tbuckley/cabot-search huggingface dataset:
Effect of weight on drop of ejection fraction for breast cancer cases receiving trastuzumab.
Authors: Khalid A. Al-Saleh, Ahmed Mohamed Abdel Warith, Abdurahman A Altheyab, Ammarah Afzel, Nashwa Abdulaziz, Arwa MOHAMMED ALI
Journal: Journal of Clinical Oncology (2014)

e11592 Background: Trastuzumab is an essential monoclonal antibody in Her -2 Neu positive breast cancer its dosing is based on actual body weight rather than body surface area. The major side effect of Trastuzumab is cardiac toxicity with risk of developing congestive heart failure. We proposed that patient with higher weight will receive higher dose of Trastuzumab with increased risk of cardiac toxicity and higher incidence of significant drop in the left ventricular ejection fraction. Methods: A retrospective review of all Her-2 Neu breast cancer patients who received Trastuzumab was performed. The drop in EF (calculated as baseline minus worst EF recorded later during the next 12 months) was measured, The EF was assessed by MUGA scan. Results: Between 2011-2013 A total of 103 study eligible patients were identified. Twenty six cases (25.2%) had definitive Trastuzumab-induced cardiomyopathy with a drop in ejection fraction more than 15%. The median number of treatment cycles for the patient with cardiomyopathy is 15 (Reflecting late occurrence). A Spearman rho has been calculated which showed a weak correlation of -0.179, P=0.046 (2-tailed). Which suggest a protective effect of higher weight. A multi-variant regression analysis including weight, age and metastatic status failed to show any significant correlation. Conclusions: dosing Trastuzumab based on the actual body weight was not associated with increases risk of cardiomyopathy. The incidence of cardiomyopathy in this patient cohort is higher than the reported in the literature.
Phase I/II study of VAL-083 in patients with recurrent glioblastoma.
Authors: Kent C. Shih, Manish R. Patel, Nicholas A. Butowski, Gerald Steven Falchook, Sani Haider Kizilbash, Jeffrey A. Bacha, Dennis Brown, Anne Steino, Richard Stephen Schwartz, Sarath Kanekal, Lorena Lopez, Howard A. Burris
Journal: Journal of Clinical Oncology (2016)

2063 Background: Glioblastoma (GBM) is the most common CNS tumor. Patients with recurrent GBM have few treatment options and dismal prognosis. O6-methylguanine-DNA-methyltransferase (MGMT) is correlated with resistance to front-line systemic therapy with temozolomide (TMZ) and poor patient outcomes. Dianhydrogalactitol (VAL-083) is a bi-functional alkylating agent that readily crosses the blood-brain barrier and has demonstrated activity independent of MGMT in multiple GBM cell lines and cancer stem cells in vitro. VAL-083 showed promise against CNS tumors in prior NCI-sponsored clinical trials. The goal of this clinical trial is to determine the appropriate dose for VAL-083 for advancement to Phase III trials as a new treatment for recurrent GBM. Methods: Study Population: Patients must have recurrent GBM following surgery, radiation, TMZ and bevacizumab. Phase I: Open-label, single-arm dose-escalation study (3+3 design). Patients received VAL-083 on days 1, 2, 3 of a 21-day cycle, until MTD was reached. Phase II: 14 additional patients enrolled at MTD to further assess safety and outcomes. Results: Phase I: 29 patients were enrolled across 9 dose cohorts (1.5 - 50 mg/m2/d) and 40 mg/m2/d confirmed as the MTD. Myelosuppression was mild; no drug-related serious adverse events were reported at doses ≤ 40 mg/m2/d. Dose limiting toxicity (G4 thrombocytopenia) was observed at higher doses. Platelet nadir occurred around day 20 and resolved rapidly and spontaneously. A dose-related and clinically meaningful survival improvement was observed. Pharmacokinetic analyses show dose-dependent linear systemic exposure with short 1-2h plasma terminal half-life; average Cmax 781 ng/mL at 40 mg/m2/d. Phase II: 14 patients have been enrolled at 40 mg/m2/d. To date, safety observations in the Phase II cohort are consistent with Phase I. Conclusions: VAL-083 at 40 mg/m2/d exhibits a favorable safety profile and a dose-related trend toward clinically meaningful improved survival in refractory GBM patients. We expect to present median overall survival in the Phase II expansion cohort and proposed Phase III study design. Clinical trial information: NCT01478178.
Using Microsimulation to Estimate the Future Health and Economic Costs of Salmonellosis under Climate Change in Central Queensland, Australia
Authors: Dimity Maree Stephen, Adrian Gerard Barnett
Journal: Environmental Health Perspectives (2017)

Background: The incidence of salmonellosis, a costly foodborne disease, is rising in Australia. Salmonellosis increases during high temperatures and rainfall, and future incidence is likely to rise under climate change. Allocating funding to preventative strategies would be best informed by accurate estimates of salmonellosis costs under climate change and by knowing which population subgroups will be most affected. Objective: We used microsimulation models to estimate the health and economic costs of salmonellosis in Central Queensland under climate change between 2016 and 2036 to inform preventative strategies. Methods: We projected the entire population of Central Queensland to 2036 by simulating births, deaths, and migration, and salmonellosis and two resultant conditions, reactive arthritis and postinfectious irritable bowel syndrome. We estimated salmonellosis risks and costs under baseline conditions and under projected climate conditions for Queensland under the A1FI emissions scenario using composite projections from 6 global climate models (warm with reduced rainfall). We estimated the resulting costs based on direct medical expenditures combined with the value of lost quality-adjusted life years (QALYs) based on willingness-to-pay. Results: Estimated costs of salmonellosis between 2016 and 2036 increased from 456.0 QALYs (95% CI: 440.3, 473.1) and AUD29,900,000 million (95% CI: AUD28,900,000, AUD31,600,000), assuming no climate change, to 485.9 QALYs (95% CI: 469.6, 503.5) and AUD31,900,000 (95% CI: AUD30,800,000, AUD33,000,000) under the climate change scenario. Conclusion: We applied a microsimulation approach to estimate the costs of salmonellosis and its sequelae in Queensland during 2016–2036 under baseline conditions and according to climate change projections. This novel application of microsimulation models demonstrates the models' potential utility to researchers for examining complex interactions between weather and disease to estimate future costs. https://doi.org/10.1289/EHP1370
FiRe: Grupo Finlandés para el Estudio de Resistencias Bacterianas (FiRe)
Authors: A Nissinen, P Huovinen
Journal: Eurosurveillance (2000)

La red FiRe, o Grupo Finlandes para el Estudio de Resistencias a los agentes Antimicrobianos, que fue creada en 1991, ha establecido un metodo estandarizado sistematico para el analisis de la sensibilidad de las bacterias a los antibioticos, mediante el cual se obtienen resultados fiables y comparables con fines diagnosticos y epidemiologicos. Los resultados del grupo FiRe muestran un aumento en la proporcion de Streptococcus pneumoniae resistentes a los macrolidos, asi como una disminucion de la sensibilidad a las fluoroquinolonas en aislamientos de salmonella de origen extranjero, pero la prevalencia de SARM en Finlandia sigue siendo baja y la Mycobacterium tuberculosis multirresistente es poco frecuente.
Abstract 18983: Complex Left Atrial Appendage Morphology Increases Risk of Cryptogenic Ischemic Stroke
Authors: Indranill Basu Ray, Gregory Schwing, Josephine Novak, Dominique Monlezun, Himabindu Boja, Bradley Deere, Jose Duque, Minnsun Park, John Lawrence, Thomas Middour, Stephen Morris, Alaa Boulad, Brendan Carry, Nidal Abi Rafeh, Gholam Ali, Asif Anwar, Thiery LeJemtel, Sheryl Martin-Schild, Mark Cassidy
Journal: Circulation (2016)

Introduction: A considerable proportion of embolic strokes are currently classified as being cryptogenic. Despite long term monitoring only a minority have been shown to have atrial fibrillation (A...
Hepatitis A Outbreak in California — Addressing the Root Cause
Authors: Margot Kushel
Journal: New England Journal of Medicine (2017)

Interview with Dr. Margot Kushel on the hepatitis A outbreak in California and the health risks associated with chronic homelessness. (09:17)Download Most people affected by California’s hepatitis A outbreak are homeless, and infectious diseases are one of many health threats they face. To address the root cause of their health problems, we will need sustained efforts to fix the housing-affordability crisis.
Abstract 15290: Predictors of 30-Day Readmission and In-Hospital Mortality of Patients With Heart Failure With Preserved Ejection Fraction: A National Population-Based Cohort Study
Authors: Saman Setareh-Shenas, Shilpkumar Arora, Hafeez Ul Hassan Virk, Nilay Patel, Byomesh Tripathi, Emad F Aziz, Umesh K Gidwani
Journal: Circulation (2016)

Background: Rising prevalence of Heart Failure with Preserved Ejection Fraction (HFpEF) and limited data on outcomes such as 30 day readmissions and short term mortality is concerning. Methods: We ...
Disentangling Immediate Adaptive Introgression from Selection on Standing Introgressed Variation in Humans
Authors: Evelyn Jagoda, Daniel J Lawson, Jeffrey D Wall, David Lambert, Craig Muller, Michael Westaway, Matthew Leavesley, Terence D Capellini, Marta Mirazón Lahr, Pascale Gerbault, Mark G Thomas, Andrea Bamberg Migliano, Eske Willerslev, Mait Metspalu, Luca Pagani
Journal: Molecular Biology and Evolution (2017)

Recent studies have reported evidence suggesting that portions of contemporary human genomes introgressed from archaic hominin populations went to high frequencies due to positive selection. However, no study to date has specifically addressed the postintrogression population dynamics of these putative cases of adaptive introgression. Here, for the first time, we specifically define cases of immediate adaptive introgression (iAI) in which archaic haplotypes rose to high frequencies in humans as a result of a selective sweep that occurred shortly after the introgression event. We define these cases as distinct from instances of selection on standing introgressed variation (SI), in which an introgressed haplotype initially segregated neutrally and subsequently underwent positive selection. Using a geographically diverse data set, we report novel cases of selection on introgressed variation in living humans and shortlist among these cases those whose selective sweeps are more consistent with having been the product of iAI rather than SI. Many of these novel inferred iAI haplotypes have potential biological relevance, including three that contain immune-related genes in West Siberians, South Asians, and West Eurasians. Overall, our results suggest that iAI may not represent the full picture of positive selection on archaically introgressed haplotypes in humans and that more work needs to be done to analyze the role of SI in the archaic introgression landscape of living humans.
Incidence of hip and knee replacement in patients with rheumatoid arthritis following the introduction of biological DMARDs: an interrupted time-series analysis using nationwide Danish healthcare registers
Authors: René Lindholm Cordtz, Samuel Hawley, Daniel Prieto-Alhambra, Pil Højgaard, Kristian Zobbe, Søren Overgaard, Anders Odgaard, Lars Erik Kristensen, Lene Dreyer
Journal: Annals of the Rheumatic Diseases (2017)

To study the impact of the introduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) and associated rheumatoid arthritis (RA) management guidelines on the incidence of total hip (THR) and knee replacements (TKR) in Denmark.Nationwide register-based cohort and interrupted time-series analysis. Patients with incident RA between 1996 and 2011 were identified in the Danish National Patient Register. Patients with RA were matched on age, sex and municipality with up to 10 general population comparators (GPCs). Standardised 5-year incidence rates of THR and TKR per 1000 person-years were calculated for patients with RA and GPCs in 6-month periods. Levels and trends in the pre-bDMARD (1996-2001) were compared with the bDMARD era (2003-2016) using segmented linear regression interrupted by a 1-year lag period (2002).We identified 30 404 patients with incident RA and 297 916 GPCs. In 1996, the incidence rate of THR and TKR was 8.72 and 5.87, respectively, among patients with RA, and 2.89 and 0.42 in GPCs. From 1996 to 2016, the incidence rate of THR decreased among patients with RA, but increased among GPCs. Among patients with RA, the incidence rate of TKR increased from 1996 to 2001, but started to decrease from 2003 and throughout the bDMARD era. The incidence of TKR increased among GPCs from 1996 to 2016.We report that the incidence rate of THR and TKR was 3-fold and 14-fold higher, respectively among patients with RA compared with GPCs in 1996. In patients with RA, introduction of bDMARDs was associated with a decreasing incidence rate of TKR, whereas the incidence of THR had started to decrease before bDMARD introduction.
Effect of once-daily, modified-release hydrocortisone versus standard glucocorticoid therapy on metabolism and innate immunity in patients with adrenal insufficiency (DREAM): a single-blind, randomised controlled trial
Authors: Andrea M Isidori, Mary Anna Venneri, Chiara Graziadio, Chiara Simeoli, Daniela Fiore, Valeria Hasenmajer, Emilia Sbardella, Daniele Gianfrilli, Carlotta Pozza, Patrizio Pasqualetti, Stefania Morrone, Angela Santoni, Fabio Naro, Annamaria Colao, Rosario Pivonello, Andrea Lenzi
Journal: The Lancet Diabetes & Endocrinology (2017)
Body-on-a-Chip Reveals Multitissue Interactions During Drug Exposure
Authors: Tracy Hampton
Journal: JAMA (2017)

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
Endobronchial epithelial-myoepithelial carcinoma of the lung
Authors: Chang Hoon Kim, Jae Seok Jeong, So Ri Kim, Yong Chul Lee
Journal: Thorax (2017)

An 83-year-old woman presented to our emergency department with mild dyspnoea. The patient had been in her usual state of health until 3 days prior to admission. Her medical history revealed no specific illness, and she was a never-smoker.

The patient’s vital signs were within normal range, and physical examination revealed decreased breath sounds in the right lower lung field. Arterial blood gas analysis showed an oxygen saturation of 97%, a partial oxygen pressure of 11.7 kPa and a partial carbon dioxide pressure of 4.9 kPa. Laboratory tests demonstrated a leucocyte count of 1.5x109/L, 76.8% of which were neutrophils, an erythrocyte sedimentation rate of 53 mm/hour and a high-sensitivity C-reactive protein level of 150.87 mg/L, suggesting the presence of an underlying inflammatory reaction. Laboratory examinations, including chemistry panels, were otherwise normal.

A chest X-ray showed highly increased density in the right lung field (figure 1A, B). Chest CT displayed an 8.3×7.1 mm endobronchial mass that completely obstructed the right middle lobar bronchus. In addition, there was concurrent obstructive pneumonitis extending distally to the endobronchial mass (figure 1C). No lymph node enlargement was detected in the mediastinum. 2-Deoxy-2-(18F)-fluoro-D-glucose (FDG) positron emission tomography (PET)/CT revealed a …
A Review of the Current Therapies, Challenges, and Future Directions of Transcranial Focused Ultrasound Technology
Authors: Vibhor Krishna, Francesco Sammartino, Ali Rezai
Journal: JAMA Neurology (2017)

Magnetic resonance imaging-guided focused ultrasound ablation has been approved for the treatment of refractory essential tremor and is being studied for other neurological indications, including dyskinesias and tremor in Parkinson disease, dystonia, neuropathic pain, obsessive-compulsive disorder, epilepsy, and brain tumors.To review the scientific foundations of FUS technology, existing neurological applications, and future advances.PubMed was searched for the past 10 years using the terms "transcranial ultrasound," "focused ultrasound," and "neurological applications." Relevant references were selected from the author's reference collection. From the 2855 unique records, 243 publications were screened. After excluding abstracts detailing in vitro studies or non-neurological applications, 86 full texts were retrieved for qualitative review.Advances in the transducer design and electronic phase correction have allowed efficient focusing of ultrasounds for transcranial treatment. The mid-frequency (650 kHz) transducer can make small (4-6 mm in diameter) and precise (accuracy of <2 mm) brain lesions. The treatment monitoring is achieved via "live" anatomical thermography imaging and clinical feedback. The initial results from its clinical application in movement disorders are encouraging. Emerging applications in epilepsy and neurobehavioral and cognitive disorders are being explored. The low-frequency (220 kHz) transducer coupled with microbubbles can potentially enable targeted drug delivery for novel applications, such as Alzheimer disease and brain tumors. Finally, neuromodulation with subthreshold sonications may allow the interrogation of brain areas previously not accessible for electrical stimulation.Transcranial focused ultrasound for both ablative and nonablative applications is noninvasive, making it suitable for selected patients who are not candidates for conventional surgical options. Future advancements in imaging and sonication algorithms will improve the safety and efficacy of this technology.
BCAS1 expression defines a population of early myelinating oligodendrocytes in multiple sclerosis lesions
Authors: Maryam K. Fard, Franziska van der Meer, Paula Sánchez, Ludovico Cantuti-Castelvetri, Sunit Mandad, Sarah Jäkel, Eugenio F. Fornasiero, Sebastian Schmitt, Marc Ehrlich, Laura Starost, Tanja Kuhlmann, Christina Sergiou, Verena Schultz, Claudia Wrzos, Wolfgang Brück, Henning Urlaub, Leda Dimou, Christine Stadelmann, Mikael Simons
Journal: Science Translational Medicine (2017)

BCAS1 expression identifies newly formed and actively myelinating oligodendrocytes in development, adulthood, and disease.
Prospective development of a patient reported outcomes (PRO) tool in desmoid tumors: A novel clinical trial endpoint.
Authors: Jean Paty, Leanne Maddux, Mrinal M. Gounder
Journal: Journal of Clinical Oncology (2017)

11022 Background: Desmoid tumors (DT) are locally aggressive and cause significant morbidity. Clinical trials in DT typically utilize response rates and progression free survival as primary endpoints. However, these endpoints do not capture improvements in clinical symptoms. To date, there are no validated PRO tools in DT to capture the patient experience and efficacy of a drug. Methods: A review of the published literature and interviews with sarcoma clinicians were used to formulate a list of signs and symptoms and impact on patients (pts). These were collected to build a conceptual model. DT pts (n = 31) with a range of anatomical locations and presentations were interviewed, initially in an open-ended fashion, followed by interrogating the conceptual model. For the concepts that pts reported, they were asked to rate how disturbing each was on a 0-10 scale (0 being not at all, and 10 being as bad as they can imagine). The pts interview data was then used to refine the conceptual model and generate two new PRO instruments Results: Pt interviews demonstrated that across tumor locations, the most frequent and disturbing symptoms were: ‘muscle’ pain (65% pts, median disturbance (MD) of 6.8), ‘nerve’ pain (73%, MD 6.0), and fatigue (65%, MD 5.0). Some symptoms were specific to tumor locations, especially abdominal tumors. Restricted range of motion (68%, MD 4.0), fear (84%, MD 6.5), sleep disturbance (77%, MD 7.5) , disfigurement (81%, MD 6.8), and impact on daily activities (65%, MD 6.8) were the most frequent and disturbing impact on pts lives. These concepts were then used to develop two new PRO instruments: the sign and symptom PRO includes 11 items; the impact on pts lives instrument includes 17 items. The instruments vary in asking pts about the last 24 hours, or the last week. Conclusions: This is the first validated PRO tool in DT. This tool adequately captures symptoms central to the DT pts experience and its impacts on their lives. The instruments are ready for implementation in a DT clinical trial for further evaluation of their measurement properties.
T-cell primary central nervous system lymphoma: A systematic literature analysis.
Authors: Hung Vo, Ashmeet Bhatia, Edwin Lok, Eric T. Wong
Journal: Journal of Clinical Oncology (2014)

e13034 Background: Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin’s lymphoma confined primarily to the central nervous system. T-cell PCNSLs comprise less than 4% of all PCNSLs and they appear to have a worse prognosis than B cell PCNSLs. The incidence is rising due to, in part, better neuroimaging modalities. The objective of this study was to gain a more in depth understanding of the clinical presentation of the disease and treatment outcomes that may affect patient survival. Methods: A systematic review of the literature was performed using PubMed database from 1983 to 2013. Search was conducted for case descriptions of T-cell PCNSL. Inclusion criteria consisted of articles having detailed information of age, gender, location of the tumor and treatment. Results: Of the 200 citations reviewed, 90 articles were identified with T-cell PCNSL and the majority of them were case reports or case series, with total number of patients being 136. There were 16 cases reported between years 1980-1990, 54 cases from 1990-2000, and 66 cases from 2000-2013. Men outnumber women by a ratio of 2:1. The median age of the patients was 42.5 (range 2 to 79) years and the median overall survival (OS) was 14.0 (95% CI 13.3 to 20.1) months for those with age ≤64 years compared to 8.0 (95% CI 4.8 to 14.1) months for those with age >64 years (P=0.0033). Fifty-one patients received methotrexate-based chemotherapy and only 46% achieved a complete response (CR). There was no difference between the Kaplan-Mier overall survival of patients diagnosed with solitary versus multiple tumors (χ2=0.3, P=0.6090), treated versus not-treated with methotrexate (χ2=0.1, P=0.7420), and achieved CR versus non-CR status after methotrexate therapy (χ2=0.4, P=0.5470). Conclusions: Compared to historical data, T-cell PCNSL appears to be more aggressive and less responsive to methotrexate-based treatment than the majority of PCNSLs. HV and AB contributed equally.