Asad Saulat Fatimi

The aortic arch remains one of the most complex segments of the thoracic aorta to treat, demanding strategies that safeguard cerebral and spinal perfusion while achieving durable proximal and distal repair. Contemporary management strategies include open hemi/total arch replacement, hybrid approaches such as frozen elephant trunk (FET) or debranching with thoracic endovascular aortic repair (TEVAR), and fully endovascular repair using branched or fenestrated devices. Updated guidelines (American College of Cardiology/American Heart Association [ACC/AHA] 2022; European Society of Cardiology [ESC] 2024) emphasize multidisciplinary, patient-specific decision-making grounded in standardized imaging, genetics, and lifelong surveillance. Procedurally, selective antegrade cerebral perfusion with moderate-to-low hypothermia has replaced routine deep hypothermic circulatory arrest for most open arch operations. Zone-based planning using Ishimaru’s map, complemented by the Modified Arch Landing Areas Nomenclature (MALAN), improves feasibility assessment and risk stratification, while entry-focused schemas like TEM (Type, Entry, Malperfusion) further refine management. Emerging data indicate that open repair remains the durability benchmark in younger populations and those with connective tissue disease, and FET enables single-stage treatment capability with acceptable early outcomes but requires vigilant neurologic protection and reintervention surveillance. An integrated, zone-driven approach guided by center expertise optimizes patient selection for open, hybrid, or endovascular options to maximize safety and durability.

Background: Women with gestational diabetes mellitus (GDM) and their offspring have an increased risk of adverse perinatal and long-term health outcomes, which may be attributable to epigenetic modification of diabetes and obesity susceptibility genes. We aimed to investigate the methylation patterns of eight genes in GDM and normoglycemic (NG) mothers, and their respective offspring. Methods: This cross-sectional study, conducted at Aga Khan University from August 2019 to December 2022, recruited pregnant women in the first trimester of gestation from the outpatient obstetrics clinic. Participants were classified as NG or GDM based on the Society of Obstetricians and Gynecologists Pakistan. Venous blood samples were collected from mothers and cord blood from neonates. Peripheral blood mononuclear cells were used for DNA extraction and methylation analysis using methylation-specific PCR. Maternal and neonatal clinical data were recorded. Statistical analysis was performed using R, including binary logistic regression to assess the association between various gene methylation levels and GDM. Results: The study found that GDM mothers had significantly higher fasting blood glucose, 2-hr OGTT, and serum carboxymethyl lysine (CML) levels compared to NG mothers, but no significant differences in neonatal birth weight or serum CML levels. Chemerin methylation was significantly lower in GDM mothers and their babies, while NAMPT, MTNR1B, FNDC5, FAT4, and FTO methylation levels were higher in GDM offspring compared to NG offspring. GDM mothers also had higher methylation levels of brain-derived neurotrophic factor gene (BDNF). Multivariable binary logistic regression identified methylation levels of maternal BDNF and neonatal MTNR1B to be independently associated with GDM. Conclusions: Our study shows a trend of epigenetic modifications in both GDM mothers and their offspring in various genes related to metabolism and inflammation, suggesting an intergenerational transmission of increased risk of developing metabolic disorders. These findings emphasize the need for high throughput studies, early screening, tight glucose control during pregnancy, and postnatal follow-up to mitigate long-term health risks.

Background: Prognostic markers for overall survival in resected pancreatic ductal adenocarcinoma are well established but remain unclear following neoadjuvant therapy. This systematic review and meta-analysis aimed to determine factors associated with overall survival following neoadjuvant therapy in resected pancreatic ductal adenocarcinoma. Methods: The PubMed, Embase, Scopus, Web of Science, and Cochrane CENTRAL databases were systematically searched from January 2010 until May 2024. Studies that reported univariable and multivariable hazard ratios were included if patients underwent neoadjuvant therapy and resection for localized pancreatic ductal adenocarcinoma. Study quality assessment was performed using the Newcastle–Ottawa scale. Meta-analysis was performed using generic inverse-variance random-effects models. Results: Among 2208 unique articles identified by the search, 92 were included in the meta-analysis. Of these, 85 were of “good” and 7 of “poor” quality. The neoadjuvant therapy regimen was described in 84 studies of which 62 included patients treated with FOLFIRINOX. Margin status, nodal disease, American Joint Committee on Cancer (AJCC) T-stage, and normalization of cancer antigen 19-9 (CA19-9) after neoadjuvant therapy were prognostic for overall survival, whereas age, sex, perineural invasion, baseline tumor size, and baseline CA19-9 were not. The test for subgroup differences between ypN substages was not statistically significant in the multivariable model. Neoadjuvant FOLFIRINOX was associated with better survival than other regimens. Conclusions: This meta-analysis identified margin status, nodal disease, AJCC T-stage, and normalization of CA19-9 after neoadjuvant therapy as prognostic factors for overall survival in patients with resected localized pancreatic ductal adenocarcinoma following neoadjuvant therapy.

Background: Current literature concerning upper extremity amputations (UEAs) is very sparse. In this study, we conducted the first multicenter retrospective analysis aiming to identify risk factors associated with unfavorable outcomes in patients undergoing nontraumatic UEAs. Methods: A retrospective cohort study was conducted using the National Surgical Quality Improvement Program database. Adult patients who underwent nontraumatic UEAs between 2005 and 2021 were divided into two cohorts based on whether they experienced 30-day major morbidity (MM). Thereafter, multivariable binary logistic regression analysis was used to identify risk factors of MM. Results: From a total of 2984 cases, MM was observed in 8.7% of patients. Factors associated with MM included American Society of Anesthesiologists classes 3 (odds ratio [OR], 2.974 [1.862 to 4.748]) and 4 (OR, 4.736 [2.857 to 7.848]), being underweight (OR, 2.370 [1.251 to 4.491]), and suffering from insulin-dependent diabetes (OR, 1.390 [1.018 to 1.898]). In addition, an infectious surgical indication was associated with an increased risk of MM compared with having a benign (OR, 0.648 [0.488 to 0.682]) or malignant (OR, 0.205 [0.091 to 0.462]) indication. Moreover, patients undergoing shoulder amputations were at an increased risk of MM compared with those undergoing amputations of the forearm/wrist (OR, 0.243 [0.072 to 0.819]) and hands/fingers (OR, 0.286 [0.095 to 0.861]). Conclusion: The risk factors identified for MM after nontraumatic UEAs should guide surgeons toward appropriately identifying high-risk patients and adequately counseling them preoperatively.

OBJECTIVES: Transannular patch (TAP) repair of tetralogy of Fallot (ToF)relieves right ventricular tract obstruction but may lead to pulmonary regurgitation. Valve-sparing (VS) procedures can avoid this situation, but there is a potential for residual pulmonary stenosis. Our goal was to evaluate clinical and echocardiographic outcomes of TAP and VS repair for ToF. METHODS: A systematic search of the PubMed, Embase, Scopus, Cochrane Central Register of Controlled Trials and Web of Science databases was carried out to identify articles comparing conventional TAP repair and VS repair for ToF. Random-effects models were used to perform meta-analyses of the clinical and echocardiographic outcomes. RESULTS: Forty studies were included in this meta-analysis with data on 11 723 participants (TAP: 6171; VS: 5045). Participants who underwent a VS procedure experienced a significantly lower cardiopulmonary bypass time [mean difference (MD): −14.97; 95% confidence interval (CI): −22.54, −7.41], shorter ventilation duration (MD: −15.33; 95% CI: −30.20, −0.46) and shorter lengths of both intensive care unit (ICU) (MD: −0.67; 95% CI: −1.29, −0.06) and hospital stays (MD: −2.30; 95% CI: [−4.08, −0.52). There was also a lower risk of mortality [risk ratio: 0.40; 95% CI: (0.27, 0.60) and pulmonary regurgitation [risk ratio: 0.35; 95% CI: (0.26, 0.46)] associated with the VS group. Most other clinical and echocardiographic outcomes were comparable in the 2 groups. CONCLUSIONS: This meta-analysis confirms the well-established increased risk of pulmonary insufficiency following TAP repair while also demonstrating that VS repairs are associated with several improved clinical outcomes. Continued research can identify the criteria for adopting a VS approach as opposed to a traditional TAP repair.

Objective: Low- and middle-income countries such as Pakistan bear the brunt of the global burden of congenital heart disease (CHD), This nationwide study assessed hospital resources and surgical practice patterns pertaining to CHD surgery across Pakistan. Methods: A nationwide hospital facility survey was conducted, targeting all health centers performing CHD surgery in Pakistan. Descriptive data analysis was performed, with categorical variables being presented as frequencies and percentages and continuous variables being reported as means and standard deviations. Results: Seventeen surgeons across 17 different centers participated in the study. Eight of 17 (47%) surgeons were under 45 years of age, while the rest were older than 45 years. More respondents were employed at public/government-owned hospitals (11/17, 65%) and at specialized cardiac centers (13/17, 76%), with a majority of centers reported as having a special ICU designated for congenital cardiac patients (11/17, 65%). With regard to operative volume, 7 of 17 (41%) centers reported more than 350 cases per year, with 7 of 17 reported >10 neonatal cases per year (6/12, 50%). Only one center reported national and international collaborations for research, most centers carrying out less than five research projects in a year. Conclusion: This study has identified key areas that require the attention of local administrative bodies as well as international organizations and societies. The existing centers in Pakistan are unable to meet the demands of the population, leaving a large number of untreated patients, especially for neonatal lesions.

Coronary artery aneurysm is defined as dilatation of a segment of coronary artery, greater than 1.5 times the diameter of the largest normal coronary artery of the patient. Major cause of coronary artery aneurysm is coronary artery disease. Coronary artery aneurysm maybe an incidental finding during coronary angiography or it may present with symptoms including chest pain, myocardial infarction or even death. We present a rare case of a 59-year-old gentleman, who had, previously, underwent multiple left heart catheterizations and percutaneous coronary interventions. He presented to us with symptomatic diffuse ectasia of the coronary arteries with proximal aneurysm in the Left Anterior Descending Artery. Coronary artery aneurysms are very rare with an incidence of about 0.02 %-0.04 % and a prevalence of 0.3 %-12 %. Right Coronary Artery is the principal site coronary artery aneurysms with a predominance of 83.8 %. The occurrence of multiple aneurysms is a very rare finding. About 73 % patients present with single aneurysms while only 27 % present with multiple aneurysms. Coronary artery aneurysms predispose to various complications including compression of the chambers, thrombosis and rupture. From the presented case it can be concluded that even though, conservative management is available, surgical repair is the gold standard treatment, especially in the presence of multiple, symptomatic and large aneurysms in order to avoid fatal ischemic complications.