Outcome and Determinants of Neutropenic Enterocolitis in Pediatric Cancer Patients.

BACKGROUND: Neutropenic enterocolitis (NEC) is a dreaded complication of chemotherapy. There is scant literature regarding incidence, clinical features, and determinants. The understanding of gut dysbiosis in NEC and pediatric cancer is evolving. METHODS: Pediatric cancer patients with neutropenia and gastrointestinal symptoms were evaluated for NEC with contrast-enhanced computed tomography abdomen. Clinical, imaging, and laboratory features were analyzed. Fecal samples were analyzed for fecal calprotectin by sandwich enzyme-linked immunoassay and gut microbiota by conventional culture and compared with healthy controls and children without NEC. RESULTS: NEC was diagnosed in 44 children based on clinical and imaging features with incidence of 7.4% (4 had recurrent episodes). Common manifestations included fever (98%), pain abdomen (88%), and diarrhea (83%). Hypoalbuminemia was observed in 78% of patients. Large bowel involvement (94%) with diffuse bowel involvement (63%) and pancolitis (64%) were common. Fecal calprotectin was significantly elevated in NEC group than non-NEC group and healthy controls (median: 87, 53, and 42 µg/g, respectively). A higher degree of gut dysbiosis was observed in children with NEC with higher isolation of Bacteroides and infrequent isolation of Lactobacilli. Mortality rate of 23% was observed. Only the presence of free fluid predicted higher mortality. Though levels of fecal calprotectin and gut dysbiosis were higher in NEC, they did not increase mortality. Isolation of Bacteroides and absence of Lactobacilli predicted a longer duration of intravenous alimentation. CONCLUSIONS: NEC caused significant morbidity and mortality in pediatric cancer patients. Gut dysbiosis was significantly higher in NEC group suggesting a role in pathogenesis and influencing outcome. This highlights the role of targeted interventions towards gut dysbiosis like prebiotics and probiotics.

Efficacy and Safety of Olanzapine in Children Receiving Highly Emetogenic Chemotherapy: A Randomized, Double-blind Placebo-controlled Phase 3 Trial.

BACKGROUND: In this trial, we evaluated the safety and efficacy of olanzapine in children receiving highly emetogenic chemotherapy. MATERIALS AND METHODS: In this study, patients aged 3 to 18 years were randomly assigned to either the olanzapine group or the placebo group. All patients received intravenous ondansetron and dexamethasone 30 minutes before highly emetogenic chemotherapy, followed by oral ondansetron for 48 hours. Participants in the olanzapine group received olanzapine once daily on days 1 and 2, while those in the control group received a placebo in the same dosage and schedule. The primary objective was: (a) to compare the complete control rates of vomiting in the delayed phase and (b) to compare the complete control rates of vomiting in acute and overall phases. The secondary objective was to evaluate the safety of olanzapine and the need for rescue medications. RESULTS: A total of 128 patients were randomly assigned either to the olanzapine group (n=63) or the control group (n=65). Complete control of vomiting between olanzapine and placebo group was 73% versus 48% ( P =0.005) in the delayed phase, 60% versus 54% ( P =0.46) in the acute phase, and 48% versus 34% ( P =0.117) in the overall phase, respectively. Grades 1 and 2 sedation was greater in the olanzapine group (46% vs. 14%; P <0.001). A significantly higher proportion of patients in the placebo group required rescue medications for vomiting compared with in the olanzapine group ( P =0.025). CONCLUSIONS: Olanzapine significantly improved complete control of vomiting in the delayed phase. A considerably lesser proportion of patients in the olanzapine group needed rescue medications.

A Novel Homozygous HAX1 Mutation in a Child With Cyclic Neutropenia: A Case Report and Review.

BACKGROUND: Cyclic neutropenia is a rare genetic disorder causing the arrest of neutrophil function and is characterized by periodic neutropenia and recurrent infections. Patients with cyclic neutropenia with autosomal dominant, sporadic, and X-linked may have mutations in the ELANE gene, and autosomal recessive cases have homozygous/compound heterozygous variants in the HAX1 gene primarily. OBSERVATION: The authors describe a novel variant in the HAX1 gene, which was detected by next-generation sequencing in an 8-year-old male child who presented with recurrent infections and neutropenia. CONCLUSION: The patient extends the clinical variability associated with HAX1 variants and highlights the importance of genetic investigations in patients with suspected cyclic neutropenia.

A rare presentation of Erdheim Chester disease in a pediatric patient subsequently cured on the LCH III protocol.

BACKGROUND: Erdheim Chester disease (ECD) is very rare in pediatrics with no standard treatment guidelines. Here we present the case of a pediatric ECD patient who was cured with a Langerhan cell histiocytosis (LCH) directed chemotherapy protocol. AIM: The aim of the report was to publish this rare presentation of ECD in pediatrics and highlight the complete response obtained to treatment. METHODS: The details of the patient were extracted by a retrospective review of her clinical records. RESULTS (CASE): An 11 years old girl presented with fever and bone pain. On investigating she had multiple lytic bony lesions scattered throughout her skeleton. A biopsy from one of the bone lesions confirmed the diagnosis to be ECD. ECD is very rare in pediatrics and this case adds to the existing list of 11 previously reported ones. Also, worth mention is the fact that the child presented with isolated skeletal involvement in form of multiple osteolytic lesions. The child was started on the LCH-III protocol on which she achieved a cure. CONCLUSION: Lytic bone lesions in a child may be present in ECD. A subset of ECD may have good response to LCH like chemotherapy.

Entomophthoromycosis in a child: Delayed diagnosis and extensive involvement.

Entomophthoromycosis is a rare fungal infection of the skin and subcutaneous tissue occurring predominantly in tropical and subtropical regions. In children, it mostly affects the lower half of the body. With this, we report a case of Entomophthoromycosis in a 6-year-old girl who presented late with extensive involvement of the upper half of the body. She responded well to treatment with potassium iodide and itraconazole. We also reviewed cases of Entomophthoromycosis reported in children.

Outcomes of Febrile Neutropenia in Children With Cancer Managed on an Outpatient Basis: A Report From Tertiary Care Hospital From a Resource-limited Setting.

In low-risk febrile neutropenia (FN) patients, outpatient management is now an accepted treatment, but there is a scarcity of data on high-risk patients. The aim of our study was to describe the outcome of FN treated primarily in an outpatient setting on the basis of the severity of illness at presentation, irrespective of the intensity of chemotherapy, and absolute neutrophil count. In this prospective study, not severely ill (NSI) patients were treated with empiric antibiotics at the daycare center (outpatient) and were admitted subsequently if there was persistent fever or any complication arose. Severely ill (SI) children were admitted to the hospital upfront. A total of 118 FN episodes among children with cancer on chemotherapy 18 years of age and younger were studied. Among NSI patients managed as outpatients (n=103), 89 patients (86%) recovered with outpatient treatment, and 14 patients required hospitalization after the median duration of 5 days (interquartile range: 4 to 6 d) of antibiotic therapy. The main indication for hospital admission in the SI group was hypotension (n=5), and in the NSI group, it was persistent fever (n=11). Overall, 5% of patients (6/118) died, and 2 of these were in the NSI group. The results of this study suggest that carefully selected NSI patients could be successfully treated at outpatient management in resource-poor settings and subsequent admission if warranted.

Brincidofovir as a Salvage Therapy in Controlling Adenoviremia in Pediatric Recipients of Hematopoietic Stem Cell Transplant.

Adenovirus infection is a well-known complication in patients receiving hematopoietic stem cell transplantation (HSCT). Brincidofovir (BCV) is an orally bioavailable lipid conjugate of cidofovir, which has activity against adenoviruses. We present a review of adenovirus infections treated with BCV which were unresponsive to cidofovir initially in 4 patients and it was used upfront in one patient. Children with adenovirus infection following HSCT treated with BCV, between July 2014 and February 2018 were recognized. Five patients including 3 male and 2 female with a median age of 10 years (range, 2.2 to 10 y) were identified. The median days of adenoviremia detection was 18 days (range, 7 to 303 d) posttransplant. The median peak viral load by quantitative polymerase chain reaction was 21,38,000 copies/mL (range, 1,77,200 to 31,97,000 copies/mL). The median time from first detection of adenoviremia to become negative was 30 days (range, 15 to 113 d). The sites involved were gastrointestinal tract in all patients and 2 patients had additional respiratory tract involvement. Two patients survived and 3 patients died of sepsis. All patients responded well to BCV and no adverse effect was noticed. We saw the good safety profile and excellent antiadenoviral activity of BCV in pediatric patients receiving HSCT without the nephrotoxicity and it may have a role in preemptive therapy.

Acute Myeloid Leukemia Presenting as a Central Nervous System Mass in a Child: A Case Report.

Extramedullary leukemia is common in pediatric acute myeloid leukemia (AML) and occurs as a solid tumor (myeloid sarcoma). We report a case of a child who presented with acute onset of paraparesis and found to have intracranial and paravertebral mass; subsequently, he was diagnosed as having AML on tissue biopsy. He was started on AML treatment protocol, and later he was in remission and myeloid sarcoma got cleared from intracranial and paravertebral region. Timely diagnosis and initiation of treatment are essential to improve survival in such cases.

Neuroblastoma presenting as opsoclonus-myoclonus: A series of six cases and review of literature.

The opsoclonus-myoclonus ataxia syndrome (OMAS) also called "Kinsbourne syndrome" or "dancing eye syndrome" is a rare but serious disorder characterized by opsoclonus, myoclonus, and ataxia, along with extreme irritability and behavioural changes. Data on its epidemiology, clinical features, and outcome are limited worldwide. The aim of the study was to evaluate the clinical profile and outcome of children with OMAS. A retrospective data of all children presented to Pediatric oncology clinic with a diagnosis of opsoclonus-myoclonus from 2013 to 2016 were collected. 6 patients with a diagnosis of OMAS were presented over a 4-year period. All 6 cases had paraneoplastic etiology. All Children had good outcome without any relapse. Paraneoplastic opsoclonus myoclonus had a good outcome in our experience.

Beals-Hecht syndrome (congenital contractural arachnodactyly) with additional craniospinal abnormality: a case report.

Beals syndrome is an autosomal-dominant connective tissue disorder, characterized by multiple flexion contractures, arachnodactyly, severe kyphoscoliosis, crumpled ear, and muscular hypoplasia. It has similarities to Marfan syndrome (MFS) in many respects. It has much fewer incidences of eye and heart anomalies compared with MFS. Beals syndrome is caused by a mutation in the fibrillin-2 gene (FBN2) in 5q23; MFS is caused by mutations in fibrillin-1. With time, there is spontaneous improvement in joint contractures, but kyphosis tends to be progressive. The neonatal form results from new mutations and tends to be severe. Prenatal molecular diagnosis is possible. Ultrasound could be used to demonstrate hypokinesia and joint contractures in presumptive cases. We present a case of a patient with Beals syndrome who presented to the emergency department with pneumonia and was found to have narrowing of the foramen magnum, with partial fusion of C2-C3 vertebral bodies. To our knowledge, this has not been documented in the literature and could be characteristic in relation to Beals syndrome.

Dexamethasone pretreatment for 24 h versus 6 h for prevention of postextubation airway obstruction in children: a randomized double-blind trial.

PURPOSE: Multidose steroid pretreatment is effective in preventing postextubation airway obstruction (PEAO) in adults, however controversy continues for children. This study was designed as a randomized, placebo-controlled, double-blind trial to compare the effect of 24-h pretreatment with dexamethasone (24hPD) versus 6-h pretreatment (6hPD) on PEAO and reintubation in children at a tertiary care hospital in a developing economy. METHODS: Hundred twenty-four children (3 months to 12 years) intubated for ≥48 h and planned to have extubation during next 24 h were randomized to receive 24hPD (0.5 mg/kg/dose, q6h, total of six doses; n = 66) or 6hPD (total of three doses; n = 58). Patients with preexistent upper airway conditions, chronic respiratory diseases, steroid therapy in last 7 days, gastrointestinal bleeding, hypertension, and hyperglycemia and those likely to have poor airway reflexes were excluded. RESULTS: The two groups were similar at baseline. 24hPD reduced the incidence of PEAO (43/66 versus 48/58; p = 0.027) with absolute risk reduction of 17 %. It also reduced the incidence of reintubation, though nonsignificantly, by half [5/61 versus 9/58; relative risk (RR), 1.09; 95 % confidence interval (CI), 0.96-1.25]. Time to recovery from PEAO among non-reintubated patients was shorter among 24hPD patients (p = 0.016). No adverse event was noted with dexamethasone use. Intubation duration >7 days and cuffed tracheal tubes were found to be independent risk factors for PEAO (odds ratio 6 and 3.12, respectively). CONCLUSIONS: 24-h pretreatment with multidose dexamethasone reduced the incidence of PEAO and the time to recover from it. 24hPD should be considered for high-risk children intubated for >48 h in the study setting. Further studies with larger sample size from different socioeconomic background are desirable to validate these findings.