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Background: The aim of this study was to investigate the clinical and laboratory parameters that can predict the severity of Multisystem Inflammatory Syndrome in Children (MIS-C) at admission., Methods: We conducted a single-center, partly retrospective, partly prospective, observational cohort study between November 1, 2020 and December 31, 2021, which included patients aged from 1 month to 19 years, meeting the diagnostic criteria of MIS-C. We categorized the patients into three subgroups based on clinical and laboratory markers and assessed the predictive value of these factors in terms of ICU administration and cardiac abnormalities., Results: 53 patients were classified in the following subgroups: Kawasaki-like disease (group 1) (47.2%, n = 25), shock with or without acute cardiac dysfunction (group 2) (32%, n = 17), fever and inflammation (group 3) (20.8%, n = 11). Subgroup analysis revealed that patients with shock and KD at initial presentation had significantly more severe manifestation of MIS-C requiring intensive care unit (ICU) treatment. Of the initial laboratory values, only CRP showed a significant difference between the 3 clinical groups, being lower in group 3. 52.6% of patients were admitted to the ICU. The median length of ICU stay was 3 days (range 3-20). ICU admission was more likely in patients with shortness of breath, renal failure (AKI) and patients with significantly increased concentrations of ferritin, D-dimer, INR and significantly milder increase concentration of fibrinogen. We found that fibrinogen and ferritin levels are independent risk factors for ICU admission. Cardiac abnormalities were found in 56.6% of total (30/53), with the following findings: decreased left ventricular function (32%), coronary abnormality (11.3%), pericardial effusion (17%), arrhythmia (32.1%) and mitral regurgitation (26.6%). Diarrhea and conjunctivitis at the initial presentation with significantly elevated CRP, Pro-BNP and blood pH concentrations were found to be a potential predisposing factor for decreased cardiac function while Pro-BNP and pH were independent risk factors for MIS-C. Regardless of the initial symptoms of MIS-C, the outcome was generally favorable., Conclusions: Clinical characteristics and baseline laboratory values ​​may help identify patients at increased risk for severe disease outcome, such as need for intensive care, presence of shock and decreased cardiac function., Trial Registration: Participation consent was not reqired and ethical considerations were unnecessary, since we did not perform any extra interventions, only the necessary and usual therapeutic and diagnostic methods were used., (© 2023. The Author(s).)

Összefoglaló. A SARS-CoV-2-fertőzés ritka gyermekkori szövődménye a sokszervi gyulladás, angol terminológiával paediatric inflammatory multisystem syndrome (PIMS). Két vagy több szerv érintettségével járó, súlyos tünetekkel induló betegségről van szó, amelynek tünetei átfedést mutatnak a Kawasaki-betegséggel, a toxikus sokk szindrómával és a makrofágaktivációs szindrómával. A PIMS-betegek intenzív terápiás osztályon vagy intenzív terápiás háttérrel rendelkező intézményben kezelendők, ahol biztosítottak a kardiológiai ellátás feltételei is. A szükséges immunterápia a klinikai prezentációtól függ. A jelen közleményben a szerzők a releváns nemzetközi irodalom áttekintését követően ajánlást tesznek a PIMS diagnosztikai és terápiás algoritmusára. Orv Hetil. 2021; 162(17): 652-667. Summary. Pediatric inflammatory multisystem syndrome (PIMS) is a rare complication of SARS-CoV-2 infection in children. PIMS is a severe condition, involving two or more organ systems. The symptoms overlap with Kawasaki disease, toxic shock syndrome and macrophage activation syndrome. PIMS patients should be treated in an intensive care unit or in an institution with an intensive care background, where cardiological care is also provided. The required specific immunotherapy depends on the clinical presentation. In this paper, after reviewing the relevant international literature, the authors make a recommendation for the diagnostic and therapeutic algorithm for PIMS. Orv Hetil. 2021; 162(17): 652-667.

DNA replication is fundamental for cell proliferation in all organisms. Nonetheless, components of the replisome have been implicated in human disease, and here we report PRIM1 encoding the catalytic subunit of DNA primase as a novel disease gene. Using a variant classification agnostic approach, biallelic mutations in PRIM1 were identified in five individuals. PRIM1 protein levels were markedly reduced in patient cells, accompanied by replication fork asymmetry, increased interorigin distances, replication stress, and prolonged S-phase duration. Consequently, cell proliferation was markedly impaired, explaining the patients' extreme growth failure. Notably, phenotypic features distinct from those previously reported with DNA polymerase genes were evident, highlighting differing developmental requirements for this core replisome component that warrant future investigation., (© 2020 Parry et al.; Published by Cold Spring Harbor Laboratory Press.)

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient-reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Hungarian language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability, and construct validity (convergent and discriminant validity). A total of 206 JIA patients (3.9% systemic, 41.3% oligoarticular, 28.2% RF-negative polyarthritis, 26.6% other categories) and 90 healthy children, were enrolled in two centres. The JAMAR components discriminated healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Hungarian version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

Purpose: The aim of this study was to quantify epithelial, stromal, and endothelial cell density, and subbasal nerve morphology in young patients with type 1 diabetes mellitus with and without diabetic retinopathy., Methods: A total of 28 young patients (mean age, 22.86 ± 9.05 years) with type 1 diabetes, with (n = 18) and without (n = 10) retinopathy, and 17 age-matched healthy control subjects (mean age, 26.53 ± 2.43 years) underwent corneal confocal microscopy (CCM)., Results: We found significantly lower epithelial (P < 0.0001) and endothelial (P = 0.001) cell densities and higher keratocyte cell density (P = 0.024) in patients with type 1 diabetes compared to controls. Significantly lower corneal nerve fiber density (P = 0.004), nerve branch density (P = 0.004), total nerve branch density (P = 0.04), and nerve fiber length (P = 0.001), and greater nerve fiber width (P = 0.04) were observed in patients with type 1 diabetes compared to control subjects. Significantly lower epithelial (P < 0.001) and endothelial (P = 0.02) cell densities, nerve branch density (P = 0.02), and nerve fiber length (P = 0.04), and significantly higher keratocyte cell density (P = 0.02) were found in patients with type 1 diabetes without retinopathy compared to control subjects., Conclusions: Corneal confocal microscopy identifies corneal cellular and small nerve fiber pathology in young patients with type 1 diabetes without retinopathy, which increases in severity in those with retinopathy. Corneal confocal microscopy appears to have considerable use as an imaging biomarker for early subclinical pathology in young patients with type 1 diabetes mellitus.

Solitary Median Maxillary Central Incisor Syndrome (SMMCI) is a rare malformation syndrome consisting of multiple, mainly midline defects. Some authors suggest that it is a mild manifestation of the wide spectrum of holoprosencephaly, others classify it rather as a distinct entity. Authors report a case of SMMCI presenting with growth retardation, mild intellectual disability and absence of puberty. Cytogenetic and molecular cytogenetic investigations could identify no abnormalities. The presence of a single maxillary incisor called for further investigations to clarify hidden anomalies, these were empty sella, panhypopituitarism, hypothyroidism, and hypoplasia of the inner genitals. Based on the above findings, growth hormone, estrogen, and L-thyroxine substitution was introduced, which resulted in satisfactory longitudinal growth and onset of sexual maturation. We suggest genetic counselling and if needed, invasive investigations in female patients with short stature and absent/delayed puberty, with or without sex chromosomal anomalies, as the adequate therapy and even the quality of life of patient depends largely on the knowledge of their anatomical and endocrine status., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

We report on two patients with congenital neutropenia, who were treated with filgrastim (recombinant human granulocyte-colony stimulating factor, G-CSF). A poor growth of bone marrow colonies and low sensitivity of colony forming units to colony stimulating factor in vitro before treatment seemed to be associated with a requirement for higher doses of G-CSF to achieve good clinical response in vivo.

The higher susceptibility to serious bacterial infections in patients with Gaucher disease (GD) may be due in part to defective function of phagocytic cells. We studied five patients with GD (type I) and examined the ability of granulocytes and mononuclear phagocytes from these patients to phagocytose and kill Staphylococcus aureus and to generate superoxide anion (O2-) on stimulation with fully opsonized bacteria. Serum-opsonized staphylococci were ingested equally by phagocytic cells from patients and controls. In the presence of normal serum, the extent of killing of S aureus and the release of O2- by granulocytes over incubation periods of 60 minutes and 30 minutes, respectively, were also equivalent for patients and controls. However, we found that killing of viable bacteria and release of O2- by the patients' monocytes was significantly lower than that in cells from controls (P < .05 for both). The magnitude of differences in killing and O2- release between patients' cells and those from controls was even more profound with monocyte-derived macrophages. Enzyme augmentation with macrophage-targeted glucocerebrosidase preparation for 6 months at doses from 7.5 to 10 U/kg/wk resulted in significant increases of functional activities and O2- generation of monocytes and macrophages along with hematologic and hepatosplenic improvements. These data suggest that mononuclear phagocytes from GD patients are defective in their ability to kill bacteria and to generate reactive oxygen intermediates. Our data also suggest that enzyme substitution may improve functions of monocytes and macrophages in patients with GD that should make them more resistant to severe bacterial infection.

We have identified two unrelated girls with chronic neutropenia [absolute neutrophil counts (ANC) 10-870 and 10-940/microL in patients 1 and 2, respectively] and severe defect in superoxide anion generation by granulocytes. Formyl-methionyl-leucyl-phenylalanine-induced superoxide release was 1.2 +/- 0.9 and 1.9 +/- 1.9% (mean +/- SEM, n = 3) of normal controls', mean value in patients 1 and 2, respectively. However, granulocytes from both patients released a normal amount of superoxide upon stimulation with phorbol myristate acetate. Patient 2 exhibited characteristic features of Duane syndrome, a rare disorder of eye movement. Treatment of the patients with recombinant granulocyte colony-stimulating factor led to significant clinical improvements and reduction of infectious complications and to increases in the ANC, to 400-2100/microL in patient 1 and to 500-3000/microL in patient 2. Treatment with 5 micrograms/kg/d resulted in increased intracellular killing of opsonized Staphylococcus aureus by granulocytes and an enhancement of superoxide release upon stimulation with formyl-methionyl-leucyl-phenylalanine in both patients up to 11.1 +/- 6.0 and 13.5 +/- 7.0% (mean +/- SEM, n = 5) of normal controls', mean value in patient 1 and patient 2, respectively. These data suggested that recombinant human granulocyte colony-stimulating factor treatment enhanced resistance to bacterial infection by stimulation of superoxide generation and increasing the bactericidal capacity of peripheral blood granulocytes.