TRPV4 Channels Promote Pathological, but Not Physiological, Cardiac Remodeling through the Activation of Calcineurin/NFAT and TRPC6.

TRPV4 channels, which respond to mechanical activation by permeating Ca2+ into the cell, may play a pivotal role in cardiac remodeling during cardiac overload. Our study aimed to investigate TRPV4 involvement in pathological and physiological remodeling through Ca2+-dependent signaling. TRPV4 expression was assessed in heart failure (HF) models, induced by isoproterenol infusion or transverse aortic constriction, and in exercise-induced adaptive remodeling models. The impact of genetic TRPV4 inhibition on HF was studied by echocardiography, histology, gene and protein analysis, arrhythmia inducibility, Ca2+ dynamics, calcineurin (CN) activity, and NFAT nuclear translocation. TRPV4 expression exclusively increased in HF models, strongly correlating with fibrosis. Isoproterenol-administered transgenic TRPV4-/- mice did not exhibit HF features. Cardiac fibroblasts (CFb) from TRPV4+/+ animals, compared to TRPV4-/-, displayed significant TRPV4 overexpression, elevated Ca2+ influx, and enhanced CN/NFATc3 pathway activation. TRPC6 expression paralleled that of TRPV4 in all models, with no increase in TRPV4-/- mice. In cultured CFb, the activation of TRPV4 by GSK1016790A increased TRPC6 expression, which led to enhanced CN/NFATc3 activation through synergistic action of both channels. In conclusion, TRPV4 channels contribute to pathological remodeling by promoting fibrosis and inducing TRPC6 upregulation through the activation of Ca2+-dependent CN/NFATc3 signaling. These results pose TRPV4 as a primary mediator of the pathological response.

Increased Incidence of In-Hospital Ischemic Stroke During SARS-CoV-2 Outbreak: A Single-Center Study.

BACKGROUND: Meta-analyses of observational studies report a 1.1-1.7% pooled risk of stroke among patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requiring hospitalization, but consultations for stroke and reperfusion procedures have decreased during the outbreak that occurred during the first half of the year 2020. It is still unclear whether a true increase in the risk of stroke exists among patients with coronavirus disease 2019 (COVID-19). In-hospital ischemic stroke (IHIS) complicated the 0.04-0.06% of all admissions in the pre-COVID-19 era, but its incidence has not been assessed among inpatients with COVID-19. We aimed to compare IHIS incidence among patients with SARS-CoV-2 infection with that of inpatients with non-COVID-19 illnesses from the same outbreak period and from previous periods. METHODS: This historical cohort study belongs to the COVID-19@Vallecas cohort. The incidence of IHIS was estimated for patients with SARS-CoV-2 hospitalized during March-April 2020 [COVID-19 cohort (CC)], for patients with non-COVID-19 medical illness hospitalized during the same outbreak period [2020 non-COVID-19 cohort (20NCC)], and for inpatients with non-COVID-19 illness admitted during March-April of the years 2016-2019 [historical non-COVID-19 cohort (HNCC)]. Unadjusted risk of IHIS was compared between the three cohorts, and adjusted incidence rate ratio (IRR) of IHIS between cohorts was obtained by means of Poisson regression. RESULTS: Overall, 8126 inpatients were included in this study. Patients in the CC were younger and more commonly men than those from the HNCC and 20NCC. Absolute risk of IHIS was 0.05% for HNCC, 0.23% for 20NCC, and 0.36% for CC, (p = 0.004 for HNCC vs. CC). Cumulative incidence for IHIS by day nine after admission, with death as a competing risk, was 0.09% for HNCC, 0.23% for 20NCC, and 0.50% for CC. In an adjusted Poisson regression model with sex, age, needing of intensive care unit admission, and cohort (HNCC as reference) as covariates, COVID-19 was an independent predictor for IHIS (IRR 6.76, 95% confidence interval 1.66-27.54, p = 0.01). A nonsignificant increase in the risk of IHIS was observed for the 20NCC (IRR 5.62, 95% confidence interval 0.93-33.9, p = 0.06). CONCLUSIONS: SARS-CoV-2 outbreak was associated with an increase in the incidence of IHIS when compared with inpatients from a historical cohort. Viral infection itself may be related to the increased risk of IHIS among patients with COVID-19, but in view of our results from the 20NCC, it is likely that other factors, such as hospital saturation and overwhelming of health systems, may have played a role in the increased frequency of IHIS.

Relevance of gastrointestinal manifestations in a large Spanish cohort of patients with systemic lupus erythematosus: what do we know?

OBJECTIVE: SLE can affect any part of the gastrointestinal (GI) tract. GI symptoms are reported to occur in >50% of SLE patients. To describe the GI manifestations of SLE in the RELESSER (Registry of SLE Patients of the Spanish Society of Rheumatology) cohort and to determine whether these are associated with a more severe disease, damage accrual and a worse prognosis. METHODS: We conducted a nationwide, retrospective, multicentre, cross-sectional cohort study of 3658 SLE patients who fulfil ≥4 ACR-97 criteria. Data on demographics, disease characteristics, activity (SLEDAI-2K or BILAG), damage (SLICC/ACR/DI) and therapies were collected. Demographic and clinical characteristics were compared between lupus patients with and without GI damage to establish whether GI damage is associated with a more severe disease. RESULTS: From 3654 lupus patients, 3.7% developed GI damage. Patients in this group (group 1) were older, they had longer disease duration, and were more likely to have vasculitis, renal disease and serositis than patients without GI damage (group 2). Hospitalizations and mortality were significantly higher in group 1. Patients in group 1 had higher modified SDI (SLICC Damage Index). The presence of oral ulcers reduced the risk of developing damage in 33% of patients. CONCLUSION: Having GI damage is associated with a worse prognosis. Patients on a high dose of glucocorticoids are at higher risk of developing GI damage which reinforces the strategy of minimizing glucocorticoids. Oral ulcers appear to decrease the risk of GI damage.

Aortic thrombus in patients with severe COVID-19: review of three cases.

Coronavirus disease 2019 (COVID-19) could predispose to both venous and arterial thromboembolism, in an exaggerated immune response to the virus, especially in severe patients. Even though aortic clots are a rare entity, the pro-coagulant nature of COVID-19 is associated with thrombosis in atypical locations and should be considered in patients with severe abnormalities in coagulation parameters. We describe a series of three cases of aortic thrombi diagnosed by computerized tomography (CT) angiography in patients with confirmed SARS-CoV-2 infection.

The influence of sex on ischemic stroke incidence, therapeutic procedures and in-hospital mortality: Results of the Spanish National Hospital Discharge.

BACKGROUND: Previous research has revealed sex-related differences in outcomes for people admitted to hospitals for ischemic stroke. We aimed to analyse the incidence, use of invasive procedures and in-hospital outcomes of ischemic stroke in Spain (2016-2018) using the Spanish National Hospital Discharge Database. We sought sex-related differences in incidence and in-hospital outcomes over time. METHODS: We estimated the incidence of ischemic stroke in men and women. We analysed comorbidities (Charlson's comorbidity index, cardiovascular risk factors, alcohol abuse and atrial fibrillation), procedures (mechanical ventilation, endovascular thrombectomy and thrombolytic therapy) and outcomes. We matched each woman with a man with identical age, type of ischemic stroke and year of hospitalisation. We built Poisson regression models to obtain adjusted incidence rate ratios (IRRs). We tested in-hospital mortality (IHM) with logistic regression analyses. RESULTS: Ischemic stroke was coded in 172 255 patients aged ≥35 years (92 524 men 53.7%). Men showed higher incidence rates (216.9 vs. 172.3/105 ; P < .001; IRR = 1.57 (95% CI:1.55-1.59) than women. After matching, the use of endovascular thrombectomy (5.1% vs. 4.0%; P < .001) and thrombolytic therapy (7.6% vs. 6.8%; P < .001) was higher among women. IHM was significantly higher in women than in matched men (11.2% vs. 10.4%; P < .001). Women had a lower IHM than matched men when endovascular thrombectomy (9.4% vs. 12.1%; P = .001) or thrombolytic therapy (6.7% vs. 8.3%; P = .003) was coded. Patients of both sexes admitted for ischemic stroke who received thrombolytic therapy had lower IHM (OR = 0.76; 95% CI:0.68-0.85 among men; and OR = 0.58; 95% CI:0.52-0.64 among women), but endovascular thrombectomy was associated with a lower IHM only among women (OR = 0.58; 95% CI:0.51-0.66). After multivariable adjusting, women admitted to the hospital for ischemic stroke had a significantly higher IHM than men (OR = 1.16; 95% CI:1.12-1.21). CONCLUSION: Men had higher incidence rates of ischemic stroke than women. Women more often underwent thrombolytic therapy and endovascular thrombectomy but had a higher IHM.

Incidence of Deep Venous Thrombosis in Patients With COVID-19 and Pulmonary Embolism: Compression Ultrasound COVID Study.

OBJECTIVES: Several reports had observed a high risk of pulmonary embolism (PE) in patients with coronavirus disease 2019 (COVID-19), most of them in the intensive care unit. Reported findings indicate that a direct viral-mediated hyperinflammatory response leads to local thromboinflammation. According to those findings, the incidence of deep venous thrombosis (DVT) in patients with COVID-19 and PE should be low. The objective of this study was to evaluate the incidence of DVT in patients with COVID-19 who developed PE. METHODS: In this prospective observational study, consecutive patients hospitalized in the internal medicine ward with a diagnosis of COVID-19 who developed PE were screened for DVT in the lower extremities with complete compression ultrasound. RESULTS: The study comprised 26 patients. Fifteen patients (57.7%) were male. The median age was 60 years (interquartile range, 54-73 years). Compression ultrasound findings were positive for DVT in 2 patients (7.7%; 95% confidence interval, 3.6%-11.7%). Patients with DVT had central and bilateral PE. In both, venous thromboembolism was diagnosed in the emergency department, so they did not receive previous prophylactic therapy with low-molecular-weight heparin. Patients without DVT had higher median d-dimer levels: 25,688 µg/dL (interquartile range, 80,000-1210 µg/dL) versus 5310 µg/dL (P < .05). CONCLUSIONS: Our study showed a low incidence of DVT in a cohort of patients with COVID-19 and PE. This observation suggests that PE in these patients could be produced mainly by a local thromboinflammatory syndrome induced by severe acute respiratory syndrome coronavirus 2 infection and not by a thromboembolic event.

Hydroxychloroquine is associated with a lower risk of polyautoimmunity: data from the RELESSER Registry.

OBJECTIVES: This article estimates the frequency of polyautoimmunity and associated factors in a large retrospective cohort of patients with SLE. METHODS: RELESSER (Spanish Society of Rheumatology Lupus Registry) is a nationwide multicentre, hospital-based registry of SLE patients. This is a cross-sectional study. The main variable was polyautoimmunity, which was defined as the co-occurrence of SLE and another autoimmune disease, such as autoimmune thyroiditis, RA, scleroderma, inflammatory myopathy and MCTD. We also recorded the presence of multiple autoimmune syndrome, secondary SS, secondary APS and a family history of autoimmune disease. Multiple logistic regression analysis was performed to investigate possible risk factors for polyautoimmunity. RESULTS: Of the 3679 patients who fulfilled the criteria for SLE, 502 (13.6%) had polyautoimmunity. The most frequent types were autoimmune thyroiditis (7.9%), other systemic autoimmune diseases (6.2%), secondary SS (14.1%) and secondary APS (13.7%). Multiple autoimmune syndrome accounted for 10.2% of all cases of polyautoimmunity. A family history was recorded in 11.8%. According to the multivariate analysis, the factors associated with polyautoimmunity were female sex [odds ratio (95% CI), 1.72 (1.07, 2.72)], RP [1.63 (1.29, 2.05)], interstitial lung disease [3.35 (1.84, 6.01)], Jaccoud arthropathy [1.92 (1.40, 2.63)], anti-Ro/SSA and/or anti-La/SSB autoantibodies [2.03 (1.55, 2.67)], anti-RNP antibodies [1.48 (1.16, 1.90)], MTX [1.67 (1.26, 2.18)] and antimalarial drugs [0.50 (0.38, 0.67)]. CONCLUSION: Patients with SLE frequently present polyautoimmunity. We observed clinical and analytical characteristics associated with polyautoimmunity. Our finding that antimalarial drugs protected against polyautoimmunity should be verified in future studies.

Infective endocarditis according to type 2 diabetes mellitus status: an observational study in Spain, 2001-2015.

BACKGROUND: The main aims of this study were to describe trends and outcomes during admission for infective endocarditis (IE) in people ≥ 40 years old with or without type 2 diabetes distributed in five time-periods (2001-2003; 2004-2006; 2007-2009; 2010-2012 and 2013-2015), using Spanish national hospital discharge data. METHODS: We estimated admission rates by diabetes status. We analyzed comorbidity, therapeutic procedures, and outcomes. We built Poisson regression models to compare the adjusted time-trends in admission rates. Type 2 diabetes cases were matched with controls using propensity score matching (PSM). We tested in-hospital mortality (IHM) in logistic regression analyses. RESULTS: We identified 16,626 hospitalizations in patients aged ≥ 40 years for IE in Spain, 2001-2015. The incidence of IE increased significantly from 6.0/100,000 per year to 13.1/100,000 per year (p < 0.001) in the population with type 2 diabetes, and from 3.9/100,000 per year to 5.5/100,000 per year (p < 0.001) in the population without diabetes, over the study period. The adjusted incidence of IE was 2.2-times higher among patients with diabetes than among those without diabetes (IRR = 2.2; 95% CI 2.1-2.3). People with type 2 diabetes less often underwent heart valve surgery than people without diabetes (13.9% vs. 17.3%; p < 0.001). Although IHM decreased significantly in both groups over time, it represented 20.8% of IE cases among diabetes patients and 19.9% among PSM matched controls (p = 0.337). Type 2 diabetes was not associated with a higher IHM in people admitted to the hospital for IE (OR = 1.1; 95% CI 0.9-1.2). CONCLUSION: Incidence rates of IE in Spain, among those with and without T2DM, have increased during the period 2001-2015 with significantly higher incidence rates in the T2DM population. In our population based study and after PSM we found that T2DM was not a predictor of IHM in IE.

Impact of type 2 diabetes mellitus in the utilization and in-hospital outcomes of surgical mitral valve replacement in Spain (2001-2015).

BACKGROUND: The main aims of this study were to examine the incidence and in-hospital outcomes of mechanical and bioprosthetic surgical mitral valve replacement (SMVR) among patients with and without T2DM. METHODS: We performed a retrospective study using the Spanish National Hospital Discharge Database from 2001 to 2015. We included patients with SMVR codified in their discharge report. We grouped admissions by diabetes status. Propensity score matching (PSM) was used to compare outcomes of isolated SMVR. RESULTS: We identified 42,937 patients (16.41% with T2DM). Incidence rates of mechanical and bioprosthetic SMVR were higher among T2DM patients than among non-T2DM patients. In both groups of patients, the use of bioprosthetic SMVR increased over time. The use of mechanical valves remained stable among T2DM patients. In T2DM and non-T2DM patients with mechanical SMVR, in hospital mortality (IHM) and MACCE decreased significantly (p < 0.001) from 2001 to 2015. T2DM patients had an overall 11.37% IHM, compared with 10.76% among non-T2DM patients (p = 0.176). Regarding MACCE figures were 14.72% vs. 14.22% (p = 0.320) after mechanical SMVR. Total crude IHM were 14.29% for T2DM patients and 15.13% for those without T2DM with bioprosthetic SMVR (p = 0.165) and 18.22 vs. 19.64%, for a MACCE (p = 0.185). Using PSM we found that the IHM and the MACCE of isolated SMVR did not differ significantly between patients with or without T2DM beside the type of valve replacement. Among T2DM patients, those who received bioprosthetic valves had higher IHM (14.29% vs. 11.37%; p = 0.003) and a higher rate of MACCE (18.22% vs. 14.72%; p = 0.001) than T2DM patients with mechanical SMVR. CONCLUSIONS: In Spain from 2001 to 2015, the incidence rates of hospitalization to undergo mechanical or bioprosthetic SMVR were higher among the population suffering T2DM than among the non-T2DM population. In both groups of patients the use of bioprosthetic SMVR increased over time and the use of mechanical valves remained stable in T2DM. T2DM patients have IHM and MACCE after mechanical and bioprosthetic SMVR which are not significantly different to those found among non-diabetic patients. Among T2DM patients, the crude IHM was significantly higher in those who received a bioprosthetic SMVR than those with mechanical SMVR.

Belimumab treatment in rhupus: A case report with severe skin involvement.

Patients with rhupus characteristically exhibit symmetric polyarthritis and clinical manifestations suggestive of systemic lupus erythematosus (malar rash, photosensitivity, hematological manifestations, serositis, and/or skin involvement) and positive anti-dsDNA. Treatment is unclear and it can include disease-modifying rheumatic drugs like hydroxyl chloroquine, or methotrexate or, in refractory cases, rituximab or abatacept. We report a case of 31-year-old female who present with rhupus with skin acute lesions treated with belimumab. This is the first case of rhupus treated with this drug described in the literature.

Gender differences in incidence and in-hospital outcomes of surgical aortic valve replacement in Spain, 2001-15.

BACKGROUND: we aim to examine trends in the incidence of surgical aortic valve replacement (SAVR) among women and men in Spain from 2001 to 2015; compare in-hospital outcomes for mechanical and bioprosthetic SAVR by gender and; to identify factors associated with in-hospital mortality (IHM) after SAVR. METHODS: We performed a retrospective study using the Spanish National Hospital Discharge Database, 2001-15. We included patients that had SAVR as procedure in their discharge report. Propensity score matching (PSM) was performed to assess the impact of gender on the outcomes of mechanical and bioprosthetic SAVR. RESULTS: We identified 86 578 patients who underwent SAVR (40% women). Incidence of SVAR was higher in men (incidence rate ratio 1.57; 95%CI 1.55-1.59). In 2001, 73.36% of the men and 71.57% of women received a mechanical prosthesis; these proportions decreased to 43.04% in men and 35.89% in women in 2015, whereas bioprosthetic SAVR increased to 56.96% and 64.11%. After PSM we found that IHM was higher in women than in matched men for mechanical (8.94% vs. 6.79%; P < 0.001) and bioprosthetic (6.51 vs. 5.42%; P = 0.001) SAVR. The mean length of hospital stay was longer (19.54 vs. 18.74 days; P < 0.001) among females than males undergoing mechanical SAVR. Higher IHM after SAVR was associated with older age, comorbidities (except diabetes and atrial fibrillation), concomitant coronary artery bypass graft and emergency room admission. CONCLUSIONS: This nation-wide analysis over 15 years of gender-specific outcomes after SAVR showed that, after PSM women have significantly higher IHM after mechanical and bioprosthetic SAVR than men.

In-hospital outcomes for solid organ transplants according to type 2 diabetes status: An observational, 15-year study in Spain.

AIMS: To describe trends and outcomes during admission for solid organ transplant in people with or without type 2 diabetes in Spain, 2001-2015. METHODS: We used national hospital discharge data to select all hospital admissions for kidney, lung, heart, and liver transplant. We estimated admission rates stratified by type 2 diabetes status. We built Poisson regression models to compare the adjusted time trends in admission rates. We tested in-hospital mortality (IHM) in logistic regression analyses. RESULTS: We identified 50 964 transplants (16.7% in people with type 2 diabetes): kidney, 30 919; lung, 2810; heart, 3649; liver, 13 586. The overall adjusted incidence rate ratios (95% confidence intervals) of admission in people with type 2 diabetes vs no diabetes were 2.4 (2.32-2.48) for kidney, 1.51 (1.33-1.70) for lung, 2.87 (2.63-3.13) for heart, and 4.16 (3.99-4.33) for liver transplant. In the multivariate analysis, IHM decreased significantly over time for all types of transplant. Type 2 diabetes independently predicted lower IHM during admission only for heart (Odds ratio, OR [95% CI] = 0.62 [0.47-0.81]) and liver transplant (OR [95% CI] = 0.69 [0.58-0.82]). CONCLUSIONS: Admission rates for solid organ transplant were higher in people with type 2 diabetes than in people without diabetes. Type 2 diabetes was associated with lower in-hospital mortality during admission for heart and liver transplant.

Selective Angiography Using the Radiofrequency Catheter: An Alternative Technique for Mapping and Ablation in the Aortic Cusps.

BACKGROUND: Ablation in aortic cusps could be necessary in up to 15% of the patients, especially in para-Hisian atrial tachycardia and ventricular arrhythmias arising from outflow tracts. Risk of coronary damage has led to recommendation of systematic coronary angiography (CA) during the procedure. Other image tests as intravascular (ICE) or transesophageal echocardiography (TEE) have been proposed. Both methods have limitations: additional vascular access for ICE and need for additional CA in some patients in case of TEE. We describe an alternative method to assess relation of catheter tip and coronary ostia during ablation in aortic cusps without additional vascular accesses by performing selective angiography with the ablation catheter. METHODS AND RESULTS: We prospectively evaluated 12 consecutive patients (69.3 ± 8.5, 6 female) who underwent ablation in right (1), left (5), and noncoronary cusps (6). We performed angiography through the ablation cooled tip radiofrequency catheter at the ablation site. Ablation was effective in 91.6% of the patients (3 patients needed additional ablation out of coronary cusps: pulmonary cusp, right ventricular outflow tract (RVOT), and coronary sinus and 1 patient underwent a second procedure because recurrence). No complications occurred neither during procedure nor follow-up (6.2 ± 3.8 months). No technical problems occurred with the ablation catheter after contrast injection. CONCLUSION: Selective angiography through a cooled-tip radiofrequency ablation catheter is feasible to assess relation of coronary ostia and ablation site when ablation in aortic cusps. It allows continuous real-time assessment of this relation, avoids the need for additional vascular accesses and no complications occurred in our series.

Transcatheter aortic valve implantation and surgical aortic valve replacement among hospitalized patients with and without type 2 diabetes mellitus in Spain (2014-2015).

BACKGROUND: Type 2 diabetes mellitus (T2DM) is strongly related to the in-hospital and short-term prognosis in patients with cardiovascular diseases needing surgical or invasive interventions. How T2DM might influence the treatment of aortic stenosis (AS) has not been completely elucidated for surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI). The aims of this study were: (1) to describe the use of aortic valve replacement procedures (TAVI and SAVR) among hospitalized patients with and without T2DM; and (2) to identify factors associated with in hospital mortality (IHM) among patients undergoing these procedures. METHODS: We analyzed data from the Spanish National Hospital Discharge Database between January 1, 2014 and December 31, 2015 for patients aged ≥ 40 years. We selected patients whose medical procedures included TAVI (ICD-9-CM codes 35.05, 35.06) and SAVR (ICD-9-CM codes 35.21, 35.22). We stratified each cohort by diabetes status: T2DM (ICD-9-CM codes 250.x0, 250.x2) and no diabetes. We retrieved data about specific comorbidities, risk factors, procedures, and specific in-hospital postoperative complications. Hospital outcome variables included IHM, and length of hospital stay (LOHS). RESULTS: We identified a total of 2141 and 16,013 patients who underwent TAVI (n = 715; 33.39% with T2DM) and SAVR (n = 4057; 25.33% with T2DM). In patients who underwent TAVI we found no differences in IHM (3.64% in T2DM vs. 5.12% in non-T2DM, p = 0.603). In the cohort of SAVR, mean LOHS was significantly lower in patients with T2DM than in non-diabetic patients (13.77 vs. 17.27 days). IHM was lower in patients with T2DM (4.36% vs. 6.31%, p < 0.01). After multivariable adjustment for both procedures, patients with T2DM had significantly lower IHM than patients without diabetes (adjusted OR 0.60; IC 95% 0.37-0.99 for TAVI and adjusted OR 0.80; IC 95% 0.66-0-96 for SAVR). CONCLUSIONS: T2DM diabetic patients with AS undergoing a valvular replacement procedure through SAVR or TAVI did not have a worse prognosis compared to non-diabetic patients during hospitalization, showing lower IHM after multivariable adjustment. However, given the limitations of administrative data more prospective studies and clinical trials aimed at evaluating the influence of these procedures in diabetic patients with AS are needed.

Type 2 diabetes is associated with a higher incidence of hospitalization for pulmonary embolism in Spain: Analysis of hospital discharge data during 2004-2013.

BACKGROUND AND OBJECTIVE: We compared the incidence and outcome of pulmonary embolism (PE) in individuals with and without type 2 diabetes mellitus (T2DM) in Spain during 2004-2013. METHODS: The study was based on National Hospital Discharge Data, and the study population comprised patients hospitalized for PE. Annual incidence rates were classified according to T2DM status. In-hospital mortality (IHM), length of hospital stay (LOHS), comorbidities and use of diagnosis and therapeutic procedures were analysed. RESULTS: We identified 123 872 discharges of patients (56 361 men and 67 511 women) with PE as their primary diagnosis (15.3% with T2DM). Incidence of discharge diagnoses of PE increased significantly in all groups. Crude rates were higher in diabetic patients. A positive association was identified between T2DM and PE: adjusted IRR was 2.00 (95% CI: 1.95-2.05) for men and 2.50 (95% CI: 2.45-2.57) for women. LOHS, readmissions and IHM decreased significantly for both groups. An association between IHM and risk factors (older age, Charlson comorbidity index >3, atrial fibrillation and cancer) was observed. T2DM was associated with higher IHM in men (OR: 1.22, 95% CI: 1.12-1.32) and women (OR: 1.24, 95% CI: 1.15-1.33). The use of computed tomography pulmonary angiography increased significantly overtime. CONCLUSION: We confirmed that in both men and women, diabetes was an independent risk factor for IHM. The incidence of discharge of patients with PE increased significantly during the study period. Diabetic men and women had a higher risk of hospitalization for PE than non-diabetic men and women. Diabetic women had higher IHM than diabetic men.

Open versus laparoscopic cholecystectomies in patients with or without type 2 diabetes mellitus in Spain from 2003 to 2013.

BACKGROUND: This study aimed to compare the rates of open and laparoscopic cholecystectomies and outcomes in patients with or without type 2 diabetes mellitus (T2DM) in Spain from 2003 to 2013. METHODS: We collected all cases of open and laparoscopic cholecystectomies using national hospital discharge data and evaluated the annual cholecystectomy rates stratified by T2DM status. We analyzed tendency for in-hospital mortality (IHM). We also analyzed the impact of T2DM on IHM in patients who underwent cholecystectomies. RESULTS: We identified 611 533 cholecystectomies (71.3% laparoscopic) in the patients, in whom 78 227 (12.8%) patients had T2DM. The rates of open cholecystectomies were 3-fold higher (130.0/105 vs 41.1/105) in patients with T2DM than in those without T2DM, and the rate of laparoscopic cholecystectomies was almost 2-fold higher (195.2/105 vs 111.8/105) in patients with T2DM. The annual rate of laparoscopic procedures showed an 11-year relative increase of 88.3% (from 117.0/105 to 220.3/105) in T2DM and 49.2% (from 79.2/105 to 118.2/105) in patients without T2DM (P<0.001), whereas the rate of open procedures showed an 11-year relative decrease of 27.6% in patients with T2DM and 37.9% in those without T2DM (P<0.001). The rate of emergency laparoscopic cholecystectomy was increased in the 11 years, whereas the rate of emergency open cholecystectomies was decreased (both P<0.001). Multivariate analysis revealed that older age, higher comorbidity and emergency cholecystectomy were associated with a higher IHM. Compared with patients without T2DM, patients with T2DM demonstrated a lower IHM after open cholecystectomy [OR=0.82 (0.78-0.87)], but a higher IHM after laparoscopic cholecystectomy [OR=1.18 (1.03-1.35)]. Time-trend analyses showed a significant reduction in IHM in patients with or without T2DM after the two procedures. CONCLUSION: The rate of cholecystectomy was higher in patients with T2DM, and laparoscopic cholecystectomy was popularized in the past 11 years both in selective and emergency cholecystectomies.

Type 2 Diabetes and Hemorrhagic Stroke: A Population-Based Study in Spain from 2003 to 2012.

AIM: The objective of this study is to compare trends in outcomes for intracerebral hemorrhagic stroke in people with or without type 2 diabetes in Spain between 2003 and 2012. METHODS: We selected all patients hospitalized for hemorrhagic stroke using national hospital discharge data. We evaluated annual incident rates stratified by diabetes status. We analyzed trends in the use of diagnostic and therapeutic procedures, patient comorbidities, in-hospital mortality (IHM), length of hospital stay, and readmission rate in 1 month. RESULTS: We identified a total of 173,979 discharges of patients admitted with hemorrhagic stroke (19.1% with diabetes). Incidences were higher among those with than those without diabetes in all the years studied. Diabetes was positively associated with stroke (incidence rate ratio [IRR] = 1.38, 95% confidence interval [CI] 1.35-1.40 for men; IRR = 1.31, 95% CI 1.29-1.34 for women). Length of stay decreased significantly and readmission rate remained stable for both groups (around 5%). We observed a significant increase in the use of decompressive craniectomy from 2002 to 2013. Mortality was positively associated with older age, with higher comorbidity and atrial fibrillation as risk factors. We found a negative association with the use of decompressive craniectomy. Mortality did not change over time among diabetic men and women. In those without diabetes, mortality decreased significantly over time. Suffering diabetes was not associated with higher mortality. CONCLUSIONS: Type 2 diabetes is associated with higher incidence of hemorrhagic stroke but not with IHM. Incidence among diabetic people remained stable over time. In both groups, the use of decompressive craniectomy has increased and is associated with a decreased mortality.

Tendencies and outcomes in endoscopic biliary sphincterotomies among people with or without type 2 diabetes mellitus in Spain, 2003-2013.

We aimed to compare incidence and outcomes for endoscopic biliary sphincterotomies in people with or without type 2 diabetes mellitus (T2DM) in Spain (2003-2013). We collected all cases of endoscopic biliary sphincterotomies using national hospital discharge data and evaluated annual incident rates stratified by T2DM status. We analyzed trends over time for in-hospital mortality (IHM) as the primary outcome and a composite of IHM or procedure-related complications (key secondary outcome). In multivariate analyses, we tested T2DM as an independent factor of IHM and IHM or complications. We identified 126,885 endoscopic biliary sphincterotomies (23,002 [18.1%] in T2DM people). Crude incidence rates of endoscopic biliary sphincterotomies were > 3-fold higher in people with vs without T2DM (85.5/105 vs 26.9/105 population, respectively). Annual incidence rates of endoscopic biliary sphincterotomies showed 11-year relative increments of 77.5% (from 60.0 to 106.5/105) in T2DM, and 53.7% (from 21.6 to 33.2/105) in non-T2DM people (p < 0.001). We found no significant changes in mortality trends over time for the populations with or without T2DM (p = 0.15 and p = 0.21, respectively). Rates of procedural pancreatitis decreased in people without T2DM (p < 0.001). In the multivariate analysis, older age, higher comorbidity and endoscopic biliary sphincterotomy during urgent admission were associated with a higher IHM. T2DM was associated with a lower IHM after an endoscopic biliary sphincterotomy (OR = 0.82 [0.74-0.92]). Time trend multivariate analyses 2003-2013 showed significant reductions in IHM over time only in people with T2DM (OR = 0.97 [0.94-1.00]). Further studies are needed to confirm a lower IHM for endoscopic biliary sphincterotomies in people with T2DM.

External validation of the RIETE and SOME scores for occult cancer in patients with venous thromboembolism: a multicentre cohort study.

INTRODUCTION: Venous thromboembolism (VTE) may be the first sign of an undiagnosed cancer. The RIETE and SOME scores aim to identify patients with acute VTE at high risk of occult cancer. In the present study, we evaluated the performance of both scores. METHODS: The scores were evaluated in a retrospective cohort from two centers. The area under the receiver-operating characteristics curve (AUC) evaluated the discriminatory performance. RESULTS: The RIETE score was applied to 815 patients with provoked and unprovoked VTE, of whom 56 (6.9%) were diagnosed with cancer. Of the 203 patients classified as high-risk, 18 were diagnosed with cancer, representing 32.1% (18/56) of the total cancer diagnoses. In the group of 612 low-risk patients, 67.9% of the cancer cases were diagnosed (38/56). Sensitivity, specificity, negative and positive predictive values, and AUC were 32%, 76%, 94%, 9%, and 0.430 (95% confidence interval [CI], 0.38‒0.47), respectively. The SOME score could be calculated in 418 patients with unprovoked VTE, of whom 33 (7.9%) were diagnosed with cancer. Of the 45 patients classified as high-risk, three were diagnosed with cancer, representing 9.1% (3/33) of the total cancer diagnoses. In the group of 373 low-risk patients, 90.9% of the cancer cases were diagnosed (30/33). Sensitivity, specificity, negative and positive predictive values, and AUC were 33%, 88%, 94%, 20%, and 0.351 (95% CI, 0.27‒0.43), respectively. CONCLUSIONS: The performance of both scores was poor. Our results highlight the need to develop new models to identify high-risk patients who may benefit from an extensive cancer screening strategy.

SLESIS-R: an improved score for prediction of serious infection in patients with systemic lupus erythematosus based on the RELESSER prospective cohort.

OBJECTIVE: To develop an improved score for prediction of severe infection in patients with systemic lupus erythematosus (SLE), namely, the SLE Severe Infection Score-Revised (SLESIS-R) and to validate it in a large multicentre lupus cohort. METHODS: We used data from the prospective phase of RELESSER (RELESSER-PROS), the SLE register of the Spanish Society of Rheumatology. A multivariable logistic model was constructed taking into account the variables already forming the SLESIS score, plus all other potential predictors identified in a literature review. Performance was analysed using the C-statistic and the area under the receiver operating characteristic curve (AUROC). Internal validation was carried out using a 100-sample bootstrapping procedure. ORs were transformed into score items, and the AUROC was used to determine performance. RESULTS: A total of 1459 patients who had completed 1 year of follow-up were included in the development cohort (mean age, 49±13 years; 90% women). Twenty-five (1.7%) had experienced ≥1 severe infection. According to the adjusted multivariate model, severe infection could be predicted from four variables: age (years) ≥60, previous SLE-related hospitalisation, previous serious infection and glucocorticoid dose. A score was built from the best model, taking values from 0 to 17. The AUROC was 0.861 (0.777-0.946). The cut-off chosen was ≥6, which exhibited an accuracy of 85.9% and a positive likelihood ratio of 5.48. CONCLUSIONS: SLESIS-R is an accurate and feasible instrument for predicting infections in patients with SLE. SLESIS-R could help to make informed decisions on the use of immunosuppressants and the implementation of preventive measures.