Physiological performance of a detergent decellularized heart valve implanted for 15 months in Vietnamese pigs: surgical procedure, follow-up, and explant inspection.

This study features the longest experimental follow-up for decellularized heart valves implanted in an animal model. Porcine aortic heart valves were decellularized according to a disclosed standardized method in which TRITON X-100 and sodium cholate (TRICOL) are used in succession, followed by a further treatment with the endonuclease Benzonase to completely remove the nucleic acid remnants. Experimental animals (n = 17), represented by Vietnamese pigs (VPs), received a decellularized aortic allograft as a substitute for the replacement of their right ventricular outflow tract. The surgical implantation of the TRICOL-treated aortic valve conduit was successful in 11 VPs, while perioperative or postoperative complications occurred in the remaining six animals. In the sham-operated group (n = 4), the native pulmonary root was excised and immediately reimplanted orthotopically in the same animal. Echocardiography demonstrated a satisfactory hemodynamic performance of the TRICOL-treated valves during follow-up as well as the absence of relevant leaflet alterations concerning thickness and motility or valve insufficiency. At explantation, macroscopic inspection of tissue-engineered heart valve conduits did not evidence calcifications and showed a decreased wall thickness, comparable to that of the reimplanted native pulmonary roots. Noteworthy, extended functional performance, recovery of DNA content, and active extracellular matrix precursor incorporation are apparently compatible with the properties of a living self-supporting substitute.

Effect on quality of life of cisplatin added to single-agent chemotherapy as first-line treatment for elderly patients with advanced non-small cell lung cancer: Joint analysis of MILES-3 and MILES-4 randomised phase 3 trials.

OBJECTIVES: To evaluate the effect on quality of life (QOL) of the addition of cisplatin to single-agent chemotherapy in the treatment of elderly patients with advanced non-small cell lung cancer (NSCLC) enrolled in two parallel phase 3 trials, MILES-3 and MILES-4. PATIENTS AND METHODS: Advanced NSCLC pts, >70 years old, performance status (PS) 0-1, were eligible. Patients were randomly assigned to chemotherapy without or with cisplatin. EORTC QLQ C30 and LC13 questionnaires were planned at baseline, end of cycle 1 and end of cycle 2 in both trials and were used for joint QOL analysis. Trial-specific data including questionnaires at non-shared time-points were used for additional analyses. Intention-to-treat strategy was applied. Analyses were adjusted for baseline QOL, stage, performance status, gender, age, size of centre, trial, histotype and non-platinum companion drug. RESULTS: Overall, 458/531 pts (86%) answered baseline questionnaire and missing rates over treatment were slightly higher among patients receiving cisplatin. Mean change in sore mouth after cycle 2 was worse with cisplatin (P = 0.02). The size of differences between arms was in the small-medium range for peripheral neuropathy and alopecia (0.25 and 0.31 after one and 0.28 and 0.36 after two cycles, respectively) and for nausea/vomiting, sore mouth and dysphagia after two cycles (0.26, 0.38 and 0.25, respectively) always in the direction of worsening with cisplatin. Using a 10% change from baseline as clinically relevant threshold to categorize response, there was no significant difference between the arms. Time to deterioration of sore mouth and alopecia, with progression/death as competitive risk, was shorter with cisplatin (HR 1.72 95%CI 1.02-2.89, P = 0.04 and HR 1.84 95%CI 1.09-3.10, P = 0.02, respectively). CONCLUSION: The addition of cisplatin to single agent chemotherapy worsens sore mouth and alopecia and does not improve any QOL items in elderly patients with advanced NSCLC.

Nitinol flexigrip sternal closure system and standard sternal steel wiring: insight from a matched comparative analysis.

OBJECTIVE: We sought to assess the efficiency of two different sternal closure techniques in preventing sternal wound instability in high-risk patients. MATERIALS AND METHODS: Between January 2009 and February 2012, 2068 consecutive cardiac patients were prospectively collected in our database. The 561 patients in whom the thermoreactive nitilium clips (Flexigrip) have been used (group A) were matched 1 : 1 with 561 patients who received a standard parasternal wiring technique (group B) on 10 available risk factors known to affect sternal wound healing (age, age >75 years, sex, diabetes mellitus, cardiac procedure, obesity, re-intervention, cross-clamp, and total operative times). The study was completed with a cost analysis. RESULTS: The two groups were well matched, although different for bilateral internal thoracic harvesting, chronic obstructive pulmonary disease, renal insufficiency, and congestive heart failure, which were significantly more frequent in group A. At 30 days of follow-up, the association of wound complication and sternal instability was significantly less frequent in group A versus group B (0.2 versus 1.6%) (P = 0.04). Overall incidence of sternal wound complication was lower in group A (2 versus 3.5%) (P = 0.28). In the presence of wound infection, a sternal wound instability was never observed in group A (P = 0.06). Overall costs were €8,701,854 and €9,243,702 in groups A and B, respectively; thus the Flexigrip closure technique offered a €541,848 cost saving. CONCLUSIONS: Flexigrip use in high-risk patients showed a lower incidence of sternal wound instability with no need for sternal re-wiring in any case, even in the presence of wound infection.

Nitinol flexigrip sternal closure system and chest wound infections: insight from a comparative analysis of complications and costs.

BACKGROUND: We sought to assess the efficiency of two different sternal closure techniques in preventing sternal wound complications (SWC). A cost analysis was also considered. METHODS: Between January 2008 and April 2010, 1,644 consecutive cardiac surgery patients who underwent cardiac surgery in our institute were prospectively collected. A total of 1,072 patients received a standard parasternal wiring technique (group A), and 572 patients received a new method of sternal closure based on the use of thermoreactive nitillium clips (Flexigrip; Praesidia SRL, Bologna, Italy [group B]). We investigated, by a propensity matched analysis, whether the use of standard or nitinol clip closure would impact on sternal wound outcome. RESULTS: In all, 464 patients of each group were matched for 17 available risk factors. Overall incidence of SWC was significantly higher in group A (4.1% versus 1.7%; p=0.03). Sternal surgical revision to treat a thoracic instability was required in a significantly higher number of patients in group A (9 patients, 1.9%) and in none of group B (p=0.004). The incidence of sternal instability, secondary to wound infection, was significantly lower in group B (p=0.05). Overall costs were €7,407,296 and €6,896,432 in group A and group B, respectively. Thus, nitinol clip closure technique offered a €510,864 cost saving compared with standard steel wiring technique. CONCLUSIONS: The Flexigrip assured a lower incidence of SWC. The use of the nitinol clip favored an improved sternal closure technique preventing mediastinitis. Additionally, the nitinol clip system proved to be cost effective in cardiac surgery.

Quality of life analysis of TORCH, a randomized trial testing first-line erlotinib followed by second-line cisplatin/gemcitabine chemotherapy in advanced non-small-cell lung cancer.

INTRODUCTION: The TORCH (Tarceva or Chemotherapy) trial randomized patients with advanced non-small-cell lung cancer to first-line erlotinib followed by second-line cisplatin/gemcitabine versus. standard inverse sequence. The trial, designed to test noninferiority in overall survival, was stopped at interim analysis because of inferior survival in the experimental arm. Quality of life (QoL), a secondary outcome, is reported here. METHODS: QoL was assessed at baseline and every 3 weeks during first-line, using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 and QLQ-lung cancer specific module (LC13). Mean changes from baseline within arms were reported. QoL response and time-to-deterioration of QoL using a competing-risk approach were compared between treatment arms. RESULTS: Six hundred and thirty patients (83%) completed baseline questionnaires. Compliance was affected by differential treatment efficacy, but was similar between arms for patients without progression or death. Significant differences in QoL responses were observed favoring chemotherapy for pain, sleeping, dyspnea, diarrhea, and favoring erlotinib for vomiting, constipation, sore mouth, and alopecia. In the small subset of patients with EGFR-mutated tumors, all selected items (global QoL, physical functioning, cough, dyspnea and pain) improved, whereas worsening or no change was observed in wild-type patients. Improvement was particularly evident in the first-line erlotinib arm as for global QoL and physical functioning. CONCLUSIONS: QoL was impacted by differential toxicity and efficacy between arms. Functional domains and global QoL did not differ, although some symptoms were better controlled with chemotherapy in unselected non-small-cell lung cancer patients.