Thesis/Dissertation Repository Medical and Dental College

COMPARISON OFARTERIAL ANDVENOUSGRAFTSINCORONARY ARTERY BYPASSGRAFT(CABG)SURGERYPATIENTSASSESSEDON COMPUTEDTOMOGRAPHYANGIOGRAPHY(CTA)

Mon, 01 Dec 2025 00:00:00 GMT

COMPARISON OFARTERIAL ANDVENOUSGRAFTSINCORONARY ARTERY BYPASSGRAFT(CABG)SURGERYPATIENTSASSESSEDON COMPUTEDTOMOGRAPHYANGIOGRAPHY(CTA) DRAREEBAYOUNUSFAROOQUI (06-113232-001) Coronary artery bypass grafting (CABG) remains the gold standard for the treatment of multivessel coronary artery disease, yet long-term success largely dependsongraft patency. Arterial conduits such as the left internal thoracic artery (LITA) offer superior durability, whereas venous grafts like the saphenous vein graft (SVG) are more prone to stenosis, occlusion, and aneurysmal changes. Regional data from South Asia remain scarce, particularly regarding the comparative outcomes of arterial and venous grafts and the influence of demographic, clinical, and anatomical factors. This study aimed to evaluate graft patency and long-term outcomes in post-CABG patients using multidetector computed tomography angiography (MDCTA), with a specific focus on graft type, anatomical parameters, comorbidities, and sociodemographic influences. This study adopted a cross-sectional prospective design and was conducted at the National Institute of Cardiovascular Diseases (NICVD) Karachi, Tando MuhammadKhan(TMK),Sukkur, and the Neurospinal and Cancer Care Institute (NCCI), in collaboration with the Bahria University Health Sciences Campus Karachi (BUHSCK). A purposive sample of 59 post-CABG patients, aged 35–79 years, who presented to the emergency room or outpatient department with cardiac symptoms such as chest pain, dyspnea, or arrhythmias, was included. Patients underwent (MDCTA) using a 128-slice Siemens SOMATOM Definition Edge scanner to assess graft patency, stenosis, or occlusion. Clinical and demographic data, comorbidities, echocardiographic findings (mitral and aortic regurgitation, Left Ventricular End Diastolic diameter (LVED), and extracardiac anatomical parameters (pericardial thickness, sternal–RV distance, and cardiac xi dominance) were recorded. Patient preparation included fasting, beta-blockers, and sublingual nitroglycerin as appropriate, with iohexol contrast administered intravenously. Image reconstruction and analysis were performed using syngo.via software with multiplanar and 3D techniques to evaluate graft lumen status and measure luminal diameters. Ethical approval was obtained from institutional review boards, and informed consent was secured from all participants. The study duration spanned two years, with data collection over seven months and subsequent analysis. Among arterial grafts, LITA demonstrated superior long-term patency, with only 8.6% showing occlusion or calcification, compared to 33.6% of venous grafts. Venous grafts were more frequently stenosed (42.1%) and demonstrated a higher prevalence of aneurysmal or ectatic changes compared to arterial conduits. Patient demographics revealed a male predominance (89.7%), and middle socioeconomic groups comprised the majority (56%). Age significantly influenced venous graft status, with patients aged 60–69 years showing the highest rates of stenosis (45.7%). Comorbidities, particularly diabetes, hypertension, and their combinations, demonstrated a significant association with venous graft occlusion (p=0.013). Continuous variable analysis revealed that arterial graft diameters averaged 1.95–2.0 mm, while venous grafts averaged 2.1–2.3 mm, with venous diameters varying more widely. BMI and LVED values showed modest but important associations with graft outcomes; higher BMI correlated with venous graft stenosis, while LVED remained relatively preserved across groups. Extracardiac changes such as increased pericardial thickness (>4 mm) and greater sternal distances showed trends toward association with venous graft failure but did not reach strong statistical significance. Importantly, anatomical site of anastomosis was strongly linked with graft outcome. Distal anastomoses showed the highest proportion of patent grafts (50.8%), whereas middle and marginal sites were more frequently stenosed or occluded (p<0.001). Native coronary vessels also demonstrated progression of atherosclerosis post-CABG, with venous graft-dependent territories showing higher calcification and mid xii segment stenosis. This study highlights the superior long-term outcomes of arterial grafts compared to venous grafts in South Asian post-CABG patients, reinforcing the importance of arterial-first strategies in surgical planning. MDCTA proved to be a reliable, noninvasive modality for long-term graft surveillance. The inclusion of clinical, demographic, and anatomical predictors—such as graft diameter, LVED, BMI, pericardial thickness, and site of anastomosis—adds novelty and practical value to patient-specific follow-up. As the first multicenter study in Pakistan to assess graft patency in relation to sociodemographic and anatomical factors, these findings emphasize the need for individualized surgical strategies, closer monitoring of venous grafts, and long-term region-specific follow-up programs. Supervised by Prof. Dr. Yasmeen Mahar

DIFFERENTIAL EXPRESSION OF LGR5 AND ITS DIAGNOSTIC SIGNIFICANCE IN NEOPLASTIC AND NON –NEOPLASTIC COLORECTAL LESIONS

Mon, 01 Dec 2025 00:00:00 GMT

DIFFERENTIAL EXPRESSION OF LGR5 AND ITS DIAGNOSTIC SIGNIFICANCE IN NEOPLASTIC AND NON –NEOPLASTIC COLORECTAL LESIONS DR MARVI ZIA (06-114232-003) Cancer stem cells (CSCs) play a major role in development, progression and in aggressive chemo-resistant behavior as they provide a continuous pool for clonal proliferation of malignant cells. LGR5, one of the most important stem cell marker is implicated very early in metamorphosis of malignant transformation. LGR5 is directly involved in cell proliferation through its effects on Wnt- β catenin pathway. In this cross- sectional study we used 109 formalin fixed paraffin embedded (FFPE) tissue samples and evaluated immuno-reactive score (IRS) of LGR5 expression in normal colonic mucosa, adenomas and colorectal cancer tissue samples. Association between LGR5 expression and various clinico-pathological parameters including grade, stage and lymph-node metastasis was assessed .The comparison of mean LGR5 IRS scores across non-neoplastic tissue, adenomas, and carcinomas was done . A binary logistic regression was performed to examine the association of LGR5 expression (high vs. low) with lesion type, T stage, N stage, and histological grade. Results: Histological type and tumour grade significantly influence LGR5 expression. Conventional Adenocarcinomas and well differentiated Grade 1 tumours exhibited strong LGR5 expression followed by moderately differentiated (Grade 2) tumors, as compared to mucinous and signet ring cell variants and poorly differentiated tumours Grade 3(p <0.001). There was a statistically significant difference in mean IRS scores among the three groups (p < 0.001). The highest mean IRS score was observed in adenomas (mean = 9.42 ± 3.06), followed by carcinomas (6.12 ± 3.62), whereas non-neoplastic tissues exhibited the lowest mean IRS score (2.15 ± 2.02). The patients with Non-Neoplastic Lesions were less likely to have high LGR5 expression (OR=0.077, p<0.001) in comparison to patients with neoplastic lesions. The study identified higher IRS score for LGR5 expression in colorectal cancers and adenoma as compared to normal mucosa, thus identifying it as a marker of neoplastic transformation. Increased LGR5 expression in adenomas and grade 1 CRC identified this stem cell marker as a significant diagnostic marker useful for early neoplastic lesion. Decline of LGR5 expression in poorly differentiated tumours verified it as a marker of poor prognosis. Supervised by Prof. Dr. Sumayyah Shawana

CLINICAL EFFICACY AND SAFETY OF GLIMEPIRIDE, EMPAGLIFLOZIN AND SITAGLIPTIN WITH METFORMIN IN TYPE 2 DIABETES MELLITUS: A DOUBLE AND TRIPLE DRUG THERAPY

Mon, 01 Dec 2025 00:00:00 GMT

CLINICAL EFFICACY AND SAFETY OF GLIMEPIRIDE, EMPAGLIFLOZIN AND SITAGLIPTIN WITH METFORMIN IN TYPE 2 DIABETES MELLITUS: A DOUBLE AND TRIPLE DRUG THERAPY DR SAIMA CHANDIO (06-115232-001) Type 2 diabetes mellitus (T2DM) is a growing global health challenge, imposing significant disease burden and economic strain. In Pakistan, the situation is particularly alarming. According to the most recent IDF Atlas (2025), approximately 34.5 million adults (aged 20–79 years) are affected in Pakistan, with an age-standardized prevalence of 31.4%, the highest in the world. This escalating prevalence underscores the urgent need for effective treatment strategies tailored to the local population. The present study was designed to evaluate and compare the clinical efficacy and safety profiles of initial double and triple combination regimens in treatment-naïve patients with T2DM. After obtaining approval from the Institutional Review Board of Bahria University Health Sciences, Karachi (IRB- BUHSCK), this open-labeled, parallel-arm, randomized clinical trial was conducted at the Diabetic Clinic of the National Medical Center, Karachi. A total of 172 diagnosed type 2 diabetic patients (males and females, aged 30–55 years) meeting inclusion criteria were enrolled through randomization via the sealed-envelope method. Participants were allocated into four parallel treatment arms 43 in each: Group A received Metformin 500 mg + Glimepiride 2 mg (fixed-dose combination, FDC); Group B received Metformin 500 mg + Empagliflozin 12.5 mg (FDC); Group C received Metformin 500 mg + Sitagliptin 50 mg (FDC); and Group D received Metformin 500 mg + Empagliflozin 12.5 mg (FDC) + Sitagliptin 50 mg once daily, in addition to lifestyle modifications. 150 patients successfully completed the study (Group A: 34; Group B: 38; Group C: 37; Group D: 41). Of 90 days, with assessments at baseline, day 45, and day 90. The primary endpoint was a reduction in HbA1c of at least ≥1% from baseline to day 90, while secondary outcomes included changes in fasting and random blood sugar, body weight, and lipid profile. Safety outcomes were evaluated through hematological, hepatic, renal, and cardiovascular profiles, while adverse effects were also monitored. Results demonstrated that all four groups achieved statistically significant glycemic improvement (p < 0.001). The greatest HbA1c reduction was observed in Group D (–1.57%), followed by Group A (–1.34%), Group B (–1.11%), and Group C (– 1.00%). Participants maintained self-monitoring weekly diaries, and assessments was done on week 6 and 12. It was hypothesized that initial triple therapy would viii achieve superior glycemic reduction and metabolic benefits compared with double- drug combinations. The triple combination (Group D: metformin + empagliflozin + sitagliptin) provided the most comprehensive benefits, improving anthropometric, glycemic, lipid, hepatic, and renal parameters. Among the dual regimens, Group A (metformin + glimepiride) achieved superior glycemic control with modest lipid improvements, while Group B (metformin + empagliflozin) was more effective for weight and triglyceride reduction with favorable effects on HDL and renal function. Group C (metformin + sitagliptin) showed the least efficacy but remained well tolerated. Overall, treatment effects followed: Group D > Group A ≈ Group B > Group C, confirming triple therapy as the most balanced strategy while dual therapies offer targeted benefits that can be individualized Supervised by Prof. Dr. Nasim Karim

“TO EVALUATE THE ASSOCIATION BETWEEN NAFLD/NASH IN PREDIABETES AND TYPE 2 DIABETES MELLITUS WITH NON-INVASIVE BIOMARKERS.”

Mon, 01 Dec 2025 00:00:00 GMT

“TO EVALUATE THE ASSOCIATION BETWEEN NAFLD/NASH IN PREDIABETES AND TYPE 2 DIABETES MELLITUS WITH NON-INVASIVE BIOMARKERS.” DR.ZAKIA NASEEM 06-117232-001 Hepatic steatosis, or the buildup of extra fat in the liver, is a hallmark of nonalcoholic fatty liver disease (NAFLD), a group of liver disorders that affect people who drink little or no alcohol. Metabolic risk factors like obesity, insulin resistance, type 2 diabetes, and dyslipidemia are frequently linked to it. NAFLD is usually diagnosed when fat accumulation is <5% in hepatocytes. In addition to fat accumulation, NASH, the more serious kind of NAFLD, additionally comprises injury to hepatocytes and liver inflammation, with or without fibrosis. Hepatocellular carcinoma, cirrhosis, and severe fibrosis can develop from NASH. The World Health Organization (WHO) estimates that 642 million adults worldwide will have diabetes mellitus (DM) by 2040, rising from the 422 million adults who had it in 2014.T2DM is a substantial contributor to morbidity and mortality and places a heavy financial strain on the healthcare systems of the world . It is characterized by a combination of inherited and environmental factors that results in relative insulin insufficiency and insulin resistance. NAFLD AND T2DM both are highly prevalent disease worldwide. According to research both have a strong relation .there are many studies that proven the relation between them globally, nonetheless, there are still discrepancies in research and clinical awareness, particularly in low- and middle-income countries, like Pakistan. We aim to detect the prevalence of NAFLD or NASH in T2DM and pre-diabetic patients. The study was conducted in NMC hospital located in Karachi, Pakistan. The patients were enrolled from the diabetic clinic, after consent was taken , questionnaire was filled with vitals and anthropometric measurement was taken ,the patient then send for blood sampling followed by ultrasound abdomen. According to our study we found that Prevalence of non-alcoholic fatty liver disease was 17.9% and 82.1% among pre-diabetes and diabetes patients respectively whereas prevalence of Non alcoholic steatohepatitis was 0% and 100% among pre-diabetes and diabetes patients respectively. We found significant association of non-alcoholic steatohepatitis with age group. Additionally, We found significant difference for age (p<0.001), LDL (p=0.006), ALT (p<0.001), AST (p<0.001) and ALT/AST ratio (p<0.001) according to non alcoholic fatty liver disease. Supervised by Prof,Dr.Shazia Shakoor