Catheter Ablation in End-Stage Heart Failure with Atrial Fibrillation.

BACKGROUND: The role of catheter ablation in patients with symptomatic atrial fibrillation and end-stage heart failure is unknown. METHODS: We conducted a single-center, open-label trial in Germany that involved patients with symptomatic atrial fibrillation and end-stage heart failure who were referred for heart transplantation evaluation. Patients were assigned to receive catheter ablation and guideline-directed medical therapy or medical therapy alone. The primary end point was a composite of death from any cause, implantation of a left ventricular assist device, or urgent heart transplantation. RESULTS: A total of 97 patients were assigned to the ablation group and 97 to the medical-therapy group. The trial was stopped for efficacy by the data and safety monitoring board 1 year after randomization was completed. Catheter ablation was performed in 81 of 97 patients (84%) in the ablation group and in 16 of 97 patients (16%) in the medical-therapy group. After a median follow-up of 18.0 months (interquartile range, 14.6 to 22.6), a primary end-point event had occurred in 8 patients (8%) in the ablation group and in 29 patients (30%) in the medical-therapy group (hazard ratio, 0.24; 95% confidence interval [CI], 0.11 to 0.52; P<0.001). Death from any cause occurred in 6 patients (6%) in the ablation group and in 19 patients (20%) in the medical-therapy group (hazard ratio, 0.29; 95% CI, 0.12 to 0.72). Procedure-related complications occurred in 3 patients in the ablation group and in 1 patient in the medical-therapy group. CONCLUSIONS: Among patients with atrial fibrillation and end-stage heart failure, the combination of catheter ablation and guideline-directed medical therapy was associated with a lower likelihood of a composite of death from any cause, implantation of a left ventricular assist device, or urgent heart transplantation than medical therapy alone. (Funded by Else Kröner-Fresenius-Stiftung; CASTLE-HTx ClinicalTrials.gov number, NCT04649801.).

An exploratory research report on brain mineralization in postoperative delirium and cognitive decline.

Delirium is a severe postoperative complication associated with poor overall and especially neurocognitive prognosis. Altered brain mineralization is found in neurodegenerative disorders but has not been studied in postoperative delirium and postoperative cognitive decline. We hypothesized that mineralization-related hypointensity in susceptibility-weighted magnetic resonance imaging (SWI) is associated with postoperative delirium and cognitive decline. In an exploratory, hypothesis-generating study, we analysed a subsample of cognitively healthy patients ≥65 years who underwent SWI before (N = 65) and 3 months after surgery (N = 33). We measured relative SWI intensities in the basal ganglia, hippocampus and posterior basal forebrain cholinergic system (pBFCS). A post hoc analysis of two pBFCS subregions (Ch4, Ch4p) was conducted. Patients were screened for delirium until the seventh postoperative day. Cognitive testing was performed before and 3 months after surgery. Fourteen patients developed delirium. After adjustment for age, sex, preoperative cognition and region volume, only pBFCS hypointensity was associated with delirium (regression coefficient [90% CI]: B = -15.3 [-31.6; -0.8]). After adjustments for surgery duration, age, sex and region volume, perioperative change in relative SWI intensities of the pBFCS was associated with cognitive decline 3 months after surgery at a trend level (B = 6.8 [-0.9; 14.1]), which was probably driven by a stronger association in subregion Ch4p (B = 9.3 [2.3; 16.2]). Brain mineralization, particularly in the cerebral cholinergic system, could be a pathomechanism in postoperative delirium and cognitive decline. Evidence from our studies is limited because of the small sample and a SWI dataset unfit for iron quantification, and the analyses presented here should be considered exploratory.

A two-stage group-sequential design for delayed treatment responses with the possibility of trial restart.

Common statistical theory applicable to confirmatory phase III trial designs usually assumes that patients are enrolled simultaneously and there is no time gap between enrollment and outcome observation. However, in practice, patients are enrolled successively and there is a lag between the enrollment of a patient and the measurement of the primary outcome. For single-stage designs, the difference between theory and practice only impacts on the trial duration but not on the statistical analysis and its interpretation. For designs with interim analyses, however, the number of patients already enrolled into the trial and the number of patients with available outcome measurements differ, which can cause issues regarding the statistical analyses of the data. The main issue is that current methodologies either imply that at the time of the interim analysis there are so-called pipeline patients whose data are not used to make a statistical decision (like stopping early for efficacy) or the enrollment into the trial needs to be at least paused for interim analysis to avoid pipeline patients. There are methods for delayed responses available that introduced error-spending stopping boundaries for the enrollment of patients followed by critical values to reject the null hypothesis in case the stopping boundaries have been crossed beforehand. Here, we will discuss other solutions, considering different boundary determination algorithms using conditional power and introducing a design allowing for recruitment restart while keeping the type I error rate controlled.

Sample size planning for rank-based multiple contrast tests.

Rank methods are well-established tools for comparing two or multiple (independent) groups. Statistical planning methods for the computing the required sample size(s) to detect a specific alternative with predefined power are lacking. In the present paper, we develop numerical algorithms for sample size planning of pseudo-rank-based multiple contrast tests. We discuss the treatment effects and different ways to approximate variance parameters within the estimation scheme. We further compare pairwise with global rank methods in detail. Extensive simulation studies show that the sample size estimators are accurate. A real data example illustrates the application of the methods.

Outcomes of Endurant II Stent Graft According to Anatomic Severity Grade Score.

OBJECTIVES: This study's objective was to evaluate Endurant II (Medtronic Inc, Minneapolis, Minnesota) stent graft's early and midterm outcomes and compare the results according to the anatomic severity grade (ASG) scores. METHODS: This was a retrospective study of patients treated with the Endurant II stent graft between January 2013 and May 2021. The patients were divided into 2 independent groups, including those with a low ASG score (score <14) and a high ASG score (score >14). RESULTS: A total of 165 consecutive patients (89% males, age 74±8 years) were included. There were 110 (67%) patients in the low-score group and 55 (33%) patients in the high-score group. Technical success was achieved in all cases. Primary clinical success at 30 days was 100% and at 1 year was 96%. Median operative time was longer in the high-score group with no statistical significance (133 vs 120 minutes, p=0.116). The median dose area product of low-score patients (50.9 Gy·cm2; IQR 22.4-75.5 Gy·cm2) was significantly lower than high-score patients (85.0 Gy·cm2; IQR 46.5-127.9 Gy·cm2) with p=0.025. Median fluoroscopic time was lower in low-score patients (17 minutes; IQR 13-24 minutes) compared with high-score patients (19 minutes; IQR 16-23 minutes) without a significant difference at p=0.148. At a midterm follow-up of 32 months (range 2-63 months), combined complications (29% vs 8%, p<0.001) and implant-related complications (13% vs 4%, p=0.043) were higher in the high-score group. Systemic complications at 30 days were higher in the high-score group without a statistically significant difference (15% vs 11%, p=0.500). The Kaplan-Meier estimate of freedom from reintervention was significantly higher in the low-risk group at 1 (97% vs 90%), 2 (96% vs 88%), and 3 years (96% vs 85%) with (p=0.035). The cumulative survival rate was significantly higher in the low-score group than high-score group (p=0.001) at 1 (99% vs 87%), 2 (98% vs 85%), and 3 years (96% vs 82%). CONCLUSIONS: Endurant II endovascular aneurysm repair seems to be safe in both low-score and high-score patients. However, patients in the high-score group showed more implant-related complications and midterm mortalities than those in the low-score group.

Neoaortoiliac system and cryopreserved human allograft for the treatment of aortic graft infections.

OBJECTIVE: To report and compare neoaortoiliac system reconstruction and cryopreserved human allograft in treating aortic graft infections. METHODS: We retrospectively analysed the data of the patients treated for aorto graft infections between January 2015 and May 2021 in our hospital. The clinical data, diagnostic procedures, and surgical options were evaluated. The primary endpoint of this study was the 30-day and 1-year mortality; secondary endpoints were major postoperative complications. RESULTS: We retrospectively reviewed a series of 31 consecutive patients (28 males; median age 72 years, range, 50-87 years) with aortic graft infection treated with NAIS (n = 20, 65%) or cryopreserved allograft (n = 11, 36%). The clinical presentation included fever attacks in 18 (58%) patients, abdominal pain in 15 (48%) patients, haemodynamic instability in 6 (19%) patients, and haematemesis in 2 (7%) patients. The median operative time of the NAIS was longer than CHA without a statistically significant difference (458 min vs. 359 min, p = .505). The postoperative morbidity for all patients was 81%, with no significant difference between NAIS and CHA groups (85% vs. 73%, p = .638). There was no limb thrombosis of the new reconstructions. Limb loss occurred in 4 (13%) patients, including 2 (10%) NAIS patients and 2 (18%) CHA patients. One NAIS patient developed complications in the form of a distal (femoral) disruption of the vein 15 days after surgery. There were no significant differences between NAIS and CHA groups in ICU stay (12 vs 8 days, .984) but in hospitalization (22 vs 33, p = .033). The most common bacteria isolated were staphylococci strains in 15 (48%). In 13 (36%) patients, candida was positive. The in-hospital 30-day and 1-year mortality for all patients was 16% (5/31) and 29% (9/31), with no significant differences between NAIS and CHA at 30 days (25% vs. 0, p = .133) or 1 year (35% vs. 18%, .429). Five NAIS patients died during the hospital stay; three of them had end-of-life decisions. After a median follow-up of 16 months (1-66 months), 12 (39%) patients died, including 9 patients with NAIS and 3 with CHA reconstructions. The causes of death included overwhelming sepsis in 5 (42%) patients, graft disruption in one (8%) NAIS patient, non-small cell lung cancer in one (8%) patient, COVID-19 in one (8%) patient and unknown causes (8%) in one. CONCLUSIONS: Non-staged neoaortoiliac system reconstruction and cryopreserved human allografts show comparable short- and midterm results for treating aortic graft infections. However, both procedures remain challenging with high morbidity and mortality rates.

Sample size planning for multiple contrast tests.

Sample size calculations for two (independent) samples are well established and applied in (pre-)clinical research. When planning several samples, which is common in, for example, preclinical studies, sample size planning tools based on analysis of variance methods are available. Since the underlying effect sizes of these methods are often hard to interpret and to provide for the sample size planning, we employ multiple contrast test procedures for sample size computations in both parametric (under normality assumption) and nonparametric designs using Steel-type tests. Since the exact distributions of the test statistics are unknown under the alternative and variance heterogeneity, we use approximate solutions. Furthermore, since no closed formula for the sample size is available, we use numerical approximations for their computation. Extensive simulation studies are finally conducted to assess the quality of the approximations. It turns out that the methods are accurate in the sense that the multiple contrast test procedures reach the target power to detect the alternative of interest with the sample size computed. The developed procedures are a valuable tool to plan (pre-)clinical trials with several samples and are easily accessible in publicly available software.

Statistical review of animal trials-A guideline.

Any experiment involving living organisms requires justification of the need and moral defensibleness of the study. Statistical planning, design, and sample size calculation of the experiment are no less important review criteria than general medical and ethical points to consider. Errors made in the statistical planning and data evaluation phase can have severe consequences on both results and conclusions. They might proliferate and thus impact future trials-an unintended outcome of fundamental research with profound ethical consequences. Unified statistical standards are currently missing for animal review boards in Germany. In order to accompany, we developed a biometric form to be filled and handed in with the proposal at the concerned local authority on animal welfare. It addresses relevant points to consider for biostatistical planning of animal experiments and can help both the applicants and the reviewers in overseeing the entire experiment(s) planned. Furthermore, the form might also aid in meeting the current standards set by the 3+3R's principle of animal experimentation: Replacement, Reduction, Refinement as well as Robustness, Registration, and Reporting. The form has already been in use by the concerned local authority of animal welfare in Berlin, Germany. In addition, we provide reference to our user guide giving more detailed explanation and examples for each section of the biometric form. Unifying the set of biostatistical aspects will help both the applicants and the reviewers to equal standards and increase quality of preclinical research projects, also for translational, multicenter, or international studies.

Motor training-related brain reorganization in patients with cerebellar degeneration.

Cerebellar degeneration progressively impairs motor function. Recent research showed that cerebellar patients can improve motor performance with practice, but the optimal feedback type (visual, proprioceptive, verbal) for such learning and the underlying neuroplastic changes are unknown. Here, patients with cerebellar degeneration (N = 40) and age- and sex-matched healthy controls (N = 40) practiced single-joint, goal-directed forearm movements for 5 days. Cerebellar patients improved performance during visuomotor practice, but a training focusing on either proprioceptive feedback, or explicit verbal feedback and instruction did not show additional benefits. Voxel-based morphometry revealed that after training gray matter volume (GMV) was increased prominently in the visual association cortices of controls, whereas cerebellar patients exhibited GMV increase predominantly in premotor cortex. The premotor cortex as a recipient of cerebellar efferents appears to be an important hub in compensatory remodeling following damage of the cerebro-cerebellar motor system.

Endothelial dysfunction and altered endothelial biomarkers in patients with post-COVID-19 syndrome and chronic fatigue syndrome (ME/CFS).

BACKGROUND: Fatigue, exertion intolerance and post-exertional malaise are among the most frequent symptoms of Post-COVID Syndrome (PCS), with a subset of patients fulfilling criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). As SARS-CoV-2 infects endothelial cells, causing endotheliitis and damaging the endothelium, we investigated endothelial dysfunction (ED) and endothelial biomarkers in patients with PCS. METHODS: We studied the endothelial function in 30 PCS patients with persistent fatigue and exertion intolerance as well as in 15 age- and sex matched seronegative healthy controls (HCs). 14 patients fulfilled the diagnostic criteria for ME/CFS. The other patients were considered to have PCS. Peripheral endothelial function was assessed by the reactive hyperaemia index (RHI) using peripheral arterial tonometry (PAT) in patients and HCs. In a larger cohort of patients and HCs, including post-COVID reconvalescents (PCHCs), Endothelin-1 (ET-1), Angiopoietin-2 (Ang-2), Endocan (ESM-1), IL-8, Angiotensin-Converting Enzyme (ACE) and ACE2 were analysed as endothelial biomarkers. RESULTS: Five of the 14 post-COVID ME/CFS patients and five of the 16 PCS patients showed ED defined by a diminished RHI (< 1.67), but none of HCs exhibited this finding. A paradoxical positive correlation of RHI with age, blood pressure and BMI was found in PCS but not ME/CFS patients. The ET-1 concentration was significantly elevated in both ME/CFS and PCS patients compared to HCs and PCHCs. The serum Ang-2 concentration was lower in both PCS patients and PCHCs compared to HCs. CONCLUSION: A subset of PCS patients display evidence for ED shown by a diminished RHI and altered endothelial biomarkers. Different associations of the RHI with clinical parameters as well as varying biomarker profiles may suggest distinct pathomechanisms among patient subgroups.

A frozen decade: Ten years outcome of atrial fibrillation ablation using a single shot device for pulmonary vein isolation.

AIMS: Cryoballoon-guided pulmonary vein isolation (CB-PVI) for symptomatic atrial fibrillation (AF) has become an established treatment option with encouraging results in terms of safety and efficacy. Data reporting on long-term data beyond a follow-up (FU) period of 5 years is scarce. This prospective study aimed to evaluate very long-term outcome after CB-PVI for AF. METHODS: Data from consecutive patients treated with CB-PVI for symptomatic and drug refractory AF between 2005 and 2012 were analyzed. Patients with a FU of ≥9 years after index CB-PVI were included. All patients were continuously followed-up in our outpatient clinic. Arrhythmia recurrence was defined as AF or atrial tachycardia (AT) lasting >30 s beyond a 3-month blanking period. RESULTS: A total of 385 patients (71% male) were included. Mean age was 58 ± 10 years and paroxysmal AF was present in 93% of patients. Mean FU duration was 124 ± 24 months. At the end of the observational period, 73% of all patients were in stable sinus rhythm after a mean of 2 ± 0.8 ablation procedures. Patients with AF/AT recurrence were older (60 ± 8 vs. 57 ± 10 years; p = .019), had a higher CHA2 DS2 -Vasc Score (2.47 ± 1.46 vs. 1.98 ± 1.50; p = .01) and presented with a larger left atrium (LA)-diameter (43 ± 5.6 vs. 40 ± 5.1 mm; p = .002). The LA-diameter was also a significant predictor for AF/AT recurrence after CB-PVI (odds ratio: 0.939, 95% confidence interval: [0.886, 0.992], p = .03). CONCLUSIONS: CB-PVI as index procedure for AF ablation resulted in favorable long-term outcome in symptomatic AF. CB-PVI might be recommended as interventional therapy in patients with lower LA remodeling.

Isolated Ruptured Paravisceral Penetrating Aortic Ulcers.

BACKGROUND: The goal of this study is to investigate the clinical presentation, treatment options, and outcomes of the patients with isolated ruptured paravisceral penetrating aortic ulcers (PV-PAU). METHODS: All patients presenting with acute aortic syndrome from 2015 to 2020 were screened, of which patients with isolated ruptured PV-PAU were included in this retrospective study. Study endpoints were the assessment of treatment options, technical success, and clinical outcome. Outcome measures included major perioperative complications and mortality. RESULTS: Sixteen patients (11 men; median age 68; IQR 60 - 75 years) presented with isolated ruptured PV-PAU were included in this study. The median follow-up was 25 months (range 1 - 51). Ruptured PV-PAUs represented 12.3% of the ruptured aortic aneurysms in all locations. PV-PAUs were found in segment A (n = 8, 50%), segment B (n = 5, 31%), and segment C (n = 3, 19%). PV-PAUs showed a mean protrusion distance of 27±10 mm, a mean neck diameter of 21 ± 7 mm, and maximal aortic diameter of 50 ± 11 mm. Five patients (31%) showed hemodynamic instability on admission and needed intense fluid resuscitation. Of those, 2 patients needed urgent laparotomy with a fast transabdominal supraceliac aortic clamping, one needed an aortic balloon occlusion to obtain rapid aortic control. The open aortic repair was the most frequently performed surgery (11/16, 69%), followed by hybrid procedures (3/16) and parallel graft chimney technique (2/16). Two patients died during the follow-up, calculating for in-hospital and 1-year mortality rates of 6 - 12%, respectively. The postoperative morbidity rate was 31%. Postoperative complications included acute renal failure (31%), pneumonia (25%), and 1case of ischemic colitis (6%). No spinal cord ischemia was reported. CONCLUSIONS: Ruptured PV-PAU is a rare and challenging diagnostic and therapeutic entity. Open aortic repair seems to be a reliable option in treating patients with isolated ruptured PV-PAUs. Hybrid procedures and parallel stent-graft techniques can only be used in selected patients.

Risk factors for elective and urgent open conversion after EVAR-a retrospective observational study.

BACKGROUND: Endovascular aortic aneurysm repair (EVAR) has become the standard procedure for treating infrarenal abdominal aortic aneurysms (AAA). Various associated complications can lead to open conversion (OC). Thorough follow-up after the procedure is mandatory for the early detection of complications. Persisting perfusion of the aneurysm, a so-called endoleak (EL), paired with structural instability because of aortic wall atrophy and impaired cell functionality induced by EVAR, results in a high risk for aortic rupture. PURPOSE: The goal of this study was to detect the risk factors for elective and urgent OC as a result of EVAR-induced pathophysiological changes inside the aortic wall. RESEARCH DESIGN: Retrospective data analysis was performed on all open aortic repairs from January 2016 to December 2020. DATA COLLECTION AND ANALYSIS: Fifty patients were identified as treated by OC for failure of an infrarenal EVAR. The patients were divided into two subgroups, here depending on the urgency of surgery. Statistical analysis of patient characteristics and outcomes was performed. RESULTS: The most common indications for OC were various types of EL (74%), resulting in an aortic rupture in 15 patients. Patients with insufficient or absent follow-up were treated more frequently in an emergency setting (16% vs. 63%). The mortality rate was higher in cases of emergency OC (3% vs. 26%). CONCLUSIONS: Particularly in cases of insufficient or absent follow-up, complications such as EL pose an enormous risk for fatal aortic rupture.

Effectiveness of different fiber post removal techniques and their influence on dentinal microcrack formation.

OBJECTIVES: The aim of this study was to evaluate the effectiveness of different fiber post removal techniques and to correlate dentinal loss with microcrack formation. MATERIALS AND METHODS: Forty-five extracted single-rooted teeth were root canal treated and fiber posts were adhesively luted. Specimens were divided into three groups (n = 15) according to the removal technique: long-shaft round bur (EndoTracer #08, Komet, Lemgo, Germany), SonicFlex Endo (KaVo, Biberach, Germany), DT Post Removal Kit (VDW, Munich, Germany). Roots were scanned before post cementation and after post removal using micro-computed tomography. Dentin loss, residual luting material, working time, and the induction of microcracks were assessed. Statistical analysis was performed by using multiple contrast tests (max-t tests, α = 0.05). Correlations between parameters dentin loss/new microcracks and dentin loss/residual material were calculated using Kendall's tau. RESULTS: Post removal with SonicFlex Endo resulted in the highest amount of removed dentin with significant differences to the round bur and the DT Post Removal Kit. No technique was found to completely remove the post and luting material. All techniques induced microcracks with the DT Post Removal Kit presenting the highest number of new defects. No correlation between dentin loss and new microcracks was observed. Deviations from the original root canal occurred in all groups, but no perforation was observed. CONCLUSIONS: All techniques resulted in dentin loss, residual luting material, and the formation of microcracks. However, no correlation between dentin loss and the induction of microcracks was observed. CLINICAL RELEVANCE: As all techniques resulted in microcrack formation and dentin loss, this study emphasizes the risk of iatrogenic damage due to post removal procedures.

Perioperative risk prediction using the POSSUM and V-POSSUM models in symptomatic carotid stenosis.

Background: This study aimed to evaluate risk factors for adverse outcomes and perioperative stroke and death in patients with symptomatic carotid stenosis undergoing open endarterectomy (CEA). The second objective was to assess the predictive value of the POSSUM and V-POSSUM models for predicting morbidity and mortality from CEA in symptomatic carotid stenosis. Patients and methods: A retrospective observational study of all patients admitted to a single center who underwent CEA for symptomatic carotid stenosis was performed. 320 patients from 1999 to 2013 were included. Postoperative complications, 30-day survival, and stroke rates were recorded. The observed outcomes were compared to the POSSUM and V-POSSUM expected mortality (observed to expected ratio (O:E)). Results: The mean age was 68.1±10.0 years. 215 patients were male (67%). Risk factors for surgical complications were: age, with a higher risk in both groups of less than 60 years and more than 75 years of age (p=0.04), a higher ASA score (p=0.04), and hyperlipidemia (p=0.017). Risk factors for the combined endpoint stroke or death were a higher ASA category (p<0.001), stroke as indication for CEA (p 0.022), and a high degree of stenosis (p=0.019). For POSSUM predicted mortality, there was a good O:E ratio in the two lowest risk groups, but a 2-fold overprediction of death or stroke in the two high-risk strata. The area under the curve (AUC) was 0.58 (95% CI: 0.43-0.73). The V-POSSUM showed a better fit in the high-risk groups, but an underprediction of mortality in the low-risk strata. Conclusions: Age and comorbid conditions are risk factors for adverse outcomes after CEA. The V-POSSUM model is better than POSSUM to predict postoperative death and stroke after CEA in patients with symptomatic carotid stenosis and a high preoperative physiological score. In patients with low physiological scores, both POSSUM and V-POSSUM show a limited predictive value.

Aortoduodenal fistulas after endovascular abdominal aortic aneurysm repair and open aortic repair.

OBJECTIVE: In the present study, we have reported and compared aortoduodenal fistulas (ADFs) after endovascular abdominal aortic aneurysm repair (EVAR) vs after open aortic repair (OAR). METHODS: We retrospectively analyzed the data from patients treated for ADFs from January 2015 to May 2020 in our hospital. The clinical data, diagnostic procedures, and surgical options were evaluated. The primary endpoints of the present study were 30-day and 1-year mortality. The secondary endpoints were major postoperative complications. RESULTS: A total of 24 patients (20 men; median age, 69 years; range, 53-82 years) were admitted with ADFs after EVAR (n = 9) or OAR (n = 15). These patients accounted for ∼4.3% of all abdominal aortic aneurysm repairs in our hospital. The median interval from the initial aortic repair and the diagnosis of ADF was 68 months (range, 6-83 months) for the ADF-EVAR group and 80 months (range, 1-479 months) for the ADF-OAR group. Three patients in the ADF-EVAR group had refused surgical treatment owing to their high surgical risk. One patient in the ADF-OAR group had undergone removal of the aortic prosthesis without replacement. Of the remaining 20 patients, 12 (ADF-EVAR group, n = 4; ADF-OAR group, n = 8) had undergone in situ replacement of the aorta and 8 (ADF-EVAR group, n = 2; ADF-OAR group, n = 6) had undergone extra-anatomic reconstruction with aortic ligation. After a mean follow-up of 26 months, no patient had experienced early limb loss. However, one case of rupture of the venous graft (ADF-EVAR), one case of aortic stump blowout (ADF-OAR), and one case of a ureteroarterial fistula with a homograft (ADF-OAR) had occurred. Overall, the incidence of postoperative complications was significantly greater after ADF-OAR (93% vs 33%; P = .036). The most frequent bacteria involved in the blood cultures were Escherichia coli (25% of patients), and Candida spp. (61%) were the predominant pathogens found on intra-abdominal smears. The in-hospital mortality rates for the ADF-EVAR and ADF-OAR group were 22% and 13%, respectively. The corresponding 1 -year mortality rates were 22% and 33%. CONCLUSIONS: Patients with ADFs after EVAR or OAR have limited overall survival. In addition to the similar therapeutic approaches, we found no significant differences in postoperative mortality between these two uncommon pathologic entities. In our study, the overall postoperative morbidity seemed greater for the ADF-OAR group.

Analysis of covariance under variance heteroscedasticity in general factorial designs.

Adjusting for baseline values and covariates is a recurrent statistical problem in medical science. In particular, variance heteroscedasticity is non-negligible in experimental designs and ignoring it might result in false conclusions. Approximate inference methods are developed to test null hypotheses formulated in terms of adjusted treatment effects and regression parameters in general analysis of covariance designs with arbitrary numbers of factors. Variance homoscedasticity is not assumed. The distributions of the test statistics are approximated using Box-type approximation methods. Extensive simulation studies show that the procedures are particularly suitable when sample sizes are rather small. A real data set illustrates the application of the methods.

Preoperative and ICU Scoring Models for Predicting the In-Hospital Mortality of Patients With Ruptured Abdominal Aortic Aneurysms.

OBJECTIVES: This study's objective was to compare several preoperative and intensive care unit (ICU) prognostic scoring systems for predicting the in-hospital mortality of ruptured abdominal aortic aneurysms (RAAAs). DESIGN: Retrospective cohort study. SETTING: Single tertiary university center. PARTICIPANTS: The study comprised 157 patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 157 patients (82% male) presented with RAAA at Charité University Hospital from January 2011 to December 2020. The mean age was 74 years (standard deviation ten years). In-hospital mortality was 29% (n = 45), of whom nine patients (6%) died en route to the operating room, 13 (8%) on the operating table, and 23 (15%) in the ICU. A total of 135 patients (86%) were admitted to the ICU. All six models demonstrated good discriminating performance between survivors and nonsurvivors. Overall, the area under the curve (AUC) for RAAA preoperative scores was greater than those for ICU scores. The largest AUC was achieved with the Vascular Study Group of New England (VSGNE) RAAA risk score (AUC = 0.87 for all patients, AUC = 0.84 for patients admitted to the ICU), followed by Hardman Index (AUC = 0.83 for all patients, AUC = 0.81 for patients admitted to the ICU), and Glasgow Aneurysm Score (AUC = 0.74 for all patients, AUC = 0.83 for patients admitted to the ICU). The largest AUC for ICU scores (only patients admitted to the ICU) was achieved with Simplified Acute Physiology Score II (0.75), followed by Sepsis-related Organ Failure Assessment (0.73), and Acute Physiology and Chronic Health Evaluation II (0.71). CONCLUSIONS: Preoperative and ICU scores can predict the mortality of patients presenting with RAAA. In addition, the discriminatory ability of preoperative scores between survivors and nonsurvivors was larger than that for ICU scores.

Endovascular and open surgical options in the treatment of uretero-arterial fistulas.

OBJECTIVE: To report and analyze the indications and results of endovascular and open surgical treatment for uretero-arterial fistula. METHODS: We retrospectively reviewed the clinical data of 25 consecutive patients with uretero-arterial fistulas admitted to our hospital from 2011 to 2020. Endpoints were technical success, freedom from open conversion, stent-graft/graft-related complications, and 30-day and one-year mortality. RESULTS: The study included 25 patients (68% female, n = 17) with 27 uretero-arterial fistulas by bilateral pathologies in two patients. The mean age was 61 ± 11 years (range 35-80). The most common predisposing factors for uretero-arterial fistula were history of pelvic operations for malignancy in 21 patients (84%), radiotherapy in 21 patients (84%), previous pelvic vascular bypass in 2 patients (8%), and iliac aneurysms in 2 patients (8%). On average, the period between the primary pelvic surgery and the diagnosis of uretero-arterial fistulas was 46 months (range 7-255). Twenty patients (80%) underwent endovascular treatment of the uretero-arterial fistulas. The primary technical success of the endovascular treatment was 95%, and the freedom from open conversion was 40% at six months and 30% at one year. Thirteen uretero-arterial fistulas (48%) underwent delayed open conversion due to recurrent bleeding in six cases (46%), stent-graft infection in three cases (23%), or pelvic abscess in four cases (31%). Primary open surgery was applied for five (20%) patients. After a mean follow-up of 34 months, early (<30 days) mortality was 8% (2/25), one-year mortality 16% (4/25), and overall mortality was 24% (6/25). CONCLUSIONS: Uretero-arterial fistula is a late complication of prior pelvic surgery, radiation, and indwelling ureteral stents. Endovascular treatment remains an effective and less invasive modality in controlling the related life-threatening arterial bleeding of the uretero-arterial fistula. Open surgical treatment is still required for patients with local sepsis, previously failed endovascular treatment or infected stent-grafts.

The nonparametric Behrens-Fisher problem in partially complete clustered data.

In randomized trials or observational studies involving clustered units, the assumption of independence within clusters is not practical. Existing parametric or semiparametric methods assume specific dependence structures within a cluster. Furthermore, parametric model assumptions may not even be realistic when data are measured in a nonmetric scale as commonly happens, for example, in quality-of-life outcomes. In this paper, nonparametric effect-size measures for clustered data that allow meaningful and interpretable probabilistic comparisons of treatments or intervention programs will be introduced. The dependence among observations within a cluster can be arbitrary. Point estimators along with their asymptotic properties for computing confidence intervals and performing hypothesis test will be discussed. Small sample approximations that retain some of the optimal asymptotic behaviors will be presented. In our setup, some clusters may involve observations coming from both intervention groups (referred to as complete clusters), while others may contain observations from one group only (referred to as incomplete clusters). In deriving the asymptotic theories, we do not impose any relation in the rate of divergence of the numbers of complete and incomplete clusters. Simulations show favorable performance of the methods for arbitrary combinations of complete and incomplete clusters. The developed nonparametric methods are illustrated using data from a randomized trial of indoor wood smoke reduction to improve asthma symptoms and a cluster-randomized trial for smoking cessation.