A meta-analysis of preclinical studies using antioxidants for the prevention of cisplatin nephrotoxicity: implications for clinical application.

Cisplatin is an effective chemotherapeutic drug whose clinical use and efficacy are limited by its nephrotoxicity, which affects mainly the renal tubules and vasculature. It accumulates in proximal and distal epithelial tubule cells and causes oxidative stress-mediated cell death and malfunction. Consequently, many antioxidants have been tested for their capacity to prevent cisplatin nephrotoxicity. In this study, we made a systematic review of the literature and meta-analyzed 152 articles, which tested the nephroprotective effect of isolated compounds or mixtures of natural origin on cisplatin nephrotoxicity in preclinical models. This meta-analysis identified the most effective candidates and examined the efficacy obtained by antioxidants administered by the oral and intraperitoneal routes. By comparing with a recent, similar meta-analysis performed on clinical studies, this article identifies a disconnection between preclinical and clinical research, and contextualizes, discusses, and integrates the existing preclinical information toward the optimized selection of candidates to be further explored (clinical level). Despite proved efficacy, this article discusses the barriers limiting the clinical development of natural mixtures, such as those in extracts from Calendula officinalis flowers and Heliotropium eichwaldii roots. On the contrary, isolated compounds are more straightforward candidates, among which arjunolic acid and quercetin stand out in this meta-analysis.

Albuminuria Pre-Emptively Identifies Cardiac Patients at Risk of Contrast-Induced Nephropathy.

Contrast-induced nephropathy (CIN) is a complication associated with the administration of contrast media (CM). The CIN diagnosis is based on creatinine, a biomarker late and insensitive. The objective proposed was to evaluate the ability of novel biomarkers to detect patients susceptible to suffering CIN before CM administration. The study was carried out with patients undergoing cardiac catheterization involving CM. Patients were divided into two groups: (1) CIN, patients who developed this pathology; (2) control, patients who did not suffer CIN. Prior to the administration of CM, urine samples were collected to measure proteinuria, N-acetyl-ß-d-glucosaminidase, neutrophil gelatinase-associated lipocalin and kidney injury molecule-1, albumin, transferrin, t-gelsolin and GM2 ganglioside activator protein (GM2AP). The risk factors advanced age, low body mass index and low estimated glomerular filtration rate; and the urinary biomarkers albumin, transferrin and GM2AP showed significant predictive capacity. Of all of them, albuminuria demonstrated the highest diagnostic power. When a cutoff point was established for albuminuria at values still considered subclinical (10-30 µg/mg Cru), it was found that there was a high incidence of CIN (40-75%). Therefore, albuminuria could be applied as a new diagnostic tool to prevent and predict CIN with P4 medicine criteria, independently of risk factors and comorbidities.

Urinary transferrin pre-emptively identifies the risk of renal damage posed by subclinical tubular alterations.

Nephrotoxicity is an important limitation to the clinical use of many drugs and contrast media. Drug nephrotoxicity occurs in acute, subacute and chronic manifestations ranging from glomerular, tubular, vascular and immunological phenotypes to acute kidney injury. Pre-emptive risk assessment of drug nephrotoxicity poses an urgent need of precision medicine to optimize pharmacological therapies and interventional procedures involving nephrotoxic products in a preventive and personalized manner. Biomarkers of risk have been identified in animal models, and risk scores have been proposed, whose clinical use is abated by their reduced applicability to specific etiological models or clinical circumstances. However, our present data suggest that the urinary level of transferrin may be indicative of risk of renal damage, where risk is induced by subclinical tubular alterations regardless of etiology. In fact, urinary transferrin pre-emptively correlates with the subsequent renal damage in animal models in which risk has been induced by drugs and toxins affecting the renal tubules (i.e. cisplatin, gentamicin and uranyl nitrate); whereas transferrin shows no relation with the risk posed by a drug affecting renal hemodynamics (i.e. cyclosporine A). Our experiments also show that transferrin increases in the urine in the risk state (i.e. prior to the damage) precisely as a consequence of reduced tubular reabsorption. Finally, urinary transferrin pre-emptively identifies subpopulations of oncological and cardiac patients at risk of nephrotoxicity. In perspective, urinary transferrin might be further explored as a wider biomarker of an important mechanism of predisposition to renal damage induced by insults causing subclinical tubular alterations.

[Concurrent lymphoproliferative and myeloproliferative disorders in three patients]. / Coexistencia de Síndrome Lifoproliferativo Crónico y Síndrome Mieloproliferativo Crónico en tres pacientes.

We present two patients with a diagnosis of chronic lymphoproliferative syndrome, chronic lymphocytic leukemia B (CLL B) and lymphoplasmacytic non-Hodgkin's lymphoma (NHL), who developed chronic myeloproliferative syndrome: polycythemia vera (PV) and Philadelphia-positive chronic myeloid leukemia (CML) respectively, and a third patient with chronic myeloproliferative syndrome, polycythemia vera (PV), who developed an undefined immunophenotype cyclin D1-positive chronic lymphoproliferative syndrome. The cases included in literature are scarce, and it is not known whether some common mechanism can explain both processes' pathogeneses and the control mechanisms of one process over the other.

Comparison of the traditional pharmaceutical validation method versus an assisted pharmaceutical validation in hospitalized patients.

OBJECTIVE: To analyze pharmaceutical interventions that have been carried out with the support of an automated system for validation of treatments vs. the traditional method without computer support. METHOD: The automated program, ALTOMEDICAMENTOS® version 0, has 925 052 data with information regarding approximately 20 000 medicines, analyzing doses, administration routes, number of days with such a treatment, dosing in renal and liver failure, interactions control, similar drugs, and enteral medicines. During eight days, in four different hospitals (high complexity with over 1 000 beds, 400-bed intermediate, geriatric and monographic), the same patients and treatments were analyzed using both systems. RESULTS: 3,490 patients were analyzed, with 42 155 different treatments. 238 interventions were performed using the traditional system (interventions 0.56% / possible interventions) vs. 580 (1.38%) with the automated one. Very significant pharmaceutical interventions were 0.14% vs. 0.46%; significant was 0.38% vs. 0.90%; non-significant was 0.05% vs. 0.01%, respectively. If both systems are simultaneously used, interventions are performed in 1.85% vs. 0.56% with just the traditional system. Using only the traditional model, 30.5% of the possible interventions are detected, whereas without manual review and only the automated one, 84% of the possible interventions are detected. CONCLUSIONS: The automated system increases pharmaceutical interventions between 2.43 to 3.64 times. According to the results of this study the traditional validation system needs to be revised relying on automated systems. The automated program works correctly in different hospitals.

Objetivo: Analizar las intervenciones farmacéuticas realizadas con el apoyo de un sistema automático de validación de tratamientos vs. el método tradicional sin apoyo informático. Metodos: El programa automatizado, ALTOMEDICAMENTOS ® version 0, cuenta con 925.052 celdas con información de aproximadamente 20.000 medicamentos, analizando dosis, vías de administración, días de tratamiento, dosificación en insuficiencia renal y hepática, control de interacciones, de medicamentos semejantes y de medicamentos por vía enteral. Durante ocho días distribuidos en cuatro hospitales diferentes (alta complejidad con más de 1.000 camas, intermedio de 400 camas, geriátrico y monográfico), los mismos pacientes y tratamientos se analizaron mediante los dos sistemas. Resultados: Se han analizado 3.490 pacientes diferentes con 42.155 tratamientos. Por el sistema tradicional se han realizado 238 intervenciones (0,56% intervenciones/posibles intervenciones) vs. 580 (1,38%) con el automatizado. Las intervenciones farmacéuticas muy significativas fueron 0,14 vs. 0,46%, las significativas 0,38 vs. 0,90%, las no significativas 0,05 vs. 0,01%. Las intervenciones fueron del 1,85% al utilizar los dos sistemas vs. 0.56% usando solo el sistema tradicional. El sistema tradicional detectó el 30,5% de las posibles intervenciones, sin embargo con el sistema automático se detectaron el 84% de dichas intervenciones. Conclusiones: La automatización multiplica entre 2,43 a 3,64 veces las intervenciones farmacéuticas. En base a los resultados de este estudio el sistema tradicional de validación debería ser modificado, apoyándose en sistemas automatizados. El programa automático funciona en diferentes hospitales.

Mutation status and immunoglobulin gene rearrangements in patients from northwest and central region of Spain with chronic lymphocytic leukemia.

The aim of this study was to investigate the frequency and mutation status of the immunoglobulin heavy variable chain (IGHV) in a cohort of 224 patients from northwest and central region of Spain diagnosed with chronic lymphocytic leukemia (CLL), and to correlate it with cytogenetic abnormalities, overall survival (OS) and time to first treatment (TTFT). 125 patients had mutated IGHV, while 99 had unmutated IGHV. The most frequently used IGHV family was IGHV3, followed by IGHV1 and IGHV4. The regions IGHV3-30, IGHV1-69, IGHV3-23, and IGHV4-34 were the most commonly used. Only 3.1% of the patients belonged to the subfamily IGHV3-21 and we failed to demonstrate a worse clinical outcome in this subgroup. The IGHV4 family appeared more frequently with mutated pattern, similar to IGHV3-23 and IGHV3-74. By contrast, IGHV1-69 was expressed at a higher frequency in unmutated CLL patients. All the cases from IGHV3-11 and almost all from IGHV5-51 subfamily belonged to the group of unmutated CLL.

Asociación de insuficiencia renal aguda con mortalidad y complicaciones en pacientes hospitalizados con cirrosis hepática / Association of acute renal failure with mortality and complications in hospitalized patients with liver cirrhosis

Resumen ANTECEDENTES: la insuficiencia renal aguda es una de las complicaciones más severas de la cirrosis y conlleva un pronóstico ominoso. Los estudios que han utilizado definiciones más actuales de daño renal agudo, como AKIN (Acute Kidney Injury Network) o RIFLE (The Risk, Injury, Failure, Loss and End-stage kidney disease criteria) se enfocan en pacientes admitidos en unidades de cuidados intensivos y no pueden generalizarse a otros pacientes hospitalizados. El Club Internacional de Ascitis (ICA por sus siglas en inglés) recientemente adoptó una definición dinámica de insuficiencia renal crónica en pacientes con cirrosis, definiéndola como el incremento de la creatinina sérica mayor o igual de 0.3 mg/dL en las últimas 48 horas o un incremento de más de 50% de la creatinina basal conocida ocurrida en los últimos siete días, estadificándose de acuerdo con los incrementos de la creatinina. OBJETIVO: evaluar la repercusión de la severidad de la insuficiencia renal aguda de acuerdo con la clasificación del Club Internacional de Ascitis en la mortalidad de los pacientes con cirrosis hepática hospitalizados, así como conocer los principales desencadenantes de insuficiencia renal aguda en pacientes con cirrosis hepática hospitalizados, los patrones de recuperación o progresión de la misma. PACIENTES Y MÉTODO: estudio transversal, observacional, no aleatorizado y multicéntrico, en el que se utilizó la definición de insuficiencia renal aguda propuesta por el Club Internacional de Ascitis. Los pacientes se captaron en un lapso de cuatro meses, del 1 de abril al 31 de julio de 2015, en el Hospital General Ticomán y en el Hospital General de Ecatepec; se solicitó consentimiento informado de los pacientes o en caso pertinente, del familiar responsable del mismo. Se excluyeron los pacientes menores de 18 años, sujetos con insuficiencia hepática aguda y los pacientes con enfermedad renal crónica. RESULTADOS: se incluyeron 45 pacientes con cirrosis hepática, de los que 36 eran hombres, con edad promedio de 46.2 años. La causa de la cirrosis hepática fue por alcohol en 40 pacientes (89%), viral en 3 (7%) y mixta en 2 (4%); la estadificación de insuficiencia renal aguda inicial fue: estadio 1: 36 (80%), estadio 2: 8 (18%) y estadio 3: 1 (2%). Ocurrieron siete defunciones (15.5%); de éstas, todos los pacientes estaban en la categoría C de la clasificación Child-Pugh, con insuficiencia renal aguda en estadio inicial 1; en 6 (13%) pacientes con progresión a estadio 3 y en estadio inicial 2; en 1 (2%) paciente con progresión a estadio 3. La severidad de la cirrosis en la escala MELD (Model for End-Stage Liver Disease) fue de 31.07±8.44 puntos en los pacientes que fallecieron versus 22.98±9.64 puntos (p=1.21) en los supervivientes. El puntaje de Child-Pugh en el grupo de pacientes fallecidos fue de 14.29±0.9 vs 0.29±2.31 en los supervivientes (p=0.001). CONCLUSIONES: la mortalidad en pacientes con cirrosis hepática e insuficiencia renal aguda fue más frecuente en pacientes con progresión al estadio de insuficiencia renal aguda y en sujetos con mayor severidad de la cirrosis hepática, valorada por Child-Pugh o por la escala MELD. Se requieren estudios de cohorte en nuestra población para validar la reciente clasificación del Club Internacional de Ascitis de la insuficiencia renal aguda en cirrosis y para determinar los factores asociados con incremento en la mortalidad en este grupo de pacientes.

Abstract BACKGROUND: Acute renal failure is one of the most severe complications of cirrhosis and entails a bad prognosis. The studies that had used most current definitions of acute kidney injury such as AKIN (Acute Kidney Injury Network) or RIFLE (The Risk, Injury, Failure, Loss and End-stage kidney disease criteria) has focused in patients admitted to the critical care units, and thus they can not be generalized to other hospitalized patients. Recently, the International Club of Ascites (ICA) adopted a dynamic definition of acute kidney failure in patient with cirrhosis, defined like increase of the creatinine level ≥0.3 mg/dL in the last 48 h; or a increase ≥50% from the basal creatinine in the last seven days, staged according the increase of creatinine. OBJECTIVES: To evaluate the impact of acute kidney injury severity according to the classification of the International Club of Ascites in the mortality of hospitalized patients with liver cirrhosis. To know the main triggers of acute kidney failure in hospitalized patients with liver cirrhosis, and to know the patterns of recovery and progression of renal failure. PATIENTS AND METHOD: A transversal, observational, no-randomized multicentric study designed. We used the definition of acute kidney failure proposed for the ICA. Patients were included from the General Hospital Ticoman and the General Hospital of Ecatepec in Mexico, in a four-month-period, from 1st April to 31st July of 2015; informed consent was obtained from the patients or in the pertinent case from the responsible familiar. Patients with less than 18 years old, with acute liver failure or chronic renal failure were excluded. RESULTS: They were included 45 patients with liver cirrhosis, 36 men, with a mean age of 46.2 years old. The etiology of the liver cirrhosis was alcohol in 40 patients (89%), viral in 3 (7%) and mixed in 2 (4%). The stage of acute liver failure was stage 1: 36 (80%), stage 2: 8 (18%) and stage 3: 1 (2%). Seven deaths occurred (15.5%), from there all the patients were classified in the C stage of the Child-Pugh Classification; death occurred with acute renal failure in initial stage 1; in 6 (13%) with progression to the stage 3 and in initial stage 2 in 1 (2%) with progression to stage 3. The severity of cirrhosis accord to the MELD classification was 31.07±8.44 points in the mortality cases, compared with 22.9±9.64 points (p=1.21) in the survivals. Child-Pugh score in the cases of death was 14.29±.9 vs 0.29±2.31 in survivals (p=0.001). CONCLUSION: Mortality in patients with liver cirrhosis and acute kidney failure was more frequent in patients with progression of the acute kidney failure, and in those with a more severe liver damage in the MELD or Child-Pugh scores. There are necessary cohort studies for the validation of the recent classification of the International Club of Ascites for Acute kidney failure in cirrhosis, and to determine the factors associated to the increase of mortality in this group of patients.

[Survey on risky sexual behavior and sexually transmitted diseases among adolescent students from Havana City, 1996]. / Encuesta sobre comportamientos sexuales riesgosos y enfermedades de transmisión sexual en estudiantes adolescentes de Ciudad de La Habana, 1996.

The observed increase of sexually transmitted diseases (STD) in Cuba aroused the interest of carrying out a study aimed at exploring risky sexual behaviours and attitudes, and histories of STD. A crosswise descriptive study was undertaken using a randomized sample taken from the universe of adolescent students in the City of Havana during 1995-96 school year. The sample was made up by 2,793 teenagers aged 11-19 years (1,370 females and 1,423 males). Previously trained experts linked to this field collected data by means of a structured interview which had been drawn up for this end. It was confirmed that more than half of adolescent students did not use condom in their sexual intercourse 57% had more than one sexual partner along the year, 40% believed it was difficult to keep only one partner whereas 35% had more than one sexual partner at the same time. Risk and protected sexual habits were noticed, with 39% for oral-genital and 21.4% for genital-anal. 22% for the interviewed adolescent said they had histories of STD.

Prevención de los accidentes en el hogar / Prevention of accidents at home

El material contiene consejos que consideramos pueden ser útiles para evitar o disminuir los accidentes en el hogar. Está dirigido, fundamentalmente a médicos y enfermeras de la familia, pediatras, maestros, administradores de salud, especialmente en el área materno-infantil y a todos aquellos que se solidaricen con esta campaña contra este flagelo que tantas vidas, lesiones e incapacitados cobra en nuestra sociedad.