Cost-effectiveness of routine mediastinoscopy in computed tomography– and positron emission tomography–screened patients with stage I lung cancer

ObjectiveAccurate preoperative staging is essential for the optimal management of patients with lung cancer. An important goal of preoperative staging is to identify mediastinal lymph node metastasis. Computed tomography and positron emission tomography may identify mediastinal lymph node metastasis with sufficient sensitivity to allow omission of mediastinoscopy. This study utilizes our experience with patients with clinical stage I lung cancer to perform a decision analysis addressing whether mediastinoscopy should be performed in clinical stage I lung cancer patients staged by computed tomography and positron emission tomography.MethodsWe retrospectively reviewed our thoracic surgery database for cases between May 1999 and May 2004. Patients deemed clinical stage I by computed tomography and positron emission tomography were chosen for further study. Individual computed tomography, positron emission tomography, and operative and pathology reports were reviewed. The postresection pathologic staging and long-term survival were recorded. A decision model was created using TreeAgePro software and our observed data for the prevalence of mediastinal lymph node metastases and for the rate of benign nodules. Data reported in the literature were also utilized to complete the decision analysis model. A sensitivity analysis of key variables was performed.ResultsA total of 248 patients with clinical stage I lung tumors were identified. One hundred seventy-eight patients (72%) underwent mediastinoscopy before resection, and 5/178 (3%) showed N2 disease. An additional 9 patients were found to have N2 metastasis in the final resected specimen, resulting in a total of 14/248 patients (5.6%) with occult mediastinal lymph node metastases. Benign nodules were found in 19/248 (8%) of patients. Decision analysis determined that mediastinoscopy added 0.008 years of life expectancy at a cost of $250,989 per life-year gained. The outcome was sensitive to the prevalence of N2 disease in the population and the benefit of induction versus adjuvant therapy for N2 lung cancer. If the prevalence of N2 disease exceeds 10$100,000 per life-year gained.ConclusionPatients with clinical stage I lung cancer staged by computed tomography and positron emission tomography benefit little from mediastinoscopy. The survival advantage it confers is very small and is dependent on the prevalence of N2 metastasis and the unproven superiority of induction therapy over adjuvant therapy

Bronchial airway anastomotic complications after pediatric lung transplantation: Incidence, cause, management, and outcome

ObjectiveAirway complications are a recognized surgical complication and an important source of morbidity after adult lung transplantation. Little is known about these complications after pediatric lung transplantation.MethodsData of pediatric lung transplants performed between January 1990 and December 2002 in a single pediatric institution were reviewed retrospectively.ResultsA total of 214 patients, with a mean age of 9.8 ± 6.1 years (range 0.01-19.7 years), underwent 239 lung transplants: 231 bilateral and 8 single. Mean follow-up was 3.4 years. Forty-two airway complications requiring interventions (stenosis = 36; dehiscence = 4; malacia = 2) developed in 30 recipients (complication rate: 9% of 470 bronchial anastomoses at risk). There were airway complications in 29 bilateral lung transplants (13%) and 1 single lung transplant (13%). Mean time to diagnosis was 51 ± 27 days (median: 53, range 1-96 days), and diagnoses were made in 90% of patients within the first 3 months after transplantation. Preoperative Pseudomonas cepacia, postoperative fungal lung infection, and days on mechanical ventilator were found to be significant risk factors on multivariate analysis (P = .002, P = .013 and P = .003, respectively). Treatment included rigid bronchoscopic dilatation in 17 patients, balloon dilatation in 13 patients, and stent placement in 12 patients. Other treatments consisted of debridement, fibrin glue application, chest tube placement, and pneumonectomy followed by retransplantation. No patients died as a direct result of airway complications. There was no significant difference in the incidence of bronchiolitis obliterans or overall survival in comparison with patients who did not have airway complications.ConclusionsAirway complications are a significant cause of morbidity after pediatric lung transplantation. The majority are successfully treated, and patient outcomes are not adversely affected

Does prior coronary angioplasty affect outcomes of surgical coronary revascularization? Insights from the STICH trial

Background: The STICH trial showed superiority of coronary artery bypass plus medical treatment (CABG) over medical treatment alone (MED) in patients with left ventricular ejection fraction (LVEF) ≤35%. In previous publications, percutaneous coronary intervention (PCI) prior to CABG was associated with worse prognosis. Objectives: The main purpose of this study was to analyse if prior PCI influenced outcomes in STICH. Methods and results: Patients in the STICH trial (n = 1212), followed for a median time of 9.8 years, were included in the present analyses. In the total population, 156 had a prior PCI (74 and 82, respectively, in the MED and CABG groups). In those with vs. without prior PCI, the adjusted hazard-ratios (aHRs) were 0.92 (95% CI = 0.74–1.15) for all-cause mortality, 0.85 (95% CI = 0.64–1.11) for CV mortality, and 1.43 (95% CI = 1.15–1.77) for CV hospitalization. In the group randomized to CABG without prior PCI, the aHRs were 0.82 (95% CI = 0.70–0.95) for all-cause mortality, 0.75 (95% CI = 0.62–0.90) for CV mortality and 0.67 (95% CI = 0.56–0.80) for CV hospitalization. In the group randomized to CABG with prior PCI, the aHRs were 0.76 (95% CI = 0.50–1.15) for all-cause mortality, 0.81 (95% CI = 0.49–1.36) for CV mortality and 0.61 (95% CI = 0.41–0.90) for CV hospitalization. There was no evidence of interaction between randomized treatment and prior PCI for any endpoint (all adjusted p > 0.05). Conclusion: In the STICH trial, prior PCI did not affect the outcomes of patients whether they were treated medically or surgically, and the superiority of CABG over MED remained unchanged regardless of prior PCI. Clinical trial registration: Clinicaltrials.gov; Identifier: NCT0002359

Multicenter double blind trial of autologous bone marrow mononuclear cell transplantation through intracoronary injection post acute myocardium infarction – MiHeart/AMI study

Background: Myocardial infarction remains as a major cause of mortality worldwide and a high rate of survivors develop heart failure as a sequel, resulting in a high morbidity and elevated expenditures for health system resources. We have designed a multicenter trial to test for the efficacy of autologous bone marrow (ABM) mononuclear cell (MC) transplantation in this subgroup of patients. The main hypothesis to be tested is that treated patients will have a significantly higher ejection fraction (EF) improvement after 6 months than controls. Methods: A sample of 300 patients admitted with ST elevation acute myocardial infarction (STEMI) and left ventricle (LV) systolic dysfunction, and submitted to successful mechanical or chemical recanalization of the infarct-related coronary artery will be selected for inclusion and randomized to either treated or control group in a double blind manner. The former group will receive 100 x 106 MC suspended in saline with 5% autologous serum in the culprit vessel, while the latter will receive placebo (saline with 5% autologous serum). Implications: Many phase I/II clinical trials using cell therapy for STEMI have been reported, demonstrating that cell transplantation is safe and may lead to better preserved LV function. Patients with high risk to develop systolic dysfunction have the potential to benefit more. Larger randomized, double blind and controlled trials to test for the efficacy of cell therapies in patients with high risk for developing heart failure are required.Brazilian Ministry of Science and Technology (MCT)/The Financing Agency for Studies and Projects (FINEP

Amiloride Enhances Antigen Specific CTL by Faciliting HBV DNA Vaccine Entry into Cells

The induction of relatively weak immunity by DNA vaccines in humans can be largely attributed to the low efficiency of transduction of somatic cells. Although formulation with liposomes has been shown to enhance DNA transduction of cultured cells, little, if any, effect is observed on the transduction of somatic tissues and cells. To improve the rate of transduction, DNA vaccine delivery by gene gun and the recently developed electroporation techniques have been employed. We report here that to circumvent requirement for such equipment, amiloride, a drug that is prescribed for hypertension treatment, can accelerate plasmid entry into antigen presenting cells (APCs) both in vitro and in vivo. The combination induced APCs more dramatically in both maturation and cytokine secretion. Amiloride enhanced development of full CD8 cytolytic function including induction of high levels of antigen specific CTL and expression of IFN-γ+perforin+granzymeB+ in CD8+ T cells. Thus, amiloride is a facilitator for DNA transduction into host cells which in turn enhances the efficiency of the immune responses

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016