Effects of the timing of administration of IgM- and IgA-enriched intravenous polyclonal immunoglobulins on the outcome of septic shock patients

Background: The administration of endovenous immunoglobulins in patients with septic shock could be beneficial and preparations enriched with IgA and IgM (ivIgGAM) seem to be more effective than those containing only IgG. In a previous study Berlot et al. demonstrated that early administration of ivIgGAM was associated with lower mortality rate. We studied a larger population of similar patients aiming either to confirm or not this finding considering also the subgroup of patients with septic shock by multidrug-resistant (MDR) pathogens. Methods: Adult patients with septic shock in intensive care unit (ICU) treated with ivIgGAM from August 1999 to December 2016 were retrospectively examined. Collected data included the demographic characteristics of the patients, the diagnosis at admission, SOFA, SAPS II and Murray Lung Injury Score (LIS), characteristics of the primary infection, the adequacy of antimicrobial therapy, the delay of administration of ivIgGAM from the ICU admission and the outcome at the ICU discharge. Parametric and nonparametric tests and logistic regression were used for statistic analysis. Results: During the study period 107 (30%) of the 355 patients died in ICU. Survivors received the ivIgGAM earlier than nonsurvivors (median delay 12 vs 14 h), had significantly lower SAPS II, SOFA and LIS at admission and a lower rate of MDR- and fungal-related septic shock. The appropriateness of the administration of antibiotics was similar in survivors and nonsurvivors (84 vs 79%, respectively, p: n.s). The delay in the administration of ivIgGAM from the admission was associated with in-ICU mortality (odds ratio per 1-h increase = 1.0055, 95% CI 1.003\u20131.009, p < 0.001), independently of SAPS II, LIS, cultures positive for MDR pathogens or fungi and onset of septic shock. Only 46 patients (14%) had septic shock due to MDR pathogens; 21 of them (46%) died in ICU. Survivors had significantly lower SAPS II, SOFA at admission and delay in administration of ivIgGAM than nonsurvivors (median delay 18 vs 66 h). Even in this subgroup the delay in the administration of ivIgGAM from the admission was associated with an increased risk of in-ICU mortality (odds ratio 1.007, 95% CI 1.0006\u20131.014, p = 0.048), independently of SAPS II. Conclusions: Earlier administration of ivIgGAM was associated with decreased risk of in-ICU mortality both in patients with septic shock caused by any pathogens and in patients with MDR-related septic shock

The genetic diagnosis of rare endocrine disorders of sex development and maturation : a survey among Endo-ERN centres

Differences of sex development and maturation (SDM) represent a heterogeneous puzzle of rare conditions with a large genetic component whose management and treatment could be improved by an accurate classification of underlying molecular conditions, and next-generation sequencing (NGS) should represent the most appropriate approach. Therefore, we conducted a survey dedicated to the use and potential outcomes of NGS for SDM disorders diagnosis among the 53 health care providers (HCP) of the European Reference Network for rare endocrine conditions. The response rate was 49% with a total of 26 HCPs from 13 countries. All HCPs, except 1, performed NGS investigations for SDM disorders on 6720 patients, 3764 (56%) with differences of sex development (DSD), including 811 unexplained primary ovarian insufficiency, and 2956 (44%) with congenital hypogonadotropic hypogonadism (CHH). The approaches varied from targeted analysis of custom gene panels (range: 11-490 genes) in 81.5% of cases or whole exome sequencing with the extraction of a virtual panel in the remaining cases. These analyses were performed for diagnostic purposes in 21 HCPs, supported by the National Health Systems in 16 cases. The likelihood of finding a variant ranged between 7 and 60%, mainly depending upon the number of analysed genes or criteria used for reporting, most HCPs also reporting variants of uncertain significance. These data illustrate the status of genetic diagnosis of DSD and CHH across Europe. In most countries, these analyses are performed for diagnostic purposes, yielding highly variable results, thus suggesting the need for harmonization and general improvements of NGS approaches.publishersversionPeer reviewe

SUCESSÃO DE PLANTAS DE COBERTURA SOBRE OS COMPONENTES DE RENDIMENTO NO FEIJOEIRO

Objetivou-se com este trabalho avaliar as influências de diferentes plantas de cobertura  sobre as características agronômicas do feijão. O experimento foi conduzido em Latossolo Vermelho Aluminoférrico, utilizando delineamento de blocos casualisados, com quatro repetições, sendo os dados submetidos ao teste Tukey e comparados por meio de contrastes ortogonais. Os tratamentos consistiram das plantas de cobertura, procedendo seu cultivo em sistema solteiro, bem como alguns consórcios, através das espécies: Linhaça (Linum usitatissimum); Azevém (Lollium multiflorum); Aveia Preta e Branca (Avena stringosa e A. sativa); Ervilhaca (Vicia Sativa); Nabo Forrageiro (Raphanus sativus) e Triticale (Triticum secale). Os atributos agronômicos do feijão avaliados foram: massa de 1000 grãos e por legume, comprimento e número de legumes por planta e parcela, população de plantas e rendimento final. Verificou-se influência direta e distinta sobre os componentes de rendimento do feijão, tendo o número de legumes a maior relação com a produtividade do feijão. Dentre as plantas antecessoras utilizadas, a Ervilhaca e Nabo Forrageiro proporcionaram maior incremento produtivo, diferentemente do Azevém, assim como a Linhaça, que resultaram nos menores rendimentos do feijã

Sucessão de plantas de cobertura sobre os componentes de rendimento no feijoeiro

The objective of this study was to evaluate the influences of different plants covering on the agronomic characteristics of beans. The experiment was conducted on Red Latossol alumino-ferric, using randomized block design with four repetitions, being the data submitted to the Tukey test and compared by orthogonal contrasts. Treatments consisted of covering plants, carrying its growth in single system, as well as some consortia, across species: Flaxseed (Linum usitatissimum); Ryegrass (Lollium multiflorum), Black and White Oats (Avena Stringosa and A. sativa), vetch (Vicia sativa), wild radish (Raphanus sativus) and Triticale (Triticum secale). The agronomic attributes evaluated of bean were: the 1000 seeds per pod, length and number of pods per plant and plot, plant population and yield. Direct and different influence was verified on the components yield of beans, vegetables and the number of the larger relationship with productivity beans. Among the plants used predecessor, the Vetch and Turnip provided larger productive increment, differently of Ryegrass, as well as flaxseed, which resulted in lower yields beans.Objetivou-se com este trabalho avaliar as influências de diferentes plantas de cobertura sobre as características agronômicas do feijão. O experimento foi conduzido em Latossolo Vermelho Aluminoférrico, utilizando delineamento de blocos casualisados, com quatro repetições, sendo os dados submetidos ao teste Tukey e comparados por meio de contrastes ortogonais. Os tratamentos consistiram das plantas de cobertura, procedendo seu cultivo em sistema solteiro, bem como alguns consórcios, através das espécies: Linhaça (Linum usitatissimum); Azevém (Lollium multiflorum); Aveia Preta e Branca (Avena stringosa e A. sativa); Ervilhaca (Vicia Sativa); Nabo Forrageiro (Raphanus sativus) e Triticale (Triticum secale). Os atributos agronômicos do feijão avaliados foram: massa de 1000 grãos e por legume, comprimento e número de legumes por planta e parcela, população de plantas e rendimento final. Verificou-se influência direta e distinta sobre os componentes de rendimento do feijão, tendo o número de legumes a maior relação com a produtividade do feijão. Dentre as plantas antecessoras utilizadas, a Ervilhaca e Nabo Forrageiro proporcionaram maior incremento produtivo, diferentemente do Azevém, assim como a Linhaça, que resultaram nos menores rendimentos do feijão

The nested graft acts by inducing the process of de-senescence of the fibroblasts in chronic venous ulcers

Senescent fibroblasts, which are present in chronic ulcers, are the reason for the wound becoming chronic. In this study, we introduce full-thickness micro skin grafts in the ulcer, a surgical technique known as a 'nested graft', which gave encouraging results leading to complete wound healing in all patients. The assessment of fibroblast cultures taken from the wound before and after treatment and comparison with fibroblasts from healthy skin showed that the fibroblasts taken from the ulcer after the nested graft treatment acquire morpho-functional characteristics overlapping those of fibroblasts from healthy skin. This surgical approach is, therefore, able to lead to the healing of chronic ulcers through the de-senescence of the fibroblasts

The influence of growth hormone treatment on glucose homeostasis in growthhormone-deficient children: A six-year follow-up study

Background: Growth hormone (GH) influences glucose homeostasis by negatively affecting insulin sensitivity, leading to a compensatory increase in insulin secretion. It has recently been reported, in animals and humans, that GH might also stimulate insulin secretion by directly affecting the growth and function of pancreatic β-cells. The aim of this work was to longitudinally study the insulin sensitivity (HOMA-S), insulin secretion [insulinogenic index (IGI)] and capacity of β-cells to adapt to changes in insulin sensitivity [oral disposition index (ODI)] in GH-deficient (GHD) children under GH treatment. Methods: We studied 99 GHD (62 male, 37 female; age 8.9 ± 3.5 years) children for a median period of 6 years (range 1.5-16.2). Every year, our patients underwent an oral glucose tolerance test, which was used to calculate the HOMA-S, IGI and ODI. Results: Although HOMA-S remained unchanged, an increase in IGI and ODI was observed, becoming significant after 6 years of treatment (1.25 ± 1.28 vs. 2.35 ± 2.38, p < 0.05 and 0.57 ± 0.68 vs. 1.50 ± 1.92, p < 0.01, respectively). Conclusion: Our results suggest a positive influence of GH treatment on the β-cell secretory capacity in children with GH deficiency

The influence of gh treatment on glucose homeostasis in girls with turner syndrome: A 7-year study

Context: Growth hormone (GH) influences glucose homeostasis mainly by negatively affecting insulin sensitivity. Objective: To longitudinally study insulin sensitivity [via homeostasis model assessment of insulin sensitivity (HOMA-S)], insulin secretion [insulinogenic index (IGI)], and capacity of b cells to adapt to changes in insulin sensitivity [oral disposition index (ODI)] in girls with Turner syndrome (TS) undergoing GH treatment. Design and Setting: Longitudinal, retrospective, 7-year study conducted in a tertiary pediatric endocrine unit and university pediatric clinic. Patients and Methods:We studied 104 patientswith TS (mean age6standard deviation, 9.163.4 years) for a median of 7.2 years. Intervention: Every year, the children underwent an oral glucose tolerance test, which was used to calculate HOMA-S, IGI, and ODI. Results: HOMA-S, IGI, and ODI did not significantly change. Conclusion: The results are reassuring, showing no negative influence of GH treatment on insulin sensitivity and on b-cell secretory capacity in girlswith TS

Autoimmune-Polyendocrinopathy-Candidiasis-Ectodermal- Dystrophy (APECED) in Calabria: clinical, immunological and genetic patterns.

Autoimmune polyendocrinopathy-candidiasis-ectodermal- dystrophy (APECED), also known as autoimmune polyendocrine syndrome type 1 (APS-1), is a very rare disease. Diagnosis requires the presence of at least two of three major clinical features: chronic mucocutaneous candidiasis, chronic hypoparathyroidism, and Addison's disease. DESIGN: In this study, we analyzed Autoimmune Regulator (AIRE) gene mutations and genotype-phenotype correlation in APECED patients originating from Calabria, a region in the south of Italy. PATIENTS AND METHODS: Four patients and their first-degree relatives were evaluated for clinical manifestations, autoantibody presence and AIRE gene mutations. RESULTS: Three patients carried a homozygous W78R mutation on exon 2, typical of patients with APECED from Apulia; the fourth patient had a homozygous R203X mutation on exon 5, typical of APECED patients from Sicily. Clinical disease expression showed wide variability. Analysis of relatives allowed the identification of 6 heterozygotes, none of whom showed major findings of APECED. CONCLUSIONS: No AIRE gene mutations specific to Calabria were found in patients with APS-1, but mutations similar to those in patients from Apulia and Sicily. Heterozygosity for AIRE gene mutation is not associated with major findings of APECED