Sex-dependent effect of socioeconomic status on cardiovascular event risk in a population-based cohort of patients with type 2 diabetes.

BACKGROUND: Socioeconomic status (SES) factors often result in profound health inequalities among populations, and their impact may differ between sexes. The aim of this study was to estimate and compare the effect of socioeconomic status indicators on incident cardiovascular disease (CVD)-related events among males and females with type 2 diabetes (T2D). METHODS: A population-based cohort from a southern European region including 24,650 patients with T2D was followed for five years. The sex-specific associations between SES indicators and the first occurring CVD event were modeled using multivariate Fine-Gray competing risk models. Coronary Heart Disease (CHD) and stroke were considered secondary outcomes. RESULTS: Patients without a formal education had a significantly higher risk of CVD than those with a high school or university education, with adjusted hazard ratios (HRs) equal to 1.24 (95%CI: 1.09-1.41) for males and 1.50 (95%CI: 1.09-2.06) for females. Patients with <18 000€ income had also higher CVD risk than those with ≥18 000€, with HRs equal to 1.44 (95%CI: 1.29-1.59) for males and 1.42 (95%CI: 1.26-1.60) for females. Being immigrant showed a HR equal to 0.81 (95%CI: 0.66-0.99) for males and 1.13 (95%CI: 0.68-1.87) for females. Similar results were observed for stroke, but differed for CHD when income is used, which had higher effect in females. CONCLUSION: Socioeconomic inequalities in CVD outcomes are present among T2D patients, and their magnitude for educational attainment is sex-dependent, being higher in females, suggesting the need to consider them when designing tailored primary prevention and management strategies.

Individualised, perioperative open-lung ventilation strategy during one-lung ventilation (iPROVE-OLV): a multicentre, randomised, controlled clinical trial.

BACKGROUND: It is uncertain whether individualisation of the perioperative open-lung approach (OLA) to ventilation reduces postoperative pulmonary complications in patients undergoing lung resection. We compared a perioperative individualised OLA (iOLA) ventilation strategy with standard lung-protective ventilation in patients undergoing thoracic surgery with one-lung ventilation. METHODS: This multicentre, randomised controlled trial enrolled patients scheduled for open or video-assisted thoracic surgery using one-lung ventilation in 25 participating hospitals in Spain, Italy, Turkey, Egypt, and Ecuador. Eligible adult patients (age ≥18 years) were randomly assigned to receive iOLA or standard lung-protective ventilation. Eligible patients (stratified by centre) were randomly assigned online by local principal investigators, with an allocation ratio of 1:1. Treatment with iOLA included an alveolar recruitment manoeuvre to 40 cm H2O of end-inspiratory pressure followed by individualised positive end-expiratory pressure (PEEP) titrated to best respiratory system compliance, and individualised postoperative respiratory support with high-flow oxygen therapy. Participants allocated to standard lung-protective ventilation received combined intraoperative 4 cm H2O of PEEP and postoperative conventional oxygen therapy. The primary outcome was a composite of severe postoperative pulmonary complications within the first 7 postoperative days, including atelectasis requiring bronchoscopy, severe respiratory failure, contralateral pneumothorax, early extubation failure (rescue with continuous positive airway pressure, non-invasive ventilation, invasive mechanical ventilation, or reintubation), acute respiratory distress syndrome, pulmonary infection, bronchopleural fistula, and pleural empyema. Due to trial setting, data obtained in the operating and postoperative rooms for routine monitoring were not blinded. At 24 h, data were acquired by an investigator blinded to group allocation. All analyses were performed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT03182062, and is complete. FINDINGS: Between Sept 11, 2018, and June 14, 2022, we enrolled 1380 patients, of whom 1308 eligible patients (670 [434 male, 233 female, and three with missing data] assigned to iOLA and 638 [395 male, 237 female, and six with missing data] to standard lung-protective ventilation) were included in the final analysis. The proportion of patients with the composite outcome of severe postoperative pulmonary complications within the first 7 postoperative days was lower in the iOLA group compared with the standard lung-protective ventilation group (40 [6%] vs 97 [15%], relative risk 0·39 [95% CI 0·28 to 0·56]), with an absolute risk difference of -9·23 (95% CI -12·55 to -5·92). Recruitment manoeuvre-related adverse events were reported in five patients. INTERPRETATION: Among patients subjected to lung resection under one-lung ventilation, iOLA was associated with a reduced risk of severe postoperative pulmonary complications when compared with conventional lung-protective ventilation. FUNDING: Instituto de Salud Carlos III and the European Regional Development Funds.

Small area variations in non-affective first-episode psychosis: the role of socioeconomic and environmental factors.

BACKGROUND: There is strong evidence supporting the association between environmental factors and increased risk of non-affective psychotic disorders. However, the use of sound statistical methods to account for spatial variations associated with environmental risk factors, such as urbanicity, migration, or deprivation, is scarce in the literature. METHODS: We studied the geographical distribution of non-affective first-episode psychosis (NA-FEP) in a northern region of Spain (Navarra) during a 54-month period considering area-level socioeconomic indicators as putative explanatory variables. We used several Bayesian hierarchical Poisson models to smooth the standardized incidence ratios (SIR). We included neighborhood-level variables in the spatial models as covariates. RESULTS: We identified 430 NA-FEP cases over a 54-month period for a population at risk of 365,213 inhabitants per year. NA-FEP incidence risks showed spatial patterning and a significant ecological association with the migrant population, unemployment, and consumption of anxiolytics and antidepressants. The high-risk areas corresponded mostly to peripheral urban regions; very few basic health sectors of rural areas emerged as high-risk areas in the spatial models with covariates. DISCUSSION: Increased rates of unemployment, the migrant population, and consumption of anxiolytics and antidepressants showed significant associations linked to the spatial-geographic incidence of NA-FEP. These results may allow targeting geographical areas to provide preventive interventions that potentially address modifiable environmental risk factors for NA-FEP. Further investigation is needed to understand the mechanisms underlying the associations between environmental risk factors and the incidence of NA-FEP.

Multimodal Prehabilitation in Heart Transplant Recipients Improves Short-Term Post-Transplant Outcomes without Increasing Costs.

(1) Background and aim: This study aimed to investigate the impact of prehabilitation on the postoperative outcomes of heart transplantation and its cost-effectiveness. (2) Methods: This single-center, ambispective cohort study included forty-six candidates for elective heart transplantation from 2017 to 2021 attending a multimodal prehabilitation program consisting of supervised exercise training, physical activity promotion, nutritional optimization, and psychological support. The postoperative course was compared to a control cohort consisting of patients transplanted from 2014 to 2017 and those contemporaneously not involved in prehabilitation. (3) Results: A significant improvement was observed in preoperative functional capacity (endurance time 281 vs. 728 s, p < 0.001) and quality-of-life (Minnesota score 58 vs. 47, p = 0.046) after the program. No exercise-related events were registered. The prehabilitation cohort showed a lower rate and severity of postoperative complications (comprehensive complication index 37 vs. 31, p = 0.033), lower mechanical ventilation time (37 vs. 20 h, p = 0.032), ICU stay (7 vs. 5 days, p = 0.01), total hospitalization stay (23 vs. 18 days, p = 0.008) and less need for transfer to nursing/rehabilitation facilities after hospital discharge (31% vs. 3%, p = 0.009). A cost-consequence analysis showed that prehabilitation did not increase the total surgical process costs. (4) Conclusions: Multimodal prehabilitation before heart transplantation has benefits on short-term postoperative outcomes potentially attributable to enhancement of physical status, without cost-increasing.

Revisiting systematic geographical variations in tonsils surgery in children in the Spanish National Health System: spatiotemporal ecological study on hospital administrative data.

OBJECTIVE: To provide new evidence on how tonsils surgery in children has geographically varied over time in the context of the Spanish National Health System. DESIGN: Observational ecological spatiotemporal study on geographical variations in medical practice, using linked administrative datasets, including virtually all surgeries performed from 2003 to 2015. SETTING: The Spanish National Health System, a quasi-federal structure with 17 autonomous communities (ACs), and 203 healthcare areas (HCAs). PARTICIPANTS: Patients aged 19 and younger residing in the HCAs and ACs. INTERVENTIONS: Tonsillectomy with adenoidectomy (T&A); and tonsillectomies alone (T). MAIN ENDPOINTS: (1) Evolution of T&A and T rates; (2) spatiotemporal variation in the risk of receiving T&A or T surgery at regional level (ACs) and HCAs; and (3) the fraction of the variation (FV) attributed to each of the components of variation-ACs, HCAs, year and interaction ACs year. RESULTS: T&A age-sex standardised rates increased over the period of analysis from 15.2 to 20.9 (5.7 points per 10 000 inhabitants). T alone remained relatively lower than T&A rates, evolving from 3.6 in 2003 to 3.9 in 2015 (0.3 points per 10 000 inhabitants). Most of the risk variation was captured at the HCAs level in both procedures (FV: 55.3% in T&A and 72.5% in T). The ACs level explained 27.6% of the FV in the risk in T&A versus 8% in T. The interaction ACs year was similar in both procedures (FV: 15.5% in T&A and 17.5% in T). The average trend hardly explained 1.46% and 1.83% of the variation, respectively. CONCLUSION: Our study showed wide persistent variations with a steady increase in rates and risk of T&A and a stagnation of T alone, where most of the variation risk was explained at HCA level.

Accuracy of a Novel Preoperative Failure Risk Model for Debridement Antibiotics and Implant Retention (DAIR) in Acute Prosthetic Joint Infection.

Given the variable success of the debridement, antibiotics and implant retention (DAIR) procedure in patients with acute prosthetic joint infection (PJI), an accurate selection of candidates is critical. In this study, we set about calculating the predictive value of a novel algorithm for predicting outcome following DAIR developed by Shohat et al. Sixty-four patients who underwent debridement for (early and late) acute PJI in a tertiary-level university hospital were selected, and the aforementioned algorithm was retrospectively applied. Patients with model scores of 40−50%, 50−60%, 60−70%, 70−80% and 80−90% displayed success rates of 33.34%, 41.18%, 57.9%, 78.27% and 100%, respectively. The receiver operating characteristic curve showed an area under the curve of 0.69. The calibration intercept value was 0, and the calibration slope value was 1. Failure rates were significantly higher for the following variables: revision surgery (p = 0.012) index surgery for reasons other than osteoarthritis (p = 0.01), and C-reactive protein level >30 mg/L (p = 0.042). This analysis demonstrated that the Shohat algorithm is associated with an optimal calibration value and a moderate predictive value for failure of a DAIR procedure in patients with acute PJI. Its validation is recommended before it can be routinely applied in daily practice.

Effect of a multicomponent exercise program and cognitive stimulation (VIVIFRAIL-COGN) on falls in frail community older persons with high risk of falls: study protocol for a randomized multicenter control trial.

BACKGROUND: Falls represent important drivers of intrinsic capacity losses, functional limitations and reduced quality of life in the growing older adult's population, especially among those presenting with frailty. Despite exercise- and cognitive training-based interventions have shown effectiveness for reducing fall rates, evidence around their putative cumulative effects on falls and fall-related complications (such as fractures, reduced quality of life and functional limitations) in frail individuals remains scarce. The main aim of this study is to explore the effectiveness program combining an individualized exercise program and an executive function-based cognitive training (VIVIFRAIL-COGN) compared to usual care in the prevention of falls and fall-related outcomes over a 1-year follow-up. METHODS: This study is designed as a four-center randomized clinical trial with a 12-week intervention period and an additional 1-year follow-up. Three hundred twenty frail or pre-frail (≥ 1 criteria of the Frailty Phenotype) older adults (≥ 75 years) with high risk of falling (defined by fall history and gait performance) will be recruited in the Falls Units of the participating centers. They will be randomized in a 1:1 ratio to the intervention group (IG) or the control group (CG). The IG will participate in a home-based intervention combining the individualized Vivifrail multicomponent (aerobic, resistance, gait and balance and flexibility) exercise program and a personalized executive function-based cognitive training (VIVIFRAIL-COGN). The CG group will receive usual care delivered in the Falls Units, including the Otago Exercise Program. Primary outcome will be the incidence of falls (event rate/year) and will be ascertained by self-report during three visits (at baseline, and 6 and 12 weeks) and telephone-based contacts at 6, 9 and 12 months after randomization. Secondarily, effects on measures of physical and cognitive function, quality of life, nutritional, muscle quality and psychological status will be evaluated. DISCUSSION: This trial will provide new evidence about the effectiveness of an individualized multidomain intervention by studying the effect of additive effects of cognitive training and physical exercise to prevent falls in older frail persons with high risk of falling. Compared to usual care, the combined intervention is expected to show additive effects in the reduction of the incidence of falls and associated adverse outcomes. TRIAL REGISTRATION: NCT04911179 02/06/2021.

COVID-19 infection and complications according to ABO blood group in the elderly: A population-based subcohort and meta-analysis.

BACKGROUND AND OBJECTIVES: It is reported that ABO antibodies have a role in COVID-19 infection and severity; however, ABO antibody titres vary with advanced age. The aim was to analyse the association between ABO blood group and risk of COVID-19 infection and complications in elderly patients, and to contrast this data with findings in the overall adult population. MATERIALS AND METHODS: A prospective cohort study of the Navarre (Spain) population aged ≥60 years and a meta-analysis of published studies including participants of ≥60 years were carried out. RESULTS: In the Navarre elderly population, a higher risk of COVID-19 infection was identified in the A versus non-A and O group and lower risk in O versus non-O, with no significant association between hospitalization, intensive care unit admission or mortality and any of the blood groups, results that coincide with those of the overall Navarre adult population. The meta-analyses using studies that included participants of ≥60 years demonstrated a higher risk of hospitalization and mortality in A versus non-A and a lower mortality risk with B versus non-B. Similar mortality results were found in the meta-analyses of the overall adult population. CONCLUSION: There are no relevant differences between the overall adult population and population aged ≥60 years in the risk of COVID-19 infection and severity according to ABO blood groups, suggesting that age-related changes in ABO would be of limited clinical significance.

Effectiveness of Statins for Primary Prevention of Cardiovascular Disease in Low- and Medium-Risk Males: A Causal Inference Approach with Observational Data.

In this study, we analyzed the effectiveness of statin therapy for the primary prevention of cardiovascular disease (CVD) in low- and medium-risk patients. Using observational data, we estimated effectiveness by emulating a hypothetical randomized clinical trial comparing statin initiators with statin non-initiators. Two approaches were used to adjust for potential confounding factors: matching and inverse probability weighting in marginal structural models. The estimates of effectiveness were obtained by intention-to-treat and per-protocol analysis. The intention-to-treat analysis revealed an absolute risk reduction of 7.2 (95% confidence interval (CI95%), -6.6-21.0) events per 1000 subjects treated for 5 years in the matched design, and 2.2 (CI95%, -3.9-8.2) in the marginal structural model. The per-protocol analysis revealed an absolute risk reduction of 16.7 (CI95%, -3.0-36) events per 1000 subjects treated for 5 years in the matched design and 5.8 (CI95%, 0.3-11.4) in the marginal structural model. The indication for statin treatment for primary prevention in individuals with low and medium cardiovascular risk appears to be inefficient, but improves with better adherence and in subjectvs with higher risk.

Intraoperative positive end-expiratory pressure and postoperative pulmonary complications: a patient-level meta-analysis of three randomised clinical trials.

BACKGROUND: High intraoperative PEEP with recruitment manoeuvres may improve perioperative outcomes. We re-examined this question by conducting a patient-level meta-analysis of three clinical trials in adult patients at increased risk for postoperative pulmonary complications who underwent non-cardiothoracic and non-neurological surgery. METHODS: The three trials enrolled patients at 128 hospitals in 24 countries from February 2011 to February 2018. All patients received volume-controlled ventilation with low tidal volume. Analyses were performed using one-stage, two-level, mixed modelling (site as a random effect; trial as a fixed effect). The primary outcome was a composite of postoperative pulmonary complications within the first week, analysed using mixed-effect logistic regression. Pre-specified subgroup analyses of nine patient characteristics and seven procedure and care-delivery characteristics were also performed. RESULTS: Complete datasets were available for 1913 participants ventilated with high PEEP and recruitment manoeuvres, compared with 1924 participants who received low PEEP. The primary outcome occurred in 562/1913 (29.4%) participants randomised to high PEEP, compared with 620/1924 (32.2%) participants randomised to low PEEP (unadjusted odds ratio [OR]=0.87; 95% confidence interval [95% CI], 0.75-1.01; P=0.06). Higher PEEP resulted in 87/1913 (4.5%) participants requiring interventions for desaturation, compared with 216/1924 (11.2%) participants randomised to low PEEP (OR=0.34; 95% CI, 0.26-0.45). Intraoperative hypotension was associated more frequently (784/1913 [41.0%]) with high PEEP, compared with low PEEP (579/1924 [30.1%]; OR=1.87; 95% CI, 1.60-2.17). CONCLUSIONS: High PEEP combined with recruitment manoeuvres during low tidal volume ventilation in patients undergoing major surgery did not reduce postoperative pulmonary complications. CLINICAL TRIAL REGISTRATION: NCT03937375 (Clinicaltrials.gov).

Methylprednisolone Pulses in Hospitalized COVID-19 Patients Without Respiratory Failure: A Randomized Controlled Trial.

Background: Corticosteroids are the cornerstone of the treatment of patients with COVID-19 admitted to hospital. However, whether corticosteroids can prevent respiratory worsening in hospitalized COVID-19 patients without oxygen requirements is currently unknown. Aims: To assess the efficacy of methylprednisolone pulses (MPP) in hospitalized COVID-19 patients with increased levels of inflammatory markers not requiring oxygen at baseline. Methods: Multicenter, parallel, randomized, double-blind, placebo-controlled trial conducted in Spain. Patients admitted for confirmed SARS-CoV-2 pneumonia with raised inflammatory markers (C-reactive protein >60 mg/L, interleukin-6 >40 pg/ml, or ferritin >1,000 µg/L) but without respiratory failure after the first week of symptom onset were randomized to receive a 3-day course of intravenous MPP (120 mg/day) or placebo. The primary outcome was treatment failure at 14 days, a composite variable including mortality, the need for ICU admission or mechanical ventilation, and clinical worsening, this last parameter defined as a PaO2/FiO2 ratio below 300; or a 15% decrease in the PaO2 from baseline, together with an increase in inflammatory markers or radiological progression. If clinical worsening occurred, patients received tocilizumab and unmasked corticosteroids. The secondary outcomes were 28-day mortality, adverse events, need for ICU admission or high-flow oxygen, length of hospital stay, SARS-CoV-2 clearance, and changes in laboratory parameters. Results: A total of 72 patients were randomized and 71 patients were analyzed (34 in the MPP group and 37 in the placebo group). Twenty patients presented with treatment failure (29.4 in the MPP group vs. 27.0% in the placebo group, p = 0.82), with no differences regarding the time to treatment failure between groups. There were no cases of death or mechanical ventilation requirements at 14 days post-randomization. The secondary outcomes were similar in MPP and placebo groups. Conclusions: A 3-day course of MPP after the first week of disease onset did not prevent respiratory deterioration in hospitalized COVID-19 patients with an inflammatory phenotype who did not require oxygen.

Role of the AB0 blood group in COVID-19 infection and complications: A population-based study.

Since the beginning of the COVID-19 pandemic, the ABO blood group has been described as a possible biological marker of susceptibility for the disease. This study evaluates the role of ABO group on the risk of SARS-CoV-2 infection and related complications in a population-based cohort including 87,090 subjects from the Navarre population (Northern Spain) with no history of SARS-CoV-2 infection and with known ABO blood group, after one year of the pandemic (May 2020 - May 2021). The risk of infection, hospitalization, Intensive Care Unit (ICU) admission and death was analyzed using multivariate logistic regression, adjusting for possible confounding variables. A lower risk of infection was observed in group 0 vs non-0 groups [OR 0.94 (95 %CI 0.90-0.99)], a higher risk of infection in group A vs non-A groups [OR 1.09 (95 %CI 1.04-1.15)] and a higher risk of infection in group A vs group 0 [OR 1.08 (95CI 1.03-1.14)] (when the 4 groups are analyzed separately). No association was observed between blood groups and hospitalization, ICU admission, or death in SARS-CoV-2 infected subjects. Regarding the risk of SARS-CoV-2 infection, we observed a protective role of group O and a greater risk in the A group.

Effect of intraoperative PEEP with recruitment maneuvers on the occurrence of postoperative pulmonary complications during general anesthesia--protocol for Bayesian analysis of three randomized clinical trials of intraoperative ventilation.

Background: Using the frequentist approach, a recent meta-analysis of three randomized clinical trials in patients undergoing intraoperative ventilation during general anesthesia for major surgery failed to show the benefit of ventilation that uses high positive end-expiratory pressure with recruitment maneuvers when compared to ventilation that uses low positive end-expiratory pressure without recruitment maneuvers. Methods: We designed a protocol for a Bayesian analysis using the pooled dataset. The multilevel Bayesian logistic model will use the individual patient data. Prior distributions will be prespecified to represent a varying level of skepticism for the effect estimate. The primary endpoint will be a composite of postoperative pulmonary complications (PPC) within the first seven postoperative days, which reflects the primary endpoint of the original studies. We preset a range of practical equivalence to assess the futility of the intervention with an interval of odds ratio (OR) between 0.9 and 1.1 and assess how much of the 95% of highest density interval (HDI) falls between the region of practical equivalence. Ethics and dissemination: The used data derive from approved studies that were published in recent years. The findings of this current analysis will be reported in a new manuscript, drafted by the writing committee on behalf of the three research groups. All investigators listed in the original trials will serve as collaborative authors.

Redo DAIR: The Game Is Seldom Worth the Candle.

Debridement, antibiotics and implant retention (DAIR) remains a commonly utilized technique in the treatment of acute prosthetic joint infections despite its inconsistent outcomes. The performance of a second DAIR after a failed first debridement is controversial as outcomes are uncertain and the final prognosis in the event of failure may be unfavorable. This study analyzes 84 cases of acute prosthetic (hip & knee) joint infection treated with DAIR between 2011 and 2020 at the same institution. In 12 failed cases, a second DAIR was performed, whose success rate was significantly lower than that of the first procedure (8% [95% CI, 0-38] vs. 57% [46-68]). Moreover, the ultimate outcome of the second failed DAIRs was unfavorable with eradication of the infection being achieved in none of the patients. Due to the high likelihood of failure and the potentially grim final prognosis following a second debridement, removal of the components should be considered.

Cardiovascular risk in patients with type 2 diabetes: A systematic review of prediction models.

AIMS: To identify all cardiovascular disease risk prediction models developed in patients with type 2 diabetes or in the general population with diabetes as a covariate updating previous studies, describing model performance and analysing both their risk of bias and their applicability METHODS: A systematic search for predictive models of cardiovascular risk was performed in PubMed. The CHARMS and PROBAST guidelines for data extraction and for the assessment of risk of bias and applicability were followed. Google Scholar citations of the selected articles were reviewed to identify studies that conducted external validations. RESULTS: The titles of 10,556 references were extracted to ultimately identify 19 studies with models developed in a population with diabetes and 46 studies in the general population. Within models developed in a population with diabetes, only six were classified as having a low risk of bias, 17 had a favourable assessment of applicability, 11 reported complete model information, and also 11 were externally validated. CONCLUSIONS: There exists an overabundance of cardiovascular risk prediction models applicable to patients with diabetes, but many have a high risk of bias due to methodological shortcomings and independent validations are scarce. We recommend following the existing guidelines to facilitate their applicability.

Sentinel node tumor burden in cutaneous melanoma. Survival with competing risk analysis and influence in relapses and non-sentinel node status: retrospective cohort study with long follow-up in a Spanish population.

Several authors have studied the potential of sentinel lymph node (SLN) tumor burden as prognostic factor but the microscopic classifications used in different study groups were variable. We examined the prognostic role of tumor burden in SLN on melanoma specific-survival and competing causes of death. We also analysed clinical and histological factors as predictors of disease relapses and additional non sentinel lymph node (NSLN) metastases. We included all patients with cutaneous melanoma that underwent SLN biopsy between 2002 and 2012 at Complejo Hospitalario de Navarra (Spain). The study end-points were death due to melanoma, melanoma relapse and involvement of NSLN. We used Fine-Gray test for competing risk analysis. A logistic regression model was performed to predict the risk of involvement of NSLN. Between 2002 and 2012, there were 348 patients who underwent SLN biopsy in our centre (308 were eligible for the study). 26.9% patients positive SLN. 88 patients died during the follow-up period and 66 (75%) died from melanoma. The 5-year cumulative incidence of melanoma death was 15.33% (95 % CI 15.25-15.42). The cumulative probability of death from melanoma was associated with gender, histological subtype, Breslow thickness, mitotic rate, ulceration and SLN tumor burden. In multivariable analysis, Breslow thickness and SLN tumor burden remained as independent prognostic factors. SLN tumor burden appears to be an important prognostic factor. It is very important reporting these characteristics in pathological reports. More prospective studies would be necessary to analyze these variables and to be able to make recommendations in management of melanoma patients.