tbuckley/cabot-search huggingface dataset:
Human Papillomavirus Vaccination Coverage Among Adolescent Girls Aged 13–17 Years — U.S.-Affiliated Pacific Islands, 2013–2023
Authors: Ashley Tippins, Glodi Mutamba, E.M. Boyd, Kelsey C. Coy, Jennifer L. Kriss
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Worldwide, cervical cancer is the fourth most common cancer among women, and the World Health Organization (WHO) Western Pacific Region, where the U.S.-affiliated Pacific Islands (USAPI) are located, accounts for one quarter of all estimated cases. Human papillomavirus (HPV) vaccines are recommended at age 11-12 years to prevent most cervical cancers. HPV vaccines were introduced across USAPI during 2007-2016, predominantly provided through school-located vaccination programs. Retrospective analysis using data from jurisdictional immunization information systems was used to estimate vaccination coverage among adolescent girls as of the last day of each calendar year during 2013-2023. This analysis measured progress toward the WHO 2030 vaccination coverage goal of ≥90% completion of the HPV vaccination series among girls by age 15 years. As of December 2023, initiation of the HPV vaccination series among adolescent girls aged 13-17 years ranged from 58.0% in Palau to 97.2% in the Northern Mariana Islands, and HPV vaccination series completion coverage ranged from 43.4% in Palau to 91.8% in the Northern Mariana Islands. HPV vaccination series completion coverage is >90% in the Northern Mariana Islands and is on track to meet WHO goals by 2030 in American Samoa. Assessment of adolescent vaccination coverage can help immunization programs monitor progress toward regional goals and identify populations and areas with low coverage. Implementing evidence-based strategies to increase vaccine access and coverage would benefit jurisdictions with lagging coverage.
Personalized Chemotherapy on the Basis of Tumor Marker Decline in Poor-Prognosis Germ-Cell Tumors: Updated Analysis of the GETUG-13 Phase III Trial
Authors: Karim Fizazi, Gwénaël Le Teuff, Aude Fléchon, Lance Pagliaro, Josef Mardiak, Lionnel Geoffrois, Brigitte Laguerre, Christine Chevreau, Remy Delva, Frederic Rolland, Christine Theodore, Guilhem Roubaud, Gwenaëlle Gravis, Jean-Christophe Eymard, Mathilde Cancel, Beata Juzyna, Maria Reckova, Natacha Naoun, Christopher Logothetis, Stephane Culine
Journal: Journal of Clinical Oncology (2024)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. GETUG-13 established that switching patients with poor-prognosis nonseminomatous germ-cell tumors with an unfavorable marker decline to intensified chemotherapy resulted in improved outcomes. Here, we report the GETUG-13 long-term efficacy and toxicity. Two hundred and sixty-three patients with International Germ Cell Cancer Consensus Group poor prognosis received one cycle of bleomycin, etoposide, and cisplatin (BEP): 51 with a favorable tumor marker decline continued with three cycles of BEP (Fav-BEP) and 203 with an unfavorable decline were randomly treated with three BEP (Unfav-BEP) cycles or a dose-dense regimen (Unfav-dose-dense; two cycles of paclitaxel-BEP-oxaliplatin + two cycles of cisplatin, ifosfamide, and bleomycin). The median follow-up was 7.1 years (range, 0.3-13.3). Five-year progression-free survival (PFS) rates were 58.9% in the Unfav-dose-dense arm and 46.7% in the Unfav-BEP arm (hazard ratio [HR], 0.65 [95% CI, 0.44 to 0.97]; P = .036). Five-year overall survival rates were 70.9% and 61.3% (HR, 0.74 [95% CI, 0.46 to 1.20]; P = .22). Side effects evolved favorably, with only three patients in the Unfav-dose-dense arm reporting grade 3 motor neurotoxicity at 1 year and no reported toxicity over grade 1 after year 2. Salvage high-dose chemotherapy plus a stem-cell transplant was used in 8% in the Unfav-dose-dense arm and 17% in the Unfav-BEP arm ( P = .035). Long-term outcomes suggest a sustained benefit of intensified chemotherapy in terms of PFS and numerically better survival, with a minimal toxicity and reduced use of salvage high-dose chemotherapy plus stem-cell transplant.
<i>Notes from the Field:</i> Tularemia Associated with Harbor Seal Necropsy — Kitsap County, Washington, October 2023
Authors: Wendy Inouye, Hanna N. Oltean, Michelle McMillan, Hanna Schnitzler, Beth Lipton, JohnAric MoonDance Peterson, Sylvia DuVernois, Kevin Snekvik, Rebecca M. Wolking, Jeannine Petersen, Elizabeth A. Dietrich, Laurel Respicio-Kingry, Gib Morrow
Journal: MMWR Morbidity and Mortality Weekly Report (2024)
Identification of leukemia stem cell subsets with distinct transcriptional, epigenetic and functional properties
Authors: Héléna Boutzen, Alex Murison, Alexa Oriecuia, Suraj Bansal, Christopher Arlidge, Jean C. Y. Wang, Mathieu Lupien, Kerstin B. Kaufmann, John E. Dick
Journal: Leukemia (2024)

The leukemia stem cell (LSC) compartment is a complex reservoir fueling disease progression in acute myeloid leukemia (AML). The existence of heterogeneity within this compartment is well documented but prior studies have focused on genetic heterogeneity without being able to address functional heterogeneity. Understanding this heterogeneity is critical for the informed design of therapies targeting LSC, but has been hampered by LSC scarcity and the lack of reliable cell surface markers for viable LSC isolation. To overcome these challenges, we turned to the patient-derived OCI-AML22 cell model. This model includes functionally, transcriptionally and epigenetically characterized LSC broadly representative of LSC found in primary AML samples. Focusing on the pool of LSC, we used an integrated approach combining xenograft assays with single-cell analysis to identify two LSC subtypes with distinct transcriptional, epigenetic and functional properties. These LSC subtypes differed in depth of quiescence, differentiation potential, repopulation capacity, sensitivity to chemotherapy and could be isolated based on CD112 expression. A majority of AML patient samples had transcriptional signatures reflective of either LSC subtype, and some even showed coexistence within an individual sample. This work provides a framework for investigating the LSC compartment and designing combinatorial therapeutic strategies in AML.
Busulfan-fludarabine versus busulfan-cyclophosphamide for allogeneic transplant in acute myeloid leukemia: long term analysis of GITMO AML-R2 trial
Authors: Gianluca Cavallaro, Anna Grassi, Chiara Pavoni, Maria Caterina Micò, Alessandro Busca, Irene Maria Cavattoni, Stella Santarone, Carlo Borghero, Attilio Olivieri, Giuseppe Milone, Patrizia Chiusolo, Pellegrino Musto, Riccardo Saccardi, Francesca Patriarca, Fabrizio Pane, Giorgia Saporiti, Paolo Rivela, Elisabetta Terruzzi, Raffaella Cerretti, Giuseppe Marotta, Angelo Michele Carella, Arnon Nagler, Domenico Russo, Paolo Corradini, Paolo Bernasconi, Anna Paola Iori, Luca Castagna, Nicola Mordini, Elena Oldani, Carmen Di Grazia, Andrea Bacigalupo, Alessandro Rambaldi
Journal: Blood Cancer Journal (2024)

We report the long-term results of a randomized trial (GITMO, AML-R2), comparing 1:1 the combination of busulfan and cyclophosphamide (BuCy2, n = 125) and the combination of busulfan and fludarabine (BuFlu, n = 127) as conditioning regimen in acute myeloid leukemia patients (median age 51 years, range 40-65) undergoing allogeneic hematopoietic stem cell transplantation. With a median follow-up of 6 years, significantly better non-relapse mortality (NRM) was confirmed in BuFlu recipients, which is sustained up to 4 years after transplant (10% vs. 20%, p = 0.0388). This difference was higher in patients older than 51 years (11% in BuFlu vs. 27% in BuCy2, p = 0.0262). The cumulative incidence of relapse, which was the first cause of death in the entire study population, did not differ between the two randomized arms. Similarly, the leukemia-free survival (LFS) and overall survival (OS) were not different in the two cohorts, even when stratifying patients per median age. Graft-and relapse-free survival (GRFS) in BuFlu arm vs. the BuCy2 arm was 25% vs. 20% at 4 years and 20% vs. 17% at 10 years. Hence, the benefit gained by NRM reduction is not offsets by an increased relapse. Leukemia relapse remains a major concern, urging the development of new therapeutic approaches.
Solitary Kidney Seeks Potassium Alkali to Lower the Pressure
Authors: Cary R. Boyd-Shiwarski, Aylin R. Rodan
Journal: Journal of the American Society of Nephrology (2024)

1Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 2Pittsburgh Center for Kidney Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 3Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah Spencer Fox Eccles School of Medicine, Salt Lake City, Utah 4Molecular Medicine Program, University of Utah Spencer Fox Eccles School of Medicine, Salt Lake City, Utah 5Department of Human Genetics, University of Utah Spencer Fox Eccles School of Medicine, Salt Lake City, Utah 6Medical Service, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah Correspondence: Dr. Aylin R. Rodan, email: [email protected] See related article, "Potassium-Alkali–Enriched Diet, Hypertension, and Proteinuria following Uninephrectomy," on pages XXX–XXX.
Long-Term Kidney Outcomes in Children with Posterior Urethral Valves
Authors: Cal H. Robinson, Mandy Rickard, Nivethika Jeyakumar, Graham Smith, Juliane Richter, Tim Van Mieghem, Joana Dos Santos, Rahul Chanchlani, Armando J. Lorenzo
Journal: Journal of the American Society of Nephrology (2024)

Key Points Among 727 children with posterior urethral valves, 32% had major adverse kidney events (death, kidney failure, or CKD) over a median of 14.2-year follow-up. Children with posterior urethral valves were at substantially higher risks of kidney failure, CKD, and hypertension than the general population. This justifies close kidney health surveillance among children with posterior urethral valves and optimized transitions to adult urologic care. Background Posterior urethral valves represent the most common cause of lower urinary tract obstruction in male infants (approximately 1/4000 live births). Long-term kidney outcomes of posterior urethral valves remain uncertain. We aimed to determine the time-varying risk of major adverse kidney events (MAKE) following children with posterior urethral valves into adulthood. Methods A population-based retrospective cohort study of all male children (&lt;2 years) diagnosed with posterior urethral valves between 1991 and 2021 in Ontario, Canada. Comparator cohorts were ( 1 ) male general population and ( 2 ) male children with pyeloplasty (both &lt;2 years). The primary outcome was MAKE (death, long-term KRT [dialysis or kidney transplant], or CKD). Time to MAKE was analyzed using multivariable-adjusted Cox proportional hazards models. We censored for provincial emigration or administrative censoring (March 31, 2022). Results We included 727 children with posterior urethral valves, 855 pyeloplasty comparators, and 1,013,052 general population comparators. The median follow-up time was 16.6 years (Q1–3, 8.6–24.5) overall. Throughout follow-up, 32% of children with posterior urethral valves developed MAKE versus 1% of the general population and 6% of pyeloplasty comparators. Their adjusted hazard ratio for MAKE was 36.6 (95% confidence interval, 31.6 to 42.4) versus the general population. The risk of developing MAKE declined over the first 5 years after posterior urethral valve diagnosis but remained elevated for &gt;30-year follow-up. Children with posterior urethral valves were also at higher risk of death, CKD, long-term KRT, hypertension, and AKI than the general population or pyeloplasty comparators. Conclusions Children with posterior urethral valves are at higher risk of adverse long-term kidney outcomes well into adulthood.
mRNA Modification and Mechanisms of Kidney Fibrosis
Authors: Midori Sakashita, Reiko Inagi
Journal: Journal of the American Society of Nephrology (2024)

Division of CKD Pathophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Correspondence: Prof. Reiko Inagi, email: [email protected] See related article, "METTL3-Mediated N6-Methyladenosine mRNA Modification and cGAS-STING Pathway Activity in Kidney Fibrosis," on pages XXX–XXX.
Regulatory and Payment Changes Addressing the Social Determinants of Kidney Health
Authors: Sri Lekha Tummalapalli, Andrew Lu, Lilia Cervantes
Journal: Journal of the American Society of Nephrology (2024)

1Division of Nephrology & Hypertension, Department of Medicine, Weill Cornell Medicine, New York, NY 2Division of Healthcare Delivery Science & Innovation, Department of Population Health Sciences, Weill Cornell Medicine, New York, NY 3The Rogosin Institute, New York, NY 4University of Pennsylvania, Philadelphia, PA 5Department of General Internal Medicine, University of Colorado Anschutz Medical Campus, Aurora aCorresponding author: Sri Lekha Tummalapalli, MD, MBA, MAS, Division of Healthcare Delivery Science & Innovation, Department of Population Health Sciences, 402 East 67th Street, New York, NY 10065, Ph: 646-962-8001, E-mail: [email protected]
Correction: Which is cheaper: a fully covered metallic stent or a choledochoscope?
Authors: Liang-Hao Hu, Ping-Ping Zhang, Ting Yang, Yan-Wei Lv
Journal: Endoscopy (2024)

Correction to: Which is cheaper: a fully covered metallic stent or a choledochoscope?Endoscopy 2024; 56(S 01): E695-E696DOI: 10.1055/a-2351-2645
Early onset Barrettʼs esophagus: new data, new challenges
Authors: Yuto Shimamura
Journal: Endoscopy (2024)

Barrett's esophagus (BE) is commonly diagnosed in individuals over 50 years of age, with increasing age being a significant risk factor [1]. Owing to its low prevalence in younger populations, most studies and clinical guidelines have focused primarily on older adults; however, the prevalence of BE in younger populations is an area of growing interest and concern, with data indicating an increasing incidence. A large dataset from the USA has shown that, while the proportion of BE patients aged 70 years and older has dropped significantly, younger patient groups have demonstrated the highest increases in BE cases, especially among those aged 30–39 years [2]. Despite extensive research on BE in the general population, data on its incidence and progression in younger individuals remain sparse.
Correlation of preoperative frailty with postoperative delirium and 1-year mortality in Chinese geriatric patients undergoing noncardiac surgery: a prospective observational cohort study
Authors: Min Zhang, Xiaojun Gao, Mengjie Liu, Zhongquan Gao, Yongle Guo, Lina Chen, Yang Liu, Xiaoning Zhang, Linlin Huang, Meng Tong, Ting Zou, Yongtao Sun
Journal: International Journal of Surgery (2024)

Zhang, Min MM; Gao, Xiaojun MM; Liu, Mengjie MD; Gao, Zhongquan MM; Guo, Yongle MM; Chen, Lina MM; Liu, Yang MM; Zhang, Xiaoning MM; Huang, Linlin BD; Tong, Meng BD; Zou, Ting BD; Sun, Yongtao Ph.D, MD Author Information
Comparative clinical efficacy and safety of biosimilar <scp>ABP</scp> 959 and eculizumab reference product in patients with paroxysmal nocturnal hemoglobinuria
Authors: Austin Kulasekararaj, Francesco Lanza, Alexandros Arvanitakis, Saskia Langemeijer, Satheesh Chonat, Anil Tombak, Vladimir Hanes, Jia Cao, Mieke Jill Miller, Alexander Colbert, Benjamin Shander, Daniel T. Mytych, Vincent Chow, Haby Henary
Journal: American Journal of Hematology (2024)

ABP 959 is a biosimilar to the eculizumab reference product (RP), which is approved for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH). This multicenter, randomized, double-blind, active-controlled, two-period crossover study randomized eculizumab RP-treated patients with PNH to one of two treatment sequences (ABP 959/eculizumab RP or eculizumab RP/ABP 959) to evaluate the clinical similarity of ABP 959 when compared with eculizumab RP. This study evaluated the efficacy of ABP 959 when compared with eculizumab RP based on control of intravascular hemolysis as measured by lactate dehydrogenase (LDH) and by the time-adjusted area under the effect curve of LDH. Secondary outcomes included safety, pharmacokinetics, and immunogenicity. Forty-two patients were randomized (20 in the ABP 959/eculizumab RP group and 22 in the eculizumab RP/ABP 959 group) across 25 centers. Similarity of efficacy was established by a ratio of geometric least squares means of LDH (ABP 959/eculizumab RP) of 1.0628, with a one-sided 97.5% upper CI of 1.1576 at week 27, and a geometric means ratio of time-adjusted area under the effect curve (ABP 959 vs. eculizumab RP) of LDH of 0.981, with a 90% CI of 0.9403-1.0239 from week 13 to 27, week 39 to 53, and week 65 to 79. All secondary efficacy endpoints were comparable between treatment groups. No new safety concerns were identified. The results of this study in patients with PNH, along with previously demonstrated similarity of analytical, nonclinical, and clinical pharmacokinetics and pharmacodynamics in healthy volunteers support a demonstration of no clinically meaningful differences between ABP 959 and eculizumab RP. Clinical Trial Registration: NCT03818607.
Evaluation of Etomidate Use and Association with Mortality Compared with Ketamine Among Critically Ill Patients
Authors: Hannah Wunsch, Nicholas A. Bosch, Anica C. Law, Emily A. Vail, May Hua, Burton H. Shen, Peter K. Lindenauer, David N. Juurlink, Allan J. Walkey, Hayley B. Gershengorn
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Uncertainty remains regarding the risks associated with single-dose use of etomidate.
PAFerroptosis Combined with Metabolic Disturbance of Mito by p52‐ZER6 for Enhanced Cancer Immunotherapy induced by Nano‐Bacilliform‐Enzyme
Authors: Zi‐yue Xi, Chuan‐yong Fan, Shuang Zhu, Gan‐yu Nie, Xin‐ran Xi, Ying‐ying Jiang, Yao Zhou, Yi‐hua Mei, Lu Xu
Journal: Advanced Healthcare Materials (2024)

Abstract The confused gene expressions and molecular mechanisms for mitochondrial dysfunction of traditional nanoenzymes is a challenge for tumor therapy. Herein, a nano‐bacilliform‐enzyme obtains the ability to inhibit p52‐ZER6 signal pathway, regulate the genes related to mitochondrial metabolism, and possess the GOx/CAT/POD‐like property. NBE acquires catalytic activity from the electronic energy transition. The tannin of NBE as a mitochondrial (Mito)‐targeting guide overloads MitoROS, and then metabolic disorder and lipid peroxidation of Mito membrane occurs, thus leading to a novel death pathway called PAFerroptosis (pyroptosis, apoptosis, and Ferroptosis). Simultaneously, in order to refrain from mitophagy, hydroxychloroquine is mixed with NBE to form a combo with strength pyroptosis. As a result, NBE/combo improves the PAFerroptosis obviously by activation of CD8+T cells and inactivation of MDSC cells, up‐regulating expression of caspase‐3 signal pathway, intercepting DHODH pathway to arrive excellent antitumor effect (93%). Therefore, this study establishes a rational nanoenzyme for mitochondrial dysfunction without mitophagy for effective antitumor therapy.
Menopausal Hormone Therapy and Ovarian and Endometrial Cancers: Long-Term Follow-Up of the Women's Health Initiative Randomized Trials
Authors: Rowan T. Chlebowski, Aaron K. Aragaki, Kathy Pan, Reina Haque, Thomas E. Rohan, Mihae Song, Jean Wactawski-Wende, Dorothy S. Lane, Holly R. Harris, Howard Strickler, Andrew M. Kauntiz, Carolyn D. Runowicz
Journal: Journal of Clinical Oncology (2024)

PURPOSE Menopausal hormone therapy's influence on ovarian and endometrial cancers remains unsettled. Therefore, we assessed the long-term influence of conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) and CEE-alone on ovarian and endometrial cancer incidence and mortality in the Women's Health Initiative randomized, placebo-controlled clinical trials. MATERIALS AND METHODS Postmenopausal women, age 50-79 years, were entered on two randomized clinical trials evaluating different menopausal hormone therapy regimens. In 16,608 women with a uterus, 8,506 were randomly assigned to once daily 0.625 mg of CEE plus 2.5 mg once daily of MPA and 8,102 placebo. In 10,739 women with previous hysterectomy, 5,310 were randomly assigned to once daily 0.625 mg of CEE-alone and 5,429 placebo. Intervention was stopped for cause before planned 8.5-year intervention after 5.6 years (CEE plus MPA) and after 7.2 years (CEE-alone). Outcomes include incidence and mortality from ovarian and endometrial cancers and deaths after these cancers. RESULTS After 20-year follow-up, CEE-alone, versus placebo, significantly increased ovarian cancer incidence (35 cases [0.041%] v 17 [0.020%]; hazard ratio [HR], 2.04 [95% CI, 1.14 to 3.65]; P = .014) and ovarian cancer mortality ( P = .006). By contrast, CEE plus MPA, versus placebo, did not increase ovarian cancer incidence (75 cases [0.051%] v 63 [0.045%]; HR, 1.14 [95% CI, 0.82 to 1.59]; P = .44) or ovarian cancer mortality but did significantly lower endometrial cancer incidence (106 cases [0.073%] v 140 [0.10%]; HR, 0.72 [95% CI, 0.56 to 0.92]; P = .01). CONCLUSION In randomized clinical trials, CEE-alone increased ovarian cancer incidence and ovarian cancer mortality, while CEE plus MPA did not. By contrast, CEE plus MPA significantly reduced endometrial cancer incidence.
Fellows’ Corner
Authors: Robert M. Wilechansky
Journal: Hepatology (2024)

1Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA 2Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA Abbreviations: 6MMP, 6-methylmercaptopurine; 6TGN, 6-thiopurine nucleotides; AIH, autoimmune hepatitis; AZA, azathioprine; CBR, complete biochemical remission; DM, diabetes mellitus; G/P, glecaprevir/pibrentasvir; MASLD, metabolic dysfunction–associated steatotic liver disease; MRI-PDFF, magnetic resonance imaging-proton density fat fraction; RCT, randomized controlled trial. Correspondence Robert M. Wilechansky, Massachusetts General Hospital, 15 Parkman St., Wang 5, Boston, MA 02114, USA. Email: [email protected]
Stimuli‐Responsive NO Delivery Platforms for Bacterial Infection Treatment
Authors: Yanling Hu, Meng Ding, Xinyi Lv, Jingai Jiang, Junjie Zhang, Dongliang Yang
Journal: Advanced Healthcare Materials (2024)

The prevalence of drug-resistant bacterial infections has emerged as a grave threat to clinical treatment and global human health, presenting one of the foremost challenges in medical care. Thus, there is an urgent imperative to develop safe and efficacious novel antimicrobial strategies. Nitric oxide (NO) is a recognized endogenous signaling molecule, which plays a pivotal role in numerous pathological processes. Currently, NO has garnered significant interest as an antibacterial agent due to its capability to eradicate bacteria, disrupt biofilms, and facilitate wound healing, all while circumventing the emergence of drug resistance. However, the inherently unstable characteristic of NO therapeutic gas renders the controlled administration of NO gases exceedingly challenging. Hence, in this review, the current challenge of bacterial infection is discussed; then it is briefly elucidated the antibacterial mechanism of NO and comprehensively delineate the recent advancements in stimulus-responsive NO delivery platforms, along with their merits, obstacles, and prospective avenues for clinical application. This review offers guidance for future advancements in NO-medicated anti-infection therapy is hoped.
Re: Wesley R. Armstrong, Amar U. Kishan, Kiara M. Booker, et al. Impact of Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography on Prostate Cancer Salvage Radiotherapy Management: Results from a Prospective Multicenter Randomized Phase 3 Trial (PSMA-SRT NCT03582774). Eur Urol 2024;86:52–60
Authors: Feng Qi
Journal: European Urology (2024)