Meaningful Patient-centered Outcomes 1 Year Following Cardiac Surgery.

OBJECTIVE: To evaluate meaningful, patient-centered outcomes including alive-at-home status and patient-reported quality of life 1 year after cardiac surgery. BACKGROUND: Long-term patient-reported quality of life after cardiac surgery is not well understood. Current operative risk models and quality metrics focus on short-term outcomes. METHODS: In this combined retrospective/prospective study, cardiac surgery patients at an academic institution (2014-2015) were followed to obtain vital status, living location, and patient-reported outcomes (PROs) at 1 year using the NIH Patient-Reported Outcomes Measurement Information System (PROMIS). We assessed the impact of cardiac surgery, discharge location, and Society of Thoracic Surgeons perioperative predicted risk of morbidity or mortality on 1-year outcomes. RESULTS: A total of 782 patients were enrolled; 84.1% (658/782) were alive-at-home at 1 year. One-year PROMIS scores were global physical health (GPH) = 48.8 ±â€Š10.2, global mental health (GMH) = 51.2 ±â€Š9.6, and physical functioning (PF) = 45.5 ±â€Š10.2 (general population reference = 50 ±â€Š10). All 3 PROMIS domains at 1 year were significantly higher compared with preoperative scores (GPH: 41.7 ±â€Š8.5, GMH: 46.9 ±â€Š7.9, PF: 39.6 ±â€Š9.0; all P < 0.001). Eighty-two percent of patients discharged to a facility were alive-at-home at 1 year. These patients, however, had significantly lower 1-year scores (difference: GPH = -5.1, GMH = -5.1, PF = -7.9; all P < 0.001). Higher Society of Thoracic Surgeons perioperative predicted risk was associated with significantly lower PRO at 1 year (P < 0.001). CONCLUSIONS: Cardiac surgery results in improved PROMIS scores at 1 year, whereas discharge to a facility and increasing perioperative risk correlate with worse long-term PRO. One-year alive-at-home status and 1-year PRO are meaningful, patient-centered metrics that help define long-term quality and the benefit of cardiac surgery.

Two-Year Outcomes of Surgical Treatment of Moderate Ischemic Mitral Regurgitation.

BACKGROUND: In a trial comparing coronary-artery bypass grafting (CABG) alone with CABG plus mitral-valve repair in patients with moderate ischemic mitral regurgitation, we found no significant difference in the left ventricular end-systolic volume index (LVESVI) or survival after 1 year. Concomitant mitral-valve repair was associated with a reduced prevalence of moderate or severe mitral regurgitation, but patients had more adverse events. We now report 2-year outcomes. METHODS: We randomly assigned 301 patients to undergo either CABG alone or the combined procedure. Patients were followed for 2 years for clinical and echocardiographic outcomes. RESULTS: At 2 years, the mean (±SD) LVESVI was 41.2±20.0 ml per square meter of body-surface area in the CABG-alone group and 43.2±20.6 ml per square meter in the combined-procedure group (mean improvement over baseline, -14.1 ml per square meter and -14.6 ml per square meter, respectively). The rate of death was 10.6% in the CABG-alone group and 10.0% in the combined-procedure group (hazard ratio in the combined-procedure group, 0.90; 95% confidence interval, 0.45 to 1.83; P=0.78). There was no significant between-group difference in the rank-based assessment of the LVESVI (including death) at 2 years (z score, 0.38; P=0.71). The 2-year rate of moderate or severe residual mitral regurgitation was higher in the CABG-alone group than in the combined-procedure group (32.3% vs. 11.2%, P<0.001). Overall rates of hospital readmission and serious adverse events were similar in the two groups, but neurologic events and supraventricular arrhythmias remained more frequent in the combined-procedure group. CONCLUSIONS: In patients with moderate ischemic mitral regurgitation undergoing CABG, the addition of mitral-valve repair did not lead to significant differences in left ventricular reverse remodeling at 2 years. Mitral-valve repair provided a more durable correction of mitral regurgitation but did not significantly improve survival or reduce overall adverse events or readmissions and was associated with an early hazard of increased neurologic events and supraventricular arrhythmias. (Funded by the National Institutes of Health and Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00806988.).

Effects of n-3 fish oil on metabolic and histological parameters in NASH: a double-blind, randomized, placebo-controlled trial.

BACKGROUND & AIMS: This study's aim was to assess the histological and metabolic effects of n-3 polyunsaturated fatty acids (PUFAs) vs. placebo while adjusting for the impact of age and weight change in NASH patients. (ClinicalTrials.gov: NCT00681408). METHODS: Forty-one subjects with non-cirrhotic NASH were enrolled, and 34 completed the study. 17 received n-3 fish oil 3000 mg/day and 17 received placebo daily for 1 year with typical counselling on caloric intake and physical activity for all subjects. RESULTS: N-3- and placebo-treated groups showed no significant difference for the primary end point of NASH activity score (NAS) reduction ⩾ 2 points without fibrosis progression after adjustment for known covariates (n-3, 4/17 (23.5%); placebo, 3/17, (17.6%), p = 0.99). Among subjects with increased or stable weight, n-3 subjects showed a larger decrease in liver fat content by MRI than placebo-treated subjects (p = 0.014 for 2nd quartile, p = 0.003 for 3rd quartile of weight change). N-3 treatment showed significant fat reduction on the paired analysis of image-assisted fat morphometry regardless of weight loss or gain. Exercise capacity remained markedly reduced in all subjects. No independent effects on markers of hepatocyte injury or insulin sensitivity indices were observed. CONCLUSION: N-3 PUFAs at 3000 mg/day for one year did not lead to an improvement in the primary outcome of histological activity in NASH patients (⩾ 2 point NAS reduction). N-3 led to reduced liver fat by multiple measures. Other metabolic effects were not seen, although no detrimental effects were apparent. Whether longer duration, higher dose, or different composition of n-3 therapy would lead to additional benefits is uncertain.

Inspiring diverse researchers in Virginia: Cultivating research excellence through a career-building program.

Historically underrepresented groups in biomedical research have continued to experience low representation despite shifting demographics. Diversity fosters inclusive, higher quality, and innovative team science. One avenue for diversifying research teams is integrating diversity-focused initiatives into Clinical and Translational Science Award (CTSA) Programs, such as the integrated Translational Health Research Institute of Virginia (iTHRIV). In 2020, iTHRIV participated in Building Up, developed by the University of Pittsburgh CTSA, and intended to increase representation and improve career support for underrepresented groups in the biomedical workforce. Drawing lessons from this study, iTHRIV implemented the "inspiring Diverse Researchers in Virginia" (iDRIV) program. This yearlong program provided education, coaching, mentoring, and sponsorship for underrepresented early career investigators in the biomedical workforce. To date, 24 participants have participated in the program across three cohorts. Participants have been predominantly female (92%), with 33% identifying as Hispanic/Latinx, 29% as Black, and 13% as Asian. Notably, 38% of scholars have subsequently achieved at least one accomplishment, such as receiving a local research honor or award and an extramural funding award from a foundation or federal agency. The iTHRIV iDRIV program serves as a model for providing career support to developing investigators from underrepresented backgrounds, with the overall goal of improving patient health.

Inspiring Diverse Researchers in Virginia: Cultivating Research Excellence Through a Career Building Program.

Historically underrepresented groups in biomedical research have continued to experience low representation despite shifting demographics. Diversity fosters inclusive, higher quality, and innovative team science. One avenue for diversifying research teams is integrating diversity-focused initiatives into Clinical and Translational Science Award (CTSA) Programs, such as the integrated Translational Health Research Institute of Virginia (iTHRIV). In 2020, iTHRIV participated in Building Up, developed by the University of Pittsburgh CTSA, intended to increase representation and improve career support for underrepresented groups in the biomedical workforce. Drawing lessons from this study, iTHRIV implemented the "inspiring Diverse Researchers in Virginia" (iDRIV) program. This year-long program provided education, coaching, mentoring, and sponsorship for underrepresented early-career investigators in the biomedical workforce. To date, 24 participants have participated in the program across three cohorts. Participants have been predominantly female (92%), with 33% identifying as Hispanic/Latinx, 29% as Black, and 13% Asian. Notably, 38% of scholars have subsequently achieved at least one accomplishment, such as receiving a local research honor or award and an extramural funding award from a foundation or federal agency. The iTHRIV iDRIV program serves as a model for providing career support to developing investigators from underrepresented backgrounds, with the overall goal of improving patient health.

Hemostats, sealants, and adhesives III: a new update as well as cost and regulatory considerations for components of the surgical toolbox.

The hemostat, sealant, and adhesive components of the surgical toolbox continue to evolve and enter clinical practice at a rapid rate. The goal of this comprehensive, sequential review is to update these components to include those now available (February 2012) as well as to explore cost and regulatory factors that impact the development and use of these materials. A unique system of definitions for organizing these components based on group, category, and class is used as a means of improving the understanding and appropriate use of these materials. The system will be used here to present the most recent additions to the toolbox, which are evaluated based on safety, efficacy, usability, and cost. These new additions include pooled human plasma fibrinogen and thrombin embedded in an equine collagen patch for cardiac surgical hemostasis, polyethylene glycol (PEG) and human serum albumin for lung surgical pneumostasis, modified PEG and trilysine amine for spinal sealing, octyl and butyl lactoyl cyanoacrylate for vascular sealing, and a variety of octyl and butyl cyanoacrylates with or without dyes and/or polyester mesh for skin closure with the creation of a bacterial barrier. The system of definitions will also be used to clarify key strategies in the current health care environment for reducing costs and for increasing understanding of Food and Drug Administration regulatory decisions for these materials.

Use of fibrin sealant as a hemostatic agent in expanded polytetrafluoroethylene graft placement surgery.

BACKGROUND: The low thrombogenicity, porosity, and limited elasticity of expanded polytetrafluoroethylene (ePTFE) vascular grafts, although beneficial, may exacerbate the problem of suture-line bleeding at vascular anastomoses and consequently lead to increased operating times. The overall objective of this prospective, randomized, controlled, subject-blinded, multicenter phase 2 study was to evaluate the efficacy and safety of a fibrin sealant containing 500 IU/mL thrombin and synthetic aprotinin (FS; marketed in the United States under the name TISSEEL) for hemostasis in subjects undergoing vascular surgery and receiving prosthetic ePTFE vascular grafts. METHODS: FS was compared with manual compression with surgical gauze pads, a standard of care for hemostasis in vascular surgery. Two FS polymerization/setting times (60 and 120 seconds) were investigated to evaluate influence on the efficacy results. Patients undergoing ePTFE graft placement surgery (N = 73) who experienced bleeding that required treatment after surgical hemostasis were randomized to be treated with FS with clamps opened at 60 seconds (FS-60; N = 26), with FS with clamps opened at 120 seconds (FS-120; N = 24), or with manual compression with surgical gauze pads (control; N = 23). The proportion of subjects achieving hemostasis at 4 minutes (primary endpoint) as well as at 6 and 10 minutes (secondary endpoints) in the three treatment groups was analyzed using logistic regression analysis, taking into account gender, age, type of intervention, severity of bleeding, systolic blood pressure, diastolic blood pressure, heparin coating of the ePTFE graft, and platelet inhibitors. RESULTS: There were substantial differences in the proportion of subjects who achieved hemostasis at the study suture line at 4 minutes from treatment application between FS-120 (62.5%) and control (34.8%) groups (a 79.6% relative improvement). Logistic regression analyses found a statistically significant treatment effect at the 10% level in the odds ratio (OR) of achieving hemostasis at 4 minutes between the FS-120 and control groups (OR = 3.98, p = 0.0991). Furthermore, it has been shown that the perioperative administration of platelet inhibitors significantly influences (OR = 3.89, p = 0.0607) hemostasis rates at the primary endpoint. No statistically significant treatment effects were found for the other factors. Logistic regression analyses performed on the secondary endpoints demonstrated a significant treatment effect of achieving hemostasis at 6 minutes (OR = 9.92, p = 0.0225) and at 10 minutes (OR = 6.70, p = 0.0708) between the FS-120 and control groups. Statistically significant effects in the logistic regression analyses were found at the 10% level in the OR of achieving hemostasis at 6 and 10 minutes, respectively, for the following factors: FS-120 versus control group (OR = 9.92; p = 0.0225 and OR = 6.70; p = 0.0708, respectively), type of intervention (OR = 0.3; p = 0.0775 and OR = 0.25; p = 0.0402, respectively), and heparin coating of the ePTFE prosthesis (OR = 4.83; p = 0.0413 and OR = 3.65; p = 0.0911, respectively). FS was safe and well-tolerated, as indicated by the lack of any related serious adverse events. CONCLUSION: The findings from this phase 2 study support the strong safety profile of FS and suggest that it is an efficacious hemostatic agent in ePTFE graft placement surgery, as well as a useful tool in peripheral vascular surgery applications.

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.

Absorbable cyanoacrylate as a vascular hemostatic sealant: a preliminary trial.

No absorbable cyanoacrylate tissue adhesive for safe internal surgical use is available. This prospective multicenter preliminary study was designed to evaluate the safety and effectiveness of an investigational absorbable cyanoacrylate (IAC) as an adjunct to hemostasis in arteriovenous shunt (AVS) procedures for dialysis access. Consenting adults (10) underwent placement of expanded polytetrafluoroethylene (ePTFE) upper extremity vascular grafts for AVS access using continuous 5-0 or 6-0 polypropylene after heparinization (> or =3000 units i.v.). Arterial anastomoses were evaluated after sealing with IAC followed by 120 seconds of polymerization time. After vascular clamp removal, the mean time to hemostasis was 9.1 +/- 28.8 seconds. Additionally, 90 per cent (9/10) and 100 per cent (10/10) achieved hemostasis by 1 and 5 minutes, respectively. No patients required further adjunctive hemostatic measures. Adverse event safety data analysis through 12 weeks revealed occlusion of graft or vessel in four patients and graft thrombosis in one patient, all thought unrelated to sealant use. Other unrelated adverse events (bleeding, death, deep venous thrombosis, edema, erythema, hematoma, infection, and rash) occurred in single patients. Thus, IAC could be a useful sealant for vascular procedures with a potentially satisfactory safety profile. Larger, randomized, multicenter, prospective trials to further evaluate the use of this material are indicated and appropriate.

Costs associated with health care-associated infections in cardiac surgery.

BACKGROUND: Health care-associated infections (HAIs) are the most common noncardiac complications after cardiac surgery and are associated with increased morbidity and mortality. Current information about their economic burden is limited. OBJECTIVES: This research was designed to determine the cost associated with major types of HAIs during the first 2 months after cardiac surgery. METHODS: Prospectively collected data from a multicenter, observational study of the Cardiothoracic Surgery Clinical Trials Network, in which patients were monitored for infections for 65 days after surgery, were merged with related financial data routinely collected by the University HealthSystem Consortium. Incremental length of stay (LOS) and cost associated with HAIs were estimated using generalized linear models, with adjustments for patient demographics, clinical history, baseline laboratory values, and surgery type. RESULTS: Among 4,320 cardiac surgery patients (mean age: 64 ± 13 years), 119 (2.8%) experienced a major HAI during the index hospitalization. The most common HAIs were pneumonia (48%), sepsis (20%), and Clostridium difficile colitis (18%). On average, the estimated incremental cost associated with a major HAI was nearly $38,000, of which 47% was related to intensive care unit services. The incremental LOS was 14 days. Overall, there were 849 readmissions; among these, 8.7% were attributed to major HAIs. The cost of readmissions due to major HAIs was, on average, nearly threefold that of readmissions not related to HAIs. CONCLUSIONS: Hospital cost, LOS, and readmissions are strongly associated with HAIs. These associations suggest the potential for large reductions in costs if HAIs following cardiac surgery can be reduced. (Management Practices and the Risk of Infections Following Cardiac Surgery; NCT01089712).

Fibrin sealant facilitates hemostasis in arteriovenous polytetrafluoroethylene grafts for renal dialysis access.

A prospective randomized study was performed to evaluate the efficacy of fibrin sealant (FS) in patients undergoing upper-extremity polytetrafluoroethylene (PTFE) graft placement for dialysis. This procedure appears to be a reproducible and clinically relevant model for evaluating FS in vascular surgery. Consenting adult patients (n = 28) undergoing placement of a PTFE graft (6 mm) were randomized to either the treatment group using FS (Hemaseel APR, Haemacure Corp., Sarasota, FL) or control comparator groups (four) of bovine thrombin (T) (Thrombogen, GenTrac Inc., Middleton, WI), pressure (P), bovine thrombin (Thrombogen, GenTrac Inc.) -soaked cellulose sponges (TG) (Gelfoam, Upjohn Co., Kalamazoo, MI), or oxidized regenerated cellulose (S) (Surgicel, Johnson & Johnson, New Brunswick, NJ). All patients received heparin (3000 IU intravenous push) before placement of vascular clamps. The mean time to hemostasis was 29.3 seconds for FS, 147.4 seconds for T, 872.2 seconds for P, 346 seconds for TG, and 1044.5 seconds for S. There were no significant adverse events. FS appeared to be a superior hemostatic agent in these vascular procedures. No complications from FS were noted.

Experience improves successful use of fibrin sealant in total knee arthroplasty: implications for surgical education.

This study evaluating fibrin sealant application in total knee arthroplasty (TKA) found significant differences in the decline in adjusted hemoglobin loss at 48 hours postoperatively in the treatment group (FS) relative to the control group (C) when the groups were segregated into early and late subgroups. The decline between the late C, 3.53 +/- 0.22 g/dL, and the late FS, 3.01 +/- 0.20 g/dL, was 0.52 g/dL (p = 0.04). The decline between the early C, 3.51 +/- 0.21 g/dL, and the early FS, 3.25 +/- 0.22 g/dL, was 0.26 g/dL (p = 0.34). This study demonstrates the importance of experience and education in successful application of tissue adhesives.

Fibrin sealant reduces perioperative blood loss in total hip replacement.

Patients (n = 81) undergoing total hip replacement (THR) were randomized to receive either standard of care plus fibrin sealant (FS) (10 mL total) or standard of care alone to evaluate the efficacy of FS for reducing blood loss in THR. Considering the 81 intent-to-treat patients, adjusted perioperative blood loss was reduced significantly in the FS group, by 197 mL [95% CI: 45 mL, 319 mL] or 23.5% [95% CI: 5.4%, 38.1%] (p = 0.014). When protocol violators were eliminated, leaving 73 patients, the adjusted FS group perioperative bleeding was reduced by 221 mL [95% CI: 63 mL, 351 mL] or 27.1% [95% CI: 7.6%, 42.5%] (p = 0.0098).

Safety and usability of hemostats, sealants, and adhesives.

Hemostats, sealants, and adhesives are an integral part of surgical patient care. Nurses who have knowledge about these agents can better help ensure safe, efficient surgical patient care. As a caregiver and patient advocate, the perioperative nurse must understand the most current information about these agents and be prepared to facilitate the transfer of this knowledge to all caregivers. Information about these agents, including the contraindications, warnings, and precautions associated with their use as well as their preparation and application, is provided here. Algorithms designed to clarify the best options for using hemostats, sealants, and adhesives are included as well.

Readmissions after cardiac surgery: experience of the National Institutes of Health/Canadian Institutes of Health research cardiothoracic surgical trials network.

BACKGROUND: Readmissions are a common problem in cardiac surgery. The goal of this study was to examine the frequency, timing, and associated risk factors for readmission after cardiac operations. METHODS: A 10-center cohort study prospectively enrolled 5,158 adult cardiac surgical patients (5,059 included in analysis) to assess risk factors for infection after cardiac operations. Data were also collected on all-cause readmissions occurring within 65 days after the operation. Major outcomes included the readmission rate stratified by procedure type, cause of readmission, length of readmission stay, and discharge disposition after readmission. Multivariable Cox regression was used to determine risk factors for time to first readmission. RESULTS: The overall rate of readmission was 18.7% (number of readmissions, 945). When stratified by the most common procedure type, readmission rates were isolated coronary artery bypass grafting, 14.9% (n = 248); isolated valve, 18.3% (n = 337); and coronary artery bypass grafting plus valve, 25.0% (n = 169). The three most common causes of first readmission within 30 days were infection (17.1% [n = 115]), arrhythmia (17.1% [n = 115]), and volume overload (13.5% [n = 91]). More first readmissions occurred within 30 days (80.6% [n = 672]) than after 30 days (19.4% [n = 162]), and 50% of patients were readmitted within 22 days from the index operation. The median length of stay during the first readmission was 5 days. Discharge in 15.8% of readmitted patients (n = 128) was to a location other than home. Baseline patient characteristics associated with readmission included female gender, diabetes mellitus on medication, chronic obstructive pulmonary disease, elevated creatinine, lower hemoglobin, and longer operation time. More complex surgical procedures were associated with an increased risk of readmission compared with the coronary artery bypass grafting group. CONCLUSIONS: Nearly 1 of 5 patients who undergo cardiac operations require readmission, an outcome with significant health and economic implications. Management practices to avert in-hospital infections, reduce postoperative arrhythmias, and avoid volume overload offer important targets for quality improvement.

Long-term satisfaction and medication dependence after antireflux surgery.

BACKGROUND: Antireflux surgery remains an important treatment for gastroesophageal reflux disease (GERD) refractory to medical management. However, there is a paucity of data on long-term surgical outcomes. The objectives of this study were to determine long-term patient satisfaction and medication dependence after antireflux surgery. METHODS: We identified all patients having antireflux surgery for GERD at our institution between 2000 and 2010. Medical records were reviewed and long-term outcomes were assessed using telephone surveys. Cox proportional hazards models were used to identify significant predictors of patient satisfaction and medication use 5 years and 10 years after surgery. RESULTS: We surveyed 195 patients receiving antireflux surgery with a median follow-up of 6.3 years; 191 of 195 operations (98%) were performed laparoscopically. Five years after surgery, 82% of patients were satisfied with their operation and 83% of patients were not taking any antireflux medication. At 10 years postoperatively, these rates drop to 59% and 38%, respectively. Of patients taking medication who received formal evaluation of their symptoms, only 38.5% (15 of 39) had evidence of reflux. Age, sex, year of operation, surgeon specialty, body mass index, and presenting symptom were not associated with long-term satisfaction or medication use. CONCLUSIONS: Antireflux surgery dramatically improves symptoms and provides excellent 5-year patient satisfaction and freedom from medication use. However, both of these outcomes decrease with follow-up out to 10 years.

Phase I trial of induction histone deacetylase and proteasome inhibition followed by surgery in non-small-cell lung cancer.

INTRODUCTION: Despite complete surgical resection survival in early-stage non-small-cell lung cancer (NSCLC) remains poor. On the basis of prior preclinical evaluations, we hypothesized that combined induction proteasome and histone deacetylase inhibitor therapy, followed by tumor resection, is feasible. METHODS: A phase I clinical trial using a two-staged multiple-agent design of bortezomib and vorinostat as induction therapy followed by consolidative surgery in patients with NSCLC was performed. Standard toxicity and maximum tolerated dose were examined. Pre- and post-treatment tumor gene-expression arrays were performed and analyzed. Pre- and post-treatment fluorodeoxyglucose-positron emission tomography imaging was used to assess tumor metabolism. Finally, serum 20S proteasome levels were analyzed with enzyme-linked immunosorbent assay, and selected intratumoral proteins were assessed by immunohistochemistry. RESULTS: Of the 34-four patients providing written consent to participate in the trial, 21 were enrolled. One patient withdrew early because of disease progression. The maximum tolerated dose was bortezomib 1.3 mg/m and vorinostat 300 mg twice daily. There were grade III dose-limiting toxicities of fatigue and hypophosphatemia, which were self-limited. There was no mortality. Thirty percent of patients (6 of 20) had more than 60% histologic necrosis of their tumor after treatment, with two having 90% or more tumor necrosis. Tumor metabolism, 20S proteasome activity, and specific protein expression did not demonstrate consistent results. Gene-expression arrays comparing pre- and post-therapy NSCLC specimens revealed robust intratumoral changes in specific genes. CONCLUSIONS: Induction bortezomib and vorinostat therapy followed by surgery in patients with operable NSCLC is feasible. Correlative gene-expression studies suggest new targets and cell-signaling pathways that may be important in modulating this combined therapy.

State-of-the-art review: Hemostats, sealants, and adhesives II: Update as well as how and when to use the components of the surgical toolbox.

The goal of this submission is to describe how and when to best use hemostats, sealants, and adhesives as well as to compare their characteristics and to update the surgical toolbox with respect to any new products approved by the Food and Drug Administration (FDA) as of this date (November 2009). The materials will be presented in 3 major groups each containing specific categories: (1) hemostats; mechanical, active, flowable, and fibrin sealant, (2) sealants; fibrin sealant, polyethylene glycol polymer, and albumin and glutaraldehyde, (3) adhesives; cyanoacrylate, albumin and glutaraldehyde, and fibrin sealant. The categories will be used for comparisons based on safety, efficacy, usability, and cost. Recommendations with respect to how and when to best use these materials will be presented. A review of the recent literature is also provided with respect to the most recent uses of these materials in specific surgical specialties.

Phase I trial of intrapleural docetaxel administered through an implantable catheter in subjects with a malignant pleural effusion.

INTRODUCTION: Malignant pleural effusion (MPE) is a common complication in patients with advanced malignancy. This dose escalation phase I study was designed to determine the maximum tolerated dose of intrapleural docetaxel administered through an implantable catheter in subjects with MPE. METHODS: Subjects with MPE (n = 15) with median age of 64.6 years and an Eastern Cooperative Oncology Group performance status of 0 to 2 at baseline were enrolled into four single dose levels of docetaxel administered intrapleurally after drainage of the pleural effusion and insertion of an intrapleural catheter. The study determined the pharmacokinetic properties, clinical response, and toxicity profile of intrapleural docetaxel. RESULTS: All patients tolerated the therapy well and there were no significant toxicities. The majority of patients had a complete radiographic response. All patients receiving dose 100 mg/m2 or higher had a complete radiographic response. One dose-limiting toxicity was encountered in the dose 50 mg/m2. Pharmacokinetic data demonstrated peak plasma concentration of docetaxel between 30 minutes and 6 hours after infusion. Pleural exposure to docetaxel was 1000 times higher than systemic exposure. CONCLUSIONS: Single-dose intrapleural administration of doxetaxel is well tolerated in patients with MPE with minimal toxicity. The excellent clinical responses in this study after treatment with intrapleural doxetaxel suggest that further investigation is warranted.

A thoracic surgeon-directed tobacco cessation intervention.

BACKGROUND: Thoracic surgeons receive little training in promoting tobacco cessation despite the impact of tobacco use on their patients. There are only a few prospective reports of tobacco cessation efforts involving thoracic surgeons in the scientific literature. The purpose of this study was to prospectively evaluate a brief tobacco cessation intervention offered by surgeons in an outpatient thoracic surgery clinic. METHODS: Adult smokers from a single-institution thoracic surgery clinic were enrolled in a single-arm prospective pilot trial between January and December 2008. Patients received a 10-minute intervention including discussing their motivation for quitting, offering tobacco cessation medication, and promoting a free telephone quitline. The primary outcome was abstinence at 3 months. Univariate logistic regression identified factors associated with tobacco cessation. RESULTS: Forty of 60 eligible smokers enrolled in the study. The mean age and standard deviation of participants was 52.1 +/- 12.6 years with a 39.9 +/- 11.2 pack-year smoking history. The 3-month quit rate was 35% (14 of 40). Fifty percent (20 of 40) of participants used at least one tobacco cessation medication. Only 7.5% (3 of 40) of patients called the quitline, but each of these participants quit smoking. Successful tobacco cessation was associated with a malignant diagnosis and being the only tobacco user in the home (odds ratio, 4.2; 95% confidence interval, 1.0 to 17.2; and odds ratio, 6.1; 95% confidence interval, 1.4 to 26.3, respectively). CONCLUSIONS: Thoracic surgeons can successfully implement a tobacco cessation program with an excellent rate of abstinence compared with reported cessation rates at 3 months from the literature. Further investigation with a larger sample size, longer follow-up, and improved utilization of the quitline is warranted.