tbuckley/cabot-search huggingface dataset:
BMJ Awards 2020: NHS chief hails clinical leaders as winners are announced
Authors: Matthew Limb
Journal: BMJ (2020)

The NHS was never a “covid only” service even at the height of the coronavirus pandemic, NHS England’s chief executive, Simon Stevens, insisted at the BMJ Awards ceremony last night.

Stevens was speaking at a virtual presentation ceremony on Wednesday 7 October, where the list of winners was announced (box). He said that 2020 would probably be the “defining year” in the NHS’s history, given how it had been tested and how covid-19 had had an impact on other services. But he said that NHS staff had responded “impressively, with conviction and with agility,” saving many lives.

They were now gearing up to counter a further increase in the prevalence of covid-19 alongside restarting a “wider range” of services, he said.

Stevens paid tribute to the winning and shortlisted teams and clinicians across the NHS. He said, “If the BMJ Awards represent anything, they represent a bottling of that clinical, can-do attitude, refracted through the lens of what patients themselves are telling us they need from services.”

Stevens said the NHS had looked after 108 000 people needing specialist inpatient care with coronavirus since the pandemic began. “Even at the peak of hospital admissions in critical care, for every coronavirus patient we were looking after in hospital we were looking after two other non-covid patients,” he said.

“So although there has undoubtedly been a short term impact on many other services, it’s just not true that the NHS was ever a covid service only.”

Stevens said other health services across the world had also been severely tested, and it was right that there would continue to be a “lively debate” about many aspects of the UK’s response and opportunities to learn from international experience. “As we now look out over the next six months and beyond, we have clearly got to …
Clinical features and time trends associated with an endoscopically normal esophagus in active eosinophilic esophagitis
Authors: Swathi Eluri, S. Ryanne Corder, Erin Kim, Manaswita Tappata, Craig C. Reed, Nicholas J. Shaheen, Evan S. Dellon
Journal: Endoscopy (2020)

A proportion of patients with active eosinophilic esophagitis (EoE) have a normal-appearing esophagus on esophagogastroduodenoscopy (EGD). We aimed to determine the associations between the baseline clinical features and the endoscopically normal esophagus in EoE, as well as time trends in reporting.In this retrospective study of active EoE cases from 2002 - 2018, patients with and without esophageal endoscopic abnormalities were compared. Multivariable logistic regression identified the independent predictors of a normal EGD. The proportion of patients with a normal EGD was determined per year, and before and after the introduction of the first EoE guidelines and the EoE Endoscopic Reference Score (EREFS).Of 878 EoE patients, 101 (11.5 %) had an endoscopically normal esophagus; they were younger (8.3 vs. 25.4 years), had shorter median symptom duration before diagnosis (2.8 vs. 5.0 years), were less likely to have dysphagia (40 % vs. 76 %) or food impaction (8 % vs. 33 %), and more likely to have abdominal pain (37 % vs. 19 %) (P < 0.01 for all). On multivariable logistic regression, independent predictors of a normal esophagus were younger age (odds ratio [OR] 0.96, 95 % confidence interval [CI] 0.94 - 0.98), abdominal pain (OR 2.03, 95 %CI 1.13 - 3.67), and lack of dysphagia (OR 0.49, 95 %CI 0.26 - 0.93). The proportion of patients with a normal esophagus decreased from 21 % before the first EoE guidelines to 7 % (P < 0.01) after introduction of the EREFS.An endoscopically normal esophagus is seen in ~10 % of active EoE patients and should not preclude biopsies; younger age, abdominal pain, and lack of dysphagia are independent predictors. The proportion of normal EGDs decreased over time, suggesting improved recognition of endoscopic findings.
Cefiderocol versus high-dose, extended-infusion meropenem for the treatment of Gram-negative nosocomial pneumonia (APEKS-NP): a randomised, double-blind, phase 3, non-inferiority trial
Authors: Richard G Wunderink, Yuko Matsunaga, Mari Ariyasu, Philippe Clevenbergh, Roger Echols, Keith S Kaye, Marin Kollef, Anju Menon, Jason M Pogue, Andrew F Shorr, Jean-Francois Timsit, Markus Zeitlinger, Tsutae D Nagata
Journal: The Lancet Infectious Diseases (2020)
Ventromedial hypothalamic primary cilia control energy and skeletal homeostasis
Authors: Ji Su Sun, Dong Joo Yang, Ann W. Kinyua, Seul Gi Yoon, Je Kyung Seong, Juwon Kim, Seok Jun Moon, Dong Min Shin, Yun-Hee Choi, Ki Woo Kim
Journal: Journal of Clinical Investigation (2020)

Dysfunction of primary cilia is related to dyshomeostasis, leading to a wide range of disorders. The ventromedial hypothalamus (VMH) is known to regulate several homeostatic processes, but those modulated specifically by VMH primary cilia are not yet known. In this study, we identify VMH primary cilia as an important organelle that maintains energy and skeletal homeostasis by modulating the autonomic nervous system. We established loss-of-function models of primary cilia in the VMH by either targeting IFT88 (IFT88-KOSF-1) using steroidogenic factor 1-Cre (SF-1-Cre) or injecting an adeno-associated virus Cre (AAV-Cre) directly into the VMH. Functional impairments of VMH primary cilia were linked to decreased sympathetic activation and central leptin resistance, which led to marked obesity and bone-density accrual. Obesity was caused by hyperphagia, decreased energy expenditure, and blunted brown fat function and was also associated with insulin and leptin resistance. The effect of bone-density accrual was independent of obesity, as it was caused by decreased sympathetic tone resulting in increased osteoblastic and decreased osteoclastic activities in the IFT88-KOSF-1 and VMH primary cilia knockdown mice. Overall, our current study identifies VMH primary cilia as a critical hypothalamic organelle that maintains energy and skeletal homeostasis.
The relationship between treatment intensity and characteristics of patients with early-stage breast cancer.
Authors: Jeffrey Franks, Nicole Caston, Courtney Williams, Andres Azuero, Monica S. Aswani, Risha Gidwani, Gabrielle Betty Rocque
Journal: Journal of Clinical Oncology (2020)

125 Background: Clinical trials are used to generate standard-of-care, yet often do not reflect patient populations treated in real-world settings. Elderly patients or patients of color who are often underrepresented in trials, which may impact what types of treatments are prescribed. This study examines how patient characteristics are associated with treatment intensity in early stage breast cancer. Methods: This retrospective cross-sectional study included women with a stage I-III breast cancer from American Society of Clinical Oncology’s CancerLinQ database treated by chemotherapy from 2005-2019. Seven standard-of-care regimens were characterized by intensity. For patients with ER+/- HER2- breast cancer, low-intensity regimens were Taxol and Cyclophosphamide or Adriamycin and Cyclophosphamide; while Taxol, Adriamycin, and Cyclophosphamide was considered high intensity. For patients with HER2+ breast cancer, the low intensity regimen was Taxol and Herceptin; while Adriamycin and Cyclophosphamide followed by Taxol and Herceptin; Taxol, Carboplatin, and Herceptin; or Taxol, Carboplatin, Herceptin, and Pertuzumab were considered high intensity. A model estimating the likelihood of intensity was calculated using log-binomial regression, in order to produce relative risks. The models were adjusted for patient demographics and cancer stage. Results: Of 24,383 patients, 51% had ER+HER2-, 20% ER-HER2-, and 29% HER2+ breast cancer. Most patients were White (60%), age 40-69 (80%), had stage II breast cancer (39%), and received higher intensity treatment (65%). Adjusted for the other covariates, patient who were Black were more likely to receive high-intensity treatment than patients who were White (61% vs 58%; RR 1.05, 95%CI 1.02-1.06. Additionally, older adults were more likely to receive low-intensity treatment, with 42% of patients over 70 receiving low intensity treatment, and 29% of patients between the ages 40 and 69 received low intensity treatment (RR 1.5, 95% CI 1.44 -1.54). Conclusions: Differences in treatment intensity were observed for patients with differing demographic characteristics. Further research is needed to determine lack of representation in clinical trials impacts on prescribing patterns, regimen intensity, and survival.
A Rare Cause of Hemoptysis in a 20-Year-Old Man
Authors: Samantha Baah, Cynthia Reyes-Barron, Nana Yaw Ohene Baah
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

"A Rare Cause of Hemoptysis in a 20-Year-Old Man." American Journal of Respiratory and Critical Care Medicine, 202(12), pp. e146–e148
Response to: ‘Correspondence to ‘Normal human enthesis harbours conventional CD4+ and CD8+ T cells with regulatory features and inducible IL-17A and TNF expression’’ by Wang and Ma
Authors: Abdulla Watad, Charlie Bridgewood, Dennis G McGonagle
Journal: Annals of the Rheumatic Diseases (2020)

Response to: 'Correspondence to 'Normal human enthesis harbours conventional CD4+ and CD8+ T cells with regulatory features and inducible IL-17A and TNF expression'' by Wang and MaWe thank Wang and Ma 1 for their comments on our description of T-cells and their cytokines profile at the normal human spinal enthesis. 2Wang and Ma 1 report on synovial T-cells in psoriatic arthritis (PsA) obtained from synovial biopsies, and amongst other things, describes that infliximab therapy leads to a reduction in interleukin (IL)-23 related pathway transcripts indicating a potential pathogenic interplay between tumour necrosis factor (TNF)-α and IL-23/IL-17 axis at the synovium. 1he enthesis and synovium form what is known as the synovio-entheseal structure complex. 3A major unresolved issue in the immunopathology of PsA, is the link between synovial and entheseal immune cells.Animal models suggest that disease either TNF or IL-23 originating enthesitis may drive synovitis, 4 5 but it is unclear if this is the case humans.It is possible that the findings of Wang and Ma 1 could be extended to the enthesis and bone but formal studies are needed since the precise link between these immune compartments is unclear.The authors' results suggest a 'dampening' of the IL-23/IL-17 axis following infliximab therapy by acting on TGF-β and aryl hydrocarbon receptor signalling, that are involved in the regulation of the 23/17 axis.These findings are of interest towards the further understanding of the link between the enthesis and synovium in PsA and spondyloarthritis.
Doctors and nurses during COVID19 pandemic: A different perception of cancer care
Authors: Lucia Bastianelli, Filippo Merloni, Nicoletta Ranallo, Luca Cantini, Lorenzo Mariotti, Alessandra Lucarelli, Zelmira Ballatore, Rossana Berardi
Journal: Clinical Cancer Research (2020)

Background: The spread of coronavirus disease brought the need to reorganize clinical activity in oncology  Cancerpatients are very vulnerable, and it is well known that their treatment has to be strictly planned  The most criticalconsiderations still relate to the entry of the virus into hospitals, the heart of health care, where cancer patients areprotected  Instead, during the COVID19 pandemic the oncologic department had to limit access to care to protectpatients from a more dangerous disease for them, witnessing a paradox of health care  This brought with it worriesin oncologic health care professionals in replanning activities in order to guarantee therapeutic continuity and qualityof care  It is well known that physicians and nurses have different role concepts and role expectations  The purposeof our study was to investigate doctors' and nurses' perception of cancer patient reorganization during the COVID19pandemic in a sample of Italian health care professionals in oncology  Methods: We submitted a survey to oncologic health care workers (physicians and nurses) of Italian NationalHealth Care System during the pandemic to investigate clinical activity reorganization and cancer patientmanagement through 12 closed questions  The survey promoted by Clinica Oncologica, AOU Riuniti di Ancona-Universita Politecnica delle Marche was electronic and anonymous  Results: A total of 383 oncology health workers completed the survey, 60 nurses (15%) and 323 physicians (85%) 60% of interviewed physicians perceived qualitatively lower than usual the therapeutic path of patients taken incharge in this historical moment, while 45% of nurses declared it was the same (P<0 01)  The continuity of themultidisciplinary team was defined as guaranteed for 68% of oncologists, while almost 40% of nurses declared tonot know it  Almost all physicians (95%) answered that their clinical activity was reorganized, compared to a lowerportion of nurses (80%) who replanned their care role (p<0 01)  Deferring treatments caused fear and anxiety in62% of physicians and 46% of nurses (P=0 027)  Conclusion: The survey underlined the need to integrate skills and involve all professional figures in planningcancer patients' treatment to guarantee optimal therapeutic strategies and a global take in charge in all its details, even during emergencies
Unresponsiveness to inhaled antigen is governed by conventional dendritic cells and overridden during infection by monocytes
Authors: James G. Bedford, Melanie Heinlein, Alexandra L. Garnham, Thi H. O. Nguyen, Tom Loudovaris, Chenghao Ge, Stuart I. Mannering, Michael Elliott, Stuart G. Tangye, Katherine Kedzierska, Daniel H. D. Gray, William R. Heath, Linda M. Wakim
Journal: Science Immunology (2020)

The nasal-associated lymphoid tissues (NALTs) are mucosal-associated lymphoid organs embedded in the submucosa of the nasal passage. NALTs represent a known site for the deposition of inhaled antigens, but little is known of the mechanisms involved in the induction of immunity within this lymphoid tissue. We find that during the steady state, conventional dendritic cells (cDCs) within the NALTs suppress T cell responses. These cDCs, which are also prevalent within human NALTs (tonsils/adenoids), express a unique transcriptional profile and inhibit T cell proliferation via contact-independent mechanisms that can be diminished by blocking the actions of reactive oxygen species and prostaglandin E2 Although the prevention of unrestrained immune activation to inhaled antigens appears to be the default function of NALT cDCs, inflammation after localized virus infection recruited monocyte-derived DCs (moDCs) to this region, which diluted out the suppressive DC pool, and permitted local T cell priming. Accommodating for inflammation-induced temporal changes in NALT DC composition and function, we developed an intranasal vaccine delivery system that coupled the recruitment of moDCs with the sustained release of antigen into the NALTs, and we were able to substantially improve T cell responses after intranasal immunization. Thus, homeostasis and immunity to inhaled antigens is tuned by inflammatory signals that regulate the balance between conventional and moDC populations within the NALTs.
Abstract 298: Predicting Pulse Status During Cardiopulmonary Resuscitation Using Dimensionality Reduction of Electrocardiogram Wavelet Transforms
Authors: Diya Sashidhar, Heemun Kwok, Jason Coult, Jennifer E Blackwood, Peter J Kudenchuk, Shiv Bhandari, Thomas Rea, J. N Kutz
Journal: Circulation (2020)

Background: Current resuscitation protocols require pausing cardiopulmonary resuscitation (CPR) to check for a pulse. However, pausing CPR during a pulseless rhythm worsens patient outcome. We designed an ECG-based algorithm that predicts pulse status during uninterrupted CPR, and evaluated its performance both with and without CPR. Methods: We evaluated 383 patients who were treated for out-of-hospital cardiac arrest using defibrillators with real-time ECG, CPR, and audio recordings. We collected paired adjacent ECG segments with and without CPR during organized rhythms. Segments were collected during the 10-s CPR period just prior to pulse check, and 5-s segments without CPR during the pulse check. ECG segments with or without a pulse were identified by the audio annotation and recorded blood pressures. Patients were randomly divided into 60% (230/383) training and 40% (153/383) test groups. From training data, we developed an algorithm to predict clinical pulse status based on the wavelet transform of the bandpass-filtered ECG, applying principle component analysis (PCA). We then trained a linear discriminant model using 3 principle component modes as input features. Model performance was evaluated on test group segments with and without CPR using receiver operating curves overall and according to initial arrest rhythm. Results: There were 230 patients (540 pulse checks) in the training set and 153 patients (372 pulse checks) in the test set. In both of these sets, about 16% (37/230 and 25/153) of the patients presented with initial non-shockable rhythm . Overall 38% (351/912) of checks had a spontaneous pulse. The areas under the receiver operating characteristic curve (AUCs) for predicting pulse status with and without CPR on test data were 0.84 and 0.89, respectively. Conclusion: A novel ECG-based algorithm demonstrates potential to improve resuscitation by predicting presence of a spontaneous pulse without pausing CPR.
Implication of Trends in Timing of Dialysis Initiation for Incidence of End-stage Kidney Disease
Authors: Chi-yuan Hsu, Rishi V. Parikh, Leonid N. Pravoverov, Sijie Zheng, David V. Glidden, Thida C. Tan, Alan S. Go
Journal: JAMA Internal Medicine (2020)

<h3>Importance</h3> In the last 2 decades, there have been notable changes in the level of estimated glomerular filtration rate (eGFR) at which patients initiate long-term dialysis in the US and around the world. How changes over time in the likelihood of dialysis initiation at any given eGFR level in at-risk patients are associated with the population burden of end-stage kidney disease (ESKD) has not been not well defined. <h3>Objective</h3> To examine temporal trends in long-term dialysis initiation by level of eGFR and to quantify how these patterns are associated with the number of patients with ESKD. <h3>Design, Setting, and Participants</h3> Retrospective cohort study analyzing data obtained from a large, integrated health care delivery system in Northern California from 2001 to 2018 in successive 3-year intervals. Included individuals, ranging in number from as few as 983 122 (2001-2003) to as many as 1 844 317 (2016-2018), were adult members with 1 or more outpatient serum creatinine levels determined in the prior year. <h3>Main Outcomes and Measures</h3> One-year risk of initiating long-term dialysis stratified by eGFR levels. Multivariable logistic regression was performed to assess temporal trends in each 3-year cohort with adjustment for age, sex, race, and diabetes status. The potential change in dialysis initiation in the final cohort (2016-2018) was estimated using the relative difference between the standardized risks in the initial cohort (2001-2003) and the final cohort. <h3>Results</h3> In the initial 3-year cohort, the mean (SD) age was 55.4 (16.3) years, 55.0% were women, and the prevalence of diabetes was 14.9%. These characteristics, as well as the distribution of index eGFR, were stable across the study period. The likelihood of receiving dialysis at eGFR levels of 10 to 24 mL/min/1.73 m<sup>2</sup>generally increased over time. For example, the 1-year odds of initiating dialysis increased for every 3-year interval by 5.2% (adjusted odds ratio, 1.052; 95% CI, 1.004-1.102) among adults with an index eGFR of 20 to 24 mL/min/1.73 m<sup>2</sup>, by 6.6% (adjusted odds ratio, 1.066; 95% CI, 1.007-1.130) among adults with an eGFR of 16 to 17 mL/min/1.73 m<sup>2</sup>, and by 5.3% (adjusted odds ratio, 1.053; 95% CI, 1.008-1.100) among adults with an eGFR of 10 to 13 mL/min/1.73 m<sup>2</sup>, adjusting for age, sex, race, and diabetes. The incidence of new cases of ESKD was estimated to have potentially been 16% (95% CI, 13%-18%) lower if there were no changes in system-level practice patterns or other factors besides timing of initiating long-term dialysis from the initial 3-year interval (2001-2003) to the final interval (2016-2018) assessed in this study. <h3>Conclusions and Relevance</h3> The present results underscore the importance the timing of initiating long-term dialysis has on the size of the population of individuals with ESKD.
Study of critically ill patients with COVID-19 in New York City – Authors' reply
Authors: Matthew J Cummings, Max R O'Donnell
Journal: The Lancet (2020)

Study of critically ill patients with COVID-19 in New York CityCummings and colleagues 1 reported the epidemiology, clinical course, and outcomes of 257 critically ill adults with laboratory-confirmed COVID-19 admitted to two hospitals in New York City.The primary outcome was the rate of in-hospital death, and each patient had at least 28 days of observation.The authors report that, as of April 28, 2020, 101 (39%) of 257 patients had died, 94 (37%) remained hospitalised, four (2%) were transferred to another hospital, and 58 (23%) were discharged alive.Surprisingly, the authors show in figure 1 of their Article 1 a cumulative incidence of in-hospital death of approximately 45% at 28 days.Given the numbers of patients at risk reported below the figure, we have identified that this result is not correct.Apparently, the authors censored the patients discharged alive (n=58) at the day of discharge.This methodological error has led to overestimation of the cumulative incidence of death, and distorted the results of the Cox proportional hazards regression.A fundamental assumption in survival analysis is that censoring should be non-informative-ie, that patients censored have the same survival prospects as those who continue to be followed up. 2 Patients discharged alive should not have been censored; their status should be considered as event-free (ie, alive) throughout the study observation period.This methodological error in the COVID-19 literature is common yet serious. 3 We kindly ask the authors to reanalyse the data, and correctly report the cumulative incidence, and the risk factors of in-hospital mortality, considering the above aspects.
Multifaceted Beneficial Effects of Erdosteine: More than a Mucolytic Agent
Authors: Mario Cazzola, Clive Page, Paola Rogliani, Luigino Calzetta, Maria Gabriella Matera
Journal: Drugs (2020)

Erdosteine is a drug approved for the treatment of acute and chronic pulmonary diseases, originally developed as a mucolytic agent. It belongs to the thiol-based family of drugs that are known to also possess potentially important antioxidant and anti-inflammatory properties, and exhibit antibacterial activity against a variety of medically important bacterial species. Erdosteine is a prodrug that is metabolized to the ring-opening compound metabolite M1 (MET 1), which has mucolytic properties. Experimental studies have documented that erdosteine prevents or reduces lung tissue damage induced by oxidative stress and, in particular, that Met 1 also regulates reactive oxygen species production. The RESTORE study, which has been the only trial that investigated the effects of a thiol-based drug in chronic obstructive pulmonary disease (COPD) frequent exacerbators, documented that erdosteine significantly reduces the risk of acute exacerbations of COPD (AECOPDs), shortens their course, and also decreases the risk of hospitalization from COPD. The preventive action of erdosteine on AECOPDs was not affected by the presence or absence of inhaled corticosteroids (ICSs) or blood eosinophil count. These findings clearly contrast with the Global Initiative for Chronic Obstructive Lung Disease strategy's approach to use erdosteine only in those COPD patients not treated simultaneously with an ICS. Furthermore, they support the possibility of using erdosteine in a step-down approach that in COPD is characterized by the withdrawal of the ICS.