tbuckley/cabot-search huggingface dataset:
Infectious Disease Physician Availability and Postgraduate Antimicrobial Stewardship Education in Japan
Authors: Toshiki Miwa, Koh Okamoto, Yuji Nishizaki, Yasuharu Tokuda
Journal: JAMA Network Open (2024)

This cross-sectional study evaluates resident physician perceptions of antimicrobial stewardship education in Japan in the presense of infectious disease physicians educators.
World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management
Authors: William Shomali, Jason Gotlib
Journal: American Journal of Hematology (2024)

Abstract Disease Overview The eosinophilias encompass a broad range of non‐hematologic (secondary or reactive) and hematologic (primary or clonal) disorders with the potential for end‐organ damage. Diagnosis Hypereosinophilia (HE) has generally been defined as a peripheral blood eosinophil count greater than 1.5 × 10 9 /L, and may be associated with tissue damage. After the exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of various tests. They include morphologic review of the blood and marrow, standard cytogenetics, fluorescence in situ hybridization, molecular testing and flow immunophenotyping to detect histopathologic or clonal evidence for an acute or chronic hematolymphoid neoplasm. Risk Stratification Disease prognosis relies on identifying the subtype of eosinophilia. After evaluation of secondary causes of eosinophilia, the 2022 World Health Organization and International Consensus Classification endorse a semi‐molecular classification scheme of disease subtypes. This includes the major category “myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions” (MLN‐eo‐TK), and the MPN subtype, “chronic eosinophilic leukemia” (CEL). Lymphocyte‐variant HE is an aberrant T‐cell clone‐driven reactive eosinophila, and idiopathic hypereosinophilic syndrome (HES) is a diagnosis of exclusion. Risk‐Adapted Therapy The goal of therapy is to mitigate eosinophil‐mediated organ damage. For patients with milder forms of eosinophilia (e.g., &lt;1.5 × 10 9 /L) without symptoms or signs of organ involvement, a watch and wait approach with close follow‐up may be undertaken. Identification of rearranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these diseases to imatinib. Pemigatinib was recently approved for patients with relapsed or refractory FGFR1 ‐rearranged neoplasms. Corticosteroids are first‐line therapy for patients with lymphocyte‐variant HE and HES. Hydroxyurea and interferon‐α have demonstrated efficacy as initial treatment and in steroid‐refractory cases of HES. Mepolizumab, an interleukin‐5 (IL‐5) antagonist monoclonal antibody, is approved by the U.S Food and Drug Administration for patients with idiopathic HES. Cytotoxic chemotherapy agents, and hematopoietic stem cell transplantation have been used for aggressive forms of HES and CEL, with outcomes reported for limited numbers of patients. Targeted therapies such as the IL‐5 receptor antibody benralizumab, IL‐5 monoclonal antibody depemokimab, and various tyrosine kinase inhibitors for MLN‐eo‐TK, are under active investigation.
Reports of COVID-19 Vaccine Adverse Events in Predominantly Republican vs Democratic States
Authors: David A. Asch, Chongliang Luo, Yong Chen
Journal: JAMA Network Open (2024)

Importance Antivaccine sentiment is increasingly associated with conservative political positions. Republican-inclined states exhibit lower COVID-19 vaccination rates, but the association between political inclination and reported vaccine adverse events (AEs) is unexplored. Objective To assess whether there is an association between state political inclination and the reporting rates of COVID-19 vaccine AEs. Design, Setting, and Participants This cross-sectional study used the AE reports after COVID-19 vaccination from the Vaccine Adverse Event Reporting System (VAERS) database from 2020 to 2022, with reports after influenza vaccines from 2019 to 2022 used as a reference. These reports were examined against state-level percentage of Republican votes in the 2020 US presidential election. Exposure State-level percentage of Republican votes in the 2020 US presidential election. Main Outcomes and Measures Rates of any AE among COVID-19 vaccine recipients, rates of any severe AE among vaccine recipients, and the proportion of AEs reported as severe. Results A total of 620 456 AE reports (mean [SD] age of vaccine recipients, 51.8 [17.6] years; 435 797 reports from women [70.2%]; a vaccine recipient could potentially file more than 1 report, so reports are not necessarily from unique individuals) for COVID-19 vaccination were identified from the VAERS database. Significant associations between state political inclination and state AE reporting were observed for all 3 outcomes: a 10% increase in Republican voting was associated with increased odds of AE reports (odds ratio [OR], 1.05; 95% CI, 1.05-1.05; P &amp;amp;lt; .001), severe AE reports (OR, 1.25; 95% CI, 1.24-1.26; P &amp;amp;lt; .001), and the proportion of AEs reported as severe (OR, 1.21; 95% CI, 1.20-1.22; P &amp;amp;lt; .001). These associations were seen across all age strata in stratified analyses and were more pronounced among older subpopulations. Conclusions and Relevance This cross-sectional study found that the more states were inclined to vote Republican, the more likely their vaccine recipients or their clinicians reported COVID-19 vaccine AEs. These results suggest that either the perception of vaccine AEs or the motivation to report them was associated with political inclination.
Intensive Glycemic Management Is Associated With Reduced Retinal Structure Abnormalities on Ocular Coherence Tomography in the DCCT/EDIC Study
Authors: Barbara Blodi, Thomas W. Gardner, Xiaoyu Gao, Jennifer K. Sun, Gayle M. Lorenzi, Lisa C. Olmos de Koo, Arup Das, Neil H. White, Rose A. Gubitosi-Klug, Lloyd P. Aiello, Ionut Bebu
Journal: Diabetes Care (2024)

To investigate quantitative and qualitative changes in retinal structure using optical coherence tomography (OCT) and their associations with systemic or other risk factors in individuals with type 1 diabetes (T1D).
Errors in Table 3, Outcome Measures, Results, Supplement 1, and Supplement 2
Journal: JAMA Network Open (2024)

Exercise vs Physical TherapyModalities for Patients With Chronic Low Back Pain: A Randomized Clinical Trial," 1 published January 7, 2022, there were errors in the article text, Table 3, andSupplements 1 and2.First, a numeric error appeared in Table 3.The value for FABQ total category at 3 months in the physical therapy modalities group given as "23.32" should have been "33.32."In addition, the trial protocol in Supplement 1 included pain as a primary outcome, which was not consistent with the published article.Other secondary outcomes were missing from the Outcomes Measures.The minimal clinically important findings in Results required updates.Finally, eTable 1 of Supplement 2 categories were given incorrectly with results of statistical tests that should not have been included for baseline characteristics, and eTable 2 contained entry errors on the rating scale for assessment of pain.
Estimated Average-Risk Colorectal Cancer Screening–Eligible Population in the US
Authors: Derek W. Ebner, John B. Kisiel, A. Mark Fendrick, Chris Estes, Kevin Li, Vahab Vahdat, Paul J. Limburg
Journal: JAMA Network Open (2024)

This cross-sectional study estimates the number of average-risk colorectal cancer screening–eligible individuals in the US since the US Preventive Services Task Force updated its recommendations in 2021.
Culprit Lesion Coronary Intervention Before Complete Angiography in ST-Elevation Myocardial Infarction
Authors: Nir Levi, Rafael Wolff, Rami Jubeh, Mony Shuvy, Yoed Steinmetz, Nimrod Perel, Tomer Maller, Itshak Amsalem, Rafael Hitter, Elad Asher, Anna Turyan, Mohammad Karmi, Amir Orlev, Dmitry Dratva, Zahi Khoury, Tal Hasin, Arik Wolak, Michael Glikson, Danny Dvir
Journal: JAMA Network Open (2024)

Rapid reperfusion during primary percutaneous coronary intervention (PCI) is associated with improved outcomes among patients with ST-elevation myocardial infarction (STEMI). Although attempts at reducing the time from STEMI diagnosis to arrival at the catheterization laboratory have been widely investigated, intraprocedural strategies aimed at reducing the time to reperfusion are lacking.
Cervical Cancer Screening via Visual Inspection With Acetic Acid and Lugol Iodine for Triage of HPV-Positive Women
Authors: Sumeng Wang, Le Dang, Shujun Liu, Remila Rezhake, Huijiao Yan, Xianzhi Duan, Le Zhang, Linlin Zhang, Lifeng Zhang, Meili Su, Fumei Guo, Cailing Yan, Meili Liu, Xiaoyan Cao, Min Sun, Youlin Qiao, Fanghui Zhao
Journal: JAMA Network Open (2024)

Importance Limited evidence supports the performance of human papillomavirus (HPV) DNA testing as a primary screening method, followed by triage with visual inspection with acetic acid, in areas with limited health care resources, as suggested by the 2021 World Health Organization guidelines. Objective To evaluate the performance of visual inspection with acetic acid and Lugol iodine as a triage method for detecting cervical precancerous lesions among HPV-positive women in 1 visit. Design, Setting, and Participants This cohort study examined the implementation of a government-led cervical cancer screening program conducted from January 1, 2016, to December 31, 2020, in Ordos City, China. Female residents, aged 35 to 64 years, who understood the screening procedures and voluntarily participated were included in the study. Women were excluded if they reported never having had sexual intercourse, were pregnant, had a hysterectomy, or had ever undergone treatment for cervical lesions. Statistical analysis was conducted from December 2022 to December 2023. Exposures The program used the careHPV DNA assay as the primary screening method, and immediate triage was performed by visual inspection if HPV screening results were positive, with a 5-year screening interval. A colposcopy was performed for the women who had suspected cancer on visual inspection results or who were HPV positive and had abnormal visual inspection results, all in 1 visit. Main Outcomes and Measures The rate of compliance with colposcopy and the detection rate of cervical intraepithelial neoplasia grade 2 or higher (CIN2+). Results The study included 187 863 women (median age, 46 years [IQR, 40-52 years]) who participated in the program and had valid HPV test results. The overall prevalence of HPV positivity was 12.8% (24 070 of 187 863), and the adherence to triage with visual inspection among HPV-positive women was 93.9% (22 592 of 24 070). Among HPV-positive women, the rate of compliance with colposcopy was 65.6% (2714 of 4137), and the CIN2+ detection rate was 2.8% (643 of 22 592). Conclusions and Relevance The findings of this cohort study suggest that the implementation of HPV testing, visual inspection, and colposcopy within 1 visit may mitigate losses to follow-up, detect precancerous lesions, and hold significant implications for screening in comparable areas with limited health care resources.
Diselenide‐Containing Polymer Based on New Antitumor Mechanism as Efficient GSH Depletion Agent for Ferroptosis Therapy
Authors: Chen Zhou, Yuhao Zhao, Mao Yang, Wang Yin, Yongsheng Li, Yan Xiao, Yingbin Liu, Meidong Lang
Journal: Advanced Healthcare Materials (2024)

Abstract Glutathione (GSH) depletion‐induced ferroptosis has emerged as a promising treatment for malignant cancer. It works by inactivating glutathione peroxidase 4 (GPX4) and facilitating lipid peroxidation. However, effectively delivering inducers and depleting intracellular GSH remains challenging due to the short half‐lives and high hydrophobicity of small‐molecule ferroptosis inducers. These inducers often require additional carriers. Herein, diselenide‐containing polymers can consume GSH to induce ferroptosis for pancreatic cancer therapy. The diselenide bonds are controllably built into the backbone of the polycarbonate with a targeting peptide CRGD (Cys‐Arg‐Gly‐Asp), which allows for self‐assembly into stable nanoparticles (denoted CRNSe) for self‐delivery. Significantly, at a concentration of 12 µg mL −1 , CRNSe binds to the active site cysteine of GSH resulting in a thorough depletion of GSH. In contrast, the disulfide‐containing analog only causes a slight decrease in GSH level. Moreover, the depletion of GSH inactivates GPX4, ultimately inducing ferroptosis due to the accumulation of lipid peroxide in BxPC‐3 cells. Both in vitro and in vivo studies have demonstrated that CRNSe exhibits potent tumor suppressive ability with few side effects on normal tissue. This study validates the anti‐tumor mechanism of diselenide‐containing polymers in addition to apoptosis and also provides a new strategy for inherently inducing ferroptosis in cancer therapy.
Over-the-Counter Birth Control Pill Now Available in US
Authors: Emily Harris
Journal: JAMA (2024)

People will be able to buy an over-the-counter contraceptive pill, marketed by Perrigo Company as Opill, at major retailers and pharmacies in the US in late March, the manufacturer announced. A 1-month pack of the progestin-only pills costs $19.99, and a 3-month supply costs $49.99.
Trends in Adolescent Suicide by Method in the US, 1999-2020
Authors: Cameron K. Ormiston, Wayne R. Lawrence, Saanie Sulley, Meredith S. Shiels, Emily A. Haozous, Catherine M. Pichardo, Erica S. Stephens, Aleah L. Thomas, David Adzrago, David R. Williams, Faustine Williams
Journal: JAMA Network Open (2024)

Adolescent suicide in the US is a major public health problem, yet temporal trends in suicide methods by demographics are understudied.
Loss of GABARAP mediates resistance to immunogenic chemotherapy in multiple myeloma
Authors: Annamaria Gulla, Eugenio Morelli, Megan Johnstone, Marcello Turi, Mehmet K. Samur, Cirino Botta, Selma Cifric, Pietro Folino, Delaney Vinaixa, Francesca Barello, Cole Clericuzio, Vanessa Katia Favasuli, Domenico Maisano, Srikanth Talluri, Rao Prabhala, Giada Bianchi, Mariateresa Fulciniti, Kenneth Wen, Keiji Kurata, Jiye Liu, Johany Penailillo, Alberto Bragoni, Anna Sapino, Paul G. Richardson, Dharminder Chauhan, Ruben D. Carrasco, Teru Hideshima, Nikhil C. Munshi, Kenneth C. Anderson
Journal: Blood (2024)

Immunogenic cell death (ICD) is a form of cell death by which cancer treatments can induce a clinically relevant antitumor immune response in a broad range of cancers. In multiple myeloma (MM), the proteasome inhibitor bortezomib is an ICD inducer and creates durable therapeutic responses in patients. However, eventual relapse and resistance to bortezomib appear inevitable. Here, by integrating patient transcriptomic data with an analysis of calreticulin (CRT) protein interactors, we found that GABA type A receptor-associated protein (GABARAP) is a key player whose loss prevented tumor cell death from being perceived as immunogenic after bortezomib treatment. GABARAP is located on chromosome 17p, which is commonly deleted in patients with high risk MM. GABARAP deletion impaired the exposure of the eat-me signal CRT on the surface of dying MM cells in vitro and in vivo, thus reducing tumor cell phagocytosis by dendritic cells and the subsequent antitumor T-cell response. Low GABARAP was independently associated with shorter survival in patients with MM and reduced tumor immune infiltration. Mechanistically, we found that GABARAP deletion blocked ICD signaling by decreasing autophagy and altering Golgi apparatus morphology, with consequent defects in the downstream vesicular transport of CRT. Conversely, upregulating autophagy using rapamycin restored Golgi morphology, CRT exposure, and ICD signaling in GABARAPKO cells undergoing bortezomib treatment. Therefore, coupling an ICD inducer, such as bortezomib, with an autophagy inducer, such as rapamycin, may improve patient outcomes in MM, in which low GABARAP in the form of del(17p) is common and leads to worse outcomes.
Magnetic Resonance Imaging, Clinical, and Biopsy Findings in Suspected Prostate Cancer
Authors: Arya Haj-Mirzaian, Kristine S. Burk, Ronilda Lacson, Daniel I. Glazer, Sanjay Saini, Adam S. Kibel, Ramin Khorasani
Journal: JAMA Network Open (2024)

Importance Multiple strategies integrating magnetic resonance imaging (MRI) and clinical data have been proposed to determine the need for a prostate biopsy in men with suspected clinically significant prostate cancer (csPCa) (Gleason score ≥3 + 4). However, inconsistencies across different strategies create challenges for drawing a definitive conclusion. Objective To determine the optimal prostate biopsy decision-making strategy for avoiding unnecessary biopsies and minimizing the risk of missing csPCa by combining MRI Prostate Imaging Reporting &amp;amp;amp; Data System (PI-RADS) and clinical data. Data Sources PubMed, Ovid MEDLINE, Embase, Web of Science, and Cochrane Library from inception to July 1, 2022. Study Selection English-language studies that evaluated men with suspected but not confirmed csPCa who underwent MRI PI-RADS followed by prostate biopsy were included. Each study had proposed a biopsy plan by combining PI-RADS and clinical data. Data Extraction and Synthesis Studies were independently assessed for eligibility for inclusion. Quality of studies was appraised using the Quality Assessment of Diagnostic Accuracy Studies 2 tool and the Newcastle-Ottawa Scale. Mixed-effects meta-analyses and meta-regression models with multimodel inference were performed. Reporting of this study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Main Outcomes and Measures Independent risk factors of csPCa were determined by performing meta-regression between the rate of csPCa and PI-RADS and clinical parameters. Yields of different biopsy strategies were assessed by performing diagnostic meta-analysis. Results The analyses included 72 studies comprising 36 366 patients. Univariable meta-regression showed that PI-RADS 4 (β-coefficient [SE], 7.82 [3.85]; P = .045) and PI-RADS 5 (β-coefficient [SE], 23.18 [4.46]; P &amp;amp;lt; .001) lesions, but not PI-RADS 3 lesions (β-coefficient [SE], −4.08 [3.06]; P = .19), were significantly associated with a higher risk of csPCa. When considered jointly in a multivariable model, prostate-specific antigen density (PSAD) was the only clinical variable significantly associated with csPCa (β-coefficient [SE], 15.50 [5.14]; P &amp;amp;lt; .001) besides PI-RADS 5 (β-coefficient [SE], 9.19 [3.33]; P &amp;amp;lt; .001). Avoiding biopsy in patients with lesions with PI-RADS category of 3 or less and PSAD less than 0.10 (vs &amp;amp;lt;0.15) ng/mL 2 resulted in reducing 30% (vs 48%) of unnecessary biopsies (compared with performing biopsy in all suspected patients), with an estimated sensitivity of 97% (vs 95%) and number needed to harm of 17 (vs 15). Conclusions and Relevance These findings suggest that in patients with suspected csPCa, patient-tailored prostate biopsy decisions based on PI-RADS and PSAD could prevent unnecessary procedures while maintaining high sensitivity.
BRCA1-Mediated Dual Regulation of Ferroptosis Exposes a Vulnerability to GPX4 and PARP Co-Inhibition in <i>BRCA1</i>-Deficient Cancers
Authors: Guang Lei, Chao Mao, Amber D. Horbath, Yuelong Yan, Shirong Cai, Jun Yao, Yan Jiang, Mingchuang Sun, Xiaoguang Liu, Jun Cheng, Zhihao Xu, Hyemin Lee, Qidong Li, Zhengze Lu, Li Zhuang, Mei-Kuang Chen, Anagha Alapati, Timothy A. Yap, Mien-Chie Hung, Mingjian James You, Helen Piwnica-Worms, Boyi Gan
Journal: Cancer Discovery (2024)

Abstract Resistance to poly (ADP-ribose) polymerase inhibitors (PARPi) limits the therapeutic efficacy of PARP inhibition in treating breast cancer susceptibility gene 1 (BRCA1)-deficient cancers. Here we reveal that BRCA1 has a dual role in regulating ferroptosis. BRCA1 promotes the transcription of voltage-dependent anion channel 3 (VDAC3) and glutathione peroxidase 4 (GPX4); consequently, BRCA1 deficiency promotes cellular resistance to erastin-induced ferroptosis but sensitizes cancer cells to ferroptosis induced by GPX4 inhibitors (GPX4i). In addition, nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and defective GPX4 induction unleash potent ferroptosis in BRCA1-deficient cancer cells upon PARPi and GPX4i co-treatment. Finally, we show that xenograft tumors derived from patients with BRCA1-mutant breast cancer with PARPi resistance exhibit decreased GPX4 expression and high sensitivity to PARP and GPX4 co-inhibition. Our results show that BRCA1 deficiency induces a ferroptosis vulnerability to PARP and GPX4 co-inhibition and inform a therapeutic strategy for overcoming PARPi resistance in BRCA1-deficient cancers. Significance: BRCA1 deficiency promotes resistance to erastin-induced ferroptosis via blocking VDAC3 yet renders cancer cells vulnerable to GPX4i-induced ferroptosis via inhibiting GPX4. NCOA4 induction and defective GPX4 further synergizes GPX4i with PARPi to induce ferroptosis in BRCA1-deficient cancers and targeting GPX4 mitigates PARPi resistance in those cancers. See related commentary by Alborzinia and Friedmann Angeli, p. 1372
CONTACT-01: A Randomized Phase III Trial of Atezolizumab + Cabozantinib Versus Docetaxel for Metastatic Non–Small Cell Lung Cancer After a Checkpoint Inhibitor and Chemotherapy
Authors: Joel Neal, Nick Pavlakis, Sang-We Kim, Yasushi Goto, Sun Min Lim, Giannis Mountzios, Elena Fountzilas, Anastasia Mochalova, Daniel C. Christoph, Alessandra Bearz, Xavier Quantin, Ramon Palmero, Vladan Antic, Elaine Chun, Tirupathi Rao Edubilli, Ya-Chen Lin, Mahrukh Huseni, Marcus Ballinger, Vilma Graupner, Dominic Curran, Piet Vervaet, Thomas Newsom-Davis
Journal: Journal of Clinical Oncology (2024)

PURPOSE Although checkpoint inhibitors have improved first-line treatment for non–small cell lung cancer (NSCLC), a therapeutic need remains for patients whose disease does not respond or who experience disease progression after anti–PD-L1/PD-1 immunotherapy. CONTACT-01 (ClinicalTrials.gov identifier: NCT04471428 ) evaluated atezolizumab plus cabozantinib versus docetaxel in patients with metastatic NSCLC who developed disease progression after concurrent or sequential treatment with anti–PD-L1/PD-1 and platinum-containing chemotherapy. METHODS This multicenter, open-label, phase III trial randomly assigned patients 1:1 to atezolizumab 1,200 mg intravenously once every 3 weeks (q3w) plus cabozantinib 40 mg orally once daily or docetaxel 75 mg/m 2 intravenously once every 3 weeks. The primary end point was overall survival (OS). RESULTS One hundred eighty-six patients were assigned atezolizumab plus cabozantinib, and 180 docetaxel. Minimum OS follow-up was 10.9 months. Median OS was 10.7 months (95% CI, 8.8 to 12.3) with atezolizumab plus cabozantinib and 10.5 months (95% CI, 8.6 to 13.0) with docetaxel (stratified hazard ratio [HR], 0.88 [95% CI, 0.68 to 1.16]; P = .3668). Median progression-free survival was 4.6 months (95% CI, 4.1 to 5.6) and 4.0 months (95% CI, 3.1 to 4.4), respectively (stratified HR, 0.74 [95% CI, 0.59 to 0.92]). Serious adverse events (AEs) occurred in 71 (38.4%) patients receiving atezolizumab plus cabozantinib and 58 (34.7%) receiving docetaxel. Grade 3/4 treatment-related AEs occurred in 73 (39.5%) patients receiving atezolizumab plus cabozantinib and 58 (34.7%) receiving docetaxel. Grade 5 AEs occurred in 14 (7.6%) and 10 (6.0%) patients in the atezolizumab plus cabozantinib and docetaxel arms, respectively (treatment-related in four [2.2%] and one [0.6%], respectively). CONCLUSION Atezolizumab plus cabozantinib after disease progression following anti–PD-L1/PD-1 immunotherapy and platinum-containing chemotherapy for metastatic NSCLC did not improve OS compared with docetaxel. Safety was consistent with known profiles of these agents.