Maddalena Gaeta

Upper Urinary Tract Recurrence Following Radical Cystectomy for Bladder Cancer: A Meta-Analysis on 13,185 Patients

PURPOSE Patients who undergo radical cystectomy for urothelial cancer are at risk for upper urinary tract disease in the remnant transitional tissue. Previous studies have identified several risk factors for upper urinary tract recurrence but the predictive value of each factor remains controversial. Furthermore, the schedule for surveillance of the upper urinary tract with imaging techniques and cytology has not been established. International guidelines do not address these topics and refer only to isolated works with a large case based analysis. We performed this meta-analysis to evaluate the effective incidence of upper urinary tract recurrence after cystectomy for bladder cancer, to analyze the risk factors so we can create subgroups of patients at high risk for recurrence and to investigate the real role of screening in the detection of upper tract lesions at an early stage. MATERIALS AND METHODS A bibliographic search covering the period from January 1970 to July 2010 was conducted using PubMed®, MEDLINE and EMBASE®. This analysis is based on the 27 studies that fulfilled the predefined inclusion criteria. Data were analyzed using a fixed effect logistic regression approach and classic meta-analysis. RESULTS A total of 13,185 participants were included in the analysis. Followup was described in 22 studies and ranged from 0.36 to 349.2 months. The overall prevalence of upper tract transitional cell cancer after cystectomy ranged from 0.75% to 6.4%. Recurrence appeared at a range of 2.4 to 164 months, and in an advanced (64.6%) or metastatic state (35.6%) as reflected in poor survival rates. Patients with low grade vs high grade lesions at cystectomy showed as strong a significant difference in incidence as those with carcinoma in situ and superficial cancer vs invasive cancers and as strong as in those without lymph node involvement, with multifocal disease, with a history of multiple urothelial recurrences, with positive ureteral margins, with positive urethral margins, with urethral involvement and a history of upper urinary tract urothelial cancer. Data do not support a statistically significant difference in recurrence among patients with a history of carcinoma in situ, solitary lesion and among various types of urinary diversion adopted. In 24 studies the followup schedule included periodic radiological assessment of the upper urinary tract and in 20 it included urinary cytology. In 14 studies in 63 of 166 patients (38%) upper urinary tract recurrence was diagnosed by followup investigation whereas in the remaining 62% diagnosis was based on symptoms. When urine cytology was used in surveillance the rate of primary detection was 7% and with upper urinary tract imaging it was 29.6%. Of 5,537 patients who underwent routine cytological examination, recurrence was diagnosed in 1.8/1,000 and of those who underwent upper urinary tract imaging recurrence was diagnosed in 7.6/1,000. CONCLUSIONS The recurrence values could appear low when considering the pan-urothelial field defect theory, but these values reflect, in part, the mortality associated with the initial bladder cancer. Based on anamnesis and pathological examination of cystectomy specimens, a group of patients is at high risk. Extensive regular followup with cytology, urography and loopgraphy yields insufficient benefits. Periodic computerized tomography with urography combines the ability to study the upper urinary tract oncologically and functionally, and the identification of any parenchymal, osseous or lymph node secondary lesion.

Clinical efficacy of ivabradine in patients with inappropriate sinus tachycardia: a prospective, randomized, placebo-controlled, double-blind, crossover evaluation.

OBJECTIVES The purpose of this study was to investigate the role of ivabradine in the treatment of symptomatic inappropriate sinus tachycardia using a double-blind, placebo-controlled, crossover design. BACKGROUND Due to its I(f) blocking properties, ivabradine can selectively attenuate the high discharge rate from sinus node cells, causing inappropriate sinus tachycardia. METHODS Twenty-one patients were randomized to receive placebo (n=10) or ivabradine 5 mg twice daily (n=11) for 6 weeks. After a washout period, patients crossed over for an additional 6 weeks. Each patient underwent symptom evaluation and heart rate assessment at the start and finish of each phase. RESULTS After taking ivabradine, patients reported elimination of >70% of symptoms (relative risk: 0.25; 95% CI: 0.18 to 0.34; p<0.001), with 47% of them experiencing complete elimination. These effects were associated with a significant reduction of heart rate at rest (from 88±11 beats/min to 76±11 beats/min, p=0.011), on standing (from 108±12 beats/min to 92±11 beats/min, p<0.0001), during 24 h (from 88±5 beats/min to 77±9 beats/min, p=0.001), and during effort (from 176±17 beats/min to 158±16 beats/min, p=0.001). Ivabradine administration was also associated with a significant increase in exercise performance. No cardiovascular side effects were observed in any patients while taking ivabradine. CONCLUSIONS In this cohort, ivabradine significantly improved symptoms associated with inappropriate sinus tachycardia and completely eliminated them in approximately half of the patients. These findings suggest that ivabradine may be an important agent for improving symptoms in patients with inappropriate sinus tachycardia.

Tourette syndrome (TS) bears a higher rate of inflammatory complications at the implanted hardware in deep brain stimulation (DBS).

BackgroundDeep brain stimulation (DBS) is a commonly performed surgical technique for the treatment of movement disorders, and recent surgical trials concerning the treatment of a wider range of disorders have recently been published. Despite DBS being non-ablative and minimally invasive, numerous complications and side effects have been recorded. In particular, concerning the growing interest in novel indications for DBS, an enthusiastic approach has put neurosurgeons at risk of underestimating some of the complications that might be associated with specific characters of the treated disease.ObjectiveOur objective was to evaluate hardware failures and rates of infective complications in correlation to the different indications to DBS, in order to ascertain whether DBS in Tourette syndrome (TS) is characterized by specific risks and pitfalls.MethodsWe retrospectively reviewed our experience of 531 procedures on 272 patients treated for various movement disorders, among which 39 patients were treated for conservative treatmentrefractory TS.ResultsA statistically significant association of infective complications was found with the TS subgroup.ConclusionsIt is our belief that specific behavioral characters of the TS patients may be put into association with this specific complication and need to be considered carefully when indicating DBS as treatment of choice for these patients.

The frequency and severity of cardiac involvement in myotonic dystrophy type 2 (DM2): Long-term outcomes

BACKGROUND Frequency and severity of cardiac involvement in DM2 are still controversial. The aims of our study were to determine the frequency and progression of cardiac and muscle involvement in a relatively large cohort of patients with DM2 throughout Italy and Germany and to provide long-term outcomes in this disorder. METHODS 104 DM2 and 117 DM1 patients underwent baseline and follow-up assessments of, ECG, 24h Holter monitoring, 2D echocardiography and electrophysiological study (EPS) when appropriate, and manual muscle strength testing (mean follow-up: 7.4 ± 4.1 for DM2 and 5.7 ± 4 years for DM1). RESULTS Overall, 10% of DM2 patients vs 31% of DM1 patients had PR ≥ 200 ms and 17% of DM2 patients vs 48% of DM1 patients had QRSD ≥ 100 ms. Six patients with DM2 vs 28 patients with DM1 required PM/ICD implantations. DM2 patients were stronger than DM1 patients at baseline, but muscle strength worsened significantly over time (p<0.0001), just as in DM1, although at a slower annual rate. CONCLUSION Our data demonstrate that the frequency and severity of cardiac involvement and of muscle weakness are reduced in DM2 compared to DM1 and that progression is slower and less severe. Nonetheless, careful cardiac evaluation is recommended in this patient population to identify patients at risk for potential major cardiac arrhythmias.

Transrectal ultrasound-guided prostate biopsies in patients taking aspirin for cardiovascular disease: A meta-analysis

INTRODUCTION The management of anti-platelet therapy in the peri-operative period is a source of great concern. The dilemma is between whether to stop these agents peri-operatively in order to reduce the risk of bleeding complications, or to continue them in order not to compromise the protection they afford against the risk of cardiovascular events. MATERIALS AND METHODS The aim of this systematic review and meta-analysis was to understand whether continued aspirin therapy is a risk factor for bleeding complications after ultrasound-guided biopsy of the prostate. A bibliographic search covering the period from January 1990 to May 2011 was conducted in PubMed, MEDLINE and EMBASE. We also included our own series in the analysis. RESULTS A total of 3218 participants were included. Haematuria was statistically more frequent (P=0.001) among patients taking aspirin than in the control group with an odds ratio estimate of 1.36 [1.13;1.64]. This increased risk was, however, due to minor bleeding. The occurrence of rectal bleeding and haematospermia was not statistically increased (P=0.33 and P=0.24, respectively) in patients taking aspirin compared to in the control group with odds ratios estimate of 1.24 [0.80;1.93] and 1.52 [0.75;3.08], respectively. DISCUSSION There is limited information of the relationship between continued use of aspirin and haemorrhagic complications after transrectal ultrasound-guided biopsy of the prostate. This is the first comprehensive analysis on this topic. CONCLUSION Continued use of aspirin does not increase the risk of overall bleeding or moderate and severe haematuria after prostatic biopsy, and thus stopping aspirin before such biopsies is unnecessary.

Role of psoriasis as independent predictor of cardiovascular disease: A meta-regression analysis

BACKGROUND Despite the proved association between psoriasis and cardiovascular risk exposure, there are no data about the role of psoriasis as an independent predictor of such risk. The aim of this study was to investigate whether any association between psoriasis and excess cardiovascular risk exposure is independent from confounding factors. METHODS Meta-analysis and meta-regression analysis were performed using data extracted from observational studies (identified by MEDLINE, EMBASE and CINAHL) investigating the relationship between psoriasis and cardiovascular disease with at least 6 points on the New Castle-Ottawa quality scale. Two reviewers with methodological expertise conducted data extraction independently. RESULTS Thirteen studies including patients with psoriasis showed an increased risk of cardiovascular disease (RR=1.24 [1.18-1.31]; P=0.0001). These patients still presented a significantly larger cardiovascular risk in the presence of smoking (RR=1.14 [CI=1.13-1.15] P<0.0001), obesity (RR=1.11 [CI=1.07-1.14] P=0.0003) and hyperlipidemia (RR=1.05 [CI=1.03-1.07] P=0.0006), but not in the presence of hypertension (RR=1.03 [CI=0.98-1.09] P=0.4647) and diabetes (RR=0.95 [CI=0.90-1.01] P=0.6502). CONCLUSIONS Patients with psoriasis carry an about 25% increased relative risk of cardiovascular disease. This risk appears to be independent of smoking, obesity and hyperlipidemia.

Role of Right Ventricle and Dynamic Pulmonary Hypertension on Determining ΔVO2/ΔWork Rate Flattening: Insights from Cardiopulmonary Exercise Test Combined with Exercise Echocardiography

Background—Several cardiovascular diseases are characterized by an impaired O2 kinetic during exercise. The lack of a linear increase of &Dgr;oxygen consumption (VO2)/&Dgr;Work Rate (WR) relationship, as assessed by expired gas analysis, is considered an indicator of abnormal cardiovascular efficiency. We aimed at describing the frequency of &Dgr;VO2/&Dgr;WR flattening in a symptomatic population of cardiac patients, characterizing its functional profile, and testing the hypothesis that dynamic pulmonary hypertension and right ventricular contractile reserve play a major role as cardiac determinants. Methods and Results—We studied 136 patients, with different cardiovascular diseases, referred for exertional dyspnoea. Cardiopulmonary exercise test combined with simultaneous exercise echocardiography was performed using a symptom-limited protocol. &Dgr;VO2/&Dgr;WR flattening was observed in 36 patients (group A, 26.5% of population) and was associated with a globally worse functional profile (reduced peak VO2, anaerobic threshold, O2 pulse, impaired VE/VCO2). At univariate analysis, exercise ejection fraction, exercise mitral regurgitation, rest and exercise tricuspid annular plane systolic excursion, exercise systolic pulmonary artery pressure, and exercise cardiac output were all significantly (P<0.05) impaired in group A. The multivariate analysis identified exercise systolic pulmonary artery pressure (odds ratio, 1.06; confidence interval, 1.01–1.11; P=0.01) and exercise tricuspid annular plane systolic excursion (odds ratio, 0.88; confidence interval, 0.80–0.97; P=0.01) as main cardiac determinants of &Dgr;VO2/&Dgr;WR flattening; female sex was strongly associated (odds ratio, 6.10; confidence interval, 2.11–17.7; P<0.01). Conclusions—In patients symptomatic for dyspnea, the occurrence of &Dgr;VO2/&Dgr;WR flattening reflects a significantly impaired functional phenotype whose main cardiac determinants are the excessive systolic pulmonary artery pressure increase and the reduced peak right ventricular longitudinal systolic function.Background—Several cardiovascular diseases are characterized by an impaired O2 kinetic during exercise. The lack of a linear increase of Δoxygen consumption (VO2)/ΔWork Rate (WR) relationship, as assessed by expired gas analysis, is considered an indicator of abnormal cardiovascular efficiency. We aimed at describing the frequency of ΔVO2/ΔWR flattening in a symptomatic population of cardiac patients, characterizing its functional profile, and testing the hypothesis that dynamic pulmonary hypertension and right ventricular contractile reserve play a major role as cardiac determinants. Methods and Results—We studied 136 patients, with different cardiovascular diseases, referred for exertional dyspnoea. Cardiopulmonary exercise test combined with simultaneous exercise echocardiography was performed using a symptom-limited protocol. ΔVO2/ΔWR flattening was observed in 36 patients (group A, 26.5% of population) and was associated with a globally worse functional profile (reduced peak VO2, anaerobic threshold,...

Physical Training and Noninvasive Ventilation in COPD Patients: A Meta-Analysis

BACKGROUND: Exercise training improves both exercise tolerance and quality of life in patients with COPD. The intensity of exercise training is crucial to achieve a true physiologic effect. However, in COPD patients, exertional dyspnea and leg fatigue mean that the patient cannot maintain intensity of training for enough time to yield a physiologic training effect. The use of noninvasive ventilation (NIV) support has been proposed as an alternative strategy to improve exercise tolerance and respiratory and cardiovascular performances. The first aim of our meta-analysis was to evaluate exercise training with NIV in terms of physiologic effects after the completion of a pulmonary rehabilitation program. The second aim was to investigate the dose-response relationship between physical improvement and training intensity. METHODS: Literature research was performed using MEDLINE, Embase, and CINAHL. Meta-analysis and meta-regressions were performed using random effects models. RESULTS: Eight studies provided a proper description of a training schedule in stable COPD patients. A similar effect between NIV and placebo was observed for the outcomes considered despite differences between studies. However, subjects experienced a relevant and statistically significant improvement after rehabilitation for almost all of the outcomes considered. Heart rate (6 beats/min [95% CI 0.94–11.01], P = .02), work load (9.73 W [95% CI 3.78–15.67], P < .001), and oxygen consumption (242.11 mL/min [95% CI 154.93–329.9], P < .001) significantly improved after training. Improvements in heart rate and work load were significantly correlated to training intensity. CONCLUSIONS: Given the small number of available studies, the small sample sizes, and the complete absence of power calculation, we think that this topic deserves a more in-depth investigation. Randomized clinical trials with larger sample sizes based on statistical power calculations and designed to investigate the effect of training duration and intensity on rehabilitation are needed to confirm results in this important field.

Prevalence and characterization of exercise oscillatory ventilation in apparently healthy individuals at variable risk for cardiovascular disease: A subanalysis of the EURO-EX trial

Introduction There has been a greater appreciation of several variables obtained by cardiopulmonary exercise testing (CPX). Exercise oscillatory ventilation (EOV) is a CPX pattern that has gained recognition as an ominous marker of poor prognosis in cardiac patients. The purpose of the present study is to characterize whether such an abnormal ventilatory pattern may also be detected in apparently healthy subjects and determine its clinical significance. Methods The study involved 510 subjects (mean age 60 ± 14 years; 49% male) with a broad cardiovascular (CV) risk factor profile who underwent CPX. Results The population was divided into two groups according to the presence (17%) or absence of EOV. Subjects with EOV were significantly older and a higher percentage was female. Risk factor profile and medication use was significantly different between subgroups, indicating subjects with EOV had a worse CV risk factor profile and were prescribed CV-focused preventive medications at a significantly higher frequency. Subjects with EOV had comparatively poorer CPX performance and gas exchange phenotype. Multivariate binary logistic regression analysis found being female was the strongest predictor of EOV (odds ratio: 2.77, 95% confidence interval (CI): 1.66-4.61, p < 0.001). A diagnosis of diabetes (odds ratio: 2.40, 95% CI: 1.34–4.15.2, p < 0.001) added significant value for predicting EOV and was retained in the regression. The likelihood for EOV for subjects who were female and diagnosed with diabetes was 3.71 (95% CI 1.88–7.30, p < 0.001). Conclusions This is the first study to examine EOV prevalence and characterization in apparently healthy persons with results supporting an in-depth definition of abnormal exercise phenotypes.

Association between a school‐based intervention and adiposity outcomes in adolescents: The Italian “EAT” project

To evaluate whether a school‐based multicomponent educational program could improve adiposity measures in middle‐school adolescents.