Síndrome inflamatorio multisistémico pediátrico (SIMS) asociado con el SARS-CoV-2: Un estudio de cohorte retrospectivo / SARS-CoV-2-associated pediatric multisystemic inflammatory syndrome: A retrospective cohort study

Introduccion: El Síndrome inflamatorio multisistémico pediátrico (SIMS) asociado con el SARS-CoV-2 es una enfermedad aguda acompañada de un síndrome hiperinflamatorio, con falla multiorgánica y shock, asociada a la infección por SARS CoV2, que produce alta morbilidad en la población pediátrica, que hasta el momento es la afectada por este síndrome. Objetivo: Evaluar las características diferenciales del síndrome multisistémico inflamatorio asociado al SARS-COV-2 (SIMS) en niños. Métodos: se realizó un estudio de cohorte retrospectivo. La definición de SIMS se basó en los criterios de la OMS. Los pacientes con COVID-19 relacionados temporalmente se incluyeron como controles. Resultados: se incluyeron 25 pacientes con SIMS y 75 controles. El modelo de regresión logística múltiple de las variables que mostraron ser significativas en el análisis univariado reveló que la edad ≥ 2 años (OR 24,7; IC del 95%: 1,03 -592,4; P = 0,048), la linfopenia (OR 9,03; IC del 95%: 2,05-39,7; P = 0,004), y el recuento de plaquetas <150x109 / L (OR 11,7; IC del 95%: 1,88-75,22; P = 0,009) se asociaron significativamente con SIMS. La presencia de una enfermedad subyacente pareció reducir el riesgo de SIMS (OR 0,06; IC del 95%: 0,01-0,3). Conclusión: El SIMS fue más común en pacientes mayores de 2 años y en aquellos con linfopenia o trombocitopenia. La enfermedad subyacente parece reducir el riesgo del mismo. (AU)

Introduction: SARS-CoV-2-associated pediatric multisystemic inflammatory syndrome (PMIS) is an acute disease accompanied by a hyperinflammatory syndrome, with multiorgan failure and shock associated with SARS CoV2 infection, producing high morbidity in the pediatric population, which so far is affected by this syndrome. Objective: To evaluate the differential characteristics of SARS-COV-2-associated PMIS in children. Methods: A retrospective cohort study was conducted. The definition of PMIS was based on WHO criteria. Patients with temporally related COVID-19 were included as controls. Results: 25 patients with PMIS and 75 controls were included. A multiple logistic regression model of the variables shown to be significant in univariate analysis revealed that age ≥ 2 years (OR 24.7; 95% CI: 1.03 -592.4; P = 0.048), lymphopenia (OR 9.03; 95% CI 2.05-39.7; P = 0.004), and platelet count < 150x109/L (OR 11.7; 95% CI: 1.88-75.22; P = 0.009) were significantly associated with PMIS. The presence of an underlying disease appeared to reduce the risk of PMIS (OR 0.06; 95% CI: 0.01-0.3). Conclusion: PMIS was more common in patients older than 2 years and in those with lymphopenia or thrombocytopenia. Underlying disease appears to reduce the risk of SMIS.(AU)

NT- Péptido natriurético cerebral en la evaluación de respuesta al tratamiento de la insuficiencia cardíaca con levosimendan en pacientes pediátricos / NT-brain natriuretic peptide in the assessment of response to levosimendan treatment in pediatric patients with heart failure

Introducción: El tratamiento de la insuficiencia cardiaca ha incorporado drogas inotrópicas de muy alto costo, como el levosimendan (LEVO). La evaluación de la respuesta a estas drogas en pediatría ofrece dificultades por lo que la medición de biomarcadores como la prohormona N-Terminal Péptido Natriurético Cerebral (NT-ProBNP) podrían ser de utilidad. Objetivo: describir la variación del NT-ProBNP y su correlación con parámetros ecocardiográficos en respuesta a la administración de levosimendan en pacientes pediátricos con insuficiencia cardiaca. Diseño: estudio descriptivo, observacional y prospectivo, sin intervención. Pacientes y métodos: se incluyeron pacientes con insuficiencia cardiaca de 0 a 18 años internados en terapia intensiva a los cuales se les pudo realizar dosaje de NT ProBNP pre LEVO. Se midió dicho péptido al 1°, 3° y 5° día post LEVO. Con cada determinación se realizó ecocardiograma doppler. Resultados: Se enrolaron 15 pacientes, mediana de edad 188,5 días (IQR 25-75: 56-475); de peso 5,475 kg (IQR 25-75: 2.8-7.5). El 80% fueron pacientes con reparación quirúrgica de cardiopatías congénitas, 13.3% con ventrículo único. La mediana de valor de NT ProBNPantes de la administración de LEVO fue 8924.5 pg./ml (IQR 25-75: 4096-20419,75). El 80% de la población presentó descenso en el valor de pro BNP post LEVO y en 10 (66.6%) el descenso fue mayor o igual al 30%. La evaluación global de la función miocárdica no presentó diferencias antes y después del LEVO. Conclusiones: El 66% de los pacientes presentó una disminución de al menos un 30% en los valores de NT ProBNP luego de la administración de levosimendan

Introduction: Very high-cost inotropic drugs, such as levosimendan (LEVO), have been incorporated in the treatment of heart failure. Evaluation of the response to these drugs in children is difficult and measurement of biomarkers such as the prohormone N-terminal pro b-type natriuretic peptide (NT-proBNP) may be of use. Objective: To describe variation of NT-ProBNP and its correlation with echocardiographic parameters in response to the administration of LEVO in pediatric patients with heart failure. Design: A prospective, descriptive, observational, non-interventional study. Patients and methods: Patients between 0 and 18 years of age with heart failure admitted to the intensive care unit in whom pre-LEVO NT-ProBNP levels could be measured were included. NT-ProBNP levels were measured at day 1, 3, and 5 post LEVO. At each measurement, a Doppler echocardiogram was performed. Results: 15 patients with a median age of 188.5 days (IQR 25-75: 56-475) and a weight of 5.475 kg (IQR 25-75: 2.8-7.5) were enrolled. Of the patients, 80% had undergone surgery for congenital heart defects, 13.3% with a single ventricle. Median NT-ProBNP levels before LEVO administration were 8924.5 pg./ml (IQR 25-75: 4096-20419.75). Overall, 80% of the patients had a decrease of post-LEVO NT-ProBNP levels and in 10 (66.6%) the decrease was greater than or equal to 30%. Overall evaluation of myocardial function did not show differences before and after LEVO administration. Conclusions: 66% of the patients presented with a decrease of at least 30% of NT-ProBNP levels after LEVO administration

Uncovering the genetic architecture of Colletotrichum lindemuthianum resistance through QTL mapping and epistatic interaction analysis in common bean.

Colletotrichum lindemuthianum is a hemibiotrophic fungal pathogen that causes anthracnose disease in common bean. Despite the genetics of anthracnose resistance has been studied for a long time, few quantitative trait loci (QTLs) studies have been conducted on this species. The present work examines the genetic basis of quantitative resistance to races 23 and 1545 of C. lindemuthianum in different organs (stem, leaf and petiole). A population of 185 recombinant inbred lines (RIL) derived from the cross PMB0225 × PHA1037 was evaluated for anthracnose resistance under natural and artificial photoperiod growth conditions. Using multi-environment QTL mapping approach, 10 and 16 main effect QTLs were identified for resistance to anthracnose races 23 and 1545, respectively. The homologous genomic regions corresponding to 17 of the 26 main effect QTLs detected were positive for the presence of resistance-associated gene cluster encoding nucleotide-binding and leucine-rich repeat (NL) proteins. Among them, it is worth noting that the main effect QTLs detected on linkage group 05 for resistance to race 1545 in stem, petiole and leaf were located within a 1.2 Mb region. The NL gene Phvul.005G117900 is located in this region, which can be considered an important candidate gene for the non-organ-specific QTL identified here. Furthermore, a total of 39 epistatic QTL (E-QTLs) (21 for resistance to race 23 and 18 for resistance to race 1545) involved in 20 epistatic interactions (eleven and nine interactions for resistance to races 23 and 1545, respectively) were identified. None of the main and epistatic QTLs detected displayed significant environment interaction effects. The present research provides essential information not only for the better understanding of the plant-pathogen interaction but also for the application of genomic assisted breeding for anthracnose resistance improvement in common bean through application of marker-assisted selection (MAS).

Comparison of inhibition of N2 fixation and ureide accumulation under water deficit in four common bean genotypes of contrasting drought tolerance.

BACKGROUND AND AIMS: Drought is the principal constraint on world production of legume crops. There is considerable variability among genotypes in sensitivity of nitrogen fixation to drought, which has been related to accumulation of ureides in soybean. The aim of this study was to search for genotypic differences in drought sensitivity and ureide accumulation in common bean (Phaseolus vulgaris) germplasm that may be useful in the improvement of tolerance to water deficit in common bean. METHODS: Changes in response to water deficit of nitrogen fixation rates, ureide content and the expression and activity of key enzymes for ureide metabolism were measured in four P. vulgaris genotypes differing in drought tolerance. KEY RESULTS: A variable degree of drought-induced nitrogen fixation inhibition was found among the bean genotypes. In addition to inhibition of nitrogen fixation, there was accumulation of ureides in stems and leaves of sensitive and tolerant genotypes, although this was higher in the leaves of the most sensitive ones. In contrast, there was no accumulation of ureides in the nodules or roots of stressed plants. In addition, the level of ureides in the most sensitive genotype increased after inhibition of nitrogen fixation, suggesting that ureides originate in vegetative tissues as a response to water stress, probably mediated by the induction of allantoinase. CONCLUSIONS: Variability of drought-induced inhibition of nitrogen fixation among the P. vulgaris genotypes was accompanied by subsequent accumulation of ureides in stems and leaves, but not in nodules. The results indicate that shoot ureide accumulation after prolonged exposure to drought could not be the cause of inhibition of nitrogen fixation, as has been suggested in soybean. Instead, ureides seem to be produced as part of a general response to stress, and therefore higher accumulation might correspond to higher sensitivity to the stressful conditions.

[Cystadenocarcinoma in situ of the urachus: a clinical case]. / Cistoadenocarcinoma in situ dell'uraco: caso clinico.

Urachal carcinoma is a rare neoplasm which represents 0.01% cancers in adults. If this neoplasm is unusual, the development of cystadenocarcinoma on a urachal cyst is still more rare. The surgical treatment of choice is en-bloc excision of umbilicus and median umbilical ligament with partial cystectomy. As the urachal cystadenocarcinoma of Authors' patient was in situ and without bladder-invasion, they performed a more conservative treatment without partial cystectomy. They believe that this treatment may be indicated in association with a close follow-up after surgery.

[Anterior sacral meningocele with Currarino's syndrome: report of two cases]. / Meningocele sacro anterior en pacientes con síndrome de Currarino: aportación de dos casos.

The anterior sacral meningocele is the congenital hernia of the thecal sac into the pelvis through a bone defect of the anterior wall of the sacrum. The association of anorectal anomaly, anterior sacral defect and presacral mass, known as Currarino's triad, can be diagnosed during the first decade of life in the eighty per cent of the cases However, in the incomplete syndrome, the symptoms appear in adults. In order to avoid late complications and due to the clear genetic origin of this uncommon pathology, the investigation of the family is of paramount importance for the early diagnosis and treatment. We review the literature and add two cases of anterior sacral meningocele with rectal fistula and incomplete Currarino's syndrome. In one of the cases the pathology is also present in another member of the same family and is complicated with meningitis. The importance of early diagnosis and treatment of these malformations and the need for fammily genetic investigation are discussed.

Meningocele sacro anterior en pacientes con síndrome de Currarino: aportación de dos casos / Anterior sacral meningocele with Currarino´s syndrome: Report of two cases

El meningocele sacro anterior es la hernia congénita del saco tecal en la pelvis a través de un defecto óseo en la pared anterior del sacro. La asociación de anomalía anorectal, defecto sacro anterior y masa presacra, conocida como triada de Currarino, puede ser diagnosticada durante la primera década de la vida, en el ochenta por cien de los casos, sin embargo, en el del síndrome incompleto, los síntomas aparecen en el adulto. Para evitar complicaciones tardías y debido a que esta rara patología tiene un claro origen genético, la investigación de la familia es de vital importancia en el diagnóstico precoz y tratamiento. Revisamos la literatura y aportamos dos casos de meningocele sacro anterior con fístula rectal y síndrome incompleto de Currarino, uno de ellos complicado con meningitis y con esta anomalía en un miembro de su familia. Se discute la importancia del diagnóstico precoz y tratamiento de estas malformaciones y la necesidad de una investigación genética familiar (AU)

In vitro improvement of chlorambucil-induced cytotoxicity by deflazacort and 6-methylprednisolone in B-cell chronic lymphocytic leukaemia.

We examined whether CLL cell chemosensitivity to in vitro exposure to chlorambucil (CLB) might be improved by the presence of deflazacort (DFZ) in comparison to 6-methylprednisolone (PDN). The PDN lethal dose (LD)50 values were low in 5 samples, intermediate in 4 and high in 7. Low, intermediate and high DFZ-LD50 values were detected in 3, 2 and 11 samples, respectively. The CBL-LD50 mean values were significantly reduced at all PDN and at the 4 highest DFZ concentrations. However, a dose-response effect was seen only in the DFZ group. Both CLB-DFZ and CLB-PDN interactions were analysed in 16 samples at 25 different dose-combinations, resulting in 400 comparisons between expected and observed leukaemic cell survival (LCS) values for each group. In particular, 45.75% and 40% dose combinations were synergistic in CLB-DFZ and CLB-PDN groups, respectively. A relatively higher number of antagonistic interactions were observed among CLB-PDN dose combinations, while analogous number of additive interactions were detected. At concentrations of CLB x1 microgram/ml the phenomenon of synergism, regardless of the steroid concentration, did occur more frequently. On the other hand, a more elevated number of antagonistic interactions were counted at CLB 100 micrograms/ ml. In conclusion, both DFZ and PDN synergize in vitro with CLB, especially at low concentrations of the alkylating agent.

Modulation of purine analogs- and chlorambucil-induced cytotoxicity by alpha-interferon and interleukin-2 in chronic lymphocytic leukemia.

The decrease in cell viability observed in vitro from the effect of chlorambucil (CLB), fludarabine (FAMP) and 2-chlorodeoxy-adenosine (CDA) on peripheral lymphocytes from 49 untreated CLL patients was investigated by the MTT colorimetric assay. The effects of recombinant-interleukin (r-IL)-2 and alpha-interferon (alpha-IFN) on drug-induced cell death were evaluated. r-IL-2 significantly increased in vitro resistance to CLB, while purine analog cytotoxicity was slightly reduced by the cytokine. The potential in vivo significance of r-IL-2, acting as a survival signal on CLB-induced cell death, is supported by the correlation between the lowest IL-2 serum levels, the highest in vitro sensitivity to CLB and a major clinical response after CLB treatment in six out of eight CLL patients. Using 25 samples, alpha-IFN enabled CLL cells to increase resistance to CLB, CDA and FAMP in 14, eight and seven samples, respectively; conversely, alpha-IFN showed a synergism with both CLB and FAMP in six samples and with CDA in four. These results correlate with immunoenzymatic assay data showing that alpha-IFN either up- or down-regulates tumor necrosis factor and IL-1 levels in supernatants of some CLL samples. Apparently, alpha-IFN plays a dual role in regulating drug-induced cell death, while IL-2 seems to solely favor cell survival in CLL.

[Current status of chemotherapy of tumors of the head and neck]. / Stato attuale della chemioterapia nei tumori testa e collo.

The literature regarding chemotherapy of cervico-facial tumours is reviewed. Owing to its modest, short-lived results intra-arterial treatment has been largely abandoned even in the case of serious complications. It is only used in selected cases as a preparation for subsequent surgical and/or radiation therapy. General, one-drug cytostatic therapy has been given fair results with objective remissions varying from 7.5 to 58%. In recent years polychemotherapy has proved more effective with remissions of from 30 to 80%. There are too few data on the polychemotherapy-immunotherapy association to draw valid conclusions.

[Results of polychemotherapy in the advanced stages of cervico-facial tumors]. / Risultati della polichemioterapia negli stadi avanzati dei tumori del distretto cervico-faciale.

An association of cyclophosphamide, fluorouracil and methotrexate already employed with success against solid tumours in other sites was used in the treatment of 62 patients with advanced tumours of the head and neck. Complete (40.32%) and partial (43.55%) regressions were obtained relatively quickly. A satisfactory period of remission occurred in patients for whom no further treatment had seemed possible, either on account of the extent of the disease, or because surgery and/or radiotherapy had already been performed.