Neoadjuvant chemotherapy and extrapleural pneumonectomy of malignant pleural mesothelioma with or without hemithoracic radiotherapy (SAKK 17/04): a randomised, international, multicentre phase 2 trial.

BACKGROUND: Postoperative hemithoracic radiotherapy has been used to treat malignant pleural mesothelioma, but it has not been assessed in a randomised trial. We assessed high-dose hemithoracic radiotherapy after neoadjuvant chemotherapy and extrapleural pneumonectomy in patients with malignant pleural mesothelioma. METHODS: We did this phase 2 trial in two parts at 14 hospitals in Switzerland, Belgium, and Germany. We enrolled patients with pathologically confirmed malignant pleural mesothelioma; resectable TNM stages T1-3 N0-2, M0; WHO performance status 0-1; age 18-70 years. In part 1, patients were given three cycles of neoadjuvant chemotherapy (cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 given every 3 weeks) and extrapleural pneumonectomy; the primary endpoint was complete macroscopic resection (R0-1). In part 2, participants with complete macroscopic resection were randomly assigned (1:1) to receive high-dose radiotherapy or not. The target volume for radiotherapy encompassed the entire hemithorax, the thoracotomy channel, and mediastinal nodal stations if affected by the disease or violated surgically. A boost was given to areas at high risk for locoregional relapse. The allocation was stratified by centre, histology (sarcomatoid vs epithelioid or mixed), mediastinal lymph node involvement (N0-1 vs N2), and T stage (T1-2 vs T3). The primary endpoint of part 1 was the proportion of patients achieving complete macroscopic resection (R0 and R1). The primary endpoint in part 2 was locoregional relapse-free survival, analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00334594. FINDINGS: We enrolled patients between Dec 7, 2005, and Oct 17, 2012. Overall, we analysed 151 patients receiving neoadjuvant chemotherapy, of whom 113 (75%) had extrapleural pneumonectomy. Median follow-up was 54·2 months (IQR 32-66). 52 (34%) of 151 patients achieved an objective response. The most common grade 3 or 4 toxic effects were neutropenia (21 [14%] of 151 patients), anaemia (11 [7%]), and nausea or vomiting (eight [5%]). 113 patients had extrapleural pneumonectomy, with complete macroscopic resection achieved in 96 (64%) of 151 patients. We enrolled 54 patients in part 2; 27 in each group. The main reasons for exclusion were patient refusal (n=20) and ineligibility (n=10). 25 of 27 patients completed radiotherapy. Median total radiotherapy dose was 55·9 Gy (IQR 46·8-56·0). Median locoregional relapse-free survival from surgery, was 7·6 months (95% CI 4·5-10·7) in the no radiotherapy group and 9·4 months (6·5-11·9) in the radiotherapy group. The most common grade 3 or higher toxic effects related to radiotherapy were nausea or vomiting (three [11%] of 27 patients), oesophagitis (two [7%]), and pneumonitis (two [7%]). One patient died of pneumonitis. We recorded no toxic effects data for the control group. INTERPRETATION: Our findings do not support the routine use of hemithoracic radiotherapy for malignant pleural mesothelioma after neoadjuvant chemotherapy and extrapleural pneumonectomy. FUNDING: Swiss Group for Clinical Cancer Research, Swiss State Secretariat for Education, Research and Innovation, Eli Lilly.

'Fast-implantable' aortic valve implantation and concomitant mitral procedures.

Concomitant aortic and mitral valve replacement or concomitant aortic valve replacement and mitral repair can be a challenge for the cardiac surgeon: in particular, because of their structure and design, two bioprosthetic heart valves or an aortic valve prosthesis and a rigid mitral ring can interfere at the level of the mitroaortic junction. Therefore, when a mitral bioprosthesis or a rigid mitral ring is already in place and a surgical aortic valve replacement becomes necessary, or when older high-risk patients require concomitant mitral and aortic procedures, the new 'fast-implantable' aortic valve system (Intuity valve, Edwards Lifesciences, Irvine, CA, USA) can represent a smart alternative to standard aortic bioprosthesis. Unfortunately, this is still controversial (risk of interference). However, transcatheter aortic valve replacements have been performed in patients with previously implanted mitral valves or mitral rings. Interestingly, we learned that there is no interference (or not significant interference) among the standard valve and the stent valve. Consequently, we can assume that a fast-implantable valve can also be safely placed next to a biological mitral valve or next to a rigid mitral ring without risks of distortion, malpositioning, high gradient or paravalvular leak. This paper describes two cases: a concomitant Intuity aortic valve and bioprosthetic mitral valve implantation and a concomitant Intuity aortic valve and mitral ring implantation.

Aortic Annulus Stabilization Technique for Rapid Deployment Aortic Valve Replacement.

NlmCategory="UNASSIGNED">Rapid deployment aortic valve replacement (RDAVR) with the use of rapid deployment valve systems represents a smart alternative to the use of standard aortic bioprosthesis for aortic valve replacement. Nevertheless, its use is still debatable in patients with pure aortic valve regurgitation or true bicuspid aortic valve because of the risk of postoperative paravalvular leak. To address this issue, an optimal annulus-valve size match seems to be the ideal surgical strategy. This article describes a new technique developed to stabilize the aortic annulus and prevent paravalvular leak after RDAVR. To confirm the feasibility, this technique was performed in six patients with severe symptomatic aortic stenosis who were scheduled to undergo aortic valve replacement at our center. All patients survived surgery and were discharged from the hospital. There were no new intracardiac conduction system disturbances observed, and a permanent pacemaker implantation was not required in any of the patients. The intraoperative and postoperative echocardiogram confirmed successful positioning of the valve, and no paravalvular leak was observed. In this preliminary experience, RDAVR through a full sternotomy or an upper hemisternotomy approach with the use of aortic annulus stabilization technique was safe, and no leak was observed. Future studies on large series of patients are necessary to confirm the safety and effectiveness of this technique in preventing paravalvular leak in patients with true bicuspid aortic valves or pure aortic regurgitation.

Association between smoking and recurrence of venous thromboembolism and bleeding in elderly patients with past acute venous thromboembolism.

BACKGROUND: While the association between smoking and arterial cardiovascular events has been well established, the association between smoking and venous thromboembolism (VTE) remains controversial. OBJECTIVES: To assess the association between smoking and the risk of recurrent VTE and bleeding in patients who have experienced acute VTE. PATIENTS/METHODS: This study is part of a prospective Swiss multicenter cohort that included patients aged ≥65years with acute VTE. Three groups were defined according to smoking status: never, former and current smokers. The primary outcome was the time to a first symptomatic, objectively confirmed VTE recurrence. Secondary outcomes were the time to a first major and clinically relevant non-major bleeding. Associations between smoking status and outcomes were analysed using proportional hazard models for the subdistribution of a competing risk of death. RESULTS: Among 988 analysed patients, 509 (52%) had never smoked, 403 (41%) were former smokers, and 76 (8%) current smokers. After a median follow-up of 29.6months, we observed a VTE recurrence rate of 4.9 (95% confidence interval [CI] 3.7-6.4) per 100 patient-years for never smokers, 6.6 (95% CI 5.1-8.6) for former smokers, and 5.2 (95% CI 2.6-10.5) for current smokers. Compared to never smokers, we found no association between current smoking and VTE recurrence (adjusted sub-hazard ratio [SHR] 1.05, 95% CI 0.49-2.28), major bleeding (adjusted SHR 0.59, 95% CI 0.25-1.39), and clinically relevant non-major bleeding (adjusted SHR 1.21, 95% CI 0.73-2.02). CONCLUSIONS: In this multicentre prospective cohort study, we found no association between smoking status and VTE recurrence or bleeding in elderly patients with VTE.

Assessing efficacy of different nucleos(t)ide backbones in NNRTI-containing regimens in the Swiss HIV Cohort Study.

BACKGROUND: The most recommended NRTI combinations as first-line antiretroviral treatment for HIV-1 infection in resource-rich settings are tenofovir/emtricitabine, abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine. Efficacy studies of these combinations also considering pill numbers, dosing frequencies and ethnicities are rare. METHODS: We included patients starting first-line combination ART (cART) with or switching from first-line cART without treatment failure to tenofovir/emtricitabine, abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine plus efavirenz or nevirapine. Cox proportional hazards regression was used to investigate the effect of the different NRTI combinations on two primary outcomes: virological failure (VF) and emergence of NRTI resistance. Additionally, we performed a pill burden analysis and adjusted the model for pill number and dosing frequency. RESULTS: Failure events per treated patient for the four NRTI combinations were as follows: 19/1858 (tenofovir/emtricitabine), 9/387 (abacavir/lamivudine), 11/344 (tenofovir/lamivudine) and 45/1244 (zidovudine/lamivudine). Compared with tenofovir/emtricitabine, abacavir/lamivudine had an adjusted HR for having VF of 2.01 (95% CI 0.86-4.55), tenofovir/lamivudine 2.89 (1.22-6.88) and zidovudine/lamivudine 2.28 (1.01-5.14), whereas for the emergence of NRTI resistance abacavir/lamivudine had an HR of 1.17 (0.11-12.2), tenofovir/lamivudine 11.3 (2.34-55.3) and zidovudine/lamivudine 4.02 (0.78-20.7). Differences among regimens disappeared when models were additionally adjusted for pill burden. However, non-white patients compared with white patients and higher pill number per day were associated with increased risks of VF and emergence of NRTI resistance: HR of non-white ethnicity for VF was 2.85 (1.64-4.96) and for NRTI resistance 3.54 (1.20-10.4); HR of pill burden for VF was 1.41 (1.01-1.96) and for NRTI resistance 1.72 (0.97-3.02). CONCLUSIONS: Although VF and emergence of resistance was very low in the population studied, tenofovir/emtricitabine appears to be superior to abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine. However, it is unclear whether these differences are due to the substances as such or to an association of tenofovir/emtricitabine regimens with lower pill burden.

Prognostic factors for progression-free and overall survival in advanced biliary tract cancer.

BACKGROUND: Biliary tract cancer is an uncommon cancer with a poor outcome. We assembled data from the National Cancer Research Institute (UK) ABC-02 study and 10 international studies to determine prognostic outcome characteristics for patients with advanced disease. METHODS: Multivariable analyses of the final dataset from the ABC-02 study were carried out. All variables were simultaneously included in a Cox proportional hazards model, and backward elimination was used to produce the final model (using a significance level of 10%), in which the selected variables were associated independently with outcome. This score was validated externally by receiver operating curve (ROC) analysis using the independent international dataset. RESULTS: A total of 410 patients were included from the ABC-02 study and 753 from the international dataset. An overall survival (OS) and progression-free survival (PFS) Cox model was derived from the ABC-02 study. White blood cells, haemoglobin, disease status, bilirubin, neutrophils, gender, and performance status were considered prognostic for survival (all with P < 0.10). Patients with metastatic disease {hazard ratio (HR) 1.56 [95% confidence interval (CI) 1.20-2.02]} and Eastern Cooperative Oncology Group performance status (ECOG PS) 2 had worse survival [HR 2.24 (95% CI 1.53-3.28)]. In a dataset restricted to patients who received cisplatin and gemcitabine with ECOG PS 0 and 1, only haemoglobin, disease status, bilirubin, and neutrophils were associated with PFS and OS. ROC analysis suggested the models generated from the ABC-02 study had a limited prognostic value [6-month PFS: area under the curve (AUC) 62% (95% CI 57-68); 1-year OS: AUC 64% (95% CI 58-69)]. CONCLUSION: These data propose a set of prognostic criteria for outcome in advanced biliary tract cancer derived from the ABC-02 study that are validated in an international dataset. Although these findings establish the benchmark for the prognostic evaluation of patients with ABC and confirm the value of longheld clinical observations, the ability of the model to correctly predict prognosis is limited and needs to be improved through identification of additional clinical and molecular markers.

Step-by-step of ultrasound-guided core-needle biopsy of the breast: review and technique

Ultrasound-guided core-needle biopsy has high sensitivity in the diagnosis of breast cancer. The present study is aimed at detailing the main steps of such procedure, including indications, advantages, limitations, follow-up and description of the technique, besides presenting a checklist including the critical steps required for an appropriate practice of the technique. In the recent years, an increasing number of patients have required breast biopsy, indicating the necessity of a proportional increase in the number of skilled professionals to carry out the procedures and histological diagnoses. A multidisciplinary approach involving the tripod clinical practice-radiology-pathology is responsible for the highest rate of accuracy of the technique and must always be adopted.

Tropheryma whipplei tricuspid endocarditis: a case report and review of the literature.

INTRODUCTION: The main clinical manifestations of Whipple's disease are weight loss, arthropathy, diarrhea and abdominal pain. Cardiac involvement is frequently described. However, endocarditis is rare and is not usually the initial presentation of the disease. To the best of our knowledge, this is the first reported case of a patient with Tropheryma whipplei tricuspid endocarditis without any other valve involved and not presenting signs of arthralgia and abdominal involvement. CASE PRESENTATION: We report a case of a 50-year-old Caucasian man with tricuspid endocarditis caused by Tropheryma whipplei, showing signs of severe shock and an absence of other more classic clinical signs of Whipple's disease, such as arthralgia, abdominal pain and diarrhea. Tropheryma whipplei was documented by polymerase chain reaction of the blood and pleural fluid. The infection was treated with a combined treatment of doxycycline, hydroxychloroquine and sulfamethoxazole-trimethoprim for one year. CONCLUSION: Tropheryma whipplei infectious endocarditis should always be considered when facing a blood-culture negative endocarditis particularly in right-sided valves. Although not standardized yet, treatment of Tropheryma whipplei endocarditis should probably include a bactericidal antibiotic (such as doxycycline) and should be given over a prolonged period of time (a minimum of one year).

Trabecular bone score in kidney transplant recipients.

UNLABELLED: It is uncertain whether bone mineral density (BMD) can accurately predict fracture in kidney transplant recipients. Trabecular bone score (TBS) provides information independent of BMD. Kidney transplant recipients had abnormal bone texture as measured by lumbar spine TBS, and a lower TBS was associated with incident fractures in recipients. INTRODUCTION: Trabecular bone score (TBS) is a texture measure derived from dual energy X-ray absorptiometry (DXA) lumbar spine images, providing information independent of bone mineral density. We assessed characteristics associated with TBS and fracture outcomes in kidney transplant recipients. METHODS: We included 327 kidney transplant recipients from Manitoba, Canada, who received a post-transplant DXA (median 106 days post-transplant). We matched each kidney transplant recipient (mean age 45 years, 39 % men) to three controls from the general population (matched on age, sex, and DXA date). Lumbar spine (L1-L4) DXA images were used to derive TBS. Non-traumatic incident fracture (excluding hand, foot, and craniofacial) (n = 31) was assessed during a mean follow-up of 6.6 years. We used multivariable linear regression models to test predictors of TBS, and multivariable Cox proportional hazard regression was used to estimate hazard ratios (HRs) per standard deviation decrease in TBS to express the gradient of risk. RESULTS: Compared to the general population, kidney transplant recipients had a significantly lower lumbar spine TBS (1.365 ± 0.129 versus 1.406 ± 0.125, P < 0.001). Multivariable linear regression revealed that receipt of a kidney transplant was associated with a significantly lower mean TBS compared to controls (-0.0369, 95 % confidence interval [95 % CI] -0.0537 to -0.0202). TBS was associated with fractures independent of the Fracture Risk Assessment score including BMD (adjusted HR per standard deviation decrease in TBS 1.64, 95 % CI 1.15-2.36). CONCLUSION: Kidney transplant recipients had abnormal bone texture as assessed by TBS and a lower lumbar spine TBS was associated with fractures in recipients.

Estudo da Determinação dos Grupos Silanóis ( º Si-OH) em Sílica: Aplicação à Materiais de Recheio Utilizados em Cromatografia Gasosa

A simple chemical method has been developed to quantify the silanol groups (º Si-OH) in silica as well as in coated chromatographic supports for use in packed - column Gas Chromatography. After adsorption of 10 mg/mL methylene blue, centrifuging action and filtration, the absorbance of the solution was inversely proportional to the silanol quantity. The difference between the absorbance of the pure solution and that of the solid - free filtrate was related to the silica weight, yielding a quantitative analysis of these groups.

Determinação espectrofotométrica de ácido ascórbico em fármacos empregando amostragem binária em fluxo

A flow system procedure for spectrophotometric determination of ascorbic acid in drugs based on [Fe3+(SCN-)n]+3-n complex decomposition by reduction is described. The flow network was constituted by a set of three-way solenoid valves, controlled by a microcomputer running a software wrote in QuickBasic 4.5 language. The feasibility of the procedure was ascertained by determining ascorbic acid in drug samples with mass ranging from 0.0018 up to 0.0180 g. The results showed an agreement of about 7% when compared with recommended method. Other profitable features such as a standard deviation of 1.5% (n = 7) and a throughput of 120 determinations per hour was also achieved.

Sistema automático para análise direta de ligas metálicas por eletrodissolução anódica e espectrometria de absorção atômica

An automatic system for the direct determination of lead and tin by atomic absorption spectrometry is described. The on-line treatment of the metallic samples was obtained by anodic electrodissolution in a flow injection system. Lead was determined by flame atomic absorption spectrometry (FAAS) and tin by graphite furnace atomic absorption spectrometry (GFAAS). A computer program managed the current source and the solenoid valves that direct the fluids. Good linear correlations between absorbance and current intensity for lead and tin were observed. Results were in agreement with the certified values. Precision was always better than 5%. The recommended procedure allows the direct determination of 60 or 30 elements/h using FAAS or GFAAS, respectively.

Titulador potenciométrico automatizado baseado em sistema de fluxo monossegmentado

A new automated system for acid-base flow titrations is proposed. In the operation mode, several sample to titrant volumetric ratios are injected in an air segmented plug. Five three way solenoid valves and three acrilic junctions, assembled in a hidrodynamic injection system, were accountable for the monosegmented reagents plug formation. A turbulent flow reactor was used for a perfect mix of reagents in the plug. The detector system employed a glass combined electrode fitted in an acrilic holder. Titrations of hydrochloric, nitric and acetic acids, in several concentrations, were performed with standard sodium hidroxide, for evaluation of the efficiency of the system. The relative standard deviation of the determinations was about ±0,5% and each titration was carried out in 3-4 minutes. A Quick BASIC 4.5® program was developed for the titrator control.

Association of early repolarization with risk of cardiac mortality in the general population

Early repolarization, which is characterized by an elevation of the J-point on 12-lead electrocardiography, is a common finding that has been considered as benign for decades. However, in the last years, it has been related with vulnerability to idiopathic ventricular fibrillation and with cardiac mortality in the general population. Recently, 4 potential ECG predictors that could differentiate the benign from the malignant form of early repolarization have been suggested. Any previous study about early repolarization has been done in Spain. Aim. To ascertain whether the presence of early repolarization pattern in a resting electrocardiogram is associated with a major risk of cardiac death in a Spanish general population and to determine whether the presence of potential predictors of malignancy in a resting electrocardiogram increases the risk of cardiac mortality in patients with early repolarization pattern. Methods. We will analyse the presence of early repolarization and the occurrence of cardiac mortality in a retrospective cohort study of 4,279 participants aged 25 to 74 years in the province of Girona. This cohort has been followed during a mean of 9.8 years. Early repolarization will be stratified according to the degree of J-point elevation (≥0.1 mV or ≥0.2 mV), the morphology of the J-wave (slurring, notching or any of these two), the ST-segment pattern (ascending or descending) and the localization (inferior leads, lateral leads, or both). Association of early repolarization with cardiac death will be assessed by adjusted Cox-proportional hazards models

Sistema automático para determinação seqüencial de cianeto livre e total empregando eletrodo tubular íon-seletivo de membrana homogênea

This study presents an automated system for potentiometric determination of free and total cyanide which employs a homogeneous membrane tubular ion-selective electrode. After the electrode is assembled, it is connected to a system composed of 3 three-way solenoid valves, sample line, carrier line, acid stream, and gas diffusion chamber. A Turbo Pascal® computer program, developed specifically for this task, automatically performs all the steps involved in data acquisition and processing. The proposed analytical procedure offers operational simplicity, since detection is performed by a tubular electrode, whose assembly is fast and easy. The system has shown reproducibility (r.s.d. < 0.5%, n=6) and high speed (30 readings/hour); it is efficient for determination of free and total cyanide in waste waters of starch processing plants. The detection limit was 1.2x10-5 and 1.5x10-5 mol L-1, for determination of free and total cyanide, respectively. The linear response range was between 1.2x10-5 and 1.0x10-2 mol L-1 for free cyanide and between 1.5x10-5 and 1.0x10-2 for total cyanide.