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CLINICAL IMPLICATIONS: In utero exposure to anti-CD20 monoclonal antibodies can result in transient B-cell depletion, delayed B-cell maturation, decreased immunoglobulin production and inadequate vaccine responses in the infant. These children require immunological follow up and personalized vaccine schedules.
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BACKGROUND: Agammaglobulinemia due to variants in IGLL1 has traditionally been considered an exceedingly rare form of severe B-cell deficiency, with only eight documented cases in the literature. Surprisingly, the first agammaglobulinemic patient identified by newborn screening (NBS) through quantification of kappa-deleting recombination excision circles harbored variants in IGLL1. OBJECTIVE: To provide a comprehensive overview of the clinical and immunological findings of patients with B-cell deficiency attributed to variants in IGLL1. METHODS: NBS programs reporting using kappa-deleting recombination excision circle assays, the European Society for Immunodeficiencies Registry, and authors of published reports featuring patients with B-cell deficiency linked to IGLL1 variants were contacted. Only patients with (likely) pathogenic variants, reduced CD19+ counts and no alternative diagnosis were included. RESULTS: The study included 13 patients identified through NBS, two clinically diagnosed patients, and two asymptomatic siblings. All had severely reduced CD19+ B-cells (< 0.1×109/L) on first evaluation, yet subsequent follow-ups indicated residual immunoglobulin production. Specific antibody responses to vaccine antigens varied, with a predominant reduction observed during infancy. Clinical outcomes were favorable with immunoglobulin G substitution. Two patients successfully discontinued substitution without developing susceptibility to infections and maintaining immunoglobulin levels. The pooled incidence of homozygous or compound heterozygous pathogenic IGLL1 variants identified by NBS in Austria, Czechia, and Switzerland was 1.3:100´000, almost double of X-linked agammaglobulinemia. CONCLUSION: B-cell deficiency resulting from IGLL1 variants appears to be more prevalent than initially believed. Despite markedly low B-cell counts, the clinical course in some patients may be milder than reported in the literature so far.
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Cromosomas Humanos Par 22 , Síndrome de DiGeorge , Linfopenia , Tamizaje Neonatal , Linfocitos T , Humanos , Recién Nacido , Linfopenia/genética , Linfopenia/diagnóstico , Cromosomas Humanos Par 22/genética , Linfocitos T/inmunología , Síndrome de DiGeorge/genética , Síndrome de DiGeorge/diagnóstico , Síndrome de DiGeorge/inmunología , Síndrome de DiGeorge/complicaciones , Duplicación Cromosómica , Masculino , FemeninoRESUMEN
Congenital athymia is a rare T-lymphocytopaenic condition, which requires early corrective treatment with thymus transplantation (TT). Athymic patients are increasingly identified through newborn screening (NBS) for severe combined immunodeficiency (SCID). Lack of relatable information resources contributes to challenging patient and family journeys during the diagnostic period following abnormal NBS results. Patient and Public Involvement and Engagement (PPIE) activities, including parental involvement in paediatrics, are valuable initiatives to improve clinical communication and parental information strategies. Parents of infants with suspected athymia were therefore invited to discuss the information they received during the diagnostic period following NBS with the aim to identify parental information needs and targeted strategies to address these adequately. Parents reported that athymia was not considered with them as a possible differential diagnosis until weeks after initial NBS results. Whilst appropriate clinical information about athymia and TT was available upon referral to specialist immunology services, improved access to easy-to-understand information from reliable sources, including from clinical nurse specialists and peer support systems, remained desirable. A roadmap concept, with written or digital information, addressing parental needs in real time during a potentially complex diagnostic journey, was proposed and is transferrable to other inborn errors of immunity (IEI) and rare diseases. This PPIE activity provides insight into the information needs of parents of infants with suspected athymia who are identified through SCID NBS, and highlights the role for PPIE in promoting patient- and family-centred strategies to improve IEI care.
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Síndromes de Inmunodeficiencia , Inmunodeficiencia Combinada Grave , Timo/anomalías , Lactante , Recién Nacido , Humanos , Niño , Tamizaje Neonatal , Padres , Inmunodeficiencia Combinada Grave/diagnóstico , Inmunodeficiencia Combinada Grave/terapiaRESUMEN
Newborn screening (NBS) for severe combined immunodeficiency (SCID) has been introduced in various countries with the aim of reducing morbidity and mortality. However, studies analyzing outcomes before and after the implementation of NBS programs remain limited. This study sought to compare the outcomes of SCID patients identified through Switzerland's national SCID NBS program, introduced in January 2019, with those of a historical cohort diagnosed between 2007 and 2019. The study included seven patients (32%) identified through NBS, and 15 (68%) born before NBS implementation and diagnosed based on clinical signs. Children in the NBS group were younger at diagnosis (median age 9 days vs 9 months, P = .002) and at hematopoietic stem cell transplantation (HSCT, median age 5 months vs 11 months, P = .003) compared to the clinical group. The NBS group had a lower incidence of infections before HSCT (29% vs 93%, P = .004). Although not statistically significant, the overall survival rate on last follow-up was higher in the NBS group (86% vs 67%, P = .62). Importantly, patients with active infections undergoing HSCT had a significantly lower overall survival probability compared to those without (P = .01). In conclusion, the introduction of NBS in Switzerland has led to earlier and often asymptomatic diagnosis of affected children, enabling timely intervention, infection prevention, and prompt treatment. These factors have contributed to higher survival rates in the NBS group. These findings underscore the critical importance of NBS for SCID, offering potential life-saving benefits through early detection and intervention.
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Trasplante de Células Madre Hematopoyéticas , Inmunodeficiencia Combinada Grave , Niño , Recién Nacido , Humanos , Lactante , Suiza/epidemiología , Tamizaje Neonatal , Inmunodeficiencia Combinada Grave/diagnóstico , Inmunodeficiencia Combinada Grave/epidemiología , Inmunodeficiencia Combinada Grave/terapia , MorbilidadRESUMEN
BACKGROUND: Newborn screening (NBS) programs for severe combined immunodeficiency facilitate early diagnosis of severe combined immunodeficiency and promote early treatment with hematopoietic stem cell transplantation, resulting in improved clinical outcomes. Infants with congenital athymia are also identified through NBS because of severe T-cell lymphopenia. With the expanding introduction of NBS programs, referrals of athymic patients for treatment with thymus transplantation have recently increased at Great Ormond Street Hospital (GOSH) (London, United Kingdom). OBJECTIVE: We studied the impact of NBS on timely diagnosis and treatment of athymic infants with thymus transplantation at GOSH. METHODS: We compared age at referral and complications between athymic infants diagnosed after clinical presentation (n = 25) and infants identified through NBS (n = 19) who were referred for thymus transplantation at GOSH between October 2019 and February 2023. We assessed whether age at time of treatment influences thymic output at 6 and 12 months after transplantation. RESULTS: The infants referred after identification through NBS were significantly younger and had fewer complications, in particular fewer infections. All deaths occurred in the group of those who did not undergo NBS, including 6 patients before and 2 after thymus transplantation because of preexisting infections. In the absence of significant comorbidities or diagnostic uncertainties, timely treatment was achieved more frequently after NBS. Treatment when younger than age 4 months was associated with higher thymic output at 6 and 12 months after transplantation. CONCLUSION: NBS contributes to earlier recognition of congenital athymia, promoting referral of athymic patients for thymus transplantation before they acquire infections or other complications and facilitating treatment at a younger age, thus playing an important role in improving their outcomes.
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Síndromes de Inmunodeficiencia , Inmunodeficiencia Combinada Grave , Lactante , Recién Nacido , Humanos , Inmunodeficiencia Combinada Grave/diagnóstico , Inmunodeficiencia Combinada Grave/terapia , Tamizaje Neonatal , TimoRESUMEN
The impact of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic on pediatric intensive care units (PICUs) is difficult to quantify. We conducted an observational study in all eight Swiss PICUs between 02/24/2020 and 06/15/2020 to characterize the logistical and medical aspects of the pandemic and their impact on the management of the Swiss PICUs. The nine patients admitted to Swiss PICUs during the study period suffering from pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) and constituting 14% (9/63) of all SARS-CoV-2 positive hospitalized patients in Swiss children's hospitals caused a higher workload [total Nine Equivalents of nursing Manpower use Score (NEMS) points, p = 0.0008] and were classified to higher workload categories (p < 0.0001) than regular PICU patients (n = 4,881) admitted in 2019. The comparison of the characteristics of the eight Swiss PICUs shows that they were confronted by different organizational issues arising from temporary regulations put in place by the federal council. These general regulations had different consequences for the eight individual PICUs due to the differences between the PICUs. In addition, the temporal relationship of these different regulations influenced the available PICU resources, dependent on the characteristics of the individual PICUs. As pandemic continues, reflecting and learning from experience is essential to reduce workload, optimize bed occupancy and manage resources in each individual PICU. In a small country as Switzerland, with a relatively decentralized health care local differences between PICUs are considerable and should be taken into account when making policy decisions.
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BACKGROUND: Risk factor management is the key to stroke prevention. Although several studies have assessed the awareness of different risk factors in the general public, there are limited data available on how well acute stroke patients know their own risk factors. The aim of this study was to assess stroke patients' informedness of their own stroke risk factors. METHODS: All consecutive eligible acute stroke and transient ischemic attack patients hospitalized at the Tartu University Hospital, Department of Neurology, during 9 months in 2010 were interviewed about different stroke risk factors within 72 hours from hospitalization. The respective information was also retrieved from medical records. RESULTS: Of the 341 patients admitted during the study period, 195 were eligible for the interview. Diabetes was the best known risk factor (89%) followed by hypertension (80%), atrial fibrillation (78%), previous stroke (77%), and heart failure and/or ischemic heart disease (66%). CONCLUSIONS: We found that acute stroke patients are best informed of their diabetes and worst informed of their ischemic heart disease and/or heart failure. There is, however, room for amelioration in the awareness of all of the studied risk factors. More attention should be addressed to explaining the risks and treatment options to patients at risk of stroke and the general population.
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Concienciación/fisiología , Factores de Riesgo , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/psicología , Anciano , Anciano de 80 o más Años , Enfermedad de la Arteria Coronaria/complicaciones , Diabetes Mellitus/fisiopatología , Femenino , Insuficiencia Cardíaca/complicaciones , Humanos , Hipertensión/complicaciones , Masculino , Persona de Mediana Edad , Medición de RiesgoRESUMEN
The aim of this study was to evaluate which factors are associated with early hospital arrival and help-seeking delays in acute stroke. All consecutive eligible patients were interviewed face-to-face within 72 h of admission. Factors associated with early arrival were assessed by univariate and multivariate analysis. The data of 195 patients were analysed. The patients who first called the emergency medical services rather than the family physician arrived earlier (odds ratio 15.9, 95% confidence interval 3.23-78.3, P<0.01). Those who contacted the emergency medical services within 30 min of symptom onset were more likely to receive thrombolysis (odds ratio 6.9, 95% confidence interval 2.6-18.4, P<0.01). The most common reasons for delaying seeking help were the hope for spontaneous recovery and perceiving the elapsed time as insignificant. The patients who call their family physician lose valuable time and their chance for thrombolysis. Many patients probably neglect symptoms because of stroke itself and therefore do not act fast enough.