tbuckley/cabot-search huggingface dataset:
Comparison of non-myeloablative lymphodepleting preconditioning regimens in patients undergoing adoptive T cell therapy
Authors: Abraham Nissani, Shaked Lev-Ari, Tomer Meirson, Elad Jacoby, Nethanel Asher, Guy Ben-Betzalel, Orit Itzhaki, Ronnie Shapira-Frommer, Jacob Schachter, Gal Markel, Michal J. Besser
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Adoptive cell therapy with T cells genetically engineered to express a chimeric antigen receptor (CAR-T) or tumor-infiltrating T lymphocytes (TIL) demonstrates impressive clinical results in patients with cancer. Lymphodepleting preconditioning prior to cell infusion is an integral part of all adoptive T cell therapies. However, to date, there is no standardization and no data comparing different non-myeloablative (NMA) regimens. Methods In this study, we compared NMA therapies with different doses of cyclophosphamide or total body irradiation (TBI) in combination with fludarabine and evaluated bone marrow suppression and recovery, cytokine serum levels, clinical response and adverse events. Results We demonstrate that a cumulative dose of 120 mg/kg cyclophosphamide and 125 mg/m 2 fludarabine (120Cy/125Flu) and 60Cy/125Flu preconditioning were equally efficient in achieving deep lymphopenia and neutropenia in patients with metastatic melanoma, whereas absolute lymphocyte counts (ALCs) and absolute neutrophil counts were significantly higher following 200 cGyTBI/75Flu-induced NMA. Thrombocytopenia was most profound in 120Cy/125Flu patients. 30Cy/75Flu-induced preconditioning in patients with acute lymphoblastic leukemia resulted in a minor ALC decrease, had no impact on platelet counts and did not yield deep neutropenia. Following cell infusion, 120Cy/125Flu patients with objective tumor response had significantly higher ALC and significant lower inflammatory indexes, such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Receiver-operating characteristics curve analysis 7 days after cell infusion was performed to determine the cut-offs, which distinguish between responding and non-responding patients in the 120Cy/125Flu cohort. NLR≤1.79 and PLR≤32.7 were associated with clinical response and overall survival. Cytokine serum levels did not associate with clinical response in patients with TIL. Patients in the 120Cy/125Flu cohort developed significantly more acute NMA-related adverse events, including thrombocytopenia, febrile neutropenia and cardiotoxicity, and stayed significantly longer in hospital compared with the 60Cy/125Flu and TBI/75Flu cohorts. Conclusions Bone marrow depletion and recovery were equally affected by 120Cy/125Flu and 60Cy/125Flu preconditioning; however, toxicity and consequently duration of hospitalization were significantly lower in the 60Cy/125Flu cohort. Patients in the 30Cy/75Flu and TBI/75Flu groups rarely developed NMA-induced adverse events; however, both regimens were not efficient in achieving deep bone marrow suppression. Among the regimens, 60Cy/125Flu preconditioning seems to achieve maximum effect with minimum toxicity.
Flat colorectal sessile serrated polyp: an example of what artificial intelligence does not easily detect
Authors: Pierre Lafeuille, Thomas Lambin, Clara Yzet, El Houcine Latif, Nathan Ordoqui, Jérôme Rivory, Mathieu Pioche
Journal: Endoscopy (2021)

In recent years, image recognition using artificial intelligence with deep learning has dramatically improved and opened the door to more detailed image analysis and real-time application in various medical fields [1] [2]. In the colorectal cancer screening area, real-time computer-aided detection systems can lead to significant increases in both polyp and adenoma detection rates [3]. The ENDO-AID CADe program working in combination with the EVIS X1 video column (Olympus, Tokyo, Japan) is also able to provide visual support during the screening process, making endoscopy easier and more efficient.
Clinical management of severe infections caused by carbapenem-resistant gram-negative bacteria: a worldwide cross-sectional survey addressing the use of antibiotic combinations
Authors: Elena Carrara, Alessia Savoldi, Laura J.V. Piddock, Francois Franceschi, Sally Ellis, Mike Sharland, Adrian John Brink, Patrick N.A. Harris, Gabriel Levy-Hara, Anusha Rohit, Constantinos Tsioutis, Hiba Zayyad, Christian Giske, Margherita Chiamenti, Damiano Bragantini, Elda Righi, Anna Gorska, Evelina Tacconelli
Journal: Clinical Microbiology and Infection (2021)

Optimal treatment of carbapenem-resistant Gram-negative bacteria (CR-GNB) infections is uncertain because of the lack of good-quality evidence and the limited effectiveness of available antibiotics. The aim of this survey was to investigate clinicians' prescribing strategies for treating CR-GNB infections worldwide.A 36-item questionnaire was developed addressing the following aspects of antibiotic prescribing: respondent's background, diagnostic and therapeutic availability, preferred antibiotic strategies and rationale for selecting combination therapy. Prescribers were recruited following the snowball sampling approach, and a post-stratification correction with inverse proportional weights was used to adjust the sample's representativeness.A total of 1012 respondents from 95 countries participated in the survey. Overall, 298 (30%) of the respondents had local guidelines for treating CR-GNB at their facility and 702 (71%) had access to Infectious Diseases consultation, with significant discrepancies according to country economic status: 85% (390/502) in high-income countries versus 59% (194/283) in upper-medium-income countries and 30% (118/196) in lower-middle-income countries/lower-income-countries). Targeted regimens varied widely, ranging from 40 regimens for CR-Acinetobacter spp. to more than 100 regimens for CR-Enterobacteriaceae. Although the majority of respondents acknowledged the lack of evidence behind this choice, dual combination was the preferred treatment scheme and carbapenem-polymyxin was the most prescribed regimen, irrespective of pathogen and infection source. Respondents noticeably disagreed around the meaning of 'combination therapy' with 20% (150/783) indicating the simple addition of multiple compounds, 42% (321/783) requiring the presence of in vitro activity and 38% (290/783) requiring in vitro synergism.Management of CR-GNB infections is far from being standardized. Strategic public health focused randomized controlled trials are urgently required to inform evidence-based treatment guidelines.
제주 지역 만성 C형간질환 환자의 유전자형의 분포
Authors: 이호준, 조유경, 김흥업, 최은광, 현소영, 강동구, 정승욱, 김현주, 김광식, 송병철
Journal: Clinical and Molecular Hepatology (2008)

목적: HCV 유전자형의 분포는 지역에 따라 다른 양상을 보이고 항바이러스치료 및 간질환의 진행에 다른 영향을 보인다고 알려져 있다. 본 연구는 지역적으로 격리된 제주 지역의 HCV 유전자형 의 분포를 확인하고 임상경과에 따른 유전자형의 차이를 확언하고자 하였다. 대상과 방법: anti-HCV가 양성 이면서 HCV-RNA가 양성인 환자 162예를 대상으로 하였다. HCV 유전자형은 유전 자형 특이 시발체를 이용하였다. 결과: HCV 유전 자형은 2a형이 62.3%로 가장 흔하였고, 다음으로 1b형 이 34.0% 그리고 2b형 이 3.7%였다. 유전자형 1형에서 유전자형 2형에 비해 연령이 높았다(63.5±11.8세 vs. 59.0±11.6세) (P=0.02). 70세 이상의 환자에서는 유전자형 1형의 빈도가 높았고 70세 미만의 연령에서는 유전자형 2형의 빈도가 높았다 (P=0.035). HCV-RNA는 유전자형 1형에서 유전자형 2형 에 비 해 높았으며 (P=0.00l), 유전자형 1형에서 HCV-RNA가 2x106 copies/mL 이상언 빈도 가 유전자형 2형 에 비 해 높았다(45.1% vs. 24.8%)(P=0.012). 그러나 진단, 성별, 잠재적 위험요소에 따른 HCV 유전형의 분포는 차이가 없었다. 결론: 제주 지역 만성 C형간질환 환자에서 유전자형은 국내의 기존 보고와는 달리 유전자형 2형이 1형보다 2배 정도 높았으며, 이는 국내에서도 지역에 따라 HCV의 유전자형의 분포가 다를 수 있음을 시사한다.
Antibody semorinemab reduces tau pathology in a transgenic mouse model and engages tau in patients with Alzheimer’s disease
Authors: Gai Ayalon, Seung-Hye Lee, Oskar Adolfsson, Corinne Foo-Atkins, Jasvinder K. Atwal, Mira Blendstrup, Helen Booler, Joseph Bravo, Robert Brendza, Flavia Brunstein, Ruby Chan, Priya Chandra, Jessica A. Couch, Akash Datwani, Barthélemy Demeule, Danielle DiCara, Rich Erickson, James A. Ernst, Oded Foreman, Dongping He, Isidro Hötzel, Michael Keeley, Michael C. M. Kwok, Julien Lafrance-Vanasse, Han Lin, Yanmei Lu, Wilman Luk, Paul Manser, Andreas Muhs, Hai Ngu, Andrea Pfeifer, Maria Pihlgren, Gautham K. Rao, Kimberly Scearce-Levie, Stephen P. Schauer, William B. Smith, Hilda Solanoy, Edmond Teng, Kristin R. Wildsmith, Daniela Bumbaca Yadav, Yong Ying, Reina N. Fuji, Geoffrey A. Kerchner
Journal: Science Translational Medicine (2021)

Semorinemab shows beneficial effects in preclinical models and engages tau in a phase 1 study of patients with Alzheimer’s disease.
Abstract 16472: Deciphering a Mechanistic Link Between Enhanced Late Sodium Current and Triggered Atrial Fibrillation Using Patient-specific and Gene-corrected Induced Pluripotent Stem Cell-derived Atrial Cardiomyocytes
Authors: Liang HONG, Olivia T Ly, Hanna Chen, Arvind Sridhar, Meihong Zhang, Erin Lambers, Brandon Chalazan, Seock-Won Youn, Mark Maienschein-Cline, Leonid Feferman, Sang-Ging Ong, Joseph C Wu, Jalees Rehman, Dawood Darbar
Journal: Circulation (2020)

Introduction: Gain-of-function mutations in SCN5A, which encodes the cardiac sodium channel, have been linked with familial atrial fibrillation (AF). However, the mechanistic link between the late sodium current (I Na,L ) and triggered arrhythmia remains unclear. Hypothesis: To characterize the electrophysiological (EP) phenotype of gain-of-function AF-linked SCN5A mutations, elucidate the underlying cellular mechanisms using patient-specific and gene-corrected (GC) induced pluripotent stem cell-derived atrial cardiomyocytes (iPSC-aCMs). Methods: We generated iPSC-aCMs from two families carrying SCN5A mutations (E428K and N470K) and control subjects. Whole-cell patch clamp and multi-electrode arrays were recorded to assess the EP phenotypes of the atrial iPSC-CMs. We corrected the E428K iPSC-aCMs using CRISPR/Cas9 gene editing approach (isogenic control). Results: The SCN5A mutation lines displayed abnormal EP properties including increased beating frequency and irregularity with triggered beats characteristic of AF ( Fig. 1 ). E428K iPSC-aCMs displayed spontaneous arrhythmogenic activity with beat-to-beat irregularity ( Fig. 1 A-D ) with the prolonged APD ( Fig. 1 E-H ) associated with enhanced I Na,L ( Fig. 1 I-L ). In contrast, expression of SCN5A -E428K in heterologous expression system failed to show enhanced I Na,L . The gene-corrected E428K iPSC-aCMs normalized the aberrant EP phenotype. Gene expression profiling revealed differential expression of calcium and potassium channel homeostasis and nitric oxide mediated signal transduction which could result in EP remodeling of atrial CMs. Conclusions: Patient-specific and gene-corrected iPSC-aCMs exhibited striking ex-vivo EP phenotype of an AF-causing SCN5A gain-of-function mutation that produced minimal changes in-vitro . We established a mechanistic link between enhanced I Na,L , ion channel remodeling and nitric oxide signaling pathways, and triggered AF.
Comparation of Digital PCR and Quantitative Pcr for Molecular Monitorization of Chronic Myeloid Leukemia Patients
Authors: Juan Manuel Alonso Dominguez, Rodrigo Iñiguez Garcia, Susana Olmedillas, Rocio N Salgado, Tamara Castaño, Carlos Blas, Diego Velasco Rodrgiguez, Gala Vega, Jose Luis Lopez Lorenzo, Pilar Giraldo, Joaquin Martinez Lopez, Pilar Llamas, Mireia Atance, Arantxa Garcías Raso
Journal: Blood (2017)
Abstract 17356: Cardiovascular Findings on Chest Computed Tomography Predict Clinical Outcomes in COVID-19
Authors: Maria Isabel Camara Planek, Stella Kyung, Max A Ruge, Jeanne du Fay de Lavallaz, Annabelle S Volgman, Kim A Williams, Tisha B Suboc, J. Alan Simmons, Anupama Rao
Journal: Circulation (2020)

Background: Computed tomography (CT) chest is routinely used for the diagnosis and management of COVID-19 patients. Though COVID-19 disease-specific pulmonary findings have been well described, the significance of concomitant cardiovascular findings on chest CT are less studied. We examined the presence of various cardiovascular findings as markers for predicting significant outcomes in COVID-19. Methods: A retrospective cohort study was conducted on 163 patients with confirmed COVID-19 who underwent chest CT. In addition to the reported pulmonary findings, specific cardiovascular CT variables were collected, including right and left ventricular dimensions, pulmonary artery and aortic size, reflux of contrast into the IVC, septal position, coronary artery and aortic calcifications. Multivariable analysis was used to determine whether cardiovascular findings predict a composite outcome consisting of in-hospital and 30-day mortality, Intensive Care Unit admission, intubation, extracorporeal membrane oxygenation, proning, and renal replacement therapy. Results: Among our cohort, aortic calcification significantly predicted an increased risk of the composite outcome (odds ratio (OR) 4.73, p &lt; 0.0001). Larger RV diameter predicted composite outcome (OR 1.08, p &lt; 0.01). RV/LV ratio &gt; 0.9 (normal ratio &lt; 0.9) showed borderline significant trend towards 30-day mortality (OR 1.12, p &lt; 0.05). A combination of cardiac findings to discriminate between patients at higher or lower risk of a negative outcome (AUC 0.67, 95% CI 0.57 - 0.76) was non-inferior to a combination of pulmonary CT findings (AUC 0.68, 95% CI 0.6 - 0.76, p = 0.81). Discussion: Our data suggest that cardiovascular findings such as a dilated right ventricle and aortic calcification are important imaging markers in symptomatic patients with COVID-19. These findings highlight the importance of right ventricular parameters and vascular disease in predicting adverse clinical outcomes in these patients. Conclusions: Cardiovascular findings should be recognized and reported when imaging patients with COVID-19. Future, higher-power analyses of long-term outcomes in our cohort are anticipated to yield further results.
Cardiac Remodeling after Transcatheter Closure of Atrial Septal Defect in the Adults
Authors: Isotani Akihiro, Arita Takeshi, Hayashi Masaomi, Miura Shiro, Yamaji Kyohei, Enomoto Soichiro, Shirai Shinichi, Yokoi Hiroyoshi, Iwabuchi Masashi
Journal: Circulation (2013)
Abstract P221: Metabolic Syndrome And Its Factors Associate With Non-calcified Coronary Plaque Burden In Chronic Inflammation: Results From A Prospective Observational Study
Authors: Meron Teklu, Wunan Zhou, Nidhi Patel, Grigory Manyak, Amit K Dey, Sundus Lateef, Domingo Uceda, Khaled Abdelrahman, Justin Rodante, Andrew Keel, Tania Machado, Colin Scott, Promita Kapoor, Alexander V Sorokin, Heather Teague, Martin Playford, Marcus Y Chen, Nehal N Mehta
Journal: Circulation (2021)

Introduction: Psoriasis is a common, inflammatory skin disease associated with systemic inflammation and heightened risk of cardiovascular diseases (CVD). Population studies have shown that psoriasis is associated with metabolic syndrome (MetSyn) and its individual components. However, the impact of MetSyn on early atherosclerosis in chronic inflammatory diseases assessed as non-calcified coronary plaque burden (NCB) by coronary computed CT angiography (CCTA) is not known. Hypothesis: We hypothesized that those with MetSyn in psoriasis would have increased NCB compared to non-MetSyn and that MetSyn and its components would associate with NCB in fully adjusted models. Methods: The cohort consisted of 336 psoriasis patients free of cardiovascular disease, of which 326 had adequate data to classify MetSyn based on the International Diabetes Federation criteria (waist circumference, triglycerides, HDL cholesterol, blood pressure and fasting glucose). Of these, 260 had quantitative CCTA data available for analyses (Stata 16). Results: Of the 260 patients, 80 had MetSyn (31%). The MetSyn group had increased cardiometabolic disease and more adverse coronary characteristics including higher non-calcified ( p &lt;.001) and high-risk plaque ( p =.02) (Table) . In fully adjusted models for Framingham risk score, lipid lowering therapy and biologic use, MetSyn (β=0.31; p&lt; .001) and its individual components of waist circumference (β=0.33; p &lt;.001), triglycerides (β=0.17; p =.005), blood pressure (β=0.18; p =.005) and fasting glucose (β=0.17; p =.009) associated with NCB. Conclusions: MetSyn and its components were associated with NCB in psoriasis suggesting that early atherosclerosis is importantly impacted by poor cardiometabolic health. Components of MetSyn should be assessed in psoriasis patients and patients educated about this heightened risk of CVD associated with MetSyn.
Flapping Scalp Sign as a Rare and Interesting Presentation in Delayed Postoperative Tension Pneumocephalus
Authors: Sunil Munakomi, Binod Bhattarai, Shashi Bhusan Sah
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
Abstract MP33: Cardiac Structure And Function Phenogroups And Risk Of Incident Heart Failure: Multi-ethnic Study Of Atherosclerosis
Authors: Michael M Hammond, Amy Krefman, Hongyan Ning, Norrina B Allen, Sanjiv J Shah, Joseph Yeboah, Donald M Lloyd-Jones, Sadiya Khan, Joao Lima, Paul Reyfman
Journal: Circulation (2021)

Introduction: Indices of cardiac structure and function, such as left ventricular (LV) mass and ejection fraction (EF), have individually been associated with development of incident heart failure (HF). Identifying HF risk groups (or phenogroups) based on imaging parameters may help inform distinct imaging phenotypes to target for prevention. Objectives: To identify phenogroups based on cardiovascular magnetic resonance imaging (cMRI) parameters in participants free of cardiovascular disease at baseline and examine longitudinal risk of incident HF. Methods: We included participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who had completed baseline cMRI between 2000 and 2002. We applied latent class analysis to define phenogroups based on cMRI parameters of right ventricular and LV structure and function (including circumferential strain) at baseline (using the Bayesian Information Criterion as well as visual inspection). We used Cox-proportional hazard models to assess the association between membership in a phenogroup and risk of incident HF adjusted for age, sex, race, hypertension, diabetes, and hyperlipidemia. Results: Of 1484 participants, 48% were female and mean age was 65 (10) years. Over a median follow-up of 13 years, a total of 91 incident HF events occurred. We identified 3 distinct phenogroups that differed in terms of cardiac structure and function. Adjusted hazards ratio (95% confidence interval) for incident HF was higher among participants in Group 3 (2.08 [1.17, 3.71]) and Group 2 (2.24 [1.15, 4.37]), compared with Group 1 as the referent ( Table ). Conclusion: Phenogroups based on cMRI were differentially associated with risk of HF. Classification of cardiovascular imaging phenogroups integrating traditional and strain parameters within the normal range may be useful in identifying risk for HF; further validation is required before implementation.
Thyrotoxic Periodic Paralysis
Authors: Michael Fralick, Shohinee Sarma
Journal: New England Journal of Medicine (2021)

A 25-year-old man presented with sudden limb paralysis. Laboratory studies revealed a potassium level of 1.6 mmol per liter. A diagnosis of thyrotoxic periodic paralysis was made; supplementation with potassium and phosphate was initiated, which resulted in abatement of the arm and leg weakness. Videos show arm and leg movement at various levels of potassium.
6P 25-year survival and benefit from tamoxifen therapy by the clinically used breast cancer markers in lymph node-negative and ER-positive/HER2-negative breast cancer
Authors: H.A. Dar, A. Johansson, A. Nordensköljd, A. Iftimi, C. Yau, G. Perez-Tenorio, C. Benz, B. Nordenskjöld, O. Stål, L. Esserman, T. Fornander, L. Lindström
Journal: Annals of Oncology (2021)
Improving the sensitivity of <i>T</i><sub>1</sub> contrast-enhanced MRI and sensitive diagnosing tumors with ultralow doses of MnO octahedrons
Authors: Lijiao Yang, Lili Wang, Guoming Huang, Xuan Zhang, Lanlan Chen, Ao Li, Jinhao Gao, Zijian Zhou, Lichao Su, Huanghao Yang, Jibin Song
Journal: Theranostics (2021)

Rationale: Sensitive and accurate imaging of cancer is essential for early diagnosis and appropriate treatment. For generally employed magnetic resonance imaging (MRI) in clinic, comprehending how to enhance the contrast effect of T1 imaging is crucial for improving the sensitivity of cancer diagnosis. However, there is no study ever to reveal the clear mechanism of how to enhance the effect of T1 imaging and accurate relationships of influencing factors. Herein, this study aims to figure out key factors that affect the sensitivity of T1 contrast-enhanced MRI (CE-MRI), thereby to realize sensitive detection of tumors with low dose of CAs. Methods: Manganese oxide (MnO) nanoparticles (NPs) with various sizes and shapes were prepared by thermal decomposition. Factors impacting T1 CE-MRI were investigated from geometric volume, surface area, crystal face to r2/r1 ratio. T1 CE-MR imaging of liver, hepatic and subcutaneous tumors were conducted with MnO NPs of different shapes. Results: The surface area and occupancy rate of manganese ions have positive impacts on the sensitivity of T1 CE-MRI, while volume and r2/r1 ratio have negative effects. MnO octahedrons have a high r1 value of 20.07 mM-1s-1 and exhibit an excellent enhanced effect in liver T1 imaging. ZDS coating facilitates tumor accumulation and cellular uptake, hepatic and subcutaneous tumors could be detected with MnO octahedrons at an ultralow dose of 0.4 mg [Mn]/kg, about 1/10 of clinical dose. Conclusions: This work is the first quantitative study of key factors affecting the sensitivity of T1 CE-MRI of MnO nanoparticles, which can serve as a guidance for rational design of high-performance positive MRI contrast agents. Moreover, these MnO octahedrons can detect hepatic and subcutaneous tumors with an ultralow dose, hold great potential for sensitive and accurate diagnosis of cancer with lower cost, less dosages and side effects in clinic.