Systematic Review of Neoadjuvant Immunotherapy for Patients With Non-Small Cell Lung Cancer.

There is a paucity of robust clinical evidence for the role of neoadjuvant immunotherapy in patients with resectable non-small cell lung cancer. The primary aim of the study was to identify the available data on the feasibility, safety and efficacy of neoadjuvant immunotherapy. A systematic review was conducted using electronic databases. Relevant studies were identified according to predefined selection criteria. Five relevant publications on 4 completed trials were identified. In most studies, >90% of patients were able to undergo surgery within the planned timeframe after neoadjuvant immunotherapy. There was a high incidence of open thoracotomy procedures, either planned or converted from a planned minimally invasive approach. Mortality ranged from 0 to 5%, but none of the reported deaths were considered directly treatment-related. Morbidities were reported according to adverse events related to neoadjuvant systemic therapy, and postoperative surgical complications. Survival outcomes were limited due to short follow-up periods. Major pathologic response ranged from 40.5 to 56.7%, whilst complete pathologic response of the primary tumor ranged from 15 to 33%. Radiological responses were reported according to RECIST criteria and fluorodeoxyglucose-avidity. This systematic review reported safe perioperative outcomes of patients who underwent resection following neoadjuvant immunotherapy. However, there was a relatively high incidence of open thoracotomy procedures, partly due to the technical challenges associated with increased fibrosis and inflammation of tissue, as well as the more advanced stages of disease in patients enrolled in the studies. Future studies should focus on identifying predictors of pathological response.

Sutureless valve and rapid deployment valves: a systematic review and meta-analysis of comparative studies.

BACKGROUND: The treatment of aortic valve disease is the most common valvular surgery in industrialized nations, with 3-9% of the population over the age of eighty having at least moderate aortic stenosis. As transcatheter aortic valve replacement (TAVR) has become more established, newer surgical prostheses have been developed with a variety of anchoring systems that do not rely solely on sutures to hold the valve in an appropriate position. The Edwards Intuity valve is a bovine pericardial prosthesis that is modelled on the widely implanted Perimount MagnaEase aortic prosthesis. The Perceval valve is a bovine pericardial valve attached to a self-expanding nitinol stent, which uses the radial force exerted on the patient's aortic annulus and aortic root by the stent portion to hold the valve in position. This meta-analysis compares the outcomes of comparative studies of these two valve systems. METHODS: This systematic review and meta-analysis compares the outcomes of rapid deployment valves (RDV) and sutureless valves (SURD) and was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and guidance. The search strategy interrogated six electronic databases. Outcomes measured included all-cause mortality at latest follow up, stroke, cross-clamp and cardiopulmonary bypass (CPB) times, pacemaker implantation rates, paravalvular leak and post-operative transvalvular gradient. RESULTS: The search strategy identified 407 unique papers for initial assessment with seven studies qualifying for inclusion in the analysis. The outcomes of 4,076 patients (1,650 RDV, 2,426 SURD) were included. There was no difference in mortality, stroke or moderate or worse paravalvular regurgitation between the two groups. SURD had significantly shorter CPB time by 15.7 minutes [95% confidence interval (CI): 4.2-27.1; P=0.007] and a shorter cross-clamp time by 11.3 minutes (95% CI: 6.3-16.3; P<0.001) compared to RDV. RDV had a lower post-operative transvalvular gradient by 2.5 mmHg (95% CI: 1.2-3.8; P<0.001) and a lower rate of mild paravalvular regurgitation (OR 2.51; 95% CI: 1.435-4.768; P=0.004). CONCLUSIONS: Both valve types have an adequate safety profile and are comparable to conventional sutured prostheses. There was a significant reduction in cross-clamp and CPB times associated with SURD. This may be of benefit for patients requiring multiple concomitant procedures and increases the utility of minimally invasive valve replacement. However, SURD was associated with higher post-operative transvalvular gradients and a higher incidence of paravalvular regurgitation.

Mini-access branch-first total arch replacement and frozen elephant trunk procedure.

Minimally-invasive surgery presents its own unique set of challenges, especially when applied to treatment of aortic arch disease. The key components of mini-access aortic arch surgery include safe circulatory control, adequate organ protection, and meticulous surgical technique. This article describes how to perform branch-first total arch replacement with the frozen elephant trunk (FET) procedure for distal arch aneurysms. The strategy employed offers the advantages of mini-access surgery, as well as sound cerebral and systemic organ protection strategies.

Ex-vivo lung perfusion versus standard protocol lung transplantation-mid-term survival and meta-analysis.

BACKGROUND: While extended criteria lung donation has helped expand the lung donor pool, utilization of lungs from donors of at least one other solid organ is still limited to around 15-30%. Ex-vivo lung perfusion (EVLP) offers the ability to expand the number of useable lung grafts through assessment and reconditioning of explanted lungs, particularly those not initially meeting criteria for transplantation. This meta-analysis aimed to examine the mid- to long-term survival and other short-term outcomes of patients transplanted with EVLP-treated lungs versus standard/cold-storage protocol lungs. METHODS: Literature search of ten medical databases was conducted for original studies involving "ex-vivo lung perfusion" and "EVLP". Included articles were assessed by two independent researchers, survival data from Kaplan-Meier curves digitized, and individual patient data imputed to conduct aggregated survival analysis. Meta-analyses of suitably reported outcomes were conducted using a random-effects model. RESULTS: Thirteen studies met inclusion criteria, with a total of 407 EVLP lung transplants and 1,765 as per standard/cold storage protocol. One study was a randomized controlled trial while the remainder were single-institution cohort series of varying design. The majority of donor lungs were from brain death donors, with EVLP lungs having significantly worse PaO2/FiO2 ratio and significantly greater rate of abnormal chest X-ray. Aggregated survival analysis of all included studies revealed no significant survival difference for EVLP or standard protocol lungs (hazard ratio 1.00; 95% confidence interval: 0.79-1.27, P=0.981). Survival at 12, 24, and 36 months for the EVLP cohort was 84%, 79%, and 74%, respectively. Survival at 12, 24, and 36 months for the standard protocol cohort was 85%, 79%, and 73%, respectively. Meta-analysis did not find a significant difference in risk of 30-day mortality or primary graft dysfunction grade 3 at 72 hours between cohorts. CONCLUSIONS: There was no significant difference in mid- to long-term survival of EVLP lung transplant patients when compared to standard protocol donor lungs. The incidence of 30-day mortality and primary graft dysfunction grade 3 at 72 hours did not differ significantly between groups. EVLP offers the potential to increase lung donor utilization while providing similar short-term outcomes and mid- to long-term survival.

Surgery for type A intramural hematoma: a systematic review of clinical outcomes.

BACKGROUND: Management of type A intramural hematoma (IMH) remains controversial, with opinions divided as to whether patients should be treated with early aggressive surgery or a more conservative approach. The present systematic review aims to evaluate the mortality and morbidities following surgery for type A IMH. METHODS: Electronic searches were performed on five databases from dates of inception to December 2018. All studies with surgical outcomes for type A intramural hematoma were identified by two independent researchers and relevant data extracted. Random-effects meta-analysis of proportions or meta-analysis of means were performed to aggregate the data. Survival data were pooled using reconstructed individual patient data derived from Kaplan-Meier curves. RESULTS: Fifteen studies with 744 patients were identified. Ten studies were from Asian countries (73% of patients). Overall mortality was 8.2% [95% confidence interval (CI): 4.6-13.9%]. Mortality from Asian centers was 5.3% (95% CI: 3.6-7.7%) and 18.9% (95% CI: 7.0-40.4%) in Western centers. Postoperative complications were poorly reported and hence not analyzable. Overall pooled survival of 343 patients from four studies at 1-, 2-, 3-, 5-, and 10-year was 91.8%, 90.2%, 89.2%, 87.7%, and 71.1%, respectively. CONCLUSIONS: There is an acceptable level of risk of death after surgery for type A IMH, though significant variations exist between results from Asian and Western centers. More detailed studies are required to clarify the controversies surrounding management of type A IMH.

Endovascular versus medical management of type B intramural hematoma: a meta-analysis.

BACKGROUND: Aortic intramural hematoma constitutes one of the three classifications of acute aortic syndrome (AAS). Type B intramural hematoma (IMH-B) is localized to the descending thoracic aorta and can be managed through medical, endovascular or surgical means. Data comparing contemporary management with thoracic endovascular aortic repair (TEVAR) versus traditional medical management (MM) is sparse and only moderate strength recommendations for TEVAR are provided in guidelines. This meta-analysis aimed to pool available data from comparative studies between TEVAR and MM and examine differences in outcomes. METHODS: Literature search of electronic medical databases was conducted to identify studies comparing TEVAR and MM for management of IMH-B. Data extraction from studies fulfilling the inclusion criteria was performed by two authors and meta-analysis using a random-effects model applied to pool baseline data and examine risk ratios (RR) for management outcomes. RESULTS: Of the initial 2,349 studies, nine studies were identified for analysis. There were 161 TEVAR patients and 166 who were medically managed. The mean age of the cohort was 62.2 years [95% confidence interval (CI): 55.8-68.7 years]. Patients with complicating features of IMH-B at presentation were more likely to appear in the TEVAR group, with more penetrating atheromatous ulcer (PAU) [risk difference (RD), 0.565, 95% CI: 0.240-0.889, P=0.001], ulcer-like projection (ULP) (RD 0.240, 95% CI: 0.965-0.384, P=0.001), and greater IMH size (mean difference, MD 5.47 mm, 95% CI: 0.320-10.6, P=0.037). There was no statistical difference between TEVAR and MM for the primary endpoints of aortic-related death (RR 0.535, 95% CI: 0.191-1.5, P=0.234) or IMH-B regression (RR 1.25, 95% CI: 0.859-1.81, P=0.246). Of the secondary endpoints, TEVAR had both significantly less dissection during follow-up (RR 0.295, 95% CI: 0.0881-0.989, P=0.048) and less rupture during follow-up (RR 0.206, 95% CI: 0.0462-0.921, P=0.039). CONCLUSIONS: A small number of series comparing TEVAR and MM for management of IMH-B are available and random-effects meta-analysis did not reveal any statistically significant difference between treatments for aortic related death or IMH-B regression at a mean follow-up of 37 months. TEVAR was found to be associated with lower risk of dissection and lower risk of rupture during follow-up. Baseline data meta-analysis showed patients with complicating features of PAU, ULP, and larger IMH size were more likely to be managed with TEVAR.

Network meta-analysis of antiplatelet therapy following coronary artery bypass grafting (CABG): none versus one versus two antiplatelet agents.

BACKGROUND: Numerous agents have been trialed following coronary artery bypass grafting (CABG) to maintain long-term graft patency. While clear evidence exists for the use of aspirin in maintaining graft patency, the role of dual-antiplatelet therapy in CABG patients is not as well established. This network meta-analysis aimed to compare the short-term post-CABG graft patency outcomes for patients with none, one or two antiplatelet agents. METHODS: Electronic databases were queried for randomized controlled trials comparing CABG graft patency rates at three months and beyond using various antiplatelet agents or placebo. Drug and graft patency data were compared using a mixed treatment comparison under a Bayesian hierarchical framework. A random-effects consistency model was applied. Direct and indirect comparisons were made between drugs and used to determine the relative efficacy for graft patency. RESULTS: The literature search identified 16 papers fulfilling the inclusion criteria, including a total of 3,133 patients with an average of 2.43 [95% confidence interval (CI): 2.20-2.66] grafts per patient. Graft types were incompletely reported, however, saphenous vein grafts (SVGs) were predominantly used [where specifically reported: 4,490 SVG, 1,226 internal mammary artery (IMA) grafts]. In all, five different agents and placebo in various regimens were compared by results of angiographic follow-up conducted at a mean of 10.4 months (95% CI: 9.28-11.5 months). Compared to placebo, aspirin alone [odds ratio (OR) 1.9; 95% credible interval (CrI): 1.3-2.8], aspirin + dipyridamole (OR 1.9; 95% CrI: 1.3-2.6), aspirin + clopidogrel (OR 2.9; 95% CrI: 1.5-5.7) and aspirin + ticagrelor (OR 3.8; 95% CrI: 1.2-13.0) significantly improved graft patency. When compared to aspirin monotherapy, aspirin + clopidogrel (OR 1.6; 95% CrI: 0.86-2.7) and aspirin + ticagrelor (OR 2.0; 95% CrI: 0.69-6.3) had OR that suggested a trend favoring patency compared to aspirin monotherapy, however, these results did not reach significance. Sub-group analysis of SVG graft patency was unable to reach significance (only eight studies with six treatment comparisons were evaluated). Secondary endpoints of death, bleeding, myocardial infarction and cerebrovascular accident were incompletely reported and were pooled but not compared between drug treatment arms. CONCLUSIONS: Aspirin monotherapy and dual antiplatelet therapy (DAPT) provided significant all-graft patency benefit compared to placebo at three months and beyond. A trend existed for DAPT to improve graft patency compared to aspirin, although this did not reach statistical significance. Further randomized controlled studies comparing aspirin monotherapy to DAPT are required to determine the utility of DAPT in CABG patients for maintaining graft patency.

Long-term survival and related outcomes for hybrid versus traditional arch repair-a meta-analysis.

BACKGROUND: Surgical interventions for aortic aneurysm and dissection remain associated with high risk of mortality and morbidity. Advances in operative techniques have led to a variety of options for the cardiac surgeon, including endovascular and hybrid approaches. Debate remains over which of these techniques provide optimal outcomes for the patient. The present systematic review and meta-analysis aims to evaluate long term patient survival and identify short-term outcomes for conventional (open) aortic arch repair and hybrid aortic arch repair (HAR). METHODS: An electronic literature search was conducted according to predefined inclusion criteria for hybrid and conventional aortic arch repair surgery. Digitized survival data was extracted from identified studies' Kaplan-Meier curves and used to re-create individual patient data for aggregated survival analysis. Post-operative morbidity and mortality were analyzed using random-effects model meta-analysis. RESULTS: Nine studies were included, containing 841 hybrid arch repair and 1,182 conventional arch repair patients. Pooled Kaplan-Meier analysis of all patients demonstrated higher survival in hybrid arch repair patients than conventional arch repair patients, however, this was noted to be sensitive to results from a particular study. Overall results showed for the hybrid repair cohort, survival at 1, 2, 3, 5 and 7 years was 87%, 85%, 83%, 78% and 75%, respectively. Survival in the conventional repair cohort at 1, 2, 3, 5 and 7 years was 84%, 82%, 80%, 75% and 71%, respectively. Statistically significant findings from meta-analysis showed hybrid arch repair was associated with lower risk of re-operation for bleeding, while conventional arch repair was associated with reduced risk of spinal cord injury. CONCLUSIONS: Pooled Kaplan-Meier analysis of all studies showed long-term survival outcomes for hybrid and conventional aortic arch repair patients are heterogeneous and sensitive to the results of particular studies. Superior results from particular centres and the low number of comparative studies mean that more data is required to make definitive findings with regards to the long-term survival outcomes of either procedure. Hybrid arch repair was associated with lower risk of re-operation for bleeding, while conventional arch repair was associated with lower risk of spinal cord injury. Surgeons should consider their own center's experience and patient suitability when deciding between hybrid or conventional aortic repair techniques.

Long term outcomes of transcatheter aortic valve implantation (TAVI): a systematic review of 5-year survival and beyond.

BACKGROUND: Transcatheter aortic valve implantation/replacement (TAVI/TAVR) is becoming more frequently used to treat aortic stenosis (AS), with increasing push for the procedure in lower risk patients. Numerous randomized controlled trials have demonstrated that TAVI offers a suitable alternative to the current gold standard of surgical aortic valve replacement (SAVR) in terms of short-term outcomes. The present review evaluates long-term outcomes following TAVI procedures. METHODS: Literature search using three electronic databases was performed up to June 2017. Studies which included 20 or more patients undergoing TAVI procedures, either as a stand-alone or concomitant procedure and with a follow-up of at least 5 years, were included in the present review. Literature search and data extraction were performed by two independent researchers. Digitized survival data were extracted from Kaplan-Meier curves in order to re-create the original patient data using an iterative algorithm and subsequently aggregated for analysis. RESULTS: Thirty-one studies were included in the present analysis, with a total of 13,857 patients. Two studies were national registries, eight were multi-institutional collaborations and the remainder were institutional series. Overall, 45.7% of patients were male, with mean age of 81.5±7.0 years. Where reported, the mean Logistic EuroSCORE (LES) was 22.1±13.7 and the mean Society of Thoracic Surgeons (STS) score was 9.2±6.6. The pooled analysis found 30-day mortality, cerebrovascular accidents, acute kidney injury (AKI) and requirement for permanent pacemaker (PPM) implantation to be 8.4%, 2.8%, 14.4%, and 13.4%, respectively. Aggregated survival at 1-, 2-, 3-, 5- and 7-year were 83%, 75%, 65%, 48% and 28%, respectively. CONCLUSIONS: The present systematic review identified acceptable long-term survival results for TAVI procedures in an elderly population. Extended follow-up is required to assess long-term outcomes following TAVI, particularly before its application is extended into wider population groups.