Clinical characteristics of unvaccinated or incompletely vaccinated children with neurological manifestations due to SARS-CoV-2 Omicron infection.

Omicron generally causes milder disease than previous strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially in fully vaccinated individuals. However, incompletely vaccinated children may develop Omicron-related complications such as those affecting the central nervous system. To characterize the spectrum of clinical manifestations of neuro-COVID and to identify potential biomarkers associated with clinical outcomes, we recruited 15 children hospitalized for Omicron-related neurological manifestations in three hospitals in Hong Kong (9 boys and 6 girls aged 1-13 years). All were unvaccinated or incompletely vaccinated. Fourteen (93.3%) were admitted for convulsion, including benign febrile seizure (n = 7), complex febrile seizure (n = 2), seizure with fever (n = 3), and recurrent breakthrough seizure (n = 2), and the remaining nonconvulsive patient developed encephalopathic state with impaired consciousness. None of the seven children with benign febrile seizure and six of eight children with other neurological manifestations had residual deficits at 9-month follow-up. SARS-CoV-2 RNA was undetectable in the cerebrospinal fluid (CSF) specimens of seven patients who underwent lumbar puncture. Spike-and-wave/sharp waves affecting the frontal lobes were detected in four of seven (57.1%) patients who underwent electroencephalogram. Children with Omicron-related neurological manifestations had significantly higher blood levels of IL-6 (p < 0.001) and CHI3L1 (p = 0.022) than healthy controls, and higher CSF levels of IL-6 (p = 0.002) than children with non-COVID-19-related febrile illnesses. Higher CSF-to-blood ratios of IL-8 and CHI3L1 were associated with longer length of stay, whereas higher ratios of IL-6 and IL-8 were associated with higher blood tau level. The role of CSF:blood ratio of IL-6, IL-8, and CHI3L1 as prognostic markers for neuro-COVID should be further evaluated.

Intrathecal Baclofen Pump Infection With Meningitis: Effective Treatment by Radical Debridement and Intrareservoir Baclofen-Vancomycin Co-Infusion.

OBJECTIVES: Intrathecal baclofen pump associated central nervous system (CNS) infection and meningitis is a rare but serious complication and may have dire consequences. Due to bacterial biofilm formation, the optimal treatment strategy is usually for removal of the pump, followed by systemic antibiotics for treatment of local and CNS infection. We describe this case of a patient with recurrent Staphylococcus aureus pump site empyema and meningitis leading to status dystonicus, who was successfully managed with radical debridement and intrareservoir baclofen-vancomycin co-infusion. MATERIALS AND METHODS: We retrospectively report a case of infected intrathecal baclofen pump with meningitis and provide a full review of literature. CONCLUSIONS: To the best of our knowledge, this is the first reported case of intrathecal baclofen (ITB)-associated pump site empyema and meningitis successfully treated with this technique. In selected cases where surgical explantation is deemed not feasible, this method can provide clinicians with an additional option for pump salvage and retention, while eradicating CNS infection and maintaining optimal control of spasticity and dystonia.

Humoral and Cellular Immunogenicity of 3 Doses of BNT162b2 in Children With Kidney Diseases.

Introduction: Patients with severe kidney diseases are at risk of complications from COVID-19; however, little is known about the effectiveness of COVID-19 vaccines in children and adolescents with kidney diseases. Methods: We investigated the immunogenicity and safety of an accelerated 3-dose primary series of COVID-19 vaccination among 59 pediatric patients with chronic kidney disease (CKD) (mean age 12.9 years; 30 male) with or without immunosuppression, dialysis, or kidney transplant. Dosage was 0.1 ml BNT162b2 to those aged 5 to 11 years, and 0.3 ml BNT162b2 to those aged 11 to 18 years. Results: Three doses of either vaccine type elicited significant antibody responses that included spike receptor-binding domain (S-RBD) IgG (90.5%-93.8% seropositive) and surrogate virus neutralization (geometric mean sVNT% level, 78.6%-79.3%). There were notable T cell responses. Weaker neutralization responses were observed among those on immunosuppression, especially those receiving higher number of immunosuppressants or on mycophenolate mofetil. Neutralization was reduced against Omicron BA.1 compared to wild type (WT, i.e., ancestral) (post-dose 3 sVNT% level; 82.7% vs. 27.4%; P < 0.0001). However, the T cell response against Omicron BA.1 was preserved, which likely confers protection against severe COVID-19. Infected patients exhibited hybrid immunity after vaccination, as evidenced by the higher Omicron BA.1 neutralization response among these infected patients who received 2 doses compared with those who were uninfected. Generally mild or moderate adverse reactions following vaccines were reported. Conclusion: An accelerated 3-dose primary series with BNT162b2 is immunogenic and safe in young children and adolescents with kidney diseases.

Common association of haemolytic uraemic syndrome with invasive Streptococcus pneumoniae infection in five Chinese paediatric patients.

Haemolytic uraemic syndrome is an important cause of acute renal impairment in childhood. We review the incidence, and clinical and laboratory features of haemolytic uraemic syndrome in a Chinese population. Five patients were identified from 2006 to 2008. All patients were young children with associated invasive Streptococcus pneumoniae pulmonary infection. Serotypes 3, 14, and 19A were confirmed in four patients. The classical post-diarrhoeal form associated with Escherichia coli (O157:H7) infection was not seen. One patient died of acute respiratory failure. Streptococcus pneumoniae infection, as an associated condition in haemolytic uraemic syndrome, is important and relatively common in Chinese patients, especially among children. The acute clinical picture is similar to that reported in the western literature, except for an uncommon association with meningitis. The medium-term renal outcome of the Chinese population appears to be more favourable than the Caucasians. Widespread vaccination against Streptococcus pneumoniae may have resulted in changes in bacterial epidemiology and clinicians should be continuously aware of this severe disease. The use of washed blood components for transfusion in the acute stage requires further study.

Evaluating different imaging strategies in children after first febrile urinary tract infection.

We conducted a retrospective multicenter review to estimate the prevalence of urological abnormalities in Chinese children with first febrile urinary tract infection (UTI) and to evaluate the selective imaging strategy recommended by the NICE guideline for detecting underlying abnormalities. Atypical UTI was defined as in the NICE UTI guideline. Overall, 576 boys and 244 girls aged below 24 months were reviewed. All underwent ultrasound (US) and micturating cystourethrogram (MCUG) and 612 underwent DMSA scans. US was abnormal in 73 (8.9%) and vesicoureteral reflux was shown in 195 patients (23.8%). A total of 126 patients were considered to have remediable urological abnormalities requiring additional surgical or medical interventions. The NICE guideline yielded excellent negative predictive values (NPV) of 100-94.4% in girls but 91% in boys. If all boys underwent US and DMSA and only those with atypical UTI or abnormal US or DMSA proceeded to MCUG, then the NPV increased to 95.2% and 97.4% for boys aged below and above 6 months, respectively. These revised strategies would substantially save invasive studies-DMSA and MCUG in 27 and 74% of girls aged below and above 6 months, respectively, or MCUG in 23 and 59% of boys aged below and above 6 months, respectively.

Membranous lupus nephritis in Chinese children--a case series and review of the literature.

We retrospectively reviewed the cases of 13 lupus nephritis children with pure membranous glomerulonephritis (MGN; Group A) and ten children with mixed proliferative and membranous nephritis (Group B). The children were identified through a territory-wide survey of patients between 1990 and 2003. All were ethnic Chinese. Age at diagnosis ranged from 3.7 to 18.6 years (Group A) and from 9.6 to 22.1 years (Group B). Female-to-male ratios were 12:1 (Group A) and 9:1 (Group B). Group A patients were more often nephrotic than Group B patients (11/13 vs. 5/10, p = 0.17). The glomerular filtration rate (GFR) at presentation was normal in all but two patients (one from each group). For induction, Group B patients consistently received prednisolone and cyclophosphamide; in contrast, the cytotoxic regimens in Group A patients varied from cyclophosphamide (five patients), mycophenolate mofetil (two patients), azathiorpine plus cyclosporine (one patient), and azathioprine alone (one patient). After a median follow-up of 7.6-7.8 years, one Group A patient had died of fulminant lupus. One survivor in Group B had a GFR < 90 ml/min per 1.73 m(2). Proteinuria persisted in five Group A patients and two Group B patients. In conclusion, Group B patients had good prognosis in terms of survival and proteinuria control. The only death occurred in Group A, and five of the 12 survivors in this group had persistent proteinuria. Further studies are needed to define the best treatment for pure lupus MGN.

Clinicopathologic analysis of renal biopsies after haematopoietic stem cell transplantation.

AIM: The ever-growing number and increasing survival of haematopoietic stem cell transplantation (HSCT) allow better recognition of its associated renal injuries. We aimed to study the clinicopathologic features of renal biopsies after HSCT by reviewing 13 percutaneous renal biopsies in our institute (Queen Mary Hospital). METHODS: A retrospective clinicopathologic study of all renal biopsies archived to the Department of Pathology, Queen Mary Hospital during the period January 1999 to December 2006 was performed. Biopsies from patients with HSCT were selected. Clinical data on presentation and follow up were retrieved from hospital records and physicians. RESULTS: In the 8-year period, a total of 2233 native renal biopsies were archived. Thirteen renal biopsies were selected from 12 patients with HSCT (11 allogeneic, one autologous). All but one patient were male. The age at renal biopsy ranged from 7 to 63 years (median: 32 years). The median interval of renal biopsy after HSCT was 24 months (range 1-134 months). Evidence of graft-versus-host disease was found in nine patients. The most common presentation was significant proteinuria (10 cases) and renal impairment (eight cases). The predominant histological changes were membranous glomerulonephritis (n = 4) and thrombotic microangiopathy (n = 4). One case of focal segmental glomerulosclerosis, IgA nephropathy, minimal change disease, acute tubular necrosis and hypertensive nephrosclerosis were also recorded. Four of our patients died at 0-11 months after renal biopsy. Of the remaining eight patients with a mean follow up of 43.6 months (range, 10-98 months), chronic renal impairment were found in three (37.5%) patients and significant proteinuria also persisted in three. One patient had cytogenetic evidence of relapse of underlying haematological malignancy after HSCT. CONCLUSION: Among the various renal lesions after HSCT, membranous glomerulonephritis and thrombotic microangiopathy were the most common. Mechanisms of renal injury varied from graft-versus-host disease-associated immune complex deposition to non-immune complex injury on endothelial cells, glomerular epithelial cells and tubular epithelium. Pathologists and clinicians should attend to the histological and temporal heterogeneity of renal injury when managing patients after HSCT.

Focal segmental glomerulosclerosis after membranous glomerulonephritis in remission: temporal diversity of glomerulopathy after bone marrow transplantation.

Heavy proteinuria after bone marrow transplantation (BMT) is rare. Pathology shows membranous glomerulonephritis (MGN) in most cases. After BMT, focal segmental glomerulosclerosis (FSGS) after resolution of MGN has not been reported. We describe a 13-year-old boy who had matched unrelated donor allogeneic BMT for relapsed acute lymphoblastic leukemia, complicated by chronic graft-versus-host disease. Nephrotic syndrome developed 1 year after BMT and renal biopsy revealed MGN. Immunosuppressive therapy achieved good clinical remission, and treatment was stopped after 15 months. He developed significant proteinuria 55 months later. The second renal biopsy showed FSGS without changes of MGN. This distinctive disease evolution gives inspiring implications. Complete morphological resolution of graft-versus-host disease-associated MGN, achieved in our case, has not been previously documented. Recurrent significant proteinuria after BMT is not necessarily due to previous renal lesion, and a repeat renal biopsy is indicated. The pathogenesis of MGN and FSGS are different, and different mechanisms of glomerular injury can interplay in a single patient after BMT. This case helps to expand our knowledge of the temporal morphological spectrum of renal lesions associated with BMT.

Biochemical and molecular diagnosis of tyrosinemia type I with two novel FAH mutations in a Hong Kong chinese patient: recommendation for expanded newborn screening in Hong Kong.

OBJECTIVES: Tyrosinemia type I is an autosomal recessive disorder in tyrosine metabolism. In areas without expanded newborn screening, patients present with acute hepatorenal failure in early infancy. Diagnosis can be elusive when clinical presentation is non-specific and biochemical abnormalities are masked by secondary changes. This is the first Hong Kong Chinese report. DESIGN AND METHODS: A two-month-old Chinese male infant with unremarkable antenatal and postnatal history presented with progressive abdominal distension for three days. He suffered from end-stage liver failure, hypoglycemia and hepatic encephalopathy. Diagnostic work-up was complicated starting from rule-out sepsis, intestinal obstruction, volvulus, peritonitis, septic ileus, poisoning to metabolic diseases. Clinical, biochemical and genetic data was described. RESULTS: The patient showed increases in multiple plasma amino acids including tyrosine, phenylalanine and methionine, and hyper-excretions of 4-hydroxyphenyl-acetate, -pyruvate, and -lactate, as well as N-acetyltyrosine which could be seen in liver failure due to both tyrosinemia type I and non-metabolic conditions. Because of the volatile nature, succinylacetone was almost undetectable. The diagnosis was confirmed by genetic analysis of FAH with two novel mutations, viz. NM_000137.2:c.1063-1G>A and NM_000137.2:c.1035_1037del. Living-related liver transplantation was done. However, the patient still suffered many complications after the severe metabolic insult with hypoxic ischemic encephalopathy, cerebral atrophy, global developmental delay and cortical visual impairment. CONCLUSIONS: Because of the lack of expanded newborn screening in Hong Kong, this child unfortunately presented in the most severe form of tyrosinemia type I. Expanded newborn screening can save life and reduce the burden of diagnostic complexity. This illustrates the need for expanded newborn screening in Hong Kong.

Gastric pneumatosis in a premature neonate.

Gastric pneumatosis is extremely rare during infancy. It has been reported in association with necrotizing enterocolitis or congenital abnormalities such as pyloric stenosis. Here, we report a case of gastric pneumatosis in a premature neonate on synchronized nasal intermittent positive pressure ventilation. No pneumatosis was noted in the rest of the bowel or esophagus. There could have been mild damage in the gastric mucosa, either related to the placement of the feeding tube or secondary to the use of indomethacin or both. The condition was further aggravated by noninvasive ventilation. An increase in intragastric pressure resulted in the submucosal dissection of air followed by the development of gastric pneumatosis. Conservative management strategies, including the use of a nasogastric tube for decompression and the withholding of feeding, successfully managed the gastric pneumatosis in our patient. An uneventful recovery was made after conservative management. Prompt recognition and evaluation of this condition were essential for making the diagnosis.

Prevalence and risk factors for hypertension in Hong Kong Chinese adolescents: waist circumference predicts hypertension, exercise decreases risk.

PURPOSE: To determine the prevalence, risk factors for and patterns of hypertension in Chinese adolescents based on a territory-wide school based screening programme in Hong Kong. METHODS: Cross-sectional anthropometric and oscillometric blood pressure (BP) measurements and lifestyle information were obtained as part of a growth survey of students from randomly selected secondary schools in Hong Kong. Those with blood pressure ≥ 95th centile were screened a second or third time. Hypertension is defined as elevated blood pressure on three separate occasions. The independent effects of age, sex, body mass index, high waist circumference (≥ 85th centile), sleep duration, family history of hypertension and frequency of exercise on hypertension were explored by multivariate analysis. RESULTS: Among the 6193 students screened, the prevalence of elevated blood pressure on the first, second and third screens was 9.54%, 2.77% and 1.44% respectively. Hypertension was more likely to be systolic. High waist circumference (≥ 85th centile) was independently associated with a higher risk of hypertension (adjusted OR 2.4), while exercising twice or more per week was protective (adjusted OR 0.28). CONCLUSIONS: The prevalence of hypertension in Hong Kong Chinese adolescents is 1.44%. The current study shows high waist circumference is a predictor of hypertension in adolescents, while increased physical activity is a protective factor. Incorporating waist circumference into screening protocols may increase the sensitivity of cardiovascular risk stratification. Healthcare providers should be strong advocates helping to prevent obesity and promote physical activity in adolescents and children.

Lupus nephritis in Chinese children--a territory-wide cohort study in Hong Kong.

We report a multicenter study of Chinese children in Hong Kong with systemic lupus erythematosus (SLE) nephritis. Children were included if: they fulfilled the ACR criteria, had significant proteinuria or casturia, were Chinese and younger than 19 years and had been diagnosed with SLE between January 1990 and December 2003. Investigators in each center retrieved data on clinical features, biopsy reports, treatment and outcome of these patients. There were 128 patients (eight boys, 120 girls; mean age: 11.9+/-2.8 years). About 50% presented with multisystem illness and 40% with nephritic/nephrotic symptoms. Negative anti-dsDNA antibodies were found in 6% of the patients. Renal biopsy revealed WHO Class II, III, IV and V nephritis in 13 (10%), 22 (17%), 69 (54%) and 13 (10%) patients, respectively. The clinical severity of the nephritis did not accurately predict renal biopsy findings. The follow-up period ranged from 1 to 16.5 years (mean+/-SD: 5.76+/-3.61 years). During the study five patients died (two from lupus flare, one from cardiomyopathy, two from infections). Four patients had endstage renal failure (ESRF) (one died during a lupus flare). All deaths and end-stage renal failure occurred in the Class IV nephritis group. Chronic organ damage was infrequent in the survivors. The actuarial patient survival rates at 5, 10 and 15 years of age were 95.3, 91.8, and 91.8%, respectively. For Class IV nephritis patients, the survival rates without ESRF at 5, 10, and 15 years were 91.5, 82.3 and 76%, respectively. The survival and chronic morbidity rates of the Chinese SLE children in the present study are comparable to those of other published studies.