Acute lymphoblastic leukemia (ALL) is the most common malignancy among children. The trial Chinese Children Leukemia Group (CCLG)‐ALL 2008 was a prospective clinical trial designed to improve ...treatment outcome of childhood ALL through the first nation‐wide collaborative study in China. Totally 2231 patients were recruited from ten tertiary hospitals in eight cities. The patients were stratified according to clinical‐biological characteristics and early treatment response. Standard risk (SR) and intermediate risk (IR) groups were treated with a modified BFM based protocol, and there was 25%‐50% dose reduction during intensification phases in the SR group. Patients in high risk (HR) group received a more intensive maintenance treatment. Minimal residual disease (MRD) monitoring with treatment adjustment was performed in two hospitals (the MRD group). Complete remission (CR) was achieved in 2100 patients (94.1%). At five years, the estimate for overall survival (OS) and event‐free survival (EFS) of the whole group was 85.3% and 79.9%, respectively. The cumulative incidence of relapse (CIR) was 15.3% at five years. The OS, EFS and CIR for the SR group were 91.5%, 87.9%, and 9.7%, respectively. The outcome of the MRD group is better than the non‐MRD group (5y‐EFS: 82.4% vs 78.3%, P = .038; 5y‐CIR: 10.7% vs 18.0%, P < .001). Our results demonstrated that the large‐scale multicenter trial for pediatric ALL was feasible in China. Dose reduction in the SR group could achieve high EFS. MRD‐based risk stratification might improve the treatment outcome for childhood ALL.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Multinational studies have reported monogenic etiologies in 25%–30% of children with steroid‐resistant nephrotic syndrome. Such large studies are lacking in Asia. We established Deciphering ...Diversities: Renal Asian Genetics Network (DRAGoN) and aimed to describe the genetic and clinical spectrums in Asians. We prospectively studied a cohort of 183 probands with suspected genetic glomerulopathies from South and Southeast Asia, of whom 17% had positive family history. Using multi‐gene panel sequencing, we detected pathogenic variants in 26 (14%) probands, of whom one‐third had COL4A4 or COL4A5 variants (n = 9, 5%). Of those with COL4A5 defects, only 25% had features suggestive of Alport syndrome. Besides traditional predictors for genetic disease (positive family history and extrarenal malformations), we identified novel predictors, namely older age (6.2 vs. 2.4 years; p = 0.001), hematuria (OR 5.6; 95% CI 2.1–14.8; p < 0.001), and proteinuria in the absence of nephrotic syndrome (OR 4.6; 95% CI 1.8–11.8; p = 0.001) at first manifestation. Among patients who first presented with proteinuria without nephrotic syndrome, the genetic diagnostic rates were >60% when a second risk factor (positive family history or extrarenal manifestation) co‐existed. The genetic spectrum of glomerulopathies appears different in Asia. Collagen IV genes may be included in sequencing panels even when suggestive clinical features are absent.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
OBJECTIVE:To investigate the involvement of human leukocyte antigen (HLA) loci in aromatic antiepileptic drug–induced cutaneous adverse reactions.
METHODS:A case-control study was performed to detect ...HLA loci involved in aromatic antiepileptic drug–induced Stevens-Johnson syndrome in a southern Han Chinese population. Between January 1, 2006, and December 31, 2015, 91 cases of Stevens-Johnson syndrome induced by aromatic antiepileptic drugs and 322 matched drug-tolerant controls were enrolled from 8 centers. Important genotypes were replicated in cases with maculopapular eruption and in the meta-analyses of data from other populations. Sequence-based typing determined the HLA-A, HLA-B, HLA-C, and HLA-DRB1 genotypes.
RESULTS:HLA-B*15:02 was confirmed as strongly associated with carbamazepine-induced Stevens-Johnson syndrome (p = 5.63 × 10). In addition, HLA-A*24:02 was associated significantly with Stevens-Johnson syndrome induced by the aromatic antiepileptic drugs as a group (p = 1.02 × 10) and by individual drugs (carbamazepine p = 0.015, lamotrigine p = 0.005, phenytoin p = 0.027). Logistic regression analysis revealed a multiplicative interaction between HLA-B*15:02 and HLA-A*24:02. Positivity for HLA-A*24:02 and/or HLA-B*15:02 showed a sensitivity of 72.5% and a specificity of 69.0%. The presence of HLA-A*24:02 in cases with maculopapular exanthema was also significantly higher than in controls (p = 0.023). Meta-analysis of data from Japan, Korea, Malaysia, Mexico, Norway, and China revealed a similar association.
CONCLUSIONS:HLA-A*24:02 is a common genetic risk factor for cutaneous adverse reactions induced by aromatic antiepileptic drugs in the southern Han Chinese and possibly other ethnic populations. Pretreatment screening is recommended for people in southern China.
Coronavirus disease 2019 (COVID-19) has impacted the provision of health services in all specialties. We aim to study the impact of COVID-19 on the utilization of pediatric hospital services ...including emergency department (ED) attendances, hospitalizations, diagnostic categories and resource utilization in Singapore.
We performed a retrospective review of ED attendances and hospital admissions among children < 18 years old from January 1st to August 8th 2020 in a major pediatric hospital in Singapore. Data were analyzed in the following time periods: Pre-lockdown (divided by the change in Disease Outbreak Response System Condition (DORSCON) level), during-lockdown and post-lockdown. We presented the data using proportions and percentage change in mean counts per day with the corresponding 95% confidence intervals (CIs).
We attended to 58,367 children with a mean age of 5.1 years (standard deviation, SD 4.6). The mean ED attendance decreased by 331 children/day during lockdown compared to baseline (p < 0.001), attributed largely to a drop in respiratory (% change - 87.9, 95% CI - 89.3 to - 86.3, p < 0.001) and gastrointestinal infections (% change - 72.4, 95%CI - 75.9 to - 68.4, p < 0.001). Trauma-related diagnoses decreased at a slower rate across the same periods (% change - 40.0, 95%CI - 44.3 to - 35.3, p < 0.001). We saw 226 children with child abuse, with a greater proportion of total attendance seen post-lockdown (79, 0.6%) compared to baseline (36, 0.2%) (p < 0.001). In terms of ED resource utilization, there was a decrease in the overall mean number of procedures performed per day during the lockdown compared to baseline, driven largely by a reduction in blood investigations (% change - 73.9, 95%CI - 75.9 to - 71.7, p < 0.001).
We highlighted a significant decrease in infection-related presentations likely attributed to the lockdown and showed that the relative proportion of trauma-related attendances increased. By describing the impact of COVID-19 on health services, we report important trends that may provide guidance when planning resources for future pandemics.
Abstract
Adenine phosphoribosyl transferase (APRT) deficiency is an autosomal recessive disorder and a rare cause of urolithiasis due to mutations in
APRT
(OMIM #102600). APRT deficiency results in ...increased urinary excretion of 2,8‐dihydroxyadenine (DHA) which can cause urolithiasis and kidney failure. However, with prompt diagnosis, patients with APRT deficiency can be treated with xanthine oxidoreductase inhibitors which decrease urinary DHA excretion and improve outcomes. We report a pair of siblings, an 11‐year‐old brother and his 14‐year‐old sister with compound heterozygous variants c.270del (p.Lys91Serfs*46) and c.484_486del (p.Leu162del) in
APRT
with variable clinical presentation of APRT deficiency. The brother presented at 17 months of age with urolithiasis and severe acute kidney injury. His elder sister remained well and asymptomatic with normal kidney function and did not develop renal calculi. Brownish disk or sphere‐like crystals with both concentric and radial markings were reported on urine microscopy in the sister on screening. The sister's diagnosis was confirmed with further laboratory evidence of absent red cell lysate APRT activity with corresponding elevated levels of urinary DHA. In conclusion, we identified a novel mutation in the
APRT
gene in a pair of siblings with greater phenotypic severity in the male.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Introduction
Posterior urethral valve (PUV) is the most common congenital cause of bladder outflow obstruction in male infants. Despite timely treatment, renal damage can still occur in the long‐term ...leading to chronic kidney disease (CKD).
Methods
A retrospective review of all PUV patients in a single tertiary institution between April 1998 and July 2019 was conducted to analyze their presentations, management and outcomes. Long‐term renal function, radiologic scans and somatic growth were evaluated.
Results
A total of 16 patients were included in this study. Two patients who defaulted all follow‐ups were excluded. Seven patients (43.7%) presented in the antenatal period; four patients (25%) presented in the neonatal period and five patients (31.3%) presented in the post‐neonatal period. Primary transurethral fulguration of valves was done in 13 patients, while three had vesicostomies as the primary procedure. Three patients had associated anterior urethral valves (AUV), which were treated endoscopically. Nine boys had additional procedures for diversion and undiversion, VUR, non‐functioning kidney and clean intermittent catheterization. Ten patients had urodynamic studies performed, of which eight patients received anticholinergic therapy. Eleven patients had DMSA scans, of which three patients had a normal study and eight patients showed unilateral reduced function. Four patients were diagnosed with CKD on long‐term follow‐up duration over 5 years. All patients were shown to have good somatic growth.
Conclusion
Patients with PUV can suffer from complications despite primary treatment. In our small cohort, a quarter of our patients developed CKD on follow‐up. Thus, patients need long‐term follow‐up to optimize bladder and renal function.
Posterior urethral valve (PUV) is the most common congenital cause of bladder outflow obstruction in male infants. Despite treatment, renal damage can still occur in the long term. We reviewed the modes of presentation, management and outcomes of male infants presenting with PUV to a single institution in Singapore.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Edible bird’s nests (EBNs) are vulnerable to adulteration due to their huge demand for traditional medicine and high market price. Presently, there are pressing needs to explore field-deployable ...rapid screening techniques to detect adulteration of EBNs. The objective of this study is to explore the feasibility of using a handheld near-infrared (VIS/SW-NIR) spectroscopic device for the determination of EBN authenticity against the benchmark performance of a benchtop mid-infrared (MIR) spectrometer. Forty-nine authentic EBNs from the different states in Malaysia and 13 different adulterants (five types) were obtained and used to simulate the adulteration of EBNs at 1, 5 and 10% adulteration by mass (a total of 15 adulterated samples). The VIS/SW-NIR and MIR spectra collated were subsequently processed, modelled and classified using multi-class discriminant analysis. The VIS/SW-NIR results showed 100% correct classification for the collagen and nutrient agar classes in authenticity classification, while for the other classes, the lowest correct classification rate was 96.3%. For MIR analysis, only the karaya gum class had 100% correct classification whilst for the other four classes, the lowest rate of correct classification was at 94.4%. In conclusion, the combination of spectroscopic analysis with chemometrics can be a powerful screening tool to detect EBN adulteration.
ObjectivesTo assess the association of clinical factors and investigation results (blood and urine) with imaging abnormalities (ultrasound of the kidneys, ureters and bladder; dimercaptosuccinic acid ...scan; and/or micturating cystourethrogram) and recurrent urinary tract infections (UTIs) in infants ≤3 months old presenting with their first febrile UTI.MethodsWe conducted a retrospective cohort study of infants ≤3 months old with first febrile UTI admitted from 2010 to 2016. Multivariable logistic regression model was used to analyse the association of imaging abnormalities and recurrent UTI with covariates selected a priori: age at presentation, maximum temperature, duration of illness at presentation, interval between start of antibiotics and fever resolution, C-reactive protein, total white cell count on the full blood count, bacteraemia, white cell count on the urinalysis and non-Escherichia coli growth in the urine culture (non-E. coli UTI).ResultsThere were 190 infants but 12 did not undergo any imaging. Median age at presentation was 63 days (IQR 41–78). Twenty-four patients had imaging abnormalities. Non-E. coli UTI (adjusted OR (aOR) 5.01, 95% CI 1.65 to 15.24, p=0.004) was independently associated with imaging abnormalities, while bacteraemia (aOR 4.93, 95% CI 1.25 to 19.43, p=0.022) and non-E. coli UTI (aOR 5.06, 95% CI 1.90 to 13.48, p=0.001) were independently associated with recurrent UTI.ConclusionNon-E. coli UTI at the first febrile UTI in infants ≤3 months old may be useful in predicting imaging abnormalities while bacteraemia and non-E. coli UTI may be useful to predict recurrent UTI.
Prospective radiographic comparative study.
To compare and understand the load-bearing properties of each functional spinal unit (FSU) using three commonly assumed, physiological, spinal postures, ...namely, the flexed (slump sitting), erect (standing) and extended (backward bending) postures.
Sagittal spinal alignment is posture-dependent and influences the load-bearing properties of the spine. The routine placement of intervertebral cages "as anterior as possible" to correct deformity may compromise the load-bearing capabilities of the spine, leading to complications.
We recruited young patients with nonspecific low back pain for <3 months, who were otherwise healthy. Each patient had EOS images taken in the flexed, erect and extended positions, in random order, as well as magnetic resonance imaging to assess for disk degeneration. Angular and disk height measurements were performed and compared in all three postures using paired t-tests. Changes in disk height relative to the erect posture were caclulated to determine the alignment-specific load-bearing area of each FSU.
Eighty-three patients (415 lumbar intervertebral disks) were studied. Significant alignment changes were found between all three postures at L1/2, and only between erect and flexion at the other FSUs. Disk height measurements showed that the neutral axis of the spine, marked by zones where disk heights did not change, varied between postures and was level specific. The load-bearing areas were also found to be more anterior in flexion and more posterior in extension, with the erect spine resembling the extended spine to a greater extent.
Load-bearing areas of the lumbar spine are sagittal alignment-specific and level-specific. This may imply that, depending on the surgical realignment strategy, attention should be paid not just to placing an intervertebral cage "as anterior as possible" for generating lordosis, but also on optimizing load-bearing in the lumbar spine.
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