Biochemical algorithm to identify individuals with ALPL variants among subjects with persistent hypophosphatasaemia

Hypophosphatasia (HPP) is a rare and underdiagnosed condition characterized by deficient bone and teeth mineralization. The aim of this study was first, to evaluate the diagnostic utility of employing alkaline phosphatase (ALP) threshold levels to identify adults with variants in ALPL among individuals with persistently low ALP levels and second, to determine the value of also including its substrates (serum pyridoxal-5′-phosphate—PLP—and urinary phosphoetanolamine-PEA) for this purpose in order to create a biochemical algorithm that could facilitate the diagnostic work-up of HPP. Results: The study population comprised 77 subjects with persistent hypophosphatasaemia. They were divided into two groups according to the presence (+GT) or absence (−GT) of pathogenic ALPL variants: 40 +GT and 37 −GT. Diagnostic utility measures were calculated for different ALP thresholds and Receiver Operating Characteristic (ROC) curves were employed to determine PLP and PEA optimal cut-off levels to predict the presence of variants. The optimal threshold for ALP was 25 IU/L; for PLP, 180 nmol/L and for PEA, 30 µmol/g creatinine. Biochemical predictive models were assessed using binary logistic regression analysis and bootstrapping machine learning technique and results were then validated. For ALP 180 nmol/L) that when combined, seem to be very useful to identify individuals with ALPL variant

Predictive model to identify multiple failure to biological therapy in patients with rheumatoid arthritis

Despite advances in the treatment of rheumatoid arthritis (RA) and the wide range of therapies available, there is a percentage of patients whose treatment presents a challenge for clinicians due to lack of response to multiple biologic and target-specific disease-modifying antirheumatic drugs (b/tsDMARDs).To develop and validate an algorithm to predict multiple failure to biological therapy in patients with RA.Observational retrospective study involving subjects from a cohort of patients with RA receiving b/tsDMARDs.Based on the number of prior failures to b/tsDMARDs, patients were classified as either multi-refractory (MR) or non-refractory (NR). Patient characteristics were considered in the statistical analysis to design the predictive model, selecting those variables with a predictive capability. A decision algorithm known as 'classification and regression tree' (CART) was developed to create a prediction model of multi-drug resistance. Performance of the prediction algorithm was evaluated in an external independent cohort using area under the curve (AUC).A total of 136 patients were included: 51 MR and 85 NR. The CART model was able to predict multiple failures to b/tsDMARDs using disease activity score-28 (DAS-28) values at 6 months after the start time of the initial b/tsDMARD, as well as DAS-28 improvement in the first 6 months and baseline DAS-28. The CART model showed a capability to correctly classify 94.1% NR and 87.5% MR patients with a sensitivity = 0.88, a specificity = 0.94, and an AUC = 0.89 (95% CI: 0.74-1.00). In the external validation cohort, 35 MR and 47 NR patients were included. The AUC value for the CART model in this cohort was 0.82 (95% CI: 0.73-0.9).Our model correctly classified NR and MR patients based on simple measurements available in routine clinical practice, which provides the possibility to characterize and individualize patient treatments during early stages.© The Author(s), 2022

Distribución geográfica de Culicidae de Argentina

Actualmente en Argentina están citadas 242 especies de mosquitos (Rossi, 2015), correspondientes a 17 géneros (Tabla 1). Como era de esperar (respondiendo posiblemente a una mayor oferta de hábitats), la mayor diversidad va en aumento hacia la zona subtropical, ya que en la región del noreste de Argentina (NEA) se halla representado el 86,47 % del total de las especies, seguida por el noroeste de Argentina (NOA) (45,49 %), Centro (39,75 %), Cuyo (11,88 %) y Patagonia (6,55 %) (Tabla 1). En su revisión bibliográfica, Rossi (2015) encontró especies con una única mención en una localidad, situación que se da para 56 especies (23 %), y especies con registros en más de 200 localidades. Se conocen especies que no han sido halladas desde su primer y única aparición, alguna con más de 60 años desde su publicación. Por otro lado, se registraron más de 400 hallazgos (en diferentes localidades) para especies de Anopheles, las más abundantes y aproximadamente unos 200 para Aedes (Ochlerotatus) albifasciatus, especie con la distribución más extensa en el país. El autor citado señaló también una merma en el número de sitios relevados en los últimos años.Centro de Estudios Parasitológicos y de Vectore

Distribution of mosquitoes in the South East of Argentina and first report on the analysis based on 18S rDNA and COI sequences

Although Mar del Plata is the most important city on the Atlantic coast of Argentina, mosquitoes inhabiting such area are almost uncharacterized. To increase our knowledge in their distribution, we sampled specimens of natural populations. After the morphological identification based on taxonomic keys, sequences of DNA from small ribosomal subunit (18S rDNA) and cytochrome c oxidase I (COI) genes were obtained from native species and the phylogenetic analysis of these sequences were done. Fourteen species from the genera Uranotaenia, Culex, Ochlerotatus and Psorophora were found and identified. Our 18S rDNA and COI-based analysis indicates the relationships among groups at the supra-species level in concordance with mosquito taxonomy. The introduction and spread of vectors and diseases carried by them are not known in Mar del Plata, but some of the species found in this study were reported as pathogen vectors

Frecuencia de prolongación del intervalo QTc en adultos infectados con VIH de Paraguay en 2020

Introduction: the prolonged QTc interval predisposes to serious arrhythmias. Various medications, including antiretrovirals, can prolong it. The objectives were to determine the demographic, clinical characteristics and the frequency of the prolonged QTc interval in patients with HIV. Methods: we conducted a prospective, observational study with a control group. Men and women, over 18 years of age, with HIV infection, who attended the National Hospital (Itauguá, Paraguay) during 2020, were included. Medical students acted as a control group. All subjects who did not give their consent and those with arrhythmias were excluded. Demographic, clinical, laboratory variables and 12-channel electrocardiogram at rest were measured. The study was approved by the Ethics Committee of the Universidad Privada del Este (Paraguay). Results: 39 HIV patients and 39 healthy controls entered the study. The mean age of the cases was 37 ± 11 years, being 59% male. The most frequent comorbidity in the cases was obesity (7.6%). The mean values ​​of urea, creatinine, K, Ca and Mg in the cases were in the normal range. Prolonged QTc was detected in 18% of the cases and in 0% of the controls. The subjects with the electrocardiographic alteration were all on antiretroviral and multiple antibiotic treatment known to be associated with prolonged Qtc. Conclusion: the frequency of prolonged QTc in HIV patients was 18% and in healthy controls it was 0%. Regular monitoring of the electrocardiogram is recommended in HIV patients receiving drugs that prolong the QT interval.Introducción: el intervalo QTc prolongado predispone a arritmias graves. Diversos medicamentos, entre ellos los antirretrovirales, pueden prolongarlo. Los objetivos fueron determinar las características demográficas, clínicas y la frecuencia del intervalo QTc prolongado en pacientes con VIH. Métodos: estudio observacional, prospectivo, con grupo control. Se incluyeron varones y mujeres, mayores de 18 años, portadores de infección por VIH, que acudieron al Hospital Nacional (Itauguá, Paraguay) durante 2020. Actuaron como grupo control los estudiantes de Medicina. Se excluyeron todos los sujetos que no dieron su consentimiento y los portadores de arritmias. Se midieron variables demográficas, clínicas, laboratoriales y electrocardiograma de 12 canales en reposo. El estudio contó con la aprobación del Comité de Ética de la Universidad Privada del Este (Paraguay). Resultados: ingresaron al estudio 39 pacientes con VIH y 39 controles sanos. La edad media de los casos fue 37 ± 11 años, siendo 59% del sexo masculino. La comorbilidad más frecuente en los casos fue la obesidad (7,6%). Los valores medios de urea, creatinina, K, Ca y Mg en los casos se hallaban en rango normal. Se detectó 18% de QTc prolongado en casos y 0% en los controles. Estos sujetos con alteración electrocardiográfica se hallaban todos en tratamiento antirretroviral y antibiótico múltiple de conocida asociación con QTc prolongado. Conclusión: la frecuencia de QTc prolongado en pacientes con VIH fue del 18% y en controles sanos fue del 0%. Se recomienda el control periódico del electrocardiograma en pacientes con VIH en tratamiento con fármacos que prolongan el intervalo QT

Miradas desde la historia social y la historia intelectual: América Latina en sus culturas: de los procesos independistas a la globalización

Fil: Benito Moya, Silvano G. A. Universidad Católica de Córdoba. Facultad de Filosofía y Humanidades; Argentina.Fil: Universidad Católica de Córdoba. Facultad de Filosofía y Humanidades; Argentina

Enchondroma versus Chondrosarcoma in Long Bones of Appendicular Skeleton: Clinical and Radiological Criteria—A Follow-Up

As of today two types of cartilage tumors remain a challenge even for the orthopedic oncologist: enchondroma (E), a benign tumor, and chondrosarcoma (LGC), a malignant and low aggressiveness tumor. A prospective study of 133 patients with a cartilaginous tumor of low aggressiveness in the long bones of the appendicular skeleton was done to prove this difficult differential diagnosis. Parameters including medical history and radiological and nuclear imaging were collected and compared to the result of the biopsy. A scale of aggressiveness was applied to each patient according to the number of aggressiveness episodes present. A comparison of the results of the biopsy with the initial diagnosis made by the orthopedic oncologist based solely on clinical data and imaging tests was also made. Finally, a management algorithm for these cases was proposed. A statistical significance for LGC resulted from the parameter as follows: pain on palpation, involvement of cortical in either the CT or MRI, and Tc99 bone scan uptake equal or superior to anterosuperior iliac crest. In our series, a tumor scoring 5 points or higher in the scale of aggressiveness can have 50% more chance of being LGC. When compared with the gold standard (the biopsy), surgeon’s initial judgement showed a sensitivity of 73.5% and a specificity of 94.1%

Fibroblast Growth Factor 21 (FGF-21) in Peritoneal Dialysis Patients: Natural History and Metabolic Implications

<div><p>Background</p><p>Human fibroblast growth factor 21 (FGF-21) is an endocrine liver hormone that stimulates adipocyte glucose uptake independently of insulin, suppresses hepatic glucose production and is involved in the regulation of body fat. Peritoneal dialysis (PD) patients suffer potential interference with FGF-21 status with as yet unknown repercussions.</p><p>Objectives</p><p>The aim of this study was to define the natural history of FGF-21 in PD patients, to analyze its relationship with glucose homeostasis parameters and to study the influence of residual renal function and peritoneal functional parameters on FGF-21 levels and their variation over time.</p><p>Methods</p><p>We studied 48 patients with uremia undergoing PD. Plasma samples were routinely obtained from each patient at baseline and at 1, 2 and 3 years after starting PD therapy.</p><p>Results</p><p>Plasma FGF-21 levels substantially increased over the first year and were maintained at high levels during the remainder of the study period (253 pg/ml (59; 685) at baseline; 582 pg/ml (60.5–949) at first year and 647 pg/ml (120.5–1116.6) at third year) (p<0.01). We found a positive correlation between time on dialysis and FGF-21 levels (p<0.001), and also, those patients with residual renal function (RRF) had significantly lower levels of FGF-21 than those without RRF (ρ -0.484, p<0.05). Lastly, there was also a significant association between FGF-21 levels and peritoneal protein losses (PPL), independent of the time on dialysis (ρ 0.410, p<0.05).</p><p>Conclusion</p><p>Our study shows that FGF-21 plasma levels in incident PD patients significantly increase during the first 3 years. This increment is dependent on or is associated with RRF and PPL (higher levels in patients with lower RRF and higher PPL). FGF-21 might be an important endocrine agent in PD patients and could act as hormonal signaling to maintain glucose homeostasis and prevent potential insulin resistance. These preliminary results suggest that FGF-21 might play a protective role as against the development of insulin resistance over time in patients undergoing a continuous glucose load.</p></div