Estado cualitativo y cuantitativo óseo generalizado en la osteonecrosis de maxilares. Efecto de los bifosfonatos

Objetivo: La osteonecrosis de maxilares (ONM) es una enfermedad recientemente descrita cuya etiopatogenia es desconocida, aunque se ha atribuido, entre otras causas, al tratamiento prolongado con bifosfonatos. Sin embargo, mientras que la ONM es una patología localizada, la acción de los bifosfonatos es generalizada, es decir, afecta a todos los huesos. No hay estudios que muestren el estado óseo general de los pacientes con ONM. Con este trabajo hemos querido estudiar en pacientes afectos de ONM dicho estado general mediante medidas cuantitativas y estimaciones cualitativas del hueso por medio de la densidad mineral ósea (DMO) y el trabecular bone score (TBS) y los parámetros ultrasonográficos en el calcáneo (QUS), además de la presencia de otras enfermedades y la toma de fármacos (especialmente los bifosfonatos) en los pacientes con ONM que pudieran participar en su etiopatogenia. Material y método: Estudio observacional y transversal de casos y controles, realizado en 304 pacientes de ambos sexos, en los que el grupo de casos (grupo I) estaba formado por 24 pacientes que habían sufrido una ONM, mientras que el grupo control (grupo II) estaba formado por 280 pacientes que no presentaban ONM y que recibían bifosfonatos desde un mínimo de 5 años por causas diversas. A todos ellos se les realizó una densitometría ósea (DXA, Hologic 4500 Discovery®) en la columna lumbar y en la extremidad proximal del fémur. Además, se les realizó mediciones del TBS en la columna lumbar, así como de los parámetros ultrasonográficos en el calcáneo (Hologic, Sahara®) en el pie dominante (QUS). Resultados: Los pacientes afectos de ONM tenían una mayor comorbilidad que los controles, con una mayor prevalencia de las siguientes enfermedades: diabetes mellitus, cáncer, artritis reumatoide, hipertiroidismo, cardiopatía, arritmias, insuficiencia cardíaca e hipercolesterolemia. Por ello, el consumo de corticoides, (orales e inhalados), anticoagulantes, hipnóticos, bifosfonatos i.v. (zoledronato), y quimioterapia antineoplásica fue también mayor entre los pacientes afectos de ONM que los pacientes controles. Sin embargo, entre los pacientes con ONM el porcentaje que tomaba bifosfonatos orales fue menor. Los valores densitométricos (DMO medida en la columna lumbar L2‐L4, cuello femoral y total de cadera) fueron más elevados en los pacientes con ONM en comparación con los de los controles. El TBS no mostró diferencias estadísticamente significativas entre ambos grupos, y los ultrasonidos presentaron valores más elevados de QUI y SOS en los pacientes con ONM que en los controles. La prevalencia de fracturas por fragilidad fue similar en ambos grupos. Conclusiones: Nuestros pacientes afectos de ONM mostraron una mayor comorbilidad y un mayor consumo de fármacos que los pacientes del grupo control, a excepción de bifosfonatos orales. Por otro lado, tanto la DMO como los parámetros ultrasonográficos mostraron valores más elevados en los pacientes con ONM que los controles. Si consideramos la DXA como una técnica medidora de la cantidad de masa ósea, y el TBS y la ultrasonografía de calcáneo técnicas estimadoras de aspectos cualitativos del hueso, podemos suponer que ni la cantidad ni la calidad óseas en general parecen estar afectadas en la ONM, siendo probablemente otro su mecanismo etiopatogénico. Los bifosfonatos orales no parecen estar entre los fármacos que participen en la etiología de la ONM, aunque sí los bifosfonatos más potentes que se administran por vía intravenosa, si bien no pueden considerarse independientemente de la patología subyacente para la cual se administran

Seroprevalence of Chikungunya Virus after Its Emergence in Brazil.

Chikungunya has had a substantial impact on public health because of the magnitude of its epidemics and its highly debilitating symptoms. We estimated the seroprevalence, proportion of symptomatic cases, and proportion of chronic form of disease after introduction of chikungunya virus (CHIKV) in 2 cities in Brazil. We conducted the population-based study through household interviews and serologic surveys during October-December 2015. In Feira de Santana, we conducted a serologic survey of 385 persons; 57.1% were CHIKV-positive. Among them, 32.7% reported symptoms, and 68.1% contracted chronic chikungunya disease. A similar survey in Riachão do Jacuípe included 446 persons; 45.7% were CHIKV-positive, 41.2% reported symptoms, and 75.0% contracted the chronic form. Our data confirm intense CHIKV transmission during the continuing epidemic. Chronic pain developed in a high proportion of patients. We recommend training health professionals in management of chronic pain, which will improve the quality of life of chikungunya-affected persons

Contribution of Candida biomarkers and DNA detection for the diagnosis of invasive candidiasis in ICU patients with severe abdominal conditions

BACKGROUND: To assess the performance of Candida albicans germ tube antibody (CAGTA), (1 → 3)-ß-D-glucan (BDG), mannan antigen (mannan-Ag), anti-mannan antibodies (mannan-Ab), and Candida DNA for diagnosing invasive candidiasis (IC) in ICU patients with severe abdominal conditions (SAC). METHODS: A prospective study of 233 non-neutropenic patients with SAC on ICU admission and expected stay ≥ 7 days. CAGTA (cutoff positivity ≥ 1/160), BDG (≥80, 100 and 200 pg/mL), mannan-Ag (≥60 pg/mL), mannan-Ab (≥10 UA/mL) were measured twice a week, and Candida DNA only in patients treated with systemic antifungals. IC diagnosis required positivities of two biomarkers in a single sample or positivities of any biomarker in two consecutive samples. Patients were classified as neither colonized nor infected (n = 48), Candida spp. colonization (n = 154) (low-grade, n = 130; high-grade, n = 24), and IC (n = 31) (intra-abdominal candidiasis, n = 20; candidemia, n = 11). RESULTS: The combination of CAGTA and BDG positivities in a single sample or at least one of the two biomarkers positive in two consecutive samples showed 90.3 % (95 % CI 74.2–98.0) sensitivity, 42.1 % (95 % CI 35.2–98.8) specificity, and 96.6 % (95 % CI 90.5–98.8) negative predictive value. BDG positivities in two consecutive samples had 76.7 % (95 % CI 57.7–90.1) sensitivity and 57.2 % (95 % CI 49.9–64.3) specificity. Mannan-Ag, mannan-Ab, and Candida DNA individually or combined showed a low discriminating capacity. CONCLUSIONS: Positive Candida albicans germ tube antibody and (1 → 3)-ß-D-glucan in a single blood sample or (1 → 3)-ß-D-glucan positivity in two consecutive blood samples allowed discriminating invasive candidiasis from Candida spp. colonization in critically ill patients with severe abdominal conditions. These findings may be helpful to tailor empirical antifungal therapy in this patient population

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049