tbuckley/cabot-search huggingface dataset:
Primary plasma cell leukemias displaying t(11;14) have specific genomic, transcriptional, and clinical features
Authors: Titouan Cazaubiel, Xavier Leleu, Aurore Perrot, Salomon Manier, Laure Buisson, Sabrina Maheo, Laura Do Souto Ferreira, Romain Lannes, Luka Pavageau, Cyrille Hulin, Jean-Pierre Marolleau, Laurent Voillat, Karim Belhadj, Marion Divoux, Borhane Slama, Sabine Brechignac, Margaret Macro, Anne-Marie Stoppa, Laurence Sanhes, Frédérique Orsini-Piocelle, Jean Fontan, Marie-Lorraine Chretien, Hélène Demarquette, Mohamad Mohty, Anais Schavgoulidze, Herve Avet-Loiseau, Jill Corre
Journal: Blood (2022)
Abstract 17138: Are Patients With Diabetes Mellitus at Increased Risk for Adverse Outcomes After Left Ventricular Assist Device Implantation? A Systematic Review and Meta-Analysis
Authors: Muhammad S Khan, Paolo C Colombo, Noman Lateef, Muhammad S Usman, Safi U Khan, Arthur R Garan, Melana Yuzefpolskaya, Ryan T Demmer
Journal: Circulation (2018)

Background: Patients with diabetes mellitus (DM) are known to have reduced life expectancy and be at increased risk for multiple morbidities including serious infection. However, published data on DM outcomes after left ventricular assist device (LVAD) implantation are sparse, inconsistent and individual studies are small with limited power. We conducted a systematic review and meta-analysis to compare survival and adverse events post-LVAD in DM versus non-DM (NDM) patients. Methods: Medline, Scopus and Cochrane Central databases were searched for studies comparing outcomes in DM and NDM patients undergoing LVAD implantation for advanced heart failure (HF) from inception-February 2018. Outcomes included all-cause mortality (30-day and one-year), device-related infection, ischemic stroke, hemorrhagic stroke and major bleeding. Results were reported as random effect risk ratios (RR) with 95 % confidence intervals. Results: We identified 5 retrospective cohort studies, at low risk of bias, reporting on 1,351 patients (n=488 DM). There was a borderline significant, increased 30-day mortality (RR: 1.57 [1.00, 2.47]; p=0.05; I 2 =0%) among DM vs. NDM. The DM and NDM groups did not differ significantly in terms of 1-year mortality (RR: 1.15 [0.98, 1.35]; p=0.08; I 2 =39%), device-related infection (RR: 1.05 [0.92, 1.19]; p=0.88; I 2 =0%), ischemic stroke (RR: 1.29 [0.91, 1.83]; p=0.69; I 2 =0%), hemorrhagic stroke (RR: 1.10 [0.42, 2.83]; p=0.85; I 2 =69%), and bleeding (RR: 1.06 [0.80, 1.40]; p=0.70; I 2 =27%). Conclusion: Following LVAD implantation, patients with DM, versus patients without, have a modestly elevated 30-day mortality rate. However, 1-year mortality rates, device related infection, and bleeding rates were not different.
Randomized comparator-controlled study evaluating efficacy and safety of pembrolizumab plus Bacillus Calmette-Guérin (BCG) in patients with high-risk nonmuscle-invasive bladder cancer (HR NMIBC): KEYNOTE-676 cohort B.
Authors: Ashish M. Kamat, Shahrokh Shariat, Gary D. Steinberg, Shaheen Riadh Alanee, Hiroyuki Nishiyama, Kijoeng Nam, Ekta Kapadia, Neal D. Shore, Noah M. Hahn
Journal: Journal of Clinical Oncology (2022)

TPS597 Background: Cohort A of the phase 2 KEYNOTE-057 study showed that pembrolizumab monotherapy provided effective antitumor activity and acceptable safety in patients with BCG-unresponsive HR NMIBC with carcinoma in situ (CIS). Pembrolizumab in combination with BCG at earlier stages of HR NMIBC might provide benefit superior to that of BCG monotherapy. The open-label, comparator-controlled, phase 3 KEYNOTE-676 study (NCT03711032) will be conducted to investigate the efficacy and safety of pembrolizumab + BCG versus BCG monotherapy in patients with HR NMIBC. Cohort A will enroll patients with persistent or recurrent HR NMIBC after BCG induction. Cohort B is a new, randomly assigned cohort that will help evaluate pembrolizumab + BCG in BCG treatment–naive patients who either never received BCG treatment or received BCG treatment &gt; 2 years before enrollment. Methods: Cohort B of KEYNOTE-676 will enroll approximately 975 patients with blinded independent central review (BICR)–confirmed HR NMIBC (T1, high-grade Ta CIS) and Eastern Cooperative Oncology Group performance status score 0-2 who underwent cystoscopy/transurethral resection of bladder tumor ≤12 weeks before randomization and had not received BCG within the past 2 years. Patients will be randomly assigned 1:1:1 to receive pembrolizumab 400 mg intravenously (IV) every 6 weeks (Q6W) + BCG reduced maintenance (≤6 months), pembrolizumab 400 mg IV Q6W + BCG full maintenance (≤18 months), or BCG monotherapy (BCG full maintenance). Stratification factors include NMIBC stage (CIS or no CIS) and PD-L1 expression (combined positive score [CPS] ≥10 or CPS &lt; 10), determined by central laboratory. Disease status will be assessed by use of cystoscopy, urine cytology, and biopsy (as applicable) every 12 weeks (Q12W) through year 2, then every 24 weeks through year 5; imaging with computed tomography urography will occur every 72 weeks. Adverse events (AEs) will be monitored throughout the study and up to 30 days after cessation of study treatment (90 days for serious AEs). The primary end point is event-free survival (EFS). Secondary end points include complete response rate by BICR, duration of response (DOR), 12-month DOR rate (CIS only), 24-month EFS rate, disease-specific survival, time to cystectomy, overall survival, and safety. The study is enrolling or planning to enroll at sites in Asia, Australia, Europe, North America, and South America. Clinical trial information: NCT03711032.
Rheumatoid Arthritis
Authors: E. G. L. Bywaters
Journal: Annals of the Rheumatic Diseases (1975)

Dr. Holt has admirably brought together a series of topics which are both currently of great interest to rheumatolo- gists and where progress is occurring.It was Dr. Holt's intention to provide a series of articles which would help 'smooth the transition from today's research to to- morrow's clinical practice'.This is an admirable objective
Undescended testicle.
Authors: T. F. Sandeman
Journal: BMJ (1966)

BOUINAL 107 merely an honest clinician) the medical board still has to give unequivocal answers to im- possible questions because of the financial benefits which depend on the answers.The Industrial Injuries Act needs com- pletely rethinking and redrafting.In its present form it encourages ill-founded claims and discourages proper clinical judgments.-I am, etc., West Runton, Lucy TURNER.Norfolk.SIR,-Your leading article on occupational dermatitis (4 December, p. 1322) provides a welcome and refreshing approach to an old and difficult problem.Present legislation often militates against the best long-term
Purpura Fulminans
Authors: C. R. Oyler
Journal: BMJ (1944)

Sept. 27.-Mild laryngitis. Streaks of pus on post-pharyngeal wall.Three days later the throat condition cleared up completely.Oct. 5.-Radiographs of chest showed previous densities com- pletely cleared up.The right.diaphragm was still raised and flat, but apart from this there was nothing abnormal.The patient was discharged on Oct. 15 for three months' rest.The myocarditis was still present, but had improved.The total amount of sulphonamides given was 103 g. over a period of 26 days.The only toxic symptom was vomiting.These drugs were discon- tinued when the white count fell to 12,000.COMMENT In this case of quinsy, venous thrombosis resulted in suppura- tion in the deep pharyngeal plexus, which eventually drained back into the pharynx through the original thrombosed vessel.This was demonstrated by the fact that light pressure produced green pus via the superior tonsillar fossa.Further complications resulted in extensive relatively sterile thrombosis through- out almost the whole of the cervical portions of the internal jugular vein.It is suggested that the rigors resulted from almost sterile pieces of clot and that the ensuing metastases produced sterile pulmonary infarcts.
Astrocytic α2-Na <sup>+</sup> /K <sup>+</sup> ATPase inhibition suppresses astrocyte reactivity and reduces neurodegeneration in a tauopathy mouse model
Authors: Carolyn N. Mann, Shamulailatpam Shreedarshanee Devi, Corey T. Kersting, Amber V. Bleem, Celeste M. Karch, David M. Holtzman, Gilbert Gallardo
Journal: Science Translational Medicine (2022)

Alzheimer's disease (AD) is the most dominant form of dementia characterized by the deposition of extracellular amyloid plaques and intracellular neurofibrillary tau tangles (NFTs). In addition to these pathologies, an emerging pathophysiological mechanism that influences AD is neuroinflammation. Astrocytes are a vital type of glial cell that contribute to neuroinflammation, and reactive astrocytes, or astrogliosis, are a well-known pathological feature of AD. However, the mechanisms by which astrocytes contribute to the neurodegenerative process in AD have not been fully elucidated. Here, we showed that astrocytic α2-Na+/K+ adenosine triphosphatase (α2-NKA) is elevated in postmortem human brain tissue from AD and progressive nuclear palsy, a primary tauopathy. The increased astrocytic α2-NKA was also recapitulated in a mouse model of tauopathy. Pharmacological inhibition of α2-NKA robustly suppressed neuroinflammation and reduced brain atrophy. In addition, α2-NKA knockdown in tauopathy mice halted the accumulation of tau pathology. We also demonstrated that α2-NKA promoted tauopathy, in part, by regulating the proinflammatory protein lipocalin-2 (Lcn2). Overexpression of Lcn2 in tauopathy mice increased tau pathology, and prolonged Lcn2 exposure to primary neurons promoted tau uptake in vitro. These studies collectively highlight the contribution of reactive astrocytes to tau pathogenesis in mice and define α2-NKA as a major regulator of astrocytic-dependent neuroinflammation.
Reflecting on medical school while playing Wordle
Authors: Pat Lok
Journal: BMJ (2022)

Wordle and medicine ![Graphic][1]</img> some similarities. They both have their own cliques, warrant a certain pattern of thinking, and instil subtle competition. To those who have never played Wordle it may present as random patterns of coloured boxes, but to Wordle players it stimulates thinking and builds a special camaraderie in the virtual world, especially when most people are still working and studying remotely. For the past two years of medical school, students have been learning virtually, as mere faces in boxes on a screen, experiencing medicine … [1]: /embed/inline-graphic-1.gif
Die Schwangerschaftsdiagnose aus dem Harne: Praktische und wissenschaftliche Ergebnisse.
Journal: JAMA (1933)

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
Erratum for the Research Article: “First exposure to the pandemic H1N1 virus induced broadly neutralizing antibodies targeting hemagglutinin head epitopes” by J. J. Guthmiller, J. Han, L. Li, A. W. Freyn, S. T. H. Liu, O. Stovicek, C. T. Stamper, H. L. Dugan, M. E. Tepora, H. A. Utset, D. J. Bitar, N. J. Hamel, S. Changrob, N.-Y. Zheng, M. Huang, F. Krammer, R. Nachbagauer, P. Palese, A. B. Ward, P. C. Wilson
Journal: Science Translational Medicine (2022)

In the Research Article “First exposure to the pandemic H1N1 virus induced broadly neutralizing antibodies targeting hemagglutinin head epitopes,” the virus strain numbers for A/Chile/1/1983, A/Texas/36/1991, and A/New Caledonia/20/1999, listed in Fig. 5C, Fig. 5D, and fig. S5C were incorrectly labeled. The strain numbers in Fig. 5C, Fig. 5D, and fig. S5C have been corrected, and Fig. 5 and fig. S5 have been updated in the online PDF and HTML (full text). These corrections do not impact the interpretation of the data or the conclusions of the paper.
Abstract 17239: Grandparents as Agents of Change for Addressing Childhood Obesity: Preliminary Data From a Caregiver Weight Loss Intervention
Authors: MinKyoung Song, Karen S Lyons, Sydnee Stoyles, Lissi Hansen, Christopher S Lee
Journal: Circulation (2018)

Introduction: Much interventional research seeks to reduce childhood obesity by capitalizing on parents’ influence as caregivers. However, few studies have investigated whether grandparent-caregivers might have a similar influence on children’s weight-related health. This dearth of evidence is surprising since there has been a rapid increase in grandparent caregiving in the U.S. Purpose: Examine for a ripple effect on weight-related outcomes in children whose grandparent-caregivers have been enrolled in a weight loss program. Methods: We recruited 9 grandparent-grandchild (aged 6 to 12 years) dyads where both members had overweight or obesity. We collected data on weight/height, physical activity/sedentary time, and dietary behaviors at baseline and at 8 weeks. Physical activity and sedentary time data were collected using accelerometers over two, seven-day cycles (after baseline and 8-weeks’ visits). Dietary data were collected using the Block Food Screener. Spearman’s rank-order correlation was used to quantify associations in changes between the dyad members. Results: Mean age was 64.3 ± 5.2 years and 9.0 ± 1.7 years for grandparents and grandchildren, respectively; 88.9% of grandparents and 66.7% of grandchildren were female. At 8 weeks: (1) there was a positive association between changes in grandparents’ BMI and changes in their grandchildren’s BMI (r=0.40; p&lt;0.01); (2) changes in grandparents’ levels of moderate-to-vigorous physical activity (MVPA)/sedentary time was positively associated with changes in grandchildren’s levels of MVPA/sedentary time (r=0.52, p&lt;0.01; r=0.55, p&lt;0.01, respectively). Conclusions: We demonstrated moderate associations between changes in children’s BMI/MVPA/sedentary time and changes in their grandparents’ BMI/MVPA/sedentary time. Our findings show that enrolling adult caregivers in weight loss programs could represent an effective delivery vehicle for improving childhood obesity. Additionally, our findings can help demonstrate to grandparent-caregivers that they can act as agents for improving health outcomes in their grandchildren by improving their own weight-related health, offering encouragement for grandparent-caregivers to enroll in weight-loss programs.
Transamidinase and Glutaminase Activities in Kidney Injury
Journal: JAMA (1963)

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
Updated biomarker results from a phase 1/2 study of olaparib and radium-223 in men with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases (COMRADE).
Authors: Rana R. McKay, Wanling Xie, Archana Ajmera, Biren Saraiya, Mamta Parikh, Edmund Folefac, Adam C. Olson, Elisabeth I. Heath, Rahul Atul Parikh, S. Percy Ivy, Eliezer Mendel Van Allen, Neal Ian Lindeman, Geoffrey Shapiro
Journal: Journal of Clinical Oncology (2022)

119 Background: Radium-223 is an α-emitting radioisotope that induces DNA double-strand breaks leading to cell death. In preclinical models, PARP inhibitors have shown efficacy as radiosensitizing agents. We designed a phase 1/2 trial to test the safety and efficacy of radium-223 + olaparib. Tissue based studies investigated homologous recombination repair (HRR) gene status. Methods: This was an open-label, multi-center, phase 1/2 study (NCT03317392) evaluating the dosing, safety and efficacy of radium-223 + olaparib. Eligible patients (pts) had mCRPC with ≥2 bone metastases without visceral metastases or lymphadenopathy &gt; 4 cm. There was no limit on prior therapy. All pts had a baseline biopsy and archival tissue was collected when available. The phase 1 used a 3+3 dose escalation design with fixed dose radium-223 (55 kBq/kg IV every 4 weeks x 6). Dose level 1 (DL1) was olaparib 200 mg PO BID; DL2 was olaparib 300 mg PO BID. The primary objective was to determine the recommended phase 2 dose (RP2D). Secondary objectives included radiographic progression-free survival (rPFS) (PCWG3 criteria), PSA response (50% decline from baseline), and alkaline phosphatase response (30% decline from baseline). HRR gene status was determined using Oncopanel tissue profiling. Results: 12 pts were enrolled on the phase 1. Median age was 68 (range 59-81) years. Median prior lines of CRPC therapies was 2 (1-5), including 3 (25%) who had received prior chemotherapy and 12 (100%) a prior novel hormone therapy. The RP2D of olaparib was 200 mg BID when combined with radium-223. Overall, PSA response and alkaline phosphatase response were 16.7% (n=2) and 67% (n=8), respectively. Median follow-up was 6.5 (range 2.8, 11.8) months, and 6-month rPFS was 57% (95% CI: 25%, 80%). 9 patients had available tissue for Oncopanel testing (7 from baseline metastasis biopsy; 2 from archival prostate tissue). Two patients were identified to have pathogenic HRR gene alterations: 1 patient with a BRCA2 mutation with rPFS of 11.63 months, 1 patient with CDK12 mutation with rPFS 2.60 months (Table). Conclusions: We demonstrate that olaparib can be safety combined with radium-223 with RP2D of 200 mg BID. Though limited by sample size, we demonstrate prolonged disease control in a pt with a BRCA2 mutation receiving radium-223 + olaparib. Additional profiling from the currently accruing phase 2 study of radium-223 +/- olaparib will further elucidate biomarkers of response. Clinical trial information: NCT03317392. [Table: see text]
Abstract 17367: Infusion of the Ketone Body β-Hydroxybutyrate Improves Left Ventricular Systolic Function in an Animal Model of Heart Failure With Reduced Ejection Fraction
Authors: Carlos G SantosGallego, Juan Antonio Requena-Ibanez, Rodolfo San Antonio, Kiyotake Ishikawa, Belén Picatoste, Alvaro Garcia-Ropero, Javier Sanz, Roger Hajjar, Valentin Fuster, Juan J Badimon
Journal: Circulation (2018)

Introduction: In vitro, ketone bodies (KB) are the most energetically efficient fuel for myocardium. Ex vivo, KB infusion in the perfusion medium of working rat hearts increases the heat of combustion (produced energy) by 31%. However, there is no report about the in vivo effects of KB on LV function. We hypothesized that KB infusion in HFREF would improve energy production and thus LV systolic function. Methods: HFREF was induced in 15 pigs by 2-hour balloon occlusion of LAD: proximal LAD (n=8, severe HREF) and mid LAD (n=7, moderate HFREF). At 2 months, LV systolic function was evaluated during saline infusion and during infusion of the KB β-hydroxybutyrate. Severe HFREF animals underwent cardiac MRI for baseline LVEF, feature tracking strains, and contractile reserve (ΔLVEF under dobutamine 5μg/kg/min). Moderate HFREF pigs underwent invasive hemodynamic assessment (dP/dt) and 3D-echocadiography (3D-LVEF and 3D-strains). Simultaneous sampling from coronary artery and coronary sinus was performed to measure myocardial fuel consumption. Results: Proximal and mid LAD occlusion resulted in severe and moderate LV systolic dysfunction, respectively. In the severe HFREF, ketone infusion improved baseline LVEF, feature-tracking strains (both longitudinal and circumferencial strain), and contractile reserve. In the moderate HFREF, ketone infusion improved 3D-LVEF, 3D-strains and dP/dt (Table). Ketone infusion switched myocardial metabolism from glucose to ketone consumption. Conclusions: Continuous infusion of the KB hydroxybutyrate improves LV systolic function independent of LV systolic dysfunction severity via a shift in myocardial fuel metabolism away from glucose oxidation (energy inefficient) toward a more energy-efficient fuel like KB. This effect can explain the mechanism of action of the benefits of SGLT2 inhibitors in heart failure, as empagliflozin-induced mild kyperketonemia may increase LV systolic function and thus improve patient outcomes.
Interleukin 33-mediated inhibition of A-type K<sup>+</sup> channels induces sensory neuronal hyperexcitability and nociceptive behaviors in mice
Authors: Yiru Wang, Xinyi Wang, Renfei Qi, Ying Lu, Yu Tao, Dongsheng Jiang, Yufang Sun, Xinghong Jiang, Chunfeng Liu, Yuan Zhang, Jin Tao
Journal: Theranostics (2022)

Background: has been implicated in nociceptive pain behaviors.However, the underlying molecular and cellular mechanisms remain unclear.Methods: Using electrophysiological recording, immunoblot analysis, immunofluorescence labeling, reverse transcription-PCR, siRNA-mediated knockdown approach and behavior tests, we determined the role of IL-33 in regulating sensory neuronal excitability and pain sensitivity mediated by A-type K + channels.Results: IL-33 decreased A-type transient outward K + currents (IA) in small-sized DRG neurons in a concentration-dependent manner, whereas the delayed rectifier currents (IDR) remained unaffected.This IL-33-induced IA decrease was dependent on suppression of the tumorigenicity 2 (ST2) receptor and was associated with a hyperpolarizing shift in the steady-state inactivation.Antagonism of Syk abrogated the IL-33-induced IA response, while inhibition of JAK2 and PKA elicited no such effect.Exposure of DRG cells to IL-33 increased the activity of Akt, but surprisingly, neither Akt nor PI3K influenced the IL-33-induced IA response.IL-33 increased the level of phosphorylated p38 mitogen-activated protein kinase (MAPK).Chemical inhibition of p38 and genetic siRNA knockdown of p38 beta (p38β), but not p38α, abrogated the IA response induced by IL-33.Moreover, IL-33 increased neuronal excitability of DRG neurons and facilitated peripheral pain sensitivity in mice; both of these effects were occluded by IA blockade.Conclusions: Our present study reveals a novel mechanism by which IL-33/ST2 suppresses IA via a Syk-dependent p38β signaling pathway.This mechanism thereby increases DRG neuronal excitability and pain sensitivity in mice.Targeting IL-33/ST2-mediated p38β signaling may represent a therapeutic approach to ameliorate pain behaviors.