tbuckley/cabot-search huggingface dataset:
HIV incidence and factors associated with HIV risk among people who inject drugs engaged with harm-reduction programmes in four provinces in South Africa: a retrospective cohort study
Authors: Adelina Artenie, Rachel Perry, Memory Mahaso, Thenjiwe Jankie, Anna L McNaughton, Jack Stone, Peter Vickerman, Andrew Scheibe
Journal: The Lancet HIV (2024)

SummaryBackgroundHIV incidence among people who inject drugs in South Africa has never been estimated. We aimed to estimate HIV incidence and associations with risk and protective factors among people who inject drugs engaged with harm-reduction services.MethodsFor this retrospective cohort study we used programmatic data collected from April 1, 2019, to March 30, 2022, by the Networking HIV and AIDS Community of South Africa, which offers harm-reduction services and HIV testing to people who inject drugs. During this 3-year period, services were delivered through drop-in centres and outreach in four South African provinces: Gauteng, KwaZulu-Natal, Western Cape, and Eastern Cape. Our cohort comprised people who inject drugs who did not self-report being HIV positive, were HIV negative at first testing, and had at least one follow-up test. Data were collected by outreach teams. We estimated HIV incidence, assuming seroconversions occurred at the midpoint between the last negative test and first positive test. We assessed associations between HIV seroconversion risk and several factors with Cox regression models, including sociodemographic characteristics, primary drugs used, uptake of interventions (ie, number of harm-reduction packs and opioid agonist treatment [OAT]), and HIV testing interval.FindingsOf 31 182 people who inject drugs accessing harm-reduction services, 20 955 (including 3409 self-reporting being HIV positive) were not tested for HIV. Of 10 227 people who tested at least once, 8152 were HIV negative at first test and of these, 2402 had at least two tests and formed the study cohort. Overall, 283 (11·8%) people who inject drugs acquired HIV over 2306·1 person-years. HIV incidence was higher in Gauteng (16·7 per 100 person-years; 95% CI 14·5–19·1) and KwaZulu-Natal (14·9 per 100 person-years; 11·3–19·3), than in the Eastern Cape (5·0 per 100 person-years; 2·3–9·6) and Western Cape (3·2 per 100 person-years; 1·9–4·9). In multivariable Cox models, HIV acquisition risk varied by race, primary drugs used, and interval between HIV tests. Additionally, people who injected drugs and received OAT in the past year had lower HIV risk (adjusted hazard ratio 0·48; 95% CI 0·22–1·03) than people who did not receive OAT, although the 95% CI was wide and crossed the null.InterpretationOur study highlights a pressing need for scale-up of HIV prevention strategies, particularly opioid agonist treatment, for people who inject drugs in South Africa. Dedicated investments are needed to develop monitoring systems for HIV incidence, risk behaviours, and uptake of interventions to ensure effective and equitable programmes.FundingWellcome Trust, Canadian Institutes of Health Research, and Global Fund to Fight AIDS, Tuberculosis and Malaria.
Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): one cohort of a phase 2, multicentre, open-label, non-comparative study
Authors: Hope S Rugo, Florence Lerebours, Eva Ciruelos, Pamela Drullinsky, Manuel Ruiz-Borrego, Patrick Neven, Yeon Hee Park, Aleix Prat, Thomas Bachelot, Dejan Juric, Nicholas Turner, Nickolas Sophos, Juan Pablo Zarate, Christina Arce, Yu-Ming Shen, Stuart Turner, Hemanth Kanakamedala, Wei-Chun Hsu, Stephen Chia
Journal: The Lancet Oncology (2024)
Serum GFAP and UCH-L1 for the identification of clinically important traumatic brain injury in children in France: a diagnostic accuracy substudy
Authors: Antoine Puravet, Charlotte Oris, Bruno Pereira, Samy Kahouadji, Philippe Gonzalo, Damien Masson, Julie Durif, Catherine Sarret, Vincent Sapin, Damien Bouvier
Journal: The Lancet Child & Adolescent Health (2024)
Efficacy and safety of filgotinib as induction and maintenance therapy for Crohn's disease (DIVERSITY): a phase 3, double-blind, randomised, placebo-controlled trial
Authors: Séverine Vermeire, Stefan Schreiber, David T Rubin, Geert D'Haens, Walter Reinisch, Mamoru Watanabe, Rajiv Mehta, Xavier Roblin, Ian Beales, Piotr Gietka, Toshifumi Hibi, Ihor Hospodarskyy, Timothy Ritter, Mark C Genovese, Paul Kwon, Eva Santermans, Franck-Olivier Le Brun, Rahul Barron, Tomasz Masior, Silvio Danese
Journal: The Lancet. Gastroenterology & hepatology (2024)
Impact of disease-modifying therapies on pregnancy outcomes in multiple sclerosis: a prospective cohort study from the German multiple sclerosis and pregnancy registry
Authors: Nadine Bast, Karen Dost-Kovalsky, Sabrina Haben, Natalia Friedmann, Laura Witt, Theresa Oganowski, Ralf Gold, Sandra Thiel, Kerstin Hellwig
Journal: The Lancet Regional Health - Europe (2024)
Effect of a youth-led early childhood care and education programme on children's development and learning in rural Sindh, Pakistan (LEAPS): a stepped-wedge cluster-randomised implementation trial
Authors: Aisha K Yousafzai, Saima Siyal, Emily E Franchett, Quanyi Dai, Karima Rehmani, Christopher R Sudfeld, Shelina Bhamani, Shahnaz Hakro, Chin R Reyes, Günther Fink, Liliana A Ponguta
Journal: The Lancet Child & Adolescent Health (2024)
Brentuximab Vedotin, Nivolumab, Doxorubicin, and Dacarbazine for Advanced-Stage Classical Hodgkin Lymphoma
Authors: Hun Ju Lee, Rod Ramchandren, Judah Friedman, Jason M. Melear, Ian W. Flinn, John M. Burke, Yuliya Linhares, Paul Alan Gonzales, Matthew Peterson, Mihir Raval, Rangaswamy Chintapatla, Tatyana A. Feldman, Habte A. Yimer, Miguel Islas-Ohlmayer, Ameet Patel, Leland Metheny, Asad Dean, Vishal Rana, Mitul D. Gandhi, John S Renshaw, Linda Ho, Michelle A. Fanale, Wenchuan Guo, Christopher A. Yasenchak
Journal: Blood (2024)
Development and Validation of the RSClinN+ Tool to Predict Prognosis and Chemotherapy Benefit for Hormone Receptor–Positive, Node-Positive Breast Cancer
Authors: Lajos Pusztai, Jess R. Hoag, Kathy S. Albain, William E. Barlow, Salomon M. Stemmer, Allison Meisner, Gabriel N. Hortobagyi, Steven Shak, James M. Rae, Rick Baehner, Priyanka Sharma, Kevin M. Kalinsky
Journal: Journal of Clinical Oncology (2024)

Clinicopathological factors and the 21-gene Oncotype DX Breast Recurrence Score (RS) test both influence prognosis. Our goal was to develop a new tool, RSClinN+, to individualize recurrence risk and chemotherapy benefit predictions by menopausal status for patients with HR+/human epidermal growth factor receptor 2-negative, lymph node-positive breast cancer by integrating the RS result with clinicopathological factors (grade, tumor size, age). We used patient-level data from 5,283 patients treated with chemoendocrine therapy (CET) versus endocrine therapy alone (ET) in the S1007 (N = 4,916) and S8814 (N = 367) trials to develop the tool. Cox proportional hazards regression models stratified by trial were used to estimate 5-year invasive disease-free survival for pre- and postmenopausal woman, respectively. The integrated RSClinN+ model was compared with RS alone and clinicopathological models using likelihood ratio tests. Absolute CET benefit was estimated as the difference between ET and CET risk estimates. Validation of RSClinN+ was performed in 592 patients with node-positive disease in the Clalit Health Services registry. RSClinN+ provides better prognostic information than RS model alone (premenopausal P = .034; postmenopausal P < .001) or clinicopathological model alone (premenopausal P = .002; postmenopausal, P < .001). In postmenopausal women, RS showed interaction with CET benefit (P = .016), with RSClinN+ absolute CET benefit ranging from <0.1% to 21.5% over RS ranges 0-50. In premenopausal patients with RS ≤25, there was no significant interaction between RS and CET benefit. In external validation, RSClinN+ risk estimates were prognostic (hazard ratio, 1.75 [95% CI, 1.38 to 2.20]) and concordant with observed risk (Lin's concordance, 0.92). RSClinN+ provides improved estimates of prognosis and absolute CET benefit for individual patients compared with RS or with clinical data alone and could be used in patient counseling.
Randomized, Phase III Trial of Mixed Formulation of Fosrolapitant and Palonosetron (HR20013) in Preventing Cisplatin-Based Highly Emetogenic Chemotherapy-Induced Nausea and Vomiting: PROFIT
Authors: Huaqiang Zhou, Yuanyuan Zhao, Mingjun Zhang, Jun Yao, Shuang Leng, Xiumin Li, Li Lin, Jinping Chen, Songnan Zhang, Xia Qin, Zhiquan Qin, Tienan Yi, Ruoyu Wang, Xiang Li, Yan Yu, Zhenghua Wang, Qinhong Zheng, Jiazhuan Mei, Aimin Zang, Na Li, Fengjun Cao, Ke Cao, Weiwei Li, Yanda Lu, Dang Lin, Yan Zhou, Runxiang Yang, Wenfeng Fang, Ningning Zhou, Yunpeng Yang, Yaxiong Zhang, Gang Chen, Ting Zhou, Xue Yang, Huan Wang, Yujiao Wang, Yan Huang, Li Zhang
Journal: Journal of Clinical Oncology (2024)

PURPOSE Mixed formulation of fosrolapitant and palonosetron (PALO), HR20013, is a novel fixed-dose intravenous antiemetic combination that could simultaneously antagonize neurokinin-1 and 5-hydroxytryptamine-3 receptors. This study was designed to evaluate the efficacy and safety of HR20013 plus dexamethasone (DEX) versus fosaprepitant (FAPR) plus PALO + DEX for preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC). METHODS This is a noninferiority study. Chemotherapy-naïve patients were randomly assigned 1:1 to receive HR20013 (day 1) or FAPR + PALO (day 1) before each cycle of cisplatin-based HEC (two cycles in total), together with oral DEX (day 1-4). The primary end point was overall (0-120 hours) complete response (CR; no vomiting/no rescue therapy) rate in cycle 1. The key secondary end point was CR rate at the beyond delayed phase (120-168 hours) in cycle 1. RESULTS Three hundred seventy-three patients were enrolled to receive HR20013 + DEX and 377 to FAPR + PALO + DEX. The overall CR rate in cycle 1 was 77.7% for HR20013 + DEX and 78.2% for FAPR + PALO + DEX (difference = –0.9% [95% CI, –6.7 to 5.0]; one-sided P &lt; .01), demonstrating that HR20013 + DEX was noninferior to FAPR + PALO + DEX. The superiority of HR20013 + DEX over FAPR + PALO + DEX in CR rate at the beyond delayed phase in cycle 1 was not met (90.3% v 86.5%; two-sided P = .11). In cycle 2, HR20013 + DEX showed greater proportions of patients reporting no impact on daily life at the delayed (24-120 hours) and beyond delayed phases compared with FAPR + PALO + DEX. The incidences of treatment-related adverse events were 35.7% during cycle 1 and 42.1% during entire study for HR20013 + DEX, versus 38.2% and 44.0% for FAPR + PALO + DEX. CONCLUSION HR20013 + DEX was noninferior to FAPR + PALO + DEX for preventing HEC-CINV and well tolerated, with the potential to reduce the impact of CINV on daily life.
Influence of Nucleophosmin ( <i>NPM1</i> ) Genotypes on Outcome of Patients With AML: An AIEOP-BFM and COG-SWOG Intergroup Collaboration
Authors: Claudia Tregnago, Maddalena Benetton, Rhonda E. Ries, Jack H. Peplinski, Todd A. Alonzo, Derek Stirewalt, Megan Othus, Nicolas Duployez, Edwin Sonneveld, Jonas Abrahamsson, Linda Fogelstrand, Nils von Neuhoff, Henrik Hasle, Dirk Reinhardt, Soheil Meshinchi, Franco Locatelli, Martina Pigazzi
Journal: Journal of Clinical Oncology (2024)

Several genomic subsets of NPM1 mutations with varying sequences (type A, B, D, etc) have been identified. Despite molecular heterogeneity, NPM1 mutations cumulatively portend a more favorable outcome, but biology and prognostic implications of different genomic subsets have not been extensively studied. In this multicentric study, we investigated the impact of NPM1 genotypes on patient's outcomes and interrogated the underlying biology of the different subtypes. Of more than 4,000 patients enrolled in multiple pediatric cooperative (AIEOP, BFM, ELAM02, NOPHO, DCOG, and COG trials), or adult (SWOG) trials, 348 pediatric and 75 adult AML patients with known NPM1 genotype and available outcome were selected for this study. Diverse NPM1 variants were correlated with the probabilities of overall survival (OS) and event-free survival. Nuclear localization and translational efficiency of the NPM1 variants was studied. Evaluation of clinical outcome on the basis of NPM1 genotypes showed that patients with type A, B, and other rare variants had similarly favorable outcomes, whereas those with type D had a significantly worse outcome (OS of 63% for type D v 86% for type non-D, P = .005). Multivariate analysis confirmed type D as an independent prognostic factor associated with inferior OS (hazard ratio, 3; P = .005). In vitro, we demonstrated that in type D versus type A synonymous variants, codon optimality plays major roles in determining gene expression levels, and translation efficiency, which resulted in a more expressed NPM1-D mRNA and protein, mediating peculiar mitochondrial gene expression. The evaluation of specific NPM1 genotypes identified AML patients with type D mutations being significantly associated with inferior outcomes, suggesting a reclassification of D cases to higher-risk groups.
Corrigendum to “Safety and efficacy of odronextamab in patients with relapsed or refractory follicular lymphoma”
Authors: T M Kim, M Taszner, S Novelli, S-G Cho, J C Villasboas, M Merli, A Jiménez-Ubieto, B Tessoulin, L M Poon, D Tucker, J Walewski, S Yi, Y Song, G Chong, E Bachy, S Guidez, A Alonso, D Jagadeesh, W Zhang, L Magnano, E Iskierka-Jażdżwska, M Tani, B Shen, A Uppala, M Zhu, S Shariff, J Brouwer-Visser, A Chaudhry, H Mohamed, S Ambati, S Luminari
Journal: Annals of Oncology (2024)
Corrigendum to “Understanding breast cancer complexity to improve patient outcomes: The St Gallen International Consensus Conference for the Primary Therapy of Individuals with Early Breast Cancer 2023”
Authors: G Curigliano, H J Burstein, M Gnant, S Loibl, D Cameron, M M Regan, C Denkert, P Poortmans, W P Weber, B Thürlimann
Journal: Annals of Oncology (2024)
Continuous Glucose Monitor Accuracy for Diabetes Management in Hospitalized Children
Authors: Neha Garg, Kamryn Lewis, Perrin C. White, Soumya Adhikari
Journal: Diabetes Care (2024)

OBJECTIVE The adoption of continuous glucose monitors (CGMs) in inpatient settings in the pediatric population has been slow because of a scarcity of data on their reliability in hospitalized children. RESEARCH DESIGN AND METHODS We retrospectively reviewed the accuracy of the Dexcom G6 CGM system in pediatric patients with diabetes admitted to our academic children’s hospital from March 2018 to September 2023. We cross-referenced the Dexcom Clarity database against an internal database of inpatient admissions to identify all children with CGM data admitted to the hospital. We recorded sensor glucose readings from Clarity and values for point-of-care (POC) glucose, blood urea nitrogen (BUN), and pH from the electronic medical record. CGM accuracy and clinical reliability were measured by mean absolute relative difference (MARD) and Clarke error grid (CEG) analyses. RESULTS There were 3,200 admissions of children with diabetes in this period, of which 277 (from 202 patients age 2–18 years) had associated CGM data. Paired CGM and POC measurements (n = 2,904) were compared, resulting in an MARD of 15.9%, with 96.6% of the values in zones A and B of the CEG analysis. Approximately 62% of paired values fell within a 15% or 15 mg/dL difference, whichever was larger (15%/15 mg/dL range), 74% within 20%/20, and 88% within 30%/30. Serum pH, sodium, and BUN had no impact on CGM values or absolute relative difference in linear regression analysis. CONCLUSIONS CGMs demonstrated acceptable accuracy in hospitalized children with diabetes. CGM data should be integrated into hospital electronic records to optimize management.
In Vivo Cardiovascular Molecular Imaging: Contributions to Precision Medicine and Drug Development
Authors: Jonathan R. Lindner, Matteo Morello
Journal: Circulation (2024)

Conventional forms of noninvasive cardiovascular imaging that evaluate morphology, function, flow, and metabolism play a vital role in individual treatment decisions, often based on guidelines. Innovations in molecular imaging have enhanced our ability to spatially quantify the expression of a wider array of disease-related proteins, genes, or cell types, or the activity of specific pathogenic pathways. These techniques, which usually rely on design of targeted imaging probes, have already been used extensively in cancer medicine and have now become part of cardiovascular care in conditions such as amyloidosis and sarcoidosis. The recognition that common cardiovascular conditions are caused by a substantial diversity of pathobiologic pathways and the diversity of therapies available for use have rekindled interest in expanding the role of molecular imaging of tissue phenotype to improve precision in diagnosis and therapeutic decision-making. The intent of this article is to raise awareness and understanding of approaches to molecular or cellular imaging of phenotype with targeted probes, and their potential to promote the principles of precision medicine. Also addressed are the diverse roles of molecular imaging to improve precision and efficiency of new drug development at the stages of candidate identification, preclinical testing, and clinical trials.
Post-ischemic inactivation of HIF Prolyl Hydroxylases in endothelium promotes maladaptive kidney repair by inducing glycolysis
Authors: Ratnakar Tiwari, Rajni Sharma, Ganeshkumar Rajendran, Gabriella S. Borkowski, Si Young An, Michael Schonfeld, James O’Sullivan, Matthew J. Schipma, Yalu Zhou, Guillaume Courbon, Benjamin R. Thomson, Valentin David, Susan E. Quaggin, Edward B. Thorp, Navdeep S. Chandel, Pinelopi P. Kapitsinou
Journal: Journal of Clinical Investigation (2024)

Ischemic acute kidney injury (AKI) is common in hospitalized patients and increases the risk for chronic kidney disease (CKD). Impaired endothelial cell (EC) functions are thought to contribute in AKI to CKD transition, but the underlying mechanisms remain unclear. Here, we identify a critical role for endothelial oxygen sensing prolyl hydroxylase domain (PHD) enzymes 1-3 in regulating postischemic kidney repair. In renal endothelium, we observed compartment-specific differences in the expression of the 3 PHD isoforms in both mice and humans. Postischemic concurrent inactivation of endothelial PHD1, PHD2, and PHD3 but not PHD2 alone promoted maladaptive kidney repair characterized by exacerbated tissue injury, fibrosis, and inflammation. scRNA-Seq analysis of the postischemic endothelial PHD1, PHD2, and PHD3-deficient (PHDTiEC) kidney revealed an endothelial hypoxia and glycolysis-related gene signature, also observed in human kidneys with severe AKI. This metabolic program was coupled to upregulation of the SLC16A3 gene encoding the lactate exporter monocarboxylate transporter 4 (MCT4). Strikingly, treatment with the MCT4 inhibitor syrosingopine restored adaptive kidney repair in PHDTiEC mice. Mechanistically, MCT4 inhibition suppressed proinflammatory EC activation, reducing monocyte-EC interaction. Our findings suggest avenues for halting AKI to CKD transition based on selectively targeting the endothelial hypoxia-driven glycolysis/MCT4 axis.
Cerebral hemodynamics and oxygen metabolism in patients with milder and severe forms of sickle cell disease and thalassemia
Authors: Liza Afzali‐Hashemi, Koen P. A. Baas, Anouk Schrantee, Erfan Nur, Chau Vu, Soyoung Choi, Silvie Suriany, John C. Wood, Aart J. Nederveen, Bart J. Biemond
Journal: HemaSphere (2024)

Abstract Silent cerebral infarcts (SCIs) are present in patients with sickle cell disease (SCD) and thalassemia, but the pathophysiology of SCIs is not fully understood. Previous studies mainly focused on cerebral hemodynamics and oxygen metabolism in patients with severe SCD (HbSS/HbSβ°) but not in milder forms of SCD (HbSC/HbSβ + ) and thalassemia despite the high prevalence of SCIs in these patients. In this work, we studied the cerebral hemodynamics and oxygen metabolism, and SCI lesion load in 75 severe and 26 mild adult SCD patients, 18 thalassemia patients (as anemic comparison group), and 30 healthy controls before and after a vasodilatory challenge with acetazolamide. Cerebral blood flow was significantly higher in patients with severe SCD and thalassemia compared to patients with mild SCD and controls ( p &lt; 0.05). Conversely, oxygen extraction fraction and cerebral metabolic rate of oxygen (CMRO 2 ) were significantly lower in patients with severe SCD and thalassemia compared to other groups ( p &lt; 0.01). In contrast, no difference in SCI volumes was found between mild and severe SCD and thalassemia patients. After acetazolamide administration, oxygen delivery increased less in severe SCD and thalassemia patients compared to other groups ( p &lt; 0.01) and CMRO 2 decreased only in severe SCD patients ( p &lt; 0.01). Given the reduced CMRO 2 values in severe SCD and thalassemia patients, we conclude that reduced cerebral oxygen consumption in these patient groups is mostly related to anemia. Our data suggest that the pathophysiology of SCIs in patients with milder forms of SCD might be more related to prior episodes of anemia or other sickle cell‐related factors.
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Authors: Yiqing Guo, Nehaben A. Gujarati, Andrew K. Chow, Brock T. Boysan, Robert Bronstein, John C. He, Monica P. Revelo, Navjot Pabla, Robert C. Rizzo, Bhaskar Das, Sandeep K. Mallipattu
Journal: Journal of the American Society of Nephrology (2024)
The Syndrome of Inappropriate Antidiuresis
Authors: Mitchell H. Rosner, Helbert Rondon-Berrios, Richard H. Sterns
Journal: Journal of the American Society of Nephrology (2024)

Abstract The syndrome of inappropriate antidiuresis (SIAD)–the most frequent cause of hypotonic hyponatremia–is mediated by nonosmotic release of arginine vasopressin (AVP), which promotes water retention by activating renal vasopressin type 2 (V2) receptors. There are numerous causes of SIAD, including malignancy, pulmonary and central nervous system diseases and medications. Rare activating mutations of the V2 receptor can also cause SIAD Determination of the etiology of SIAD is important because removal of the stimulus for inappropriate AVP secretion offers the most effective therapy. Treatment of SIAD is guided by symptoms and their severity as well as the level of plasma sodium. In the absence of severe symptoms which require urgent intervention, many clinicians focus on fluid restriction as a first-line treatment. Second-line therapeutic options include loop diuretics and salt tablets, urea, and V2 receptor antagonists.
Gene-engineered polypeptide hydrogels with on-demand oxygenation and ECM-cell interaction mimicry for diabetic wound healing
Authors: Xiao-Ting Xie, Cheng-Hao Gao, Lin-Fang Tan, Liang-Xi Chen, Jin-Xuan Fan, Wei Xiong, Kai Cheng, Yuan-Di Zhao, Bo Liu
Journal: Biomaterials (2024)
Immigration Status Checks, Emergency Medicaid Utilization, and Health Care Access for Uninsured Individuals with Kidney Disease
Authors: Katherine Rizzolo, Ryan Murray, Jade Teakell, Eric Kerns, Prakrati Acharya, Priti Patel, Prachi Sharma, Lilia Cervantes
Journal: Journal of the American Society of Nephrology (2024)

Rizzolo, Katherine; Murray, Ryan; Teakell, Jade; Kerns, Eric; Acharya, Prakrati; Patel, Priti; Sharma, Prachi; Cervantes, Lilia; on behalf of the Expanding Access to Kidney Care for Uninsured Individuals Workgroup of the ASN Health Care Justice Committee Author Information