Pneumopericardium in a child - "halo sign" on chest x-ray: A Case Report.

A 5 year old boy with acute ly mphoblastic leukaemia on chemotherapy presented with chest pain and vomiting for two days after an elective procedure under general anaesthesia. H is ches t x-ray was remarkabl e for a promin ent halo sign, an air gap surrounding the he art indicat ing a large pneumope ricardium. Alth ough the pneu mo pericardium could not be appre ciated on an echocardiogram, the child developed clinical sig ns of cardiac t amponade. Attem pts to evacu ate the pneumopericardium were unsuccessful leading to death.

Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study.

BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and aggressive cancer predisposition syndrome. Because a scarcity of data on this condition contributes to management challenges and poor outcomes, we aimed to describe the clinical spectrum, cancer biology, and impact of genetics on patient survival in CMMRD. METHODS: In this cohort study, we collected cross-sectional and longitudinal data on all patients with CMMRD, with no age limits, registered with the International Replication Repair Deficiency Consortium (IRRDC) across more than 50 countries. Clinical data were extracted from the IRRDC database, medical records, and physician-completed case record forms. The primary objective was to describe the clinical features, cancer spectrum, and biology of the condition. Secondary objectives included estimations of cancer incidence and of the impact of the specific mismatch-repair gene and genotype on cancer onset and survival, including after cancer surveillance and immunotherapy interventions. FINDINGS: We analysed data from 201 patients (103 males, 98 females) enrolled between June 5, 2007 and Sept 9, 2022. Median age at diagnosis of CMMRD or a related cancer was 8·9 years (IQR 5·9-12·6), and median follow-up from diagnosis was 7·2 years (3·6-14·8). Endogamy among minorities and closed communities contributed to high homozygosity within countries with low consanguinity. Frequent dermatological manifestations (117 [93%] of 126 patients with complete data) led to a clinical overlap with neurofibromatosis type 1 (35 [28%] of 126). 339 cancers were reported in 194 (97%) of 201 patients. The cumulative cancer incidence by age 18 years was 90% (95% CI 80-99). Median time between cancer diagnoses for patients with more than one cancer was 1·9 years (IQR 0·8-3·9). Neoplasms developed in 15 organs and included early-onset adult cancers. CNS tumours were the most frequent (173 [51%] cancers), followed by gastrointestinal (75 [22%]), haematological (61 [18%]), and other cancer types (30 [9%]). Patients with CNS tumours had the poorest overall survival rates (39% [95% CI 30-52] at 10 years from diagnosis; log-rank p<0·0001 across four cancer types), followed by those with haematological cancers (67% [55-82]), gastrointestinal cancers (89% [81-97]), and other solid tumours (96% [88-100]). All cancers showed high mutation and microsatellite indel burdens, and pathognomonic mutational signatures. MLH1 or MSH2 variants caused earlier cancer onset than PMS2 or MSH6 variants, and inferior survival (overall survival at age 15 years 63% [95% CI 55-73] for PMS2, 49% [35-68] for MSH6, 19% [6-66] for MLH1, and 0% for MSH2; p<0·0001). Frameshift or truncating variants within the same gene caused earlier cancers and inferior outcomes compared with missense variants (p<0·0001). The greater deleterious effects of MLH1 and MSH2 variants as compared with PMS2 and MSH6 variants persisted despite overall improvements in survival after surveillance or immune checkpoint inhibitor interventions. INTERPRETATION: The very high cancer burden and unique genomic landscape of CMMRD highlight the benefit of comprehensive assays in timely diagnosis and precision approaches toward surveillance and immunotherapy. These data will guide the clinical management of children and patients who survive into adulthood with CMMRD. FUNDING: The Canadian Institutes for Health Research, Stand Up to Cancer, Children's Oncology Group National Cancer Institute Community Oncology Research Program, Canadian Cancer Society, Brain Canada, The V Foundation for Cancer Research, BioCanRx, Harry and Agnieszka Hall, Meagan's Walk, BRAINchild Canada, The LivWise Foundation, St Baldrick Foundation, Hold'em for Life, and Garron Family Cancer Center.

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.

Antimicrobial sensitivity patterns of enteric fever in Pakistan: a comparison of years 2009 and 2019.

BACKGROUND: Pakistan is one of the endemic regions for typhoid fever and paratyphoid fever. This study aimed to identify the evolving antimicrobial sensitivity patterns of Salmonella species causing enteric fever and its implications on the clinical prescribing of antimicrobials. METHODS: This was a retrospective descriptive study conducted at a university hospital. Antimicrobial resistance was defined in terms of non-resistant, multidrug resistant (MDR) and extended drug resistant (XDR) as per WHO guidance. Data were collected from the years 2009 and 2019. Chi squared was applied to test for statistical significance (p < 0.05). RESULTS: A total of 200 patients (100 from 2009 and 100 from 2019) were included in the study. Non-resistant enteric fever cases reduced from 100% in 2009 to 44% in 2019, whereas the MDR and XDR enteric fever cases increased to 16% and 40%, respectively (p < 0.05). Cross tabulation carried out for individual drugs showed an independent rise in the sensitivities of individual first-line antimicrobials. CONCLUSION: Antimicrobial resistant enteric fever has become a big challenge for Pakistan. The choice of antibiotic prescription has narrowed down to broader spectrum antimicrobials making it difficult to treat, leading to increased morbidity and mortality.

An Unusual Presentation of a Patient with Leg Ulcers: A Case Report.

Leg ulcers have been a common presentation in clinics; disruptions in the mechanism of ulcer healing are vascular insufficiency, anemia, metabolic disturbances, neuropathy, and autoimmunity. The term 'non-transfusion-dependent thalassemia' encompasses the milder forms of thalassemia traits that require intermittent or no transfusion at all, and are mostly associated with leg ulcers. We present the case of a 19-year-old female with beta-thalassemia major who presented with non-healing leg ulcers and anemia. The clinical findings and lab evidence suggested hemolytic anemia evidenced by pathologic fractures, hepato-splenomegaly, and normal iron studies. Hemoglobin electrophoresis confirmed beta-thalassemia major with its complications including adrenal insufficiency and pathological fractures, all of which remained well compensated till the second decade of life.

Correlation Between Neck Circumference and Gestational Diabetes Mellitus and Associated Risk Factors During Pregnancy.

Introduction Due to normal physiological changes in various anthropometric indices during pregnancy, the routine measurements of body weight, height, waist circumference, and waist-to-hip ratio are deemed inappropriate in predicting obesity and risk of gestational diabetes mellitus in pregnancy. Neck circumference is a novel marker to determine the risk of gestational diabetes in pregnancy. We conducted this study to determine the correlation between neck circumference and gestational diabetes mellitus and its associated risk factors. Methods This was an observational, cross-sectional study conducted at Jinnah Allama Iqbal Institute of Diabetes and Endocrinology (JAIDE), Allama Iqbal Medical College/ Jinnah Hospital, Lahore from July 2017 to March 2018. Pregnant females at 16 weeks of gestation underwent measurement of weight, height, body mass index, neck, and waist circumference. At the 24th gestational week, an oral glucose test was conducted and fasting lipid profile, serum albumin, and uric acid were measured. Pearson's correlation was used to see any correlation between neck circumference and gestational diabetes and its associated risk factors. Results There were 90 subjects in the study with a mean age 30.8 ± 3.2 (range: 26 - 34) years. The waist and neck circumference at 16 weeks of gestation measured 104.2 ± 9.0 cm and 36.1 ± 2.8 cm, respectively. Age, weight, waist circumference, and body mass index were positively and significantly correlated with neck circumference (p-value < 0.05). After adjusting for age, the correlation between neck circumference and weight, waist circumference, and body mass index (BMI) was statistically significant with a p-value < 0.05. Analysis of the receiver operating curve revealed that the cut-off value of neck circumference for predicting gestational diabetes was 35.70 cm with a sensitivity of 51.4% and specificity of 81.2%. Conclusion Neck circumference at the 16th gestational week is a reliable and valid tool to predict gestational diabetes mellitus at 24 weeks of gestation.