tbuckley/cabot-search huggingface dataset:
Validation of the age-adjusted shock index for pediatric casualties in Iraq and Afghanistan
Authors: Camaren M. Cuenca, Matthew A. Borgman, Michael D. April, Andrew D. Fisher, Steven G. Schauer
Journal: Military Medical Research (2020)

Abstract Background Pediatric casualties account for a notable proportion of encounters in the deployed setting based on the humanitarian medical care mission. Previously published data demonstrates that an age-adjust shock index may be a useful tool in predicting massive transfusion and death in children. We seek to determine if those previous findings are applicable to the deployed, combat trauma setting. Methods We queried the Department of Defense Trauma Registry (DODTR) for all pediatric subjects admitted to US and Coalition fixed-facility hospitals in Iraq and Afghanistan from January 2007 to January 2016. This is a secondary analysis of casualties seeking to validate previously published data using the shock index, pediatric age-adjusted. We then used previously published thresholds to determine patients outcome for validation by age grouping, 1–3 years (1.2), 4–6 years (1.2), 7–12 years (1.0), 13–17 years (0.9). Results From January 2007 through January 2016 there were 3439 pediatric casualties of which 3145 had a documented heart rate and systolic pressure. Of those 502 (16.0%) underwent massive transfusion and 226 (7.2%) died prior to hospital discharge. Receiver operating characteristic (ROC) thresholds were inconsistent across age groups ranging from 1.0 to 1.9 with generally limited area under the curve (AUC) values for both massive transfusion and death prediction characteristics. Using the previously defined thresholds for validation, we report sensitivity and specificity for the massive transfusion by age-group: 1–3 (0.73, 0.35), 4–6 (0.63, 0.60), 7–12 (0.80, 0.57), 13–17 (0.77, 0.62). For death, 1–3 (0.75, 0.34), 4–6 (0.66–0.59), 7–12 (0.64, 0.52), 13–17 (0.70, 0.57). However, negative predictive values (NPV) were generally high with all greater than 0.87. Conclusions Within the combat setting, the age-adjusted pediatric shock index had moderate sensitivity and relatively poor specificity for predicting massive transfusion and death. Better scoring systems are needed to predict resource needs prior to arrival, that perhaps include other physiologic metrics. We were unable to validate the previously published findings within the combat trauma population.
Abstract A30: Claudin-4-dependent mechanisms of high-grade serous ovarian cancer progression
Authors: Patricia Webb, Margaret C. Neville, Heidi Baumgartner-Wilson, Miriam D. Post, Andrew Goodspeed, Benjamin G. Bitler
Journal: Clinical Cancer Research (2020)

Abstract In The Cancer Genome Atlas, Claudins-3, -4, and -7 are highly expressed in high-grade serous ovarian cancer (HGSOC). While claudins-3 and -7 are often expressed at tight junctions, claudin-4 (CLDN4) appears to be cytoplasmic, both in normal cells where it is expressed rarely and in a model of HGSOC, often used to study cellular interactions in this disease, OVCAR3 cells. CLDN4 expression reduces response to paclitaxel and conveys worse overall survival. We, therefore, wanted to further elucidate CLDN4-dependent mechanisms of cancer progression and therapeutic response. To address CLDN4 biology, we utilized immunohistochemical (IHC) analysis, loss-of-function studies, and several nonbiased approaches, including RNA-sequencing and proteomics. The IHC showed CLDN4 protein localized in the Golgi compartment with GM130 and around the cells at sites of cell-cell contact. Knocking down CLDN4 by 80% in OVCAR3 cells led them to undergo a transition from a more epithelial morphology to a mesenchymal phenotype (EMT). RNA-Seq analysis supports this morphologic interpretation by showing an increase in mRNA for genes coding for mesenchymal proteins such as fibronectin-1 (FN1), CD44, VIM, TNC, MMP2, and SNAI2 and a decrease in epithelial genes such as E-cadherin (CDH1), CD24, KRT18, and KRT19. RNA-Seq analysis of non-membrane protein kinases showed a 2-fold increase in PLAU, MSN, CAV1, CAV2, and EPHA2 and a 2-fold decrease in IGFBP2 and ERBB2, results that correlate well with the sensitivity of cancer cells to the BCR-ABL inhibitor, dasatinib. To determine the proteins that associate with CLDN4, we performed biotin ligase analysis (Bio-ID) fusing biotin protein ligase to CLDN4 and introducing the gene for the fusion protein into both OVCAR3 and OVCAR8 cells. Of the 36 proteins repeatedly more highly biotinylated in the presence of CLDN4-biotin ligase, 20 were identified as plasma membrane proteins and eight as Golgi localized by Gene Ontology analysis. Notably, we discovered a tyrosine protein kinase, YES1, to be biotinylated in both cell lines. YES1 is a poor prognostic indicator in HGSOC and promotes signal propagation following receptor tyrosine kinase activation, which contributes to a plethora of downstream outputs, including cell-cell adhesion and cell survival. These findings imply that CLDN4 expression is related to EMT and knockdown of CLDN4 could increase the sensitivity HGSOC to inhibitors such as dasatinib (BCR-ABL) or saracatinib (c-Yes). Citation Format: Patricia Webb, Margaret C. Neville, Heidi Baumgartner-Wilson, Miriam D. Post, Andrew Goodspeed, Benjamin G. Bitler. Claudin-4-dependent mechanisms of high-grade serous ovarian cancer progression [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A30.
Ophthalmologists are fined for illegal price fixing for self paying patients
Authors: Clare Dyer
Journal: BMJ (2020)

The private hospital group Spire Healthcare and seven ophthalmologists have admitted taking part in an illegal price fixing agreement over the charges for an initial consultation for self paying patients at a hospital in the north of England.

Spire was fined £1.2m (€1.3m; $1.5m) and six of the consultants were fined sums between £642 and £2978 after an investigation by the Competition and Markets Authority (CMA). The seventh, who blew the whistle on the deal, was not fined.

The fines reflect a discount of 20%, applied because all the parties …
Initial and Repeated Point Prevalence Surveys to Inform SARS-CoV-2 Infection Prevention in 26 Skilled Nursing Facilities — Detroit, Michigan, March–May 2020
Authors: Guillermo V. Sanchez, Caitlin Biedron, Lauren R. Fink, Kelly M. Hatfield, Jordan Micah F. Polistico, Monica P. Meyer, Rebecca S. Noe, Casey E. Copen, Amanda K. Lyons, Gonzalo Gonzalez, Keith Kiama, Mark Lebednick, Bonnie K. Czander, Amen Agbonze, Aimee R. Surma, Avnish Sandhu, Valerie H. Mika, Tyler Prentiss, John Zervos, Donia A. Dalal, Amber M. Vasquez, Sujan C. Reddy, John Jernigan, Paul E. Kilgore, Marcus J. Zervos, Teena Chopra, Carla P. Bezold, Najibah K. Rehman
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Skilled nursing facilities (SNFs) are focal points of the coronavirus disease 2019 (COVID-19) pandemic, and asymptomatic infections with SARS-CoV-2, the virus that causes COVID-19, among SNF residents and health care personnel have been described (1-3). Repeated point prevalence surveys (serial testing of all residents and health care personnel at a health care facility irrespective of symptoms) have been used to identify asymptomatic infections and have reduced SARS-CoV-2 transmission during SNF outbreaks (1,3). During March 2020, the Detroit Health Department and area hospitals detected a sharp increase in COVID-19 diagnoses, hospitalizations, and associated deaths among SNF residents. The Detroit Health Department collaborated with local government, academic, and health care system partners and a CDC field team to rapidly expand SARS-CoV-2 testing and implement infection prevention and control (IPC) activities in all Detroit-area SNFs. During March 7-May 8, among 2,773 residents of 26 Detroit SNFs, 1,207 laboratory-confirmed cases of COVID-19 were identified during three periods: before (March 7-April 7) and after two point prevalence surveys (April 8-25 and April 30-May 8): the overall attack rate was 44%. Within 21 days of receiving their first positive test results, 446 (37%) of 1,207 COVID-19 patients were hospitalized, and 287 (24%) died. Among facilities participating in both surveys (n = 12), the percentage of positive test results declined from 35% to 18%. Repeated point prevalence surveys in SNFs identified asymptomatic COVID-19 cases, informed cohorting and IPC practices aimed at reducing transmission, and guided prioritization of health department resources for facilities experiencing high levels of SARS-CoV-2 transmission. With the increased availability of SARS-CoV-2 testing, repeated point prevalence surveys and enhanced and expanded IPC support should be standard tools for interrupting and preventing COVID-19 outbreaks in SNFs.
Development of potential COVID-19 vaccines continues to accelerate
Authors: Tony Kirby
Journal: The Lancet Microbe (2020)

Never before has the world come together as it has to find a vaccine and treatments for COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). At the time of writing (June, 2020) multiple vaccine candidates are in phase 1, 2, and 3 trials, while other promising candidates are finishing their preclinical trials. An update on four of these candidate vaccines is provided here.
Remote monitoring of oxygen saturation in individuals with COVID-19 pneumonia
Authors: Orla O'Carroll, Rachel MacCann, Aoife O'Reilly, Eleanor M. Dunican, Eoin R. Feeney, Silke Ryan, Aoife Cotter, Patrick W. Mallon, Michael P. Keane, Marcus W. Butler, Cormac McCarthy
Journal: European Respiratory Journal (2020)

<b>Remote monitoring of oxygen saturation in cases of COVID-19 pneumonia may facilitate discharge, relieving burden on bed demand and allowing safe follow-up for this disease in which the sequelae are unknown</b>https://bit.ly/3cTXnZU
Teriparatide Promotes Bone Healing in Medication-Related Osteonecrosis of the Jaw: A Placebo-Controlled, Randomized Trial
Authors: Ie-Wen Sim, Gelsomina L. Borromeo, Claudine Tsao, Rita Hardiman, Michael S. Hofman, Christian Papatziamos Hjelle, Musib Siddique, Gary J. R. Cook, John F. Seymour, Peter R. Ebeling
Journal: Journal of Clinical Oncology (2020)

Medication-related osteonecrosis of the jaw (MRONJ) is an infrequent but morbid and potentially serious condition associated with antiresorptive and antiangiogenic therapies. Although MRONJ can be prevented by optimizing oral health, management of established cases is supportive and remains challenging. Teriparatide, an osteoanabolic agent that improves bone healing in preclinical studies and in chronic periodontitis, represents a potential treatment option.In a double-blind, randomized, controlled trial, 34 participants with established MRONJ, with a total of 47 distinct MRONJ lesions, were allocated to either 8 weeks of subcutaneous teriparatide (20 µg/day) or placebo injections, in addition to calcium and vitamin D supplementation and standard clinical care. Participants were observed for 12 months, with primary outcomes that included the clinical and radiologic resolution of MRONJ lesions. Secondary outcomes included osteoblastic responses as measured biochemically and radiologically and changes in quality of life.Teriparatide was associated with a greater rate of resolution of MRONJ lesions (odds ratio [OR], 0.15 v 0.40; P = .013), and 45.4% of lesions resolved by 52 weeks compared with 33.3% in the placebo group. Teriparatide was also associated with reduced bony defects at week 52 (OR, 8.1; P = .017). The incidence of adverse events was balanced between groups, including nausea, anorexia, and musculoskeletal pain, most of mild severity.Teriparatide improves the rate of resolution of MRONJ lesions and represents an efficacious and safe treatment for it.
Allogeneic bone marrow transplantation with post-transplant cyclophosphamide for patients with HIV and haematological malignancies: a feasibility study
Authors: Christine M Durand, Adam A Capoferri, Andrew D Redd, Marianna Zahurak, Daniel I S Rosenbloom, Ayla Cash, Robin K Avery, Javier Bolaños-Meade, Catherine M Bollard, C Korin Bullen, Charles Flexner, Ephraim J Fuchs, Joel Gallant, Doug E Gladstone, Christopher D Gocke, Richard J Jones, Yvette L Kasamon, Jun Lai, Mark Levis, Leo Luznik, Kieren A Marr, Holly L McHugh, Seema Mehta Steinke, Paul Pham, Christopher Pohlmeyer, Keith Pratz, Shmuel Shoham, Nina Wagner-Johnston, Daniel Xu, Janet D Siliciano, Thomas C Quinn, Robert F Siliciano, Richard F Ambinder
Journal: The Lancet HIV (2020)
Durable benefit from immunotherapy and accompanied lupus erythematosus in pancreatic adenocarcinoma with DNA repair deficiency
Authors: Xionghao Pang, Juanjuan Qian, Hua Jin, Lei Zhang, Lin Lin, Yuli Wang, Yi Lei, Zeqiang Zhou, Meixiang Li, Henghui Zhang
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Clinical trials showed limited benefit of anti-PD-1 (programmed cell death 1) monotherapy in pancreatic adenocarcinoma patients and immune-related adverse events caused by immune checkpoint inhibitors were rarely reported in pancreatic adenocarcinoma. Here, we report the first case of durable benefit along with systemic lupus erythematosus following immunotherapy in mismatch repair-proficient pancreatic cancer. Case presentation We describe a 57-year-old woman with resected stage ⅢB pancreatic cancer who underwent several lines of conventional chemotherapy after multiple lymph node metastases. When the disease progressed again, the patient received an off-label treatment with pembrolizumab (100 mg every 3 weeks). After four cycles of immunotherapy treatment, CA19-9 level rapidly decreased to normal and the lymph node metastases reduced dramatically in volume, demonstrating a partial response to the therapy by RECIST 1.1 criteria. She continued on pembrolizumab and a total of eight cycles of administration she had received. Her lesions showed consistent reduction in size even when the medication had been stopped. Actually the patient experienced durable benefit from anti-PD-1 therapy for more than 4 years and she is still in good condition without tumor relapses to date. Besides, she was diagnosed with systemic lupus erythematosus 2 months after the last dose of pembrolizumab. Molecular profiling identified two deleterious PALB2 alterations including a germline mutation ( PALB2 c.3114–1G&gt;A) and a somatic mutation ( PALB2 c.2514+1G&gt;C) in this patient, suggesting the potential of DNA homologous recombination deficiency. Multiplex immunohistochemistry and RNA-seq results revealed a brisk immune cell infiltration in her resected primary lesion. Additionally, humanleukocyte antigen (HLA) typing assay identified two previously reported systemic lupus erythematosus risk alleles HLA-DRB1*15:01 and HLA-DQB1*06:02 in this patient. Conclusions The deleterious mutations of PALB2 closely related to homologous recombination deficiency or alterations of DNA damage response and repair genes might be promising biomarkers for predicting efficacy of immune checkpoint inhibitors in pancreatic adenocarcinoma. Genetic correlation behind immunotherapy-induced systemic lupus erythematosus and associated mechanism remain to be elucidated.
Cystic fibrosis: NHS England strikes deal to offer triple combination treatment
Authors: Gareth Iacobucci
Journal: BMJ (2020)

NHS England has announced that patients with cystic fibrosis will be able to access triple combination treatment after it struck a deal with Vertex Pharmaceuticals.

The deal to offer Kaftrio was announced by NHS England (NHSE) chief executive Simon Stevens on 30 June, ahead of a licence for the treatment being granted by the European Medicines Agency in the coming weeks.

NHSE said three in five patients with cystic fibrosis could benefit from the new triple combination treatment. …
Limiting Supplemental Nutrition Assistance Program Eligibility May Increase Sudden Death
Authors: Danielle Davari, Mojtaba Mirzaei, Ross J. Simpson
Journal: JAMA Internal Medicine (2020)

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 Internal Medicine 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 Internal Medicine journal
Covid-19 and the future of mental health in primary care
Authors: Miquel Roca, Caterina Vicens, Margarita Gili
Journal: BMJ (2020)

The spread of covid-19 has had a profound effect on the global economy, and the likelihood that the pandemic will lead to a huge recession and outstrip the financial crisis of 2008 is high.

Kisely and colleagues1 and Gold,2 along with Greenberg and colleagues,3 have pointed out the urgent need for strategies to minimise the psychological distress of healthcare workers. Current evidence indicates that after the pandemic …
COVID-19 Testing in Patients with Cancer: Does One Size Fit All?
Authors: Ainhoa Madariaga, Michelle McMullen, Semira Sheikh, Rajat Kumar, Fei-Fei Liu, Camilla Zimmermann, Shahid Husain, Gelareh Zadeh, Amit M. Oza
Journal: Clinical Cancer Research (2020)

The COVID-19 global pandemic has drastically impacted cancer care, posing challenges in treatment and diagnosis. There is increasing evidence that cancer patients, particularly those who have advanced age, significant comorbidities, metastatic disease, and/or are receiving active immunosuppressive therapy may be at higher risk of COVID-19 severe complications. Controlling viral spread from asymptomatic carriers in cancer centers is paramount, and appropriate screening methods need to be established. Universal testing of asymptomatic cancer patients may be key to ensure safe continuation of treatment and appropriate hospitalized patients cohorting during the pandemic. Here we perform a comprehensive review of the available evidence regarding SARS-CoV-2 testing in asymptomatic cancer patients, and describe the approach adopted at Princess Margaret Cancer Centre (Toronto, Canada) as a core component of COVID-19 control.
House dust microbiota in relation to adult asthma and atopy in a US farming population
Authors: Mi Kyeong Lee, Annah B. Wyss, Megan U. Carnes, Marie Richards, Christine G. Parks, Laura E. Beane Freeman, Peter S. Thorne, David M. Umbach, M. Andrea Azcarate-Peril, Shyamal D. Peddada, Stephanie J. London
Journal: Journal of Allergy and Clinical Immunology (2020)

Bacterial exposure from house dust has been associated with asthma and atopy in children but whether these relationships are present in adults remains unclear.We sought to examine associations of house dust microbiota with adult asthma, atopy, and hay fever.Vacuumed bedroom dust samples from the homes of 879 participants (average age, 62 years) in the Agricultural Lung Health Study, a case-control study of asthma nested within a farming cohort, were subjected to 16S rRNA amplicon sequencing to characterize bacterial communities. We defined current asthma and hay fever using questionnaires and current atopy by blood specific IgE level > 0.70 IU/mL to 1 or more of 10 common allergens. We used linear regression to examine whether overall within-sample bacterial diversity differed by outcome, microbiome regression-based kernel association test to evaluate whether between-sample bacterial community compositions differed by outcome, and analysis of composition of microbiomes to identify differentially abundant bacterial taxa.Overall diversity of bacterial communities in house dust was similar by asthma status but was lower (P < .05) with atopy or hay fever. Many individual bacterial taxa were differentially abundant (false-discovery rate, <0.05) by asthma, atopy, or hay fever. Several taxa from Cyanobacteria, Bacteroidetes, and Fusobacteria were more abundant with asthma, atopy, or hay fever. In contrast, several taxa from Firmicutes were more abundant in homes of individuals with adequately controlled asthma (vs inadequately controlled asthma), individuals without atopy, or individuals without hay fever.Microbial composition of house dust may influence allergic outcomes in adults.
Abstract 11406: Assessment of a Novel Radiation Reduction Protocol for Pediatric and Adult Congenital Device Implantation
Authors: Bradley C Clark, Christopher M Janson, Scott R Ceresnak, Frank Osei, William J Bonney, Lynn Nappo, Robert H Pass
Journal: Circulation (2018)

Introduction: Device implantation requires fluoroscopic guidance, which carries inherent risks of ionizing radiation to patients and staff. We evaluated the impact of a novel low-dose fluoroscopic ...
The biphasic role of prolyl hydroxylase domain protein 2 (PHD2/EGLN1) in modulating tumor-forming potential
Authors: KangAe Lee, John LaPres, Justin McCormick, Sandra O'Reilly
Journal: Cancer Research (2007)

LB-202  Hypoxia is a common feature of solid tumors and the ability of cancer cells to adapt to hypoxia is important for tumor progression. The cellular response to hypoxic stress is controlled by a family of prolyl hydroxylases (PHDs) and the transcription factor hypoxia-inducible factor 1 (HIF1). To investigate the relationship between PHD, HIF1 activity, and cellular transformation we characterized the expression levels of PHD isoforms across a lineage of human fibroblast cell strains. These cells, derived one from the other, each one having acquired a characteristic related to malignant transformation, until the last change gave rise to a cell strain that by acquiring one more change, e.g., an RAS oncogene, becomes capable of forming malignant tumors in athymic mice with a short latency. Using these cells we have shown that PHD2 represents the primary HIF prolyl hydroxylase within this lineage of cells and that PHD2 levels decrease as the cell exhibits more transformed characteristics. When PHD2 levels were altered with RNAi in non-tumorigenic fibroblasts we found that moderate decreases in PHD2 activity can lead to malignant transformation, whereas cells with a more severe loss of PHD2 were unable to form tumors. Consistent with these results, direct chemical inhibition of PHD2 activity in transformed cells reverses a cell’s transformed characteristics. Moreover, we found that overexpression of PHD2 in malignant fibroblasts leads to loss of the tumor-forming ability. These changes correlated with HIF1-activated glycolytic rates, vascularization, and the ability to grow under hypoxic stress. These findings suggest a biphasic model for the relationship between PHD2 activity and malignant transformation: With a slight decrease in PHD2 activity the cells gain an advantage such as enhanced glycolysis and angiogenesis and become malignantly transformed. As PHD2 activity is further decreased, the pro-death response might become the dominant signal and the increased adaptation would be overwhelmed. The dual nature of this response is presumably due to PHD2’s ability to alter the cellular balance between hypoxic-induced adaptation and pro-death responses.