tbuckley/cabot-search huggingface dataset:
Perioperative lenvatinib combined with tislelizumab plus transcatheter arterial chemoembolization in resectable hepatocellular carcinoma with high-risk of recurrence: A prospective, single-arm, phase 2 trial.
Authors: Jia-Yi Wu, Yang-Kai Fu, Tianfu Wen, Shuang-Jia Wang, Jiafei Chen, Zhibo Zhang, Chongyuan Liu, Wei Wang, Lu Fang, Zhong Tang, Yufeng Chen, Maolin Yan
Journal: Journal of Clinical Oncology (2024)

503 Background: Early recurrence is common after surgery for hepatocellular carcinoma (HCC) and associated with poor prognosis. There is no standard of care neoadjuvant therapy. The combinations of lenvatinib, anti-PD-1 antibodies and transcatheter arterial chemoembolization (TACE) (triple therapy) has shown better trend in tumor response and survival outcomes on unresectable HCC. This study aims to explore the efficacy and safety of triple therapy in the neoadjuvant therapy of resectable HCC patients with high-risk of recurrence. Methods: This prospective, single-arm, phase 2 trial (ChiCTR2100048249) enrolled patients with primary resectable HCC who had not received prior anti-tumor therapy. TACE will be performed once on Day 1. Tislelizumab (an anti-PD-1 antibody, 200 mg) intravenously once every 3 weeks and lenvatinib (bodyweight ≥ 60 kg, 12 mg; &lt; 60 kg, 8 mg) orally daily was initiated within 7-10 days after TACE treatment. Surgery was performed 8 weeks after treatment. After 4-8 weeks of surgery, patients continued to receive tislelizumab and lenvatinib for 6 months. Primary endpoint was relapse-free survival (RFS). Secondary endpoints were objective response rate (ORR) by mRECIST, major pathological reactions, R0 resection rates, overall survival, and adverse events (AE). Results: From April 2022 to June 2023, 29 patients (median age, 54 years) from ten Chinese hospitals were enrolled, all Child-Pugh A and ECOG PS 0, mostly males (79.3%) and HBV infection (93.1%). According to mRECIST, the ORR was 89.7% (26/29, CR 4, PR 22), and the DCR was 96.7% (28/29). No grade 3 or above AE were observed. The most common AE were rash (4/29, 13.8%), thrombocytopenia (3/29, 10.3%), fatigue (3/29, 10.3%), elevated aspartate aminotransferase (2/29, 6.9%), elevated alanine aminotransferase (2/29, 6.9%), and hypertension (2/29, 6.9%). In 29 patients, 26 patients had received surgical treatment (R0 resection rates were 100%), 20 patients (20/26, 76.9%) achieved major pathological reaction (necrosis &gt; 90%), and 4 patients (4/26, 15.4%) achieved complete pathological response. 2 patient (6.9%) refused surgery. 1 patient (3.4%) developed disease progression and lost the chance of surgery. After a median follow-up of 8.0 months (interquartile range 4.6-12.3 months), one patient died of severe pneumonia caused by COVID-19 infection 9.9 months after operation. Tumor recurrence was detected in 3 patients. The 6- and 12-month RFS rates were 90% and 82.5%, respectively. Median RFS and overall survival were not reached. Conclusions: Lenvatinib, tislelizumab, and TACE were safe and showed promising efficacy as a neoadjuvant therapy for resectable HCC with high risk of recurrence. Clinical trial information: ChiCTR2100048249.
Tumor evolution reconstruction is heavily influenced by algorithmic and experimental choices
Authors: Rija Zaidi, Simone Zaccaria
Journal: Cancer Research (2024)

Abstract Tumor progression is an evolutionary process during which cells acquire distinct genetic alterations. Several cancer evolutionary studies reconstruct this evolutionary process by applying bulk DNA sequencing to a tumor sample to infer the presence of genetic alterations using various tumor evolutionary algorithms. Through a comprehensive benchmarking effort of these algorithms, a recent study by Salcedo and colleagues found that algorithmic and experimental choices are the main drivers of the accuracy of tumor evolution reconstruction, shedding new light on interpreting previous studies and suggesting a useful path forward for the research community.
PAR2 on oral cancer cells and nociceptors contributes to oral cancer pain that can be relieved by nanoparticle-encapsulated AZ3451
Authors: Divya Bhansali, Nguyen H Tu, Kenji Inoue, Shavonne Teng, Tianyu Li, Hung D Tran, Dong H Kim, Jessy Dong, Chloe J Peach, Badr Sokrat, Dane D Jensen, John C Dolan, Seiichi Yamano, Valeria Mezzano Robinson, Nigel W Bunnett, Donna G Albertson, Kam W Leong, Brian L Schmidt
Journal: Biomaterials (2024)
Improving prognostic accuracy in lung transplantation using unique features of isolated human lung radiographs
Authors: Bonnie T Chao, Andrew T Sage, Micheal C McInnis, Jun Ma, Micah Grubert Van Iderstine, Xuanzi Zhou, Jerome Valero, Marcelo Cypel, Mingyao Liu, Bo Wang, Shaf Keshavjee
Journal: npj Digital Medicine (2024)
Endovascular Ablation of the Greater Splanchnic Nerve in Heart Failure With Preserved Ejection Fraction
Authors: Marat Fudim, Barry A. Borlaug, Rajeev C. Mohan, Matthew J. Price, Peter Fail, Parag Goyal, Scott L. Hummel, Teona Zirakashvili, Tamaz Shaburishvili, Ravi B. Patel, Vivek Y. Reddy, Christopher D. Nielsen, Stanley J. Chetcuti, Devraj Sukul, Rajiv Gulati, Luke Kim, Keith Benzuly, Sumeet S. Mitter, Liviu Klein, Nir Uriel, Ralph S. Augostini, John E. Blair, Krishna Rocha-Singh, Daniel Burkhoff, Manesh R. Patel, Sami I. Somo, Sheldon E. Litwin, Sanjiv J. Shah
Journal: JAMA Cardiology (2024)

Greater splanchnic nerve ablation may improve hemodynamics in patients with heart failure and preserved ejection fraction (HFpEF).
Global Impact of Optimal Implementation of Guideline-Directed Medical Therapy in Heart Failure
Authors: Amber B. Tang, Boback Ziaeian, Javed Butler, Clyde W. Yancy, Gregg C. Fonarow
Journal: JAMA Cardiology (2024)

Importance Guideline-directed medical therapy (GDMT) remains underutilized on a global level, with significant disparities in access to treatment worldwide. The potential global benefits of quadruple therapy on patients with heart failure with reduced ejection fraction (HFrEF) have not yet been estimated. Objective To assess the projected population-level benefit of optimal GDMT use globally among patients with HFrEF. Design, Setting, and Participants Estimates for HFrEF prevalence, contraindications to GDMT, treatment rates, and the number needed to treat for all-cause mortality at 12 months were derived from previously published sources. Potential lives saved from optimal implementation of quadruple therapy among patients with HFrEF was calculated globally and a sensitivity analysis was conducted to account for uncertainty in the existing data. Main Outcomes and Measures All-cause mortality. Results Of an estimated 28.89 million people with HFrEF worldwide, there were 8 235 063 (95% CI, 6 296 020-10 762 972) potentially eligible for but not receiving β-blockers, 20 387 000 (95% CI, 15 867 004-26 184 996) eligible for but not receiving angiotensin receptor–neprilysin inhibitors, 12 223 700 (95% CI, 9 376 895-15 924 973) eligible for but not receiving mineralocorticoid receptor antagonists, and 21 229 170 (95% CI, 16 537 400-27 242 688) eligible for but not receiving sodium glucose cotransporter-2 inhibitors. Optimal implementation of quadruple GDMT could potentially prevent 1 188 277 (95% CI, 767 933-1 914 561) deaths over 12 months. A large proportion of deaths averted were projected in Southeast Asia, Eastern Mediterranean and Africa, and the Western Pacific regions. Conclusions and Relevance Improvement in use of GDMT could result in substantial mortality benefits on a global scale. Significant heterogeneity also exists across regions, which warrants additional study with interventions tailored to country-level differences for optimization of GDMT worldwide.
Incidence, In-Hospital and Long-Term Mortality, and Sequelae of Epidermal Necrolysis in Adults
Authors: Thomas Bettuzzi, Bénédicte Lebrun-Vignes, Saskia Ingen-Housz-Oro, Emilie Sbidian
Journal: JAMA Dermatology (2024)

The incidence of epidermal necrolysis (EN), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), varies across studies. While in-hospital mortality rates range from 15% to 20%, contributors to long-term mortality have been rarely evaluated and remain unknown.
Validation of the Delphi Consensus Diagnostic Criteria for Necrobiotic Xanthogranuloma
Authors: Fatima Bassir, Kailyn Valido, Kaitlin R. Maciejewski, William Damsky, Caroline A. Nelson
Journal: JAMA Dermatology (2024)

This diagnostic study validates the Delphi consensus diagnostic criteria for necrobiotic xanthogranuloma compared with its mimics.
Comparing Deprivation vs Vulnerability Index Performance Using Medicare Beneficiary Surgical Outcomes
Authors: Kimberly A. Rollings, Grace A. Noppert, Jennifer J. Griggs, Andrew M. Ibrahim, Philippa J. Clarke
Journal: JAMA Surgery (2024)

Health care researchers, professionals, payers, and policymakers are increasingly relying on publicly available composite indices of area-level socioeconomic deprivation to address health equity. Implications of index selection, however, are not well understood.
Bullous Pemphigoid Severity and Levels of Antibodies to BP180 and BP230
Authors: Po-Yi Chou, Chia-Ling Yu, Chiao-Ni Wen, Yu-Kang Tu, Ching-Chi Chi
Journal: JAMA Dermatology (2024)

The correlation between serum levels of autoantibodies against bullous pemphigoid (BP) antigens 180 (BP180) and 230 (BP230) with BP disease severity is unclear.
Trajectory of Cognitive Decline Before and After Stroke in 14 Population Cohorts
Authors: Jessica W. Lo, John D. Crawford, Darren M. Lipnicki, Richard B. Lipton, Mindy J. Katz, Pierre-Marie Preux, Maëlenn Guerchet, Eleonora d’Orsi, Anna Quialheiro, Cassiano Ricardo Rech, Karen Ritchie, Ingmar Skoog, Jenna Najar, Therese Rydberg Sterner, Elena Rolandi, Annalisa Davin, Michele Rossi, Steffi G. Riedel-Heller, Alexander Pabst, Susanne Röhr, Mary Ganguli, Erin Jacobsen, Beth E. Snitz, Kaarin J. Anstey, Allison E. Aiello, Henry Brodaty, Nicole A. Kochan, Yen-Ching Chen, Jen-Hau Chen, Pascual Sanchez-Juan, Teodoro del Ser, Meritxell Valentí, Antonio Lobo, Concepción De-la-Cámara, Elena Lobo, Perminder S. Sachdev
Journal: JAMA Network Open (2024)

Poststroke cognitive impairment is common, but the cognitive trajectory following a first stroke, relative to prestroke cognitive function, remains unclear.
Tranexamic Acid During Radical Cystectomy
Authors: Rodney H. Breau, Luke T. Lavallée, Ilias Cagiannos, Franco Momoli, Gregory L. Bryson, Salmaan Kanji, Christopher Morash, Alexis F. Turgeon, Ryan Zarychanski, Brett L. Houston, Daniel I. McIsaac, Ranjeeta Mallick, Greg A. Knoll, Girish Kulkarni, Jonathan Izawa, Fred Saad, Wassim Kassouf, Vincent Fradet, Ricardo Rendon, Bobby Shayegan, Adrian Fairey, Darrel E. Drachenberg, Dean Fergusson
Journal: JAMA Surgery (2024)

Among cancer surgeries, patients requiring open radical cystectomy have the highest risk of red blood cell (RBC) transfusion. Prophylactic tranexamic acid (TXA) reduces blood loss during cardiac and orthopedic surgery, and it is possible that similar effects of TXA would be observed during radical cystectomy.
Strategic Changes in Organ Allocation Policy and Outcomes in Pediatric Acute Liver Failure
Authors: Sarah Bangerth, Shrestha Vijayendra, Johanna Ascher-Bartlett, Kambiz Etasami, Rohit Kohli, Juliet Emamaullee
Journal: JAMA Surgery (2024)

This cohort study analyzes the impact of the Organ Procurement and Transplantation Network’s policy changes on mortality and post–liver transplant survival for pediatric patients on the waitlist.
Eight-Week Supplementation With <i>Bifidobacterium lactis</i> HN019 and Functional Constipation
Authors: Jing Cheng, Carl Gao, Reeta Ala-Jaakkola, Sofia D. Forssten, Markku Saarinen, Ashley Hibberd, Arthur C. Ouwehand, Alvin Ibarra, Dingqiang Li, Anders Nordlund, Yingxin Wang, Xizhong Shen, Haixia Peng, Xinjian Wan, Xiangjun Meng
Journal: JAMA Network Open (2024)

Importance Probiotic supplementation may improve bowel movements. However, large, properly designed studies are lacking. Objective To evaluate the potential benefit of Bifidobacterium animalis subsp lactis HN019 on constipation, expressed as complete spontaneous bowel movements (CSBMs). Design, Setting, and Participants This randomized triple-blind placebo-controlled clinical trial with 2 weeks of run-in and 8 weeks of intervention was conducted from December 25, 2020, to February 28, 2022, at 5 hospitals in Shanghai, China. Participants included healthy volunteers with functional constipation according to Rome III criteria, 18 to 70 years of age, and a body mass index (calculated as the weight in kilograms divided by the height in meters squared) of less than 30.0. Eligibility after the run-in phase required the randomized participants to have 3 or fewer CSBMs/wk. Data were analyzed from September 29, 2022, to March 23, 2023, and reported as intention to treat. Intervention Participants were randomized to receive probiotic ( B lactis HN019, 7.0 × 10 9 colony forming units (CFU)/d in maltodextrin at the start of the study and 4.69 × 10 9 CFU/d at the end of the study or maltodextrin placebo once a day for 8 weeks. Main Outcomes and Measures Primary outcome was change in CSBMs. Secondary outcomes included use of rescue medication, stool consistency, degree of straining for each bowel movement, abdominal pain, and bloating. Further, dietary habits and physical activity were recorded. Fecal samples were analyzed for moisture content, short-chain fatty acids, branched-chain fatty acids, microbiota composition, and calprotectin. Results Of the 283 individuals assessed for eligibility, 229 were randomized to either the placebo (n = 117) or the HN019 (n = 112) group. One participant in the placebo group discontinued due to COVID-19 restrictions. The 229 participants (194 [84.7% female) had a median age of 45 (38-52) years, mean (SD) BMI of 22.8 (2.5), and a mean (SD) of 0.77 (1.0) CSBM/wk. There was no difference in the change of weekly CSBMs from baseline to the end of study between the HN019 (least-square mean change, 0.80 [95% CI, 0.54-1.05]) and placebo (least-square mean change, 0.66 [95% CI, 0.41-0.90]) groups. Conclusions and Relevance Although probiotics have been reported to improve bowel function, this large, well-conducted randomized clinical trial did not confirm such results. Daily consumption of B lactis HN019 at the tested dose of 4.69 × 10 9 CFU did not outperform placebo to increase CSBMs. Trial Registration Chinese Clinical Trial Registry Identifier: ChiCTR2000029215
Lithium Aspartate for Long COVID Fatigue and Cognitive Dysfunction
Authors: Thomas Guttuso, Jingtao Zhu, Gregory E. Wilding
Journal: JAMA Network Open (2024)

Importance Neurologic post–COVID-19 condition (PCC), or long COVID, symptoms of fatigue and cognitive dysfunction continue to affect millions of people who have been infected with SARS-CoV-2. There currently are no effective evidence-based therapies available for treating neurologic PCC. Objective To assess the effects of lithium aspartate therapy on PCC fatigue and cognitive dysfunction. Design, Setting, and Participants A randomized, double-blind, placebo-controlled trial (RCT) enrolling participants in a neurology clinic from November 28, 2022, to June 29, 2023, with 3 weeks of follow-up, was conducted. Subsequently, an open-label lithium dose-finding study with 6 weeks of follow-up was performed among the same participants enrolled in the RCT. Eligible individuals needed to report new, bothersome fatigue or cognitive dysfunction persisting for more than 4 weeks after a self-reported positive test for COVID-19, Fatigue Severity Scale-7 (FSS-7) or Brain Fog Severity Scale (BFSS) score of 28 or greater, Beck Depression Inventory-II score less than 24, and no history of a condition known to cause fatigue or cognitive dysfunction. All participants in the RCT were eligible for the dose-finding study, except for those who responded to the placebo. Intention-to-treat analysis was used. Intervention Lithium aspartate, 10 to 15 mg/d, or identically appearing placebo for 3 weeks followed by open-label lithium aspartate, 10 to 15 mg/d, for 2 weeks. In the subsequent dose-finding study, open-label lithium aspartate dosages up to 45 mg/d for 6 weeks were given. Main Outcomes and Measures Change in sum of FSS-7 and BFSS scores. The scores for each measure range from 7 to 49, with higher scores indicating more severe symptoms. Secondary outcomes included changes from baseline in the scores of additional questionnaires. Results Fifty-two participants were enrolled (30 [58%] males; mean [SD] age, 58.54 [14.34] years) and 26 were randomized to treatment with lithium aspartate (10 females) and 26 to placebo (12 female). Two participants assigned to lithium aspartate were lost to follow-up and none withdrew. No adverse events were attributable to lithium therapy. There were no significant intergroup differences for the primary outcome (−3.6; 95% CI, −16.6 to 9.5; P = .59) or any secondary outcomes. Among 3 patients completing a subsequent dose-finding study, open-label lithium aspartate, 40 to 45 mg/d, was associated with numerically greater reductions in fatigue and cognitive dysfunction scores than 15 mg/d, particularly in 2 patients with serum lithium levels of 0.18 and 0.49 mEq/L compared with 1 patient with a level of 0.10 mEq/L. Conclusions and Relevance In this RCT, therapy with lithium aspartate, 10 to 15 mg/d, was ineffective for neurologic PCC fatigue and cognitive dysfunction. Another RCT is required to assess the potential benefits of higher lithium dosages for treating neurologic PCC. Trial Registration ClinicalTrials.gov Identifier: NCT05618587 and NCT06108297
Mental Disorders and Suicidality in Transgender and Gender-Diverse People
Authors: Heidi Eccles, Alex Abramovich, Karen A. Patte, Tara Elton-Marshall, Nicole Racine, Mark A. Ferro, Jordan Edwards, Kelly K. Anderson, Tracie O. Afifi, Marie-Claude Geoffroy, Mila Kingsbury, Ian Colman
Journal: JAMA Network Open (2024)

This cross-sectional study examines the prevalence and risk of mental disorders, substance use disorders, and suicidal behaviors among transgender and gender-diverse (TGD) and cisgender Canadians.
Youth Firearm Mortality in the Americas From 2015 to 2022
Authors: Michelle Degli Esposti, Christian D. Pulcini, Eric William Fleegler, Eugenio Weigend Vargas, Laura Vargas, Adriana Yock-Corrales, Stephen Hargarten
Journal: JAMA Network Open (2024)

This cross-sectional study uses national vital statistics on firearm mortality to investigate trends in firearm deaths among youths in the US, Brazil, Mexico, and Colombia.
Dialysis for Chronic Kidney Failure
Authors: Jennifer E. Flythe, Suzanne Watnick
Journal: JAMA (2024)

Importance More than 3.5 million people worldwide and 540 000 individuals in the US receive maintenance hemodialysis or peritoneal dialysis for the treatment of chronic kidney failure. The 5-year survival rate is approximately 40% after initiation of maintenance dialysis. Observations Hemodialysis and peritoneal dialysis remove metabolic waste and excess body water and rebalance electrolytes to sustain life. There is no recommended estimated glomerular filtration rate (eGFR) threshold for initiating dialysis, and patient-clinician shared decision-making should help determine when to initiate dialysis. Persistent signs and symptoms of uremia (eg, nausea, fatigue) and volume overload (eg, dyspnea, peripheral edema), worsening eGFR, metabolic acidosis, and hyperkalemia inform the timing of therapy initiation. A randomized clinical trial reported no mortality benefit to starting dialysis at higher eGFR (10-14 mL/min/1.73 m 2 ) vs lower eGFR (5-7 mL/min/1.73 m 2 ) levels. Observational data suggested no differences in 5-year mortality with use of hemodialysis vs peritoneal dialysis. Cardiovascular (eg, arrhythmias, cardiac arrest) and infection-related complications of maintenance dialysis are common. In the US, hemodialysis catheter–related bloodstream infections occur at a rate of 1.1 to 5.5 episodes per 1000 catheter-days and affect approximately 50% of patients within 6 months of catheter placement. Peritonitis occurs at a rate of 0.26 episodes per patient-year and affects about 30% of individuals in the first year of peritoneal dialysis therapy. Chronic kidney failure–related systemic complications, such as anemia, hyperphosphatemia, hypocalcemia, and hypertension, often require pharmacologic treatment. Hypotension during dialysis, refractory symptoms (eg, muscle cramps, itching), and malfunction of dialysis access can interfere with delivery of dialysis. Conclusions and Relevance In 2021, more than 540 000 patients in the US received maintenance hemodialysis or peritoneal dialysis for treatment of chronic kidney failure. Five-year survival rate after initiation of maintenance dialysis is approximately 40%, and the mortality rate is similar with hemodialysis and peritoneal dialysis. Decisions about dialysis initiation timing and modality are influenced by patient symptoms, laboratory trajectories, patient preferences, and therapy cost and availability and should include shared decision-making.
Spending by the Veterans Health Administration for Medicare Advantage Dual Enrollees, 2011-2020
Authors: David J. Meyers, Aaron L. Schwartz, Lan Jiang, Jean Yoon, Amal N. Trivedi
Journal: JAMA (2024)

This study assesses veterans’ dual enrollment in the Veterans Health Administration (VHA) and Medicare Advantage and VHA spending from 2011 through 2020.
The Psychotherapy in MDMA-Assisted Psychotherapy
Authors: Ioana Alina Cristea, Pim Cuijpers, Joar Øveraas Halvorsen
Journal: JAMA Psychiatry (2024)

This Viewpoint discusses the critical yet overlooked role of the psychotherapy component in assessing the validity of the trials of midomafetamine/3,4-methylenedioxymethamphetamine (MDMA)–assisted psychotherapy for posttraumatic stress disorder.