tbuckley/cabot-search huggingface dataset:
Richard Lacey: microbiologist who came under fire for claiming a link between mad cow disease and variant CJD in humans
Authors: John Illman
Journal: BMJ (2019)

Photo credit: UPPA/PHOTOSHOT

Richard Lacey was the dissident University of Leeds medical microbiologist who was ridiculed in 1990 for suggesting a possible link between the cattle disease bovine spongiform encephalopathy (BSE) and its human variant, Creutzfeldt-Jakob disease (CJD).

Vindicated in 1996, Lacey stands out as one of the most controversial figures in British medicine over the past 50 years. He was acclaimed as brave, fearless, and totally principled and as one of the few academics who did not weigh his career prospects against his beliefs. He was also denounced as a panic monger with a penchant for worst case scenarios based more on guesswork than solid science.

Lacey’s supporters included his former colleague Stephen Dealler, who said: “Sometimes we need people to stand up and say what other scientists—and government—would rather not be true.”

Lacey hit back at his critics in the early 1990s with the polemics Unfit for Human Consumption, Hard to Swallow , and Mad Cow Disease . Unusually, if not uniquely, for an academic, he …
Prostatectomy in men with clinically positive lymph nodes.
Authors: Fady Ghali, Stephen Ryan, Moritz Hansen, Matthew Hayn, Jesse Sammon, Reith Sarkar, James Don Murphy, A. Karim Kader, Brent Rose
Journal: Journal of Clinical Oncology (2019)

327 Background: A prostate cancer (PCa) patient with non-metastatic but clinical positive lymph nodes (cN+) represents a difficult clinical scenario. We compared OS after RP in cN- (High Risk), cN+/pN- (Discordant), and cN+/pN+ (Concordant). Methods: The National Cancer Database was queried for all PCa patients from 2004-2013. Inclusion criteria were known age and PSA at diagnosis, biopsy Gleason score, TNM staging (cT1-3B, cN0/1, M0/X), margin, nodal status and primary treatment modality. cN+ was separated into two cohorts: pN- (Discordant) and pN+ (Concordant). RPs for High Risk PCa (cT3a/b or GS ≥ 8 or PSA &gt; 20) with cN- was used as a comparison. OS was analyzed with Kaplan Meier (KMA) and Cox proportional hazard model combing demographic, clinical, and pathological factors. Results: 4944 cN+ men were identified (21.7% RP, 27.5% systemic therapy only). 794 RPs had completed records. Discordant and Concordant represented 18.8% and 81.2% with median follow-up 48 and 48.9 months, and 13 and 97 deaths, respectively. KMA pairwise OS of High Risk (n=35, 502) verses Discordant was not significant (p=0.28) but was significant verses Concordant (p &lt; 0.001). There was no difference in OS on KMA between Discordant and Concordant (p=0.11). OS on Cox proportional hazard model, High Risk and Discordant had no observable difference (p=1.22). Concordant pathology had much worsened OS (HR 1.829, p &lt; 0.001), as well as Medicaid/Medicare patients (HR 1.344, p &lt; 0.001), biopsy Gleason score ≥ 8 (HR 1.350, p=0.0019), pathologic T stage (pT3a HR 1.567, pT3b 2.396, p &lt; 0.001), and positive surgical margin (HR 1.257, p &lt; 0.001). Conclusions: In a large cohort of nonmetastatic PCa patients with cN+ disease, &gt; 27% were treated with systemic therapy based on clinical staging, but 18.8% of cN+ RPs were incorrectly staged. There was no difference in OS between cN- High Risk patients and pathologic Discordant (cN+/pN-) men, and the much worse OS in men with pN+. Study is needed for more accurate clinical staging tools to identify the pathologically discordant population.
Analyzing Frequently Mutated Genes and the Association With Tumor Mutation Load
Authors: Yosef E. Maruvka, Nicholas J. Haradhvala, Gad Getz
Journal: JAMA Oncology (2019)

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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Oncology journal
Racial disparities in survivorship care adherence among Medicare beneficiaries with prostate cancer.
Authors: Ravi Bharat Parikh, Sumedha Chhatre, S. Bruce Malkowicz, Bingnan Li, Ravishankar Jayadevappa
Journal: Journal of Clinical Oncology (2019)

72 Background: African-American men with prostate cancer have higher cancer-related and all-cause mortality than their Caucasian counterparts. Differences in adherence to guideline-based survivorship care may contribute to these disparities. Methods: Using the SEER-Medicare database, we conducted a retrospective cohort study of men ≥66 years old treated for localized prostate cancer between 2008 and 2011 who had at least two visits with a specialist or primary care physician after diagnosis. Patients were followed until 2013. We calculated rates of bone mineral density screening (among men treated with androgen deprivation therapy) and colorectal cancer screening after diagnosis, stratified by race and provider seen. We analyzed the association between continuity of care (CoC) and adherence to colorectal cancer screening after calculating a CoC index. Results: Among 107262 men with localized prostate cancer, adherence to colorectal cancer and bone mineral density screening was higher for Non-Hispanic White and Hispanic men compared to African-American men (Table). Adherence to screening was slightly higher for men who followed with primary care physicians compared to specialists. After adjusting for relevant covariates and number of providers, higher CoC with primary care physicians was associated with improved adherence to colorectal screening among Non-Hispanic Whites (OR = 1.25, 95% CI = 1.11-1.40), African-Americans (OR = 1.39, CI = 1.05-1.84) and Hispanics (OR = 2.74, CI = 1.27-5.90). However, higher CoC with specialists was significantly associated with colon cancer screening only among African Americans (OR 1.59, 95% CI 1.25-2.04). Conclusions: Among a large cohort of men with localized prostate cancer, the association between CoC and guideline-based survivorship care varied by type of provider and by racial and ethnic group. [Table: see text]
Targeting MAPK phosphorylation of Connexin43 provides neuroprotection in stroke
Authors: Moises Freitas-Andrade, Nan Wang, John F. Bechberger, Marijke De Bock, Paul D. Lampe, Luc Leybaert, Christian C. Naus
Journal: The Journal of Experimental Medicine (2019)

Connexin43 (Cx43) function is influenced by kinases that phosphorylate specific serine sites located near its C-terminus. Stroke is a powerful inducer of kinase activity, but its effect on Cx43 is unknown. We investigated the impact of wild-type (WT) and knock-in Cx43 with serine to alanine mutations at the protein kinase C (PKC) site Cx43S368A, the casein kinase 1 (CK1) sites Cx43S325A/328Y/330A, and the mitogen-activated protein kinase (MAPK) sites Cx43S255/262/279/282A (MK4) on a permanent middle cerebral artery occlusion (pMCAO) stroke model. We demonstrate that MK4 transgenic animals exhibit a significant decrease in infarct volume that was associated with improvement in behavioral performance. An increase in astrocyte reactivity with a concomitant decrease in microglial reactivity was observed in MK4 mice. In contrast to WT, MK4 astrocytes displayed reduced Cx43 hemichannel activity. Pharmacological blockade of Cx43 hemichannels with TAT-Gap19 also significantly decreased infarct volume in WT animals. This study provides novel molecular insights and charts new avenues for therapeutic intervention associated with Cx43 function.
Abstract P145: Outcomes of an EMR-Enabled Acute Ischemic Stroke Care Path in a Primary Stroke Center
Authors: Aaron Dunn, Selena Pasadyn, Francis May, Dolora Wisco
Journal: Circulation (2019)

Background: One major challenge in health care is to improve value, which is best measured at the disease or treatment level. Evidenced-based, standardized care has been proposed and studied as one potential method to drive this process. We hypothesize that enablement of the Acute Ischemic Stroke (AIS) Care Path within the electronic medical record (EMR) improves clinical outcomes of patients with acute ischemic stroke. Methods: We compared the length of stay (LOS), in-patient mortality, rate of hospital readmission within 30 days, NIH Stroke Scale (NIHSS) at admission in patients, and post-discharge modified Rankin Scale (mRS) with ischemic stroke in the periods before (January to December 2015) and after (January to December 2016) EMR-enablement of the AIS Care Path. Results: A total of 1,858 patients were diagnosed with acute ischemic stroke during the entire study period. Patients presented with more severe stroke symptoms, as evidenced by a higher NIHSS at admission in the post-intervention period (11.4 ± 0.7 vs 10.5 ± 0.7, p=0.05). There was no difference in LOS (5.2 ± 0.3 days vs 5.3 ± 0.2 days, p=0.41), and there was a significant reduction in rate of hospital readmission within 30 days of discharge (8.9 ± 2.0 vs 10.7 ± 2.0, p=0.05). There were trends toward decreased in-patient mortality (2.6 ± 0.7% vs 3.3 ± 1.5%, p=0.22) and improved functional outcomes (2.3 ± 0.3 vs 2.6 ± 0.4, p=0.20) after EMR-enablement of the AIS Care Path. Conclusion: EMR-enablement of the AIS Care Path, a means of further standardizing stroke care, was associated with lower readmission and trends toward lower mortality and improved functional outcomes.
Abstract 17823: Etiology of Gender Differences in Cardiac Troponin I Concentrations
Authors: Brendan M Everett, Tanja Zeller, Robert J Glynn, Paul M Ridker, Stefan Blankenberg
Journal: Circulation (2013)

Background: The distribution of circulating cardiac troponin differs in men and women. The etiology of these differences, and their clinical implications, remain unclear. Methods and Results: Using...
A comparison of prostate biopsy rates among urologists in a large group practice and implications of PSA screening.
Authors: David Uri Lipsitz, Gavri Eshet, Jason Scott White
Journal: Journal of Clinical Oncology (2015)

e16024 Background: In 2012 USPSTF issued recommendations against PSA screening. The purpose of this study was to see if this recommendation has changed the prostate biopsy rates in a large, community urology practice. We also wanted to determine whether the rate of positive prostate biopsies correlated to the frequency that biopsies were performed by the urologist. Based on data presented at ASCO-GU in 2014 by Kapoor et al, the average positive biopsy rate was 40.3% in a survey of 440,000 biopsies from 2006-2011. Methods: We analyzed the prostate biopsy data for the years of 2012-2014 for our 34-urologist group comparing total number of biopsies and the rate of positivity per urologist. The number of practicing urologists was constant over those years. We stratified urologists into 2 groups: 1) those that performed fewer than 50 biopsies/year and 2) those that performed 50 or greater yearly. We then compared their pooled positive biopsy rates for each stratum. Our hypothesis was that there would be no difference in positive biopsy rates between those 2 groups. Results: Regarding the USPSTF’s possible impact on number of prostate biopsies, the number of biopsies each year are as follows: 2012--1692; 2013--1788; and 2014--1711. This represents less than a 5% change over each year. The average positive biopsy rate was 52.5% with the total number of biopsies performed annually by each urologist ranging from 2 to 121. Using a two sample proportion hypothesis for large sample sizes, z = 0.58 which yields a p-value of 0.55. Therefore, there was not a statistically significant difference between the two groups in terms of rates of positive biopsies. Conclusions: There were no changes in the number of biopsies performed since the USPSTF recommendations on PSA in 2012. This may indicate that physicians are evaluating PSA levels at the same rates in 2013/2014. Our 52.5% positive rate is higher than the published average. There was no difference in rates of prostate cancer detection for those urologists who performed under 50 biopsies vs. those who performed 50 of greater biopsies yearly. This may indicate that urologists who biopsy the prostate infrequently are still able to detect cancer at the same rates as those who more frequently biopsy.
Spermatogenesis of tumor-bearing testes in germ cell testicular cancer patients.
Authors: Keisuke Suzuki
Journal: Journal of Clinical Oncology (2015)

e15569 Background: Oncologic testicular sperm extraction (onco-TESE) is a key modality for fertility preservation in cases of inadequate pretreatment sperm collection and azoospermic men with testicular cancer. However, because the application of onco-TESE might not always be feasible, it is important to discern the hallmarks of cases where onco-TESE has been associated with successful outcomes. Methods: This study is a retrospective analysis performed in a single university hospital in 2002–2014.Participants were 102 male patients (104 testes) who underwent inguinal orchiectomy and were diagnosed with a germinoma at the Dokkyo Medical University Koshigaya Hospital. In each specimen, the Johnsen Score Count (JSC) in seminiferous tubles at each established distance from the tumor margin (1 mm, 2.5 mm, 5 mm, 7.5 mm, 10 mm, and 12.5 mm) was determined. We analyzed relationships between age, tumor histopathologic type, tumor size (maximum diameter), distance from a tumor, non-tumor tissue width and JSC. Results: The 104 specimens consisted of 78 seminomas and 26 non-seminomatous TGCTs. The average JSC was 4.7±2.4 in seminomas and 3.9±2.5 in non-seminomatous germ cell tumors, with no significant difference between the 2 subtypes. Simple linear regression analysis showed negative influence of age and tumor size on spermatogenesis, but multiple linear regression analysis showed no relationship between tumor size and spermatogenesis. Greater distance of seminiferous tubules were located, the better spermatogenesis was preserved. Mature spermatozoa were identified in 93.0% of specimens with noncancerous testicular tissue width (NCTW) ≥ 7.5 mm and in 41.3% of those with NCTW < 7.5 mm. Conclusions: Younger age and wide NCTW are positive predictor of spermatogenesis in TGCT patients.
A biodiversity hypothesis
Authors: Tari Haahtela
Journal: Allergy (2019)

Biodiversity hypothesis states that contact with natural environments enriches the human microbiome, promotes immune balance and protects from allergy and inflammatory disorders. We are protected by two nested layers of biodiversity, microbiota of the outer layer (soil, natural waters, plants, animals) and inner layer (gut, skin, airways). The latter inhabits our body and is colonized from the outer layer. Explosion of human populations along with cultural evolution is profoundly changing our environment and lifestyle. Adaptive immunoregulatory circuits and dynamic homeostasis are at stake in the newly emerged urban surroundings. In allergy, and chronic inflammatory disorders in general, exploring the determinants of immunotolerance is the key for prevention and more effective treatment. Loss of immunoprotective factors, derived from nature, is a new kind of health risk poorly acknowledged until recently. The paradigm change has been implemented in the Finnish allergy programme (2008-2018), which emphasized tolerance instead of avoidance. The first results are promising, as allergy burden has started to reduce. The rapidly urbanizing world is facing serious biodiversity loss with global warming, which are interconnected. Biodiversity hypothesis of health and disease has societal impact, for example, on city planning, food and energy production and nature conservation. It has also a message for individuals for health and well-being: take nature close, to touch, eat, breathe, experience and enjoy. Biodiverse natural environments are dependent on planetary health, which should be a priority also among health professionals.
Abstract 010: Heart Disease and Arrhythmia in a Sample Experiencing Homelessness: Epidemiology, Prior History and Risk Factors
Authors: Ben King
Journal: Circulation (2019)

Background: Adults experiencing homelessness experience 40-50% greater mortality risk from heart disease than the general population. Research has identified several risk factors, including poor glycemic, hypertension, and hyperlipidemia control, high prevalence of cigarette smoking, and elevated homocysteine levels from smoking and poor nutrition. Implemented in 2014, the Vulnerability Index - Service Prioritization Decision Assistance Tool (VI-SPDAT v1) is a 50 question survey intended to proscribe appropriate levels of intervention, and prioritize the waiting list for housing services. Method: The VI-SPDAT was used to assess a cohort of individuals experiencing homelessness (n=4,739 unique participants) seeking subsidized housing services in a single county in Texas. The results of the self-report survey’s medical questions were validated through linkage to the community’s Health Information Exchange (HIE) for indigent populations. Confirmatory Factor Analysis tests were performed on all first-time assessments, and modification indices were used to optimize a 5 factor model of global vulnerability in the homeless population. Logistic regression was used to identify independent covariates associated with reported heart disease within various sections (explicit domains) within the measure. Results: One quarter of all individuals assessed with the VI-SPDAT reported a history of heart disease or arrhythmia (24.98%). Criterion validation of the tool using HIE data supported that this prevalence estimate was possibly even under-reported, with diagnostic data available for 3,240 participants and a 38.67% prevalence of heart disease or arrhythmia (26.44%, adjusted for full sample). Rates of the condition were elevated for females (27.5% vs 24.0%), non-Hispanic participants (25.7% vs 21.7%), and those experiencing chronic homelessness (HUD definition; 26.8% vs 22.5%). Behavioral and cognitive health conditions associated with heart disease included problems with concentration, history of traumatic brain injury, ED visits for mental health symptom management, and poor medication adherence (all p&lt;0.001). Social risk factors such as being the victim of an attack, associating with perceived bad influences, having people they don’t like in their lives, and being forced or tricked into doing things by others were all associated with heart disease (all p&lt;0.001). Discussion: This research presents a rare window into the complex interrelationships of social and medical vulnerability that surround cardiovascular diseases in a sample of extremely vulnerable individuals. Analytical techniques applied to this data show several relationships not previously explored in the literature, and support the existing evidence of heightened cardiovascular risk due to multiple exposures more common in those experiencing homelessness.
Occurrence of Extensive Cutaneous Human Papillomavirus Infection After Initiation of Tofacitinib Therapy
Authors: Florence Brunet-Possenti, Charlotte Charpentier, Yoram Bouhnik, Lydia Deschamps, Diane Descamps, Hélène Moins-Teisserenc, Vincent Descamps
Journal: JAMA Dermatology (2019)

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 Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Dermatology journal
Prophylactic Cranial Irradiation vs Observation in Patients With Locally Advanced Non–Small Cell Lung Cancer
Authors: Alexander Sun, Chen Hu, Stuart J. Wong, Elizabeth Gore, Gregory Videtic, Swati Dutta, Mohan Suntharalingam, Yuhchyau Chen, Laurie E. Gaspar, Hak Choy
Journal: JAMA Oncology (2019)

Brain metastasis (BM) rates are high in locally advanced non-small cell lung cancer (LA-NSCLC), approaching rates seen in small cell lung cancer, where prophylactic cranial irradiation (PCI) is standard of care. Although PCI decreases the incidence of BM in LA-NSCLC, a survival advantage has not yet been shown.To determine if PCI improves survival in LA-NSCLC.Radiation Therapy Oncology Group (RTOG) 0214 was a randomized phase 3 clinical trial in stage III NSCLC stratified by stage (IIIA vs IIIB), histologic characteristics (nonsquamous vs squamous) and therapy (no surgery vs surgery). The study took place at 291 institutions in the United States, Canada, and internationally. Of 356 patients with stage III NSCLC entered onto this study, 16 were ineligible; therefore, 340 patients were randomized.Observation vs PCI.The primary outcome was overall survival (OS). The secondary end points were disease-free survival (DFS) and incidence of BM.Of the 340 total participants, mean (SD) age was 61 years; 213 of the participants were men and 127 were women. The median follow-up time was 2.1 years for all patients, and 9.2 years for living patients. The OS for PCI was not significantly better than observation (hazard ratio [HR], 0.82; 95% CI, 0.63-1.06; P = .12; 5- and 10-year rates, 24.7% and 17.6% vs 26.0% and 13.3%, respectively), while the DFS (HR, 0.76; 95% CI, 0.59-0.97; P = .03; 5- and 10-year rates, 19.0% and 12.6% vs 16.1% and 7.5% for PCI vs observation) and BM (HR, 0.43; 95% CI, 0.24-0.77; P = .003; 5- and 10-year rates, 16.7% vs 28.3% for PCI vs observation) were significantly different. Patients in the PCI arm were 57% less likely to develop BM than those in the observation arm. Younger patients (<60 years) and patients with nonsquamous disease developed more BM. On multivariable analysis, PCI was associated with decreased BM and improved DFS, but not improved OS. Multivariable analysis within the nonsurgical arm suggests that PCI effectively prolongs OS, DFS, and BM.In patients with stage III LA-NSCLC without progression of disease after therapy, PCI decreased the 5- and 10-year rate of BM and improved 5- and 10-year DFS, but did not improve OS. Although this study did not meet its primary end point, the long-term results reveal many important findings that will benefit future trials. Identifying the appropriate patient population and a safe intervention is critical.ClinicalTrials.gov identifier: NCT00048997.