tbuckley/cabot-search huggingface dataset:
Outbreak of KPC-2-producing Klebsiella pneumoniae endowed with ceftazidime-avibactam resistance mediated through a VEB-1-mutant (VEB-25), Greece, September to October 2019
Authors: Irene Galani, Ilias Karaiskos, Maria Souli, Vassiliki Papoutsaki, Lamprini Galani, Aikaterini Gkoufa, Anastasia Antoniadou, Helen Giamarellou
Journal: Eurosurveillance (2020)

From September to October 2019, seven patients colonised or infected with a ceftazidime-avibactam (CZA)-resistant Klebsiella pneumoniae carbapenemase (KPC)-2-producing K. pneumoniae were detected in two intensive care units of a Greek general hospital. The outbreak strain was sequence type (ST)147 and co-produced KPC-2 and the novel plasmid-borne Vietnamese extended-spectrum β-lactamase (VEB)-25 harbouring a K234R substitution associated with CZA resistance. Epidemiological investigations revealed that the resistance was probably acquired by horizontal transmission independently from previous CZA exposure.
Trait-Based Assessments of Climate-Change Impacts on Interacting Species
Authors: Matthias Schleuning, Eike Lena Neuschulz, Jörg Albrecht, Irene M.A. Bender, Diana E. Bowler, D. Matthias Dehling, Susanne A. Fritz, Christian Hof, Thomas Mueller, Larissa Nowak, Marjorie C. Sorensen, Katrin Böhning-Gaese, W. Daniel Kissling
Journal: Trends in Ecology & Evolution (2020)
What Is the Optimal Primary Care Panel Size?
Authors: Neil M. Paige, Eric A. Apaydin, Jeremy D. Goldhaber-Fiebert, Selene Mak, Isomi M. Miake-Lye, Meron M. Begashaw, Jessica M. Severin, Paul G. Shekelle
Journal: Annals of Internal Medicine (2020)

Background: Primary care for a panel of patients is a central component of population health, but the optimal panel size is unclear. Purpose: To review evidence about the association of primary care panel size with health care outcomes and provider burnout. Data Sources: English-language searches of multiple databases from inception to October 2019 and Google searches performed in September 2019. Study Selection: English-language studies of any design, including simulation models, that assessed the association between primary care panel size and safety, efficacy, patient-centeredness, timeliness, efficiency, equity, or provider burnout. Data Extraction: Independent, dual-reviewer extraction; group consensus rating of certainty of evidence. Data Synthesis: Sixteen hypothesis-testing studies and 12 simulation modeling studies met inclusion criteria. All but 1 hypothesis-testing study were cross-sectional assessments of association. Three studies each provided low-certainty evidence that increasing panel size was associated with no or modestly adverse effects on patient-centered and effective care. Eight studies provided low-certainty evidence that increasing panel size was associated with variable effects on timely care. No studies assessed the effect of panel size on safety, efficiency, or equity. One study provided very-low-certainty evidence of an association between increased panel size and provider burnout. The 12 simulation studies evaluated 5 models; all used access as the only outcome of care. Five and 2 studies, respectively, provided moderate-certainty evidence that adjusting panel size for case mix and adding clinical conditions to the case mix resulted in better access. Limitation: No studies had concurrent comparison groups, and published and unpublished studies may have been missed. Conclusion: Evidence is insufficient to make evidence-based recommendations about the optimal primary care panel size for achieving beneficial health outcomes. Primary Funding Source: Veterans Affairs Quality Enhancement Research Initiative.
Baby’s death at Margate hospital was “wholly avoidable,” says coroner
Authors: Clare Dyer
Journal: BMJ (2020)

The death of a baby boy seven days after his emergency delivery at a hospital hit by a maternity care scandal was “wholly avoidable,” a coroner has ruled.

Assistant coroner Christopher Sutton-Mattocks ruled that neglect was partly to blame for Harry Richford’s death at Queen Elizabeth the Queen Mother Hospital in Margate, Kent, in November 2017. The coroner heard that Harry was born by emergency caesarean section not crying or moving, in an operating theatre in which staff were “panicking.” He was delivered by a locum doctor who had not …
Annals Graphic Medicine - Progress Notes: Navigating Discharge
Authors: Michael Natter
Journal: Annals of Internal Medicine (2020)

Web Exclusives21 January 2020Annals Graphic Medicine - Progress Notes: Navigating DischargeFREEMichael Natter, MDMichael Natter, MDNYU School of Medicine, New York, New York (M.N.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G19-0083 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: NYU School of Medicine, New York, New York (M.N.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G19-0002.Author/Illustrator Information: Michael Natter, MD, is a current internal medicine resident at NYU School of Medicine and a graduate of Sidney Kimmel Medical College of Thomas Jefferson University in Philadelphia. His artwork is inspired by his medical training, patient encounters, and the human condition. A type 1 diabetic, Dr. Natter views himself as a patient as well as a doctor and plans to pursue a fellowship in endocrinology to help others who also share his disease. You can find more of his illustrations, stories, and comics on Instagram (www.instagram.com/mike.natter) and Twitter (@mike_natter).About Progress Notes: Progress Notes explores the everyday emotional, clinical, humorous, and ethical challenges of the medical residency training process. As implied by the title of the series, these pieces act as a visual bildungsroman, graphically dissecting the subtext of what it means to be a young doctor in today's medical world. Progress Notes appears monthly in Annals Graphic Medicine at Annals.org. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 21 January 2020Volume 172, Issue 2Page: W36-W37KeywordsConflicts of interestDisclosureEmotionsEndocrinologyFellowshipsGraduate medical educationResidency ePublished: 21 January 2020 Issue Published: 21 January 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Will We Ever Make Headway in Severe Traumatic Brain Injury Treatment Trials?
Authors: Nick M. Murray, Zachary D. Threlkeld, Karen G. Hirsch
Journal: JAMA Neurology (2020)

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
Decitabine and Vorinostat with Chemotherapy in Relapsed Pediatric Acute Lymphoblastic Leukemia: A TACL Pilot Study
Authors: Michael J. Burke, Rumen Kostadinov, Richard Sposto, Lia Gore, Shannon M. Kelley, Cara Rabik, Jane B. Trepel, Min-Jung Lee, Akira Yuno, Sunmin Lee, Deepa Bhojwani, Sima Jeha, Bill H. Chang, Maria Luisa Sulis, Michelle L. Hermiston, Paul Gaynon, Van Huynh, Anupam Verma, Rebecca Gardner, Kenneth M. Heym, Robyn M. Dennis, David S. Ziegler, Theodore W. Laetsch, Javier E. Oesterheld, Steven G. Dubois, Jessica A. Pollard, Julia Glade-Bender, Todd M. Cooper, Joel A. Kaplan, Midhat S. Farooqi, Byunggil Yoo, Erin Guest, Alan S. Wayne, Patrick A. Brown
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Treatment failure from drug resistance is the primary reason for relapse in acute lymphoblastic leukemia (ALL). Improving outcomes by targeting mechanisms of drug resistance is a potential solution. Patients and Methods: We report results investigating the epigenetic modulators decitabine and vorinostat with vincristine, dexamethasone, mitoxantrone, and PEG-asparaginase for pediatric patients with relapsed or refractory B-cell ALL (B-ALL). Twenty-three patients, median age 12 years (range, 1–21) were treated in this trial. Results: The most common grade 3–4 toxicities included hypokalemia (65%), anemia (78%), febrile neutropenia (57%), hypophosphatemia (43%), leukopenia (61%), hyperbilirubinemia (39%), thrombocytopenia (87%), neutropenia (91%), and hypocalcemia (39%). Three subjects experienced dose-limiting toxicities, which included cholestasis, steatosis, and hyperbilirubinemia (n = 1); seizure, somnolence, and delirium (n = 1); and pneumonitis, hypoxia, and hyperbilirubinemia (n = 1). Infectious complications were common with 17 of 23 (74%) subjects experiencing grade ≥3 infections including invasive fungal infections in 35% (8/23). Nine subjects (39%) achieved a complete response (CR + CR without platelet recovery + CR without neutrophil recovery) and five had stable disease (22%). Nine (39%) subjects were not evaluable for response, primarily due to treatment-related toxicities. Correlative pharmacodynamics demonstrated potent in vivo modulation of epigenetic marks, and modulation of biologic pathways associated with functional antileukemic effects. Conclusions: Despite encouraging response rates and pharmacodynamics, the combination of decitabine and vorinostat on this intensive chemotherapy backbone was determined not feasible in B-ALL due to the high incidence of significant infectious toxicities. This study is registered at http://www.clinicaltrials.gov as NCT01483690.
Isoniazid-resistant tuberculosis: A problem we can no longer ignore
Authors: Giorgia Sulis, Madhukar Pai
Journal: PLoS Medicine (2020)

For decades, people working in tuberculosis (TB) knew that monoresistance to isoniazid (INH) was common.INH has been in clinical use since the 1950s, and drug resistance was expected because its use became widespread.But this knowledge did not necessarily lead to testing for INH-resistant, rifampicin-susceptible TB (Hr-TB) or to the use of special drug regimens for this form of TB.Indeed, for decades, no drug-susceptibility testing (DST) for any drug was done unless patients failed first-line therapy or had risk factors for drug-resistant TB (DR-TB).Simply put, we chose to ignore the problem.When the TB world woke up to the need for universal DST and included it as a key goal in the End TB Strategy released in 2015, the focus became rapid testing for rifampicin resistance (RR) as a means of achieving universal DST.Novel technologies such as Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) were rolled out in 2010, but the technology did not include INH-resistance testing [1].Even today, access to any DST remains low, and when performed, DST is often limited to RR [2].In 2020, we can no longer hide from this worrisome problem because Hr-TB is much more common than RR and could seriously jeopardize progress in the fight against TB.This is confirmed by an analysis of aggregated drug resistance data from 2003 to 2017 across 156 countries presented in the accompanying research study by Anna Dean and colleagues in PLOS Medicine, showing that-on average-7.4%(95% CI 6.5-8.4) of new cases and 11.4% (9.4-13.4) of previously treated patients have Hr-TB [3].The overall prevalence of INH resistance (with or without concomitant RR) ranged between 10.7% (9.6-11.9)and 27.2% (24.6-29.9)depending on the treatment history and reached even more alarming levels in certain countries, particularly in the European and Western Pacific regions.The analysis by Dean and colleagues highlights major flaws in national surveillance systems, which go hand in hand with limited laboratory capacity.The small sample sizes available from some countries make national prevalence estimates imprecise.Furthermore, the diversity of detection methods employed across settings along with the widespread lack of quality control underscores the need for improved surveillance by countries.From a clinical standpoint, if INH resistance is not detected, new patients are managed as if they had pansusceptible TB, with a substantially increased risk of treatment failure or relapse and a greater propensity to acquire further resistance [4].Yet, most research and policy efforts so far have been focused solely on RR as a proxy for multidrug-resistant (MDR)-TB.This means that hundreds of thousands of patients with Hr-TB are staying in the shadows, not receiving appropriate care, and all too often ending up developing MDR-TB.
Therapeutic potential of FLANC, a novel primate-specific long non-coding RNA in colorectal cancer
Authors: Martin Pichler, Cristian Rodriguez-Aguayo, Su Youn Nam, Mihnea Paul Dragomir, Recep Bayraktar, Simone Anfossi, Erik Knutsen, Cristina Ivan, Enrique Fuentes-Mattei, Sang Kil Lee, Hui Ling, Tina Catela Ivkovic, Guoliang Huang, Li Huang, Yoshinaga Okugawa, Hiroyuki Katayama, Ayumu Taguchi, Emine Bayraktar, Rajat Bhattacharya, Paola Amero, William Ruixian He, Anh M Tran, Petra Vychytilova-Faltejskova, Christiane Klec, Diana L Bonilla, Xinna Zhang, Sanja Kapitanovic, Bozo Loncar, Roberta Gafà, Zhihui Wang, Vittorio Cristini, Samir M Hanash, Menashe Bar-Eli, Giovanni Lanza, Ondrej Slaby, Ajay Goel, Isidore Rigoutsos, Gabriel Lopez-Berestein, George Adrian Calin
Journal: Gut (2020)

To investigate the function of a novel primate-specific long non-coding RNA (lncRNA), named FLANC, based on its genomic location (co-localised with a pyknon motif), and to characterise its potential as a biomarker and therapeutic target.FLANC expression was analysed in 349 tumours from four cohorts and correlated to clinical data. In a series of multiple in vitro and in vivo models and molecular analyses, we characterised the fundamental biological roles of this lncRNA. We further explored the therapeutic potential of targeting FLANC in a mouse model of colorectal cancer (CRC) metastases.FLANC, a primate-specific lncRNA feebly expressed in normal colon cells, was significantly upregulated in cancer cells compared with normal colon samples in two independent cohorts. High levels of FLANC were associated with poor survival in two additional independent CRC patient cohorts. Both in vitro and in vivo experiments demonstrated that the modulation of FLANC expression influenced cellular growth, apoptosis, migration, angiogenesis and metastases formation ability of CRC cells. In vivo pharmacological targeting of FLANC by administration of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine nanoparticles loaded with a specific small interfering RNA, induced significant decrease in metastases, without evident tissue toxicity or pro-inflammatory effects. Mechanistically, FLANC upregulated and prolonged the half-life of phosphorylated STAT3, inducing the overexpression of VEGFA, a key regulator of angiogenesis.Based on our findings, we discovered, FLANC as a novel primate-specific lncRNA that is highly upregulated in CRC cells and regulates metastases formation. Targeting primate-specific transcripts such as FLANC may represent a novel and low toxic therapeutic strategy for the treatment of patients.
Methotrexate treatment for patients with psoriasis and risk of cutaneous melanoma: a nested case–control study
Authors: S. Polesie, M. Gillstedt, J. Paoli, A. Osmancevic
Journal: British Journal of Dermatology (2020)

Background Cutaneous malignant melanoma (CMM) is a highly immunogenic tumour. Patients with an impaired immune system have an enhanced risk for CMM and a worse prognosis. Methotrexate (MTX) is an anti-inflammatory and immunosuppressive drug frequently used to treat patients with psoriasis. An association between MTX and risk of CMM has previously been demonstrated in patients with rheumatoid arthritis. Objectives To investigate whether MTX increases the risk of CMM among patients with psoriasis. Methods A nested case–control investigation from a Swedish cohort of patients with psoriasis was conducted. Data were obtained from available Swedish registers and included 395 patients with psoriasis who had previously been cancer-free and had a first CMM in the time period from 1 January 2010 to 31 December 2016. A total of 10 randomly selected cancer-free patients with psoriasis were matched per case with respect to age (same birth year) and sex. The accumulated MTX doses in both groups were obtained. Crude odds ratios (ORs) for the proportion of MTX in the respective group were calculated using conditional logistic regression analyses. Results Of 395 patients with psoriasis who had CMM, 97 (25%) had filled a prescription of MTX; of 3950 controls, the corresponding number was 954 (24%). In a conditional logistic regression analysis, no association between MTX exposure (ever use) and risk for CMM was observed (OR 1·0, 95% confidence interval 0·8–1·3). Moreover, no indication of a dose–response association was observed. Conclusions In this Swedish nested case–control study, the use of MTX was not associated with an enhanced risk for CMM. These findings are reassuring for dermatologists in everyday clinical practice. What is already known about this topic? Methotrexate (MTX) treatment has been linked to an increased risk for cutaneous malignant melanoma (CMM) in an Australian cohort of patients with rheumatoid arthritis. In a previous retrospective Swedish cohort investigation, patients who had exclusively been prescribed MTX by a dermatologist did not have an enhanced risk for CMM compared with MTX-unexposed individuals. Nevertheless, this cohort did not specifically include patients with psoriasis. What does this study add? This Swedish nested case–control investigation included 395 previously cancer-free patients with psoriasis who had CMM (cases) and 3950 matched cancer-free patients with psoriasis (controls). No association between MTX exposure and risk for CMM in patients with psoriasis was observed. The results are reassuring for dermatologists using MTX to treat patients with psoriasis. Linked Comment: Haugaard and Egeberg. Br J Dermatol 2020; 183:608–609.
The Bedford Murder: An Evidence-Based Clinical Mystery
Authors: S. Satya-Murti
Journal: JAMA (2003)

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
US executive heart screening programmes violate “do not harm” rule, say medics
Authors: Janice Hopkins Tanne
Journal: BMJ (2020)

US “executive screening programmes” offer expensive cardiovascular testing even though the tests are not justified and often not covered by insurance, according to a report published in JAMA Internal Medicine .1

Leading US medical centres offer “executive screening” at prices ranging from $995 (£760; €901) to $25 000 to wealthy people who can pay out of pocket for tests not covered by insurance. Professional organisations usually do not recommend the tests for asymptomatic people and there is no evidence they reduce deaths from heart disease.

Not only is this bad medicine but …
Specific Ige-binding epitopes of hevein can be reconstructed to an immunologically nonreactive antimicrobial protein (AMP) from Amaranthus caudatus
Authors: P Karisola, J Mikkola, H Alenius, TL Reunala, K Turjanmaa, N Kalkkinen, T Palosuo, M Kulomaa
Journal: Journal of Allergy and Clinical Immunology (2001)
S-1 plus oxaliplatin versus S-1 plus cisplatin as first-line treatment for advanced diffuse-type or mixed-type gastric/gastroesophageal junction adenocarcinoma: A randomized, phase 3 trial.
Authors: Rui-hua Xu, Zhi-Qiang Wang, Lin Shen, Wei Wang, Jian-Wei Lu, Guanghai Dai, Jian-Ming Xu, Yan-Qiao Zhang, Xiao-Bing Chen, Yan-Hong Deng, Yun-Bo Zhao, Nan-Feng Fan, Gengsheng Yu, Wangjun Liao, Xia Yuan, You-En Lin, Guo-Long Liu, Qing-Feng Zou
Journal: Journal of Clinical Oncology (2019)

4017 Background: Diffuse-type or mixed-type gastric adenocarcinoma is associated with poor prognosis, and more effective treatment is needed. In Asia, S-1 plus cisplatin (SP) is the standard first-line chemotherapy regimen for advanced gastric cancer. Nevertheless, some clinical data suggested that oxaliplatin-based chemotherapy might be more efficacious and more tolerant than cisplatin-based chemotherapy. Methods: This trial is a multicenter, randomized, parallel-group, open-label, phase 3 trial in China. Patients aged 18-75 years, with PS 0-2, adequate organ function, histology confirmed, unresectable, advanced diffuse-type or mixed-type gastric adenocarcinoma/GEJA were randomized 1:1 to S-1 plus oxaliplatin group (SOX) (S-1: 40-60mg bid on d1-14, q3w; oxaliplatin: 130 mg/m2 on d1, q3w) or SP group (S-1: 40-60mg bid on d1-14, q3w; cisplatin: 60 mg/m2 d1, q3w). The primary endpoint was overall survival (OS) in the full analysis set (FAS). The secondary endpoints were progression-free survival (PFS), time to treatment failure (TTF) and safety. Results: Between Jul 2013 and Jul 2018, 576 patients were randomized and 558 initiated treatment (279 patients/group). The median number of chemotherapy cycles was four in each group. In the FAS, the SOX group showed improved OS (13.0 vs. 11.8 months, HR = 0.764, 95% CI: 0.636-0.918), PFS (5.7 vs. 4.9 months, HR = 0.752, 95%CI: 0.632-0.895), and TTF (5.2 vs. 4.7 months, HR = 0.763, 95%CI: 0.641-0.909) compared with the SP group. In terms of grade≥3 adverse events, SOX showed lower occurrences of neutropenia (10.0% vs. 22.9%), leukopenia (9.7% vs. 21.9%), anemia (4.3% vs. 14.3%),vomiting (3.9% vs. 10.4%), nausea (2.2% vs. 10.4%), anorexia (2.2% vs. 6.8%), and febrile neutropenia (2.5% vs. 6.8%) than SP (all P &lt; 0.05). The occurrence of grade≤2 sensory neuropathy(41.6% vs. 12.2%, P &lt; 0.001)was higher with SOX than with SP. Conclusion: Compared with SP, SOX was more effective and less toxic (except neurosensory toxicity ) in patients with previously untreated advanced diffuse-type or mixed-type gastric adenocarcinoma/GEJA. Clinical trial information: NCT01824459.
Thrombin activation of PAR-1 contributes to microvascular stasis in mouse models of sickle cell disease
Authors: Erica M. Sparkenbaugh, Chunsheng Chen, Tomasz Brzoska, Julia Nguyen, Shaobin Wang, Gregory M. Vercellotti, Nigel S. Key, Prithu Sundd, John D. Belcher, Rafal Pawlinski
Journal: Blood (2020)