Vitamin D supplementation and COVID-19 risk: a population-based, cohort study.

PURPOSE: To analyze the associations between cholecalciferol or calcifediol supplementation, serum 25-hydroxyvitamin D (25OHD) levels and COVID-19 outcomes in a large population. METHODS: All individuals ≥ 18 years old living in Barcelona-Central Catalonia (n = 4.6 million) supplemented with cholecalciferol or calcifediol from April 2019 to February 2020 were compared with propensity score-matched untreated controls. Outcome variables were SARS-CoV2 infection, severe COVID-19 and COVID-19 mortality occuring during the first wave of the pandemic. Demographical data, comorbidities, serum 25OHD levels and concomitant pharmacological treatments were collected as covariates. Associations between cholecalciferol or calcifediol use and outcome variables were analyzed using multivariate Cox proportional regression. RESULTS: Cholecalciferol supplementation (n = 108,343) was associated with slight protection from SARS-CoV2 infection (n = 4352 [4.0%] vs 9142/216,686 [4.2%] in controls; HR 0.95 [CI 95% 0.91-0.98], p = 0.004). Patients on cholecalciferol treatment achieving 25OHD levels ≥ 30 ng/ml had lower risk of SARS-CoV2 infection, lower risk of severe COVID-19 and lower COVID-19 mortality than unsupplemented 25OHD-deficient patients (56/9474 [0.6%] vs 96/7616 [1.3%]; HR 0.66 [CI 95% 0.46-0.93], p = 0.018). Calcifediol use (n = 134,703) was not associated with reduced risk of SARS-CoV2 infection or mortality in the whole cohort. However, patients on calcifediol treatment achieving serum 25OHD levels ≥ 30 ng/ml also had lower risk of SARS-CoV2 infection, lower risk of severe COVID-19, and lower COVID-19 mortality compared to 25OHD-deficient patients not receiving vitamin D supplements (88/16276 [0.5%] vs 96/7616 [1.3%]; HR 0.56 [CI 95% 0.42-0.76], p < 0.001). CONCLUSIONS: In this large, population-based study, we observed that patients supplemented with cholecalciferol or calcifediol achieving serum 25OHD levels ≥ 30 ng/ml were associated with better COVID-19 outcomes.

Carotid atherosclerosis in virologically suppressed HIV patients: comparison with a healthy sample and prediction by cardiovascular risk equations.

OBJECTIVES: To compare the prevalence of carotid atherosclerosis in virologically suppressed HIV patients with that of a community sample, and to evaluate the capacity of various cardiovascular risk (CVR) equations for predicting carotid atherosclerosis. METHODS: This was a cross-sectional study with two randomly selected groups: HIV patients from an HIV unit and a control group drawn from the community. Participants were matched by age (30-80 years) and sex without history of cardiovascular disease. Carotid plaque, common carotid intima-media thickness (cc-IMT) and subclinical atherosclerosis (carotid plaque and/or cc-IMT > 75th percentile) were assessed by carotid ultrasound. The Systematic Coronary Risk Evaluation (SCORE), Framingham, REGICOR, reduced Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D), and COMVIH equations were applied, and their abilities to predict carotid plaque were compared using the area under the curve (AUC). RESULTS: Each group included 379 subjects (77.8% men, age 49.7 years). Duration of antiretroviral therapy was 15.5 years. There were no differences between the groups for carotid plaque (HIV, 33.2%; control, 31.3%), mean cc-IMT (HIV, 0.63 mm; control, 0.61 mm) or subclinical atherosclerosis (HIV, 42.9%; control, 47.9%). Thymidine analogues were independently associated with subclinical atherosclerosis in HIV-infected patients. CVR equations revealed AUCs between 0.715 and 0.807 for prediction of carotid plaque; prediction was better in the control group and did not improve when HIV-adapted scales were used. CONCLUSIONS: The features of carotid atherosclerosis did not differ between the HIV-infected and the control group, although CVR equations were more predictive for carotid plaque in controls than in HIV-infected patients. HIV-specific equations did not improve prediction.

Search for CP-violating nuclear magnetic quadrupole moment using the LuOH+ cation.

The time-reversal and spatial parity violating interaction of the nuclear magnetic quadrupole moment (MQM) of the 175Lu and 176Lu nuclei with electrons in the molecular cation LuOH+ is studied. The resulting effect is expressed in terms of fundamental parameters, such as quantum chromodynamics angle θ¯, quark electric dipole moment (EDM), and chromo-EDM. For this, we have estimated the magnetic quadrupole moments of 175Lu and 176Lu nuclei and calculated the molecular constant that characterizes the interaction of the MQM with electrons in the considered molecules. Additionally, we predict the hyperfine structure constants for the ground electronic state of LuOH+. In the molecular calculations, both the correlation and relativistic effects including the Gaunt interaction have been considered. According to the calculated expressions in terms of the fundamental constants, we conclude that LuOH+ can be a promising system to measure the nuclear MQM.

A comparative study of different surgical techniques for the management of distal ureter during laparoscopic radical nephroureterectomy. / Estudio comparativo de diferentes técnicas quirúrgicas para el manejo del uréter distal durante la nefroureterectomía laparoscópica.

OBJECTIVES: To compare the oncological outcomes between two open surgical techniques and two endoscopic approaches for the management of the distal ureter during laparoscopic radical nephroureterectomy (LRNU). MATERIAL AND METHODS: Retrospective review of 152 patients submitted to LRNU for the management of upper urinary tract tumors between 2007-2014. We analyzed the potential impact of two different open surgical (extravesical vs intravesical) and two endoscopic (resection of ureteral orifice and fragment removal vs endoscopic bladder cuff) techniques on the development of bladder recurrence, distant/local recurrence and cancer-specific survival (CSS). RESULTS: A total of 152 patients with a mean age of 69.9 years (±10.1) underwent LRNU. We reported 62 pTa-T1 (41%), 35 pT2 (23%) and 55 pT3-4 (36%). Thirty-two were low grade (21.1%) and 120 high grade (78.9%). An endoscopic approach was performed in 89 cases (58.5%), 32 with resection (36%) and 57 with bladder cuff (64%), and open approach in 63 (41.5%), 42 intravesical (66.7%) and 21 extravesical (33.3%). Within a median follow-up of 32 months (3-120), 38 patients (25%) developed bladder recurrence, 42 distant/local recurrence (27.6%) and 34 died of tumor (22.4%). In the univariate analysis, the type of endoscopic technique was not related to bladder recurrence (P=.961), distant/local recurrence (P=.955) nor CSS (P=.802). The open extravesical approach was not related to bladder recurrence (P=.12) but increased distant/local recurrence (P=.045) and decreased CSS (P=.034) compared to intravesical approach. CONCLUSIONS: LRNU outcomes are not dependant on the type of endoscopic approach performed. The open extravesical approach is a more difficult technique and could worsen the oncological outcomes when compared to the intravesical.

Office stent placement under local anesthesia is a safe and efficient procedure for the management of multiple ureteral disorders. / La colocación de catéteres doble J con anestesia local en régimen ambulatorio es un procedimiento seguro y eficiente para el manejo de distintas patologías ureterales.

OBJECTIVE: To assess the outcomes of ureteral stent placement under local anesthesia for the management of multiple ureteral disorders. METHODS: Retrospective study of 45 consecutive ureteral stents placed under local anesthesia from January 2015 to July 2016. Inclusion criteria were hemodynamically stable patients with urinary obstruction, urinary fistula or for prophylactic ureteral localization during surgery. Five minutes before the procedure, 10ml of lidocaine gel and 50ml of lidocaine solution were instilled in the bladder. A 4.8Fr ureteral stent was placed using a 15.5Fr flexible cystoscope under fluoroscopic control. Characteristics of procedures and outcomes were analysed. RESULTS: A total of 45 procedures (33 placement, 12 replacements) were attempted in 37 patients, of which 40 (89%) were successful. There were 10 male (27%) and 27 female patients (73%) with a mean age of 58.6 years (±17.5). Main indications for stent placement were stones (37.8%), extrinsic ureteral compression (28.9%) and surgery ureteral localization (22.2%). The reasons for failing to complete a procedure were the inability to pass the guidewire/stent in 4 cases (8.8%) or to identify the ureteral orifice in 1 (2.2%). Postoperative complications occurred in 8 patients (17.8%) (7 Clavien I, 1 Clavien IIIa). No procedure was prematurely terminated due to pain. Statistical analysis did not find significant successful predictors. The outpatient setting provided a fourfold cost decrease. CONCLUSIONS: Ureteral stent placement can be safely and effectively performed under local anesthesia in the office cystoscopy room. This procedure could free operating room time, reduce costs and minimize side effects of general anesthesia.

Abnormally High Ankle-Brachial Index is Associated with All-cause and Cardiovascular Mortality: The REGICOR Study.

INTRODUCTION: The clinical significance of a high ankle brachial index (ABI) and its relationship to cardiovascular disease (CVD) and mortality is controversial. The aim of this study was to estimate the association between abnormally high ABI ≥ 1.4 and coronary heart disease (CHD), cerebrovascular disease, and all-cause mortality in a Mediterranean population without CVD. METHODS: A prospective population based cohort study of 6352 subjects was followed up for a median 6.2 years. Subjects under 35 years, with a history of CVD or an ABI < 0.9 were excluded. All CHD events (angina, myocardial infarction, coronary revascularisation), cerebrovascular events (stroke, transient ischaemic attack), and all-cause mortality were recorded. RESULTS: A total of 5679 subjects fulfilled the inclusion criteria, of which 5517 (97.1%) had a normal ABI whereas 162 (2.9%) had an ABI ≥ 1.4. The profile of individuals with abnormally high ABI revealed as independent related factors age (OR = 1.0; p = .045), female sex (OR = 0.4; p < .01), diabetes (OR = 1.9; p = .02), and lower diastolic blood pressure (OR = 0.9; p < .001). During follow-up 309 (5.4%) participants presented with a CV event and 286 (5.0%) died. An ABI ≥ 1.4 was associated with a higher incidence of CV events in the univariate (HR = 1.7) but not in the multivariate survival Cox regression analysis. An ABI ≥ 1.4 was independently associated with all-cause mortality (HR = 2.0; IC 95% 1.32-2.92) and cardiovascular mortality (HR = 3.1; IC 95% 1.52-6.48). CONCLUSIONS: In subjects without CVD, those with abnormally high ABI do not have a greater CV event rate than those with a normal ABI. However, there seems to be a trend towards higher mortality risk, supporting the guidelines that consider this subgroup to be a high risk population.

Edible Nanoemulsions as Carriers of Active Ingredients: A Review.

There has been growing interest in the use of edible nanoemulsions as delivery systems for lipophilic active substances, such as oil-soluble vitamins, antimicrobials, flavors, and nutraceuticals, because of their unique physicochemical properties. Oil-in-water nanoemulsions consist of oil droplets with diameters typically between approximately 30 and 200 nm that are dispersed within an aqueous medium. The small droplet size usually leads to an improvement in stability, gravitational separation, and aggregation. Moreover, the high droplet surface area associated with the small droplet size often leads to a high reactivity with biological cells and macromolecules. As a result, lipid digestibility and bioactive bioavailability are usually higher in nanoemulsions than conventional emulsions, which is an advantage for the development of bioactive delivery systems. In this review, the most important factors affecting nanoemulsion formation and stability are highlighted, and a critical analysis of the potential benefits of using nanoemulsions in food systems is presented.

Short communication: Progressive motility of frozen-thawed canine semen is highest five minutes after thawing.

Progressive motility is usually estimated by visual inspection using a light contrast microscope at X 100 immediately after semen collection or immediately after thawing frozen semen. Standard operating procedures have never been established for this test. The objective of this experiment was to examine time-dependent changes of motility after thawing cryopreserved canine semen. Semen of 35 dogs was collected, and volume, concentration, progressive motility, morphology, membrane integrity and HOS test were evaluated. For cryopreservation, CaniPRO® Freeze A&B was used. Semen was thawed and diluted using CaniPRO® culture medium. After thawing, semen was evaluated as before. In addition, every sample was evaluated for progressively motile sperm cells 0, 5, 20 and 60 min after thawing. Progressive semen motility was significantly highest five minutes after thawing.

People with epilepsy receive more statins than the general population but have no higher cardiovascular risk: results from a cross-sectional study.

BACKGROUND AND PURPOSE: Epilepsy has been associated with cardiovascular comorbidity. Risk prediction equations are the standard tools in primary prevention of cardiovascular disease. Our aim was to compare the prevalence of cardiovascular risk factors (CVRFs), cardiovascular risk and statin use in people with epilepsy (PWE) and the general population. METHODS: The CVRFs and cardiovascular risk score were compared between 815 PWE from an outpatient register and 5336 participants from a general population cohort. RESULTS: People with epilepsy had less hypertension (43.3% vs. 50.4%), less diabetes (15.8% vs. 19.2%), more dyslipidemia (40.2% vs. 34.6%) and lower cardiovascular risk than the general population (P < 0.01). No etiology was associated with a worse CVRF profile or higher cardiovascular risk. Patients taking enzyme-inducing antiepileptic drugs (EIAEDs) had more dyslipidemia than the general population (41.6% vs. 34.6%) but similar cardiovascular risk. Independently of risk or CVRFs, PWE had 60% more probability of receiving statins than the general population. CONCLUSIONS: People with epilepsy had more dyslipidemia, related to EIAEDs, and lower cardiovascular risk but still took more statins than the general population. Physicians should use clinical judgement to decide on further treatment of CVRFs in PWE who are below the recommended risk threshold for treatment and should consider lipid abnormalities a potential side-effect of EIAEDs. Other therapy options may need to be evaluated before starting lipid-lowering treatment.

Application of impedance spectroscopy for the characterization of hams during post-salting / Aplicación de la espectroscopia de impedancia para la caracterización de jamones durante el post-salado

Background: The smart control for food and feed technologies consist in the development of new methods that facilitate the control of productive processes guaranteeing the quality and safety of agrofood products. The importance given to this research line is a clear indicator of the interest of all of the agents implicated in promoting the introduction of innovative technologies. The goal is to implement new, fast, economical, analytical techniques, which constitute a real alternative to traditional control procedures. Objective: The aim of this study was to evaluate the use of an electronic sensor based on the impedance spectroscopy technique for the characterization of hams during the post-salting step (8, 10, 12 and 14 weeks). Materials and methods: 60 hams from three different categories (fat, semi-fat and lean), were tray salted under the conditions of a company (xNaCl = 0.11 g/g dry matter). For each time, samples were first evaluated with the electronic method (non-destructive analysis) and then analytical determinations of: mass variation, moisture content, fat content, salt content and water activity were performed on each ham in different zones. The electric data were evaluated using Principal Component Analysis (PCA) and regression with Partial Least Squares (PLS) through the analytical data. Results: The PCA analysis discriminated between the different evaluated zones. At eighth week 79.06% of the variance was explained and at tenth week, the 82.53%. No relation was observed for the different ham categories. The correlation between the impedance signal and the analytical determinations showed the best cross validation coefficient (R2CV) values for moisture content (0.75) and water activity (0.73). Conclusions: The impedance spectroscopy technique generated different signals between the zones of analysis during the first two post-salting times, eight and ten weeks, in which physicochemical differences were also observed as a consequence of the variation in the salt concentration between zones.

Antecedentes: El control inteligente de los alimentos y las tecnologías alimentarias, consiste en el desarrollo de nuevos métodos que facilitan el control de los procesos productivos y garantizan la calidad y seguridad de los productos agroalimentarios. La relevancia concedida a esta línea de investigación es un claro indicador del interés de todos los agentes implicados en impulsar la introducción de tecnologías innovadoras. La meta es implementar nuevas técnicas analíticas rápidas y económicas, que constituyan una alternativa real a los procedimientos tradicionales de control. Objetivo: Evaluar el uso de un sensor electrónico basado en la técnica de la espectroscopia de impedancia para la caracterización de jamones durante el post-salado (8, 10, 12 y 14 semanas). Materiales y métodos: 60 jamones de tres categorías diferentes (grasa, semigrasa y magra) fueron salados en bandeja bajo las condiciones de una empresa (xNaCl = 0.11 g/g base seca). A cada tiempo establecido, las muestras seleccionadas se evaluaron utilizando el método electrónico (análisis no destructivo) y se realizaron determinaciones analíticas de: variación de masa, contenido de humedad, contenido de grasa, contenido de sal y actividad de agua, en diferentes zonas de la muestra. La información electrónica se analizó mediante análisis de componentes principales (PCA) y correlaciones (PLS) entre la señal de impedancia y las determinaciones analíticas. Resultados: El análisis de PCA discriminó entre las diferentes zonas de análisis evaluadas. A la octava semana se explicó un 79.06% de la varianza de las muestras y a la décima, un 82.53%. No hubo relación entre las diferentes categorías de jamones. La correlación estadística de la señal de impedancia con las determinaciones analíticas mostró los mejores valores de coeficiente de validación cruzada (R2CV) para el contenido de humedad (0.75) y la actividad de agua (0.73). Conclusiones: La técnica de espectroscopia de impedancia generó señales diferentes entre las zonas de análisis durante los dos primeros tiempos de post-salado, ocho y diez semanas, en los que también se observaron diferencias fisicoquímicas como consecuencia de la variación en la concentración salina entre zonas.

Prognostic value of a pre-freeze hypo-osmotic swelling test on the post-thaw quality of dog semen.

Throughout cryopreservation, sperm are exposed to major osmotic challenges. Only intact membranes of sperm cells are able to regulate these volumetric changes, which can be determined by the hypo-osmotic swelling test (HOS test). Correlations between the HOS test and conventional semen variables are inconsistent. Therefore, the objectives of this study were (1) to examine relationships between HOS test results and standard semen variables before freezing and after thawing and (2) to evaluate the prognostic value of the HOS assessments on post-thaw quality of dog semen. Semen of 35 dogs was collected and analyzed before freezing and after thawing following a 7-day freeze-thaw interval. Conventional semen variables such as sperm cell motility, membrane integrity morphology were evaluated and the HOS test was conducted with results from this test being recorded. In fresh semen the HOS test was positively correlated with progressive motility of sperm cells: r=0.52, sperm cell membrane integrity: r=0.50 and normal sperm cell morphology: r=0.46 (P<0.05). In frozen-thawed semen, the data obtained with the HOS test were positively correlated with progressive sperm cell motility: r=0.67 and membrane integrity: r=0.86 (P<0.05). The data obtained with the HOS test in fresh semen were positively correlated with sperm cell membrane integrity: r=0.50 normal sperm cell morphology: r=0.55 and data from the HOS test (r=0.43; P<0.05) with frozen-thawed semen. For the prediction of individual cryopreservation capacity, results from assessment of the fresh semen variables of good and poor semen quality were statistically compared. Based on these results, it is not possible to predict the quality of frozen-thawed dog semen using the HOS test.

Peripheral Arterial Disease Incidence and Associated Risk Factors in a Mediterranean Population-based Cohort. The REGICOR Study.

OBJECTIVES: The reported incidence of lower extremity peripheral arterial disease (PAD) in Western countries ranges between 530 and 2,380 per 100,000 person years. The aims of this study were to determine the incidence of PAD and identify associated risk factors in a Mediterranean population. METHODS: Cardiovascular risk factors, the Edinburgh questionnaire, and ankle brachial index (ABI) were collected from 5,434 individuals, aged 35-79 years, from a population based cohort study at baseline and after a mean of 5.7 years follow up. PAD was defined as ABI <0.9 or a clinical diagnosis during follow up. Logistic and regression tree analyses were used to identify factors associated with PAD. RESULTS: In total, 118 new cases of confirmed PAD were identified. The cumulative population incidence rate of PAD was 377 cases per 100,000 person years. For symptomatic PAD, this figure was 102 per 100,000 person years. The most important risk factors for PAD were current (OR 2.30; 95% CI 1.27-4.16) or former smoking (OR 2.02; 95% CI 1.19-3.43), diabetes (OR 1.78; 95% CI 1.17-2.72), age (OR 1.04; 95% CI 1.02-1.07), history of cardiovascular disease (OR 2.06; 95% CI 1.22-3.51), triglycerides level (OR 1.56; 95% CI 1.07-2.29), and systolic blood pressure (OR 1.02; 95% CI 1.01-1.03). In the population ≤65 years the most relevant risk factor was diabetes, whereas in those >65 years smoking was the leading factor. Long-term uncontrolled diabetes was the strongest risk factor for PAD (OR 10.14; 95% CI 3.57-28.79). CONCLUSION: The incidence of lower extremity PAD is lower in the Mediterranean area than has been reported for other areas. The data suggest that patients with long-term uncontrolled diabetes and former and current smokers older than 65 years should be considered for PAD screening.

Effects of Wearing Compression Stockings on the Physical Performance of T2DM Men with MetS.

Metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) are associated with macro- and microcirculatory complications that reduce physical performance. Wearing compression garments to potentially optimize hemodynamics has been discussed. This study investigates the effects of wearing compression stockings on physical performance-related variables in type 2 diabetic men with metabolic syndrome (n=9, 57±12 years, BMI: 36±4 kg/m(2)). Participants served as their own controls in a randomized 3*3 crossover study wearing below-knee stockings with either compression (24 or 30 mmHg ankle pressure) or no compression. Venous pooling and lower limb oxygenation profiles were determined with near-infrared spectroscopy and arterial oxygen saturation was determined using a pulse oxymeter. Measurements were performed in the supine lying position, during standing, following 10 tiptoe exercises and after submaximal intensity cycling. In addition, lactate and erythrocyte deformability were analyzed in capillary blood pre- and post-exercise. Erythrocyte deformability was analyzed using a laser-assisted optical rotational red cell analyzer. No significant differences in any variables when wearing different compression or regular stockings were evident at any point of measurement. This study did not reveal any beneficial effects of wearing compression stockings at rest and during acute bouts of moderately intense exercise in this particular patient group.

Oncogenic CARMA1 couples NF-κB and ß-catenin signaling in diffuse large B-cell lymphomas.

Constitutive activation of the antiapoptotic nuclear factor-κB (NF-κB) signaling pathway is a hallmark of the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphomas (DLBCL). Recurrent oncogenic mutations are found in the scaffold protein CARMA1 (CARD11) that connects B-cell receptor (BCR) signaling to the canonical NF-κB pathway. We asked how far additional downstream processes are activated and contribute to the oncogenic potential of DLBCL-derived CARMA1 mutants. To this end, we expressed oncogenic CARMA1 in the NF-κB negative DLBCL lymphoma cell line BJAB. By a proteomic approach we identified recruitment of ß-catenin and its destruction complex consisting of APC, AXIN1, CK1α and GSK3ß to oncogenic CARMA1. Recruitment of the ß-catenin destruction complex was independent of CARMA1-BCL10-MALT1 complex formation or constitutive NF-κB activation and promoted the stabilization of ß-catenin. The ß-catenin destruction complex was also recruited to CARMA1 in ABC DLBCL cell lines, which coincided with elevated ß-catenin expression. In line, ß-catenin was frequently detected in non-GCB DLBCL biopsies that rely on chronic BCR signaling. Increased ß-catenin amounts alone were not sufficient to induce classical WNT target gene signatures, but could augment TCF/LEF-dependent transcriptional activation in response to WNT signaling. In conjunction with NF-κB, ß-catenin enhanced expression of immunosuppressive interleukin-10 and suppressed antitumoral CCL3, indicating that ß-catenin can induce a favorable tumor microenvironment. Thus, parallel activation of NF-κB and ß-catenin signaling by gain-of-function mutations in CARMA1 augments WNT stimulation and is required for regulating the expression of distinct NF-κB target genes to trigger cell-intrinsic and extrinsic processes that promote DLBCL lymphomagenesis.

Endurance training alters enzymatic and rheological properties of red blood cells (RBC) in type 2 diabetic men during in vivo RBC aging.

This study examines the effects of endurance training on red blood cells (RBC) in seventeen non-insulin-dependent type 2 diabetic men with a special focus on in vivo RBC aging. Venous blood was collected pre- and post-training at rest. RBC from whole blood and RBC separated according to cell age by density-gradient centrifugation were analyzed. RBC deformability was measured by ektacytometry. Immunohistochemical staining was performed to quantify the RBC-nitric oxide (NO) synthase activation (RBC-NOSSer1177) because RBC-NOS-produced NO can contribute to increased RBC deformability. The proportion of "young" RBC was significantly higher post-training. RBC deformability of all RBC (RBC of all ages) remained unaltered post-training. During RBC aging, RBC deformability decreased in both pre- and post-training. However, the training significantly increased RBC deformability in "young" and reduced their deformability in aging RBC. RBC-NOS activation remained unaltered in all RBC post-training. It tendentially increased in aging RBC pre-training, but did not change during aging post-training. The training significantly reduced RBC-NOS activation in "old" RBC. Endurance training may improve the RBC system (higher amount of "young" RBC which are more deformable). It remains speculative whether changes in older RBC (reduced RBC-NOS activation and deformability) could lead to more rapid elimination of aged RBC.

Registry of the Spanish Network for Systemic Sclerosis: Survival, Prognostic Factors, and Causes of Death.

Systemic sclerosis (SSc) is a rare, multisystem disease showing a large individual variability in disease progression and prognosis. In the present study, we assess survival, causes of death, and risk factors of mortality in a large series of Spanish SSc patients. Consecutive SSc patients fulfilling criteria of the classification by LeRoy were recruited in the survey. Kaplan-Meier and Cox proportional-hazards models were used to analyze survival and to identify predictors of mortality. Among 879 consecutive patients, 138 (15.7%) deaths were registered. Seventy-six out of 138 (55%) deceased patients were due to causes attributed to SSc, and pulmonary hypertension (PH) was the leading cause in 23 (16.6%) patients. Survival rates were 96%, 93%, 83%, and 73% at 5, 10, 20, and 30 years after the first symptom, respectively. Survival rates for diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc were 91%, 86%, 64%, and 39%; and 97%, 95%, 85%, and 81% at 5, 10, 20, and 30 years, respectively (log-rank: 67.63, P < 0.0001). The dcSSc subset, male sex, age at disease onset older than 65 years, digital ulcers, interstitial lung disease (ILD), PH, heart involvement, scleroderma renal crisis (SRC), presence of antitopoisomerase I and absence of anticentromere antibodies, and active capillaroscopic pattern showed reduced survival rate. In a multivariate analysis, older age at disease onset, dcSSc, ILD, PH, and SRC were independent risk factors for mortality. In the present study involving a large cohort of SSc patients, a high prevalence of disease-related causes of death was demonstrated. Older age at disease onset, dcSSc, ILD, PH, and SRC were identified as independent prognostic factors.

Adding low ankle brachial index to classical risk factors improves the prediction of major cardiovascular events. The REGICOR study.

OBJECTIVES: Cardiovascular risk estimation is a key element of current primary prevention strategies, despite its limited accuracy. Several biomarkers are being tested to assess their capacity to improve coronary (CHD) and cardiovascular (CVD) prediction. One of these biomarkers is ankle brachial index (ABI). The aim of this study was to assess whether the inclusion of ABI improved the predictive capacity of the Framingham-REGICOR risk function in an area of low CVD incidence. METHODS: A total of 5248 individuals, aged 35-74 years, from a prospective population-based cohort study were followed up for a median 5.9 years. Baseline ABI was measured using a standardized method. All incident CHD (angina, myocardial infarction, coronary revascularization, CHD death) and CVD (also including fatal and non-fatal stroke) events were recorded. Improvements in discrimination (ΔC-statistics) and reclassification by net reclassification index (NRI) were assessed. RESULTS: During follow-up, 111 and 64 subjects presented with a coronary or cerebrovascular event. Pathological ABI (≤0.9) was associated with increased CHD and CVD risk (HR: 2.08 and HR: 2.24, respectively; p-value<0.001). Including ABI in the Framingham-REGICOR function improved both its discrimination and its reclassification capacity for CVD events but not for CHD events; the ΔC-statistic for CVD events was 0.007 (95% Confidence Interval: 0.001; 0.017) and the NRI was 0.029 (95% CI: 0.014-0.045; p-value<0.001). CONCLUSION: Inclusion of the ABI improves the predictive capacity of the Framingham-REGICOR risk function. The study results indicate the potential value of including this simple test in cardiovascular risk stratification and support current guidelines recommendations.

Anti-CD22 and anti-CD79B antibody drug conjugates are active in different molecular diffuse large B-cell lymphoma subtypes.

Antibody drug conjugates (ADCs), in which cytotoxic drugs are linked to antibodies targeting antigens on tumor cells, represent promising novel agents for the treatment of malignant lymphomas. Pinatuzumab vedotin is an anti-CD22 ADC and polatuzumab vedotin an anti-CD79B ADC that are both linked to the microtubule-disrupting agent monomethyl auristatin E (MMAE). In the present study, we analyzed the activity of these agents in different molecular subtypes of diffuse large B-cell lymphoma (DLBCL) both in vitro and in early clinical trials. Both anti-CD22-MMAE and anti-CD79B-MMAE were highly active and induced cell death in the vast majority of activated B-cell-like (ABC) and germinal center B-cell-like (GCB) DLBCL cell lines. Similarly, both agents induced cytotoxicity in models with and without mutations in the signaling molecule CD79B. In line with these observations, relapsed and refractory DLBCL patients of both subtypes responded to these agents. Importantly, a strong correlation between CD22 and CD79B expression in vitro and in vivo was not detectable, indicating that patients should not be excluded from anti-CD22-MMAE or anti-CD79B-MMAE treatment because of low target expression. In summary, these studies suggest that pinatuzumab vedotin and polatuzumab vedotin are active agents for the treatment of patients with different subtypes of DLBCL.