Influence of elevated-CRP level-related polymorphisms in non-rheumatic Caucasians on the risk of subclinical atherosclerosis and cardiovascular disease in rheumatoid arthritis

Association between elevated C-reactive protein (CRP) serum levels and subclinical atherosclerosis and cardiovascular (CV) events was described in rheumatoid arthritis (RA). CRP, HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 exert an influence on elevated CRP serum levels in non-rheumatic Caucasians. Consequently, we evaluated the potential role of these genes in the development of CV events and subclinical atherosclerosis in RA patients. Three tag CRP polymorphisms and HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 were genotyped in 2,313 Spanish patients by TaqMan. Subclinical atherosclerosis was determined in 1,298 of them by carotid ultrasonography (by assessment of carotid intima-media thickness-cIMT-and presence/absence of carotid plaques). CRP serum levels at diagnosis and at the time of carotid ultrasonography were measured in 1,662 and 1,193 patients, respectively, by immunoturbidimetry. Interestingly, a relationship between CRP and CRP serum levels at diagnosis and at the time of the carotid ultrasonography was disclosed. However, no statistically significant differences were found when CRP, HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 were evaluated according to the presence/absence of CV events, carotid plaques and cIMT after adjustment. Our results do not confirm an association between these genes and CV disease in RA

SMAD3 rs17228212 Gene Polymorphism Is Associated with Reduced Risk to Cerebrovascular Accidents and Subclinical Atherosclerosis in Anti-CCP Negative Spanish Rheumatoid Arthritis Patients

Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis and increased risk of cardiovascular (CV) disease. Previous genome-wide association studies have described SMAD3 rs17228212 polymorphism as an important signal associated with CV events. The aim of the present study was to evaluate for the first time the relationship between this gene polymorphism and the susceptibility to CV manifestations and its potential association with the presence of subclinical atherosclerosis assessed by the evaluation of carotid intima-media thickness (cIMT) in patients with RA

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Low Physical Activity and Its Association with Diabetes and Other Cardiovascular Risk Factors: A Nationwide, Population-Based Study.

Low physical activity (PA), or sedentary lifestyle, is associated with the development of several chronic diseases. We aimed to investigate current prevalence of sedentariness and its association with diabetes and other cardiovascular risk factors. PA was evaluated in a population-based, cross-sectional, randomly sampled study conducted in 2009-2010 in Spain. International Physical Activity Questionnaire (SF-IPAQ) was used to assess PA. 4991 individuals (median age 50 years, 57% women) were studied. Prevalence of sedentariness was 32.3% for men and 39% for women (p < 0.0001). Sex differences were particularly notable (age*sex interaction, p = 0.0024) at early and older ages. Sedentary individuals had higher BMI (28 vs. 27 kg/m2) and obesity prevalence (37 vs. 26%). Low PA was present in 44, 43, and 38% of individuals with known diabetes (KDM), prediabetes/unknown-diabetes (PREDM/UKDM), and normal glucose regulation (p = 0.0014), respectively. No difference between KDM and PREDM/UKDM (p = 0.72) was found. Variables independently associated (p < 0.05) with sedentariness were age, sex, BMI, central obesity, Mediterranean diet adherence, smoking habit, HDL-cholesterol, triglycerides and dyslipidemia. Low PA is on the rise in Spain, especially among women. Sedentariness is associated with several cardiovascular risk factors and may be responsible for the increasing prevalence of obesity and diabetes in this country.This work was supported by the Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM; ISCIII Ministerio de Ciencia e Innovación), Ministerio de Sanidad y Consumo and the Spanish Diabetes Society (SED)

Patients with Crohn's disease have longer post-operative in-hospital stay than patients with colon cancer but no difference in complications' rate

BACKGROUNDRight hemicolectomy or ileocecal resection are used to treat benign conditions like Crohn's disease (CD) and malignant ones like colon cancer (CC).AIMTo investigate differences in pre- and peri-operative factors and their impact on post-operative outcome in patients with CC and CD.METHODSThis is a sub-group analysis of the European Society of Coloproctology's prospective, multi-centre snapshot audit. Adult patients with CC and CD undergoing right hemicolectomy or ileocecal resection were included. Primary outcome measure was 30-d post-operative complications. Secondary outcome measures were post-operative length of stay (LOS) at and readmission.RESULTSThree hundred and seventy-five patients with CD and 2,515 patients with CC were included. Patients with CD were younger (median = 37 years for CD and 71 years for CC (P &lt; 0.01), had lower American Society of Anesthesiology score (ASA) grade (P &lt; 0.01) and less comorbidity (P &lt; 0.01), but were more likely to be current smokers (P &lt; 0.01). Patients with CD were more frequently operated on by colorectal surgeons (P &lt; 0.01) and frequently underwent ileocecal resection (P &lt; 0.01) with higher rate of de-functioning/primary stoma construction (P &lt; 0.01). Thirty-day post-operative mortality occurred exclusively in the CC group (66/2515, 2.3%). In multivariate analyses, the risk of post-operative complications was similar in the two groups (OR 0.80, 95%CI: 0.54-1.17; P = 0.25). Patients with CD had a significantly longer LOS (Geometric mean 0.87, 95%CI: 0.79-0.95; P &lt; 0.01). There was no difference in re-admission rates. The audit did not collect data on post-operative enhanced recovery protocols that are implemented in the different participating centers.CONCLUSIONPatients with CD were younger, with lower ASA grade, less comorbidity, operated on by experienced surgeons and underwent less radical resection but had a longer LOS than patients with CC although complication's rate was not different between the two groups

Distribution of introduced and native fish in Patagonia (Argentina): patterns and changes in fish assemblages

The interaction between native fishes and salmonids introduced in Patagonia at the beginning of the 20th Century, developed at the same time as the environmental change. The phenomenon of global warming has led to the formulation of predictions in relation to changes in the distribution of species, in the latitudinal dimension, both at intralacustrine, or small streams levels. The aim of the present work includes three main objectives: a) to compose a general and updated picture of the latitudinal distribution range of native and alien fishes, b) to analyze the historical changes in the relative abundance of Percichthys trucha, Odontesthes sp., and salmonids in lakes and reservoirs, and c) to relate the diversity and relative abundance of native and salmonid fishes to the environmental variables of lakes and reservoirs. We analysed previous records and an ensemble of data about new locations along the northern border of the Patagonian Province. We compared current data about the relative abundance of native fishes and salmonids in lakes and reservoirs, with previous databases (1984–1987). All samplings considered were performed during spring-summer surveys and include relative abundance, as proportions of salmonids, P. trucha, and Odontesthes sp. For the first time, we found changes in fish assemblages from twenty years back up to the present: a significant decline in the relative abundances of salmonids and an increase of P. trucha. We studied the association between the diversity and relative abundance of native and salmonid fishes and the environmental variables of lakes and reservoirs using Canonical Correspondence Analysis. Relative abundance showed mainly geographical cues and the diversity relied largely on morphometric characteristics. Relative abundance and diversity seem to have a common point in the lake area, included into the PAR concept. Native abundance and alien diversity were negatively related with latitude. Greater native diversity was observed in lakes with high PAR compared with salmonids. Historical changes such as southward dispersion, relative abundance changes, and geographical patterns for relative abundance and diversity are basic concepts needed not only in future research but also in management design for Patagonian fish populations.Facultad de Ciencias Naturales y Muse

BRCA1 and BRCA2 mutations in males with familial breast and ovarian cancer syndrome. Results of a Spanish multicenter study

Producción CientíficaMale breast cancer (MBC) is a rare disease that represents <1 % of all breast cancers (BCs). We analyze the results of a multicenter study performed in Spanish familial MBC including family history of hereditary breast and ovarian cancer syndrome (HBOCS) and clinicopathological features. We also study the relationship between BRCA1/BRCA2 mutational status in male relatives affected with cancer (MAC) and, family history and tumor types. The study included 312 men index cases with family history of HBOCS and 61 MAC BRCA1/2 mutation-carriers. Family history, histological grade (HG), clinicopathological and immunohistochemistry data were collected. BRCA1/2 mutation analyses were performed by direct sequencing or screening methods and the large rearrangements by multiplex ligation dependent probe amplification. We found 49 mutation-carriers (15.7 %), 95.9 % with BRCA2 mutations. BRCA2 mutation-carriers were associated with families with at least one MBC and one BC in female (type II; p = 0.05). Strong association were found between the presence of pathogenic mutations in MBCs and the advanced HG (p = 0.003). c.658_659delTG, c.2808_2811delACAA, c.6275_6276delTT and c.9026_9030delATCAT were the most prevalent mutations. In 61 MAC we found 20 mutations in BRCA1 and 41 in BRCA2. For MAC we show that mutational status was differentially associated with family history (p = 0.018) and tumor type, being BRCA2 mutations linked with BC and prostatic cancer (p = 0.018). MBC caused by BRCA1/2 mutations define two types of MBCs. The most frequent caused by BRCA2 mutation linked to type II families and the rarest one attributed to BRCA1 mutation. Tumor associated with MAC suggest that only BRCA2 mutations have to do with a specific type of cancer (BC and prostatic cancer); but the linkage to tumors is questionable for BRCA1 mutations

Rare variants in calcium homeostasis modulator 1 (CALHM1) found in early onset alzheimer's disease patients alter calcium homeostasis

Calcium signaling in the brain is fundamental to the learning and memory process and there is evidence to suggest that its dysfunction is involved in the pathological pathways underlying Alzheimer’s disease (AD). Recently, the calcium hypothesis of AD has received support with the identification of the non-selective Ca2+-permeable channel CALHM1. A genetic polymorphism (p. P86L) in CALHM1 reduces plasma membrane Ca2+ permeability and is associated with an earlier age-at-onset of AD. To investigate the role of CALHM1 variants in early-onset AD (EOAD), we sequenced all CALHM1 coding regions in three independent series comprising 284 EOAD patients and 326 controls. Two missense mutations in patients (p.G330D and p.R154H) and one (p.A213T) in a control individual were identified. Calcium imaging analyses revealed that while the mutation found in a control (p.A213T) behaved as wild-type CALHM1 (CALHM1-WT), a complete abolishment of the Ca2+ influx was associated with the mutations found in EOAD patients (p.G330D and p.R154H). Notably, the previously reported p. P86L mutation was associated with an intermediate Ca2+ influx between the CALHM1-WT and the p.G330D and p.R154H mutations. Since neither expression of wild-type nor mutant CALHM1 affected amyloid ß-peptide (Aß) production or Aß-mediated cellular toxicity, we conclude that rare genetic variants in CALHM1 lead to Ca2+ dysregulation and may contribute to the risk of EOAD through a mechanism independent from the classical Aß cascade.This study was supported by grants from Instituto de Salud Carlos III (PI12/01311, PI10/000587, Red HERACLES RD12/0042/0014), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, Spain), Spanish Ministry of Economy and Competiveness (SAF2012-38140), FEDER Funds, and Generalitat de Catalunya (SGR05-266). Council of the Academy of Finland, EVO grant 5772708 of Kuopio University Hospital, the Strategic Funding of the University on Eastern Finland (UEF-Brain) (to M.H and H.S). M.A.V. is the recipient of an ICREA Academia Awar