tbuckley/cabot-search huggingface dataset:
Prostate Cancer Incidence 5 Years After US Preventive Services Task Force Recommendations Against Screening
Authors: Ahmedin Jemal, MaryBeth B Culp, Jiemin Ma, Farhad Islami, Stacey A Fedewa
Journal: JNCI Journal of the National Cancer Institute (2020)

Abstract Background Previous studies reported that prostate cancer incidence rates in the United States declined for local-stage disease and increased for regional- and distant-stage disease following the US Preventive Services Task Force recommendations against prostate-specific antigen-based screening for men aged 75 years and older in 2008 and for all men in 2012. It is unknown, however, whether these patterns persisted through 2016. Methods Based on the US Cancer Statistics Public Use Research Database, we examined temporal trends in invasive prostate cancer incidence from 2005 to 2016 in men aged 50 years and older stratified by stage (local, regional, and distant), age group (50-74 years and 75 years and older), and race and ethnicity (all races and ethnicities, non-Hispanic Whites, and non-Hispanic Blacks) with joinpoint regression models to estimate annual percent changes. Tests of statistical significance are 2-sided (P &amp;lt; .05). Results For all races and ethnicities combined, incidence for local-stage disease declined beginning in 2007 in men aged 50-74 years and 75 years and older, although the decline stabilized during 2013-2016 in men aged 75 years and older. Incidence decreased by 6.4% (95% CI = 4.9%-9% to 7.9%) per year from 2007 to 2016 in men aged 50-74 years and by 10.7% (95% CI = 6.2% to 15.0%) per year from 2007 to 2013 in men aged 75 years and older. In contrast, incidence for regional- and distant-stage disease increased in both age groups during the study period. For example, distant-stage incidence in men aged 75 years and older increased by 5.2% (95% CI = 4.2% to 6.1%) per year from 2010 to 2016. Conclusions Regional- and distant-stage prostate cancer incidence continue to increase in the United States in men aged 50 years and older, and future studies are needed to identify reasons for the rising trends.
Allogeneic stem cell transplantation for peripheral T cell lymphomas: a retrospective study in 285 patients from the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)
Authors: Anne-Claire Mamez, Axelle Dupont, Didier Blaise, Patrice Chevallier, Edouard Forcade, Patrice Ceballos, Mohamad Mohty, Felipe Suarez, Yves Beguin, Regis Peffault De Latour, Marie-Thérèse Rubio, Olivier Tournilhac, Stéphanie Nguyen
Journal: Journal of Hematology & Oncology (2020)

Abstract Background Peripheral T cell lymphomas form a heterogeneous group with a usually dismal prognostic. The place of allogeneic stem cell transplantation to treat PTCL is debated. Methods We retrospectively analyzed the overall survival (OS), event-free survival (EFS), relapse, and transplant-related mortality (TRM) and associated variables in 285 adults with non-primary cutaneous PTCL (PCTL-NOS (39%), angioimmunoblastic T cell lymphomas (29%), anaplastic T cell lymphomas (15%), and other subtypes (17%)), who received alloSCT in 34 centers between 2006 and 2014. Results AlloSCT was given as part of front-line therapy ( n = 138) to 93 patients in first complete response (CR) and 45 in first partial response (PR), and of salvage therapy ( n = 147) to 116 patients for second or more CR/PR and 31 for progressive disease. Reduced-intensity conditioning (RIC) was given to 172 patients (62%), while 107 (38%) received myeloablative conditioning (MAC). The median follow-up was 72.4 months. The 2- and 4-year OS were 65% and 59%, respectively, and the cumulative incidence of relapse was 18% after 1 year and 19% after 2 years. TRM was 21% at 1 year, 24% after 2 years, and 28% after 4 years. In multivariate analysis, grade III–IV acute GvHD (HR = 2.57, 95% CI 1.53–4.31; p = 0.00036), low Karnofsky score &lt; 80% (HR = 5.14, 95% CI 2.02–13.06; p = 0.00058), and progressive disease status before transplant (HR = 2.21, 95% CI 1.25–3.89; p = 0.0062) were significantly associated with a reduced OS. Conclusions The data demonstrate in the largest retrospective cohort of non-cutaneous PTCL so far reported that alloSCT after RIC or MAC is an effective strategy, even in chemoresistant patients.
Treatment of relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with the BTK inhibitor zanubrutinib: phase 2, single-arm, multicenter study
Authors: Wei Xu, Shenmiao Yang, Keshu Zhou, Ling Pan, Zengjun Li, Jianfeng Zhou, Sujun Gao, Daobin Zhou, Jianda Hu, Ru Feng, Haiwen Huang, Meng Ji, Haiyi Guo, Jane Huang, William Novotny, Shibao Feng, Jianyong Li
Journal: Journal of Hematology & Oncology (2020)

Abstract Background Bruton tyrosine kinase (BTK) inhibitors have demonstrated a high degree of efficacy in the treatment of B cell malignancies characterized by constitutive B cell receptor activation, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Methods The efficacy and safety of zanubrutinib, an investigational highly selective BTK inhibitor, was evaluated in this single-arm, phase 2 study of Chinese patients with relapsed/refractory CLL/SLL. The primary endpoint was overall response rate as assessed by an independent review committee. Results Of the 91 evaluable patients, 77 (84.6%) achieved a response, with three (3.3%), 54 (59.3%), and 20 (22%) patients achieving a complete response, partial response, and partial response with lymphocytosis, respectively, after a median follow-up of 15.1 months. The estimated 12-month event-free rate for duration of response was 92.9%. The most commonly reported grade ≥ 3 adverse events (AEs) were neutropenia (44%), thrombocytopenia (15.4%), lung infection/pneumonia (13.2%), upper respiratory tract infection (9.9%), and anemia (8.8%). The 12-month overall survival rate was 96%. Eight (9.0%) patients discontinued zanubrutinib due to AEs, and seven (8.0%) patients required at least one dose reduction. Conclusion Treatment of patients with relapsed/refractory CLL/SLL with zanubrutinib was generally well tolerated and resulted in a high overall response rate, thereby conferring a favorable benefit-risk profile. Trial registration Prospectively registered in China public registry (CTR20160890) on December 7, 2016: http://www.chinadrugtrials.org.cn/ . Retrospectively registered in ClinicalTrials.gov ( NCT03206918 ) on July 2, 2017.
Trial Design and Endpoints in Hepatocellular Carcinoma: AASLD Consensus Conference
Authors: Josep M. Llovet, Augusto Villanueva, Jorge A. Marrero, Myron Schwartz, Tim Meyer, Peter R. Galle, Riccardo Lencioni, Tim F. Greten, Masatoshi Kudo, Sumithra J. Mandrekar, Andrew X. Zhu, Richard S. Finn, Lewis R. Roberts
Journal: Hepatology (2020)
4P Independent validation of the PAM50-based chemoendocrine score (CES) as pathologic complete response (pCR) and disease-free survival (DFS) predictor in hormone receptor (HR)+/HER2+ breast cancer (BC)
Authors: T. Pascual, A. Fernandez-Martinez, M. Tanioka, M.V. Dieci, S. Pernas Simon, J. Gavila Gregori, V. Guarneri, J. Cortés, P. Villagrasa, M.J. Vidal, B. Adamo, M. Muñoz, G. Griguolo, A. Llombart Cussac, M. Oliveira, L. Paré, L.A. Carey, C.M. Perou, A. Prat
Journal: Annals of Oncology (2020)
Cognitive Screening of Older Practitioners
Authors: Chanaka Wijeratne
Journal: JAMA (2020)

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Kindlin-2 deficiency induces fatal intestinal obstruction in mice
Authors: Xiaokun He, Jiagui Song, Zeyu Cai, Xiaochun Chi, Zhenbin Wang, Decao Yang, Sian Xie, Jing Zhou, Yi Fu, Wei Li, Wei Kong, Jun Zhan, Hongquan Zhang
Journal: Theranostics (2020)

Rationale: Smooth muscle-motility disorders are mainly characterized by impaired contractility and functional intestinal obstruction. Some of these cases are caused by genetic mutations of smooth muscle genes ACTA2, ACTG2, MYH11, MYLK and LMOD1. Still the etiology is complex and multifactorial and the underlying pathology is poorly understood. Integrin interaction protein Kindlin-2 is widely expressed in striated and smooth muscle cells (SMC). However, the function of Kindlin-2 in the smooth muscle remains elusive. Methods: We generated two mouse models using different cre promoter transgenic mice, Kindlin-2fl/fl SM22α-cre+ (cKO mice) and Kindlin-2fl/fl; MYH-cre+ (iKO mice). Embryos and adult tissues were prepared for hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC) and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) apoptosis assay. We investigated ultrastructure changes of mouse smooth muscle using transmission electron microscopy (TEM) and measured smooth muscle contractile force in mounting aortic and intestinal rings using the multiwire myograph system (DMT 620M). In addition, cell traction force microscopy (CTFM) was applied to observe the functional change of primary SMC after Kindlin-2 depletion by RNAi. Results: Depletion of Kindlin-2 encoding gene Fermt2 in embryonic smooth muscles leads to apoptosis, downregulates the key components of SMC, impairs smooth muscle development, and finally causes embryonic death at E14.5. Tamoxifen-induced Kindlin-2-specific knockout in adult mouse smooth muscle showed decreased blood pressure, intestinal hypoperistalsis, and eventually died of intestinal obstruction. Kindlin-2 depletion also leads to downregulated Myh11, α-SMA, and CNN, shortened myofilament, broken myofibrils, and impaired contractility of the smooth muscles in iKO mice. Mechanistically, loss of Kindlin-2 decreases Ca2+ influx in primary vascular smooth muscle cells (PVSMC) by downregulating the expression of calcium-binding protein S100A14 and STIM1. Conclusion: We demonstrated that Kindlin-2 is essential for maintaining the normal structure and function of smooth muscles. Loss of Kindlin-2 impairs smooth muscle formation during embryonic development by inducing apoptosis and jeopardizes the contraction of adult smooth muscle by blocking Ca2+ influx that leads to intestinal obstruction. Mice with Kindlin-2 depletion in adult smooth muscle could be a potent animal model of intestinal obstruction for disease research, drug treatment and prognosis.
Abstract 11942: Myopathy and Rhabdomyolysis With Concomitant Use of Ticagrelor and High-intensity Statins in the Elderly
Authors: Mohamed Mohamoud, Daniel Woronow, Nicole Haug, Daniel Bak, Eileen Wu, Corinne Woods, Monica Munoz, Grace Chai, Danijela Stojanovic, Ting-Ying Huang
Journal: Circulation (2019)

Introduction: Ticagrelor and high-intensity statins are recommended for secondary prevention of ASCVD events. We evaluated FDA Adverse Event Reporting System (FAERS) reports of myopathy/rhabdomyoly...
Human Parvovirus B19
Authors: Larry J. Anderson, Thomas J. Török
Journal: New England Journal of Medicine (1989)

The two articles on human parvovirus B19 infection in this issue of the Journal 1 , 2 make important contributions to our understanding of the epidemiology and treatment of the disease. Since its discovery in 1975, B19 has been shown to have a number of distinct clinical presentations.3 It is a common infection, especially among school-age children; consequently, in most studies, more than 50 percent of adults have serologic evidence of past infection. The illness most often associated with infection is erythema infectiosum, or fifth disease. A patient with erythema infectiosum is typically healthy except for an erythematous rash on the face (slapped-cheek . . .
A Bon VOYAGER for Peripheral Artery Disease
Authors: Mark A. Creager
Journal: New England Journal of Medicine (2020)

Peripheral artery disease is prevalent, affecting more than 200 million persons worldwide.1 As a manifestation of systemic atherosclerosis, it is associated with an increased risk of myocardial infarction, stroke, and death from cardiovascular causes, and because of its presence in arteries of the extremities, it impairs walking capacity and may lead to critical limb-threatening ischemia and amputation.2 Yet peripheral artery disease is woefully underrecognized and is often not adequately treated with appropriate evidence-based therapies to preserve life and limb. As compared with patients with known coronary artery disease and peripheral artery disease, patients with established peripheral artery disease only are . . .
Topical Steroid Addicts
Authors: Albert M. Kligman
Journal: JAMA (1976)

<h3>To the Editor.—</h3> It is no longer news that steroids have profound inhibitory effects on both the epidermis and dermis; the atrophic effects are visualized as thinning, telangiectasia, and striae. It is, however, bad news that physicians heedlessly and almost automatically prescribe potent steroids for virtually all inflammatory skin lesions that cannot be accurately diagnosed or classified. This produces instant satisfaction, but all too often converts the patient into a steroid-addict. We have stressed that the long-term application of fluorinated steroids to the face produces persistent disorders such as rosacealike syndromes and acne (229:60, 1974). The genitalia are another off limits area for dispensation of potent steroids. I wish to summarize the experiences of three men who finally ended up in my hands for a nonhealing lesion of the shaft of the penis. The history and findings were identical. Each had initially seen a general practitioner for a localized, oozing
Failure to vasodilate in response to salt loading blunts renal blood flow and causes salt-sensitive hypertension
Authors: Jing Wu, Larry N Agbor, Shi Fang, Masashi Mukohda, Anand R Nair, Pablo Nakagawa, Avika Sharma, Donald A Morgan, Justin L Grobe, Kamal Rahmouni, Robert M Weiss, James A McCormick, Curt D Sigmund
Journal: Cardiovascular Research (2020)

Salt-sensitive (SS) hypertension is accompanied by impaired vasodilation in the systemic and renal circulation. However, the causal relationship between vascular dysfunction and salt-induced hypertension remains controversial. We sought to determine whether primary vascular dysfunction, characterized by a failure to vasodilate during salt loading, plays a causal role in the pathogenesis of SS hypertension. Mice selectively expressing a peroxisome proliferator-activated receptor γ dominant-negative mutation in vascular smooth muscle (S-P467L) exhibited progressive SS hypertension during a 4 week high salt diet (HSD). This was associated with severely impaired vasodilation in systemic and renal vessels. Salt-induced impairment of vasodilation occurred as early as 3 days after HSD, which preceded the onset of SS hypertension. Notably, the overt salt-induced hypertension in S-P467L mice was not driven by higher cardiac output, implying elevations in peripheral vascular resistance. In keeping with this, HSD-fed S-P467L mice exhibited decreased smooth muscle responsiveness to nitric oxide (NO) in systemic vessels. HSD-fed S-P467L mice also exhibited elevated albuminuria and a blunted increase in urinary NO metabolites which was associated with blunted renal blood flow and increased sodium retention mediated by a lack of HSD-induced suppression of NKCC2. Blocking NKCC2 function prevented the salt-induced increase in blood pressure in S-P467L mice. We conclude that failure to vasodilate in response to salt loading causes SS hypertension by restricting renal perfusion and reducing renal NO through a mechanism involving NKCC2 in a mouse model of vascular peroxisome proliferator-activated receptor γ impairment.
Quantification of carotid plaque lipid content with magnetic resonance T2 mapping in patients undergoing carotid endarterectomy
Authors: A W Halliday, Alkhalil, Biasiolli, Chai, Galassi, L Li, C Darby, L Hands, Magee, Perkins, Sideso, Jezzard, Robson, Handa, R Choudhury
Journal: PLoS Medicine (2017)
39P Role of early circulating tumour cell (CTC) monitoring for prediction of clinical outcome in patients with HER-2 negative metastatic breast cancer receiving first-line treatment with bevacizumab and paclitaxel
Authors: I. Álvarez-López, E. González, L.M. Manso, J.L. Alonso, J.J. Cruz-Hernández, V. Carañana Ballerini, I. Gallegos, M. Quindós Varela, J.J. Illaramendi, E. Vicente, A.I. Ballesteros Garcia, F. Ayala de la Pena, A. Perelló, J. Vidal, A. Llombart Cussac
Journal: Annals of Oncology (2020)
Social distancing for covid-19: is 2 metres far enough?
Authors: Robert C Schroter
Journal: BMJ (2020)

<h3>Abstract</h3> Memory reprocessing following acquisition enhances memory consolidation. Specifically, neural activity during encoding is thought to be ‘replayed’ during subsequent slow-wave sleep (SWS). This natural tendency of memory replay can be induced by external cueing, known as “targeted memory reactivation”. Here, we analyzed data from a published study (van Dongen, Takashima, et al. 2012), where auditory cues reactivated learned visual object-location memories during SWS. Memory replay during sleep presumably involves a shift in connectivity across the brain. Therefore, we characterized the effects of memory reactivation on brain network connectivity using graph-theory. We found that cue presentation during SWS introduced increased network integration of the occipital cortex, a visual region that was also active during the object retrieval task. Importantly, enhanced network integration of the occipital cortex showed a behavioural benefit and predicted overnight memory stabilization. Furthermore, occipital cortex displayed enhanced connectivity with mnemonic regions, namely the hippocampus, parahippocampal gyrus, thalamus and medial prefrontal cortex during cue versus control sound presentation. Finally, network integration of early occipital cortex during cueing in SWS was related to increased activation of the bilateral parahippocampal gyrus, a region involved in coding for spatial associative information, at the post-sleep test. Together, these results support a neural mechanism where cue-induced replay during sleep promotes memory consolidation by increased integration of task-relevant perceptual regions with mnemonic regions.
Meta‐analysis results do not reflect the real safety of biologics in psoriasis*
Authors: S. Afach, A. Chaimani, T. Evrenoglou, L. Penso, E. Brouste, E. Sbidian, L. Le Cleach
Journal: British Journal of Dermatology (2020)

In reported systematic reviews and meta-analyses of randomized controlled trials (RCTs) assessing treatments for psoriasis, the proportion of serious adverse events (SAEs) did not differ between treatments and placebo. Including cases of psoriasis worsening as SAEs may explain the lack of difference.This systematic review and meta-analysis aimed to explore this possibility.Among the 140 RCTs included in the Living Network Cochrane Review (last search on 8 May 2019), we selected those comparing a biologic treatment against placebo. The primary outcome was the numbers of SAEs in the treatment and placebo arms after excluding cases of psoriasis worsening. Secondary outcomes were the number of adverse events (AEs) of special interest. The trial was registered on PROSPERO (CRD42019124495).We analysed 51 RCTs. Of these, 21 included at least one anti-tumour necrosis factor (TNF)-α arm, 15 one anti-interleukin (IL)-17 arm, 11 one anti-IL-23 arm and nine one anti-IL-12/23 arm. With cases of psoriasis worsening included, the risk of occurrence of SAEs between biologic treatments and placebo did not differ: risk ratio (RR) 1·09, 95% confidence interval (CI) 0·88-1·36. After excluding cases of psoriasis worsening, the RR became significant (RR 1·30, 95% CI 1·02-1·65). By drug class, the RRs were for anti-TNF-α, 1·68 (95% CI 1·11-2·54; no missing data); anti-IL-17, 1·28 (95% CI 0·88-1·85; no missing data); anti-IL-23, 0·95 (95% CI 0·59-1·52; no missing data) and anti-IL-12/23, 1·18 (95% CI 0·72-1·94; no missing data). We were unable to examine potential differences in AEs of special interest between biologic treatments and placebo arms because of the small number of events.On excluding cases of worsening psoriasis, the risk of occurrence of SAEs is higher in the biologic than in the placebo arm. Given the rare events, we could not highlight whether this higher risk of SAEs was related to AEs of special interest. Reporting of SAEs in clinical trials has to be changed to provide more transparency through the separate reporting of disease flares leading to hospital admission and other SAEs.
Abstract 10979: Coronary Pressure and Flow Pre and Post TAVI: Analysis of Patients With Severe Aortic Stenosis and Coronary Artery Disease: Implications for Clinical Assessment of Functional Coronary Significance
Authors: Yousif Ahmad
Journal: Circulation (2018)

Introduction: The effect of aortic stenosis on coronary pressure and flow has not been studied. Methods: 30 patients with severe AS and CAD were included. Intracoronary pressure and flow was measur...
Evaluation of an augmented reality platform for austere surgical telementoring: a randomized controlled crossover study in cricothyroidotomies
Authors: Edgar Rojas-Muñoz, Chengyuan Lin, Natalia Sanchez-Tamayo, Maria Eugenia Cabrera, Daniel Andersen, Voicu Popescu, Juan Antonio Barragan, Ben Zarzaur, Patrick Murphy, Kathryn Anderson, Thomas Douglas, Clare Griffis, Jessica McKee, Andrew W. Kirkpatrick, Juan P. Wachs
Journal: npj Digital Medicine (2020)

Telementoring platforms can help transfer surgical expertise remotely. However, most telementoring platforms are not designed to assist in austere, pre-hospital settings. This paper evaluates the system for telementoring with augmented reality (STAR), a portable and self-contained telementoring platform based on an augmented reality head-mounted display (ARHMD). The system is designed to assist in austere scenarios: a stabilized first-person view of the operating field is sent to a remote expert, who creates surgical instructions that a local first responder wearing the ARHMD can visualize as three-dimensional models projected onto the patient's body. Our hypothesis evaluated whether remote guidance with STAR could lead to performing a surgical procedure better, as opposed to remote audio-only guidance. Remote expert surgeons guided first responders through training cricothyroidotomies in a simulated austere scenario, and on-site surgeons evaluated the participants using standardized evaluation tools. The evaluation comprehended completion time and technique performance of specific cricothyroidotomy steps. The analyses were also performed considering the participants' years of experience as first responders, and their experience performing cricothyroidotomies. A linear mixed model analysis showed that using STAR was associated with higher procedural and non-procedural scores, and overall better performance. Additionally, a binary logistic regression analysis showed that using STAR was associated to safer and more successful executions of cricothyroidotomies. This work demonstrates that remote mentors can use STAR to provide first responders with guidance and surgical knowledge, and represents a first step towards the adoption of ARHMDs to convey clinical expertise remotely in austere scenarios.