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Background: The CDC and ACIP recommend COVID-19 vaccination for patients with inborn errors of immunity (IEI). Not much is known about vaccine safety in IEI, and whether vaccination attenuates infection severity in IEI., Objective: To estimate COVID-19 vaccination safety and examine effect on outcomes in patients with IEI., Methods: We built a secure registry database in conjunction with the US Immunodeficiency Network to examine vaccination frequency and indicators of safety and effectiveness in IEI patients. The registry opened on January 1, 2022, and closed on August 19, 2022., Results: Physicians entered data on 1245 patients from 24 countries. The most common diagnoses were antibody deficiencies (63.7%). At least one COVID-19 vaccine was administered to 806 patients (64.7%), and 216 patients received vaccination prior to the development of COVID-19. The most common vaccines administered were mRNA-based (84.0%). Seventeen patients were reported to seek outpatient clinic or emergency room care for a vaccine-related complication, and one patient was hospitalized for symptomatic anemia. Eight hundred twenty-three patients (66.1%) experienced COVID-19 infection. Of these, 156 patients required hospitalization (19.0%), 47 required ICU care (5.7%), and 28 died (3.4%). Rates of hospitalization (9.3% versus 24.4%, p < 0.001), ICU admission (2.8% versus 7.6%, p = 0.013), and death (2.3% versus 4.3%, p = 0.202) in patients who had COVID-19 were lower in patients who received vaccination prior to infection. In adjusted logistic regression analysis, not having at least one COVID-19 vaccine significantly increased the odds of hospitalization and ICU admission., Conclusion: Vaccination for COVID-19 in the IEI population appears safe and attenuates COVID-19 severity., (© 2024. The Author(s).)

Cardiovascular manifestations are common (35-100%) in the multisystem inflammatory syndrome in children. Our study aimed to analyze treatment impact and cardiovascular involvement in patients with multisystem inflammatory syndrome in children. The retrospective cohort included 81 patients treated between April 2020 and December 2021 (9.3±4.6 years). Elevated cardiac troponin I and pro-B-type natriuretic peptide were observed in 34.2% and 88.5% of patients, respectively. Myocardial dysfunction was observed in 50.6%. Children older than 10 years had a 4-fold increased risk of myocardial dysfunction (odds ratio [OR] 3.6, 95% confidence interval [CI] 1.4-8.9; p=0.006). A moderate negative correlation was proved between left ventricle ejection fraction and C-reactive protein (rr = - 0.48; p < 0.001). More than one-fifth of the patients presented with shock. Coronary artery dilatation was observed in 6.2% of patients. Mild pericardial effusion was detected in 27.1% of children. On standard electrocardiogram, 52.6% of children had negative T waves in the inferior and/or precordial leads; transient QTc prolongation was registered in 43% of patients. Treatment failure was observed in 19 patients. Patients initially treated with intravenous immunoglobulins had 10-fold higher chances for treatment failure than patients treated with corticosteroids (OR 10.6, 95% CI 3,18 - 35.35; p < 0.001). Cardiovascular manifestations were observed in more than half of the patients, with acute myocardial dysfunction being the most common, especially in children older than 10 years. We established a negative association between the degree of elevation of inflammatory markers and left ventricular ejection fraction. Patients treated with intravenous immunoglobulins who had cardiovascular manifestations had treatment failures more frequently than patients treated with corticosteroids.

Introduction . The COVID-19 pandemic was recognized as a collective trauma and as a major threat to mental health. Recent literature focused on the stress symptomatology or post-traumatic stress disorder associated to the COVID-19 exposure. The concept that people have a natural inclination toward growth, even under stressful and threatening events, gathered less attention. Previous research has analyzed antecedents of post-traumatic growth (PTG) with non-conclusive results. Methods . The present research aimed at including findings on PTG from personality traits, i.e., sense of control and self-mastery, and distal condition of nurturance and support received by others, i.e., cognitive and affective well-being. Analyses were based on 4934 interviews with adults (M age = 57.81 years, 55.5% women) from the Swiss Household Panel study. Results . Relationships over time emerged between sense of control and self-mastery on PTG and worries, measured after two years, via the mediation of cognitive and affective well-being. Conclusion . Results come from a large study in a design seldom employed in this type of research and can inform both research and interventions., Competing Interests: Competing interestsThe authors have declared that no competing interests exist., (© The Author(s) 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: The aim of the study is to evaluate the effect of the presence of antiphospholipid antibodies on the clinical and laboratory manifestations, disease activity and outcomes of the disease in patients with childhood-onset systemic lupus erythematosus (cSLE)., Methods: We conducted a 10-year cross-sectional study with a retrospective analysis of clinical and laboratory parameters and outcome of the disease (kidney, nervous system involvement, thrombosis). For the purpose of the study, patients were divided into cohort groups based on the presence of antiphospholipid antibodies (aPLA), named the aPLA positive group, or their absence, named the aPLA negative group. Values of aPLA were defined in reference laboratories. The disease activity was measured by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, whereas tissue damage degree was measured by Systemic Lupus International Collaborating Clinics/American College of Rheumatology-Damage Index (SLICC/ACR DI; SDI; DI)., Results: Research in our center showed that patients with cSLE often had hematological, cutaneous, and non-thrombotic neurological manifestations. Antiphospholipid antibodies may be present transiently or permanently. A significant change in the titer value was observed in the IgG isotype of aCLA. The presence of higher values of IgM β2GP1 at the beginning indicates that higher disease activity can be expected. Higher disease activity correlates with greater tissue damage. Additionally, it has been shown that aPLA positive patients have two and a half times higher risk of tissue damage than aPLA negative ones., Conclusion: Our study shows that the presence of antiphospholipid antibodies in patients with childhood onset systemic lupus erythematosus may indicate a higher risk of tissue damage, but since it is a rare disease in childhood, prospective and multicenter studies are necessary to assess the importance of the presence of these antibodies.

Introduction: The J Project (JP) physician education and clinical research collaboration program was started in 2004 and includes by now 32 countries mostly in Eastern and Central Europe (ECE). Until the end of 2021, 344 inborn errors of immunity (IEI)-focused meetings were organized by the JP to raise awareness and facilitate the diagnosis and treatment of patients with IEI., Results: In this study, meeting profiles and major diagnostic and treatment parameters were studied. JP center leaders reported patients' data from 30 countries representing a total population of 506 567 565. Two countries reported patients from JP centers (Konya, Turkey and Cairo University, Egypt). Diagnostic criteria were based on the 2020 update of classification by the IUIS Expert Committee on IEI. The number of JP meetings increased from 6 per year in 2004 and 2005 to 44 and 63 in 2020 and 2021, respectively. The cumulative number of meetings per country varied from 1 to 59 in various countries reflecting partly but not entirely the population of the respective countries. Altogether, 24,879 patients were reported giving an average prevalence of 4.9. Most of the patients had predominantly antibody deficiency (46,32%) followed by patients with combined immunodeficiencies (14.3%). The percentages of patients with bone marrow failure and phenocopies of IEI were less than 1 each. The number of patients was remarkably higher that those reported to the ESID Registry in 13 countries. Immunoglobulin (IgG) substitution was provided to 7,572 patients (5,693 intravenously) and 1,480 patients received hematopoietic stem cell therapy (HSCT). Searching for basic diagnostic parameters revealed the availability of immunochemistry and flow cytometry in 27 and 28 countries, respectively, and targeted gene sequencing and new generation sequencing was available in 21 and 18 countries. The number of IEI centers and experts in the field were 260 and 690, respectively. We found high correlation between the number of IEI centers and patients treated with intravenous IgG (IVIG) (correlation coefficient, cc, 0,916) and with those who were treated with HSCT (cc, 0,905). Similar correlation was found when the number of experts was compared with those treated with HSCT. However, the number of patients treated with subcutaneous Ig (SCIG) only slightly correlated with the number of experts (cc, 0,489) and no correlation was found between the number of centers and patients on SCIG (cc, 0,174)., Conclusions: 1) this is the first study describing major diagnostic and treatment parameters of IEI care in countries of the JP; 2) the data suggest that the JP had tremendous impact on the development of IEI care in ECE; 3) our data help to define major future targets of JP activity in various countries; 4) we suggest that the number of IEI centers and IEI experts closely correlate to the most important treatment parameters; 5) we propose that specialist education among medical professionals plays pivotal role in increasing levels of diagnostics and adequate care of this vulnerable and still highly neglected patient population; 6) this study also provides the basis for further analysis of more specific aspects of IEI care including genetic diagnostics, disease specific prevalence, newborn screening and professional collaboration in JP countries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Abolhassani, Avcin, Bahceciler, Balashov, Bata, Bataneant, Belevtsev, Bernatowska, Bidló, Blazsó, Boisson, Bolkov, Bondarenko, Boyarchuk, Bundschu, Casanova, Chernishova, Ciznar, Csürke, Erdős, Farkas, Fomina, Galal, Goda, Guner, Hauser, Ilyina, Iremadze, Iritsyan, Ismaili-Jaha, Jesenak, Kelecic, Keles, Kindle, Kondratenko, Kostyuchenko, Kovzel, Kriván, Kuli-Lito, Kumánovics, Kurjane, Latysheva, Latysheva, Lázár, Markelj, Markovic, Maródi, Mammadova, Medvecz, Miltner, Mironska, Modell, Modell, Mosdósi, Mukhina, Murdjeva, Műzes, Nabieva, Nasrullayeva, Naumova, Nagy, Onozó, Orozbekova, Pac, Pagava, Pampura, Pasic, Petrosyan, Petrovic, Pocek, Prodeus, Reisli, Ress, Rezaei, Rodina, Rumyantsev, Sciuca, Sediva, Serban, Sharapova, Shcherbina, Sitkauskiene, Snimshchikova, Spahiu-Konjusha, Szolnoky, Szűcs, Toplak, Tóth, Tsyvkina, Tuzankina, Vlasova and Volokha.)

Faced with the rapid expansion of the online gambling offer, a growing number of jurisdictions around the world are developing legislation to regulate online gambling. The new Swiss Act on gambling extends legalization of online gambling from already authorized lottery-type to casino-type gambling. In this context, the present study examines offline and online gambling behaviors in emerging-adult males as a particularly at-risk population for gambling addiction. A sample of 1,869 young males completed a questionnaire assessing offline and online gambling behaviors as well as severity of problem gambling. Results show that 62.1% of the respondents were lifetime gamblers while 46.7% were past-year gamblers. Among the latter, 76.4% had gambled only within offline venues, 21.4% had gambled at both offline and online sites, and 2.2% had gambled online only. Furthermore, 17.6% of past-year gamblers were at moderate-risk of developing problem gambling whilst 3.6% were problem gamblers. Association analysis showed that, compared to non-problem gamblers, at-risk and problem gamblers played online at higher rates. These findings contribute to the growing literature on youth gambling behaviors and on offline-online transitions. In the context of the growing online gambling supply, the evolution of youth gambling behaviors should be monitored through periodical assessments., (© 2022. The Author(s).)

Background and Purpose: Venomous animals express numerous Kunitz-type peptides. The mambaquaretin-1 (MQ1) peptide identified from the Dendroaspis angusticeps venom is the most selective antagonist of the arginine-vasopressin V2 receptor (V2R) and the only unique Kunitz-type peptide active on a GPCR. We aimed to exploit other mamba venoms to enlarge the V2R-Kunitz peptide family and gain insight into the MQ1 molecular mode of action., Experimental Approach: We used a bio-guided screening assay to identify novel MQs and placed them phylogenetically. MQs were produced by solid-phase peptide synthesis and characterized in vitro by binding and functional tests and in vivo by diuresis measurement in rats., Key Results: Eight additional MQs were identified with nanomolar affinities for the V2R, all antagonists. MQs form a new subgroup in the Kunitz family, close to the V2R non-active dendrotoxins and to two V2R-active cobra toxins. Sequence comparison between active and non-active V2R Kunitz peptides highlighted five positions, among which four are involved in V2R interaction and belong to the two large MQ1 loops. We finally determined that eight positions, part of these two loops, interact with the V2R. The variant MQ1-K39A showed a higher affinity for the hV2R, but not for the rat V2R., Conclusions and Implications: A new function and mode of action is associated with the Kunitz peptides. The number of MQ1 residues involved in V2R binding is large and may explain its absolute selectivity. MQ1-K39A represents the first step in the improvement of the MQ1 design from a medicinal perspective., (© 2022 The British Pharmacological Society.)

Background: In multisystem inflammatory syndrome in children (MIS-C) temporarily associated with coronavirus disease-19 (COVID-19), myocardial damage has been reported., Materials and Methods: A retrospective observational cohort study included children under 18 who had a myocardial injury related to COVID-19 treated in mother and child health institute from April 2020 to August 2020. Myocardial injury related to COVID-19 was manifested by elevated serum cardiac troponin and NT-proBNP with LV dysfunction, arrhythmias, and coronary arteries (CAs) dilatation or aneurysms. During the short-term follow-up, cardiac testing (electrocardiography, laboratory analysis, echocardiography, 24-h Holter monitoring, exercise stress test, and cardiac magnetic resonance) was performed., Results: Six male adolescents (14.7 ± 2.4 years) were included in the analysis (2/6 had MIS-C shock syndrome). All patients had elevated acute-phase reactants and NT-proBNP, whereas troponins were elevated in 5/6 patients. Echocardiography revealed left ventricular (LV) systolic dysfunction (EF 45.2 ± 6.9%); 2/6 had dilated CAs. IVIG was prescribed to all patients with MIS-C. Four patients required inotropic drug support. During hospitalization, a significant reduction of CRP, LDH, NT-proBNP, and D-dimer ( P < 0.05) was registered. LV systolic function recovery was registered 3 days after applied therapy ( P < 0.001). None of the patients developed dilated cardiomyopathy or CA aneurysms., Conclusions: With early recognition and adequate MIS-C therapy, children recovered entirely, maintained in the short-term follow-up period., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Research in Medical Sciences.)

Background: Cardiovascular complications with myocarditis in multisystem inflammatory syndrome in children (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 infection have been reported, but the optimal therapeutic strategy remains unknown., Methods: A retrospective cohort study included 19 patients with acute left ventricular systolic dysfunction associated with MIS-C, average years of age 13.2 ± 3.8, treated from April 2020 to April 2021., Results: Treatment failure (TF) was observed in 8 patients (in the intravenous immunoglobulin [IVIG] group 7/10; in the corticosteroid [CS] group 1/9). The independent risk factor for TF was IVIG treatment (odds ratio [OR] 18.6, 95% confidence interval [CI] 1.6-222.93, P = 0.02). Patients initially treated with CS became afebrile during in-hospital day 1 (1.5, interquartile range [IQR] 1-2), while IVIG-treated patients became afebrile on in-hospital day 4 (IQR 2-4.25), after CS was added. The C-reactive protein (CRP) significantly declined in CS-treated patients on day 2 (P = 0.01), while in the IVIG group, CRP decreased significantly on the fourth day (P = 0.04). Sodium and albumin levels were higher on third in-hospital day in the CS group than in the IVIG group (P = 0.015, P = 0.03). A significant improvement and normalization of ejection fraction (EF) during the first 3 days was observed only in the CS group (P = 0.005). ICU stays were shorter in the CS group (4, IQR 2-5.5) than in the IVIG group (IVIG group 7, IQR 6-8.5) (P = 0.002)., Conclusions: Among children with MIS-C with cardiovascular involvement, treatment with CS was associated with faster normalization of LV EF, fever, laboratory analysis, and shorter ICU than IVIG-treated patients., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Myocarditis has spontaneous resolution in 50% of patients. Our study aimed to define risk factors for developing dilated cardiomyopathy (DCM) and death in pediatric patients with acute myocarditis (AM)., Methods: The retrospective cohort study included all patients with treated AM. The Mother and Child Health Institute from January 2011 to March 2019., Results: In the study, 62 patients were included, 40 boys and 22 girls (11.15±5.86 years) with AM. Twelve out of sixty-two children had acute fulminant myocarditis. Four patients died in the acute phase of AM, and 11 developed DCM. Follow up was 27.14±36.52 months. Patients with poor outcome (DCM development) were under the age of seven (odds ratio [OR] 10.1; p=0.003), more likely to be girls (OR 4.6; p=0.03), and had fulminant myocarditis (OR 27.0; <0.001). An ejection fraction (EF) <55% and fractional shortening (FS) <30% increased risk of DCM 13- and 5-fold, respectively, but patients with EF between 40 and 55% remain at highest risk of developing DCM. There was a 12-fold increased risk for DCM in patients with left ventricular end-diastolic diameter Z score >2+. The receiver operator curve showed that the lactate dehydrogenase (LDH) cut-off value for developing DCM was 1780 mmol/l (sensitivity 80%, specificity 100%)., Conclusion: Acute fulminant myocarditis was an independent risk factor for DCM. Children with EF between 40 and 50% at admission were at highest risk of developing DCM. Lactate dehydrogenase value could be a significant prognostic value for the outcome of pediatric myocarditis., (Copyright © 2021 Sociedade Portuguesa de Cardiologia. Published by Elsevier España, S.L.U. All rights reserved.)

Real-time reverse transcription polymerase chain reaction (RT-qPCR) is the most sensitive and specific assay and, therefore, is the "gold standard" diagnostic method for the diagnosis of SARS-CoV-2 infection. The aim of this study was to compare and analyze the detection performance of three different commercially available SARS-CoV-2 nucleic acid detection kits: Sansure Biotech, GeneFinder TM , and TaqPath TM on 354 randomly selected samples from hospitalized COVID-19 patients. All PCR reactions were performed using the same RNA isolates and one real-time PCR machine. The final result of the three evaluated kits was not statistically different ( p = 0.107), and also had a strong positive association and high Cohen's κ coefficient. In contrast, the average Ct values that refer to the ORF1ab and N gene amplification were significantly different ( p < 0.001 and p < 0.001, respectively), with the lowest obtained by the TaqPath TM for the ORF1ab and by the Sansure Biotech for the N gene. The results show a high similarity in the analytical sensitivities for SARS-CoV-2 detection, which indicates that the diagnostic accuracy of the three assays is comparable. However, the SanSure Biotech kit showed a bit better diagnostic performance. Our findings suggest that the imperative for improvement should address the determination of cut-off Ct values and rapid modification of the primer sets along with the appearance of new variants.

Background: Acute myocarditis (AM) is defined as inflammation of the myocardium. The aim of our study is a comparative analysis of the differences between AM related and unrelated to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., Methods: The retrospective study included children with AM treated from January 2018 to November 2020., Results: The study included 24 patients; 7 of 24 had AM related to SARS-CoV-2 and they were older than 7. They were more likely to have abdominal pain (P = 0.014), headache (P = 0.003), cutaneous rash (P = 0.003), and conjunctivitis (P = 0.003), while fulminant myocarditis was commonly registered in AM unrelated to SARS-CoV-2 (P = 0.04). A multisystem inflammatory syndrome in children associated with COVID-19 was diagnosed in six adolescents. Patients with AM related SARS-CoV-2 had lower serum cardiac troponin I (cTnI) (P = 0.012), and platelets (P < 0.001), but had a higher C-reactive protein (CRP) value (P = 0.04), and N-terminal-pro hormone BNP in comparison to patients with AM unrelated to SARS-CoV-2. The patients with AM related to SARS-CoV-2 had significant reduction of CRP (P = 0.007). Inotropic drug support was used for shorter durations in patients with AM related to SARS-CoV-2, than in others (P = 0.02). Children with AM related to SARS-CoV-2 had significant improvement of left ventricle systolic function on the third day in hospital (P = 0.001). Patients with AM unrelated to SARS-CoV-2 AM had more frequent adverse outcomes (P = 0.04; three died and four dilated cardiomyopathy)., Conclusions: In contrast to patients with AM unrelated to SARS-CoV-2, patients with AM related to SARS-CoV-2 had a higher CRP value, polymorphic clinical presentation, shorter durations of inotropic drugs use as well as prompt recovery of left ventricle systolic function., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The predisposing factors for pericarditis recurrence in the pediatric population have not yet been established. This study aimed to define the risk factors for the unfavorable prognosis of pediatric acute pericarditis., Methods: This was a retrospective study that included all patients with acute pericarditis treated from 2011 to 2019 at a tertiary referent pediatric center., Results: The study included 72 children. Recurrence was observed in 22.2% patients. Independent risk factors for recurrence were: erythrocyte sedimentation rate≥50mm/h (p=0.003, OR 186.3), absence of myocarditis (p=0.05, OR 15.2), C-reactive protein≥125mg/L (p=0.04, OR 1.5), and non-idiopathic etiology pericarditis (p=0.003, OR 1.3). Corticosteroid treatment in acute pericarditis was associated with a higher recurrence rate than treatment with non-steroid anti-inflammatory therapy (p=0.04). Furthermore, patients treated with colchicine in the primary recurrence had lower recurrence rate and median number of repeated infections than those treated without colchicine (p=0.04; p=0.007, respectively)., Conclusion: Independent risk factors for recurrence are absence of myocarditis, non-idiopathic etiology pericarditis, C-reactive protein≥125mg/L, and erythrocyte sedimentation rate≥50mm/h. Acute pericarditis should be treated with non-steroid anti-inflammatory therapy. A combination of colchicine and non-steroid anti-inflammatory drugs could be recommended as the treatment of choice in recurrent pericarditis., (Copyright © 2020 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Primary health care workers (HCWs) provide almost all vaccine services in Croatia, so they play an essential role in vaccine recommendations and uptake. The aim of this study was to determine the level of vaccine hesitancy among primary HCWs, to identify differences between nurses and physicians in attitudes, beliefs and behaviours towards vaccination, and to determine predictors of vaccine hesitancy among HCWs. We conducted a cross-sectional study from July to December in 2018 among physicians and nurses employed in the services of epidemiology, public health, school medicine, pediatrics and general practice/family medicine in Primorje-Gorski Kotar County, a primarily urban region with a population around 300 000 in the northern part of Croatia. The list of primary HCWs offices was obtained from the Croatian Health Insurance Fond website. We used a self-administered questionnaire on their attitudes, beliefs and behaviours relative to vaccination. Obtained response rate was 65.5% (324/495) of eligible primary HCWs; 64.1% (143/223) of physicians and 66.5% (181/272) of nurses. Seventeen percent of HCWs were identified as vaccine hesitant, and in univariate analysis, we observed an association between HCWs occupation and their own vaccination against flu (p = 0.001), measles (p = 0.016) and HPV (p = 0.025). Nurses and physicians differed (p < 0.001) in their general attitude, beliefs and behaviours towards vaccination, with a higher level of hesitancy among nurses. In multiple logistic regression, those more likely to be vaccine-hesitant were nurses (AOR = 5.73, 95%CI = 2.48-13.24), those who were uncertain or would never receive a vaccine against measles (AOR=11.13; 95%CI=5.37-23.10) and HPV (AOR=5.02; 95%CI=2.60-9.74), as well as those who had encountered a serious adverse event following immunization (AOR=7.55; 95%CI=3.13-19.18). As personal hesitancy may have a negative impact on vaccination education and recommendations, and therefore vaccine coverage, it is necessary to implement interventions to increase vaccination knowledge and confidence among primary health care workers, especially nurses., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)