Intraoperative MRI versus 5-ALA in high-grade glioma resection: a network meta-analysis.

OBJECTIVE: High-grade gliomas (HGGs) continue to carry poor prognoses, and patient outcomes depend heavily on the extent of resection (EOR). The utility of conventional image-guided surgery is limited by intraoperative brain shift. More recent techniques to maximize EOR, including intraoperative imaging and the use of fluorescent dyes, combat these limitations. However, the relative efficacy of these two techniques has never been systematically compared. Thus, the authors performed an exhaustive systematic review in conjunction with quantitative network meta-analyses to evaluate the comparative effectiveness of 5-aminolevulinic acid (5-ALA) and intraoperative MRI (IMRI) in optimizing EOR in HGG. They secondarily analyzed associated progression-free and overall survival and performed subgroup analyses by level of evidence. METHODS: PubMed, Embase, Cochrane Central, and Web of Science were searched for studies evaluating conventional neuronavigation, IMRI, and 5-ALA in HGG resection. The primary study endpoint was the proportion of patients attaining gross-total resection (GTR), defined as 100% elimination of contrast-enhancing lesion on postoperative MRI. Secondary endpoints included overall and progression-free survival and subgroup analyses for level of evidence. Comparative efficacy analysis of IMRI and 5-ALA was performed using Bayesian network meta-analysis models. RESULTS: This analysis included 11 studies. In a classic meta-analysis, both IMRI (OR 4.99, 95% CI 2.65-9.39, p < 0.001) and 5-ALA (OR 2.866, 95% CI 2.127-3.863, p < 0.001) were superior to conventional navigation in achieving GTR. Bayesian network analysis was employed to indirectly compare IMRI to 5-ALA, and no significant difference in GTR was found between the two (OR 1.9 favoring IMRI, 95% CI 0.905-3.989, p = 0.090). A handful of studies additionally suggested that the use of either IMRI (2 and 4 studies, respectively) or 5-ALA (2 and 2 studies, respectively) improves progression-free and overall survival. CONCLUSIONS: IMRI and 5-ALA are individually superior to conventional neuronavigation for achieving GTR of HGG. Between IMRI and 5-ALA, neither method is clearly more effective. Future studies evaluating the comparative cost and surgical time associated with IMRI and 5-ALA will better inform any cost-benefit analysis.

Sex-Based Differences in Outcomes After Mitral Valve Surgery for Severe Ischemic Mitral Regurgitation: From the Cardiothoracic Surgical Trials Network.

OBJECTIVES: This study investigated sex-based differences in outcomes after mitral valve (MV) surgery for severe ischemic mitral regurgitation (SIMR). BACKGROUND: Whether differences in outcomes exist between men and women after surgery for SIMR remains unknown. METHODS: Patients enrolled in a randomized trial comparing MV replacement versus MV repair for SIMR were included and followed for 2 years. Endpoints for this analysis included all-cause mortality, major adverse cardiovascular and cerebrovascular events (MACCE) (defined as the composite of death, stroke, hospitalization for heart failure, worsening New York Heart Association functional class or MV re-operation), quality of life (QOL), functional status, and percentage of change in left ventricular end-systolic volume index (LVESVI) from baseline through 2 years. RESULTS: Of 251 patients enrolled in the trial, 96 (38.2%) were women. Compared with men, women had smaller LV volumes and effective regurgitant orifice areas (EROA) but greater EROA/left ventricular (LV) end-diastolic volume ratios. At 2 years, women had higher rates of all-cause mortality (27.1% vs. 17.4%, respectively; adjusted hazard ratio [adjHR]: 1.85; 95% confidence interval [CI]: 1.05 to 3.26; p = 0.03) and of MACCE (49.0% vs. 38.1%, respectively; adjHR: 1.58; 95% CI: 1.06 to 2.37; p = 0.02). Women also reported worse QOL and functional status at 2 years. There were no significant differences in the percentage of change over 2 years in LVESVI between women and men (adjß: -10.4; 95% CI: -23.4 to 2.6; p = 0.12). CONCLUSIONS: Women with SIMR displayed different echocardiographic features and experienced higher mortality and worse QOL after MV surgery than men. There were no significant differences in the degree of reverse LV remodeling between sexes. (Comparing the Effectiveness of Repairing Versus Replacing the Heart's Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation [Severe Ischemic Mitral Regurgitation]; NCT00807040).

Analysis of Local Control and Pain Control After Spine Stereotactic Radiosurgery Reveals Inferior Outcomes for Hepatocellular Carcinoma Compared With Other Radioresistant Histologies.

PURPOSE: This study aimed to evaluate the efficacy of stereotactic radiosurgery (SRS) for spinal metastases from hepatocellular carcinoma (HCC) compared with other radioresistant histologies (renal cell carcinoma [RCC], melanoma, and sarcoma) in terms of local control (LC) and pain control. METHODS AND MATERIALS: We performed a retrospective review of patients treated with SRS to the spine for metastatic HCC, RCC, melanoma, and sarcoma between January 2007 and May 2014. Radiographic assessments of LC, overall survival, and patient-reported pain control were analyzed as univariable analyses and with various patient- and treatment-related parameters as multivariable analyses (MVA). RESULTS: Of the 96 patients treated with SRS, 41 patients had radioresistant histologies, including 18 HCC, 1 mixed HCC and cholangiocarcinoma, 15 RCC, 6 melanoma, and 1 leiomyosarcoma. Extraosseous disease was present in 63% of patients (74% in HCC; 55% in non-HCC; P = not significant). Spinal cord compression was present in 29% of patients (32% in HCC; 27% in non-HCC; P = not significant), and 24% of patients had decompressive surgery before SRS (26% in HCC; 23% in non-HCC; P = not significant). With a median follow-up time of 8.7 months, the actuarial 3-, 6-, and 12-month LC rates were 71%, 61%, 41%, respectively, for HCC, and 94%, 94%, and 85%, respectively, for non-HCC. The median time to local failure was 3 months for HCC and 11 months for non-HCC. On MVA, there was a strong trend toward inferior LC with HCC (P = .059). Of the 28 patients with pretreatment pain, pain relief was achieved in 93% of patients, but the 2 patients who did not experience pain relief both had HCC. The actuarial 3-, 6-, and 12-month pain control rates were 68%, 51%, 17%, respectively, for HCC, and 100%, 89%, and 89%, respectively, for non-HCC (P = .023), and remained significant on MVA (P = .034). CONCLUSIONS: Compared with other radioresistant histologies, HCC has inferior LC and pain relief after SRS. Whether HCC may benefit from further dose escalation or combined treatment with new therapies is an area of future research.

Diabetes Is Associated With Reduced Stress Hyperlactatemia in Cardiac Surgery.

OBJECTIVE: Hyperglycemia and hyperlactatemia are associated with increased morbidity and mortality in critical illness. We evaluated the relationship among hyperlactatemia, glycemic control, and diabetes mellitus (DM) after cardiac surgery. RESEARCH DESIGN AND METHODS: This was a retrospective cohort study of 4,098 cardiac surgery patients treated between 2011 and 2015. Patients were stratified by DM and glucose-lowering medication history. Hyperglycemia (glucose >180 mg/dL), hypoglycemia (<70 mg/dL), and the hyperglycemic index were assessed postoperatively (48 h). The relationship between lactate and glucose levels was modeled using generalized linear regression. Mortality was analyzed using an extended Cox regression model. RESULTS: Hyperglycemia occurred in 26.0% of patients without DM (NODM), 46.5% with DM without prior drug treatment (DMNT), 62.8% on oral medication (DMOM), and 73.8% on insulin therapy (DMIT) (P < 0.0001). Hypoglycemia occurred in 6.3%, 9.1%, 8.8%, and 10.8% of NODM, DMNT, DMOM, and DMIT, respectively (P = 0.0012). The lactate levels of all patients were temporarily increased with surgery. This increase was greater in patients who also had hyperglycemia or hypoglycemia and was markedly attenuated in patients with DM. Peak lactate was 5.8 mmol/L (95% CI 5.6, 6.0) in NODM with hyperglycemia vs. 3.3 (95% CI 3.2, 3.4) without hyperglycemia; in DMNT: 4.8 (95% CI 4.4, 5.2) vs. 3.4 (95% CI 3.1, 3.6); in DMOM: 3.8 (95% CI 3.5, 4.1) vs. 2.9 (95% CI 2.7, 3.1); and in DMIT: 3.3 (95% CI 3.0, 3.5) vs. 2.7 (95% CI 2.3, 3.0). Increasing lactate levels were associated with increasing mortality; increasing glucose reduced this effect in DM but not in NODM (P = 0.0069 for three-way interaction). CONCLUSIONS: Stress hyperlactatemia is markedly attenuated in patients with DM. There is a three-way interaction among DM, stress hyperlactatemia, and stress hyperglycemia associated with mortality after cardiac surgery.

A Prospective Multi-Institutional Cohort Study of Mediastinal Infections After Cardiac Operations.

BACKGROUND: Mediastinal infections are a potentially devastating complication of cardiac operations. This study analyzed the frequency, risk factors, and perioperative outcomes of mediastinal infections after cardiac operations. METHODS: In 2010, 5,158 patients enrolled in a prospective study evaluating infections after cardiac operations and their effect on readmissions and mortality for up to 65 days after the procedure. Clinical and demographic characteristics, operative variables, management practices, and outcomes were compared for patients with and without mediastinal infections, defined as deep sternal wound infection, myocarditis, pericarditis, or mediastinitis. RESULTS: There were 43 mediastinal infections in 41 patients (cumulative incidence, 0.79%; 95% confidence interval [CI] 0.60% to 1.06%). Median time to infection was 20.0 days, with 65% of infections occurring after the index hospitalization discharge. Higher body mass index (hazard ratio [HR] 1.06; 95% CI, 1.01 to 1.10), higher creatinine (HR, 1.25; 95% CI, 1.13 to 1.38), peripheral vascular disease (HR, 2.47; 95% CI, 1.21 to 5.05), preoperative corticosteroid use (HR, 3.33; 95% CI, 1.27 to 8.76), and ventricular assist device or transplant surgery (HR, 5.81; 95% CI, 2.36 to 14.33) were associated with increased risk of mediastinal infection. Postoperative hyperglycemia (HR, 3.15; 95% CI, 1.32 to 7.51) was associated with increased risk of infection in nondiabetic patients. Additional length of stay attributable to mediastinal infection was 11.5 days (bootstrap 95% CI, 1.88 to 21.11). Readmission rates and mortality were five times higher in patients with mediastinal infection than in patients without mediastinal infection. CONCLUSIONS: Mediastinal infection after a cardiac operation is associated with substantial increases in length of stay, readmissions, and death. Reducing these infections remains a high priority, and improving post-operative glycemic management may reduce their risk in patients without diabetes.

Secondary surgical-site infection after coronary artery bypass grafting: A multi-institutional prospective cohort study.

OBJECTIVE: To analyze patient risk factors and processes of care associated with secondary surgical-site infection (SSI) after coronary artery bypass grafting (CABG). METHODS: Data were collected prospectively between February and October 2010 for consenting adult patients undergoing CABG with saphenous vein graft (SVG) conduits. Patients who developed a deep or superficial SSI of the leg or groin within 65 days of CABG were compared with those who did not develop a secondary SSI. RESULTS: Among 2174 patients identified, 65 (3.0%) developed a secondary SSI. Median time to diagnosis was 16 days (interquartile range 11-29) with the majority (86%) diagnosed after discharge. Gram-positive bacteria were most common. Readmission was more common in patients with a secondary SSI (34% vs 17%, P < .01). After adjustment, an open SVG harvest approach was associated with an increased risk of secondary SSI (adjusted hazard ratio [HR], 2.12; 95% confidence interval [CI], 1.28-3.48). Increased body mass index (adjusted HR, 1.08, 95% CI, 1.04-1.12) and packed red blood cell transfusions (adjusted HR, 1.13; 95% CI, 1.05-1.22) were associated with a greater risk of secondary SSI. Antibiotic type, antibiotic duration, and postoperative hyperglycemia were not associated with risk of secondary SSI. CONCLUSIONS: Secondary SSI after CABG continues to be an important source of morbidity. This serious complication often occurs after discharge and is associated with open SVG harvesting, larger body mass, and blood transfusions. Patients with a secondary SSI have longer lengths of stay and are readmitted more frequently.

A multi-institutional cohort study confirming the risks of Clostridium difficile infection associated with prolonged antibiotic prophylaxis.

OBJECTIVES: The incidence and severity of Clostridium difficile infection (CDI) have increased rapidly over the past 2 decades, particularly in elderly patients with multiple comorbidities. This study sought to characterize the incidence and risks of these infections in cardiac surgery patients. METHODS: A total of 5158 patients at 10 Cardiothoracic Surgical Trials Network sites in the US and Canada participated in a prospective study of major infections after cardiac surgery. Patients were followed for infection, readmission, reoperation, or death up to 65 days after surgery. We compared clinical and demographic characteristics, surgical data, management practices, and outcomes for patients with CDI and without CDI. RESULTS: C difficile was the third most common infection observed (0.97%) and was more common in patients with preoperative comorbidities and complex operations. Antibiotic prophylaxis for >2 days, intensive care unit stay >2 days, and postoperative hyperglycemia were associated with increased risk of CDI. The median time to onset was 17 days; 48% of infections occurred after discharge. The additional length of stay due to infection was 12 days. The readmission and mortality rates were 3-fold and 5-fold higher, respectively, in patients with CDI compared with uninfected patients. CONCLUSIONS: In this large multicenter prospective study of major infections following cardiac surgery, CDI was encountered in nearly 1% of patients, was frequently diagnosed postdischarge, and was associated with extended length of stay and substantially increased mortality. Patients with comorbidities, longer surgery time, extended antibiotic exposure, and/or hyperglycemic episodes were at increased risk for CDI.

Hybrid Coronary Revascularization for the Treatment of Multivessel Coronary Artery Disease: A Multicenter Observational Study.

BACKGROUND: Hybrid coronary revascularization (HCR) combines minimally invasive surgical coronary artery bypass grafting of the left anterior descending artery with percutaneous coronary intervention (PCI) of non-left anterior descending vessels. HCR is increasingly used to treat multivessel coronary artery disease that includes stenoses in the proximal left anterior descending artery and at least 1 other vessel, but its effectiveness has not been rigorously evaluated. OBJECTIVES: This National Institutes of Health-funded, multicenter, observational study was conducted to explore the characteristics and outcomes of patients undergoing clinically indicated HCR and multivessel PCI for hybrid-eligible coronary artery disease, to inform the design of a confirmatory comparative effectiveness trial. METHODS: Over 18 months, 200 HCR and 98 multivessel PCI patients were enrolled at 11 sites. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE) (i.e., death, stroke, myocardial infarction, repeat revascularization) within 12 months post-intervention. Cox proportional hazards models were used to model time to first MACCE event. Propensity scores were used to balance the groups. RESULTS: Mean age was 64.2 ± 11.5 years, 25.5% of patients were female, 38.6% were diabetic, and 4.7% had previous stroke. Thirty-eight percent had 3-vessel coronary artery disease, and the mean SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score was 19.7 ± 9.6. Adjusted for baseline risk, MACCE rates were similar between groups within 12 months post-intervention (hazard ratio [HR]: 1.063; p = 0.80) and during a median 17.6 months of follow-up (HR: 0.868; p = 0.53). CONCLUSIONS: These observational data from this first multicenter study of HCR suggest that there is no significant difference in MACCE rates over 12 months between patients treated with multivessel PCI or HCR, an emerging modality. A randomized trial with long-term outcomes is needed to definitively compare the effectiveness of these 2 revascularization strategies. (Hybrid Revascularization Observational Study; NCT01121263).

Rate Control versus Rhythm Control for Atrial Fibrillation after Cardiac Surgery.

BACKGROUND: Atrial fibrillation after cardiac surgery is associated with increased rates of death, complications, and hospitalizations. In patients with postoperative atrial fibrillation who are in stable condition, the best initial treatment strategy--heart-rate control or rhythm control--remains controversial. METHODS: Patients with new-onset postoperative atrial fibrillation were randomly assigned to undergo either rate control or rhythm control. The primary end point was the total number of days of hospitalization within 60 days after randomization, as assessed by the Wilcoxon rank-sum test. RESULTS: Postoperative atrial fibrillation occurred in 695 of the 2109 patients (33.0%) who were enrolled preoperatively; of these patients, 523 underwent randomization. The total numbers of hospital days in the rate-control group and the rhythm-control group were similar (median, 5.1 days and 5.0 days, respectively; P=0.76). There were no significant between-group differences in the rates of death (P=0.64) or overall serious adverse events (24.8 per 100 patient-months in the rate-control group and 26.4 per 100 patient-months in the rhythm-control group, P=0.61), including thromboembolic and bleeding events. About 25% of the patients in each group deviated from the assigned therapy, mainly because of drug ineffectiveness (in the rate-control group) or amiodarone side effects or adverse drug reactions (in the rhythm-control group). At 60 days, 93.8% of the patients in the rate-control group and 97.9% of those in the rhythm-control group had had a stable heart rhythm without atrial fibrillation for the previous 30 days (P=0.02), and 84.2% and 86.9%, respectively, had been free from atrial fibrillation from discharge to 60 days (P=0.41). CONCLUSIONS: Strategies for rate control and rhythm control to treat postoperative atrial fibrillation were associated with equal numbers of days of hospitalization, similar complication rates, and similarly low rates of persistent atrial fibrillation 60 days after onset. Neither treatment strategy showed a net clinical advantage over the other. (Funded by the National Institutes of Health and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT02132767.).

The VA augmentation and switching treatments for improving depression outcomes (VAST-D) study: Rationale and design considerations.

Because two-thirds of patients with Major Depressive Disorder do not achieve remission with their first antidepressant, we designed a trial of three "next-step" strategies: switching to another antidepressant (bupropion-SR) or augmenting the current antidepressant with either another antidepressant (bupropion-SR) or with an atypical antipsychotic (aripiprazole). The study will compare 12-week remission rates and, among those who have at least a partial response, relapse rates for up to 6 months of additional treatment. We review seven key efficacy/effectiveness design decisions in this mixed "efficacy-effectiveness" trial.