tbuckley/cabot-search huggingface dataset:
Evaluation of Immune Response and Disease Status in Systemic Lupus Erythematosus Patients Following <scp>SARS</scp>–<scp>CoV</scp>‐2 Vaccination
Authors: Peter M. Izmirly, Mimi Y. Kim, Marie Samanovic, Ruth Fernandez‐Ruiz, Sharon Ohana, Kristina K. Deonaraine, Alexis J. Engel, Mala Masson, Xianhong Xie, Amber R. Cornelius, Ramin S. Herati, Rebecca H. Haberman, Jose U. Scher, Allison Guttmann, Rebecca B. Blank, Benjamin Plotz, Mayce Haj‐Ali, Brittany Banbury, Sara Stream, Ghadeer Hasan, Gary Ho, Paula Rackoff, Ashira D. Blazer, Chung‐E Tseng, H. Michael Belmont, Amit Saxena, Mark J. Mulligan, Robert M. Clancy, Jill P. Buyon
Journal: Arthritis & Rheumatology (2021)

To evaluate seroreactivity and disease flares after COVID-19 vaccination in a multiethnic/multiracial cohort of patients with systemic lupus erythematosus (SLE). Ninety SLE patients and 20 healthy controls receiving a complete COVID-19 vaccine regimen were included. IgG seroreactivity to the SARS-CoV-2 spike receptor-binding domain (RBD) and SARS-CoV-2 microneutralization were used to evaluate B cell responses; interferon-γ (IFNγ) production was measured by enzyme-linked immunospot (ELISpot) assay in order to assess T cell responses. Disease activity was measured by the hybrid SLE Disease Activity Index (SLEDAI), and flares were identified according to the Safety of Estrogens in Lupus Erythematosus National Assessment-SLEDAI flare index. Overall, fully vaccinated SLE patients produced significantly lower IgG antibodies against SARS-CoV-2 spike RBD compared to fully vaccinated controls. Twenty-six SLE patients (28.8%) generated an IgG response below that of the lowest control (<100 units/ml). In logistic regression analyses, the use of any immunosuppressant or prednisone and a normal anti-double-stranded DNA antibody level prior to vaccination were associated with decreased vaccine responses. IgG seroreactivity to the SARS-CoV-2 spike RBD strongly correlated with the SARS-CoV-2 microneutralization titers and correlated with antigen-specific IFNγ production determined by ELISpot. In a subset of patients with poor antibody responses, IFNγ production was similarly diminished. Pre- and postvaccination SLEDAI scores were similar in both groups. Postvaccination flares occurred in 11.4% of patients; 1.3% of these were severe. In a multiethnic/multiracial study of SLE patients, 29% had a low response to the COVID-19 vaccine which was associated with receiving immunosuppressive therapy. Reassuringly, severe disease flares were rare. While minimal protective levels remain unknown, these data suggest that protocol development is needed to assess the efficacy of booster vaccination.
Of Occlusions, Inclusions, and Exclusions: Time to Reclassify Infarctions?
Authors: Mullasari Ajit Sankardas, Venkatakrishnan Ramakumar, Faraz Ahmed Farooqui
Journal: Circulation (2021)

lassification of myocardial infarction (MI) has hitherto been on the basis of the presence or absence of ST-segment-elevation on the ECG.The landmark FTT (Fibrinolytic Therapy Trialists') collaborative group meta-analysis and the subsequent study of patient subpopulations revealed that the largest benefit of immediate reperfusion therapy was in individuals with ST-segment-elevation MI (STEMI) with a tendency toward net harm in patients who had either ST depression or a normal ST-segment on their ECG. 1 Apart from being on the basis of extensive clinical trial data, the classification also had the advantages of practical application.Patients with STEMI can be quickly identified by bedside ECG and often have complete angiographic occlusion of a culprit vessel.Although this has remained the standard for decades, ST-segment-elevation may not encompass the entire population of patients with acute MI with occlusion or who may benefit from emergent revascularization.
How can I keep in touch with colleagues?
Authors: Abi Rimmer
Journal: BMJ (2021)

How can I keep in touch with colleagues?Frequently changing roles and workplaces can make it hard to stay in touch with colleagues.Abi Rimmer hears some tips on how to stay connected Abi Rimmer Virtual communication is essentialSabrina Das, obstetrician and gynaecologist with Médecins Sans Frontières (MSF) in Yemen, says, "I'm on sabbatical working in Yemen with MSF.Keeping in touch with colleagues from the UK has been vitally important to me as an informal support system.I am the only international MSF obstetrician and gynaecologist working on this project, and my ability to move around the area is severely curtailed.
O-1 Results from a global phase 2 study of tislelizumab, an investigational PD-1 antibody, in patients with unresectable hepatocellular carcinoma
Authors: M. Ducreux, G. Abou-Alfa, Z. Ren, J. Edeline, Z. Li, E. Assenat, L. Rimassa, J. Blanc, P. Ross, W. Fang, S. Hu, T. Zhang, A. Tran, H. Pan, C. Yen, J. Wu, V. Li, S. Chica-Duque, P. Merle, A. Cheng
Journal: Annals of Oncology (2021)
Abstract 9619: Identification of Response to Cardiac Resynchronization Therapy by Radial Strain: Influence of Cardiomyopathy Type
Authors: Mi Young Park, Robert K Altman, Mary Orencole, Prabhat Kumar, Jagmeet P Singh, Michael H Picard
Journal: Circulation (2011)

Background: The use of speckle tracking derived radial strain by echocardiography (echo) to predict response to cardiac resynchronization therapy (CRT) has yielded variable results. We aimed to examine factors influencing the usefulness of radial dyssynchrony after CRT to evaluate CRT response. Method: Serial assessments of radial dyssynchrony by speckle tracking strain were performed after CRT in 98 patients (49 non-ischemic and 49 ischemic etiology) who were followed in our multidisciplinary clinic. Radial dyssynchrony (RD) was defined as a difference in time to peak strain of ≥130ms between anteroseptum and posterior wall (AS-P delay) at the mid LV level. Response to CRT was defined as a decrease in LV end systolic volume (ESV) of ≥15% or absolute increase in LVEF of &gt;5% on 6 month echo compared to baseline. Results: There was no difference in baseline EF between 66 responders and 32 nonresponders (25 ± 6 vs 24 ± 6 %; p=0.540). LV ESV index differed at baseline between groups (75 ± 24 vs 90± 31 ml/m 2 ; p=0.017). For the total population, AS-P delay was not different on 1 st follow up echo (echo 1, 54 ± 23 days) and 2 nd follow up echo (echo 2, 215 ± 42 days) after CRT (132 ± 90 vs 126 ± 104 ms; p=NS). The prevalence of RD decreased over time (echo 1 vs echo 2, 49% vs 41%; p=0.000). In responders, the AS-P delay was reduced at echo 2 compared to echo 1 (123 ± 85 vs 93 ± 73 ms; p= 0.011). For the nonresponders, the AS-P delay showed a trend to increase (147 ± 96 vs 191 ± 128 ms; p=0.091). The improvement in AS-P delay in responders was due to non-ischemic cardiomyopathy responders (117 ± 83 to 74 ± 51 ms; p=0.003) as no change was noted in ischemic etiology responders (134 ± 90 vs 123 ± 88 ms; p=NS). The prevalence of RD also decreased in responders over time (44% vs 25%; p=0.001) due to non-ischemic etiology responders (40% vs 14%; p = 0.005). Nonresponders showed increased prevalence of RD over time (59% vs 72%, p=0.000). Conclusion: Serial RD assessment by speckle tracking after CRT is feasible and correlates well with other measures of CRT response in non-ischemic cardomyopathy patients while it appear to be of limited value in ischemic cardiomyopathy. Thus, when examining the value of AS-P delay in CRT populations, the prevalence of cardiomyopathy type is critical.
Risk stratification for colorectal cancer in individuals with subtypes of serrated polyps
Authors: Dan Li, Amanda R Doherty, Menaka Raju, Liyan Liu, Nan Ye Lei, Laura B Amsden, Jeffrey K Lee, Theodore R Levin, Douglas A Corley, Lisa J Herrinton
Journal: Gut (2021)

Objective The longitudinal risk of colorectal cancer (CRC) associated with subtypes of serrated polyps (SPs) remains incompletely understood. Design This community-based, case–control study included 317 178 Kaiser Permanente Northern California members who underwent their first colonoscopy during 2006–2016. Nested within this population, we identified 695 cases of CRC and 3475 CRC-free controls (matched 5:1 to cases for age, sex and year of colonoscopy). Two expert pathologists reviewed the tissue slides of all SPs identified on the first colonoscopy and reclassified them to sessile serrated lesions (SSLs), hyperplastic polyps (HPs) and traditional serrated adenomas. SPs with borderline characteristics of SSLs but insufficient to make a definitive diagnosis were categorised as unspecified SPs. The association with development of CRC was assessed using multivariable logistic regression. Results Compared with individuals with no polyp, the adjusted ORs (aORs) for SSL alone or with synchronous adenoma were 2.9 (95% CI: 1.8 to 4.8) and 4.4 (95% CI: 2.7 to 7.2), respectively. The aORs for SSL with dysplasia, large proximal SSL,and small proximal SSL were 10.3 (95% CI: 2.1 to 50.3), 12.8 (95% CI: 3.5 to 46.9) and 1.9 (95% CI: 0.8 to 4.7), respectively. Proximal unspecified SP also conferred an increased risk (aOR: 5.8, 95% CI: 2.2 to 15.2). Women with SSL were associated with higher risk (aOR: 4.4; 95% CI: 2.3 to 8.2) than men (aOR: 1.7; 95% CI: 0.8 to 3.8). Conclusion Increased risk of CRC was observed in individuals with SSLs, particularly large proximal ones or with dysplasia, supporting close endoscopic surveillance. Proximal unspecified SPs were also associated with increased risk of CRC and should be managed as SSLs.
Cognitive Decline Associated With Anesthesia and Surgery in Older Patients
Authors: Susana Vacas, Daniel J. Cole, Maxime Cannesson
Journal: JAMA (2021)

This JAMA Insights article reviews how changes in the brain related to aging may contribute to decreased cognitive reserve, susceptibility to the stresses of surgery and anesthesia, and increased risk of neurologic injury from anesthesia and surgery in older patients.
Cilastatin Ameliorates Rhabdomyolysis-induced AKI in Mice
Authors: Katsuyuki Matsushita, Kiyoshi Mori, Turgay Saritas, Mahaba B. Eiwaz, Yoshio Funahashi, Megan N. Nickerson, Jessica F. Hebert, Adam C. Munhall, James A. McCormick, Motoko Yanagita, Michael P. Hutchens
Journal: Journal of the American Society of Nephrology (2021)

Significance Statement Rhabdomyolysis causes severe AKI and death in settings such as earthquakes and armed conflict. Specific treatment is not available and care is difficult to provide in these austere environments. Skeletal muscle myoglobin is a renal toxin that causes AKI in this syndrome. Proximal tubular megalin participates in myoglobin endocytosis and may be an AKI mediator. The authors demonstrate in a mouse model that proximal tubular megalin plays a critical role in rhabdomyolysis-induced AKI. In this model, proximal tubule–specific megalin deletion ameliorated AKI, and this effect was recapitulated by administration of cilastatin, a megalin inhibitor. This translational study thus identifies megalin as a mediator of rhabdomyolysis-induced AKI and suggests a novel mechanism by which it may be possible to ameliorate this condition. Background Rhabdomyolysis, the destruction of skeletal muscle, is a significant cause of AKI and death in the context of natural disaster and armed conflict. Rhabdomyolysis may also initiate CKD. Development of specific pharmacologic therapy is desirable because supportive care is nearly impossible in austere environments. Myoglobin, the principal cause of rhabdomyolysis-related AKI, undergoes megalin-mediated endocytosis in proximal tubule cells, a process that specifically injures these cells. Methods To investigate whether megalin is protective in a mouse model of rhabdomyolysis-induced AKI, we used male C57BL/6 mice and mice (14–32 weeks old) with proximal tubule–specific deletion of megalin. We used a well-characterized rhabdomyolysis model, injection of 50% glycerol in normal saline preceded by water deprivation. Results Inducible proximal tubule–specific deletion of megalin was highly protective in this mouse model of rhabdomyolysis-induced AKI. The megalin knockout mice demonstrated preserved GFR, reduced proximal tubule injury (as indicated by kidney injury molecule-1), and reduced renal apoptosis 24 hours after injury. These effects were accompanied by increased urinary myoglobin clearance. Unlike littermate controls, the megalin-deficient mice also did not develop progressive GFR decline and persistent new proteinuria. Administration of the pharmacologic megalin inhibitor cilastatin to wild-type mice recapitulated the renoprotective effects of megalin deletion. This cilastatin-mediated renoprotective effect was dependent on megalin. Cilastatin administration caused selective proteinuria and inhibition of tubular myoglobin uptake similar to that caused by megalin deletion. Conclusions We conclude that megalin plays a critical role in rhabdomyolysis-induced AKI, and megalin interference and inhibition ameliorate rhabdomyolysis-induced AKI. Further investigation of megalin inhibition may inform translational investigation of a novel potential therapy.
Efficacy and Safety of Upadacitinib vs Dupilumab in Adults With Moderate-to-Severe Atopic Dermatitis
Authors: Andrew Blauvelt, Henrique D. Teixeira, Eric L. Simpson, Antonio Costanzo, Marjolein De Bruin-Weller, Sebastien Barbarot, Vimal H. Prajapati, Peter Lio, Xiaofei Hu, Tianshuang Wu, John Liu, Barry Ladizinski, Alvina D. Chu, Kilian Eyerich
Journal: JAMA Dermatology (2021)

Atopic dermatitis (AD) is a chronic, recurrent, inflammatory skin disease with an unmet need for treatments that provide rapid and high levels of skin clearance and itch improvement.
Illness duration and symptom profile in symptomatic UK school-aged children tested for SARS-CoV-2
Authors: Erika Molteni, Carole H Sudre, Liane S Canas, Sunil S Bhopal, Robert C Hughes, Michela Antonelli, Benjamin Murray, Kerstin Kläser, Eric Kerfoot, Liyuan Chen, Jie Deng, Christina Hu, Somesh Selvachandran, Kenneth Read, Joan Capdevila Pujol, Alexander Hammers, Tim D Spector, Sebastien Ourselin, Claire J Steves, Marc Modat, Michael Absoud, Emma L Duncan
Journal: The Lancet Child & Adolescent Health (2021)
THE HOSPITAL POLICY OF THE LABOUR PARTY
Journal: BMJ (1922)

COIr-REiE-FNDENCE.( TiMEDitTx -~~~~~~~~~~~~~~EDICAL JOUsLNAZ the Dublin Zoo.A good m-any lions are bred there, aud a very intelligent keeper discussed their healtlh and up- bringing.He said the chief trouble they had with them-l was rickets, but since they lhad increased the amount of fat in their diet no cases of rickets had occurred.This would tend to slhow that the food factor is of greater inmportance, as the lion hiouse is light and airy.-Iam, etc.,
21st ESICM Annual Congress
Authors: F Pene, B Zuber, C Rousseau, F Ouaaz, E Courtine, A Tazi, J Mira, J Chiche, E Martin, V Fanelli, V Elia, L Mascia, L Sorbo, E Hirsch, V Ranieri, A Scott, K O'dea, J Smythe, J Handy, M Takata, Y Claessens, J Toubiana, D Grimaldi, F Pe `ne, G Bismuth, P Zolfaghari, M Singer, M Duchen, A Dyson, S Moncada, M Palacios-Callender, R Stidwill
Journal: Intensive Care Medicine (2008)

INTRODUCTION.Host infection by pathogens triggers an innate immune response leading to a systemic inflammatory response, often followed by an immune dysfunction which can favour the emergence of secondary infections.Dendritic cells (DCs) have a unique ability to link innate and adaptive immunity and may be centrally involved in the regulation of sepsis-induced immune suppression.We previously reported that polymicrobial sepsis durably affects the functions of DCs and confers long-term susceptibility to P. aeruginosa pneumonia.In this study, we assessed the contribution of DCs to lung defence towards secondary P. aeruginosa pneumonia. METHODS.We used a murine model of sublethal polymicrobial sepsis through cecal ligature and puncture (CLP).In this model, a short course of antibiotics and volume resuscitation allows long-term survival of 70% of mice.Eight days after CLP, we induced a secondary pneumonia through intratracheal instillation of P. aeruginosa (serotype PAO1) in post-septic mice.Bone marrow-derived DCs (BMDCs) were generated through 7-day culture of medullar progenitors in medium supplemented with GM-CSF.Concomitant to bacterial inoculation, we intratracheally administrated exogenous BMDCs into post-septic mice.Bacterial lung clearance was evaluated through quantitative culture of bronchoalveolar lavage (BAL) fluid.The lung response was assessed 4 and 24 hours after instillation through quantification of protein level, inflammatory cells, myeloperoxydase (MPO) activity and cytokine levels in the BAL fluid.RESULTS.After intratracheal instillation of 5x10 6 CFUs of P. aeruginosa, all sham-operated mice survived while post-septic mice displayed high susceptibility with a 80-percent mortality rate.As compared to sham-operated mice, post-septic mice displayed marked lung damage with early recruitment of neutrophils, cytokine imbalance with decreased IL-12p70 production and increased IL-10 release, but no defective bacterial lung clearance.Co-administration of 10 6 exogenous BMDCs into post-septic mice challenged with P. aeruginosa dramatically improved the survival rate to 70%.Intratracheal instillation of BMDCs did not improve bacterial clearance, but delayed neutrophil recruitment and subsequently reduced the MPO activity in BAL fluid.In addition, BMDCs strongly attenuated the early peak of TNF-alpha and restored a positive Il-12p70/IL-10 balance.CONCLUSION.Adoptive transfer of BMDCs reverses sepsis-induced immune suppression in a relevant model of secondary P. aeruginosa pneumonia.Unexpectedly, the mechanism of action of BMDCs did not involve enhanced antibacterial activity, but occurred by dampening the pulmonary inflammatory response.
P-218 STAT3 signaling inhibition in regulatory T cells improves immune response to RT in PDAC
Authors: M. Piper, B. Van Court, A. Mueller, D. Nguyen, J. Gadwa, T. Bickett, R. Schulick, W. Messersmith, M. Del Chiaro, K. Goodman, A. Dent, R. Kedl, L. Lenz, S. Karam
Journal: Annals of Oncology (2021)
‘Fish-eye’ polypectomy defect: a new sign during endoscopic mucosal resection?
Authors: Sergei Vosko, Neal Shahidi, Sunil Gupta, W Arnout van Hattem, Michael J Bourke
Journal: Gut (2021)

A 75-year-old man was referred for the endoscopic management of an 80 mm large non-pedunculated colorectal polyp (LNPCP) in the sigmoid colon.

The lesion was evaluated under white-light (figure 1A), narrow-band imaging and near-focus. Granular nodular-mixed type morphology was identified with a homogeneous surface pattern (Kudo IV, Japan NBI Expert Team IIA) consistent with benign adenomatous histopathology.



Figure 1 
80mm large non-pedunculated colorectal polyp (LNPCP) in the sigmoid colon.



Piecemeal endoscopic mucosal resection was performed (figure 1A,B). After successful resection of the first specimen, defect evaluation revealed a hole within a white cautery ring, most consistent with a perforation without contamination (sydney deep mural injury (DMI) classification type IV1; figure 1D). A viscous amorphous …
Durable remissions may be achieved with tositumomab and I131 tositumomab in recurrent and refractory B cell lymphoma.
Authors: AJ Davies, JA Radford, Azs Rohatiner, K Britton, S Owens, DP Deakin, S Howell, BM Carrington, JA Lawrence, IN Micallef, S Vinnicombe, J Clayton, J Matthews, M Harris, A Norton, TA Lister
Journal: Leukemia (2003)
Website of the week: Adolescents and health
Authors: Trevor Jackson
Journal: BMJ (2001)

In many ways, the internet seems made for teenagers. It allows them to shop, chat to their friends, catch up on the latest pop, sport, and fashion gossip, research their school or college essays, go job hunting, and indulge any slightly dodgy fringe interests without having to leave their bedroom. Any curfew obsessed home secretary must be delighted. A wealth of information abounds about teenagers' health needs, with hundreds of excellent sites offering advice on acne, drugs, alcohol, sex, pregnancy, eating disorders, and other mental health issues. PatientUK (patients.co.uk) provides links to some of the best UK based sites, such as Mind, Body & Soul (www.mindbodysoul.gov.uk/), LifeBytes (www.lifebytes.gov.uk/index_flash.html), and Doctor Ann's Virtual Surgery (www.doctorann.org/).

All these sites recognise the need to address eating disorders, the subject of two reports in this week's BMJ (p 1002). What is surprising is how little information there is on the web about the special needs of teenagers in hospital. A paper in this week's BMJ (p 957) indicates that the use of hospital beds increases rather than decreases through adolescence. Yet there are few dedicated wards for adolescents, who tend to be placed either in adult wards or in children's units, along with Mickey Mouse murals, dolls' houses, and teddy. It seems that someone might have developed a forum for such teenagers, a place where they could exchange information about such things as treatments, visiting hours, and the effects on schoolwork of long hospital stays. “Teens Together” (www.candlelighters.net/newsletter/current/page6.html) is a Canadian based teen programme designed to promote communication and interaction between teenagers affected with cancer. But there seems to be no general site, or if there is it's a well kept secret. However, some organisations concerned with children's health, such as Action for Sick Children, have useful sections on their websites about teenagers in hospital (www.actionforsickchildren.org/teenagers.html) that may help to answer the questions of parents, general practitioners, and even teenagers themselves.
The COVID-19 Pandemic and Drug Prescribing in Ontario Nursing Homes—From Confinement Syndrome to Unconfined Prescribing
Authors: Christina Reppas-Rindlisbacher, Paula A. Rochon, Nathan M. Stall
Journal: JAMA Network Open (2021)

Michael A. Campitelli, MPH; Susan E. Bronskill, PhD; Laura C. Maclagan, MSc; Daniel A. Harris, MPH; Cecilia A. Cotton, PhD; Mina Tadrous, PharmD, PhD; Andrea Gruneir, PhD; David B. Hogan, MD; Colleen J. Maxwell, PhD
High-frequency temperature monitoring for early detection of febrile adverse events in patients with cancer
Authors: Christopher Flora, Jonathan Tyler, Caleb Mayer, David E. Warner, Shihan N. Khan, Vibhuti Gupta, Ryan Lindstrom, Amanda Mazzoli, Michelle Rozwadowski, Thomas M. Braun, Monalisa Ghosh, Daniel B. Forger, Sung Won Choi, Muneesh Tewari
Journal: Cancer Cell (2021)
The long shadow of socioeconomic deprivation over the modern management of acute myeloid leukemia: time to unravel the challenges
Authors: M. Joseph John, Philip Kuriakose, Mark Smith, Eve Roman, Sudhir Tauro
Journal: Blood Cancer Journal (2021)

Abstract Biological and non-biological variables unrelated to acute myeloid leukemia (AML) preclude standard therapy in many settings, with “real world” patients under-represented in clinical trials and prognostic models. Here, using a case-based format, we illustrate the impact that socioeconomic and anthropogeographical constraints can have on optimally managing AML in 4 different healthcare systems. The granular details provided, emphasize the need for the development and targeting of socioeconomic interventions that are commensurate with the changing landscape of AML therapeutics, in order to avoid worsening the disparity in outcomes between patients with biologically similar disease.