Childhood Medulloblastoma.

Medulloblastoma is the most common malignant brain tumour in children and is a major cause of mortality and morbidity, particularly in low- and middle-income countries. It has been risk-stratified on the basis of clinical (age, metastasis and extent of resection) and histological subtypes (classic, desmoplastic and anaplastic). However, recently medulloblastoma has been sub-grouped by using a variety of different genomic approaches, such as gene expression profiling, micro-ribonucleic acid profiling and methylation array into 4 groups, namely Wingless, Sonic hedgehog, Group 3 and Group 4. This new sub-grouping has important therapeutic and prognostic implications. After acute leukaemia, brain tumour is the second most common malignancy in the paediatric age group. The improvement in outcome of acute lymphoblastic leukaemia in low- and middle-income countries reflects the relative simplicity of diagnostic procedures and management. Unlike leukaemia, the management of brain tumours requires a complex multidisciplinary approach, including neuro-radiologists, neurosurgeons with a paediatric expertise, neuropathologists, radiation oncologists and neuro-oncologists. In addition, the equipment required for the diagnosis (magnetic resonance imaging scan, histological, molecular and genetic techniques) and the management (operating room, radiation facilities) is a limiting factor in countries with limited resources. In Pakistan, there are very few centres able to treat children with brain tumours. The current literature review was planned to provide an update on the management of this tumour.

Upshaw-Schulman Syndrome With c.2728C>T Mutation in ADAMTS13 Gene.

Congenital thrombotic thrombocytopenic purpura is a rare autosomal recessive disorder presenting with hemolytic anemia, thrombocytopenia, micro vascular thrombosis, and end organ damage. Here, we present a case of a 7-year-old girl having recurrent neonatal hemolysis, developmental delay, frequent seizures, and thrombocytopenia. Characteristic clinical picture and gene sequencing of a disintegrin and metalloproteinase with thrombospondin motifs 13 confirmed the diagnosis of Upshaw-Schulman syndrome. She was treated successfully with plasma infusion. The patient is alive at 6-month post follow-up, and on regular plasma therapy. Congenital thrombotic thrombocytopenic purpura should be considered in the differential diagnosis of thrombocytopenia with hemolytic anemia in infants.

Clinical Features and Treatment Outcomes of Children With Anaplastic Large Cell Lymphoma in Pakistan: A Multicenter Study.

BACKGROUND: Different approaches have been adopted in the treatment of anaplastic large cell lymphoma (ALCL); there is a lack of consensus with regard to standard treatment. Because of paucity of data from low and middle-income countries, we reviewed the clinical features and treatment outcomes of children with ALCL. METHODS: All ALCL patients under 16 years of age diagnosed from 2005 to 2015 at Aga Khan University Hospital and The Indus Hospital were identified. Clinical features and treatment outcomes were analyzed. RESULTS: Thirty-two (n=32) patients met the inclusion criteria. Cervical Lymphadenopathy was the most common presentation (34.3%, n=11). Advanced disease was seen in 68.7% (n=22) (stages III and IV). Fourteen (42.4%) were treated on ALCL-99, 30.3% (n=10) on multicenter protocol-842 regimen, 9% (n=3) on adriamycin-prednisolone-oncovin (doxorubicin, prednisone, vincristine) regimen, and 16% (n=5) were treatment abandonments. Five-year overall survival was 70.6% (95% confidence interval: 47.8%-84.9%), and 5-year event-free survival (EFS) considering treatment abandonment and death as an event was 52.3 % (95% confidence interval: 23.5%-74.8%). CONCLUSIONS: Significant therapy-related mortality (27.7%) was observed. Treatment abandonment and therapy-related toxicity were the major barriers for better outcomes. However, less intensive outpatient regimens, such as adriamycin-prednisolone-oncovin regimen, may decrease the number of hospitalizations, hence reducing treatment abandonment in the low and middle-income country.

Effectiveness of simple strategies in reducing multidrug resistant blood stream infections in Neonatal Intensive Care Unit of tertiary care hospital in Karachi, Pakistan.

OBJECTIVES: To report reduction in transmission of multidrug resistant organisms from the neonatal intensive care unit after the implementation of simple risk-reduction strategies. METHODS: Using a pre-and-post design, the study was carried out from June 2010 to December 2011 at the neonatal intensive care unit of Aga Khan University Hospital, Karachi, which is 12-bed, level III facility. The intervention comprised hand washing certification for all staff, use of chlorhexidine instead of povodine iodine for skin preparation, use of non-sterile gloves for diaper change, implementation of barrier nursing for clinically-suspected and culture-proven infections, provision of separate intubation and central line trolley for each room and limiting the use of umbilical catheters to 7 days. Data is reported for 3-month pre-intervention period, one-month implementation phase, and for 3-month post-intervention phase. Data for 12 months post-implementation is reported to show sustainability. RESULTS: The average pre intervention rates of bloodstream infections due to extended spectrurm 3 lactamase, Acinetobacter, Pseudomonas and methicillin resistant staphylococcus aureus were 4.7, 3.3, 1.2 and zero respectively. The average number of admissions during the 3 phases was almost similar (49, 46 and 53 respectively). There was sustained reduction in rates for all organisms 12 months after the intervention period. CONCLUSION: Nosocomial transmission of multi drug resistant organisms within the neonatal intensive care unit can be effectively reduced by adopting simple strategies.

Capacity building for pediatric neuro-oncology in Pakistan- a project by my child matters program of Foundation S.

Introduction: Initiated in June 2019, this collaborative effort involved 15 public and private sector hospitals in Pakistan. The primary objective was to enhance the capacity for pediatric neuro-oncology (PNO) care, supported by a My Child Matters/Foundation S grant. Methods: We aimed to establish and operate Multidisciplinary Tumor Boards (MTBs) on a national scale, covering 76% of the population (185.7 million people). In response to the COVID-19 pandemic, MTBs transitioned to videoconferencing. Fifteen hospitals with essential infrastructure participated, holding monthly sessions addressing diagnostic and treatment challenges. Patient cases were anonymized for confidentiality. Educational initiatives, originally planned as in-person events, shifted to a virtual format, enabling continued implementation and collaboration despite pandemic constraints. Results: A total of 124 meetings were conducted, addressing 545 cases. To augment knowledge, awareness, and expertise, over 40 longitudinal lectures were organized for healthcare professionals engaged in PNO care. Additionally, two symposia with international collaborators and keynote speakers were also held to raise national awareness. The project achieved significant milestones, including the development of standardized national treatment protocols for low-grade glioma, medulloblastoma, and high-grade glioma. Further protocols are currently under development. Notably, Pakistan's first pediatric neuro-oncology fellowship program was launched, producing two graduates and increasing the number of trained pediatric neuro-oncologists in the country to three. Discussion: The initiative exemplifies the potential for capacity building in PNO within low-middle income countries. Success is attributed to intra-national twinning programs, emphasizing collaborative efforts. Efforts are underway to establish a national case registry for PNO, ensuring a comprehensive and organized approach to monitoring and managing cases. This collaborative initiative, supported by the My Child Matters/Foundation S grant, showcases the success of capacity building in pediatric neuro-oncology in low-middle income countries. The establishment of treatment protocols, fellowship programs, and regional tumor boards highlights the potential for sustainable improvements in PNO care.

A retrospective review on antibiotic use in acute watery diarrhea in children in a tertiary care hospital of Karachi, Pakistan.

INTRODUCTION: Responsible for at least one in nine pediatric deaths, diarrheal diseases are the leading, global cause of death. Further abetted by improper antibiotic use in a hospital setting, children with acute watery diarrhea can see prolonged hospital stays, and unwanted adverse effects such as antibiotic resistance. Hence, this study is aimed to identify the association between antibiotic usage for the treatment of acute watery diarrhea in children, and the impact this line of management has on the duration of their hospital stay. METHODS: A retrospective review was conducted at the department of Pediatric of Aga Khan University Hospital (AKUH) in Karachi. A total of 305 records of children aged 6 months to 5 years who were admitted with a diagnosis of acute watery diarrhea from June 2017 -December 2018 was screened, of which 175 fulfilled the eligibility criteria. A predesigned questionnaire was used to collect demographic information, comorbidities, and clinical features, severity of dehydration, clinical examination, treatment received, and laboratory investigations. The primary outcome of this study was the length of hospital stay measured against the number of hours a child stayed in hospital for treatment of acute watery diarrhea. The statistical analysis was carried out using STATA version 14 to reach conclusive results. RESULTS: 175 patients presented with acute watery diarrhea, out of which 106 (60.6%) did not receive antibiotics. The median (IQR) age of the group that did not receive antibiotics was 12.0 (12.0) months compared to 15.0 (12.0) months for the group that did receive antibiotics. In both groups, there were more males than females, less than 15% of the patients were severely malnourished (WHZ score -3SD) and less than 10% of the patients were severely dehydrated. The median (IQR) length of hospital stay (hours) was 32.0 (19.0) respectively for the group that did not receive antibiotic and 41.0 (32.0) for the group that did receive antibiotic therapy. The expected length of hospital stay for the group that received antibiotic therapy was 0.22 hours higher than the group that did not. Finally, as compared to females, hospital stay for males was longer by 0.25 hours. CONCLUSION: In conclusion, antibiotic use was associated with a prolonged hospital stay in children with acute watery diarrhea as compared to children who did not receive antibiotics. Large scale robust prospective studies are needed to establish this association using this observational data.