Gorham-Stout disease: remission with sirolimus therapy.

Gorham-Stout disease (GSD) is a rare, non-hereditary, bone disease characterised by progressive osteolysis as a result of uncontrolled proliferation of endothelial-lined vessels replacing normal bone. We present a baby-girl with the classic radiological features of GSD and compatible clinical and histological findings, who developed progressive disease for over 2 years despite propranolol treatment. Propranolol treatment was stopped and sirolimus monotherapy started which resulted in near-complete resolution after 1 year, with no recurrence after discontinuation of treatment. This case not only illustrates the typical features of GSD on a variety of imaging modalities, but is also the first report showing stark contrast in response between propranolol and sirolimus treatment for GSD, highlighting how targeting lymphatic, rather than solely angiomatous, proliferation at the vascular endothelial growth factor-level may be a future direction.

Deep genomic characterization highlights complexities and prognostic markers of pediatric acute myeloid leukemia.

Pediatric acute myeloid leukemia (AML) is an uncommon but aggressive hematological malignancy. The poor outcome is attributed to inadequate prognostic classification and limited treatment options. A thorough understanding on the genetic basis of pediatric AML is important for the development of effective approaches to improve outcomes. Here, by comprehensively profiling fusion genes as well as mutations and copy number changes of 141 myeloid-related genes in 147 pediatric AML patients with subsequent variant functional characterization, we unveil complex mutational patterns of biological relevance and disease mechanisms including MYC deregulation. Also, our findings highlight TP53 alterations as strong adverse prognostic markers in pediatric AML and suggest the core spindle checkpoint kinase BUB1B as a selective dependency in this aggressive subgroup. Collectively, our present study provides detailed genomic characterization revealing not only complexities and mechanistic insights into pediatric AML but also significant risk stratification and therapeutic strategies to tackle the disease.

Clinical Characteristics and Outcomes of Acute Childhood Encephalopathy in a Tertiary Pediatric Intensive Care Unit.

AIM: Childhood encephalopathy comprises a wide range of etiologies with distinctive distribution in different age groups. We reviewed the pattern of encephalopathy admitted to the pediatric intensive care unit (PICU) of a tertiary children's hospital. METHODS: We reviewed the medical records and reported the etiologies, clinical features, and outcomes of children with encephalopathy. RESULTS: Twenty-four admissions to the PICU between April 2019 and May 2020 were reviewed. The median (interquartile range) age was 10.0 (14.7) years and 62.5% were boys. Confusion (66.7%) was the most common presentation. Adverse effects related to medications (33.3%) and metabolic disease (20.8%) were predominant causes of encephalopathies in our study cohort. Methotrexate was responsible for most of the medication-associated encephalopathy (37.5%), whereas Leigh syndrome, pyruvate dehydrogenase deficiency and Wernicke's encephalopathy accounted for those with metabolic disease. The median Glasgow Coma Scale (GCS) on admission was 12.5 (9.0). Antimicrobials (95.8%) and antiepileptic drugs (60.9%) were the most frequently given treatment. Children aged 2 years or younger were all boys (P = 0.022) and had a higher proportion of primary metabolic disease (P = 0.04). Intoxication or drug reaction only occurred in older children. The mortality was 8.3%, and over half of the survivors had residual neurological disability upon PICU discharge. Primary metabolic disease (P = 0.002), mechanical ventilation (P = 0.019), failure to regain GCS back to baseline level (P = 0.009), and abnormal cognitive function on admission (P = 0.03) were associated with cerebral function impairment on PICU discharge. CONCLUSIONS: Primary metabolic encephalopathy was prevalent in younger children, whereas drug-induced toxic encephalopathy was common among older oncology patients. Survivors have significant neurologic morbidity. Failure to regain baseline GCS was a poor prognostic factor for neurological outcomes.

ABCC4, ITPA, NUDT15, TPMT and their interaction as genetic predictors of 6-mercaptopurine intolerance in chinese patients with acute lymphoblastic leukemia.

Inter-individual variance in 6-mercaptopurine (6-MP) dose intensity is common in patients with acute lymphoblastic leukemia (ALL). We aimed to evaluate the association of common variants of ABCC4, ITPA, NUDT15, and TPMT with 6-MP dose intensity and toxicity in pediatric ALL patients. In this cohort, 13.8% of patients were intolerant to 6-MP with actual dosage less than 50% of scheduled dose. Twenty percent of patients were found to be heterozygous or homozygous mutated with NUDT15. NUDT15 c.415C > T and the genotype-predicted NUDT15 activity were significantly associated with 6-MP intolerance. TPMT*3C variants were not common in this cohort (2.8%). NUDT15 polymorphisms and genotype predicted NUDT15 activity were significantly associated with 6-MP dose intensity and leukopenia episodes. Combination of ABCC4 and ITPA variants (ABCC4 c.912G > T and ITPA c.94C > A) also showed significant positive association with 6-MP intolerance in Chinese children with ALL. Further study on pharmacogenetic screening for ALL patients to avoid 6-MP induced toxicity is recommended.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.1973628.

Continuous Renal Replacement Therapy (CRRT) for Nonrenal Indications among Critically Ill Children with Malignancy.

The role of continuous renal replacement therapy (CRRT) has been expanding beyond support for acute kidney injury (AKI) in recent years. Children with malignancy are particularly at risk of developing conditions that may require CRRT. We reported three children with malignancy who received CRRT for non-AKI indications. Patient 1 was a 17-year-old teenage girl who developed refractory type B lactic acidosis due to relapse of acute lymphoblastic leukemia (ALL). Her peak lactate level was 18 mmol/L, and the lowest pH and bicarbonate level was 7.13 and 6.0 mmol/L, respectively. She received three sessions of high-volume hemodiafiltration to bring down the lactate level. Patient 2 was a 15-year-old male with T-cell ALL who developed cytokine storm requiring mechanical ventilatory and high-dose inotropic support due to necrotizing enterocolitis complicated by pneumoperitoneum and Klebsiella pneumoniae septicemia. He received two sessions of hemoperfusion using a specific filter capable of endotoxin absorption and cytokine removal and was successfully weaned off all inotropes after the treatment. Patient 3 was an 8-year-old boy who received bone marrow transplantation and developed worsening hyperbilirubinemia and deteriorating liver function. He received a session of single-pass albumin dialysis for bilirubin removal prior to liver biopsy. Except for mild electrolyte disturbances, no major CRRT complication was encountered. Our report demonstrated that CRRT is an effective and safe procedure for a wide spectrum of nonrenal conditions among children with oncological diagnoses in the pediatric intensive care unit. However, the optimal dose, regime, timing of initiation, and monitoring target for these indications remain to be determined.

Longitudinal dynamics of gut bacteriome, mycobiome and virome after fecal microbiota transplantation in graft-versus-host disease.

Fecal microbiota transplant (FMT) has emerged as a potential treatment for severe colitis associated with graft-versus-host disease (GvHD) following hematopoietic stem cell transplant. Bacterial engraftment from FMT donor to recipient has been reported, however the fate of fungi and viruses after FMT remains unclear. Here we report longitudinal dynamics of the gut bacteriome, mycobiome and virome in a teenager with GvHD after receiving four doses of FMT at weekly interval. After serial FMTs, the gut bacteriome, mycobiome and virome of the patient differ from compositions before FMT with variable temporal dynamics. Diversity of the gut bacterial community increases after each FMT. Gut fungal community initially shows expansion of several species followed by a decrease in diversity after multiple FMTs. In contrast, gut virome community varies substantially over time with a stable rise in diversity. The bacterium, Corynebacterium jeikeium, and Torque teno viruses, decrease after FMTs in parallel with an increase in the relative abundance of Caudovirales bacteriophages. Collectively, FMT may simultaneously impact on the various components of the gut microbiome with distinct effects.

t(1;22)(p13;q13) Acute Megakaryoblastic Leukemia Complicated by Hepatic Fibrosis: Antifibrosis Therapy?

BACKGROUND: There is no established effective treatment for patients with t(1;22)(p13;q13) acute megakaryoblastic leukemia (AMKL) and hepatic fibrosis. OBSERVATION: Here we report the outcomes of 2 t(1;22)(p13;q13) AMKL patients with hepatic fibrosis. One patient died from liver failure despite the control of leukemia. The other patient was successfully treated with reduced-intensity chemotherapy and antifibrosis therapy with tretinoin and α-tocopheryl acetate, the hepatic fibrosis resolved and leukemia was in remission for 3 years. CONCLUSIONS: Reduced-intensity chemotherapy plus antifibrosis therapy with tretinoin and α-tocopheryl acetate could be a treatment option for these patients with t(1;22)(p13;q13) AMKL and hepatic fibrosis.

Double-unit unrelated cord blood transplantation for thalassemia major: Comparison with HLA-identical sibling bone marrow transplantation.

UCBT recipients with TM are at high risk of EF related to low number of stem cells and prior alloimmunization after multiple blood transfusions. Here, we evaluated the safety and efficacy of double-unit UCBT using TT-containing conditioning regimens in TM. Retrospective analysis of children who underwent double-unit UCBT for TM in the Prince of Wales Hospital between August 2007 and January 2017, and outcome of double-unit UCBT for TM was compared with outcome of HLA-matched sibling BMT. Ten patients, median age 4.2 years, received double-unit UCBT. All patients except one engrafted at a median of 19 days. None of the patients with successful engraftment had grade III or IV aGVHD. Among nine patients with successful engraftment, six of nine patients evaluable after day 100 developed cGVHD. All patients with cGVHD were well controlled after treatment with steroids and/or supportive care and maintained good quality of life. In comparison with patients receiving BMT, those given UCBT had slower platelet recovery, and more cGVHD. With a median follow-up of 272 months after BMT and 84 months after UCBT, the 8-year OS after BMT and UCBT was 92% and 90% (P = .84), whereas 8-year DFS after BMT and UCBT was 87% and 80% (P = .54). UCB could be an acceptable source of stem cells for transplantation of TM patients when HLA-matched family bone marrow donors are NA.

Septicemia after chemotherapy for childhood acute lymphoblastic leukemia in China: A multicenter study CCCG-ALL-2015.

BACKGROUND: Septicemia is an important cause of treatment-related mortality and treatment failure in pediatric acute lymphoblastic leukemia (ALL) in developing countries. A multicenter CCCG-ALL-2015 study was conducted in China and factors associated with septicemia and mortality were studied. METHODS: Patients participated in CCCG-ALL-2015 study from January 2015 to December 2017 were included. Patients with documented septicemia were identified from the Data Center and additional data were collected. RESULTS: A total of 4080 patients were recruited in the study and 527 patients with septicemia were identified (12.9%, 95% CI 11.9%-13.9%). The intermediate risk (IR)/high risk (HR) group had significantly higher incidence of septicemia as compared with low risk (LR) group, 17.1% vs 9.1% (OR 2.07, 95% CI 1.71-2.49, P < .001). Induction phase was the period with majority of septicemia episodes happened, 66.8% in LR and 56.1% in IR/HR groups. Gram-positive bacteria accounted for 54.1%, gram-negative bacteria 44.5%, and fungus 1.4% of positive cultures. Multidrug-resistant organisms were detected in 20.5% of all organisms. The mortality rate after septicemia was 3.4% (95% CI 1.9%-4.9%). Multiple logistic regression identified female gender, comorbid complications, and fungal infection as risk factors associated with mortality. Gram-negative septicemia was associated with higher mortality, 4.9% vs 1.4% (OR 0.28, 95% CI 0.09-0.88, P = .02). There was marked variation in the incidence of septicemia among the 18 centers, from 4.8% to 29.1%. CONCLUSION: Overall the incidence and pattern of septicemia in this multicenter study in China was similar to the reports of western countries. The septicemia-related mortality rate was low. There was marked variation in the incidence of septicemia among the centers.

Excellent outcome of acute lymphoblastic leukaemia with TCF3-PBX1 rearrangement in Hong Kong.

OBJECTIVE: The aim of this study was to review clinical outcomes and prognosis of paediatric patients with acute lymphoblastic leukaemia (ALL) with TCF3-PBX1 rearrangement. PATIENTS: All children in Hong Kong diagnosed with ALL with TCF3-PBX1 rearrangement over the past two decades were included. METHODS: Six hundred and twenty-four newly diagnosed patients with ALL from four consecutive studies were enrolled from 1997 to 2016. Patients carrying TCF3-PBX1 rearrangement and patients at intermediate risk without the gene expression were compared for clinical characteristics, overall survival and event-free survival (EFS). RESULTS: The TCF3-PBX1 rearrangement was detected in 30 of 624 patients (4.8%). Results were consistent across the consecutive clinical trials employed in the past two decades. Compared with 239 intermediate risk patients without TCF3-PBX1 rearrangement, the 5-year overall survival and EFS for patients with TCF3-PBX1 rearrangement was superior, with both at 100% (P = 0.12 and P = 0.029). CONCLUSION: This population-based study over the past 20 years demonstrated that patients with TCF3-PBX1 rearrangement had favourable EFS compared with other intermediate risk patients treated with a similar chemotherapy backbone.

Hepatitis B infection acquired after haematopioetic stem cell transplant through horizontal mode.

A 22 month old child with thalassaemia major received unrelated umbilical cord blood transplantation. She was born to mother of HBsAg carrier and received hepatitis B immunoglobulin at birth and hepatitis B vaccination. She was HBsAg negative and anti-HBs positive before transplantation. After transplant, she was taken care by her mother and found to be HBsAg positive at 2 year post-transplant. Genotyping of the mother's and child's HBV status confirmed to be of same genotype and demonstrated horizontal transmission in post-transplant setting. Passive immunization of HBV may be considered in early post-transplant phase to prevent horizontal transmission of HBV, and antiviral treatment of the carer should be offered to prevent transmission of infection to immunocompromised child.

School-based surveillance for influenza vaccine effectiveness during 2014-2015 seasons in Hong Kong.

BACKGROUND: Influenza imposes substantial healthcare burden in children, which can be prevented by vaccination. Influenza vaccination coverage varies widely among childhood populations worldwide, which has significant impact on herd immunity and usefulness of influenza vaccine. However, there are limited real-life data on influenza vaccine effectiveness (VE) in children. OBJECTIVE: This prospective study aimed to investigate clinical spectrum of childhood influenza and VE in preventing influenza in Hong Kong children. METHODS: A total of 623 children were recruited from 15 kindergartens and primary schools. Parents completed a questionnaire on subjects' health and influenza vaccination history. Flocked nasopharyngeal swabs (FNPSs) were collected in biweekly school visits during 2014-2015 influenza seasons. Influenza A and B viruses were detected and typed by molecular assays. RESULTS: A total of 2633 FNPS samples were collected, with two or more samples being obtained from 607 (97.4%) of subjects. Thirty-six (11.2%) subjects had influenza A or B in 2014, whereas all 19 (6.3%) subjects identified in 2015 had influenza A. Ninety-nine subjects reported influenza-like illness (ILI), and nine illness visits were arranged. Influenza vaccination was protective against ILI but not mild laboratory-confirmed influenza by surveillance. Moderate overall influenza VE of 42%-52% was observed for ILI, and subgroup analyses showed much higher VE for both ILI (70.9% vs 34.6%) and mild laboratory-confirmed influenza (44.0% vs -6.2%) in school-age children than preschoolers who were vaccinated within 12 months. CONCLUSIONS: Mild laboratory-confirmed influenza infection is common in children during influenza seasons. Influenza vaccination is effective against ILI but not mild infection identified by surveillance.

Ad Hoc Influenza Vaccination During Years of Significant Antigenic Drift in a Tropical City With 2 Seasonal Peaks: A Cross-Sectional Survey Among Health Care Practitioners.

We evaluated the acceptability of an additional ad hoc influenza vaccination among the health care professionals following seasons with significant antigenic drift.Self-administered, anonymous surveys were performed by hard copy questionnaires in public hospitals, and by an on-line platform available to all healthcare professionals, from April 1st to May 31st, 2015. A total of 1290 healthcare professionals completed the questionnaires, including doctors, nurses, and allied health professionals working in both the public and private systems.Only 31.8% of participating respondents expressed an intention to receive the additional vaccine, despite that the majority of them agreed or strongly agreed that it would bring benefit to the community (88.9%), save lives (86.7%), reduce medical expenses (76.3%), satisfy public expectation (82.8%), and increase awareness of vaccination (86.1%). However, a significant proportion expressed concern that the vaccine could disturb the normal immunization schedule (45.5%); felt uncertain what to do in the next vaccination round (66.0%); perceived that the summer peak might not occur (48.2%); and believed that the summer peak might not be of the same virus (83.5%). Furthermore, 27.8% of all respondents expected that the additional vaccination could weaken the efficacy of previous vaccinations; 51.3% was concerned about side effects; and 61.3% estimated that there would be a low uptake rate. If the supply of vaccine was limited, higher priority groups were considered to include the elderly aged ≥65 years with chronic medical conditions (89.2%), the elderly living in residential care homes (87.4%), and long-stay residents of institutions for the disabled (80.7%). The strongest factors associated with accepting the additional vaccine included immunization with influenza vaccines in the past 3 years, higher perceived risk of contracting influenza, and higher perceived severity of the disease impact.The acceptability to an additional ad hoc influenza vaccination was low among healthcare professionals. This could have a negative impact on such additional vaccination campaigns since healthcare professionals are a key driver for vaccine acceptance. The discordance in perceived risk and acceptance of vaccination regarding self versus public deserves further evaluation.

Perforin gene mutation in familial haemophagocytic lymphohistiocytosis: the first reported case from Hong Kong.

Familial haemophagocytic lymphohistiocytosis is a rare but invariably fatal disease without haematopoietic stem cell transplantation. Genetic defect identification is useful for confirming a clinical diagnosis, predicting the risk of future recurrence, and defining haemophagocytic lymphohistiocytosis predisposition in asymptomatic family members. Notably, familial haemophagocytic lymphohistiocytosis type 2 associates with mutations in the perforin gene (PRF1) which is the most frequent subtype of familial haemophagocytic lymphohistiocytosis. Although perforin gene mutations have been described in Asians, they are largely reported from Japan. The case reported here is the first familial haemophagocytic lymphohistiocytosis type 2 patient in Hong Kong with an identified perforin gene mutation.

A pilot randomized study to assess immunogenicity, reactogenicity, safety and tolerability of two human papillomavirus vaccines administered intramuscularly and intradermally to females aged 18-26 years.

Intradermal administration of human papillomavirus (HPV) vaccines could be dose-sparing and cost-saving. This pilot randomized study assessed Cervarix(®) and Gardasil(®) administered either intramuscularly or intradermally, in different doses (full-dose or reduced to 20%) by different methods (needle and syringe or PharmaJet needle-free jet injection device). Following an initial reactogenicity study of 10 male subjects, sexually naïve women aged 18-26 years were randomized to the eight study groups to receive vaccine at 0, 2 and 6 months. 42 female subjects were enrolled and complete data were available for 40 subjects. Intradermal administration of either vaccine raised no safety concerns but was more reactogenic than intramuscular administration, although still tolerable. All subjects demonstrated a seroconversion (titre≥1:320) by Day 95. Further evaluation of intradermal HPV vaccination and its potential for cost reduction in resource poor settings is warranted.

Pathological fracture as the presenting feature in pediatric osteosarcoma.

BACKGROUND: Pathological fracture is an uncommon presentation in patients with long bone osteosarcoma. PROCEDURES: We retrospectively reviewed the database of all patients with histologically proven osteosarcoma under the age of 18 years from 1991 to 2011 in a tertiary pediatric oncology referral center. Five patients with pathological fractures as the first presentation of osteosarcoma were identified. The treatment strategies and complications were evaluated. Ten sex-, age-, and site- matched osteosarcoma patients without pathological fracture were selected as controls. The incidence of distant metastases and outcome, including local recurrence and survival, were compared between the index (with pathological fracture) and the control (without pathological fracture) groups. RESULTS: In the index group, all five patients were boys and the mean age of onset was 13.1 years (range 9.2-14.9). Three patients (60%, 3/5) received amputation and two (40%) had wide local excision of the tumor. Pathological fracture group showed higher rate of lung (60% vs. 10%, P = 0.04) and bone (60% vs. 10%, P = 0.04) metastases at presentation, and shorter overall 5-year survival (P = 0.04) than the control group. There was no significant difference of local recurrence (20%, P = 1.00) between these two groups regardless of the type of operation. CONCLUSION: Osteosarcoma complicated by pathological fracture as first presentation had higher incidence of lung and bone metastases at presentation and worse survival rate when compared with patients without pathological fracture.

Paediatric intra-axial posterior fossa tumours: pictorial review.

Paediatric brain tumours commonly arise in the posterior cranial fossa. Early diagnosis is often challenging due to initial non-specific clinical symptoms, especially in very young children. The typical MR features of tumours in this region including medulloblastoma, ependymoma, juvenile pilocytic subtype of cerebellar astrocytoma, brain stem glioma and atypical teratoid-rhabdoid tumour are illustrated. Diffusion-weighted imaging and apparent diffusion coefficient values combined with signal characteristics on conventional MR sequences can usually differentiate low-grade from high-grade tumours. Prompt diagnosis is crucial as total surgical resection, which is only possible in localised disease, improves prognosis. A practical MR flow chart is introduced for differentiating different types of posterior cranial fossa tumours, which might be useful in clinical practice.

A pale Chinese boy with recurrent painful digital swelling.

Thalassaemia is the most common haemoglobinopathy in the Chinese population. However, recurrent painful digital swelling is not a typical manifestation of this well-known hereditary condition. We describe a case of co-inheritance of beta-thalassaemia and sickle cell trait in a Chinese family and a child who suffered from sickle cell/beta-thalassaemia with recurrent dactylitis. This report highlights awareness of this rare condition in the Chinese population, since acute manifestations can be life-threatening and mimic other emergency conditions. Prompt management can prevent further complications and avoid unnecessary interventions due to delay in diagnosis. A detailed family history and examination of the patient's peripheral blood smear is crucial to reach a correct diagnosis.

Malignant pigmented clear cell epithelioid cell tumor (PEComa) in an adolescent boy with widespread metastases: a rare entity in this age group.

Malignant pigmented clear cell epithelioid cell tumor of the kidney is a rare variant of perivascular epithelioid cells tumors (PEComa) or epithelioid angiomyolipoma (AML). PEComa is characteristically composed purely of epitheloid cells. The fat cells and the blood vessels that are typical of classic AML are absent. Most epithelioid AML cases are benign; however, malignant epithelioid AML of the kidney has been occasionally reported in adults in association with tuberous sclerosis. We report the radiological-pathological features of a malignant pigmented clear cell epithelioid renal tumor in a 15-year-old boy presenting with extensive metastases but without clinical evidence of tuberous sclerosis.