tbuckley/cabot-search huggingface dataset:
Intersectionality of stigmas and health-related quality of life in people ageing with HIV in China, Europe, and Latin America
Authors: Evelyn Hsieh, Rosa Polo, Han-Zhu Qian, Maria J Fuster-RuizdeApodaca, Julia del Amo
Journal: The Lancet Healthy Longevity (2022)

People ageing with HIV face crucial challenges that can compromise their long-term health, one of which is stigma. HIV-related stigma can interact with other coexistent inequities to create a unique oppression system that results in traumatic experiences. This intersectionality of stigmas represents a new inequality that is greater than the sum of the original component inequalities. In this Series paper we review the literature regarding the intersectionality of HIV-related and ageing-related stigma and health-related quality of life among people ageing with HIV in China, Europe, and Latin America—three regions that represent distinct epidemiological and cultural trends in terms of HIV and ageing. Substantial gaps in the literature were identified, in particular a scarcity of data from Latin America. We also found inconsistencies between countries in terms of definitions and reporting practices related to people ageing with HIV. Research that fully considers the intersectional stigmas faced by this vulnerable population will contribute to advancing the United Nations 2030 Agenda for Sustainable Development.
The identification of prevalent tuberculosis disease through infection screening among high-risk migrants in the Netherlands
Authors: Ineke Spruijt, Chantal Joren, Henrieke Schimmel, Frouke Procee, Yalda Alam, Susan van den Hof, Connie Erkens
Journal: European Respiratory Journal (2022)

<b>TB symptom and TB infection screening has potential to replace current chest radiography screening among high TB risk migrants in low burden countries. Screening programmes should be evaluated through epidemiological data and assessing progression rates.</b>https://bit.ly/362r25u
Association of Dual Medicare and Medicaid Eligibility With Outcomes and Spending for Cancer Surgery in High-Quality Hospitals
Authors: Kathryn Taylor, Adrian Diaz, Usha Nuliyalu, Andrew Ibrahim, Hari Nathan
Journal: JAMA Surgery (2022)

<h3>Importance</h3> Although dual eligibility (DE) status for Medicare and Medicaid has been used for social risk stratification in value-based payment programs, little is known about the interplay between hospital quality and disparities in outcomes and spending by social risk. <h3>Objective</h3> To assess whether treatment at high-quality hospitals mitigates DE-associated disparities in outcomes and spending for cancer surgery. <h3>Design, Setting, and Participants</h3> Retrospective cohort study from January 1, 2014, to December 31, 2018, evaluating inpatient surgery at acute care hospitals. A total of 119 757 Medicare beneficiaries aged 65 years or older who underwent colectomy, rectal resection, lung resection, or pancreatectomy were evaluated. Data were analyzed between November 1, 2020, and April 30, 2021. <h3>Exposures</h3> Medicare and Medicaid DE status and hospital quality. <h3>Main Outcomes and Measures</h3> Postoperative complications, readmission, and mortality by DE status and hospital quality. <h3>Results</h3> Overall, 119 757 Medicare beneficiaries underwent colectomy, rectal resection, lung resection, or pancreatectomy. The mean (SD) age was 75.3 (6.7) years, 61 617 (51.5%) were women, 7677 (6.4%) were Black, 106 099 (88.6%) were White, and 5981 (5.0%) identified as another race or ethnicity; 11.3% had DE status. Dually eligible patients were more likely to be discharged to a facility (colectomy, 15.0% [95% CI, 14.7%-15.3%] vs 23.9% [95% CI, 22.9%-24.9%]; proctectomy, 18.7% [95% CI, 18.0%-19.3%] vs 26.9% [95% CI, 24.9%-28.9%]; lung resection, 11.0% [95% CI, 10.7%-11.3%] vs 17.9% [95% CI, 16.8%-18.9%]; pancreatectomy, 23.5% [95% CI, 22.5%-24.4%] vs 30.0% [95% CI, 26.5%-33.5%]). Differences in postacute care use persisted even after accounting for postoperative complications and contributed to variation in spending. Compared with the lowest-quality hospitals, DE patients had improved rates of discharge to a facility (22.7% vs 19.3%) and spending ($22 577 vs $20 100) but rates remained increased compared with Medicare patients even at the highest-quality hospitals. <h3>Conclusions and Relevance</h3> The findings of this study indicate that, even among the highest-quality hospitals, DE patients had poorer outcomes and higher spending. Dually eligible patients were more likely to be discharged to a facility and therefore incurred higher postacute care costs. Although treatment at high-quality hospitals is associated with reduced differences in outcomes, DE patients remain at high risk for adverse postoperative outcomes and increased readmissions and postacute care use.
Genomic characterization of functional high-risk multiple myeloma patients
Authors: Cinnie Yentia Soekojo, Tae-Hoon Chung, Muhammad Shaheryar Furqan, Wee Joo Chng
Journal: Blood Cancer Journal (2022)

Multiple myeloma (MM) patients with suboptimal response to induction therapy or early relapse, classified as the functional high-risk (FHR) patients, have been shown to have poor outcomes. We evaluated newly-diagnosed MM patients in the CoMMpass dataset and divided them into three groups: genomic high-risk (GHR) group for patients with t(4;14) or t(14;16) or complete loss of functional TP53 (bi-allelic deletion of TP53 or mono-allelic deletion of 17p13 (del17p13) and TP53 mutation) or 1q21 gain and International Staging System (ISS) stage 3; FHR group for patients who had no markers of GHR group but were refractory to induction therapy or had early relapse within 12 months; and standard-risk (SR) group for patients who did not fulfill any of the criteria for GHR or FHR. FHR patients had the worst survival. FHR patients are characterized by increased mutations affecting the IL-6/JAK/STAT3 pathway, and a gene expression profile associated with aberrant mitosis and DNA damage response. This is also corroborated by the association with the mutational signature associated with abnormal DNA damage response. We have also developed a machine learning based classifier that can identify most of these patients at diagnosis.
Targeting of the alpha<sub>v</sub>beta<sub>3</sub>integrin complex by CAR-T cells leads to rapid regression of diffuse intrinsic pontine glioma and glioblastoma
Authors: Dustin A Cobb, Jacopo de Rossi, Lixia Liu, Erin An, Daniel W Lee
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Diffuse intrinsic pontine glioma (DIPG) and glioblastoma (GBM) are two highly aggressive and generally incurable gliomas with little therapeutic advancements made in the past several decades. Despite immense initial success of chimeric antigen receptor (CAR) T cells for the treatment of leukemia and lymphoma, significant headway into the application of CAR-T cells against solid tumors, including gliomas, is still forthcoming. The integrin complex alpha v beta 3 (α v β 3 ) is present on multiple and diverse solid tumor types and tumor vasculature with limited expression throughout most normal tissues, qualifying it as an appealing target for CAR-T cell-mediated immunotherapy. Methods Patient-derived DIPG and GBM cell lines were evaluated by flow cytometry for surface expression of α v β 3 . Second-generation CAR-T cells expressing an anti-α v β 3 single-chain variable fragment were generated by retroviral transduction containing either a CD28 or 4-1BB costimulatory domain and CD3zeta. CAR-T cells were evaluated by flow cytometry for CAR expression, memory phenotype distribution, and inhibitory receptor profile. DIPG and GBM cell lines were orthotopically implanted into NSG mice via stereotactic injection and monitored with bioluminescent imaging to evaluate α v β 3 CAR-T cell-mediated antitumor responses. Results We found that patient-derived DIPG cells and GBM cell lines express high levels of surface α v β 3 by flow cytometry, while α v β 3 is minimally expressed on normal tissues by RNA sequencing and protein microarray. The manufactured CAR-T cells consisted of a substantial frequency of favorable early memory cells and a low inhibitory receptor profile. α v β 3 CAR-T cells demonstrated efficient, antigen-specific tumor cell killing in both cytotoxicity assays and in in vivo models of orthotopically and stereotactically implanted DIPG and GBM tumors into relevant locations in the brain of NSG mice. Tumor responses were rapid and robust with systemic CAR-T cell proliferation and long-lived persistence associated with long-term survival. Following tumor clearance, TCF-1 + α v β 3 CAR-T cells were detectable, underscoring their ability to persist and undergo self-renewal. Conclusions These results highlight the potential of α v β 3 CAR-T cells for immunotherapeutic treatment of aggressive brain tumors with reduced risk of on-target, off-tumor mediated toxicity due to the restricted nature of α v β 3 expression in normal tissues.
Neural control of immune cell trafficking
Authors: Scott N. Mueller
Journal: The Journal of Experimental Medicine (2022)

Leukocyte trafficking between blood and tissues is an essential function of the immune system that facilitates humoral and cellular immune responses. Within tissues, leukocytes perform surveillance and effector functions via cell motility and migration toward sites of tissue damage, infection, or inflammation. Neurotransmitters that are produced by the nervous system influence leukocyte trafficking around the body and the interstitial migration of immune cells in tissues. Neural regulation of leukocyte dynamics is influenced by circadian rhythms and altered by stress and disease. This review examines current knowledge of neuro–immune interactions that regulate leukocyte migration and consequences for protective immunity against infections and cancer.
Increased Genioglossus Muscle FDG Activity Due to Using Pacifier
Authors: Celia Tong, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2022)

Abstract An 18-month-old girl with history of liver transplant underwent FDG PET/CT to evaluate posttransplant lymphoproliferative disorder. In addition to multistation hypermetabolic lymphadenopathy and abnormal activity in the liver, stomach, and small bowel, in keeping with known posttransplant lymphoproliferative disorder, the images also showed focal activity in the submental region. This submental activity persisted on 2 separate follow-up FDG PET/CT studies, even though other foci of abnormal activity resolved after chemotherapy. Records revealed that the patient was sucking on a pacifier prior to all 3 FDG PET/CT studies, and the submental uptake corresponded with genioglossus muscle activity.
Association of Clonal Hematopoiesis of Indeterminate Potential with Worse Kidney Function and Anemia in Two Cohorts of Patients with Advanced Chronic Kidney Disease
Authors: Caitlyn Vlasschaert, Amy J.M. McNaughton, Michael Chong, Elina K. Cook, Wilma Hopman, Bryan Kestenbaum, Cassianne Robinson-Cohen, Jocelyn Garland, Sarah M. Moran, Guillaume Paré, Catherine M. Clase, Mila Tang, Adeera Levin, Rachel Holden, Michael J. Rauh, Matthew B. Lanktree
Journal: Journal of the American Society of Nephrology (2022)

Significance Statement Clonal hematopoiesis of indeterminate potential (CHIP), a premalignant expansion of clonal leukocytes caused by acquired somatic mutations in myeloid stem/progenitor cells, occurs in 10%–15% of the general population aged 65 years or older. This proinflammatory condition appears causally associated with cardiovascular disease and death. The authors found that 43 of 172 (25%) individuals with advanced CKD had CHIP. Those with CHIP had a 2.2-fold greater risk of kidney failure over 5 years of follow-up and were more likely to have complications of CKD (including anemia) compared with those without CHIP. More research, including studies in animal models, is needed to understand the relationship between CHIP and CKD. CHIP-related inflammation might offer a novel therapeutic target for those with CHIP and CKD. Background Clonal hematopoiesis of indeterminate potential (CHIP) is an inflammatory premalignant disorder resulting from acquired genetic mutations in hematopoietic stem cells. This condition is common in aging populations and associated with cardiovascular morbidity and overall mortality, but its role in CKD is unknown. Methods We performed targeted sequencing to detect CHIP mutations in two independent cohorts of 87 and 85 adults with an eGFR&lt;60 ml/min per 1.73m 2 . We also assessed kidney function, hematologic, and mineral bone disease parameters cross-sectionally at baseline, and collected creatinine measurements over the following 5-year period. Results At baseline, CHIP was detected in 18 of 87 (21%) and 25 of 85 (29%) cohort participants. Participants with CHIP were at higher risk of kidney failure, as predicted by the Kidney Failure Risk Equation (KFRE), compared with those without CHIP. Individuals with CHIP manifested a 2.2-fold increased risk of a 50% decline in eGFR or ESKD over 5 years of follow-up (hazard ratio 2.2; 95% confidence interval, 1.2 to 3.8) in a Cox proportional hazard model adjusted for age, sex, and baseline eGFR. The addition of CHIP to 2-year and 5-year calibrated KFRE risk models improved ESKD predictions. Those with CHIP also had lower hemoglobin, higher ferritin, and higher red blood cell mean corpuscular volume versus those without CHIP. Conclusions In this exploratory analysis of individuals with preexisting CKD, CHIP was associated with higher baseline KFRE scores, greater progression of CKD, and anemia. Further research is needed to define the nature of the relationship between CHIP and kidney disease progression.
Error in Abstract and Methods
Journal: JAMA Oncology (2022)

Caicun Zhou, PhD, MD; Suresh S. Ramalingam, MD; Tae Min Kim, MD, PhD; Sang-We Kim, MD; James Chih-Hsin Yang, MD; Gregory J. Riely, MD; Tarek Mekhail, MD; Danny Nguyen, MD; Maria R. Garcia Campelo, MD; Enriqueta Felip, MD; Sylvie Vincent, PhD; Shu Jin, MS; Celina Griffin, PharmD; Veronica Bunn, PhD; Jianchang Lin, PhD; Huamao M. Lin, PhD; Minal Mehta, MBBS; Pasi A. Jänne, MD, PhD
Invasive aspergillosis-on-chip: A quantitative treatment study of human Aspergillus fumigatus infection
Authors: T.N.M. Hoang, Z. Cseresnyés, S. Hartung, M. Blickensdorf, C. Saffer, K. Rennert, A.S. Mosig, M. von Lilienfeld-Toal, M.T. Figge
Journal: Biomaterials (2022)

Invasive pulmonary aspergillosis is associated with a high mortality rate and poses a direct threat to immunocompromised patients. Here, we present the invasive aspergillosis-on-chip (IAC) model to investigate Aspergillus fumigatus infection in vitro. The model allows the study of the lateral growth and the invasive behaviour of fungal hyphae from the epithelium into the endothelial cell layer in an alveolus-on-chip model. We established an algorithm-based analysis pipeline for three-dimensional confocal microscopy images to visualize and quantify fungal morphology, including hyphal growth and branching. Human macrophages in the IAC model partially inhibited the growth of the fungus, contributed to the release of proinflammatory cytokines (IL-1, IL-6, TNF) and chemokines (IL-8 and MCP-1) associated with an increased number of invasive hyphae. Similar to in vivo, the application of the fungistatic drug caspofungin limited the fungal growth and resulted in morphological changes of the hyphal tree previously described in other studies. The IAC infection model allows the identification and characterization of cellular infection targets and in vitro testing of antifungal drugs in clinically relevant concentrations. It thus represents a promising tool to broaden the understanding of pathogenicity and pathophysiology of invasive aspergillosis.
Glycemic Control and Clinical Outcomes in U.S. Patients With COVID-19: Data From the National COVID Cohort Collaborative (N3C) Database
Authors: Rachel Wong, Margaret Hall, Rohith Vaddavalli, Adit Anand, Neha Arora, Carolyn T. Bramante, Victor Garcia, Steven Johnson, Mary Saltz, Jena S. Tronieri, Yun Jae Yoo, John B. Buse, Joel Saltz, Joshua Miller, Richard Moffitt, Tellen Bennett, Elena Casiraghi, Christopher Chute, Peter DeWitt, Michael Evans, Kenneth Gersing, Andrew Girvin, Melissa Haendel, Jeremy Harper, Janos Hajagos, Stephanie Hong, Jared Huling, Emily Pfaff, Jane Reusch, Til Sturmer, Kenneth Wilkins, Jacob Wooldridge
Journal: Diabetes Care (2022)

OBJECTIVE The purpose of the study is to evaluate the relationship between HbA1c and severity of coronavirus disease 2019 (COVID-19) outcomes in patients with type 2 diabetes (T2D) with acute COVID-19 infection. RESEARCH DESIGN AND METHODS We conducted a retrospective study using observational data from the National COVID Cohort Collaborative (N3C), a longitudinal, multicenter U.S. cohort of patients with COVID-19 infection. Patients were ≥18 years old with T2D and confirmed COVID-19 infection by laboratory testing or diagnosis code. The primary outcome was 30-day mortality following the date of COVID-19 diagnosis. Secondary outcomes included need for invasive ventilation or extracorporeal membrane oxygenation (ECMO), hospitalization within 7 days before or 30 days after COVID-19 diagnosis, and length of stay (LOS) for patients who were hospitalized. RESULTS The study included 39,616 patients (50.9% female, 55.4% White, 26.4% Black or African American, and 16.1% Hispanic or Latino, with mean ± SD age 62.1 ± 13.9 years and mean ± SD HbA1c 7.6% ± 2.0). There was an increasing risk of hospitalization with incrementally higher HbA1c levels, but risk of death plateaued at HbA1c &amp;gt;8%, and risk of invasive ventilation or ECMO plateaued &amp;gt;9%. There was no significant difference in LOS across HbA1c levels. CONCLUSIONS In a large, multicenter cohort of patients in the U.S. with T2D and COVID-19 infection, risk of hospitalization increased with incrementally higher HbA1c levels. Risk of death and invasive ventilation also increased but plateaued at different levels of glycemic control.
Tumor Coverage vs Healthy Tissue Sparing—What Is the Balance When Palliation Is the Goal?
Authors: Ashley A. Weiner, Joel E. Tepper
Journal: JAMA Oncology (2022)

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Oral Contraceptives and the Risk of Myocardial Infarction
Journal: New England Journal of Medicine (1981)

Back-ground An association between the use of oral contraceptives and the risk of myocardial infarction has been found in some, but not all, studies.We investigated this association, according to the type of progestagen included in third-generation (i.e., desogestrel or gestodene) and second-generation (i.e., levonorgestrel) oral contraceptives, the dose of estrogen, and the presence or absence of prothrombotic mutations.Methods In a nationwide, population-based, casecontrol study, we identified and enrolled 248 women 18 through 49 years of age who had had a first myocardial infarction between 1990 and 1995 and 925 control women who had not had a myocardial infarction and who were matched for age, calendar year of the index event, and area of residence.Subjects supplied Information on oral-contraceptive use and major cardiovascular risk factors.An analysis for factor V Leiden and the G20210A mutation in the prothrombin gene was conducted in 217 patients and 763 controls.Results The odds ratio for myocardial infarction among women who used any type of combined oral contraceptive, äs compared with nonusers, was 2.0 (95 percent confidence interval, 1.5 to 2.8).The adjusted odds ratio was 2.5 (95 percent confidence interval, 1.5 to 4.1) among women who used second-generation oral contraceptives and 1.3 (95 percent confidence interval, 0.7 to 2.5) among those who used third-generation oral contraceptives.Among women who used oral contraceptives, the odds ratio was 2.1 (95 percent confidence interval, 1.5 to 3.0) for those without a prothrombotic mutation and 1.9 (95 percent confidence interval, 0.6 to 5.5) for those with a mutation.Conclusions The risk of myocardial infarction was increased among women who used second-generation oral contraceptives.The results with respect to the use of third-generation oral contraceptives were inconclusive but suggested that the risk was Iower than the risk associated with second-generation oral contraceptives.The risk of myocardial infarction was similar among women who used oral contraceptives whether or not they had a prothrombotic mutation.
EULAR recommendations for the management and vaccination of people with rheumatic and musculoskeletal diseases in the context of SARS-CoV-2: the November 2021 update
Authors: Robert B M Landewé, Féline P B Kroon, Alessia Alunno, Aurélie Najm, Johannes WJ Bijlsma, Gerd-Rüdiger R Burmester, Roberto Caporali, Bernard Combe, Richard Conway, Jeffrey R Curtis, Ori Elkayam, Laure Gossec, Marloes W Heijstek, Lukas Haupt, Annamaria Iagnocco, John D Isaacs, István Ábel Juhász, Suzi Makri, Xavier Mariette, Iain B McInnes, Puja Mehta, Ulf Mueller-Ladner, Hendrik Schulze-Koops, Josef S Smolen, Dieter Wiek, Kevin L Winthrop, Victoria Navarro-Compán, Pedro M Machado
Journal: Annals of the Rheumatic Diseases (2022)

The first EULAR provisional recommendations on the management of rheumatic and musculoskeletal diseases (RMDs) in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), largely based on expert opinion, were published in June 2020. Since then, an unprecedented number of clinical studies have accrued in the literature. Several SARS-CoV-2 vaccines have been approved for population-wide vaccination programmes in EULAR-affiliated countries. Studies regarding vaccination of patients with (inflammatory) RMDs have released their first results or are underway. EULAR found it opportune to carefully review to what extent the initially consensus expert recommendations stood the test of time, by challenging them with the recently accumulated body of scientific evidence, and by incorporating evidence-based advice on SARS-CoV-2 vaccination. EULAR started a formal (first) update in January 2021, performed a systematic literature review according to EULAR’s standard operating procedures and completed a set of updated overarching principles and recommendations in July 2021. Two points to consider were added in November 2021, because of recent developments pertaining to additional vaccination doses.