Assessment of different continence definitions in the context of the randomized multicenter prospective LAP-01 trial-Does the best definition change over time?

BACKGROUND: A uniform definition of continence is urgently needed to allow the comparison of study results and to estimate patient outcomes after radical prostatectomy (RP). To identify a practical definition that includes both objective and subjective aspects in a tangible way, we assessed different continence definitions and evaluated which best reflects the patients' subjective perception of continence. METHODS: Our analyses included 718 patients that underwent either robot-assisted radical prostatectomy (RARP) or laparoscopic radical prostatectomy (LRP) in a multicenter randomized patient-blinded trial. Continence was assessed through patient questionnaires prior to and at 3, 6 and 12 months after surgery which included the number of pads used per day, the ICIQ-SF and the question "Do you suffer from incontinence? (yes/no)" to assess subjective continence. We used Krippendorff's Alpha to calculate the agreement of different continence definitions with the subjective perception. RESULTS: At 3 months, the "0/safety pad" definition shows the highest agreement by alpha = 0.70 (vs. 0.63 for "0 pads" and 0.37 for "0-1 pad"). At 6 and 12 months "0 pads" is the better match, with alpha values of 0.69 (vs. 0.62 and 0.31) after 6 months and 0.70 (vs. 0.65 and 0.32) after 12 months. The ICIQ-SF score shows good correlation with the subjective continence at 3 months (alpha = - 0.79), the coefficient then decreasing to - 0.69 and - 0.59 at 6 and 12 months. CONCLUSION: The best continence definition according to the patients' perspective changes over time, "0 pads" being the superior criterion in the long-term. We recommend using the 0-pad definition for standardized continence reporting, as it is simple yet as accurate as possible given the inevitably high subjectivity of continence perception. 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.

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.

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.

Evaluation of the HFA-PEFF Score: results from the prospective DIAST-CHF cohort.

AIMS: Although the number of patients suffering from heart failure with preserved ejection fraction (HFpEF) increases, the routine diagnosis remains a challenge. In the absence of a pathognomonic sign for HFpEF or specific treatment strategies, a prognosis-based characterization of suspected patients remains promising for both the risk stratification of the patients and a disease definition. The Heart Failure Association (HFA) of the European Society of Cardiology has introduced an algorithm with different levels of likelihood regarding the diagnosis of HFpEF, the HFA-PEFF score. We aimed to evaluate the predictive value of this algorithm in a large cohort regarding mortality, symptom burden, and the functional status. METHODS AND RESULTS: DIAST-CHF is a multicentre, population-based, prospective, observational study in subjects with at least one risk factor for HFpEF between the age of 50 and 85. We calculated the HFA-PEFF score (n = 1668) and analysed the risk groups for overall mortality, cardiovascular hospitalization, and submaximal functional capacity (6-min walk distance) at baseline and after a follow-up period of 10 years. Patients with high HFA-PEFF score values 5&6 showed a higher mortality than those with an intermediate score (score values 2-4) and low score values (high 21.3% vs. intermediate 10.1% vs. low 4.3%, P < 0.001). Also, the burden of MACE (death, cardiovascular hospitalization, new myocardial infarction, first diagnosis of HF) was increased in the high score values group (high 40.7% vs. intermediate 25.9% vs. low 13.9%, P < 0.001). Similarly, patients with higher scores had higher cumulative incidences of cardiovascular hospitalizations (P = 0.011). Subjects with higher scores also had lower 6-min walk distance both at baseline and during follow-up. CONCLUSIONS: The HFA-PEFF score provides a reliable instrument to stratify suspected HFpEF patients by their risk for mortality, symptom burden, and functional status in cohort at risk with a follow-up period of 10 years. As high HFA-PEFF scores are associated with worse outcome, the HFA-PEFF algorithm describes a defining approach towards HFpEF.

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.

Robotic-assisted Versus Laparoscopic Radical Prostatectomy: 12-month Outcomes of the Multicentre Randomised Controlled LAP-01 Trial.

BACKGROUND: Recently, our LAP-01 trial demonstrated superiority of robotic-assisted laparoscopic radical prostatectomy (RARP) over conventional laparoscopic radical prostatectomy (LRP) with respect to continence at 3 mo. OBJECTIVE: To compare the continence, potency, and oncological outcomes between RARP and LRP in the 12-mo follow-up. DESIGN, SETTING, AND PARTICIPANTS: In this multicentre, randomised, patient-blinded controlled trial, patients referred for radical prostatectomy to four hospitals in Germany were randomly assigned (3:1) to undergo either RARP or LRP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Continence was assessed as a patient-reported outcome through validated questionnaires. Secondary endpoints included potency and oncological outcomes. Data were statistically analysed by bivariate tests and multivariable models. RESULTS AND LIMITATIONS: At 12 mo, follow-up data were available for 701 of 782 patients. Continence at 6 and 12 mo after surgery was better in RARP patients, however no longer statistically significant (p = 0.068 and 0.38, respectively). Patients who were potent at baseline and underwent nerve-sparing surgery reported significantly higher potency after RARP, as defined by the capability to maintain an erection sufficient for intercourse at 3 (p = 0.005), 6 (p = 0.018), and 12 mo (p = 0.013). There were no statistically significant differences in oncological outcomes at 12 mo. It is a limitation that the influence of different anastomotic techniques was not investigated in this study. CONCLUSIONS: Both LRP and RARP offer a high standard of therapy for prostate cancer patients. However, robotic assistance offers better functional outcomes in specific areas such as potency and early continence in patients who are eligible for nerve-sparing RP. PATIENT SUMMARY: We compared outcomes 12 mo after radical prostatectomy between robotic-assisted and conventional laparoscopy. Both methods were equivalent with respect to oncological outcomes. Better recovery of continence in patients with robotic-assisted surgery, which was observed at 3 mo, blurred up to 12 mo. A benefit of robotic-assisted surgery was also observed in potency.

Epithelial-mesenchymal transition (EMT) in vulvar cancer with and without inguinal lymph node involvement.

PURPOSE: Epithelial-mesenchymal transition (EMT) is associated with increased metastatic spread and poor prognosis. Data on vulvar carcinoma are limited. METHODS: Thirty-two cases of squamous cell carcinoma of the vulva (16 with and 16 without inguinal lymph node metastases) and their lymph node deposits were evaluated for immunohistochemical expression of EMT markers (vimentin, cyclin D1, e-cadherin), p16, p53 and Ki-67. Results of EMT-immunostainings were compared to lymph node involvement and expression of p53 and p16. The micro-anatomical staining pattern for EMT markers comparing the tumor center with the front of invasion was analysed in each tumor. RESULTS: There was no difference in the expression of EMT markers between node negative and node positive tumors. Staining for vimentin and cyclin D1 was seen within tumor cells at the front of invasion in 100 and 84.4% of the tumors, respectively. The majority of cases (68.7%) showed negative or reduced staining for e-cadherin in this micro-anatomical localization. Tumor cells within the lymph node metastases showed positive staining for e-cadherin in 75% and for cyclin D1 in 49% of the cells but were negative for vimentin in 13 out of 16 cases (81.3%). Tumors with aberrant p53 staining represented a non-significant higher vimentin but significantly higher cyclin D1 expression at the front of invasion than those with p53 wild-type pattern. CONCLUSION: The present study shows no differences in the expression of EMT markers between node positive and node negative vulvar cancers. The evaluation of immunostaining within the micro-anatomical context indicates that an EMT-phenotype is restricted to the tumor cells at the front of invasion. Paired analyses of vulvar carcinomas and their lymph node deposits suggest mesenchymal-epithelial transition (MET) in the metastatic deposits. Immunohistochemical staining results may suggest that EMT is more prevalent in vulvar cancer with aberrant p53 staining.

Long-Term Follow-up of Enhanced Holter-Electrocardiography Monitoring in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Prolonged electrocardiography (ECG)-monitoring in stroke patients improves the detection of paroxysmal atrial fibrillation (pAF). However, most randomized studies only had short follow-up. We aimed to provide 3-year follow-up data for AF detection and stroke recurrence risk. METHODS: We randomized 402 patients aged ≥60 years with acute ischemic strokes without AF to either enhanced and prolonged monitoring (EPM; 3×10-day Holter-ECG-monitoring) or standard-of-care (≥24 hours ECG-monitoring). The endpoint of the current analysis was AF within 36 months analyzed by intention to treat. Long-term follow-up was performed for 36 months. RESULTS: Two hundred and seventy-four patients (80%) participated in the extended follow-up (median duration of follow-up was 36 months [interquartile range, 12 to 36]). During the first 6 months, more AF was documented in the EPM arm compared to the control arm (13.5% vs. 5.1%; 95% confidence interval, 2.9% to 14.4%; P=0.004). During months 6 to 36, AF was less detected in the EPM intervention arm than in the control arm (2.0% vs. 7.3%; 95% confidence interval, 0.7% to 9.9%; P=0.028). Overall, the detection rate of AF within 36 months was numerically higher within the EPM group (15.0% vs. 11.1%, P=0.30). Numerically less patients in the EPM arm had recurrent ischemic strokes (5.5% vs. 9.1%, P=0.18), transient ischemic attacks (3.0% vs. 4.5%, P=0.44) or died (4.5% vs. 6.6%, P=0.37). CONCLUSIONS: Enhanced and prolonged ECG monitoring increased AF detection during the first six months, but there was significantly more clinical AF during months 6 to 36 observed in the usual-care arm. This suggests that EPM leads to an earlier detection of clinically relevant AF.

NT-proBNP as a marker for atrial fibrillation and heart failure in four observational outpatient trials.

AIMS: Heart failure (HF) and atrial fibrillation (AF) frequently coexist and are both associated with increased levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP). It is known that AF impairs the diagnostic accuracy of NT-proBNP for HF. The aim of the present study was to compare the diagnostic and predictive accuracy of NT-proBNP for HF and AF in stable outpatients with cardiovascular risk factors. METHODS AND RESULTS: Data were obtained from the DIAST-CHF trial, a prospective cohort study that recruited individuals with cardiovascular risk factors and followed them up for 12 years. Data were validated in three independent population-based cohorts using the same inclusion/exclusion criteria: LIFE-Adult (n = 2869), SHIP (n = 2013), and SHIP-TREND (n = 2408). Serum levels of NT-proBNP were taken once at baseline. The DIAST-CHF study enrolled 1727 study participants (47.7% female, mean age 66.9 ± 8.1 years). At baseline, patients without AF or HF (n = 1375) had a median NT-proBNP of 94 pg/mL (interquartile range 51;181). In patients with AF (n = 93), NT-proBNP amounted to 667 (215;1130) pg/mL. It was significantly higher than in the first group (P < 0.001) and compared with those with only HF [n = 201; 158 (66;363) pg/mL; P < 0.001]. The highest levels of NT-proBNP [868 (213;1397) pg/mL] were measured in patients with concomitant HF and AF (n = 58; P < 0.001 vs. control and vs. HF, P = 1.0 vs. AF). In patients with AF, NT-proBNP levels did not differ between those with HF and preserved ejection fraction (EF) > 50% [n = 38; 603 (175;1070) pg/mL] and those without HF (P = 1.0). Receiver-operating characteristic curves of NT-proBNP showed a similar area under the curve (AUC) for the detection of AF at baseline (0.84, 95% CI [0.79-0.88]) and for HF with EF < 50% (0.78 [0.72-0.85]; P = 0.18). The AUC for HF with EF > 50% was significantly lower (0.61 [0.56-0.65]) than for AF (P = 0.001). During follow-up, AF was newly diagnosed in 157 (9.1%) and HF in 141 (9.6%) study participants. NT-proBNP was a better predictor of incident AF during the first 2 years (AUC: 0.79 [0.75-0.83]) than of newly diagnosed HF (0.59 [0.55-0.63]; P < 0.001). Data were validated in three independent population-based cohorts (LIFE-Adult, n = 2869; SHIP, n = 2013; and SHIP-TREND, n = 2408). CONCLUSIONS: In stable outpatients, NT-proBNP is a better marker for prevalent and incident AF than for HF. In AF patients, the diagnostic value of NT-proBNP for HF with EF > 50% is very limited.

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.

Out-of-Hospital Management of Diabetic Emergencies in Germany: Structural and Process Quality.

AIMS: To collect and analyse representative data of structural and process quality in the management of diabetic emergencies in Germany in 2020. METHODS: A standardised questionnaire comprising detailed items concerning clinically relevant parameters on the structural and process quality of out-of-hospital management of diabetic emergencies was sent nationwide to medical directors of emergency medical service districts (EMSDs). Results were compared with those from a similar study conducted in 2001. RESULTS: The return rate of the questionnaires represented 126 EMSDs, serving a total population of > 40.1 million. Only 4% of ambulances carried glucagon (6% in 2001). In 2020, blood glucose determination increased significantly to 71% of all emergency interventions and to 29% of suspected cardiac emergencies (24% and 15%, respectively, in 2001). In 100% of EMSDs severe hypoglycaemia (SH) was treated by paramedics by administering intravenous dextrose before the arrival of a doctor compared to 63% in 2001. The potential value of nasal glucagon was acknowledged by 43% of responders. In selected patients, treatment of SH was conducted without hospital admission in 78% of EMDs (60% in 2001). Fifty-three percent of medical directors acknowledged the need for further training in diabetic emergencies (47% in 2001). Cooperation for medical education between emergency teams and a diabetes centre was reported by 14% (41% in 2001). CONCLUSION: Structural and process quality of the management of diabetic emergencies in Germany has improved considerably since 2001. Persisting deficiencies could be improved by providing better medical equipment in ambulances and ongoing education to the entire emergency teams.

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 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.

Proximal aortic aneurysms: correlation of maximum aortic diameter and aortic wall thickness.

OBJECTIVES: The goal of therapy of proximal aortic aneurysms is to prevent an aortic catastrophe, e.g. acute dissection or rupture. The decision to intervene is currently based on maximum aortic diameter complemented by known risk factors like bicuspid aortic valve, positive family history or rapid growth rate. When applying Laplace's law, wall tension is determined by pressure × radius divided by aortic wall thickness. Because current imaging modalities lack precision, wall thickness is currently neglected. The purpose of our study was therefore to correlate maximum aortic diameter with aortic wall thickness and known indices for adverse aortic events. METHODS: Aortic samples from 292 patients were collected during cardiac surgery, of whom 158 presented with a bicuspid aortic valve and 134, with a tricuspid aortic valve. Aortic specimens were obtained during the operation and stored in 4% formaldehyde. Histological staining and analysis were performed to determine the thickness of the aortic wall. RESULTS: Patients were 62 ± 13 years old at the time of the operation; 77% were men. The mean aortic dimensions were 44 mm, 41 mm and 51 mm at the aortic root, sinotubular junction and ascending aorta, respectively. Aortic valve stenosis was the most frequent (49%) valvular dysfunction, followed by aortic valve regurgitation (33%) and combined dysfunction (10%). The maximum aortic diameter at the ascending level did not correlate with the thickness of the media (R = 0.07) or the intima (R = 0.28) at the convex sample site. There was also no correlation of the ascending aortic diameter with age (R = -0.18) or body surface area (R = 0.07). The thickness of the intima (r = 0.31) and the media (R = 0.035) did not correlate with the Svensson index of aortic risk. Similarly, there was a low (R = 0.29) or absent (R = -0.04) correlation between the aortic size index and the intima or media thickness, respectively. There was a similar relationship of median thickness of the intima in the 4 aortic height index risk categories (P < 0.001). CONCLUSIONS: Aortic diameter and conventional indices of aortic risk do not correlate with aortic wall thickness. Other indices may be required in order to identify patients at high risk for aortic complications.

Robotic-assisted Versus Laparoscopic Surgery: Outcomes from the First Multicentre, Randomised, Patient-blinded Controlled Trial in Radical Prostatectomy (LAP-01).

BACKGROUND: The LAP-01 trial was designed to address the lack of high-quality literature comparing robotic-assisted (RARP) and laparoscopic (LRP) radical prostatectomy. OBJECTIVE: To compare the functional and oncological outcomes between RARP and LRP at 3 mo of follow-up. DESIGN, SETTING, AND PARTICIPANTS: In this multicentre, randomised, patient-blinded controlled trial, patients referred for radical prostatectomy to four hospitals in Germany were randomly assigned (3:1) to undergo either RARP or LRP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was time to continence recovery at 3 mo based on the patient's pad diary. Secondary outcomes included continence and potency as well as quality of life in addition to oncological outcomes for up to 3 yr of follow-up. Time to continence was analysed by log-rank test and depicted by the Kaplan-Meier method. Continuous measurements were analysed by means of linear mixed models. RESULTS AND LIMITATIONS: A total of 782 patients were randomised. The primary endpoint was evaluable in 718 patients (547 RARPs; full analysis set). At 3 mo, the difference in continence rates was 8.7% in favour of RARP (54% vs 46%, p = 0.027). RARP remained superior to LRP even after adjustment for the randomisation stratum nerve sparing and age >65 yr (hazard ratio = 1.40 [1.09-1.81], p = 0.008). A significant benefit in early potency recovery was also identified, while similar oncological and morbidity outcomes were documented. It is a limitation that the influence of different anastomotic techniques was not investigated in this study. CONCLUSIONS: RARP resulted in significantly better continence recovery at 3 mo. PATIENT SUMMARY: In this randomised trial, we looked at the outcomes following radical prostate surgery in a large German population. We conclude that patients undergoing robotic prostatectomy had better continence than those undergoing laparoscopic surgery when assessed at 3 mo following surgery. Age and the nerve-sparing technique further affected continence restoration.

The diagnostic and prognostic value of galectin-3 in patients at risk for heart failure with preserved ejection fraction: results from the DIAST-CHF study.

AIMS: Galectin-3 (Gal-3) predicts long-term outcome among patients with heart failure (HF) with preserved ejection fraction (HFpEF). The ability of Gal-3 to diagnose and predict incident HFpEF in a cohort at risk for HFpEF is of particular interest. We aimed to determine the association between Gal-3 and clinical manifestations of HFpEF, the relationship between Gal-3 and all-cause mortality, or the composite of cardiovascular hospitalization and death. METHODS AND RESULTS: The observational Diast-CHF study included patients aged 50 to 85 years with ≥1 risk factor for HF (e.g. hypertension, diabetes mellitus, and atherosclerotic disease) or previously suspected HF. Patients were followed for 10 years. The association between Gal-3, evidence of diastolic dysfunction, and Framingham criteria for HF was examined. All deaths and hospitalizations were adjudicated as cardiovascular or non-cardiovascular. The analysis population was composed of 1386 subjects (67 years old, 50.9% female). The area under the receiver operating characteristic curve to diagnose HFpEF was 0.71. At a cut-off value of 13.57 ng/mL, sensitivity was 0.61 and specificity was 0.73 for Gal-3, and the diagnostic power to detect HFpEF was superior to N-terminal pro-brain natriuretic peptide (area under the receiver operating characteristic curve 0.59, P > 0.001). Baseline Gal-3 was associated with risk factors for HF (P < 0.001). Higher levels of Gal-3 predicted incident HFpEF (P < 0.05), adjusted all-cause mortality (P < 0.001), and the adjusted composite of cardiovascular hospitalization and death (P < 0.001), both independent from N-terminal pro-brain natriuretic peptide. CONCLUSIONS: Gal-3 differentiated patients with HFpEF from an overall cohort of well-characterized patients with risk factors for HFpEF. Independent of other factors, baseline Gal-3 levels were associated with a higher risk for incident HFpEF, mortality, or the composite of cardiovascular hospitalization and death over 10 year follow-up. In conjunction with clinical parameters, Gal-3 adds a statistically significant value for the diagnosis of HFpEF within this study, yet the clinical relevance remains debatable.

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.

Risk Factors for Deep Surgical Site Infection in Patients With Operatively Treated Tibial Plateau Fractures: A Retrospective Multicenter Study.

OBJECTIVES: To identify the potential controllable risk factors for surgical site infection (SSI). DESIGN: A retrospective cohort study. SETTING: Seven Level-I trauma centers. PATIENTS/PARTICIPANTS: Patients with OTA/AO 41 B or C tibial plateau fractures (n = 2106). INTERVENTION: Various surgical treatments for tibial plateau fractures. MAIN OUTCOME MEASUREMENTS: The primary outcome was SSI after the index operation. The secondary outcomes were the risk factors for SSI, identified using backward stepwise generalized multiple regression analysis. RESULTS: Of the 2106 enrolled patients, 94 had deep SSIs. The average SSI rate was 4.5%. Fracture morphology revealed type B injuries in 57.5% and type C in 42.5% of the patients. Univariate regression analysis revealed that several factors, namely, number of comorbidities [>6 vs. none; odds ratio (OR) 8.01, 95% confidence interval (CI) 2.8-22.8, P < 0.001], diabetes mellitus (OR 3.5, 95% CI 2.0-6.3, P < 0.001), high body mass index (OR 1.3, 95% CI 1.1-1.6, P = 0.001), OTA/AO fracture type C (OR 5.6, 95% CI 3.3-9.5, P < 0.001), compartment syndrome (OR 9.1, 95% CI 5.7-14.8, P < 0.001), and open fracture (OR 6.6, 95% CI 3.7-11.7, P < 0.001), were associated with a significantly higher SSI risk. Analysis of microbial sensitivity tests revealed that 55.1% of the pathogens were resistant to perioperative antibiotic prophylaxis. CONCLUSIONS: Most of the identified risk factors cannot be controlled or are subject to other factors that are difficult to control. However, our data suggest that the choice of perioperative antibiotic prophylaxis may influence the rate of SSI. This possibility should be investigated in a prospective randomized controlled trial. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.