, Hongzheng Wang, Xiaoxuan Yu, Yingjie Qing, Zhanyu Wang, Mengyuan Zhu, Jingyan Xu, Qinglong Guo, Hui Hui
Journal: Acta Pharmaceutica Sinica B (2021)

The integrity of lysosomes is of vital importance to survival of tumor cells. We demonstrated that LW-218, a synthetic flavonoid, induced rapid lysosomal enlargement accompanied with lysosomal membrane permeabilization in hematological malignancy. LW-218-induced lysosomal damage and lysosome-dependent cell death were mediated by cathepsin D, as the lysosomal damage and cell apoptosis could be suppressed by depletion of cathepsin D or lysosome alkalization agents, which can alter the activity of cathepsins. Lysophagy, was initiated for cell self-rescue after LW-218 treatment and correlated with calcium release and nuclei translocation of transcription factor EB. LW-218 treatment enhanced the expression of autophagy-related genes which could be inhibited by intracellular calcium chelator. Sustained exposure to LW-218 exhausted the lysosomal capacity so as to repress the normal autophagy. LW-218-induced enlargement and damage of lysosomes were triggered by abnormal cholesterol deposition on lysosome membrane which caused by interaction between LW-218 and NPC intracellular cholesterol transporter 1. Moreover, LW-218 inhibited the leukemia cell growth
Metabolic differences between bronchial epithelium from healthy individuals and patients with asthma and the effect of bronchial thermoplasty
Authors: Abilash Ravi, Annika W.M. Goorsenberg, Annemiek Dijkhuis, Barbara S. Dierdorp, Tamara Dekker, Michel van Weeghel, Yanaika S. Sabogal Piñeros, Pallav L. Shah, Nick H.T. ten Hacken, Jouke T. Annema, Peter J. Sterk, Frédéric M. Vaz, Peter I. Bonta, René Lutter
Journal: Journal of Allergy and Clinical Immunology (2021)

Asthma is a heterogeneous disease with differences in onset, severity, and inflammation. Bronchial epithelial cells (BECs) contribute to asthma pathophysiology.We determined whether transcriptomes of BECs reflect heterogeneity in inflammation and severity in asthma, and whether this was affected in BECs from patients with severe asthma after their regeneration by bronchial thermoplasty.RNA sequencing was performed on BECs obtained by bronchoscopy from healthy controls (n = 16), patients with mild asthma (n = 17), patients with moderate asthma (n = 5), and patients with severe asthma (n = 17), as well as on BECs from treated and untreated airways of the latter (also 6 months after bronchial thermoplasty) (n = 23). Lipidome and metabolome analyses were performed on cultured BECs from healthy controls (n = 7); patients with severe asthma (n = 9); and, for comparison, patients with chronic obstructive pulmonary disease (n = 7).Transcriptome analysis of BECs from patients showed a reduced expression of oxidative phosphorylation (OXPHOS) genes, most profoundly in patients with severe asthma but less profoundly and more heterogeneously in patients with mild asthma. Genes related to fatty acid metabolism were significantly upregulated in asthma. Lipidomics revealed enhanced levels of lipid species (phosphatidylcholines, lysophosphatidylcholines. and bis(monoacylglycerol)phosphate), whereas levels of OXPHOS metabolites were reduced in BECs from patients with severe asthma. BECs from patients with mild asthma characterized by hyperresponsive production of mediators implicated in neutrophilic inflammation had decreased expression of OXPHOS genes compared with that in BECs from patients with mild asthma with normoresponsive production. BECs obtained after thermoplasty had significantly increased expression of OXPHOS genes and decreased expression of fatty acid metabolism genes compared with BECs obtained from untreated airways.BECs in patients with asthma are metabolically different from those in healthy individuals. These differences are linked with inflammation and asthma severity, and they can be reversed by bronchial thermoplasty.