tbuckley/cabot-search huggingface dataset:
Diagnosis and management of bronchopulmonary dysplasia
Authors: Margaret Gilfillan, Anita Bhandari, Vineet Bhandari
Journal: BMJ (2021)

Abstract Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in infants and is associated with increased mortality, respiratory morbidity, neurodevelopmental impairment, and increased healthcare costs. In parallel with advances made in the field of neonatal intensive care, the phenotype of BPD has evolved from a fibrocystic disease affecting late preterm infants to one of impaired parenchymal development and dysregulated vascular growth predominantly affecting infants born before 29 weeks’ gestational age. BPD has been shown to have significant lifelong consequences. Adults with BPD have been found to have abnormal lung function tests, reduced exercise tolerance, and may be at increased risk for developing chronic obstructive pulmonary disease. Evidence shows that BPD occurs secondary to genetic-environmental interactions in an immature lung. In this review, we evaluate the various clinical definitions, imaging modalities, and biomarker data that are helpful in making an early diagnosis of BPD. In addition, we evaluate recent evidence about the prevention and treatment of BPD. We discuss the invasive and non-invasive ventilation strategies and pharmacological agents used in the early, evolving, and established phases of BPD.
Preferences for and barriers to gender affirming surgeries in transgender and non-binary individuals
Authors: Bita Tristani-Firouzi, Jacob Veith, Andrew Simpson, Kelly Hoerger, Andy Rivera, Cori A. Agarwal
Journal: International Journal of Transgender Health (2021)

Background: The transgender/non-binary community continues to be an underserved population in medicine, and our understanding of their interests, disinterests, and barriers to transition-related healthcare is quite limited, especially among the diverse gender identities within the transgender/non-binary umbrella. Aim: To determine the interests, disinterests and barriers to gender affirming surgeries for transgender men, transgender women and non-binary individuals of any birth-assigned sex. Methods: An anonymous, online survey using REDcap was applied across all 50 states and advertised through social media, healthcare organization websites and flyers. The responses of individuals greater than 18 years of age who identified as transgender or non-binary were analyzed. Results: Compared to the 2015 US Transgender Survey, interest in gender affirming surgeries was higher across all gender identities surveyed and for all procedures, by an average of 38%. Interest overall in gender affirming procedures varied greatly among gender identity groups as well as with age differences. Barriers were found to be a mixture of lack of resources for recovery, financial, and a fear of complications. Discussion: Our results highlight that a desire for these procedures is unique for each individual and should never be assumed for transgender/non-binary patients. In order to better aid this underserved population, the medical community must further work to mitigate the barriers to gender affirming procedures by decreasing cost, investigating ways to increase access to resources for recovery, and improving outcomes for each of the gender affirming surgeries.
Abstract 13688: Endothelial Alpha Hemoglobin is a Nitrite Reductase
Authors: Thomas C Keller, Alexander S Keller, Steven Brooks, Rakesh P Patel, Linda Columbus, Miriam Cortese-Krott, Hans Ackerman, Brant E Isakson
Journal: Circulation (2019)

Nitrite reduction to produce vasoactive nitric oxide (NO) is well-established as a mechanism of hypoxia-dependent vasodilation. Canonically, erythrocyte hemoglobin is the major source of nitrite-de...
P66.09 Differential Orthopedia Homeobox (OTP) Expression in Pulmonary Carcinoids is Regulated Through Methylation
Authors: L. Moonen, L. Mangiante, N. Alcala, D. Leunissen, L. Lap, A. Gabriel, L. Hillen, G. Roemen, A. Koch, M. Van Engeland, A. Dingemans, M. Foll, L. Fernandez-Cuesta, J. Derks, E. Speel
Journal: Journal of Thoracic Oncology (2021)
Long-term effectiveness of adding COMT or MAOB inhibitors compared to dopamine agonists in poorly controlled Parkinson's disease – the PD MED trial
Authors: Richard Gray, Smitaa Patel, Natalie Rowland, Caroline Rick, Rebecca Woolley, Sharon Muzerengi, Alastair Gray, Crispin Jenkinson, Emma McIntosh, Keith Wheatley, Adrian Williams, Carl E Clarke
Journal: JAMA Neurology (2021)
Tyrosine phosphatases regulate resistance to ALK inhibitors in ALK+ anaplastic large cell lymphoma
Authors: Elif Karaca Atabay, Carmen Mecca, Qi Wang, Chiara Ambrogio, Ines Mota, Nina Prokoph, Giulia Mura, Cinzia Martinengo, Enrico Patrucco, Giulia Leonardi, Jessica Hossa, Achille Pich, Luca Mologni, Carlo Gambacorti-Passerini, Laurence Brugières, Birgit Geoerger, Suzanne D. Turner, Claudia Voena, Taek-Chin Cheong, Roberto Chiarle
Journal: Blood (2021)
FP13.04 CHECK Lung Protocol: CT Lung Cancer Screening is Useful to Adjuvant Comorbid Diseases Diagnosis
Authors: P.A. Schulze, J. De Mattos, C.E. Escovar, M. Zereu, A. Rubin, S. Camargo, T. Mohammed, N. Verma, F. Torres, B. Hochhegger
Journal: Journal of Thoracic Oncology (2021)
Late‐onset hematological complications post <scp>COVID</scp>‐19: An emerging medical problem for the hematologist
Authors: Eleni Korompoki, Maria Gavriatopoulou, Despina Fotiou, Ioannis Ntanasis‐Stathopoulos, Meletios A. Dimopoulos, Evangelos Terpos
Journal: American Journal of Hematology (2021)

Coronavirus disease 19 (COVID-19) is considered a multisystemic disease. Several studies have reported persistent symptoms or late-onset complications after acute COVID-19, including post-COVID-19 hematological disorders. COVID-19-induced coagulopathy, an immunothrombotic state, has been linked to thromboembolic and hemorrhagic events. Late-onset thrombocytopenia related to immune system dysregulation has also been reported as a rare manifestation post COVID-19. Close monitoring of laboratory dynamics is considered essential to identify timely abnormal values that need further investigation, providing supportive care whenever indicated. The role of hematologists is essential in terms of the multidisciplinary approach of long COVID-19. This review summarizes all the available evidence on post-acute COVID-19 hematological complications.
Abstract P109: Detection of Haplotypes Underlying a Coronary Artery Calcification Linkage Peak in the Family Heart Study
Authors: James E Hicks, Michael A Province
Journal: Circulation (2017)

Coronary artery calcification (CAC) is the buildup of calcium deposits in the arteries leading to the heart, and is an indicator of atherosclerosis. CAC is known to have a genetic component, and a genome-wide linkage screen in the Family Heart Study identified significant evidence of linkage on chromosome 9 in the area near rs13293430, but no common variant in the linkage region showed significant evidence of association. Linkage screens attempt to identify covariance due to common ancestry at a genomic locus. This is robust to the presence of rare variation or multiple variants in a region, but is unable to identify the genomic feature causing the signal and additional research is needed to identify potential causative variants. Pairs of individuals who have inherited a locus from a common ancestor will share an identical sequence of alleles (a haplotype) within the region. To identify haplotypes influencing the trait in the region, a mixed effects model was used. CAC was modeled as a trait influenced by polygenic effects and locus-specific haplotype effects. This model has the benefit of jointly estimating the effect of each haplotype while separating the haplotype effect from the background polygenic effect. From the study, 2,687 individuals of European descent from 508 pedigrees with CAC scores were genotyped on the Illumina Human 1M-DuoV3 single nucleotide polymorphisms (SNP) array. Of these, 180 individuals from 23 pedigrees were for subsequent analysis due to membership in a pedigree contributing to the linkage signal. CAC scores were determined by cardiac CT scan and adjusted for age, sex, and principal components before analysis. Phased haplotypes were generated for 906,856 common SNPs across the genome using SHAPEIT. The region between 25Mb and 35Mb (3,500 SNPs) was divided into 250kb sections, and within each section haplotypes were created based on 24 evenly spaced SNPs. Statistical significance for each region was determined by likelihood ratio test. Haplotype analysis identified two regions showing strong evidence of association (p&amp;lt;10 -7 ) with CAC. The region 28-28.25Mb is located completely within the gene LINGO2, which has been associated with BMI and cholesterol. The region 27.5-27.75Mb contains MOBKL2B, IFNK and C9orf72. Additional work will be needed to validate haplotypes used in the model and identify the particular haplotype influencing the trait.
Diagnostic Test Accuracy of 18F-FDG PET or PET/CT for Characterization of Histologic Type of Thymic Epithelial Tumor
Authors: Keunyoung Kim, Joon-Hoon Jeong, Seong-Jang Kim
Journal: Clinical Nuclear Medicine (2021)

Purpose This study investigated diagnostic accuracies of 18 F-FDG PET or PET/CT for characterization of histologic type of thymic epithelial tumors (TETs) through a systematic review and meta-analysis. Patients and Methods The PubMed, Cochrane database, and EMBASE database, from the earliest available date of indexing through August 31, 2020, were searched for studies evaluating diagnostic performance of 18 F-FDG PET or PET/CT for characterization of TET. We determined the sensitivities and specificities, calculated positive and negative likelihood ratios (LR+ and LR−), and constructed summary receiver operating characteristic curves. Results The pooled sensitivity of 18 F-FDG PET or PET/CT was 0.89 (95% confidence interval [CI], 0.80–0.95), and the pooled specificity was 0.77 (95% CI, 0.63–0.87) for differentiation between thymic cancer and thymoma. Likelihood ratio syntheses gave an overall positive likelihood ratio (LR+) of 3.9 and negative likelihood ratio (LR−) of 0.14. The pooled diagnostic odds ratio was 28 (95% CI, 13–63). The pooled sensitivity was 0.90 (95% CI, 0.75–0.96), and the pooled specificity was 0.81 (95% CI, 0.68–0.89) for differential diagnosis of a low-risk or high-risk TET. LR+ was 4.7 and LR− was 0.12. The pooled diagnostic odds ratio was 38 (95% CI, 12–121). In meta-regression analysis, no variable was the source of the study heterogeneity. Conclusions 18 F-FDG PET or PET/CT has excellent diagnostic performances for characterization of TET. Further large multicenter studies would be necessary to establish the diagnostic accuracy of 18 F-FDG PET or PET/CT for differentiation of histologic type of TET.
IDH wild-type grade 2 diffuse astrocytomas: prognostic factors and impact of treatments within molecular subgroups
Authors: Roberta Rudà, Francesco Bruno, Tamara Ius, Antonio Silvani, Giuseppe Minniti, Andrea Pace, Giuseppe Lombardi, Luca Bertero, Stefano Pizzolitto, Bianca Pollo, Marco Conti Nibali, Alessia Pellerino, Enrica Migliore, Miran Skrap, Lorenzo Bello, Riccardo Soffietti
Journal: Neuro-Oncology (2021)

Abstract Background Prognostic factors and role of treatments are not well known in isocitrate dehydrogenase (IDH) wild-type (wt) grade 2 astrocytomas. The aim of this study was to define in these tumors clinical features, molecular characteristics, and prognostic factors, with particular focus on molecular subgroups defined by cIMPACT-NOW update 3. Methods We analyzed 120 patients with confirmed diagnosis of grade 2 IDHwt astrocytoma according to WHO 2016, collected from seven Italian centers between 1999 and 2017. Results Median PFS and OS of the whole cohort were 18.9 and 32.6 months. Patients older than 40 years and patients with modest contrast enhancement on MRI had a shorter PFS and OS. Gross total resection yielded superior PFS and OS over non-gross total resection. PFS and OS of patients with either pTERT mutation or EGRF amplification were significantly shorter. The prognostic value of age, contrast enhancement on MRI, and extent of surgery was different within the molecular subgroups. Gross total resection was associated with increased PFS (not reached versus 14 months, p = 0.023) and OS (117.9 versus 20 months, p = 0.023) in patients without EGFR amplification, and with increased OS in those without pTERT mutation (NR vs 53.7 months, p = 0.05). Conversely, for patients with EGFR amplification or pTERT mutation, gross total resection did not yield a significant survival benefit. Conclusion Patients without EGFR amplification and pTERT mutation could be observed after gross total resection.
Use of whole genome sequencing to determine genetic basis of suspected mitochondrial disorders: cohort study
Authors: Katherine R Schon, Rita Horvath, Wei Wei, Claudia Calabrese, Arianna Tucci, Kristina Ibañez, Thiloka Ratnaike, Robert D S Pitceathly, Enrico Bugiardini, Rosaline Quinlivan, Michael G Hanna, Emma Clement, Emma Ashton, John A Sayer, Paul Brennan, Dragana Josifova, Louise Izatt, Carl Fratter, Victoria Nesbitt, Timothy Barrett, Dominic J McMullen, Audrey Smith, Charulata Deshpande, Sarah F Smithson, Richard Festenstein, Natalie Canham, Mark Caulfield, Henry Houlden, Shamima Rahman(, Patrick F Chinnery
Journal: BMJ (2021)

Abstract Objective To determine whether whole genome sequencing can be used to define the molecular basis of suspected mitochondrial disease. Design Cohort study. Setting National Health Service, England, including secondary and tertiary care. Participants 345 patients with suspected mitochondrial disorders recruited to the 100 000 Genomes Project in England between 2015 and 2018. Intervention Short read whole genome sequencing was performed. Nuclear variants were prioritised on the basis of gene panels chosen according to phenotypes, ClinVar pathogenic/likely pathogenic variants, and the top 10 prioritised variants from Exomiser. Mitochondrial DNA variants were called using an in-house pipeline and compared with a list of pathogenic variants. Copy number variants and short tandem repeats for 13 neurological disorders were also analysed. American College of Medical Genetics guidelines were followed for classification of variants. Main outcome measure Definite or probable genetic diagnosis. Results A definite or probable genetic diagnosis was identified in 98/319 (31%) families, with an additional 6 (2%) possible diagnoses. Fourteen of the diagnoses (4% of the 319 families) explained only part of the clinical features. A total of 95 different genes were implicated. Of 104 families given a diagnosis, 39 (38%) had a mitochondrial diagnosis and 65 (63%) had a non-mitochondrial diagnosis. Conclusion Whole genome sequencing is a useful diagnostic test in patients with suspected mitochondrial disorders, yielding a diagnosis in a further 31% after exclusion of common causes. Most diagnoses were non-mitochondrial disorders and included developmental disorders with intellectual disability, epileptic encephalopathies, other metabolic disorders, cardiomyopathies, and leukodystrophies. These would have been missed if a targeted approach was taken, and some have specific treatments.
Autophagy in mesenchymal progenitors protects mice against bone marrow failure after severe intermittent stress
Authors: Theresa Landspersky, Mehmet Saçma, Jennifer Rivière, Judith S. Hecker, Franziska Hettler, Erik Hameister, Katharina Brandstetter, Rouzanna Istvánffy, Sandra Romero Marquez, Romina Ludwig, Marilena Götz, Michèle Buck, Martin Wolf, Matthias Schiemann, Jürgen Ruland, Dirk Strunk, Akiko Shimamura, Kasiani Myers, Terry P. Yamaguchi, Matthias Kieslinger, Heinrich Leonhardt, Florian Bassermann, Katharina S. Götze, Hartmut Geiger, Christina Schreck, Robert A. J. Oostendorp
Journal: Blood (2021)

The cellular mechanisms required to ensure homeostasis of the hematopoietic niche and the ability of this niche to support hematopoiesis upon stress remain elusive. We here identify Wnt5a in Osterix+ mesenchymal progenitor and stem cells (MSPCs) as a critical factor for niche-dependent hematopoiesis. Mice lacking Wnt5a in MSPCs suffer from stress-related bone marrow (BM) failure and increased mortality. Niche cells devoid of Wnt5a show defective actin stress fiber orientation due to an elevated activity of the small GTPase CDC42. This results in incorrect positioning of autophagosomes and lysosomes, thus reducing autophagy and increasing oxidative stress. In MSPCs from patients from BM failure states which share features of peripheral cytopenia and hypocellular BM, we find similar defects in actin stress fiber orientation, reduced and incorrect colocalization of autophagosomes and lysosomes, and CDC42 activation. Strikingly, a short pharmacological intervention to attenuate elevated CDC42 activation in vivo in mice prevents defective actin-anchored autophagy in MSPCs, salvages hematopoiesis and protects against lethal cytopenia upon stress. In summary, our study identifies Wnt5a as a restriction factor for niche homeostasis by affecting CDC42-regulated actin stress-fiber orientation and autophagy upon stress. Our data further imply a critical role for autophagy in MSPCs for adequate support of hematopoiesis by the niche upon stress and in human diseases characterized by peripheral cytopenias and hypocellular BM.
OA08.01 Trends in Within-Class Changes in US Prices of Drugs used for Metastatic Non-Small Cell Lung Cancer from 2015 to 2020
Authors: A. Desai, C. Jensen, C. Scheckel, J. Orme, S. Rakshit, S. Singh, N. Shah, K. Leventakos, A. Adjei
Journal: Journal of Thoracic Oncology (2021)
ERS clinical practice guidelines: high-flow nasal cannula in acute respiratory failure
Authors: Simon Oczkowski, Begüm Ergan, Lieuwe Bos, Michelle Chatwin, Miguel Ferrer, Cesare Gregoretti, Leo Heunks, Jean-Pierre Frat, Federico Longhini, Stefano Nava, Paolo Navalesi, Aylin Ozsancak Uğurlu, Lara Pisani, Teresa Renda, Arnaud W. Thille, João Carlos Winck, Wolfram Windisch, Thomy Tonia, Jeanette Boyd, Giovanni Sotgiu, Raffaele Scala
Journal: European Respiratory Journal (2021)

High-flow nasal cannula (HFNC) has become a frequently used noninvasive form of respiratory support in acute settings; however, evidence supporting its use has only recently emerged. These guidelines provide evidence-based recommendations for the use of HFNC alongside other noninvasive forms of respiratory support in adults with acute respiratory failure (ARF).The European Respiratory Society task force panel included expert clinicians and methodologists in pulmonology and intensive care medicine. The task force used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methods to summarise evidence and develop clinical recommendations for the use of HFNC alongside conventional oxygen therapy (COT) and noninvasive ventilation (NIV) for the management of adults in acute settings with ARF.The task force developed eight conditional recommendations, suggesting the use of 1) HFNC over COT in hypoxaemic ARF; 2) HFNC over NIV in hypoxaemic ARF; 3) HFNC over COT during breaks from NIV; 4) either HFNC or COT in post-operative patients at low risk of pulmonary complications; 5) either HFNC or NIV in post-operative patients at high risk of pulmonary complications; 6) HFNC over COT in nonsurgical patients at low risk of extubation failure; 7) NIV over HFNC for patients at high risk of extubation failure unless there are relative or absolute contraindications to NIV; and 8) trialling NIV prior to use of HFNC in patients with COPD and hypercapnic ARF.HFNC is a valuable intervention in adults with ARF. These conditional recommendations can assist clinicians in choosing the most appropriate form of noninvasive respiratory support to provide to patients in different acute settings.
P32.02 2020 in Hindsight: Newly Diagnosed Lung Cancer Patients in the Time of COVID-19 at a Tertiary Canadian Cancer Centre
Authors: L. Petersen, A. Gibson, K. Gerat, L. Kinch, A. Elegbede, K. Brennan, M. Dean, G. Bebb
Journal: Journal of Thoracic Oncology (2021)
Sixty seconds on . . . “The Gasman’s Shanty”
Authors: John Illman
Journal: BMJ (2021)

It’s a music video about the heroics of anaesthetists (https://www.youtube.com/watch?v=8wm2hSdBtXU), written, produced, and directed by . . . guess who?

Spot on. Richard Marks of London’s Royal Free Hospital, to be precise. He probably thought it up in the theatre while drinking coffee, checking his phone, and doing the crossword—you know, the …
High Opioid Prescribing Profiles Among Gastroenterologists: A Nationwide Analysis
Authors: Wendi G. LeBrett, Preetha S. Iyengar, Anna H. Lee, Frank W. Chen, Lin Chang
Journal: Clinical Gastroenterology and Hepatology (2021)

Chronic opioid use is associated with adverse effects on the gastrointestinal (GI) tract and increased morbidity.1-3 Despite efforts to de-escalate opioid use, 10% of outpatient GI visits are associated with an opioid prescription.4 Although we previously described declining opioid prescriptions to Medicare patients by most gastroenterologists,5 opioid prescriptions for GI conditions have increased.4 Considerable variation in opioid prescribing behavior exists in the general physician population, and a small percentage of high prescribers are responsible for driving opioid prescriptions.6,7 The aims of this study are (1) to examine the impact of high opioid prescribers (HPs) on overall prescription volume in gastroenterology and (2) identify characteristics associated with HPs.
Association of Infectious Mononucleosis in Childhood and Adolescence With Risk for a Subsequent Multiple Sclerosis Diagnosis Among Siblings
Authors: Yin Xu, Ayako Hiyoshi, Kelsi A. Smith, Fredrik Piehl, Tomas Olsson, Katja Fall, Scott Montgomery
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Epstein-Barr virus and its acute manifestation, infectious mononucleosis (IM), are associated with an increased risk of multiple sclerosis (MS). Whether this association is confounded by susceptibility to infection is still debated. <h3>Objective</h3> To assess whether hospital-diagnosed IM during childhood, adolescence, or young adulthood is associated with subsequent MS diagnosis independent of shared familial factors. <h3>Design, Setting, and Participants</h3> This population–based cohort study used the Swedish Total Population Register to identify individuals born in Sweden from January 1, 1958, to December 31, 1994. Participants aged 20 years were followed up from January 1, 1978, to December 31, 2018, with a median follow-up of 15.38 (IQR, 8.68-23.55; range, 0.01-40.96) years. Data were analyzed from October 2020 to July 2021. <h3>Exposure</h3> Hospital-diagnosed IM before 25 years of age. <h3>Main Outcomes and Measures</h3> Diagnoses of MS from 20 years of age were identified. Risk of an MS diagnosis associated with IM in childhood (birth to 10 years of age), adolescence (11-19 years of age), and early adulthood (20-24 years of age [time-dependent variable]) were estimated using conventional and stratified (to address familial environmental or genetic confounding) Cox proportional hazards regression. <h3>Results</h3> Of the 2 492 980 individuals (1 312 119 men [52.63%] and 1 180 861 women [47.37%]) included, 5867 (0.24%) had an MS diagnosis from 20 years of age (median age, 31.50 [IQR, 26.78-37.54] years). Infectious mononucleosis in childhood (hazard ratio [HR], 1.98; 95% CI, 1.21-3.23) and adolescence (HR, 3.00; 95% CI, 2.48-3.63) was associated with an increased risk of an MS diagnosis that remained significant after controlling for shared familial factors in stratified Cox proportional hazards regression (HRs, 2.87 [95% CI, 1.44-5.74] and 3.19 [95% CI, 2.29-4.46], respectively). Infectious mononucleosis in early adulthood was also associated with risk of a subsequent MS diagnosis (HR, 1.89; 95% CI, 1.18-3.05), but this risk was attenuated and was not significant after controlling for shared familial factors (HR, 1.51; 95% CI, 0.82-2.76). <h3>Conclusions and Relevance</h3> These findings suggest that IM in childhood and particularly adolescence is a risk factor associated with a diagnosis of MS, independent of shared familial factors.