Cristian Ricci

Timing Matters in Hip Fracture Surgery: Patients Operated within 48 Hours Have Better Outcomes. A Meta-Analysis and Meta-Regression of over 190,000 Patients

Background To assess the relationship between surgical delay and mortality in elderly patients with hip fracture. Systematic review and meta-analysis of retrospective and prospective studies published from 1948 to 2011. Medline (from 1948), Embase (from 1974) and CINAHL (from 1982), and the Cochrane Library. Odds ratios (OR) and 95% confidence intervals for each study were extracted and pooled with a random effects model. Heterogeneity, publication bias, Bayesian analysis, and meta-regression analyses were done. Criteria for inclusion were retro- and prospective elderly population studies, patients with operated hip fractures, indication of timing of surgery and survival status. Methodology/Principal Findings There were 35 independent studies, with 191,873 participants and 34,448 deaths. The majority considered a cut-off between 24 and 48 hours. Early hip surgery was associated with a lower risk of death (pooled odds ratio (OR) 0.74, 95% confidence interval (CI) 0.67 to 0.81; P<0.000) and pressure sores (0.48, 95% CI 0.38 to 0.60; P<0.000). Meta-analysis of the adjusted prospective studies gave similar results. The Bayesian probability predicted that about 20% of future studies might find that early surgery is not beneficial for decreasing mortality. None of the confounders (e.g. age, sex, data source, baseline risk, cut-off points, study location, quality and year) explained the differences between studies. Conclusions/Significance Surgical delay is associated with a significant increase in the risk of death and pressure sores. Conservative timing strategies should be avoided. Orthopaedic surgery services should ensure the majority of patients are operated within one or two days.

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.

Effects of long-term disease-modifying antirheumatic drugs on endothelial function in patients with early rheumatoid arthritis.

Rheumatoid arthritis (RA) is associated with enhanced atherosclerosis and impaired endothelial function early after the onset of the disease and cardiovascular (CV) disease represents one of the leading causes of morbidity and mortality. It is well known that disease modifying antirheumatic drugs (DMARDs) are able to improve the course of the disease and the quality of life of these patients, but little is known about the effects of DMARDs on CV risk and endothelial dysfunction. Our goal was to examine the effects of long-term therapy with DMARDs on endothelial function and disease activity in early RA (ERA). Twenty-five ERA patients (mean age 52 ± 14.6 years, disease duration 6.24 ± 4.10 months) without evidence of CV involvement were evaluated for disease activity score (DAS-28), 2D-echo derived coronary flow reserve (CFR), common carotid intima-media thickness (IMT) and plasma asymmetric dimethylarginine (ADMA) levels at baseline and after 18 months of treatment with DMARDs (10 patients with methotrexate and 10 with adalimumab). DMARDs significantly reduced DAS-28 (6.0 ± 0.8 vs. 2.0 ± 0.7; P < 0.0001) and improved CFR (2.4 ± 0.2 vs. 2.7 ± 0.5; P < 0.01). Common carotid IMT and plasma ADMA levels did not show significant changes. The present study shows that DMARDs, beyond the well known antiphlogistic effects, are able to improve coronary microcirculation without a direct effect on IMT and ADMA, clinical markers of atherosclerosis. Treatment strategies in ERA patients with high inflammatory activity must be monitored to identify beneficial effects on preclinical markers of vascular function.

Associations of Objectively Assessed Physical Activity and Sedentary Time with All-Cause Mortality in US Adults: The NHANES Study

Background Sedentary behavior is related to increased mortality risk. Whether such elevated risk can be offset by enhanced physical activity has not been examined using accelerometry data. Materials and Methods We examined the relations of sedentary time and physical activity to mortality from any cause using accelerometry data among 1,677 women and men aged 50 years or older from the National Health and Nutrition Examination Survey (NHANES) 2003–2004 cycle with follow-up through December 31, 2006. Results During an average follow-up of 34.67 months and 4,845.42 person-years, 112 deaths occurred. In multivariate Cox proportional hazard models, greater sedentary time (≥ median of 8.60 hours/day) was associated with increased risk of mortality from any cause (relative risk (RR) = 2.03; 95% confidence interval (CI) = 1.09-3.81). Low level of moderate to vigorous physical activity (< median of 6.60 minutes/day) was also related to enhanced all-cause mortality risk (RR = 3.30; 95% CI = 1.33-8.17). In combined analyses, greater time spent sedentary and low levels of moderate to vigorous physical activity predicted a substantially elevated all-cause mortality risk. As compared with the combination of a low sedentary level and a high level of moderate to vigorous physical activity, the risks of mortality from all causes were 4.38 (95% CI = 1.26-15.16) for low levels of both sedentary time and physical activity, 2.79 (95% CI = 0.77-10.12) for greater time spent sedentary and high physical activity level, and 7.79 (95% CI = 2.26-26.82) for greater time spent sedentary and low physical activity level. The interaction term between sedentary time and moderate to vigorous physical activity was not statistically significant (p = 0.508). Conclusions Both high levels of sedentary time and low levels of moderate to vigorous physical activity are strong and independent predictors of early death from any cause. Whether a high physical activity level removes the increased risk of all-cause mortality related to sedentariness requires further investigation.

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.

Silent cardiovascular involvement in patients with diffuse systemic sclerosis: a controlled cross-sectional study.

An association between systemic autoimmune diseases and atherosclerosis has been described in many connective tissue diseases, and this association is known to lead to increased cardiovascular morbidity and mortality. Systemic sclerosis (SSc) is characterized by multisystem organ inflammation, endothelial wall damage, and vasculopathy. There are many markers of endothelial dysfunction and/or atherosclerotic risk, such as asymmetric dimethylarginine (ADMA), arterial stiffness parameters, carotid intima‐media thickness (CIMT), and coronary flow reserve (CFR) assessed by transthoracic echocardiography. The aim of this pilot study was to use various endothelial and atherosclerosis markers to identify early cardiovascular involvement in a group of SSc patients.

Robotic treadmill training improves cardiovascular function in spinal cord injury patients.

BACKGROUND Body weight supported treadmill training (BWSTT) assisted with a robotic driven gait orthosis (DGO) is an emerging tool in rehabilitating patients with lost sensorimotor function. Few information about the effects of BWSTT on cardiovascular system are available. The purpose of this study was to determine the effects of BWSTT on: 1) left ventricular (LV) systo-diastolic function; 2) coronary flow reserve (CFR); 3) endothelial function in patients with lost sensorimotor function due to neurologic lesions. METHODS Fourteen adults (males 10, age 50.6±17.1years) with motor incomplete spinal cord injuries (SCI) due to trauma or spondylotic diseases underwent standard echocardiographic examination, non invasive assessment of CFR by dipyridamole stress echo and determination of plasma asymmetric dimethylarginine (ADMA) levels at baseline and after 6weeks of BWSTT. RESULTS At post training evaluation we observed lower LV end-diastolic (P=0.0164) and end-systolic volumes (P=0.0029) with increased ejection fraction (EF) (P=0.0266). We also observed a LV interventricular septum (IVS) (P=0.00469) increase. At the same time, we detected an improvement of LV diastolic function as witnessed by the reduction of isovolumic relaxation time (IVRT) (P=0.0404) and deceleration time (DT) (P=0.0405) with an increased E/A ratio (P=0.0040). Improved CFR (P=0.020) and reduced plasma ADMA levels (P=0.0005) have been observed too, in association with a reduction of the inflammatory status (C-reactive protein (CRP) (P=0.0022) and erythrocyte sedimentation rate (ESR) (P=0.0005)). CONCLUSION For the first time, this study demonstrated that 6weeks of BWSTT improved not only the sensorimotor function but also systo-diastolic LV function, CFR and endothelial dysfunction associated with a reduction of the inflammatory status in patients with incomplete SCI.

Replacing Sedentary Time with Physical Activity in Relation to Mortality

INTRODUCTION Data evaluating mortality benefit from replacing sedentary time with physical activity are sparse. We explored reallocating time spent in sedentary behavior to physical activity of different intensities in relation to mortality risk. METHODS Women and men age 50-85 yr from the National Health and Nutrition Examination Survey 2003-2004 and 2005-2006 cycles with follow-up through December 31, 2011, were included. Sedentary time and physical activity were assessed using an ActiGraph accelerometer. Isotemporal substitution models were used to estimate the effect of replacing one activity behavior with another activity behavior for the same amount of time while holding total accelerometer wear time constant. RESULTS During a mean follow-up of 6.35 yr, 697 deaths from any cause occurred. Replacing 30 min of sedentary time with an equal amount of light activity was associated with 14% reduced risk of mortality (multivariable-adjusted hazard ratio (HR), 0.86; 95% confidence interval (CI), 0.83-0.90). Replacement of sedentary time with moderate to vigorous activity was related to 50% mortality risk reduction (HR, 0.50; 95% CI, 0.31-0.80). We also noted a 42% reduced risk of mortality when light physical activity was replaced by moderate to vigorous activity (HR, 0.58; 95% CI, 0.36-0.93). CONCLUSION Replacing sedentary time with an equal amount of physical activity may protect against preterm mortality. Replacement of light physical activity with moderate to vigorous activity is also associated with protection from premature mortality.

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.