Severed hemoparasitosis complicated in a thoroughbred horses from Venezuela

Equine piroplasmosis (EP) is the disease caused by protozoan hemoparasites Babesia caballi and/or B. (Theileria equi). The aim of this study was to report of case of severed hemoparasitosis complicated in a Thoroughbred horse from Venezuela. The equine present acute abdominal pain in 24 hours and complicated post 48 hours and death in the 72 hours. Temperature oscillate 41;2°C. Icterus and hematury severed. We realized a multidisciplinary study clinical, laboratory, biochemistry, necropsy, histopathology. Hematies: 10.6 mm³, Hb: 16.4 g/dL, Hto: 48%, plaques 305mm³, Leucocites 4.7 x/mm³, Neutrophiles 47%, Lymphocytes 44%, Monocites 1%, Eosinophyles 7%. Total Protein 7,2g/dL, Albumine 2.8g/dL, globulin 4.4g/dL, glicemia 85mg/dL, urea 29mg/dL, creatinine 3.0 mg/dL. BT 3.07mg/dL, BD 0.33mg/dL, BI 2.74mg/dL, GOT 416UI/I,CK 183 UI/I, Na 136mmol/dL, K 3.0 mmol/dL, Cl 98 mmol/dL, fibrinogeno 300mg/dL. Giemsa staining of blood smears followed by careful microscopic examination can reveal the intraerythrocytic parasites in acute cases. B. caballi can appear pyriform-shaped and occurs in pairs whereas B. equi appears as four pyriform parasites in a Maltese-cross formation. On necropsy, were observed severed icterus oral and mucosa, xantomathosis of subcutaneous tissue. Poliserositis, ascitis, anasarca. In the abdominal cavity was observed massive hemoperitoneum severe, adhesive fibrinous peritonitis by diapedesis. Spleen with hemosiderosis severed. Peritonitis fibrinous adhesive in external surface of small intestine. Severe disseminate coagulate intravascular, hemolisis acute and bacteraemia, septicaemia. In conclusion were reported of case of severed hemoparasitosis complicated in a Thoroughbred horse from Venezuela.La Piroplasmosis equina (EP) es una enfermedad causada por el protozoo hemoparásitos Babesia caballi y / o B. (Theileria equi). El objetivo de este estudio fue reportar un caso de hemoparasitosis severa complicada en un caballo Pura Sangre de Venezuela. El equino presento dolor abdominal agudo en 24 horas y 48 horas edema de miembros posteriores y muerte en las 72 horas. La temperatura oscilo entre 41, 2 º C, presento ictericia y hematuria. Se realizó un estudio multidisciplinario clínicos, de laboratorio, bioquímica, necropsia e histopatología. Hematíes: 10,6 mm ³, Hb: 16,4 g / dl, Hto: 48%, plaquetas de 305 mm ³, los Leucocitos 4,7 x / mm ³, neutrófilos 47%, linfocitos 44%, monocitos 1%, Eosinofilos 7%. Total de proteínas 7,2 g / dl, Albúmina 2.8g/dL, 4.4g/dL globulina, glicemia 85mg/dL, urea 29mg/ dL, creatinina 3,0 mg / dl. BT 3.07mg/dL, BD 0.33mg/dL, BI 2.74mg/dL, GOT 416UI / l, CK 183 UI / l, Na 136mmol/dL, K 3,0 mmol / dl, Cl 98 mmol / dL, fibrinógeno 300mg/dL. El frotis de sangre coloreado con Giemsa seguido por el examen microscópico revelo parásitos intraeritrocíticos. B. caballi puede aparecer en forma piriforme y se produce en parejas, mientras que B. equi aparece como cuatro parásitos piriformes en una formación de Cruz-Malta. En la necropsia, se observo la mucosa oral y conjuntival icterica, xantomathosis del tejido subcutáneo. Poliserositis, ascitis, anasarca. En la cavidad abdominal se observó hemoperitoneo masivo peritonitis fibrinosa severa adhesiva por diapédesis. Bazo con hemosiderosis, Coagulación intravascular diseminada, hemólisis aguda, bacteremia y septicemia. Se reporto un caso de hemoparasitosis severa complicado en un caballo pura sangre de Venezuela

Newborn screening for medium-chain acyl-CoA dehydrogenase deficiency: regional experience and high incidence of carnitine deficiency

Background Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most common inherited defect in the mitochondrial fatty acid oxidation pathway, resulting in significant morbidity and mortality in undiagnosed patients. Newborn screening (NBS) has considerably improved MCADD outcome, but the risk of complication remains in some patients. The aim of this study was to evaluate the relationship between genotype, biochemical parameters and clinical data at diagnosis and during follow-up, in order to optimize monitoring of these patients. Methods We carried out a multicenter study in southwest Europe, of MCADD patients detected by NBS. Evaluated NBS data included free carnitine (C0) and the acylcarnitines C8, C10, C10:1 together with C8/C2 and C8/C10 ratios, clinical presentation parameters and genotype, in 45 patients. Follow-up data included C0 levels, duration of carnitine supplementation and occurrence of metabolic crises. Results C8/C2 ratio and C8 were the most accurate biomarkers of MCADD in NBS. We found a high number of patients homozygous for the prevalent c.985A > G mutation (75%). Moreover, in these patients C8, C8/C10 and C8/C2 were higher than in patients with other genotypes, while median value of C0 was significantly lower (23 μmol/L vs 36 μmol/L). The average follow-up period was 43 months. To keep carnitine levels within the normal range, carnitine supplementation was required in 82% of patients, and for a longer period in patients homozygotes for the c.985A>G mutation than in patients with other genotypes (average 31 vs 18 months). Even with treatment, median C0 levels remained lower in homozygous patients than in those with other genotypes (14 μmol/L vs 22 μmol/L). Two patients died and another three suffered a metabolic crisis, all of whom were homozygous for the c.985 A>G mutation. Conclusions Our data show a direct association between homozygosity for c.985A>G and lower carnitine values at diagnosis, and a higher dose of carnitine supplementation for maintenance within the normal range. This study contributes to a better understanding of the relationship between genotype and phenotype in newborn patients with MCADD detected through screening which could be useful in improving follow-up strategies and clinical outcome

Calorie restriction rescues mitochondrial dysfunction in Adck2-Deficient skeletal muscle

ADCK2 haploinsufficiency-mediated mitochondrial coenzyme Q deficiency in skeletal muscle causes mitochondrial myopathy associated with defects in beta-oxidation of fatty acids, aged-matched metabolic reprogramming, and defective physical performance. Calorie restriction has proven to increase lifespan and delay the onset of chronic diseases associated to aging. To study the possible treatment by food deprivation, heterozygous Adck2 knockout mice were fed under 40% calorie restriction (CR) and the phenotype was followed for 7 months. The overall glucose and fatty acids metabolism in muscle was restored in mutant mice to WT levels after CR. CR modulated the skeletal muscle metabolic profile of mutant mice, partially rescuing the profile of WT animals. The analysis of mitochondria isolated from skeletal muscle demonstrated that CR increased both CoQ levels and oxygen consumption rate (OCR) based on both glucose and fatty acids substrates, along with mitochondrial mass. The elevated aerobic metabolism fits with an increase of type IIa fibers, and a reduction of type IIx in mutant muscles, reaching WT levels. To further explore the effect of CR over muscle stem cells, satellite cells were isolated and induced to differentiate in culture media containing serum from animals in either ad libitum or CR diets for 72 h. Mutant cells showed slower differentiation alongside with decreased oxygen consumption. In vitro differentiation of mutant cells was increased under CR serum reaching levels of WT isolated cells, recovering respiration measured by OCR and partially beta-oxidation of fatty acids. The overall increase of skeletal muscle bioenergetics following CR intervention is paralleled with a physical activity improvement, with some increases in two and four limbs strength tests, and weights strength test. Running wheel activity was also partially improved in mutant mice under CR. These results demonstrate that CR intervention, which has been shown to improve age-associated physical and metabolic decline in WT mice, also recovers the defective aerobic metabolism and differentiation of skeletal muscle in mice caused by ADCK2 haploinsufficiency.This work was supported by Junta de Andalucía grant BIO-177, the Instituto de Salud Carlos III FIS grant FIS PI20/00541, CIBERER (U729)-ISCIII, the FEDER Funding Program from the European Union and the Spanish Ministry of Science, Innovation and Universities grant RED2018-102576-T. This work was supported by the Spanish Ministry of Education, Culture and Sports through fellowship FPU16/03264 to JH-C, and the Association Française contre les Myopathies (AFM) through fellowship grant #22450 to CV-G. This work was funded in part by the Intramural Research Program of the National Institute on Aging, NIH. This research was also supported by the Instituto de Salud Carlos III (PI19/01310) (Co-funded by the European Union) and by the Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) (2017: SGR 1428) and the CERCA

Binding Potassium to Improve Treatment With Renin-Angiotensin-Aldosterone System Inhibitors: Results From Multiple One-Stage Pairwise and Network Meta-Analyses of Clinical Trials.

This manuscript presents findings from the first dichotomous data pooling analysis on clinical trials (CT) regarding the effectiveness of binding potassium. The results emanated from pairwise and network meta-analyses aiming evaluation of response to commercial potassium-binding polymers, that is, to achieve and maintain normal serum potassium (n = 1,722), and the association between this response and an optimal dosing of renin-angiotensin-aldosterone system inhibitors (RAASi) needing individuals affected by heart failure (HF) or resistant hypertension, who may be consuming other hyperkalemia-inducing drugs (HKID) (e.g., β-blockers, heparin, etc.), and frequently are affected by chronic kidney disease (CKD) (n = 1,044): According to the surface under the cumulative ranking area (SUCRA), sodium zirconium cyclosilicate (SZC) (SUCRA >0.78), patiromer (SUCRA >0.58) and sodium polystyrene sulfonate (SPS) (SUCRA <0.39) were different concerning their capacity to achieve normokalemia (serum potassium level (sK+) 3.5-5.0 mEq/L) or acceptable kalemia (sK+ ≤ 5.1 mEq/L) in individuals with hyperkalemia (sK+ >5.1 mEq/L), and, when normokalemia is achieved, patiromer 16.8-25.2 g/day (SUCRA = 0.94) and patiromer 8.4-16.8 g/day (SUCRA = 0.41) can allow to increase the dose of spironolactone up to 50 mg/day in subjects affected by heart failure (HF) or with resistant hypertension needing treatment with other RAASi. The potential of zirconium cyclosilicate should be explored further, as no data exists to assess properly its capacity to optimize dosing of RAASi, contrarily as it occurs with patiromer. More research is also necessary to discern between benefits of binding potassium among all type of hyperkalemic patients, for example, patients with DM who may need treatment for proteinuria, patients with early hypertension, etc. Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020185614, CRD42020185558, CRD42020191430

A precision medicine test predicts clinical response after idarubicin and cytarabine induction therapy in AML patients

Complete remission (CR) after induction therapy is the first treatment goal in acute myeloid leukemia (AML) patients and has prognostic impact. Our purpose is to determine the correlation between the observed CR/CRi rate after idarubicin (IDA) and cytarabine (CYT) 3 + 7 induction and the leukemic chemosensitivity measured by an ex vivo test of drug activity. Bone marrow samples from adult patients with newly diagnosed AML were included in this study. Whole bone marrow samples were incubated for 48 h in well plates containing IDA, CYT, or their combination. Pharmacological response parameters were estimated using population pharmacodynamic models. Patients attaining a CR/CRi with up to two induction cycles of 3 + 7 were classified as responders and the remaining as resistant. A total of 123 patients fulfilled the inclusion criteria and were evaluable for correlation analyses. The strongest clinical predictors were the area under the curve of the concentration response curves of CYT and IDA. The overall accuracy achieved using MaxSpSe criteria to define positivity was 81%, predicting better responder (93%) than non-responder patients (60%). The ex vivo test provides better yet similar information than cytogenetics, but can be provided before treatment representing a valuable in-time addition. After validation in an external cohort, this novel ex vivo test could be useful to select AML patients for 3 + 7 regimen vs. alternative schedules

A precision medicine test predicts clinical response after idarubicin and cytarabine induction therapy in AML patients

Complete remission (CR) after induction therapy is the first treatment goal in acute myeloid leukemia (AML) patients and has prognostic impact. Our purpose is to determine the correlation between the observed CR/CRi rate after idarubicin (IDA) and cytarabine (CYT) 3 + 7 induction and the leukemic chemosensitivity measured by an ex vivo test of drug activity. Bone marrow samples from adult patients with newly diagnosed AML were included in this study. Whole bone marrow samples were incubated for 48 h in well plates containing IDA, CYT, or their combination. Pharmacological response parameters were estimated using population pharmacodynamic models. Patients attaining a CR/CRi with up to two induction cycles of 3 + 7 were classified as responders and the remaining as resistant. A total of 123 patients fulfilled the inclusion criteria and were evaluable for correlation analyses. The strongest clinical predictors were the area under the curve of the concentration response curves of CYT and IDA. The overall accuracy achieved using MaxSpSe criteria to define positivity was 81%, predicting better responder (93%) than non-responder patients (60%). The ex vivo test provides better yet similar information than cytogenetics, but can be provided before treatment representing a valuable in-time addition. After validation in an external cohort, this novel ex vivo test could be useful to select AML patients for 3 + 7 regimen vs. alternative schedules

Implantación de un sistema integral de gestión del conocimiento para los procesos de innovación docente de la Universidad de Salamanca

Memoria ID-0312. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2014-2015