Efficacy and safety of perioperative ketamine for the prevention of chronic postsurgical pain: A meta-analysis.

STUDY OBJECTIVE: Assessment of the efficacy and safety of perioperative intravenous ketamine in reducing incidence and severity of chronic postsurgical pain. STUDY DESIGN: A systematic review and meta-analysis of randomized controlled trials (RCTs). DATA SOURCES: The following data sources were systematically searched: MEDLINE, CENTRAL, and EMBASE (till 02/2021). PATIENTS: Adult patients undergoing any surgery. INTERVENTIONS: Perioperative use of intravenous ketamine as an additive analgesic drug compared to placebo, no active control treatment, and other additive drugs. MEASUREMENTS: Primary outcomes were number of patients with chronic postsurgical pain after 6 months and ketamine related adverse effects. Secondary outcomes were chronic postsurgical pain incidence after 3 and 12 months, chronic postsurgical neuropathic pain incidence, chronic postsurgical moderate to severe pain incidence, intensity of chronic postsurgical pain at rest, and during movement, oral morphine consumption after 3, 6, and 12 months and incidence of opioid-related adverse effects. MAIN RESULTS: Thirty-six RCTs were included with a total of 3572 patients. Ketamine compared to placebo may result in no difference in the number of patients with chronic postsurgical pain after 6 months (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.71-1.05; I2 = 34%; 16 studies; low-certainty evidence). Ketamine may reduce the incidence of chronic postsurgical neuropathic pain after 3 months in comparison to placebo (RR 0.78, 95% CI 0.62-0.99, I2 = 31%, seven trials, low-certainty evidence). Ketamine compared to placebo may increase the risk for postoperative nystagmus (RR 9.04, 95% CI 1.15-70.90, I2 30%, two trials, low-certainty evidence) and postoperative visual disturbances (RR 2.29, 95% CI 1.05-4.99, I2 10%, seven trials, low-certainty evidence). CONCLUSIONS: There is low-certainty evidence that perioperative ketamine has no effect on chronic postsurgical pain in adult patients. Low-certainty evidence suggests that ketamine compared to placebo may reduce incidence of chronic postsurgical neuropathic pain after 3 months. Questions like ideal dosing, treatment duration and more patient-related outcome measures remain unanswered, which warrants further studies. PROTOCOL REGISTRATION: Prospero CRD42021223625, 07.01.2021.

Intravenous and Inhaled Milrinone in Adult Cardiac Surgery Patients: A Pairwise and Network Meta-Analysis.

OBJECTIVE: To summarize the evidence on the hemodynamic, echocardiographic, and clinical effects of inhaled and intravenous milrinone (iMil and IvMil) in adult cardiac surgery patients. DESIGN: Systematic review, pairwise and network meta-analysis. SETTING: Multi-institutional. PARTICIPANTS: Adult cardiac surgery patients. INTERVENTIONS: Comparison between iMil and IvMil versus other agents or placebo. MEASUREMENTS AND MAIN RESULTS: The primary endpoints were mean pulmonary artery pressure (MPAP) and peripheral vascular resistance (PVR). Secondary endpoints included the following: (1) mean arterial pressure, heart rate, and cardiac index (CI); (2) echocardiographic data; and (3) clinical outcomes. Random model, leave-one-out-analysis, and meta-regression were used. Thirty studies (6 iMil and 24 IvMil) were included for a total of 1,438 patients (194 iMil and 521 IvMil). IvMil was associated with a lower MPAP, lower PVR, and higher CI compared to placebo (standardized mean difference [SMD] = -0.22 [95% CI = -0.48 to 0.05], SMD = -0.49 [95% CI = -0.71 to -0.27], and SMD = 0.94 [95% CI = 0.51 to 1.37]). No difference in any outcome was found between iMil and placebo. At network meta-analysis, significantly lower PVR and shorter hospital length of stay were found for IvMil compared to iMil (SMD = -0.82 [95% CI = -1.53 to -0.10] and SMD = -0.50 [95% CI = -0.95 to -0.05], respectively). CONCLUSION: These results support the clinical use of IvMil in cardiac surgery patients. No evidence at present supports the adoption of iMil.

Characteristics and anatomic distribution of early vs late stroke after cardiac surgery.

BACKGROUND: The primary objective of this study was to identify the specific predictors of early and late stroke in patients after open heart surgery. Secondary outcomes included (a) risk factors for perioperative stroke, (b) anatomic location of stroke according to time of presentation, and (c) the impact of stroke on operative mortality. METHODS: Adult patients undergoing open cardiac surgery with cardiopulmonary bypass from 2006 to 2016 at the New York Presbyterian Hospital/Weill Cornell Medicine were retrospectively reviewed. In total 7957 patients were included. We compared the demographic and perioperative variables in three groups: no stroke, early stroke, and late stroke using regression analysis. RESULTS: The incidence of perioperative stroke for the entire study period was 1.5% (117 of 7957). Early stroke occurred in 84 (71.8%) patients, whereas late stroke occurred in 33 (28.2%). Early strokes were usually embolic events (64 of 66, 97.0%, P = .66) on the right side (30 of 66, 45.5%, P < .001), in the anterior circulation (38 of 66, 57.6%, P = .001), or in multiple distributions (28 of 66, 42.4%, P = .002). Late strokes were more likely left-sided (16 of 28, 57.1%, P < .001) and uncommonly in both the anterior and posterior hemispheres (1 of 28, 3.6%, P = .001). Stroke, regardless of timing, was a significant predictor of operative mortality (odds ratio, 11.0, confidence interval, 6.1-19.7, P < .001). CONCLUSIONS: Early and late strokes after cardiac surgery have distinct incidence, location, and likely etiology. Both early and late strokes portend a very high incidence of operative mortality.

Open repair of descending and thoracoabdominal aortic aneurysms in octogenarians.

OBJECTIVE: Despite improved outcomes for open repair of descending thoracic aneurysm (DTA) and thoracoabdominal aortic aneurysm (TAAA), these operations remain challenging in octogenarians. Patients unsuitable for thoracic endovascular aortic repair require open surgery to avoid catastrophic rupture. We analyzed our results for DTA/TAAA repair in these elderly patients. METHODS: Our institutional aortic database was queried to identify those ≥80 years old and those <80 years old undergoing open DTA/TAAA repair. Logistic and Cox regression analyses were used to account for confounders and to identify predictors of perioperative and long-term outcomes. RESULTS: From 1997 to 2017, there were 783 patients who underwent open repair of DTA or TAAA; 96 (12.3%) were ≥80 years old. Octogenarians were more likely to be female (P = .018), with chronic pulmonary disease (P = .012), severe peripheral vascular disease (P < .001), and hypertension (P = .025). Degenerative aneurysms were more common among octogenarians (P < .001), whereas chronic and acute dissections were more common among those younger than 80 years (P < .001 for both). Operative mortality was 5.6% and was not negatively affected by advanced age (<80 years, 5.7%; ≥80 years, 5.6%; P = .852). Other than an increased incidence of left recurrent nerve palsy in the younger cohort (<80 years, 6.7%; ≥ 80 years, 1.0%; P = .029), there were no significant differences in the incidence of major postoperative complications. Logistic regression modeling showed that age ≥80 years was not predictive of operative mortality or postoperative complications. A greater percentage of octogenarians had aortic reconstruction with a clamp and sew strategy (85.4% vs 61.6%; P < .001), which led to significantly shorter cross-clamp times in this cohort (26.6 minutes vs 30.7 minutes; P < .004). In octogenarians, the incidence of major postoperative adverse events was associated with extent II aneurysms (odds ratio, 2.6; P < .025). Short- and long-term survival was significantly reduced in octogenarians. CONCLUSIONS: In select octogenarians, open repair of DTA/TAAA can be performed with acceptable risk. A simplified surgical approach may provide the best opportunity for a successful outcome.

Editor's Choice - Aortic Re-operation After Replacement of the Proximal Aorta: A Systematic Review and Meta-Analysis.

OBJECTIVE/BACKGROUND: The aim was to estimate risk of aortic re-operation, and re-operative morbidity and mortality, following replacement of the proximal aorta for aneurysm or dissection. METHODS: A meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and the Meta-Analysis of Observational Studies in Epidemiology guidelines. A comprehensive literature review was performed to identify all articles reporting aortic re-operation after proximal aortic replacement. The proximal aorta was defined as extending to the origin of the brachiocephalic trunk. The incidence rate for aortic re-operation (IRAR) was calculated, and stratified based on presence/absence of connective tissue disorders, as well as initial surgical indication. Pooled in hospital mortality and post-operative complication rates were estimated. RESULTS: In total, 7821 patients who underwent proximal aortic replacement from 47 studies were included: 8.3% (n = 649) had Marfan syndrome (MS). During a weighted mean follow up of 4.7 ± 0.3 years, 11.5% (n = 903) underwent aortic re-operation. Mean weighted time between initial surgery and re-operation was 5.2 ± 0.2 years. IRAR was 2.4% per person-year (PPY) (confidence interval [CI] 2.1-2.8%). Patients with MFS had a threefold higher IRAR (6.0% PPY, CI 4.1-8.8%) than did patients without a connective tissue disorders (2.3% PPY, CI 1.9-2.7%; p < .001). IRAR was 2.5% PPY (CI 2.1-3.0%) after operation for dissection and 1.3% PPY (CI 0.9-2.0%) after operation for aneurysm (p = .004 for subgroup differences). IRAR proximal and distal to the left subclavian artery was 1.2% PPY (CI 1.0-1.5%) and 1.3% PPY (CI 1.1-1.6%), respectively. The pooled in hospital mortality and complication rates after re-operation were 14.31% (CI 11.28-17.99%) and 18.08% (CI 10.54-29.25%), respectively. On meta-regression, initial operation for dissection was the only significant predictor of aortic re-operation (beta = .030, p = .001). CONCLUSION: Aortic re-operation occurs at a mean rate of 2.4% per person-year in the five years after proximal aortic replacement and is strongly associated with initial operation for dissection.

Nonbacterial Thrombotic Endocarditis Presenting with Leg Pain and a Left Atrial Mass Lesion.

Systemic lupus erythematosus (SLE) is a major cause of nonbacterial thrombotic endocarditis (NBTE) associated with intracardiac sterile vegetations. It is rare for vegetations to present as an atrial tumor. This report describes a 48-year-old female with SLE and antiphospholipid syndrome complicated by recurrent thrombosis on anticoagulation. A large left atrial mass lesion was detected on echocardiography during a work-up for leg burning. Infective endocarditis could not be confirmed, and hence left atrial mass lesion was the most likely diagnosis. The patient was managed surgically and the pathology report revealed fibrin networks in a pattern similar to that of thrombosis, characteristic of NBTE.

The radial artery: Results and technical considerations.

BACKGROUND: The radial artery (RA) is a frequently used conduit for coronary artery bypass graft (CABG). We review the results of the use of the RA in CABG patients and discuss the unique technical considerations when using this conduit. METHODS: A literature search was performed in PubMed through December 2017 on the comparative efficacy of the RA to other conduits and technical considerations for the use of the RA in CABG surgery. RESULTS: When compared to the saphenous vein graft, the RA proved to be superior in graft patency in multiple randomized clinical trials. The RA was associated with better clinical outcomes in observational studies. The debate over the second best arterial conduit remains unresolved between the RA and the right internal thoracic artery. Preoperative evaluation of the patient's coronary anatomy and the quality of the RA is imperative to achieve the best clinical outcome with RA grafting. CONCLUSION: With careful preoperative planning and attention to technical details, the RA is an excellent choice as the second conduit for CABG surgery.

A 20-Year Experience With Resection of Primary Cardiac Tumors and Metastatic Tumors of the Heart.

BACKGROUND: Cardiac tumors are uncommon, occurring in less than 1% of the population, and are comprised of numerous tumor types. Management of certain tumors types such as sarcoma have evolved and improved in the recent era. We evaluate the outcomes of patients who underwent resection of benign or malignant cardiac tumors with a focused review of cardiac sarcomas. METHODS: Institutional data were reviewed from 1997 to 2017, and 180 patients who underwent tumor resection were identified. Outcomes and survival were examined based on tumor type. RESULTS: Two-thirds of patients (119 of 180) had benign tumors. Of 61 malignant tumors, 23 were sarcomas, 24 were cavoatrial tumors, and 8 were T4 lung tumors. In the sarcoma group, operative mortality was 2 of 23 (9.1%). Neoadjuvant therapy was administered to 8 of 23 patients (34.8%) with R0 resection achieved in 5 of 8 patients (62.5%). R0 resection was successful in 7 of 15 patients (46.7%) without neoadjuvant therapy. Mean survival with neoadjuvant therapy was 2.76 ± 3.85 years versus 1.28 ± 1.31 years without neoadjuvant therapy (p = 0.428). Mean survival with R0 resection was 2.79 ± 4.23 years compared with 1.64 ± 1.63 years without (p = 0.407). In the T4 lung tumor group, operative mortality was zero and R0 resection was achieved in 6 of 8 (75%). The cavoatrial tumors were mostly renal cell carcinoma resected with a mortality of 4.5%. CONCLUSIONS: Cardiac tumors are comprised of diverse tumor types. Indications for, and benefits of, resecting benign tumors and many malignant tumor types are clear, and operative outcomes are generally good. Cardiac sarcomas benefit from neoadjuvant therapy, which improves the rate of complete resection, thus improving survival.

High-dose versus low-dose opioid anesthesia in adult cardiac surgery: A meta-analysis.

STUDY OBJECTIVE: We performed a systematic comparison of high-dose and low-dose opioid anesthesia in cardiac surgery. DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). SETTING: Operating room. PATIENTS: 1400 adult patients undergoing cardiac surgery using general anesthesia. INTERVENTIONS: All RCTs comparing the effects of various doses of intravenous opioids (morphine, fentanyl, sufentanil, and remifentanil) during adult cardiac surgery using general anesthesia published until May 2018 (full-text English articles reporting data from human subjects) were included. MEASUREMENTS: Primary outcome was intensive care unit (ICU) length of stay (LOS). Secondary outcomes were ventilation time, use of vasopressors, perioperative myocardial infarction, perioperative stroke, and hospital LOS. MAIN RESULTS: Eighteen articles were included (1400 patients). There was no difference in ICU LOS between studies using high or low dose of opioids (both short-acting and long-acting) (standard mean difference [SMD]-0.02, 95%CI: -0.15-0.11, P = 0.74). Similarly, there was no difference in secondary outcomes of ventilation time (SMD-0.27, 95%CI: -0.63-0.09, P = 0.14), use of vasopressors (OR 0.61, 95%CI: 0.29-1.30, P = 0.20), myocardial infarction (risk difference 0.00, 95% CI: -0.02-0.03, P = 0.70), stroke (RD 0.00, 95% CI: -0.01-0.01, P = 0.92) and hospital LOS (SMD 0.03, 95% CI: -0.26-0.33, P = 0.84). At meta-regression, there was no effect of age, gender, or type of opioid on the difference between groups. CONCLUSIONS: Our data suggest that low-dose opioids, both short acting and long acting, are safe and effective to use in adult cardiac surgery patients, independent of the clinical characteristics of the patients and the type of opioid used. In view of the current opioid epidemic, low-dose opioid anesthesia should be considered for cardiac surgery patients.

Pneumonitis as a complication of immune system targeting drugs?-a meta-analysis of anti-PD/PD-L1 immunotherapy randomized clinical trials.

BACKGROUND: Anti-PD/PD-L1-targeted immunotherapy is associated with remarkably high rates of durable clinical responses in patients across a range of tumor types, although their high incidence of skin, gastrointestinal, and endocrine side effects with their use. The risk of pneumonitis associated with checkpoint inhibition therapy is not well described. METHODS: A systematic review of the literature was conducted on randomized clinical trials (RCTs) comparing anti-PD/PD-L1 mono-immunotherapy (IMM) to chemotherapy (CTH) protocols in cancer patients. The primary endpoint was the pneumonitis rate in IMM compared to CTH. Secondary endpoints were (I) high-grade pneumonitis rate in IMM compared to CTH and (II) tumor response rate, progression-free survival (PFS), and overall survival (OS) between IMM and CTH. Random model and leave-one-out-analysis were performed. RESULTS: Thirteen RCTs studying 7,246 patients were included; 3,704 (51.12%) patients in the IMM arm and 3,542 (48.88%) patients in the chemotherapy arm. Seven non-small cell lung cancer (NSCLC) RCTs were included with 4,164 patients; 2,101 in the IMM arm and 2,063 patients in the CTH arm. Three RCTs were on melanoma patients (n=1,390). Nine RCTs compared mono-immunotherapy to CTH [docetaxel in 5 studies (38.5%), platinum-based in 2 studies (15.4%), dacarbazine in 1 study (7.7%) and everolimus in 1 study]. Both high-grade and all-grade pneumonitis were higher among patients in the IMM arm when compared to the CTH arm (OR =4.39, 95% CI: 1.65-11.69, P=0.003 and OR =2.46, 95% CI: 1.29-4.6, P=0.007). Tumor response rate was significantly better in the immunotherapy arm (OR =2.31, 95% CI: 1.62-3.29, P<0.001). PFS and OS were longer in patients who received IMM compared to patients in the CTH arm (HR =0.75, 95% CI: 0.65-0.85, P<0.001, and HR =0.71, 95% CI: 0.66-0.77, P<0.001). CONCLUSIONS: The incidence of high-grade and all-grade pneumonitis is higher in anti-PD-1 therapy but not in anti-PD-L1 therapy when compared to traditional CTH regimens for NSCLC and melanoma. High-grade adverse events were otherwise more common in the CTH arm. Tumor response rate, PFS, and OS are all substantially improved with IMM over CTH. These results can be used to guide therapy selection and set expectations for treatment effect in these patients.

Radial artery versus saphenous vein as the second conduit for coronary artery bypass surgery: A meta-analysis.

OBJECTIVE: Individual studies may be limited by sample size to detect differences in late survival between radial artery (RA) or saphenous vein graft (SVG) as a second conduit for coronary artery bypass surgery. Here we undertook a meta-analysis of the best evidence available on the comparison of early and late clinical outcomes of the RA and the SVG. METHODS: MEDLINE and EMBASE were searched for studies comparing use of the RA versus SVG for isolated coronary artery bypass surgery. Time-to-event outcomes for long-term mortality, repeat revascularization, and myocardial infarction (MI) were extracted as incidence rate ratios (IRR) with 95%confidence intervals (95% CI). Odds ratios (OR) were extracted for perioperative mortality, stroke, and MI. A random effects meta-analysis was performed. Sensitivity analyses included leave-one-out-analyses and meta-regression. RESULTS: Among 1201 articles, 14 studies (20,931 patients) were included (mean follow-up: 6.6 years). Operative mortality was 1.25% in the RA versus 1.33% in the SVG group (OR, 0.93; 95% CI, 0.68-1.28). No difference in perioperative MI (OR, 0.96; 95% CI, 0.59-1.56) or stroke (OR, 0.70; 95% CI, 0.43-1.13) was found between RA and SVG. Long-term mortality (mean follow-up 6.6 years) was 24.5% in RA versus 34.2% in SVG group (IRR, 0.74; 95% CI, 0.63-0.87, P < .001). No difference in follow-up MI or repeat revascularization was found (IRR, 0.76; 95% CI, 0.42-1.36 and IRR, 0.68; 95% CI, 0.42-1.09 respectively). At meta-regression, RA survival advantage was independent of age, sex, diabetes, and ventricular function. CONCLUSIONS: Compared with the SVG, using the RA as the second conduit is associated with a 26% relative risk reduction in mortality at 6.6-year follow-up.

Early Versus Delayed Stroke After Cardiac Surgery: A Systematic Review and Meta-Analysis.

Background Although it is traditionally regarded as a single entity, perioperative stroke comprises 2 separate phenomena (early/intraoperative and delayed/postoperative stroke). We aimed to systematically evaluate incidence, risk factors, and clinical outcome of early and delayed stroke after cardiac surgery. Methods and Results A systematic review ( MEDLINE , EMBASE , Cochrane Library) was performed to identify all articles reporting early (on awakening from anesthesia) and delayed (after normal awakening from anesthesia) stroke after cardiac surgery. End points were pooled event rates of stroke and operative mortality and incident rate of late mortality. Thirty-six articles were included (174 969 patients). The pooled event rate for early stroke was 0.98% (95% CI 0.79% to 1.23%) and was 0.93% for delayed stoke (95% CI 0.77% to 1.11%; P=0.68). The pooled event rate of operative mortality was 28.8% (95% CI 17.6% to 43.4%) for early and 17.9% (95% CI 14.0% to 22.7%) for delayed stroke, compared with 2.4% (95% CI 1.9% to 3.1%) for patients without stroke ( P<0.001 for early versus delayed, and for perioperative stroke, early stroke, and delayed stroke versus no stroke). At a mean follow-up of 8.25 years, the incident rate of late mortality was 11.7% (95% CI 7.5% to 18.3%) for early and 9.4% (95% CI 5.9% to 14.9%) for delayed stroke, compared with 3.4% (95% CI 2.4% to 4.8%) in patients with no stroke. Meta-regression demonstrated that off-pump was inversely associated with early stroke (ß=-0.009, P=0.01), whereas previous stroke (ß=0.02, P<0.001) was associated with delayed stroke. Conclusions Early and delayed stroke after cardiac surgery have different risk factors and impacts on operative mortality as well as on long-term survival.

Cardiotoxicity with immune system targeting drugs: a meta-analysis of anti-PD/PD-L1 immunotherapy randomized clinical trials.

Background: With antiprogrammed death receptor-1 (anti-PD-L1) therapy, a recent meta-analysis reported higher incidence of cutaneous, endocrine and gastrointestinal complications especially with dual anti-PD-L1 immunotherapy (IMM). Methods: Our primary outcome was assessment of all cardiotoxicity grades in IMM compared with different treatments, thus a systemic review and a meta-analysis on randomized clinical trials (RCTs) were done. Results: We included 11 RCTs with 6574 patients (3234 patients in IMM arm vs 3340 patients in the other arm). Three non-small-cell lung cancer RCTs, seven melanoma RCTs and only one prostatic cancer RCT met the inclusion criteria. There were five RCTs that compared monoimmunotherapy to chemotherapy "(n = 2631 patients)". No difference exists in all cardiotoxicity grades or high-grade cardiotoxicity (p > 0.05). Lung cancer exhibited a higher response rate and lower mortality in IMM. Conclusion: There was no reported statistically significant cardiotoxicity associated with anti-PD/PD-L1 use. Lung cancer subgroups showed better response and survival rates.

Radial Artery Versus Right Internal Thoracic Artery Versus Saphenous Vein as the Second Conduit for Coronary Artery Bypass Surgery: A Network Meta-Analysis of Clinical Outcomes.

Background There remains uncertainty regarding the second-best conduit after the internal thoracic artery in coronary artery bypass grafting. Few studies directly compared the clinical results of the radial artery ( RA ), right internal thoracic artery ( RITA ), and saphenous vein ( SV ). No network meta-analysis has compared these 3 strategies. Methods and Results MEDLINE and EMBASE were searched for adjusted observational studies and randomized controlled trials comparing the RA , SV , and/or RITA as the second conduit for coronary artery bypass grafting. The primary end point was all-cause long-term mortality. Secondary end points were operative mortality, perioperative stroke, perioperative myocardial infarction, and deep sternal wound infection ( DSWI ). Pairwise and network meta-analyses were performed. A total of 149 902 patients (4 randomized, 31 observational studies) were included ( RA , 16 201, SV , 112 018, RITA, 21 683). At NMA , the use of SV was associated with higher long-term mortality compared with the RA (incidence rate ratio, 1.23; 95% CI , 1.12-1.34) and RITA (incidence rate ratio, 1.26; 95% CI , 1.17-1.35). The risk of DSWI for SV was similar to RA but lower than RITA (odds ratio, 0.71; 95% CI , 0.55-0.91). There were no differences for any outcome between RITA and RA , although DSWI trended higher with RITA (odds ratio, 1.39; 95% CI , 0.92-2.1). The risk of DSWI in bilateral internal thoracic artery studies was higher when the skeletonization technique was not used. Conclusions The use of the RA or the RITA is associated with a similar and statistically significant long-term clinical benefit compared with the SV . There are no differences in operative risk or complications between the 2 arterial conduits, but DSWI remains a concern with bilateral ITA when skeletonization is not used.

Bilateral internal thoracic artery use in coronary bypass surgery: is there a benefit?

PURPOSE: Over the past three decades, there have been a plethora of retrospective observational data and meta-analyses which support the hypothesis of improved clinical outcomes using bilateral internal thoracic arteries (BITA) when compared to saphenous vein grafts (SVGs). However, recently published results have brought this thinking into doubt. We discuss the existing literature on the subject and attempt to clarify the appropriate use of BITA in coronary artery bypass surgery (CABG). METHODS: A review of all existing meta-analyses on BITA was conducted to better understand the utility of BITA in CABG. A review of the largest randomized controlled trials on the subject was then compared to the observational data. RESULTS: In all existing meta-analyses, BITA shows a significant advantage over the use of a single internal thoracic artery (SITA) with SVGs. The two largest randomized controlled trials evaluating BITA failed to show a survival advantage and brought into question the complications associated with BITA. CONCLUSIONS: At present, the use of multiple arterial grafts remains a reasonable choice, particularly in young patients, provided that their use does not increase the operative risk. Further evidence currently being collected may lend a definitive answer in the near future.

Single Versus Multi-Incisional Video-Assisted Thoracic Surgery: A Systematic Review and Meta-analysis.

BACKGROUND: Video-Assisted Thoracic Surgery (VATS) is conventionally performed through multiple small incisions (C-VATS). Recent studies have reported encouraging results with the single-incision VATS (S-VATS) over the conventional technique. However, these studies were either small in size, unfocused, nonuniform, retrospective, lacking follow-up information, or focused on pain. We aim to validate previously reported results in a single large meta-analysis, including only the best evidence studies available. METHODS: Systematic review of the PubMed archive was conducted to include only full English articles with Newcastle Ottawa Scale score ≥7. The primary outcome was the complications rate while secondary outcomes were operative time, resected lymph nodes (LNs), chest tube duration, estimated blood loss, length of postoperative stay (LOS), and postoperative pain on day 1 after surgery. Odds ratio and standard mean difference were used as effect estimates. Random model and leave-one-out analysis were used. RESULTS: A total of 39 studies were included with 4635 patients (1686 S-VATS versus 2949 C-VATS). S-VATS has resulted in significantly less postoperative pain (P < .001), blood loss (P = .006), LOS (P < .001), and chest tube duration (P < .001). In lung cancer patients, the number of retrieved LNs was similar to that of C-VATS (P > .05). Subgroup comparison of the rate of complications between lung resections versus other intrathoracic procedures, lung cancer versus pneumothorax, and lung cancer versus other lung-only lesions did not show any significant differences between the groups. CONCLUSION: Performing S-VATS technique has shown superior postoperative outcomes over the C-VATS technique in the treatment of thoracic disorders. Substantial benefit was confirmed in terms of less postoperative pain, blood loss, drainage time, and postoperative hospital stay.

Lung cancer patients have the highest malignancy-associated suicide rate in USA: a population-based analysis.

PURPOSE: Previous studies have reported that psychological and social distresses associated with a cancer diagnosis have led to an increase in suicides compared to the general population. We sought to explore lung cancer-associated suicide rates in a large national database compared to the general population, and to the three most prevalent non-skin cancers [breast, prostate and colorectal cancer (CRC)]. METHODS: The Surveillance, Epidemiology and End Results (SEER) database (1973-2013) was retrospectively reviewed to identify cancer-associated suicide deaths in all cancers combined, as well as for each of lung, prostate, breast or CRCs. Suicide incidence and standardised mortality ratio (SMR) were estimated using SEER*Stat-8.3.2 program. Suicidal trends over time and timing from cancer diagnosis to suicide were estimated for each cancer type. RESULTS: Among 3,640,229 cancer patients, 6,661 committed suicide. The cancer-associated suicide rate was 27.5/100,000 person years (SMR = 1.57). The highest suicide risk was observed in patients with lung cancer (SMR = 4.17) followed by CRC (SMR = 1.41), breast cancer (SMR = 1.40) and prostate cancer (SMR = 1.18).Median time to suicide was 7 months in lung cancer, 56 months in prostate cancer, 52 months in breast cancer and 37 months in CRC (p < 0.001).We noticed a decreasing trend in suicide SMR over time, which is most notable for lung cancer compared to the other three cancers. In lung cancer, suicide SMR was higher in elderly patients (70-75 years; SMR = 12), males (SMR = 8.8), Asians (SMR = 13.7), widowed patients (SMR = 11.6), undifferentiated tumours (SMR = 8.6), small-cell lung cancer (SMR = 11.2) or metastatic disease (SMR = 13.9) and in patients who refused surgery (SMR = 13). CONCLUSION: The cancer-associated suicide rate is nearly twice that of the general population of the United States of America. The suicide risk is highest among the patients with lung cancer, particularly elderly, widowed, male patients and patients with unfavourable tumour characteristics. The identification of high-risk patients is of extreme importance to provide proper psychological assessment, support and counselling to reduce these rates.

Percutaneous coronary intervention versus coronary bypass surgery for unprotected left main disease: a meta-analysis of randomized controlled trials.

BACKGROUND: This meta-analysis of randomized controlled trials (RCTs) was aimed at comparing coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI) for the treatment of unprotected left main coronary disease. METHODS: All RCTs randomizing patients to any type of PCI with stents vs. CABG for left main disease (LMD) were included. Primary outcome was a composite of follow-up death/myocardial infarction/stroke/repeat revascularization. Secondary outcomes were peri-procedural mortality and the individual components of the primary outcome. Incidence rate ratio (IRR) or odds ratio (OR) and 95% confidence intervals (CIs) were pooled using a generic inverse variance method with random effects model. Subgroup analyses were done based on: (I) type of PCI [bare metal stents (BMS) vs. drug-eluting stents (DES)] and; (II) mean SYNTAX score tertiles. Leave one-out analysis and meta-regression were performed. RESULTS: Six trials were included (4,700 patients; 2,349 PCI and 2,351 CABG). Follow-up ranged from 2.33 to 5 years. PCI was associated with higher risk of follow-up death/myocardial infarction/stroke/repeat revascularization (IRR =1.328, 95% CI, 1.114-1.582, P=0.002) and of repeated revascularization (IRR =1.754, 95% CI, 1.470-2.093, P<0.001). The risk of peri-procedural mortality (OR =0.866, 95% CI, 0.460-1.628, P=0.654), follow-up mortality (IRR =0.947, 95% CI, 0.711-1.262, P=0.712), myocardial infarction (IRR =1.342, 95% CI, 0.827-2.179, P=0.234) and stroke (IRR =0.800, 95% CI, 0.374-1.710, P=0.565) were similar between groups. No differences were found between DES and BMS subgroups. The risk of follow-up death/myocardial infarction/stroke/repeat revascularization with PCI was higher in all SYNTAX tertiles, with a progressive increase from the 1st to the 3rd tertile. At meta-regression, higher mean SYNTAX score was associated with higher risk for the primary outcome in the PCI group (beta =0.02, P=0.05), whereas no association was found with female gender, mean age, or diabetes. CONCLUSIONS: CABG remains the therapy of choice for the treatment of unprotected LMD, especially for patients with a high SYNTAX score.

Unmeasured Confounders in Observational Studies Comparing Bilateral Versus Single Internal Thoracic Artery for Coronary Artery Bypass Grafting: A Meta-Analysis.

BACKGROUND: Observational studies suggest a survival advantage with bilateral single internal thoracic artery (BITA) versus single internal thoracic artery grafting for coronary surgery, whereas this conclusion is not supported by randomized trials. We hypothesized that this inconsistency is attributed to unmeasured confounders intrinsic to observational studies. To test our hypothesis, we performed a meta-analysis of the observational literature comparing BITA and single internal thoracic artery, deriving incident rate ratio for mortality at end of follow-up and at 1 year. We postulated that BITA would not affect 1-year survival based on the natural history of coronary artery bypass occlusion, so that a difference between groups at 1 year could not be attributed to the intervention. METHODS AND RESULTS: We searched MEDLINE and Pubmed to identify all observational studies comparing the outcome of BITA versus single internal thoracic artery. One-year and long-term mortality for BITA and single internal thoracic artery were compared in the propensity-score-matched (PSM) series, that is, the form of observational evidence less prone to confounders. Thirty-eight observational studies (174 205 total patients) were selected for final comparison. In the 12 propensity-score-matched series (34 019 patients), the mortality reduction for BITA was similar at 1 year and at the end of follow-up (incident rate ratio, 0.70; 95% confidence interval, 0.60-0.82 versus 0.77; 95% confidence interval, 0.70-0.85; P for subgroup difference=0.43). CONCLUSIONS: Unmeasured confounders, rather than biological superiority, may explain the survival advantage of BITA in observational series.

Off- Versus On-Pump Coronary Surgery and the Effect of Follow-Up Length and Surgeons' Experience: A Meta-Analysis.

Background The debate on the relative benefits of off-pump and on-pump coronary artery bypass surgery ( OPCABG and ONCABG ) is still open. We aimed to provide an updated and complete summary of the evidence on the differences between OPCABG and ONCABG and to explore whether the length of the follow-up and the surgeons' experience in OPCABG modify the comparative results. Methods and Results All randomized clinical trials comparing OPCABG and ONCABG were included. Primary outcome was follow-up mortality. Secondary outcomes were operative mortality, perioperative stroke, perioperative myocardial infarction, and late repeated revascularization. Subgroup analyses were performed based on the length of the follow-up and the percentage of crossover from the OPCABG group (used as a surrogate of surgeon experience with OPCABG ). One hundred four trials were included (20 627 patients, OPCABG : 10 288; ONCABG : 10 339). Weighted mean follow-up time was 3.7 years (range 1-7.5 years). OPCABG was associated with a higher risk of follow-up mortality (incidence rate ratio 1.11, 95% confidence interval 1.00-1.23, P=0.05). The difference was significant only for trials with mean follow-up of ≥3 years and for studies with a crossover rate of ≥10%. There was a trend toward lower risk of perioperative stroke and higher need for late repeated revascularization in the OPCABG arm. Conclusions OPCABG is associated with a higher incidence of incomplete revascularization, an increased need for repeated revascularization, and decreased midterm survival compared with ONCABG . Surgeon inexperience in OPCABG is associated with late mortality.