Dose and volume de-escalation of radiotherapy in head and neck cancer.

Radiotherapy plays a key role in the treatment of head and neck cancer. However, irradiation of the head and neck region is associated with high rates of acute and chronic toxicity. Technological advances have led to better visualisation of target volumes and critical structures and improved dose conformality in the treatment volume. Despite this, acute toxicity has not been substantially reduced and late toxicity has a significant impact on patients' quality of life. The greater radiosensitivity of tumours associated with the HPV and the development of new imaging techniques have encouraged research into new deintensified strategies to reduce the side effects of radiotherapy. The aim of this paper is to review the literature on the strategies of de-escalated treatment in dose and/or volume in head and neck cancer.

Oligometastatic non-small cell lung cancer: Current management.

BACKGROUND: In the past decade, major developments have improved the survival of patients with oligometastatic non-small cell lung cancer (NSCLC). About 20% - 50% of patients with NSCLC present with oligometastases at diagnosis. For this group of patients, it seems that an increase in survival would justify aggressive local therapies. The development of minimally invasive surgery and advanced radiotherapy techniques like stereotactic body radiation therapy (SBRT) makes local control possible for selected patients with metastatic NSCLC. The advantage of SBRT over surgery is that it is a non-invasive technique, with minimum side effects, and is more suitable for fragile and elderly patients, non-candidates for surgery, or patients who refuse surgery. AIM: The purpose of this review is to summarize the latest scientific evidence on the management of oligometastatic NSCLC, focusing on the role of radiotherapy. RELEVANCE FOR PATIENTS: The initial treatment recommended for patients with oligometastatic NSCLC is systemic therapy. Patients should be considered for radical treatment to both the primary tumor and oligometastases. Aggressive local therapy comprises surgery and/or definitive radiotherapy such as SRS or SBRT, and may be preceded or followed by systemic treatment. Recent clinical evidence from Phase II trials reports benefits in terms of PFS in patients with good performance status and long disease-free periods, with good response to systemic therapy, especially in EGFR wild-type tumors. Phase I and II trials have shown that radiotherapy combined with immunotherapy can improve tumor response rate and possibly overall survival. The recommendation is also to include OM patients in ongoing clinical trials.

Prospective study of five-year outcomes and postoperative complications after total temporomandibular joint replacement with two stock prosthetic systems.

To evaluate and compare outcomes and complications associated with reconstruction of the temporomandibular joint (TMJ), we prospectively analysed the data of 70 patients who had their joints replaced with stock prostheses during the period 2004-14 and who had been followed up for five years. We used two types of stock prostheses: the metal-on-metal Christensen system (CS), and the ultra-high-molecular-weight-polyethylene-on-metal Biomet® system (BS). Data were collected at 3, 6, 12, 24, 36, 48, and 60 months postoperatively and compared with preoperative measurements. Five years after the replacement there was an increase in mean (SD) mouth opening from 2.0 (0.6) to 4.0 (0.5cm) (p=0.012) in the CS, and from 2.5 (1.0) cm to 4.1 (0.6) cm (p=0.018) in the BS. The mean (SD) reductions in visual analogue pain scores were from 6.9 (1.6) to 2.0 (1.4) (p=0.001) in the CS, and 6.5 (1.4) to 1.5 (1.1) (p=0.001) in the BS. There were no significant differences in improvements in mouth opening or reduction in pain between the two groups. However, there were differences in the number of implants that failed, which led to removal and replacement of 2/14 prostheses in the CS group and 3/77 in the BS group (p=0.06). The results supported the placement of stock prostheses, as evidenced by a low incidence of complications and adverse events, and a long-term improvement in function and reduction in pain in the TMJ. The BS group had significantly fewer prosthetic failures than the CS group.

Dexmedetomidine metabolic clearance is not affected by fat mass in obese patients.

BACKGROUND: Obesity has been associated with reduced dexmedetomidine clearance, suggesting impaired hepatic function or reduced hepatic blood flow. The aim of this study was to clarify the effect of obesity in dexmedetomidine metabolic clearance. METHODS: Forty patients, ASA I-III, 18-60 yr old, weighing 47-126 kg, scheduled for abdominal laparoscopic surgery, were enrolled. Anaesthetic agents (propofol, remifentanil, and dexmedetomidine) were dosed based on lean body weight measured by dual X-ray absorptiometry. Serial venous samples were drawn during and after dexmedetomidine infusion. A pharmacokinetic analysis was undertaken using non-linear mixed-effect models. In the modelling approach, the total body weight, lean body weight, and adjusted body weight were first tested as size descriptors for volumes and clearances. Hepatic blood flow, liver histopathology, liver enzymes, and gene expression of metabolic enzymes (UGT2B10 and UGT1A4) were tested as covariates of dexmedetomidine metabolic clearance. A decrease in NONMEM objective function value (ΔOFV) of 3.84 points, for an added parameter, was considered significant at the 0.05 level. RESULTS: A total of 637 dexmedetomidine serum samples were obtained. A two-compartmental model scaled to measured lean weight adequately described the dexmedetomidine pharmacokinetics. Liver blood flow was a covariate for dexmedetomidine clearance (ΔOFV=-5.878). Other factors, including fat mass, histopathological damage, and differential expression of enzymes, did not affect the dexmedetomidine clearance in the population studied (ΔOFV<3.84). CONCLUSIONS: We did not find a negative influence of obesity in dexmedetomidine clearance when doses were adjusted to lean body weight. Liver blood flow showed a significant effect on dexmedetomidine clearance. CLINICAL TRIAL REGISTRATION: NCT02557867.

Body size phenotypes comprehensively assess cardiometabolic risk and refine the association between obesity and gut microbiota.

OBJECTIVE: The gut microbiota associates with obesity and related disorders, but recent meta-analyses have found that this association is, at best, of small effect. We argue that such analyses are flawed by the use of body mass index (BMI) as sole proxy for disease, and explore a classification method that distinguishes the cardiometabolic health status of individuals to look for more comprehensive associations between gut microbes and health. DESIGN: We analyzed a 441 community-dwelling cohort on which we obtained demographic and health information, anthropometry and blood biochemistry data that served to categorize participants according to BMI, cardiometabolic health status and body size phenotypes. In addition, the participants donated fecal samples from which we performed 16S rRNA gene sequencing to analyze the gut microbiota. RESULTS: We observed that health-related variables deteriorate with increased BMI, and that there are further discrepancies within a given BMI category when distinguishing cardiometabolically healthy and unhealthy individuals. Regarding the gut microbiota, both obesity and cardiovascular disease associate with reductions in α-diversity; having lean, healthy individuals the most diverse microbiotas. Moreover, the association between the gut microbiota and health stems from particular consortia of microbes; the prevalence of consortia involving pathobionts and Lachnospiraceae are increased in obese and cardiometabolically abnormal subjects, whereas consortia including Akkermansia muciniphila and Methanobrevibacter, Oscillospira and Dialister have higher prevalence in cardiometabolically healthy and normoweight participants. CONCLUSIONS: The incorporation of cardiometabolic data allows a refined identification of dissimilarities in the gut microbiota; within a given BMI category, marker taxa associated with obesity and cardiometabolic disease are exacerbated in individuals with abnormal health status. Our results highlight the importance of the detailed assessment and classification of individuals that should be carried out prior to the evaluation of obesity treatments targeting the gut microbiota.

Evaluation of total alloplastic temporo-mandibular joint replacement with two different types of prostheses: A three-year prospective study.

BACKGROUND: Temporo-Mandibular Joint (TMJ) replacement has been used clinically for years. The objective of this study was to evaluate outcomes achieved in patients with two different categories of TMJ prostheses. MATERIAL AND METHODS: All patients who had a TMJ replacement (TMJR) implanted during the study period from 2006 through 2012 were included in this 3-year prospective study. All procedures were performed using the Biomet Microfixation TMJ Replacement System, and all involved replacing both the skull base component (glenoid fossa) and the mandibular condyle. RESULTS: Fifty-seven patients (38 females and 19 males), involving 75 TMJs with severe disease requiring reconstruction (39 unilateral, 18 bilateral) were operated on consecutively, and 68 stock prostheses and 7 custom-made prostheses were implanted. The mean age at surgery was 52.6±11.5 years in the stock group and 51.8±11.7 years in the custom-made group. In the stock group, after three years of TMJR, results showed a reduction in pain intensity from 6.4±1.4 to 1.6±1.2 (p<0.001), and an improvement in jaw opening from 2.7±0.9 cm to 4.2±0.7 cm (p<0.001). In the custom-made group, after three years of TMJR, results showed a reduction in pain intensity from 6.0±1.6 to 2.2±0.4 (p<0.001), and an improvement in jaw opening from 1.5±0.5 cm to 4.3±0.6 cm (p<0.001). No statistically significant differences between two groups were detected. CONCLUSIONS: The results of this three-year prospective study support the surgical placement of TMJ prostheses (stock prosthetic, and custom-made systems), and show that the approach is efficacious and safe, reduces pain, and improves maximum mouth opening movement, with few complications. As such, TMJR represents a viable technique and a stable long-term solution for cranio-mandibular reconstruction in patients with irreversible end-stage TMJ disease. Comparing stock and custom-made groups, no statistically significant differences were detected with respect to pain intensity reduction and maximum mouth opening improvement.

Criopreservação do plasma rico em plaquetas de equinos / Equine platelet-rich plasma cryopreservation

Avaliou-se o congelamento do plasma rico em plaquetas (PRP) de equinos, a -196ºC em nitrogênio líquido, utilizando-se como crioprotetor o DMSO em duas concentrações (3% e 6%), e, como ponto final, a avaliação da morfologia e da agregometria plaquetária. Foram utilizadas 12 amostras de PRP em duas repetições. Previamente ao congelamento, as amostras foram submetidas a um resfriamento lento (-0,07ºC/minuto) até a temperatura final de 4-5ºC. A criopreservação do PRP equino, incluindo um resfriamento lento a 4-5ºC, previamente ao congelamento a -197ºC em nitrogênio líquido, foi similar para as concentrações do crioprotetor DMSO a 3% ou 6%, quando avaliado o percentual de ativação e de agregação plaquetária.

Equine platelet-rich plasma (PRP) frozen at -196°C in liquid nitrogen using DMSO as a cryoprotectant in two different concentrations (3% and 6%) was evaluated, using platelet morphology and aggregometry as the final parameters. Twelve PRP samples were used in two repetitions. The samples were submitted to slow cooling prior to frozen (-0.07°C/minute) until they reached the temperature of 4-5°C. Platelet cryopreserved in 3% or 6% DMSO, presented similar efficacy when the percentage of activation and platelet aggregation was evaluated.

Two-year prospective study of outcomes following total temporomandibular joint replacement.

The purpose of this 2-year prospective study was to investigate outcomes achieved with a stock temporomandibular joint (TMJ) replacement system in the management of end-stage TMJ disorders. Fifty-two patients requiring reconstruction (36 unilateral/16 bilateral) were operated on during the period 2006-2012; 68 total prostheses were implanted (Biomet Microfixation TMJ Replacement System). The mean age at surgery was 52.6±11.5 years. Changes in the values of inclusion diagnostic criteria at entry were assessed. These included persistent and significant TMJ pain, functional impairment after failure of other surgical therapies, and imaging evidence consistent with advanced TMJ disease of more than 1-year duration. Subjects were excluded if they presented insufficient quantity/quality of bone to support the TMJ replacement, severe hyperfunctional habits, active infectious disease, or an inability to follow postoperative instructions. Over the 2 years of postoperative follow-up, mean pain intensity was reduced from 6.4±1.4 to 1.6±1.2 (P<0.001), and jaw opening was improved from 2.7±0.9cm to 4.2±0.7cm (P<0.001). During the study period, three of 68 implants (4%) were explanted and new TMJ replacements fitted. The results of this study support the view that the surgical placement of stock TMJ prostheses provides significant long-term improvements in pain and function, with few complications.

Evaluation of the anti-inflammatory effects of two platelet-rich gel supernatants in an in vitro system of cartilage inflammation.

OBJECTIVES: To study, in normal cartilage explants (CEs) challenged with lipopolysaccharide (LPS), the temporal effects (at 48 and 96h) of leukocyte- and platelet-rich gel (L-PRG) and pure platelet-rich gel (P-PRG) supernatants on the production and degradation of platelet-associated growth factors (GFs) (platelet-derived GF isoform BB [PDGF-BB] and transforming growth factor beta-1 [TGF-ß1]), pro-inflammatory (tumour necrosis factor alpha [TNF-α]) and anti-inflammatory cytokines (interleukin 4 [IL-4] and IL-1 receptor antagonist [IL-1ra]). METHODS: CEs from six horses were challenged with LPS and cultured for 96h with L-PRG and P-PRG supernatants at concentrations of 25% and 50%, respectively. The CE culture medium was changed every 48h and used for determination, by ELISA, of PDGF-BB, TGF-ß1, TNF-α, IL-4 and IL-1ra. RESULTS: Both the 25% and 50% PRG supernatants produced a different molecular profile in the culture media, unlike that of the CE challenged with LPS only. 50% L-PRG produced the most sustained release of growth factors and anti-inflammatory cytokines, although it produced the highest TNF-α release. PDGF-BB was significantly correlated with IL-1ra and TNF-α concentrations, whereas TNF-α was correlated with IL-4. CONCLUSIONS: 50% L-PRG supernatant produced a more sustained concentration of growth factors and anti-inflammatory cytokines than the other hemoderivatives evaluated. This substance could be evaluated in animal models of arthritis or in patients with arthropathies.

Platelet-rich fibrin sealant as a treatment for complex perianal fistulas: a multicentre study.

INTRODUCTION: The incidence of perianal fistulas is high, and this condition has a profoundly negative impact on patients' quality of life. The problem is greater when the fistula tract is high because treatment is necessarily complex (limited surgery may lead to recurrence, while aggressive surgery is associated with higher rates of faecal incontinence). To achieve a balance between these two options, we suggest that complex fistulas should be treated by sealing the tract with platelet-rich fibrin. Our objective is to evaluate the medium- to long-term results obtained from the treatment of complex perianal fistulas by sealing with platelet-rich fibrin. MATERIAL AND METHODS: Prospective longitudinal multicentre study involves three colorectal surgeons working at three hospitals. The study period was October 2010 to June 2013, during which a total of 60 patients were treated for complex fistulas. In all cases, the intervention consisted of curetting the fistula tract, sealing it with platelet-rich fibrin and closing the internal orifice. We evaluated the clinical outcomes (clinical examination and pelvic magnetic resonance (MRI)) and the quality of life results, both general (SF-36) and gastrointestinal (GIQLI questionnaire) in periodic reviews during consultation. RESULT: The median follow-up period was 24 months (11-43 months), during which in 40 patients (66.66 %) the fistulas remained closed, with a zero rate of faecal incontinence. The results of the quality of life questionnaires are comparable (indeed, they are better in some items for the cured patients) to those of the reference population. CONCLUSION: In our opinion, this procedure is safe and its results are promising in terms of clinical outcome and medium- to long-term quality of life.

Potential advantages of volumetric arc therapy in head and neck cancer.

BACKGROUND: Intensity-modulated radiation therapy (IMRT) uses solid compensators or multileaf collimators to modulate the intensity of radiation in each field, delivering highly conformal dose distributions. This technique allows treating volumes with concave shapes when the target is close to a critical structure. The movement of multileaf collimator under computer control can modulate the dose in 3 main ways: IMRT with static field with segments, IMRT with dynamic delivery, and IMRT rotational therapy. Volumetric modulated arc therapy (VMAT) is a novel radiation technique that creates conformal distributions with variable gantry speed, dynamic movements of multileaf collimator, and variations in dose rate. The purpose of this study was to review the basis of VMAT, highlighting the differences with other IMRT techniques.

Search for solar axions by the CERN axion solar telescope with 3He buffer gas: closing the hot dark matter gap.

The CERN Axion Solar Telescope has finished its search for solar axions with (3)He buffer gas, covering the search range 0.64 eV ≲ ma ≲ 1.17 eV. This closes the gap to the cosmological hot dark matter limit and actually overlaps with it. From the absence of excess x rays when the magnet was pointing to the Sun we set a typical upper limit on the axion-photon coupling of gaγ ≲ 3.3 × 10(-10) GeV(-1) at 95% C.L., with the exact value depending on the pressure setting. Future direct solar axion searches will focus on increasing the sensitivity to smaller values of gaγ, for example by the currently discussed next generation helioscope International AXion Observatory.

Bilateral first branchial cleft anomaly with evidence of a genetic aetiology.

Anomalies of the first branchial cleft (FBC) are uncommon, and recognizing them can be difficult. Although present at birth, many cases do not become evident until later in childhood or adolescence, with an initial clinical presentation in adulthood being encountered only rarely. Typically, FBC anomalies present as a unilateral cyst, sinus, or fistula associated with the external auditory canal, or with swelling or an inflammatory opening in the peri-auricular/parotid area. They are commonly misdiagnosed and are often treated inadequately before being excised completely. A 40-year-old woman presented to the maxillofacial outpatient clinic with an episode of bilateral pre-auricular tumefaction, initially diagnosed as temporomandibular dysfunction syndrome. This was associated with bilateral pre-auricular pain that increased with mandibular movements. In relation to the patient's history, and given the bilateral presence of a pre-auricular pit, a diagnosis of FBC anomaly was made. Further investigation showed a related asymptomatic history in five other cases across four generations of the same family. The authors describe here the case, the diagnostic methodology, and the wide local excision technique used for removal of the branchial sinus.

Intra-articular injections of autologous platelet concentrates in dogs with surgical reparation of cranial cruciate ligament rupture: a pilot study.

OBJECTIVES: The objective of this study was to evaluate by clinical, radiographic, and force plate gait analyses the effect of post-surgical intra-articular injections of autologous platelet concentrates (PC) in a small group of dogs with cranial cruciate ligament (CCL) rupture. METHODS: The ten dogs used in this study were initially presented with CCL rupture and underwent ligament replacement surgery by fascia lata autograft guided by arthroscopy. Six dogs received three intra-articular injections of PC (PC group); one dose was injected immediately after surgery, and two additional doses were injected at two-week intervals. The remaining four dogs received only nutraceuticals (control group). All dogs were evaluated by clinical examination, serial radiography, and force plate gait analyses at monthly intervals up to 90 days. RESULTS: The clinical follow-up of the PC-treated group indicated a better outcome than the control group. Radiographic evaluation was not conclusive. Values of peak vertical reaction force and vertical impulse of the affected limbs were only significantly larger on the 90th postoperative day in the PC group compared to the control group. CLINICAL SIGNIFICANCE: Our results indicate that autologous PC might improve functional outcome after intra-articular cranial cruciate ligament repair. The effect of PC when using other repair procedures warrants additional studies.

Uso de plasma rico em plaquetas intra-articulares como tratamento pós-cirúrgico da ruptura do ligamento cruzado cranial num cão / The use of intra-articular platelet rich-plasma as a postsurgical treatment of cranial cruciate ligament rupture in a dog

Relata-se o caso de um cão que recebeu injeções intra-articulares de plasma rico em plaquetas (PRP) durante o pós-operatório do tratamento cirúrgico de ruptura do ligamento cruzado cranial (RLCCr). Os resultados clínicos e da avaliação da marcha mediante plataforma de força neste paciente sugerem a utilização de injeções intra-articulares de PRP como terapia pós-cirúrgica no tratamento da RLCCr.

We report the case of a dog that received intra-articular injections of platelet-rich plasma (PRP) during the postoperative period of surgical treatment of cranial cruciate ligament (CCL) rupture. Clinical, and gait analysis by the force plate in this patient might suggest the use of intra-articular injections of PRP as a post-surgical therapy in the treatment of CCL rupture.

Search for sub-eV mass solar axions by the CERN Axion Solar Telescope with 3He buffer gas.

The CERN Axion Solar Telescope (CAST) has extended its search for solar axions by using (3)He as a buffer gas. At T=1.8 K this allows for larger pressure settings and hence sensitivity to higher axion masses than our previous measurements with (4)He. With about 1 h of data taking at each of 252 different pressure settings we have scanned the axion mass range 0.39 eV≲m(a)≲0.64 eV. From the absence of excess x rays when the magnet was pointing to the Sun we set a typical upper limit on the axion-photon coupling of g(aγ)≲2.3×10(-10) GeV(-1) at 95% C.L., the exact value depending on the pressure setting. Kim-Shifman-Vainshtein-Zakharov axions are excluded at the upper end of our mass range, the first time ever for any solar axion search. In the future we will extend our search to m(a)≲1.15 eV, comfortably overlapping with cosmological hot dark matter bounds.

Peritoneal concentrations of transforming growth factor beta in horses with colic.

REASONS FOR PERFORMING THE STUDY: In man, peritoneal transforming growth factor beta (TGF-beta) is associated with peritoneal diseases and subsequent adhesion formation. No studies on plasma and peritoneal TGF-beta concentrations in horses with colic are available. OBJECTIVES: 1) To determine both plasma and peritoneal TGF-beta(1) and TGF-beta(3) concentrations in horses with different types of colic (not previously subjected to abdominal surgery); 2) to compare these concentrations according to the type of peritoneal fluid (transudate, modified transudate and exudate); and 3) to compare and correlate plasma and peritoneal concentrations of TGF-beta(1) and TGF-beta(3) and the types of peritoneal fluid according to the colic group and outcome. METHODS: Peritoneal fluid and plasma samples from 78 horses with colic and 8 healthy horses were obtained. Patients were classified according to diagnosis (obstructions, enteritis, ischaemic disorders and peritonitis), peritoneal fluid analysis (transudate, modified transudate and exudate), and outcome (survivors and nonsurvivors). Plasma and peritoneal TGF-beta(1) and TGF-beta(3) concentrations were determined by ELISA. Data were analysed by parametric and nonparametric tests. P< or =0.05 was considered as statistically significant. RESULTS: Concentrations of peritoneal fluid TGF-beta(1) were significantly (P = 0.01) higher in horses with peritonitis in comparison with all other colic groups and controls. Horses with ischaemic lesions had significantly (P = 0.01) higher concentrations of peritoneal TGF-beta(1) in comparison with controls and the group of horses with obstructions. Peritoneal TGF-beta(1) concentration also was significantly (P = 0.01) higher in exudates in comparison with transudates. Peritoneal TGF-beta(1) and TGF-beta(3) concentrations and plasma TGF-beta(1) concentration were significantly increased in nonsurvivors compared to survivors (P = 0.001, P = 0.004 and P = 0.05, respectively). CONCLUSIONS: Peritoneal TGF-beta(1) concentration was higher in horses with severe gastrointestinal diseases (ischaemic intestinal lesions and peritonitis), in horses with an altered peritoneal fluid (exudate), and in nonsurvivors. POTENTIAL RELEVANCE: Peritoneal TGF-beta concentration increases in horses with severe gastrointestinal disease as an anti-inflammatory response.

Cdc42p controls yeast-cell shape and virulence of Paracoccidioides brasiliensis.

Paracoccidioides brasiliensis is characterized by a multiple budding phenotype and a polymorphic cell growth, leading to the formation of cells with extreme variations in shape and size. Since Cdc42 is a pivotal molecule in establishing and maintaining polarized growth for diverse cell types, as well as during pathogenesis of certain fungi, we evaluated its role during cell growth and virulence of the yeast-form of P. brasiliensis. We used antisense technology to knock-down PbCDC42's expression in P. brasiliensis yeast cells, promoting a decrease in cell size and more homogenous cell growth, altering the typical polymorphism of wild-type cells. Reduced expression levels also lead to increased phagocytosis and decreased virulence in a mouse model of infection. We provide genetic evidences underlying Pbcdc42p as an important protein during host-pathogen interaction and the relevance of the polymorphic nature and cell size in the pathogenesis of P. brasiliensis.

Differences in cardiovascular mortality in smokers, past-smokers and non-smokers: findings from the FRENA registry.

BACKGROUND: The influence of smoking on outcome in patients with coronary artery disease (CAD) is controversial. Even less is known about its influence in patients with cerebrovascular (CVD), or peripheral artery (PAD) disease. PATIENTS AND METHODS: FRENA is an ongoing, observational registry of consecutive outpatients with symptomatic CAD, CVD, or PAD. We reviewed their cardiovascular mortality according to smoking status. RESULTS: As of May 2008, 2501 patients had been enrolled in FRENA. Of these, 439 (18%) were current smokers, 1086 (43%) past-smokers, 976 (39%) had never smoked. Current- and past-smokers were 10 years younger, more often males, and more likely to have chronic lung disease, but had diabetes, hypertension, heart failure, or renal insufficiency less often than non-smokers. Over a mean follow-up of 14 months, 123 patients died (cardiovascular death, 68). On univariate analysis, current smokers had a significantly lower rate of cardiovascular death: 1.1 (95% CI: 0.4-2.4) per 100 patient-years in current smokers; 1.9 (95% CI: 1.2-2.8) in past-smokers; 3.5 (95% CI: 2.5-4.7) in non-smokers, with no differences between patients with CAD, CVD or PAD. Mean age at cardiovascular death was 82+/-6.4; 70+/-9.9 and 67+/-15 years, respectively. On multivariate analysis, smoking status was not independently associated with a lower risk for cardiovascular death. CONCLUSIONS: Current and past-smokers with CAD, CVD or PAD had a less than half cardiovascular mortality than those who never smoked, but this may be explained by the confounding effect of additional variables. They died over 10 years younger than non-smokers.