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ABSTRACT Purpose: This study aimed to examine the prevalence of myopic eyes over 11 years (2008-2018) in a private clinic and a public assistance service. Methods: We retrospectively evaluated 6332 individuals (12,664 eyes) between 5 and 25 years old, seen at a private clinic-CEMO (2,663 individuals) and a public service-HOIP (3,669 individuals) from 2008 to 2018. We evaluated the prevalence of myopic eyes (EE ≤-0.50) and high myopic eyes (EE ≤-6.00). Results: Sex and services did not show statistical differences. The variation in the prevalence of myopic and high myopic eyes showed a random pattern during the study period (this prevalence could not be increased). Prevalences ranged from 20.7% (in 2017) to 32.4% (in 2015) for myopic eyes and from 1.6% (in 2009 and 2016) to 3.3% (in 2015) for eyes with high myopia. The prevalence of myopia showed a statistically significant increase based on the age group. Conclusion: The prevalence of myopic eyes did not increase in our study. The mean prevalence of myopic eyes was similar in the private clinic and public service.

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ABSTRACT Optic neuritis is an important cause of unilateral and acute visual loss in young adults, but other differential diagnoses should be considered, especially when the disease has an atypical presentation. This report presents the case of a young woman with reduced visual acuity in her right eye, associated with optic disc edema and a relative afferent pupillary defect, that was initially misdiagnosed as optic neuritis and subsequently found to have paracentral acute middle maculopathy, possibly secondary to subtle impending central retinal vein occlusion. This case emphasizes the need to remember that retinal vascular diseases can occasionally mimic optic neuritis. Detailed anamnesis and ophthalmic examination can avoid unnecessary interventions.

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ABSTRACT Purpose: To compare the refractive prediction error of Hill-radial basis function 3.0 with those of 3 conventional formulas and 11 combination methods in eyes with short axial lengths. Methods: The refractive prediction error was calculated using 4 formulas (Hoffer Q, SRK-T, Haigis, and Hill-RBF) and 11 combination methods (average of two or more methods). The absolute error was determined, and the proportion of eyes within 0.25-diopter (D) increments of absolute error was analyzed. Furthermore, the intraclass correlation coefficients of each method were computed to evaluate the agreement between target refractive error and postoperative spherical equivalent. Results: This study included 87 eyes. Based on the refractive prediction error findings, Hoffer Q formula exhibited the highest myopic errors, followed by SRK-T, Hill-RBF, and Haigis. Among all the methods, the Haigis and Hill-RBF combination yielded a mean refractive prediction error closest to zero. The SRK-T and Hill-RBF combination showed the lowest mean absolute error, whereas the Hoffer Q, SRK-T, and Haigis combination had the lowest median absolute error. Hill-radial basis function exhibited the highest intraclass correlation coefficient, whereas SRK-T showed the lowest. Haigis and Hill-RBF, as well as the combination of both, demonstrated the lowest proportion of refractive surprises (absolute error >1.00 D). Among the individual formulas, Hill-RBF had the highest success rate (absolute error ≤0.50 D). Moreover, among all the methods, the SRK-T and Hill-RBF combination exhibited the highest success rate. Conclusions: Hill-radial basis function showed accuracy comparable to or surpassing that of conventional formulas in eyes with short axial lengths. The use and integration of various formulas in cataract surgery for eyes with short axial lengths may help reduce the incidence of refractive surprises.

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BACKGROUND: ISG15 deficiency is a mixed syndrome of Mendelian susceptibility to mycobacterial infections (MSMD), a rare inherited condition characterized primarily by recurrent infections from low-virulence mycobacteria and monogenic type I interferonopathy. OBJECTIVE: To characterize the laboratory and molecular features of two patients from different families affected by the same ISG15 variant. METHODS: We began with clinical characterization and investigation, assessed IL-12/IFN-γ production, performed genetic characterization through WES and Sanger sequencing, conducted an in silico molecular analysis of the genetic ISG15 variant's protein impact, and utilized RNAseq for transcriptome analysis to understand pathway impacts on ISG15-deficient subjects from unrelated families. RESULTS: A mutation in the ISG15 gene was identified, affecting two patients treated in different hospitals and cities in Brazil (Fortaleza and Sao Paulo), who are also members of unrelated families. Both patients showed low IFN-γ production when stimulated with BCG or BCG + IL-12. ISG15 deficiency presented with two distinct clinical phenotypes: infectious and neurological. It was identified that both patients are homozygous for the variant (c.83 T > A). Furthermore, it was observed that the mutant protein p.L28Q results in an unstable protein with increased flexibility (ΔΔG: -2.400 kcal/mol). Transcriptome analysis revealed 1321 differentially expressed genes, with significant upregulation in interferon pathways, showing higher expression in patients compared to controls. CONCLUSION: This study describes the first reported cases in Brazil of two unrelated patients with the same ISG15 mutation c.83 T > A, exhibiting infectious features such as mycobacterial infections and systemic candidiasis, neurological findings, and skin lesions, without adverse reactions to the BCG vaccine. CLINICAL IMPLICATIONS: Reporting ISG15 gene mutations in Brazilian patients enhances understanding of genetic susceptibilities, guiding effective diagnostics and treatment. Identifying high-risk individuals aids clinical practices, genetic counseling, and influences public health policies. We have identified the first case in Brazil of the same ISG15 variant c.83 T > A that was identified in two unrelated patients with distinct clinical phenotypes, infectious and neurological.

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Propionic and methylmalonic acidemias (PAcidemia and MMAcidemia, respectively) are genetic disorders clinically characterized by metabolic decompensation associated with life-threatening encephalopathic episodes in the neonatal period. Adequate and rapid therapeutic management is essential for patients' survival and prognosis. In this study, a restricted protein diet associated with L-carnitine (LC) supplementation was shown to decrease mortality and morbidity in patients affected by these disorders probably by decreasing the accumulation of the major metabolites and therefore their toxicity. Since oxidative stress was proposed as a contributing mechanism of tissue damage in PAcidemia and MMAcidemia and LC has potent antioxidant properties, our objective in this work was to investigate the effects of a long-term therapy consisting of reduced protein intake associated with LC supplementation on oxidative damage markers in patients affected by these diseases. We measured urinary isoprostanes, di-tyrosine, and oxidized guanine species, which reflect oxidative damage to lipids, proteins, and DNA/RNA, respectively, as well as the concentrations of NO products (nitrate plus nitrite) in patients untreated or submitted to short-term or a long-term treatment. Results revealed significant increases of isoprostanes, di-tyrosine, and oxidized guanine species, as well as a moderate nonsignificant increase of NO levels in the untreated patients, relatively to controls. Furthermore, these altered markers were attenuated after short-term treatment and normalized after prolonged treatment. In conclusion, data from this work show for the first time that long-standing treatment of patients with disorders of the propionate pathway can protect against oxidative damage. However, it remains to be elucidated whether oxidative stress identified in this study directly correlates with the clinical conditions of the affected patients.

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BACKGROUND: Uncorrected refractive errors and amblyopia are reported as the two main causes of childhood visual impairment and blindness worldwide. Our purpose was to evaluate refractive status, ocular alignment and effective refractive error coverage (eREC) of school-aged children from low-income areas of Sao Paulo city, Brazil. METHODS: Data from the "Ver na Escola" Project were used for the current study. Children enrolled in the selected schools had an ophthalmic exam including eye alignment assessed by cover test, automatized and subjective dynamic and static refraction. The associations of demographic variables with occurrence and magnitude of refractive errors and eREC were investigated by multiple logistic regressions and multilevel mixed effect models. RESULTS: A total of 17,973 children (51.12% females) with mean ± sd age 8.24 ± 3.54 years old examined from July 2018 to July 2019, were included in the study. Most of the participants (73%) showed orthoposition of the visual axis for both distance and near. Heterophoria was found in about 25% of participants (N = 4,498), with 71.7% of them (N= 3,222) classified as exophoria. Less than 2% (N = 232) showed strabismus, most of them (N = 160) esotropia. Overall, 1,370 (7.70%) of participants had myopia and 577 (3.24%) had hyperopia. Age was found to be significantly associated with increasing static subjective refraction spherical equivalent (Coefficient: -0.18; 95% Confidence Interval (CI): -0.21 to -0.16; p < 0.001). Female sex (Odds Ratio (OR) = 1.13; 95%CI: 1.01-1.27; p = 0.027) and older age (OR = 1.17; 95%CI: 1.16-1.19; p < 0,001) were significantly associated with myopia diagnosis. Older age decreased the odds of hyperopia (OR = 0.95; 95%CI: 0.93-0.98; p < 0.001). The overall effective refractive coverage was 51.76% and was significantly associated with age group, ranging from 32.25% in children aged 3 to 7 years to 61.35% in children aged 8 to 12 years. CONCLUSIONS: Most children have shown eye alignment for both distance and near assessments and no refractive error. Myopia was observed in 7.70% of the population and it was associated with older age and female sex. Hyperopia was observed in 3.24% and was associated with younger age. The overall eREC was 51.76%, significantly associated with age.

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Objectives. To describe the results of a 16-year experience of a state-coverage expanded newborn screening program (NBSP) in Northeast México. Methods. Between 2002 and 2017, dried blood spots of newborns were screened for congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH), biotinidase deficiency, galactosemia, cystic fibrosis, and glucose-6-phosphate dehydrogenase (G6PD) deficiency via immunofluorescence and amino and fatty acid disorders and organic acidemias using tandem mass spectrometry. Frequency rates were determined. Results. Overall, 192 487 samples were processed; 99.4% had negative results, and 598 were diagnosed. The frequency was 3.01/1000 newborns. G6PD deficiency, CH, amino acidemia, organic acidemia, cystic fibrosis, CAH, fatty acid oxidation disorder, galactosemia, and biotinidase deficiency cases were 1:773, 1:962, 1:4277, 1:4476, 1:11,322, 1:10,693, 1:10,693, 1:38,497, and 1:64,162, respectively. Conclusion. Using different technologies in NBSP increased the number of conditions detected, facilitating infant morbidity and mortality prevention. The frequency of disorders depends on the population's genetic background and diagnostic capacity.

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BACKGROUND: Activated phosphoinositide 3-kinase delta syndrome (APDS) [OMIM 615513] is an inborn error of immunity with autosomal dominant inheritance caused by a pathogenic variant in the PIK3CD gene. The prevalence ratio of APDS is < 1: 1,000,000 newborns. The main clinical features of APDS are sinopulmonary infections, benign lymphoproliferation, autoinflammatory disease, and a major risk of lymphoid neoplasms. CLINICAL CASE: A 17-year-old female with a history of pneumonia at 9 months of age subsequently developed recurrent respiratory tract infections, bronchiectasis, perforated otitis media, unilateral tonsillar lymphoid hyperplasia, pansinusitis, recurrent oral candidiasis, and chronic rhinitis. Laboratory studies reported persistent leukopenia and lymphopenia, low CD4 lymphocyte subpopulation, and persistently elevated immunoglobulin M immunoglobulin studies with values up to 692 mg/dL. An inborn error of immunity next-generation sequencing and multiplex ligation-dependent probe amplification analysis detected a heterozygous pathogenic variant in the PIK3CD gene, compatible with APDS. Treatment with monthly injectable gamma globulin and prophylactic antibiotics was started, allowing better control of the infectious processes. CONCLUSION: This is the second case of APDS reported in Mexico in the literature. It is important to be aware of this condition to make a timely diagnosis, which requires a high clinical suspicion and immunological and genetic studies to provide adequate treatment and prevent complications.

INTRODUCCIÓN: El síndrome de la Fosfoinositida 3-cinasa delta activado (Activated Phosphoinositide 3-kinase δ síndrome, APDS) [OMIM 615513] es un error innato de la inmunidad con patrón de herencia autosómica dominante causada por una variante patogénica heterocigota del gen PIK3CD. Su prevalencia es < 1: 1,000,000 nacidos vivos. Las principales manifestaciones clínicas son infecciones sinopulmonares, linfoproliferación benigna, autoinmunidad y aumento del riesgo de malignización linfoide. CASO CLÍNICO: Femenino de 17 años de vida con antecedentes de neumonía a los 9 meses de edad, posteriormente infecciones de vías respiratorias recurrentes, bronquiectasias, otitis media perforada, hiperplasia linfoide de amigdala unilateral, pansinusitis, candidiasis oral recurrente y rinitis crónica. Los estudios de laboratorio reportaron leuco linfopenia persistente, subpoblación linfocitaria con CD4 baja y estudios de inmunoglobulinas con IgM persistentemente elevada con valor de hasta 692 mg/dl. Se realizó estudio molecular de secuenciación de siguiente generación (NGS por sus siglas en inglés Next-Generation Sequencing) y amplificación de sondas dependientes de ligandos múltiples (MLPA por sus siglas en inglés Multiplex Ligation-dependent Probe Amplification) dirigido a errores innatos de la inmunidad que detectó una variante patogénica en estado heterocigoto en el gen PIK3CD, compatible con APDS. Se inició tratamiento con gammaglobulina intravenosa mensual y antibiótico profiláctico, permitiendo mejor control de los procesos infecciosos. CONCLUSIONES: Este es el segundo caso reportado en la literatura de APDS en México, por lo que es importante su conocimiento para poder realizar un diagnóstico oportuno, para el cual se requiere una alta sospecha clínica, además de estudios inmunológicos y genéticos, con la finalidad de otorgar el tratamiento adecuado y prevenir complicaciones.

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Resumen El análisis de los ácidos orgánicos urinarios juega un papel crucial en el diagnóstico y seguimiento de pacientes con trastornos metabólicos congénitos. La falta de datos completos, las variaciones en los hábitos alimentarios entre países y el aumento del consumo de alimentos procesados subrayan la necesidad de realizar investigaciones actualizadas. Con el fin de establecer los intervalos de confianza y medianas de ácidos orgánicos urinarios se evaluaron mediante cromatografía gaseosa acoplada a espectrometría de masas, 125 muestras de orina de pacientes sanos, con edades comprendidas entre 2 días y 13 años. Los resultados fueron analizados teniendo en cuenta el grupo etario, y evidenciaron que las concentraciones de la mayoría de los ácidos orgánicos urinarios varían de acuerdo a la edad, lo que enfatiza la importancia de los valores de referencia emparejados con la edad para interpretar los datos de los pacientes. Existen pocos informes en esta área; sin embargo, la comparación de estos resultados con los valores de referencia informados por otros trabajos muestra una concordancia razonable y las pocas disparidades podrían atribuirse a factores genéticos o influencias dietéticas. Se presentan resultados e interpretaciones de niños previamente diagnosticados con trastornos metabólicos y otras afecciones, lo que confirma la confiabilidad de nuestros datos y métodos analíticos. Este estudio proporciona datos de referencia esenciales para los profesionales clínicos, destaca la importancia de los valores de referencia específicos de la edad para diagnosticar y tratar con precisión a pacientes con trastornos metabólicos y sirve como recurso fundamental para futuras investigaciones en este campo.

Abstract Analysis of urinary organic acids plays a crucial role in the diagnosis and monitoring of patients with congenital metabolic disorders. The lack of complete data, variations in dietary habits between countries, and increasing consumption of processed foods highlight the need for up-to-date research. In order to establish the confidence intervals and medians of urinary organic acids, 125 urine samples from healthy patients, aged between 2 days and 13 years, were evaluated by gas chromatography coupled to mass spectrometry. The results were analysed taking into account the age group, showing that the concentrations of most urinary organic acids vary according to age, which emphasises the importance of paired age reference values to interpret patient data. There are few reports in this area; however, comparing our results with those reference values reported by other papers demonstrates reasonable agreement, and minor disparities could be attributed to genetic factors or dietary influences. Results and interpretations from children previously diagnosed with metabolic disorders and other conditions are presented, confirming the reliability of our data and analytical methods. This study provides essential reference data for clinicians, highlighting the importance of age-specific reference values to accurately diagnose and treat patients with metabolic disorders and serves as a critical resource for future research in this field.

Resumo A análise dos ácidos orgânicos urinários desempenha um papel crucial no diagnóstico e monitoramento de pacientes com distúrbios metabólicos congênitos. A falta de dados completos, as variações nos hábitos alimentares entre países e o aumento do consumo de alimentos processados destacam a necessidade de realizar pesquisas atualizadas. Para estabelecer os intervalos de confiança e medianas de ácidos orgânicos urinários, 125 amostras de urina de pacientes saudáveis, com idades entre 2 dias e 13 anos, foram avaliadas por cromatografia gasosa acoplada à espectrometria de massa. Os resultados foram analisados levando em consideração o grupo etário, evidenciando que as concentrações da maioria dos ácidos orgânicos urinários variam de acordo com a idade, o que destaca a importância dos valores de referência pareados com a idade para interpretar os dados dos pacientes. Há poucos relatos nesta área; no entanto, a comparação destes resultados com os valores de referência informados por outros trabalhos demonstra uma concordância razoável, e as poucas disparidades poderiam ser atribuídas a fatores genéticos ou influências dietéticas. São apresentados resultados e interpretações de crianças previamente diagnosticadas com distúrbios metabólicos e outras condições, o que confirma a confiabilidade de nossos dados e métodos analíticos. Este estudo fornece dados de referência essenciais para profissionais clínicos, enfatizando a importância dos valores de referência específicos da idade para diagnosticar e tratar com precisão pacientes com distúrbios metabólicos, e serve como recurso fundamental para futuras pesquisas nesse campo.

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The lungs are integral to immune defense, and inborn errors of immunity (IEI) often manifest as lung disease. Lung complications of IEI can involve the airways, alveolar spaces, interstitium, vasculature, and pleura. Accurate identification of these lung disease patterns requires a thorough clinical history, physical examination, and high-resolution computed tomography (HRCT), as lung imaging patterns guide further respiratory and immunological evaluations. Respiratory assessment may also include pulmonary function tests, bronchoscopy with bronchoalveolar lavage, and, in some cases, lung biopsy. Additionally, molecular diagnosis of underlying immune defects, typically through comprehensive clinical phenotyping, functional immune studies, and genetic testing, is crucial for informing patient management and guiding targeted therapies. Importantly, given the complexity of IEI, a multidisciplinary approach is necessary. Furthermore, ongoing research is required to refine therapies and improve outcomes for lung complications.

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Abstract Objective: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied. Method: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children's Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations. Results: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4% (p = 0.006). Conclusion: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.

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Introducción: Los errores de prescripción abarcan una amplia gama de faltas que pueden ir desde una selección incorrecta del medicamento hasta la ausencia de información importante en la receta médica, estos últimos llamados errores de omisión, los cuales pueden afectar la salud del paciente. Sin embargo, en México no hay reportes sobre errores de omisión en centros de atención de primer nivel, los cuales son las instituciones que atienden la mayoría de los problemas de salud de la población. Objetivo: Determinar la prevalencia de los errores de omisión identificados en las prescripciones médicas emitidas en un centro de salud de primer nivel de la Ciudad de México en el año 2021. Métodos: Se trata de un estudio observacional, transversal y retrospectivo. Se analizaron 11 tipos de errores de omisión presentes en las recetas médicas de acuerdo con la normativa mexicana vigente. Se estimó la prevalencia de cada tipo de error y se calculó la tasa de errores de omisión. Resultados: Se analizó un total de 5822 recetas médicas y se encontraron 3424 errores de omisión. La tasa de error fue de 1,08 errores por receta. Los errores más frecuentemente encontrados fueron la omisión de la relación diagnóstico/medicamento (38,91 %), la forma farmacéutica (30,54 %) y la concentración (12,11 %). Discusión: Se encontró una alta prevalencia de errores de omisión en las prescripciones médicas en el centro de salud sede del estudio en el año 2021. Es necesario implementar sistemas de apoyo al personal de salud con miras a disminuir los errores de prescripción.

Introduction: Prescription errors cover a wide range of errors that can range from an incorrect selection of the medication to the lack of important information in the medical prescription, the latter called omission errors, which can affect the patient's health. However, in Mexico there are no reports on omission errors in first-level care centers, which are the institutions that address the majority of the population's health problems. Objective: To determine the prevalence of omission errors identified in medical prescriptions issued in a first-level health center in Mexico City in 2021. Methods: This is an observational, cross-sectional and retrospective study. Eleven types of omission errors present in medical prescriptions were analyzed according to current Mexican regulations. The prevalence of each type of error was estimated and the rate of omission errors was calculated. Results: A total of 5822 medical prescriptions were analyzed and 3424 omission errors were found. The error rate was 1.08 errors per prescription. The most frequently found errors were the omission of the diagnosis/medication relationship (38.91%), the pharmaceutical form (30.54%) and the concentration (12.11%). Discussion: A high prevalence of omission errors was found in medical prescriptions at the health center that hosted the study in 2021. It is necessary to implement support systems for health professionals with a view to reducing prescription errors.

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There are few cerebrotendineous xanthomatosis (CTX) case series and observational studies including a significant number of Latin American patients. We describe a multicenter Brazilian cohort of patients with CTX highlighting their clinical phenotype, recurrent variants and assessing possible genotype-phenotype correlations. We analyzed data from all patients with clinical and molecular or biochemical diagnosis of CTX regularly followed at six genetics reference centers in Brazil between March 2020 and August 2023. We evaluated 38 CTX patients from 26 families, originating from 4 different geographical regions in Brazil. Genetic analysis identified 13 variants in the CYP27A1 gene within our population, including 3 variants that had not been previously described. The most frequent initial symptom of CTX in Brazil was cataract (27%), followed by xanthomas (24%), chronic diarrhea (13.5%), and developmental delay (13.5%). We observed that the median age at loss of ambulation correlates with the age of onset of neurological symptoms, with an average interval of 10 years (interquartile range 6.9 to 11 years). This study represents the largest CTX case series ever reported in South America. We describe phenotypic characteristics and report three new pathogenic or likely pathogenic variants.

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Geographic and sociodemographic aspects may influence the natural history and epidemiology of mucopolysaccharidoses (MPS). The main objective in this work was to evaluate the clinical, molecular, and geographic profile of MPS in a population from Ceará (Northeast Brazil). For this, we have performed a descriptive cross-sectional study based on clinical evaluation, interviews with patients and/or family members, and review of medical records of 76 MPS patients. MPS II was the most common type, with the most affected individuals presenting missense pathogenic variants. Patients with MPS I proved to be the most severe clinical phenotype, presenting the first symptoms (mean: 7.1 months; SD = 4.5) and being diagnosed earlier (2.2 years; SD = 2.1) in comparison with the other types. In addition, we have shown that 13 individuals with MPS VI were born of consanguineous marriages in small, nearby cities, in a place where geographical isolation, consanguinity, and clusters of genetic diseases were previously reported. Ten of these individuals (at least, seven different families) presented a rare pathogenic variant in the ARSB gene, c.1143-8T > G in homozygosity, previously reported only among Iberian and South American patients. The results presented here provide a comprehensive picture of MPS in an important state of the Brazilian Northeast, a region that concentrates many risk factors for rare genetic diseases, such as endogamy, inbreeding, and reproductive isolation. We discuss the possible evolutionary processes and biosocial dynamics that can help to explain this finding in terms of population medical genetics and public health.

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More frequent among adults, phenocopies may be caused by somatic mutations or anti-cytokine autoantibodies, mimicking the phenotypes of primary immunodeficiencies. A fourteen-year-old girl was referred for a two-year history of weight loss and multiple recurrent abscesses, complicated recurrent pneumonia, pyelonephritis, osteomyelitis, and septic shock, without fever. She had started with nausea, hyporexia, and weight loss, then with abscesses in her hands, knee, ankle, and spleen. She also developed a rib fracture and left thoracic herpes zoster. The patient was cachectic, with normal vital signs, bilateral crackles on chest auscultation, tumefaction of the knee joint, and poorly healed wounds in hands and chest, oozing a yellowish fluid. Chest computed tomography revealed multiple bilateral bronchiectases. Laboratory workup reported chronic anemia, leukocytosis, neutrophilia, mild lymphopenia, thrombocytosis, pan-hypergammaglobulinemia, and elevated acute serum reactants. Lymphocyte subsets were low but present. Mycobacterium tuberculosis was detected via polymerase chain reaction in a bone biopsy specimen from ankle osteomyelitis. Whole-exome sequencing failed to identify a monogenic defect. Interleukin-12 was found markedly elevated in the serum of the patient. Phosphorylation of STAT4, induced by increasing doses of IL-12, was neutralized by patient serum, confirming the presence of anti-IL12 autoantibodies. IL-12 and IL-23 are crucial cytokines in the defense against intracellular microorganisms, the induction of interferon-gamma production by lymphocytes, and other inflammatory functions. Patients who develop neutralizing serum autoantibodies against IL12 manifest late in life with weight loss, multiple recurrent abscesses, poor wound healing, and fistulae. Treatment with anti-CD20 monoclonal antibodies was effective.

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Background: Newborn screening (NBS) for the early detection of inborn errors of immunity (IEI) has been implemented in a few countries. The objective of this study was to verify the situation and define obstacles to the implementation of NBS worldwide. Methods: A questionnaire was developed by the Inborn Errors of Immunity Committee of the World Allergy Organization (WAO) with 17 questions regarding NBS for IEI in the physician's workplace, NBS test type, problems hindering NBS implementation, reimbursement for IEI therapy, presence of a national IEI registry, referral centers, molecular diagnosis, hematopoietic stem cell transplantation centers, gene therapy, and immunoglobulin replacement therapy. The survey was sent by email once a week to doctors and others associated with WAO and the main immunology societies worldwide as a Google Form™ to be completed during September and October 2021. Results: Two hundred twenty-nine questionnaires were completed, of which 216 (94.3%) were completed by physicians. One hundred seventy-six (76.8%) physicians were both allergists and immunologists. The agreement between allergists/immunologists and non-allergists/non-immunologists for the question "Is there NBS for IEI in the country you work in?" was good (κ = 0,64: 95% CI 0.55-0.69). Ninety-eight (42.8%) participants were from Latin America, 35 (15.3%) from North America, 29 (12.6%) from Europe, 18 (7.9%) from Africa, 44 (19.2%) from Asia, and 5 (2.2%) from Oceania. More than half the participants (n = 124, 54.2%) regularly treated patients with IEI, followed by occasional treatment (n = 77, 33.6%), or never (n = 28, 12.2%). Of the respondents, 14.8% reported that their countries performed NBS for IEI, whereas 42.2% reported their countries did not. T-cell receptor excision circles was the most widely used technique in some countries, with 75 (59.9%) for the diagnosis of NBS for IEI, followed by combined use with kappa deleting-recombination excision circles. Only 13 participants (10.3%) underwent neonatal exon screening in their respective countries. Financial and technical issues were among the major obstacles to the implementation of NBS for IEI. Conclusions: This pilot study showed that few countries have implemented NBS for IEI, despite the presence of immunology referral centers and the availability of hematopoietic stem cell transplantation and intravenous immunoglobulin replacement therapy. The findings highlight the difficulties, mainly financial and technical, hindering wide application of NBS. Sharing experiences, technologies, and resources at the international level can help overcome these difficulties.

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Common variable immunodeficiency is a heterogeneous symptomatic group of inborn errors of immunity that mainly affects antibodies production and/or function, predisposing patients to recurrent and severe infections. More than half of them usually develop autoimmunity, lymphoproliferation, enteropathy, and malignancies. Among these conditions, chronic lung disease such as granulomatous-lymphocytic interstitial lung disease is one of the leading causes of death in these patients. Recently, many genes that play a key role in B and T cells' development, maintenance, and/or cytokines signaling pathways have been implicated in the pathogenesis of the disease. Here, we describe the first Argentinian patient presenting with common variable immunodeficiency and granulomatous-lymphocytic interstitial lung disease, harboring two in cis heterozygous variants in the SOCS1 gene.

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Background: Polypharmacy and the use of high-alert medications in patients with nasally placed feeding tube (NPFT) increase the risks of drug related problems. Objective: Characterize drugs prescribed to patients with NPFT and compare the rates of polypharmacy and high-alert medication use at admission and hospital discharge. Design and setting: Multicenter cross-sectional study with 327 participants. Methods: Data of patients with NPFT were obtained from the medical records and recorded in an electronic data collection tool. Mean number of drugs, polypharmacy and number of high-alert medications prescribed on admission and at discharge were compared using Wilcoxon or McNemar's tests. Generalized Estimating Equations analyzed the relationship between polypharmacy and high-alert medications according to age and time point. Primary reason for hospital admission, level of consciousness, severity of comorbid diseases and patient care complexity were also assessed. Results: Most patients were male, older people, hospitalized for circulatory system diseases and had at least one comorbidity. On admission, a significant number of patients were alert (59.9%), at high risk for death (43.1%) and high dependent on nursing care (35.4%). Additionally, 92% patients were on polypharmacy on admission, versus 84.7% at hospital discharge (p = 0,0011). The occurrence of polypharmacy was independent of age (p = 0.2377). >17% of all drugs prescribed were high-alert medications, with no statistically significant difference between admission and discharge (p = 0,3957). There was no statistical evidence that the use of high-alert medications increases with age (n = 0,5426). Conclusions: These results support the planning of multidisciplinary qualified actions for patients using NPFT.