tbuckley/cabot-search huggingface dataset:
Alpha-Fetoprotein as a Potential Surrogate Biomarker for Atezolizumab + Bevacizumab Treatment of Hepatocellular Carcinoma
Authors: Andrew X. Zhu, Farshid Dayyani, Chia-Jui Yen, Zhenggang Ren, Yuxian Bai, Zhiqiang Meng, Hongming Pan, Paul Dillon, Shivani K. Mhatre, Vincent E. Gaillard, Sairy Hernandez, Robin Kate Kelley, Bruno Sangro
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Atezolizumab + bevacizumab is the new standard of care for systemic treatment-naïve, unresectable hepatocellular carcinoma (HCC). This exploratory study investigated on-treatment alpha-fetoprotein (AFP) response as a potential surrogate biomarker of prognosis for the combination therapy. Experimental Design: Data from Group A of the phase Ib GO30140 study were used to identify the optimal time for AFP measurement and AFP cutoffs to differentiate patients by their best confirmed response per independent review facility–assessed RECIST (IRF-RECIST) version 1.1: responders from nonresponders and patients with disease control from primary progressors. We applied these cutoffs to independent data from the atezolizumab + bevacizumab arm of the phase III IMbrave150 trial to distinguish patients based on (i) overall survival (OS) and progression-free survival (PFS) per IRF-RECIST 1.1 and (ii) best confirmed response per IRF-RECIST 1.1. Results: We derived AFP cutoffs of ≥75% decrease and ≤10% increase from baseline at 6 weeks to identify responders and those who had disease control, respectively. These cutoffs had high sensitivity and specificity in GO30140. In IMbrave150 patients, sensitivity was 0.59 and specificity was 0.86 for the ≥75% decrease AFP cutoff; the sensitivity was 0.77 and specificity was 0.44 for the ≤10% increase AFP cutoff. Both AFP cutoffs were associated with longer OS and PFS, particularly in patients with hepatitis B virus etiology (HR &amp;lt; 0.5; P &amp;lt; 0.01). Conclusions: AFP response at 6 weeks after initiating treatment is a potential surrogate biomarker of prognosis for patients with HCC receiving atezolizumab + bevacizumab. See related commentary by Cappuyns and Llovet, p. 3405
Bacteria may be in the liver, but the jury is still out
Authors: Nichole A. Broderick, Laszlo Nagy
Journal: Journal of Clinical Investigation (2022)

A fundamental and highly contested issue in microbiome research is whether internal organs such as the liver, brain, placenta, pancreas, and others are sterile and privileged or harbor a detectable and functional microbial biomass. In this issue of the JCI, Leinwand, Paul, et al. addressed this question using an array of diverse techniques and reported that normal healthy liver possesses a microbiome that is selectively recruited from the gut. They further showed that liver-enriched microbes contributed to shaping the immune network of this organ. Here, we attempt to put their findings into the context of other organs, discuss the technical challenges of defining such microbial communities, and provide some perspective about the road ahead for the field.
CD99 as a novel therapeutic target on leukemic progenitor cells in FLT3-ITDmut AML
Authors: Serena Travaglini, Tiziana Ottone, Daniela Francesca Angelini, Valentina Fiori, Sabrina Dominici, Nelida Ines Noguera, Martyna Śniegocka, Silvia Antonelli, Maria Antonietta Irno Consalvo, Marco De Bardi, Cristina Banella, Mariadomenica Divona, Francesco Marchesi, Silvia Masciarelli, Francesco Fazi, Marco Pieraccioli, Raffaele Palmieri, Gottardo De Angelis, Francesco Buccisano, Adriano Venditti, Luca Battistini, Mauro Magnani, Maria Teresa Voso
Journal: Leukemia (2022)
Corrigendum to “What Experts Think About Prostate Cancer Management During the COVID-19 Pandemic: Report from the Advanced Prostate Cancer Consensus Conference 2021” [Eur Urol 82(1):6–11]
Authors: Fabio Turco, Andrew Armstrong, Gerhardt Attard, Tomasz M. Beer, Himisha Beltran, Anders Bjartell, Alberto Bossi, Alberto Briganti, Rob G. Bristow, Muhammad Bulbul, Orazio Caffo, Kim N. Chi, Caroline Clarke, Noel Clarke, Ian D. Davis, Johann de Bono, Ignacio Duran, Ros Eeles, Eleni Efstathiou, Jason Efstathiou, Christopher P. Evans, Stefano Fanti, Felix Y. Feng, Karim Fizazi, Mark Frydenberg, Dan George, Martin Gleave, Susan Halabi, Daniel Heinrich, Celestia Higano, Michael S. Hofman, Maha Hussain, Nicholas James, Rob Jones, Ravindran Kanesvaran, Raja B. Khauli, Laurence Klotz, Raya Leibowitz, Christopher Logothetis, Fernando Maluf, Robin Millman, Alicia K. Morgans, Michael J. Morris, Nicolas Mottet, Hind Mrabti, Declan G. Murphy, Vedang Murthy, William K. Oh, Onyeanunam Ngozi Ekeke, Piet Ost, Joe M. O'Sullivan, Anwar R. Padhani, Christopher Parker, Darren M.C. Poon, Colin C. Pritchard, Danny M. Rabah, Dana Rathkopf, Robert E. Reiter, Mark Rubin, Charles J. Ryan, Fred Saad, Juan Pablo Sade, Oliver Sartor, Howard I. Scher, Neal Shore, Iwona Skoneczna, Eric Small, Matthew Smith, Howard Soule, Daniel Spratt, Cora N. Sternberg, Hiroyoshi Suzuki, Christopher Sweeney, Matthew Sydes, Mary-Ellen Taplin, Derya Tilki, Bertrand Tombal, Levent Türkeri, Hiroji Uemura, Hirotsugu Uemura, Inge van Oort, Kosj Yamoah, Dingwei Ye, Almudena Zapatero, Silke Gillessen, Aurelius Omlin
Journal: European Urology (2022)
Association of Septal Myectomy With Quality of Life in Patients With Left Ventricular Outflow Tract Obstruction From Hypertrophic Cardiomyopathy
Authors: Milind Y. Desai, Albree Tower-Rader, Natalie Szpakowski, Amgad Mentias, Zoran B. Popovic, Nicholas G. Smedira
Journal: JAMA Network Open (2022)
High prevalence of multidrug-resistant Gram-negative bacteria carriage in children screened prospectively for multidrug resistant organisms at admission to a paediatric hospital, Hamburg, Germany, September 2018 to May 2019
Authors: Safiullah Najem, Dorothée Eick, Johannes Boettcher, Annette Aigner, Mona Aboutara, Ines Fenner, Konrad Reinshagen, Ingo Koenigs
Journal: Eurosurveillance (2022)

BackgroundIncreasing resistance to antibiotics poses medical challenges worldwide. Prospective data on carriage prevalence of multidrug resistant organisms (MDRO) in children at hospital admission are limited and associated risk factors are poorly defined.AimTo determine prevalence of MDRO carriage in children at admission to our paediatric hospital in Hamburg and to identify MDRO carriage risk factors.MethodsWe prospectively obtained and cultured nasal/throat and inguinal/anal swabs from children (≤ 18 years) at admission between September 2018 and May 2019 to determine prevalence of meticillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Gram-negative bacteria (MRGN) and vancomycin-resistant enterococcus (VRE) and associated species. We collected medical histories using a questionnaire and evaluated 31 risk factors using logistic regression models.ResultsMDRO carriage prevalence of 3,964 children was 4.31% (95% confidence interval (CI): 3.69-5.00). MRSA carriage prevalence was 0.68% (95% CI: 0.44-0.99), MRGN prevalence was 3.64% (95% CI: 3.07-4.28) and VRE prevalence 0.08% (95% CI: 0.02-0.22). MDRO carriage was associated with MRGN history (odds ratio (OR): 6.53; 95% CI: 2.58-16.13), chronic condition requiring permanent care (OR: 2.67; 95% CI: 1.07-6.13), antibiotic therapy (OR: 1.92, 95% CI: 1.24-2.94), living in a care facility (OR: 3.34; 95% CI: 0.72-12.44) and refugee status in previous 12 months (OR: 1.91; 95% CI: 0.27-8.02). Compared to established practice, screening using risk-factors had better diagnostic sensitivity (86.13%; 95% CI: 80.89-91.40) and specificity (73.54%; 95% CI: 72.12-74.97).ConclusionMRGN carriage was higher than MRSA and VRE. Extended risk-factor-based admission screening system seems warranted.
Use of Immune Checkpoint Inhibitor Pembrolizumab in the Treatment of High-Risk, Early-Stage Triple-Negative Breast Cancer: ASCO Guideline Rapid Recommendation Update
Authors: Larissa A. Korde, Mark R. Somerfield, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2022)

ASCO Rapid Recommendations Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options.
Daratumumab plus lenalidomide/bortezomib/dexamethasone in Black patients with transplant-eligible newly diagnosed multiple myeloma in GRIFFIN
Authors: Ajay K. Nooka, Jonathan L. Kaufman, Cesar Rodriguez, Andrzej Jakubowiak, Yvonne Efebera, Brandi Reeves, Tanya Wildes, Sarah A. Holstein, Larry D. Anderson, Ashraf Badros, Leyla Shune, Ajai Chari, Huiling Pei, Annelore Cortoos, Sharmila Patel, J. Blake Bartlett, Jessica Vermeulen, Thomas S. Lin, Paul G. Richardson, Peter Voorhees
Journal: Blood Cancer Journal (2022)

Daratumumab plus lenalidomide
Long-term outcomes for ibrutinib–rituximab and chemoimmunotherapy in CLL: updated results of the E1912 trial
Authors: Tait D. Shanafelt, Xin Victoria Wang, Curtis A. Hanson, Elisabeth M. Paietta, Susan O’Brien, Jacqueline Barrientos, Diane F. Jelinek, Esteban Braggio, Jose F. Leis, Cong Christine Zhang, Steven E. Coutre, Paul M. Barr, Amanda F. Cashen, Anthony R. Mato, Avina K. Singh, Michael P. Mullane, Richard F. Little, Harry Erba, Richard M. Stone, Mark Litzow, Martin Tallman, Neil E. Kay
Journal: Blood (2022)

Abstract Herein, we present the long-term follow-up of the randomized E1912 trial comparing the long-term efficacy of ibrutinib–rituximab (IR) therapy to fludarabine, cyclophosphamide, and rituximab (FCR) and describe the tolerability of continuous ibrutinib. The E1912 trial enrolled 529 treatment-naïve patients aged ≤70 years with chronic lymphocytic leukemia (CLL). Patients were randomly assigned (2:1 ratio) to receive IR or 6 cycles of FCR. With a median follow-up of 5.8 years, median progression-free survival (PFS) is superior for IR (hazard ratio [HR], 0.37; P &amp;lt; .001). IR improved PFS relative to FCR in patients with both immunoglobulin heavy chain variable region (IGHV) gene mutated CLL (HR: 0.27; P &amp;lt; .001) and IGHV unmutated CLL (HR: 0.27; P &amp;lt; .001). Among the 354 patients randomized to IR, 214 (60.5%) currently remain on ibrutinib. Among the 138 IR-treated patients who discontinued treatment, 37 (10.5% of patients who started IR) discontinued therapy due to disease progression or death, 77 (21.9% of patients who started IR) discontinued therapy for adverse events (AEs)/complications, and 24 (6.8% of patients who started IR) withdrew for other reasons. Progression was uncommon among patients able to remain on ibrutinib. The median time from ibrutinib discontinuation to disease progression or death among those who discontinued treatment for a reason other than progression was 25 months. Sustained improvement in overall survival (OS) was observed for patients in the IR arm (HR, 0.47; P = .018). In conclusion, IR therapy offers superior PFS relative to FCR in patients with IGHV mutated or unmutated CLL, as well as superior OS. Continuous ibrutinib therapy is tolerated beyond 5 years in the majority of CLL patients. This trial was registered at www.clinicaltrials.gov as #NCT02048813.
Errors in Figure 2
Journal: JAMA Network Open (2022)

Ximena Cid-Serra, MD, PhD; Alistair Royse, MBBS, MD; David Canty, MD, PhD; Douglas F. Johnson, MD, PhD; Andrea B. Maier, MD, PhD; Tim Fazio, MD; Doa El-Ansary, BAppSc, PhD; Colin F. Royse, MBBS, MD
Clarifying Best Practices for Early Childhood Development
Authors: Bolajoko O. Olusanya, M. K. C. Nair
Journal: JAMA Pediatrics (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
BMP2/SMAD pathway activation in JAK2/p53-mutant megakaryocyte/erythroid progenitors promotes leukemic transformation
Authors: Bing Li, Wenbin An, Hua Wang, Timour Baslan, Shoron Mowla, Aishwarya Krishnan, Wenbin Xiao, Richard P. Koche, Ying Liu, Sheng F. Cai, Zhijian Xiao, Andriy Derkach, Ilaria Iacobucci, Charles G. Mullighan, Kristian Helin, Scott W. Lowe, Ross L. Levine, Raajit K. Rampal
Journal: Blood (2022)
LncRNA DACH1 protects against pulmonary fibrosis by binding to SRSF1 to suppress CTNNB1 accumulation
Authors: Jian Sun, Tongzhu Jin, Zhihui Niu, Jiayu Guo, Yingying Guo, Ruoxuan Yang, Qianqian Wang, Huiying Gao, Yuhan Zhang, Tianyu Li, Wenxin He, Zhixin Li, Wenchao Ma, Wei Su, Liangliang Li, Xingxing Fan, Hongli Shan, Haihai Liang
Journal: Acta Pharmaceutica Sinica B (2022)

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with unknown etiology and limited therapeutic options. Activation of fibroblasts is a prominent feature of pulmonary fibrosis. Here we report that lncRNA DACH1 (dachshund homolog 1) is downregulated in the lungs of IPF patients and in an experimental mouse model of lung fibrosis. LncDACH1 knockout mice develop spontaneous pulmonary fibrosis, whereas overexpression of LncDACH1 attenuated TGF-β1-induced aberrant activation, collagen deposition and differentiation of mouse lung fibroblasts. Similarly, forced expression of LncDACH1 not only prevented bleomycin (BLM)-induced lung fibrosis, but also reversed established lung fibrosis in a BLM model. Mechanistically, LncDACH1 binding to the serine/arginine-rich splicing factor 1 (SRSF1) protein decreases its activity and inhibits the accumulation of Ctnnb1. Enhanced expression of SRSF1 blocked the anti-fibrotic effect of LncDACH1 in lung fibroblasts. Furthermore, loss of LncDACH1 promoted proliferation, differentiation, and extracellular matrix (ECM) deposition in mouse lung fibroblasts, whereas such effects were abolished by silencing of Ctnnb1. In addition, a conserved fragment of LncDACH1 alleviated hyperproliferation, ECM deposition and differentiation of MRC-5 cells driven by TGF-β1. Collectively, LncDACH1 inhibits lung fibrosis by interacting with SRSF1 to suppress CTNNB1 accumulation, suggesting that LncDACH1 might be a potential therapeutic target for pulmonary fibrosis.
Pre-transplant EASIX and sepsis after allogeneic stem cell transplantation
Authors: Felix Korell, Nicholas Schreck, Carsten Müller-Tidow, Peter Dreger, Thomas Luft, Tobias Liebregts, Stefan Schönland, Ute Hegenbart, Aleksandar Radujkovic, Michael Schmitt, Axel Benner
Journal: Intensive Care Medicine (2022)
Application of intralesional traction assistance with traction wire to endoscopic submucosal dissection for colorectal neoplasms
Authors: Takayuki Nasu, Mitsuru Esaki, Yoshihisa Shoguchi, Xiaopeng Bai, Yosuke Minoda, Haruei Ogino, Eikichi Ihara
Journal: Endoscopy (2022)

Endoscopic submucosal dissection (ESD) is commonly performed for large colorectal neoplasms as a local treatment [1]. Several assistive traction methods have been developed to overcome the technical difficulties of ESD [2] [3] [4] [5]. We present a case of colorectal neoplasm that was successfully treated with intralesional traction-assisted ESD using a novel traction device ([Fig. 1]). This device, which consists of two clips equipped with a half-moon-shaped memory traction wire, allows a clear view of the submucosal layer by elevating the lesion with the shape memory force of the wire.
CD34+CD19−CD22+ B-cell progenitors may underlie phenotypic escape in patients treated with CD19-directed therapies
Authors: Clara Bueno, Susana Barrera, Alex Bataller, Valentín Ortiz-Maldonado, Natalina Elliot, Sorcha O’Byrne, Guanlin Wang, Montse Rovira, Francisco Gutierrez-Agüera, Juan L. Trincado, María González-González, Mireia Morgades, Marc Sorigué, Paloma Bárcena, Samanta Romina Zanetti, Montse Torrebadell, Nerea Vega-Garcia, Susana Rives, Mar Mallo, Francesc Sole, Adam J. Mead, Irene Roberts, Supat Thongjuea, Bethan Psaila, Manel Juan, Julio Delgado, Alvaro Urbano-Ispizúa, Josep María Ribera, Alberto Orfao, Anindita Roy, Pablo Menendez
Journal: Blood (2022)

CD19-directed immunotherapies have revolutionized the treatment of advanced B-cell acute lymphoblastic leukemia (B-ALL). Despite initial impressive rates of complete remission (CR) many patients ultimately relapse. Patients with B-ALL successfully treated with CD19-directed T cells eventually relapse, which, coupled with the early onset of CD22 expression during B-cell development, suggests that preexisting CD34+CD22+CD19- (pre)-leukemic cells represent an "early progenitor origin-related" mechanism underlying phenotypic escape to CD19-directed immunotherapies. We demonstrate that CD22 expression precedes CD19 expression during B-cell development. CD34+CD19-CD22+ cells are found in diagnostic and relapsed bone marrow samples of ∼70% of patients with B-ALL, and their frequency increases twofold in patients with B-ALL in CR after CD19 CAR T-cell therapy. The median of CD34+CD19-CD22+ cells before treatment was threefold higher in patients in whom B-ALL relapsed after CD19-directed immunotherapy (median follow-up, 24 months). Fluorescence in situ hybridization analysis in flow-sorted cell populations and xenograft modeling revealed that CD34+CD19-CD22+ cells harbor the genetic abnormalities present at diagnosis and initiate leukemogenesis in vivo. Our data suggest that preleukemic CD34+CD19-CD22+ progenitors underlie phenotypic escape after CD19-directed immunotherapies and reinforce ongoing clinical studies aimed at CD19/CD22 dual targeting as a strategy for reducing CD19- relapses. The implementation of CD34/CD19/CD22 immunophenotyping in clinical laboratories for initial diagnosis and subsequent monitoring of patients with B-ALL during CD19-targeted therapy is encouraged.
Reopenable clip over-the-line method with muscle layer grasping clips for large duodenal post-endoscopic submucosal dissection defects
Authors: Tatsuma Nomura, Shinya Sugimoto, Taishi Temma, Jun Oyamada, Keiichi Ito, Akira Kamei
Journal: Endoscopy (2022)

Postoperative perforation and bleeding are serious complications of duodenal endoscopic submucosal dissection (ESD) [1]. We previously described the reopenable clip over-the-line method (ROLM), a technique used to close mucosal defects after ESD using a line and a reopenable clip [2] [3] [4]. However, large mucosal defects remain incompletely closed even after ROLM, as complete closure is difficult to achieve. Therefore, we devised ROLM with muscle layer grasping clips (ROLM-M), which completely closes the mucosal defect and muscle layer without any dead space between the mucosa and muscle layers.
When Hong Kong’s “dynamic zero” covid-19 strategy met omicron, low vaccination rates sent deaths soaring
Authors: Arisina Ma, Jane Parry
Journal: BMJ (2022)

When Hong Kong's "dynamic zero" covid-19 strategy met omicron, low vaccination rates sent deaths soaring How did Hong Kong go from being an exemplar of covid-19 control, to the place with the worst covid-19 death rate in the world?Arisina Ma, 1 Jane Parry 2It was a shocking image, unlike anything we had seen before in a Hong Kong hospital, 1 even during the devastating SARS outbreak in 2003.A photograph taken on the accident and emergency ward at the Queen Elizabeth Hospital showed three older patients, at least one visibly conscious.Tucked around their beds were six filled body bags on stretchers.The photo circulated on social media on 11 March 2022 and was verified as being taken at the hospital earlier that month.Hong Kong's mortuaries were full, and clearly no one had a plan to deal with this many dead bodies.
A bioactive compliant vascular graft modulates macrophage polarization and maintains patency with robust vascular remodeling
Authors: Alexander Stahl, Dake Hao, Janos Barrera, Dominic Henn, Sien Lin, Seyedsina Moeinzadeh, Sungwoo Kim, William Maloney, Geoffrey Gurtner, Aijun Wang, Yunzhi Peter Yang
Journal: Bioactive Materials (2022)

Conventional synthetic vascular grafts are associated with significant failure rates due to their mismatched mechanical properties with the native vessel and poor regenerative potential. Though different tissue engineering approaches have been used to improve the biocompatibility of synthetic vascular grafts, it is still crucial to develop a new generation of synthetic grafts that can match the dynamics of native vessel and direct the host response to achieve robust vascular regeneration. The size of pores within implanted biomaterials has shown significant effects on macrophage polarization, which has been further confirmed as necessary for efficient vascular formation and remodeling. Here, we developed biodegradable, autoclavable synthetic vascular grafts from a new polyurethane elastomer and tailored the grafts' interconnected pore sizes to promote macrophage populations with a pro-regenerative phenotype and improve vascular regeneration and patency rate. The synthetic vascular grafts showed similar mechanical properties to native blood vessels, encouraged macrophage populations with varying M2 to M1 phenotypic expression, and maintained patency and vascular regeneration in a one-month rat carotid interposition model and in a four-month rat aortic interposition model. This innovative bioactive synthetic vascular graft holds promise to treat clinical vascular diseases.