Background and Objective: Mutations in the CYB5R3 gene cause reduced NADH-dependent cytochrome b5 reductase enzyme function and consequently lead to recessive congenital methemoglobinemia (RCM). RCM exists as RCM type I (RCM1) and RCM type II (RCM2). RCM1 leads to higher methemoglobin levels causing only cyanosis, while in RCM2, neurological complications are also present along with cyanosis. Materials and Methods: In the current study, a consanguineous Pakistani family with three individuals showing clinical manifestations of cyanosis, chest pain radiating to the left arm, dyspnea, orthopnea, and hemoptysis was studied. Following clinical assessment, a search for the causative gene was performed using whole exome sequencing (WES) and Sanger sequencing. Various variant effect prediction tools and ACMG criteria were applied to interpret the pathogenicity of the prioritized variants. Molecular dynamic simulation studies of wild and mutant systems were performed to determine the stability of the mutant CYB5R3 protein. Results: Data analysis of WES revealed a novel homozygous missense variant NM_001171660.2: c.670A > T: NP_001165131.1: p.(Ile224Phe) in exon 8 of the CYB5R3 gene located on chromosome 22q13.2. Sanger sequencing validated the segregation of the identified variant with the disease phenotype within the family. Bioinformatics prediction tools and ACMG guidelines predicted the identified variant p.(Ile224Phe) as disease-causing and likely pathogenic, respectively. Molecular dynamics study revealed that the variant p.(Ile224Phe) in the CYB5R3 resides in the NADH domain of the protein, the aberrant function of which is detrimental. Conclusions: The present study expanded the variant spectrum of the CYB5R3 gene. This will facilitate genetic counselling of the same and other similar families carrying mutations in the CYB5R3 gene.

Wheat pill (zinc or aluminum phosphide) is used as rodenticide in wheat and rice storage reservoirs also known as rice pill. In developing countries like Pakistan there has been an increase in the number of aluminum phosphide (wheat-pill) poisoning with suicidal intent due to easy accessibility. It has high mortality rate, with no antidote available. A young female presented with wheat pill poisoning in June 2019, upon arrival she had classical signs and symptoms of wheat pill poisoning although during her stay she developed cardiac arrythmias leading to shock, Hematuria, Pleural effusion, and hyperglycemia due to acute pancreatitis. Due to the appropriate recognition and management of complications, patient was able to recuperate. felicitous transfer to Intensive Care Unit and prompt recognition of complications can lead to virtuous outcomes. We recommend that there should be nationwide cognizance campaign regarding the lethal consequences of wheat-pill consumption by humans and proper Continuous...

Background: The present study was designed to assess the comparative performance of the Simplified Acute Physiology Score III (SAPS III) and sequential organ failure assessment (SOFA) score in predicting mortality among critically ill ICU patients. Methodology: A cross-sectional study was conducted from January 2019 to December 2019, including 162 patients admitted to the medical intensive care unit (ICU) of PIMS, Islamabad. The SOFA and SAPS III scores were calculated for all patients on admission. Outcome parameters included death or discharge from the hospital and disability. The receiver operating characteristic (ROC) curve was constructed for the studied models, and the scores were correlated with mortality. Results: The overall mortality rate in the studied population was 46.9%. The mean SAPS III and SOFA scores were 55.26±18.46 and 14.41±5.67, respectively. The area under the ROC curve (aROC) for the SAPS III was 0.71 at a cut-off value of 43.5, whereas the aROC for SOFA was 0.64 at a cut-off score of 12.5. The ROC curve for predicting hospital mortality exhibited that both SAPS III and SOFA scores were sensitive predictors of mortality, given SAPS III had relatively better prediction (85%) compared to SOFA (76%). Conclusion: It is concluded that SAPS III and SOFA scores are sensitive predictors of mortality; however, SAPs score is better at predicting mortality than SOFA score.

Objective: To determine the quality of life of stroke survivors and their caregivers presenting to tertiary care setup. Method: The descriptive study was conducted from July to December 2019 at the Neurology Department, Pakistan Institute of Medical Sciences, Islamabad, Pakistan, and comprised patients of either gender with ischemic or haemorrhagic stroke aged 40-70 years and their caregivers. Data was collected using the stroke-specific quality of life Scale and the caregiver quality of life questionnaire. Data was analysed using SPSS 20. Results: Of the 80 patients, 50(62.5%) were males and 30(37.5%) were females. The overall mean age was 61.46±11.80 years, and 56(70%) were aged >55 years. Among the patients, speaking power, mobility and mood were more affected with mean levels of 15.51±8.63, 22.63±8.33 and 19.08±7.05, respectively. The domains of social role, self-care and upper extremity function were also affected with mean values of 19.022±7.06, 15.71±8.81 and 18.88±7.02, respectively. Among the caregivers, the levels physical wellbeing and functional wellbeing were high 15.07±5.65 and 15.35±5.76, respectively. There were differences in terms of age and gender but the difference was not significant (p>0.05). Conclusion: The quality of life of stroke survivors was low, and that of caregivers was also quite compromised. Key Words: Haemorrhagic stroke, Ischemic stroke, Caregivers, Quality of life, SSQOL, CQLQ, Stroke survivors.

A descriptive, cross-sectional study, was conducted in the Department of Internal Medicine and Ophthalmology, Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from May to November 2018. The aim was ot ascertain the frequency of elevated serum lipids and diabetic retinopathy; and compare the serum lipid levels with severity of diabetic retinopathy among Type II diabetic patients. A total of 262 patients having Type II diabetes aged 35 to 65 years were included. Patients were characterised into three groups of desirable, borderline, and high-risk, based on the serum lipid profile. Direct fundoscopy/slit lamp examination was steered, and they were graded according to the severity of diabetic retinopathy. There were 42.7% and 57.3% men and women, respectively, with mean age of 52.21 years. Among the patients, 17.2% had mild, 38.9% had non-proliferative diabetic retinopathy (NPDR) and 16.4% had severe proliferative diabetic retinopathy (PDR). Only, 21.8% patients had normal lipid level and 27.5% had severe dyslipidemia. Gender did not have association with the advancement of diabetic retinopathy. However, age and hyperlipidemia showed significant association with the development and severity of diabetic retinopathy. Several risk factors play a vital role in the development, morbidity, and progression of diabetic eye disease. Age and dyslipidemia are signifi-cant factors in the severe disease.