tbuckley/cabot-search huggingface dataset:
Differential Treatment Effects of Subgroup Analyses in Phase 3 Oncology Trials From 2004 to 2020
Authors: Alexander D. Sherry, Andrew W. Hahn, Zachary R. McCaw, Joseph Abi Jaoude, Ramez Kouzy, Timothy A. Lin, Bruce Minsky, C. David Fuller, Tomer Meirson, Pavlos Msaouel, Ethan B. Ludmir
Journal: JAMA Network Open (2024)

Importance Subgroup analyses are often performed in oncology to investigate differential treatment effects and may even constitute the basis for regulatory approvals. Current understanding of the features, results, and quality of subgroup analyses is limited. Objective To evaluate forest plot interpretability and credibility of differential treatment effect claims among oncology trials. Design, Setting, and Participants This cross-sectional study included randomized phase 3 clinical oncology trials published prior to 2021. Trials were screened from ClinicalTrials.gov. Main Outcomes and Measures Missing visual elements in forest plots were defined as a missing point estimate or use of a linear x-axis scale for hazard and odds ratios. Multiplicity of testing control was recorded. Differential treatment effect claims were rated using the Instrument for Assessing the Credibility of Effect Modification Analyses. Linear and logistic regressions evaluated associations with outcomes. Results Among 785 trials, 379 studies (48%) enrolling 331 653 patients reported a subgroup analysis. The forest plots of 43% of trials (156 of 363) were missing visual elements impeding interpretability. While 4148 subgroup effects were evaluated, only 1 trial (0.3%) controlled for multiple testing. On average, trials that did not meet the primary end point conducted 2 more subgroup effect tests compared with trials meeting the primary end point (95% CI, 0.59-3.43 tests; P = .006). A total of 101 differential treatment effects were claimed across 15% of trials (55 of 379). Interaction testing was missing in 53% of trials (29 of 55) claiming differential treatment effects. Trials not meeting the primary end point were associated with greater odds of no interaction testing (odds ratio, 4.47; 95% CI, 1.42-15.55, P = .01). The credibility of differential treatment effect claims was rated as low or very low in 93% of cases (94 of 101). Conclusions and Relevance In this cross-sectional study of phase 3 oncology trials, nearly half of trials presented a subgroup analysis in their primary publication. However, forest plots of these subgroup analyses largely lacked essential features for interpretation, and most differential treatment effect claims were not supported. Oncology subgroup analyses should be interpreted with caution, and improvements to the quality of subgroup analyses are needed.
Effect of Feminizing Hormone Therapy on QTc Interval
Authors: Lachlan M. Angus, Tina Lin, Shalem Y. Leemaqz, Ada S. Cheung
Journal: JAMA Network Open (2024)

This secondary analysis of a randomized clinical trial investigates the effect of spironolactone and cyproterone acetate hormone therapy on the QT interval corrected for heart rate among transgender women and nonbinary or transfeminine individuals.
Participation in Virtual Prehabilitation and Outcomes Following Thoracic Cancer Surgery
Authors: Jun J. Mao, Daniela Molena, Krupali Desai, Raymond E. Baser, Christina Seluzicki, Gaetano Rocco, David Jones
Journal: JAMA Network Open (2024)

This cohort study evaluates the association of a virtual synchronized prehabilitation program with perioperative outcomes among patients undergoing thoracic cancer surgery.
Shorter Dual Antiplatelet Therapy for Older Adults After Percutaneous Coronary Intervention
Authors: Dae Yong Park, Jiun-Ruey Hu, Yasser Jamil, Michelle D. Kelsey, W. Schuyler Jones, Jennifer Frampton, Ajar Kochar, Wilbert S. Aronow, Abdulla A. Damluji, Michael G. Nanna
Journal: JAMA Network Open (2024)

Importance The optimal duration of dual antiplatelet therapy (DAPT) for older adults after percutaneous coronary intervention (PCI) is uncertain because they are simultaneously at higher risk for both ischemic and bleeding events. Objective To investigate the association of abbreviated DAPT with adverse clinical events among older adults after PCI. Data Sources The Cochrane Library, Google Scholar, Embase, MEDLINE, PubMed, Scopus, and Web of Science were searched from inception to August 9, 2023. Study Selection Randomized clinical trials comparing any 2 of 1, 3, 6, and 12 months of DAPT were included if they reported results for adults aged 65 years or older or 75 years or older. Data Extraction and Synthesis The Preferred Reporting Items for Systematic Reviews and Meta-Analyses ( PRISMA ) reporting guideline was used to abstract data and assess data quality. Risk ratios for each duration of DAPT were calculated with alternation of the reference group. Main Outcomes and Measures The primary outcome of interest was net adverse clinical events (NACE). Secondary outcomes were major adverse cardiovascular events (MACE) and bleeding. Results In 14 randomized clinical trials comprising 19 102 older adults, no differences were observed in the risks of NACE or MACE for 1, 3, 6, and 12 months of DAPT. However, 3 months of DAPT was associated with a lower risk of bleeding compared with 6 months of DAPT (relative risk [RR], 0.50 [95% CI, 0.29-0.84]) and 12 months of DAPT (RR, 0.57 [95% CI, 0.45-0.71]) among older adults. One month of DAPT was also associated with a lower risk of bleeding compared with 6 months of DAPT (RR, 0.68 [95% CI, 0.54-0.86]). Conclusions and Relevance In this systematic review and meta-analysis of different durations of DAPT for older adults after PCI, an abbreviated DAPT duration was associated with a lower risk of bleeding without any concomitant increase in the risk of MACE or NACE despite the concern for higher-risk coronary anatomy and comorbidities among older adults. This study, which represents the first network meta-analysis of this shortened treatment for older adults, suggests that clinicians may consider abbreviating DAPT for older adults.
Perspectives of Oncologists on the Ethical Implications of Using Artificial Intelligence for Cancer Care
Authors: Andrew Hantel, Thomas P. Walsh, Jonathan M. Marron, Kenneth L. Kehl, Richard Sharp, Eliezer Van Allen, Gregory A. Abel
Journal: JAMA Network Open (2024)

Artificial intelligence (AI) tools are rapidly integrating into cancer care. Understanding stakeholder views on ethical issues associated with the implementation of AI in oncology is critical to optimal deployment.
Same Old Challenges in Subgroup Analysis—Should We Do More About Methods Implementation?
Authors: Stefan Schandelmaier, Gordon Guyatt
Journal: JAMA Network Open (2024)

Alexander D. Sherry, MD; Andrew W. Hahn, MD; Zachary R. McCaw, PhD; Joseph Abi Jaoude, MD; Ramez Kouzy, MD; Timothy A. Lin, MD, MBA; Bruce Minsky, MD; C. David Fuller, MD, PhD; Tomer Meirson, MD; Pavlos Msaouel, MD, PhD; Ethan B. Ludmir, MD
Pathological polyploidy and liver repair failure in RAD51-deficient mice
Authors: Andrew W. Duncan
Journal: Hepatology (2024)

Department of Pathology, Pittsburgh Liver Research Center, McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA 15219 Correspondence Andrew W. Duncan, Department of Pathology, Pittsburgh Liver Research Center, McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA 15219. Email: [email protected], Twitter: @DuncanWAndrew
Nutritional aspects of prehabilitation in adults with cirrhosis awaiting liver transplant
Authors: Christofer Cruz, Carla M. Prado, Chelsia Gillis, Robert Martindale, Chantal Bémeur, Jennifer C. Lai, Puneeta Tandon
Journal: Hepatology (2024)

Malnutrition, sarcopenia (low muscle mass), and physical frailty have gained increasing recognition in candidates for liver transplant (LT) as these conditions can impact postoperative functional capacity. Multidimensional prehabilitation programs have been proposed as a safe intervention in adults awaiting LT but the nutritional pillar of prehabilitation has been understudied. This review summarizes the nutritional recommendations for prehabilitation for individuals with cirrhosis awaiting LT. Three major aspects of nutritional prehabilitation are discussed: (1) Assess: Evaluate nutritional status and assess for malnutrition, sarcopenia, and frailty to guide the nutritional prehabilitation intervention intensity, increasing across universal, targeted, and specialist levels; (2) Intervene: Prescribe a nutritional prehabilitation intervention to meet established nutrition guidelines in cirrhosis with a targeted focus on improving nutritional status and muscle health; (3) Reassess: Follow-up based on the required intensity of nutritional care with as needed intervention adjustment. Topics covered in the review include nutritional care levels for prehabilitation, energy prescriptions across body mass index strata, detailed considerations around protein intake (amount, distribution, and quality), carbohydrate and fat intake, other nutritional considerations, and the potential role of dietary supplements and nutraceuticals. Future research is warranted to more accurately evaluate energy needs, evaluate emerging dietary supplementation strategies, and establish the role of nutraceuticals alongside food-based interventions. While the general principles of nutritional prehabilitation are ready for immediate application, future large-scale randomized controlled trials in this space will help to quantify the benefit that can be gained by transitioning the LT approach from passive "transplant waitlist time" to active "transplant preparation time."
A perspective on muscle phenotyping in musculoskeletal research
Authors: Ines Foessl, Cheryl L. Ackert-Bicknell, Erika Kague, Faidra Laskou, Franz Jakob, David Karasik, Barbara Obermayer-Pietsch, Nerea Alonso, Åshild Bjørnerem, Maria Luisa Brandi, Björn Busse, Ângelo Calado, Alper Han Cebi, Maria Christou, Kathleen M. Curran, Jannie Dahl Hald, Maria Donatella Semeraro, Eleni Douni, Emma L. Duncan, Ivan Duran, Melissa M. Formosa, Yankel Gabet, Samuel Ghatan, Artemis Gkitakou, Eva Maria Hassler, Wolfgang Högler, Terhi J. Heino, Gretl Hendrickx, Patricia Khashayar, Douglas P. Kiel, Fjorda Koromani, Bente Langdahl, Philippe Lopes, Outi Mäkitie, Antonio Maurizi, Carolina Medina-Gomez, Evangelia Ntzani, Claes Ohlsson, Vid Prijatelj, Raquel Rabionet, Sjur Reppe, Fernando Rivadeneira, Gennady Roshchupkin, Neha Sharma, Kent Søe, Unnur Styrkarsdottir, Pavel Szulc, Anna Teti, Jon Tobias, Amina Valjevac, Jeroen van de Peppel, Bram van der Eerden, Bert van Rietbergen, Tatjana Zekic, M. Carola Zillikens
Journal: Trends in Endocrinology and Metabolism (2024)

Musculoskeletal research should synergistically investigate bone and muscle to inform approaches for maintaining mobility and to avoid bone fractures. The relationship between sarcopenia and osteoporosis, integrated in the term 'osteosarcopenia', is underscored by the close association shown between these two conditions in many studies, whereby one entity emerges as a predictor of the other. In a recent workshop of Working Group (WG) 2 of the EU Cooperation in Science and Technology (COST) Action 'Genomics of MusculoSkeletal traits Translational Network' (GEMSTONE) consortium (CA18139), muscle characterization was highlighted as being important, but currently under-recognized in the musculoskeletal field. Here, we summarize the opinions of the Consortium and research questions around translational and clinical musculoskeletal research, discussing muscle phenotyping in human experimental research and in two animal models: zebrafish and mouse.
Mesenchymal stem cells alleviate mouse liver fibrosis by inhibiting pathogenic function of intrahepatic B cells
Authors: Xudong Feng, Bing Feng, Jiahang Zhou, Jinfeng Yang, Qiaoling Pan, Jiong Yu, Dandan Shang, Lanjuan Li, Hongcui Cao
Journal: Hepatology (2024)

Background and Aims: The immunomodulatory characteristics of mesenchymal stem cells (MSCs) make them a promising therapeutic approach for liver fibrosis (LF). Here, we postulated that MSCs could potentially suppress the pro-fibrotic activity of intrahepatic B cells, thereby inhibiting LF progression. Approach and Results: Administration of MSCs significantly ameliorated LF as indicated by reduced myofibroblast activation, collagen deposition, and inflammation. The treatment efficacy of MSCs can be attributed to decreased infiltration, activation, and pro-inflammatory cytokine production of intrahepatic B cells. Single-cell RNA sequencing revealed a distinct intrahepatic B cell atlas, and a subtype of naive B cells (B-II) was identified, which were markedly abundant in fibrotic liver, displaying mature features with elevated expression of several proliferative and inflammatory genes. Transcriptional profiling of total B cells revealed that intrahepatic B cells displayed activation, proliferation, and pro-inflammatory gene profile during LF. Fibrosis was attenuated in mice ablated with B cells (μMT) or in vivo treatment with anti-CD20. Moreover, fibrosis was recapitulated in μMT after adoptive transfer of B cells, which in turn could be rescued by MSC injection, validating the pathogenic function of B cells and the efficacy of MSCs on B cell-promoted LF progression. Mechanistically, MSCs could inhibit the proliferation and cytokine production of intrahepatic B cells through exosomes, regulating the Mitogen-activated protein kinase and Nuclear factor kappa B signaling pathways. Conclusions: Intrahepatic B cells serve as a target of MSCs, play an important role in the process of MSC-induced amelioration of LF, and may provide new clues for revealing the novel mechanisms of MSC action.
Single-cell–based molecular classification in systematic treatment of hepatocellular carcinoma: From in silico to bedside
Authors: Tuo Deng, Gang Chen
Journal: Hepatology (2024)

1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China 2Zhejiang-Germany Interdisciplinary Joint Laboratory of Hepatobiliary-Pancreatic Tumor and Bioengineering, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China 3Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China Correspondence Gang Chen, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. Email: [email protected]
Ampicillin susceptibility testing of Haemophilus influenzae in the routine clinical laboratory by the EUCAST methodology compared to broth microdilution and the presence of ftsI gene mutations
Authors: Patrick D.J. Sturm, Noud T.H. Hermans, Adri G.M. van der Zanden, Cas J.A. Peters, Tanja Schülin
Journal: Clinical Microbiology and Infection (2024)
Prominent role of gut dysbiosis in the pathogenesis of cystic fibrosis-related liver disease in mice
Authors: Anna Bertolini, Mytien Nguyen, Syeda Andleeb Zehra, Shakila Afroz Taleb, Tory Bauer-Pisani, Noah Palm, Mario Strazzabosco, Romina Fiorotto
Journal: Journal of Hepatology (2024)
In situ neutrophil apoptosis and macrophage efferocytosis mediated by Glycyrrhiza protein nanoparticles for acute inflammation therapy
Authors: Xiong Liu, Xiangjun Ou, Tiantian Zhang, Xiaonan Li, Qi Qiao, Liyuan Jia, Zhangxi Xu, Fangming Zhang, Tianyi Tian, Hongbing Lan, Conglian Yang, Li Kong, Zhiping Zhang
Journal: Journal of Controlled Release (2024)
Bispecific fibrous glue synergistically boosts vascular normalization and antitumor immunity for advanced renal carcinoma therapy
Authors: Xiu-Hai Wu, Jia-Qi Wang, Man-Di Wang, Ting Xiao, Yu Wang, Jia-Yuan Niu, Lu Wang, Da-Yong Hou, Bo Fu, Zimo Liu, Hao Wang, Wanhai Xu
Journal: Biomaterials (2024)
Randomized, Double-Blind Phase III Study of Pazopanib Versus Placebo in Patients With Metastatic Renal Cell Carcinoma Who Have No Evidence of Disease After Metastasectomy: ECOG-ACRIN E2810
Authors: Leonard J. Appleman, Se Eun Kim, Wayne B. Harris, Sumanta K. Pal, Michael R. Pins, Jill Kolesar, Neeraj Agarwal, Rahul A. Parikh, Daniel A. Vaena, Christopher W. Ryan, Mehmood Hashmi, Brian A. Costello, David Cella, Janice P. Dutcher, Robert S. DiPaola, Naomi B. Haas, Lynne I. Wagner, Michael A. Carducci
Journal: Journal of Clinical Oncology (2024)

Patients with no evidence of disease (NED) after metastasectomy for renal cell carcinoma are at high risk of recurrence. Pazopanib is an inhibitor of vascular endothelial growth factor receptor and other kinases that improves progression-free survival in patients with metastatic RCC (mRCC). We conducted a randomized, double-blind, placebo-controlled multicenter study to test whether pazopanib would improve disease-free survival (DFS) in patients with mRCC rendered NED after metastasectomy.
Significant Airway Obstruction by Carbonaceous Fibrin Casts in a Child with Smoke Inhalation Injury
Authors: Annemarie G. Wolfe, Paul C. Stillwell, Livia A. Veress
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Significant Airway Obstruction by Carbonaceous Fibrin Casts in a Child with Smoke Inhalation Injury." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Safety, Efficacy, and Biological Data of T-Cell–Enabling Oncolytic Adenovirus TILT-123 in Advanced Solid Cancers from the TUNIMO Monotherapy Phase I Trial
Authors: Santeri A. Pakola, Katriina J. Peltola, James H.A. Clubb, Elise Jirovec, Lyna Haybout, Tatiana V. Kudling, Tuomo Alanko, Riitta Korpisaari, Susanna Juteau, Marjut Jaakkola, Jorma Sormunen, Jukka Kemppainen, Annabrita Hemmes, Teijo Pellinen, Mirte van der Heijden, Dafne C.A. Quixabeira, Claudia Kistler, Suvi Sorsa, Riikka Havunen, Joao M. Santos, Victor Cervera-Carrascon, Akseli Hemminki
Journal: Clinical Cancer Research (2024)

Abstract Purpose: TILT-123 (igrelimogene litadenorepvec) is an oncolytic adenovirus armed with TNFa and IL2, designed to induce T-cell infiltration and cytotoxicity in solid tumors. Patients and Methods: TUNIMO (NCT04695327) was a single-arm, multicenter phase I dose-escalation trial designed to assess the safety of TILT-123 in advanced solid cancers refractory to standard therapy. Patients received intravenous and intratumoral TILT-123. The primary endpoint was safety by adverse events (AE), laboratory values, vital signs, and electrocardiograms. Secondary endpoints included tumor response, pharmacokinetics, and predictive biomarkers. Results: Twenty patients were enrolled, with a median age of 58 years. Most prevalent cancer types included sarcomas (35%), melanomas (15%) and ovarian cancers (15%). No dose-limiting toxicities were observed. The most frequent treatment-related AEs included fever (16.7%), chills (13.0%), and fatigue (9.3%). Ten patients were evaluable for response on day 78 with RECIST 1.1, iRECIST or PET-based evaluation. The disease control rate by PET was 6/10 (60% of evaluable patients) and 2/10 by RECIST 1.1 and iRECIST(20%of evaluable patients). Tumor size reductions occurred in both injected and non-injected lesions. TILT-123 was detected in injected and non-injected tumors, and virus was observed in blood after intravenous and intratumoral injections. Treatment resulted in reduction of lymphocytes in blood, with concurrent lymphocyte increases in tumors, findings compatible with trafficking. Conclusions: TILT-123 was safe and able to produce antitumor effects in local and distant lesions in heavily pre-treated patients. Good tolerability of TILT-123 facilitates combination studies, several of which are ongoing (NCT04217473, NCT05271318, NCT05222932, and NCT06125197). See related commentary by Silva-Pilipich and Smerdou, p. 3649
Accuracy of cone‐beam computed tomography in imaging the components of the periodontal phenotype
Authors: Ralf Schulze, Emilio Couso‐Queiruga, Christos Katsaros
Journal: Periodontology 2000 (2024)

The components and dimensions of the periodontal and peri-implant phenotype have a high relevance in contemporary dental research and should be taken into consideration in the decision-making process in the management of a variety of clinical scenarios to optimize the outcomes of therapy. Various assessment methods for quantifying and classifying the phenotypical dimensions have emerged and developed in recent decades. Nevertheless, the use of cone-beam computed tomography (CBCT) scans remains the most commonly used approach worldwide. However, the accuracy to adequately imaging and measuring the dimensions of the hard and soft tissue components around teeth may represent a significant challenge in different clinical scenarios due to factors such as the age of the patient and motion during the scan, presence of metallic artifacts causing streaks and gray-value distortion, overlapping of soft tissue structures, machine performance, file processing, and small voxel size among others. These factors pose a particular challenge when tiny structures are under investigation, for example, the buccal/lingual bony or soft tissue layer of lower/upper incisors. Therefore, this review addresses the underlying technical information of the use of CBCT scans, and suggests some recommendations on the utilization of this method of assessment to optimally use it despite its' system-inherent limitations.
Tuberculosis — United States, 2023
Authors: Paula M. Williams, Robert H. Pratt, William L. Walker, Sandy F. Price, Rebekah J. Stewart, Pei-Jean I. Feng
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

After 27 years of declining U.S. tuberculosis (TB) case counts, the number of TB cases declined considerably in 2020, coinciding with the COVID-19 pandemic.For this analysis, TB case counts were obtained from the National TB Surveillance System.U.S. Census Bureau population estimates were used to calculate rates overall, by jurisdiction, birth origin, race and ethnicity, and age group.Since 2020, TB case counts and rates have increased each year.During 2023, a total of 9,615 TB cases were provisionally reported by the 50 U.S. states and the District of Columbia (DC), representing an increase of 1,295 cases (16%) as compared with 2022.The rate in 2023 (2.9 per 100,000 persons) also increased compared with that in 2022 (2.5).Forty states and DC reported increases in 2023 in both case counts and rates.National case counts increased among all age groups and among both U.S.-born and non-U.S.-born persons.Although TB incidence in the United States is among the lowest in the world and most U.S. residents are at minimal risk, TB continues to cause substantial global morbidity and mortality.This postpandemic increase in U.S. cases highlights the importance of continuing to engage communities with higher TB rates and their medical providers in TB elimination efforts and strengthening the capacity in public health programs to carry out critical disease control and prevention strategies.