Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease.

AIMS: REVEAL was the first randomized controlled trial to demonstrate that adding cholesteryl ester transfer protein inhibitor therapy to intensive statin therapy reduced the risk of major coronary events. We now report results from extended follow-up beyond the scheduled study treatment period. METHODS AND RESULTS: A total of 30 449 adults with prior atherosclerotic vascular disease were randomly allocated to anacetrapib 100 mg daily or matching placebo, in addition to open-label atorvastatin therapy. After stopping the randomly allocated treatment, 26 129 survivors entered a post-trial follow-up period, blind to their original treatment allocation. The primary outcome was first post-randomization major coronary event (i.e. coronary death, myocardial infarction, or coronary revascularization) during the in-trial and post-trial treatment periods, with analysis by intention-to-treat. Allocation to anacetrapib conferred a 9% [95% confidence interval (CI) 3-15%; P = 0.004] proportional reduction in the incidence of major coronary events during the study treatment period (median 4.1 years). During extended follow-up (median 2.2 years), there was a further 20% (95% CI 10-29%; P < 0.001) reduction. Overall, there was a 12% (95% CI 7-17%, P < 0.001) proportional reduction in major coronary events during the overall follow-up period (median 6.3 years), corresponding to a 1.8% (95% CI 1.0-2.6%) absolute reduction. There were no significant effects on non-vascular mortality, site-specific cancer, or other serious adverse events. Morbidity follow-up was obtained for 25 784 (99%) participants. CONCLUSION: The beneficial effects of anacetrapib on major coronary events increased with longer follow-up, and no adverse effects emerged on non-vascular mortality or morbidity. These findings illustrate the importance of sufficiently long treatment and follow-up duration in randomized trials of lipid-modifying agents to assess their full benefits and potential harms. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) 48678192; ClinicalTrials.gov No. NCT01252953; EudraCT No. 2010-023467-18.

Cervical re-injection of indocyanine green to improve sentinel lymph node detection in endometrial cancer.

OBJECTIVES: To evaluate the role of cervical re-injection of indocyanine green (ICG) to increase the detection rate of sentinel lymph node (SLN) in patients with endometrial cancer (EC) who underwent robotic-assisted surgical staging. METHODS: We retrospectively identified consecutive EC patients undergoing robotic-assisted staging with SLN biopsy at our Institution between June 2016 and April 2020. Patients were excluded if they had open abdominal surgical approach, neoadjuvant chemotherapy, and advanced stage [International Federation of Gynecology and Obstetrics (FIGO) stage III-IV] at diagnosis. According to our SLN protocol, in case of either unilateral or no SLN detection, we performed an ipsilateral or bilateral cervical re-injection of ICG. RESULTS: In total, 251 patients meeting inclusion criteria were included in the analysis. At first injection, bilateral detection was achieved in 184 (73.3%), unilateral detection in 57 (22.7%), and no detection in 10 (4.0%) patients. Cervical re-injection was performed in 51 of 67 patients with failed bilateral mapping. After cervical re-injection, bilateral detection rate increased to 94.5% (222/235), while unilateral and no detection were 5.1% (12/235) and 0.4% (1/235), respectively. CONCLUSIONS: Our results suggest that cervical re-injection of ICG, in case of failed bilateral mapping of SLN, brings about a significant improvement in SLN detection rates, therefore reducing the number of side-specific required lymphadenectomies.

Comparison between laparoscopy and laparotomy in the surgical re-staging of granulosa cell tumors of the ovary.

OBJECTIVE: To evaluate the role of laparoscopic (LPS) and laparotomic (LPT) re-staging in patients with incompletely surgically staged ovarian granulosa cell tumors (OGCT). METHODS: We conducted a medical chart retrospective analysis of all patients with sex cord stromal tumors (SCSTs) who were managed in our division between March 1994 and March 2017. After a complete review of surgical and pathological notes, patients with incomplete staging were restaged according to the FIGO guidelines. Statistical analysis was conducted using Statistical Package version 20.0 for Windows (SPSS, Inc., Chicago, Illinois). RESULTS: Out of a total of 170 patients SCSTs, 84 patients (49,5%) received primary surgery that included a hysterectomy; 86 patients (50,5%) underwent fertility-sparing surgery. Eighty-one patients (48%) with diagnosis of OGCT were incompletely surgically staged at another institution. We evaluated our results in terms of laparoscopic approach (56 patients) and open treatment (25 patients). Among the IA patient's group, 1 was upstaged to IIB stage and 2 to IIIB; among patients with IC stage, 1 was upstaged to IIA, 2 to IIB and 1 to IIIB stage. Adjuvant chemotherapy was given to the upstaged patients with final stage IIB-IIIC. No statistically significant difference between laparoscopy and open-surgery was detected in terms of upstaged patients after second surgery (p = 0,36). CONCLUSION: According to our series, laparoscopic restaging compared to the open approach seems to be a feasible and efficient technique to complete surgical staging in patients with GCTs incorrectly staged. Surgical restaging seems to upstage a considerable number of OGCT, mainly in the initial stage IC group of patients. However, the impact of restaging on final outcome and survival remains to be demonstrated.

Changes in body weight and pulse: outcome events in overweight and obese subjects with cardiovascular disease in the SCOUT trial.

BACKGROUND/OBJECTIVES: The Sibutramine Cardiovascular OUTcomes (SCOUT) trial showed a significantly increased relative risk of nonfatal cardiovascular events, but not mortality, in overweight and obese subjects receiving long-term sibutramine treatment with diet and exercise. We examined the relationship between early changes (both increases and decreases) in pulse rate, and the impact of these changes on subsequent cardiovascular outcome events in both the placebo and sibutramine groups. SUBJECTS/METHODS: 9804 males and females, aged ⩾55 years, with a body mass index of 27-45 kg m(-)(2) were included in this current subanalysis of the SCOUT trial. Subjects were required to have a history of cardiovascular disease and/or type 2 diabetes mellitus with at least one cardiovascular risk factor, to assess cardiovascular outcomes. The primary outcome event (POE) was a composite of nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death. Time-to-event analyses of the POE were performed using Cox regression models. RESULTS: During the initial 6-week sibutramine treatment period, the induced pulse rate increase was related to weight change (1.9±7.7 beats per minute (bpm) with weight increase; 1.4±7.3 bpm, 0-5 kg weight loss; 0.6±7.4 bpm, ⩾5 kg weight loss). Throughout the subsequent treatment period, those continuing on sibutramine showed a consistently higher mean pulse rate than the placebo group. There was no difference in POE rates with either an increase or decrease in pulse rate over the lead-in period, or during lead-in baseline to 12 months post randomization. There was also no relationship between pulse rate at lead-in baseline and subsequent cardiovascular events in subjects with or without a cardiac arrhythmia. CONCLUSION: Baseline pulse rate and changes in pulse rate may not be an important modifier nor a clinically useful predictor of outcome in an individual elderly cardiovascular obese subject exposed to weight management.

The obesity paradox in heart failure patients with preserved versus reduced ejection fraction: a meta-analysis of individual patient data.

BACKGROUND: In heart failure (HF), obesity, defined as body mass index (BMI) ≥30 kg m(-2), is paradoxically associated with higher survival rates compared with normal-weight patients (the 'obesity paradox'). We sought to determine if the obesity paradox differed by HF subtype (reduced ejection fraction (HF-REF) versus preserved ejection fraction (HF-PEF)). PATIENTS AND METHODS: A sub-analysis of the MAGGIC meta-analysis of patient-level data from 14 HF studies was performed. Subjects were divided into five BMI groups: <22.5, 22.5-24.9 (referent), 25-29.9, 30-34.9 and ≥35 kg m(-2). Cox proportional hazards models adjusted for age, sex, aetiology (ischaemic or non-ischaemic), hypertension, diabetes and baseline blood pressure, stratified by study, were used to examine the independent association between BMI and 3-year total mortality. Analyses were conducted for the overall group and within HF-REF and HF-PEF groups. RESULTS: BMI data were available for 23 967 subjects (mean age, 66.8 years; 32% women; 46% NYHA Class II; 50% Class III) and 5609 (23%) died by 3 years. Obese patients were younger, more likely to receive cardiovascular (CV) drug treatment, and had higher comorbidity burdens. Compared with BMI levels between 22.5 and 24.9 kg m(-2), the adjusted relative hazards for 3-year mortality in subjects with HF-REF were: hazard ratios (HR)=1.31 (95% confidence interval=1.15-1.50) for BMI <22.5, 0.85 (0.76-0.96) for BMI 25.0-29.9, 0.64 (0.55-0.74) for BMI 30.0-34.9 and 0.95 (0.78-1.15) for BMI ≥35. Corresponding adjusted HRs for those with HF-PEF were: 1.12 (95% confidence interval=0.80-1.57) for BMI <22.5, 0.74 (0.56-0.97) for BMI 25.0-29.9, 0.64 (0.46-0.88) for BMI 30.0-34.9 and 0.71 (0.49-1.05) for BMI ≥35. CONCLUSIONS: In patients with chronic HF, the obesity paradox was present in both those with reduced and preserved ventricular systolic function. Mortality in both HF subtypes was U-shaped, with a nadir at 30.0-34.9 kg m(-2).

Neoadjuvant chemotherapy prior to pelvic exenteration in patients with recurrent cervical cancer: single institution experience.

OBJECTIVES: The aim of the study is to evaluate the response to neoadjuvant chemotherapy (NACHT) of patients with recurrent cervical cancer who were poor candidates for pelvic exenteration (PE), and the impact on DFS and OS. METHODS: A retrospective data collection extracted from medical records of 61 patients submitted to pelvic exenteration was performed: 30 underwent up-front exenterative procedure whereas 31 received NACHT. RESULTS: The median tumor size was significantly (P=0.0006) larger in the NACHT group compared to the up-front PE one (43.9 mm vs 28 mm), and a significant (P=0.04) higher percentage of patients (45 vs 20%) had lateral pelvic wall invasion in the NACHT group. No statistically significant difference in early and late complications was observed in the two groups. Median overall survival in study population was 42.9 months (95% CI: 22.2, 180.8). Median overall survival times as well as recurrence free survival times were not significantly different between NACHT (42.9 months and 36.1 months for OS and DFS respectively) vs. No NACHT (111.9 months and 48.1 months for OS and DFS respectively). There was an overall significant difference in DFS between negative and positive margins but the curves were similar for NACHT and up-front PE groups stratified by resection margin status. CONCLUSIONS: In our series, though small and retrospective, NACHT prior to PE represents a feasible therapeutic option without intra-operative and early post-operative mortality or worsening of early and late complication rate and with acceptable long-term survival and DFS for recurrent cervical cancer patients who are poor candidates for up-front pelvic exenteration.

The effects of a multimodal training program on burnout syndrome in gynecologic oncology nurses and on the multidisciplinary psychosocial care of gynecologic cancer patients: an Italian experience.

OBJECTIVE: In cancer care, the burden of psycho-emotional elements involved on the patient-healthcare provider relationship cannot be ignored. The aim of this work is to have an impact on the level of burnout experienced by European Institute of Oncology (IEO) gynecologic oncology nurses (N = 14) and on quality of multidisciplinary team work. METHOD: We designed a 12 session multimodal training program consisting of a 1.5 hour theoretical lesson on a specific issue related to gynecologic cancer patient care, 20 minute projection of a short film, and 1.75 hours of role-playing exercises and experiential exchanges. The Link Burnout Questionnaire (Santinello, 2007) was administered before and after the completion of the intervention. We also monitored the number of patients referred to the Psycho-oncology Service as an indicator of the efficacy of the multidisciplinary approach. RESULTS: After the completion of the program, the general level of burnout significantly diminished (p = 0.02); in particular, a significant decrease was observed in the "personal inefficacy" subscale (p = 0.01). The number of patients referred to the Psycho-oncology Service increased by 50%. SIGNIFICANCE OF RESULTS: Nurses are in the first line of those seeing patients through the entire course of the disease. For this reason, they are at a particularly high risk of developing work-related distress. Structured training programs can be a valid answer to work-related distress, and feeling part of a multidisciplinary team helps in providing patients with better psychosocial care.

Characteristics and outcomes in patients with a prior myocardial infarction treated with extended dual antiplatelet therapy with ticagrelor 60 mg: findings from ALETHEIA, a multi-country observational study.

BACKGROUND: Guidelines recommend extended dual antiplatelet therapy, including ticagrelor 60 mg twice daily, in high-risk post-myocardial infarction (MI) patients who have tolerated 12 months and are not at high bleeding risk. The real-world utilization and bleeding and ischaemic outcomes associated with long-term ticagrelor 60 mg in routine clinical practice have not been well described. METHODS: Register and claims data from the USA (Optum Clinformatics, IBM MarketScan, and Medicare) and Europe (Sweden, Italy, UK, and Germany) were extracted. Patients initiating ticagrelor 60 mg ≥12 months after MI, meeting eligibility criteria for the PEGASUS-TIMI (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin - Thrombolysis in Myocardial Infarction 45) 54 trial, were included. The cumulative incidence of the composite of MI, stroke, or all-cause mortality and that of bleeding requiring hospitalization were calculated. Meta-analyses were performed to combine estimates from each source. RESULTS: A total of 7035 patients treated with ticagrelor 60 mg met eligibility criteria. Median age was 67 years and 29% were females; 12% had a history of multiple MIs. The majority (95%) had been treated with ticagrelor 90 mg prior to initiating ticagrelor 60 mg. At 12 months from initiation of ticagrelor 60 mg, the cumulative incidence [95% confidence interval (CI)] of MI, stroke, or mortality was 3.33% (2.73-4.04) and was approximately three-fold the risk of bleeding (0.96%; 0.69-1.33). CONCLUSIONS: This study provides insights into the use of ticagrelor 60 mg in patients with prior MI in clinical practice. Observed event rates for ischaemic events and bleeding generally align with those in the pivotal trials, support the established safety profile of ticagrelor, and highlight the significant residual ischaemic risk in this population.Clinical Trials.gov Registration NCT04568083.

Relationship between HbA1c levels and risk of cardiovascular adverse outcomes and all-cause mortality in overweight and obese cardiovascular high-risk women and men with type 2 diabetes.

AIMS/HYPOTHESIS: The optimal HbA(1c) concentration for prevention of macrovascular complications and deaths in obese cardiovascular high-risk patients with type 2 diabetes remains to be established and was therefore studied in this post hoc analysis of the Sibutramine Cardiovascular OUTcomes (SCOUT) trial, which enrolled overweight and obese patients with type 2 diabetes and/or cardiovascular disease. METHODS: HRs for meeting the primary endpoint (nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death) and all-cause mortality were analysed using Cox regression models. RESULTS: Of 8,252 patients with type 2 diabetes included in SCOUT, 7,479 had measurements of HbA(1c) available at baseline (i.e. study randomisation). Median age was 62 years (range 51-86 years), median BMI was 34.0 kg/m(2) (24.8-65.1 kg/m(2)) and 44% were women. The median HbA(1c) concentration was 7.2% (3.8-15.9%) (55 mmol/l [18-150 mmol/l]) and median diabetes duration was 7 years (0-57 years). For each 1 percentage point HbA(1c) increase, the adjusted HR for the primary endpoint was 1.17 (95% CI 1.11, 1.23); no differential sex effect was observed (p = 0.12 for interaction). In contrast, the risk of all-cause mortality was found to be greater in women than in men: HR 1.22 (1.10, 1.34) vs 1.12 (1.04, 1.20) for each 1 percentage point HbA(1c) increase (p = 0.02 for interaction). There was no evidence of increased risk associated with HbA(1c) ≤ 6.4% (≤ 46 mmol/l). Glucose-lowering treatment regimens, diabetes duration or a history of cardiovascular disease did not modify the associations. CONCLUSIONS/INTERPRETATION: In overweight, cardiovascular high-risk patients with type 2 diabetes, increasing HbA(1c) concentrations were associated with increasing risks of cardiovascular adverse outcomes and all-cause mortality.

Systematic lymphadenectomy in ovarian cancer at second-look surgery: a randomised clinical trial.

BACKGROUND: The role of systematic aortic and pelvic lymphadenectomy (SAPL) at second-look surgery in early stage or optimally debulked advanced ovarian cancer is unclear and never addressed by randomised studies. METHODS: From January 1991 through May 2001, 308 patients with the International Federation of Gynaecology and Obstetrics stage IA-IV epithelial ovarian carcinoma were randomly assigned to undergo SAPL (n=158) or resection of bulky nodes only (n=150). Primary end point was overall survival (OS). RESULTS: The median operating time, blood loss, percentage of patients requiring blood transfusions and hospital stay were higher in the SAPL than in the control arm (P<0.001). The median number of resected nodes and the percentage of women with nodal metastases were higher in the SAPL arm as well (44% vs 8%, P<0.001 and 24.2% vs 13.3%, P:0.02). After a median follow-up of 111 months, 171 events (i.e., recurrences or deaths) were observed, and 124 patients had died. Sites of first recurrences were similar in both arms. The adjusted risk for progression and death were not statistically different (hazard ratio (HR) for progression=1.18, 95% confidence interval (CI)=0.87-1.59; P=0.29; 5-year progression-free survival (PFS)=40.9% and 53.8%; HR for death=1.04, 95% CI=0.733-1.49; P=0.81; 5-year OS=63.5% and 67.4%, in the SAPL and in the control arm, respectively). CONCLUSION: SAPL in second-look surgery for advanced ovarian cancer did not improve PFS and OS.

Maintained intentional weight loss reduces cardiovascular outcomes: results from the Sibutramine Cardiovascular OUTcomes (SCOUT) trial.

AIM: The Sibutramine Cardiovascular OUTcomes trial showed that sibutramine produced greater mean weight loss than placebo but increased cardiovascular morbidity but not mortality. The relationship between 12-month weight loss and subsequent cardiovascular outcomes is explored. METHODS: Overweight/obese subjects (N = 10 744), ≥55 years with cardiovascular disease and/or type 2 diabetes mellitus, received sibutramine plus weight management during a 6-week Lead-in Period before randomization to continue sibutramine (N = 4906) or to receive placebo (N = 4898). The primary endpoint was the time from randomization to first occurrence of a primary outcome event (non-fatal myocardial infarction, non-fatal stroke, resuscitated cardiac arrest or cardiovascular death). RESULTS: For the total population, mean weight change during Lead-in Period (sibutramine) was -2.54 kg. Post-randomization, mean total weight change to Month 12 was -4.18 kg (sibutramine) or -1.87 kg (placebo). Degree of weight loss during Lead-in Period or through Month 12 was associated with a progressive reduction in risk for the total population in primary outcome events and cardiovascular mortality over the 5-year assessment. Although more events occurred in the randomized sibutramine group, on an average, a modest weight loss of approximately 3 kg achieved in the Lead-in Period appeared to offset this increased event rate. Moderate weight loss (3-10 kg) reduced cardiovascular deaths in those with severe, moderate or mild cardiovascular disease. CONCLUSIONS: Modest weight loss over short-term (6 weeks) and longer-term (6-12 months) periods is associated with reduction in subsequent cardiovascular mortality for the following 4-5 years even in those with pre-existing cardiovascular disease. While the sibutramine group experienced more primary outcome events than the placebo group, greater weight loss reduced overall risk of these occurring in both groups.

Prognostic significance of serum uric acid in outpatients with chronic heart failure is complex and related to body mass index: data from the IN-CHF Registry.

BACKGROUND AND AIMS: In the field of cardiovascular diseases, elevated levels of serum uric acid (UA) reflect a marked activation of the xanthine oxidase pathway with increase in free radicals production; it is often associated with an inflammatory state, oxygen consumption and endothelial dysfunction. All these associations have been also confirmed in heart failure (HF) but the pathophysiological role of UA in this setting is not well understood. The aim of this study was to evaluate the prognostic role of UA in outpatients enrolled in the Italian Registry of Congestive Heart Failure (IN-CHF). METHODS AND RESULTS: All patients met the European Society of Cardiology (ESC) criteria for diagnosis of HF. We considered patients with complete clinical data and UA level available at the baseline and at 1-year follow-up. The study population was composed of 877 patients aged 63 ± 12 years. One-year mortality was 10.8% and dead patients had a higher level of UA than survivors (7.1 mg dl⁻¹ vs 6.6 mg dl⁻¹, p < 0.0207). In multivariable full model of analysis, UA did not result in an independent predictor of death in overall population, but only in patients with low body mass index (BMI) (≤22 kg m⁻²) (hazard ratio (HR): 2.38, 95% confidence interval (CI) 1.36-4.18). In this subgroup, a statistically significant gradual relationship between UA and survival was detected starting from values higher than 8 mg dl⁻¹. CONCLUSION: Elevated level of UA is not an independent predictor of mortality in chronic HF, but it markedly worsens outcome if associated with low level of BMI. This association is likely an indicator of chronic inflammatory and catabolic state.

Addition of either pioglitazone or a sulfonylurea in type 2 diabetic patients inadequately controlled with metformin alone: impact on cardiovascular events. A randomized controlled trial.

BACKGROUND AND AIMS: Metformin is the first-line therapy in type 2 diabetes. In patients inadequately controlled with metformin, the addition of a sulfonylurea or pioglitazone are equally plausible options to improve glycemic control. However, these drugs have profound differences in their mechanism of action, side effects, and impact on cardiovascular risk factors. A formal comparison of these two therapies in terms of cardiovascular morbidity and mortality is lacking. The TOSCA.IT study was designed to explore the effects of adding pioglitazone or a sulfonylurea on cardiovascular events in type 2 diabetic patients inadequately controlled with metformin. METHODS: Multicentre, randomized, open label, parallel group trial of 48 month duration. Type 2 diabetic subjects, 50-75 years, BMI 20-45 Kg/m(2), on secondary failure to metformin monotherapy will be randomized to add-on a sulfonylurea or pioglitazone. The primary efficacy outcome is a composite endpoint of all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, and unplanned coronary revascularization. Principal secondary outcome is a composite ischemic endpoint of sudden death, fatal and non-fatal myocardial infarction and stroke, endovascular or surgical intervention on the coronary, leg or carotid arteries, major amputations. Side effects, quality of life and economic costs will also be evaluated. Efficacy, safety, tolerability, and study conduct will be monitored by an independent Data Safety Monitoring Board. End points will be adjudicated by an independent external committee. CONCLUSIONS: TOSCA.IT is the first on-going study investigating the head-to-head comparison of adding a sulfonylurea or pioglitazone to existing metformin treatment in terms of hard cardiovascular outcomes. REGISTRATION: Clinicaltrials.gov ID NCT00700856.

Circulating cardiovascular biomarkers in recurrent atrial fibrillation: data from the GISSI-atrial fibrillation trial.

OBJECTIVE: we evaluated the prognostic role of circulating cardiovascular biomarkers in patients with a history of recent atrial fibrillation (AF). BACKGROUND: predicting long-term maintenance of sinus rhythm in patients with AF is difficult. METHODS: plasma concentrations of three specific cardiac markers [high-sensitivity troponin T (hsTnT), N-terminal probrain natriuretic peptide (NT-proBNP) and mid-regional proatrial natriuretic peptide (MR-proANP)] and three stable fragments of vasoactive peptides [mid-regional proadrenomedullin (MR-proADM), copeptin (CT-proAVP) and CT-proendothelin-1 (CT-proET-1)] were measured at baseline and after 6 and 12 months in 382 patients enrolled in the GISSI-AF study, a prospective randomized trial to determine the effect of valsartan to reduce the recurrence of AF. The association between these markers, clinical characteristics and recurrence of AF was tested by univariate and multivariate Cox models. RESULTS: mean patient age was 68 ± 9 years (37.2% females). A total of 84.8% of patients had a history of hypertension. In total, 59.7% qualified for history of AF because of successful cardioversion, 11.8% because of two or more episodes of AF in the 6 months preceding randomization and 28.5% because of both. Patients in AF at 6 or 12 months (203 (53.1%) with first recurrence) had significantly higher concentrations of most biomarkers. Despite low baseline levels, higher concentrations of hsTnT {adjusted hazard ratio (HR) [95% confidence intervals (CIs) for 1 SD increment] (1.15 [1.04-1.28], P = 0.007), MR-proANP (1.15 [1.01-1.30], P = 0.04), NT-proBNP (1.24 [1.11-1.39], P = 0.0001) and CT-proET-1 (1.16 [1.01-1.33], P = 0.03) independently predicted higher risk of a first recurrence of AF. Changes over time of MR-proANP tended to predict subsequent recurrence (adjusted HR [95%CI]) (1.53 [0.98-2.37], P = 0.06). CONCLUSION: circulating markers of cardiomyocyte injury/strain and endothelin are related to recurrence of AF in patients in sinus rhythm with a history of recent AF.

Effect of canrenone on left ventricular mechanics in patients with mild systolic heart failure and metabolic syndrome: the AREA-in-CHF study.

BACKGROUND AND AIM: We analyzed the effect of the mineralocorticoid receptor antagonist canrenone on LV mechanics in patients with or without metabolic syndrome (MetS) and compensated (Class II NYHA) heart failure (HF) with reduced ejection fraction (EF≤45%) on optimal therapy (including ACE-i or ARB, and ß-blockers). METHODS AND RESULTS: From a randomized, double-blind placebo-controlled trial (AREA-in-CHF), patients with (73 on canrenone [Can] and 77 on placebo [Pla]), based on modified ATPIII definition (BMI≥30kg/m(2) instead of waist girth) or without MetS (146 by arm). In addition to traditional echocardiographic parameters, we also evaluated myocardial mechano-energetic efficiency (MME) based on a previously reported method. At baseline, Can and Pla did not differ in age, BMI, blood pressure (BP), metabolic profile, BNP, and PIIINP. Compared with MetS-Pla, and controlling for age, sex and diabetes, at the final control MetS-Can exhibited increased MME, preserved E/A ratio, and decreased atrial dimensions (0.04

Weight and blood pressure response to weight management and sibutramine in diabetic and non-diabetic high-risk patients: an analysis from the 6-week lead-in period of the sibutramine cardiovascular outcomes (SCOUT) trial.

OBJECTIVE: To assess treatment responses to sibutramine and weight management in diabetic patients during the lead-in period of the Sibutramine Cardiovascular OUTcomes (SCOUT) trial. METHODS: SCOUT is an ongoing, prospective, randomized, double-blind, placebo-controlled outcome trial in cardiovascular high-risk overweight/obese patients. A total of 10 742 patients received single-blind sibutramine and individualized weight management during the 6-week lead-in period; 84% had a history of type 2 diabetes mellitus and additional co-morbidities. Post-hoc analyses assessed anthropomorphic and vital sign responses between patients with and without diabetes. RESULTS: Concomitant antidiabetic medication use was reported by 86% of the diabetic patients (approximately 30% required insulin-alone or in combination). Body weight and waist circumference decreased in diabetic patients: median 2.1 kg; 2.0 cm (both men and women); for those on insulin: 1.9 kg; 1.5/2.0 cm (men/women); without insulin: 2.3 kg; 2.0 cm (both men and women); blood pressure (BP) was also reduced (median systolic/diastolic 3.5/1.0 mmHg) with larger reductions in diabetic patients who were hypertensive and/or lost the most weight (>5%). In diabetic patients who entered with BP at target (<130/<85 mmHg) but did not lose weight (N = 245), increases of 3.5/2.0 mmHg were observed. Non-diabetic patients had greater weight losses (2.5 kg) but smaller reductions in BP (systolic/diastolic -2.5/-0.5 mmHg). Pulse rate increases were less in diabetic vs. non-diabetic patients (1.5 vs. 2.0 bpm). CONCLUSION: In these high-risk diabetic patients, sibutramine and lifestyle modifications for 6 weeks resulted in small, but clinically relevant, median reductions in body weight, waist circumference and BP. A small median increase in pulse rate was recorded.

Early oral versus "traditional" postoperative feeding in gynecologic oncology patients undergoing intestinal resection: a randomized controlled trial.

BACKGROUND: A randomized controlled trial was performed to assess the outcome of early oral postoperative feeding (EOF) compared with traditional oral feeding (TOF) in gynecologic oncology patients undergoing laparotomy with associated intestinal resection. METHODS: Patients aged 18-75 years, undergoing elective laparotomy, and with preoperative diagnosis of gynecologic malignancy, were eligible. Exclusion criteria included infectious conditions, intestinal obstruction, severe malnutrition, American Society of Anesthesiologists (ASA) score > or =4, and postoperative stay in the intensive care unit lasting >24 h. Patients allocated to EOF received liquid diet in the first postoperative day and then regular diet. Patients received traditional feeding scheme until resolution of postoperative ileus to start liquid diet. The primary end-point of the trial was length of hospital stay. RESULTS: Between January 1st, 2007 and March 15th, 2008, 40 patients were randomized to receive either EOF or TOF. Hospital stay in patients who received EOF (n = 18) was 6.9 days versus 9.1 days in the TOF group (n = 22) (P = 0.022). Requirements for analgesic and antiemetic drugs, intensity of pain, intestinal function recovery, mean levels of postoperative satisfaction, postoperative complications, and quality-of-life scores did not differ between the two groups. CONCLUSION: Early resumption of oral intake is feasible and safe in gynecologic oncology patients undergoing intestinal resection as part of a planned surgical procedure. Moreover, significant reduction in length of hospital stay was demonstrated.

Blood pressure changes associated with sibutramine and weight management - an analysis from the 6-week lead-in period of the sibutramine cardiovascular outcomes trial (SCOUT).

OBJECTIVE: To explore vital sign changes among patient subgroups during the 6-week lead-in period of the sibutramine cardiovascular outcomes (SCOUT) trial. METHODS: SCOUT is an ongoing, double-blind, randomized, placebo-controlled outcome trial in overweight/obese patients at high risk of a cardiovascular event. During the 6-week lead-in period, 10,742 patients received sibutramine and weight management. Vital sign changes were assessed post hoc by initial blood pressure (mmHg) categorized as normal (<130/<85), high-normal (130 to <140/85 to <90) or hypertensive (>or=140/>or=90); weight change categories (weight gain/no weight change, >0 to 2.5% weight loss, >2.5 to 5% weight loss and >5% weight loss) and current antihypertensive medication class use (none, one, or two or more). To assess the impact of sibutramine on blood pressure and pulse rate, only patients (N = 10,025) who reported no change in the class of antihypertensive medication used and who did not report an increase in antihypertensive medication use were analysed. RESULTS: At entry, approximately 50% of patients were hypertensive and 26% were high-normal. In hypertensive patients, blood pressure changes (mmHg) decreased by median [5th, 95th percentile] of -6.5 systolic [-27.0, 8.0] and -2.0 diastolic [-15.0, 8.0] (p < 0.001). Hypertensive patients with no weight loss or with weight gain had median decreases of -3.5 systolic [-26.0, 10.0] and -1.5 diastolic [-16.0, 9.0] (p < 0.001). Normotensive patients had median increases of 1.5 systolic [-15.0, 19.5] and 1.0 diastolic [-10.5, 13.0] (p < 0.001) attenuated with increasing weight loss. Approximately 43% of patients initially categorized as hypertensive had a lower blood pressure category at end-point. Concomitant antihypertensive medication classes did not affect blood pressure reductions. Pulse rates were uniformly elevated (median 1-4 bpm, p < 0.001) across blood pressure and weight change categories. CONCLUSIONS: In hypertensive patients (>or=140/>or=90), blood pressure decreases were observed during 6-week treatment with sibutramine even when body weight was unchanged. In patients with normal blood pressure (<130/<85), weight loss of >5% induced decreases in systolic blood pressure; otherwise, small increases were observed. Small pulse rate increases were observed regardless of blood pressure or weight change status.

Recommendations for a standardised educational program in robot assisted gynaecological surgery: Consensus from the Society of European Robotic Gynaecological Surgery (SERGS).

BACKGROUND: The Society of European Robotic Gynaecological Surgery (SERGS) aims at developing a European consensus on core components of a curriculum for training and assessment in robot assisted gynaecological surgery. METHODS: A Delphi process was initiated among a panel of 12 experts in robot assisted surgery invited through the SERGS. An online questionnaire survey was based on a literature search for standards in education in gynaecological robot assisted surgery. The survey was performed in three consecutive rounds to reach optimal consensus. The results of this survey were discussed by the panel and led to consensus recommendations on 39 issues, adhering to general principles of medical education. RESULTS: On review there appeared to be no accredited training programs in Europe, and few in the USA. Recommendations for requirements of training centres, educational tools and assessment of proficiency varied widely. Stepwise and structured training together with validated assessment based on competencies rather than on volume emerged as prerequisites for adequate and safe learning. An appropriate educational environment and tools for training were defined. Although certification should be competence based, the panel recommended additional volume based criteria for both accreditation of training centres and certification of individual surgeons. CONCLUSIONS: Consensus was reached on minimum criteria for training in robot assisted gynaecological surgery. To transfer results into clinical practice, experts recommended a curriculum and guidelines that have now been endorsed by SERGS to be used to establish training programmes for robot assisted surgery.