Influence of Vitamins on Secondary Reactive Oxygen Species Production in Sera of Patients with Resectable NSCLC.

BACKGROUND: Singlet oxygen (¹O2) oxidizes targets through the production of secondary reactive oxygen species (SOS). Cancers induce oxidative stress changing with progression, the resulting antioxidant status differing from one patient to the other. The aim of this study was to determine the oxidative status of patients with resectable Non-Small cell lung cancers (NSCLC) and the potential influence of antioxidants, compared to sera from healthy donors. MATERIALS AND METHODS: Serum samples from 10 women and 28 men, 19 adenocarcinomas (ADK), 15 patients N1 or M1 were submitted to a photoreaction producing ¹O2. Then, samples were supplemented with vitamins (Vit C, Vit E), or glutathione (GSH). RESULTS: Squamous cell carcinomas (SCC) and metastatic SCCs induced a lower SOS rate. While Vit C increased SOS in controls as in patients with metastases, Vit E or the combination of Vit E and C strongly reduced SOS. GSH alone lightly decreased SOS in controls but had no effect in patients either alone or combined with Vit C. CONCLUSION: In "early" lung cancers, SOS are comparable or lower than for healthy persons. The role of Vitamins varies with gender, cancer type, and metastases. This suggests that an eventual supplementation should be performed on a per-patient basis to evidence any effect.

Renal insufficiency, mortality, and drug management in heart transplant. Results of the CARIN study.

Renal insufficiency (RI) is a frequent complication in heart transplant (HT) patients. The main objectives of the Cardiac trAnsplantation and Renal INsufficiency (CARIN) study were to follow the evolution of renal function after heart transplantation (HTx), to identify the factors associated with the decline of renal function, to describe the impact of RI on mortality during 3 years after the HT, and to observe the renal profile of the prescriptions. CARIN was a French retrospective, multicentric, study. Data were collected for patients who received a HT between 2000 and 2005. Data collection was performed at five time points: before HTx (T0), 1(T1), 6(T6), 12 (T12), and 36 (T36) months after HTx. Glomerular filtration rate (GFR) was estimated with aMDRD formula. RI was defined as GFR < 60 ml/min/1.73 m². Four hundred and forty-one patients from five HT centers were included. The prevalences of RI were 28.8% (T0), 54.0% (T1), 50.4% (T6), 51.6% (T12), and 59.6% (T36). Age and cyclosporine were independently linked to the decline of renal function. Hypertension and GFR < 60 at T0 were independent risk factors of mortality. 48.7-64.7% of the nonimmunosuppressive prescriptions were drugs that required dosage adjustment in RI patients or for which no data were available concerning administration in RI patients. RI is highly frequent after HTx. Because RI is a risk factor of mortality, any sparing renal strategies have to be undertaken.

Relapse of Serratia marcescens sternal osteitis 15 years after the first episode.

Sternal osteitis, a potential consequence of cardiac surgery, remains rare. The bacteria involved belong mostly to the genus Staphylococcus. Sternal infections caused by Serratia marcescens are exceptional. We report an unusual recurrence of sternal infection with S. marcescens, 15 years after the initial episode. The identities of the isolates were determined by genomic analysis.

Disseminated Scedosporium/Pseudallescheria infection after double-lung transplantation in patients with cystic fibrosis.

We report a case of disseminated Scedosporium/Pseudallescheria infection due to Pseudallescheria boydii sensu stricto after lung transplantation in a patient with cystic fibrosis. Dissemination occurred under voriconazole. Despite surgery and combination therapy with voriconazole, caspofungin, and terbinafine, the patient died 8 months after transplantation. Previously reported cases are reviewed.

Prospective preoperative mediastinal lymph node staging by integrated positron emission tomography-computerised tomography in patients with non-small-cell lung cancer.

OBJECTIVE: Mediastinal lymph node staging determines the treatment strategy for non-small-cell lung cancer. This study aims to evaluate prospectively the accuracy of preoperative integrated 18-fluoro-2-deoxy-D-glucose positron emission tomography-computerised tomography ((18)FDG PET-CT) for mediastinal lymph node staging. METHODS: Preoperative integrated (18)FDG PET-CT was used to analyse mediastinal lymph nodes in patients with non-small-cell lung cancer. Nodal stations were identified according to the American Thoracic Society mapping system. Lymph nodes with a standardised uptake value (SUVmax) >3 were considered to be positive. The mediastinal lymph nodes were harvested during lung resection and the results of integrated (18)FDG PET-CT were compared to the mediastinal lymph node histology results. RESULTS: A total of 51 patients were enrolled in this study. The mean interval between integrated (18)FDG PET-CT and surgery was 31+/-15.8 days (range: 2-78 days). The mean mediastinal lymph node harvested and station number per patient during surgery were 11.8+/-5.6 (range: 2-27) and 3.8+/-1 (range: 2-6), respectively. The incidence of N2 pathological disease was 19.6%. The integrated (18)FDG PET-CT sensitivity and specificity were 40+/-30% and 85+/-11%, respectively. The positive and negative predictive values were 40+/-30% and 85+/-11%, respectively. False-positive results (six patients) were mainly due to inflammatory lymph nodes. False-negative results (six patients) were mainly due to infra-centimetrical, malignant lymph node invasion. CONCLUSION: The sensitivity of integrated (18)FDG PET-CT for mediastinal lymph node staging in patients selected for surgery is low. When positive mediastinal lymph nodes are detected, invasive mediastinal staging must be performed. On the other hand, the specificity is high: patients with negative integrated (18)FDG PET-CT can be operated upon without invasive mediastinal staging.

Risk factors for mortality in patients with mediastinitis after cardiac surgery.

BACKGROUND: Patients with mediastinitis after cardiac surgery have higher morbidity and mortality. AIMS: Describe the characteristics of patients with mediastinitis, determine the mortality within one month, and assess the risk factors associated with mortality. METHODS: Retrospective cohort study including all adult patients with mediastinitis during the 2002-2006 period at the Nantes University Hospital. Multivariate analysis by logistic regression and Kaplan-Meier curve of survey were done. RESULTS: Nearly 5574 patients were operated during the study period, with a mediastinitis incidence rate of 0.7%, 28 patients (72%) had coronary artery bypass graft. The mortality rate increased from de 12.8% during hospital stay to 20.5% within one year. Only two deaths were associated with mediastinitis. The occurrence of a co-infection was the only independent risk factor associated with mortality (OR 13, P<0.04). The instantaneous risk of death was increased by 7 in patient with co-infection, particularly mechanical ventilator-associated pneumonia (CR 1,97). CONCLUSION: Mortality varied according to the duration of surveillance, and mediastinitis was not the major cause of death. Mechanical ventilator-associated pneumonia after mediastinitis increases the mortality and needs specific prevention.

CardioWest (Jarvik) total artificial heart: a single-center experience with 42 patients.

BACKGROUND: When implanted in patients with biventricular failure, the CardioWest total artificial heart has asserted itself over time as a reliable bridge-to-transplant device that as yet is used by only a few international teams. The aim of this single-center retrospective study is to assess both the comorbidity and survival of patients awaiting heart transplants while receiving circulatory support with a CardioWest total artificial heart. METHODS: From 1990 to December 2006, 42 patients received a CardioWest total artificial heart at our center. Mean age at the time of implantation was 45.7 +/- 9.5 years, and 40 patients (95%) were men. Idiopathic or dilated cardiomyopathy was diagnosed in 45.2% (n = 19) of the patients and ischemic cardiomyopathy in 42.8% (n = 18). Average body surface area was 1.9 +/- 0.22 m(2). RESULTS: Duration of support was 1 to 292 days (mean, 101 +/- 86 days). Twelve patients died (28.5%) while receiving device support, and 30 patients (71.5%) underwent transplantation. Actuarial survival rates for the transplanted patients were 90% (n = 25), 81% (n = 14), and 76% (n = 10) at 1, 5, and 10 years, respectively. Causes of death during device support included multiorgan failure in 6 (50%), sepsis in 2, acute respiratory distress syndrome in 2, alveolar hemorrhage in 1, and other cause in 1. There were no device malfunctions that led to patient death. Adverse events included stroke in 3 patients (7%) and infections in 35 patients (85%) during support. CONCLUSIONS: The CardioWest total artificial heart is an excellent bridge-to-transplant device for patients with biventricular failure. Our study demonstrates excellent safety, reliability, and efficiency. Exceptional outcome after transplantation underlines its capacity to aid in end-organ recovery.

Outcome of heart transplants 15 to 20 years ago: graft survival, post-transplant morbidity, and risk factors for mortality.

OBJECTIVES: The study was conducted to determine the long-term outcome of patients who underwent heart transplantation 15 to 20 years ago, in the cyclosporine era, and identify risk factors for death. METHODS: A retrospective analysis was done of 148 patients who had undergone heart transplantation between 1985 and 1991 at a single center. Operative technique and immunosuppressive treatment were comparable in all patients. RESULTS: Actuarial survival rates were 75% (n = 111), 58% (n = 86), and 42% (n = 62) at 5, 10, and 15 years, respectively. The mean follow-up period was 12.1 +/- 5.6 years for patients who survived more than 3 months after transplantation (n = 131). The major causes of death were malignancy (35.8%) and cardiac allograft vasculopathy (24.7%). No death related to acute rejection was reported after the first month of transplantation. Graft coronary artery disease was detected on angiography in 66 (50.3%), and 7 (5.3%) had retransplantation. Malignancies developed in 131 patients (48.1%), including skin cancers in 31 (23.6%), solid tumors in 26 (19.8%), and hematologic malignancies in 14 (10.6%). Severe renal function requiring dialysis or renal transplantation developed in 27 patients (20.6%). By multivariable analysis, the only pre-transplant risk factor found to affect long-term survival was a history of cigarette use (p < 0.0004). CONCLUSIONS: Long-term survival at 15 years after cardiac transplantation remains excellent in the cyclosporine era. Controlling acute allograft rejection can be achieved but seems to carry a high rate of cancers and renal dysfunction. History of cigarette use affects significantly long-term survival in our study.

Pseudocoarctation as cause of a refractory hypertension.

Pseudocoarctation of the aorta is an abnormality of the descending portion of the aortic arch at the level of the isthmus without a real pressure gradient. We report a case of a stenotic pseudocoarctation causing severe refractory hypertension.

Influence of donor characteristics on outcome after lung transplantation: a multicenter study.

BACKGROUND: The liberalization of lung-donor criteria and the use of marginal donors have been advocated to face the current shortage of donors in lung transplantation. However, the impact of donor characteristics on the outcome of lung transplantation is still largely unknown. We aimed to determine, on a large cohort of patients, the effect of donors characteristics on short- and long-term outcome of lung transplantation METHODS: Between 1988 and 1998, a total of 785 adult patients underwent single-lung transplantation (n = 270), bilateral-lung transplantation (n = 251), and heart-lung transplantation (n = 264) in 7 centers in France. We constructed several multivariate models to assess the relationship between donor characteristics and early gas exchange, duration of mechanical ventilation, and long-term survival after lung transplantation. RESULTS: Among donor characteristics, donor gas exchange before harvest was found to be significantly associated with recipient early gas exchange, duration of mechanical ventilation, and long-term survival after adjustment for potential confounding variables. Moreover, nonlinear modeling showed a steep increase in the relative risk of death when donor PaO2/FiO2 before harvest was below 350 (hazard ratio 1.43; 95% confidence interval 1.10-1.85; p = 0.01). Donor and recipient sex mismatch were also found to be significantly associated with long-term survival. CONCLUSIONS: Although liberalization of lung-donor criteria may be considered to overcome the shortage of lung donors, our data suggest that the violation of the gas-exchange criterion should be avoided.

A single solution for multiple organ procurement and preservation.

Two or three different solutions may be used to preserve thoracic and abdominal organs during a single procurement. The aim of this prospective, multi-center, noncomparative study was to evaluate the safety and efficacy of Celsior (study solution, solution S) as a flushing and cold storage solution for both thoracic and abdominal organs. Between August 1999 and July 2000, 72 consecutive multiple-organ procurements were performed using solution S as the sole solution for flushing out and cold-storing thoracic and abdominal grafts. Two hundred and sixty-four grafts were implanted into 245 recipients (131 kidneys, 9 kidney-pancreases, 69 livers, 34 hearts and 6 heart-lungs). The mean cold ischemia time was 21 h for kidneys (26%>24 h); 11 h 26 min for pancreases, 9 h 16 min for livers (23%>12 h), and 2 h 58 min for hearts and lungs. No cardiac failure or arrhythmia occurred on graft reperfusion. Fourteen percent of kidney recipients had delayed graft function. The mean serum creatinine level at 3 months was 123 +/- 41 micromol/l. All pancreas recipients were insulin-free at 3 months. Primary graft nonfunction occurred in one liver recipient. Complete hepatic artery thrombosis occurred in six liver recipients during the first month; four of these patients had a risk factor for thrombosis. All but three of the heart recipients were in sinus rhythm on day 1, and 65% were extubated on day 1. Inotropic drugs were necessary during the first 72 h in 25% of heart recipients. Twelve-month patient and graft survival rates were, respectively, 100% and 96% (kidney), 100% and 89% (pancreas), 88% and 83% (liver), 77.5% (heart) and 67% (heart-lung). These results suggest that Celsior, a ready-to-use solution, is safe and effective for multiple organ procurement and preservation.

Graft ischemic time and outcome of lung transplantation: a multicenter analysis.

RATIONALE: The effect of graft ischemic time on early graft function and long-term survival of patients who underwent lung transplantation remains controversial. Consequently, graft ischemic time has not been incorporated in the decision-making process at the time of graft acceptance. OBJECTIVES: To investigate the relationship between graft ischemic time and (1) early graft function and (2) long-term survival after lung transplantation. MEASUREMENTS AND MAIN RESULTS: The data from 752 patients who underwent single lung transplantation (n = 258), bilateral lung transplantation (n = 247), and heart-lung transplantation (n = 247) in seven French transplantation centers during a 12-year period were reviewed. Independent data quality control was done to ensure the quality of the collected variables. Mean graft ischemic time was 245.8 +/- 96.4 minutes (range 50-660). After adjustment on 11 potential confounders, graft ischemic time was associated with the recipient Pa(O2)/FI(O2) ratio recorded within the first 6 hours and with long-term survival in patients undergoing single or double lung transplantation but not in patients undergoing heart-lung transplantation. The relationship between graft ischemic time and survival appears to be of cubic form with a cutoff value of 330 minutes. These results were unaffected by the preservation fluid employed. CONCLUSIONS: The results of this large cohort of patients suggest a close relationship between graft ischemic time and both early gas exchange and long-term survival after single and double lung transplantation. Such relationship was not found in patients undergoing heart-lung transplantation. The expected graft ischemic time should be incorporated in the decision-making process at the time of graft acceptance.

Pneumothorax after left pneumonectomy: implantation of an intrapleural prosthesis.

Postpneumonectomy syndrome is defined as an airway obstruction due to mediastinal shift and rotation after pneumonectomy. A patient who had undergone a left pneumonectomy for bronchial carcinoma 13 years before presented with tension pneumothorax of her remaining lung. Although all factors relevant to the development of postpneumonectomy syndrome were ascertained, the patient had a pneumothorax rather than an airway obstruction. This pneumothorax was treated surgically. The goal of this operation was to reduce the right pleural cavity volume by implanting an intrapleural prosthesis in the pneumonectomy cavity. This treatment is identical to that used for postpneumonectomy syndrome, which allows the right lung to be rejoined with the thoracic wall.

Bivalvular mechanical mitral-aortic valve replacement in 254 patients: long-term results--a 22-year follow-up.

BACKGROUND: We have retrospectively studied 254 patients who underwent a bivalvular mechanical mitral-aortic replacement in the cardiovascular and thoracic surgery unit of Nantes from 1979 to 1989. The follow-up was 22 years (1979 to 2001). The last patient was operated on 12 years before the end of the follow-up. METHODS: All mitral prostheses were St. Jude Medical (SJM) bileaflet valves, and the aortic prostheses were 124 monodisc Björk-Shiley valves, 3 Sorin prostheses, and 127 St. Jude Medical bileaflet prostheses. The mean age was 56.8 +/- 8.5 years with a sex ratio equal to 1. Rheumatism as the etiology predominated with 79.5%. Ninety-seven percent of the patients were followed for a total of 2,779 patient-years and a mean of 11.7 years. RESULTS: Operative mortality was 7.08%. Freedom from overall mortality and valve-related mortality at 22 years were 45.7% +/- 3.6% and 73.1% +/- 3%, respectively. The linearized rates of thromboembolic and hemorrhagic events were 1.07% and 0.9% per patient-year, respectively. Multivariate analysis showed age (p < 0.002), sex (p < 0.01), and degenerative etiology (p = 0.04) as independent factors of late mortality, and age, sex, degenerative disease, and tricuspid pathology were related to valve-related mortality. CONCLUSIONS: This study shows good results after mechanical mitral-aortic replacement in terms of survival rate and quality of life in surviving patients, and outlines the factors influencing long-term results as compared with isolated mitral valve replacement.

Does the pretransplant UNOS status modify the short- and long-term cardiac transplant prognosis?

BACKGROUND: We compared the morbidity and mortality rates of patients who had urgent heart transplantation or transplantation after bridging with a ventricular assist device, with the rates of patients whose clinical stability allowed them to wait at home. METHODS: From March 1985 to December 2000, 404 patients underwent heart transplantation in a single center. There were 273 patients with UNOS status 2 (US 2), 103 patients with UNOS Status 1A (US 1A), and 28 patients with UNOS Status 1B (US 1B). We compared the groups retrospectively with respect to pretransplantation status and operative results. RESULTS: Despite more severely impaired hemodynamics and a significantly higher preoperative infection rate in US 1A and 1B patients, there were no statistically significant differences in survival rates among the three groups. Donor sex and age, cytomegalovirus and toxoplasmosis, mismatch rate, ischemic time, method of myocardial protection, and operative technique did not differ statistically among the three groups. Length of intensive care unit stay, postoperative morbidity, first year postoperative rejection rate, and graft occlusive vascular disease rate were statistically similar among the three groups. Although pretransplantation cancer assessment was less complete in US 1A and 1B than in US 2 patients, the late-cancer rate was not statistically different among the three groups. CONCLUSIONS: These data suggest that urgently transplanted patients have both early and long term morbidity and mortality similar to those of patients waiting for transplantation at home or with a ventricular assist device.

[Lung and heart-lung transplantation in cystic fibrosis]. / Transplantation pulmonaire dans la mucoviscidose.

Lung transplantation is a valid treatment in cystic fibrosis patients at end stage of the disease. It is decided when the vital prognosis seems to be engaged within two years. Patients are put on the waiting list after they have been checked out according to their individual potential risks and difficulties. The waiting time on list may be prolonged and should be used to optimize nutritional status (gastrostomy) and to take into account the psychological aspect of the project. The choice between double lung transplantation and heart lung transplantation depends on teams experience. Survival rate is increasing (until 90% and 78% survival rate at 1 and 5 years). Contra-indications are represented by a dependence on invasive assisted ventilation before referral to transplant, and adhesions after surgical pleurectomy. Long term results depend on bronchiolitis obliterans which is for some teams an opportunity to discuss the possibility of retransplantation.

Myocardial preservation using Celsior solution in cardiac transplantation: early results and 5-year follow-up of a multicenter prospective study of 70 cardiac transplantations.

BACKGROUND: Several storage methods using a wide variety of extracellular or intracellular solutions applied either as continuous perfusion, intermittent perfusion, or simple immersion of the heart have been commonly used. We have performed a prospective randomized multicenter study of 70 cardiac transplantation recipients to evaluate the Celsior solution for cardiac preservation. METHODS: Seventy consecutive patients were included in this trial and received a cardiac graft arrested and preserved with Celsior. The first follow-up period was 1 month. The mean age of the recipients was 49 years (range, 28 to 66 years), and 81.7% were male. The main disease was nonobstructive cardiomyopathy (64.3%). The age range of donors was between 14 and 56 years with a mean of 33 years. The majority of grafts (73%) were stored in 1 L of Celsior. A midterm follow-up at 5 years was performed and was 100% complete. RESULTS: The operative mortality (<30-day) rate was 6 of 70 (8.6%). Sixty-three patients (90%) had at least satisfactory hemodynamic measurements on day 2. The first postoperative echocardiograms showed good myocardial performance for 90% of the grafts. Actuarial survival rate at 5 years was 75% +/- 5.1%. CONCLUSIONS: The use of Celsior in cardiac transplantation was safe and very effective. This solution proved very valuable in at-risk patients.