tbuckley/cabot-search huggingface dataset:
Quantifying unmet prevention needs among MSM in Europe through a multi-site bio-behavioural survey
Authors: Massimo Mirandola, Lorenzo Gios, Nigel Sherriff, Ulrich Marcus, Igor Toskin, Magdalena Rosinska, Susanne Schink, Sharon Kühlmann-Berenzon, Barbara Suligoi, Cinta Folch, Christiane Nöstlinger, Sonia Dias, Danica Stanekova, Irena Klavs, Saulius Caplinskas, Alexandru Rafila, Carolina Marin, Ivailo Alexiev, Lev Zohrabyan, Teymur Noori, Cinthia Menel-Lemos
Journal: Eurosurveillance (2018)

IntroductionThe HIV epidemic represents an important public health issue in Europe particularly among men who have sex with men (MSM). Global AIDS Monitoring indicators (GAM) have been widely and jointly promoted as a set of crucial standardised items to be adopted for monitoring and responding to the epidemic.MethodsThe Sialon II study, implemented in 13 European cities (2013-14), was a complex multi-centre integrated bio-behavioural cross-sectional survey targeted at MSM, with a concomitant collection of behavioural and biological (oral fluid or blood specimens) data. Rigorous sampling approaches for hard-to-reach populations were used (time-location sampling and respondent-driven sampling) and GAM indicators were calculated; sampling frames were adapted to allow weighted estimates of GAM indicators.Results4,901 MSM were enrolled. HIV prevalence estimates ranged from 2.4% in Stockholm to 18.0% in Bucharest. When exploring city-level correlations between GAM indicators, prevention campaigns significantly correlated with levels of condom use and level of HIV testing among MSM.ConclusionThe Sialon II project has made an important contribution to the monitoring and evaluation of the HIV epidemic across Europe, integrating the use of GAM indicators within a second generation HIV surveillance systems approach and in participatory collaboration with MSM communities. It influenced the harmonisation of European data collection procedures and indicators via GAM country reporting and contributed essential knowledge informing the development and implementation of strategic, evidence-based HIV prevention campaigns for MSM.
Inclisiran Lowers LDL-C and PCSK9 Irrespective of Diabetes Status: The ORION-1 Randomized Clinical Trial
Authors: Lawrence A. Leiter, Hwee Teoh, David Kallend, R. Scott Wright, Ulf Landmesser, Peter L.J. Wijngaard, John J.P. Kastelein, Kausik K. Ray
Journal: Diabetes Care (2018)

OBJECTIVE To evaluate the efficacy and safety of inclisiran by diabetes status. RESEARCH DESIGN AND METHODS ORION-1 (ClinicalTrials.gov, NCT02597127) randomized 501 subjects with atherosclerotic cardiovascular disease (ASCVD) or ASCVD risk equivalents and high LDL cholesterol (LDL-C), despite maximally tolerated LDL-C–lowering therapies, to one or two doses of placebo or inclisiran. Levels of lipids and proprotein convertase subtilisin/kexin type 9 (PCSK9) at baseline and day 180 were compared. RESULTS Inclisiran was associated with marked declines in LDL-C (median −28% to −52%, P &amp;lt; 0.0001 and −28% to −55%, P &amp;lt; 0.005 for all doses in the without- and with-diabetes groups, respectively) and PCSK9. The inclisiran-treated groups also had lower apolipoprotein B, non-HDL cholesterol, and lipoprotein(a) but higher HDL cholesterol. Inclisiran had an adverse profile similar to that of placebo, and adverse events were proportionally balanced in the baseline with- and without-diabetes groups. CONCLUSIONS PCSK9-targeted siRNA-driven strategies may provide a novel therapeutic option for managing dyslipidemia in the presence and absence of diabetes.
Letter to the Editor: Liver Stiffness in Noncirrhotic Portal Hypertension: The Devil Is in the Diagnosis
Authors: Stefania Gioia, Silvia Nardelli, Oliviero Riggio
Journal: Hepatology (2018)

Potential conflict of interest: Nothing to report. To the Editor: We have read with great interest the article by Vuppalanchi et al.,1 who studied the diagnostic role of liver stiffness measurements (LSMs) in patients with noncirrhotic portal hypertension (NCPH) due to hepatic (nodular regenerative hyperplasia [NRH]) or prehepatic origin (portal vein thrombosis [PVT]). The role of LSMs in identifying a cirrhosis as the cause of the portal hypertension is well established,2 and the evidence of PVT in any imaging technique is sufficient to attribute the cause of portal hypertension to PVT and does not require further histological or elastographical confirmation. However, in patients who are first observed for the clinical manifestation of PVT, the possibility that this condition is due to an undiagnosed pre‐existing hepatic NCPH is authentic, and it is not usually ruled out by the diagnostic work‐up suggested by the current guidelines, which do not routinely include the liver biopsy.3 In our series,4 32% of histologically proven hepatic NCPH developed PVT during the follow‐up. The correct diagnosis of PVT secondary to hepatic NCPH may have relevant therapeutic consequences. In fact, a missed diagnosis may lead to an erroneous stop of anticoagulant therapy, which should be carried lifelong, because the slowing down of the portal flow is the real cause of PVT and is irreversible. For this reason, we appreciated the purpose of the study and in particular the possibility to distinguish patients with hepatic or prehepatic NCPH on the basis of their LSM. In our opinion, the observation that one‐third of patients with PVT had liver stiffness values greater than 10 KPa may be simply due to the inclusion of patients initially affected by an undiagnosed hepatic NCPH in the PVT group. The explanation given by the authors that the abnormal LSM—despite the lack of fibrosis in the PVT group—is likely due to an elevated free hepatic venous pressure is also possible, but the co‐existence of a high caval pressure that is independent of the liver disease needs to be hypothesized. Thus, the Devil is actually in the diagnosis. In our opinion, the Vuppalanchi et al. observations are clinically relevant. In fact, if their results are confirmed, the diagnostic work‐up of the patients with PVT should include the LSM—at least in identifying those with abnormal values being submitted to liver biopsy. However, the role of liver biopsy in distinguishing between PVT due to (or not due to) hepatic NCPH should be re‐evaluated. In fact, histological features such as perisinuosoidal fibrosis, sinusoidal dilatation, paraportal shunts, and NRH have also been described in patients with PVT,5 unless the Devil was already present in the diagnosis of the previous literature.
Abstract 18313: Gender Differences in the Early Mortality of Octogenarian Patients with Acute Myocardial Infarction From a Registry Database in Japan
Authors: Takafumi Yamane, Junichi Kotani, Hiroki Sakamoto, Masaharu Ishihara, Toshihisa Anzai, Wataru Shimizu, Satoshi Yasuda, Hideo Kusuoka, Hiroyuki Yokoyama
Journal: Circulation (2012)

Background: During the previous 2 decades studies have consistently shown that younger women hospitalized with an acute myocardial infarction (AMI) have a poorer prognosis than their men peers. However, gender differences in elderly patients especially in octogenarians are not fully discussed. We evaluated gender differenes in ogtogenarians patients with AMI in Japan, which is highly progressive aging society. Methods and Results: We established the multicenter registry to collect data of patients with AMI. 3691 patients enrolled into a registry from 27 hospitals during 2005 and 2009. Among these patients, 755 patients were octogenarians ( age equal or older than 80), and 383 were male and 372 were female. Female was more likely to be older (84.2±3.9 vs 85.7±4.3, p&lt;0.0001) and longer from the onset of symptom to admission, more likely to have heart failure in admission. However, there was no change in the rate of hypertension, dyslipidemia, diabetes between both gender. Primary percutaneous coronary intervention (PCI) was performed at a high frequency in both groups (male vs female, 78.9% vs 75.5%, p=0.28). In patients with AMI female &lt;80 years old had higher in-hospital mortality than male of the same age (male vs female, 4.4% vs 9.5%, p&lt;0.0001), but not in octogenarian patients (male vs female, 14.6% vs 19.9%, p=0.055). In multivariable analysis, female was stronger predictor of in-hospital mortality in non-octogenarian patients (Odds Ratio 2.7, 95%CI 1.6-4.3, p&lt;0.0001), than in octogenarian patients (Odds Ratio 1.4, 95%CI 0.78-2.4, p=0.27). Conclusions: In octogenarian AMI patients, gender differences of baseline characteristics are not so strong as non-octogenarian patients, and female was not so strong predictor of in-hospital mortality.
BRAF and NRAS mutations in subtypes of papillary thyroid cancer
Authors: Madhu S. Kumar, Zubair W. Baloch, Patricia Volpe, Virginia A. Livolsi, Marcia S. Brose
Journal: Cancer Research (2004)

88  Earlier studies have demonstrated activating mutations in components of the MAP kinase cascade in papillary thyroid cancer (PTC), including BRAF codon 599 and NRAS codon 61. Subsequent analysis of these mutations in PTC has found activating BRAF mutations in 29-69% of cases and activating NRAS mutations in 5% of cases. In order to further characterize PTC, we set out to determine the rate of BRAF and NRAS mutations in the various histopathological subtypes. Taking advantage of a collection of PTC samples sent to our institution for evaluation, we extracted DNA from paraffin sections of 75 thyroid cancer samples, 54 of which were PTC. We screened these samples for mutations in BRAF codon 599 (exon 15) and NRAS codon 61 (exon 3) using direct sequencing. The number of each subtype of PTC is listed in Table 1. We have completed analysis of BRAF mutations in 45 samples thus far. To date, we have observed 7 definitive BRAF mutations (21%) in PTCs screened. We have found 5 BRAF mutations in the follicular variants (28%), 1 in the tall cell variants (11%), and 1 mutation in the classic PTCs (17%). We have found no BRAF mutations in either the benign tissues or anaplastic carcinomas. We continue to acquire new samples to expand our analysis of the various subtypes. We will present our final data including the results of the NRAS analysis and the results of the additional samples. In conclusion, BRAF mutations appear to be most prevalent in the follicular variant of PTC. Correlation of BRAF and NRAS mutations with specific histopathological features will expand our understanding of the molecular mechanisms and clinical behavior of PTC and lead to the development of new therapeutic modalities for patients that fail radioactive iodine therapy.
Smoking habits among adolescents with asthma – data from a population‐based birth cohort
Authors: Ulrika Hellberg, Jesse Thacher, Niklas Andersson, Göran Pershagen, Erik Melén, Anna Bergström, Inger Kull
Journal: Allergy (2018)

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The IL-15–AKT–XBP1s signaling pathway contributes to effector functions and survival in human NK cells
Authors: Yufeng Wang, Yibo Zhang, Ping Yi, Wenjuan Dong, Ansel P. Nalin, Jianying Zhang, Zheng Zhu, Lichao Chen, Don M. Benson, Bethany L. Mundy-Bosse, Aharon G. Freud, Michael A. Caligiuri, Jianhua Yu
Journal: Nature Immunology (2018)
<i>Notes from the Field:</i> An Outbreak of <i>Salmonella</i> Agbeni Infections Linked to Turtle Exposure — United States, 2017
Authors: Lia Koski, Lauren Stevenson, Jasmine Huffman, Amy Robbins, Julia Latash, Enoma Omoregie, Kelly Kline, Megin Nichols
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

In June 2017, PulseNet, the national molecular subtyping network for foodborne disease surveillance, identified 17 Salmonella Agbeni clinical isolates with indistinguishable XbaI enzyme pattern (outbreak strain) by pulsed-field gel electrophoresis.
Erythematous Papule on the Glans Penis
Authors: Mónica Munera-Campos, Adrià Plana-Pla, Ariadna Quer
Journal: JAMA Dermatology (2018)

A 60-year-old man with a history of IgA kappa multiple myeloma was referred for evaluation of an indolent, erythematous papule on his glans penis of 2 weeks’ duration; he denied sexual risk behavior and reported no recent changes in medication. What is your diagnosis?
Prevalence of palliative care consultations in phase I pediatric oncology trials.
Authors: Andrea Joan Cuviello, Andrea Beri, Renee D Boss, Nirali N. Shah, Brigitte C. Widemann, Lori Wiener
Journal: Journal of Clinical Oncology (2018)

108 Background: In 2015 the Psychosocial Standards of Care Project for Childhood Cancer published 15 evidence-based standards for pediatric psychosocial care for children with cancer and their families. One standard endorses incorporation of palliative care to “reduce suffering throughout the disease process, regardless of disease status”. Patients enrolling on phase I studies represent a unique cohort within pediatric oncology, as they generally represent a patient population that has not responded to standard therapies and a chance of cure is limited. Phase I trials, primarily designed to test safety and feasibility, offer a low chance of therapeutic benefit and high risk of death. This study aims to define the prevalence of palliative medicine consultation for phase I patients. Methods: A retrospective chart review of pediatric patients enrolled in a National Cancer Institute (NCI) Pediatric Oncology Branch Phase I clinical trial between 2015-present, using the NIH Biomedical Translational Research Information System (BTRIS). Palliative Care Consult Notes, Advance Directive information, diagnoses and medications were captured. Results: We reviewed the records of 126 phase I patients; 66% were male, 47% were &gt;18 years, 67% had relapsed/refractory leukemia, and 46% are now recorded as deceased. Palliative medicine was consulted in &lt;20% of patients; all consultations were for symptom management, primarily pain control (91%). Only 9% of patients had an advance directive prior to enrollment at the NCI. During therapy at the NCI, an additional 20% of patients completed an advance directive, just over a third (35%) of which were patients who received palliative medicine consultation. Conclusions: Palliative care was infrequently consulted in a highly vulnerable patient population where survival outcomes are poor and disease or therapy side effects are substantial. Efforts to increase the use of palliative care services in this population may improve the quality of life for children and families. Future directions include working to standardize the involvement of palliative medicine for pediatric patients enrolling onto phase I clinical trials.
Inactivation of DNA repair—prospects for boosting cancer immune surveillance
Authors: Anna Truini, Giovanni Germano, Alberto Bardelli
Journal: Genome Medicine (2018)

The emergence of drug resistance depends on the ability of the genome of cancer cells to constantly mutate and evolve under selective pressures. The generation of new mutations is accelerated when genes involved in DNA repair pathways are altered. Notably, although the emergence of new mutations fosters drug resistance, new variants can nevertheless become novel antigens that promote immune surveillance and even restrict cancer growth.
Need for international classification of gabapentin as a controlled substance
Authors: Alyssa M Peckham, David A Sclar
Journal: BMJ (2018)

Mayor notes that the United Kingdom will reclassify pregabalin and gabapentin—that is, gabapentinoids—as class C controlled substances in April 2019. This change was proposed, in part, owing to the increased rate of death associated with gabapentinoid misuse.1 The reclassification will require a physical prescriber signature for each prescription, rather …
<i>PATJ</i> Low Frequency Variants Are Associated With Worse Ischemic Stroke Functional Outcome
Authors: Marina Mola-Caminal, Caty Carrera, Carolina Soriano-Tárraga, Eva Giralt-Steinhauer, Rosa M. Díaz-Navarro, Sílvia Tur, Carmen Jiménez, Aina Medina-Dols, Natàlia Cullell, Nuria P. Torres-Aguila, Elena Muiño, Ana Rodríguez-Campello, Angel Ois, Elisa Cuadrado-Godia, Rosa M. Vivanco-Hidalgo, Mar Hernandez-Guillamon, Montse Solé, Pilar Delgado, Alejandro Bustamante, Teresa García-Berrocoso, Maite Mendióroz, Mar Castellanos, Joaquín Serena, Joan Martí-Fàbregas, Tomás Segura, Gemma Serrano-Heras, Victor Obach, Marc Ribó, Carlos A. Molina, José Alvarez-Sabín, Ernest Palomeras, Mar Freijo, Maria A. Font, Jonathan Rosand, Natalia S. Rost, Cristina Gallego-Fabrega, Jin-Moo Lee, Laura Heitsch, Laura Ibanez, Carlos Cruchaga, Chia-Ling Phuah, Robin Lemmens, Vincent Thijs, Arne Lindgren, Jane Maguire, Kristiina Rannikmae, Catherine L. Sudlow, Christina Jern, Tara M. Stanne, Erik Lorentzen, Lucía Muñoz-Narbona, Antonio Dávalos, Elena López-Cancio, Bradford B. Worrall, Daniel Woo, Steven J. Kittner, Braxton D. Mitchell, Joan Montaner, Jaume Roquer, Jurek Krupinski, Xavier Estivill, Raquel Rabionet, Cristòfol Vives-Bauzá, Israel Fernández-Cadenas, Jordi Jiménez-Conde
Journal: Circulation Research (2019)

Rationale: Ischemic stroke is among the leading causes of adult disability. Part of the variability in functional outcome after stroke has been attributed to genetic factors but no locus has been consistently associated with stroke outcome. Objective: Our aim was to identify genetic loci influencing the recovery process using accurate phenotyping to produce the largest GWAS (genome-wide association study) in ischemic stroke recovery to date. Methods and Results: A 12-cohort, 2-phase (discovery-replication and joint) meta-analysis of GWAS included anterior-territory and previously independent ischemic stroke cases. Functional outcome was recorded using 3-month modified Rankin Scale. Analyses were adjusted for confounders such as discharge National Institutes of Health Stroke Scale. A gene-based burden test was performed. The discovery phase (n=1225) was followed by open (n=2482) and stringent joint-analyses (n=1791). Those cohorts with modified Rankin Scale recorded at time points other than 3-month or incomplete data on previous functional status were excluded in the stringent analyses. Novel variants in PATJ (Pals1-associated tight junction) gene were associated with worse functional outcome at 3-month after stroke. The top variant was rs76221407 (G allele, β=0.40, P =1.70×10 −9 ). Conclusions: Our results identify a set of common variants in PATJ gene associated with 3-month functional outcome at genome-wide significance level. Future studies should examine the role of PATJ in stroke recovery and consider stringent phenotyping to enrich the information captured to unveil additional stroke outcome loci.
Generation of renal Epo-producing cell lines by conditional gene tagging reveals rapid HIF-2 driven Epo kinetics, cell autonomous feedback regulation, and a telocyte phenotype
Authors: Faik Imeri, Karen A. Nolan, Andreas M. Bapst, Sara Santambrogio, Irene Abreu-Rodríguez, Patrick Spielmann, Svende Pfundstein, Silvana Libertini, Lisa Crowther, Ilaria M.C. Orlando, Sophie L. Dahl, Anna Keodara, Willy Kuo, Vartan Kurtcuoglu, Carsten C. Scholz, Weihong Qi, Edith Hummler, David Hoogewijs, Roland H. Wenger
Journal: Kidney International (2018)
Mystery Myelitis in Children
Authors: Bridget Kuehn
Journal: JAMA (2018)

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Abstract 21050: Long Term Survival and Neurological Status of Patients With Tracheostomy After Cardiac Arrest
Authors: Sachin Agarwal, Omar Curiel, Evie Sobczak, Alex M Presciutti, David Roh, Soojin Park, Jan Claassen
Journal: Circulation (2017)

Background: Overall survival and functional status is poor in patients that undergo a tracheostomy after respiratory failure. Little data exists on cardiac arrest (CA) patients’ in-hospital and long-term survival, and neurological status after tracheostomy. Methods: We retrospectively reviewed 509 consecutive patients that were more than 18 years of age, admitted to one of the intensive care units between 12/2007 and 12/2015, resuscitated following either in-hospital or out-of-hospital CA, and considered for targeted temperature management. Tracheostomy and other data was collected via chart review. Chi-square and Wilcoxon rank sum tests were used for analysis. Survival and Cerebral Performance Category score (CPC) at discharge and one year were compared between patients with and without tracheostomy. Results: Of 509 patients, 389 (76.4%) did not undergo a tracheostomy, 83 (16.3%) had new tracheostomies placed during the hospitalization, and 37 (7.3%) had pre-existing tracheostomy before the index cardiac event. In comparison to the non-tracheostomy group, the new tracheostomies patients had a greater number of in-hospital arrests with shorter duration of median return of spontaneous circulation, while the pre-existing tracheostomy group was older, worse CPC on admission, were mostly living in a subacute nursing facility, had lower rates of ventricular tachycardia/fibrillation as initial rhythm, and lower rates of therapeutic hypothermia. At the time of hospital discharge, there were 64/83 (77%) survivors in the new tracheostomy group, 104/389 (26.7%) in the non-tracheostomy, and 7/37 (19%) in the pre-existing tracheostomy group. Available one year data on 53 patients in the new tracheostomy group showed a 55% (n=29) survival rate, with neurological status as follows: {CPC 1: 7 (24%), CPC 2: 6 (21%), CPC 3: 8 (27.5%), CPC 4: 8 (27.5%)} compared to 66/81 (81%), {(CPC 1: 34 (51%), CPC 2: 15 (23%), CPC 3: 16 (24%), CPC 4: 1 (0.01%)} in the non-tracheostomy group (p=0.005). Conclusions: Cardiac arrest survivors that undergo a tracheostomy have reduced survival and poor neurological status at one year compared to those discharged without receiving a tracheostomy. Pre-existing tracheostomy patients suffer from high rates of in-hospital mortality.