Neutrophil functions in late preterm neonates with respiratory distress syndrome

Background: Studies that have addressed the effects of respiratory distress syndrome (RDS) on neutrophil function suggested that neutrophil functions other than the generation of the respiratory burst are not impaired. Yet, results have been confusing and in some cases contradictory.Objectives: The aim of this cross-sectional controlled study is to assess neutrophil number and function in late preterm neonates with RDS.Methods: Thirty patients underwent clinical and laboratory evaluation including complete blood counts and tests of neutrophil functions (CD11b, CD62L and Dihydrorhodamine 123 by flowcytometry) in comparison to 15 healthy term controls. RDS was assessed clinically and radiologically (chest x-ray).Results: Fifty percent of patients (12 females and 18 males) had grade II respiratory distress followed by grade III then grade I. DHR, CD 11b and CD62L results were lower among the patients group (mean ± SD: 62.1± 12.23, 63.22 ± 11.41, 15.03 ± 8.7 respectively). There were no significant correlations between neutrophils count, DHR, CD11b and CD62L. Only CD11b was significantly lower with higher grades of RDS.Conclusion: Neonates with RDS show variable affection of neutrophil functions. Further studies are recommended to elucidate the exact mechanisms by which RDS can affect neutrophil functions and whether these effects are associated with increased incidence of infections.Keywords: Neutrophils, function, respiratory distress syndrome, late preterm, innate immunity, infections, adhesion molecule

Non-osteopenic Bone Pathology After Allo-hematopoietic Stem Cell Transplantation in Patients with Inborn Errors of Immunity

PURPOSE: There is a lack of data on post-HSCT non-osteopenic bone pathology specifically for children with inborn errors of immunity (IEI). We collected data on non-osteopenic bone pathology in children with IEI post-HSCT over two decades in a large tertiary pediatric immunology center. METHODS: Descriptive study with data analysis of bone pathology in allo-HSCT for IEI was performed between 1/1/2000 to 31/12/2018 including patients alive at follow-up to July 2022. Records were analyzed for bone pathology and risk factors. Exclusion criteria included isolated reduced bone density, fractures, and skeletal anomalies due to underlying IEI and short stature without other bone pathology. Bone pathologies were divided into 5 categories: bone tumors; skeletal dysplasia; avascular necrosis; evolving bone deformities; slipped upper femoral epiphysis. RESULTS: A total of 429 children received HSCT between 2000 and 2018; 340 are alive at last assessment. Non-osteopenic bone pathology was observed post-HSCT in 9.4% of patients (32/340, mean 7.8 years post-HSCT). Eleven patients (34%) had > 1 category of bone pathology. Seventeen patients (17/32; 53%) presented with bilateral bone pathology. The majority of patients received treosulfan-based conditioning (26/32; 81.2%). Totally, 65.6% (21/32) of patients had a history of prolonged steroid use (> 6 months). Pain was the presenting symptom in 66% of patients, and surgical intervention was required in 43.7%. The highest incidence of bone pathologies was seen in Wiskott-Aldrich syndrome (WAS) (n = 8/34; 23.5%) followed by hemophagocytic lymphohistiocytosis patients (n = 3/16; 18.8%). CONCLUSION: Non-osteopenic bone pathology in long-term survivors of allo-HSCT for IEI is not rare. Most patients did not present with complaints until at least 5 years post-HSCT highlighting the need for ongoing bone health assessment for patients with IEI. Children presenting with stunted growth and bone pathology post-HSCT should undergo skeletal survey to rule out development of post-HSCT skeletal dysplasia. Increased rates and complexity of bone pathology were seen amongst patients with Wiskott-Aldrich syndrome

Curation and expansion of Human Phenotype Ontology for defined groups of inborn errors of immunity.

BACKGROUND: Accurate, detailed, and standardized phenotypic descriptions are essential to support diagnostic interpretation of genetic variants and to discover new diseases. The Human Phenotype Ontology (HPO), extensively used in rare disease research, provides a rich collection of vocabulary with standardized phenotypic descriptions in a hierarchical structure. However, to date, the use of HPO has not yet been widely implemented in the field of inborn errors of immunity (IEIs), mainly due to a lack of comprehensive IEI-related terms. OBJECTIVES: We sought to systematically review available terms in HPO for the depiction of IEIs, to expand HPO, yielding more comprehensive sets of terms, and to reannotate IEIs with HPO terms to provide accurate, standardized phenotypic descriptions. METHODS: We initiated a collaboration involving expert clinicians, geneticists, researchers working on IEIs, and bioinformaticians. Multiple branches of the HPO tree were restructured and extended on the basis of expert review. Our ontology-guided machine learning coupled with a 2-tier expert review was applied to reannotate defined subgroups of IEIs. RESULTS: We revised and expanded 4 main branches of the HPO tree. Here, we reannotated 73 diseases from 4 International Union of Immunological Societies-defined IEI disease subgroups with HPO terms. We achieved a 4.7-fold increase in the number of phenotypic terms per disease. Given the new HPO annotations, we demonstrated improved ability to computationally match selected IEI cases to their known diagnosis, and improved phenotype-driven disease classification. CONCLUSIONS: Our targeted expansion and reannotation presents enhanced precision of disease annotation, will enable superior HPO-based IEI characterization, and hence benefit both IEI diagnostic and research activities

Controlo químico de infestantes

Uma planta é considerada infestante quando nasce espontaneamente num local e momento indesejados, podendo interferir negativamente com a cultura instalada. As infestantes competem com as culturas para o espaço, a luz, água e nutrientes, podendo atrasar e prejudicar as operações de colheita, depreciar o produto final e assegurarem a reinfestação nas culturas seguintes. Dado o modo de propagação diferenciado das diversas espécies de infestantes, com as anuais a propagarem-se por semente e as perenes ou vivazes a assegurarem a sua propagação através de órgãos vegetativos (rizomas, bolbos, tubérculos, etc.), assim, também o seu controlo quer químico, quer mecânico terá que ser diferenciado, ou seja, para controlar infestantes anuais será suficiente destruir a sua parte aérea, enquanto para controlar infestantes perenes teremos que destruir os seus órgãos reprodutivos. O controlo de infestantes poderá ser químico, através da utilização de herbicidas, ou mecânico pela utilização de alfaias agrícolas, tais como a charrua de aivecas, a charrua de discos, a grade de discos, o escarificador e a fresa. Quando a técnica utilizada na instalação das culturas é a sementeira directa, o controlo das infestantes terá que ser obrigatoriamente químico, enquanto se o recurso à mobilização do solo for a técnica mais utilizada (sistema de mobilização tradicional ou sistema de mobilização reduzida), o controlo das infestantes tanto poderá ser químico como mecânico. Neste trabalho iremos abordar apenas, o controlo químico de infestantes

The Human Phenotype Ontology in 2024: phenotypes around the world.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs

Characterization of greater middle eastern genetic variation for enhanced disease gene discovery

The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics

Early Diagnosis of Classic Homocystinuria in Kuwait through Newborn Screening: A 6-Year Experience

Kuwait is a small Arabian Gulf country with a high rate of consanguinity and where a national newborn screening program was expanded in October 2014 to include a wide range of endocrine and metabolic disorders. A retrospective study conducted between January 2015 and December 2020 revealed a total of 304,086 newborns have been screened in Kuwait. Six newborns were diagnosed with classic homocystinuria with an incidence of 1:50,000, which is not as high as in Qatar but higher than the global incidence. Molecular testing for five of them has revealed three previously reported pathogenic variants in the CBS gene, c.969G>A, p.(Trp323Ter); c.982G>A, p.(Asp328Asn); and the Qatari founder variant c.1006C>T, p.(Arg336Cys). This is the first study to review the screening of newborns in Kuwait for classic homocystinuria, starting with the detection of elevated blood methionine and providing a follow-up strategy for positive results, including plasma total homocysteine and amino acid analyses. Further, we have demonstrated an increase in the specificity of the current newborn screening test for classic homocystinuria by including the methionine to phenylalanine ratio along with the elevated methionine blood levels in first-tier testing. Here, we provide evidence that the newborn screening in Kuwait has led to the early detection of classic homocystinuria cases and enabled the affected individuals to lead active and productive lives

BCG vaccination in patients with severe combined immunodeficiency: Complications, risks, and vaccination policies

BACKGROUND: Severe combined immunodeficiency (SCID) is a syndrome characterized by profound T-cell deficiency. BCG vaccine is contraindicated in patients with SCID. Because most countries encourage BCG vaccination at birth, a high percentage of patients with SCID are vaccinated before their immune defect is detected. OBJECTIVES: We sought to describe the complications and risks associated with BCG vaccination in patients with SCID. METHODS: An extensive standardized questionnaire evaluating complications, therapeutics, and outcomes regarding BCG vaccination in patients given a diagnosis of SCID was widely distributed. Summary statistics and association analysis was performed. RESULTS: Data on 349 BCG-vaccinated patients with SCID from 28 centers in 17 countries were analyzed. Fifty-one percent of the patients had BCG-associated complications, 34% disseminated and 17% localized (a 33,000- and 400-fold increase, respectively, over the general population). Patients receiving early vaccination (≤1 month) showed an increased prevalence of complications (P = .006) and death caused by BCG-associated complications (P < .0001). The odds of experiencing complications among patients with T-cell numbers of 250/μL or less at diagnosis was 2.1 times higher (95% CI, 1.4-3.4 times higher; P = .001) than among those with T-cell numbers of greater than 250/μL. BCG-associated complications were reported in 2 of 78 patients who received antimycobacterial therapy while asymptomatic, and no deaths caused by BCG-associated complications occurred in this group. In contrast, 46 BCG-associated deaths were reported among 160 patients treated with antimycobacterial therapy for a symptomatic BCG infection (P < .0001). CONCLUSIONS: BCG vaccine has a very high rate of complications in patients with SCID, which increase morbidity and mortality rates. Until safer and more efficient antituberculosis vaccines become available, delay in BCG vaccination should be considered to protect highly vulnerable populations from preventable complications.Fil: Gómez Raccio, Andrea C.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; ArgentinaFil: Orellana, Julio Cesar. Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. División de Alergia e Inmunología Clínica; ArgentinaFil: Liberatore, Diana. Hospital Italiano; ArgentinaFil: Bezrodnik, Liliana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Marciano, Beatriz E.. National Institutes of Health; Estados UnidosFil: Huang, Chiung Yu. National Institutes of Health; Estados UnidosFil: Joshi, Gyan. National Institutes of Health; Estados UnidosFil: Rezaei, Nima. Teheran University of Medical Sciences. Children's Medical Center Hospital. Pediatric Center of Excellence; IránFil: Costa Carvalho, Beatriz. Federal University of São Paulo; BrasilFil: Cunha, Luciana. Federal University of Minas Gerais; BrasilFil: Pinto, Jorge A.. Federal University of Minas Gerais; BrasilFil: Espinosa Padilla, Sara E.. Secretaría de Salud. Instituto Nacional de Pediatría; MéxicoFil: Hernandez Nieto, Leticia. Secretaría de Salud. Instituto Nacional de Pediatría; MéxicoFil: Elfeky, Reem A.. Ain Shams University; EgiptoFil: Ariga, Tadashi. Hokkaido University Graduate School of Medicine; JapónFil: Toshio, Heike. Kyoto University Hospital; JapónFil: Dogu, Figen. Ankara University Medical School; TurquíaFil: Cipe, Funda. Ankara University Medical School; TurquíaFil: Formankova, Renata. Charles University; República Checa. University Hospital Motol; República ChecaFil: Nuñez Nuñez, M. Enriqueta. Western National Medical Center; MéxicoFil: Gonçalo Marques, Jose. Santa María Hospital. Lisbon Academic Center; PortugalFil: Pereira, María I.. Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. División de Alergia e Inmunología Clínica; ArgentinaFil: Listello, Viviana. Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. División de Alergia e Inmunología Clínica; ArgentinaFil: Slatter, Mary A.. Great North Children's Hospital; Reino UnidoFil: Nademi, Zohreh. Great North Children's Hospital; Reino UnidoFil: Kowalczyk, Danuta. Children's University Hospital. Department of Clinical Immunology and Transplantology; PoloniaFil: Fleisher, Thomas A.. National Institutes of Health; Estados UnidosFil: Davies, Graham. Great Ormond Street Hospital for Children; Reino UnidoFil: Neven, Bénédicte. Necker Hospital. Immunology-Hematology and Rheumatology Service; FranciaFil: Rosenzweig, Sergio D.. National Institute of Health. National Institute of Allergy and Infectious. Laboratory of Host Defenses. Primary Immunodeficiency Clinic and Infectious Diseases Susceptibility Unit; Estados Unido