tbuckley/cabot-search huggingface dataset:
Integrating Social Needs into Health Care: An Implementation Science Perspective
Authors: Maura Kepper, Callie Walsh-Bailey, Constance Owens-Jasey, Rose Gunn, Rachel Gold
Journal: Annual Review of Public Health (2024)

Unmet social needs (e.g., housing instability, food insecurity, transportation barriers) impact a patient's ability to participate in health-seeking behaviors (e.g., physical activity, routine preventive care) and to achieve optimal health. A rapidly growing number of health care systems are incorporating social needs screening and assistance into clinical workflows, yet many implementation and sustainability challenges exist and require collaboration with social service organizations. This review highlights implementation approaches used within this rapidly changing US landscape and uses implementation science frameworks to systematically identify multilevel barriers to and facilitators of implementing and sustaining social needs care. Policies and economic investments are necessary as they determine critical barriers and facilitators within the clinical and social service contexts. Implementation may be further strengthened by cross-sector engagement, evidence-based implementation strategies, and capacity building within clinical and social service organizations. Successful, sustained implementation of social needs care may improve the quality of health care, population health, and health equity.
Immune-mediated colitis after immune checkpoint inhibitor therapy
Authors: Sophie Giesler, Roxane Riemer, Theresa Lowinus, Robert Zeiser
Journal: Trends in Molecular Medicine (2024)

Immune checkpoint inhibitors (ICIs) have led to improved outcome in patients with various types of cancer. Due to inhibition of physiological anti-inflammatory mechanisms, patients treated with ICIs may develop autoimmune inflammation of the colon, associated with morbidity, decreased quality of life (QoL), and mortality. In this review, we summarize clinical and pathophysiological aspects of immune-mediated colitis (ImC), highlighting novel treatment options. In the colon, ICIs trigger resident and circulating T cell activation and infiltration of myeloid cells. In addition, the gut microbiota critically contribute to intestinal immune dysregulation and loss of barrier function, thereby propagating local and systemic inflammation. Currently available therapies for ImC include corticosteroids, antitumor necrosis factor-α (TNF-α)- and anti-integrin α
Africa's mpox strategic preparedness and response plan: a coordinated continental effort to boost health security
Authors: Nicaise Ndembi, Ngashi Ngongo, Moréniké Oluwátóyìn Foláyan, Jean Marie Yameogo, Fiona Braka, Salam Abdou Gueye, Moeti Matshidiso, Jean Kaseya
Journal: The Lancet Global Health (2024)
Evaluating culture-free targeted next-generation sequencing for diagnosing drug-resistant tuberculosis: a multicentre clinical study of two end-to-end commercial workflows
Authors: Rebecca E Colman, Marva Seifert, Andres De la Rossa, Sophia B Georghiou, Christine Hoogland, Swapna Uplekar, Sacha Laurent, Camilla Rodrigues, Priti Kambli, Nestani Tukvadze, Nino Maghradze, Shaheed V Omar, Lavania Joseph, Anita Suresh, Timothy C Rodwell
Journal: The Lancet Infectious Diseases (2024)
Watchful Waiting versus Antibiotics for Acute Otitis Media in Pediatric Patients
Authors: Julie R. Barzilay, Mary Anne Jackson, David Tunkel
Journal: New England Journal of Medicine (2024)

This case vignette of a 13-month-old girl with fever and acute otitis media in one ear is accompanied by two essays, one recommending watchful waiting with close follow-up and the other supporting prescription of antibiotics.
Total Hip Replacement or Resistance Training for Severe Hip Osteoarthritis
Authors: Thomas Frydendal, Robin Christensen, Inger Mechlenburg, Lone R Mikkelsen, Claus Varnum, Anders E Graversen, Per Kjærsgaard-Andersen, Peter H Revald, Christian Hofbauer, Manuel J Bieder, Haidar Qassim, Mohammad S Munir, Stig S Jakobsen, Sabrina M Nielsen, Kim G Ingwersen, Søren Overgaard
Journal: New England Journal of Medicine (2024)

BackgroundTotal hip replacement is routinely recommended for severe hip osteoarthritis, but data from randomized trials are lacking regarding comparison of the effectiveness of this procedure with that of nonsurgical treatment such as resistance training.MethodsWe conducted a multicenter, randomized, controlled trial to compare total hip replacement with resistance training in patients 50 years of age or older who had severe hip osteoarthritis and an indication for surgery. The primary outcome was the change in patient-reported hip pain and function from baseline to 6 months after the initiation of treatment, assessed with the use of the Oxford Hip Score (range, 0 to 48, with higher scores indicating less pain and better function). Safety was also assessed.Download a PDF of the Plain Language Summary.ResultsA total of 109 patients (mean age, 67.6 years) were randomly assigned to total hip replacement (53 patients) or resistance training (56 patients). In an intention-to-treat analysis, the mean increase (indicating improvement) in the Oxford Hip Score was 15.9 points in patients assigned to total hip replacement and 4.5 points in patients assigned to resistance training (difference, 11.4 points; 95% confidence interval, 8.9 to 14.0; P<0.001). At 6 months, 5 patients (9%) who had been assigned to total hip replacement had not undergone surgery, and 12 patients (21%) who had been assigned to resistance training had undergone total hip replacement. The incidence of serious adverse events at 6 months was similar in the two groups; the majority of such events were known complications of total hip replacement.ConclusionsIn patients 50 years of age or older who had severe hip osteoarthritis and an indication for surgery, total hip replacement resulted in a clinically important, superior reduction in hip pain and improved hip function, as reported by patients, at 6 months as compared with resistance training. (Funded by the Danish Rheumatism Association and others; PROHIP ClinicalTrials.gov number, NCT04070027.) Quick Take Hip Replacement for Severe Hip Osteoarthritis 1m 52s
A Case of Vertical Transmission of Oropouche Virus in Brazil
Authors: Carlos Garcia Filho, Antônio Silva Lima Neto, Ana Maria Peixoto Cabral Maia, Luiz Osvaldo Rodrigues da Silva, Robson da Costa Cavalcante, Higor da Silva Monteiro, Kamilla Carneiro Alves Marques, Rebeca de Souza Oliveira, Sami de Andrade Cordeiro Gadelha, Deborah Nunes de Melo, Anacelia Gomes de Matos Mota, Shirlene Telmos Silva de Lima, Karene Ferreira Cavalcante, Larissa Maria Façanha Duarte, Ítalo José Mesquita Cavalcante, Leda Maria Simões Mello, Carlos Henrique Alencar, Cintia Damasceno Dos Santos Rodrigues, Carla Santos de Oliveira, Fernanda de Bruycker-Nogueira, Felipe Gomes Naveca, André Ricardo Ribas Freitas, Luciano Pamplona de Góes Cavalcanti
Journal: New England Journal of Medicine (2024)
Valemetostat monotherapy in patients with relapsed or refractory non-Hodgkin lymphoma: a first-in-human, multicentre, open-label, single-arm, phase 1 study
Authors: Dai Maruyama, Eric Jacobsen, Pierluigi Porcu, Pamela Allen, Kenji Ishitsuka, Shigeru Kusumoto, Tomoko Narita, Kensei Tobinai, Francine Foss, Kunihiro Tsukasaki, Tatyana Feldman, Yoshitaka Imaizumi, Koji Izutsu, Satoko Morishima, Nobuhiko Yamauchi, Junichiro Yuda, Jonathan E Brammer, Toyotaka Kawamata, Jia Ruan, Kisato Nosaka, Atae Utsunomiya, Jie Wang, Jasmine Zain, Yasuyuki Kakurai, Hideyuki Yamauchi, Yoshiyuki Hizukuri, Noha Biserna, Masaya Tachibana, Ai Inoue, Steven M Horwitz
Journal: The Lancet Oncology (2024)
Identification of red flags for IgG4-related disease: an international European Reference Network for Rare Connective Tissue Diseases framework
Authors: Emanuel Della-Torre, Rosaria Talarico, Jose Ballarin, Emanuele Bozzalla-Cassione, Chiara Cardamone, Cosimo Cigolini, Francesco Ferro, Tomas Fonseca, George E Fragoulis, Ilaria Galetti, Maria Gerosa, José Hernández-Rodríguez, Marco Lanzillotta, Diana Marinello, Thierry Martin, Fernando Martinez-Valle, Maria Maślińska, Michele Moretti, Marta Mosca, Ulf Müller-Ladner, Cecilia Nalli, Giovanni Orsolini, Cristina Pamfil, Guillermo Perez-Garcia, Roberta Priori, Giacomo Quattrocchio, Andreas Ramming, Francesca Regola, Vasco C Romão, Augusto Silva, Jan A M van Laar, Maria Jose Vicente-Edo, Shlomo Vinker, Tobias Alexander
Journal: The Lancet Rheumatology (2024)
Case 34-2024: A 69-Year-Old Man with Dyspnea after Old Myocardial Infarction
Authors: Kevin Heaton, Emily K Zern, Aferdita Spahillari, Conor D Barrett
Journal: New England Journal of Medicine (2024)

A 69-year-old man with a history of MI and cardiomyopathy presented with 2 days of dyspnea. Regular tachycardia (124 beats per min), diaphoresis, and rales were present. A diagnosis was made.
Glucagon-Like Peptide-1 Receptor Agonists and Osteoarthritis
Authors: David T Felson
Journal: New England Journal of Medicine (2024)

Osteoarthritis is one of the world's leading causes of disability. Roughly 4.3% of adults have painful knee osteoarthritis, with knee pain on most days1; the prevalence of disease is much higher than this among older persons. The main nonsurgical treatments include nonsteroidal antiinflammatory drugs (NSAIDs) — which can be dangerous for older persons who are most often affected by this disease — and exercise, to which adherence is often poor. Acetaminophen has only modest efficacy and, as a consequence, has been removed from some treatment guidelines. New treatments are desperately needed.2-4 In this issue of the Journal, Bliddal et al.5 . . .
Valemetostat for patients with relapsed or refractory peripheral T-cell lymphoma (VALENTINE-PTCL01): a multicentre, open-label, single-arm, phase 2 study
Authors: Pier Luigi Zinzani, Koji Izutsu, Neha Mehta-Shah, Stefan K Barta, Kenji Ishitsuka, Raul Córdoba, Shigeru Kusumoto, Emmanuel Bachy, Kate Cwynarski, Giuseppe Gritti, Anca Prica, Eric Jacobsen, Tatyana Feldman, Yann Guillermin, Daisuke Ennishi, Dok Hyun Yoon, Eva Domingo Domenech, Jasmine Zain, Jie Wang, Jin Seok Kim, Marjolein van der Poel, Jin Jin, Sutan Wu, Yang Chen, Takaya Moriyama, Ai Inoue, Keiko Nakajima, Steven M Horwitz
Journal: The Lancet Oncology (2024)
Nivolumab plus ipilimumab versus carboplatin-based doublet as first-line treatment for patients with advanced non-small-cell lung cancer aged ≥70 years or with an ECOG performance status of 2 (GFPC 08–2015 ENERGY): a randomised, open-label, phase 3 study
Authors: Hervé Léna, Laurent Greillier, Claire Cropet, Olivier Bylicki, Isabelle Monnet, Clarisse Audigier-Valette, Lionel Falchero, Alain Vergnenègre, Pierre Demontrond, Margaux Geier, Florian Guisier, Stéphane Hominal, Chrystèle Locher, Romain Corre, Christos Chouaid, Charles Ricordel
Journal: The Lancet Respiratory Medicine (2024)
Improving the Outcome of Bad-Acting Hormone Receptor–Positive Breast Cancer
Authors: William J Gradishar
Journal: New England Journal of Medicine (2024)

The treatment approach for patients with estrogen receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative metastatic breast cancer has changed dramatically over the past 20 years. In the past, the usual approach involved administering the available single agents (tamoxifen, aromatase inhibitors, and fulvestrant) sequentially until endocrine sensitivity was exhausted and then pivoting to chemotherapy. Although a variety of mechanisms of resistance to endocrine therapy were identified during preclinical work, clinical options to exploit these findings were largely lacking until recently. Drug development began to focus on signaling pathways and somatic mutations that transform endocrine-sensitive breast cancer into a drug-resistant phenotype . . .
Inavolisib-Based Therapy in <i>PIK3CA</i> -Mutated Advanced Breast Cancer
Authors: Nicholas C Turner, Seock-Ah Im, Cristina Saura, Dejan Juric, Sibylle Loibl, Kevin Kalinsky, Peter Schmid, Sherene Loi, Patrapim Sunpaweravong, Antonino Musolino, Huiping Li, Qingyuan Zhang, Zbigniew Nowecki, Roland Leung, Eirini Thanopoulou, Noopur Shankar, Guiyuan Lei, Thomas J Stout, Katherine E Hutchinson, Jennifer L Schutzman, Chunyan Song, Komal L Jhaveri
Journal: New England Journal of Medicine (2024)

BackgroundInavolisib is a highly potent and selective inhibitor of the alpha isoform of the p110 catalytic subunit of the phosphatidylinositol 3-kinase complex (encoded by PIK3CA) that also promotes the degradation of mutated p110α. Inavolisib plus palbociclib–fulvestrant has shown synergistic activity in preclinical models and promising antitumor activity in early-phase trials.MethodsIn a phase 3, double-blind, randomized trial, we compared first-line inavolisib (at an oral dose of 9 mg once daily) plus palbociclib–fulvestrant (inavolisib group) with placebo plus palbociclib–fulvestrant (placebo group) in patients with PIK3CA-mutated, hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative locally advanced or metastatic breast cancer who had had relapse during or within 12 months after the completion of adjuvant endocrine therapy. The primary end point was progression-free survival as assessed by the investigator.Download a PDF of the Plain Language Summary.ResultsA total of 161 patients were assigned to the inavolisib group and 164 to the placebo group; the median follow-up was 21.3 months and 21.5 months, respectively. The median progression-free survival was 15.0 months (95% confidence interval [CI], 11.3 to 20.5) in the inavolisib group and 7.3 months (95% CI, 5.6 to 9.3) in the placebo group (hazard ratio for disease progression or death, 0.43; 95% CI, 0.32 to 0.59; P<0.001). An objective response occurred in 58.4% of the patients in the inavolisib group and in 25.0% of those in the placebo group. The incidence of grade 3 or 4 neutropenia was 80.2% in the inavolisib group and 78.4% in the placebo group; grade 3 or 4 hyperglycemia, 5.6% and 0%, respectively; grade 3 or 4 stomatitis or mucosal inflammation, 5.6% and 0%; and grade 3 or 4 diarrhea, 3.7% and 0%. No grade 3 or 4 rash was observed. Discontinuation of any trial agent because of adverse events occurred in 6.8% of the patients in the inavolisib group and in 0.6% of those in the placebo group.ConclusionsIn patients with PIK3CA-mutated, hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer, inavolisib plus palbociclib–fulvestrant led to significantly longer progression-free survival than placebo plus palbociclib–fulvestrant, with a greater incidence of toxic effects. The percentage of patients who discontinued any trial agent because of adverse events was low. (Funded by F. Hoffmann–La Roche; INAVO120 ClinicalTrials.gov number, NCT04191499.) Quick Take Addition of PI3Kα Inhibition in Breast Cancer 2m 23s
Ten-Year Outcomes after Bariatric Surgery in Adolescents
Authors: Justin R Ryder, Todd M Jenkins, Changchun Xie, Anita P Courcoulas, Carroll M Harmon, Michael A Helmrath, Stephanie Sisley, Marc P Michalsky, Mary Brandt, Thomas H Inge
Journal: New England Journal of Medicine (2024)

A study documents the long-term durability of weight loss and remission of related conditions after bariatric surgery, as well as the greater health benefits in adolescents than would be expected in similarly treated adults.
Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis
Authors: Henning Bliddal, Harold Bays, Sébastien Czernichow, Joanna Uddén Hemmingsson, Jøran Hjelmesæth, Thomas Hoffmann Morville, Anna Koroleva, Jesper Skov Neergaard, Patricia Vélez Sánchez, Sean Wharton, Alicja Wizert, Lars E Kristensen
Journal: New England Journal of Medicine (2024)

BackgroundWeight reduction has been shown to alleviate symptoms of osteoarthritis of the knee, including pain. The effect of glucagon-like peptide-1 receptor agonists on outcomes in knee osteoarthritis among persons with obesity has not been well studied.MethodsWe conducted a 68-week, double-blind, randomized, placebo-controlled trial at 61 sites in 11 countries. Participants with obesity (a body-mass index [BMI; the weight in kilograms divided by the square of the height in meters] of ≥30) and a clinical and radiologic diagnosis of moderate knee osteoarthritis with at least moderate pain were randomly assigned, in a 2:1 ratio, to receive once-weekly subcutaneous semaglutide (2.4 mg) or placebo, in addition to counseling on physical activity and a reduced-calorie diet. The primary end points were the percentage change in body weight and the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score (on a scale of 0 to 100, with higher scores reflecting worse outcomes) from baseline to week 68. A key confirmatory secondary end point was the physical-function score on the 36-Item Short Form Health Survey (SF-36), version 2 (on a scale of 0 to 100, with higher scores indicating greater well-being).Download a PDF of the Plain Language Summary.ResultsA total of 407 participants were enrolled. The mean age was 56 years, the mean BMI 40.3, and the mean WOMAC pain score 70.9. A total of 81.6% of the participants were women. The mean change in body weight from baseline to week 68 was −13.7% with semaglutide and −3.2% with placebo (P<0.001). The mean change in the WOMAC pain score at week 68 was −41.7 points with semaglutide and −27.5 points with placebo (P<0.001). Participants in the semaglutide group had a greater improvement in SF-36 physical-function score than those in the placebo group (mean change, 12.0 points vs. 6.5 points; P<0.001). The incidence of serious adverse events was similar in the two groups. Adverse events that led to permanent discontinuation of the trial regimen occurred in 6.7% of the participants in the semaglutide group and in 3.0% in the placebo group, with gastrointestinal disorders being the most common reason for discontinuation.ConclusionsAmong participants with obesity and knee osteoarthritis with moderate-to-severe pain, treatment with once-weekly injectable semaglutide resulted in significantly greater reductions in body weight and pain related to knee osteoarthritis than placebo. (Funded by Novo Nordisk; STEP 9 ClinicalTrials.gov number, NCT05064735.) Quick Take Semaglutide in Obesity and Knee Osteoarthritis 2m 27s
Molecular Mechanisms of Neurofilament Alterations and its Application in Assessing Neurodegenerative Disorders
Authors: Shanmukha Sreeya Devarakonda, Shaik Basha, Anjana Pithakumar, Thoshna L B, Darshan Chikkanayakanahalli Mukunda, Jackson Rodrigues, Ameera K, Shimul Biswas, Aparna Ramakrishna Pai, Sushma Belurkar, Krishna Kishore Mahato
Journal: Ageing Research Reviews (2024)

Neurofilaments are intermediate filaments present in neurons. These provide structural support and maintain the size and shape of the neurons. Dysregulation, mutation, and aggregation of neurofilaments raise the levels of these proteins in the blood and cerebrospinal fluid (CSF), which are characteristic features of axonal damage and certain rare neurological diseases, such as Giant Axonal Neuropathy and Charcot-Mare-Tooth disease. Understanding the structure, dynamics, and function of neurofilaments has been greatly enhanced by a diverse range of biochemical and preclinical investigations conducted over more than four decades. Recently, there has been a resurgence of interest in post-translational modifications of neurofilaments, such as phosphorylation, aggregation, mutation, oxidation, etc. Over the past twenty years, several rare disorders have been studied from structural alterations of neurofilaments. These disorders are monitored by fluid biomarkers such as neurofilament light chains. Currently, there are many tools, such as Enzyme-Linked Immunosorbent Assay, Electrochemiluminescence Assay, Single-Molecule Array, Western/immunoblotting, etc., in use to assess the neurofilament proteins in Blood and CSF. However, all these techniques utilize expensive, non-specific, or antibody-based methods, which make them unsuitable for routine screening of neurodegenerative disorders. This provides room to search for newer sensitive, cost-effective, point-of-care tools for rapid screening of the disease. For a long time, the molecular mechanisms of neurofilaments have been poorly understood due to insufficient research attempts, and a deeper understanding of them remains elusive. Therefore, this review aims to highlight the available literature on molecular mechanisms of neurofilaments and the function of neurofilaments in axonal transport, axonal conduction, axonal growth, and neurofilament aggregation, respectively. Further, this review discusses the role of neurofilaments as potential biomarkers for the identification of several neurodegenerative diseases in clinical laboratory practice.
Onvansertib in Combination With Chemotherapy and Bevacizumab in Second-Line Treatment of <i>KRAS</i> -Mutant Metastatic Colorectal Cancer: A Single-Arm, Phase II Trial
Authors: Daniel H. Ahn, Maya Ridinger, Timothy L. Cannon, Lawrence Mendelsohn, Jason S. Starr, Joleen M. Hubbard, Anup Kasi, Afsaneh Barzi, Errin Samuëlsz, Anju Karki, Ramanand A. Subramanian, Divora Yemane, Roy Kim, Chu-Chiao Wu, Peter J.P. Croucher, Tod Smeal, Fairooz F. Kabbinavar, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2024)

PURPOSE This phase II study evaluated the efficacy and tolerability of onvansertib, a polo-like kinase 1 (PLK1) inhibitor, in combination with fluorouracil, leucovorin, and irinotecan (FOLFIRI) + bevacizumab for the second-line treatment of KRAS -mutant metastatic colorectal cancer (mCRC). PATIENTS AND METHODS This multicenter, open-label, single-arm study enrolled patients with KRAS -mutated mCRC previously treated with oxaliplatin and fluorouracil with or without bevacizumab. Patients received onvansertib (15 mg/m 2 once daily on days 1-5 and 15-19 of a 28-day cycle) and FOLFIRI + bevacizumab (days 1 and 15). The primary end point was the objective response rate (ORR), and secondary endpoints included progression-free survival (PFS), duration of response (DOR), and tolerability. Translational and preclinical studies were conducted in KRAS -mutant CRC. RESULTS Among the 53 patients treated, the confirmed ORR was 26.4% (95% CI, 15.3 to 40.3). The median DOR was 11.7 months (95% CI, 9.4 to not reached). Grade 3/4 adverse events were reported in 62% of patients. A post hoc analysis revealed that patients with no prior bevacizumab treatment had a significantly higher ORR and longer PFS compared with patients with prior bevacizumab treatment: ORR of 76.9% versus 10.0% (odds ratio of 30.0, P &lt; .001) and median PFS of 14.9 months versus 6.6 months (hazard ratio of 0.16, P &lt; .001). Our translational findings support that prior bevacizumab exposure contributes to onvansertib resistance. Preclinically, we showed that onvansertib inhibited the hypoxia pathway and exhibited robust antitumor activity in combination with bevacizumab through the inhibition of angiogenesis. CONCLUSION Onvansertib in combination with FOLFIRI + bevacizumab showed significant activity in the second-line treatment of patients with KRAS -mutant mCRC, particularly in patients with no prior bevacizumab treatment. These findings led to the evaluation of the combination in the first-line setting (ClinicalTrails.gov identifier: NCT06106308 ).
Sensory neuroimmune signaling in the pathogenesis of Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN)
Authors: Xiaobao Huang, Suiting Ao, Rui Xu, Xuemei Gao, Shiling Qi, Yarong Liang, Peiying Feng, Ruzeng Xue, Yingying Ren, Jiande Han, Fengxian Li, Coco Chu, Fang Wang
Journal: Journal of Allergy and Clinical Immunology (2024)