Children's Hospital

We describe mortality in children living with HIV in Vietnam during the COVID-19 pandemic. We followed 1234 children (median age 11.9 years) at three hospitals during 2020–2023; 260 had COVID-19. Eleven (8.9%) children died, mostly due to poorly controlled HIV. Mortality was higher than in the pre-pandemic period (2016–2019) (0.29 vs 0.09 per 100 person-years; p = 0.033), likely due to decreased access to treatment, testing, and medical intervention during the lockdown, as well as financial difficulties.

Objective Tic disorders are neurodevelopmental conditions that manifest in childhood or adolescence and can significantly impact the quality of life of affected children and their families to varying degrees. Integrated traditional Chinese and Western medicine treatment strategies have demonstrated more pronounced efficacy and better safety profiles. However, there is currently no standardized clinical expert consensus on this approach. To address this, the National Administration of Traditional Chinese Medicine initiated a project, and the China Association of Chinese Medicine assembled a team of authoritative domestic experts to develop this expert consensus, aiming to provide practical and feasible integrated treatment strategies for clinical practice. Methods This consensus identified clinical issues through research, conducted literature reviews, and established evidence based on systematic evaluations. Expert surveys, two rounds of Delphi questionnaires, and expert consensus meetings were conducted to formulate a series of recommendations. Results We established a multidisciplinary consensus development panel. Based on systematic literature reviews, Delphi questionnaires, and consensus meetings, ten clinical issues were identified. Ultimately, a series of recommendations were developed, considering the balance of benefits and risks, the certainty of evidence, clinical feasibility, accessibility, and clinical acceptability. Conclusions These recommendations comprehensively address key issues in the field of integrated traditional Chinese and Western medicine treatment, including indications for the use of Chinese or Western medicine alone or in combination, specific treatment protocols, methods for dose reduction and discontinuation, evaluation intervals, and the management of adverse reactions.

The aim of this study was to perform a comparative analysis of robot-assisted versus laparoscopic Ladd's procedure on peri- and postoperative outcomes. All Ladd’s procedures performed on patients with congenital intestinal malrotation between January 2020 and December 2023 were identified. Peri- and postoperative data were collected and compared between robot-assisted and laparoscopic groups. Fifty-seven robot-assisted and 38 laparoscopic Ladd’s procedure cases were identified and compared for outcomes. No robotic cases were converted to open procedure, while four laparoscopic cases were converted to open procedure ( p = 0.048). Although robotic cases suffered higher hospitalization costs ( p < 0.001), the postoperative complication rate was lower for the robotic group compared to the laparoscopic group ( p = 0.038). Robot-assisted Ladd's surgery is safe and effective for the treatment of congenital intestinal malrotation in children, reducing the difficulty of surgery, but at increased cost.

Distal radius fractures are the most common upper limb fractures, with volar plating being the preferred surgical approach, particularly for intra-articular and unstable fractures. While complications primarily involve flexor tendon irritation or rupture, extensor tendon injuries associated with volar plating are rare. This report discusses a 23-year-old male who experienced limited active range of motion (ROM) in the thumb and index finger of his right hand 2 years after volar plating for a distal radius fracture. Imaging studies, including radiography and MRI, confirmed satisfactory fracture healing. However, 2 screws were found protruding beyond the dorsal cortex of the distal radius. One screw extended over the Lister's tubercle, and another occupied the fourth compartment of the wrist. MRI also revealed the absence of the extensor indicis proprius (EIP) and extensor pollicis longus (EPL) tendons at the wrist level, suggesting tendon rupture. The plate and screws were removed via a palmar approach, and a 2-stage tendon graft procedure was performed to restore function. At the 1-year follow-up, the patient demonstrated excellent functional recovery, with no deficits in extending the thumb and index finger. This case highlights the risk of delayed multirupture of extensor tendons following volar plating of distal radius fractures, even after prolonged intervals postsurgery. Such complications, though rare, necessitate early recognition and management to prevent long-term functional impairments. Orthopedic and hand surgeons should consider this possibility during follow-ups and take preventive measures, such as ensuring screw lengths do not exceed the dorsal cortex during the initial procedure. By presenting this case, we aim to raise awareness of this potential complication and provide insights into its diagnosis, management, and prevention.

Persistent proteinuria is an independent risk factor for poor prognosis in immunoglobulin A vasculitis nephritis (IgAVN). Recent studies have shown that telitacicept effectively reduces proteinuria levels in patients with IgA nephropathy (IgAN). The treatment has been associated with a significant decrease in galactose-deficient IgA1 (Gd-IgA1) levels. This study aims to elucidate the effectiveness and safety of telitacicept in treating refractory childhood IgAVN. This is a single-center, retrospective observational study of seven children with IgAVN who had previously received glucocorticoids and at least one immunosuppressive therapy but still exhibited proteinuria. Telitacicept was administered subcutaneously once a week. Dosage was 80 mg for individuals weighing < 40 kg and 160 mg for those weighing > 40 kg. The study encompassed seven children, comprising two boys and five girls, with a median age of 15 years. Among the participants, six children (85.7%) exhibited a reduction in proteinuria, ranging from − 23.6 to − 97.5% compared to baseline levels. Conversely, one child (14.3%) did not show any decrease in proteinuria. Throughout the follow-up period, two children (28.6%) achieved complete remission, characterized by proteinuria level below 0.2 g/day/1.73 m2 and negative dipstick test for blood. Additionally, all participants demonstrated a significant decline in urinary red blood cell counts. In terms of medication administration, all patients discontinued the use of steroids and immunosuppressants. Furthermore, there was a reduction in the incidence of hospitalizations. Importantly, no serious adverse reactions were reported. Telitacicept has demonstrated both efficacy and safety in treating children with refractory IgAVN. A higher resolution version of the Graphical abstract is available as Supplementary information

Schistosomal appendicitis (SA) is a rare but serious complication of schistoso-miasis, a parasitic disease affecting over 250 million people worldwide. A recent retrospective study by Wang et al provides important insights into the clinicopath-ological characteristics of SA. The study compared 136 cases of SA to 5418 cases of non-SA over a ten-year period. Key findings include a higher average age of SA patients (61.73 years vs 35.8 years for non-SA), a higher proportion of acute on chronic appendicitis (33.1% vs 16%), and a significantly higher incidence of colorectal cancer (11.7% vs 2.2%). Despite these differences, SA remains a diagnostic challenge due to its nonspecific clinical presentation and lack of specific laboratory findings. The study also highlights the persistent prevalence of SA, accounting for 1.6%-3.4% of all appendicitis cases each year from 2013 to 2023. These findings underscore the need for enhanced awareness, early detection, and prompt treatment of SA in endemic regions. Given the association with colorectal cancer, patients with SA require thorough screening and follow-up. Further research into the pathogenesis and diagnostic markers of SA is warranted. As the global battle against schistosomiasis continues, targeted efforts to diagnose and manage SA can significantly improve patient outcomes.

Eligibility for antiretroviral therapy is no longer based on immune criteria. In a global cohort of 97,453 children, between 2005 and 2021, we observed large declines in CD4 measurement, from 51% to 12% among <5 seconds, and from 74% to 20% among those 5–14 years of age. Lack of CD4 testing may negatively affect clinical care and surveillance of severe immune suppression.

Sodium butyrate (NaB), a histone deacetylase (HDAC) inhibitor derived from dietary sources, demonstrates its potential in improving liver fibrosis in mice. This study explored NaB’s impact on liver fibrosis through histone crotonylation. In vitro, NaB significantly inhibited the growth of TGF-β-stimulated LX2 hepatic stellate cells and reduced the expression of fibrotic markers ACTA2, the encoding gene of αSMA, and COL1A1 proportionally to the dosage. In vivo, NaB treatment of CCl4-induced ICR mice led to notable gains in liver function and a marked suppression in liver fibrosis. NaB inhibited Hdac2 and Hdac3 expression leading to increased H4K8 crotonylation, and modulated key fibrosis-related genes, providing a mechanistic basis for its therapeutic potential. Trichostatin A (TSA) exhibited similar effects to NaB, supporting the importance of HDAC inhibition in modulating these pathways. Overall, NaB’s modulation of HDAC activity and histone crotonylation reveals a novel mechanism underlying its impact on liver fibrosis, highlighting its promise as a treatment for liver disease.

Background: Vitamin D-dependent rickets type 1A (VDDR1A) is a rare autosomal recessive disorder caused by mutations in the CYP27B1 gene, leading to a deficiency in active vitamin D (1,25-dihydroxyvitamin D). This study examines the genotypic and phenotypic characteristics of VDDR1A in Vietnamese children. Patients and Methods: A retrospective analysis was conducted on 19 Vietnamese children diagnosed with VDDR1A. Clinical, radiological, biochemical, and molecular data were collected. Rickets Severity Scores (RSSs), biochemical parameters, and height standard deviation scores (HtSDSs) were used to assess the severity of the condition. Results: The study included 19 children from 17 families (ten males and nine females). The median age of rickets diagnosis was 19.2 months, while with VDDR1A, the median time of diagnosis was 7.5 months. Common symptoms among the children included thickened wrists and ankles (19/19), genu varum or genu valgum (18/19), failure to thrive (18/19), rachitic rosary (12/19), and delayed walking (11/19). The radiographic features showed that all children had cupping, splaying, and fraying, twelve children had rachitic rosary, and six exhibited pseudofractures. The biochemical findings showed severe hypocalcemia, normal or mildly low serum phosphate, elevated alkaline phosphatase and parathyroid hormone levels, and normal serum 25-hydroxyvitamin D levels. Genetic analysis identified biallelic CYP27B1 variants, including one known pathogenic frameshift mutation, c.1319_1325dup p.(Phe443Profs*24), one novel likely pathogenic missense variant, c.616C>T p.(Arg206Cys), and one novel pathogenic frameshift mutation, c.96_97del p.(Ala33Thrfs*299). The c.1319_1325dup p.(Phe443Profs*24) variant was the most common, present in 18 out of 19 children. Conclusions: The children with VDDR1A in this study presented with growth failure and skeletal deformities. Key findings included severe hypocalcemia, elevated alkaline phosphatase and parathyroid hormone levels, normal or elevated 25(OH)D, and high RSSs. Predominant frameshift mutations in CYP27B1, especially c.1319_1325dup, highlighted the importance of early genetic diagnosis for optimal management. Additionally, two novel CYP27B1 variants were identified, expanding the known mutation spectrum of VDDR1A.

Introduction Childhood tuberculous meningitis (TBM) is a devastating disease. The long-standing WHO recommendation for treatment is 2 months of intensive phase with isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E), followed by 10 months of isoniazid and rifampicin. In 2022, WHO released a conditional recommendation that 6 months of intensified antituberculosis therapy (ATT) could be used as an alternative for drug-susceptible TBM. However, this has never been evaluated in a randomised clinical trial. Trials evaluating ATT shortening regimens using high-dose rifampicin and drugs with better central nervous system penetration alongside adjuvant anti-inflammatory therapy are needed to improve outcomes. Methods and analysis The S hortened Intensive Therapy for Children with T u be r culous M e ningitis (SURE) trial is a phase 3, randomised, partially blinded, factorial trial being conducted in Asia (India and Vietnam) and Africa (Uganda, Zambia and Zimbabwe). It is coordinated by the Medical Research Council Clinical Trial Unit at University College London (MRCCTU at UCL). 400 children (aged 29 days to <18 years) with clinically diagnosed TBM will be randomised, using a factorial design, to either a 24-week intensified regimen (isoniazid (20 mg/kg), rifampicin (30 mg/kg), pyrazinamide (40 mg/kg) and levofloxacin (20 mg/kg)) or the standard 48-week ATT regimen and 8 weeks of high-dose aspirin or placebo. The primary outcome for the first randomisation is all-cause mortality, and for the second randomisation is the paediatric modified Rankin Scale (mRS), both at 48 weeks. Nested substudies include pharmacokinetics, pharmacogenetics, pathophysiology, diagnostics and prognostic biomarkers, in-depth neurodevelopmental outcomes, MRI and health economics. Ethics and dissemination Local ethics committees at all participating study sites and respective regulators approved the SURE protocol. Ethics approval was also obtained from UCL, UK (14935/001). Informed consent from parents/carers and assent from age-appropriate children are required for all participants. Results will be published in international peer-reviewed journals, and appropriate media will be used to summarise results for patients and their families and policymakers. Trial registration ISRCTN40829906 (registered 13 November 2018).

Background Hutchinson–Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by accelerated aging, impaired growth, disrupted lipid metabolism, and reduced lifespan. Methods Prior research has primarily focused on cardiovascular manifestations, our research sheds light on multiple organs that underwent significant age-related changes validated by tissue cross-sections H&E, Masson's trichrome, and β-galactosidase staining. Results Among these pathologies tissues, the lung was severely affected and substantiated by clinical data of pulmonary anomalies from our HGPS patients. Biochemical and histological analyses of lung tissue from the HGPS mouse model revealed elevated Progerin expression, abnormal NAD metabolism, cellular senescence markers (higher level of p16 and p27, lower level of ki67), and various age-related morphology changes, including fibrosis, inflammation, and thickening of alveolar walls. Transcriptomic analyses of lung tissue indicated that down-regulated genes ( Thy1 , Tnc , Cspg4 , Ccr1 ) were associated with extracellular space, immune response, calcium signaling pathway, osteoclast differentiation, and lipid binding pathway. Conclusions This study unveiled the previously overlooked organs involved in HGPS pathogenesis and suggested a specific emphasis on the lung. Our findings suggest that pulmonary abnormalities may contribute to disease progression, warranting further investigation into their role in HGPS monitoring and management. Graphical abstract

Williams–Beuren syndrome (WBS, OMIM-no.194050) is a rare congenital genetic disorder primarily marked by developmental delays and cardiovascular anomalies, with potential involvement of metabolic dysregulation. Despite this, the metabolic features of WBS have not been extensively studied. Thus, our objective was to examine the serum metabolome profile in children with WBS, elucidating metabolic changes and associated pathways in the disorder. We recruited 25 children with WBS (mean age 5.0 ± 2.6 years, 40% female) from the Children’s Hospital affiliated to Zhejiang University between 2020 and 2023. An age and sex matched healthy control group (N = 25) were recruited from the Health Management Center in the same hospital. Clinical information of WBS were extracted from the medical records. Blood samples were obtained for untargeted metabolomics analysis using UPLC-MS/MS. The metabolomic profiles of WBS patients were compared to those of healthy controls to identify metabolites with differential abundance. Enrichment analysis was conducted to identify potentially impacted KEGG pathways. Associations between metabolites and phenotypes were evaluated. Children with WBS exhibited a unique metabolic profile compared to healthy controls, as evidenced by the identification of 465 untargeted metabolites in serum. Of these metabolites, 169 showed differential abundance in WBS children. The top enriched KEGG pathways in WBS children included nicotine addiction, cholesterol metabolism, arginine biosynthesis, retrograde endocannabinoid signaling. Additionally, there were indications of potential metabolic alterations in the l-tryptophan pathway, with a shift from serotonin to l-kynurenine, as well as disruptions in bile acid metabolism. Metabolome data in children with WBS showed neurological and amino acid metabolism changes, indicating multisystem involvement and developmental delay. This data can help monitor and manage the disease, but further studies are needed to understand the underlying mechanisms and consequences.

Background We aimed to determine the incidence of early Fontan failure (EFF) in a contemporary series of patients from Vietnam and identify risk factors for EFF. Methods A total of 145 consecutive patients underwent the Fontan procedure at E hospital in Vietnam from August 2012 through December 2019. We analyzed predictive factors for EFF based on clinical evaluation, literature review, and our institutional database. The primary outcome assessed was EFF. Results The incidence of EFF was 9.66%. In a univariate analysis of preoperative data, the anatomic diagnosis of unbalanced atrioventricular (AV) septal defect, situs inversus, AV valve regurgitation, large aortopulmonary circulation on Doppler echocardiogram, elevated pulmonary artery pressure (PAP), and elevated pulmonary vascular resistance (PVR) were significantly associated with EFF. Four intraoperative risk factors influencing EFF included pulmonary artery reconstruction, AV valve repair, bleeding, and elevated PAP. Postoperative edema was also significantly associated with EFF. A total of 22 potential independent variables were put into a model with multivariate logistic regression analysis. A final reduced model following utilizing a stepwise backward selection strategy indicated preoperative elevated PAP (odds ratio [OR]: 1.84, 95% CI: 1.12-3.00, P = .016), AV valve repair at Fontan (OR: 65.85, 95%CI: 1.95-2228.14, P = .020), and postoperative elevated PAP (OR: 1.66, 95%CI: 1.19-2.33, P = .004) were independent predictors for EFF. Conclusion Early Fontan failure was relatively high in our case series and was associated with a significant mortality rate. Patients with single ventricle physiology having preoperative elevated PAP, intraoperative AV valve repair, and postoperative elevated PAP were identified as independent risk factors to predict EFF. Particularly, in the context of a developing country with limited health care resources, a comprehensive management strategy that targets the variable predictors for EFF should be incorporated with previously known risk factors to avoid EFF.

Introduction The pathognomonic feature of dengue shock syndrome (DSS) is a transient capillary leak syndrome resulting in profound intravascular volume depletion. WHO management guidelines recommend particular parenteral fluid regimens during the critical leakage phase, including synthetic colloid solutions in certain circumstances. We set out to describe the actual fluid management strategies employed in different settings and to investigate relationships with clinical outcomes. Methods We performed a retrospective review of paediatric DSS cases managed at seven hospitals across Malaysia, Myanmar and Vietnam. We explored the effects of both initial resuscitation (crystalloid alone or mixed crystalloid/colloid in the first 2 hours) and general management: group 1 (conservative-colloid, crystalloid only), group 2 (intermediate-colloid, colloid for 1–4 hours) or group 3 (liberal-colloid, continuous colloid for more than 4 hours) categorised according to the fluid given over the first 6 hours in clinically stable patients. We incorporated an inverse probability weighting score to adjust for potential differences in baseline severity. Results Among all 691 patients, respiratory compromise (HR 2.08, p=0.022), requirement for nasal continuous positive airway pressure (NCPAP)/ventilation (OR 2.34, p<0.045) and days in hospital after DSS onset (risk ratio, RR 1.33, p=0.032) were significantly worse for mixed crystalloid/colloid versus crystalloid-only initial resuscitation regimens, after adjusting for baseline severity. Among the 547/691 children who stabilised within 2 hours, although a liberal-colloid general management strategy (group 3) was associated with a reduction in recurrent shock episodes (RR 0.13, p=0.043) when compared with a conservative-colloid strategy (group 1), the risks for respiratory compromise (OR 8.84, p<0.001) and requirement for NCPAP/ventilation (OR 8.16, p<0.001) were markedly increased. Additionally, the respective costs for group 3 vs group 1 were significantly higher. Conclusions The study highlights the potential benefits and risks of using colloid solutions in children with DSS. Formal randomised trials could help determine the most effective and safe parenteral fluid regimens for paediatric DSS. In the meantime, prolonged use of colloid solutions may be inappropriate, especially in settings without access to respiratory support.

This study aimed to investigate the clinical characteristics according to Tessier classification and evaluate the surgical outcomes in patients with rare craniofacial cleft (RCC) primary repair. A retrospective study on 30 patients with RCC was conducted at the Department of Craniofacial and Plastic Surgery of the Vietnam National Hospital of Pediatrics. Rare craniofacial cleft was recorded according to Tessier’s classification and was analyzed for gender, affected side, clinical characteristics, and associated abnormalities. Primary surgical correction was based on the concept of aesthetic units with multiple Z-plasty. Preoperative deformities and postoperative outcomes were evaluated with anthropometric measurements using the Versnel scoring system. The most common type was Tessier 7 cleft (T7), followed by T0. There was no difference between the frequency of males and females. Patients with unilateral cleft accounted for a larger proportion than bilateral cleft (76.5% versus 23.5%; P = 0.029 <0.05). The median and paramedian cleft groups (T0, T1, T30) affected orbit 22.2%—nose 77.8%—mouth 44.4%. The oblique clefts (T3, T4, T5, T11) affected orbit 100%—nose 50%—mouth 50%. The transverse cleft group (T6, T7, T8) affected mouth 94.1%—ear 29.4%. Rare craniofacial cleft may present alone or in a syndrome (Treacher Collin, Goldenhar, Hemifacial atrophy), or in combination with other abnormalities. Repairing RCC with aesthetic units with multiple Z-plasty has improved facial balance and restored key landmarks with acceptable scar position. The Versnel scoring system can serve as an objective instrument to measure the surgical outcomes of RCC repair and can be used to evaluate the influence of growth.

Hypopituitarism is a condition characterized by the deficiency of several hormones produced by the pituitary gland. Genetic factors play an important role. Variants in the POU1F1 gene are associated with combined pituitary hormone deficiency 1 (CPHD1), which manifests as deficiencies in growth hormone (GH), thyroid-stimulating hormone (TSH), and prolactin (PRL). This study aimed to analyze the phenotype, genotype, treatment, and outcomes of Vietnamese patients with deficiency. Six patients from five unrelated families, initially diagnosed with hypopituitarism, were enrolled in this study. Data on physical characteristics, biochemical tests, treatment, outcomes, and follow-up were collected. Exome sequencing and Sanger sequencing were conducted to identify disease-causing variants in five probands and their families. All six patients exhibited anterior pituitary hypoplasia on brain magnetic resonance imaging and presented with TSH, GH, and PRL deficiencies. Exome sequencing identified three variants in the POU1F1 gene: c.428G>A p.(Arg143Gln), c.557T>G p.(Leu186Arg), and c.811C>T p.(Arg271Trp). The c.811C>T p.(Arg271Trp) variant was found in three patients, while c.557T>G p.(Leu186Arg) is a novel variant. Based on the ACMG classification, these variants were categorized as likely pathogenic or pathogenic variants. All patients were definitively diagnosed with CPHD1 caused by POU1F1 variants. All patients received levothyroxine and recombinant human growth hormone (rhGH) replacement therapy, leading to considerable growth. During the first year of treatment, all patients showed excellent growth response, with height increases ranging from 11 to 24 cm. After three years of treatment, two patients achieved normal height. One of the six patients developed scoliosis during treatment, which resolved after a one-year pause in rhGH therapy. Upon resuming treatment, no recurrence of scoliosis was observed. Our findings reveal the importance of early hormone testing and genetic analysis in improving the care and outcomes for patients with combined pituitary hormone deficiency.