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Express improvement of acute stroke care accessibility in large regions using a centralized telestroke network.
No full textAcute ischemic stroke therapy has improved in recent decades, decreasing the rates of disability and death among stroke patients. Unfortunately, all health care systems have geographical disparities in infrastructure for stroke patients. A centralized telestroke network might be a low-cost strategy to reduce differences in terms of geographical barriers, equitable access, and quality monitoring across different hospitals. We aimed to quantify changes in stroke patients' geographic access to specialized evaluation by neurologists and to intravenous acute stroke reperfusion treatments following the rapid implementation of a centralized telestroke network in the large region of Andalusia (8.5 million inhabitants). We conducted an observational study using spatial and analytical methods to examine how a centralized telestroke network influences the quality and accessibility of stroke care for a large region. In the pre-implementation period, 5,005,477 (59.72% of the Andalusian population) had access to specialized stroke care in less than 30 min. After the 5-month process of implementing the telestroke network, 7,832,988 (93.5%) inhabitants had an access time of less than 30 min, bridging the gap in acute stroke care in rural hospitals. A centralized telestroke network may be an efficient tool to reduce the differences in stroke care access and quality monitoring across different hospitals, especially in large regions with low population density.S
Impact of interstitial lung disease on the survival of systemic sclerosis with pulmonary arterial hypertension (vol 12, 5289, 2022)
No full textTo assess severity markers and outcomes of patients with systemic sclerosis (SSc) with or without pulmonary arterial hypertension (PAH-SSc/non-PAH-SSc), and the impact of interstitial lung disease (ILD) on PAH-SSc. Non-PAH-SSc patients from the Spanish SSc registry and PAH-SSc patients from the Spanish PAH registry were included. A total of 364 PAH-SSc and 1589 non-PAH-SSc patients were included. PAH-SSc patients had worse NYHA-functional class (NYHA-FC), worse forced vital capacity (FVC) (81.2 ± 20.6% vs 93.6 ± 20.6%, P < 0.001), worse tricuspid annular plane systolic excursion (TAPSE) (17.4 ± 5.2 mm vs 19.9 ± 6.7 mm, P < 0.001), higher incidence of pericardial effusion (30% vs 5.2%, P < 0.001) and similar prevalence of ILD (41.8% vs. 44.9%). In individuals with PAH-SSc, ILD was associated with worse hemodynamics and pulmonary function tests (PFT). Up-front combination therapy was used in 59.8% and 61.7% of patients with and without ILD, respectively. Five-year transplant-free survival rate was 41.1% in PAH-SSc patients and 93.9% in non-PAH-SSc patients (P < 0.001). Global survival of PAH-SSc patients was not affected by ILD regardless its severity. The multivariate survival analysis in PAH-SSc patients confirmed age at diagnosis, worse NYHA-FC, increased PVR, reduced DLCO, and lower management with up-front combination therapy as major risk factors. In conclusion, in PAH-SSc cohort risk of death was greatly increased by clinical, PFT, and hemodynamic factors, whereas it was decreased by up-front combination therapy. Concomitant ILD worsened hemodynamics and PFT in PAH-SSc but not survival regardless of FVC impairment.S
Cardiometabolic characterization in metabolic dysfunction-associated fatty liver disease.
No full textTo better understand the patient's heterogeneity in fatty liver disease (FLD), metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed by international experts as a new nomenclature for nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the cardiovascular risk, assessed through coronary artery calcium (CAC) and epicardial adipose tissue (EAT), of patients without FLD and patients with FLD and its different subtypes. Cross sectional study of 370 patients. Patients with FLD were divided into 4 groups: FLD without metabolic dysfunction (non-MD FLD), MAFLD and the presence of overweight/obesity (MAFLD-OW), MAFLD and the presence of two metabolic abnormalities (MAFLD-MD) and MAFLD and the presence of T2D (MAFLD-T2D). MAFLD-OW included two subgroups: metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). The patients without FLD were divided into 2 groups: patients without FLD and without MD (non-FLD nor MD; reference group) and patients without FLD but with MD (non-FLD with MD). EAT and CAC (measured through the Agatston Score) were determined by computed tomography. Compared with the reference group (non-FLD nor MD), regarding EAT, patients with MAFLD-T2D and MAFLD-MUHO had the highest risk for CVD (OR 15.87, 95% CI 4.26-59.12 and OR 17.60, 95% CI 6.71-46.20, respectively), patients with MAFLD-MHO were also at risk for CVD (OR 3.62, 95% CI 1.83-7.16), and patients with non-MD FLD did not have a significantly increased risk (OR 1.77; 95% CI 0.67-4.73). Regarding CAC, patients with MAFLD-T2D had an increased risk for CVD (OR 6.56, 95% CI 2.18-19.76). Patients with MAFLD-MUHO, MAFLD-MHO and non-MD FLD did not have a significantly increased risk compared with the reference group (OR 2.54, 95% CI 0.90-7.13; OR 1.84, 95% CI 0.67-5.00 and OR 2.11, 95% CI 0.46-9.74, respectively). MAFLD-T2D and MAFLD-OW phenotypes had a significant risk for CVD. MAFLD new criteria reinforced the importance of identifying metabolic phenotypes in populations as it may help to identify patients with higher CVD risk and offer a personalized therapeutic management in a primary prevention setting.S
Use of glucocorticoids megadoses in SARS-CoV-2 infection in a spanish registry: SEMI-COVID-19.
No full textTo describe the impact of different doses of corticosteroids on the evolution of patients with COVID-19 pneumonia, based on the potential benefit of the non-genomic mechanism of these drugs at higher doses. Observational study using data collected from the SEMI-COVID-19 Registry. We evaluated the epidemiological, radiological and analytical scenario between patients treated with megadoses therapy of corticosteroids vs low-dose of corticosteroids and the development of complications. The primary endpoint was all-cause in-hospital mortality according to use of corticosteroids megadoses. Of a total of 14,921 patients, corticosteroids were used in 5,262 (35.3%). Of them, 2,216 (46%) specifically received megadoses. Age was a factor that differed between those who received megadoses therapy versus those who did not in a significant manner (69 years [IQR 59-79] vs 73 years [IQR 61-83]; p There is no difference in mortality with megadoses versus low-dose, but there is a lower incidence of infectious complications with glucocorticoid megadoses
Unhealthy gestational weight gain: Are we neglecting inadequate gestational weight gain?
No full textTo evaluate the prevalence of unhealthy gestational weight gain and analyze the role of women´s knowledge about the recommendations, expectations, beliefs, counseling, and information provided by midwives as potential factors contributing to failure to meet recommendations. A retrospective cross-sectional study was performed in a tertiary Hospital in Seville (Spain) between March and September 2019. A sample of 500 singleton pregnant women at or over 37 weeks of gestation completed a self-administered questionnaire during a prenatal visit. Gestational weight gain was categorized as healthy/excessive/inadequate, according to the Institute of Medicine, for 409 women. Descriptive, bivariate, and multivariate analysis was performed. Inadequate and excessive gestational weight gain were 33.4% and 33.9%, respectively. A multivariate model for excessive gestational weight gain showed pre-gestational body mass index was a risk factor, while exercise and believing the weight gain was healthy were protective factors. The model for inadequate gestational weight gain showed knowledge of recommendations was a protective factor while believing gestational weight was healthy was a risk factor. Unhealthy gestational weight gain is common. Inadequate gain from women with healthy pre-pregnancy body mass index who believed their gain was healthy, was almost as common as excessive gestational weight gain. As shown by our predictive model beliefs regarding healthy gestational weight gain may act either as a protective factor, in the excessive gain model, or as a risk factor, in the inadequate gain model, depending on women´s pre-pregnancy body mass index and despite knowledge of the recommendations. Inadequate weight gain, and not only excessive gain, should be properly addressed during pregnancy. Healthy gestational weight gain should be approached by midwives with a combination of one-to-one and group antenatal care, where believes regarding healthy gestational weight gain should be addressed. Midwives should remain alert as we may be facing a new trend: increasing numbers of women presenting with inadequate gestational weight gain; with negative health implications for a healthy population. We recommend that midwives pay attention to women with a healthy pre-pregnancy Body Mass Index and who believe that their weight gain is correct because this profile frequently had an inadequate gestational weight gain.S
T2 Biomarkers as Predictors of Exacerbations of Chronic Obstructive Pulmonary Disease
No full textIntroduction: Type 2 (T2) biomarkers such as blood eosinophil count (BEC) and FeNO have been related to a higher risk of exacerbations in COPD. It is unknown whether combining these biomarkers could be useful in forecasting COPD exacerbations. Methods: COPD patients were enrolled in this prospective, multicenter, observational study and followed up for 1 year, during which BEC were analysed at baseline (V0) while FeNO analyses were performed at baseline (V0), 6 months (V1) and 12 months (V2). The risk of moderate or severe exacerbation during follow up was assessed by Cox regression analysis, and the predictive capacity of both measurements was assessed by ROC curves and the DeLong test. Statistical significance was assumed at
XPC-PARP complexes engage the chromatin remodeler ALC1 to catalyze global genome DNA damage repair.
No full textCells employ global genome nucleotide excision repair (GGR) to eliminate a broad spectrum of DNA lesions, including those induced by UV light. The lesion-recognition factor XPC initiates repair of helix-destabilizing DNA lesions, but binds poorly to lesions such as CPDs that do not destabilize DNA. How difficult-to-repair lesions are detected in chromatin is unknown. Here, we identify the poly-(ADP-ribose) polymerases PARP1 and PARP2 as constitutive interactors of XPC. Their interaction results in the XPC-stimulated synthesis of poly-(ADP-ribose) (PAR) by PARP1 at UV lesions, which in turn enables the recruitment and activation of the PAR-regulated chromatin remodeler ALC1. PARP2, on the other hand, modulates the retention of ALC1 at DNA damage sites. Notably, ALC1 mediates chromatin expansion at UV-induced DNA lesions, leading to the timely clearing of CPD lesions. Thus, we reveal how chromatin containing difficult-to-repair DNA lesions is primed for repair, providing insight into mechanisms of chromatin plasticity during GGR
Influence of Diagnostic Delay on Survival Rates for Patients with Colorectal Cancer.
No full textColorectal cancer affects men and women alike. Sometimes, due to clinical-pathological factors, the absence of symptoms or the failure to conduct screening tests, its diagnosis may be delayed. However, it has not been conclusively shown that such a delay, especially when attributable to the health system, affects survival. The aim of the present study is to evaluate the overall survival rate of patients with a delayed diagnosis of colorectal cancer. This observational, prospective, multicenter study was conducted at 22 public hospitals located in nine Spanish provinces. For this analysis, 1688 patients with complete information in essential variables were included. The association between diagnostic delay and overall survival at five years, stratified according to tumor location, was estimated by the Kaplan-Meier method. Hazard ratios for this association were estimated using multivariable Cox regression models. The diagnostic delay ≥ 30 days was presented in 944 patients. The presence of a diagnostic delay of more than 30 days was not associated with a worse prognosis, contrary to a delay of less than 30 days (HR: 0.76, 0.64-0.90). In the multivariate analysis, a short delay maintained its predictive value (HR: 0.80, 0.66-0.98) regardless of age, BMI, Charlson index or TNM stage. A diagnostic delay of less than 30 days is an independent factor for short survival in patients with CRC. This association may arise because the clinical management of tumors with severe clinical characteristics and with a poorer prognosis are generally conducted more quickly.This study was supported by public grants from Instituto de Salud Carlos III (PI09/90397, PS09/00314, PS09/00746, PI09/90453, PI09/00910, PI09/90460, PI09/90490, PI13/01692, PI13/00013, PI18/01181, PI18/01589, PS0900805 & PI0900441) and was co-funded by the European Regional
Development Fund.S
Evaluation of the association of alleles of intolerance risk to metotrexate in rheumatoid arthritis patients under treatment with biologic therapies.
No full textMetotrexate (MTX) is the first-line treatment for rheumatoid arthritis (RA) both in monotherapy and in combination with biologic disease-modifying antirheumatic drugs (bDMARDs), it is usually well tolerated but adverse events (AEs) may appear causing toxicity that requires suspension of the treatment. The objectives of this study were to determine the prevalence of certain polymorphisms among patients that receive bDMARD in monotherapy or in combination with MTX to confirm their relevance as biomarkers of intolerance, and to evaluate the influence of certain polymorphisms in the effectiveness of monotherapy or combined treatment in patients, through “Disease Activity Score 28” (DAS28), Simple Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI) and each one of its components. A retrospective observational multicentric study (University Hospital Complex, Granada; Carlos de Haya Hospital, Malaga; and University Hospital Reina Sofia, Cordoba) was conducted, with a case-control design including 227 patients with RA (criteria ACR/EULAR), of which 120 received MTX and bDMARD combined therapy (cases) and others only bDMARD (controls). All of them had been or were currently treated with MTX, remained with stable doses of bDMARD, and had a DNA sample stored before inclusion in the study. DNA was isolated from total peripheral blood and by fluorescent probe HybProbe and/or Taqman, 10 polymorphisms of 10 protein-coding genes involved in the metabolism and toxicity of MTX according to current evidence were determined. Besides the type of polymorphism, data on disease activity were analysed (DAS28VSG, DAS28PCR, SDAI, CDAI) at the start of the MTX intake, of the BT, and in the inclusion visit. A descriptive and comparative study was carried out on all that, and afterwards an assessment was made through a multiple logistic regression analysis (MLR) on the risk of intolerance to MTX. An analysis was carried out on 227 patients (120 cases and 107 controls) with an average age of 60 (12.1), being women 78.4%, with a time of evolution since diagnosis of 14.84 (7.78) years. 48.9% registered adverse events (AE) MTX-related, mainly gastrointestinal, hepatobiliary, and skin-subcutaneous tissue. The percentage of AE appearance was superior in the monotherapy group than in the group with combined therapy. The most prevalent polymorphism (84.6% [95% CI: 84.09%–85.11%]) and in cases (86.0% [95% CI: 79.43%–92.57%]) was homozygous CC (ITPase-c94a); in controls, homozygous GG (GGH-T401C) (87.5% [95% CI: 81.58%–93.42%]). There were no significant differences in the parameters of activity between groups; in both, patients were better basally controlled than at the start of the MTX intake and/or bDMARD. Being homozygous-AA for the DHFR gene was significantly associated (p<0.05) with the appearance of AE (none of the 4 homozygous AA patients for that gene had AE). In MLR, homozygous GG (ref. heterozygous AG) in polymorphism GGH-T401C, being homozygous CC (ref. heterozygous TC) in polymorphism ABCC2-C24T, and PCR (mg/dL) at the start of bDMARD resulted as independent predictive factors of MTX intolerance. Polymorphisms T401C for the GGH gene and C24T for the ABCC2 gene, and PCR at the start of the bDMARD, resulted as independent predictive factors of MTX intolerance.S
Prospective evaluation of 92 serum protein biomarkers for early detection of ovarian cancer.
No full textCA125 is the best available yet insufficiently sensitive biomarker for early detection of ovarian cancer. There is a need to identify novel biomarkers, which individually or in combination with CA125 can achieve adequate sensitivity and specificity for the detection of earlier-stage ovarian cancer. In the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we measured serum levels of 92 preselected proteins for 91 women who had blood sampled ≤18 months prior to ovarian cancer diagnosis, and 182 matched controls. We evaluated the discriminatory performance of the proteins as potential early diagnostic biomarkers of ovarian cancer. Nine of the 92 markers; CA125, HE4, FOLR1, KLK11, WISP1, MDK, CXCL13, MSLN and ADAM8 showed an area under the ROC curve (AUC) of ≥0.70 for discriminating between women diagnosed with ovarian cancer and women who remained cancer-free. All, except ADAM8, had shown at least equal discrimination in previous case-control comparisons. The discrimination of the biomarkers, however, was low for the lag-time of >9-18 months and paired combinations of CA125 with any of the 8 markers did not improve discrimination compared to CA125 alone. Using pre-diagnostic serum samples, this study identified markers with good discrimination for the lag-time of 0-9 months. However, the discrimination was low in blood samples collected more than 9 months prior to diagnosis, and none of the markers showed major improvement in discrimination when added to CA125.S