Vanishing Bile Duct Syndrome Secondary to Hodgkin Lymphoma in a Child.

Vanishing bile duct syndrome (VBDS) is a condition resulting from progressive destruction and loss of intrahepatic bile ducts leading to cholestasis, biliary cirrhosis, and liver failure. It occurs secondary to various pathologic conditions like autoimmune diseases, graft versus host disease, drug reactions, and as a paraneoplastic syndrome in malignancies. We here described a 9-year-old girl who presented with cervical lymphadenopathy and jaundice. This child was diagnosed as a case of Hodgkin lymphoma. All other causes of cholestasis were ruled out by appropriate investigations (particularly autoimmune, metabolic, infections, and drug-induced possibilities). On liver biopsy, her diagnosis was established as VBDS. In view of hepatic dysfunction, alternative chemotherapy with dexamethasone, high-dose cytarabine, and cisplatin (DHAP) was given, and she was started on hepatoprotective measures with ursodeoxycholic acid. Hepatic function gradually improved after the initiation of chemotherapy. VBDS is considered a dismal paraneoplastic syndrome with a high-case fatality. This case report highlights the importance of early recognition and initiation of appropriate full-dose chemotherapy as the only way to achieve complete resolution of VBDS.

Impact of exclusive breast feeding until six months of age on common illnesses: A prospective observational study.

Objectives: The WHO recommends exclusive breast feeding (EBF) for all infants for the first six months of life. National Family Health Survey-4 (2015-16) shows EBF rates of only 54.9%. We conducted a prospective study to assess prevalence of EBF and incidences of illnesses in infants from birth till six months of age. Methods: Healthy term infants born in our hospital between December 2017 and November 2018 were recruited at birth. Structured diary cards were given to mothers to record feeding patterns, occurrence and severity of illnesses. Mothers were interviewed at 6, 10, 14 and 26 weeks or contacted by telephone at 18 and 22 weeks. Data were analyzed using SPSS IBM Statistics 22. Results: The prevalence of EBF among 450 infants (M:F = 1.3:1) who completed the study was 47% at 6 months. 185 (69 EBF + 116 non-EBF) of 450 infants reported a total of 242 illnesses, most commonly respiratory (82.6%) followed by gastrointestinal (11.6%). Number of illnesses per infant was 0.45 and 0.6 in EBF group and non-EBF group respectively (p = 0.015). Illness incidences in EBF infants were significantly lower during all successive time intervals after 10 weeks of age. Logistic regression analysis confirmed significantly lower illness incidences in EBF infants at 10-14 weeks [OR = 0.27 (CI 0.12-0.64)] and 18-22 weeks [OR = 0.50 (CI 0.27-0.90)]. Conclusions: The prevalence of EBF is suboptimal in our setting, with illness incidences significantly higher in non-EBF children. Appropriate intervention strategies need to be tailored to reinforce early initiation and continuation of EBF throughout the first six months of life.

ZFTA (Zinc Finger Translocation Associated) Fusion in Supratentorial Ependymomas: Low Prevalence in South Asians and No Correlation with Survival.

BACKGROUND: Supratentorial ependymomas (STEs) are an aggressive group of ependymomas, topographically distinct from their posterior fossa and spinal counterparts. Zinc finger translocation associated (ZFTA) fusion-positive cases have been reported to account for the majority of STEs, although data on its association with poorer outcomes are inconsistent. MATERIALS AND METHODS: We assessed the prevalence of the ZFTA fusion by reverse-transcription polymerase chain reaction and fluorescence in situ hybridization in a cohort of 61 patients (68 samples) with STE. Our primary outcome was to determine the role of the ZFTA fusion on progression-free and overall survival of patients with STE. Our secondary objectives were to assess the impact of ZFTA fusion on nuclear factor (NF)-kB pathway signaling via surrogate markers of this pathway, namely COX-2, CCND1, and L1 cell adhesion molecule. RESULTS: ZFTA fusion was noted in 21.3% of STEs in our cohort. The presence of this rearrangement did not significantly impact the progression-free or overall survival of patients with STEs and was not associated with upregulation of markers of the NF-kB pathway. Only gross total resection was significantly associated with better progression-free survival. CONCLUSIONS: In contradiction to previous reports from across the world, the ZFTA fusion is far less prevalent among our population. It does not appear to drive NF-kB signaling or significantly affect outcomes. Gross total resection must be attempted in all cases of STE and adjuvant radiation and/or chemotherapy employed when gross total resection is not achieved.

The Unique Balancing Act of Managing Children With Cancer and COVID-19 Infection: A Single Center Experience From South India.

Children with cancer are vulnerable to severe infections. Balancing the intensive treatment of cancer, with the potential risk of coronavirus disease-2019 (COVID-19) related morbidity and mortality is a unique challenge. Children with cancer testing positive for severe acute respiratory syndrome coronavirus 2 virus by reverse-transcription polymerase chain reaction at our center were studied. Thirty-seven children tested positive for COVID-19 during the study period. The severity of the illness was mild, moderate, severe, and critical in 10 (27%), 13 (35%), 12 (32%), and 2 (5%) patients, respectively. Of the 14 patients with a severe/critical illness, 2 had oncological emergencies, 4 had dengue co-infection, and 1 had an inguinal bacterial abscess. All patients were discharged in a stable condition. Modification of the treatment protocol was performed in 11 (33%) of 33 patients who were on active treatment for cancer. There was a median delay of 32.5 days to administer the next cycle of chemotherapy in patients who acquired COVID-19 during cancer treatment. Six of 7 patients who were retested after 14 days remained positive by reverse-transcription polymerase chain reaction. Children with cancer with COVID-19 recover with good supportive care. Curative chemotherapy can be administered safely with appropriate modifications in children with cancer with COVID-19.

Paediatric mucormycosis: tailoring surgical strategies to compliment antifungal chemotherapy. Different strokes for different folks.

Children manifesting soft-tissue fungal infections are uncommonly seen, more so the subgroup of invasive soft-tissue mucormycosis. Invasive fungal infections in various organs respond differently and are often complicated by an immune-compromised host. Repeated and aggressive clearance of disease till an infection-clear margin is obtained is the mainstay of surgical therapy. This is coupled with appropriate antifungal therapy and the management of any underlying medical conditions. From our experience, we propose a surgical algorithm for therapy of soft-tissue mucormycosis in children.

Molecular correlates of cerebellar mutism syndrome in medulloblastoma.

BACKGROUND: Cerebellar mutism syndrome (CMS) is a common complication following resection of posterior fossa tumors, most commonly after surgery for medulloblastoma. Medulloblastoma subgroups have historically been treated as a single entity when assessing CMS risk; however, recent studies highlighting their clinical heterogeneity suggest the need for subgroup-specific analysis. Here, we examine a large international multicenter cohort of molecularly characterized medulloblastoma patients to assess predictors of CMS. METHODS: We assembled a cohort of 370 molecularly characterized medulloblastoma subjects with available neuroimaging from 5 sites globally, including Great Ormond Street Hospital, Christian Medical College and Hospital, the Hospital for Sick Children, King Hussein Cancer Center, and Lucile Packard Children's Hospital. Age at diagnosis, sex, tumor volume, and CMS development were assessed in addition to molecular subgroup. RESULTS: Overall, 23.8% of patients developed CMS. CMS patients were younger (mean difference -2.05 years ± 0.50, P = 0.0218) and had larger tumors (mean difference 10.25 cm3 ± 4.60, P = 0.0010) that were more often midline (odds ratio [OR] = 5.72, P < 0.0001). In a multivariable analysis adjusting for age, sex, midline location, and tumor volume, Wingless (adjusted OR = 4.91, P = 0.0063), Group 3 (adjusted OR = 5.56, P = 0.0022), and Group 4 (adjusted OR = 8.57 P = 9.1 × 10-5) tumors were found to be independently associated with higher risk of CMS compared with sonic hedgehog tumors. CONCLUSIONS: Medulloblastoma subgroup is a very strong predictor of CMS development, independent of tumor volume and midline location. These findings have significant implications for management of both the tumor and CMS.

Palonosetron is a Better Choice Compared With Ondansetron for the Prevention of Chemotherapy-induced Nausea and Vomiting (CINV) in a Resource-limited Pediatric Oncology Center: Results From a Randomized Control Trial.

Palonosetron (PG) is a newer, safe, and effective long-acting 5-HT3 antagonist commonly used in adults, but data in children are limited. A randomized controlled trial was carried out among children with cancer during their first cycle of moderate or highly emetogenic chemotherapy to receive either PG or ondansetron (OG) with the aim of comparing their efficacy, safety, and cost-effectiveness. In total, 200 children (mean age, 8 y, male:female=1.8:1) were recruited, 100 in each arm. Complete response, defined as no vomiting, in acute (<24 h), delayed (24 to 120 h), and overall phases (0 to 120 h) was observed in 88%, 88%, and 81% of cases, respectively, for PG versus 84%, 79%, and 72%, respectively, for OG (P=0.42, 0.09 and 0.21, respectively). Complete protection rates, defined as no nausea and vomiting in children above 6 years of age, in acute, delayed, and overall phases were 84%, 81%, and 73%, respectively, for PG versus 79%, 67%, and 60%, respectively, for OG (P=0.44, 0.06 and 0.10, respectively). Overall, the efficacy and safety of PG in the prevention of chemotherapy-induced nausea and vomiting was comparable with OG, but PG was a more cost-effective and suitable choice for busy centers in resource-limited countries.

Effect of prophylactic or therapeutic administration of paracetamol on immune response to DTwP-HepB-Hib combination vaccine in Indian infants.

BACKGROUND: Vaccination is considered as the most cost effective method for preventing infectious diseases. Low grade fever is a known adverse effect of vaccination. In India, it is a common clinical practice to prescribe paracetamol either prophylactically or therapeutically to manage fever. Some studies have shown that paracetamol interferes with antibody responses following immunization. This manuscript reports the outcome of a post hoc analysis of data from a clinical trial of a pentavalent vaccine in Indian infants where paracetamol was not used or was used either as prophylaxis or for treatment of fever. METHODS: Pre and post vaccine antibody levels against Diphtheria, Tetanus, Pertussis, Hepatitis B, Haemophilus influenzae type B were assessed in no paracetamol and paracetamol groups. The paracetamol group was further divided into prophylactic and treatment groups. RESULTS: Similar rates of seroprotection/seroresponse for anti-D, anti-T, anti-wP, anti-PT, anti-HBs and anti-PRP were observed in all the groups. There was no clear tendency for difference in percentage seroprotection/seroresponse and geometric mean (GM) titers in any of the groups. CONCLUSION: The study found no evidence that paracetamol usage either as prophylactic or for treatment impact immunological responses to DTwP-HepB-Hib combination vaccine. [Clinical trial registry of India (study registration number CTRI/2012/08/002872)].

Safety, immune lot-to-lot consistency and non-inferiority of a fully liquid pentavalent DTwp-HepB-Hib vaccine in healthy Indian toddlers and infants.

Pentavalent combination vaccines are important tools to strengthen the immunization programs in numerous countries throughout the world. A large number of countries have recognized the value of combination vaccines and have introduced whole cell pentavalent vaccines into their immunization programs. A phase III, multi-center, randomized, single blinded study of a fully liquid pentavalent DTwP-HepB-Hib investigational vaccine (Shan5™) was conducted across India in 2 cohorts: 15 toddlers were evaluated for safety and immunogenicity following a single booster dose (Cohort 1) followed by 1085 infants (Cohort 2) evaluated for immunogenicity and safety following 3-dose primary immunization of the investigational vaccine or a locally licensed comparator vaccine (Pentavac SD). Immune consistency analysis among 3 lots of the investigational vaccine, and immune non-inferiority analysis of pooled (3 lots) data of investigational vaccine vs. comparator vaccine were carried out in cohort 2. The vaccines demonstrated comparable safety and immune responses in cohort 1. In cohort 2, equivalent immune consistency among 3 lots was observed for all antigens except whole cell pertussis antigens, where a marginal variation was observed which was linked to the low power of the test and concluded to not have any clinical significance. Immune non-inferiority against the comparator vaccine was demonstrated for all 5 antigens. Safety results were comparable between vaccine groups. This investigational, fully-liquid, whole-cell pertussis (wP) containing new pentavalent vaccine was found to be safe and immunologically non-inferior to the licensed comparator vaccine.

Study of Common Illnesses Before and After Vaccination: A Risk interval Approach.

OBJECTIVE: To compare the proportion of children who developed a specified illness in the 7 day post-vaccination window, with the background rate of the same event in the 7 day pre-vaccination window. STUDY DESIGN: Risk interval approach (Self-controlled case-series). SETTING: Well Baby Clinic of Christian Medical College, Vellore. PARTICIPANTS: 1602 healthy infants and under-six children presenting for routine vaccination. OUTCOME MEASURES: Episode of any illness. METHODS: The interviewer enquired about any adverse event or illness experienced by the child for each day of the week preceding the administration of age-appropriate vaccines. A second interview (telephonic) was conducted by the same interviewer one week following vaccine administration to enquire about adverse event(s) experienced by the child for each day of the subsequent week using a similar protocol. RESULTS: With multiple vaccines delivered at appropriate ages, common childhood illnesses that could be reported as adverse events following immunization, except fever (RR=5.7, 95% CI=4.50-7.35), occurred at higher rates pre-vaccination. Risk Ratios of fever following whole cell (RR=9.3, 95% CI=6.43-13.52) and acellular (RR=8.5, 95% CI=3.82-18.91) vaccines were similar, with both showing a decreasing trend with increasing age. The gastrointestinal adverse event profile [diarrhea (RR=0.6, 95% CI=0.14-2.51) and vomiting (RR=1.0, 95% CI=0.14-7.10)] for rotavirus vaccine was similar pre- and post-immunization. CONCLUSIONS: Since most adverse events to vaccines are also common childhood illnesses, estimating the background rates of common illnesses is important to accurately ascertain a causal relationship.

Steroid-responsive anemia in patients of Ghosal hematodiaphyseal dysplasia: simple to diagnose and easy to treat.

Ghosal hematodiaphyseal dysplasia (GHDD) is a recently recognized cause of steroid-responsive anemia. We would like to report 3 cases of GHDD who presented in early childhood with moderate to severe anemia, splenomegaly, and a hypocellular marrow with increased reticulin. They were easily diagnosed with long-bone x-rays showing diaphyseal and metaphyseal widening and loss of diaphyseal constriction. All cases dramatically responded to oral steroid and no longer needed blood transfusion. They required steroid at low doses for long term (up to 5 y). GHDD is easy to diagnose with long-bone radiography and consistently responds to steroid. It should therefore be considered as a differential diagnosis of unusual anemia in early childhood, especially in children from the Middle East or the Indian subcontinent.

Liver metastasis in an adolescent treated for third ventricle germ cell tumor.

Systemic dissemination of intracranial germ cell tumors (GCTs) occur only in 3% of cases and the common sites are bone, lungs, and lymph nodes. Metastasis to the liver is rare. As far as we could find, only six cases of liver metastasis of intracranial GCTs have been reported so far. We report an adolescent girl who presented with hepatic relapse 2½ years after successful completion of treatment of intracranial GCT. She was treated with chemotherapy and right hepatectomy and is doing well 30 months after treatment for the metastatic disease.

Immunogenicity of a three dose and five dose oral human rotavirus vaccine (RIX4414) schedule in south Indian infants.

AIM: This study was undertaken to compare the immunogenicity of a three dose and five dose schedule of an oral live-attenuated human rotavirus vaccine, Rotarix in south Indian infants. METHOD: Healthy infants (N=90), six to seven weeks of age were enrolled to receive three doses (n=45) or five doses of Rotarix vaccine (n=45) along with other scheduled vaccines, each dose separated by a four week interval. Blood samples were taken before vaccination and one month post-dose three in the Rotarix three dose group and one month post-dose five in the Rotarix five dose group; all were tested for anti-rotavirus IgA by an antibody sandwich enzyme immunoassay. RESULTS: At baseline, >50% of infants had >20 units of anti-rotavirus IgA. The seroconversion rates after three and five doses were low and not significantly different in the two groups. However, among vaccine responders, children seropositive at baseline showed a much greater absolute increase in IgA antibody levels than children seronegative at baseline. CONCLUSIONS: Rotarix vaccine showed low immunogenicity in south Indian children and increasing the number of doses did not increase the proportion of infants seroconverting after vaccination.

Disseminated protothecosis.

Here is presented, a rare case of disseminated protothecosis in a 10-year-old boy with combined immunodeficiency, hitherto unreported from India. Even though it is difficult to diagnose clinically, observation of the sporangiospores within the sporangium in culture gives the accurate laboratory identification of Prototheca spp. In this patient, failure to eradicate the infection with amphotericin B and recurrence with olecranon bursitis along with skin lesions and splenomegaly was observed. Disseminated protothecosis in a child with combined immunodeficiency and failure to eradicate the infection with amphotericin B is reported.

"Candidatus Rickettsia kellyi," India.

We report the first laboratory-confirmed human infection due to a new rickettsial genotype in India, "Candidatus Rickettsia kellyi," in a 1-year-old boy with fever and maculopapular rash. The diagnosis was made by serologic testing, polymerase chain reaction detection, and immunohistochemical testing of the organism from a skin biopsy specimen.

High-dose granulocyte colony-stimulating factor mobilizes a higher proportion of early CD34(+) CD33(-) hemopoietic progenitors in children receiving treatment for solid tumors.

A relationship between dose of granulocyte colony-stimulating factor (G-CSF) and maturational stage of the progenitors mobilized in healthy adult donors has been suggested. In this study we characterize the progenitors mobilized by 2 different dosages of G-CSF in children receiving autologous grafts after intensive treatment for solid tumors.