tbuckley/cabot-search huggingface dataset:
Letter to the Editor: Response to “Liver Transplantation for Acute Liver Failure Due to Dengue Fever”
Authors: Harshad Devarbhavi
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. To The Editor: I read with great interest the excellent report by Galante and colleagues regarding liver transplantation carried out in a patient with dengue virus–induced acute liver failure (ALF).1 Their report highlights the catastrophic suddenness with which dengue ALF commonly presents compared with ALF from conventional hepatitis virus. Dengue ALF is considered, albeit incorrectly, a consequence of secondary liver failure, and because of this, liver transplantation is not an accepted indication and is therefore not normally considered.2 However, as reported,1 the patient recovered swiftly from ALF and the associated profound circulatory disturbance after a timely liver transplantation, indicating the pivotal role played by the liver microcirculatory disturbance in causing ALF. This information receives scarce attention, and the report by Galante and coworkers will likely broaden the knowledge on the mechanism of dengue ALF. However, a few points need to be addressed by the authors: The authors ascribed the ~40% steatosis in the liver explant to a preexisting disease; steatosis is one of the hallmark features in liver biopsy specimens from patients with dengue hepatitis,3 although the exact reasons are not clear. The massive rise in transaminases (aspartate aminotransferase > 20,000 IU/L and alanine aminotransferase > 4,000 IU/L) reported by Galante et al.1 and other series in dengue ALF4 often occurs when patients are hemodynamically stable. In the absence of shock, these biochemical features may be ascribed to liver‐specific sinusoidal microcirculatory dysfunction leading to ischemia. These features may lead to reversal of portal blood flow and portal hypertension and have been described in dengue ALF but not in other viral liver infections.5 So, it would be interesting to know whether this feature was present in the authors' report. One of the classic teachings in hepatology is to investigate extrahepatic sources for a massive rise in transaminases, particularly when total bilirubin is mildly or modestly elevated, such as in the authors' report. Further, dengue‐induced rhabdomyolysis has been described. Was the creatinine phosphokinase level measured or was rhabdomyolysis ruled out? Dengue virus is not a classic hepatotropic virus.2 Therefore, liver immunohistochemistry for dengue viral antigen and its location in hepatocytes or its microcirculation will throw more light on the pathogenesis of dengue hepatitis in general and in ALF in particular. Because the entire explant is available for analysis, this information is very important to understand the pathogenesis of the disease.
Free Medications Boost Treatment Adherence
Authors: Anita Slomski
Journal: JAMA (2019)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
<i>Notes from the Field:</i> First Reported Case of <i>Shewanella haliotis</i> in the Region of the Americas — New York, December 2018
Authors: Dakai Liu, Roberto Hurtado Fiel, Lucy Shuo Cheng, Takuya Ogami, Lulan Wang, Vishnu Singh, George David Rodriguez, Daniel Hagler, Chun-Chen Chen, William Harry Rodgers
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

On December 18, 2018, a man aged 87 years was evaluated in a hospital emergency department in Flushing, New York, for right lower abdominal quadrant pain.Evaluation included a computed tomography scan, which showed acute appendicitis with multiple abscesses measuring ≤3 cm.The patient was admitted, a percutaneous drain was placed, and 5 mL of an opaque jelly-like substance was aspirated and sent for culture and testing for antimicrobial sensitivities.Gram stain of the culture revealed gram-negative rods, and culture revealed monomicrobial 1-2-mm yellowish-brown mucoid colonies.† Sequencing of the isolate's 16S ribosomal RNA revealed >99.8% homology with Shewanella haliotis strain DW01 in the GenBank database.Antimicrobial susceptibility testing indicated that the isolate was susceptible to aminoglycosides, fluoroquinolones, certain penicillins, and broad-spectrum cephalosporins (Table ).Biochemical tests were performed to characterize isolate (Supplementary Table, https://stacks.cdc.gov/view/cdc/83522). Phylogenetic analysis indicates that S. haliotis strain DW01 is the most recent ancestor of this clinical isolate.This is the first documented case of a S. haliotis appendix infection.S. haliotis is an emerging human pathogen, first isolated from abalone gut microflora in 2007 (1).The geographic distribution of human infections caused by S. haliotis is concentrated in Asia, with most reports coming from China, Japan, South Korea, and Thailand (2).No cases of S. haliotis human infections had been reported in the World Health Organization's Region of the Americas.The patient was treated empirically with intravenous piperacillin-tazobactam while in the hospital and was discharged with a prescription for oral amoxicillin-clavulanic acid.At a follow-up visit 13 days later, he was recovering well.Empiric treatment of Shewanella spp.can be challenging; limited and varying antibiotic susceptibility profiles have been reported * These authors contributed equally to the report.† After inoculation of specimen on sheep blood agar, chocolate agar, and MacKonkey agar plates and incubation at 98.6°F (37°C), beta-hemolysis was observed on the blood agar plates.
Reply to Murakami et al.
Authors: Yosuke Kataoka, Yosuke Tsuji, Kingo Hirasawa, Kengo Takimoto, Tomonori Wada, Satoshi Mochizuki, Ken Ohata, Yoshiki Sakaguchi, Keiko Niimi, Satoshi Ono, Shinya Kodashima, Nobutake Yamamichi, Mitsuhiro Fujishiro, Kazuhiko Koike
Journal: Endoscopy (2019)

See also:Endoscopic tissue shielding to prevent bleeding after endoscopic submucosal dissection: a prospective multicenter randomized controlled trialEndoscopy 2019; 51(07): 619-627DOI: 10.1055/a-0860-5280See also:Do polyglycolic acid sheets really prevent bleeding after endoscopic submucosal dissection? An opinion from physiological viewpointsEndoscopy 2020; 52(01): 76-76DOI: 10.1055/a-1021-8624
General election: 10 doctors are elected as MPs
Authors: Tom Moberly, Gareth Iacobucci
Journal: BMJ (2019)

Ten doctors have been elected as MPs in the 2019 UK general election. With one seat remaining to be declared on 13 December 2019, the Conservatives have won 364 seats, giving them a majority of 76.

More than 50 doctors stood as prospective parliamentary candidates in the 2019 general election, with most representing the Conservative Party or the Liberal Democrats.1

Of the 10 doctors elected, eight represent the Conservative Party, while Labour’s Rosena Allin-Khan (an emergency medicine doctor) held her seat in Tooting, south London, and the Scottish National Party’s Philippa Whitford (a breast surgeon) did so in Central Ayrshire.

Three of the eight Tory doctors are newly elected, two of whom won their seats from Labour: James Davies (a GP, elected in Vale of Clwyd) and Kieran Mullan (an emergency medicine doctor, Crewe and Nantwich). The third, Ben Spencer (a …
A call for global action for rare diseases in Africa
Authors: Gareth S. Baynam, Stephen Groft, Francois H. van der Westhuizen, Safiyya D. Gassman, Kelly du Plessis, Emily P. Coles, Eda Selebatso, Moses Selebatso, Boikobo Gaobinelwe, Tebogo Selebatso, Dipesalema Joel, Virginia A. Llera, Barend C. Vorster, Barbara Wuebbels, Benjamin Djoudalbaye, Christopher P. Austin, Judit Kumuthini, John Forman, Petra Kaufmann, James Chipeta, Désirée Gavhed, Annika Larsson, Maja Stojiljkovic, Ann Nordgren, Emilio J. A. Roldan, Domenica Taruscio, Durhane Wong-Rieger, Kristen Nowak, Gemma A. Bilkey, Simon Easteal, Sarah Bowdin, Juergen K. V. Reichardt, Sergi Beltran, Kenjiro Kosaki, Clara D. M. van Karnebeek, Mengchun Gong, Zhang Shuyang, Ruty Mehrian-Shai, David R. Adams, Ratna D. Puri, Feng Zhang, Nicholas Pachter, Maximilian Muenke, Christoffer Nellaker, William A. Gahl, Helene Cederroth, Stephanie Broley, Maryke Schoonen, Kym M. Boycott, Manuel Posada
Journal: Nature Genetics (2019)
Acalabrutinib monotherapy in patients with Waldenström macroglobulinemia: a single-arm, multicentre, phase 2 study
Authors: Roger G Owen, Helen McCarthy, Simon Rule, Shirley D'Sa, Sheeba K Thomas, Olivier Tournilhac, Francesco Forconi, Marie José Kersten, Pier Luigi Zinzani, Sunil Iyengar, Jaimal Kothari, Monique C Minnema, Efstathios Kastritis, Thérèse Aurran-Schleinitz, Bruce D Cheson, Harriet Walter, Daniel Greenwald, Dih-Yih Chen, Melanie M Frigault, Ahmed Hamdy, Raquel Izumi, Priti Patel, Helen Wei, Sun Ku Lee, Diana Mittag, Richard R Furman
Journal: The Lancet Haematology (2019)
Immune imbalance and activation are associated with lower lung function in youth with perinatally acquired HIV
Authors: Engi F. Attia, Denise Jacobson, Wendy Yu, Claudia S. Crowell, Elizabeth Maleche-Obimbo, Paige L. Williams, T. Eoin West, Sandra K. Burchett, Meyer Kattan, Andrew A. Colin, Sherry Eskander, Michael H. Chung, Kristina Crothers, William T. Shearer
Journal: Journal of Allergy and Clinical Immunology (2019)
Paternal occupational exposure to chemicals and secondary sex ratio: results from the Japan Environment and Children's Study
Authors: Sho Adachi, Junko Sawaki, Narumi Tokuda, Hiroyuki Tanaka, Hideaki Sawai, Yasuhiro Takeshima, Hiroaki Shibahara, Masayuki Shima
Journal: The Lancet Planetary Health (2019)

BackgroundDeclining proportions of male births have been reported in several industrialised countries. Previous reports have shown that exposure to certain chemical substances might influence the secondary sex ratio (SSR). We assessed the associations between paternal occupational exposure to chemicals and the SSR of their children using the Japan Environment and Children's Study (JECS), a large-scale birth cohort study.MethodsData on paternal occupational exposure to various agents and other covariates were collected using a self-administered questionnaire to partners of pregnant female participants enrolled in the JECS. After adjusting for potential confounders, multivariable modified Poisson regression models were used to evaluate associations between paternal occupational exposures and the SSR of their children. This study was registered in the UMIN Clinical Trials Registry, number UMIN000030786.FindingsThe JECS study gathered data on 103 062 pregnancies, 104 065 fetuses, and 51 898 partners of pregnant women. Among 50 283 children with data on paternal occupational exposures, 25 657 were male and 24 626 were female. The proportion of boys whose fathers were regularly occupationally exposed to insecticides was 0·445 (males, n=293; females, n=366; 95% CI 0·406–0·483), which was lower than the proportion of boys whose fathers were not exposed to insecticides. After adjusting for confounding factors, regular paternal occupational exposure to insecticides (adjusted relative risk 0·86, 95% CI 0·78–0·96) and medical disinfectants (0·95, 0·90–1·00) were significantly associated with lower SSRs among their offspring compared with the offspring of fathers not exposed to these substances.InterpretationA declining proportion of boys could potentially be due to fathers working in environments in which they are exposed to chemicals. The associations between poorer semen quality and levels of reproductive and thyroid hormones require investigation.FundingMinistry of the Environment of Japan.
Tranexamic Acid Improves Outcomes in TBI
Authors: Anita Slomski
Journal: JAMA (2019)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Immunotherapy in patients with relapsed/refractory HIV-related lymphomas
Authors: M. Popova, Y. Rogacheva, I. Tsygankov, K. Lepik, Y. Zalyalov, L. Stelmakh, I. Moiseev, S. Bondarenko, N. Mikhaylova, V. Baykov, B. Afanasyev
Journal: Annals of Oncology (2019)
Integrin β4–Targeted Cancer Immunotherapies Inhibit Tumor Growth and Decrease Metastasis
Authors: Shasha Ruan, Ming Lin, Yong Zhu, Lawrence Lum, Archana Thakur, Runming Jin, Wenlong Shao, Yalei Zhang, Yangyang Hu, Shiang Huang, Elaine M. Hurt, Alfred E. Chang, Max S. Wicha, Qiao Li
Journal: Cancer Research (2019)

Abstract Integrin β4 (ITGB4) has been shown to play an important role in the regulation of cancer stem cells (CSC). Immune targeting of ITGB4 represents a novel approach to target this cell population, with potential clinical benefit. We developed two immunologic strategies to target ITGB4: ITGB4 protein–pulsed dendritic cells (ITGB4-DC) for vaccination and adoptive transfer of anti-CD3/anti-ITGB4 bispecific antibody (ITGB4 BiAb)–armed tumor-draining lymph node T cells. Two immunocompetent mouse models were utilized to assess the efficacy of these immunotherapies in targeting both CSCs and bulk tumor populations: 4T1 mammary tumors and SCC7 head and neck squamous carcinoma cell line. Immunologic targeting of ITGB4 utilizing either ITGB4-DC or ITGB4 BiAb-T cells significantly inhibited local tumor growth and metastases in both the 4T1 and SCC7 tumor models. Furthermore, the efficacy of both of these ITGB4-targeted immunotherapies was significantly enhanced by the addition of anti–PD-L1. Both ITGB4-targeted immunotherapies induced endogenous T-cell cytotoxicity directed at CSCs as well as non-CSCs, which expressed ITGB4, and immune plasma–mediated killing of CSCs. As a result, ITGB4-targeted immunotherapy reduced not only the number of ITGB4high CSCs in residual 4T1 and SCC7 tumors but also their tumor-initiating capacity in secondary mouse implants. In addition, treated mice demonstrated no apparent toxicity. The specificity of these treatments was demonstrated by the lack of effects observed using ITGB4 knockout 4T1 or ITGB4-negative CT26 colon carcinoma cells. Because ITGB4 is expressed by CSCs across a variety of tumor types, these results support immunologic targeting of ITGB4 as a promising therapeutic strategy. Significance: This study identifies a novel mechanism of resistance to anti–PD-1/PD-L1 immunotherapy mediated by HPV E5, which can be exploited using the HPV E5 inhibitor rimantadine to improve outcomes for head and neck cancer patients.
Antibiotic prescribing without documented indication in ambulatory care clinics: national cross sectional study
Authors: Michael J Ray, Gregory B Tallman, David T Bearden, Miriam R Elman, Jessina C McGregor
Journal: BMJ (2019)

Abstract Objectives To identify the frequency with which antibiotics are prescribed in the absence of a documented indication in the ambulatory care setting, to quantify the potential effect on assessments of appropriateness of antibiotics, and to understand patient, provider, and visit level characteristics associated with antibiotic prescribing without a documented indication. Design Cross sectional study. Setting 2015 National Ambulatory Medical Care Survey. Participants 28 332 sample visits representing 990.9 million ambulatory care visits nationwide. Main outcome measures Overall antibiotic prescribing and whether each antibiotic prescription was accompanied by appropriate, inappropriate, or no documented indication as identified through ICD-9-CM (international classification of diseases, 9th revision, clinical modification) codes. Survey weighted multivariable logistic regression was used to evaluate potential risk factors for receipt of an antibiotic prescription without a documented indication. Results Antibiotics were prescribed during 13.2% (95% confidence interval 11.6% to 13.7%) of the estimated 990.8 million ambulatory care visits in 2015. According to the criteria, 57% (52% to 62%) of the 130.5 million prescriptions were for appropriate indications, 25% (21% to 29%) were inappropriate, and 18% (15% to 22%) had no documented indication. This corresponds to an estimated 24 million prescriptions without a documented indication. Being an adult male, spending more time with the provider, and seeing a non-primary care specialist were significantly positively associated with antibiotic prescribing without an indication. Sulfonamides and urinary anti-infective agents were the antibiotic classes most likely to be prescribed without documentation. Conclusions This nationally representative study of ambulatory visits identified a large number of prescriptions for antibiotics without a documented indication. Antibiotic prescribing in the absence of a documented indication may severely bias national estimates of appropriate antibiotic use in this setting. This study identified a wide range of factors associated with antibiotic prescribing without a documented indication, which may be useful in directing initiatives aimed at supporting better documentation.
Abstract I18: Retooling a blood-based biomarker into a theranostic agent
Authors: Jason S. Lewis
Journal: Cancer Research (2019)

Abstract Over the past 30 years, our ability to noninvasively diagnose, localize, and treat many forms of cancer has grown significantly. However, the biomolecular basis of many malignancies—most notably pancreatic cancer—remains convoluted, and technical advances have not translated to significantly improved survival rates. This is reflected in 1- and 5-year survival rates of 27% and 6%, respectively, for pancreatic cancer diagnoses. Given the tremendous current focus on the creation of new therapeutics for treating pancreatic cancer, the development of companion technologies that can safely, accurately, and unambiguously aid in the early diagnosis, staging, and treatment monitoring of pancreatic cancer is a vitally important—yet unmet—clinical need. The remarkable specificity and selectivity of antibodies for cancer biomarkers have made immunoglobulins some of the most flexible and adaptable tools in modern medicine. For therapeutic purposes, a wide range of nonlabeled antibodies has now entered the clinic. Antibody-based PET and SPECT imaging agents are not far behind. For example, an array of 89Zr-labeled radioimmunoconjugates has shown significant promise in both preclinical and clinical studies. CA19-9 levels in the serum are routinely used for diagnosis, risk stratification, and follow-up of PDAC. While CA19-9 is a shed antigen entering the circulation, the concentration is much higher in the tumor tissue, making it a potential target for in vivo imaging with radiolabeled antibodies. Our studies show that a tumor antigen secreted to the circulation can be used for sensitive detection of primary tumors and metastatic disease by immuno-PET. For example, in proof-of-concept preclinical studies, we were able to visualize pancreatic cancer xenograft and orthotopic models of early- and late-stage disease with excellent tumoral uptake and target-to-non-target ratios using the 89Zr-labeled human monoclonal antibody [89Zr]Zr-DFO-HuMab-5B1 (MVT-2163, NCT02687230). This 5B1 radioimmunoconjugate scaffold has also been deployed with therapeutic beta- and alpha-emitting radionuclides, creating an effective radiotherapeutic paradigm for the imaging and therapy of PDAC. In conclusion, our study shows that a tumor antigen secreted by PDAC to the circulation can be used for sensitive detection of primary tumors and metastatic disease by immuno-PET. This significantly broadens the number of molecular targets that can be used for PET imaging and provides new opportunities for noninvasive characterization of tumors in pancreatic cancer patients. Citation Format: Jason S. Lewis. Retooling a blood-based biomarker into a theranostic agent [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr I18.
Non-coding RNAs underlie genetic predisposition to breast cancer
Authors: Mahdi Moradi Marjaneh, Jonathan Beesley, Tracy A. O’Mara, Pamela Mukhopadhyay, Lambros T. Koufariotis, Stephen Kazakoff, Nehal Hussein, Laura Fachal, Nenad Bartonicek, Kristine M. Hillman, Susanne Kaufmann, Haran Sivakumaran, Chanel E. Smart, Amy E. McCart Reed, Kaltin Ferguson, Jodi M. Saunus, Sunil R. Lakhani, Daniel R. Barnes, Antonis C. Antoniou, Marcel E. Dinger, Nicola Waddell, Douglas F. Easton, Alison M. Dunning, Georgia Chenevix-Trench, Stacey L. Edwards, Juliet D. French
Journal: Genome biology (2020)

Abstract Background Genetic variants identified through genome-wide association studies (GWAS) are predominantly non-coding and typically attributed to altered regulatory elements such as enhancers and promoters. However, the contribution of non-coding RNAs to complex traits is not clear. Results Using targeted RNA sequencing, we systematically annotated multi-exonic non-coding RNA (mencRNA) genes transcribed from 1.5-Mb intervals surrounding 139 breast cancer GWAS signals and assessed their contribution to breast cancer risk. We identify more than 4000 mencRNA genes and show their expression distinguishes normal breast tissue from tumors and different breast cancer subtypes. Importantly, breast cancer risk variants, identified through genetic fine-mapping, are significantly enriched in mencRNA exons, but not the promoters or introns. eQTL analyses identify mencRNAs whose expression is associated with risk variants. Furthermore, chromatin interaction data identify hundreds of mencRNA promoters that loop to regions that contain breast cancer risk variants. Conclusions We have compiled the largest catalog of breast cancer-associated mencRNAs to date and provide evidence that modulation of mencRNAs by GWAS variants may provide an alternative mechanism underlying complex traits.
Expert-level diagnosis of nasal polyps using deep learning on whole-slide imaging
Authors: Qingwu Wu, Jianning Chen, Huiyi Deng, Yong Ren, Yueqi Sun, Weihao Wang, Lianxiong Yuan, Haiyu Hong, Rui Zheng, Weifeng Kong, Xuekun Huang, Guifang Huang, Lunji Wang, Yana Zhang, Lanqing Han, Qintai Yang
Journal: Journal of Allergy and Clinical Immunology (2019)