Systematic review and meta-analysis of long-term oncological outcomes of lateral lymph node dissection for metastatic nodes after neoadjuvant chemoradiotherapy in rectal cancer.

BACKGROUND: Standard Western management of rectal cancers with pre-treatment metastatic lateral lymph nodes (LLNs) is neoadjuvant (chemo)radiotherapy (nCRT) followed by total mesorectal excision (TME). In recent years, there is growing interest in performing an additional lateral lymph node dissection (LLND). The aim of this systematic review and meta-analysis was to investigate long-term oncological outcomes of nCRT followed by TME with or without LLND in patients with pre-treatment metastatic LLNs. METHODS: PubMed, Ovid MEDLINE, Embase, Cochrane Library and Clinicaltrials.gov were searched to identify comparative studies reporting long-term oncological outcomes in pre-treatment metastatic LLNs of nCRT followed by TME and LLND (LLND+) vs. nCRT followed by TME only (LLND-). Newcastle-Ottawa risk-of-bias scale was used. Outcomes of interest included local recurrence (LR), disease-free survival (DFS), and overall survival (OS). Summary meta-analysis of aggregate outcomes was performed. RESULTS: Seven studies, including 946 patients, were analysed. One (1/7) study was of good-quality after risk-of-bias analysis. Five-year LR rates after LLND+ were reduced (range 3-15%) compared to LLND- (11-27%; RR = 0.40, 95%CI [0.25-0.62], p < 0.0001). Five-year DFS was not significantly different after LLND+ (range 61-78% vs. 46-79% for LLND-; RR = 0.72, 95%CI [0.51-1.02], p = 0.143), and neither was five-year OS (range 69-91% vs. 72-80%; RR = 0.72, 95%CI [0.45-1.14], p = 0.163). CONCLUSION: In rectal cancers with pre-treatment metastatic LLNs, nCRT followed by an additional LLND during TME reduces local recurrence risk, but does not impact disease-free or overall survival. Due to the low quality of current data, large prospective studies will be required to further determine the value of LLND.

Anemia and iron deficiency in patients with atrial fibrillation.

Atrial fibrillation (AF) is the most common cardiac tachyarrhythmia and has a rising global prevalence. Given the increasing burden of AF-related symptoms and complications, new approaches to management are required. Anemia and iron deficiency are common conditions in patients with AF. Furthermore, emerging evidence suggests that the presence of anemia may be associated with worse outcome in these patients. The role of anemia and iron deficiency has been extensively explored in other cardiovascular states, such as heart failure and ischemic heart disease. In particular, the role of iron repletion amongst patients with heart failure is now an established treatment modality. However, despite the strong bidirectional inter-relationship between AF and heart failure, the implications of anemia and iron-deficiency in AF have been scarcely studied. This area is of mechanistic and clinical relevance given the potential that treatment of these conditions may improve symptoms and prognosis in the increasing number of individuals with AF. In this review, we summarise the current published literature on anemia and iron deficiency in patients with AF. We discuss AF complications such as stroke, bleeding, and heart failure, in addition to AF-related symptoms such as exercise intolerance, and the potential impact of anemia and iron deficiency on these. Finally, we summarize current research gaps on anemia, iron deficiency, and AF, and underscore potential research directions.

Rationale and design of the IRON-AF study: a double-blind, randomised, placebo-controlled study to assess the effect of intravenous ferric carboxymaltose in patients with atrial fibrillation and iron deficiency.

INTRODUCTION: Atrial fibrillation (AF) is associated with significantly impaired quality-of-life. Iron deficiency (ID) is prevalent in patients with AF. Correction of ID in other patient populations with intravenous iron supplementation has been shown to be a safe, convenient and effective way of improving exercise tolerance, fatigue and quality-of-life. The IRON-AF (Effect of Iron Repletion in Atrial Fibrillation) study is designed to assess the effect of iron repletion with intravenous ferric carboxymaltose in patients with AF and ID. METHODS AND ANALYSIS: The IRON-AF study is a double-blind, randomised controlled trial that will recruit at least 84 patients with AF and ID. Patients will be randomised to receive infusions of either ferric carboxymaltose or placebo, given in repletion and then maintenance doses. The study will have follow-up visits at weeks 4, 8 and 12. The primary endpoint is change in peak oxygen uptake from baseline to week 12, as measured by cardiopulmonary exercise testing (CPET) on a cycle ergometer. Secondary endpoints include changes in quality-of-life and AF disease burden scores, blood parameters, other CPET parameters, transthoracic echocardiogram parameters, 6-minute walk test distance, 7-day Holter/Event monitor burden of AF, health resource utilisation and mortality. ETHICS AND DISSEMINATION: The study protocol has been approved by the Central Adelaide Local Health Network Human Research Ethics Committee, Australia. The results of this study will be disseminated through publications in peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12620000285954).

Left atrial, pulmonary vein, and left atrial appendage anatomy in Indigenous individuals: Implications for atrial fibrillation.

BACKGROUND: Indigenous Australians experience a greater burden of AF. Whether this is in-part due to differences in arrhythmogenic structures that appear to contribute to AF differences amongst other ethnicities is not known. METHODS: We studied forty individuals matched for ethnicity and other AF risk factors. Computed tomography imaging was used to characterise left atrial (LA), pulmonary vein (PV), and left atrial appendage (LAA) anatomy. RESULTS: There were no significant differences in LA diameters or volumes between Indigenous and non-Indigenous Australians. Similarly, we could not detect any consistent differences in PV number, morphology, diameters, or ostial characteristics according to ethnicity. LAA analyses suggested that Indigenous Australians may have a greater proportion of non chickenwing LAA type, and a tendency for eccentric, oval-shaped LAA ostia; however, there were no other differences seen with regards to LAA volume or depth. Indexed values for LA, PV and LAA anatomy corrected for body size were broadly similar. CONCLUSIONS: In a cohort of individuals matched for AF risk factors, we could find no strong evidence of ethnic differences in LA, PV, and LAA characteristics that may explain a predisposition of Indigenous Australians for atrial arrhythmogenesis. These findings, in conjunction with our previous data showing highly prevalent cardiometabolic risk factors in Indigenous Australians with AF, suggest that it is these conditions that are more likely responsible for the AF substrate in these individuals. Continued efforts should therefore be directed towards risk factor management in an attempt to prevent and minimise the effects of AF in Indigenous Australians.

Atrial Fibrillation in Remote Indigenous and Non-Indigenous Individuals Hospitalised in Central Australia.

BACKGROUND: The epidemiology of atrial fibrillation (AF) amongst Indigenous populations remains poorly characterised. We studied hospitalisations for AF in Central Australia, the most populous Indigenous region in the country. METHODS: Patients with a diagnosis of AF admitted to Alice Springs Hospital, the only secondary health care facility and provider of cardiac care in remote Central Australia, were identified from 2006 to 2016. Age and gender-specific hospitalised AF prevalence, comorbidities, and CHA2DS2-VASc scores were ascertained. RESULTS: Of 57,056 admitted patients over the study period, 1,210 (2.1%; 46% Indigenous) had a diagnosis of AF. For Indigenous and non-Indigenous individuals <45 years, hospitalised AF prevalence per 10,000 population was 105 (CI 84-131) and 50 (CI 36-68) in males (ratio=2.10), and 98 (CI 77-123) and 12 (CI 6-23) in females (ratio=7.92), respectively. For Indigenous and non-Indigenous individuals ≥65 years, hospitalised AF prevalence per 10,000 was 1,577 (CI 1,194-2,026) and 2,326 (CI 2,047-2,623) in males (ratio=0.68), and 1,713 (CI 1,395-2,069) and 1,897 (1,623-2,195) in females (ratio=0.90). Indigenous individuals had higher rates of cardiometabolic comorbidities, particularly at younger ages. CHA2DS2-VASc scores were greater in Indigenous individuals, particularly those <45 years (2.5±1.5 versus 0.7±1.1, p<0.001). CONCLUSIONS: The prevalence of hospitalised AF amongst Indigenous people in remote Central Australia was significantly higher than in non-Indigenous individuals, particularly in younger age groups and females. Indigenous individuals with hospitalised AF also had a markedly greater prevalence of cardiometabolic comorbidities and elevated stroke risk. These data suggest that AF may be contributing to the gap in morbidity and mortality experienced by Indigenous Australians.

Associations of anemia with stroke, bleeding, and mortality in atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: Anemia frequently coexists with atrial fibrillation (AF) and has been variably associated with worse outcomes. We performed a systematic review and meta-analysis to comprehensively assess the effect of anemia on mortality, stroke/systemic thromboembolism, and bleeding events in patients with AF. METHODS: MEDLINE and Embase were searched from inception until May 2020. Studies examining associations of anemia with the above outcomes in AF patients were included, and maximally adjusted hazard ratios (HRs) meta-analysed. PROSPERO registration number CRD42020171113. RESULTS: Twenty-eight studies involving 365 484 patients (41% female, mean age 74.7 years) were included. The average study follow-up ranged from 0.2 to 4.0 years, and the prevalence of anemia was 16%. Anemia was associated with a 78% increase in all-cause mortality (HR, 1.78; 95% confidence interval [CI], 1.44-2.20), 60% increase in cardiovascular mortality (HR, 1.60; 95% CI, 1.17-2.19), 134% increase in noncardiovascular mortality (HR, 2.34; 95% CI, 1.58-3.47) 15% increase in stroke/systemic thromboembolism (HR, 1.15; 95% CI, 1.01-1.31), 78% increase in major bleeding (HR, 1.78; 95% CI, 1.54-2.05), and 77% increase in gastrointestinal bleeding (HR, 1.77; 95% CI, 1.23-2.55). Sensitivity analyses including studies that reported odds ratios did not result in any material change. CONCLUSION: Anemia is a frequently observed comorbidity in patients with AF, and is associated with an increased risk of all-cause, cardiovascular and noncardiovascular mortality, stroke/systemic thromboembolism, and major and gastrointestinal bleeding. Future studies are required to explore the causes of anemia in AF, and whether investigation and treatment may be clinically beneficial in affected individuals.

Trends in the use, complications, and costs of permanent pacemakers in Australia: A nationwide study from 2008 to 2017.

OBJECTIVE: To characterize contemporary pacemaker procedure trends. METHODS: Nationwide analysis of pacemaker procedures and costs between 2008 and 2017 in Australia. The main outcome measures were total, age- and gender-specific implant, replacement, and complication rates, and costs. RESULTS: Pacemaker implants increased from 12,153 to 17,862. Implantation rates rose from 55.3 to 72.6 per 100,000, a 2.8% annual increase (incidence rate ratio [IRR] 1.028; 95% CI, 1.02-1.04; p < .001). Pacemaker implants in the 80+ age group were 17.37-times higher than the < 50 group (95% CI 16.24-18.59; p < .001), and in males were 1.48-times higher than in females (95% CI 1.42-1.55; p < .001). However, there were similar increases according to age (p = .10) and gender (p = .68) over the study period. Left ventricular lead rates were stable (IRR 0.995; 95% CI 0.98-1.01; p = .53). Generator replacements decreased from 20.5 to 18.3 per 100,000 (IRR 0.975; 95% CI 0.97-0.98; p < .001). Although procedures for generator-related complications were stable (IRR 0.995; 95% CI 0.98-1.01; p = .54), those for lead-related complications decreased (IRR 0.985; 95% CI 0.98-0.99; p < .001). Rates for all pacemaker procedures were consistently greater in males (p < .001). Although annual costs of all pacemaker procedures increased from $178 million to $329 million, inflation-adjusted costs were more stable, rising from $294 million to $329 million. CONCLUSIONS: Increasing demand for pacemaker implants is driven by the ageing population and rising rates across all ages, while replacement and complication procedure rates appeared more stable. Males have consistently greater pacemaker procedure rates than females. Our findings have significant clinical and public health implications for healthcare resource planning.

Prognostic value of coronary artery calcium scoring and computed tomography coronary angiography in remote Indigenous and non-Indigenous Australians.

BACKGROUND: The long-term prognostic utility of coronary calcification and coronary artery disease on computed tomography coronary angiography (CTCA) in remote Indigenous and non-Indigenous Australians is not known. METHODS: Consecutive patients undergoing CTCA from 2013 to 2017 in Central Australia were followed-up for major adverse cardiovascular events (MACE). RESULTS: 347 patients were included (50 ± 12 years; 47% female; 39% Indigenous). 172 (50.0%) exhibited coronary calcification. CTCA demonstrated no coronary artery disease (CAD) in 137 (39.5%), non-obstructive CAD in 149 (42.9%), and obstructive CAD in 61 (17.6%) patients. Although Indigenous ethnicity was associated with coronary calcification and baseline CAD in age- and gender-adjusted models, this association was non-significant after accounting for comorbidities. Over 4.6 years (IQR 3.52-5.68) of follow-up, MACE incidence rates per 100 person-years were 2.92 (CI 1.92-4.44) and 0.48 (CI 0.18-1.27) in those with and without calcification respectively (p = 0.001), and 0.15 (CI 0.02-1.09), 1.32 (CI 0.69-2.54), and 6.23 (CI 3.81-10.16) in patients with no, non-obstructive, and obstructive CAD respectively (p < 0.001). Coronary calcification and obstructive CAD were associated with 5-fold (HR 5.25, 95% CI 1.66-16.59, p = 0.005) and 6-fold (HR 6.35, 95% CI 2.70-14.89, p < 0.001) greater hazards of MACE respectively in multivariable models, with no significant interaction by ethnicity in these associations seen. CONCLUSIONS: The prognostic value of coronary calcification and CAD on CTCA amongst remote Indigenous individuals appears similar to that seen in non-Indigenous populations. Our data suggest that coronary artery calcium scoring and CTCA can be used to risk-stratify in remote settings where a normal study is associated with an excellent prognosis for at least two years.

Predictors of Anticoagulation Use in Indigenous and Non-Indigenous Australians With Atrial Fibrillation.

OBJECTIVE: Prior studies have demonstrated that anticoagulation underutilisation for atrial fibrillation (AF) and elevated stroke risk is common. However, there is little data on factors associated with appropriate anticoagulation, particularly in Indigenous Australians who face a disproportionate burden of AF and stroke. We thus sought to determine factors associated with anticoagulation use in Australians with AF. DESIGN: Administrative, clinical, prescriptive and laboratory data were linked and aggregated over a 12-year period. SETTING: Single tertiary teaching hospital. PARTICIPANTS: 19,305 (98%) and 308 (2%) consecutive non-Indigenous and Indigenous Australians with AF identified from administrative databases. MAIN OUTCOME MEASURES: Associations of anticoagulation use according to ethnicity. RESULTS: Significant independent predictors of anticoagulation use included hypertension (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.17-1.34; p<0.001), diabetes (OR 1.14, 95% CI 1.05-1.24; p=0.002), heart failure (OR 1.54 95% CI 1.43-1.66; p<0.001) and prior stroke or transient ischaemic attack (OR 2.07, 95% CI 1.84-2.33; p<0.001). In contrast, increasing age (OR 0.99, 95% CI 0.98-0.99; p<0.001), female gender (OR 0.88, 95% CI 0.82-0.93; p<0.001), and vascular disease (OR 0.72, 95% CI 0.64-0.80; p<0.001) were significant predictors of no anticoagulation. Hypertension was associated with less anticoagulation use in Indigenous compared to non-Indigenous Australians (p=0.02). CONCLUSIONS: Anticoagulation for AF was suboptimal in both Indigenous and non-Indigenous Australians. Older age, female gender, and comorbid vascular disease were found to be negatively associated with anticoagulation. Importantly, hypertension may also be under-recognised as a stroke risk factor in Indigenous Australians. Future efforts to encourage anticoagulation use in accordance with guideline recommendations is likely to reduce the burden of AF-related stroke in both Indigenous and non-Indigenous populations.

Four different ileorectal anastomotic configurations following total colectomy.

Ileorectal and ileosigmoid anastomoses are typically performed following total colectomy and subtotal colectomy, respectively. The current literature provides extensive description of more common anastomoses such as after right hemicolectomy or anterior resection. However, there is little focus in the literature on the ileorectal or ileosigmoid anastomotic technique, despite these anastomoses having a relatively high complication rate. The purpose of the current study is to describe four standardized ileorectal or ileosigmoid anastomotic configurations, with commentary on specific challenges and theoretical advantages and disadvantages of each.