Sohaib Virk

Association Between HbA1c Variability and Risk of Microvascular Complications in Adolescents With Type 1 Diabetes

CONTEXT There is a paucity of data regarding the association between glycosylated hemoglobin (HbA1c) variability and risk of microvascular complications in adolescents with type 1 diabetes (T1D). OBJECTIVE To investigate the association between HbA1c variability and risk of microvascular complications in adolescents with T1D. DESIGN Prospective cohort study from 1990 to 2014 (median follow-up, 8.1 y). SETTING Tertiary pediatric hospital. PARTICIPANTS A total of 1706 adolescents (aged 12-20 minimum diabetes duration 5 y) with median age of 15.9 years (interquartile range, 14.3-17.5) and diabetes duration of 8.1 years (6.3-10.8). MAIN OUTCOME MEASURES Glycemic variability was computed as the SD of all HbA1c measurements (SD-HbA1c) after diagnosis. Retinopathy was detected using 7-field fundal photography, renal function assessed using albumin excretion rate, peripheral neuropathy detected using thermal and vibration threshold testing, and cardiac autonomic neuropathy (CAN) detected using time- and frequency-domain analyses of electrocardiogram recordings. Generalized estimating equations were used to examine the relationship between complications outcomes and HbA1c variability, after adjusting for known risk factors, including HbA1c, diabetes duration, blood pressure, and lipids. RESULTS In multivariable analysis, SD-HbA1c was associated with early retinopathy (odds ratio [OR] 1.32; 95% confidence interval, 1.00-1.73), albuminuria (OR 1.81; 1.04-3.14), increased log10 albumin excretion rate (OR 1.10; 1.05-1.15) and CAN (OR 2.28; 1.23-4.21) but not peripheral neuropathy. CONCLUSIONS Greater HbA1c variability predicts retinopathy, early nephropathy, and CAN, in addition to established risk factors, in adolescents with T1D. Minimizing long term fluctuations in glycemia may provide additional protection against the development of microvascular complications.

Insulin Pump Therapy Is Associated with Lower Rates of Retinopathy and Peripheral Nerve Abnormality

Objective To compare rates of microvascular complications in adolescents with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI). Research Design and Methods Prospective cohort of 989 patients (aged 12–20 years; diabetes duration >5 years) treated with CSII or MDI for >12 months. Microvascular complications were assessed from 2000–14: early retinopathy (seven-field fundal photography), peripheral nerve function (thermal and vibration threshold testing), autonomic nerve abnormality (heart rate variability analysis of electrocardiogram recordings) and albuminuria (albumin creatinine ratio/timed overnight albumin excretion). Generalized estimating equations (GEE) were used to examine the relationship between treatment and complications rates, adjusting for socio-economic status (SES) and known risk factors including HbA1c and diabetes duration. Results Comparing CSII with MDI: HbA1C was 8.6% [70mmol/mol] vs. 8.7% [72 mmol/mol]) (p = 0.7), retinopathy 17% vs. 22% (p = 0.06); microalbuminuria 1% vs. 4% (p = 0.07), peripheral nerve abnormality 27% vs. 33% (p = 0.108) and autonomic nerve abnormality 24% vs. 28% (p = 0.401). In multivariable GEE, CSII use was associated with lower rates of retinopathy (OR 0.66, 95% CI 0.45–0.95, p = 0.029) and peripheral nerve abnormality (OR 0.63, 95% CI 0.42–0.95, p = 0.026), but not albuminuria (OR 0.46, 95% CI 0.10–2.17, p = 0.33). SES was not associated with any of the complication outcomes. Conclusions In adolescents, CSII use is associated with lower rates of retinopathy and peripheral nerve abnormality, suggesting an apparent benefit of CSII over MDI independent of glycemic control or SES.

Impact of Obesity on Outcomes in Adults Undergoing Elective Posterior Cervical Fusion

Study Design. Retrospective study of prospectively collected data. Objective. To determine the effect of obesity (body mass Index > 30) on postoperative morbidity and mortality after elective posterior cervical fusion in adults. Summary of Background Data. In those with spine disease, obesity has been shown to portend poorer general and disease-specific functional health status. The effect of obesity on outcomes after spine surgery, especially posterior cervical fusion, however, remains unclear. Previous studies have been contradictory to one another and largely limited by small sample sizes. Methods. The American College of Surgeons National Surgical Quality Improvement Program is a large multicenter clinical registry that prospectively collects preoperative risk factors, intraoperative variables, and 30-day postoperative morbidity and mortality outcomes from about 400 hospitals nationwide. Current Procedural Terminology codes were used to query the database for adults who underwent posterior cervical fusion between 2005 and 2012. Patients were separated into cohorts based on obesity status. Univariate analysis and multivariate logistic regression were used to analyze the effect of obesity on postoperative morbidity and mortality. Results. There was a significantly higher rate of only venous thromboembolism (VTE) in the obese group compared with nonobese cohort (3.5% vs. 0.6%, P = 0.015). On multivariate analysis, obesity was found to be an independent predictor (odds ratio 6.15; 95% confidence interval [CI], 1.26–30.20; P = 0.02) for VTE. Conclusion. The present study demonstrated that patients with obesity can safely undergo posterior cervical fusion surgery. Although obesity predisposed to an elevated risk of VTE, postoperative mortality and morbidity were otherwise not significantly increased in this population. Level of Evidence: 3

Equivalent outcomes after coronary artery bypass graft surgery performed by consultant versus trainee surgeons: A systematic review and meta-analysis

OBJECTIVE In recent years, concerns have been raised about the learning opportunities available to cardiac surgical trainees. This meta-analysis was conducted to assess the impact of trainee operator status on clinical outcomes after coronary artery bypass graft (CABG) surgery. METHODS Medline, EMBASE, and the Cochrane Library were systematically searched for studies that reported CABG outcomes according to the training status of the primary operator (consultant vs trainee). Data were independently extracted by 2 investigators; a meta-analysis was conducted according to predefined clinical endpoints. RESULTS Sixteen observational studies (n = 52,966) met criteria for inclusion, with 8 studies (n = 36,479) reporting propensity-adjusted analyses. Trainee cases were associated with increased aortic crossclamp duration (mean difference: 4.80; 95% confidence interval [CI], 0.76-8.83) and cardiopulmonary bypass duration (mean difference: 4.24; 95% CI, 0.00-8.47). Perioperative mortality was similar for CABG performed primarily by trainees versus consultants (odds ratio 0.98; 95% CI, 0.81-1.18). No significant difference was found in the incidence of perioperative stroke, myocardial infarction, acute renal failure, reoperation for bleeding, or wound infection. Trainee operator status was not associated with increased midterm mortality (hazard ratio 1.00; 95% CI, 0.90-1.11). In subgroup analysis that included 5 studies and 8025 patients, off-pump CABG trainee cases were not associated with increased perioperative mortality or morbidity. CONCLUSIONS With appropriate supervision, conventional CABG can be performed by trainee surgeons without an adverse impact on perioperative outcomes or midterm survival. Data regarding off-pump CABG are limited, and further research is warranted to ascertain the impact of trainee operator status on long-term outcomes after off-pump CABG.

p16 expression independent of human papillomavirus is associated with lower stage and longer disease-free survival in oral cavity squamous cell carcinoma.

There is limited information regarding the incidence of p16 expression, its association with human papillomavirus (HPV) and prognosis in oral cavity squamous cell carcinoma (OSCC). The role of p16 in OSCC is evaluated in 215 cases using tissue microarrays (TMAs). p16 immunohistochemistry and HPV in situ hybridisation were performed on TMAs following histopathology review of 215 patients with OSCC in the Sydney Head and Neck Cancer Institute database. Thirty-seven (17.2%) cases showed p16 expression without association with HPV. p16 expression significantly decreased with increasing pT category (p=0.002). p16 expression was associated with longer disease-specific survival on univariable analysis (p=0.044) but not on multivariable analysis adjusting for depth of invasion. Amongst patients receiving adjuvant radiotherapy, patients with p16 expression had significantly longer disease-free and overall survival. p16 expression was seen in early stage OSCCs and was associated with better survival following surgery and radiotherapy. While not an independent predictor of survival, p16 may mediate its effects by contributing to reduced proliferative capacity, leading to smaller tumour size and lower invasive potential.

Margin to tumor thickness ratio – A predictor of local recurrence and survival in oral squamous cell carcinoma

OBJECTIVES To assess whether small oral squamous cell carcinomas (OSCC) require the same margin clearance as large tumors. We evaluated the association between the ratio of the closest margin to tumor size (MSR) and tumor thickness (MTR) with local control and survival. METHODS AND METHODS The clinicopathologic and follow up data were obtained for 501 OSCC patients who had surgical resection with curative intent at our institution. MTR and MSR were computed and their associations with local control and survival were assessed using multivariable Cox-regression model. Survival curves were generated using the Kaplan-Meier method. RESULTS MTR was a better predictor of disease control than MSR. MTR was a predictor of local failure (p=0.033) and disease specific death (p=0.038) after adjusting for perineural invasion, lymphovascular involvement, nodal status, and radiotherapy. A threshold MTR value of 0.3 was identified, above which the risk of local recurrence was low. CONCLUSION The ratio of margin to tumor thickness was an independent predictor for local recurrence and disease specific death in this cohort. A MTR>0.3 can serve as a useful tool for adjuvant therapy planning as it combines tumor thickness and margin clearance, two well established prognostic factors. The minimum safe margin can be calculated by multiplying the tumor thickness by 0.3. Further prospective studies in other institutions are warranted to confirm the prognostic utility of MTR and assess the generalizability of our threshold values.

Preoperative atrial fibrillation portends poor outcomes after coronary bypass graft surgery: A systematic review and meta-analysis

Abstract Objectives This systematic review and meta-analysis was performed to evaluate the impact of pre-operative atrial fibrillation (preAF) on early and late outcomes after coronary artery bypass graft (CABG) surgery. Methods Medline, EMBASE and CENTRAL were systematically searched for studies that reported CABG outcomes according to the presence or absence of preAF. Data were independently extracted by two investigators; a meta-analysis was conducted according to predefined clinical endpoints. A subgroup analysis was performed based on revascularization strategy (off-pump or on-pump CABG). Results Twelve observational studies (n=389,998) met criteria for inclusion, with eight studies (n=381,479) reporting propensity-matched or adjusted analyses. Peri-operative mortality was higher overall in patients with preAF (odds ratio [OR] 1.64; 95% confidence interval [CI], 1.29–2.09; p Conclusion PreAF portends poorer peri-operative and long-term outcomes in patients undergoing CABG, regardless of revascularization strategy.

p16 expression in cutaneous squamous cell carcinoma of the head and neck is not associated with integration of high risk HPV DNA or prognosis

Head and neck cutaneous squamous cell carcinoma (HNcSCC) can present with cervical metastases without an obvious primary. Immunohistochemistry for p16 is established as a surrogate marker of human papillomavirus (HPV) in oropharyngeal cancer. p16 expression in HNcSCC needs to be elucidated to determine its utility in predicting the primary site. The aim of this study was to evaluate the rate of p16 expression in HNcSCC and its association with prognostic factors and survival. p16 immunohistochemistry was performed on 166 patients with high risk HNcSCC (2000-2013) following histopathology review. Chromogenic in situ hybridisation (CISH) for HPV was performed. Fifty-three (31.9%) cases showed strong, diffuse nuclear and cytoplasmic p16 expression including 14 (41%) non-metastatic and 39 (29.5%) metastatic tumours (p=0.21). HPV CISH was negative in all cases. p16 expression significantly increased with poorer differentiation (p=0.033), but was not associated with size (p=0.30), depth of invasion (p=0.94), lymphovascular invasion (p=0.31), perineural invasion (p=0.69), keratinisation (p=0.99), number of involved nodes (p=0.64), extranodal extension (p=0.59) or survival. Nearly 32% of HNcSCCs, particularly poorly differentiated HNcSCCs, show p16 expression. A primary HNcSCC should be considered in p16 positive neck node metastases in regions with high prevalence of HNcSCC. p16 expression is not associated with improved survival in HNcSCC.

Catheter Ablation of Ventricular Tachycardia in Patients With a Ventricular Assist Device

OBJECTIVES This is a systematic review summarizing the procedural characteristics and outcomes of ventricular assist device (VAD)-related ventricular tachycardia (VT) ablation. BACKGROUND Drug-refractory VT refractory commonly develops post-VAD implantation. Procedural and outcome data come from small series or case reports. METHODS An electronic search was performed using major databases. Primary outcomes were VT recurrence, mortality, and cardiac transplantation. Secondary endpoints were acute procedural success and procedural complications. RESULTS Eighteen studies were included, with a total of 110 patients (mean age 59.6 ± 11 years, 89% men; VT storm 34%). Scar-related re-entry was the predominant mechanism of VT (90.3%) and cannula-related VT in 19.3% cases. Electroanatomical mapping interference occurred in 1.8% of cases; there were no reports of catheter entrapment. Noninducibility of clinical VT was achieved in 77.9%; procedural complications occurred in 9.4%. At a mean follow-up of 263.5 ± 267.0 days, VT recurred in 43.6%, 23.4% underwent cardiac transplant, and 48.1% died. There were no procedural-related deaths and no death was directly related to ventricular arrhythmia. In follow-up, there was a significant reduction in implantable cardioverter-defibrillator therapies or shocks (57.1% vs. 23.8%). Ablation allowed VT storm termination in 90% of patients. CONCLUSIONS VAD-related VT is predominantly related to pre-existing intrinsic myocardial scar rather than inflow cannula site insertion. Catheter ablation is a reasonable treatment strategy, albeit with expectedly high rate of recurrence, transplantation, and mortality related to severe underlying disease.

Mechanical Circulatory Support During Catheter Ablation of Ventricular Tachycardia: Indications and Options

Mapping of scar-related ventricular tachycardia (VT) in structural heart disease is fundamentally driven by identifying the critical isthmus of conduction that supports re-entry in and around myocardial scar. Mapping can be performed using activation and entrainment techniques during VT, or by substrate mapping performed in stable sinus or paced rhythm. Activation and entrainment mapping requires the patient to be in continuous VT, which may not be haemodynamically tolerated, or, if tolerated, may lead to adverse sequelae related to impaired end organ perfusion. Mechanical circulatory support (MCS) devices may facilitate haemodynamic stability and preserve end organ perfusion during sustained VT to permit mapping for long periods. Available options for haemodynamic support include an intra-aortic balloon pump (IABP), TandemHeart left atrial to femoral artery bypass system (CardiacAssist Inc., Pittsburgh, PA, USA), Impella left ventricle (LV) to aorta flow-assist system (Abiomed, Danvers, MA, USA), and extracorporeal membrane oxygenation (ECMO); the bypass and assist devices provide far better augmentation of cardiac output than IABP. MCS has potential key advantages including maintenance of vital organ perfusion, reduction of intra-cardiac filling pressures, reduction of LV volumes, wall stress, and myocardial consumption of oxygen, and improvement of coronary perfusion during prolonged periods of VT induction and/or mapping. Observational studies show MCS allows for longer duration of mapping, and increased likelihood of VT termination, without an increased risk of peri-procedural mortality or VT recurrence in follow-up, despite being used in a significantly sicker cohort of patients. However, MCS has increased risk of complications related to vascular access, bleeding, thromboembolic risk, mapping system interference, increase procedural complexity and increased cost. Acute haemodynamic decompensation occurs in ∼11% of patients undergoing VT ablation, and is associated with increased mortality. Prospectively identifying patients at risk of acute haemodynamic decompensation in the peri-procedural period may allow prophylactic MCS. Although observational studies of MCS in patients at high risk of haemodynamic decompensation are encouraging, its benefit needs to be proven in randomised trials. This review will summarise the indication for MCS, forms of MCS, procedural outcomes, complications and utility of MCS during VT ablation.