tbuckley/cabot-search huggingface dataset:
Prognostic Value of the 13C‐Methacetin Breath Test in Adults with Acute Liver Failure and Non‐acetaminophen Acute Liver Injury
Authors: Robert J. Fontana, R. Todd Stravitz, Valerie Durkalski, James Hanje, Bilal Hameed, David Koch, Adrian Reuben, Daniel Ganger, Jody Olson, Iris Liou, Brendan M. McGuire, Kristen Clasen, William M. Lee
Journal: Hepatology (2021)

The 13 C-methacetin breath test (MBT) is a noninvasive, quantitative hepatic metabolic function test. The aim of this prospective, multicenter study was to determine the utility of initial and serial 13 C-MBT in predicting 21-day outcomes in adults with acute liver failure (ALF) and non-acetaminophen acute liver injury (ALI).The 13 C-MBT BreathID device (Exalenz Biosciences, Ltd.) provided the percent dose recovery (PDR) for a duration of 60 minutes after administration of 13 C-methacetin solution as the change in exhaled 13 CO2 /12 CO2 compared with pre-ingestion ratio on study days 1, 2, 3, 5, and 7. Results were correlated with 21-day transplant-free survival and other prognostic indices. A total of 280 subjects were screened for enrollment between May 2016 and August 2019. Median age of the 62 enrolled patients with adequate data was 43 years, 79% were Caucasian, 76% had ALF with the remaining 24% having ALI. The mean PDR peak on day 1 or day 2 was significantly lower in nonsurvivors compared with transplant-free survivors (2.3%/hour vs. 9.1%/hour; P < 0.0001). In addition, serial PDR peaks were consistently lower in nonsurvivors versus survivors (P < 0.0001). The area under the receiver operating characteristic curve (AUROC) of the 13 C-MBT in the combined cohort was 0.88 (95% CI: 0.79-0.97) and higher than that provided by King's College (AUROC = 0.70) and Model for End-Stage Liver Disease scores (AUROC = 0.83). The 13 C-MBT was well tolerated with only two gastrointestinal adverse events reported.The 13 C-MBT is a promising tool to estimate the likelihood of hepatic recovery in patients with ALF and ALI. Use of the PDR peak data from the 13 C-MBT point-of-care test may assist with medical decision making and help avoid unnecessary transplantation in critically ill patients with ALF and ALI.
Assessment of Immune Checkpoint Inhibitors and Genomic Alterations by Body Mass Index in Advanced Renal Cell Carcinoma
Authors: Aly-Khan A. Lalani, Ziad Bakouny, Subrina Farah, Frede Donskov, Shaan Dudani, Daniel Y. C. Heng, Toni K. Choueiri
Journal: JAMA Oncology (2021)

An elevated body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) has been associated with an increased risk of renal cell carcinoma (RCC). 1 Previously, higher BMI was shown to be a positive prognostic factor for patients with metastatic clear cell RCC (mRCC) who were treated during the vascular endothelial growth factor (VEGF)-targeted therapy era. 2 However, the treatment landscape has shifted to include immune checkpoint inhibitors (ICIs) for most patients.We investigated t h i s o b e s it y p a r a d ox i n p at i e nt s w it h m RC C w h o were treated with programmed cell death 1 protein/ programmed cell death 1 ligand 1 (PD-1/PD-L1)-based ICIs and explored potential genomic alterations according to BMI status.
CheckMate 9KD Arm B final analysis: Efficacy and safety of nivolumab plus docetaxel for chemotherapy-naïve metastatic castration-resistant prostate cancer.
Authors: Karim Fizazi, Pablo González Mella, Daniel Castellano, Jose Nicolas Minatta, Arash Rezazadeh, David R. Shaffer, Juan Carlos Vazquez Limon, Héctor Manuel Sánchez López, Andrew J. Armstrong, Lisa Horvath, Carlos Dzik, Neha P. Amin, Jia Li, Keziban Unsal-Kacmaz, Margitta Retz, Fred Saad, Daniel Peter Petrylak, Russell Kent Pachynski
Journal: Journal of Clinical Oncology (2021)

12 Background: CheckMate 9KD (NCT03338790) is a phase 2 trial of nivolumab (NIVO; anti-PD-1) in combination with rucaparib, docetaxel (DOCE), or enzalutamide for patients with metastatic castration-resistant prostate cancer (mCRPC). DOCE is a standard-of-care chemotherapy for mCRPC that may potentiate antitumor immune responses, thus supporting its use in combination with NIVO, which has shown limited antitumor activity in mCRPC as monotherapy. We report final analysis results for Arm B (NIVO + DOCE) of CheckMate 9KD. Methods: Arm B enrolled patients with chemotherapy-naive mCRPC with ongoing androgen deprivation therapy and ≤ 2 prior novel antiandrogen therapies (NATs; i.e., abiraterone, enzalutamide, etc.). Patients received NIVO 360 mg + DOCE 75 mg/m 2 Q3W + prednisone 5 mg BID for ≤ 10 cycles, followed by NIVO 480 mg Q4W until disease progression/unacceptable toxicity (up to 2 years). Coprimary endpoints were objective response rate (ORR) and prostate-specific antigen response rate (PSA-RR; defined as a ≥ 50% PSA reduction). Secondary endpoints included radiographic progression-free survival (rPFS), overall survival (OS), and safety. Results: Of 84 treated patients with a median age of 71 years (range: 53-88), 27% had visceral disease and 54% had measurable disease. The median number of docetaxel cycles was 8; the median number of nivolumab doses was 11. Median follow up was 15.2 months. The table displays the efficacy outcomes, which appear to show comparable ORR in patients receiving versus not receiving prior NAT. There was 1 (2.2%) complete objective response and 17 (37.8%) partial responses in 45 patients with measurable disease. Any-grade treatment-related AEs (TRAEs) occurred in 95.2% of patients, most commonly fatigue (39.3%), diarrhea (35.7%), and alopecia (34.5%). Grade 3-4 TRAEs occurred in 47.6% of patients, most commonly neutropenia (16.7%). TRAEs led to discontinuation in 29.8% of patients. The most common immune-related AEs were GI (35.7%) or skin-related (26.2%). There were 3 treatment-related deaths (1 pneumonitis related to NIVO; 2 pneumonias related to DOCE). Conclusions: NIVO + DOCE has encouraging clinical activity in patients with chemotherapy-naïve mCRPC, regardless of prior NAT, with a safety profile consistent with those of the individual agents. These outcomes support the ongoing phase 3 CheckMate 7DX trial of NIVO + DOCE vs placebo + DOCE for mCRPC (NCT04100018). Clinical trial information: NCT03338790. [Table: see text]
Abstract PO-048: Visual nucleotyping identifies chromatin phenotypes triggered by genome editing
Authors: Vivek Nandakumar, Sandra Stehling-Sun, William Kerwin, Alister Funnell, John Stamatoyannopoulos
Journal: Clinical Cancer Research (2021)

Abstract Optical microscopy has the potential to provide rapid phenotypic readout of cellular states. Here we show that automated optical phenotyping of nuclei is capable of rapidly and reliably discriminating the effects of targeted mutations to chromatin remodelers, which are major players in oncogenesis and targets for therapeutic intervention. Smarca4 is a chromatin remodeler frequently mutated in cancer. We investigated whether nuclear morphometry and concomitant supervised machine learning approaches on standard optical microscopy images of nuclear-DNA stained cells could reliably discern Smarca4-/- lung cancer cells from isogenic Smarca4+/+ clones that were derived by precision genome editing. We used TALEN-based editing on A549 lung cancer cells to generate isogenic Smarca4+/+ clones, performed conventional 2D 40x optical imaging of DAPI-stained cell nuclei from parental (Smarca4-/-) and edited (Smarca4+/+) cells, quantified a set of numerical parameters (features) that reflected various intuitive attributes of nuclear morphology and chromatin texture of the cell nuclei, and finally tested the efficacy of supervised machine learning algorithms containing these features to distinguish between the two cell categories. We found that the parental and edited A549 cells exhibited similar nuclear size and shape attributes but showed measurable differences in subtle chromatin texture. Additionally, classifiers based on these chromatin texture features were able to accurately distinguish the smarca4-rescued cells from the smarca4-mutant cells. Our results thus demonstrate the promise of quantitative chromatin phenotyping for genome editing applications in oncology. Citation Format: Vivek Nandakumar, Sandra Stehling-Sun, William Kerwin, Alister Funnell, John Stamatoyannopoulos. Visual nucleotyping identifies chromatin phenotypes triggered by genome editing [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PO-048.
Giardiasis Outbreaks — United States, 2012–2017
Authors: Erin E. Conners, Allison D. Miller, Neha Balachandran, Brittany M. Robinson, Katharine M. Benedict
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Giardiasis is a diarrheal disease caused by the parasite Giardia duodenalis, the most common cause of intestinal parasite infections in the United States.Transmission occurs when Giardia cysts spread from feces to water, food, surfaces, or skin and are then ingested.Illness is characterized by gastrointestinal symptoms, including diarrhea, abdominal cramps, greasy stools, bloating or gas, nausea, vomiting, weight loss, and dehydration.Approximately 50% of infections are asymptomatic (1,2).Most symptomatic Giardia infections are self-limited in duration; however, some persons might experience a reoccurrence of symptoms or develop long-term complications (3).During 2012-2017, public health officials from 26 states reported 111 giardiasis outbreaks (760 cases) to the National Outbreak Reporting System (NORS).Three main modes of transmission for these outbreaks were identified: water exposure in 29 (26%) outbreaks, person-to-person contact in 28 (25%) outbreaks, and contaminated food in six (5%) outbreaks.A single transmission mode could not be determined in 48 (43%) of the outbreaks.Private residences and child care facilities were the most common settings of outbreaks for all the transmission modes combined.To prevent and control giardiasis outbreaks, CDC recommends prompt diagnosis, maintaining good hand hygiene, cleaning and disinfecting home environments and child care facilities, and monitoring water quality in private wells.A giardiasis outbreak is defined as the occurrence of two or more cases of illness epidemiologically linked to a common exposure (1).Health department officials from across the United States (state, local, and District of Columbia), U.S. territories,* and freely associated states † voluntarily report outbreaks to NORS.This study included giardiasis outbreak reports submitted to NORS by December 30, 2019 and data reported during 2012-2017 (the year of the earliest case illness onset date through the most recent year for which data were available).NORS data summarized in this study include primary case counts, hospitalizations, and deaths; transmission mode; exposures and settings; and earliest onset date.Negative binomial regression analysis was conducted to assess for annual trends in outbreak counts using SAS (version 9.4; SAS Institute).This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy.§
Cardiac disease from accelerated FEV<sub>1</sub>decline and acute exacerbations: time to rethink comorbidities in COPD
Authors: Yunus Çolak
Journal: European Respiratory Journal (2021)

COPD is a prevalent disease in middle-aged and older adults associated with significant morbidity and mortality [1]. Individuals with COPD have an increased risk of different comorbidities, which complicates management of an already troublesome disease [2, 3]. One of these comorbidities is cardiovascular disease, which is believed to arise from shared risk factors, such as tobacco smoke, and the higher prevalence of major cardiovascular risk factors in individuals with COPD [4]. Nonetheless, even after accounting for all these risk factors, there remains an association between COPD and cardiovascular disease suspected to involve such diverse mechanisms as hypoxia and systemic inflammation [4]. Acute exacerbations but not accelerated FEV1 decline is associated with increased cardiovascular comorbidity risk in patients with COPD <https://bit.ly/36AuDV6>
Nicola Jean Campbell
Authors: Anne Troy, Ewen Forrest
Journal: BMJ (2021)

Nicola Jean Campbell was born in Salford. Her parents, Mary and Joe Campbell, were very proud when she went to the University of Liverpool to study medicine as she had wanted to be a doctor from an early age. She started her anaesthesia career in 1996 at the Countess of Chester Hospital, where she certainly made her mark with her future consultant colleagues. Nicola completed the rest of her anaesthetic training in the North West Deanery, during which she undertook a year long obstetric anaesthesia fellowship in Ottawa, Canada, in …
Tumor-associated neutrophils and macrophages interaction contributes to intrahepatic cholangiocarcinoma progression by activating STAT3
Authors: Zhengjun Zhou, Pengcheng Wang, Rongqi Sun, Jia Li, Zhiqiang Hu, Haoyang Xin, Chubin Luo, Jian Zhou, Jia Fan, Shaolai Zhou
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Tumor-associated neutrophils (TANs) and macrophages (TAMs) can each influence cancer growth and metastasis, but their combined effects in intrahepatic cholangiocarcinoma (ICC) remain unclear. Methods We explored the distributions of TANs and TAMs in patient-derived ICC samples by multiplex immunofluorescent staining and tested their separate and combined effects on ICC in vitro and in vivo. We then investigated the mechanistic basis of the effects using PCR array, western blot analysis and ELISA experiments. Finally, we validated our results in a tissue microarray composed of primary tumor tissues from 359 patients with ICC. Results The spatial distributions of TANs and TAMs were correlated with each other in patient-derived ICC samples. Interaction between TANs and TAMs enhanced the proliferation and invasion abilities of ICC cells in vitro and tumor progression in a mouse xenograft model of ICC. TANs and TAMs produced higher levels of oncostatin M and interleukin-11, respectively, in co-culture than in monoculture. Both of those cytokines activated STAT3 signaling in ICC cells. Knockdown of STAT3 abolished the protumor effect of TANs and TAMs on ICC. In tumor samples from patients with ICC, increased TAN and TAM levels were correlated with elevated p-STAT3 expression. All three of those factors were independent predictors of patient outcomes. Conclusions TANs and TAMs interact to promote ICC progression by activating STAT3.
Travel from the United Kingdom to the United States by a Symptomatic Patient Infected with the SARS-CoV-2 B.1.1.7 Variant — Texas, January 2021
Authors: Moriam Ojelade, Annette Rodriguez, Dante Gonzalez, Denzel Otokunrin, Srikanth Ramachandruni, Elizabeth Cuevas, Kelly Moon, Carla Gutiérrez Tyler, Melissa Freeland, Mark Anderson, Kambria Haire, Yuridia Orozco, Fija Scipio, Yuri Springer, Emilie Prot, Jennifer A. Shuford
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

In December 2020, the B.1.1.7 genetic variant of SARS-CoV-2, the virus that causes COVID-19, was first reported after emergence and rapid circulation in the United Kingdom (1). Evidence suggests that the B.1.1.7 variant is more efficiently transmitted than are other SARS-CoV-2 variants, and widespread circulation could thereby increase SARS-CoV-2 infection and hospitalization rates (1,2). The first reported SARS-CoV-2 B.1.1.7 variant case in the United States was confirmed by sequencing in Colorado on December 29, 2020.* This report describes a person who traveled from the United Kingdom to the United States after experiencing COVID-19-compatible symptoms† and was eventually confirmed to be infected with the B.1.1.7 variant.
Large colorectal mucosal defect closure post-endoscopic submucosal dissection using the reopenable clip over line method and modified locking-clip technique
Authors: Tatsuma Nomura, Shinya Sugimoto, Mayu Kawabata, Jun Oyamada, Akira Kamei
Journal: Endoscopy (2021)

Mucosal defects during extensive colorectal endoscopic submucosal dissection (ESD) cause post-ESD bleeding [1], and a method to close these defects has not yet been established. In recent years, the usefulness of a method for closing mucosal defects after colorectal ESD using a line and clips has been reported [2]. Therefore, we invented a new clip-line closure method called the "reopenable clip over line method" (ROLM), which uses a line (0.23-mm nylon line) and reopenable clips (SureClip; 8 or 16 mm; MC Medical, Tokyo, Japan) to close large colorectal mucosal defects. We also proposed a method of fixing the line to the first and second clips after the mucosal defect had been closed with thread-assisted mucosal defect closure using the locking-clip technique (LCT) [3]. However, LCT is difficult technically because it requires fixation by threading a line through the gap between the teeth at the base of the clip (EZ clip, HX-610-90S; Olympus) in the intestinal tract [4]. Therefore, we proposed a modified LCT (M-LCT) that involves performing the LCT by inserting the line through the gap between the teeth at the base of the clip before it is passed through the accessory channel of the endoscope.
A Link Between Cardiovascular Risk Management and Alzheimer Disease Is Still Elusive
Authors: Susan M. Landau, Theresa M. Harrison
Journal: JAMA Neurology (2021)

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 Neurology 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 Neurology journal
Relapsed/Refractory International Prognostic Index (R/<scp>R‐IPI</scp>): An international prognostic calculator for relapsed/refractory diffuse large B‐cell lymphoma
Authors: Matthew J. Maurer, Lasse H. Jakobsen, Raphael Mwangi, Norbert Schmitz, Umar Farooq, Cristopher R. Flowers, Peter de Nully Brown, Carrie A. Thompson, Henrik Frederiksen, David Cunningham, Judit Jørgensen, Viola Poeschel, Grzegorz Nowakowski, John F. Seymour, Francesco Merli, Corinne Haioun, Hervé Ghesquieres, Marita Ziepert, Hervé Tilly, Gilles Salles, Qian Shi, Tarec C. El‐Galaly, Thomas M. Habermann
Journal: American Journal of Hematology (2021)

Disease progression after frontline therapy for Diffuse large B-cell lymphoma (DLBCL) is a clinically significant event. Patients who experience early progression or have refractory disease have especially poor outcomes. Simple, clinically applicable prognostic tools are needed for selecting patients for consideration for novel therapies and prognostication in the relapsed/refractory (R/R) setting. Model building was performed in patients from the Surrogate endpoints in aggressive lymphoma (SEAL) consortium with disease progression after frontline immunochemotherapy. The primary endpoint was overall survival (OS) measured from date of progression. Validation was performed in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER) and Danish National Lymphoma Register (LYFO) cohorts. Model performance was assessed using time-dependent concordance indices (c-statistic) and calibration with metrics evaluated at 2 years from progression. Note, 1234 of 5112 patients treated with frontline immunochemotherapy in the SEAL consortium developed progressive disease. Time to progression on immunochemotherapy and age at progression were strongly associated with post-progression OS (both p < 0.001). A prognostic model was developed incorporating spline fit for both variables. The model had good concordance in the discovery (0.67) and validation sets (LYFO c = 0.64, MER c = 0.68) with generally good calibration. Time to progression on frontline therapy is strongly associated with post-progression OS in DLBCL. We developed and validated a simple to apply clinical prognostic tool in the R/R setting. The useful prediction of expected outcomes in R/R DLBCL and can inform treatment decisions such as considerations for CAR-T therapy as well as trial designs. The model is available in smartphone-based point of care applications.
Activity and safety of cabozantinib (cabo) in brain metastases (BM) from metastatic renal cell carcinoma (mRCC): An international multicenter study.
Authors: Laure Hirsch, Nieves Martinez Chanza, Subrina Farah, Ronan Flippot, Nityam Rathi, Katharine Collier, Guillermo de Velasco, Emmanuel Seront, Benoit Beuselinck, Wenxin Xu, Isaac Alexander Bowman, Elaine Tat Lam, Hannah Elizabeth Dzimitrowicz, Yousef Zakharia, Rana R. McKay, Mehmet Asim Bilen, Laurence Albiges, Wanling Xie, Lauren C Harshman, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2021)

310 Background: Cabo shows robust clinical activity in mRCC. Patients (pts) with BM have been underrepresented in clinical trials and effective systemic therapy is lacking. We retrospectively characterized the clinical activity and toxicity of cabo in pts with BM from RCC. Methods: Consecutive medical records from mRCC pts with BM treated with cabo monotherapy across 15 institutions were reviewed. Pts were grouped by radiologic presence (cohort 1) or absence (cohort 2) of progressing intracranial metastases. Brain-directed local therapy was allowed but radiological confirmation of intracranial progression at cabo start was required in cohort 1. Radiological response rate was investigator-assessed by modified RECIST 1.1 for intracranial and RECIST 1.1 for extracranial responses. Time to treatment failure (TTF) and overall survival (OS) were estimated by Kaplan-Meier. Results: We identified 69 pts with BM from RCC, 25 (36%) in cohort 1 and 44 (64%) in cohort 2. Majority were IMDC intermediate/poor (87%) and received cabo as ≥2nd line (75%). Median time from mRCC diagnosis to BM was 19.1 months (mos) (IQR 4.4-39.5). Overall, median number of BM was 3 (range 1-27) and median size of largest lesion was 1.2 cm (range 0.2-6.6) with frontal (62%) and parietal (48%) as the most frequent localizations. Prior brain directed therapy was used in 65% and 93% of pts in cohort 1 and 2 respectively. Median follow-up after cabo initiation was 11 mos (range 4-72). Twenty three percent of pts remained on therapy while 52% discontinued for progression and 9% for toxicity. Intracranial response rate was 61% (95%CI 39%-80%), with 3 complete responses, for cohort 1 and 57% (95%CI 41%-72%) for cohort 2. Only 10% (n = 7) had intracranial progression as best response. For cohort 1, extracranial response was 52% (95%CI 31%-72%), median TTF was 9.9 mos (95%CI 5.9-14.0) and OS was 14.7 mos (95%CI 7.7-23.0). For cohort 2, extracranial response was 41% (95%CI 26%-57%), TTF was 9.0 mos (95%CI 4.6-11.4) and OS was 14.1 mos (95%CI 11.0-22.0). Most common adverse events were fatigue (77%) and diarrhea (46%). Eight pts received concomitant brain-directed treatment during cabo therapy without neurological toxicities. Conclusions: Cabo shows significant intracranial activity and acceptable safety profile in pts with BM from RCC. [Table: see text]