tbuckley/cabot-search huggingface dataset:
An Observational Study of the Efficacy of Cisatracurium Compared with Vecuronium in Patients with or at Risk for Acute Respiratory Distress Syndrome
Authors: Peter D. Sottile, Tyree H. Kiser, Ellen L. Burnham, P. Michael Ho, Richard R. Allen, R. William Vandivier, Marc Moss
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

The neuromuscular blocking agent cisatracurium may improve mortality for patients with moderate-to-severe acute respiratory distress syndrome (ARDS). Other neuromuscular blocking agents, such as vecuronium, are commonly used and have different mechanisms of action, side effects, cost, and availability in the setting of drug shortages.To determine whether cisatracurium is associated with improved outcomes when compared with vecuronium in patients at risk for and with ARDS.Using a nationally representative database, patients who were admitted to the ICU with a diagnosis of ARDS or an ARDS risk factor, received mechanical ventilation, and were treated with a continuous infusion of neuromuscular blocking agent for at least 2 days within 2 days of hospital admission were included. Patients were stratified into two groups: those who received cisatracurium or vecuronium. Propensity matching was used to balance both patient- and hospital-specific factors. Outcomes included hospital mortality, duration of mechanical ventilation, ICU and hospital duration, and discharge location.Propensity matching successfully balanced all covariates for 3,802 patients (1,901 per group). There was no significant difference in mortality (odds ratio, 0.932; P = 0.40) or hospital days (-0.66 d; P = 0.411) between groups. However, patients treated with cisatracurium had fewer ventilator days (-1.01 d; P = 0.005) and ICU days (-0.98 d; P = 0.028) but were equally likely to be discharged home (odds ratio, 1.19; P = 0.056).When compared with vecuronium, cisatracurium was not associated with a difference in mortality but was associated with improvements in other clinically important outcomes. These data suggest that cisatracurium may be the preferred neuromuscular blocking agent for patients at risk for and with ARDS.
Usefulness of midregional pro-adrenomedullin as a marker of organ damage and predictor of mortality in patients with sepsis
Authors: Enrique Bernal-Morell, Eva García-Villalba, Maria del Carmen Vera, Blanca Medina, Monica Martinez, Victoria Callejo, Salvador Valero, Cesar Cinesi, Pascual Piñera, Antonia Alcaraz, Irene Marin, Angeles Muñoz, Alfredo Cano
Journal: Journal of Infection (2017)
Brexit could mean delays for cancer treatments and less safe medicines
Authors: Adrian O’Dowd
Journal: BMJ (2017)

Patients could face delays in receiving lifesaving treatments and their medicines may be less safe if the UK does not secure a good post-Brexit deal and transitional arrangements, experts have warned MPs.

Speaking at an evidence session of the parliamentary health committee on 5 December for its inquiry into the potential effects of Brexit on the supply chain of medicines, medical devices, and other medical products, witnesses warned of the dangers of disrupting drug supply chains between the UK and the EU after Brexit.

MPs asked witnesses what a realistic worst case scenario could be after Britain leaves the EU. Martin Sawer, executive director of the Healthcare Distribution Association, which represents the UK’s major drug …
To progress understanding of disease triggers and modifiers in sarcoidosis, stratification is the key
Authors: Coline H.M. van Moorsel
Journal: European Respiratory Journal (2017)

The vast majority of sarcoidosis literature starts with something similar to the following sentence "Sarcoidosis is a multi-system granulomatous disease of unknown aetiology predominantly affecting the lung". The unknown cause continues to inspire researchers to search for a possible trigger, especially if new and high-throughput methods are at their disposal. The histological hallmark of sarcoidosis is epithelioid cell granuloma. Formation of granuloma is a common reaction towards, for example, bacterial agents. Evidence for bacterial involvement in sarcoidosis consist of presence of bacterial peptides inside lung granuloma and other products derived from sarcoidosis patients, the ability of these products to produce a granulomatous reaction in human and in mice, and the success of anti-microbial therapy in patients [1, 2]. Although active infection has not been found, bacteria, and in particular mycobacteria, are thought to be a causative or disease modifying factor in sarcoidosis. To progress understanding in sarcoidosis, stratification is the key: a call for disease phenotyping <http://ow.ly/k0T630gCgOb>
Palliative chemotherapy (CT) for advanced non-small cell lung cancer (NSCLC): Investigating disparities between patients who are treated versus those who are not.
Authors: Stephanie Yasmin Brule, Khalid Salim Al-Baimani, Hannah Jonker, Tinghua Zhang, Paul Wheatley-Price
Journal: Journal of Clinical Oncology (2015)

e17681 Background: Palliative CT in advanced NSCLC is associated with improved overall survival (OS) and quality of life, yet many patients remain untreated. In this study, we explored the differences between patients who did not receive palliative CT versus those who did, with a goal of better understanding and supporting the untreated. Methods: We performed a retrospective analysis of all newly diagnosed patients with advanced NSCLC seen at our institution between 2009 and 2012. Demographics, treatment, and survival data were collected. Fisher’s exact test assessed the association between CT use and baseline characteristics. Multivariate analysis of OS was performed using Cox regression models. Results: In total, 528 patients were seen: 291 (55%) received ≥ 1 line palliative CT, while 237 (45%) received none. Demographics were as follows: Median age 67, 55% male, 50% ECOG performance status (PS) 0-1, 48% with > 5% weight loss. Untreated patients were older (median 71 v 64, p < 0.01) and less fit (ECOG 0-1 in 27% v 69%, p < 0.01). More had weight loss (57% v 41%, p < 0.01), anemia (7% v 4%, p = 0.01), thrombocytosis (28% v 23%, p < 0.01), leukocytosis (38% v 32%, p < 0.01), and renal impairment (10% v 5%, p < 0.01). Reasons for no treatment included poor performance status (67%) and patient choice (23%). Median OS was shorter among untreated patients (3.9 v 10.7 months, HR 1.80 [95% CI 1.4-2.3], p < 0.01). In multivariate analysis, in addition to not receiving systemic therapy, factors associated with shorter OS were age, PS, weight loss, leukocytosis and thrombocytosis. Conclusions: Unsurprisingly, patients who did not receive CT had more poor prognostic features and worse OS. However, it is of concern that despite being seen in an active academic center, nearly half of all patients with advanced NSCLC received no anti-cancer treatment, most commonly due to poor PS. Current research primarily seeks to improve outcomes amongst those receiving systemic therapy, but this suggests that the lung cancer community must urgently advocate for the untreated. This should include more rapid diagnosis prior to functional decline, and development of therapies effective in a sicker population.
Heart surgery units will stay open as long as they meet standards
Authors: Anne Gulland
Journal: BMJ (2017)

Three heart surgery units threatened with closure have been given a reprieve, as NHS England launches new standards on congenital heart disease.

Units in Leicester, Leeds, and the Royal Brompton in London will continue to provide specialist surgical and interventional congenital heart disease services for adults and children provided that they meet certain criteria, NHS England has said.

The units were earmarked for closure in 2012,1 in a review designed to concentrate cardiac surgery in fewer, bigger units dealing with more cases after the scandal of excess deaths of children having heart surgery at the Bristol Royal Infirmary in the early1990s.2 But …
Oxford Surgical Collaborative for Audit and Research (OxSCAR): The UK’s Youngest Trainee-Led Collaborative
Authors: J.M. O'Callaghan, P. Holton, E. Gammeri, S. Flach, K. Jones, J.M. Findlay, K. Harvey, J. Isherwood, G. Van Boxel
Journal: International Journal of Surgery (2017)
Depletion of Airway Submucosal Glands and TP63<sup>+</sup>KRT5<sup>+</sup> Basal Cells in Obliterative Bronchiolitis
Authors: Anthony M. Swatek, Thomas J. Lynch, Adrianne K. Crooke, Preston J. Anderson, Scott R. Tyler, Leonard Brooks, Marina Ivanovic, Julia A. Klesney-Tait, Michael Eberlein, Tahuanty Pena, David K. Meyerholz, John F. Engelhardt, Kalpaj R. Parekh
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: Obliterative bronchiolitis (OB) is a major cause of mortality after lung transplantation. Depletion of airway stem cells (SCs) may lead to fibrosis in OB.Objectives: Two major SC compartments in airways are submucosal glands (SMGs) and surface airway p63 (also known as TP63 [tumor protein 63])-positive/K5 (also known as KRT5 [keratin 5])-positive basal cells (BCs). We hypothesized that depletion of these SC compartments occurs in OB.Methods: Ferret orthotopic left lung transplants were used as an experimental model of OB, and findings were corroborated in human lung allografts. Morphometric analysis was performed in ferret and human lungs to evaluate the abundance of SMGs and changes in the expression of phenotypic BC markers in control, lymphocytic bronchiolitis, and OB airways. The abundance and proliferative capacity of proximal and distal airway SCs was assessed using a clonogenic colony-forming efficiency assay.Measurements and Main Results: Ferret allografts revealed significant loss of SMGs with development of OB. A progressive decline in p63+/K5+ and increase in K5+/K14+ and K14+ BC phenotypes correlated with the severity of allograft rejection in large and small ferret airways. The abundance and proliferative capacity of basal SCs in large allograft airways declined with severity of OB, and there was complete ablation of basal SCs in distal OB airways. Human allografts mirrored phenotypic BC changes observed in the ferret model.Conclusions: SMGs and basal SC compartments are depleted in large and/or small airways of lung allografts, and basal SC proliferative capacity declines with progression of disease and phenotypic changes. Global airway SC depletion may be a mechanism for pulmonary allograft failure.
Association of Cumulative Childhood Adversity and Adolescent Violent Offending With Suicide in Early Adulthood
Authors: Emma Björkenstam, Anders Hjern, Charlotte Björkenstam, Kyriaki Kosidou
Journal: JAMA Psychiatry (2017)

Childhood adversity (CA) is associated with an increased risk of suicide in young adulthood that might be explained by maladaptive trajectories during adolescence. Although adolescent violent offending is linked with suicide, little is known about its role in the association between CA and suicide.To examine whether adolescent violent offending mediates the association between CA and suicide in early adulthood.This population-based, longitudinal cohort study with a follow-up time spanning 5 to 9 years included 476 103 individuals born in Sweden between 1984 and 1988. The study population was prospectively followed up from 20 years of age until December 31, 2013, with respect to suicide. Data analysis was performed from January 1, 1984, to December 31, 2013.Register-based CAs included parental death, parental substance abuse and psychiatric disorder, parental criminal offending, parental separation, public assistance recipiency, child welfare intervention, and residential instability. Adolescent violent offending was defined as being convicted of a violent crime between the ages of 15 and 19 years.Estimates of risk of suicide after 20 years of age (from 2004 if born in 1984 and from 2008 if born in 1988) until the end of 2013 were calculated as incidence rate ratios (IRRs) with 95% CIs using Poisson regression analysis. Adjustments were made for demographics and psychiatric disorder. In addition, binary mediation analysis with logistic regression was used.A total of 476 103 individuals (231 699 [48.7%] female) were included in the study. Those with a conviction for violent offending had been exposed to all CAs to a greater extent than those with no violent offending. Cumulative CA was associated with risk of suicide in nonconvicted (adjusted IRR, 2.4; 95% CI, 1.5-3.9) and convicted youths, who had a higher risk of suicide (adjusted IRR, 8.5; 95% CI, 4.6-15.7). Adolescent violent offending partly mediated the association between CA and suicide.Individuals with a history of CA who also engage in violent offending in adolescence have a high risk of suicide. Interventions to prevent externalizing behavior during childhood and increased support to youths with delinquent behavior may have the potential to prevent suicide related to CA.
Rules on reporting trials must be better enforced, say health integrity groups
Authors: Deborah Cohen
Journal: BMJ (2017)

Unregulated reporting of clinical trials opens the door to fraud and corruption, undermining medical advances and public health objectives, a report has warned.

The report,1 by a consortium of “health integrity organisations,” urges governments to enforce current rules to ensure that patients, doctors, and scientists can access the full results of all clinical trials.

The consortium includes Transparency International Pharmaceuticals & Healthcare, TranspariMED, Cochrane, and the Collaboration for Research Integrity and Transparency at Yale University.

Till Bruckner, lead author of the study and founder of TranspariMED, told The BMJ that the report explains the problem of hidden and misreported trials in a language that policy makers can understand and, crucially, provides concrete recommendations that they can act …
Association between microcephaly, Zika virus infection, and other risk factors in Brazil: final report of a case-control study
Authors: Thalia Velho Barreto de Araújo, Ricardo Arraes de Alencar Ximenes, Demócrito de Barros Miranda-Filho, Wayner Vieira Souza, Ulisses Ramos Montarroyos, Ana Paula Lopes de Melo, Sandra Valongueiro, Maria de Fátima Pessoa Militão de Albuquerque, Cynthia Braga, Sinval Pinto Brandão Filho, Marli Tenório Cordeiro, Enrique Vazquez, Danielle di Cavalcanti Souza Cruz, Claudio Maierovitch Pessanha Henriques, Luciana Caroline Albuquerque Bezerra, Priscila Mayrelle da Silva Castanha, Rafael Dhalia, Ernesto Torres Azevedo Marques-Júnior, Celina Maria Turchi Martelli, Laura Cunha Rodrigues, Carmen Dhalia, Marcela Santos, Fanny Cortes, Wanderson Kleber de Oliveira, Giovanini Evelim Coelho, Juan Jose Cortez-Escalante, Carlos Frederico Campelo de Albuquerque de Melo, Pilar Ramon-Pardo, Sylvain Aldighieri, Jairo Mendez-Rico, Marcos Espinal, Leuridan Torres, Adriano Nassri Hazin, Ana Van der Linden, Monica Coentro, George Santiago Dimech, Romildo Siqueira de Assuncao, Patricia Ismael de Carvalho, Valdete Felix Oliveira
Journal: The Lancet Infectious Diseases (2017)
Retirada de prótesis esofágicas metálicas autoexpandibles parcialmente cubiertas en un solo gesto mediante ruptura del ingrowth con balón de acalasia, alternativa eficaz al stent-in-stent
Authors: C Sendra Fernández, M De Los Ángeles Mejías Manzano, S Sobrino Rodriguez
Journal: Endoscopy (2017)

Las prótesis esofágicas metálicas auxtoexpandibles han revolucionado el manejo de la patología esofágica. La retirada de las parcialmente cubiertas (PMAPC) se ve dificultada por el ingrowth de la mucosa en la porción descubierta. En estos casos, la ESGE recomienda con baja calidad de evidencia, la técnica stent-in-stent.
Reply to Morales-Quinteros <i>et al.</i>: Precision Medicine for Extracorporeal CO<sub>2</sub> Removal for Acute Respiratory Distress Syndrome: CO<sub>2</sub> Physiological Considerations
Authors: Ewan C. Goligher, Marcelo B. P. Amato, Arthur S. Slutsky
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
The RNA genome of hepatitis E virus robustly triggers an antiviral interferon response
Authors: Wenshi Wang, Yijin Wang, Changbo Qu, Shan Wang, Jianhua Zhou, Wanlu Cao, Lei Xu, Buyun Ma, Mohamad S. Hakim, Yuebang Yin, Tiancheng Li, Maikel P. Peppelenbosch, Jingmin Zhao, Qiuwei Pan
Journal: Hepatology (2017)

The outcomes of hepatitis E virus (HEV) infection are diverse, ranging from asymptomatic carrier, self-limiting acute infection, and fulminant hepatitis to persistent infection. This is closely associated with the immunological status of the host. This study aimed to understand the innate cellular immunity as the first-line defense mechanism in response to HEV infection. Phosphorylation of signal transducer and activator of transcription 1, a hallmark of the activation of antiviral interferon (IFN) response, was observed in the liver tissues of the majority of HEV-infected patients but not in the liver of uninfected individuals. In cultured cell lines and primary liver organoids, we found that HEV RNA genome potently induced IFN production and antiviral response. This mechanism is conserved among different HEV strains, including genotypes 1, 3, and 7 as tested. Interestingly, single-stranded HEV RNA is sufficient to trigger the antiviral response, without the requirement of viral RNA synthesis and the generation of an RNA replicative form or replicative intermediate. Surprisingly, the m7 G cap and poly A tail are not required, although both are key features of the HEV genome. Mechanistically, this antiviral response occurs in a retinoic acid-inducible gene-I-independent, melanoma differentiation-associated protein 5-independent, mitochondrial antiviral signaling protein-independent, and β-catenin-independent but IRF3-dependent and IRF7-dependent manner. Furthermore, the integrity of the Janus kinase-signal transducer and activator of transcription pathway is essentially required.HEV infection elicits an active IFN-related antiviral response in vitro and in patients, triggered by the viral RNA and mediated by IFN regulatory factors 3 and 7 and the Janus kinase-signal transducer and activator of transcription cascade; these findings have revealed new insights into HEV-host interactions and provided the basis for understanding the pathogenesis and outcome of HEV infection. (Hepatology 2018;67:2096-2112).
Mannose receptor high, M2 dermal macrophages mediate nonhealing <i>Leishmania major</i> infection in a Th1 immune environment
Authors: Sang Hun Lee, Melanie Charmoy, Audrey Romano, Andrea Paun, Mariana M. Chaves, Frederick O. Cope, David A. Ralph, David L. Sacks
Journal: The Journal of Experimental Medicine (2017)

The origin and functional specialization of dermal macrophages in cutaneous infections have been little studied. In this paper, we show that a strain of Leishmania major (L. major Seidman [LmSd]) that produces nonhealing cutaneous lesions in conventionally resistant C57BL/6 mice was more efficiently taken up by M2-polarized bone marrow (BM)–derived macrophages (BMDMs) in vitro and by mannose receptor (MR)hi dermal macrophages in vivo compared with a healing strain (L. major Friedlin V1). Both in steady and in T helper type 1 (Th1) cell–driven inflammatory states, the MRhi dermal macrophages showed M2 characteristics. The dermal macrophages were radio resistant and not replaced by monocytes or adult BM-derived cells during infection, but were locally maintained by IL-4 and IL-10. Notably, the favored infection of M2 BMDMs by LmSd in vitro was MR dependent, and genetic deletion of MR or selective depletion of MRhi dermal macrophages by anti–CSF-1 receptor antibody reversed the nonhealing phenotype. We conclude that embryonic-derived, MRhi dermal macrophages are permissive for parasite growth even in a strong Th1-immune environment, and the preferential infection of these cells plays a crucial role in the severity of cutaneous disease.
Abstract 16775: Glycemic Variability Correlated With Vascular Stiffness and LV Filling Pressure at 1 Year After Onset of First ST-segment Elevation Myocardial Infarction: MRI and Tissue Doppler Analysis
Authors: Jin Kirigaya, Noriaki Iwahashi, Hironori Takahashi, Yuugo Minamimoto, Yasushi Matsuzawa, Katsutaka Hashiba, Nobuhiko Maejima, Kiyoshi Hibi, Toshiaki Ebina, Masami Kosuge, Kazuo Kimura
Journal: Circulation (2016)

Introduction:  Glycemic Variability (GV) may play an important role in patients with ST-segment elevation myocardial infarction (STEMI). But the clinical significance of GV is not fully understood in patients with a first STEMI.   Methods:  Consecutive 148 patients with a first STEMI (64±12 years, 88% male, max CPK=2964 IU/L, LAD 80/LCX 15/RCA 53), who had undergone reperfusion therapy within 12 hours after onset were enrolled. We analyzed GV by a continuous glucose monitoring system (CGM: iPRO2, Medtronic) at 2 weeks and mean amplitude of glycemic excursions (MAGE) as the parameter of GV. The infarct size was evaluated by using late-gadolinium enhancement (CMR-LGE) at 1 week. The cardio-ankle vascular stiffness index (CAVI) is not affected by blood pressure at the time of examination, thereby we examined CAVI at 2 weeks as the parameter of arterial stiffness. We assessed cardiac function measured by echocardiography and BNP at 12 months from discharge. E/e’ was measured as the marker of left ventricular (LV) filling pressure.   Results:  MAGE had significant relationship with CAVI (r=0.177; p   Conclusions:  MAGE correlated with arterial stiffness and predicted elevated LV filling pressure at 12 months in patients with a first STEMI.
Transplanting hepatitis C virus–positive livers into hepatitis C virus–negative patients with preemptive antiviral treatment: A modeling study
Authors: Jagpreet Chhatwal, Sumeyye Samur, Emily D. Bethea, Turgay Ayer, Fasiha Kanwal, Chin Hur, Mark S. Roberts, Norah Terrault, Raymond T. Chung
Journal: Hepatology (2017)

Under current guidelines, hepatitis C virus (HCV)‐positive livers are not transplanted into HCV‐negative recipients because of adverse posttransplant outcomes associated with allograft HCV infection. However, HCV can now be cured post‐LT (liver transplant) using direct‐acting antivirals (DAAs) with &gt;90% success; therefore, HCV‐negative patients on the LT waiting list may benefit from accepting HCV‐positive organs with preemptive treatment. Our objective was to evaluate whether and in which HCV‐negative patients the potential benefit of accepting an HCV‐positive (i.e., viremic) organ outweighed the risks associated with HCV allograft infection. We developed a Markov‐based mathematical model that simulated a virtual trial of HCV‐negative patients on the LT waiting list to compare long‐term outcomes in patients: (1) willing to accept any (HCV‐negative or HCV‐positive) liver versus (2) those willing to accept only HCV‐negative livers. Patients receiving HCV‐positive livers were treated preemptively with 12 weeks of DAA therapy and had a higher risk of graft failure than those receiving HCV‐negative livers. The model incorporated data from published studies and the United Network for Organ Sharing (UNOS). We found that accepting any liver regardless of HCV status versus accepting only HCV‐negative livers resulted in an increase in life expectancy when Model for End‐Stage Liver Disease (MELD) was ≥20, and the benefit was highest at MELD 28 (0.172 additional life‐years). The magnitude of clinical benefit was greater in UNOS regions with higher HCV‐positive donor organ rates, that is, Regions 1, 2, 3, 10, and 11. Sensitivity analysis demonstrated that model outcomes were robust. Conclusion: Transplanting HCV‐positive livers into HCV‐negative patients with preemptive DAA therapy could improve patient survival on the LT waiting list. Our analysis can help inform clinical trials and minimize patient harm. (H epatology 2018;67:2085‐2095).