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1.
Nephrol Dial Transplant ; 39(2): 328-340, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-37550217

RESUMO

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.


Assuntos
Diabetes Mellitus Tipo 2 , Glomerulonefrite , Nefropatias , Adulto , Humanos , Pessoa de Meia-Idade , Estudos de Coortes , Nefropatias/complicações , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/complicações , Proteinúria/etiologia , Proteinúria/complicações , Albumina Sérica , Sódio , Glucose , Diabetes Mellitus Tipo 2/complicações
2.
Nephrol Dial Transplant ; 37(7): 1270-1280, 2022 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-33779754

RESUMO

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.


Assuntos
Glomerulonefrite Membranoproliferativa , Glomerulonefrite , Falência Renal Crônica , Adolescente , Adulto , Complemento C3/análise , Glomerulonefrite/complicações , Glomerulonefrite/epidemiologia , Humanos , Rim , Falência Renal Crônica/complicações , Proteinúria/complicações , Proteinúria/etiologia , Estudos Retrospectivos , Adulto Jovem
3.
Eur Phys J E Soft Matter ; 45(6): 52, 2022 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-35633426

RESUMO

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.


Assuntos
Convecção , Poliestirenos , Cicloexanos , Polímeros , Solventes , Tolueno
4.
Am J Kidney Dis ; 77(5): 684-695.e1, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33359150

RESUMO

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.


Assuntos
Complemento C3/imunologia , Glomerulonefrite Membranoproliferativa/patologia , Túbulos Renais/patologia , Insuficiência Renal/patologia , Adolescente , Adulto , Atrofia , Criança , Estudos de Coortes , Progressão da Doença , Feminino , Fibrose , Taxa de Filtração Glomerular , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/imunologia , Glomerulonefrite/metabolismo , Glomerulonefrite/patologia , Glomerulonefrite Membranoproliferativa/tratamento farmacológico , Glomerulonefrite Membranoproliferativa/imunologia , Glomerulonefrite Membranoproliferativa/metabolismo , Humanos , Imunossupressores/uso terapêutico , Rim/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Proteinúria , Insuficiência Renal/imunologia , Insuficiência Renal/metabolismo , Reprodutibilidade dos Testes , Estudos Retrospectivos , Adulto Jovem
5.
BMC Infect Dis ; 20(1): 477, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631257

RESUMO

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.


Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/mortalidade , Hospitalização , Pneumonia/epidemiologia , Pneumonia/mortalidade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Comorbidade , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Estudos Retrospectivos , Fatores Sexuais , Espanha/epidemiologia
6.
BMC Infect Dis ; 19(1): 973, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730464

RESUMO

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.


Assuntos
Infecções Comunitárias Adquiridas/diagnóstico , Complicações do Diabetes/diagnóstico , Pneumonia/diagnóstico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Infecções Comunitárias Adquiridas/complicações , Comorbidade , Complicações do Diabetes/complicações , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Pneumonia/complicações , Atenção Primária à Saúde , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Espanha
7.
Clin Kidney J ; 16(6): 985-995, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37260991

RESUMO

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.

8.
Clin Kidney J ; 15(9): 1737-1746, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36003665

RESUMO

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.

9.
Vaccine ; 39(35): 5002-5006, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34304929

RESUMO

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.


Assuntos
Coinfecção , Influenza Humana , Pneumonia Pneumocócica , Pneumonia Viral , Adolescente , Idoso , Coinfecção/epidemiologia , Hospitalização , Humanos , Influenza Humana/complicações , Influenza Humana/epidemiologia , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/epidemiologia , Estudos Retrospectivos , Estações do Ano , Espanha/epidemiologia
10.
Clin J Am Soc Nephrol ; 15(9): 1287-1298, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32816888

RESUMO

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.


Assuntos
Complemento C3/análise , Glomerulonefrite/tratamento farmacológico , Imunossupressores/uso terapêutico , Ácido Micofenólico/uso terapêutico , Adolescente , Corticosteroides/uso terapêutico , Adulto , Criança , Progressão da Doença , Quimioterapia Combinada , Feminino , Glomerulonefrite/diagnóstico , Glomerulonefrite/imunologia , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Recidiva , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Espanha , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
12.
Phys Rev E ; 99(1-1): 012602, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30780374

RESUMO

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.

14.
Enferm Clin ; 27(2): 79-86, 2017.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27640931

RESUMO

OBJECTIVE: To determine the incidence and risk factors of phlebitis associated to the care of peripheral vascular catheters (PVC). METHOD: Prospective cohort study at the Central University Hospital of Asturias (Spain). A total of 178PVC were observed daily until their extraction. The incidence of phlebitis was measured using the Visual Infusion Phlebitis Scale, that distinguishes between gradei (possible phlebitis) andii (phlebitis). The independent diagnoses of phlebitis made by staff nurses were also collected. Finally, data about the insertion and the care of the PVC was also obtained. The incidence of phlebitis and the validity of the diagnoses made by staff nurses were calculated and the risk factors of phlebitis were determined by means of logistic regression. RESULTS: 5.6% of the PVC presented phlebitis, 21.3% possible phlebitis and 11.2% had phlebitis according to nurses' criteria. The staff nurses had a sensitivity of 100%, a specificity of 94% and a positive predictive value of 50% in the diagnosis of phlebitis. After adjusting for potential confounders, the use of an extension tube as an accessory of the PVC was an independent predictor of phlebitis (odds ratio: 4.8; P=.04), but a PVC size of 22/24 gauges was associated with lower phlebitis incidence (odds ratio: 0.2; P=.02). CONCLUSIONS: Clinical phlebitis assessment is difficult because the agreement for phlebitis diagnosis is low. To minimize the incidence of phlebitis would be recommended to choose the smallest PVC size possible and to avoid using an extension tube as an accessory of the PVC.


Assuntos
Cateterismo Periférico/efeitos adversos , Flebite/epidemiologia , Flebite/etiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
15.
Transplantation ; 101(9): 2102-2110, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28403126

RESUMO

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.


Assuntos
Antígenos de Neoplasias/imunologia , Carcinoma de Células Escamosas/induzido quimicamente , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Neoplasias Cutâneas/induzido quimicamente , Linfócitos T Reguladores/efeitos dos fármacos , Evasão Tumoral/efeitos dos fármacos , Idoso , Inibidores de Calcineurina/efeitos adversos , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Estudos Transversais , Citocinas/imunologia , Citocinas/metabolismo , Substituição de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Fenótipo , Inibidores de Proteínas Quinases/efeitos adversos , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Resultado do Tratamento
19.
Clin Kidney J ; 9(3): 381-6, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27274821

RESUMO

BACKGROUND: Variability in the management of glomerulonephritis may negatively impact efficacy and safety. However, there are little/no data on actual variability in the treatment of minimal change disease (MCD)/focal segmental glomerulosclerosis (FSGS) in adults. We assessed Spanish practice patterns for the management of adult nephrotic syndrome due to MCD or FSGS. The absence of reasonably good evidence on treatment for a disease often increases the variability substantially. Identification of evidence-practice gaps is the first necessary step in the knowledge-to-action cyclical process. We aim to analyse the real clinical practice in adults in hospitals in Spain and compare this with the recently released Kidney Disease: Improving Global Outcomes clinical practice guideline for glomerulonephritis. METHODS: Participating centres were required to include all adult patients (age >18 years) with a biopsy-proven diagnosis of MCD or FSGS from 2007 to 2011. Exclusion criteria included the diagnosis of secondary nephropathy. RESULTS: We studied 119 Caucasian patients with biopsy-proven MCD (n = 71) or FSGS (n = 48) from 13 Spanish hospitals. Of these patients, 102 received immunosuppressive treatment and 17 conservative treatment. The initial treatment was steroids, except in one patient in which mycophenolate mofetil was used. In all patients, the steroids were given as a single daily dose. The mean duration of steroid treatment at initial high doses was 8.7 ± 13.2 weeks and the mean global duration was 38 ± 32 weeks. The duration of initial high-dose steroids was <4 weeks in 41% of patients and >16 weeks in 10.5% of patients. We did find a weak and negative correlation between the duration of whole steroid treatment in the first episode and the number of the later relapses (r = -0.24, P = 0.023). There were 98 relapses and they were more frequent in MCD than in FSGs patients (2.10 ± 1.6 versus 1.56 ± 1.2; P = 0.09). The chosen treatment was mainly steroids (95%). Only seven relapses were treated with another drug as a first-line treatment: two relapses were treated with mycophenolate and five relapses were treated with anticalcineurinics. A second-line treatment was needed in 29 patients (24.4%), and the most frequent drugs were the calcineurin inhibitors (55%), followed by mycophenolate mofetil (31%). Although cyclophosphamide is the recommended treatment, it was used in only 14% of the patients. CONCLUSIONS: We found variation from the guidelines in the duration of initial and tapered steroid therapy, in the medical criteria for classifying a steroid-resistant condition and in the chosen treatment for the second-line treatment. All nephrologists started with a daily dose of steroids as the first-line treatment. The most frequently used steroid-sparing drug was calcineurin inhibitors. Cyclophosphamide use was much lower than expected.

20.
Asia Pac Psychiatry ; 6(1): 23-7, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24019245

RESUMO

INTRODUCTION: The purpose of the present study is to compare the role of spiritual and religious beliefs in the prevention of suicidal risk among depressive women with suicidal ideation or attempts, treated in the psychiatric unit of a general hospital in Santiago de Chile (Servicio de Psiquiatría del Hospital del Salvador) between 2010 and 2011. METHOD: The relationship among severity of depression, suicidal risk, and religiosity is explored in women treated in Servicio de Psiquiatría del Hospital del Salvador. The sociodemographic and clinical characteristics of believers (n = 121) and nonbelievers (n = 22) were compared, and their global mental health was assessed, as well as their rating in scales for depression, anxiety, aggressivity, and impulsivity. RESULTS: Most of the patients self-reported to belong to Catholic or other Christian churches. There were few statistically significant differences between them and nonbelievers, who were younger, had more years of education, were more frequently employed, and lived alone or with their parents. When comparing the least religious and the most religious quartiles, there were no differences in the type of affective disorder, attendance to temples, or self-appraisal of religiosity. Nonbelievers had more history of previous suicidal attempts and had more relatives committing suicide. DISCUSSION: In a country where most of the population is believer, self-reported religiosity seems to have a nonsignificant association with suicidality and severity of depression. Our results could be biased given the small number of nonbelievers in the sample.


Assuntos
Transtorno Depressivo/psicologia , Religião , Ideação Suicida , Tentativa de Suicídio/prevenção & controle , Adulto , Assistência Ambulatorial , Chile , Feminino , Hospitalização , Hospitais Gerais , Humanos , Escalas de Graduação Psiquiátrica , Fatores de Risco , Espiritualidade
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