Intensive heart rhythm monitoring to decrease ischemic stroke and systemic embolism-the Find-AF 2 study-rationale and design.

BACKGROUND: Atrial fibrillation (AF) is one of the most frequent causes of stroke. Several randomized trials have shown that prolonged monitoring increases the detection of AF, but the effect on reducing recurrent cardioembolism, ie, ischemic stroke and systemic embolism, remains unknown. We aim to evaluate whether a risk-adapted, intensified heart rhythm monitoring with consequent guideline conform treatment, which implies initiation of oral anticoagulation (OAC), leads to a reduction of recurrent cardioembolism. METHODS: Find-AF 2 is a randomized, controlled, open-label parallel multicenter trial with blinded endpoint assessment. 5,200 patients ≥ 60 years of age with symptomatic ischemic stroke within the last 30 days and without known AF will be included at 52 study centers with a specialized stroke unit in Germany. Patients without AF in an additional 24-hour Holter ECG after the qualifying event will be randomized in a 1:1 fashion to either enhanced, prolonged and intensified ECG-monitoring (intervention arm) or standard of care monitoring (control arm). In the intervention arm, patients with a high risk of underlying AF will receive continuous rhythm monitoring using an implantable cardiac monitor (ICM) whereas those without high risk of underlying AF will receive repeated 7-day Holter ECGs. The duration of rhythm monitoring within the control arm is up to the discretion of the participating centers and is allowed for up to 7 days. Patients will be followed for at least 24 months. The primary efficacy endpoint is the time until recurrent ischemic stroke or systemic embolism occur. CONCLUSIONS: The Find-AF 2 trial aims to demonstrate that enhanced, prolonged and intensified rhythm monitoring results in a more effective prevention of recurrent ischemic stroke and systemic embolism compared to usual care.

Quality of life after robotic-assisted and laparoscopic radical prostatectomy: Results of a multicenter randomized controlled trial (LAP-01).

BACKGROUND: To explore cross-sectional and longitudinal differences in general health-related and prostate cancer-specific quality of life (QoL) after robotic-assisted (RARP) and laparoscopic (LRP) radical prostatectomy and to analyze predictive variables for QoL outcomes. METHODS: In this multicenter, randomized controlled trial, prostate cancer patients were randomly assigned 3:1 to undergo either RARP or LRP. Patient-reported outcomes were prospectively collected before and 1, 3, 6, 12 months after radical prostatectomy and included QoL as a secondary outcome. Validated questionnaires were used to assess general health-related (EORTC QLQ-C30) and prostate cancer-specific (QLQ-PR25) QoL. Cross-sectional and longitudinal contrasts were analyzed through linear mixed models. Predictive variables for QoL outcomes were identified by general linear modeling. RESULTS: Of 782 randomized patients, QoL was evaluable in 681 patients. In terms of general QoL, the cross-sectional analysis showed only small differences between study arms, whereas longitudinal comparison indicated an advantage of RARP on recovery: RARP patients reported an earlier return to baseline in global health status (3 vs. 6 months) and social functioning (6 vs. 12 months). In role functioning, only the RARP arm regained baseline scores. Regarding prostate-specific QoL, LRP patients experienced more urinary symptoms and reported 3.2 points (95% confidence interval 0.4-6, p = 0.024) higher mean scores at 1-month follow-up and in mean 2.9 points (0.1-5, p = 0.042) higher urinary symptoms scores at 3-month follow-up than RARP patients. There were no other significant differences between treatment groups. Urinary symptoms, sexual activity, and sexual function remained significantly worse compared with baseline at all time points in both arms. CONCLUSIONS: Compared with LRP, the robotic approach led to an earlier return to baseline in several domains of general health-related QoL and better short-term recovery of urinary symptoms. Predictive variables such as the scale-specific baseline status and bilateral nerve-sparing were confirmed.

Age-stratified outcomes after radical prostatectomy in a randomized setting (LAP-01): do younger patients have more to lose?

OBJECTIVE: Age is known to have an impact on outcomes after radical prostatectomy (RP). However, age differences can be investigated from a cross-sectional as well as from a longitudinal perspective. This study combines both perspectives. MATERIALS AND METHODS: LAP-01 is the first multicenter randomized patient blinded trial comparing outcomes after robotic-assisted and laparoscopic RP. This study stratified the entire population that received nerve-sparing surgery and was potent at baseline by the following ages: ≤ 60 years, 61-65 years, and > 65 years. Potency was assessed using the IIEF-5. The EORTC QLQ-C30 was used for global health perception and the EORTC QLQ-PR25 for urinary symptoms. Continence was assessed by the number of pads used. Longitudinal change was assessed using either validated anchor-based criteria or the 1 or 0.5-standard-deviation criterion. Worsening of continence was measured by increasing numbers of pads. RESULTS: 310 patients were included into this study. Older patients had a significantly higher risk for worsening of continence at 3 and 6 months (OR 2.21, 95% CI [1.22, 4.02], p = 0.009 and OR 2.00, 95% CI [1.16, 3.46], p = 0.013, respectively); at 12 months, the odds of worsening did not differ significantly between age groups. Potency scores were better in younger patients from a cross-sectional perspective, but longitudinal change did not differ between the age groups. In contrast, global health perception was better in older patients from a cross-sectional perspective and longitudinal decreases were significantly more common among the youngest patients, at 12 months (36.9% vs. 24.4%, p = 0.038). CONCLUSION: From a cross-sectional perspective, function scores were better in younger patients, but from a longitudinal perspective, age differences were found in continence only. In contrast, global health scores were better in older patients from a cross-sectional and longitudinal perspective. TRIAL REGISTRATION: The LAP-01 trial was registered with the U.S. National Library of Medicine clinical trial registry (clinicaltrials.gov), NCT number: NCT03682146, and with the German Clinical Trial registry (Deutsches Register Klinischer Studien), DRKS ID number: DRKS00007138.

Anti-gravity treadmill rehabilitation improves gait and muscle atrophy in patients with surgically treated ankle and tibial plateau fractures after one year: A randomised clinical trial.

OBJECTIVE: To compare the one-year postoperative outcomes of anti-gravity treadmill rehabilitation with those of standard rehabilitation in patients with ankle or tibial plateau fractures. DESIGN: An open-label prospective randomised study. SETTING: Three trauma centres. SUBJECTS: Patients were randomised into the intervention (anti-gravity treadmill) or control (standard protocol) rehabilitation group. MAIN MEASURES: The primary endpoint was changes in the Foot and Ankle Outcome Score for ankle fractures and Knee Injury and Osteoarthritis Outcome Score for tibial plateau fractures from baseline to 12 months after operation. Secondary endpoints were the subscores of these scores, muscle atrophy (leg circumference at 20 cm above and 10 cm below the knee joint) and the Dynamic Gait Index. RESULTS: Initially, 73 patients (37 vs 36) underwent randomisation. After 12 months, 29 patients in the intervention group and 24 patients in the control group could be analysed. No significant difference was noted in the Foot and Ankle Outcome Score (80.8 ± 18.4 and 78.4 ± 21.1) and Knee Injury and Osteoarthritis Outcome Score (84.8 ± 15.2 and 81.7 ± 17.0). The change in the Dynamic Gait Index from 12 weeks to 12 months differed significantly between the groups (P = 0.04). Patients with tibial plateau fractures had a 3 cm wider thigh circumference in the intervention group than those in the control group (95% confidence interval: -0.2 to 6.3 cm, P = 0.08). CONCLUSION: One year after surgery, patients who had undergone anti-gravity treadmill rehabilitation showed better gait than patients in the control group, and those with tibial plateau fractures had less muscle atrophy.

Extended Pelvic Lymph Node Dissection Does Not Affect Functional Outcomes during Bilateral Nerve-Sparing Radical Prostatectomy.

INTRODUCTION: A possible association between extended pelvic lymph node dissection (ePLND) in radical prostatectomy (RPE) and functional outcomes such as erectile function (EF) and continence recovery has been previously considered. This association stems from the direct proximity of ePLND to the pelvic plexus. In this paper, we aimed to critically examine an association of ePLND with functional outcomes in patients who underwent bilateral nerve-sparing RPE. METHODS: 272 out of 782 patients from a randomized, patient-blinded, multicenter trial were retrospectively classified into two groups based on the D'Amico criteria: 114 had no PLND and 158 had ePLND. Continence (no pad/safety pad) and EF (Index of Erectile Function-5 [IIEF-5] questionnaire ≥17; sufficient erection for sexual intercourse) were assessed at 3, 6, and 12 months as well as postsurgical complications (Clavien-Dindo Classification). RESULTS: After 12 months of follow-up, no significant difference for potency could be found between men without and subjected to ePLND: IIEF-5 ≥17 (23.2% vs. 27.2%; p = 0.55) and sufficient erection for intercourse (44.1% vs. 45.6%; p = 0.84). A multiple linear regression analysis demonstrated that while preoperative EF (p < 0.001), pathological tumor stage (p = 0.027), and robot-assisted bilateral nerve-sparing RPE (p < 0.001) were independent predictors of EF recovery, the same did not apply to ePLND. No association was detected for continence recovery (94.2% vs. 89.7%; p = 0.22) and complications of any grade after surgery (11.4% vs. 16.5%; p = 0.24). CONCLUSION: ePLND is not associated with increased risk of erectile dysfunction, incontinence or complications after bilateral nerve-sparing RPE.

Comorbidities, substance abuse, weight and age are independent risk factors for postoperative complications following operation for proximal humerus fractures: a retrospective analysis of 1109 patients.

INTRODUCTION: This study aimed to investigate the influence of epidemiologic parameters on complications that needed operative revision of operatively treated proximal humerus fractures. METHODS: We performed a retrospective single-center study in a level 1 trauma center. We included all patients with operatively treated proximal humerus fractures from January 1 2005 to December 31 2015. We characterized our cohort and subgroup using descriptive statistics. The primary outcome was postoperative complications. For this purpose, postoperative complications were defined in advance, an operative revision was necessary on a general rule. The secondary outcome was a model of the risk factors for complications created with multiple logistic regression. RESULTS: We included 1109 patients. The average age was 67.2 years (± 16.4), and 71.4% of the fractures occurred in women. A total of 644 patients (58.1%) had between one to three comorbidities, and 27.8% had four or more. The fracture morphology was as follows: 3 part 41.8%, 4 part 26.9%, 2 part 24.3%, and dislocation fracture 6.7%. Complications occurred in 150 patients (13.5%). The number of comorbidities [odds ratio (OR) 2.85, p < 0.01], body weight (OR 1.15, p = 0.02), and substance abuse (OR 1.82, p = 0.04) significantly correlated with the risk of complications. We achieved a sensitivity of 48% and a specificity of 74% for the variables body weight, substance abuse, age, and comorbidities CONCLUSION: The epidemiologic parameters, comorbidities, substance abuse, weight, and age are independent risk factors for complications. If these factors are present, one can predict a postoperative complication requiring surgical revision with low sensitivity and moderate specificity. Therefore, concerning the high number of multi-morbid patients with proximal humerus fractures, an increased postoperative complication rate can be expected. LEVEL OF EVIDENCE: Level of evidence IV.

Impact of anti-gravity treadmill rehabilitation therapy on the clinical outcomes after fixation of lower limb fractures: A randomized clinical trial.

OBJECTIVE: To compare the effects of anti-gravity treadmill rehabilitation with those of standard rehabilitation on surgically treated ankle and tibial plateau fractures. DESIGN: Open-label prospective randomized multicenter study. SETTING: Three level 1 trauma centers. SUBJECTS: Patients with tibial plateau or ankle fractures who underwent postoperative partial weight-bearing were randomized into the intervention (anti-gravity treadmill use) or control (standard rehabilitation protocol) groups. MAIN MEASURES: The primary endpoint was the change in the Foot and Ankle Outcome Score for ankle fractures and total Knee injury and Osteoarthritis Outcome Score for tibial plateau fractures (0-100 points) from baseline (T1) to six weeks after operation (T4) in both groups. Leg circumference of both legs was measured to assess thigh muscle atrophy in the operated leg. RESULTS: Thirty-seven patients constituted the intervention and 36 the control group, respectively; 14 patients dropped out during the follow-up period. Among the 59 remaining patients (mean age 42 [range, 19-65] years), no difference was noted in the Foot and Ankle Outcome Score (54.2 ± 16.1 vs. 56.0 ± 16.6) or Knee injury and Osteoarthritis Outcome Score (52.8 ± 18.3 vs 47.6 ± 17.7) between the intervention and control groups 6 weeks after operation. The change in the leg circumference from T1 to T4 was greater by 4.6 cm in the intervention group (95% confidence interval: 1.2-8.0, P = 0.005). No adverse event associated with anti-gravity treadmill rehabilitation was observed. CONCLUSION: No significant difference was noted in patient-reported outcomes between the two groups. Significant differences in muscular atrophy of the thigh were observed six weeks after operation.

Impact of surgical site infection on patients' outcome after fixation of tibial plateau fractures: a retrospective multicenter study.

BACKGROUND: Surgical site infection (SSI) occurs in 3-10 % of patients with surgically treated tibial plateau fractures. This study aimed to evaluate the impact of SSI on patients' outcome after fixation of tibial plateau fractures. METHODS: We conducted a retrospective multicenter study in seven participating level I trauma centers between January 2005 and December 2014. All participating centers followed up with patients with SSI. In addition, three centers followed up with patients without SSI as a reference group. Descriptive data and follow-up data with patient-reported outcome scores (Knee Injury and Osteoarthritis Outcome Score [KOOS] and Lysholm knee scoring scale score) were evaluated. RESULTS: In summary, 287 patients (41 with SSI and 246 without SSI; average 50.7 years) with an average follow-up of 75.9 ± 35.9 months were included in this study. Patients with SSI had a significantly poorer overall KOOS (KOOS5) (48.7 ± 23.2 versus [vs.] 71.5 ± 23.5; p < 0.001) and Lysholm knee scoring scale score (51.4 ± 24.0 vs. 71.4 ± 23.5; p < 0.001) than patients without SSI. This significant difference was also evident in the KOOS subscores for pain, symptoms, activities of daily living (ADL), and quality of life (QoL). SSI remained an important factor in multivariable models after adjusting for potential confounders. Clinically relevant differences in the KOOS5 and KOOS subscores for symptoms, pain, and ADL were found between those with SSI and without SSI even after adjustment. Furthermore, the number of previous diseases, Arbeitsgemeinschaft für Osteosynthesefragen Foundation (AO) C fractures, and compartment syndrome were found to be additional factors related to poor outcome. CONCLUSIONS: Compared to previous studies, validated patient-reported outcome scores demonstrated that the impact of SSI in patients with surgically treated tibial plateau fractures is dramatic, in terms of not only pain and symptoms but also in ADL and QoL, compared to that in patients without SSI.

Treatment of established status epilepticus in the elderly - a study protocol for a prospective multicenter double-blind comparative effectiveness trial (ToSEE).

BACKGROUND: Status epilepticus (SE) is a common neurological emergency condition that especially affects the elderly and old population. Older people with SE frequently have non-convulsive SE (NCSE) and are also at special risk of suffering a poor outcome. The application of benzodiazepines fails to control SE in about one third of the cases. For benzodiazepine refractory SE (BRSE) in elderly, there is little evidence that would justify the choice of one of the commonly used antiepileptic drugs. The present study aims to generate evidence for the treatment of BRSE in this age group. METHODS: We will conduct a prospective, randomized, double-blind comparative effectiveness study in more than twenty hospitals in Germany over a four-year period. Four hundred and seventy-seven elderly patients (≥ 65 years old) diagnosed with BRSE will be allocated by 1:1 randomization to receive either levetiracetam or valproate. All types of SE will be considered. For the diagnosis NCSE a verification by EEG is required. Levetiracetam or valproate will be administered in one single infusion. The primary endpoint is the stable cessation of ictal activity 15 min after the start of infusion persisting for the following 45 min of observation. EEG recording is maintained over the whole observation period, clinical examinations are conducted in predefined intervals. In case of treatment success patients and study staff remain blinded until 60 min after the start of the infusion. Adverse events will be recorded until the end of the study. EEG data will be reviewed by two external independent experts. To obtain data about the further treatment of SE, intrahospital complications and the functional outcome in the short term the study participants will be observed until the day of discharge or day 30 whichever is earliest. DISCUSSION: ToSEE is the first study which shall deliver evidence for the SE-therapy in the elderly and old population in a controlled prospective comparator study. By design it also shall collect information about therapy regimes and outcome aspects of this disease. TRIAL REGISTRATION: The trial has been registered at the German Clinical Trials Register on 3 July, 2020 ( DRKS00022308 ,  https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00022308 ).

Myoglobin clearance with continuous veno-venous hemodialysis using high cutoff dialyzer versus continuous veno-venous hemodiafiltration using high-flux dialyzer: a prospective randomized controlled trial.

BACKGROUND: Myoglobin clearance in acute kidney injury requiring renal replacement therapy is important because myoglobin has direct renal toxic effects. Clinical data comparing different modalities of renal replacement therapy addressing myoglobin clearance are limited. This study aimed to compare two renal replacement modalities regarding myoglobin clearance. METHODS: In this prospective, randomized, single-blinded, single-center trial, 70 critically ill patients requiring renal replacement therapy were randomized 1:1 into an intervention arm using continuous veno-venous hemodialysis with high cutoff dialyzer and a control arm using continuous veno-venous hemodiafiltration postdilution with high-flux dialyzer. Regional citrate anticoagulation was used in both groups to maintain the extracorporeal circuit. The concentrations of myoglobin, urea, creatinine, ß2-microglobulin, interleukin-6 and albumin were measured before and after the dialyzer at 1 h, 6 h, 12 h, 24 h and 48 h after initiating continuous renal replacement therapy. RESULTS: Thirty-three patients were allocated to the control arm (CVVHDF with high-flux dialyzer) and 35 patients to the intervention arm (CVVHD with high cutoff dialyzer). Myoglobin clearance, as a primary endpoint, was significantly better in the intervention arm than in the control arm throughout the whole study period. The clearance values for urea and creatinine were higher in the control arm. There was no measurable albumin clearance in both arms. The clearance data for ß2-microglobulin and interleukin-6 were non-inferior in the intervention arm compared to those for the control arm. Dialyzer lifespan was 57.0 [38.0, 72.0] hours in the control arm and 70.0 [56.75, 72.0] hours in the intervention arm (p = 0.029). CONCLUSIONS: Myoglobin clearance using continuous veno-venous hemodialysis with high cutoff dialyzer and regional citrate anticoagulation is better than that with continuous veno-venous hemodiafiltration with regional citrate anticoagulation. TRIAL REGISTRATION: German Clinical Trials Registry (DRKS00012407); date of registration 23/05/2017. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00012407 .

Surgical resection based on ontogenetic cancer field theory for cervical cancer: mature results from a single-centre, prospective, observational, cohort study.

BACKGROUND: Previous findings from our centre suggest that carcinoma of the cervix propagates within ontogenetic cancer fields, tissue compartments defined by staged morphogenesis. We aimed to determine whether surgical treatment that accounts for stage-associated, ontogenetic cancer fields and their associated lymphoid tissues results in locoregional tumour control without the need for adjuvant radiotherapy. METHODS: We did the final clinical and histopathological evaluation of data from, the single-centre, observational, cohort study, the Leipzig School Mesometrial Resection Study. Patients of any age with stage IB1, IB2, IIA1, IIA2, or IIB cervical cancer (according to 2009 International Federation of Gynecology and Obstetrics [FIGO]) had total mesometrial resection or extended mesometrial resection and therapeutic lymph node dissection, done on the basis of ontogenetic cancer fields. We defined sentinel node, first-line, second-line, and third-line lymph node regions as progressive regional cancer fields. Primary outcomes were disease-specific survival and recurrence-free survival, and treatment-related morbidity (assessed with the Franco-Italian glossary). Applying Cox proportional hazard models, ontogenetic local (T) and regional (N) tumour staging was compared with pathological T and N staging. This trial is registered with the German Clinical Trials Register, number DRKS00015171. FINDINGS: Between Oct 16, 1999, and June 27, 2017, 523 patients were treated per protocol and followed up for a median of 61·8 months (IQR 49·3-94·8). In 495 patients with cervical cancer treated with cancer field surgery, 5-year disease-specific survival was 89·4% (95% CI 86·5-92·4) and recurrence-free survival was 83·1% (79·7-86·6). In the per-protocol population of 523 patients, treatment-related morbidity comprised 112 (21%) grade 2 and 15 (3%) grade 3 complications. The most common moderate and severe treatment-related complications and sequelae were wound dehiscence (17 [3%]), hydronephrosis (17 [3%]), bowel obstruction (26 [5%]), and lymph oedema (33 [6%]). One patient (<1%), who received total mesometrial resection, died from postoperative brain infarction. INTERPRETATION: Total or extended mesometrial resection with therapeutic lymph node dissection based on ontogenetic cancer fields results in good survival outcomes of patients with cervical cancer in our institution, but needs to be investigated further in multicentre trials. FUNDING: Leipzig School of Radical Pelvic Surgery, University of Leipzig Medical School, and the Gynecologic Oncology Research Foundation.

Comparison of various continence definitions in a large group of patients undergoing radical prostatectomy: a multicentre, prospective study.

BACKGROUND: Due to the usage of various measurement methods and definitions, comparing continence rates after radical prostatectomy is a challenging task. This study compares continence rates based on different methods and aims to identify the definition for continence which agrees best with the patients' subjective assessment of continence. Additionally, continence was controlled for multiple influencing factors. METHODS: This prospective multicentre study was carried out in seven hospitals throughout Germany. Before and at 3, 6, and 12 months after surgery self-reporting questionnaires were completed and returned by 329 (84.4%) of 390 eligible patients. The questionnaires were independently evaluated and analysed by a third party. Association of continence with demographic, operative, and tumour factors in an ongoing comprehensive prostate cancer database was evaluated. RESULTS: The continence rate drops substantially for patients undergoing radical prostatectomy but increases again with time. Concrete numbers vary considerably depending on definition - 44% at 3 months and 68% at 12 months after surgery (0 pads) vs. 71 and 90% (0-1 pads). Significant confounding variables regarding continence rate are nerve-sparing procedure, categorized Gleason score, rehabilitative cure treatment, and pelvic floor training. The definition of 0 pads for continence coincides greater than 0-1 pads with the patients' self-assessment of being continent. CONCLUSION: A standardized definition for continence would be desirable, as it is one of the most important preconditions to guarantee sound comparison of continence rates. Since there are enough other factors that make comparison difficult, we suggest using the definition of "0 pads". It is easily measured objectively, leaves no room for interpretation, and agrees best with the patients' self-assessment.

Cardiac Surgery in Patients with Parkinson's Disease: A Retrospective Analysis of a High-Risk Cohort.

BACKGROUND: Little is known about the perioperative course of patients with Parkinson's disease (PD) undergoing cardiac surgery. The objective of this study was to identify the influence of PD on the perioperative course and to improve treatment. METHODS: Perioperative data were analyzed retrospectively from 130 patients undergoing cardiac surgery between September 2001 and April 2013 who had PD and were compared using 1:1 matched-pair analysis with 130 controls not affected by PD. RESULTS: The 30-day all-cause mortality (4.6 vs. 9.2%; p = 0.21; odds ratio [OR] = 0.45; 95% confidence interval [CI]: 0.16, 1.31) and the overall all-cause mortality (27.7 vs. 28.5%; hazard ratio [HR] = 0.96 [0.56, 1.66]; p = 1.00) were not significantly different between PD patients and the control group. Emergency surgery (p = 0.04; OR = 3.20; 95% CI: 1.06, 9.66) and postoperative pneumonia (p < 0.001; OR = 11.3; 95% CI: 3.06, 41.6) were associated with 30-day mortality. Independent predictors of all-cause mortality were age at surgery (p = 0.01; OR = 3.58; 95% CI: 1.38, 9.30), NYHA (New York Heart Association) classification stage IV (p = 0.02; OR = 17.3; 95% CI: 1.52, 198), and postoperative pneumonia (p = 0.05; OR = 46.4; 95% CI: 0.97, 2219). We did not observe an association of PD with short- or long-term all-cause mortality after adjustment for associated covariates. CONCLUSIONS: We found that PD is not a significant risk factor for perioperative morbidity and mortality in our cohort. Our study showed that patients with PD had outcomes that were similar to those of non-PD patients.

Evaluation of risk factors for a fulminant Clostridium difficile infection after cardiac surgery: a single-center, retrospective cohort study.

BACKGROUND: Clostridium difficile (CD) is the most common pathogen causing nosocomial diarrhea. The clinical presentation ranges from mild diarrhea to severe complications, including pseudomembranous colitis, toxic megacolon, sepsis, and multi-organ failure. When the disease takes a fulminant course, death ensues rapidly in severe and complex cases. Preventive screening or current prophylactic therapies are not useful. Therefore, this study was conducted to detect risk factors for a fulminant CD infection (CDI) in patients undergoing cardiac surgery. METHODS: Between April 1999 and April 2011, a total of 41,466 patients underwent cardiac surgery at our institution. A review of our hospital database revealed 1256 patients (3.0%) with post-operative diarrheal disease who tested positive for CD; these patients comprised the cohort of this observational study. A fulminant CDI occurred in 153 of these patients (12.2%), which was diagnosed on the basis of gastrointestinal complications, e.g. pseudomembranous colitis, and/or the need for post-cardiac surgery laparotomy. Demographic, peri-operative, and survival data were analyzed, and predictors of a fulminant CDI were assessed by binary logistic regression analysis. RESULTS: The 30-day mortality was 6.1% (n = 77) for the entire cohort, with significantly higher mortality among patients with a fulminant CDI (21.6% vs. 4.0%, p <  0.001). Overall mortality (27.7%, n = 348) was also higher for patients with a fulminant course of the disease (63.4% vs. 22.8%, p <  0.001), and a laparotomy was required in 36.6% (n = 56) of the fulminant cases. Independent predictors of a fulminant CDI were: diabetes mellitus type 2 (OR 1.74, CI 1.15-2.63, p = 0.008), pre-operative ventilation (OR 3.52, CI 1.32-9.35, p = 0.012), utilization of more than 8 units of red blood cell concentrates (OR 1.95, CI 1.01-3.76, p = 0.046) or of more than 5 fresh-frozen plasma units (OR 3.38, CI 2.06-5.54, p <  0.001), and a cross-clamp time > 130 min (OR 1.93, CI 1.12-3.33, p = 0.017). CONCLUSIONS: We identified several independent risk factors for the development of a fulminant CDI after cardiac surgery. Close monitoring of high-risk patients is important in order to establish an early onset of therapy and thus to prevent a CDI from developing a fulminant course after cardiac surgery.

Coronary Collateral Growth Induced by Physical Exercise: Results of the Impact of Intensive Exercise Training on Coronary Collateral Circulation in Patients With Stable Coronary Artery Disease (EXCITE) Trial.

BACKGROUND: A well-developed coronary collateral circulation provides a potential source of blood supply in coronary artery disease. However, the prognostic importance and functional relevance of coronary collaterals is controversial with the association between exercise training and collateral growth still unclear. METHODS AND RESULTS: This prospective, open-label study randomly assigned 60 patients with significant coronary artery disease (fractional flow reserve ≤0.75) to high-intensity exercise (group A, 20 patients) or moderate-intensity exercise (group B, 20 patients) for 4 weeks or to a control group (group C, 20 patients). The primary end point was the change of the coronary collateral flow index (CFI) after 4 weeks. Analysis was based on the intention to treat. After 4 weeks, baseline CFI increased significantly by 39.4% in group A (from 0.142±0.07 at beginning to 0.198±0.09 at 4 weeks) in comparison with 41.3% in group B (from 0.143±0.06 to 0.202±0.09), whereas CFI in the control group remained unchanged (0.7%, from 0.149±0.09 to 0.150±0.08). High-intensity exercise did not lead to a greater CFI than moderate-intensity training. After 4 weeks, exercise capacity, Vo2 peak and ischemic threshold increased significantly in group A and group B in comparison with group C with no difference between group A and group B. CONCLUSIONS: A significant improvement in CFI was demonstrated in response to moderate- and high-intensity exercise performed for 10 hours per week. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01209637.

Endothelial Function in Children and Adolescents Is Mainly Influenced by Age, Sex and Physical Activity　- An Analysis of Reactive Hyperemic Peripheral Artery Tonometry.

BACKGROUND: As adolescents rarely experience cardiovascular events, surrogate markers of atherosclerosis are useful to justify and monitor effects of primary prevention and therapy of risk factors. Endothelial function assessed by reactive hyperemic peripheral arterial tonometry (RH-PAT) resulting in a reactive hyperemic index (RHI) is a noninvasive method with limited data for use in children and adolescents.Methods and Results:We performed a total of 931 RHI measurements in 445 high-school students, aged 10-17 years, over a time period of 5 years. Students were randomized by class to 60 min physical exercise (PE) at school daily (intervention group), or 2 units of 45-min PE weekly (control group). To characterize the factors influencing the RHI, anthropometry, cardiopulmonary exercise testing, blood cholesterol and quality of life were assessed and used to build mixed linear models. Main influential factors were age, with an increase of RHI from 1.53±0.42 in the youngest to 1.96±0.59 in the oldest students, sex, with higher values in girls, and physical activity. This increase adjusted by age and sex was estimated as 0.11 [0.08, 0.14] per year. RHI was higher in the intervention group by 0.09 [-0.05, 0.23] in comparison with the control group. CONCLUSIONS: If RH-PAT is used in research or as a clinical tool in adolescents, the shown age- and sex-dependence of RHI have to be taken in account.

Cardioprotection by combined intrahospital remote ischaemic perconditioning and postconditioning in ST-elevation myocardial infarction: the randomized LIPSIA CONDITIONING trial.

AIMS: Remote ischaemic conditioning (RIC) and postconditioning (PostC) are both potent activators of innate protection against ischaemia-reperfusion injury and have demonstrated cardioprotection in experimental and clinical ST-elevation myocardial infarction (STEMI) trials. However, their combined effects have not been studied in detail. The aim of this study was to evaluate if the co-application of intrahospital RIC and PostC has a more powerful effect on myocardial salvage compared with either PostC alone or control. METHODS AND RESULTS: This prospective, controlled, single-centre study randomized 696 STEMI patients to one of the following three groups: (i) combined intrahospital RIC + PostC in addition to primary percutaneous coronary intervention (PCI); (ii) PostC in addition to PCI; and (iii) conventional PCI (control). The primary endpoint myocardial salvage index was assessed by cardiac magnetic resonance (CMR) imaging within 3 days after infarction. Secondary endpoints included infarct size and microvascular obstruction (MVO) assessed by CMR. The combined clinical endpoint consisted of death, reinfarction, and new congestive heart failure within 6 months. The primary endpoint myocardial salvage index was significantly greater in the combined RIC + PostC group when compared with the control group (49 [interquartile range 30-72] vs. 40 [interquartile range 16-68], P = 0.02). Postconditioning alone failed to improve myocardial salvage when compared with conventional PCI (P = 0.39). The secondary endpoints, including infarct size and MVO, showed no significant differences between groups. Clinical follow-up at 6 months revealed no differences in the combined clinical endpoint between groups (P = 0.44). CONCLUSION: Combined intrahospital RIC + PostC in conjunction with PCI in STEMI significantly improves myocardial salvage in comparison with control and PostC. CLINICALTRIALSGOV: NCT02158468.

Patient discomfort following catheter ablation and rhythm device surgery.

AIMS: Proper management of post-interventional pain relieves unwarranted patient distress and enhances patient satisfaction. There have been only a limited number of investigations into patient discomfort following electrophysiological interventions. This study aims to quantify pain after interventional procedures, including ablation of atrial fibrillation (AF) or ventricular tachycardia (VT), as well as implant or explant of pacemakers or implantable cardioverter defibrillators. METHODS AND RESULTS: One-hundred and two consecutive patients (mean age 66 years, 70 men) were asked to quantify post-interventional pain on a numeric rating scale (NRS 0-10) every 2 h during a period of 24 h after their intervention (49 ablations in deep propofol sedation, 53 device surgeries in local anaesthesia with mepivacaine 1%) and to specify the type of pain. Pain was classified as moderate to severe in case of NRS > 3. Post-operative pain medication included non-opioid and opioid analgesics as per the treating physicians' discretion. Sixty-one patients (60%) suffered from moderate-to-severe pain within the first 24 h after the procedure, despite the use of analgesics in 47 patients (46%). Pain was present in an early period (0-6 h) in 54% and in a late period (8-24 h) in 40% of patients. Patients complained of back pain (44%), pain at the site of the device pocket (39%), pain at the groin after puncture (7%), and pericarditic pain (5%). Multivariate analysis identified female gender (P = 0.046) associated with early post-interventional pain while age, diabetes mellitus, body mass index, type of intervention, and procedure time were not related to early or late post-interventional pain. CONCLUSION: The findings highlight the high prevalence and the poor predictability of moderate-to-severe post-interventional pain within the first 24 h after catheter ablation and cardiac device surgery procedures, despite the use of peri-interventional analgesics. These findings highlight the need for more careful pain assessment and management programmes.

Initial Experience With a Percutaneous Approach to Redo Mitral Valve Surgery: Management and Procedural Success.

OBJECTIVE: The purpose of the study was to report the anesthetic management and immediate procedural success in the initial 20 patients undergoing percutaneous transapical mitral valve replacement. DESIGN: Retrospective review of collected data. SETTING: University-affiliated heart center. PARTICIPANTS: Twenty patients with mitral regurgitation or stenosis due to a degenerated valve or ring in the mitral position. INTERVENTIONS: TEE-guided transapical mitral valve replacement under general anesthesia and early extubation by means of an established fast-track protocol. MEASUREMENTS AND MAIN METHODS: Twenty patients underwent transapical mitral valve replacement by a beating heart procedure, avoiding cardiopulmonary bypass. The valve was either deployed due to a previously implanted bioprosthetic valve (valve-in-valve group), which degenerated, or a ring (valve-in-ring group), which predominantly showed regurgitation. There was a significant increase in the mitral valve opening area in stenosed valve pathology from 1.3-1.9 sq. cm (p = 0.004), and an increase in ejection fraction from 40% to 45% (p = 0.52). In the valve-in-ring group, valve area increased from 2.0 sq. cm to 2.6 sq. cm (p = 0.21), with an increase in ejection fraction from 30% to 35% (p = 0.18). Eighteen patients underwent successful deployment of the valve. The anesthesia duration for the procedure lasted 185.5 ± 25.4 minutes. CONCLUSIONS: There was a significant increase in opening area of the valve and improvement in ejection fraction in this patient group. TEE and fluoroscopy-guided imaging is necessary for the procedure's success and is an evolving alternative treatment for high-risk mitral valve patients who would otherwise be considered inoperable for routine surgery using sternotomy.

The relation between hypointense core, microvascular obstruction and intramyocardial haemorrhage in acute reperfused myocardial infarction assessed by cardiac magnetic resonance imaging.

BACKGROUND: Intramyocardial haemorrhage (IMH) and microvascular obstruction (MVO) represent reperfusion injury after reperfused ST-elevation myocardial infarction (STEMI) with prognostic impact and "hypointense core" (HIC) appearance in T2-weighted images. We aimed to distinguish between IMH and MVO by using T2 (*)-weighted cardiovascular magnetic resonance imaging (CMR) and analysed influencing factors for IMH development. METHODS AND RESULTS: A total of 151 patients with acute STEMI underwent CMR after primary angioplasty. T2-STIR sequences were used to identify HIC, late gadolinium enhancement to visualise MVO and T2 (*)-weighted sequences to detect IMH. IMH(+)/IMH(-) patients were compared considering infarct size, myocardial salvage, thrombolysis in myocardial infarction (TIMI) flow, reperfusion time, ventricular volumes, function and pre-interventional medication. Seventy-six patients (50%) were IMH(+), 82 (54%) demonstrated HIC and 100 (66%) MVO. IMH was detectable without HIC in 16 %, without MVO in 5% and HIC without MVO in 6%. Multivariable analyses revealed that IMH was associated with significant lower left ventricular ejection fraction and myocardial salvage index, larger left ventricular volume and infarct size. Patients with TIMI flow grade ≤1 before angioplasty demonstrated IMH significantly more often. CONCLUSIONS: IMH is associated with impaired left ventricular function and higher infarct size. T2 and HIC imaging showed moderate agreement for IMH detection. T2 (*) imaging might be the preferred CMR imaging method for comprehensive IMH assessment. KEY POINTS: Intramyocardial haemorrhage is a common finding in patients with acute reperfused myocardial-infarction. T 2 (*) imaging should be the preferred CMR method for assessment of intramyocardial haemorrhage. Intramyocardial haemorrhage can be considered as an important influencing factor on patient's outcome.