tbuckley/cabot-search huggingface dataset:
Abstract 13223: Influence of Troponin Elevation on Short- And Long-Term Mortality in Severe Sepsis and Septic Shock
Authors: Saraschandra Vallabhajosyula, Jacob C Jentzer, Jeffrey B Geske, Kianoush B Kashani, Ognjen Gajic, Rahul Kashyap
Journal: Circulation (2016)

Background: Troponin-T (TnT) elevation is common in severe sepsis and septic shock, but the impact on mortality and other clinical outcomes remains uncertain. Methods: This was a retrospective review of adult patients with severe sepsis and septic shock admitted to all the intensive care units (ICU) at Mayo Clinic, Rochester from January 2012 to December 2014. Patients with congenital heart disease or pre-existing moderate or greater valvular disease were excluded. TnT elevation was defined as initial TnT ≥0.1 ng/mL or rise in 3- and 6-hour TnT ≥0.03 ng/mL. Primary outcomes included ICU, hospital, 28-day and 1-year mortality and secondary outcomes were need for and duration of non-invasive ventilation or invasive mechanical ventilation, ICU readmission, and ICU and hospital length of stay. Two-tailed p &lt;0.05 was considered statistically significant. Results: During this three-year period, TnT was measured in 372/765 patients (49%) with septic shock with TnT elevation noted in 329/372 (88%) patients. In patients with and without TnT elevation, initial TnT was 0.14±0.26 vs. 0.14±0.02 ng/mL, p =0.57 and peak TnT was 0.20±0.36 vs. 0.08±0.11 ng/mL, p &lt;0.001. Severity of illness scores, laboratory values, vasopressor use, clinical parameters and medications were similar between patients with and without TnT elevation, except that patients with TnT elevation were older and had more frequent history of coronary atherosclerosis, chronic kidney disease, heart failure and atrial fibrillation (all p &lt;0.05). There was no significant difference in ICU mortality [43 (13%) vs. 8 (19%), p =0.34] and hospital mortality [75 (23%) vs. 12 (28%), p =0.45] between patients with and without TnT elevation. Long-term follow-up of 220/329 (67%) patients showed no significant difference in 28-day mortality [97/216 (45%) vs. 1/4 (25%); p =0.63] or 1-year mortality [163/216 (75%) vs. 4/4 (100%); p =0.58]. There was no significant difference in any of the secondary outcomes between patients with and without elevated TnT (all p &gt;0.05). There was no difference in mortality with increasing quartiles of peak TnT. Conclusions: Troponin elevation is associated with older age and higher comorbidity burden, but does not predict mortality in patients with severe sepsis and septic shock.
Primary myelofibrosis: 2019 update on diagnosis, risk‐stratification and management
Authors: Ayalew Tefferi
Journal: American Journal of Hematology (2018)

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by stem cell-derived clonal myeloproliferation that is often but not always accompanied by JAK2, CALR, or MPL mutations; additional disease features include bone marrow stromal reaction including reticulin fibrosis, abnormal cytokine expression, anemia, hepatosplenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression, and shortened survival.Diagnosis of PMF is based on bone marrow morphology. Presence of JAK2, CALR, or MPL mutation, expected in ∼ 90% of the patients, is supportive but not essential for diagnosis. The revised 2016 World Health Organization (WHO) classification system distinguishes "prefibrotic" from "overtly fibrotic" PMF; the former might mimic ET in its presentation and it is prognostically relevant to distinguish the two.Two new prognostic systems for PMF have recently been introduced: GIPSS (genetically inspired prognostic scoring system) and MIPSS70+ version 2.0 (mutation- and karyotype-enhanced international prognostic scoring system). GIPSS is based exclusively on mutations and karyotype. MIPSS70+ version 2.0 utilizes both genetic and clinical risk factors. GIPSS features four and MIPSS70+ version 2.0 five risk categories. MIPSS70+ version 2.0 requires an online score calculator (http://www.mipss70score.it) while GIPPS offers a lower complexity prognostic tool.Observation alone is advised for MIPSS70+ version 2.0 "low" and "very low" risk disease (estimated 10-year survival 56%-92%); allogeneic stem cell transplant is the preferred treatment of choice for "very high" and "high" risk disease (estimated 10-year survival 0-13%); treatment-requiring patients with intermediate-risk disease (estimated 10-year survival 30%) are best served by participating in clinical trials. All other treatment approaches, including the use of JAK2 inhibitors, are mostly palliative and should not be used in the absence of clear treatment indications. Conventional treatment for anemia includes androgens, prednisone, thalidomide and danazol, for symptomatic splenomegaly hydroxyurea and ruxolitinib and for constitutional symptoms ruxolitinib. Splenectomy is considered for drug-refractory splenomegaly and involved field radiotherapy for nonhepatosplenic EMH and extremity bone pain.
Abstract 274: Defective Branched Chain Amino Acid Catabolism Impairs Exercise Endurance
Authors: Lauren Abell, Rufeng Shi, Dan Shao, Stephen Kolwicz, Rong Tian
Journal: Circulation Research (2017)

The branched chain amino acids (BCAA), leucine, isoleucine and valine, are essential for mammalians, and they play a positive role in exercise capacity, muscle development, and a lean body phenotype. BCAA supplementation is commonly paired with exercise in order to promote muscle growth, increase resistance to fatigue and reduce muscle soreness. On the other hand, elevated serum BCAA is strongly and positively correlated with the development of insulin resistance, coronary heart disease, and type II diabetes, and is predictive of patient response to therapeutics and intervention outcomes. We have previously shown that defective BCAA catabolism in mice impaired glucose metabolism in the heart and increased susceptibility to stress-induced cardiac damage. In this study we sought to determine the effects of elevated BCAA levels on skeletal muscle performance and response to exercise training using mouse models with systemically elevated BCAA levels. Supplementation of BCAA (1.5mg/g bodyweight/day, ratio of Leu:Ile:Val = 1.5:0.8:1) was administered to mice with impairment of BCAA catabolism due to the deletion of mitochondrial-localized protein phosphatase 2C (KO), a key enzyme in activating BCAA catabolism, and their littermate controls (CON). Mice were subjected to one week of daily exercise training via forced treadmill running and an exercise capacity test was performed at the beginning and end of training. Baseline maximum running time was decreased in the KO compared to CON (mean 73.4 and 82.5 min, respectively). One week of training resulted in increased exercise capacity in CON with an attenuated increase in KO mice (mean 136 and 112 min, respectively). BCAA supplementation did not further improve exercise capacity in CON (mean 131 min) and abrogated the response to training in KO (mean 70.1 min). Reduced exercise capacity positively correlated with elevated serum BCAA levels. Additionally, KO supplemented with BCAAs demonstrated elevated serum succinate, alanine and glutamate levels, which are metabolic markers of physiological stress. We conclude that short term supplementation of BCAA has no benefit for exercise capacity and accumulation of BCAAs has a negative effect on endurance exercise capacity.
Incretin-Based Therapies and Diabetic Retinopathy: Real-World Evidence in Older U.S. Adults
Authors: Tiansheng Wang, Jin-Liern Hong, Emily W. Gower, Virginia Pate, Seema Garg, John B. Buse, Til Stürmer
Journal: Diabetes Care (2018)

OBJECTIVE Recent large trials yield conflicting results on the association between incretin-based therapies (IBTs) and diabetic retinopathy (DR). We examined whether IBTs increase DR risk compared with other antihyperglycemics. RESEARCH DESIGN AND METHODS We implemented an active comparator, new-user cohort design using a nationwide 20% random sample of fee-for-service U.S. Medicare beneficiaries aged 65 years or older with Parts A, B, and D coverage between 2007 and 2015. We identified the following cohorts without prior treatment for retinopathy: dipeptidyl peptidase 4 inhibitors (DPP4i) versus sulfonylureas (SU), DPP4i versus thiazolidinediones (TZD), glucagon-like peptide-1 receptor agonists (GLP1RA) versus long-acting insulin (LAI), and GLP1RA versus TZD. Primary outcome was advanced diabetic retinopathy requiring treatment (ADRRT), defined as a procedure code for retinopathy treatment. Incident diabetic retinopathy (IDR), identified by a diagnosis code, was a secondary outcome. We estimated propensity scores to balance confounders and adjusted hazard ratios (95% CI) using weighted Cox proportional hazards models. RESULTS We identified 213,652 eligible patients. During a median duration of 0.58 to 0.87 years across comparisons, with a rate from 6.0 to 12.8 per 1,000 person-years, IBTs were not associated with increased ADRRT or IDR risk. The adjusted hazard ratios (95% CI) for ADRRT were 0.91 (0.79–1.04) by comparing DPP4i to SU (n = 39,292 and 87,073); 0.91 (0.75–1.11), DPP4i to TZD (n = 51,410 and 22,231); 0.50 (0.39–0.65), GLP1RA to LAI (n = 9,561 and 82,849); and 0.75 (0.53–1.06), GLP1RA to TZD (n = 10,355 and 27,345). CONCLUSIONS Our population-based cohort study of older U.S. adults with diabetes suggests that IBTs used for approximately 1 year do not increase the DR risk.
Gastrointestinal ultrasound in inflammatory bowel disease: experience from the Chinese IBD Elite Union
Authors: Ren Mao, Yujun Chen, Xiaoyan Xie, Minhu Chen
Journal: Gut (2018)

We read with great interest a recent review by Bryant et al 1 presenting a pragmatic guide of GI ultrasound (GIUS) in IBD clinical practice. We agree with the authors that the uptake of GIUS outside Europe has been slow and GIUS is underused in many countries. Here we would like to introduce the status, challenge and opportunity of GIUS implementation in IBD clinical practice in a different region of the world, namely China. We have witnessed a striking increase in the incidence of IBD in China in the last decade.2 The concept of multidisciplinary team (MDT) care consisting of gastroenterologist, colorectal surgeon, radiologist, pathologist, dietitian, and so on has been integrated into daily clinical …
Association of adjuvant hepatic artery infusion chemotherapy after resection of colorectal liver metastases with improved survival in patients with both right- and left-sided primary tumors.
Authors: Sepideh Gholami, Nancy E. Kemeny, Mithat Gonen, Andrea Cercek, Peter Kingham, Vinod P. Balachandran, Peter J. Allen, Ronald P. DeMatteo, William R. Jarnagin, Michael Ian D'Angelica
Journal: Journal of Clinical Oncology (2018)

776 Background: Patients with a right-sided (R) and/or KRAS-mutated (KRAS-MUT) primary tumors have inferior outcomes compared to patients with left sided (L) and/or KRAS-wildtype (KRAS-WT) cancers. Adjuvant hepatic artery pump infusion (HAI) chemotherapy improves overall survival (OS) in patients with colorectal liver metastases (CRLM). We investigated the impact of HAI in relation to the laterality and KRAS status of the primary tumors. Methods: Patients with resected CRLM and available KRAS-status, treated with and without adjuvant HAI were reviewed from a prospective institutional database. Rectal tumors were excluded. Correlations between adjuvant HAI, clinicopathological factors including laterality, KRAS status and OS were analyzed. Cox proportional hazard regression was used to assess survival outcomes comparing R (cecum to transverse colon, excluding appendix) versus L (splenic flexure to sigmoid) colon cancers. Results: 490 patients (R, n = 183; L, n = 307) were evaluated between 1993-2012 (median follow up of 6.5 years). Fifty-six percent (n = 277) received adjuvant HAI. Adjuvant HAI was associated with improved median OS in both R (7.0 vs. 4.4 years, p = 0.006) and L tumors (10.5 vs. 5.4 years, p &lt; 0.01). On multivariate analysis, HAI remained associated with improved OS (HR 4.49, p = 0.001) independent of primary tumor site and other clinical predictors (Table). Conclusions: Adjuvant HAI after resection of CRLM is independently associated with improved OS regardless of laterality of primary tumor. Treatment with adjuvant HAI correlates with improved prognosis in patients with resectable L/KRAS-MUT and R/KRAS-WT tumors. The biological difference for these outcomes requires further investigation. [Table: see text]
Natural history of small nonfunctioning pancreatic neuroendocrine tumors.
Authors: Jin Ho Choi, Sang Hyub Lee, Young Hoon Choi, Jinwoo Kang, Woo Hyun Paik, Ji Kon Ryu, Yong-Tae Kim
Journal: Journal of Clinical Oncology (2018)

515 Background: Asymptomatic sporadic nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) are rare disease but are diagnosed more frequently than before. The aim of this study was to evaluate the natural course of small NF-PNETs. Methods: We performed retrospective study of patients with suspected NF-PNETs from 1999 to 2015. Patients older than 18 years with NF-PNETs diagnosed either by pathology or other clinical evidences were included. Patients with clinical symptoms of hormonal hypersecretion, more than 20 mm in size, local invasion, nodal or distant metastasis, less than two follow-up imaging studies , and follow-up period of less than 6 months were excluded. Results: Small NF-PNETs in patients initially recommended surveillance (n = 69; mean age, 58.9 ± 11.1 yrs) were mainly located in the pancreatic head (n = 32, 46.4%) with mean mass size of 10.9 ± 3.1 mm. The average follow-up period was 52.2 ± 38.7 months. Tumor size changes during the follow-up period were as follows: increased (n = 9, 13.0%), sustained (n = 58, 84.1%), decreased (n = 2, 2.9%). The mean growth rate of increasing tumor was 0.9 ± 2.9 mm/year. Non-hypervascular tumors showed a tendency to increase in size compared to hypervascular tumor. (P = 0.04) Thirteen patients (18.8%) underwent surgery during the follow-up at average 32.9 ± 42.6 months later. According to the WHO 2010 grade classification, grade 1 was found in 18 patients, grade 2 in 1 patient, and grade 3 in 0 patient. The pathologic AJCC TNM stages of surgically resected tumors were Ia in 7 patients, Ib in 1 patient, IIa in 2 patient, IIb in 1 patients. Two patients (10.0%) received reoperation for recurred tumors at 34 and 50 months after surgery. Two patients (2.9%) showed distant metastasis after surgery but no disease-related death occurred. Conclusions: Most of small NF-PNETs do not increase in the size and seldom show metastasis during follow-up. Wait-and-see strategy can be applied for NF-PNETs less than 2cm in size.
In drug-induced, immune-mediated hepatitis, interleukin-33 reduces hepatitis and improves survival independently and as a consequence of FoxP3+ T-cell activity
Authors: Merylin Cottagiri, Maeva Nyandjo, Matthew Stephens, Joel J. Mantilla, Hirohisa Saito, Ian R. Mackay, Noel R. Rose, Dolores B. Njoku
Journal: Cellular and Molecular Immunology (2018)
A Suspect Screening Method for Characterizing Multiple Chemical Exposures among a Demographically Diverse Population of Pregnant Women in San Francisco
Authors: Aolin Wang, Roy R. Gerona, Jackie M. Schwartz, Thomas Lin, Marina Sirota, Rachel Morello-Frosch, Tracey J. Woodruff
Journal: Environmental Health Perspectives (2018)

Background: In utero exposure to environmental chemicals can adversely impact pregnancy outcomes and childhood health, but minimal biomonitoring data exist on the majority of chemicals used in commerce. Objectives: We aimed to profile exposure to multiple environmental organic acids (EOAs) and identify novel chemicals that have not been previously biomonitored in a diverse population of pregnant women. Methods: We used liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) to perform a suspect screen for 696 EOAs, (e.g., phenols and phthalate metabolites) on the maternal serum collected at delivery from 75 pregnant women delivering at two large San Francisco Hospitals. We examined demographic differences in peak areas and detection frequency (DF) of suspect EOAs using a Kruskal-Wallis Rank Sum test or Fisher's exact test. We confirmed selected suspects by comparison with their respective reference standards. Results: We detected, on average, 56 [standard deviation (SD)]: 8) suspect EOAs in each sample (range: 32–73). Twelve suspect EOAs with DF≥ 60 were matched to 21 candidate compounds in our EOA database, two-thirds of which are novel chemicals. We found demographic differences in DF for 13 suspect EOAs and confirmed the presence of 6 priority novel chemicals: 2,4-Di-tert-butylphenol, Pyrocatechol, 2,4-Dinitrophenol, 3,5-Di-tert-butylsalicylic acid, 4-Hydroxycoumarin, and 2′-Hydroxyacetophenone (or 3′-Hydroxyacetophenone). The first two are high-production-volume chemicals in the United States. Conclusion: Suspect screening in human biomonitoring provides a viable method to characterize a broad spectrum of environmental chemicals to prioritize for targeted method development and quantification. https://doi.org/10.1289/EHP2920
Outbreak of vancomycin-resistant Enterococcus faecium clone ST796, Switzerland, December 2017 to April 2018
Authors: Nasstasja Wassilew, Helena MB Seth-Smith, Eveline Rolli, Yvonne Fietze, Carlo Casanova, Urs Führer, Adrian Egli, Jonas Marschall, Niccolò Buetti
Journal: Eurosurveillance (2018)

A large outbreak of vancomycin-resistant enterococci (VRE) is affecting four hospitals in the Canton of Bern, Switzerland, since December 2017. Of 89 cases identified as carriers, 77 (86.5%) VRE isolates were virtually indistinguishable using whole genome sequencing, and identified as multilocus sequence type (MLST) ST796. This clone, previously only described in Australia and New Zealand, is characterised by rapid spread and the ability to cause bloodstream infections. It requires a multifaceted infection prevention effort.
High-Resolution Contrast-Enhanced Micro-Computed Tomography to Identify the Cardiac Conduction System in Congenitally Malformed Hearts
Authors: Robert S. Stephenson, Caroline B. Jones, Rafael Guerrero, Jichao Zhao, Robert H. Anderson, Jonathan C. Jarvis
Journal: JACC. Cardiovascular imaging (2018)

MALFORMEDhearts from the Alder Hey archive,
New Zealand Obese Mice as a Translational Model of Obesity-related Obstructive Sleep Apnea Syndrome
Authors: David Marcel Baum, Blanca Morales Rodriguez, Valérie Attali, Margaux Cauhapé, Isabelle Arnulf, Philippe Cardot, Laurence Bodineau, Marie-Noëlle Fiamma
Journal: American Journal of Respiratory and Critical Care Medicine (2018)
Strengthening the capabilities of families and communities to improve child health in low and middle income countries
Authors: Audrey Prost, David Sanders, Anthony Costello, Joanna Vogel, Abdullah H Baqui, Nirmala Nair, Magali Romedenne, Ketan Chitnis, Geoffrey Bisoborwa, Tanya Doherty
Journal: BMJ (2018)

Audrey Prost and colleagues discuss how best to enable families and communities to improve child health The concept of community involvement in delivery of healthcare gained prominence after the 1978 Alma Ata conference on primary care.1 Many countries established large scale community health worker programmes with paid or voluntary workers to provide preventive, promotive, and curative care focusing on women and children. During the millennium development goal period, the HIV/AIDS epidemic in sub-Saharan Africa, combined with generalised shortages of skilled health personnel in low and middle income countries,2 increased the need for health workers. This resulted in persistently low coverage of high impact interventions for children and growing equity gaps within and between countries.3 The involvement of families and communities has emerged as important for increasing access to health services, particularly for those in rural and hard to reach areas.4 Health providers can support families to provide adequate home care for children's healthy growth and development. Families also need to be able to respond appropriately when children are sick, seek appropriate timely assistance, and follow recommended treatments. The global Integrated Management of Childhood Illness (IMCI) strategy was launched by WHO and Unicef in 1997. It included a component focusing on communities, known as community IMCI or C-IMCI. This component advocated 16 key family practices to improve maternal and child health (box 1). These were expanded to provide detailed recommendations in the Facts for life booklet.5 However, implementation has been uneven.67 Box 1 ### Key family practices for improving child health and nutrition #### For physical growth and mental developmentRETURN TO TEXT
Mortality attributable to hot and cold ambient temperatures in India: a nationally representative case-crossover study
Authors: Sze Hang Fu, Antonio Gasparrini, Peter S. Rodriguez, Prabhat Jha
Journal: PLoS Medicine (2018)

Background Most of the epidemiological studies that have examined the detrimental effects of ambient hot and cold temperatures on human health have been conducted in high-income countries. In India, the limited evidence on temperature and health risks has focused mostly on the effects of heat waves and has mostly been from small scale studies. Here, we quantify heat and cold effects on mortality in India using a nationally representative study of the causes of death and daily temperature data for 2001–2013. Methods and findings We applied distributed-lag nonlinear models with case-crossover models to assess the effects of heat and cold on all medical causes of death for all ages from birth (n = 411,613) as well as on stroke (n = 19,753), ischaemic heart disease (IHD) (n = 40,003), and respiratory diseases (n = 23,595) among adults aged 30–69. We calculated the attributable risk fractions by mortality cause for extremely cold (0.4 to 13.8°C), moderately cold (13.8°C to cause-specific minimum mortality temperatures), moderately hot (cause-specific minimum mortality temperatures to 34.2°C), and extremely hot temperatures (34.2 to 39.7°C). We further calculated the temperature-attributable deaths using the United Nations' death estimates for India in 2015. Mortality from all medical causes, stroke, and respiratory diseases showed excess risks at moderately cold temperature and hot temperature. For all examined causes, moderately cold temperature was estimated to have higher attributable risks (6.3% [95% empirical confidence interval (eCI) 1.1 to 11.1] for all medical deaths, 27.2% [11.4 to 40.2] for stroke, 9.7% [3.7 to 15.3] for IHD, and 6.5% [3.5 to 9.2] for respiratory diseases) than extremely cold, moderately hot, and extremely hot temperatures. In 2015, 197,000 (121,000 to 259,000) deaths from stroke, IHD, and respiratory diseases at ages 30–69 years were attributable to moderately cold temperature, which was 12- and 42-fold higher than totals from extremely cold and extremely hot temperature, respectively. The main limitation of this study was the coarse spatial resolution of the temperature data, which may mask microclimate effects. Conclusions Public health interventions to mitigate temperature effects need to focus not only on extremely hot temperatures but also moderately cold temperatures. Future absolute totals of temperature-related deaths are likely to depend on the large absolute numbers of people exposed to both extremely hot and moderately cold temperatures. Similar large-scale and nationally representative studies are required in other low- and middle-income countries to better understand the impact of future temperature changes on cause-specific mortality.
Abstract 18200: Sortilin Levels Correlated With Renal Function and Reduced by Strong Statins With Increased PCSK9 in Primary Dyslipidemia
Authors: Atsushi Nohara, Masa-aki Kawashiri, Hayato Tada, Hiroaki Hattori, Tadao Iwasaki, Mie Yoshida, Mika Mori, Chiaki Nakanishi, Kunimasa Yagi, Akihiro Inazu, Masakazu Yamagishi, Hiroshi Mabuchi
Journal: Circulation (2016)

Sortilin is encoded by the well-known cardiovascular risk gene SORT1, however Sortilin seems to modulate cardiovascular disease not only with lipids, and its function has not been well elucidated. ...