Sodium-glucose cotransporter 2 inhibition in primary and secondary glomerulonephritis.

BACKGROUND: The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the management glomerular/systemic autoimmune diseases with proteinuria in real-world clinical settings is unclear. METHODS: This is a retrospective, observational, international cohort study. Adult patients with biopsy-proven glomerular diseases were included. The main outcome was the percentage reduction in 24-h proteinuria from SGLT2i initiation to 3, 6, 9 and 12 months. Secondary outcomes included percentage change in estimated glomerular filtration rate (eGFR), proteinuria reduction by type of disease and reduction of proteinuria ≥30% from SGLT2i initiation. RESULTS: Four-hundred and ninety-three patients with a median age of 55 years and background therapy with renin-angiotensin system blockers were included. Proteinuria from baseline changed by -35%, -41%, -45% and -48% at 3, 6, 9 and 12 months after SGLT2i initiation, while eGFR changed by -6%, -3%, -8% and -10.5% at 3, 6, 9 and 12 months, respectively. Results were similar irrespective of the underlying disease. A correlation was found between body mass index (BMI) and percentage proteinuria reduction at last follow-up. By mixed-effects logistic regression model, serum albumin at SGLT2i initiation emerged as a predictor of ≥30% proteinuria reduction (odds ratio for albumin <3.5 g/dL, 0.53; 95% CI 0.30-0.91; P = .02). A slower eGFR decline was observed in patients achieving a ≥30% proteinuria reduction: -3.7 versus -5.3 mL/min/1.73 m2/year (P = .001). The overall tolerance to SGLT2i was good. CONCLUSIONS: The use of SGLT2i was associated with a significant reduction of proteinuria. This percentage change is greater in patients with higher BMI. Higher serum albumin at SGLT2i onset is associated with higher probability of achieving a ≥30% proteinuria reduction.

Autosomal dominant polycystic kidney disease in young adults.

Background: The clinical manifestations of autosomal dominant polycystic kidney disease (ADPKD) usually appear in adulthood, however pediatric series report a high morbidity. The objective of the study was to analyze the clinical characteristics of ADPKD in young adults. Methods: Family history, hypertension, albuminuria, estimated glomerular filtration rate (eGFR) and imaging tests were examined in 346 young adults (18-30 years old) out of 2521 patients in the Spanish ADPKD registry (REPQRAD). A literature review searched for reports on hypertension in series with more than 50 young (age <30 years) ADPKD patients. Results: The mean age of this young adult cohort was 25.24 (SD 3.72) years. The mean age at diagnosis of hypertension was 21.15 (SD 4.62) years, while in the overall REPQRAD population was aged 37.6 years. The prevalence of hypertension was 28.03% and increased with age (18-24 years, 16.8%; 25-30 years, 36.8%). Although prevalence was lower in women than in men, the age at onset of hypertension (21 years) was similar in both sexes. Mean eGFR was 108 (SD 21) mL/min/1.73 m2, 38.0% had liver cysts and 3.45% of those studied had intracranial aneurysms. In multivariate analyses, hematuria episodes and kidney length were independent predictors of hypertension (area under the curve 0.75). The prevalence of hypertension in 22 pediatric cohorts was 20%-40%, but no literature reports on hypertension in young ADPKD adults were found. Conclusions: Young adults present non-negligible ADPKD-related morbidity. This supports the need for a thorough assessment of young adults at risk of ADPKD that allows early diagnosis and treatment of hypertension.

Development and validation of a nomogram to predict kidney survival at baseline in patients with C3 glomerulopathy.

Background: C3 glomerulopathy is a rare and heterogeneous complement-driven disease. It is often challenging to accurately predict in clinical practice the individual kidney prognosis at baseline. We herein sought to develop and validate a prognostic nomogram to predict long-term kidney survival. Methods: We conducted a retrospective, multicenter observational cohort study in 35 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases. The dataset was randomly divided into a training group (n = 87) and a validation group (n = 28). The least absolute shrinkage and selection operator (LASSO) regression was used to screen the main predictors of kidney outcome and to build the nomogram. The accuracy of the nomogram was assessed by discrimination and risk calibration in the training and validation sets. Results: The study group comprised 115 patients, of whom 46 (40%) reached kidney failure in a median follow-up of 49 months (range 24-112). No significant differences were observed in baseline estimated glomerular filtration rate (eGFR), proteinuria or total chronicity score of kidney biopsies, between patients in the training versus those in the validation set. The selected variables by LASSO were eGFR, proteinuria and total chronicity score. Based on a Cox model, a nomogram was developed for the prediction of kidney survival at 1, 2, 5 and 10 years from diagnosis. The C-index of the nomogram was 0.860 (95% confidence interval 0.834-0.887) and calibration plots showed optimal agreement between predicted and observed outcomes. Conclusions: We constructed and validated a practical nomogram with good discrimination and calibration to predict the risk of kidney failure in C3 glomerulopathy patients at 1, 2, 5 and 10 years.

Stabilized convection in a ternary mixture with two Soret coefficients of opposite sign.

We performed ground-based experiments on the sample polystyrene-toluene-cyclohexane in order to complement the experimental activities in microgravity conditions related to the ESA projects DCMIX4 and Giant Fluctuations. After applying a stabilizing thermal gradient by heating from above a layer of the fluid mixture, we studied over many hours the density variations in the bidimensional horizontal field by means of a Shadowgraph optical setup. The resulting images evidence the appearance of convective instability after a diffusive time associated with the binary molecular solvent consisting of toluene and cyclohexane, confirming the negative sign of the Soret coefficient of this mixture. After a larger diffusive time related to mass diffusion of the polystyrene in the binary solvent, convection was suppressed by the increasing stabilizing density gradient originated by the Soret-induced concentration gradient of the polymer. This is compatible with a positive sign of the Soret coefficient of the polymer in the binary solvent.

Longitudinal change in proteinuria and kidney outcomes in C3 glomerulopathy.

INTRODUCTION: The association between a change in proteinuria over time and its impact on kidney prognosis has not been analysed in complement component 3 (C3) glomerulopathy. This study aims to investigate the association between the longitudinal change in proteinuria and the risk of kidney failure. METHODS: This was a retrospective, multicentre observational cohort study in 35 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases. Patients diagnosed with C3 glomerulopathy between 1995 and 2020 were enrolled. A joint modelling of linear mixed-effects models was applied to assess the underlying trajectory of a repeatedly measured proteinuria, and a Cox model to evaluate the association of this trajectory with the risk of kidney failure. RESULTS: The study group consisted of 85 patients, 70 C3 glomerulonephritis and 15 dense deposit disease, with a median age of 26 years (range 13-41). During a median follow-up of 42 months, 25 patients reached kidney failure. The longitudinal change in proteinuria showed a strong association with the risk of this outcome, with a doubling of proteinuria levels resulting in a 2.5-fold increase of the risk. A second model showed that a ≥50% proteinuria reduction over time was significantly associated with a lower risk of kidney failure (hazard ratio 0.79; 95% confidence interval 0.56-0.97; P < 0.001). This association was also found when the ≥50% proteinuria reduction was observed within the first 6 and 12 months of follow-up. CONCLUSIONS: The longitudinal change in proteinuria is strongly associated with the risk of kidney failure. The change in proteinuria over time can provide clinicians a dynamic prediction of kidney outcomes.

Burden of pneumonia in patients with viral and bacterial coinfection in Spain during six consecutive influenza seasons, from 2009-10 to 2014-15.

PURPOSE: Lower respiratory infections remain the most lethal communicable disease worldwide. Viral and bacterial coinfections (VBC) are common complications in patients with seasonal influenza and are associated with around 25% of all influenza-related deaths. The burden of pneumonia in patients with VBC in Spain is poorly characterized. To address this question, we aimed to provide population data over a period of six consecutive influenza seasons, from 2009-10 to 2014-15. METHODS: We used the discharge report from the Minimum Basic Data Set (MBDS), published annually by the Spanish Ministry of Health, to retrospectively analyse hospital discharge data in individuals aged ≥60 years with a diagnosis of pneumonia and influenza, based on the International Classification of Diseases (ICD-9-CM codes 480-486 and 487-488, respectively), from 1 October 2009 to 30 September 2015. RESULTS: In total, 1933 patients ≥60 years old were hospitalized for pneumonia and influenza, of whom 55.2% were male. The median age was 74 years (interquartile range [IRQ] 15); half of the patients were ≥75 years old. Influenza was the main diagnosis in 64.4% of the patients, and all-cause pneumonia in 15.8%, half of whom were assigned a diagnostic code for pneumococcal pneumonia. The mean annual hospitalization rate was 2.99 per 100,000 population (95% CI 2.9-3.1) throughout the study period, while the highest rate, 5.6 per 100,000 population (95% CI 5.2-6.0), was observed in the 2013-14 season. The mean annual mortality rate was 0.5 deaths per 100,000 population (95% CI 0.4-0.6) and in-hospital case fatality rate was 16.1% (95% CI 14.5-17.8). CONCLUSIONS: In Spain, community-acquired pneumonia and influenza continue to be an important cause of hospitalization and mortality in patients over 60 years of age. There is an urgent need to further develop prevention strategies such as joint vaccination for both pathologies.

Formación multinivel (atención primaria-hospital) mediante simulación con conexión en tiempo real en tiempos de COVID-19. Una herramienta a considerer / Simultaneous hospital/primary care real time simulation during COVID-19 alert

No disponible

Validation of a Histologic Scoring Index for C3 Glomerulopathy.

RATIONALE & OBJECTIVE: A previous study that evaluated associations of kidney biopsy findings with disease progression in patients with C3 glomerulopathy (C3G) proposed a prognostic histologic index (C3G-HI) that has not yet been validated. Our objective was to validate the performance of the C3G-HI in a new patient population. STUDY DESIGN: Multicenter, retrospective cohort study. SETTING & PARTICIPANTS: 111 patients fulfilling diagnostic criteria of C3G between January 1995 and December 2019, from 33 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases (GLOSEN). PREDICTORS: Demographic, clinical parameters, C3G-HI total activity score, and the C3G-HI total chronicity score. OUTCOME: Time to kidney failure. ANALYTICAL APPROACH: Intraclass correlation coefficients and κ statistic were used to summarize inter-rater reproducibility for assessment of histopathology in kidney biopsies. The nonlinear relationships of risk of kidney failure with the total activity score and total chronicity score were modeled using Cox proportional hazards analysis that incorporated cubic splines. RESULTS: The study group included 93 patients with C3 glomerulonephritis and 18 with dense-deposit disease. Participants had an overall meanage of 35±22 (SD) years. Forty-eight patients (43%) developed kidney failure after a mean follow-up of 65±27 months. The overall inter-rater reproducibility was very good for the total activity score (intraclass correlation coefficient [ICC]=0.63) and excellent for total chronicity score (ICC=0.89). Baseline estimated glomerular filtration rate (eGFR), 24-hour proteinuria, and treatment with immunosuppression were the main determinants of kidney failure in a model with only clinical variables. Only tubular atrophy and interstitial fibrosis were identified as predictors in a model with histological variables. When the total activity score and total chronicity score were added to the model, only the latter was identified as an independent predictor of kidney failure. LIMITATIONS: Only a subset of the kidney biopsies was centrally reviewed. Residual confounding. CONCLUSIONS: We validated the performance of C3G-HI as a predictor of kidney failure in patients with C3G. The total chronicity score was the principal histologic correlate of kidney failure.

Mycophenolate Mofetil in C3 Glomerulopathy and Pathogenic Drivers of the Disease.

BACKGROUND AND OBJECTIVES: C3 glomerulopathy is a complement-mediated disease arising from abnormalities in complement genes and/or antibodies against complement components. Previous studies showed that treatment with corticosteroids plus mycophenolate mofetil (MMF) was associated with improved outcomes, although the genetic profile of these patients was not systematically analyzed. This study aims to analyze the main determinants of disease progression and response to this therapeutic regimen. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective, multicenter, observational cohort study in 35 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases. Patients diagnosed with C3 glomerulopathy (n=81) or dense deposit disease (n=16) between January 1995 and March 2018 were enrolled. Multivariable and propensity score matching analyses were used to evaluate the association of clinical and genetic factors with response to treatment with corticosteroids and MMF as measured by proportion of patients with disease remission and kidney survival (status free of kidney failure). RESULTS: The study group comprised 97 patients (84% C3 glomerulopathy, 16% dense deposit disease). Forty-two patients were treated with corticosteroids plus MMF, and this treatment was associated with a higher rate of remission and lower probability of kidney failure (79% and 14%, respectively) compared with patients treated with other immunosuppressives (24% and 59%, respectively), or ecluzimab (33% and 67%, respectively), or conservative management (18% and 65%, respectively). The therapeutic superiority of corticosteroids plus MMF was observed both in patients with complement abnormalities and with autoantibodies. However, patients with pathogenic variants in complement genes only achieved partial remission, whereas complete remissions were common among patients with autoantibody-mediated forms. The main determinant of no remission was baseline proteinuria. Relapses occurred after treatment discontinuation in 33% of the patients who had achieved remission with corticosteroids plus MMF, and a longer treatment length of MMF was associated with a lower risk of relapse. CONCLUSIONS: The beneficial response to corticosteroids plus MMF treatment in C3 glomerulopathy appears independent of the pathogenic drivers analyzed in this study.

Incidence, mortality, and lethality of hospitalizations for community-acquired pneumonia with comorbid cardiovascular disease in Spain (1997-2015).

BACKGROUND: The probability of hospitalization in patients suffering from community-acquired pneumonia (CAP) with an underlying comorbidity, such as a cardiac pathology, is 73-fold higher than that in CAP patients without a comorbidity. Although previous studies have investigated patients with cardiac events and pneumonia, they have not studied the burden of disease in depth at the population level. The objective of this study is to provide population-level data on patients ≥60 years old who were hospitalized with pneumonia with comorbid cardiovascular disease (CVD) in Spain over a period of 19 years (1997-2015). METHODS: This is a retrospective study based on a minimum basic data set (MBDS). The following variables were collected: age, sex, re-admission (yes/no), hospital stay (days), and other diagnoses. Hospitalization rate (per 100,000 inhabitants), mortality rate (per 100,000 inhabitants), and lethality rate (%) were obtained, and the 95% confidence interval of each rate was calculated. Analyses were stratified by age (categorized into 4-year intervals), sex, and year of admission. Differences were assessed for significance with the chi-squared test for proportions and the Poisson model for rates. Logistic regression was run with in-hospital survival as the dependent variable and sex, age, year of admission, and re-admission (yes/no) as the independent variables. The level of significance was p < 0.005. RESULTS: The total number of patients ≥60 years old hospitalized for pneumonia with comorbid CVD was 99,346. The rates of hospitalization, mortality, and lethality increased significantly with age over the 19 years. Men had higher rates of hospitalization and mortality. The probability of a patient with CAP and CVD dying was correlated with male sex, older age, hospital re-admission, and having been hospitalized earlier in the study period. CONCLUSIONS: Community-acquired pneumonia with comorbid cardiovascular disease continues to be a major cause of hospitalization in Spain, especially in the elderly population, making it necessary to develop more preventive strategies for this group of patients.

Benchmarking estratégico aplicado a la gestión de riesgos asistenciales en Quirónsalud / No disponible

INTRODUCCIÓN: La metodología del benchmarking estratégico aplicado a la gestión de riesgos comenzó a utilizarse en el año 2016 en la Compañía Quirónsalud y fue el punto de partida para la implantación de los objetivos de calidad asistencial y de seguridad del paciente. OBJETIVO GENERAL: Realizar un seguimiento continuo y sistemático de las líneas estratégicas marcadas en la Estrategia de Seguridad del Paciente y evaluar su grado de cumplimiento. METODOLOGÍA: Mediante un análisis de debilidades, amenazas, fortalezas y oportunidades (DAFO), se identificaron 17 riesgos, para los que se establecieron objetivos e indicadores. Se utilizó la información disponible en el Conjunto Mínimo Básico de Datos (CMBD) y los indicadores definidos por la Agency for Healthcare Research and Quality (AHRQ), los indicadores de calidad de la hospitalización del grupo Helios (EIQI ́s) y el indicador de cirugía precoz en fractura de cadera de la Organización para la Cooperación y el Desarrollo Económico (OCDE). También se incorporaron los indicadores en el Observatorio de Resultados del Servicio Madrileño de Salud (SERMAS) y los de la Central de Resultados del Servicio Catalán de Salud (CatSalut). RESULTADOS: Entre los resultados obtenidos en 2019 cabe destacar el porcentaje de hospitales que han experimentado una mejora continuada en los indicadores. Implantación de rondas de seguridad trimestrales con participación de la dirección >90%. El % Checklists en cirugía programada >85%. El % de pacientes ingresados con registro de la 5ª constante > 79%. El % de intervenciones por fractura de cadera a las 48h tras ingreso > 78%.Los porcentajes de compromiso (abordaje del objetivo) y de cumplimiento (alcanzar la meta corporativa o superar lo pactado con la Dirección Corporativa) de los indicadores, han experimentado un crecimiento progresivo en los últimos años situándose en 2019 en un 94% y en un 85% respectivamente. CONCLUSIONES: El benchmarking estratégico mejora la eficacia en la gestión de riesgos asistenciales porque permite realizar análisis comparados, identificar y compartir buenas prácticas e introduce el elemento de competencia entre los hospitales promoviendo el compromiso con la estrategia

INTRODUCTION: The strategic benchmarking methodology applied to risk management began to be applied at Quirónsalud Company in 2016. This was the starting point for the implementation of the Company's healthcare quality objectives, including the patient safety objectives. GENERAL OBJECTIVE: To assess the degree to which Quirónsalud facilities comply with the strategy lines set forth in the group-wide patient-safety strategy program. METHODS: Through an analysis of strengths, weaknesses, opportunities and threats (SWOT), 17 threats were identified. This were used to set company-wide targets and indicators. The set of quality indicators were obtained from the information available in the minimum basic data set (MBDS), the indicators defined by the Agency for Healthcare Research and Quality (AHRQ), the hospital-quality indicators of the Helios group (EIQI ́s) and the early hip fracture surgery indicator of the Organization for Economic Co-operation and Development (OECD). In addition, some of the indicators included in the Observatorio de Resultados del Servicio Madrileño de Salud (SERMAS) and the Central de Resultados de Servicio Catalán de Salud (CatSalut) were also incorporated. RESULTS: Among the results obtained in year 2019, the percentage of hospitals that have experienced continuous improvement in the indicators should be highlighted. Implementation of quarterly executive walkarounds > 90%. The % of checklists used in elective surgery > 85%. The % of inpatients evaluated for the 'Fifth Vital Sign' > 79%. The % of hip-fracture surgeries performed within 48h of admission > 78%.There has been a progressive increase over recent years in the degree of commitment to (target approach) and fulfillment (achieve the corporate goal or exceed what was agreed with the Corporate Management) of indicators (94% and 85%, respectively).CONCLUSIONS: Strategic benchmarking improves effective management of care-related risks by allowing comparative analysis, enabling organizations to identify and share best practices, and by introducing an element of competition between hospitals, thereby driving commitment to organization-wide strategy

Differences between diabetic and non-diabetic patients with community-acquired pneumonia in primary care in Spain.

BACKGROUND: Diabetes is one of the underlying risk factors for developing community-acquired pneumonia (CAP). The high prevalence of diabetes among population and the rising incidence of this illness, converts it as an important disease to better control and manage, to prevent its secondary consequences as CAP. The objective of this research is to describe the characteristics of the patients with diabetes and the differences with the no diabetes who have had an episode of CAP in the context of the primary care field. METHODS: A retrospective, observational study in adult patients (> 18 years-old) who suffer from CAP and attended at primary care in Spain between 2009 and 2013 was developed using the Computerized Database for Pharmacoepidemiological Studies in Primary Care (BIFAP). We carried out a descriptive analysis of the first episodes of CAP, in patients with or without diabetes as comorbidity. Other morbidity (CVA, Anaemia, Arthritis, Asthma, Heart disease, Dementia, Depression, Dysphagia, Multiple sclerosis, Epilepsy, COPD, Liver disease, Arthrosis, Parkinson's disease, Kidney disease, HIV) and life-style factors were also included in the study. RESULTS: A total of 51,185 patients were included in the study as they suffer from the first episode of CAP. Of these, 8012 had diabetes as comorbidity. There were differences between sex and age in patients with diabetes. Patients without diabetes were younger, and had less comorbidities including those related to lifestyles such as smoking, alcoholism, social and dental problems than patients with diabetes. CONCLUSIONS: Patients who developed an episode of CAP with diabetes have more risk factors which could be reduced with an appropriate intervention, including vaccination to prevent successive CAP episodes and hospitalization. The burden of associated factors in these patients can produce an accumulation of risk. Health care professional should know this for treating and control these patients in order to avoid complications. Diabetes and those other risk factors associated could be reduced with an appropriate intervention, including vaccination to prevent the first and successive CAP episodes and the subsequent hospitalization in severe cases.

Propagating modes in a binary liquid mixture under thermal stress.

Nonequilibrium temperature and concentration fluctuations inside a binary liquid mixture under the action of a temperature gradient relax back to equilibrium either due to conduction and diffusion at large wave numbers, or due to the quenching determined by gravity at small wave numbers. We investigate the dynamics of nonequilibrium fluctuations in a binary liquid mixture of polystyrene and toluene heated from above under stationary conditions in a thermodiffusion experiment. We show that the strong gravitational stabilization at small wave numbers determines the appearance of propagating modes of nonequilibrium fluctuations as detected through the structure function of shadowgraph images. The propagating modes are the combined effect of temperature and velocity nonequilibrium fluctuations induced by the buoyancy force. The experimental results are in good agreement with a fluctuating hydrodynamics theroretical model including the coupling of fluctuations of velocity, temperature and concentration.

Effector Antitumor and Regulatory T Cell Responses Influence the Development of Nonmelanoma Skin Cancer in Kidney Transplant Patients.

BACKGROUND: Chronic immunosuppression promotes nonmelanocytic squamous cell carcinoma (SCC) after kidney transplantation. Adaptive and innate immunity play a key role controlling tumor growth and are influenced by different immunosuppressive agents. We hypothesized that functional impairment of tumor-specific T cell responses due to calcineurin inhibitors (CNI) could contribute to SCC development, whereas conversion to mammalian target of rapamycin inhibitors (mTOR-i) could recover this protective immune response. METHODS: Peripheral tumor-specific T cell responses against main SCC-derived antigens using the IFN-γ enzyme-linked immunospot assay and intratumor (IT) and circulating immune phenotypes (CD4 + T, CD8 + T, CD20 + B, CD56 + NK, FOXP3 + regulatory T [Treg] cells) were explored in a cross-sectional analysis in 59 kidney transplant patients with SCC on CNI (KT-CNI-SCC) or mTOR-i (KT-mTORi-SCC), 25 nontransplants developing SCC (NoKT-SCC) and 6 healthy controls. Moreover, 25 KT-CNI-SCC were switched to mTOR-i and evaluated after 12 months. RESULTS: Kidney transplant patients showed lower IT infiltrates and tumor-specific T cell responses than NoKT-SCC, and intratumoral and circulating FOXP3 + Treg cells were higher in KT-mTORi-SCC (P < 0.05). Tumor-specific T cell responses were significantly lower in KT-CNI-SCC than KT-mTORi-SCC and NoKT-SCC and predicted SCC relapses (area under the curve = 0.837; P < 0.05). One-year after mTOR-i conversion, a significant increase in FOXP3 + Treg cell numbers and tumor-specific T cell responses were observed, reaching similar levels than KT-mTORi-SCC and NoKT-SCC patients. CONCLUSIONS: Tumor-specific T cell responses are strongly impaired in CNI-treated patients but recover after mTOR-i conversion, reducing SCC relapses.