tbuckley/cabot-search huggingface dataset:
Association of Net Worth and Ambulatory Blood Pressure in Early Middle-aged African American Women
Authors: Telisa Spikes, Raphiel Murden, Izraelle I. McKinnon, Samantha Bromfield, Miriam E. Van Dyke, Renee H. Moore, Frederic F. Rahbari-Oskoui, Arshed Quyummi, Viola Vaccarino, Tené T. Lewis
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Low socioeconomic status (SES) in the form of educational level and income has been linked to greater cardiovascular risk across cohorts; however, associations have been inconsistent for African American individuals. Net worth, a measure of overall assets, may be a more relevant metric, especially for African American women, because it captures longer-term financial stability and economic reserve. <h3>Objective</h3> To examine whether net worth is associated with increased ambulatory blood pressure (ABP), a marker of cardiovascular disease (CVD) risk, independent of educational level and income, in young to middle-aged African American women. <h3>Design, Setting, and Participants</h3> A cross-sectional, community-based study conducted in the southeastern US was performed using 48-hour ambulatory BP monitoring. Participants included 384 African American women aged 30 to 46 years without clinical CVD recruited between December 16, 2016, and March 21, 2019; data analysis was performed from September 2020 to December 2021. <h3>Exposures</h3> Self-reported net worth (total financial assets minus debts), self-reported educational level, and self-reported income. <h3>Main Outcomes and Measures</h3> Mean daytime and nighttime BP levels, assessed via 48-hour ABP monitoring and sustained hypertension (ABP daytime and clinic BP ≥130/80 mm Hg). <h3>Results</h3> The 384 African American women in this study represented a range of SES backgrounds; mean (SD) age was 38.0 (4.3) years. Excluding 66 women who were not receiving antihypertensive medications, in linear regression models adjusted for age, marital status, educational level, family income, and family size, women reporting a negative net worth (debt) had higher levels of daytime (β = 6.7; SE = 1.5;<i>P</i> &lt; .001) and nighttime (β = 6.4; SE = 1.4;<i>P</i> &lt; .001) systolic BP, compared with women reporting a positive net worth. Similar associations were observed with sustained hypertension: women reporting a negative net worth had 150% higher odds (odds ratio, 2.5; 95% CI, 1.3-4.7) of sustained hypertension than those reporting a positive net worth. Associations remained significant after additional adjustments for smoking, body mass index, psychosocial stress due to debt, and depressive symptoms and were similar, although attenuated, when women receiving antihypertensive medications were included and treatment was controlled for in all analyses. <h3>Conclusions and Relevance</h3> In this cross-sectional study, having a negative net worth (ie, debt) was associated with elevated BP in African American women, independent of traditional indicators of SES. This finding suggests that limited assets or a lack of economic reserve may be associated with poor CVD outcomes in this at-risk group.
A mutation-based gene set predicts survival benefit after immunotherapy across multiple cancers and reveals the immune response landscape
Authors: Junyu Long, Dongxu Wang, Anqiang Wang, Peipei Chen, Yu Lin, Jin Bian, Xu Yang, Mingjun Zheng, Haohai Zhang, Yongchang Zheng, Xinting Sang, Haitao Zhao
Journal: Genome Medicine (2022)

Abstract Background Immune checkpoint inhibitor (ICI) therapy has revolutionized the treatment of many cancers. However, the limited population that benefits from ICI therapy makes it necessary to screen predictive biomarkers for stratifying patients. Currently, many biomarkers, such as tumor mutational burden (TMB), have been used in the clinic as indicative biomarkers. However, some high-TMB patients with mutations in genes that are closely related to immunotherapeutic resistance are not sensitive to ICI therapy. Thus, there is a need to move beyond TMB and identify specific genetic determinants of the response to ICI therapy. In this study, we established a comprehensive mutation-based gene set across different tumor types to predict the efficacy of ICI therapy. Methods We constructed and validated a mutational signature to predict the prognosis of patients treated with ICI therapy. Then, the underlying immune response landscapes of different subtypes were investigated with multidimensional data. Results This study included genomic and clinical data for 12,647 patients. An eleven-gene mutation-based gene set was generated to divide patients into a high-risk group and a low-risk group in a training cohort (1572 patients with 9 types of cancers who were treated with ICI therapy). Validation was performed in a validation cohort (932 patients with 5 types of cancers who were treated with ICI therapy). Mutations in these 11 genes were associated with a better response to ICI therapy. In addition, the mutation-based gene set was demonstrated to be an independent prognostic factor after ICI therapy. We further explored the role of the immune context in determining the benefits of immunotherapy in 10,143 patients with 33 types of cancers and found distinct immune landscapes for the high- and low-risk groups. Conclusions The mutation-based gene set developed in this study can be used to reliably predict survival benefit across cancers in patients receiving ICI therapy. The close interplay between the extrinsic and intrinsic immune landscapes in the identified patient subgroups and the subgroups’ differing responses to ICI therapy could guide immunotherapy treatment decisions for cancer patients.
Suppression of Plasma Renin Activity in Primary Aldosteronism
Authors: Jerome W. Conn
Journal: JAMA (1985)

THE OCCURRENCE in a hypertensive patient of increased production of aldosterone, and of the hypokalemia which often accompanies it, is due either to the presence of an aldosterone-secreting adrenocortical tumor (primary aldosteronism), or the presence of a functional renal hemodynamic change which stimulates the renal juxtaglomerular cells to secrete into the blood abnormally large amounts of renin. In the latter case, an increased quantity of angiotensin II is thus generated. Angiotensin II has been established to be a potent stimulus for the secretion of aldosterone by the adrenal cortices of man.<sup>1,2</sup>Although increased secretion of aldosterone can be induced in man by other mechanisms, it is now clear that, when hypersecretion of aldosterone occurs in human renal hypertension (secondary aldosteronism), it is the result of increased activity of the renin-angiotensin system. This seems to be true whether the decreased "stretch"<sup>3</sup>at the renal baroreceptor site (the juxtaglomerular cells)
Tfh-cell-derived interleukin 21 sustains effector CD8+ T cell responses during chronic viral infection
Authors: Ryan Zander, Moujtaba Y. Kasmani, Yao Chen, Paytsar Topchyan, Jian Shen, Shikan Zheng, Robert Burns, Jennifer Ingram, Can Cui, Nikhil Joshi, Joseph Craft, Allan Zajac, Weiguo Cui
Journal: Immunity (2022)
Tocilizumab in patients with new onset polymyalgia rheumatica (PMR-SPARE): a phase 2/3 randomised controlled trial
Authors: Michael Bonelli, Helga Radner, Andreas Kerschbaumer, Daniel Mrak, Martina Durechova, Jutta Stieger, Rusmir Husic, Peter Mandl, Josef S Smolen, Christian Dejaco, Daniel Aletaha
Journal: Annals of the Rheumatic Diseases (2022)

Background Polymyalgia rheumatica is the second most common inflammatory rheumatic disease of people &gt;50 years. Glucocorticoid therapy is highly effective, but many patients require treatment for several years. Effective glucocorticoid sparing agents are still needed. Methods In this double-blind, multi-centre phase 2/3 clinical trial, we randomly assigned 36 patients with new onset polymyalgia rheumatica from three centres to receive subcutaneous tocilizumab (162 mg per week) or placebo for 16 weeks (1:1 ratio). All patients received oral prednisone, tapered from 20 mg to 0 mg over 11 weeks. The primary endpoint was the proportion of patients in glucocorticoid-free remission at week 16; key secondary endpoints, including time to first relapse and cumulative glucocorticoid dose at weeks 16 and 24, were evaluated. Results From 20 November 2017 to 28 October 2019 39 patients were screened for eligibility; 19 patients received tocilizumab and 17 placebo. Glucocorticoid-free remission at week 16 was achieved in 12 out of 19 patients on tocilizumab (63.2%) and 2 out of 17 patients receiving placebo (11.8%, p=0.002), corresponding to an OR of 12.9 (95 % CI: 2.2 to 73.6) in favour of tocilizumab. Mean (±SD) time to first relapse was 130±13 and 82±11 days (p=0.007), respectively, and the median (IQR) cumulative glucocorticoid dose was 727 (721–842) mg and 935 (861–1244) mg (p=0.003), respectively. Serious adverse events were observed in five placebo patients and one tocilizumab patient. Conclusion In patients with new onset polymyalgia rheumatica undergoing rapid glucocorticoid tapering, tocilizumab was superior to placebo regarding sustained glucocorticoid-free remission, time to relapse and cumulative glucocorticoid dose. Trial registration number NCT03263715
T2-high asthma phenotypes across lifespan
Authors: Nicole Maison, Jimmy Omony, Sabina Illi, Dominik Thiele, Chrysanthi Skevaki, Anna-Maria Dittrich, Thomas Bahmer, Klaus Friedrich Rabe, Markus Weckmann, Christine Happle, Bianca Schaub, Meike Meyer, Svenja Foth, Ernst Rietschel, Harald Renz, Gesine Hansen, Matthias Volkmar Kopp, Erika von Mutius, Ruth Grychtol, Oliver Fuchs, Barbara Roesler, Nils Welchering, Naschla Kohistani-Greif, Johanna Kurz, Katja Landgraf-Rauf, Kristina Laubhahn, Claudia Liebl, Markus Ege, Alexander Hose, Esther Zeitlmann, Mira Berbig, Carola Marzi, Christina Schauberger, Ulrich Zissler, Carsten Schmidt-Weber, Isabell Ricklefs, Gesa Diekmann, Lena Liboschik, Gesche Voigt, Laila Sultansei, Gyde Nissen, Inke R. König, Anne-Marie Kirsten, Frauke Pedersen, Henrik Watz, Benjamin Waschki, Christian Herzmann, Mustafa Abdo, Heike Biller, Karoline I. Gaede, Xenia Bovermann, Alena Steinmetz, Berrit Liselotte Husstedt, Catharina Nitsche, Vera Veith, Marlen Szewczyk, Folke Brinkmann, Aydin Malik, Nicolaus Schwerk, Christian Dopfer, Mareike Price, Adan Chari Jirmo, Anika Habener, David S. DeLuca, Svenja Gaedcke, Bin Liu, Mifflin-Rae Calveron, Stefanie Weber, Tom Schildberg, Silke van Koningsbruggen-Rietschel, Miguel Alcazar
Journal: European Respiratory Journal (2022)

Rationale In adults, personalised asthma treatment targets patients with type 2 (T2)-high and eosinophilic asthma phenotypes. It is unclear whether such classification is achievable in children. Objectives To define T2-high asthma with easily accessible biomarkers and compare resulting phenotypes across all ages. Methods In the multicentre clinical All Age Asthma Cohort (ALLIANCE), 1125 participants (n=776 asthmatics, n=349 controls) were recruited and followed for 2 years (1 year in adults). Extensive clinical characterisation (questionnaires, blood differential count, allergy testing, lung function and sputum induction (in adults)) was performed at baseline and follow-ups. Interleukin (IL)-4, IL-5 and IL-13 were measured after stimulation of whole blood with lipopolysaccharide (LPS) or anti-CD3/CD28. Measurements and main results Based on blood eosinophil counts and allergen-specific serum IgE antibodies, patients were categorised into four mutually exclusive phenotypes: “atopy-only”, “eosinophils-only”, “T2-high” (eosinophilia + atopy) and “T2-low” (neither eosinophilia nor atopy). The T2-high phenotype was found across all ages, even in very young children in whom it persisted to a large degree even after 2 years of follow-up. T2-high asthma in adults was associated with childhood onset, suggesting early origins of this asthma phenotype. In both children and adults, the T2-high phenotype was characterised by excessive production of specific IgE to allergens (p&lt;0.0001) and, from school age onwards, by increased production of IL-5 after anti-CD3/CD28 stimulation of whole blood. Conclusions Using easily accessible biomarkers, patients with T2-high asthma can be identified across all ages delineating a distinct phenotype. These patients may benefit from therapy with biologicals even at a younger age.
Interpretation of the Efficacy of Multidisciplinary Geriatric Assessment Intervention on Chemotherapy-Related Toxic Effects in Older Adults With Cancer—Reply
Authors: Daneng Li, Mina S. Sedrak, William Dale
Journal: JAMA Oncology (2022)

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Long-term culture-expanded alveolar macrophages restore their full epigenetic identity after transfer in vivo
Authors: Sethuraman Subramanian, Clara Jana-Lui Busch, Kaaweh Molawi, Laufey Geirsdottir, Julien Maurizio, Stephanie Vargas Aguilar, Hassiba Belahbib, Gregory Gimenez, Ridzky Anis Advent Yuda, Michaela Burkon, Jérémy Favret, Sara Gholamhosseinian Najjar, Bérengère de Laval, Prashanth Kumar Kandalla, Sandrine Sarrazin, Lena Alexopoulou, Michael H. Sieweke
Journal: Nature Immunology (2022)
Youth and Parent Satisfaction With Clinical Use of the GlucoWatch G2 Biographer in the Management of Pediatric Type 1 Diabetes
Journal: Diabetes Care (2005)

OBJECTIVE—A continuous glucose monitor satisfaction scale (CGM-SAT) was evaluated during a 6-month randomized controlled trial of the GlucoWatch G2 Biographer (GW2B) in youths with type 1 diabetes. RESEARCH DESIGN AND METHODS—At the end of the 6-month trial, 97 parents and 66 older children who had been randomized to the GW2B group completed the CGM-SAT, which assesses satisfaction on 37 items using a five-point Likert scale. Descriptive analysis, calculation of several reliability estimates, and assessment of concurrent validity were performed. RESULTS—The CGM-SAT demonstrated high internal reliability (Cronbach’s α = 0.95 for parents and 0.94 for youths aged ≥11 years), split-half reliability (ρ = 0.91 for parents and 0.93 for youths), and parent-adolescent agreement (ρ = 0.68, P &amp;lt; 0.001). Convergent validity was supported by marginally significant associations with treatment adherence and frequency of GW2B use. CGM-SAT scores did not correlate significantly with changes in treatment adherence, quality of life, or diabetes-related anxiety from baseline to 6 months. Mean scores on CGM-SAT items indicated that 81% of parental responses and 73% of youths’ responses were less favorable than “neutral.” Descriptive analysis indicated the GW2B requires substantial improvement before it can achieve widespread clinical utility and acceptance. CONCLUSIONS—The results supported the psychometric properties of the CGM-SAT. The CGM-SAT warrants further research use and cross-validation with other continuous glucose monitors. This study provides a benchmark for comparison with new glucose sensors.
Fixed-duration ibrutinib plus venetoclax for first-line treatment of CLL: primary analysis of the CAPTIVATE FD cohort
Authors: Constantine S. Tam, John N. Allan, Tanya Siddiqi, Thomas J. Kipps, Ryan Jacobs, Stephen Opat, Paul M. Barr, Alessandra Tedeschi, Livio Trentin, Rajat Bannerji, Sharon Jackson, Bryone J. Kuss, Carol Moreno, Edith Szafer-Glusman, Kristin Russell, Cathy Zhou, Joi Ninomoto, James P. Dean, William G. Wierda, Paolo Ghia
Journal: Blood (2022)

CAPTIVATE (NCT02910583) is an international phase 2 study in patients aged ≤70 years with previously untreated chronic lymphocytic leukemia (CLL). Results from the cohort investigating fixed-duration (FD) treatment with ibrutinib plus venetoclax are reported. Patients received 3 cycles of ibrutinib lead-in then 12 cycles of ibrutinib plus venetoclax (oral ibrutinib [420 mg/d]; oral venetoclax [5-week ramp-up to 400 mg/d]). The primary endpoint was complete response (CR) rate. Hypothesis testing was performed for patients without del(17p) with prespecified analyses in all treated patients. Secondary endpoints included undetectable minimal residual disease (uMRD) rates, progression-free survival (PFS), overall survival (OS), and safety. Of the 159 patients enrolled and treated, 136 were without del(17p). The median time on study was 27.9 months, and 92% of patients completed all planned treatment. The primary endpoint was met, with a CR rate of 56% (95% confidence interval [CI], 48-64) in patients without del(17p), significantly higher than the prespecified 37% minimum rate (P < .0001). In the all-treated population, CR rate was 55% (95% CI, 48-63); best uMRD rates were 77% (peripheral blood [PB]) and 60% (bone marrow [BM]); 24-month PFS and OS rates were 95% and 98%, respectively. At baseline, 21% of patients were in the high tumor burden category for tumor lysis syndrome (TLS) risk; after ibrutinib lead-in, only 1% remained in this category. The most common grade ≥3 adverse events (AEs) were neutropenia (33%) and hypertension (6%). First-line ibrutinib plus venetoclax represents the first all-oral, once-daily, chemotherapy-free FD regimen for patients with CLL. FD ibrutinib plus venetoclax achieved deep, durable responses and promising PFS, including in patients with high-risk features.
Persistence and effectiveness of the IL-12/23 pathway inhibitor ustekinumab or tumour necrosis factor inhibitor treatment in patients with psoriatic arthritis: 1-year results from the real-world PsABio Study
Authors: Laure Gossec, Stefan Siebert, Paul Bergmans, Kurt de Vlam, Elisa Gremese, Beatríz Joven-Ibáñez, Tatiana V Korotaeva, Frederic Lavie, Wim Noël, Michael T Nurmohamed, Petros P Sfikakis, Elke Theander, Josef S Smolen
Journal: Annals of the Rheumatic Diseases (2022)

Objective We evaluated real-world treatment persistence and effectiveness at 1 year following initiation of IL-12/23 inhibitor ustekinumab or a tumour necrosis factor inhibitor (TNFi) for psoriatic arthritis (PsA). Methods PsABio ( NCT02627768 ), a prospective, observational study, followed patients with PsA prescribed first-line to third-line ustekinumab or TNFi. Drug persistence, effectiveness (achievement of clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) low disease activity (LDA)/remission and minimal disease activity/very low disease activity (MDA/VLDA)), and safety were assessed every 6 months. In addition to descriptive statistics, propensity score (PS)-adjusted comparisons across cohorts were performed. Results At 1 year, overall persistence was similar in the ustekinumab (n=317/438, 72.4%) and TNFi (n=321/455, 70.5%) groups. PS-adjusted HR (95% CI) for stopping/switching ustekinumab versus TNFi was 0.82 (0.60; 1.13). cDAPSA LDA (including remission)/remission was achieved in 55.9%/22.1% of ustekinumab-treated and 67.1%/31.7% of TNFi-treated patients; PS-adjusted ORs (95% CI) were 0.80 (0.57; 1.10) for cDAPSA LDA and 0.73 (0.49; 1.07) for remission. MDA/VLDA was achieved in 34.2%/11.9% of ustekinumab-treated and 43.1%/12.6% of TNFi-treated patients; PS-adjusted ORs (95% CI) were 0.89 (0.63; 1.26) for MDA and 0.90 (0.54; 1.49) for VLDA. The safety profiles were similar in both groups. Conclusion In the real-world PsABio Study, after 1 year of treatment, although unadjusted persistence was numerically slightly higher for ustekinumab versus TNFi and unadjusted effectiveness was numerically slightly higher for TNFi versus ustekinumab, the PS-adjusted comparisons demonstrated comparable overall persistence, effectiveness and safety for both modes of action in PsA.
The burden of asthma, hay fever and eczema in adults in 17 countries: GAN Phase I study
Authors: Kevin Mortimer, Maia Lesosky, Luis García-Marcos, M. Innes Asher, Neil Pearce, Eamon Ellwood, Karen Bissell, Asma El Sony, Philippa Ellwood, Guy B. Marks, Antonela Martínez-Torres, Eva Morales, Virginia Perez-Fernandez, Steven Robertson, Charlotte E. Rutter, Richard J. Silverwood, David P. Strachan, Chen-Yuan Chiang
Journal: European Respiratory Journal (2022)

Aims Asthma, hay fever and eczema are three common chronic conditions. There have been no recent multi-country data on the burden of these three conditions in adults; the aims of this study are to fill this evidence gap. Methods The Global Asthma Network Phase I is a multi-country cross-sectional population-based study using the same core methodology as the International Study of Asthma and Allergies in Childhood Phase III. It provides data on the burden of asthma, hay fever and eczema in children and adolescents, and, for the first time, in their parents/guardians. Results Data were available from 193 912 adults (104 061 female; mean± sd age 38±7.5 years) in 43 centres in 17 countries. The overall prevalence (range) of symptoms was 6.6% (0.9–32.7%) for current wheeze, 4.4% (0.9–29.0%) for asthma ever, 14.4% (2.8–45.7%) for hay fever ever and 9.9% (1.6–29.5%) for eczema ever. Centre prevalence varied considerably both between countries and within countries. There was a moderate correlation between hay fever ever and asthma ever, and between eczema ever and hay fever ever at the centre level. There were moderate to strong correlations between indicators of the burden of disease reported in adults and the two younger age groups. Conclusion We found evidence for a substantial burden of asthma, hay fever ever and eczema ever in the countries examined, highlighting the major public health importance of these diseases. Prevention strategies and equitable access to effective and affordable treatments for these three conditions would help mitigate the avoidable morbidity they cause.