Prognostic benefit of catheter ablation of atrial fibrillation in heart failure: An updated meta-analysis of randomized controlled trials.

Background: The prognostic role of catheter ablation of atrial fibrillation (AF) in patients with heart failure (HF) remains uncertain, with guideline recommendations largely based on a single trial. We conducted a meta-analysis of randomized controlled trials (RCTs) assessing the prognostic impact of AF ablation in patients with HF. Methods: Electronic databases were searched for RCTs comparing 'AF ablation' versus 'other care' (medical therapy and/or atrioventricular node ablation with pacing) in patients with HF. Primary endpoints were ≥1-year mortality, HF hospitalization and change in left ventricular ejection fraction (LVEF). Meta-analyses were performed using random-effects modelling. Results: Nine RCTs (n = 1462) met inclusion criteria. Compared to 'other care', AF ablation significantly reduced ≥1-year mortality (relative risk [RR] 0.65; 95% confidence intervals [CI], 0.49-0.87) and HF hospitalization (RR 0.64; 95% CI, 0.51-0.81). AF ablation demonstrated significantly greater improvement in LVEF (mean difference [MD] 5.4; 95% CI, 4.4-6.4), 6-min walk test distance (MD 21.5 meters; 95% CI, 4.6-38.4) and quality of life as measured by Minnesota Living with Heart Failure Questionnaire score (MD 7.2; 95% CI, 2.8-11.7). Meta-regression analyses showed the beneficial impact of AF ablation on LVEF was significantly blunted by higher prevalence of ischaemic cardiomyopathy. Conclusions: Our meta-analysis demonstrates AF ablation is superior to 'other care' in improving mortality, HF hospitalization, LVEF and quality of life in patients with HF. However, the highly selected study populations in included RCTs and effect modification mediated by etiology of HF suggests these benefits do not uniformly apply across the HF population.

A Caseating Tricuspid Mass in an Adult With Eisenmenger Syndrome Secondary to Aorto-Pulmonary Window.

We present the case of a 55-year old Caucasian man with Eisenmenger syndrome secondary to uncorrected aorto-pulmonary window, whose clinical course has been complicated by recurrent cerebral abscesses and dynamic tricuspid annular caseation with probable pulmonary embolization. (Level of Difficulty: Intermediate.).

Anteroposterior Versus Anterolateral Electrode Position for Direct Current Cardioversion of Atrial Fibrillation: A Meta-Analysis of Randomised Controlled Trials.

OBJECTIVE: Data regarding optimal electrode positioning for direct current cardioversion (DCCV) of atrial fibrillation (AF) has been inconsistent. This meta-analysis was conducted to systematically compare the efficacy of anteroposterior (AP) versus anterolateral (AL) electrode placement for DCCV of AF. METHODS: Electronic databases were searched for randomised controlled trials (RCTs) comparing AP versus AL electrode positioning in patients undergoing DCCV for AF. Primary endpoints were first-shock success and overall DCCV success. Subgroup analysis was performed by defibrillator waveform (monophasic versus biphasic). Meta-regression analyses were performed to assess for significant moderators. RESULTS: Twelve (12) RCTs, including a total of 2,046 patients, met inclusion criteria. Neither first-shock success (relative risk [RR] 0.92; 95% CI 0.79-1.07; p=0.28) nor overall DCCV success (RR 1.01; 95% CI 0.96-1.05; p=0.78) were significantly different with AP versus AL electrode positioning. The mean number of shocks (mean difference [MD] 0.3, 95% CI -0.4 to 0.9), energy level of first successful shock (MD 3 joules; 95% CI -20 to 27) and cumulative energy delivered (MD 39 joules; 95% CI -168 to 246) were similar in AP versus AL arms. In subgroup analysis of six RCTs using biphasic defibrillators, improvement in first-shock success (RR 0.85; 95% CI 0.69-1.03; p=0.10) and overall DCCV success (RR 0.97; 95% CI 0.93-1.01; p=0.09) with AL electrode positioning did not reach statistical significance. Meta-regression analyses identified older age, higher body mass index, and longer AF duration as significant moderators favouring AL electrode positioning. CONCLUSIONS: Pooled analysis of randomised data overall does not show a significant difference in efficacy between AP versus AL electrode positioning. Meta-regression and subgroup analyses suggest that, in contemporary practice with use of biphasic defibrillators, there may be a subset of AF patients in whom AL electrode positioning improves efficacy of DCCV.

Catheter Ablation for Ventricular Tachycardia in Ischaemic Versus Non-Ischaemic Cardiomyopathy: A Systematic Review and Meta-Analysis.

BACKGROUND: There are differences in substrate and ablation approaches for ventricular tachycardia (VT) in ischaemic (ICM) and non-ischaemic cardiomyopathy (NICM). OBJECTIVE: To perform a systematic review and meta-analysis comparing clinical and procedural characteristics/outcomes of VT ablation in ICM versus NICM. METHODS: Electronic databases were searched for comparative studies reporting outcomes of VT ablation in patients with ICM and NICM. Primary outcomes were acute procedural success, VT recurrence and long-term mortality. Meta-analyses were performed using random-effects modelling. RESULTS: Thirty-one (31) studies (7,473 patients; 4,418 ICM and 3,055 NICM) were included. Patients with ICM were significantly older (67.0 vs 55.3 yrs), more commonly male (89% vs 79%), had lower left ventricular ejection fraction (29% vs 38%) were less likely to undergo epicardial access (11% vs 36%) and were more likely to require haemodynamic support during ablation (relative risk [RR] 1.30; 95% CI 1.01-1.69). Acute procedural success (i.e. non-inducibility of VT) was higher in the ICM cohort (RR 1.10, 95% CI 1.05-1.15). Recurrence of VT at follow-up was significantly lower in the ICM cohort (RR 0.77; 95% CI 0.70-0.84). Peri-procedural mortality, incidence of procedural complications and long-term mortality were not significantly different between the cohorts. CONCLUSIONS: NICM and ICM patients undergoing VT ablation are fundamentally different in their clinical characteristics, ablation approaches, acute procedural outcomes and likelihood of VA recurrence. VT ablation in NICM has a lower likelihood of procedural success with increased risk of VA recurrence, consistent with known challenging arrhythmia substrate.

Slow gait speed is associated with worse postoperative outcomes in cardiac surgery: A systematic review and meta-analysis.

BACKGROUND: Frailty is associated with poorer outcomes in cardiac surgery, but the heterogeneity in frailty assessment tools makes it difficult to ascertain its true impact in cardiac surgery. Slow gait speed is a simple, validated, and reliable marker of frailty. We performed a systematic review and meta-analysis to examine the effect of slow gait speed on postoperative cardiac surgical patients. METHODS: PubMED, MEDLINE, and EMBASE databases were searched from January 2000 to August 2021 for studies comparing slow gait speed and "normal" gait speed. Primary outcome was in-hospital mortality. Secondary outcomes were composite mortality and major morbidity, AKI, stroke, deep sternal wound infection, prolonged ventilation, discharge to a healthcare facility, and ICU length of stay. RESULTS: There were seven eligible studies with 36,697 patients. Slow gait speed was associated with increased likelihood of in-hospital mortality (risk ratio [RR]: 2.32; 95% confidence interval [CI]: 1.87-2.87). Additionally, they were more likely to suffer from composite mortality and major morbidity (RR: 1.52; 95% CI: 1.38-1.66), AKI (RR: 2.81; 95% CI: 1.44-5.49), deep sternal wound infection (RR: 1.77; 95% CI: 1.59-1.98), prolonged ventilation >24 h (RR: 1.97; 95% CI: 1.48-2.63), reoperation (RR: 1.38; 95% CI: 1.05-1.82), institutional discharge (RR: 2.08; 95% CI: 1.61-2.69), and longer ICU length of stay (MD: 21.69; 95% CI: 17.32-26.05). CONCLUSION: Slow gait speed is associated with poorer outcomes in cardiac surgery. Frail patients are twofold more likely to die during hospital admission than nonfrail counterparts and are at an increased risk of developing various perioperative complications.

Contact Force and Ablation Index.

Radiofrequency ablation of arrhythmias depends on durable lesion formation. Catheter tip-tissue contact force (CF) is a key determinant of lesion quality; excessive CF is associated with major complications, whereas insufficient CF increases the risk of electrical reconnection and arrhythmia recurrence. In recent years, CF-sensing catheters have emerged with the ability to directly measure CF and provide operators with real-time feedback. CF-guided ablation has been associated with improved outcomes in observational studies. However, randomized controlled trials have not shown any reduction in procedural durations, fluoroscopy exposure, incidence of major complications, or long-term arrhythmia recurrence with use of CF-sensing catheters.

Catheter Ablation Versus Medical Therapy for Atrial Fibrillation in Patients With Heart Failure: A Meta-Analysis of Randomised Controlled Trials.

BACKGROUND: Catheter ablation (CA) is highly efficacious for symptomatic atrial fibrillation (AF) but data predominantly comes from patients with preserved ventricular function. We performed an updated systematic review and meta-analysis of randomised controlled trials (RCT) comparing CA versus medical therapy for AF associated with heart failure (HF). METHODS: Medline, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for RCTs reporting clinical outcomes of CA versus medical therapy for AF in HF patients with ≥6 months' follow-up (atrioventricular-node ablation/device therapy studies excluded). Primary endpoint was change in left ventricular ejection fraction (LVEF). Secondary endpoints were 6-minute walk test (6MWT) distance, quality of life (QoL; measured by the Minnesota Living with Heart Failure Questionnaire [MLHFQ]), peri-procedural mortality, major peri-procedural complications and mid-term (≥1-year) survival. RESULTS: Six RCTs (n=772 patients; mean age 62±11years, LVEF 30±9%) were included. Catheter ablation, compared to medical therapy was associated with: greater improvement in LVEF (mean difference [MD] 5.67%; 95% Confidence Interval [CI], 3-8; I2=87%; p<0.001), greater increase in 6MWT distance (MD 25.1 metres; 95% CI, 0.6-50; I2=94%; p=0.04), improved QoL with greater reduction in MLHFQ scores (MD 9.03; 95% CI, 2.5-15.6; I2=47%; p=0.007), and significantly reduced mid-term mortality (relative risk 0.52; 95% CI, 0.4-0.8; I2=0%; p=0.001). Freedom from AF after ≥1 procedure was 71%; major complications occurred in 8% of patients. CONCLUSION: Catheter ablation is superior to medical therapy for AF in patients with heart failure resulting in greater improvement in LVEF, quality of life and functional status, with a survival benefit.

Updated systematic review and meta-analysis of the impact of contact force sensing on the safety and efficacy of atrial fibrillation ablation: discrepancy between observational studies and randomized control trial data.

AIMS: Despite widespread adoption of contact force (CF) sensing technology in atrial fibrillation (AF) ablation, randomized data suggests lack of improvement in clinical outcomes. We aimed to assess the safety and efficacy of CF-guided vs. non CF-guided AF ablation. METHODS AND RESULTS: Electronic databases were searched for randomized controlled trials (RCTs) and controlled observational studies (OS) comparing outcomes of AF ablation performed with vs. without CF guidance. The primary efficacy endpoint was freedom from AF at follow-up. The primary safety endpoint was major peri-procedural complications. Secondary endpoints included procedural, fluoroscopy, and ablation duration. Subgroup analyses were performed by AF type and study design. Nine RCTs (n = 903) and 26 OS (n = 8919) were included. Overall, CF guidance was associated with improved freedom from AF [relative risk (RR) 1.10; 95% confidence interval (CI) 1.02-1.18], and reduced total procedure duration [mean difference (MD) 15.33 min; 95% CI 6.98-23.68], ablation duration (MD 3.07 min; 95% CI 0.29-5.84), and fluoroscopy duration (MD 5.72 min; 95% CI 2.51-8.92). When restricted to RCTs however, CF guidance neither improved freedom from AF (RR 1.03; 95% CI 0.95-1.11), independent of AF type, nor did it reduce procedural, fluoroscopy, or ablation duration. Contact force guidance did not reduce the incidence of major peri-procedural complications (RR 0.89; 95% CI 0.64-1.24). CONCLUSION: Meta-analysis of randomized data demonstrated that CF guidance does not improve the safety or efficacy of AF ablation, despite initial observational data showing dramatic improvement. Rigorous evaluation in randomized trials is needed before widespread adoption of new technologies.

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.

Impact of Concomitant Urologic Intervention on Clinical Outcomes After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

INTRODUCTION: The impact of concomitant urologic procedures (UPs) on perioperative and long-term outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is uncertain. METHODS: In total, 935 consecutive CRS/HIPEC procedures were performed between 1996 and 2016 in Sydney, Australia. Among these, 73 (7.8%) involved concomitant UP. The association of concomitant UP with 21 perioperative outcomes and overall survival was assessed using univariate and multivariate analyses. RESULTS: In-hospital mortality was 1.8%. Patients requiring UP were more likely to require transfusion of ≥5 units of red blood cells (P=0.031) and have a complete cytoreduction (79% vs. 60%, P<0.001). On multivariate analysis, UP was not associated with in-hospital mortality (2.7% vs. 1.7%, P=0.407) or grade III/IV morbidity (52% vs. 41%, P=0.376). The incidence of ureteric fistula (4% vs. 1%, P=0.004), return to theater (26% vs. 14%, P=0.005) and digestive fistula (22% vs. 11%, P=0.005) was higher in the UP group. The addition of a UP did not significantly impact overall survival for appendiceal cancer (P=0.162), colorectal cancer (P=0.315), or pseudomyxoma peritonei (P=0.120). CONCLUSIONS: Addition of a UP was not associated with an increased risk of grade III/IV morbidity or poorer long-term survival after CRS/HIPEC.

Heart Valve Surgery Performed by Trainee Surgeons: Meta-Analysis of Clinical Outcomes.

BACKGROUND: Cardiac surgical units must balance trainee education with the duty to provide optimal patient care. This is particularly challenging with valvular surgery, given the lower volume and increased complexity of these procedures. The present meta-analysis was conducted to assess the impact of trainee operator status on clinical outcomes following valvular surgery. METHODS: Medline, Embase and CENTRAL databases were systematically searched for studies reporting clinical outcomes according to the training status of the primary operator (consultant or trainee). Data were extracted and meta-analysed according to pre-defined endpoints. RESULTS: Eleven observational studies met the inclusion criteria, reporting on five patient cohorts undergoing mitral valve surgery (n=3975), six undergoing aortic valve replacement (AVR) (n=6236) and three undergoing combined AVR and coronary artery bypass grafting (CABG) (n=3495). Perioperative mortality was not significantly different between trainee and consultant cases for mitral valve surgery (odds ratio [OR] 0.92; 95% confidence interval [CI], 0.62-1.37), AVR (OR 0.67; 95% CI, 0.37-1.24), or combined AVR and CABG (OR 1.07; 95% CI, 0.40-2.85). The incidences of perioperative stroke, myocardial infarction, arrhythmias, acute renal failure, reoperation or wound infection were not significantly different between trainee and consultant cases. There was a paucity of mid-term survival data. CONCLUSIONS: Valvular surgery cases performed primarily by trainees were not associated with adverse perioperative outcomes. These findings suggest the rigorous design of cardiac surgical trainee programs can sufficiently mitigate trainee deficiencies. However, studies with longer follow-up duration and echocardiographic data are required to assess long-term durability and safety.

Mitral valve surgery and coronary artery bypass grafting for moderate-to-severe ischemic mitral regurgitation: Meta-analysis of clinical and echocardiographic outcomes.

OBJECTIVE: This meta-analysis was conducted to compare clinical and echocardiographic outcomes following isolated coronary artery bypass grafting (CABG) versus CABG and mitral valve (MV) surgery in patients with moderate-to-severe ischemic mitral regurgitation (IMR). METHODS: Seven databases were systematically searched to identify relevant studies. For eligibility, studies were required to report on the primary endpoint of perioperative or late mortality. Data were analyzed according to predefined clinical endpoints. RESULTS: Four randomized controlled trials (RCTs) (n = 505) and 15 observational studies (OS) (n = 3785) met the criteria for inclusion. Compared with isolated CABG, concomitant CABG and MV surgery was not associated with increased perioperative mortality (RCTs: relative risk [RR] 0.89, 95% confidence interval [CI], 0.26-3.02; OS: RR 1.40, 95% CI, 0.88-2.23). CABG and MV surgery was associated with significantly lower incidence of moderate-to-severe MR at follow-up (RCTs: RR 0.16, 95% CI, 0.04-0.75; OS: RR 0.20, 95% CI, 0.09-0.48). Late mortality was similar between the surgical approaches in RCTs (hazard ratio [HR] 1.20, 95% CI, 0.57-2.53) and OS (HR 0.99, 95% CI, 0.81-1.21). There were no significant differences in echocardiographic outcomes. These results remained consistent in subgroup analyses restricted to patients with strictly moderate IMR. CONCLUSIONS: In patients with moderate-to-severe IMR, the addition of MV surgery to CABG was not associated with increased perioperative mortality. Although concomitant MV surgery reduced recurrence of moderate-to-severe MR at follow-up, this was not associated with a reduction in late mortality. Larger trials with longer follow-up duration are required to further assess long-term survival and freedom from reintervention.

Systematic review and meta-analysis on the impact of preoperative atrial fibrillation on short- and long-term outcomes after aortic valve replacement.

INTRODUCTION: This systematic review and meta-analysis was performed to evaluate the impact of preoperative atrial fibrillation (preAF) on early and late outcomes after aortic valve replacement (AVR). EVIDENCE ACQUISITION: Medline, EMBASE, and CENTRAL were systematically searched for studies that reported AVR 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. Studies including patients undergoing concomitant atrial fibrillation surgery were excluded. EVIDENCE SYNTHESIS: Six observational studies with 8 distinct AVR cohorts (AVR± concomitant surgery) met criteria for inclusion, including a total of 6693 patients. Of these, 1014 (15%) presented with preAF. Overall, perioperative mortality was increased in patients with preAF (odds ratio [OR] 2.33; 95% CI: 1.48-3.67; P<0.001). Subgroup analysis of patients undergoing isolated AVR also demonstrated preAF as a risk factor for perioperative mortality (OR 2.49; 95% CI: 1.57-3.95; P<0.001). PreAF was also associated with acute renal failure (OR 1.42; 95% CI: 1.07-1.89; P=0.02) but not stroke (OR 1.11; 95% CI: 0.59-2.12; P=0.74). Late mortality was significantly higher in patients with preAF (hazard ratio [HR] 1.75; 95% CI: 1.33-2.30; P<0.001). This relationship remained true when only patients who underwent isolated AVR were analyzed (HR 1.97; 95% CI: 1.11-3.51; P=0.02). CONCLUSIONS: PreAF is associated with an increased risk of early- and late-mortality after AVR. These data support the more widespread utilization of concomitant AF ablation.

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.

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.

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.