tbuckley/cabot-search huggingface dataset:
Impact of scribes on emergency medicine doctors’ productivity and patient throughput: multicentre randomised trial
Authors: Katherine Walker, Michael Ben-Meir, William Dunlop, Rachel Rosler, Adam West, Gabrielle O’Connor, Thomas Chan, Diana Badcock, Mark Putland, Kim Hansen, Carmel Crock, Danny Liew, David Taylor, Margaret Staples
Journal: BMJ (2019)

Abstract Objectives To evaluate the changes in productivity when scribes were used by emergency physicians in emergency departments in Australia and assess the effect of scribes on throughput. Design Randomised, multicentre clinical trial. Setting Five emergency departments in Victoria used Australian trained scribes during their respective trial periods. Sites were broadly representative of Australian emergency departments: public (urban, tertiary, regional referral, paediatric) and private, not for profit. Participants 88 physicians who were permanent, salaried employees working more than one shift a week and were either emergency consultants or senior registrars in their final year of training; 12 scribes trained at one site and rotated to each study site. Interventions Physicians worked their routine shifts and were randomly allocated a scribe for the duration of their shift. Each site required a minimum of 100 scribed and non-scribed shifts, from November 2015 to January 2018. Main outcome measures Physicians’ productivity (total patients, primary patients); patient throughput (door-to-doctor time, length of stay); physicians’ productivity in emergency department regions. Self reported harms of scribes were analysed, and a cost-benefit analysis was done. Results Data were collected from 589 scribed shifts (5098 patients) and 3296 non-scribed shifts (23 838 patients). Scribes increased physicians’ productivity from 1.13 (95% confidence interval 1.11 to 1.17) to 1.31 (1.25 to 1.38) patients per hour per doctor, representing a 15.9% gain. Primary consultations increased from 0.83 (0.81 to 0.85) to 1.04 (0.98 to 1.11) patients per hour per doctor, representing a 25.6% gain. No change was seen in door-to-doctor time. Median length of stay reduced from 192 (interquartile range 108-311) minutes to 173 (96-208) minutes, representing a 19 minute reduction (P&lt;0.001). The greatest gains were achieved by placing scribes with senior doctors at triage, the least by using them in sub-acute/fast track regions. No significant harm involving scribes was reported. The cost-benefit analysis based on productivity and throughput gains showed a favourable financial position with use of scribes. Conclusions Scribes improved emergency physicians’ productivity, particularly during primary consultations, and decreased patients’ length of stay. Further work should evaluate the role of the scribe in countries with health systems similar to Australia’s. Trial registration ACTRN12615000607572 (pilot site); ACTRN12616000618459.
Local and Systemic Immunity against Respiratory Syncytial Virus Induced by a Novel Intranasal Vaccine. A Randomized, Double-Blind, Placebo-controlled Clinical Trial
Authors: Stephanie Ascough, Iris Vlachantoni, Mohini Kalyan, Bert-Jan Haijema, Sanna Wallin-Weber, Margriet Dijkstra-Tiekstra, Muhammad S. Ahmed, Maarten van Roosmalen, Roberto Grimaldi, Qibo Zhang, Kees Leenhouts, Peter J. Openshaw, Christopher Chiu
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Needle-free intranasal vaccines offer major potential advantages, especially against pathogens entering via mucosal surfaces. As yet, there is no effective vaccine against respiratory syncytial virus (RSV), a ubiquitous pathogen of global importance that preferentially infects respiratory epithelial cells; new strategies are urgently required.Objectives: Here, we report the safety and immunogenicity of a novel mucosal RSV F protein vaccine linked to an immunostimulatory bacterium-like particle (BLP).Methods: In this phase I, randomized, double-blind, placebo-controlled trial, 48 healthy volunteers, aged 18-49 years, were randomly assigned to receive placebo or SynGEM (low or high dose) intranasally by prime-boost administration. The primary outcome was safety and tolerability, with secondary objectives assessing virus-specific immunogenicity.Measurements and Main Results: There were no significant differences in adverse events between placebo and vaccinated groups. SynGEM induced systemic plasmablast responses and significant, durable increases in RSV-specific serum antibody in healthy, seropositive adults. Volunteers given low-dose SynGEM (140 μg F, 2 mg BLP) required a boost at Day 28 to achieve plateau responses with a maximum fold change of 2.4, whereas high-dose recipients (350 μg F, 5 mg BLP) achieved plateau responses with a fold change of 1.5 after first vaccination that remained elevated up to 180 days after vaccination, irrespective of further boosting. Palivizumab-like antibodies were consistently induced, but F protein site ∅-specific antibodies were not detected, and virus-specific nasal IgA responses were heterogeneous, with the strongest responses in individuals with lower pre-existing antibody levels.Conclusions: SynGEM is thus the first nonreplicating intranasal RSV subunit vaccine to induce persistent antibody responses in human volunteers.Clinical trials registered with www.clinicaltrials.gov (NCT02958540).
Abstract 16900: Hospital Variation in Time to Epinephrine Administration for Pediatric In-hospital Cardiac Arrest
Authors: Tia T Raymond, Amy Praestgaard, Robert Berg, Vinay Nadkarni, Christopher Parshuram
Journal: Circulation (2017)

Background: In pediatric patients with in-hospital cardiac arrest (IHCA) due to non-shockable rhythms (PEA and asystole), delays in epinephrine administration are associated with worse survival. However, the extent and reason for hospital variation in delayed epinephrine administration and its effect on hospital-level outcomes is unknown. Methods: Within GWTG-R, we identified 1462 patients ( =1 dose of epinephrine in an eligible hospital. Eligible hospitals had reported >6 months data and had >=5 events. Hierarchical logistic regression models incorporated hospital and patient-level factors to quantify hospital variation in delayed epinephrine administration (>5 minutes), and its association with hospital rates of event, 24-hour, and discharge survival. Results: Overall, 218 (14.9%) patients had a delay in epinephrine administration, with a median hospital rate of 15.6% (IQR 7.1%-25%). Odds of delay in epinephrine administrat...
The Rising Number of Adult T Cell Leukemia Lymphoma (ATLL) Cases in Non-Hispanic Blacks and Its Association with Poor Outcomes
Authors: Urvi A Shah, Nishi Shah, Baozhen Qiao, Ana Acuna Villaorduna, Aditi Shastri, Ioannis Mantzaris, Olga Derman, Noah Kornblum, Ira Braunschweig, B. Hilda Ye, Amit Verma, Murali Janakiram
Journal: Blood (2018)
Author Correction: Metformin inhibits gluconeogenesis via a redox-dependent mechanism in vivo
Authors: Anila K. Madiraju, Yang Qiu, Rachel J. Perry, Yasmeen Rahimi, Xian-Man Zhang, Dongyan Zhang, João-Paulo G. Camporez, Gary W. Cline, Gina M. Butrico, Bruce E. Kemp, Gregori Casals, Gregory R. Steinberg, Daniel F. Vatner, Kitt F. Petersen, Gerald I. Shulman
Journal: Nature Medicine (2019)
Identification of lenalidomide resistance pathways in myeloma and targeted resensitization using cereblon replacement, inhibition of STAT3 or targeting of IRF4
Authors: Yuan Xiao Zhu, Chang-Xin Shi, Laura A. Bruins, Xuewei Wang, Daniel L. Riggs, Brooke Porter, Jonathan M. Ahmann, Cecilia Bonolo de Campos, Esteban Braggio, P. Leif Bergsagel, A. Keith Stewart
Journal: Blood Cancer Journal (2019)

Abstract To understand immunomodulatory drug (IMiD) resistance in multiple myeloma (MM), we created isogenic human multiple myeloma cell lines (HMCLs) sensitive and resistant to lenalidomide, respectively. Four HMCLs were demonstrated to be resistant to all IMiDs including lenalidomide, pomalidomide, and CC-220, but not to Bortezomib. In three HMLCs (MM.1.SLenRes, KMS11LenRes and OPM2LenRes), CRBN abnormalities were found, including chromosomal deletion, point mutation, and low CRBN expression. The remaining HMCL, XG1LenRes, showed no changes in CRBN but exhibited CD147 upregulation and impaired IRF4 downregulation after lenalidomide treatment. Depletion of CD147 in XG1LenRes and three additional HMCLs had no significant impact on MM viability and lenalidomide response. Further analysis of XG1LenRes demonstrated increased IL6 expression and constitutive STAT3 activation. Inhibition of STAT3 with a selective compound (PB-1-102) re-sensitized XG1LenRes to lenalidomide. Since XG1LenRes harbors a truncated IRF4 that is not downregulated by lenalidomide, we targeted IRF4/MYC axis with a selective inhibitor of the bromodomain of CBP/EP300 (SGC-CBP30), which restored lenalidomide response in XG1LenRes. This strategy also appeared to be more broadly applicable as SGC-CBP30 could re-sensitize two resistant HMCLs with low but detectable CRBN expression to lenalidomide, suggesting that targeting CBP/E300 is a promising approach to restore IMiD sensitivity in MM with detectable CRBN expression.
A Phase I, Open-Label, Multicenter, Dose-escalation Study of the Oral Selective FGFR Inhibitor Debio 1347 in Patients with Advanced Solid Tumors Harboring <i>FGFR</i> Gene Alterations
Authors: Martin H. Voss, Cinta Hierro, Rebecca S. Heist, James M. Cleary, Funda Meric-Bernstam, Josep Tabernero, Filip Janku, Leena Gandhi, A. John Iafrate, Darrell R. Borger, Nobuya Ishii, Youyou Hu, Yulia Kirpicheva, Valerie Nicolas-Metral, Anna Pokorska-Bocci, Anne Vaslin Chessex, Claudio Zanna, Keith T. Flaherty, Jose Baselga
Journal: Clinical Cancer Research (2019)

To investigate tolerability, efficacy, and pharmacokinetics/pharmacodynamics of Debio 1347, a selective FGFR inhibitor.This was a first-in-human, multicenter, open-label study in patients with advanced solid tumors harboring FGFR1-3 gene alterations. Eligible patients received oral Debio 1347 at escalating doses once daily until disease progression or intolerable toxicity. Dose-limiting toxicities (DLT) were evaluated during the first 4 weeks on treatment, pharmacokinetics/pharmacodynamics postfirst dose and after 4 weeks.A total of 71 patients were screened and 58 treated with Debio 1347 at doses from 10 to 150 mg/day. Predominant tumor types were breast and biliary duct cancer, most common gene alterations were FGFR1 amplifications (40%) and mutations in FGFR2 (12%) and FGFR3 (17%); 12 patients (21%) showed FGFR fusions. Five patients at three dose levels had six DLTs (dry mouth/eyes, hyperamylasemia, hypercalcemia, hyperbilirubinemia, hyperphosphatemia, and stomatitis). The maximum tolerated dose was not reached, but dermatologic toxicity became sometimes dose limiting beyond the DLT period at ≥80 mg/day. Adverse events required dose modifications in 52% of patients, mostly due to dose-dependent, asymptomatic hyperphosphatemia (22%). RECIST responses were seen across tumor types and mechanisms of FGFR activation. Six patients, 3 with FGFR fusions, demonstrated partial responses, 10 additional patients' tumor size regressions of ≤30%. Plasma half-life was 11.5 hours. Serum phosphate increased with Debio 1347 plasma levels and confirmed target engagement at doses ≥60 mg/day.Preliminary efficacy was encouraging and tolerability acceptable up to 80 mg/day, which is now used in an extension part of the study.
Cardamonin from a medicinal herb protects against LPS-induced septic shock by suppressing NLRP3 inflammasome
Authors: Zhilei Wang, Guang Xu, Yuan Gao, Xiaoyan Zhan, Nan Qin, Shubin Fu, Ruisheng Li, Ming Niu, Jiabo Wang, Youping Liu, Xiaohe Xiao, Zhaofang Bai
Journal: Acta Pharmaceutica Sinica B (2019)

Aberrant activation of NLRP3 inflammasome has been implicated in the pathogenesis of diverse inflammation-related diseases, and pharmacological molecules targeting NLRP3 inflammasome are of considerable value to identifying potential therapeutic interventions. Cardamonin (CDN), the major active ingredient of the traditional Chinese medicinal herb Alpinia katsumadai, has exerted an excellent anti-inflammatory activity, but the mechanism underlying this role is not fully understood. Here, we show that CDN blocks canonical and noncanonical NLRP3 inflammasome activation triggered by multiple stimuli. Moreover, the suppression of CDN on inflammasome activation is specific to NLRP3, not to NLRC4 or AIM2 inflammasome. Besides, the inhibitory effect is not dependent on the expression of NF-κB-mediated inflammasome precursor proteins. We also demonstrate that CDN suppresses the NLRP3 inflammasome through blocking ASC oligomerization and speckle formation in a dose-dependent manner. Importantly, CDN improves the survival of mice suffering from lethal septic shock and attenuates IL-1β production induced by LPS in vivo, which is shown to be NLRP3 dependent. In conclusion, our results identify CDN as a broad-spectrum and specific inhibitor of NLRP3 inflammasome and a candidate therapeutic drug for treating NLRP3 inflammasome-driven diseases.
Wide QRS Tachycardia in a Man With a Medical History of Atrial Fibrillation
Authors: Eric A. Bucklew, Steven E. Reis, Krishna Kancharla
Journal: JAMA Internal Medicine (2019)

A man in his 70s with stage 4 chronic kidney disease and atrial fibrillation presented with 1 month of progressive dyspnea on exertion, orthopnea, and worsening lower extremity edema. What is your diagnosis?
Abstract P3-10-28: The impact of HER2-directed targeted therapy on HER2-positive DCIS of the breast
Authors: GD Lewis, W Haque, A Farach, SS Hatch, EB Butler, MR Schwartz, E Bonefas, BS Teh
Journal: Cancer Research (2019)

Abstract Purpose/Objectives: In invasive breast cancer, HER2 is a well-established negative prognostic factor. However, its significance on the prognosis of ductal carcinoma in situ (DCIS) of the breast is unclear. As a result, the impact of adding HER2-directed therapy to HER2-positive DCIS is unknown and is currently the subject of ongoing clinical trials. In this study, we aim to determine the impact of HER2 status on DCIS patient outcomes as well as the possible impact of HER2-directed targeted therapy on survival outcomes for HER2-positive DCIS patients. Materials/Methods: The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy-proven DCIS diagnosed from 2004-2015. Only patients with known estrogen receptor (ER) status, progesterone receptor (PR) status, and HER2 status were included in the analysis. Patients were divided into two groups based on the adjuvant therapy they received: systemic therapy (assumed to be HER2-directed targeted therapy) or no systemic therapy. Statistics included multivariable logistic regression to determine factors predictive of receiving systemic therapy, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling to determine variables associated with OS. Results: Altogether, 1927 patients met inclusion criteria; 430 (22.3%) received HER2-directed targeted therapy, while 1497 (77.7%) did not. Patients who received HER2-directed targeted therapy were likely more likely to be ER-negative. Patients who received HER2-directed targeted therapy had a higher 5-year OS compared to patients that did not (97.7% vs. 95.8%, p = 0.043). This survival benefit remained on multivariate analysis. Factors associated with worse OS on multivariate analysis included Charlson-Deyo Comorbidity Score ≥ 2 and no receipt of hormonal therapy. Conclusions: In the largest study to date evaluating HER2-positive DCIS patients, the receipt of HER2-directed targeted therapy was associated with an improvement in OS. The results of currently ongoing clinical trials are needed to confirm this finding. Citation Format: Lewis GD, Haque W, Farach A, Hatch SS, Butler EB, Schwartz MR, Bonefas E, Teh BS. The impact of HER2-directed targeted therapy on HER2-positive DCIS of the breast [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-10-28.
Similar Appearance on Dynamic Images of Meckel Scintigraphy Caused by Different Etiologies
Authors: Zhe Wen, Lorianne Salerno, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2019)

Positive gastric mucosa Meckel diverticulum generally shows nonmoving activity in the right abdomen, which appears early in the study at about the same time of the appearance of the stomach. However, a stoma from ileostomy can result in similar findings on dynamic images. The difference between a true Meckel diverticulum and stoma can be exposed by lateral views.
Sunlight‐Driven Wearable and Robust Antibacterial Coatings with Water‐Soluble Cellulose‐Based Photosensitizers
Authors: Ruonan Jia, Weiguo Tian, Haotian Bai, Jinming Zhang, Shu Wang, Jun Zhang
Journal: Advanced Healthcare Materials (2019)

Abstract Herein, a simple, effective, and general strategy is demonstrated to obtain a water‐soluble and nontoxic cellulose‐based photosensitizer (CPS) with enhanced photodynamic antibacterial activity through introducing protoporphyrin IX (PpIX) and quaternary ammonium salt (QAS) groups onto the cellulose backbone. The synergistic effect of the anchoring and diluting effect of the cellulose backbone and the electrostatic repulsion between QAS groups effectively inhibit the π–π stacking of PpIX groups, thus the as‐prepared CPS exhibits markedly enhanced reactive oxygen species (ROS) yield. Meanwhile, the positively charged QAS groups endow the CPS with water‐solubility and a strong attractive force to bacteria. As a result, the CPS can rapidly and efficiently kill drug‐resistant bacteria strains, including E. coli and S. aureus , with a low light dose (2.4 J cm −2 ) and low concentration of PpIX groups (0.35 × 10 −6 m ). Benefiting from the excellent processability and formability, the CPS is readily applied as a sunlight‐driven wearable and robust antibacterial coating by a spray coating and later crosslinking procedure.
Abstract 17636: Computational Drug Repurposing Identifies Lgals8 and Nherf1 as Regulators of Endothelial Metabolic Activation Relevant to Pulmonary Hypertension
Authors: Vinny Negi, Gil Speyer, Adam Handen, Jingsi Zhao, Miranda Tai, Qiujun Yu, Ying Tang, Deepak Kumar, Catherine Corey, Sruti Shiva, Seungchan Kim, Imad Al Ghouleh, Stephen Y Chan
Journal: Circulation (2017)

Background & Hypothesis: Pulmonary hypertension (PH) is a fatal and under-studied vascular disease. Owing to parallels in the pathogenesis of cancer and PH, application of knowledge aided network b...
Depression Stresses the Immune Response and Promotes Prostate Cancer Growth
Authors: Hemn Mohammadpour, Mark J. Bucsek, Bonnie L. Hylander, Elizabeth A. Repasky
Journal: Clinical Cancer Research (2019)

Depression induces secretion of neuropeptide Y from prostate cancer cells, which, in turn, recruits myeloid-derived suppressor cells (MDSC) to the tumor; tumor cells and MDSCs secrete IL6, which activates STAT3 within cancer cells. Prostate cancer samples from depressed patients reveal a similar phenotype, suggesting new treatment strategies based upon blockade of β2-adrenergic receptors and/or neuropeptide Y.See related article by Cheng et al., p. 2621.
Survival benefit of gastric resection in the setting of metastatic gastric cancer.
Authors: Trang Nguyen, Brooke Vuong, Mansen Wang, Trevan D Fischer, Melanie Goldfarb, Anton J. Bilchik, Leland Jay Foshag
Journal: Journal of Clinical Oncology (2019)

166 Background: Prognosis remains poor for metastatic gastric cancer. Gastrectomy in the setting of stage IV disease is typically reserved for palliation of symptoms such as bleeding or obstruction. The potential survival benefit of resection on survival is controversial. The objective of this study is to determine using the National Cancer Database (NCDB) whether there was an increase in overall survival in patients diagnosed with metastatic cancer who underwent a gastrectomy in addition to chemotherapy. Methods: The NCDB was queried between 2004-2014 for patients with metastatic gastric cancer (adenocarcinoma, mucinous adenocarcinoma, or signet ring carcinoma) who received chemotherapy. Kaplan-Meier analysis and multivariate Cox proportional hazards regression analysis was done using SAS software. Results: A total of 20,599 patients met inclusion criteria. A minority of these patients (2,508; 12.2%) underwent gastric resection in addition to chemotherapy. The median overall survival for those who underwent gastrectomy was 14.1 months compared to 8.6 months for chemotherapy alone (p &lt; 0.0001). Other factors influencing survival included age, race, Charlson-Deyo co-morbidity index, year of diagnosis, primary tumor site, grade, and metastasis to multiple organs. Following multivariate analysis, patients who underwent gastrectomy and chemotherapy had a 36% lower risk of death compared to patients that had received chemotherapy alone (HR 0.64, 95% CI 0.48–0.80, P &lt; 0.0001). Conclusions: In this population analysis, the addition of gastrectomy to chemotherapy was associated with improved overall survival for patients with stage IV gastric cancer and should be considered for patients that are surgical candidates. Patients who underwent gastrectomy had a 36% decreased risk of death compared to those who had chemotherapy alone. However, only a small proportion of patients in the United States received multimodality treatment.
Incidence, Predictors, and Outcomes of In-Hospital Percutaneous Coronary Intervention Following Coronary Artery Bypass Grafting
Authors: Fahad Alqahtani, Khaled M. Ziada, Vinay Badhwar, Gurpreet Sandhu, Charanjit S. Rihal, Mohamad Alkhouli
Journal: Journal of the American College of Cardiology (2019)
Effect of Sentinel Node Biopsy in Clinically N0, BRAF V600E–Mutated, Small Papillary Thyroid Carcinoma
Authors: Marco Puccini, Gianpiero Manca, Carlo Maria Neri, Giuseppe Boni, Virginia Coli, Ludovico Maria Garau, Patrick M. Colletti, Domenico Rubello, Piero Buccianti
Journal: Clinical Nuclear Medicine (2019)

BRAF V600E mutation papillary thyroid cancer (PTC) is more aggressive with a higher risk of lymph node involvement and a poorer prognosis. Prior studies failed to demonstrate the superiority of prophylactic lymphadenectomy. We investigated the utility of additional radio-guided sentinel node biopsy (SNB).We analyzed 15 patients with N0 PTC by ultrasound and BRAF mutation on preoperative biopsy treated with total thyroidectomy (TT) or TT + prophylactic central neck dissection (PCND) alone or with SNB. Conventional surgery was performed before SNB. We recorded primary tumor diameter, multifocality, extrathyroid infiltration, neoplastic emboli, and tall cell variant. At follow-up, we evaluated basal and stimulated thyroglobulin and ultrasound or radioiodine scintigraphy.Of 15 consecutive patients, 5 received conventional surgery alone, and 10 had SNB. For the first group, 4 underwent TT, and 1 had TT + PCND. Among the SNB group, 1 had no sentinel node detected and underwent a simple TT, 2 had TT + PCND+ SNB in the lateral compartment, and 7 had TT + SNB in 1 to 3 neck compartments. Micrometastases were found in 1 of 3 PCND specimens. Sentinel node biopsy revealed metastasis in 3 of 6 central compartment biopsies, in 2 of 6 biopsies in the ipsilateral lateral compartment, and in none of 2 biopsies in the contralateral compartment. Sentinel node biopsy allowed the removal of micrometastases in 4 of 10 patients. At 53 months' (mean) follow-up, no relapse was documented.Radio-guided SNB correctly and efficiently stages cN0 BRAF-mutated PTC patients. Sentinel node biopsy could limit time-consuming, risk-exposing compartmental prophylactic dissections.