Rationale and design of a randomised trial of trientine in patients with hypertrophic cardiomyopathy.

AIMS: Hypertrophic cardiomyopathy (HCM) is characterised by left ventricular hypertrophy (LVH), myocardial fibrosis, enhanced oxidative stress and energy depletion. Unbound/loosely bound tissue copper II ions are powerful catalysts of oxidative stress and inhibitors of antioxidants. Trientine is a highly selective copper II chelator. In preclinical and clinical studies in diabetes, trientine is associated with reduced LVH and fibrosis, and improved mitochondrial function and energy metabolism. Trientine was associated with improvements in cardiac structure and function in an open-label study in patients with HCM. METHODS: The Efficacy and Mechanism of Trientine in Patients with Hypertrophic Cardiomyopathy (TEMPEST) trial is a multicentre, double-blind, parallel group, 1:1 randomised, placebo-controlled phase II trial designed to evaluate the efficacy and mechanism of action of trientine in patients with HCM. Patients with a diagnosis of HCM according to the European Society of Cardiology Guidelines and in New York Heart Association classes I-III are randomised to trientine or matching placebo for 52 weeks. Primary outcome is change in left ventricular (LV) mass indexed to body surface area, measured using cardiovascular magnetic resonance. Secondary efficacy objectives will determine whether trientine improves exercise capacity, reduces arrhythmia burden, reduces cardiomyocyte injury, improves LV and atrial function, and reduces LV outflow tract gradient. Mechanistic objectives will determine whether the effects are mediated by cellular or extracellular mass regression and improved myocardial energetics. CONCLUSION: TEMPEST will determine the efficacy and mechanism of action of trientine in patients with HCM. TRIAL REGISTRATION NUMBERS: NCT04706429 and ISRCTN57145331.

Mortality and clinical characteristics of multisystem inflammatory syndrome in children (MIS-C) associated with covid-19 in critically ill patients: an observational multicenter study (MISCO study).

BACKGROUND: The clinical presentation and severity of Multisystem Inflammatory Syndrome in Children associated with COVID-19 (MIS-C) is widespread and presents a very low mortality rate in high-income countries. This research describes the clinical characteristics of MIS-C in critically ill children in middle-income countries and the factors associated with the rate of mortality and patients with critical outcomes. METHODS: An observational cohort study was conducted in 14 pediatric intensive care units (PICUs) in Colombia between April 01, 2020, and January 31, 2021. Patient age ranged between one month and 18 years, and each patient met the requirements set forth by the World Health Organization (WHO) for MIS-C. RESULTS: There were seventy-eight children in this study. The median age was seven years (IQR 1-11), 18 % (14/78) were under one year old, and 56 % were male. 35 % of patients (29/78) were obese or overweight. The PICU stay per individual was six days (IQR 4-7), and 100 % had a fever upon arrival to the clinic lasting at least five days (IQR 3.7-6). 70 % (55/78) of patients had diarrhea, and 87 % (68/78) had shock or systolic myocardial dysfunction (78 %). Coronary aneurysms were found in 35 % (27/78) of cases, and pericardial effusion was found in 36 %. When compared to existing data in high-income countries, there was a higher mortality rate observed (9 % vs. 1.8 %; p=0.001). When assessing the group of patients that did not survive, a higher frequency of ferritin levels was found, above 500 ngr/mL (100 % vs. 45 %; p=0.012), as well as more cardiovascular complications (100 % vs. 54 %; p = 0.019) when compared to the group that survived. The main treatments received were immunoglobulin (91 %), vasoactive support (76 %), steroids (70.5 %) and antiplatelets (44 %). CONCLUSIONS: Multisystem Inflammatory Syndrome in Children due to SARS-CoV-2 in critically ill children living in a middle-income country has some clinical, laboratory, and echocardiographic characteristics similar to those described in high-income countries. The observed inflammatory response and cardiovascular involvement were conditions that, added to the later presentation, may explain the higher mortality seen in these children.

Inusual complicación en cirugía laparoscópica de urgencia: sección accidental de catéter de derivación ventriculoperitoneal / An unusual complication in urgent laparoscopic surgery: Accidental transection of a ventriculoperitoneal shunt

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Acute intraocular pressure changes during isometric exercise and recovery: The influence of exercise type and intensity, and participant´s sex.

We assessed the intraocular pressure (IOP) behaviour during a 1-minute period of isometric physical effort and the immediate 1-minute of recovery in the mid-thigh clean pull and squat exercises at three different intensities. Twenty physically active individuals performed the isometric mid-thigh clean pull and squat exercises at three intensities (0% [low-intensity], 25% [medium-intensity] and 50% [high-intensity] of the maximum isometric force). IOP was semi-continuously measured by rebound tonometry. There was a statistically significant effect of exercise intensity on IOP (p < 0.001, ƞp² = 0.416), observing that IOP increments were positively associated with exercise intensity. The mid-thigh clean pull and squat exercises did not demonstrate differences (p = 0.510), and also, no differences were observed between men and women (p = 0.683). The IOP changes during the isometric physical effort showed a positive linear behaviour in all conditions (r = 0.70 to 0.96). IOP returned to baseline levels after 8 seconds of recovery.  Our data showed a progressive and instantaneous IOP increment during isometric exercise, which was positively associated with exercise intensity. IOP changes were independent on the type of exercise and participant´s sex. After exercise, IOP rapidly (≈ 8 seconds) returned to baseline levels.

The European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) Registry Annual Report 2015: a summary.

BACKGROUND: This article summarizes the European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) Registry's 2015 Annual Report. It describes the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 2015 within 36 countries. METHODS: In 2016 and 2017, the ERA-EDTA Registry received data on patients who were undergoing RRT for ESRD in 2015, from 52 national or regional renal registries. Thirty-two registries provided individual patient-level data and 20 provided aggregated-level data. The incidence, prevalence and survival probabilities of these patients were determined. RESULTS: In 2015, 81 373 individuals commenced RRT for ESRD, equating to an overall unadjusted incidence rate of 119 per million population (pmp). The incidence ranged by 10-fold, from 24 pmp in Ukraine to 232 pmp in the Czech Republic. Of the patients commencing RRT, almost two-thirds were men, over half were aged ≥65 years and a quarter had diabetes mellitus as their primary renal diagnosis. Treatment modality at the start of RRT was haemodialysis for 85% of the patients, peritoneal dialysis for 11% and a kidney transplant for 4%. By Day 91 of commencing RRT, 82% of patients were receiving haemodialysis, 13% peritoneal dialysis and 5% had a kidney transplant. On 31 December 2015, 546 783 individuals were receiving RRT for ESRD, corresponding to an unadjusted prevalence of 801 pmp. This ranged throughout Europe by more than 10-fold, from 178 pmp in Ukraine to 1824 pmp in Portugal. In 2015, 21 056 kidney transplantations were performed, equating to an overall unadjusted transplant rate of 31 pmp. This varied from 2 pmp in Ukraine to 94 pmp in the Spanish region of Cantabria. For patients commencing RRT during 2006-10, the 5-year unadjusted patient survival probabilities on all RRT modalities combined was 50.0% (95% confidence interval 49.9-50.1).

Effect of Chlorpyrifos 0,0-dietil 0-(3, 5, 6-tricloro-2-piridil fosforotioato) in juvenile of tilapia (Oreochromis spp) males / Efecto del Clorpirifos 0,0-dietil 0-(3, 5, 6-tricloro-2-piridil fosforotioato) en machos juveniles de tilapia (Oreochromis spp) / Efeito de Clorpirifós 0,0 dietil-0 - (3, 5 fosforotioato, 6-tricloro-2-piridil) em tilápias juvenis masculinos (Oreochromis spp)

Chlorpyrifos is a highly toxic insecticide to freshwater organisms and little is known regarding its potential to affect endocrine systems at sublethal concentrations. The induction of vitellogenin (Vtg) is a fairly sensitive marker of the effects of estrogenic compounds in juvenile fish. Objective: to evaluate histological changes and Vtg production in juvenile male tilapia (Oreochromis spp) exposed to sublethal concentrations of the insecticide Lorsban® EC (active ingredient chlorpyriphos). Methods: juvenile tilapia were exposed to 4, 8, and 12 μg/L of chlorpyrifos for 28 days in a semistatic system, with tanks receiving a 50% (v/v) daily water change to maintain nominal concentrations of the insecticide throughout the experiment. Subgroups of 3 animals from each concentration batch were euthanized on days 7, 14, 21 and 28 days, and samples of liver, gonads, gills, kidney and brain tissues were taken for routine histopathology examination. Liver and gonads were also processed by immunohistochemistry using monoclonal antikillifish vitellogenin Vtg ND - 5F8 to detect Vtg. Results: we found significant statistical difference (p<0.05) for some injuries to the brain (degeneration and gliosis of the optic tectum), kidneys (vacuolar nephrosis and tubular hyaline granules), and liver (karyomegaly, binucleation, and hyaline granules in hepatocytes). Similarly we verified the induction of vitellogenin synthesis in liver and gonads, finding significant difference (p<0.05) in the expression of this protein between the control group and 4 mg / L with respect to treatment of 8 and 12 mg / L. Conclusion: the results obtained on the induction of vitellogenin in males suggest a general effect of blocking concentrations of Chlorpyrifos for the possible induction of this protein. The mechanisms are not known at this time.

Hasta donde se conoce, no hay estudios en tilapias juveniles (Oreochromis spp), que valoren el potencial de disrupción endocrina del Clorpirifos por análisis histológico e inmunohistoquímico de la inducción de la Vitelogenina (Vtg) hepática. Objetivo: determinar los efectos de la exposición subaguda al Clorpirifos en órganos blanco de disrupción en peces juveniles machos de tilapia. Métodos: el experimento de dosis subletal, se realizó en un sistema semiestático, con recambio diario del 50% del volumen de agua manteniendo la concentración nominal en cada grupo experimental mediante la adición de la mitad de la dosis hasta el día 28. Las concentraciones de Clorpirifos para la exposición fueron 4, 8, y 12 μg/L. Con cada concentración se trataron 12 juveniles, con tres replicas para cada concentración. Los 12 peces del grupo control no recibieron tratamiento. Se realizó el estudio anatomopatológico de tres animales por grupo, por cada semana los días 7, 14, 21 y 28 de estudio. Se efectuó la toma de muestras para estudio histopatológico de hígado, gónadas, branquias, riñón y encéfalo y se procesaron por histopatología de rutina. Las muestras de hígado y gónada también se procesaron por inmunohistoquímica. Resultados: el análisis MANOVA encontró diferencia significativa (p<0.05) para lesiones en encéfalo (degeneración tectum óptico), riñón (gránulos hialinos) e hígado (cariomegalia), constituyéndose en órganos de impacto de los efectos del Clorpirifos a bajas dosis. Se verificó la inducción de Vtg en hígado y gónada de los animales expuestos, encontrando diferencia estadística significativa (p<0.05) en la expresión de esta proteína entre el grupo control y de 4 μg/L con relación a los grupos de 8 y 12 μg/L. Conclusión: los resultados obtenidos sobre la inducción de Vtg en machos sugieren un efecto antogonista del Clorpirifos sobre los Receptores Estrogénicos (REs), con una posible disminución en la síntesis de ésta proteína. Los mecanismos no se conocen en el momento.

O clorpirifos é um insecticida altamente tóxico para os organismos de água doce. Porém, pouco se sabe acerca de seu potencial efeito no sistema endócrino em concentrações subletais. A indução de vitelogenina hepática (Vtg) é um marcador bastante sensível do efeito de componentes estrogênicos em peixes juvenis. Objetivo: determinar os efeitos da exposição subaguda ao clorpirifos em órgãos alvo de disrupção endócrina em machos juvenis de tilápia. Métodos: o experimento foi realizado em um sistema semi-estático com recambio diário de 50% do volume de água, com manutenção da concentração nominal em cada grupo experimental mediante a adição da metade da dose de clorpirifos até o dia 28. Três grupos de 12 peixes foram tratados com concentrações de clorpirifos de 4, 8 y 12 μg/L, respectivamente, com três réplicas para cada grupo. Um grupo controle não recebeu nenhum tratamento. Realizou-se o estudo anatomopatológico de rotina do fígado, gônadas, brânquias, rins e encéfalo de três animais por grupo nos dias 7, 14, 21 e 28. As amostras de fígado e gônada foram também processadas por inmunoistoquímica usando um anticorpo monoclonal para detectar Vtg (anti-killifish Vtg ND-5F8). Resultados: mediante análise MANOVA encontrou-se diferença significativa (p<0.05) para lesões no encéfalo (degeneração do tectum óptico), rim (grânulos hialinos) e fígado (cariomegalia), fato que demonstra que estes são os órgãos alvo dos efeitos do clorpirifos a baixas doses. Verificou-se a indução de Vtg no fígado e gônada dos animais expostos, com diferença estatística significativa (p<0.05) na expressão desta proteína entre o grupo controle e o grupo de 4 μg/L com relação aos grupos de 8 e 12 μg/L. Conclusão: os resultados obtidos sobre a indução de Vtg em machos sugerem um efeito antagonista do clorpirifos sobre os receptores estrogênicos, com uma possível diminuição na síntese desta proteína. Os mecanismos ainda são desconhecidos.

[Global HIV epidemiology and current migration]. / Epidemiologia del VIH/sida en el mundo y el fenómeno migratorio actual.

One of the current characteristics of migration is its tendency to concentrate in industrialized countries, as well as its feminization and diversity. From a healthcare point of view, the phenomenon of migration has aroused interest in the possible transfer of transmissible infectious diseases from some regions to others and the impact that this could have on public health. When discussing immigration and AIDS, there is a risk of stigmatizing vulnerable people, who are generally healthy. Some of the infectious diseases these people contract are partly due to the conditions experienced on the journey or once they are settled in the host country. The epidemiological pattern of HIV transmission in immigrants is the same as that in their countries of origin. Although the distribution of HIV subtypes is more or less localized, there is a tendency toward progressive dispersion of all subtypes in different geographical areas and toward new recombinant subtypes.

Epidemiologia del VIH/sida en el mundo y el fenómeno migratorio actual / Global HIV epidemiology and current migration

Una de las características actuales de la inmigración es su tendencia a concentrarse en los países industrializados, así como su feminización y su diversidad. Desde el punto de vista sanitario, el fenómeno migratorio ha despertado interés por el posible trasvase de enfermedades infecciosas transmisibles de unas zonas a otras, y el impacto que ello puede suponer en el ámbito de la salud pública. Cuando se habla de inmigración y sida se corre el peligro de estigmatizar a unas personas vulnerables, que generalmente son una población sana. Algunas enfermedades infecciosas que estos pacientes acaban presentando, en parte, se deben a las condiciones que experimentan durante el periplo migratorio o una vez establecidos en el país de acogida. Los inmigrantes siguen el patrón epidemiológico de transmisión del virus de la inmunodeficiencia humana (VIH) de su país de origen. A pesar de la distribución más o menos localizada de los subtipos del VIH, la tendencia es la de la dispersión progresiva de todos ellos en distintas áreas geográficas y hacia nuevos subtipos recombinantes

One of the current characteristics of migration is its tendency to concentrate in industrialized countries, as well as its feminization and diversity. From a healthcare point of view, the phenomenon of migration has aroused interest in the possible transfer of transmissible infectious diseases from some regions to others and the impact that this could have on public health. When discussing immigration and AIDS, there is a risk of stigmatizing vulnerable people, who are generally healthy. Some of the infectious diseases these people contract are partly due to the conditions experienced on the journey or once they are settled in the host country. The epidemiological pattern of HIV transmission in immigrants is the same as that in their countries of origin. Although the distribution of HIV subtypes is more or less localized, there is a tendency toward progressive dispersion of all subtypes in different geographical areas and toward new recombinant subtypes

Immunohistochemical expression of RANK, GRalpha and CTR in central giant cell granuloma of the jaws.

The aim was to evaluate the phenotypic expression of various cellular osteotropic factors in central giant cell granuloma (CGCG). Paraffin-embedded tissue from 27 aggressive and 10 non-aggressive cases of CGCG was assessed for the expression of RANK, GRalpha and CTR using immunohistochemistry. In addition, a staining-intensity-distribution (SID) score (proportion of stained cells x staining intensity) was used to assess immunoreactivity of each marker. The results showed that the multinucleated giant cells (MGC), mononuclear stromal cells (MSC) and endothelial cells were intensely positives for GRalpha, moderate for RANK and weak-to-moderate for CTR in all clinical groups, whereas spindle-shaped cells were intensely immunoreactive to GRalpha and unreactive to CTR and RANK. Although neither difference in RANK and GRalpha expression nor the SID score between the clinical forms of CGCG was observed, a statistically significant difference for CTR was evident. Furthermore, the comparison of the marker expression and SID score showed a significant correlation for all three markers within the clinical groups, except for GRalpha in the non-aggressive lesions where a weak and no significant correlation was detected. It was concluded that although the MGC share some similarities with the osteoclasts, they demonstrate phenotypic differences from each other that suggest a distinct precursor. The expression of RANK, GRalpha and CTR also suggest a role for these receptors in the resorptive activity of different cellular groups in CGCG and may lead to a more effective use of therapeutic inhibitors of bone resorption for the treatment of these disorders.