Construction and preliminary validation of a tool to measure the needs of adolescents and young adults (AYA) diagnosed with cancer: the QUestionnaire nEEd Cancer AYAs: QUEEC-AYAs.

CONTEXT: In France, 2300 adolescents and young adults (AYAs, 15-25 years old) are diagnosed with cancer each year. As soon as the disease is diagnosed, a number of physical, psychological and social needs may arise. The aim of this study is to develop a tool to measure unmet needs that will allow the specificities of AYAs to be understood while allowing health care staff to mobilise the necessary actors to resolve them. METHODS: We developed the Questionnaire nEEd Cancer AYAs (QUEEC-AYAs questionnaire), from two existing questionnaires: the Cancer Needs Questionnaire Young People and the Needs Assessment & Service Bridge. A main sample of 103 AYAs then received and completed the questionnaire in order to conduct an exploratory factor analysis. RESULTS: The final structure of the QUEEC-AYAs is composed of 7 dimensions and 48 items: information (8 items), cancer care team (6 items), Physical health (4 items), Emotional health (14 items), Sexual & reproductive health (6 items), Health behaviors & wellness (4 items), Daily life (6 items). The questionnaire has a good acceptability and all domains have a Cronbach's alphas value above 0.80. CONCLUSION: The QUEEC-AYAs is the first measure of the psychosocial needs of AYAs available in French. Its systematic use in health care services should improve the coordination of care required by AYAs during and after treatment. TRIAL REGISTRATION: This study was approved by the ethics committee of the Paoli-Calmettes Institute (IRB # IPC 2021-041, 2021 May 20).

Evaluation of COVID-19 impact on DELAYing diagnostic-therapeutic pathways of lung cancer patients in Italy (COVID-DELAY study): fewer cases and higher stages from a real-world scenario.

INTRODUCTION: COVID-19 has disrupted the global health care system since March 2020. Lung cancer (LC) patients (pts) represent a vulnerable population highly affected by the pandemic. This multicenter Italian study aimed to evaluate whether the COVID-19 outbreak had an impact on access to cancer diagnosis and treatment of LC pts compared with pre-pandemic time. METHODS: Consecutive newly diagnosed LC pts referred to 25 Italian Oncology Departments between March and December 2020 were included. Access rate and temporal intervals between date of symptoms onset and diagnostic and therapeutic services were compared with the same period in 2019. Differences between the 2 years were analyzed using the chi-square test for categorical variables and the Mann-Whitney U test for continuous variables. RESULTS: A slight reduction (-6.9%) in newly diagnosed LC cases was observed in 2020 compared with 2019 (1523 versus 1637, P = 0.09). Newly diagnosed LC pts in 2020 were more likely to be diagnosed with stage IV disease (P < 0.01) and to be current smokers (someone who has smoked more than 100 cigarettes, including hand-rolled cigarettes, cigars, cigarillos, in their lifetime and has smoked in the last 28 days) (P < 0.01). The drop in terms of new diagnoses was greater in the lockdown period (percentage drop -12% versus -3.2%) compared with the other months included. More LC pts were referred to a low/medium volume hospital in 2020 compared with 2019 (P = 0.01). No differences emerged in terms of interval between symptoms onset and radiological diagnosis (P = 0.94), symptoms onset and cytohistological diagnosis (P = 0.92), symptoms onset and treatment start (P = 0.40), and treatment start and first radiological revaluation (P = 0.36). CONCLUSIONS: Our study pointed out a reduction of new diagnoses with a shift towards higher stage at diagnosis for LC pts in 2020. Despite this, the measures adopted by Italian Oncology Departments ensured the maintenance of the diagnostic-therapeutic pathways of LC pts.

[Does the announcement of cancer at the time of Non Muscle-Invasive Bladder Cancer diagnosis affect quality of life and adherence of patients? Data from the French prospective cohort VICAN]. / L'annonce du cancer au diagnostic de Tumeur de vessie non infiltrant le muscle modifie-t-elle la qualité de vie et l'observance des patients ? Données de la cohorte prospective française VICAN.

INTRODUCTION: The information provided at the time of diagnosis of Non Muscle-Invasive Bladder Cancer (NMIBC) is highly variable. Well-informed patient are more involved in shared decisions. The objective of our study was to assess the information perceived by the patient at the time of NMIBC diagnosis and its impact on quality of life. METHODS: The VICAN french cohort involved a representative sample of 4174 cancer patients and 5 years survivors. Patients reported outcomes (PROs) were collected by phone and self-questionnaire. Among the 118 NMIBC patients, the term used to define the pathology at diagnosis was prospectively evaluated. The impact on quality of life (using SF-12, EORTC-QLQ-C30 and HAD scale) and on adherence to the care protocol (endoscopic monitoring) has been assessed. RESULTS: Only 26.8% of patients reported hearing the word « Cancer ¼ at the time of NMIBC diagnosis. Conversely, 73.2% of them reported others terms, including « Tumor ¼ (22%), « Polyp ¼ (24%), and « Carcinoma ¼ (17.1%). There was no difference in terms of physical, mental quality of life and anxiety, regardless of the term used. Adherence to the follow-up endoscopic protocol was better in the group of patients hearing the word "Cancer". CONCLUSION: Three quarters of patients treated for NMIBC did not integrate the concept of « Cancer ¼ at the time of diagnosis. Quality of life and anxiety did not differ significantly depending on the term used at diagnosis. However, adherence to care protocol appears to be higher when using the word "Cancer". LEVEL OF EVIDENCE: 3.

Role of meteorological factors in the spread of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic in Italy.

OBJECTIVE: Understanding the evolutionary dynamics of the Coronavirus disease 2019 (COVID-19) pandemic in the coming months is a matter of great importance and urgency for governments worldwide, making fundamental decisions based on what is known about the transmission mechanisms of the virus and its survival in the environment. The present study aimed to evaluate the impact of demographic variables, solar radiation and relative humidity on the spread of the COVID-19 pandemic of the various regions in Italy. MATERIALS AND METHODS: The retrospective longitudinal study was conducted, and data used in this study was obtained from the Italian Health Ministry. Descriptive statistics included mean, frequency, and percentage, and results presented by graphs were calculated. RESULTS: The infection trend was investigated by comparing it with the demographic situation and the irradiation indices of solar ultraviolet light that are detected with the changing seasons. The present study reported that the geographic areas with higher population density and lower solar radiation during the autumn and winter months were most affected by SARS-CoV-2. CONCLUSIONS: The analysis carried out can provide a predictive model for the future phases of the COVID-19 pandemic in Italy, regardless of the adoption of lockdown measures and behavioral factors.

The lung immuno-oncology prognostic score (LIPS-3): a prognostic classification of patients receiving first-line pembrolizumab for PD-L1 ≥ 50% advanced non-small-cell lung cancer.

BACKGROUND: To stratify the prognosis of patients with programmed cell death-ligand 1 (PD-L1) ≥ 50% advanced non-small-cell lung cancer (aNSCLC) treated with first-line immunotherapy. METHODS: Baseline clinical prognostic factors, the neutrophil-to-lymphocyte ratio (NLR), PD-L1 tumour cell expression level, lactate dehydrogenase (LDH) and their combination were investigated by a retrospective analysis of 784 patients divided between statistically powered training (n = 201) and validation (n = 583) cohorts. Cut-offs were explored by receiver operating characteristic (ROC) curves and a risk model built with validated independent factors by multivariate analysis. RESULTS: NLR < 4 was a significant prognostic factor in both cohorts (P < 0.001). It represented 53% of patients in the validation cohort, with 1-year overall survival (OS) of 76.6% versus 44.8% with NLR > 4, in the validation series. The addition of PD-L1 ≥ 80% (21% of patients) or LDH < 252 U/l (25%) to NLR < 4 did not result in better 1-year OS (of 72.6% and 74.1%, respectively, in the validation cohort). Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 [P < 0.001, hazard ratio (HR) 2.04], pretreatment steroids (P < 0.001, HR 1.67) and NLR < 4 (P < 0.001, HR 2.29) resulted in independent prognostic factors. A risk model with these three factors, namely, the lung immuno-oncology prognostic score (LIPS)-3, accurately stratified three OS risk-validated categories of patients: favourable (0 risk factors, 40%, 1-year OS of 78.2% in the whole series), intermediate (1 or 2 risk factors, 54%, 1-year OS 53.8%) and poor (>2 risk factors, 5%, 1-year OS 10.7%) prognosis. CONCLUSIONS: We advocate the use of LIPS-3 as an easy-to-assess and inexpensive adjuvant prognostic tool for patients with PD-L1 ≥ 50% aNSCLC.

[Radon exposure: also in this case it is better to open the window]. / Esposizione al Radon : anche in questo caso è meglio aprire la finestra.

Although many areas of the Italian territory are of volcanic origin, there is not much attention to the prevention of risks due to exposure to Radon gas. This gas is produced during the decay of uranium present in volcanic rocks and, if inhaled, its further decay produces radioactive radiation responsible for damage to lung tissues. It is estimated that these radiations are responsible for 10% of lung cancers. In conditions of poor air exchange, the concentration of Radon gas can easily reach high concentrations, particularly in underground rooms or on the ground floor that are in direct contact with the ground. In these territories, the designers of new buildings do not always consider this risk and the population is also poorly informed on the behavior to be adopted for prevention.

Corrigendum to "Circulating Cancer Stem Cell-Derived Extracellular Vesicles as a Novel Biomarker for Clinical Outcome Evaluation".

[This corrects the article DOI: 10.1155/2019/5879616.].

Circulating Cancer Stem Cell-Derived Extracellular Vesicles as a Novel Biomarker for Clinical Outcome Evaluation.

The recent introduction of the "precision medicine" concept in oncology pushed cancer research to focus on dynamic measurable biomarkers able to predict responses to novel anticancer therapies in order to improve clinical outcomes. Recently, the involvement of extracellular vesicles (EVs) in cancer pathophysiology has been described, and given their release from all cell types under specific stimuli, EVs have also been proposed as potential biomarkers in cancer. Among the techniques used to study EVs, flow cytometry has a high clinical potential. Here, we have applied a recently developed and simplified flow cytometry method for circulating EV enumeration, subtyping, and isolation from a large cohort of metastatic and locally advanced nonhaematological cancer patients (N = 106); samples from gender- and age-matched healthy volunteers were also analysed. A large spectrum of cancer-related markers was used to analyse differences in terms of peripheral blood circulating EV phenotypes between patients and healthy volunteers, as well as their correlation to clinical outcomes. Finally, EVs from patients and controls were isolated by fluorescence-activated cell sorting, and their protein cargoes were analysed by proteomics. Results demonstrated that EV counts were significantly higher in cancer patients than in healthy volunteers, as previously reported. More interestingly, results also demonstrated that cancer patients presented higher concentrations of circulating CD31+ endothelial-derived and tumour cancer stem cell-derived CD133 + CD326- EVs, when compared to healthy volunteers. Furthermore, higher levels of CD133 + CD326- EVs showed a significant correlation with a poor overall survival. Additionally, proteomics analysis of EV cargoes demonstrated disparities in terms of protein content and function between circulating EVs in cancer patients and healthy controls. Overall, our data strongly suggest that blood circulating cancer stem cell-derived EVs may have a role as a diagnostic and prognostic biomarker in cancer.

Bilateral synovial cyst of the thoracic spine causing paraparesis.

Spinal synovial cysts are degenerative extradural lesions mostly found in the lumbar region, and more rarely at cervical or thoracic levels and in a bilateral presentation. We report a patient with a history of progressive paraparesis associated with bilateral cervicothoracic synovial cysts, causing spinal canal narrowing and cord compression, ultimately resulting in myelopathy. A review of the literature summarizes previous reports on this topic. Surgical excision of the extradural mass, decompression of the spinal canal and instrumented fusion were performed, improving lower limb deficit and gait. Post-surgical MRI showed evidence of complete cyst resection, and good arthrodesis consolidation with adequate sagittal balance. Surgical excision is indicated in case of medical treatment failure or increasing symptom severity. Given the strong pathophysiological link between synovial cysts and spinal instability, concomitant instrumented fusion may help improve outcome.

Q-TWiST analysis of patients with metastatic castrate naive prostate cancer treated by androgen deprivation therapy with or without docetaxel in the randomised phase III GETUG-AFU 15 trial.

BACKGROUND: Early chemotherapy has recently become a new standard of care for patients with metastatic castrate-naive prostate cancer (mCNPC). The survival benefit is evident in patients with high-volume disease, but less clear in those with low-volume disease. Here, we assessed the trade-offs between toxicity and survival using a Quality-adjusted Time Without Symptoms of disease and Toxicity of treatment (Q-TWiST) analysis. PATIENTS AND METHODS: This analysis was performed from the data of the Genito-Urinary Oncology Group (GETUG)-AFU 15 phase III trial evaluating the benefits of docetaxel (D) combined with androgen deprivation therapy (ADT) versus ADT alone in 385 mCNPC patients. Overall survival was partitioned into three periods, namely toxic phase of treatment (TOX), time before progression without toxicity (TWIST), and progression (PROG). These health states were weighted according to patients' utility to determine quality-adjusted survival times. In threshold analyses, utility for TOX and PROG were varied from 0 to 1. RESULTS: A better quality-adjusted survival was found in the ADT + D arm when the utility for PROG and TOX states were ≤0.2 and ≥ 0.8, respectively. When the utility for PROG was 0.4 or more, ADT + D and ADT alone yielded similar quality-adjusted survival. When patients were stratified into high-volume versus low-volume disease, we found a significant Q-TWiST benefit in favour of the ADT + D arm only for high-volume patients when the utility for PROG was less than 0.35, while we found no benefit in low-volume disease patients, whatever the coefficients tested. CONCLUSION: Early docetaxel may provide significant quality-adjusted survival benefits for patients with mCNPC, especially those with high-volume disease, depending on the values assigned to the times spent in the toxicity phase and after PROG. The Q-TWiST methodology is a useful tool for decision-making regarding trade-offs between survival, PROG and toxicity.

Results of Infrainguinal Bypass in Acute Limb Ischaemia.

OBJECTIVE/BACKGROUND: To assess the outcomes of infrainguinal bypass performed for acute limb ischaemia, as well as the predictors of patency, mortality, and amputation. METHODS: This was a retrospective cohort study of patients undergoing infrainguinal bypass between 1998 and 2014. The cohort was stratified according to the indication for surgery into two groups: group A (acute limb ischaemia) and group B (chronic lower extremity ischaemia). Comparative analysis was performed on comorbidities, surgical technique, and outcomes, as well as prognostic factors in group A. RESULTS: In total, 702 bypasses were performed (group A, n = 107; group B, n = 595). Differences between groups were detected in age (65.9 vs. 70.9 years; p = .03), diabetes (16% vs. 49%; p < .01), renal insufficiency (6% vs. 13%; p = .05), stroke (7% vs. 14%; p = .04), and coronary artery disease (13% vs. 28%; p < .01). Patients with acute limb ischaemia more often required general anaesthesia (47% vs. 12%; p < .01) and a short bypass was more often performed (32% vs. 7%; p < .01). Median follow up was 23 and 24 months for groups A and B, respectively. No differences were found in patency rates at 1, 12, and 24 months between groups, but group B had a higher re-intervention rate during follow up. Primary patency in group A was 84%, 63%, and 58%, and in group B it was 88%, 62%, and 53% at 1, 12, and 24 months, respectively (p = .77). Assisted primary patency in group A was 85%, 72%, and 67%, and in group B it was 90%, 74%, and 66% at 1, 12, and 24 months, respectively (p = .61). Secondary patency in group A was 90%, 78%, and 75%, and in group B it was 94%, 80%, and 74% at 1, 12, and 24 months, respectively (p = .80). The freedom from re-intervention rate in group A was 91%, 74%, and 68%, and in group B it was 92%, 76%, and 71%, respectively (p = .04). Acute limb ischaemia was an independent risk factor for amputation (odds ratio [OR] 4.96, 95% confidence interval [CI] 1.74-14.09; p < .01) and mortality (OR 4.13, 95% CI 1.53-11.14; p = .01) at 30 days. In group A, female sex, prosthetic conduit, and need of distal thrombectomy were independently associated with worse patency rates. Poor intra-operative runoff was correlated with higher amputation rates. CONCLUSION: Among those undergoing infrainguinal bypass, patients who present with acute limb ischaemia constitute a subset showing higher early rates of amputation and death. In this subset of patients, worse outcomes may be expected for women, prosthetic conduits, need for distal thrombectomy, and patients with poor intra-operative runoff.

Serum uric acid levels during dual antiplatelet therapy with ticagrelor or clopidogrel: Results from a single-centre study.

BACKGROUND AND AIMS: New antithrombotic therapies have significantly improved the outcomes of patients with acute coronary syndrome (ACS), where the introduction of ticagrelor has provided the greatest mortality benefits. However, ticagrelor treatment has been associated with a potential increase in the serum uric acid (SUA) levels, which may influence endothelial dysfunction and prothrombotic status, thereby affecting the risk of acute cardiovascular events in patients requiring dual antiplatelet therapy (DAPT). The present study aimed to compare the impact of antiplatelet agents such as ticagrelor or clopidogrel on SUA levels and their effect on platelet reactivity. METHODS AND RESULTS: We included patients admitted for ACS or elective percutaneous coronary intervention (PCI) and discharged with ASA (acetylsalicylic acid; 100-160 mg) and clopidogrel (75 mg) or ticagrelor (90 mg twice a day). Chemistry was assessed at admission (baseline) and after a 30-90-day period of DAPT (together with platelet reactivity). The absolute and percentage variations of SUA after DAPT introduction were considered. Multiple-electrode aggregometry was used to assess platelet function. A total of 378 patients were enrolled, with 145 treated with aspirin and clopidogrel (AC) and 233 with aspirin and ticagrelor (AT). The AC patients were older (p = 0.003) and more often showed elective PCI as an indication to DAPT (<0.001); they received chronic therapy with ARB (angiotensin II receptor blocker; p = 0.001), nitrates (p = 0.044), CCB (calcium channel blocker; p = 0.005) and diuretics (p = 0.044). The AT patients displayed a higher percentage of ACS diagnosis (p < 0.001) and received chronic therapy with ACE (angiotensin-converting enzyme) inhibitors (p = 0.001), beta blockers (p = 0.001) and statins (p = 0.013). The AC patients displayed higher platelet reactivity at COL (collagen) test, ASPI test and ADP (adenosine diphosphate) test (p = 0.03, 0.001 and <0.001, respectively) and a higher percentage of HRPR (high residual platelet reactivity) in the ADP test (p = 0.001). No difference was found in the baseline uric acid and creatinine levels between AC and AT patients. At 30-90 days, a significant absolute and percentage increase in the SUA levels was found in AT as compared to AC patients (0.204 mg/dl vs. -0.165 mg/dl, p = 0.034; 6.26% vs. -0.005%, p = 0.018, respectively). Results were not influenced by variations in renal function. At multivariate analysis, in fact, ticagrelor therapy emerged as an independent predictor of increase in the uric acid levels (odds ratio (OR; 95% confidence interval (CI)) = 2.79 (1.66-4.67), p < 0.001). However, the variation in the SUA levels did not affect platelet reactivity or HRPR in both AC and AT patients. CONCLUSION: An increase in the SUA levels at 30-90 days was observed in patients receiving chronic DAPT with ticagrelor, but not clopidogrel treatment. However, the changes in the SUA levels do not influence platelet aggregation.

Uric acid and high-residual platelet reactivity in patients treated with clopidogrel or ticagrelor.

BACKGROUND AND AIM: High residual platelet reactivity (HRPR) is still an important challenge, despite the advent of new potent ADP-antagonists. Therefore it is of extreme importance to identify factors that can influence platelet activation. Serum uric acid (SUA) has been largely addressed in the past as a possible risk factor for coronary artery disease, with a possible association with platelets hyperreactivity. So far no studies have assessed the role of serum uric acid on the response to dual antiplatelet therapy. Therefore, the aim of our study was to evaluate the impact of uric acid levels on platelet function in patients treated with dual antiplatelet therapy (DAPT) with clopidogrel or ticagrelor. METHODS AND RESULTS: We scheduled for platelet function assessment at 30-90 days post-discharge patients treated with DAPT (ASA + clopidogrel or ticagrelor) for an ACS or elective percutaneous coronary intervention (PCI). Platelet function was assessed by whole blood impedance aggregometry (Multiplate(®)-Roche Diagnostics AG), HRPR was considered for ASPI test >862 AU(∗)min (for ASA) and ADP test values ≥417 AU* min (for ADP-antagonists). RESULTS: We included a total of 493 patients (262 were on ASA and clopidogrel and 231 on ASA and ticagrelor). Patients were divided according to quartiles of serum uric acid levels measured at the time of platelet aggregation assessment (Group 1 <4.6 mg/dL, n = 114; Group 2, 4.7-5.8 mg/dL, n = 133; Group 3, 5.9-6.8 mg/dL, n = 124; Group 4, >6.9, n = 122). Patients with higher uric acid levels were older, more often smokers, with history of hypertension and previous coronary artery bypass surgery and renal failure and were more often on therapy with diuretics at admission. Patients with higher SUA had higher triglycerides and fibrinogen. Uric acid levels did not influence ASPI, COL, TRAP and ADP tests. High residual platelet reactivity (HRPR) was observed in 1.5% of patients treated with ASA, with no difference according to SUA quartiles (p = 0.60), confirmed at multivariate analysis after correction for baseline confounders (adjusted OR[95%CI] = 1.05 [0.44-2.52], p = 0.90). HRPR for ADP-antagonists was observed in 23.6% of patients, with no difference according to SUA quartiles (p = 0.47); this result was confirmed also after correction for baseline confounders (adjusted OR[95%CI] = 1.04 [0.84-1.28], p = 0.73). Moreover, no association was found between HRPR and uric acid levels both among patients treated with clopidogrel (p = 0.35) or ticagrelor (p = 0.74), that was confirmed after correction for baseline confounding factors (adjusted OR[95%CI] = 1.18 [0.90-1.55], p = 0.23) and (adjusted OR[95%CI] = 0.96 [0.63-1.47], p = 0.85). The absence of association between SUA and platelet reactivity was confirmed at linear regression analysis both with clopidogrel (r = 0.03, p = 0.55) or ticagrelor (r = -0.01, p = 0.85). CONCLUSION: This is the first large study showing that in patients receiving DAPT, uric acid levels do not influence response to ticagrelor and clopidogrel or the effectiveness of ASA.

Advanced age and high-residual platelet reactivity in patients receiving dual antiplatelet therapy with clopidogrel or ticagrelor.

UNLABELLED: ESSENTIALS: Dual antiplatelet therapy (DAPT) in elderly patients requires balancing bleedings and thrombosis. Impact of age on high residual on-treatment platelet reactivity (HRPR) on DAPT was studied. A reduced effectiveness of adenosine diphosphate antagonists was observed over 70 years of age. The occurrence of HRPR was increased among elderly patients with both clopidogrel and ticagrelor. BACKGROUND: The aim of the present study was to evaluate the impact of age on platelet function and the occurrence of high residual on-treatment platelet reactivity (HRPR) in patients treated with dual antiplatelet therapy (DAPT) using acetylsalicilic acid (ASA) and clopidogrel or ticagrelor. METHODS: Patients treated with DAPT (ASA and clopidogrel or ticagrelor) were scheduled for platelet function assessment at 30-90 days post-discharge. By whole blood impedance aggregometry, HRPR was considered for ASPI test values > 862 AU*min (for ASA) and adenosine diphosphate (ADP) test values > 417 AU*min (for ADP antagonists). Elderly patients were defined as those aged ≥ 70 years. RESULTS: Among 494 patients on DAPT, 224 (45.3%) were ≥ 70 years old. ADP-mediated platelet aggregation increased with decades of age (279.3 ± 148.6 vs. 319.6 ± 171.1 vs. 347.3 ± 190.1 vs. 345.7 ± 169.2), whereas no difference was observed for ASA response. A reduced effectiveness of ADP antagonists was observed among elderly patients; in fact, among the 117 patients displaying HRPR (23.7%), a higher prevalence was observed among patients over 70 years old (30.4% vs. 18.1%; adjusted odds ratio (OR) [95% confidence interval (CI)] = 2.19 [1.29-3.71]). Similar results were obtained among the 266 clopidogrel-treated patients (38.5% vs. 27.9%; adjusted OR [95% CI] = 2.91 [1.46-5.8]) and in the 228 patients receiving ticagrelor (19.1% vs. 8.1%; adjusted OR [95% CI] = 2.55 [1.02-8.59]). CONCLUSION: In patients receiving dual antiplatelet therapy, advanced age is independently associated with a reduced effectiveness of ADP antagonists and a higher rate of HRPR with both clopidogrel and ticagrelor.

Impact of gender difference on vitamin D status and its relationship with the extent of coronary artery disease.

BACKGROUND AND AIM: There has been a surge of interest in the cardiovascular effects of vitamin D (25(OH)D), preventing the processes leading to vascular wall degeneration and coronary artery disease (CAD). Gender differences have been suggested for vitamin D status, with a higher rate of deficiency occurring especially in post-menopausal women, increasing the risk of bone fractures and osteoporosis. However, to date, few studies have evaluated the differences in 25(OH)D levels according to gender and their impact on the extent of CAD, which was therefore the aim of the present study. METHODS AND RESULTS: In patients undergoing coronary angiography, fasting samples were collected for the assessment of 25(OH)D levels. Significant CAD was defined as at least one vessel stenosis >50%, while severe CAD was defined as left main and/or three-vessel disease. Of the 1811 patients included, 530 (29.3%) were females, who displayed older age (p < 0.001), higher rate of renal failure (p < 0.001), hypertension (p = 0.05), treatment with angiotensin-receptor blockers (p = 0.03) and diuretics (p < 0.001), acute presentation (p < 0.001), higher platelet count (p < 0.001), glycosylated haemoglobin (p = 0.02) and cholesterol (p = 0.001), but an inverse relationship with smoking (p < 0.001), previous cardiovascular events (p < 0.001), treatment with statins and acetylsalicylic acid (ASA) (p < 0.001), body mass index (p = 0.002), haemoglobin (p < 0.001), leucocytes (p = 0.03) and triglycerides (p < 0.001). Female gender was associated with lower vitamin D levels (14.5 ± 10.9 vs. 15.9 ± 9.5, p = 0.007) and independently associated with severe vitamin D deficiency (41.9% vs. 30.4%, p < 0.001; adjusted odds ratio (OR) (95% confidence interval (CI)) = 1.42 (1.08-1.87), p = 0.01). Lower tertiles of vitamin D were associated with an increased prevalence and severity of CAD in females (adjusted OR (95% CI = 1.26 (1.10-1.44), p = 0.001 for CAD; adjusted OR (95% CI) = 1.6 (1.39-1.87), p < 0.001 for severe CAD). In males, vitamin D status was independently related to the prevalence (adjusted OR (95% CI) = 1.28 (1.02-1.61), p = 0.03) of CAD, but not the extent of CAD (adjusted OR (95% CI) = 1.02 (0.86-1.2), p = 0.84). CONCLUSION: Gender significantly affects vitamin D status. The lower 25(OH)D levels observed in females, as compared to males, play a more relevant role in conditioning the severity of CAD.

Impact of diabetes on neutrophil-to-lymphocyte ratio and its relationship to coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) is the leading cause of mortality among diabetic patients, and the neutrophil-to-lymphocyte ratio (NLR) has recently emerged from among inflammatory parameters as a potential indicator of vascular complications and poorer outcome in patients with diabetes. This study aimed to evaluate: 1) the impact of diabetes on NLR; and 2) the role of NLR on the extent of CAD among diabetic patients undergoing coronary angiography. METHODS: Consecutive patients undergoing coronary angiography were included. Diabetic status and main chemistry parameters were assessed at the time of admission. Significant CAD was defined as at least one vessel with stenosis>50%, while severe CAD was left main and/or three-vessel disease, as evaluated by quantitative coronary angiography (QCA). RESULTS: Diabetes was observed in 1377 of 3756 patients (36.7%); they were older, and displayed higher-risk cardiovascular profile and more complex CAD. Diabetic status was also associated with a significant increase in NLR (P=0.004). Among diabetics, higher NLR tertile values were related to ageing (P<0.001), dyslipidaemia (P<0.001), renal failure (P<0.001), body mass index (P<0.001), previous percutaneous coronary revascularization (P=0.004) and cerebrovascular events (P=0.003), acute presentation (P<0.001), treatment at admission with beta-blockers/statins/ASA (all P<0.001), diuretics (P=0.01) or clopidogrel (P=0.04), platelet count (P=0.03), white blood cell count, creatinine, glycaemia and C-reactive protein (P<0.001), and inversely related to haemoglobin, triglyceride levels (P<0.001) and smoking (P=0.03). NLR was associated with multivessel disease (P<0.001), degree of stenosis (P=0.01), type C lesions (P=0.02), coronary calcifications and intracoronary thrombus (P<0.001), but inversely with in-stent restenosis (P=0.003) and TIMI flow grade (P=0.02). Also, NLR was directly related to CAD prevalence (P<0.001; adjusted OR [95% CI]: 1.62 [1.27-2.07], P<0.001) and CAD severity (P<0.001; adjusted OR [95% CI]: 1.19 [1.00-1.43], P=0.05). CONCLUSION: NLR is increased among diabetic patients and, in such patients, is independently associated with the prevalence and severity of CAD. Further studies are now needed to confirm present results and to evaluate the underlying pathophysiological mechanisms behind our findings.

Uric acid levels and the risk of Contrast Induced Nephropathy in patients undergoing coronary angiography or PCI.

BACKGROUND AND AIM: Contrast Induced Nephropathy (CIN) is a common complication of procedures that require the use of contrast media, and seems to be mediated by oxidative stress and reactive oxygen species generation. Hyperuricemia is characterized by inhibited nitric oxide system and enhanced synthesis of reactive oxygen species. However, few studies have so far investigated the association between hyperuricemia and CIN that is therefore the aim of the current study among patients undergoing coronary angiography or percutaneous intervention. METHODS AND RESULTS: We analyzed a total of 1950 patients with Creatinine clearance <90 ml/min) undergoing elective or urgent coronary angiography and/or angioplasty. Patients were divided according to tertiles of baseline uric acid (Group 1, ≤ 5.5 mg/dL n = 653; Group 2, 5.6-7.0 mg/dL, n = 654; Group 3, ≥ 7.0 mg/dL, n = 643). CIN was defined as an absolute ≥ 0.5 mg/dl or a relative ≥ 25% increase in the serum creatinine level at 24 or 48 h after the procedure. Patients with higher uric acid levels were older, previous smokers, with higher prevalence of hypertension and diabetes, but with lower family history of CAD. They had more often history of a previous CABG and baseline renal dysfunction. Patients of the third Tertile had also higher levels of white blood cells, higher triglycerides and lower HDL-cholesterol and higher percentage of dilated cardiomyopathy/valvular disease as indication for angiography and consequently a lower prevalence of PCI. Patients with higher SUA were more often on therapy with ACE inhibitors and diuretics, but less often with statins, nitrate, ASA and Clopidogrel at admission. The occurrence of CIN was observed in 251 patients (12.9%), and was significantly associated with uric acid levels (12.3% in Group 1, 10.4% in Group 2 and 16.0% in Group 3; p = 0.04). Similar results were observed when the analysis was performed according to each tertiles values in both male and female gender. The association between elevated uric acid (≥ 7 mg/dl) and CIN was confirmed by multivariate analysis after correction for baseline confounding (Adjusted OR [95%CI] = 1.42 [1.04-1.93], p = 0.026). Similar results were observed across major subgroups of high-risk patients, such as patients with diabetes, female gender, renal failure, hypertension, and elderly. CONCLUSIONS: This is the first large study showing that among patients undergoing coronary angiography or percutaneous interventions elevated uric acid level is independently associated with an increased risk of CIN.

Breast cancer patients' views on the use of genomic testing to guide decisions about their postoperative chemotherapy.

BACKGROUND/AIMS: Incorporating gene expression profiling into routine clinical practices is beginning to be recommended as part of breast cancer treatment. The aim of the present study was to investigate the decision-making involved in genomic testing from the perspective of patients enrolled in a genomics-based clinical trial of adjuvant chemotherapy. METHODS: The prospective SA02 clinical trial was designed to assess the clinical benefits of a genomic test on axillary lymph node-positive (N+) early breast cancer patients. The patients enrolled in the SA02 trial were defined by 'good prognosis' genomic test results consistent with the delivery of postoperative anthracycline-based chemotherapy without taxane. The present companion study was presented by oncologists to 64 out of the 88 patients enrolled. Data were collected using self-administered questionnaires. RESULTS: The response rate was 67% (questionnaires were returned 35 days on average after enrolment in the trial). Only 33% of the respondents accurately recalled or described their genomic test results. Although most N+ patients classically undergo anthracycline/taxane adjuvant chemotherapy, 23% of the present respondents did not recall participating in the clinical study involving chemotherapy without taxanes. Recall was mainly associated with higher risk perception of chemotherapy-related side effects and better understanding of test results. Among the respondents who recalled participating in the trial, 39% experienced decisional conflicts. CONCLUSIONS: Devoting greater efforts to explaining genomic test results to patients could be highly relevant in terms of the trade-off between the risk of unnecessary chemotherapy-related side effects and the loss of survival time possibly resulting from less aggressive treatment.