tbuckley/cabot-search huggingface dataset:
Xpert MTB/RIF Assay as a Substitute for Smear Microscopy in an Intermediate-Burden Setting
Authors: Hyun-Seung Lee, Seung-Jung Kee, Ju-Hyeon Shin, Yong-Soo Kwon, Sejong Chun, Jun Hyung Lee, Eun Jeong Won, Hyun-Jung Choi, Soo Hyun Kim, Myung-Geun Shin, Jong-Hee Shin, Soon-Pal Suh
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Use of Xpert MTB/RIF assay as a substitute for smear microscopy in routine clinical practice remains unexplored in an intermediate-tuberculosis-burden setting.To compare the diagnostic performance of Xpert and smear microscopy, based on sampling time and location, correlation of Xpert semiquantitative category with smear grade and time to culture positivity, and compliance of reporting time with defined standard time.Consecutive sputum samples collected from 2,952 suspected pulmonary tuberculosis patients over a 3-year period were tested by Xpert, smear microscopy, and liquid culture as part of routine diagnostics in South Korea.Based on the analysis of a single sputum specimen per patient, of 2,952 samples, 263 (8.9%) were culture-confirmed tuberculosis and 265 (9.0%) were nontuberculous mycobacteria. The overall sensitivity and specificity were 74.1% and 97.5% for Xpert versus 38.8% and 96.7% for smear microscopy, respectively (P < 0.0001; P > 0.05). Of 82 smear-positive nontuberculous mycobacteria, 81 (98.8%) were accurately excluded by Xpert. Sampling time and location significantly affected the performance of smear microscopy but not that of Xpert. Xpert semiquantitative category strongly correlated with smear grade (γGoodman-Kruskal = 0.982; P < 0.0001) and time to culture positivity (γGoodman-Kruskal = -0.962; P < 0.0001). Median reporting time and its compliance rate within 24 hours were 3.1 hours and 96.3% for Xpert versus 19.1 hours and 88.7% for smear microscopy, respectively (P < 0.0001; P < 0.05).Xpert provides faster, more stable, and superior results compared with smear microscopy, in addition to its strong correlation with smear grade. Xpert might replace smear microscopy as the first-line diagnostic test for pulmonary tuberculosis in routine clinical practice in an intermediate-burden setting.
Abstract 18563: Sigmar1 Protects the Heart Against Ischemia/Reperfusion Injury
Authors: Shafiul Alam, Abdullah S. Chowdhury, A. Wayne Orr, Jeanne James, Hanna Osinska, Jeffery Molkentin, Burns C. Blaxall, Jeffrey Robbins, John N. Lorenz, Md. Shenuarin Bhuiyan
Journal: Circulation (2016)

Introduction: Accumulative evidence indicates that increased expression and presumably activity of molecular chaperones are protective against cardiac hypertrophic remodling and ischemia/reperfusio...
Abstract 20253: Insulin Resistance Traits but Not Cardiometabolic Dyslipidemia Interact With PNPLA3-rs738409 G-allele to Exacerbate Nonalcoholic Fatty Liver Disease
Authors: Llilda Barata, Mary F Feitosa, Lawrence F Bielak, Brian Halligan, Abigail Baldridge, Jie Yao, Albert V Smith, Gauti Kjartan, Laura Yerges-Armstrong, Xiuqing Guo, Laura J Rasmussen-Torvik, Jeffrey R O’Connell, Patricia A Peyser, Ingrid Borecki, Elizabeth K Speliotes, Michael Province
Journal: Circulation (2016)

Non-alcoholic fatty liver disease (NAFLD) is a complex disease caused by an excessive deposition of fat in the liver. NAFLD is correlated with the presence of related metabolic diseases including o...
Standardizing documentation and improving communication on an academic inpatient solid tumor oncology consult service.
Authors: Chrystal Ann Landry, Alaina J Kessler, Aarti Sonia Bhardwaj, Cardinale B. Smith
Journal: Journal of Clinical Oncology (2018)

171 Background: As the number of patients living with cancer increases, a growing proportion of hospital inpatients will have an advanced cancer diagnosis. Data suggests that an unscheduled hospitalization for a patient with advanced cancer strongly predicts a median survival of less than 6 months. As hospitalists more frequently become the primary team taking care of admitted cancer patients, communication between a patient's oncologic care team and inpatient primary providers is crucial. We sought to implement and assess the impact of improved oncology consult documentation of patient prognosis on outcomes of advanced cancer patients admitted to our hospitalist medicine teaching services. Methods: We implemented an EMR-based oncology consult note template which required documentation of prognosis, potential future treatment options (if available), and advance care planning. We reviewed all patients with stage IV solid tumors admitted to the hospitalist teaching service for 8 weeks prior and 8 weeks post-template implementation for comparison. We utilized descriptive statistics and chi-squared testing as appropriate for analysis. Results: We evaluated 51 patients in the pre- and 36 patients in the post-intervention groups. Post-intervention, there was an improvement in documentation of prognosis (29.4% vs. 52.8%, p = 0.03), advanced care planning (37.2% vs. 83.3%, p &lt; 0.0001), and in number of palliative care consults (58.8% vs. 83.3%, p = 0.02). On average, goals of care conversations occurred 2 days earlier in the post-intervention group (11 vs 9 days). Similarly, there was a decrease in inpatient chemotherapy administration (3 cases vs. 0), unit codes (2 vs. 0) and in-hospital death (23.5% vs. 11.1%). Conclusions: Creation of an oncology consult note template which incorporates current oncologic prognostic information improved documentation of prognosis and advance care planning as well as outcomes for advanced solid tumor oncology patients and enhanced inter-service communication. Based on these results, continued and targeted interventions are planned to further improve inter-service communication.
<i>Listeria Monocytogenes</i>–Induced Rhombencephalitis—A Paradoxical Disease of Immunocompetent Patients—Reply
Authors: Serena Ruggieri, Laura De Giglio
Journal: JAMA Neurology (2018)

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Targeting the C5 subclass of high-grade serous ovarian cancer using patient-derived xenografts: Microtubule polymerisation inhibitors.
Authors: Valerie Heong, Monique Topp, Sumitra Ananda, Orla McNally, Geoffrey John Lindeman, Paul Haluska, Matthew Wakefield, Elizabeth M. Swisher, David SP Tan, Huang Ruby, David Bowtell, Clare L. Scott
Journal: Journal of Clinical Oncology (2015)

e22202 Background: The most common epithelial ovarian cancer subtype, high-grade serous ovarian cancer (HGSC), can be divided into four subgroups based on molecular characteristics. The C5/Stem-A subgroup is characterized by MYCN pathway activation, stem cell like behaviour, and specific dependency on genes involved in microtubule dynamics. Analysis of C5/Stem-A-like cell lines demonstrated increased sensitivity to the tubulin depolymerising agent, vinorelbine, compared with non C5/stem-A cell lines. As commonly used HGSC cell lines are suboptimal experimental models, we used patient-derived xenografts (PDX) that retain pathological and immunohistochemical features of primary tumors, to explore this hypothesis in vivo Methods: A cohort of 12 HGSC PDX were generated from tumor tissue transplanted into NOD-SCID-IL2Rγnull mice and identified as "C5-like" using MYCN pathway (MYCN, HMGA2, LIN28B) expression analysis by qRT-PCR or by Affymetrix gene expression analysis. Additional molecular analyses performed included qRT-PCR and western blots for the drug resistance marker, CCNE1 and sequencing of DNA repair genes. In vivo platinum response was evaluated for each individual PDX as it provides prognostic information. In vivo response to vinorelbine was then evaluated in light of the individual molecular phenotype and platinum response of each PDX. Results: 11 out of 12 "C5-like" PDX displayed MYCN pathway activation. Two PDX over-expressed CCNE1 and three PDX harboured mutations in DNA repair genes (marker of drug response). Four HGSC PDX were sensitive to cisplatin, two were resistant and five were refractory (one pending). Analysis of vinorelbine response revealed four PDX (of six tested to date) responded for more than 50 days when treated with vinorelbine, one of which was refractory to cisplatin. Two other PDX had disease stabilization with vinorelbine, one of which was refractory to cisplatin Conclusions: Microtubule depolymerising agents appear to be an effective therapeutic option in targeting the C5/Stem-A subclass of HGSC and genes involved in microtubule dynamics should be interrogated to understand the underlying mechanism to enhance therapeutic options
TEKT4 Promotes Papillary Thyroid Cancer Cell Proliferation, Colony Formation, and Metastasis through Activating PI3K/Akt Pathway
Authors: Zhouci Zheng, Xiaofen Zhou, Yefeng Cai, Endong Chen, Xiaohua Zhang, Ouchen Wang, Qingxuan Wang, Haiguang Liu
Journal: Endocrine Pathology (2018)
Hearing loss in adults: getting earwax removed is a problem
Authors: Judith H Harvey
Journal: BMJ (2018)

Earwax is unglamorous, but clear ears make a huge difference to many patients’ hearing and so to their social functioning. That the National Institute for Health and Care Excellence has tackled the problem is good.1 But given that the evidence on how best to manage it is so weak and the options limited, the guidelines contain little to overcome the current barriers faced by …
Teams aren’t enough: Considering multiteam systems for better cancer care.
Authors: Elizabeth Hunter Lazzara, Marissa Shuffler, Chelsea Lenoble, Sallie Weaver, Veronica Chollette
Journal: Journal of Clinical Oncology (2018)

231 Background: Cancer is a complex disease that manifests differently. Quality care relies on the coordinated integration of many providers with varied background, experience, and expertise. Because care coordination spans across multiple processes (e.g., detection, diagnosis, and treatment), levels (e.g., individuals and teams), provider types (e.g., nurse and physician), specialties (e.g., surgery, radiology, and oncology), we argue that a team-based approach is necessary but solely insufficient. The current system provides care that is fragmented and evidence suggests such fragmentation is associated with missed opportunities, repetitive testing and increased costs. To mitigate fragmentation, effective cancer care requires the synthesis of multiple teams. A single team is characterized by two or more individuals working interdependently towards a shared goal. However, due to the complexity of cancer care, effective care coordination warrants multiple teams with collective, shared goals as well as potentially different, proximal goals. Effective multiteam systems (MTSs) need guidance, particularly for cancer care where this thinking is still relatively novel. With this in mind, the purpose of this paper is to contribute a theoretically grounded foundation and initial guiding principles that can inform efforts to mitigate the fragmentation in cancer care by providing insights on how to facilitate optimal MTSs. Methods: We culled the MTS literature to distill principles that are applicable for cancer care. Results: We offer seven recommendations that practitioners and healthcare delivery researchers can use to strengthen the integrated, coordinative efforts of cancer care: (1) Define the specific cancer care MTS &amp; potential future component teams; (2) Determine critical interdependencies among the component teams; (3) Identify optimal boundary spanner(s); (4) Educate the boundary spanner on the role and responsibilities; (5) Explicate the shared and competing goals; (6) Establish a salient social identity; and (7) Incorporate pre-briefs and debriefs with ‘unlikely’ team members. Conclusions: We posit that a MTS approach is more accurate and more fruitful for examining and improving the delivery of cancer care across the cancer continuum.
Abstract 10869: Role of Myocardial Perfusion, Sympathetic Denervation, and Scar Size in Predicting Inducibility of Ventricular Arrhythmia in Ischemic Cardiomyopathy
Authors: Mischa T Rijnierse, Cornelis P Allaart, Stefan de Haan, Hendrik J Harms, Marc C Huisman, Aernout M Beek, Adriaan A Lammertsma, Albert C van Rossum, Paul Knaapen
Journal: Circulation (2015)

Introduction: Myocardial perfusion, scar size, sympathetic denervation and innervation-perfusion mismatch, obtained from positron emission tomography (PET) and late gadolinium enhanced cardiovascular magnetic resonance imaging (LGE-CMR), may all provide better risk prediction of ventricular arrhythmias (VA). There may, however, be overlap between these risk markers, as some are based on similar pathophysiology. The aim of this study was to assess the role of PET and LGE-CMR derived risk markers in predicting VA inducibility in the same patient population. Methods: Patients (n=52, 66 ± 9 years, 90% male, LVEF 29 ± 6%) with ischemic cardiomyopathy and left ventricular ejection fraction (LVEF) ≤35% who were referred for primary prevention implantable cardioverter-defibrillator (ICD) implantation were included. LGE-CMR was performed to assess LV volumes, function, and scar size. [ 15 O]H 2 O PET and [ 11 C]HED PET were performed to assess both resting and hyperemic myocardial blood flow (MBF), and sympathetic innervation. Perfusion and innervation defects, and mismatch were calculated. After ICD implantation, an electrophysiological study (EPS) was performed and was considered positive in case of sustained VA. Results: Patients with positive EPS (n=25) showed lower hyperemic MBF (1.36 ± 0.39 vs. 1.71 ± 0.39 mL·min -1 ·g -1 , P =0.003), larger innervation defect size (28 ± 12 vs. 21 ± 13%, P =0.048), and tended to have larger scar size (24 ± 13 vs. 18 ± 9 g, P =0.07) and perfusion defect size (22 ± 13 vs. 15 ± 11%, P =0.06) compared with EPS negative patients (n=27). No differences were observed in LV volumes, LVEF, and innervation-perfusion mismatch size. Multivariable analysis revealed that impaired hyperemic MBF was the only independent predictor for VA inducibility (OR 0.78, 95% CI 0.65-0.94, P =0.007). A combination of risk markers did not yield incremental predictive value over hyperemic MBF alone. Conclusion: Of all previously validated risk markers for VA, impaired hyperemic MBF was the only independent predictor of VA inducibility. Moreover, a combined approach of different imaging variables did not have incremental value. These results may suggest that quantitative PET perfusion imaging may be promising for risk prediction of VA.
Abstract 12827: Serum Levels of High-Density Lipoprotein-Associated Paraoxonase-1 Predict Recurrent Cardiovascular Events After Drug-Eluting Stent Implantation in Patients With Stable Angina Pectoris
Authors: Tomotaka Yoshiyama, Kei Yunoki, Ryushi Komatsu, Kazuo Haze, Takahiko Naruko, Kenichi Sugioka, Masashi Nakagawa, Mayumi Inaba, Minoru Yoshiyama, Makiko Ueda
Journal: Circulation (2014)

Background: It is well established there is an inverse relationship between high-density lipoprotein (HDL) cholesterol and the risk for coronary artery disease, with its antioxidant properties attributed mainly to the HDL-bound enzyme, paraoxonase-1 (PON-1). We reported that plasma levels of myeloperoxidase, a pro-oxidant enzyme released from activated neutrophils that alters the atheroprotective function of HDL to a dysfunctional form, has a significant inverse correlation with PON-1 levels, especially in female patients with stable angina pectoris (SAP) (Atherosclerosis, 231, 308-314, 2013). Drug-eluting stents (DES) reduce the rate of restenosis, although recurrent angina and repeat revascularization remain major limitations. We investigated whether PON-1 levels predict cardiovascular events in patients with SAP undergoing DES implantation. Methods: Serum PON-1 concentration and activity were measured on admission in 191 SAP patients and 99 control subjects. We also assessed the prognostic significance...
AMに固有のモノクローナル抗体により明らかになる、培養メサンギウム細胞におけるアドレノメデュリン(AM)の産生と作用
Authors: Michibata H, Mukoyama M, Tanaka I, Goto M, Nakagawa M, Ishibashi R, Suga S, Akaji K, Fujiwara Y, Kiso Yi, Nakao K
Journal: Journal of the American Society of Nephrology (1995)
Cystic Fibrosis in Art
Authors: Eliza Jane Temple Milliken
Journal: JAMA (2018)

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Abstract 13875: Torsade de Pointes Arrhythmias Arise at the Site of Maximal Heterogeneity of Repolarization in the Chronic Complete AV-block Dog
Authors: A Dunnink, TRG Stams, HDM Beekman, A Bossu, SC Wijers, VMF Meijborg, JMT de Bakker, MA Vos
Journal: Circulation (2015)

Introduction: The chronic complete atrioventricular block (CAVB) dog model is highly sensitive for drug-induced Torsade de Pointes (TdP) arrhythmias. Focal mechanisms have been considered as trigger for the onset of TdP, however, its exact mechanism remains unclear. In this study, detailed mapping of the heart was performed to assess intraventricular heterogeneity of repolarization in relation to the initation of TdP. Methods: In 6 animals, 48 needles, each containing 4 electrodes, were inserted in the ventricles. During right ventricular apex pacing (cycle length: 1000-1500ms) local unipolar electrograms were recorded before and after administration of dofetilide. Activation- and repolarization times (RT) were measured at baseline and before occurrence of the first TdP or at 5 minutes after start of dofetilide infusion in inducible and non-inducible dogs. Maximal RT differences were calculated in the left ventricle 1) within adjacent electrodes in different planes (transmural, apex-base, anterior-posterior) and 2) within a square of 4 needles (3D dispersion). Results: TdP could be induced in 3 out of 6 animals. No difference in mean RT was observed between inducible and non-inducible dogs both at baseline (343±30 vs. 345±17ms) and after dofetilide administration (582±73 vs. 508±15ms). Maximal dispersion of RT was not different between both groups at baseline: 36±32 vs. 32±7ms (transmural), 50±20 vs. 42±9ms (apex-base), 71±28 vs. 47±13ms (anterior-posterior), 83±19 vs. 70±6ms (3D dispersion). After dofetilide infusion anterior-posterior (203±28 vs. 142±34ms, p=0.04) and 3D dispersion (268±41 vs. 176±48ms, p=0.03) showed a higher RT difference in the inducible animals. No differences were observed for transmural (124±14 vs. 116±18ms, p=0.557) and apex-base dispersion (142±12 vs. 121±23ms, p=0.229). The initiating beat of the TdP arose consistently from the region with the largest local spatial dispersion of repolarization moments. Conclusion: TdP arises from a region with maximal heterogeneity of repolarization and animals susceptible for TdP demonstrate higher RT differences. These results suggest that a certain gradient of repolarization moments is required in order to initiate TdP in CAVB dogs.
Imaging progression-free survival: How much does it matter to patients?
Authors: Jennifer O'Donnell, Andrew George Robinson, Christopher M. Booth, Rachel Koven, Elizabeth A. Eisenhauer, Michael Donald Brundage
Journal: Journal of Clinical Oncology (2018)

99 Background: Progression-free survival (PFS) is often used as a clinical trials outcome for evaluating new therapies for solid tumors. While PFS is a validated surrogate for overall survival (OS) or quality of life (QOL) in some settings, it is increasingly used in contexts where surrogacy is not established. The end point is a composite of survival, symptomatic progression, and imaging-only progression. The intrinsic value of asymptomatic (imaging-only) progression from the patient perspective is not known. Methods: Patients with advanced metastatic cancer (lung, colorectal, or ovarian) who had completed at least 3 months of chemotherapy and were attending a routine ambulatory clinic were recruited and participated in a structured discrete choice trade-off exercise. The interview guide and visual aids were developed by a multidisciplinary team including patient representatives. Participants were provided with a hypothetical clinical scenario and associated treatment options. Treatment options presented had the same OS time but longer time to imaging progression and were associated with various levels of toxicity and treatment time. A sliding scale was used for duration of imaging-only PFS to determine each patient’s willingness to trade longer time for a given level of toxicity. Results: 20 (11M, 9F) patients participated in interviews (Nov 2017 - Jun 2018). Given the scenario 85% (n = 17) of patients chose treatment with less toxicity and treatment duration even if associated with a shorter imaging-only PFS. Two patients chose a trade-off for a more toxic treatment with an increase in imaging PFS by 18 months and 24 months respectively. One patient chose to always opt for most aggressive treatment irrespective of PFS benefit and toxicity. Conclusions: Patients with metastatic cancer currently being treated with palliative chemotherapy overwhelmingly considered imaging-only PFS to be of low value when it was associated with increased toxicity but not with longer OS. In situations where surrogacy for OS and QOL has not been established, endpoints that de-emphasise the importance of imaging are required.
Distinct patterns of clonal evolution in patients with concurrent myelo- and lymphoproliferative neoplasms
Authors: James A. Kennedy, Jessie J. F. Medeiros, Stephanie M. Dobson, Andrea Arruda, Mahadeo A. Sukhai, Tracy Stockley, Anne Tierens, Mark D. Minden, Suzanne Kamel-Reid, John E. Dick, Vikas Gupta
Journal: Blood (2018)