The unexpected social cost of inguinal hernioplasty procedures derived from the COVID-19 pandemic: Surgical trend analysis based on an Italian hospital series.

BACKGROUND: The majority of inguinal hernias are usually paucisymptomatic, so are restored electively. The main purpose of this study is to assess the trends in hernia repair surgery before and during the pandemic period, analyzing an Italian hospital series of 390 patients, in an attempt to quantify the negative impact regarding social costs derived from the Covid-19 outbreak. Moreover, we want to focus on the concept of apparently minor pathology as hernioplasty which could represent a life-threatening condition for patients. METHODS: The study population consisted of all patients operated for inguinal hernia in a General Surgery Unit from 2019 to 2021, divided into a pre-pandemic and a pandemic period. RESULTS: The Covid-19 pandemic increased urgent operations in a complicated setting. A statistically significant difference was found regarding the trend of hospitalization length as well as a strong positive correlation between the severity of hernia and the hospitalization length. CONCLUSIONS: During the pandemic, it has been registered a mishandling of inguinal hernias to the detriment of both the healthcare system and patients, due to multifactorial issues and, in particular, to the restrictions imposed by the regional government that erroneously declassed hernia pathology as a minor problem for public health. We do believe that patients, after diagnosis of inguinal hernia, should learn the Taxis maneuver for its feasibility and ease of execution, in order to reduce access to emergencies in many cases and likewise to better pain and discomfort perceived, even in the event of unexpected worldwide healthcare scenario.

Moving toward Precision Medicine in Acute Coronary Syndromes: A Multimodal Assessment of Non-Culprit Lesions.

Patients with acute coronary syndrome and multivessel disease experience several recurrent adverse events that lead to poor outcomes. Given the complexity of treating these patients, and the extremely high risk of long-term adverse events, the assessment of non-culprit lesions becomes crucial. Recently, two trials have shown a possible clinical benefit into treat non-culprit lesions using a fraction flow reserve (FFR)-guided approach, compared to culprit-lesion-only PCI. However, the most recent FLOW Evaluation to Guide Revascularization in Multivessel ST-elevation Myocardial Infarction (FLOWER-MI) trial did not show a benefit of the use of FFR-guided PCI compared to an angiography-guided approach. Otherwise, intracoronary imaging using optical coherence tomography (OCT), intravascular ultrasound (IVUS), or near-infrared spectroscopy (NIRS) could provide both quantitative and qualitative assessments of non-culprit lesions. Different studies have shown how the characterization of coronary lesions with intracoronary imaging could lead to clinical benefits in these peculiar group of patients. Moreover, non-invasive evaluations of NCLs have begun to take ground in this context, but more insights through adequately powered and designed studies are needed. The aim of this review is to outline the available techniques, both invasive and non-invasive, for the assessment of multivessel disease in patients with STEMI, and to provide a systematic guidance on the assessment and approach to these patients.

Estimated Direct Costs of Renal Cancer by Stage of Disease at Diagnosis and Phase of Its Management: A Whole-Disease Model.

BACKGROUND: Renal cell carcinoma (RCC) is the seventh most common neoplasm in high-income countries. New clinical pathways have been developed to deal with this tumor, which includes costly drugs that pose an economic threat to the sustainability of healthcare services. This study provides an estimate of the direct costs of care for patients with RCC by stage of disease (early vs. advanced) at diagnosis, and disease management phase along the pathway recommended by local and international guidelines. MATERIALS AND METHODS: Considering the clinical pathway for RCC adopted in the Veneto region (north-east Italy) and the latest guidelines, we developed a very detailed "whole-disease" model that covers the probabilities of all potentially necessary diagnostic and therapeutic actions involved in the management of RCC. Based on the cost of each procedure according to the Veneto Regional Authority's official reimbursement tariffs, we estimated the total and average per-patient costs by stage of disease (early or advanced) and phase of its management. RESULTS: In the first year after diagnosis, the mean expected cost of a patient with RCC is €12,991 if it is localized or locally-advanced and reaches €40,586 if it is advanced. For early disease, the main cost is incurred by surgery, whereas medical therapy (first and second line) and supportive care become increasingly important for metastatic disease. CONCLUSION: It is crucially important to examine the direct costs of care for RCC, and to predict the burden on healthcare services of new oncological therapies and treatments, as the findings could be useful for policy-makers planning the allocation of resources.

Risk Management Activities in a Lung Cancer Multidisciplinary Team at a Comprehensive Cancer Center: Results of a Prospective Analysis.

PURPOSE: The objective of the study was to highlight sources of harm that could negatively affect the lung cancer multidisciplinary team (MDT) activities to reduce the level of risk of each factor. METHODS: A modified Delphi approach was used by a board of multi-health care professionals of the lung cancer MDT to identify the main processes, subprocesses, and risk factors of the multidisciplinary pathway of patients with lung cancer. A semiquantitative matrix was built with a five-point scale for probability of harm (likelihood) and severity of harm (consequences) according to the international risk management standards (ISO 31000-2018). The risk level was calculated by multiplying likelihood × consequences. Mitigation strategies have been identified and applied by the MDT to reduce risks to acceptable levels. RESULTS: Three main processes (outpatient specialist visit, MDT discussion, and MDT program implementation), eight related subprocesses, and 16 risk factors were identified. Four risk factors (25%) were related to outpatient specialist visit, seven (43.75%) to case discussion, and five (31.25%) to program implementation. Overall, two risk factors were assigned a low-risk level (12.5%), 11 a moderate-risk level (68.75%), one (6.25%) a high-risk level, and two (12.5%) a very high-risk level. After the implementation of mitigation measures, the new semiquantitative risk analysis showed a reduction in almost all hazardous situations: two risk factors (12.5%) were given a very low level, six (37.5%) a low level, seven (43.75%) a moderate level, and one (6.25%) a very high level. CONCLUSION: An interdisciplinary risk assessment analysis is applicable to MDT activities by using an ad hoc risk matrix: if the hazard is identified and monitored, the risk could be reduced and managed in a short time.

Renal cell carcinoma: the population, real world, and cost-of-illness.

BACKGROUND: The RCC treatment landscape has evolved dramatically over the past decade. The purpose of this study is to present a real-world data estimation of RCC's cost-of-illness for this tumour's clinical pathway. METHODS: This investigation is a population-based cohort study using real-world data, which considers all RCC incident cases diagnosed in Local Unit 6 of the Province of Padua in 2016 and 2017 as registered by the Veneto Cancer Registry. Data on drug prescriptions, the use of medical devices, hospital admissions, and visits to outpatient clinics and emergency departments were collected by means of administrative databases. We evaluated the costs of all healthcare procedures performed in the 2 years of follow-up post-RCC diagnosis. The overall and annual average real-world costs per patient, both as a whole and by single item, were calculated and stratified by stage of disease at diagnosis. RESULTS: The analysis involved a population of 148 patients with a median age of 65.8 years, 66.22% of whom were male. Two years after diagnosis, the average total costs amounted to €21,429 per patient. There is a steady increment in costs with increasing stage at diagnosis, with a total amount of €41,494 spent 2 years after diagnosis for stage IV patients, which is 2.44 times higher than the expenditure for stage I patients (€17,037). In the first year, hospitalization appeared to be the most expensive item for both early and advanced disease. In the second year, however, outpatient procedures were the main cost driver in the earlier stages, whereas anticancer drugs accounted for the highest costs in the advanced stages. CONCLUSIONS: This observational study provides real-world and valuable estimates of RCC's cost-of-illness, which could enable policymakers to construct dynamic economic cost-effectiveness evaluation models based on real world costs' evaluation.

Cost-effectiveness analysis of the new oncological drug durvalumab in Italian patients with stage III non-small cell lung cancer.

BACKGROUND: The monoclonal antibody durvalumab, an immune-checkpoint inhibitor (ICI) antiprogrammed death ligand 1 (PD-L1), is available for unresectable stage III NSCLC patients as consolidation therapy following induction chemoradiotherapy, with very promising overall survival (OS) and progression-free survial (PFS) results in registration trials. The purpose of this study was to provide policymakers with an estimate of the cost-effectiveness of durvalumab in the treatment of non-small cell lung cancer (NSCLC). METHODS: The study developed a Markov model covering a 5-year period to compare costs and outcomes of treating PD-L1 positive patients with or without durvalumab. We conducted a series of sensitivity analyses (Tornado analysis and Monte Carlo simulation) by varying some parameters to assess the robustness of our model and identify the parameters with the greatest impact on cost-effectiveness. RESULTS: Prior to the release of durvalumab, the management of NSCLC over a 5-year period cost €33 317 per patient, with an average life expectancy of 2.01 years. After the introduction of the drug, this increased to €37 317 per patient, with an average life expectancy of 2.13 years. Treatment with durvalumab led to an incremental cost-effectiveness ratio (ICER) of €35 526 per year. OS is the variable that contributes the most to the variability of the ICER. CONCLUSIONS: The study observed that durvalumab is a cost-effective treatment option for patients with unresectable stage III NSCLC.

Malignant Melanoma: Direct Costs by Clinical and Pathological Profile.

INTRODUCTION: A number of studies have examined the impact of tumor stage on direct health care costs of patients with melanoma. This study aimed to investigate the association between the direct costs for melanoma and the patients' clinical and histological characteristics. METHODS: The present analysis included 1368 patients diagnosed with melanoma in 2017 in the Veneto Region (northeast Italy) and recorded in a regional population-based melanoma registry. The costs were assessed taking monthly and total direct costs into account. Log-linear multivariable analysis was used to identify the clinical and histological cost drivers, focusing on monthly and total direct costs per patient incurred during the first 2 years after a patient's diagnosis. RESULTS: On multivariable analysis, besides the stage of melanoma, also the presence of mitoses (> 2) was associated with higher monthly direct costs [odds ratio (OR) 1.55, 95% confidence interval (CI) 1.15-2.08, p = 0.004] in respect to cases with 0-2 mitoses. Vertical growth was associated with higher costs compared with radial growth (OR 1.28, 95% CI 1.00-1.64, p = 0.055). Moreover, the association between the absence of tumor-infiltrating lymphocytes (TILs) and higher monthly direct costs reached statistical significance (OR 1.31, 95% CI 1.05-1.64, p = 0.017). There were no differences in monthly direct costs by patients' sex or age, ulceration, or tumor site. CONCLUSION: This study showed that not only tumor stage but also other clinical and histopathologic characteristics have an impact on the direct monthly and total costs of treating melanoma. Further studies on the cost-effectiveness of the various options for managing this disease should take these variables into account, as well as tumor stage, as cost drivers.

Impact of Sex on the Functional Assessment of Intermediate Coronary Lesions by Instantaneous Wave-Free Ratio.

Sex differences in coronary physiology and in the pathogenesis of coronary artery disease (CAD) have been previously described. Contrasting data have been reported, so far, about the impact of sex on the assessment of the functional significance of intermediate coronary stenoses by fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR). The present study aimed at assessing the sex differences in the results of iFR in a cohort of patients undergoing coronary angiography. METHODS: We included patients undergoing coronary angiography and the functional assessment of intermediate (40 to 70%) coronary lesions in 2 centers. iFR measurement was performed by pressure-recording guidewire and automatically calculated at the core laboratory using the manufacturers' dedicated software. Quantitative parameters of the coronary lesions were calculated by an automatic edge-detection system. Minimal luminal diameter (MLD), reference diameter (RD), percent diameter stenosis, and length of the lesion were measured. Positive iFR was considered for values < 0.90. RESULTS: We included 325 patients undergoing coronary angiography and iFR evaluation of 371 intermediate coronary stenoses, including 20.6% of women. Females were older, displayed lower body weight and hemoglobin, lower rate of active smoking (p < 0.001) and previous PCI (p = 0.04), lower platelet count (p = 0.001) and creatinine (p = 0.02). Systolic blood pressure and heart rate at admission were more elevated in women (p = 0.001 and p = 0.05, respectively). At angiography, multivessel coronary artery disease was more uncommon (p = 0.001) and proximal lesions were more frequently assessed by iFR (p = 0.04). Mean values of iFR did not differ with sex and neither the percentage of positive iFR (19.1% vs 18.8%, p = 0.99, adjusted OR[95%CI] = 0.51[0.18-1.48], p = 0.22). CONCLUSION: Among patients undergoing functional assessment of intermediate coronary lesions by instantaneous wave-free ratio, no impact of sex was observed on the absolute values or the rate of positivity of iFR.

Incident reporting reduction during the COVID-19 pandemic in a tertiary Italian hospital: A retrospective analysis.

BACKGROUND: Incident reporting (IR) is one of the most used systems to gain knowledge of adverse events (AEs) and to identify sources of risk. During COVID-19 pandemic, several organizational changes have been implemented to respond adequately and effectively to the emergency; this required the suspension of most deferrable activities. OBJECTIVE: The aim of this study is to investigate whether IR attitude of health workers has been reduced during the pandemic event. METHOD: A retrospective analysis was conducted at the Azienda Ospedale - Università di Padova (Italy), considering IR of years 2019 and 2020. To standardize the effects of the decrease in admissions, we considered the number of incidents per 1000 admissions. RESULTS: Data shows that during the first (March-May 2020) and second waves (October-December 2020) of the COVID-19 pandemic there was a statistically significant reduction in the rate of IR for every 1000 admissions (P = 0.001-Wilcoxon test), especially for AEs and in COVID-19 units. CONCLUSION: This study shows a reduction in IR especially during the first and second pandemic waves of COVID-19 in year 2020. Education and training interventions could be fundamental to raise awareness of the importance of IR in health workers, as this could provide opportunities to understand what is impacting on safety in a particular healthcare context and enable continuous improvement.

Quality management of cutaneous melanoma: impact on short-term outcomes and costs.

Promoting standardization and quality assurance (QA) may guarantee better outcomes for patients and ensure a better allocation of healthcare system resources. The present study tested the association between process quality indicators of the clinical pathway for melanoma and both patient short-term mortality and budget utilization. Specific indicators were selected to assess quality of processes in different phases of the pathway as well as the pathway as a whole. Cox regression models were run for each phase to test the association between adherence to the quality indicator and overall mortality. A Tobit regression analysis was used to identify any association between adherence to the quality indicators and total costs over the two years after melanoma was diagnosed. This retrospective cohort study concerned 1,222 incident cases of melanoma in the Veneto Region (north-east of Italy). Adherence to the clinical pathway as a whole was associated with a significant decrease in risk of death (HR= 0.40; 95% CI: 0,19 -0,77). Adherence to quality processes in the diagnostic phase (HR= 0.55 95% CI: 0.31- 0.95) and surgical phase (HR= 0.33 95% CI: 0.16- 0.61) significantly reduced the hazard risk. Tobit regression revealed a significant increase in overall costs for patients who adhered to the whole pathway in comparison with those who did not (ß= 2,393.24; p= 0.013). This study suggests that adherence to the quality of management of clinical pathways modifies short-term survival as well as mean cost of care for patients with cutaneous melanoma. Physicians should be encouraged to improve their compliance with clinical care pathways for their melanoma patients, and steadily growing associated costs emphasize the need for policy makers to invest exclusively in treatments of proven efficacy.

Non-Small-Cell Lung Cancer: Real-World Cost Consequence Analysis.

PURPOSE: The present work aimed at conducting a real-world data analysis on the management costs and survival analysis comparing data from non-small-cell lung cancer (NSCLC) cases diagnosed in the Veneto region before (2015) and after (2017) the implementation of a regional diagnostic and therapeutic pathway including all new diagnostic and therapeutic strategies. METHOD: This study considered 254 incidental cases of NSCLC in 2015 and 228 in 2017 within the territory of the Padua province (Italy), as recorded by the Veneto Cancer Registry. Tobit regression analysis was performed to verify if total and each item costs (2 years after NSCLC diagnosis) are associated with index year, adjusting by year of diagnosis, sex, age, and stage at diagnosis. Logistic regression models were run to study overall mortality at 2 years, adjusting by the same covariates. RESULTS: The 2017 cohort had a lower mortality odd (odds ratio, 0.93; P = .02) and a significant increase in the average overall costs (P = .009) than the 2015 cohort. The Tobit regression analysis by cost item showed a very significant increase in the average cost of drugs (coefficient = 5,953, P = .008) for the 2017 cohort, as well as a decrease in the average cost of hospice care (coefficient = -1,822.6, P = .022). CONCLUSION: Our study showed a survival improvement for patients with NSCLC as well as an economic burden growth. Physicians should therefore be encouraged to follow new clinical care pathways, while the steadily rising related costs underscore the need for policymakers and health professionals to pursue.

Preprocedural ß-Blockers in the Functional Assessment of Intermediate Coronary Lesions by Instantaneous Wave-Free Ratio.

AIM: Instantaneous wave-free ratio (iFR) has emerged as the strategy of choice for the assessment of intermediate coronary lesions. The impact of preprocedural ß-blockers therapy on the iFR was the aim of this study. METHODS: We included patients undergoing functional assessment of intermediate (40%-70%) coronary lesions in 2 centers. The iFR measurement was performed by pressure-recording guidewire and calculated at the core laboratory using the manufacturers' dedicated software. Minimal luminal diameter, reference diameter, percent diameter stenosis, and length of the lesion were measured. Positive iFR was considered for values <0.90. RESULTS: We included 197 patients undergoing functional evaluation of 223 coronary lesions. Patients on ß-blockers (69%) had more frequently hypertension (P = .05); previous myocardial infarction (P = .01); therapy with clopidogrel (P = .02), statins, and aspirin; and acute coronary syndrome at presentation (P < .001, respectively). Mean iFR values were slightly higher in patients on ß-blockers (0.94 ± 0.06 vs 0.92 ± 0.06, P = .11). The rate of positive iFR was significantly lower with ß-blockers (14.9% vs 27.5%, P = .04). On multivariate analysis, ß-blockers use was a predictor of the significance of coronary stenoses (odds ratio [OR] = 0.48; 95% CI = 0.23-0.98; P = .05) together with lesion length (OR = 1.04; 95% CI = 1.01-1.07; P = .007). CONCLUSION: Among patients undergoing iFR, preprocedural ß-blockers are associated with higher absolute values and a lower rate of positive iFR.

Impact of aging on the effects of intracoronary adenosine, peak hyperemia and its duration during fractional flow reserve assessment.

INTRODUCTION: Functional assessment of coronary stenoses is crucial for determining the correct therapeutic strategy. Age-related modifications in cardiovascular function could alter the functional significance of an intermediate coronary lesion. Therefore, the aim of the present study was to investigate the impact of age on fractional flow reserve (FFR) measurements in patients with intermediate coronary artery disease. METHODS: We included patients undergoing coronary angiography at our Division of Cardiology from June 2008 to February 2019 for elective indication or recent acute coronary syndrome and receiving FFR assessment for an intermediate coronary stenosis (angiographic 40-70% stenoses). FFR measurement was performed by pressure-recording guidewire (Prime Wire; Volcano Imaging System Philips Healthcare, San Diego, California, USA), after induction of hyperemia with intracoronary boluses of adenosine (from 60 to 720 µg, with dose doubling at each step). RESULTS: We included in our study 276 patients, undergoing FFR evaluation on 314 lesions, that were divided according to age (< or ≥70 years). Elderly patients displayed a higher cardiovascular risk profile and received more often specific therapy. We found significantly higher FFR values and lower Delta FFR and time to recovery in patients with age ≥70 years old even with high-dose adenosine. Elderly patients showed a trend in lower percentage of positive FFRs, especially with high-dose (P = 0.09). Overall, any FFR ≤ 0.80 was observed in 33.5% of younger patients and 21.1% of patients ≥70 years (P = 0.02). Results were confirmed after correction for baseline differences [adjusted odds ratio (95% confidence interval) = 0.60 (0.33-1.09), P = 0.08]. CONCLUSION: This is one of the first studies investigating the impact of age on the measurement of FFR with high-dose adenosine. Patients with age >70 years old with intermediate CAD are more likely to have higher FFR values and lower duration of hyperemia after adenosine boluses, as compared with younger patients.

Statins and Elderly: From Clinical Trials to Daily Practice.

Elderly patients represent a rising social problem, due to the exponential growth of persons in these age groups and their atherothrombotic burden. The management of this population still raises several challenges, requiring a balance between elevated cardiovascular risk, clinical complexity, frailty and co-morbidities. Statins represent the main pillar in cardiovascular prevention, lowering serum cholesterol and reducing mortality and ischemic events, especially in high-risk patients. Yet, elderly patients have often been excluded from major clinical trials of statins, thus limiting the experience with these drugs in advanced age. Moreover, important barriers to the use of statins in the elderly exist due to potential risks attributed to altered metabolism, comorbidities, polypharmacy and drug-drug interactions and financial constraints. This situation has led to a "statin paradox", since high-risk elderly patients, that would most benefit from the use of statins, may be undertreated with these drugs in real life. The vague indications provided by guidelines mean that this issue is still debated, especially regarding primary prevention. Nevertheless, the benefits in outcome offered by statins cannot be neglected. Efforts should be made in order to focus on the importance of statin use in the elderly and to provide clinicians with adequate tools for case by case decisions.

Impact of increasing dose of intracoronary adenosine on peak hyperemia duration during fractional flow reserve assessment.

BACKGROUND: Fractional Flow Reserve (FFR) is currently indicated as a first line strategy for the functional assessment of intermediate coronary stenoses. However, the protocol for inducing hyperemia still lacks standardization. Intracoronary adenosine boli, with a progressive increase to high-dosage, have been proposed as a sensitive and accurate strategy for the classification of coronary stenoses, although being potentially affected by the achievement of plateau of the effect and by a less prolonged and stable hyperemia as compared to intravenous administration. Therefore, the aim of the present study was to define the conditioning parameters and assess the impact of increasing-dose intracoronary adenosine on peak hyperemia duration in patients undergoing FFR for intermediate coronary stenoses. METHODS: FFR was assessed in patients with intermediate (40 to 70%) lesions by pressure-recording guidewire (Prime Wire, Volcano), after induction of hyperemia with intracoronary boli of adenosine (from 60 to 1440 µg, with dose doubling at each step). Hyperemic duration was defined as the time for the variation form minimum FFR ±â€¯0.02 and time to recovery till baseline values. RESULTS: We included 87 patients, undergoing FFR evaluation of 101 lesions. Mean peak hyperemia duration and time to recovery significantly increased with adenosine doses escalation (p = 0.02 and p < 0.001). Peak hyperemia duration and time to recovery with 1440 µg adenosine were 14.5 ±â€¯12.6 s and 45.2 ±â€¯30.7 s, respectively. Hyperemia duration was not related to Quantitative Coronary Angiography (QCA) parameters or FFR values. In fact, a similar increase in the time of hyperemic peak was noted when comparing patients with positive or negative FFR (pbetween = 0.87) or patients with lesions < or ≥20 mm (pbetween = 0.92) and lesions involving left main coronary or proximal left anterior descending artery (LAD) (pbetween = 0.07). A linear relationship was observed between time to recovery and FFR variations, with a greater time to baseline required in patients with FFR ≤ 0.80 (p = 0.003) and in lesions ≥ 20 mm (p = 0.006), but not in LAD/LM lesions (p = 0.55). CONCLUSIONS: The present study shows a progressive raise in the duration of peak hyperemia and time to recovery, after the administration of increasing doses of intracoronary adenosine for the assessment of FFR. Therefore, considering the potential advantages of a high-dose adenosine protocol, allowing a more prolonged hyperemia and a more precise and reliable measurement of FFR, further larger studies with such FFR strategy should certainly be advocated to confirm its safety and benefits, before its routinely use recommendation.

Evaluating safety, efficacy, and cost-effectiveness of PICC securement by subcutaneously anchored stabilization device.

PURPOSE: In recent years, a large variety of medical devices has become available. Every device must be efficient, safe and cost effective, but it is not enough to use it properly without considering the environment in which it will be employed. We applied this kind of analysis to subcutaneously anchored sutureless devices (SAS). METHODS: This is a one-center prospective observational study on safety, effectiveness and cost effectiveness of an SAS device (SecurAcath, Interrad) for securement of peripherally inserted central catheter (PICC) in 30 adult cancer patients with treatment expected to be >60 days. RESULTS: During 4963 catheter days and after 709 dressing changes (documented by 373 pictures), the use of SAS was associated with no episode of PICC dislodgement and a lower incidence of complications if compared to traditional securement devices. Insertion, management and removal of SAS were not associated with an increased pain perception by the patients. Cost effectiveness was particularly evident for long dwelling PICCs. CONCLUSIONS: Our study suggests that SAS is a highly effective and cost-effective method for securement of medium- to long-term PICCs with expected duration longer than 30 days. The introduction of SAS had a positive impact on our healthcare organization.

Impact of atorvastatin or rosuvastatin co-administration on platelet reactivity in patients treated with dual antiplatelet therapy.

BACKGROUND: Residual high-on treatment platelet reactivity (HRPR) still represents a challenging matter in patients with coronary artery disease. Drug-to-drug interaction has been suggested between some statin and antiplatelet agents, despite their co-administration is mandatory in patients after an acute cardiovascular event or coronary stenting. Therefore, the aim of the current study was to investigate any impact of rosuvastatin or atorvastatin co-administration on platelet reactivity in patients receiving dual antiplatelet therapy (DAPT). METHODS: Our population is represented by patients on DAPT (ASA and either clopidogrel 75 mg or ticagrelor 90 mg b.i.d) after an ACS or percutaneous revascularization, and receiving rosuvastatin or atorvastatin. Platelet function was assessed by Multiplate Impedance Aggregometry (Roche Diagnostics AG). RESULTS: We included a total of 374 patients, 240 (64.2%) receiving atorvastatin, 134 (35.8%) rosuvastatin. Rosuvastatin treated patients were more often using beta-blockers (p = 0.05), diuretics (p = 0.04) and displayed higher HDL (p < 0.001) and lower LDL cholesterol (p < 0.001). The prevalence of HRPR for ASA was low, with no difference according to statin type (0.8% vs 1.5%, p = 0.62, adjusted OR[95%CI] = 2[0.23-16.6], p = 0.52). Concerning ADP-antagonists, in the 163 patients treated with clopidogrel, rosuvastatin co-administration was associated with a significantly increased rate of HRPR (55.6%vs 32%, p = 0.01, adjusted OR[95%CI] = 2.69[1.22-5.96], p = 0.015) with higher ADP-mediated platelet reactivity (p = 0.01) and TRAP-test results (p = 0.04). On the contrary, in the 211 ticagrelor treated patients, statin type did not affect mean platelet reactivity or the prevalence of HRPR with ticagrelor (10.5% vs 11.2%, p = 0.99, adjusted OR[95%CI] = 0.86[0.34-2.22], p = 0.76) CONCLUSIONS: Among patients receiving DAPT, rosuvastatin but not atorvastatin is associated with an increased rate of HRPR for clopidogrel, without any influence on the antiplatelet effect of ASA or ticagrelor. Therefore, cautiousness should be exerted for clopidogrel and rosuvastatin therapeutic association.

Impact of sex on uric acid levels and its relationship with the extent of coronary artery disease: A single-centre study.

BACKGROUND: Serum uric acid (SUA) elevation has been largely addressed in the past as a possible risk factor for cardiovascular disease. However, uric acid has not clearly emerged as independent risk factor for coronary artery disease. Several studies in literature have assessed sex-related differences in the association between elevated SUA levels and cardiovascular events with conflicting results. Therefore, aim of the current study was to evaluate the relationship between uric acid levels and the extent of coronary artery disease in male and female patients undergoing coronary angiography. METHODS: Our population is represented by 3520 consecutive patients undergoing coronary angiography from March 2007 to October 2012. Patients were divided according to Tertiles of SUA (Males, Group 1, ≤5.5 mg/dL-0.33 mmol/mol, n = 762, Group 2, 5.5-6.8 mg/dL-0.33-0.40 mmol/mol, n = 829 and Group 3 ≥6.8 mg/dL-0.40 mmol/mol, n = 851), (Females, Group 1, ≤4.8 mg/dL-0.28 mmol/mol, n = 349, Group 2, 4.8-6.3 mg/dL-0.28-0.37 mmol/mol, n = 359 and Group 3 ≥ 6.3 mg/dL-0.37 mmol/mol, n = 370). Fasting samples were collected for uric acid levels assessment. Coronary disease was defined for at least 1 vessel stenosis >50% as evaluated by QCA. Severe coronary disease was defined as three-vessel disease and/or left main disease. RESULTS: Among 3520 patients, we identified 2442 men (69.4%) and 1078 women (30.6%). Males had higher levels of uric acid than women (6.33 ± 1.7 vs 5.8 ± 1.9 - p < 0.001). The association between elevated uric acid (≥7 mg/dl or 0.42 mmol/l) and male gender was confirmed after correction for baseline confounding factors (Adjusted OR = 1.28 [1.01-1.62], p = 0.004). Males displayed a significantly higher prevalence and extent of CAD (p < 0.001) and more complex coronary lesions (p < 0.001). However, no significant relationship was observed between uric acid and CAD (Adjusted OR [95%CI] = 0.90 [0.76-1.06], p = 0.22) or severe CAD (Adjusted OR [95%CI] = 0.89 [0.79-1.01], p = 0.08). Among females, higher SUA levels were significantly associated with higher prevalence of severe CAD (p < 0.001) (Adjusted OR [95% CI] = 1.29 [1.03-1.62], p = 0.03). CONCLUSION: Our study showed that uric acid levels are significantly higher in men. However, high uric acid levels are associated with severe CAD only in women. Future large studies are certainly needed to confirm our findings and to evaluate the effects of SUA lowering therapies on cardiovascular prevention and outcome, especially in women.

No-reflow reversibility: a study based on serial assessment of multiple biomarkers.

No-reflow after primary percutaneous coronary intervention (pPCI) may be reversible. 40 patients undergoing pPCI were evaluated by assessing either improvement or lack of changes regarding angiographic and electrocardiographic indexes of no-reflow between admission and pre-discharge. Myeloperoxidase (MPO; in nanograms per milliliter), C-reactive protein (CRP; in milligrams per liter), endothelin-1 (ET-1; in nanograms per milliliter), angiopoietin-2 (Ang-2, in picograms per milliliter), and their pre-discharge/basal values variations (Δ) were related to no-reflow evolution. ΔMPO and ΔCRP were greater in patients with sustained no-reflow or lack of ST-segment resolution (STR) as compared with those with reversible no-reflow or lack of STR (p = 0.033, p = 0.04, p < 0.001, and p = 0.001, respectively), whereas ΔET-1 was similar in the two groups. ΔAng-2 was greater in patients with sustained no-reflow or lack of STR as compared with those with reversible no-reflow or lack of STR (p = 0.01 and 0.044, respectively). Bigger ΔMPO, ΔCRP (increasing levels), and ΔAng-2 (decreasing levels) are associated with sustained no-reflow, thus they might have a role in no-reflow evolution.