tbuckley/cabot-search huggingface dataset:
Hereditary cancer risk assessment in the community urology practice setting.
Authors: Neal D. Shore, Lauren Lenz, Darl D. Flake, Stephanie Meek, Thaylon Davis, Karen Copeland, Rob Finch, William Schiff, Howard Korman, Manoj Rao, Laurence Belkoff, Richard D'Anna, Thomas Slavin, Todd Cohen
Journal: Journal of Clinical Oncology (2022)

278 Background: Professional guidelines recommend hereditary cancer risk assessment (HCRA) for men with prostate cancer to inform both risk of cancer (primary or subsequent) and treatment decisions. The objectives of the study were to evaluate the feasibility of integrating a HCRA protocol in urology practice for patients with prostate cancer and determine the response of providers and patients to the HCRA protocol. Methods: This prospective study was divided into 4 segments: process integration (4 wks.), practice (4 wks.), post-integration (8 wks.), and follow up (10 wks.). Study site staff were trained to perform HCRA for men with prostate cancer (integration). The sites then incorporated recommendations from the integration process into their normal practice workflow (practice). During the post-integration period, the HCRA process was implemented with eligible patients consented to participate. Eligible patients were ≥18 years old, had a personal history of prostate cancer, and met National Comprehensive Cancer Network guidelines for genetic testing (2.2018). Patients and providers completed surveys regarding testing ≥ 8 weeks of test delivery or 1 week of end of data collection period, respectively (follow up). Results: In the 8 weeks prior to the study, 4.2% of patients completed testing at the study sites. During the study, 8.4% of patients completed testing, about 1/2 of eligible patients screened. Of all patients who completed testing and consented for their results to be summarized (N = 182), 10.4% (N = 19) tested positive for a single pathogenic variant (PV; monoallelic MUTYH N = 4; BRCA2 N = 3; ATM, BRCA1, BRIP1, CHEK2, HOXB13 N = 2 each; RAD51C, RAD51D N = 1 each). Not all men who tested positive or a PV reported a family history of cancer and not all PVs detected were in known prostate cancer risk genes. During follow up, most providers (61.0%) felt HCRA was as important as other assessments regularly performed and 68.3% planned to continue to use the HCRA process. In contrast, only 9.8% of providers did not believe HCRA was as important and 12.2% did not plan to continue to use the process. Of the patients that responded to the survey (N = 166), most had shared (62.0%) or planned to share (25.3%) their results with family members post-testing. Conclusions: Urologists and patients responded favorably to HCRA protocol integration. Based on this study, education around and incorporation of an HCRA process in a community urology practice setting for men with prostate cancer appears effective at increasing appropriate uptake of genetic testing. Clinical trial information: NCT04015102.
Clinical Summaries
Journal: Circulation (2008)

Although implantable cardioverter-defibrillators reduce death resulting from ventricular tachycardia (VT), episodes of VT decrease quality of life and predict increased rates of death.Antiarrhythmic drugs are often used to suppress VT but have potential adverse effects and relatively poor efficacy.In the largest study to date of catheter ablation for recurrent monomorphic VT caused by coronary artery disease, we prospectively evaluated radiofrequency catheter ablation using an irrigated catheter combined with an electroanatomic mapping system to facilitate substrate mapping during sinus rhythm.In contrast to prior studies, patients with hemodynamically unstable, unmappable VTs and multiple VTs were included because these VTs are often present in patients with ICDs.Despite a population with severely depressed ventricular function and drugrefractory, frequent VT, ablation abolished recurrent VT in approximately half of the patients.Of those in whom VT recurred, the frequency of episodes was substantially reduced for many, allowing reduction or withdrawal of antiarrhythmic drugs for some patients.The procedure mortality rate was 3%, and there were no strokes.The 1-year mortality rate was 18%, with ventricular arrhythmias and heart failure accounting for Ͼ70% of deaths.The present study demonstrates that patients with recurrent sustained VT and coronary artery disease are a high-risk population with substantial death risk despite implantable cardioverter-defibrillators.Catheter ablation is a reasonable option to reduce VT episodes, even if multiple and unmappable VTs are present.See p 2773.
Abstract 17307: TGR5 Contributes to Improved Perivascular Adipose Tissue Function (PVAT) After Vertical Sleeve Gastrectomy in Mice
Authors: Karolina E Zaborska, Eumee K Cha, Darline Garibay, Praveen K Sethupathy, Bethany P Cummings
Journal: Circulation (2018)

PVAT is a critical regulator of vascular contractility and its dysfunction contributes to obesity-induced hypertension (HTN). Bariatric surgery, such as vertical sleeve gastrectomy (VSG), causes high rates of HTN remission prior to weight loss, and rescues PVAT function by increasing nitric oxide (NO) production. We have previously validated a VSG mouse model that recapitulates the body weight-independent lowering of blood pressure. VSG increases bile acid (BA) signaling through the BA receptor, TGR5. TGR5 stimulates NO production from endothelial cells (ECs) but the role of TGR5 signaling in adipocyte NO production is unknown. We hypothesized that VSG increases NO bioavailability within PVAT in a TGR5-dependent manner. High fat diet (HFD)-fed male C57BLmice underwent VSG or sham surgery ( n =4-6) Sham (S) mice were food restricted to match body weight to VSG mice. Vascular contractility was reduced in VSG mice (Max contraction (%): S: 30±2, VSG: 23±3; P &lt;0.05). To assess the role of TGR5 on NO production within PVAT, we performed western blotting on mesenteric PVAT from VSG or sham-operated HFD-fed TGR5 WT and KO mice. eNOS phosphorylation was increased in PVAT in VSG WT, but not VSG KO (western blot quantification (AU): S WT: 1.0±0.1, VSG WT: 1.3±0.1, S KO: 1.1±0, VSG KO: 1.0±0.1; P &lt;0.05). To determine how TGR5 regulates PVAT NO production, we assessed the impact of TGR5 on microRNA-21 (miR-21) expression. MiR-21 stimulates NO production in ECs but its role in adipocytes in unknown. Thus, we hypothesized that TGR5 regulates NO production within PVAT by upregulating miR-21. MiR-21 expression was increased in PVAT from VSG-operated TGR5 WT mice but not KO compared to sham controls (western blot quantification (AU): S WT: 0.9±0.1, VSG WT: 2.1±0.5, S KO: 0.7±0.6, VSG KO: 0.6±0.1; P &lt;0.05). We further investigated whether TGR5 activation and miR-21 overexpression stimulate NO production in adipocytes. Mature 3T3-L1 adipocytes were treated with INT-777 or transfected with miR-21 mimic. TGR5 activation and miR-21 overexpression increased eNOS phosphorylation ( P &lt;0.05). In conclusion, our data suggest that VSG increases NO bioavailability in PVAT by activating adipocyte TGR5 signaling and upregulating miR-21 expression.
Abstract 328: Hemodynamic Comparison of Zucker Diabetic Fatty Rats to Their Lean Littermates After Asphyxial Cardiac Arrest
Authors: Claudius Balzer, Franz Baudenbacher, Michele M Salzman, William J Cleveland, Susan Eagle, Matthias L Riess
Journal: Circulation (2018)

Patients with metabolic syndrome are at higher risk for cardiac arrest (CA), and also have worse neurologic outcome after CA related to their comorbidities (e.g., Type 2 Diabetes Mellitus [T2DM]). Using Zucker Diabetic Fatty (ZDF) rats as a new and relevant model with common comorbidities for CA and cardiopulmonary resuscitation (CPR), we hypothesized that T2DM is associated with a lower chance for return of spontaneous circulation (ROSC) and/or a worse outcome regarding heart function after asphyxial CA compared to their lean littermates. Two groups of rats (8 ZDF, 7 lean) were monitored for 37±2 weeks. The rats were anesthetized and intubated; heart rate was monitored by subcutaneous ECG needles. Femoral artery and vein were cannulated for continuous blood pressure measurement and delivery of fluids and medications, respectively. Before ventilation was stopped to initiate asphyxial CA, rocuronium was given. After 8 minutes of CA, ventilation was re-initiated with FiO 2 1.0, epinephrine and sodium-bicarbonate were administered, and pneumatic chest compression were started with 200 compressions per minute. Chest compressions were stopped when a systolic blood pressure of 120 mmHg was achieved. During 4 hours of observation, vital parameters were closely monitored, blood gases were measured, and ejection fraction (EF %) was assessed with ultrasound. Data are mean ± SD. Statistics: Unpaired student’s t-test (two-tailed), α.05. At baseline, ZDF rats showed significantly higher blood glucose levels (504±52 vs 174±14 mg/dl) compared to their lean littermates. All ZDF and lean rats achieved ROSC, and measurements taken directly after ROSC and after the first hour showed no relevant differences. After four hours, there was no difference in heart rate between ZDF and lean rats. However, diabetic rats had a significantly higher mean arterial blood pressure (142±24vs. 107±19 mmHg) and ejection fraction (42±16%vs 20±8%) compared to their lean littermates. The hypothesis that ROSC-rate in diabetic rats would be lower could not be proven. Conversely, the ZDF rats showed a significantly higher blood pressure related to an increased EF%. Further analysis in this study will focus on the impact of T2DM on cardiac and neurological ischemia-reperfusion injury.
Erratum
Journal: JNCI Journal of the National Cancer Institute (1989)

In the article Genetic Changes in Human Adrenocortical Carcinomas by Yano et al published in the April 5, 1989 issue, figures 2 and 3 were inadvertently switched. Figure 3 appears with the legend to figure 2 and figure 2 appears with the legend to figure 3. The editors regret this error.
No association found between body checking experience and injury or concussion rates in adolescent ice hockey players
Authors: Paul Eliason, Brent E Hagel, Luz Palacios-Derflingher, Jean-Michel Galarneau, Vineetha Warriyar K V, Stephan Bonfield, Amanda Marie Black, Shelina Babul, Martin Mrazik, Constance Lebrun, Carolyn Emery
Journal: British Journal of Sports Medicine (2022)

Objectives To compare rates of injury and concussion among U-15 (ages 13–14 years) ice hockey players playing in leagues allowing body checking, but who have a varying number of years of body checking experience. Methods This 5-year longitudinal cohort included U-15 ice hockey players playing in leagues where policy allowed body checking. Years of body checking experience were classified based on national/local body checking policy. All ice hockey game-related injuries were identified using a validated injury surveillance methodology. Players with a suspected concussion were referred to a study sport medicine physician. Multiple multilevel Poisson regression analysis was performed, adjusting for important covariates and a random effect at a team level (offset by game exposure hours), to estimate injury and concussion incidence rate ratios (IRRs). Results In total, 1647 players participated, contributing 1842 player-seasons (195 players participating in two seasons). Relative to no body checking experience, no significant differences were found in the adjusted IRRs for game-related injury for players with 1 year (IRR=0.94; 95% CI: 0.69 to 1.28) or 2+ years (IRR=0.89; 95% CI: 0.56 to 1.40) body checking experience. No differences were found in the rates of concussion for players with 1 year (IRR=0.79; 95% CI: 0.51 to 1.22) but was significantly lower for players with 2+ years (IRR=0.51; 95% CI: 0.28 to 0.94) compared with no body checking experience. Conclusions Among ice hockey players aged 13–14 years participating in leagues permitting body checking, the adjusted rates of all injury were not significantly different between those that had body checking experience and those that did not. While the rates of concussion were significantly lower among those with 2+ years of body checking experience, the number of concussions potentially prevented in U-15 does not offset the number of concussions prevented through policy disallowing body checking at U-13.
Author commentary on Marta Rodríguez-Carrasco et al.
Authors: Marta Rodríguez-Carrasco, Eduardo Albéniz, Pradeep Bhandari, Torsten Beyna, Michael Bourke, Ahyeon Min, Philip Chiu, Simon Chu, Hon Yip, Pierre Deprez, Fabian Emura, Alessandro Repici, Noriko Suzuki, Naohisa Yahagi, Yoko Kubosawa, Cesare Hassan, Mário Dinis-Ribeiro
Journal: Endoscopy (2021)

Marta Rodríguez-Carrasco et al. COVID-19 and endoscopic management of superficial gastrointestinal neoplastic lesions: a multinational cross-sectional survey.
Talapro-3: A phase 3, double-blind, randomized study of enzalutamide (ENZA) plus talazoparib (TALA) versus placebo plus enza in patients with DDR gene mutated metastatic castration-sensitive prostate cancer (mCSPC).
Authors: Neeraj Agarwal, Arun Azad, Karim Fizazi, Joaquin Mateo, Nobuaki Matsubara, Neal D. Shore, Jayeta Chakrabarti, Hsiang-Chun Chen, Silvana Lanzalone, Alexander Niyazov, Fred Saad
Journal: Journal of Clinical Oncology (2022)

TPS221 Background: TALA is a poly(ADP-ribose) polymerase inhibitor (PARPi) approved as monotherapy for germline BRCA1/2-mutated HER 2-negative advanced breast cancer. PARPi have demonstrated substantial clinical efficacy in metastatic castration-resistant prostate cancers (mCRPC) with alterations in DNA damage response (DDR) genes involved directly or indirectly in homologous recombination repair (HRR). Phase 3 study findings (de Bono et al. N Engl J Med. 2020;382:2091-2102) resulted in the approval of olaparib for mCRPC. ENZA is an androgen receptor (AR) inhibitor and established therapy for mCSPC. Since PARP activity has been shown to support AR function, PARP inhibition is expected to increase sensitivity to AR-directed therapies. In addition, AR blockade downregulates HRR gene regulation, which has been hypothesized to induce a “ BRCAness ” phenotype . A phase 2 study of TALA monotherapy (TALAPRO-1) demonstrated robust antitumor activity in men with heavily pretreated, HRR-mutated mCRPC . The Phase 3, double-blind, randomized trial TALAPRO-3 (NCT04821622) herein presented will compare the combination of TALA plus ENZA versus placebo plus ENZA in men with mCSPC with DDR/HRR alterations. Methods: Approximately 550 patients with mCSPC harboring DDR/HRR alterations will be randomized to TALA (0.5 mg once daily) plus ENZA (160 mg once daily) or placebo (once daily) plus ENZA (160 mg once daily). Key eligibility criteria include age ≥18 years; histological diagnosis of prostate cancer; alterations in 12 DDR/HRR genes known to sensitize to PARPi ( ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C); and metastatic disease (no brain metastases). Primary endpoint is rPFS (time to radiographic progression in soft tissue per RECIST 1.1 or in bone per PCWG3 criteria by investigator, or death). Secondary endpoints include overall survival, safety, and patient-reported outcomes. Patient recruitment is planned at approximately 285 sites in 27 countries, including the US and Europe, South America, South Africa, and Asia-Pacific. Clinical trial information: NCT04821622.
Melioidosis
Authors: B. S. Khaira, W. B. Young, P. d. V. Hart
Journal: BMJ (1959)

SARCOMA INDUCED BY IRON-DEXTRAN COMPLEXBRrM ou 949 an increased incidence of carcinoma of the lung were asbestos workers, moulders and fopndrymen, and chromate workers, and pointing out that asbestos and chromate contain varying amounts of iron in their chemical composition.In this context there is further support from the work of Campbell (1940, 1943), who exposed mice of a strain susceptible to lung cancer to an atmosphere laden with ferric oxide.He found that 32.7% of the mice exposed to the dust developed tumours of the lung compared with 9.6% of the controls, while mice exposed to a mixture of silica and ferric oxide showed a tumour incidence halfway between these figures (19.4%).Mode of Action of Iron.-It has been observed that the histiocytes at the site of injection and elsewhere in the body (for example, Kupffer cells) contain, in addition to iron pigment, globules of a lipofuscin pigment of ceroid nature.The development of ceroid throughout the tissues of the body is one of the characteristics of vitamin-E deficiency (Mason, 1944), and in recent experiments Golberg and Smith (1958) have shown that the ceroid developing through iron overload can be largely prevented by supplementing the diet with a-tocopherol.It may therefore be inferred that one way in which iron influences intracellular metabolism is by blocking the antioxidant activity of vitamin E and possibly other antioxidants in the cell.The destruction oI interference with these natural antioxidants allows oxidation of unsaturated fats to form the yellow pigment which is termed ceroid (Casselman, 1951).It remains to be shown whether this action of iron in the cell has any relation to the development of malignant change. SummaryIn the adult rat weekly-repeated intramuscular injections of iron-dextran complex induced sarcoma at the site of injection.A bi-weekly series of similar injections, begun in weanling rats and stopped after 12 weeks, also induced sarcoma at the site of injection some seven months later.I wish to thank Professor J. S. Young for continuous encouragement and advice during this work, and Professor A. Haddow for a helpful discussion
Outcomes and factors associated with reclassification in a multiethnic cohort enrolled in active surveillance for prostate cancer.
Authors: Denzel Zhu, Justin Loloi, Evan Shreck, Marnie Abeshouse, Alexander Sankin, Kara Watts, Joshua M. Stern, Ahmed A. Aboumohamed, Evan Kovac
Journal: Journal of Clinical Oncology (2022)

242 Background: Active surveillance (AS) is the standard of care for low-risk prostate cancer (PCa). However, there is limited data exploring factors associated with reclassification among non-Hispanic Black (NHB) and Hispanic men enrolled in AS. In this study, we examined factors associated with reclassification among men enrolled in AS within a multiethnic population. Methods: We identified men enrolled in AS from 2005-2019 at our institution, and collected demographic/clinical data. We then compared characteristics among men who experienced pathologic reclassification while on AS vs men who did not. Reclassification was defined as either type 1 (Grade Group (GG) 1 to GG2) or type 2 (GG1 to ≥GG3). Our AS protocol generally consists of biannual prostate specific antigen (PSA) testing and prostate biopsy every 1-3 years. Prostate MRI is used to guide decisions on selective basis. Logistic regression was used to determine factors associated with reclassification. Results: Among 197 men enrolled into an AS protocol within our institution, 133 (67.5%) did not experience reclassification by the end of follow-up while 64 (32.5%) did (Table). Median follow-up time was 12 months (IQR: 7-20), and 2-year overall reclassification-free rates were 59.3% (95% CI: 59.2-59.4). 2-year deferred treatment rates were 26.4% (95% CI: 26.3-26.5) for radical prostatectomy (RP) and 16.9% (95% CI: 16.8-17.0) for radiation therapy (RT). NHB and Hispanic men composed 87 (44.2%) and 70 (35.5%) of our cohort, respectively. Higher PSA at diagnosis was associated with adverse reclassification (OR=1.02, 95% CI: 1.01-1.05, p=0.002), and there was a trend towards NHB men having higher odds of experiencing reclassification (OR=2.78, 95% CI: 0.85-9.10) although the result was not statistically significant (p=0.09). Conclusions: In a diverse, multiethnic cohort, rates of adverse reclassification on AS were relatively low. The only factor predictive of reclassification while on AS was higher median PSA at diagnosis; however, NHB men did have a trend towards a higher odds of reclassification. Our results suggest that men who are NHB or have higher PSA at diagnosis may benefit from increased surveillance intensity, as they are more likely to experience reclassification while on AS.[Table: see text]
Classified Advertising
Journal: JAMA (1989)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Biographical Essay
Authors: John H. Talbott
Journal: JAMA (1969)

Sir William Osler, judged by many to be the greatest clinician of our times, was born at Bond Head, Ontario, Canada, the son of English parents who migrated to frontier Upper Canada to take up mission work.<sup>1</sup>Osler was educated at the Anglican school in Weston; there the warden introduced him to Browne's<i>Religio Medici</i>, his lifelong literary companion. Although Osler had intended to take holy orders, he began the study of medicine at the University of Toronto; in 1872, he finished at McGill University. During the following two years he visited medical centers in Europe, with the longest residence in London, where he studied physiology under Burdon-Sanderson at University College. This, the first of a long series of "braindusting" excursions back and forth across the Atlantic, made him as much a part of European as American medicine. Osler returned to Canada intending to enter general practice. However, after
Parkinson's disease.
Authors: N P Quinn, F A Husain
Journal: BMJ (1986)

matter lucency ("Binswanger change") on computed tomography.Matters are complicated by the fact that the infarcts may be too small to be demonstrable on computed tomography and also that idiopathic Parkinson's disease and lacunar infarction are often associated since both conditions are common among the elderly.Only in the minority with coincidental