X-linked lymphoproliferative disease (XLP1) is an inborn error of immunity (IEI) with severe immune dysregulation caused by a mutation in the
gene resulting in the absence or dysfunction of signaling ...lymphocytic activation molecule (SLAM)-associated protein (SAP). The severe acute respiratory syndrome (SARS) caused by SARS-coronavirus (CoV), a highly pathogenic CoV, has been shown to only cause mild diseases in Asian children. We report on a 5-year-old Nepalese boy with agammaglobulinemia and probable SARS who died of diffuse alveolar damage 22 days after admission amid the SARS outbreak. The index patient and his younger brother were genetically confirmed to have XLP1. In the current coronavirus disease 2019 (COVID-19) pandemic, most children also had mild disease only. Children with severe COVID-19 would warrant investigations for underlying IEI, particularly along the pathways leading to immune dysregulation.
There has been a lack of high-quality evidence concerning the association between childhood maltreatment and psychiatric diagnoses particularly for Axis II disorders. This study aimed to examine the ...association between childhood maltreatment exposure and Axis I and Axis II psychiatry disorders using electronic health records. In this study, the exposed group (n = 7473) comprised patients aged 0 to 19 years with a first-time record of maltreatment episode between January 1, 2001 and December 31, 2010, whereas the unexposed group (n = 26,834) comprised individuals of the same gender and age who were admitted into the same hospital in the same calendar year and month but had no records of maltreatment in the Hong Kong Clinical Data Analysis and Reporting System (CDARS). Data on their psychiatric diagnoses recorded from the date of admission to January 31, 2019 were extracted. A Cox proportional hazard regression model was fitted to estimate the hazard ratio (HR, plus 95% CIs) between childhood maltreatment exposure and psychiatric diagnoses, adjusting for age at index visit, sex, and government welfare recipient status. Results showed that childhood maltreatment exposure was significantly associated with subsequent diagnosis of conduct disorder/ oppositional defiant disorder (adjusted HR, 10.99 95% CI 6.36, 19.01), attention deficit hyperactivity disorder (ADHD) (7.28 5.49, 9.65), and personality disorders (5.36 3.78, 7.59). The risk of psychiatric disorders following childhood maltreatment did not vary by history of childhood sexual abuse, age at maltreatment exposure, and gender. Individuals with a history of childhood maltreatment are vulnerable to psychiatric disorders. Findings support the provision of integrated care within the primary health care setting to address the long-term medical and psychosocial needs of individuals with a history of childhood maltreatment.
Allergists addressing gastrointestinal (GI) symptoms during oral immunotherapy (OIT) may be biased toward diagnoses related to OIT; however, non-OIT causes may occur. Although there is currently a ...lack of robust data for evidence-based treatment recommendations, we provide 3 real-world illustrative cases along with a proposed management algorithm for GI symptoms encountered during OIT. This algorithm was developed because of a significant clinical need, given the number of new-to-OIT providers that include practicing allergists, trainees transitioning into practice, and allied health care providers who manage GI symptoms in OIT patients. We developed the algorithm based on the opinions of community and academic allergy clinics across Canada with significant clinical experience offering infant, preschool, and school-aged OIT patients, with gastroenterologist input. Further research is needed to fill the knowledge gaps in the management of GI symptoms during OIT before formal recommendations can be suggested.
Comirnaty is safe and provides good antibody response, including for patients aged 12 to 15 years with clinical efficacy in protecting against severe acute respiratory syndrome coronavirus 2 ...(SARS-CoV-2) infection of 100%.1 On 14 June 2021, the Food and Health Bureau, Hong Kong SAR Government lowered the age limit for receiving the Comirnaty vaccine to greater than or equal to12 years.2 Since April 2021, there have been reports that myocarditis and pericarditis occur more frequently in adolescents and young adults after mRNA COVID-19 vaccinations internationally.3 4 5 In Hong Kong, Comirnaty is the only mRNA technology platform COVID-19 vaccine available, but others are available elsewhere (eg, from Moderna). Myocarditis and pericarditis have many virological and immunological causes, and are known to occur after vaccination; for example, the incidence of myocarditis after smallpox vaccination is around 12 to 16.1 per million vaccinated individuals.6Myocarditis can also occur after SARS-CoV-2 infection alone or as a consequence of multisystem inflammatory syndrome in children after COVID-19 or paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2.3 7 8 Reported cases of myocarditis after mRNA COVID-19 vaccination are mostly male adolescents and young adults aged between 12 and 24 years who received the second dose of the mRNA vaccine.9 10 11 12 13 14These heart complications are exceedingly rare, but are increasingly reported as hundreds of million doses of mRNA COVID-19 vaccines have been administered worldwide.4 5 9 10 The typical symptoms of myocarditis and pericarditis are chest pain, shortness of breath, and palpitations occurring within 1 week (usually 2-4 days) after vaccination. The Centers for Disease Control and Prevention and the Food and Health Bureau of Hong Kong SAR Government endorse the use of Comirnaty vaccine in adolescents mainly because the benefits of vaccination exceed the risks of SARS-CoV-2 infection.15 Although there is no alternative vaccine for this age-group currently available, data are being gathered on CoronaVac, which utilises the inactivated virus platform.
Chronic granulomatous disease (CGD) is an inborn error of immunity (IEI), characterised by recurrent bacterial and fungal infections. It is inherited either in an X-linked (XL) or autosomal recessive ...(AR) mode. Phenome refers to the entire set of phenotypes expressed, and its study allows us to generate new knowledge of the disease. The objective of the study is to reveal the phenomic differences between XL and AR-CGD by using Human Phenotype Ontology (HPO) terms.
We collected data on 117 patients with genetically diagnosed CGD from Asia and Africa referred to the Asian Primary Immunodeficiency Network (APID network). Only 90 patients with sufficient clinical information were included for phenomic analysis. We used HPO terms to describe all phenotypes manifested in the patients.
XL-CGD patients had a lower age of onset, referral, clinical diagnosis, and genetic diagnosis compared with AR-CGD patients. The integument and central nervous system were more frequently affected in XL-CGD patients. Regarding HPO terms, perianal abscess, cutaneous abscess, and elevated hepatic transaminase were correlated with XL-CGD. A higher percentage of XL-CGD patients presented with BCGitis/BCGosis as their first manifestation. Among our CGD patients, lung was the most frequently infected organ, with gastrointestinal system and skin ranking second and third, respectively.
species,
, and
were the most frequent pathogens to be found.
Phenomic analysis confirmed that XL-CGD patients have more recurrent and aggressive infections compared with AR-CGD patients. Various phenotypic differences listed out can be used as clinical handles to distinguish XL or AR-CGD based on clinical features.
Previous studies support the effectiveness of sesame oral immunotherapy (S-OIT) in patients >4 years old using maintenance doses of 1200 mg protein. However, tahini is often not palatable to ...children, and high-maintenance doses may not be possible for preschoolers.
We studied the safety and effectiveness outcomes of preschoolers with sesame allergy who underwent low-dose S-OIT of 200 mg protein.
Preschoolers with sesame allergy, with a history of objective reaction to sesame, and with either a positive skin prick test result (wheal diameter ≥3 mm) or sesame-specific IgE level ≥0.35 kU/L were included. Doses were escalated every 2 to 4 weeks until the maintenance dose of 200 mg of sesame protein was reached. The maintenance dose was continued daily for 1 year, followed by exit oral food challenge (OFC). Primary safety outcomes included allergic reactions grade 2 or higher and the need for epinephrine therapy during buildup. The primary effectiveness outcome was proportion of patients tolerating a minimum of 2000 mg sesame protein at exit OFC.
Twenty-eight preschoolers (median age, 33.5 months) were enrolled to receive S-OIT. During the buildup phase, 9 subjects (32.1%) had no reaction, and 8 (28.6%) and 11 (39.3%) had grade 1 and 2 reactions, respectively. One patient (3.57%) received epinephrine for a grade 2 reaction. Twenty-one (91.3%) of 23 eligible subjects underwent exit OFC; 18 (85.7%) of these 21 patients successfully completed exit OFC. One (4.8%) and 2 (9.5%) subjects had grade 1 and 2 reactions, respectively, during OFC.
A lower and age-appropriate maintenance dose is safe and effective in desensitizing preschoolers with sesame allergy.
Vaccine-related myocarditis associated with the BNT162b2 vaccine is a rare complication, with a higher risk observed in male adolescents. However, the contribution of genetic factors to this ...condition remains uncertain. In this study, we conducted a comprehensive genetic association analysis in a cohort of 43 Hong Kong Chinese adolescents who were diagnosed with myocarditis shortly after receiving the BNT162b2 mRNA COVID-19 vaccine. A comparison of whole-genome sequencing data was performed between the confirmed myocarditis cases and a control group of 481 healthy individuals. To narrow down potential genomic regions of interest, we employed a novel clustering approach called ClusterAnalyzer, which prioritised 2,182 genomic regions overlapping with 1,499 genes for further investigation. Our pathway analysis revealed significant enrichment of these genes in functions related to cardiac conduction, ion channel activity, plasma membrane adhesion, and axonogenesis. These findings suggest a potential genetic predisposition in these specific functional areas that may contribute to the observed side effect of the vaccine. Nevertheless, further validation through larger-scale studies is imperative to confirm these findings. Given the increasing prominence of mRNA vaccines as a promising strategy for disease prevention and treatment, understanding the genetic factors associated with vaccine-related myocarditis assumes paramount importance. Our study provides valuable insights that significantly advance our understanding in this regard and serve as a valuable foundation for future research endeavours in this field.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
HLA‐B*15:11 is associated with carbamazepine (CBZ)‐induced severe cutaneous adverse drug reactions (SCARs) in Japanese and some Asian populations, but such data remains relatively limited ...in Chinese. Routine HLA‐B*15:02 screening is mandatory before CBZ commencement, however, SCARs related to CBZ were still observed in non‐HLA*B‐15:02 carriers.
Objective
We aimed to find out the prevalence of HLA‐B*15:11 in Chinese patients and its associations with CBZ‐induced SCARs.
Method
We screened 8,328 blood samples collected for HLA allele typing before CBZ commencement during the period of January 2014 to December 2019. In HLA‐B*15:02 negative Chinese patients, HLA‐B*15:11 status were further screened, and the incidence of SCARs in the CBZ group was compared with the control group without CBZ use.
Result
In this cohort, 1416 out of 8328 patients (17%) tested HLA‐B*15:02 positive and were advised to avoid CBZ, while 80 (0.96%) were found to be HLA‐B*15:11 positive. In 6911 (83%) patients who tested HLA‐B*15:02 negative, 70 (1.01%) were HLA‐B*15:11 positive. Five out of 70 (7.14%) patients had SCARs. The incidence of SCARs in HLA‐B*15:11 carriers who received CBZ was significantly higher than those without CBZ (17.4% 4/23 vs. 2.13% 1/47, P = 0.037*). The odds ratio was 9.68 (95% CI 1.02–92.4, P = 0.048*). These included: one Stevens‐Johnson syndrome (SJS), two DRESS, and one MPE after CBZ use, while one developed MPE after phenytoin use in control.
Conclusion
HLA‐B*15:11 is a potential risk factor of CBZ‐induced SCARs in HLA‐B*15:02 negative Chinese patients. Further screening of HLA‐B*15:11 status in those HLA‐B*15:02 negative patients is recommended to avoid undesirable SCARs.
Despite concerns about the negative effects of social distancing and prolonged school closures on children's lifestyle and physical activity (PA) during the COVID-19 pandemic, robust evidence is ...lacking on the impact of the pandemic-related school closures and social distancing on children's wellbeing and daily life. This study aimed to examine changes in the PA levels, sleep patterns, and screen time of school-aged children during the different phases of the COVID-19 outbreak in Hong Kong using a repeated cross-sectional design. School students (grades 1 to 12) were asked to report their daily electronic device usage and to fill in a sleep diary, recording their daily sleep onset and wake-up time. They were equipped with a PA monitor, Actigraph wGT3X-BT, to obtain objective data on their PA levels and sleep patterns. Students were recruited before the pandemic (September 2019-January 2020;
= 577), during school closures (March 2020-April 2020;
= 146), and after schools partially reopened (October 2020-July 2021;
= 227). Our results indicated lower PA levels, longer sleep duration, and longer screen time among participants recruited during school closures than those recruited before the COVID-19 outbreak. Primary school students were found to sleep on average for an extra hour during school closures. The later sleep onset and increased screen time documented during school closures persisted when schools partially reopened. Our findings illustrate the significant impact of social distancing policies during the COVID-19 pandemic on the sleep pattern, screen time, and PA level in school-aged children in Hong Kong. Professionals should urgently reinforce the importance of improving physically activity, good sleep hygiene, and regulated use of electronic devices for parents and school-aged children during this unprecedented time.
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