Kasvuhormoonravi saanud laste kliiniline kirjeldus ja ravi efektiivsus – Tartu Ülikooli Kliinikumi lastekliiniku viimase 12 aasta kogemus

Taust. Kasvuhormoonravi sagedaimad näidustused lastel on kasvuhormooni puudulikkus (KHP), Turneri sündroom (TS) ja Praderi-Willi sündroom (PWS). Ravi põhieesmärk on suurendada lõplikku kehapikkust. Eesmärk. Töö sihiks oli kirjeldada 2002.–2013. aasta TÜ Kliinikumi lastekliinikus kasvuhormoonravi saanud patsiente ning uurida ravi efektiivsust. Metoodika. Analüüsiti nimetatud ajaperioodil ravi saanud laste haiguslugusid. Kehapikkuste võrdlemiseks teisendati need standarditud skoorideks (SDS). Ravi efektiivsust hinnati kui kehapikkuse SDSi juurdekasvu ravi jooksul. Tulemused. Ravi sai 65 patsienti. Näidustuseks olid KHP (n = 37, neist 27 poissi), TS (n = 18), PWS (n = 7, kõik tüdrukud), üsasisene kasvupeetus (1 tüdruk), krooniline neerupuudulikkus (1 poiss) ja idiopaatiline lühike kasv (1 tüdruk). Mediaanvanus ravi alustamisel oli KHP-rühmas 9,3 (2,4–15,3) a, TSi-rühmas 10,5 (7,0–14,7) a ja PWSi-rühmas 8,1 (1,5–11,2). Ravi lõpetanud laste (n = 32) kehapikkuse SDSi mediaanjuurdekasv oli KHP-rühmas +2,1 (1,0–3,5), TSi-rühmas +1,6 (0,4–2,0) ning PWSi-rühmas +1,3 (0,2–2,1). Järeldused. Poisse oli KHP-rühmas ligi kolm korda rohkem ning see viitab KHP aladiagnoosimisele tüdrukutel, poiste puudumine PWSi-rühmas aga selle aladiagnoosimisele poistel. Nii KHP, TSi kui ka PWSi puhul oli vanus ravi alustamisel ja ravi efektiivsus sarnane kirjanduses tooduga. Õigeaegse diagnoosi ja ravi alustamise eelduseks on, et laste kasvu jälgitakse kasvugraafiku alusel regulaarselt ning veelgi järjekindlamalt.Eesti Arst 2015; 94(1):12–1

Impact of newborn screening for SCID on the management of congenital athymia

BACKGROUND: Newborn screening (NBS) programmes for severe combined immunodeficiency (SCID) facilitate early SCID diagnosis and promote early treatment with haematopoietic stem cell transplantation, resulting in improved clinical outcomes. Infants with congenital athymia are also identified through NBS due to severe T-cell lymphopaenia. With the expanding introduction of NBS programmes, 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 the age at referral and complications between athymic infants diagnosed after clinical presentation (N=25) and patients identified through NBS (N=19), referred for thymus transplantation at GOSH between 10/2019 and 02/2023. We assessed whether age at time of treatment influences thymic output at 6 and 12 months after transplantation. RESULTS: Infants referred after NBS identification were significantly younger and had less complications, in particular less infections. All deaths occurred in the non-NBS group, including six patients before and two after thymus transplantation because of pre-existing infections. In the absence of significant co-morbidities or diagnostic uncertainties, timely treatment was more frequently achieved after NBS. Treatment at <4 months of age was associated with higher thymic output at 6- and 12-months post-transplantation. CONCLUSION: NBS contributes to earlier recognition of congenital athymia, promoting referral of athymic patients for thymus transplantation prior to acquiring infections or other complications, and facilitating treatment at younger age, thus playing an important role in improving their outcomes

Impact of newborn screening for SCID on the management of congenital athymia

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

Reducing Mortality and Morbidity in Children with Severe Combined Immunodeficiency in Switzerland: the Role of Newborn Screening

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

The SARS-CoV-2 Pandemic Impacts the Management of Swiss Pediatric Intensive Care Units

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 &lt; 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

Diagnostic evaluation of paediatric autoimmune lymphoproliferative immunodeficiencies (ALPID): a prospective cohort study

BACKGROUND Lymphoproliferation and autoimmune cytopenias characterise autoimmune lymphoproliferative syndrome. Other conditions sharing these manifestations have been termed autoimmune lymphoproliferative syndrome-like diseases, although they are frequently more severe. The aim of this study was to define the genetic, clinical, and immunological features of these disorders to improve their diagnostic classification. METHODS In this prospective cohort study, patients were referred to the Center for Chronic Immunodeficiency in Freiburg, Germany, between Jan 1, 2008 and March 5, 2022. We enrolled patients younger than 18 years with lymphoproliferation and autoimmune cytopenia, lymphoproliferation and at least one additional sign of an inborn error of immunity (SoIEI), bilineage autoimmune cytopenia, or autoimmune cytopenia and at least one additional SoIEI. Autoimmune lymphoproliferative syndrome biomarkers were determined in all patients. Sanger sequencing followed by in-depth genetic studies were recommended for patients with biomarkers indicative of autoimmune lymphoproliferative syndrome, while IEI panels, exome sequencing, or genome sequencing were recommended for patients without such biomarkers. Genetic analyses were done as decided by the treating physician. The study was registered on the German Clinical Trials Register, DRKS00011383, and is ongoing. FINDINGS We recruited 431 children referred for autoimmune lymphoproliferative syndrome evaluation, of whom 236 (55%) were included on the basis of lymphoproliferation and autoimmune cytopenia, 148 (34%) on the basis of lymphoproliferation and another SoIEI, 33 (8%) on the basis of autoimmune bicytopenia, and 14 (3%) on the basis of autoimmune cytopenia and another SoIEI. Median age at diagnostic evaluation was 9·8 years (IQR 5·5-13·8), and the cohort comprised 279 (65%) boys and 152 (35%) girls. After biomarker and genetic assessments, autoimmune lymphoproliferative syndrome was diagnosed in 71 (16%) patients. Among the remaining 360 patients, 54 (15%) had mostly autosomal-dominant autoimmune lymphoproliferative immunodeficiencies (AD-ALPID), most commonly affecting JAK-STAT (26 patients), CTLA4-LRBA (14), PI3K (six), RAS (five), or NFκB (three) signalling. 19 (5%) patients had other IEIs, 17 (5%) had non-IEI diagnoses, 79 (22%) were unresolved despite extended genetics (ALPID-U), and 191 (53%) had insufficient genetic workup for diagnosis. 16 (10%) of 161 patients with a final diagnosis had somatic mutations. Alternative classification of patients fulfilling common variable immunodeficiency or Evans syndrome criteria did not increase the proportion of genetic diagnoses. INTERPRETATION The ALPID phenotype defined in this study is enriched for patients with genetic diseases treatable with targeted therapies. The term ALPID might be useful to focus diagnostic and therapeutic efforts by triggering extended genetic analysis and consideration of targeted therapies, including in some children currently classified as having common variable immunodeficiency or Evans syndrome. FUNDING Deutsche Forschungsgemeinschaft under Germany's Excellence Strategy. TRANSLATION For the German translation of the abstract see Supplementary Materials section