In Pakistan, most children with life-threatening illnesses present at advanced stages and succumb to death, leaving families emotionally traumatised. Parental bereavement leads to long-term psychosocial and financial hardships for families, thus highlighting the need for bereavement care as a crucial part of paediatric palliative care. This study explores key challenges around lack of bereavement care in the healthcare infrastructure in Pakistan and identifies opportunities to establish this programme for grieving families. This study presents a secondary qualitative analysis derived from a larger parent study exploring parental experiences following the death of a child. Participants included bereaved parents 2–5 years after their child’s death from oncologic or non-oncologic illnesses at Aga Khan University Hospital, Karachi. A qualitative, phenomenological design was implemented, with semi-structured interviews. Data collection continued until thematic saturation was achieved. Thematic analysis was conducted using DeDoose software. Nineteen bereaved parents were interviewed, including parents of children with oncological (n = 10) and non-oncological (n = 9) diseases. No clear thematic differences were observed between parents of children with oncologic and non-oncologic conditions. Parents described gaps in communication with healthcare teams, particularly in receiving emotional support, which led to feelings of isolation. Many faced barriers to accessing psychological care, including limited awareness, cultural stigma, and financial constraints. Parents expressed concerns about siblings struggling silently with grief, highlighting the need for bereavement resources and professional psychological support for them as well. Cultural norms around grief expression were also seen as a challenge, hindering emotional processing, and delaying healing within families. Parents also identified a lack of institutional bereavement care practices, such as a condolence message or note and any educational materials. Bereavement care in Pakistan remains underexplored in the literature. This highlights critical gaps and provides context-specific recommendations for establishing bereavement services based on parental recommendations. Key opportunities for improvement include institutional initiatives for structured bereavement care and addressing societal taboos around grief expression. These changes can foster an environment where bereaved families receive the support they need.

Haematopoietic stem cell transplantation (HSCT) from an HLA-identical sibling is the primary curative therapy for acquired aplastic anemia (AA). Outcomes from large cohorts in low- and middle-income countries (LMIC) are scarce. To evaluate survival outcomes of patients with acquired AA undergoing matched sibling donor (MSD) HSCT in Pakistan and to identify key transplant- and patient-related factors influencing outcomes in a resource-limited, LMIC setting. Multicenter retrospective cohort study. We retrospectively analyzed 596 consecutive patients with acquired AA who underwent HSCT from an HLA-identical sibling donor at seven Pakistani centers between January 2001 and August 2023. Patients receiving haploidentical, unrelated, or other alternative-donor grafts were excluded. Overall survival (OS) was estimated using Kaplan-Meier method. Univariable and multivariable Cox regression identified predictors of OS; logistic regression identified predictors of graft failure. Median age at transplant was 18 yr (IQR:13 to 24), median time to neutrophil and platelet engraftment was 12 d (11 to 14 d) and 19 d (14 to 28 d), respectively. Primary graft failure occurred in 39 (6.6%) and secondary graft failure in 52 (8.8%) patients. Incidence of acute and chronic graft-versus-host disease was 70 (11.2%) and 97 (19%), respectively. At a median follow-up of 59.4 mo (95% CI 47.9 to 68.4), OS was 69.6%. The leading cause of mortality was graft failure and poor graft function in 91 (49.4%) followed by sepsis in 60 (32.6%) patients. On multivariable Cox regression, RCC <20 (adjusted HR 0.43, 95% CI 0.25 to 0.73, P = .002), CSA + MMF prophylaxis (adjusted HR 2.57, 95% CI 1.47 to 4.51, P = .001), and BMH + PBSC stem cell source (adjusted HR 0.61, 95% CI 0.36 to, P = .001) were independent predictors of OS. MSD-HSCT achieves durable survival for AA patients in resource-limited settings. Early referral strategies, infection control, and optimization of graft characteristics are required to improve survival in these settings.

Background: Cisplatin is central to medulloblastoma treatment, but causes ototoxicity in children. Sodium thiosulfate (STS) is a potential otoprotective agent, though evidence from resource limited countries is limited. This study evaluated STS for preventing cisplatin-induced hearing loss in patients with medulloblastoma. Methods: A retrospective study was conducted at Aga Khan University Hospital, comprising children aged 0-18 years, with medulloblastoma treated with cisplatin-based chemotherapy between 2014 and 2024. Patients were grouped into pre-STS (cisplatin alone) and STS (cisplatin plus STS). Pre and post-treatment audiometric and clinical assessments were reviewed, with hearing loss classified as mild, moderate, or severe. A p-value < 0.05 considered statistically significant. Results: Thirty-three patients (Pre-STS: 16, 48.5%; STS: 17, 51.5%) were included with a median age of 9.5 years. Six patients (18.2%) had prior hearing loss. All patients were treated with postoperative craniospinal radiation and cisplatin-containing chemotherapy. Hearing loss was observed in eight patients (50%) within the pre-STS group and in two patients (11.8%) within the STS group. Electrolyte levels remained stable in patients administered STS, with no clinically significant adverse events reported. A total of 8 patients died during follow-up, with similar overall survival observed in the pre-STS and STS groups. Conclusion: STS use with cisplatin was associated with a significant reduction in CIHL in medulloblastoma patients, without added toxicity or adverse survival impact. Its low cost and favorable safety profile make it a valuable otoprotective strategy in resource limited settings. Prospective studies with standardized audiometric follow-up are needed to guide broader implementation.

Introduction Aplastic anemia (AA) is a potentially fatal disorder with a higher reported incidence in low middle income countries (LMICs). Management of AA is challenging in developing countries. Objective The purpose of current study is to document survival outcomes of AA patients receiving MRD HSCT in Pakistan. Methods This is a retrospective multicenter study on behalf of Aplastic Anemia working party of Pakistan Blood and Marrow Transplant (PBMT) group. The study included 716 patients receiving MRD-HSCT between January 2001 – August 2023 from 7 centers. Overall survival (OS) was calculated from diagnosis to the last follow-up or death date. Disease-free survival (DFS) was the time from the diagnosis to relapse or death. Statistical test were applied using Social Sciences (SPSS) version 26. P value <0.05 was considered statistically significant Results The median age at transplant was 18 years (range, 2-55 years) . Median RCC and platelet transfusion at the time of transplant were 14 (0-255) and 30 (0-390) respectively and ferritin levels were 1209 ng/ml (95-18270 ng/ml). Graft versus host disease prophylaxis used was Cyclosporine (CsA) alone in 39.9% and CsA+ methotrexate (MTX) in 47.7% patients. Fludarabine (120-150mg/m2), cyclophosphamide(Cy) 120-160 mg/kg, anti-thymocyte globulin 20 mg/kg was used as conditioning in 52.1% (n-373) patients, Cy 200 mg/kg-ATG 20 mg/kg in 20.4% (n=146) patients. Stem cell source was bone marrow harvest (BMH) in 323 (45.1%), BMH with peripheral blood stem cells(PBSC) in 180 (25.1%) patients and PBSC in 194 (27.1%) patients. Median CD34 dose was 5.25 × 106/kg. Median time to neutrophil engraftment was 13.2 days (9-22 days) and 17 days (13-97 days) for platelet engraftment. Primary graft failure was present in 43 (7.7%) of evaluable 552 patients and secondary graft failure in 66 (12.9%) patients. Among 189 deaths, most common causes of mortality were sepsis in 32% (n=60) and graft failure in 24% (n=45) .Cumulative incidence of acute and chronic GVHD was 10.6% and 19.4% respectively. At median follow-up of 53 months (95% confidence interval [CI], 40.2-70.7), OS was 73.5% while DFS was 71.4%. OS(75.5%) was significantly better for patients receiving BMH+PBSC as graft source as compared to BMH alone(70.4%) and PBSC alone (64.8%), p=.01.Multivariate analysis showed higher mortality for patients not receiving ATG (HR:1.71; 95% CI: 0.95-3.06, P= 0.01), RCC transfusion >30 units (HR,1.34; 95%CI 0.71-2.54, P=0.003) and use of CsA + mycophenolate mofetil as GVHD prophylaxis (HR:2.47; 95%CI:1.46- 4.18, p-0.003). Of 61 evaluable patients, 31 (50.8%) had children post-transplant. Conclusion Allogeneic HSCT remains the treatment of choice for severe and very severe AA in LMICs. Survival outcomes are lower than developed countries and can be improved by better infection control and adopting optimized conditioning regimens.

Pediatric Hodgkin lymphoma (HL) treatment has increasingly shifted toward response-adapted protocols, aiming to minimize radiotherapy and employ intensive chemotherapy such as OEPA/COPDAC. We retrospectively reviewed treatment outcomes and toxicities in pediatric HL patients treated with OEPA/COPDAC between 2015 and 2019 at a tertiary care center in Pakistan, a resource limited country, following the Euronet PHL-C1 protocol with radiotherapy reserved for inadequate interim responses. Clinical features, treatment-related toxicities, and hospital admissions were documented. The cohort included 20 patients with a median age of 12 years; 13 (65%) achieved complete remission after OEPA induction and avoided radiotherapy. Toxicities were frequent-15 (75%) after OEPA-1 and 13 (68%) after OEPA-2-most commonly gastrointestinal symptoms and febrile neutropenia. Hospitalization was required in 9 (45%) after the first cycle and 11 (58%) after the second, with one treatment-related death from febrile neutropenia. At median follow-up, overall survival was 95% (95% CI: 69.47-99.28%) and event-free survival was 85% (95% CI: 60.38-94.90%). These findings highlight that OEPA/COPDAC achieves high survival rates even in advanced-stage pediatric HL within low-resource settings. However, the substantial toxicity burden and frequent hospitalizations underscore the need for enhanced supportive care and further evaluation in larger, long-term studies.

Objectives: To evaluate bleeding events, mortality, recurrence and prescribing practices in paediatric and adolescent patients of venous thromboembolism using direct acting oral anticoagulants (DOACs). Method: The descriptive, retrospective study was conducted from November 2021 to May 2022 at the Aga Khan University Hospital and comprised data from 2017 to 2021 of patients from birth to 18 years who received DOACs for prophylaxis or treatment purposes of venous thromboembolism. Data was analysed using STATA MP.15. Results: Of the 45 patients, 37(82.2%) were males and 8(17.8%) were females. The overall median age was 16 years (interquartile range: 12.5-18 years). Of the total, 33(73.3%) patients were treated for acute venous thromboembolism, while 12(26.7%) received anticoagulants as prophylaxis. Complete thrombus resolution was achieved in 15(45.5%) patients, partial resolution in 3 (9.1%), and no resolution in 4(12.1%). Recurrence of venous thromboembolism occurred in 2(6%) patients. Enoxaparin was prescribed in 24(53.3%) cases, rivaroxaban in 14(31.1%) and heparin in 7(15.6%). There were 13(28.9%) deaths in the cohort. Conclusion: Rivaroxaban may be safe in the management of paediatric venous thromboembolism, with no major bleeding complications observed in our study. Key Words: Rivaroxaban, Direct oral anticoagulants, Paediatric, Low middle-income country.

BACKGROUND: Globally, almost 40% of children < 5 years of age suffer from anemia, according to the World Health Organization (WHO) report. Children admitted to noncritical hospital settings may be overlooked for evaluation of anemia while getting treatment for their medical and surgical issues. AIMS: This study aimed to evaluate the frequency, clinical associations, and complications of anemia in pediatric patients in noncritical care settings. MATERIALS AND METHODS: This retrospective cohort study was conducted at an academic medical center hospital in Pakistan. In 2023, patients aged 2–18 and both sexes were studied for anemia and its severity using WHO-defined hemoglobin cutoffs. The clinical and laboratory details were collected through an in-house computerized system and analyzed through SPSS v19. RESULTS: We scanned 3001 admitted children, and 346 (11.5%) were anemic, with moderate anemia in 204/346 (59%). Hypochromic microcytic anemia was the most frequent (n = 189 or 54.6%). Children between 5 and 11 years were the predominant group (126/346 or 36%) suffering from anemia. Evaluation of anemia was conducted in only 75/346 (21.6%), and treatment was given to 106/346 (30.6%) patients. Median (IQR1-3) hemoglobin in patients (n = 77) who received red cell transfusions was significantly less (8.6 g/dl (7.7–9.7) compared to those who did not (10.6 g/dl [9.6–10.9] (P = 0.000). CONCLUSIONS: Our findings highlight that pediatric anemia remains underrecognized and undertreated in noncritical hospital settings, particularly among children aged 5–11 years. The lack of evaluation or treatment in two-thirds of cases underscores an urgent need for systematic screening protocols and targeted guidelines to improve anemia management in similar healthcare environments.

Pediatric liver masses encompass a diverse spectrum of benign and malignant lesions, with distinct patterns based on patient age. Optimal imaging is critical for timely diagnosis, management, and prognosis. This pictorial minireview categorizes pediatric liver masses by age group to guide hepatology and radiology practice, with an emphasis on imaging characteristics. In children from birth to six years of age, the most common liver masses include hepatoblastoma, the most common primary hepatic malignancy in this age group; infantile hemangioma, a benign vascular tumor with a characteristic appearance on imaging; and mesenchymal hamartoma, a rare developmental lesion. For children older than six years, liver masses are distinct, with hepatocellular carcinoma being the predominant malignant lesion. Benign masses such as focal nodular hyperplasia and hepatocellular adenoma also emerge in this age range, often linked to hormonal influences or metabolic disorders. The masses observed across all pediatric age groups include hepatic cysts, choledochal cysts, hydatid cysts, pyogenic and amebic abscesses, tuberculosis, lymphoma, and metastases, each presenting with unique imaging features essential for differential diagnosis. This minireview provides a comprehensive, age-based overview of pediatric liver masses, focusing on clinical presentation and key imaging findings to support accurate diagnosis and optimize management strategies in clinical hepatology, particularly in low resource settings.

Pediatric thrombocytopenia is frequently observed in critical care and oncology settings with an increased risk of bleeding and platelet transfusions. However, little is known about low platelets in childhood during seasonal influence. This study aimed to evaluate the frequency and severity of pediatric thrombocytopenia in the postflood period. The patients 1 to 18 years of age with thrombocytopenia (platelet count <150×109/L) were studied from August to December 2022 after institutional ethical approval (ERC-Path-2022-8044-23395). Data was collected from electronic health records and laboratory information systems. Of 2318 admitted patients, 192 (8.3%) including 128 males and 64 females had thrombocytopenia. The median (IQR) age was 12 (8 to 15) years. Mild, moderate, and severe thrombocytopenia were seen in 109 (56.8%), 76 (39.5%), and 7 (3.6%) patients, respectively. Concomitant leucopenia was observed in 77 of 192 patients (40.1%). Infection was the predominant cause of low platelets (N=175 or 91.1%). Only 15 patients (7.8%) had grade 1/2 bleeding. Overall, 176 patients (92%) were discharged in stable conditions and no mortality was observed. The frequency of pediatric thrombocytopenia in the noncritical and nononcological care settings was <10% and mostly observed in association with underlying infections. The frequency of bleeding manifestation and platelet transfusions was minimal in this group.

BACKGROUND:microRNAs regulate various cellular pathways and may serve as medium-term prognostic markers in neurocognitive function, as suggested by adult studies. However, no comparable data exist for children with central nervous system tumors. This pilot study explored miRNA expression and its correlation with 12-month posttreatment neurocognitive function in children and young adults (5-21 years) with primary brain tumors. METHODS:The study was conducted at Aga Khan University Hospital and Jinnah Postgraduate Medical Center (November 2020 to July 2023). This study analyzed serum levels of miR-21, miR-146a, miR-296-5p, miR-210, and miR-10b using reverse transcriptase quantitative PCR. Neurocognitive assessments using Slosson Intelligence Test, Raven's Progressive Matrices, and Wechsler Intelligence Scale were performed at pretreatment and 12 months posttreatment. The paired t-test was used to assess miRNA expressions, and correlation analysis assessed relationships between pretreatment miRNA expression and neurocognitive outcomes. RESULTS:Of the 48 patients, serum samples were available for analysis from 34 (71%) patients each at pretreatment and 48 hours post-surgery, and 13 (27%) patients at 12 months posttreatment. A statistically significant negative correlation was found between pretreatment miR-210 levels and perceptual reasoning scores at 12 months posttreatment (ρ=-0.59), and a positive correlation between pretreatment miR-10b levels and processing speed scores (ρ=0.49). However, there were no differences in microRNA expressions between pretreatment and 48 hours post-surgery (n=34), pretreatment and 12 months posttreatment (n=13), or 48 hours post-surgery and 12 months posttreatment. CONCLUSION:This pilot exploratory study found two statistically significant correlations: a negative correlation between pretreatment miR-210 levels and 12 months posttreatment perceptual reasoning scores and a positive correlation between miR-10b expression and 12 months posttreatment speed scores. Further studies are needed to understand the protective or restorative function of miR-10b in cognitive processes and the detrimental role of miR-210 in cognitive processes to evaluate their potential future use as prognostic biomarkers for neurocognitive outcomes in children and young people with primary brain tumors.

Moyamoya disease (MMD) is a rare, chronic cerebrovascular disorder involving progressive bilateral stenosis of the internal carotid artery and its branches, forming abnormal collateral networks that appear as a “puff of smoke” on angiography. While the term MMD is used when the condition is idiopathic, it is called moyamoya syndrome (MMS) when associated with underlying systemic conditions. Reports of MMS with β-thalassemia major are rare, with fewer than 6 cases documented; herein, we report a case of a 6-year-old female, a known case of β-thalassemia major, who exhibited left-sided hemiparesis, revealing radiological and clinical features consistent with MMS. MRI, CTA, EEG, and Echocardiography were used as diagnostic workups to confirm the diagnosis. The patient was treated with hyper-transfusion therapy and pharmacological management, with an ongoing consideration of surgical intervention. The rarity of the occurrence of moyamoya syndrome in β-thalassemia major patients has been discussed, with emphasis on the importance of early recognition and intervention to mitigate neurological complications. This case contributes to the limited literature on β-thalassemia major and MMS occurring together, underscoring the need for heightened clinical awareness and timely management strategies.