The Cardiovascular Event Risk Associated with Tyrosine Kinase Inhibitors and the Lipid Profile in Patients with Chronic Myeloid Leukemia.

BACKGROUND: Second- and third-generation tyrosine kinase inhibitors (TKIs) are now available to treat chronic-phase chronic myeloid leukemia (CP-CML) in the first and second line. However, vascular adverse events (VAEs) have been reported for patients with CML treated with some TKIs. METHODS: We retrospectively evaluated the cumulative incidence (CI) and cardiovascular risk for 210 patients included in the Canarian Registry of CML. RESULT: With a mean follow up of 6 years, 19/210 (9.1%) patients developed VAEs, all of whom presented at least one cardiovascular risk factor at diagnosis. The mean time to VAE presentation was 54 months from the start of TKI treatment. We found a statistically significant difference between the CI for nilotinib-naïve vs. nilotinib-treated patients (p = 0.005), between dasatinib-naïve and dasatinib-treated patients (p = 0.039), and for patients who received three lines of treatment with first-line imatinib vs. first-line imatinib (p < 0.001). From the multivariable logistic regression analyses, the Framingham risk score (FRS) and patients with three lines of TKI with first-line imatinib were the only variables with statistically significant hazard ratios for VAE development. Significant increases in HDL-C and total cholesterol may also be predictive for VAE. CONCLUSIONS: In conclusion, it is important to estimate the cardiovascular risk at the diagnosis of CML as it can help determine whether a patient is likely to develop a VAE during TKI treatment.

Presence of Myeloid Mutations in Patients with Chronic Myeloid Leukemia Increases Risk of Cardiovascular Event on Tyrosine Kinase Inhibitor Treatment.

For chronic myeloid leukemia (CML) patients with a known risk of cardiovascular events (CVE), imatinib is often recommended for first-line tyrosine kinase inhibitor (TKI) treatment rather than a second-generation TKI (2G-TKI) such as nilotinib or dasatinib. To date, very few studies have evaluated the genetic predisposition associated with CVE development on TKI treatment. In this retrospective study of 102 CML patients, 26 CVEs were reported during an average follow-up of over 10 years. Next-generation sequencing identified pathogenic/likely pathogenic mutations in genes associated with myeloid malignancies in 24.5% of the diagnostic samples analyzed. Patients with a recorded CVE had more myeloid mutations (0.48 vs. 0.14, p = 0.019) and were older (65.1 vs. 55.7 years, p = 0.016). Age ≥ 60 years and receiving a 2G-TKI in first-line were CVE risk factors. The presence of a pathogenic somatic myeloid mutation was an independent risk factor for CVE on any TKI (HR 2.79, p = 0.01), and significantly shortened the CV event-free survival of patients who received first-line imatinib (by 70 months, p = 0.011). Indeed, 62% of patients on imatinib with mutations had a CVE vs. the 19% on imatinib with a mutation and no CVE. In conclusion, myeloid mutations detectable at diagnosis increase CVE risk, particularly for patients on imatinib, and might be considered for first-line TKI choice.

Occupational risk perception and its associated factors among nurses and physicians in Peruvian health facilities.

Introduction: A high perceived risk is related to lower rates of occupational accidents in the health personnel. Objectives: To determine the levels of occupational risk perception and its associated factors in nurses and physicians from health facilities in Peru during 2016. Methods: An analytical cross-sectional study was conducted with secondary data from the National Survey of Health Users Satisfaction (Encuesta Nacional de Satisfacción de Usuarios en Salud) 2016. The problem variable was the occupational risk perception, and sociodemographic variables and variables related to occupational risk exposure were included as possible associated factors. Crude and adjusted ordinal logistic regression models were developed to determine the associated factors. All estimates were weighted according to the National Survey of Health Users Satisfaction 2016 complex sampling. Results: Levels of perceived occupational risk were similar between nurses and physicians. Weekly working hours, having a previous work accident, and receiving protective equipment were found to be associated with occupational risk perception in nurses. Age, institution of origin, having a specialty, suffering from a chronic disease, and receiving occupational risk training were found to be associated with occupational risk perception in physicians. Conclusions: In Peru, the levels of occupational risk perception in nurses and physicians are similar. However, the associated factors differ according to the profession. These findings may contribute to the norms or laws related to the occupational safety of health personnel.

Introducción: Una alta percepción de riesgo está relacionada con menores tasas de accidentes laborales en el personal sanitario. Objetivos: Determinar los niveles de percepción de riesgo ocupacional y sus factores asociados en enfermeros y médicos de establecimientos de salud del Perú durante el 2016. Métodos: Se realizó un estudio transversal analítico de los datos secundarios de la Encuesta Nacional de Satisfacción de Usuarios en Salud 2016. La variable problema fue la percepción de riesgo ocupacional y cómo posibles factores asociados se incluyeron variables sociodemográficas y variables relacionadas con la exposición a riesgos laborales. Se elaboraron modelos crudos y ajustados de una regresión logística ordinal para determinar los factores asociados. Todos los cálculos se ponderaron según el muestreo complejo de la Encuesta Nacional de Satisfacción de Usuarios en Salud 2016. Resultados: Los niveles de percepción de riesgo ocupacional fueron semejantes entre enfermeros y médicos. Las horas de trabajo semanal, tener un accidente de trabajo previo y recibir equipos de protección resultaron ser factores asociados a la percepción de riesgo ocupacional en los enfermeros. La edad, la institución de procedencia, tener una especialidad, tener una enfermedad crónica y recibir capacitaciones en riesgo laboral resultaron ser factores asociados a la percepción de riesgo ocupacional en los médicos. Conclusiones: En el Perú, los niveles de percepción de riesgo ocupacional en enfermeros y médicos son semejantes. Sin embargo, los factores asociados difieren según la profesión. Estos hallazgos pueden contribuir con las normas o leyes relacionadas con la seguridad en el trabajo del personal sanitario.

Nutritional status and human milk intake of exclusively breast-fed infants at high altitude in La Paz, Bolivia.

Breast-feeding habits are related to the nutritional status and the risk of illness and death in children under 2 years of age. For the first 6 months, infants should be exclusively breast-fed. This study aimed to evaluate the relationship between the infant's nutritional status and human milk intake by breast-fed infants at high altitude. A quantitative, descriptive, correlational study was conducted including mother/baby pairs of infants aged 2-6 months. The amount of human milk consumed by the infants was assessed by the deuterium oxide dose-to-mother technique. The lipid content of human milk was measured by creamatocrit, and anthropometric measurements were performed. A total of eighteen mother/baby pairs were assessed. The mean human milk intake was 888 (sd 149) g/d, and the intake of water from other sources was 24·3 (sd 29·8) g/d. The lipid content in human milk was 41 (sd 12) g/l. The infant's nutritional indicators were normal in all cases. A moderate positive correlation was found between milk volume and z scores weight-for-length r 0·58 (P=0·01), BMI-for-age r 0·56 (P=0·01) and weight-for-age r 0·45 (P=0·05). There was no correlation with length-for-age z score. The mean of breast milk intake in this study was similar to that found in other studies in the world. The lipid content is comparable to similar studies and was within the normal range. Children older than 3 months showed signs of stunting despite adequate volume and lipid content of breast milk.

Drug-to-drug interactions of tyrosine kinase inhibitors in chronic myeloid leukemia patients. Is it a real problem?

With tyrosine kinase inhibitors (TKI), chronic myeloid leukemia (CML) patients are achieving similar rates of survival to the general population and some treatment aspects such as adherence and drug-to-drug interactions (DDI) are becoming increasingly important. Our aim was to investigate the frequency and real clinical consequences of DDI between TKI and concurrent medications in CML. We performed a retrospective multicenter study including 105 patients receiving 134 TKI treatments. Sixty-three patients (60%) had at least one potential DDI. The mean number of concomitant medications was 4.8 (0-19). The mean number of DDI by TKI treatment was 1.2 (0-8); it increased with the number of concomitant medications and age in a significant manner. A total of 159 DDI were detected, involving 55 different drugs. The most common drug classes involved were proton pump inhibitors, statins, and antidepressants. A DDI-related clinical effect (toxicity and/or lack of efficacy) was suspected during the common course of patient follow-up in only five patients (4.7%). This number increased to 20% when data were centrally reviewed. Most of the adverse events (AE) attributed to DDIs were mild. The most common were diarrhea, vomiting, edema, cramps, and transaminitis. Nilotinib and dasatinib showed a tendency towards a higher risk of DDI compared with imatinib. There were no significant differences in AE frequency or in treatment response between patients with or without DDI. Due to their frequency, and their potential to cause clinically relevant effects, DDI are an important aspect of CML management.

EFFECT OF DIFFERENT ECOSYSTEMS AND MANAGEMENT PRACTICES ON TOXOPLASMA GONDII AND NEOSPORA CANINUM INFECTIONS IN WILD RUMINANTS IN SPAIN.

Toxoplasma gondii and Neospora caninum are two major abortifacient protozoans in domestic small ruminants and cattle, respectively, and they also parasitize a wide range of wildlife. Numerous serosurveys have been conducted in wild ruminants worldwide. However, the potential effect of different ecosystems and management practices on these infections has not been investigated. We studied the prevalence of antibodies to T. gondii and N. caninum in wild ruminants between 2007 and 2012 from four national wildlife reserves: three open space reserves in northwest Spain (Ancares, Mampodre, and Riaño) and a fenced reserve in central Spain (Quintos de Mora). Sera from roe deer ( Capreolus capreolus ) and chamois ( Rupicapra rupicapra ) were collected in Ancares (roe deer), Mampodre (both species), and Riaño (both species), whereas red deer ( Cervus elaphus ) sera were collected only in Quintos de Mora. The results of immunofluorescence antibody tests showed a T. gondii antibody prevalence significantly higher in red deer (13%; 17/131) than in roe deer (2%; 5/228) and chamois (4%; 6/149) (P<0.05, Fisher's exact test). Moreover, N. caninum -specific antibodies were only detected in 1% of animals (2/131 red deer, 2/228 roe deer, and 2/149 chamois). Management measures were implemented in the Quintos de Mora reserve and T. gondii antibody prevalence in red deer decreased from 13% to 2% after 5 yr. In contrast, N. caninum antibody prevalences were very low (<2%) over the years. The results suggest a low frequency of sylvatic life cycles in the hunting reservations studied, so interconnection between sylvatic and domestic life cycles is unlikely. Regardless, a sustainable exploitation of natural resources in wildlife reserves may help to reduce the prevalence of T. gondii infection.

Reversible chemical restraint of free-range cattle with a concentrated combination of tiletamine-zolazepam, ketamine, and detomidine.

The aim of this study was to determine the efficacy of a concentrated combination of tiletamine-zolazepam [TZ, 0.53 mg/kg body weight (BW)], ketamine (Ket, 0.53 mg/kg BW), and detomidine (Det, 0.04 mg/kg BW) in the immobilization of free-range cattle for clinical procedures. The combination was administered intramuscularly to 53 animals. Anesthesia was reversed with the α2-adrenoceptor antagonist atipamezole. Locoregional anesthesia was provided with lidocaine when required. The TZKD combination induced suitable immobilization for minor surgical procedures or medical treatments. Anesthetic onset was rapid, taking a mean of 6.1 min [standard deviation (SD) 2.8 min]. The duration of anesthesia depended on the time of administration of the antagonist; the animals recovered in the standing position in 12.9 ± 8.9 min after the administration of atipamezole. The quality of anesthesia and analgesia were satisfactory. In conclusion, this TZKD combination can be used for both immobilization and minor surgical procedures in free-range cattle.

L'objectif de la présente étude était de déterminer l'efficacité d'une combinaison concentrée de tiletamine-zolazepan [TZ, 0,53 mg/kg de poids corporel (BW)], kétamine (Ket, 0,53 mg/kg de BW), et detomidine (Det, 0,04 mg/kg BW) pour l'immobilisation de bovins libres au pâturage aux fins de procédures cliniques. La combinaison fut administrée à 53 animaux par voie intramusculaire. L'anesthésie a été renversée avec l'atipamézole, antagoniste des adrénocepteurs-α2. Au besoin, l'anesthésie locorégionale a été induite avec de la lidocaïne. La combinaison TZKD a induit une immobilisation adéquate pour des procédures chirurgicales mineures ou des traitements médicaux. L'initiation de l'anesthésie était rapide, avec une moyenne de 6,1 minutes [écart-type (SD) 2,8 min]. La durée de l'anesthésie dépendait du temps de l'administration de l'antagoniste; les animaux récupérant en position debout en 12,9 ± 8,9 min après l'administration de l'atipamézole. La qualité de l'anesthésie et de l'analgésie était satisfaisante. En conclusion, la combinaison TZKD peut être utilisée pour l'immobilisation et la réalisation de procédures chirurgicales mineures chez les bovins au pâturage.(Traduit par Docteur Serge Messier).

Long-term prognostic significance of response in multiple myeloma after stem cell transplantation.

For establishing the true effect of different response categories in patients with multiple myeloma (MM) treated with autologous stem cell transplantation, we evaluated, after a median follow-up of 153 months, 344 patients with MM who received a transplant between 1989 and 1998. Overall survival (OS) at 12 years was 35% in complete response (CR) patients, 22% in near complete response (nCR), 16% in very good partial response (VGPR), and 16% in partial response (PR) groups. Significant differences in OS and progression-free survival were found between CR and nCR groups (P = .01 and P = .002, respectively), between CR and VGPR groups (P = .0001 and P = .003), or between CR and PR groups (P = .003 and P = < 10(-5)); no differences were observed between the nCR and VGPR groups (P = .2 and P = .9) or between these groups and the PR group (P = .1 and P = .8). A landmark study found a plateau phase in OS after 11 years; 35% patients in the CR group and 11% in the nCR+VGPR+PR group are alive at 17 years; 2 cases had relapsed in the nCR+VGPR+PR group. In conclusion, MM achieving CR after autologous stem cell transplantation is a central prognostic factor. The relapse rate is low in patients with > 11 years of follow-up, possibly signifying a cure for patients in CR.

Relevance of renin expression by real-time PCR in acute myeloid leukemia.

The search for useful molecular markers in the diagnosis of AML and in the follow-up of minimal residual disease (MRD) has been the focus of many recent studies. Previous research showed that, while normal bone marrow cells lack expression of renin, myeloid blasts have been reported to do so. The aim was to study the expression of the renin gene by the use of real-time quantitative PCR (RQ-PCR) at diagnosis in acute myeloid leukemia patients (AML) and to assess its possible relevance in the prognosis and outcome of such patients. This study analysed 76 samples from patients with AML, with follow-up of positive patients. Thirty-one patients (41%) were positive for renin gene expression at diagnosis. All renin-positive patients at diagnosis showed no expression during complete remission (CR), but expression recurred in those experiencing relapse and persisted when the disease was refractory to treatment. Although the results suggest that the sub-group of renin-positive AML patients might have a worse outcome and a higher relapse rate (at 5 years, the projected rate of disease-free survival was 18.5 +/- 9.8% for renin-positive and 23.5 +/- 8.8% for renin-negative patients), no significant differences were found. It is believed that further studies should aim to validate whether such a difference exists, using a much larger and homogeneus group of patients.

Nodular onchocercosis of red deer in central Spain.

The presence of nodular onchocercosis was investigated post-mortem in 142 red deer (11 calves, 35 yearlings and 96 adults) shot from February 1998 to January 1999, and July-November 1999 in "Quintos de Mora" (Toledo, central Spain), a game property belonging to the National Wildlife Reserves. Between 6 and 13 animals were analysed monthly by inspection for subcutaneous nodules of Onchocerca spp. Subcutaneous nodules of Onchocerca sp. were detected in 24% of the animals. Anatomical locations for nodules were the back and flanks. Infection ranged from 1 to 29 nodules per animal. Adult worms collected from nodules were identified as O. flexuosa. No apparent seasonal trend was observed either in prevalence or in mean intensity of infection, which fluctuated between 48% (5+/-8 nodules) in winter 1998 and 5% (1+/-0 nodules) in summer 1999. Prevalence of infection was significantly higher in adult (30%) than in young animals (9% in calves, 11% in yearlings), although no age effect on intensity was observed. The size of the nodules was measured to evaluate the age of infection. Small (recent) nodules (5-6mm of diameter) were collected in late spring, summer and fall; medium-sized nodules (12-15 mm) were in second half of summer, fall and winter, and large (mature) nodules (20-25 mm) in fall, winter and part of spring. Significant differences were found among host age groups.

Tandem transplants with different high-dose regimens improve the complete remission rates in multiple myeloma. Results of a Grupo Español de Síndromes Linfoproliferativos/Trasplante Autólogo de Médula Osea phase II trial.

Between 1994 and 1999, 88 multiple myeloma (MM) patients were included in a phase II study to evaluate a tandem autologous stem cell transplantation (ASCT) programme. The first was conditioned with melphalan 200 mg/m2 (MEL200-ASCT1), and the second with cyclophosphamide, etoposide and BCNU (CBV-ASCT2). All patients were in response after MEL200-ASCT1. A control group of MM patients with response to a single ASCT was selected to compare outcomes. After MEL200-ASCT1, 26 patients (30%) achieved complete remission (CR). Of the remaining 48 evaluable patients, 16 (33%) achieved CR with CBV-ASCT2. The final CR rate was 48%. The 5-year survival (OS) was 55%[95% confidence interval (CI) 43-67%] while the event-free survival (EFS) was 28% (95% CI 15-39%). CR status after CBV-ASCT2 was the most important prognostic factor for OS and EFS (P = 0.00001), although no differences in outcomes were detected when the patients in CR after MEL200-ASCT1 were compared with those who obtained CR after CBV-ASCT2. Univariate and multivariate analyses showed improved OS and EFS for the tandem series as compared with the control series treated with a single MEL200-ASCT. However, in a stratified comparison by response, there were no prognostic differences between tandem patients and control patients treated with a single ASCT. In summary, our study suggests that the benefit of a second high-dose therapy course depends on its capacity to result in CR for MM patients who have not attained CR after ASCT1.

Renin expression in hematological malignancies and its role in the regulation of hematopoiesis.

It has been demonstrated that some myeloid blasts express renin, but normal bone marrow (BM) does not display this expression. The aim of the present work was to analyze the renin expression in different hematological malignancies and different myeloid cell lines. We investigated the expression of renin by RT-PCR in BM from patients with hematological malignancies (106 patients), in nine normal BM from healthy donors and in leukemic cell lines (K562, KU812, MEG-01, U-937 and HL60), as well in K562 cell line subjected to differentiation treatments. We have observed renin expression in cells from acute myeloid leukemia (AML), chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL) cases. The highest frequency was observed in AML-non acute promyelocytic leukemia(APL) cases (47.2% of the cases). The disappearance of this expression was associated with the status of complete remission of AML. Renin is expressed in some myeloid human leukemia cell lines such as K562, KU812 and MEG-01. However, when K562 cells were treated with inducers of growth inhibition and/or differentiation, the expression did not disappear, indicating that renin expression is associated with a blastic phenotype rather than with cell proliferation. The obtained findings suggest that the renin expression could have a role on the disease development and could be used as an aberrant marker of leukemia.

Effect of high altitude on protein metabolism in Bolivian children.

In Bolivia, malnutrition in children is a major health problem that may be caused by inadequate protein, energy, and micronutrient intake; exposure to bacterial and parasitic infections; and life in a multistress environment (high altitude, cold, cosmic radiation, low ambient humidity). However, no data on protein absorption and utilization at high altitude were available. Therefore, we evaluated the effect of altitude on protein metabolism in Bolivian children. We measured protein utilization using leucine labeled with a stable isotope ((13)C) in two groups of healthy prepubertal children matched for age. Group 1 (n = 10) was examined at high altitude (HA) in La Paz (3600 m), and group 2 (n = 10) at low altitude (LA) in Santa Cruz (420 m). The nutritional status did not differ between groups but, as was to be expected, the HA group had higher hemoglobin concentration than the LA group. The children consumed casein that was intrinsically labeled with L-(1-(13)C) leucine and expired (13)CO(2) was analyzed. Samples of expired air were measured by isotope ratio mass spectrometer in Clermont-Ferrand. It was found that cumulative leucine oxidation ((13)CO(2)) at 300 min after ingestion was 19.7 +/- 4.9% at HA and 25.2 +/- 3.2% at LA. These results showed that protein absorption and/or utilization is significantly affected by altitude.

Descentralización de los Servicios de Salud en Venezuela: ¿dónde estamos y hacia dónde vamos? / Descentralization of the health services in Venezuela: were is and toward were well?

El presente trabajo tiene la finalidad de dar a conocer un proceso poco conocido en Venezuela, a diferencia del resto de América Latina. La descentralización de los servicios de salud en Venezuela es un continuo y de profundos cambios, el cual se encuentra en una etapa de redefinición. Se inicia este trabajo estableciendo la definición de descentralización, se plasman los procesos similares en América Latina, se analizan los antecedentes del proceso en Venezuela, su inicio en el año 1989 con la promulgación de la Ley Orgánica de Descentralización, Delimitación y Transferencias de Competencias del Poder Público. Se abordan los fundamentos jurídicos de esta Ley y los de los reglamentos parciales. Se hace un recuento de los convenios de transferencia y cogestión firmados con los estados desde 1993. Se analiza la Ley Orgánica de Salud y la Ley Orgánica del Sistema de Seguridad Social Integral, en relación al proceso de descentralización de los servicios de salud. Se presentan las conclusiones del proceso, se elaboran recomendaciones a la luz de los cambios surgidos en la realidad del país, que han sido propulsados por la Asamblea Constituyente, los cuales en un futuro, quedarán plasmados en la nueva Constitución Nacional

Anemia por deficiencia de hierro en la región Andina: definición y estrategias de intervención / Iron deficiency anemia in the Andean region: definition and interventions strategies

La anemia es una enfermedad sistémica que afecta a diferentes órganos y funciones. Puede estar causada por una inadecuada producción de eritrocitos, tener un origen congénito o deberse a infecciones o fenómenos inmunológicos. Sin embargo, su causa más frecuente es la deficiencia de hierro, desorden nutricional muy común a nivel internacional

Definición de la anemia en la altura: efecto de una suplementación con hierro y folatos sobre los indicadores hematológicos y evaluación del estado nutricional de los niños del altiplano boliviano / sss

El presente documento tiene el propósito de evaluar lo bien fundado de los umbrales de hemoglobina adaptados a la altura propuestos por la OMS para estas poblaciones de niños. Estudiar los valores de los indicadores hematológicos de dos poblaciones de niños de 6 meses a 9 años del Altiplano boliviano. Definir los valores normales de estos indicadores en particular del índice de hemoglobina, para estas poblaciones