tbuckley/cabot-search huggingface dataset:
Abstract 303: The Impact of Pediatric Resuscitation Events on Overall Emergency Department Flow
Authors: Peter McBride, Matthew Ainsley, Xuemei Zhang, Andrew Johnson, Aaron Donoghue, Sage Myers
Journal: Circulation (2019)

Background: Pediatric resuscitation events are infrequent but resource-intensive events which pull staff, leaving higher patient:provider ratios and less access to the resources in the emergency department (ED). There is a paucity of literature on the impact of these events on overall ED flow. Objective: Use novel, prospective, comprehensive data collection to evaluate the impact of resuscitation events on the time to physician evaluation (eval) for patients arriving to the ED after a resuscitation event. Methods: Data from all resuscitation events occurring in the ED are logged prospectively. Resuscitation dates were matched to 2 control dates by census within 2 weeks and with no resuscitation events within 3 hours of time zero. A difference-in-differences evaluation compared median time to physician eval for all ED patients arriving pre and post time zero between cases and controls. Multivariate linear mixed-effects models were used to compare time to physician eval post-resuscitation between cases and controls. Results: 459 resuscitation dates were matched to 812 control dates. A higher median time to physician eval was found for cases, as compared to controls, which lasted for 2 hours after the time of the event (see Figure). A significant difference in time to physician eval post-resuscitation was found for cases (p=0.003) in multivariate models (see Table). Conclusions: Pediatric resuscitation events occurring in a large, high-resource, pediatric ED impact overall flow of the ED. Initiatives to redistribute care during resuscitation events, and evaluation of the impact of these interventions, could help ensure timely and appropriate care delivery to all ED patients.
CD31 as a Therapeutic Target in Atherosclerosis
Authors: Giuseppina Caligiuri
Journal: Circulation Research (2020)

The potential of CD31 as a therapeutic target in atherosclerosis has been considered ever since its cloning in the 1990s, but the exact role played by this molecule in the biologic events underlying atherosclerosis has remained controversial, resulting in the stalling of any therapeutic perspective. Due to the supposed cell adhesive properties of CD31, specific monoclonal antibodies and recombinant proteins were regarded as blocking agents because their use prevented the arrival of leukocytes at sites of acute inflammation. However, the observed effect of those compounds likely resulted from the engagement of the immunomodulatory function of CD31 signaling. This was acknowledged only later though, upon the discovery of CD31's 2 intracytoplasmic tyrosine residues called immunoreceptor tyrosine inhibitory motifs. A growing body of evidence currently points at a therapeutic potential for CD31 agonists in atherothrombosis. Clinical observations show that CD31 expression is altered at the surface of leukocytes infiltrating unhealed atherothrombotic lesions and that the physiological immunomodulatory functions of CD31 are lost at the surface of blood leukocytes in patients with acute coronary syndromes. On the contrary, translational studies using candidate therapeutic molecules in laboratory animals have provided encouraging results: synthetic peptides administered to atherosclerotic mice as systemic drugs in the acute phases of atherosclerotic complications favor the healing of wounded arteries, whereas the immobilization of CD31 agonist peptides onto coronary stents implanted in farm pigs favors their peaceful integration within the coronary arterial wall.
Health Utility Weighting of the Modified Rankin Scale
Authors: Alexander D. Rebchuk, Zoe R. O’Neill, Elena K. Szefer, Michael D. Hill, Thalia S. Field
Journal: JAMA Network Open (2020)

<h3>Importance</h3> The utility-weighted modified Rankin Scale (UW-mRS) has been proposed as a patient-centered alternative primary outcome for stroke clinical trials. However, to date, there is no clear consensus on an approach to weighting the mRS. <h3>Objective</h3> To characterize the between-study variability in utility weighting of the mRS in a population of patients who experienced stroke and its implications when applied to the results of a clinical trial. <h3>Data Sources</h3> In this systematic review and meta-analysis, MEDLINE, Embase, and PsycINFO were searched from January 1987 through May 2019 using major search terms for stroke, health utility, and mRS. <h3>Study Selection</h3> Original research articles published in English were reviewed. Included were studies with participants 18 years or older with ischemic or hemorrhagic stroke, transient ischemic attack, or subarachnoid hemorrhage, with mRS scores and utility weights evaluated concurrently. A total of 5725 unique articles were identified. Of these, 283 met criteria for full-text review, and 24 were included in the meta-analysis. <h3>Data Extraction and Synthesis</h3> PRISMA guidelines for systematic review were followed. Data extraction was performed independently by multiple researchers. Data were pooled using mixed models. <h3>Main Outcomes and Measures</h3> The mean utility weights and 95% CIs were calculated for each mRS score and health utility scale. Geographic differences in weighting for the EuroQoL 5-dimension (EQ-5D) and Stroke Impact Scale–based UW-mRS were explored using inverse variance–weighted linear models. The results of 18 major acute stroke trials cited in current guidelines were then reanalyzed using the UW-mRS weighting scales identified in the systematic review. <h3>Results</h3> The meta-analysis included 22 389 individuals; the mean (SD) age of participants was 65.9 (4.0) years, and the mean (SD) proportion of male participants was 58.2% (7.5%). For all health utility scales evaluated, statistically significant differences were observed between the mean utility weights by mRS score. For studies using an EQ-5D–weighted mRS, between-study variance was higher for worse (mRS 2-5) compared with better (mRS 0-1) scores. Of the 18 major acute stroke trials with reanalyzed results, 3 had an unstable outcome when using different UW-mRSs. <h3>Conclusions and Relevance</h3> Multiple factors, including cohort-specific characteristics and health utility scale selection, can influence mRS utility weighting. If the UW-mRS is selected as a primary outcome, the approach to weighting may alter the results of a clinical trial. Researchers using the UW-mRS should prospectively and concurrently obtain mRS scores and utility weights to characterize study-specific outcomes.
Malcolm Keith Sykes
Authors: Michael Ward, Pierre Foëx
Journal: BMJ (2020)

Malcolm Keith Sykes was one of the most prominent British anaesthetists of the second half of the 20th century. His career extended from 1950 to 1991, a period of major advances in anaesthesia and critical care, to which he made considerable contributions.

Born in Somerset in 1925, Keith Sykes went to Cambridge University to read natural science tripos before studying clinical medicine at University College Hospital (UCH). He began his professional training as house physician at UCH and house surgeon at Norfolk and Norwich. He then undertook national service in Germany, where in addition to his duties as regimental medical officer he also learnt to administer anaesthetics. Later, at a British military hospital in Hamburg he was the sole anaesthetist. On returning to the UK he sat the Diploma of Anaesthesia, starting his formal training in anaesthetics at UCH.

During his training he was awarded a Rickman Godlee travelling scholarship, which allowed him to visit centres in the USA for a year, mostly in Boston at the Massachusetts General Hospital under Professor Henry Beecher, to gain experience in research. This confirmed his wishes to pursue an academic career in anaesthesia. He also visited many …
Personalized Cancer Follow-Up Care Pathways: A Delphi Consensus of Research Priorities
Authors: Corinne R Leach, Catherine M Alfano, Jessica Potts, Lisa Gallicchio, K Robin Yabroff, Kevin C Oeffinger, Erin E Hahn, Lawrence N Shulman, Shawna V Hudson
Journal: JNCI Journal of the National Cancer Institute (2020)

Development of personalized, stratified follow-up care pathways where care intensity and setting vary with needs could improve cancer survivor outcomes and efficiency of health-care delivery. Advancing such an approach in the United States requires identification and prioritization of the most pressing research and data needed to create and implement personalized care pathway models. Cancer survivorship research and care experts (n = 39) participated in an in-person workshop on this topic in 2018. Using a modified Delphi technique-a structured, validated system for identifying consensus-an expert panel identified critical research questions related to operationalizing personalized, stratified follow-up care pathways for individuals diagnosed with cancer. Consensus for the top priority research questions was achieved iteratively through 3 rounds: item generation, item consolidation, and selection of the final list of priority research questions. From the 28 research questions that were generated, 11 research priority questions were identified. The questions were categorized into 4 priority themes: determining outcome measures for new care pathways, developing and evaluating new care pathways, incentivizing new care pathway delivery, and providing technology and infrastructure to support self-management. Existing data sources to begin answering questions were also identified. Although existing data sources, including cancer registry, electronic medical record, and health insurance claims data, can be enhanced to begin addressing some questions, additional research resources are needed to address these priority questions.
Regional Variation in Rates of Total Knee Arthroplasty Among Medicare Beneficiaries
Authors: Michael M. Ward, Abhijit Dasgupta
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Rates of total knee arthroplasty vary widely across the United States. Whether this variation is associated with differences in patient characteristics or physician practice is unknown. <h3>Objectives</h3> To determine regional variations in rates of total knee arthroplasty after accounting for the prevalence of knee arthritis and other potentially associated patient risk factors and to assess the correlation of these variations with measures of access to care and surgical indications. <h3>Design, Setting, and Participants</h3> This retrospective national cohort study used Medicare data on more than 24 million deidentified beneficiaries annually from 2011 to 2015. Individuals included had fee-for-service coverage, were 65 to 89 years of age, and resided in 1 of 306 health referral regions. Data were analyzed from September 13, 2018, to August 15, 2019. <h3>Main Outcomes and Measures</h3> Rate of primary total knee arthroplasty indexed to the national rate using observed to expected ratios. The expected numbers of arthroplasty procedures were derived from estimates based on beneficiaries’ demographic and clinical characteristics. Observed to expected ratios were confounded by race/ethnicity; thus race/ethnicity–stratified analyses were conducted. <h3>Results</h3> In 2011, there were 218 282 total knee arthroplasty procedures among 24 583 706 white Medicare beneficiaries (mean [SD] age 74.2 [6.9] years; 54.6% women). The rate of arthroplasty during the study period (5 years) was 9.3 per 1000 person-years. Adjustment for clinical characteristics reduced the spread in observed to expected ratios among regions by 29% compared with adjustment for age and sex alone. However, substantial variation remained, with observed to expected ratios that ranged from 0.61 in Newark, New Jersey, to 1.82 in Idaho Falls, Idaho. High ratios were primarily present in the upper Midwest, Great Plains, and Mountain West regions. Higher ratios were associated with regions where beneficiaries had fewer outpatient visits (Spearman correlation [<i>r</i>], −0.64; 95% CI, −0.70 to −0.56) and with regions having more surgeons per capita who performed knee arthroplasty (<i>r</i> = 0.27; 95% CI, 0.16-0.37). Higher ratios were associated with higher rates of arthroplasty procedures among beneficiaries with dementia (<i>r</i> = 0.36; 95% CI, 0.25-0.46), peripheral vascular disease (<i>r</i> = 0.52; 95% CI, 0.42-0.61), and skin ulcers (<i>r</i> = 0.43; 95% CI, 0.32-0.53), which are relative contraindications to arthroplasty. <h3>Conclusions and Relevance</h3> Substantial regional variation in rates of total knee arthroplasty remained after adjustment for patient characteristics. Coexistence of high observed to expected ratios and high rates among patients at greater surgical risk suggested overuse of knee arthroplasty in some regions.
FDG PET/CT Imaging of Pancreatic Plasmacytoma
Authors: Wen-Shan Huang, Yongjiang Zheng, Jia-Wen Chen, Gui-Xiong Zhang, Jie-Hua Xu
Journal: Clinical Nuclear Medicine (2020)

Abstract A 56-year-old man underwent 18 F-FDG PET/CT to evaluate possible pancreatic cancer, which was revealed by CT. The images showed a solid lesion with peripherally increased FDG activity in the tail of the pancreas, as well as hypermetabolic lesions in the lumbar spine and rib. Pathological examination following lumbar biopsy demonstrated multiple myeloma. Five months after chemotherapy, follow-up FDG PET/CT showed cystic change in the pancreatic lesion without elevated metabolism.
Michael Joseph Noronha
Authors: Richard Newton
Journal: BMJ (2020)

Born in Dar Es Salam, Tanzania, where his parents had moved from Goa in India, Michael Joseph Noronha was the sixth of eight children. The family moved to Pune, India, when he was 5, and at the age of 15 he moved to Dublin with his older brother and sister. He studied medicine and passed with flying colours.

After house jobs in Dublin, Bradford, and Edinburgh, Michael retuned to Bradford as a registrar in general medicine. A research post at Leeds …
Mohs micrographic surgery with MART-1 immunostaining has durable low local recurrence rates for in situ and invasive melanomas
Authors: Thuzar M. Shin, Shannon Nugent, Leora Aizman, David M. Weiner, Victoria O'Malley, Joseph F. Sobanko, Jeremy R. Etzkorn, Emily Y. Chu, Rosalie Elenitsas, Cerrene N. Giordano, H. William Higgins II, Christopher J. Miller
Journal: Journal of the American Academy of Dermatology (2020)
Factors Associated With Chemoradiation Therapy Interruption and Noncompletion Among Patients With Squamous Cell Anal Carcinoma
Authors: Michael J. Raphael, Gary Ko, Christopher M. Booth, Susan B. Brogly, Wenbin Li, Maria Kalyvas, Timothy P. Hanna, Sunil V. Patel
Journal: JAMA Oncology (2020)

Definitive chemoradiation for anal cancer is effective but may be associated with toxic effects, and some patients may not be able to complete the planned treatment. Identifying factors associated with treatment interruption and noncompletion is important to target quality improvement efforts.To identify rates of chemoradiation treatment interruption or noncompletion and factors associated with this among patients with anal cancer treated in routine clinical practice.In this population-based, retrospective cohort study, the Ontario Cancer Registry was used to identify all incident cases of squamous cell anal cancer treated with curative-intent radiation from 2007 to 2015 in Ontario, Canada. Final analysis of data was performed on August 9, 2019.Curative-intent radiation therapy.Treatment interruption was defined as more than 7 days between fractions of radiation. Radiation completion was defined as receipt of 45 Gy or more and 25 fractions of radiation. Chemoradiation completion was defined as radiation completion and 2 doses of combination chemotherapy. Associations between patient factors and treatment interruption and noncompletion were estimated with log-binomial models. Cox proportional hazard models were used to estimate the association of treatment interruption or noncompletion with all-cause death, cancer-specific death, and the combined outcome of colostomy or death.Overall, 1125 patients with stage I-III anal cancer were treated with curative-intent radiation. Treatment interruptions occurred in 262 (23%). Radiation and chemoradiation noncompletion occurred in 199 (18%) and 280 (25%), respectively. No associations were found to correlate with an increased risk of treatment interruption. Patients older than 70 years were less likely to complete chemoradiation (risk ratio [RR], 0.60; 95% CI, 0.52-0.70), compared with those younger than 50 years. Patients with a higher number of comorbidities were also less likely to complete chemoradiation (RR, 0.70; 95% CI, 0.51-0.95). Patients who did not complete chemoradiation had a higher risk of requiring salvage abdominoperineal resection (RR, 1.54; 95% CI, 1.03, 2.31), overall death (hazard ratio [HR], 1.54; 95% CI, 1.23-1.92), cancer-specific death (HR, 1.59; 95% CI, 1.14-2.22), and colostomy or death (HR, 1.80; 95% CI: 1.10-2.93). Treatment interruptions longer than 7 days were not associated with death.Many patients undergoing curative-intent chemoradiation for anal cancer experienced treatment interruption or noncompletion. Quality improvement initiatives to optimize treatment continuity and completion are needed.
Novel specialized cell state and spatial compartments within the germinal center
Authors: Domenick E. Kennedy, Michael K. Okoreeh, Mark Maienschein-Cline, Junting Ai, Margaret Veselits, Kaitlin C. McLean, Yogesh Dhungana, Hong Wang, Junmin Peng, Hongbo Chi, Malay Mandal, Marcus R. Clark
Journal: Nature Immunology (2020)
James Oscar Max Clark Craig
Authors: Alastair Fraser, Mary Crofton, Caroline Rubin
Journal: BMJ (2020)

James Oscar Max Clark Craig originally trained as a GP and pursued a career in surgery with the Royal Air Force before studying radiology. He was appointed consultant radiologist to St Mary’s Hospital, London, in 1963.

A flamboyant and popular doctor he was renowned for his excellent radiological opinion and as a teacher. He made a major contribution …
JAK inhibitors as promising agents for refractory Takayasu arteritis
Authors: Ryu Watanabe
Journal: Annals of the Rheumatic Diseases (2020)

JAK inhibitors as promising agents for refractory Takayasu arteritis I read with great interest the article 'Successful remission with tofacitinib in a patient with refractory Takayasu arteritis complicated by ulcerative colitis' by Kuwabara et al. 1 In this article, the authors reported a patient with both Takayasu arteritis (TAK) and ulcerative colitis (UC) who was successfully treated with tofacitinib, an inhibitor of Janus kinase (JAK).The critical message of this report is that, although inhibitors of tumour necrosis factor α and interleukin (IL)-6 failed to induce remission, symptoms and arterial inflammation on imaging were promptly ameliorated by tofacitinib. 1 Because our group reported the efficacy of JAK inhibitors on experimental large-vessel vasculitis in mice for the first time, 2 I would like to comment on this report.First, UC is not an uncommon complication in TAK, with a complication rate of approximately 6%. 3 4 However, it has been reported that TAK patients with UC have a different genetic background from TAK patients without UC in HLA-B52:01 positivity, and that the age of TAK onset in the former group is younger than that in the latter. 4Thus, it may be possible that JAK inhibitors are more likely to be effective in patients with both diseases.It is necessary to test whether JAK inhibitors are efficacious in TAK patients without UC as well.Second, a genome-wide association study revealed IL-12B as a susceptibility gene in TAK, and IL-12 plays a critical role in T helper 1 (Th1) differentiation. 5 6In addition, patients with TAK have a higher serum concentration of IL-23 than healthy individuals, and IL-23 promotes IL-17 production by CD4 + T cells. 7 8Both IL-12 and IL-23 are critically involved in the pathophysiology of TAK and activate JAK2 and Tyk2. 9Because tofacitinib primarily inhibits JAK1 and JAK3, baricitinib, an inhibitor of JAK1 and JAK2, may be a better option in some patients.Third, the authors seem to believe that the efficacy of tofacitinib is mediated by blocking Th1-derived and Th17-derived cytokines.However, JAK inhibitors, including tofacitinib, target not only CD4 + T cells but also macrophages and natural killer cells, 2 10 which have recently emerged as a promising target in TAK. 11Because TAK is a multifactorial disease in which many cytokines and cell populations interact with each other in the disease mechanism, multicytokine blockade with JAK inhibitors rather than single cytokine inhibition may be reasonable.Whether JAK inhibitors can be considered as first-choice immunosuppressive agents added to glucocorticoids (GCs) or even an alternative to GCs for TAK remains unclear.However, although there are some concerns with JAK inhibitors, such as herpes zoster and malignancies, given the significant burden of GCs on patients with TAK, I believe this issue should be discussed in the future.
Remission in systemic lupus erythematosus: testing different definitions in a large multicentre cohort
Authors: Francesca Saccon, Margherita Zen, Mariele Gatto, Domenico Paolo Emanuele Margiotta, Antonella Afeltra, Fulvia Ceccarelli, Fabrizio Conti, Alessandra Bortoluzzi, Marcello Govoni, Giulia Frontini, Gabriella Moroni, Francesca Dall'Ara, Angela Tincani, Viola Signorini, Marta Mosca, Anna Chiara Frigo, Luca Iaccarino, Andrea Doria
Journal: Annals of the Rheumatic Diseases (2020)

Objectives Remission in systemic lupus erythematosus (SLE) is defined through a combination of ‘clinical SLE Disease Activity Index (cSLEDAI)=0’, ‘physician's global assessment (PGA) &lt;0.5’ and ‘prednisone (PDN) ≤5 mg/day’. We investigated the performance of these items, alone or in combination, in defining remission and in predicting SLICC/ACR Damage Index. Methods We tested seven potential definitions of remission in SLE patients followed-up for ≥5 years: PDN ≤5 mg/day; PGA &lt;0.5; cSLEDAI=0; PGA &lt;0.5 plus PDN ≤5 mg/day; cSLEDAI=0 plus PGA &lt;0.5; cSLEDAI=0 plus PDN ≤5 mg/day; cSLEDAI=0 plus PDN ≤5 mg/day plus PGA &lt;0.5. The effect of these definitions on damage was evaluated by Poisson regression analysis; the best performance was identified as the lowest Akaike and Bayesian information criterion (AIC and BIC). Positive and negative predictive values in identifying no damage increase were calculated. Results We included 646 patients (mean±SD disease duration 9.2±6.9 years). At multivariate analysis, ≥2 consecutive year remission according to all definitions protected against damage (OR, 95% CI: PGA &lt;0.5 0.631, 0.444 to 0.896; cSLEDAI=0 0.531, 0.371 to 0.759; PGA &lt;0.5 plus PDN ≤5 mg/day 0.554, 0.381 to 0.805; cSLEDAI=0 plus PGA &lt;0.5 0.574, 0.400 to 0.826; cSLEDAI=0 plus PDN ≤5 mg/day 0.543, 0.376 to 0.785; cSLEDAI=0 plus PDN ≤5 mg/day plus PGA &lt;0.5 0.532, 0.363 to 0.781, p&lt;0.01 for all), except PDN ≤5 mg/day, which required four consecutive years (OR 0.534, 95% CI 0.325 to 0.877, p=0.013). Positive and negative predictive values were similar; however, cSLEDAI=0 showed the best performance (AIC 1082.90, BIC 1109.72, p&lt;0.0001). Adding PGA &lt;0.5 and/or PDN ≤5 mg/day to cSLEDAI=0 decreased remission duration (−1.8 and −1.5 year/patient, respectively) without increasing cSLEDAI=0 performance in predicting damage accrual. Conclusions cSLEDAI=0 is the most attainable definition of remission, while displaying the best performance in predicting damage progression in the short-to-mid-term follow-up.
Obscured Meckel’s Diverticulum by the Urinary Bladder
Authors: Elahe Pirayesh
Journal: Clinical Nuclear Medicine (2020)

Abstract We describe a case of a 5-year-old boy with a history of intermittent melena underwent 99m TcO 4 − scintigraphy. On dynamic images, no abnormal activity was noted. After voiding and also in the lateral view, the focus of activity was noted in the superior and anterior aspect of the urinary bladder, compatible with a Meckel's diverticulum, which was confirmed pathologically as well.