Squamous Cell Carcinoma of Nasal Vestibule and Pyramid: Outcomes and Reconstructive Strategies.

OBJECTIVES: Squamous cell carcinoma of nasal vestibule and pyramid is rare, thus classification, treatment protocol, and indications for elective neck treatment are still controversial. Nasal reconstruction is challenging, as well, and prosthesis is still used. STUDY DESIGN: Retrospective cohort study. METHODS: Retrospective review of patients surgically treated from 2010 to 2018 in a single Institution. Advanced tumors were further treated with adjuvant irradiation. Reconstruction strategy included grafts, locoregional and free flaps, and was customized on layers removed. RESULTS: Forty-five patients were enrolled. The 5-year overall survival and disease-free survival were 81.9% ± 7.45% and 61.9% ± 9.09%, respectively. Wang's classification, site of origin, extent of surgery and margins status significantly correlated with prognosis and recurrence rate. Regional recurrences occurred in patients affected by advanced tumors who did not receive any form of elective neck treatment. CONCLUSION: Multidisciplinary management and a proper reconstructive algorithm are recommended. Adjuvant irradiation and elective neck treatment should be advocated for advanced stage high-risk patients. LEVEL OF EVIDENCE: 4. Laryngoscope, 131:E1198-E1208, 2021.

Multidisciplinary treatment algorithm for the management of sinonasal cancers with orbital invasion: A retrospective study.

BACKGROUND: Sinonasal cancers frequently involve the orbit with resulting controversies on whether to remove or preserve the orbital contents. METHODS: Retrospective review of patients with primary sinonasal cancer involving the orbit, treated according to a multidisciplinary protocol tailored to tumor histology and extent of orbital invasion in two tertiary care referral centers over a 20-year period. RESULTS: The oncological and functional outcomes of 163 patients were analyzed. The degree of orbital involvement significantly affected both overall (P < .0001) and disease-free (P < .0001) survival. Orbital apex invasion was an independent negative prognostic factor (5-year overall survival, 14.6% ± 7.5%), with dismal prognosis regardless of the treatment adopted. An appropriate use of induction chemotherapy and endoscopic-assisted surgery allowed for orbital preservation in 76.6% of cases; 96% of patients treated using an orbit-sparing approach maintained a functional eye after treatment. CONCLUSION: The multimodal treatment algorithm herein proposed was able to maximize orbital preservation rates with acceptable oncological and functional outcomes.

Endoscopic Endonasal Reconstruction of Anterior Skull Base Defects: What Factors Really Affect the Outcomes?

OBJECTIVE: Endoscopic endonasal surgery has evolved in recent decades, requiring comparable advances in reconstructive techniques. This study aimed to retrospectively review outcomes of endoscopic anterior skull base reconstruction and to analyze factors associated with failures. METHODS: Data from patients who underwent endoscopic endonasal anterior skull base reconstruction in a single institution between 1998 and 2017 were collected. Patients were stratified according to selected risk factors: sex; age; previous surgery; disease treated (cerebrospinal fluid leaks, benign tumors, malignant tumors); single or multiple defects; defect dimension (<1 cm2, 1-2 cm2, 2-6 cm2, >6 cm2) and site (olfactory cleft, ethmoidal roof, planum sphenoidalis, posterior wall of frontal sinus); reconstruction technique (overlay graft, multilayer grafts, pedicled flap) and materials used; postoperative radiotherapy; and year of surgery. Statistical significance was assessed using Fisher exact test. Univariate logistic regression was implemented to analyze the association between risk factors and failures. RESULTS: Inclusion criteria were met by 513 cases with median follow-up of 96 months (range, 12-257 months). Success rate for initial repair was 95% (487/513), with 100% success rate for secondary closure after revision surgery. Failures were not significantly related to sex (P = 0.54), reconstruction technique (P = 0.28), location of defect (P = 0.65), dimension (P = 0.69), disease (P = 0.83), or postoperative radiotherapy (P = 0.83). Year of surgery, considered as a continuous variable, was associated with a statistically significant reduction of failures (odds ratio = 0.89, P = 0.005). CONCLUSIONS: Endoscopic surgery is safe and effective for anterior skull base reconstruction. Refinements in surgical technique and increasing experience have contributed to improved success rates.

The clinicopathological spectrum of olfactory neuroblastoma and sinonasal neuroendocrine neoplasms: Refinements in diagnostic criteria and impact of multimodal treatments on survival.

OBJECTIVES: To provide a comprehensive review of the clinical and histopathological features of olfactory neuroblastoma (ONB) and other sinonasal neuroendocrine neoplasms (NENs), in order to refine diagnostic criteria, analyze treatment outcomes, and identify prognostic factors. METHODS: Data from an Italian multi-institutional database were analyzed. Patients were treated surgically via a minimally-invasive endoscopic approach followed by adjuvant radiotherapy or radiochemotherapy. Neoadjuvant cisplatin/etoposide chemotherapy was administered in cases of poorly-differentiated tumors. A centralized pathology review was performed in all cases. Patients were prospectively observed for survival. Overall (OS) and Disease-free survival (DFS) estimates were determined from Kaplan-Meier analysis and compared using the log-rank test. Statistically significant variables were entered in a multivariate Cox regression model. RESULTS: 98 patients with a median follow-up of 53months were included. Morphology review and the incorporation of cytokeratin 8/18 in the immunohistochemical panel modified the final diagnosis in 8/98 (8.2%) cases. The neoplasms were ultimately classified into four groups with different immunohistochemical profiles and clinical behaviors: ONB in 67 cases (5-year-OS, 91.6%); NEC (poorly-differentiated neuroendocrine carcinoma) in 22 cases (5-year-OS, 42.6%); MiNEN (mixed neuroendocrine/non-neuroendocrine neoplasm) in five cases (5-year-OS, 0%,0/5 cases); and NET (well-differentiated neuroendocrine tumor) in four cases (5-year-OS, 50%, 2/4 cases). Hyams grade and Ki67 index were independent prognostic factors for ONB. Neoadjuvant chemotherapy appeared to be associated with improved OS and DFS for NEC, independent of other clinicopathological variables. CONCLUSIONS: Induction chemotherapy improves survival outcomes in patients affected by poorly-differentiated tumors. Recent advances in histopathological diagnosis, including CK8/18 staining, allow to plan the most appropriate range of multimodal treatments.

Prognostic value of pretreatment peripheral blood markers in paranasal sinus cancer: Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio.

BACKGROUND: Pretreatment hematological markers have emerged as prognostic factors for several cancers. The purpose of this study was to present our investigation of the value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting recurrence and mortality for patients with primary sinonasal cancers (SNCs). METHODS: We carried out a retrospective review of patients with SNC who had been treated using endoscopic approaches from 2002 to 2014 at a single institute. The endpoints analyzed were overall survival (OS) and disease-free survival (DFS). RESULTS: Of 365 patients treated, 215 fulfilled the inclusion criteria. Analysis of epithelial tumors (adenocarcinoma and carcinoma) and advanced-stage cancers (pT3-T4) showed shorter OS and DFS in those patients with higher NLR and PLR. Furthermore, the NLR and PLR were revealed as independent prognostic factors for DFS, with a reduced risk of recurrence in patients with NLR <2.6 (hazard ratio [HR], 0.39; p = .02) and PLR <156.9 (HR, 0.34; p = .001). CONCLUSION: High pretreatment NLR and PLR are associated with poor prognosis in patients affected by epithelial advanced-stage SNC. © 2016 Wiley Periodicals, Inc. Head Neck 39: 730-736, 2017.

Sex Profile and Risk Assessment With Cardiopulmonary Exercise Testing in Heart Failure: Propensity Score Matching for Sex Selection Bias.

BACKGROUND: In heart failure (HF), women show better survival despite a comparatively low peak oxygen consumption (V˙o2): this raises doubt about the accuracy of risk assessment by cardiopulmonary exercise testing (CPET) in women. Accordingly, we aimed to check (1) whether the predictive role of well-known CPET risk indexes, ie, peak V˙o2 and ventilatory response (V˙e/V˙co2 slope), is sex independent and (2) if sex-related characteristics that impact outcome in HF should be considered as associations that may confound the effect of sex on survival. METHODS: The study population consisted of 2985 patients with HF, 498 (17%) of whom were women, from the multicentre Metabolic Exercise Test Data Combined with Cardiac and Kidney Indexes (MECKI): the end point was cardiovascular death within a 3-year period. RESULTS: During the follow-up, 305 (12%) men and 39 (8%) women (P = 0.005) died, and female sex was linked to better survival on univariate analysis (P = 0.008) and independent of peak V˙o2 and V˙e/V˙co2 slope on multivariate analysis. According to propensity score matching for female sex to exclude a sex selection bias and sample discrepancy, 498 men were selected: the standardized percentage bias ranged from 20.8 (P < 0.0001) to 3.3 (P = 0.667). After clinical profile harmonizing, female sex was predictive of HF at univariate analysis. CONCLUSIONS: The low peak V˙o2 and female association with better outcome in HF might be counterfeit: the female prognostic advantage is lost when sex-specific differences are correctly taken into account with propensity score matching, suggesting that for an effective and efficient HF model, adjustment must be made for sex-related characteristics.

The metabolic exercise test data combined with Cardiac And Kidney Indexes (MECKI) score and prognosis in heart failure. A validation study.

BACKGROUND: The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score is a prognostic model to identify heart failure (HF) patients at risk for cardiovascular mortality (CVM) and urgent heart transplantation (uHT) based on 6 routine clinical parameters: hemoglobin, sodium, kidney function by the Modification of Diet in Renal Disease (MDRD) equation, left ventricle ejection fraction (LVEF), percentage of predicted peak oxygen consumption (VO2) and VE/VCO2 slope. OBJECTIVES: MECKI score must be generalizable to be considered useful: therefore, its performance was validated in a new sequence of HF patients. METHODS: Both the development (MECKI-D) and the validation (MECKI-V) cohorts were composed of consecutive HF patients with LVEF <40% able to perform a symptom-limited cardiopulmonary exercise testing. The CVM or uHT rates were analyzed at one, two and three years in both cohorts: all patients with a censoring time shorter than the scheduled follow-up were excluded, while those with events occurring after 1, 2 and 3 years were considered as censored. RESULTS: MECKI-D and MECKI-V consisted of 2009 and 992 patients, respectively. MECKI-V patients had a higher LVEF, higher peak VO2 and lower VE/VCO2 slope, higher prescription of beta-blockers and device therapy: after the 3-year follow-up, CVM or uHT occurred in 206 (18%) MECKI-D and 44 (13%) MECKI-V patients (p<0.000), respectively. MECKI-V AUC values at one, two and three years were 0.81 ± 0.04, 0.76 ± 0.04, and 0.80 ± 0.03, respectively, not significantly different from MECKI-D. CONCLUSIONS: MECKI score preserves its predictive ability in a HF population at a lower risk.

Prognostic value of dipyridamole stress cardiac magnetic resonance in patients with known or suspected coronary artery disease: a mid-term follow-up study.

OBJECTIVES: Dipyridamole stress cardiac magnetic resonance (CMR) evaluates the key phases (perfusion and wall motion) of the ischemic cascade. We sought to determine the prognostic value of dipyridamole stress-CMR in consecutive patients symptomatic for chest pain. METHODS: Seven hundred and ninety-three consecutive patients symptomatic for chest pain underwent dipyridamole stress-CMR and were followed up for 810 ± 665 days. Patients were classified in group 1 (no- reversible ischemia), group 2 (stress perfusion defect alone), and group 3 [stress perfusion defect plus abnormal wall motion (AWM)]. End points were "all cardiac events" (myocardial infarction, cardiac death and revascularization) and "hard cardiac events" (all cardiac events excluding revascularization). RESULTS: One hundred and ninety-five (24 %) all cardiac events and 53 (7 %) hard cardiac events were observed. All and hard cardiac event rates in groups 1, 2, and 3 were 11 %, 49 %, 69 % and 4 %, 8 %, 21 %, respectively, with a higher rate in group 2 vs. group 1 (p<0.01) and group 3 vs. groups 1 and 2 (p<0.01). Multivariate analysis showed the presence of late gadolinium enhancement and stress perfusion defect plus AWM as independent predictors of all and hard cardiac events. CONCLUSIONS: Dipyridamole stress-CMR improves prognostic stratification of patients through differentiation between the different components of the ischemic cascade. KEY POINTS: • Dipyridamole stress cardiac magnetic resonance helps to assess coronary artery disease. • Novel technique to study the key phases of myocardial ischemia. • Combined assessment of perfusion and motion defects. • Dipyridamole stress imaging has additional value for predicting cardiac events.

Exercise Performance Is a Prognostic Indicator in Elderly Patients With Chronic Heart Failure--Application of Metabolic Exercise Cardiac Kidney Indexes Score.

BACKGROUND: In patients with chronic heart failure (HF) the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score, is a predictor of cardiovascular death and urgent heart transplantation. We investigated the relationship between age, exercise tolerance and the prognostic value of the MECKI score. METHODS AND RESULTS: We analyzed data from 3,794 patients with chronic systolic HF. The primary endpoint was a composite of cardiovascular death and urgent heart transplantation. Older patients had higher prevalence of comorbidities and lower exercise performance compared with younger subjects (peak V̇O2, 925 vs. 1,351 L/min; P<0.0001; V̇E/V̇CO2slope, 33.2 vs. 28.3; P>0.0001). The rate of the primary endpoint was 19% in the highest age quartile and 14% in the lowest quartile. At multivariable analysis, the independent predictors of the primary endpoint were left ventricular ejection fraction (LVEF), eGFR, peak V̇O2, serum Na(+)and the use of ß-blockers in patients aged ≥70 years, and LVEF, eGFR and peak V̇O2in younger subjects. The MECKI risk score increased across age subgroups, but on receiver operating characteristic curve analysis its prognostic power was similar in both patients aged ≥70 and <70 years. CONCLUSIONS: Older patients with HF are a high-risk population with lower exercise performance. The MECKI score increased according to age and maintained its prognostic value also in older patients.

Treatment strategies for primary early-stage sinonasal adenocarcinoma: A retrospective bi-institutional case-control study.

OBJECTIVE: To investigate different treatment strategies for primary early-stage (pT1-T2) sinonasal adenocarcinomas. METHODS: Retrospective case-control study. From 2000 to 2011, 61 cases were radically resected using an endoscopic endonasal approach. Surgery as a single treatment modality was adopted for 33 patients (study group) while it was followed by postoperative radiotherapy (poRT) in 28 patients (control group). RESULTS: Median follow-up was 61 and 67 months for the study and control group respectively. Patients were stratified according to the pT classification and no statistically significant differences were found in terms of Overall (OS) and Recurrence-free (RFS) survival. When analyzing the high-grade tumors (47 cases), statistically significant differences were observed between the control and study groups both in terms of OS (90.5% ± 6.5% versus 57.6% ± 15.4%, P = 0.03) and RFS (92.3% ± 7.39% versus 80.2% ± 8.88%, P = 0.05). Using multivariate analysis, OS was independently determined by poRT (Hazard Ratio = 0.16; P = 0.03) thus confirming its protective role for high-grade adenocarcinomas. CONCLUSION: Our preliminary results suggest that endoscopic endonasal surgery could be used as a single treatment modality for primary early-stage low-grade sinonasal adenocarcinoma, resected with negative margins. Surgery followed by poRT offers the best treatment strategy not only for advanced-stage lesions but also for high-grade adenocarcinomas, regardless of the stage of disease at presentation.

Prognostic role of atrial fibrillation in patients affected by chronic heart failure. Data from the MECKI score research group.

BACKGROUND: Atrial fibrillation (AF) is common in heart failure (HF). It is unclear whether AF has an independent prognostic role in HF. The aim of the present study was to assess the prognostic role of AF in HF patients with reduced ejection fraction (EF). METHODS: HF patients were followed in 17 centers for 3.15years (1.51-5.24). Study endpoints were the composite of cardiovascular (CV) death and heart transplant (HTX) and all-cause death. Data analysis was performed considering the entire population and a 1 to 1 match between sinus rhythm (SR) and AF patients. Match process was done for age±5, gender, left ventricle EF±5, peakVO2±3 (ml/min/kg) and recruiting center. RESULTS: A total of 3447 patients (SR=2882, AF=565) were included in the study. Considering the entire population, CV death and HTX occurred in 114 (20%) AF vs. 471 (16%) SR (p=0.026) and all-cause death in 130 (23%) AF vs. 554 (19.2%) SR patients (p=0.039). At univariable Cox analysis, AF was significantly related to prognosis. Applying a multivariable model based on all variables significant at univariable analysis (EF, peakVO2, ventilation/carbon dioxide relationship slope, sodium, kidney function, hemoglobin, beta-blockers and digoxin) AF was no longer associated with adverse outcomes. Matching procedure resulted in 338 couples. CV death and HTX occurred in 63 (18.6%) AF vs. 74 (21.9%) SR (p=0.293) and all-cause death in 71 (21%) AF vs. 80 (23.6%) SR (p=0.406), with no survival differences between groups. CONCLUSION: In systolic HF AF is a marker of disease severity but not an independent prognostic indicator.

Feasibility of combined unipolar and bipolar voltage maps to improve sensitivity of endomyocardial biopsy.

BACKGROUND: Endomyocardial biopsy (EMB) has a low sensitivity. Electroanatomic voltage mapping (EVM) is effective in guiding EMB thanks to its ability in identifying and locating low-voltage regions. The analysis of unipolar EVM can correlate with epicardial pathological involvement. We evaluated the unipolar EVM in EMB areas to determine whether it can increase EMB sensitivity in diagnosing epicardial diseases. METHODS AND RESULTS: We performed endocardial bipolar EVM-guided EMBs in 29 patients and we analyzed unipolar EVM at withdrawal sites. Eighty myocardial samples were collected (mean, 2.8±0.9; median, 3 fragments per patient) and 60 were suitable for histological analysis. Ten specimens (17%) were collected from an area with discordant normal bipolar/low-voltage unipolar EVM and they were diagnostic or suggestive for arrhythmogenic right ventricular dysplasia/cardiomyopathy in 6 patients, for myocarditis and sarcoidosis in 1 patient each. Six samples (10%) were collected from an area with discordant low-voltage bipolar/normal unipolar EVM and they showed nonspecific features. The sensitivity of unipolar EVMs for a diagnostic biopsy finding EMB was significantly higher compared with bipolar EVMs analyzed according to samples (P<0.01) and patients (P=0.008). The specificity of unipolar EMB was better than bipolar EMB when analyzed for all samples (P=0.0014) but the difference did not reach statistical significance when analyzed by patient (P=0.083). The diagnostic yield was 63.3% for the bipolar and 83.3% for the unipolar EVM. CONCLUSIONS: These findings suggest that use of a combined bipolar/unipolar map may be able to improve the diagnostic yield of endomyocardial ventricular biopsy.

Renal function and peak exercise oxygen consumption in chronic heart failure with reduced left ventricular ejection fraction.

BACKGROUND: Chronic kidney disease is associated with sympathetic activation and muscle abnormalities, which may contribute to decreased exercise capacity. We investigated the correlation of renal function with peak exercise oxygen consumption (V̇O2) in heart failure (HF) patients. METHODS AND RESULTS: We recruited 2,938 systolic HF patients who underwent clinical, laboratory, echocardiographic and cardiopulmonary exercise testing. The patients were stratified according to estimated glomerular filtration rate (eGFR). Mean follow-up was 3.7 years. The primary outcome was a composite of cardiovascular death and urgent heart transplantation at 3 years. On multivariable regression, eGFR was predictor of peakV̇O2(P<0.0001). Other predictors were age, sex, body mass index, HF etiology, NYHA class, atrial fibrillation, resting heart rate, B-type natriuretic peptide, hemoglobin, and treatment. After adjusting for significant covariates, the hazard ratio for primary outcome associated with peakV̇O2<12 ml·kg(-1)·min(-1)was 1.75 (95% confidence interval (CI): 1.06-2.91; P=0.0292) in patients with eGFR ≥60, 1.77 (0.87-3.61; P=0.1141) in those with eGFR of 45-59, and 2.72 (1.01-7.37; P=0.0489) in those with eGFR <45 ml·min(-1)·1.73 m(-2). The area under the receiver-operating characteristic curve for peakV̇O2<12 ml·kg(-1)·min(-1)was 0.63 (95% CI: 0.54-0.71), 0.67 (0.56-0.78), and 0.57 (0.47-0.69), respectively. Testing for interaction was not significant. CONCLUSIONS: Renal dysfunction is correlated with peakV̇O2. A peakV̇O2cutoff of 12 ml·kg(-1)·min(-1)offers limited prognostic information in HF patients with more severely impaired renal function.

Comparison of cardiac computed tomography versus cardiac magnetic resonance for characterization of left atrium anatomy before radiofrequency catheter ablation of atrial fibrillation.

BACKGROUND: The outcome of radiofrequency catheter ablation (RFCA) has been improved by the pivotal role of cardiovascular imaging such as cardiac computed tomography (CCT) or cardiac magnetic resonance (CMR) for the characterization of left atrium (LA) anatomy before RFCA. The aim of this study is to compare the procedural characteristics, overall radiation exposure and clinical outcomes between RFCA guided by image integration with CCT versus CMR. METHODS: Four-hundred patients with drug-refractory paroxysmal or persistent AF referred to RCFA were matched with the propensity score matching analysis to CCT (n: 200) or CMR (n: 200) for evaluation of LA before RFCA procedure. Left atrium diameter, left atrium volume, variant of pulmonary veins' anatomy, pulmonary veins' ostial dimensions, procedural characteristics, overall radiation exposure and rate of AF recurrence after RFCA were measured and compared between the two groups. RESULTS: The 2 groups were homogeneous with similar follow-up (557 ± 302 vs. 523 ± 265 days, respectively, p:0.24). The CCT group showed higher LA volume vs. CMR group (117 ± 46 vs. 101 ± 40 mL, p<0.001). No differences were observed regarding procedural characteristics. AF recurrence at follow-up was similar (29% vs. 26%, p:0.5) despite a higher radiation exposure in the CCT group vs. CMR group (40.4 ± 23.7 mSv vs. 32.8 ± 23.5 mSv, p<0.005). LA volume detected by CMR was the most robust independent predictor of AF recurrence at multivariate analysis [(HR: 1.08 (1.01-1.15), p: 0.02]. CONCLUSIONS: CCT and CMR provide similar information before RFCA. However, RFCA CMR-guided is associated with a lower overall cumulative radiation despite similar outcome in comparison with CCT-guided RFCA.

Surfactant-derived proteins as markers of alveolar membrane damage in heart failure.

BACKGROUND: In heart failure (HF) alveolar-capillary membrane is abnormal. Surfactant-derived proteins (SPs) and plasma receptor for advanced-glycation-end-products (RAGE) have been proposed as lung damage markers. METHODS: Eighty-nine chronic HF and 17 healthy subjects were evaluated by echocardiography, blood parameters, carbon monoxide lung diffusion (DLCO) and cardiopulmonary exercise test. We measured immature SP-B, mature SP-B, SP-A, SP-D and RAGE plasma levels. RESULTS: Immature SP-B (arbitrary units), mature SP-A (ng/ml) and SP-D (ng/ml), but not mature SP-B (ng/ml) and RAGE (pg/ml) levels, were higher in HF than in controls [immature SP-B: 15.6 (13.1, 75th-25th interquartile range) Vs. 11.1 (6.4), p<0.01; SP-A, 29.6 (20.1) Vs. 18.3 (13.5), p = 0.01; SP-D: 125 (90) Vs. 78 (58), p<0.01]. Immature SP-B, SP-A, SP-D and RAGE values were related to DLCO, peak oxygen consumption, ventilatory efficiency, and brain natriuretic peptide (BNP), whereas plasma mature SP-B was not. The DLCO Vs. immature SP-B correlation was the strongest one. At multivariate analysis, RAGE was associated to age and creatinine, SP-A to DLCO and BNP, SP-D to BNP, mature SP-B to DLCO and creatinine, and immature SP-B only but strongly to DLCO. CONCLUSIONS: Immature SP-B is the most reliable biological marker of alveolar-capillary membrane function in HF.

Sicurezza e comfort dei pazienti con impianto di pacemaker mobilizzati dopo 24 e 48 ore: studio retrospettivo.

Safety and comfort of patients mobilized 24 and 48 hours after a pacemaker implantation: a retrospective study. Background. In Italy bed rest times after a pacemaker implantation (PI) may vary between 24 and 72 hours, although previous studies showed that early mobilization does not increase the risk of complications. Objective. To observe the safety and comfort of mobilization 24 and 48 hours after PI. Methods. Observational retrospective study on clinical records of consecutive patients undergoing PI from January 2009 to April 2012 in Monzino Hospital in Milan and with a bed rest of 24 or 48 hours. Results. A total of 411 patients were included (Group 48h n=251, Group 24h: n=160). Complications occurred more frequently in the Group 48h: haematomas (3.2% vs 1.9% OR:1.71, p=0.4269); lead dislocations (1.9% vs. 0.6%; OR:3.23 p=0.2863). Patients with longer bed rest received more analgesics for back pain (BP) or pacemaker pocket pain (PPP) (BP: 12% vs 3.1%; OR:4.21; p=0.0036; PPP 13.1% vs 3.7% OR:3.88; p=0.0029). Conclusions. The mobilization after 24 hours to PI increased patients' comfort without increasing risks. Future studies are warranted to explore the effects of a bed rest shorter than 24 hours.

Potentially spurious correlations between arterial size, flow-mediated dilation, and shear rate.

The use of indices formed from the ratio of 2 variables often generates spurious correlations with other variables that are mathematically coupled. In this context, we examined the correlations between percent flow-mediated dilation, baseline diameter, and shear rate. In a sample of 315 participants, with and without substantial vascular risk factors, the observed correlation coefficients between the variables were of a similar magnitude to those reported in the literature. We then applied a Monte Carlo procedure based on random permutations to remove any physical or physiological explanation for these correlations. We found that the median residual correlation coefficients were comparable with those observed in our original sample. When the confounding influence of artery size was adjusted for, the mean difference in percent flow-mediated dilation between high-risk and low-risk samples was halved. These findings indicate that the widely reported correlations between flow-mediated dilation, basal artery diameter, and shear rate have a substantial spurious component. This is because percent flow-mediated dilation and shear rate are mathematically coupled to artery size.

Nitric oxide synthetic pathway in patients with microvascular angina and its relations with oxidative stress.

A decreased nitric oxide (NO) bioavailability and an increased oxidative stress play a pivotal role in different cardiovascular pathologies. As red blood cells (RBCs) participate in NO formation in the bloodstream, the aim of this study was to outline the metabolic profile of L-arginine (Arg)/NO pathway and of oxidative stress status in RBCs and in plasma of patients with microvascular angina (MVA), investigating similarities and differences with respect to coronary artery disease (CAD) patients or healthy controls (Ctrl). Analytes involved in Arg/NO pathway and the ratio of oxidized and reduced forms of glutathione were measured by LC-MS/MS. The arginase and the NO synthase (NOS) expression were evaluated by immunofluorescence staining. RBCs from MVA patients show increased levels of NO synthesis inhibitors, parallel to that found in plasma, and a reduction of NO synthase expression. When summary scores were computed, both patient groups were associated with a positive oxidative score and a negative NO score, with the CAD group located in a more extreme position with respect to Ctrl. This finding points out to an impairment of the capacity of RBCs to produce NO in a pathological condition characterized mostly by alterations at the microvascular bed with no significant coronary stenosis.

Nitric oxide synthetic pathway in red blood cells is impaired in coronary artery disease.

BACKGROUND: All the enzymatic factors/cofactors involved in nitric oxide (NO) metabolism have been recently found in red blood cells. Increased oxidative stress impairs NO bioavailability and has been described in plasma of coronary artery disease (CAD) patients. The aim of the study was to highlight a potential dysfunction of the metabolic profile of NO in red blood cells and in plasma from CAD patients compared with healthy controls. METHODS: We determined L-arginine/NO pathway by liquid-chromatography tandem mass spectrometry and high performance liquid chromatography methods. The ratio of oxidized and reduced forms of glutathione, as index of oxidative stress, was measured by liquid-chromatography tandem mass spectrometry method. NO synthase expression and activity were evaluated by immunofluorescence staining and ex-vivo experiments of L-[(15)N2]arginine conversion to L-[(15)N]citrulline respectively. RESULTS: Increased amounts of asymmetric and symmetric dimethylarginines were found both in red blood cells and in plasma of CAD patients in respect to controls. Interestingly NO synthase expression and activity were reduced in CAD red blood cells. In contrast, oxidized/reduced glutathione ratio was increased in CAD and was associated to arginase activity. CONCLUSION: Our study analyzed for the first time the whole metabolic pathway of L-arginine/NO, both in red blood cells and in plasma, highlighting an impairment of NO pathway in erythrocytes from CAD patients, associated with decreased NO synthase expression/activity and increased oxidative stress.