Leonardo Fuks

Long-term follow-up of flexible bronchoscopic treatment for bronchial carcinoids with curative intent.

Background. Typical pulmonary carcinoids represent less than 5% of primary lung tumors. In patients with typical bronchial carcinoid, formal surgical resection still remains the gold-standard treatment. Data regarding long-term outcome in using flexible bronchoscope-based modalities under conscious sedation is very limited. Objectives. We sought to investigate, over extended follow-up period, the effectiveness of endobronchial resection for carcinoid tumors with curative intent using flexible bronchoscopy. Methods. Nd:YAG laser photoresection using flexible bronchoscope under conscious sedation. Follow-up included repeat bronchoscopy every 6 months and chest CT every year. Results. Ten patients aged 24 to 70 years with endobronchial carcinoid were treated. The tumor location was variable: 2 left Main bronchus, 1 left upper lobe bronchus, 2 right main bronchus, 2 right middle lobe bronchus and 3 right lower lobe bronchus. No major complications were observed. The patients required between 2 and 4 procedures. Patients were followed for a median period of 29 months with no evidence of tumor recurrence. Conclusions. Endobronchial laser photoresection of typical bronchial carcinoids using flexible bronchsocopy under conscious sedation is an effective treatment modality for a subgroup of patients that provides excellent long-term results that are similar to outcome obtained by more invasive procedures.

Herpes zoster after lung transplantation: incidence, timing, and outcome.

BACKGROUND Although herpes zoster is a common complication of lung transplantation, the epidemiologic data are limited. The aims of the present study were to determine the incidence and clinical manifestations of herpes zoster in a large cohort of lung transplant recipients and to identify risk factors associated with its development. METHODS The files of all adult patients who underwent lung transplantation at a major tertiary medical center from January 2001 to December 2007 were reviewed. Data were extracted on background, transplant-related, and posttransplantation factors. The occurrence and clinical characteristics of all episodes of herpes zoster were recorded. RESULTS Of the 198 lung transplant recipients, 23 had a herpes zoster infection, of whom 18 had herpes in a single dermatome. Disseminated cutaneous infection was documented in 4 cases (17%) and visceral involvement in 1. The median duration of follow-up was 34 months (range, 1 to 85 months). There were no recurrent infections. Postherpetic neuralgia was detected in 26% of cases. Antiviral prophylaxis, primarily for cytomegalovirus, was effective (during treatment) against herpes zoster. The incidence of herpes zoster was higher in patients treated with rabbit antithymocyte globulin. CONCLUSIONS The occurrence of herpes zoster peaks between 12 and 36 months after lung transplantation. Additional immunosuppression may increase the risk. Further studies on preventive strategies against herpes zoster in this population are warranted.

Voriconazole and itraconazole in lung transplant recipients receiving tacrolimus (FK 506): efficacy and drug interaction

Kramer MR, Amital A, Fuks L, Shitrit D. Voriconazole and itraconazole in lung transplant recipients receiving tacrolimus (FK 506): efficacy and drug interaction. 
Clin Transplant 2011: 25: E163–E167.

Characterization of Novel Multiantigenic Vaccine Candidates with Pan-HLA Coverage against Mycobacterium tuberculosis

ABSTRACT The low protection by the bacillus Calmette-Guérin (BCG) vaccine and existence of drug-resistant strains require better anti-Mycobacterium tuberculosis vaccines with a broad, long-lasting, antigen-specific response. Using bioinformatics tools, we identified five 19- to 40-mer signal peptide (SP) domain vaccine candidates (VCs) derived from M. tuberculosis antigens. All VCs were predicted to have promiscuous binding to major histocompatibility complex (MHC) class I and II alleles in large geographic territories worldwide. Peripheral mononuclear cells (PBMC) from healthy naïve donors and tuberculosis patients exhibited strong proliferation that correlated positively with Th1 cytokine secretion only in healthy naïve donors. Proliferation to SP VCs was superior to that to antigen-matched control peptides with similar length and various MHC class I and II binding properties. T-cell lines induced to SP VCs from healthy naïve donors had increased CD44high/CD62L+ activation/effector memory markers and gamma interferon (IFN-γ), but not interleukin-4 (IL-4), production in both CD4+ and CD8+ T-cell subpopulations. T-cell lines from healthy naïve donors and tuberculosis patients also manifested strong, dose-dependent, antigen-specific cytotoxicity against autologous VC-loaded or M. tuberculosis-infected macrophages. Lysis of M. tuberculosis-infected targets was accompanied by high IFN-γ secretion. Various combinations of these five VCs manifested synergic proliferation of PBMC from selected healthy naïve donors. Immunogenicity of the best three combinations, termed Mix1, Mix2, and Mix3 and consisting of 2 to 5 of the VCs, was then evaluated in mice. Each mixture manifested strong cytotoxicity against M. tuberculosis-infected macrophages, while Mix3 also manifested a VC-specific humoral immune response. Based on these results, we plan to evaluate the protection properties of these combinations as an improved tuberculosis subunit vaccine.

Limitations in exercise and functional capacity in long-term postpneumonectomy patients.

INTRODUCTION: Pneumonectomy results in impairments of pulmonary function and exercise intolerance associated with respiratory limitations. However, exercise capacity and functional capacity are less known at long-term followup. The aims of this study were to assess exercise tolerance and functional capacity among long-term postpneumonectomy patients and to identify the limiting factors in exercise related to comorbidities and which lung was involved. METHODS: Seventeen postpneumonectomy patients aged 59 ± 13 years and 5.5 ± 4.2 years postoperation were prospectively studied. Pulmonary function tests (PFTs), cardiopulmonary exercise test (CPET), Doppler-echocardiography, 6-minute walk test (6MWT) distance, and “senior fitness tests” (SFTs) were conducted with all patients. RESULTS: Exercise capacity and PFT were diminished ( O2 peak; 11.5 ± 3.3 mL−1·kg−1·min−1, 48 ± 17% predicted, forced vital capacity % predicted; 55 ± 13, FEV1% predicted; 46 ± 14, respectively). Most patients presented with low exercise cardiovascular parameters and normal breathing reserve (17 ± 12 L) during CPET. No significant differences were shown between right and left pneumonectomy and comorbidities related to exercise limitations (&khgr;2= 1.96, P = .376). Functional capacity in walking and SFTs were near normal (6MWT distance; 490 ± 15 m, 89 ± 25% predicted). Echocardiography showed normal left ventricle systolic function (ejection fraction, 60 ± 4%) with mildly elevated systolic pulmonary arterial pressure (38 ± 12 mm Hg). CONCLUSIONS: Long-term postpneumonectomy patients demonstrated decreased exercise capacity, limited primarily by the cardiovascular system regardless of lung resection side or comorbidities, although tests of functional capacity were near normal. Most patients can maintain near normal life in activities of daily living, but the long-term cardiopulmonary exercise function should be considered for meticulous evaluation and clinical care to preserve physiological reserves.

Postcoital hemoptysis: Our experience and review of the literature

Hemoptysis after physical activity is a well-known phenomenon. Hemoptysis following sexual intercourse is rarely reported. We describe three patients with hemoptysis occurring only after sexual activity and not following other types of physical effort. The underlying causes were congestive heart failure, uncontrolled hypertension and Takayasu arteritis. The literature is reviewed. We conclude that hemoptysis can present rarely following sexual activity and is usually associated with cardiovascular decompensation. It is always necessary to search for other underlying diseases. We suggest that patients with unexplained hemoptysis should be specifically asked about postcoital hemoptysis should be included in the differential diagnosis of every patient with unexplained hemoptysis.

Step oximetry test: a validation study

Introduction Step climbing is a potentially useful modality for testing exercise capacity. However, there are significant variations between test protocols and lack of consistent validation against gold standard cycle ergometry cardiopulmonary exercise testing (CPET). The purpose of the study was to validate a novel technique of exercise testing using a dedicated device. Methods We built a step oximetry device from an adapted aerobics step and pulse oximeter connected to a computer. Subjects performed lung function tests, a standard incremental cycle CPET and also a CPET while stepping on and off the step oximetry device to maximal exertion. Data from the step oximetry device were processed and correlated with standard measurements of pulmonary function and cycle CPET. Results We recruited 89 subjects (57 years, 50 men). Oxygen uptake (VO2) was 0.9 mL/kg/min (95% CI −3.6 to 5.4) higher in the step test compared with the gold standard cycle CPET, p<0.001. VO2 in the two techniques was highly correlated (R=0.87, p<0.001). Work rate during stair climbing showed the best correlation with VO2 (R=0.69, p<0.0001). Desaturation during step climbing correlated negatively with diffusion capacity for carbon monoxide (r=−0.43, p<0.005). No adverse events occurred. Conclusions The step oximetry test was a maximal test of exertion in the subjects studied, achieving slightly higher VO2 than during the standard test. The test was safe to perform and well tolerated by the patients. Parameters derived from the step oximetry device correlated well with gold standard measurements. The step oximetry test could become a useful and standardisable exercise test for clinical settings where advanced testing is not available or appropriate.

Minor and intermediate surgeries in lung transplant recipients.

Only limited data exist regarding the incidence and outcome of surgical procedures following lung transplantation (LTX).