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A subset of patients has long-lasting symptoms after mild to moderate Coronavirus disease 2019 (COVID-19). In a prospective observational cohort study, we analyze clinical and laboratory parameters in 42 post-COVID-19 syndrome patients (29 female/13 male, median age 36.5 years) with persistent moderate to severe fatigue and exertion intolerance six months following COVID-19. Further we evaluate an age- and sex-matched postinfectious non-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome cohort comparatively. Most post-COVID-19 syndrome patients are moderately to severely impaired in daily live. 19 post-COVID-19 syndrome patients fulfill the 2003 Canadian Consensus Criteria for myalgic encephalomyelitis/chronic fatigue syndrome. Disease severity and symptom burden is similar in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome and non-COVID-19/myalgic encephalomyelitis/chronic fatigue syndrome patients. Hand grip strength is diminished in most patients compared to normal values in healthy. Association of hand grip strength with hemoglobin, interleukin 8 and C-reactive protein in post-COVID-19 syndrome/non-myalgic encephalomyelitis/chronic fatigue syndrome and with hemoglobin, N-terminal prohormone of brain natriuretic peptide, bilirubin, and ferritin in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome may indicate low level inflammation and hypoperfusion as potential pathomechanisms. Some patients experience long-lasting symptoms after coronavirus disease (COVID-19). Here the authors report the clinical and laboratory parameters in patients with post-COVID-19 syndrome from a prospective observational cohort study. [ABSTRACT FROM AUTHOR]

Aim To compare the efficacy of reciprocating and rotary Ni Ti-instruments in removing filling material from curved root canals using micro-computed tomography. Methodology Sixty curved root canals were prepared and filled with gutta-percha and sealer. After determination of root canal curvatures and radii in two directions as well as volumes of filling material, the teeth were assigned to three comparable groups ( n = 20). Retreatment was performed using Reciproc, ProTaper Universal Retreatment or Hedström files. Percentages of residual filling material and dentine removal were assessed using micro- CT imaging. Working time and procedural errors were recorded. Statistical analysis was performed by variance procedures. Results No significant differences amongst the three retreatment techniques concerning residual filling material were detected ( P > 0.05). Hedström files removed significantly more dentine than ProTaper Universal Retreatment ( P < 0.05), but the difference concerning dentine removal between both Ni Ti systems was not significant ( P > 0.05). Reciproc and ProTaper Universal Retreatment were significantly faster than Hedström files ( P = 0.0001). No procedural errors such as instrument fracture, blockage, ledging or perforation were detected for Hedström files. Three perforations were recorded for ProTaper Universal Retreatment, and in both NiTi groups, one instrument fracture occured. Conclusions Remnants of filling material were observed in all samples with no significant differences between the three techniques. Hedström files removed significantly more dentine than ProTaper Universal Retreatment, but no significant differences between both NiTi systems were detected. Procedural errors were observed with ProTaper Universal Retreatment and Reciproc. [ABSTRACT FROM AUTHOR]

The object of this study was to assess the clinical usefulness of computer-assisted diagnosis (CAD) in the interpretation of early-research, benign and malignant mammograms in dependence on readers’ experience with CAD. CAD was applied on digital mammograms of 303 patients who were divided into three groups: early-research ( n = 103), benign ( n = 102) and malignant group ( n = 98). Mammograms were analyzed by three readers with different experience in evaluating mammograms (medical student, an assistant and an attending physician specifically trained in mammography). All images were presented accidentally with and without the influence of CAD and from different patient groups. The mammograms were classified according to BI-RADS classification. To evaluate readers’ sensitivity and specificity with and without the application of the CAD system, ROC analysis and the corresponding area under the curve (AUC) were evaluated for each reader. Afterwards significant differences of the accuracy according to readers experience and according to the assistance of the CAD system were calculated. All readers have an account of accuracy by using CAD in both patient groups. The highest benefit has the student (10% increase of the AUC) followed by the resident (4%) and at least followed by the mammography fellow (3%). There are significant varieties of the accuracy in addiction to the readers’ experience and to the examination method with and without CAD system. Patient group has not a significant influence to the elevation of accuracy by using the CAD. All three readers have nearly the same increase of AUC in the examinations of malignant and early-research group summarized and of the malignant group only. Finally, the increase of accuracy depends on the readers’ experience. For all patient groups CAD-application causes a steeply increase of the ROC curve and consequently a gain of sensitivity. [ABSTRACT FROM AUTHOR]

Rödig T, Sedghi M, Konietschke F, Lange K, Ziebolz D, Hülsmann M. Efficacy of syringe irrigation, RinsEndo® and passive ultrasonic irrigation in removing debris from irregularities in root canals with different apical sizes. International Endodontic Journal, 43, 581–589, 2010. Aim To compare of the efficacy of syringe irrigation, RinsEndo® (Dürr Dental, Bietigheim, Germany) and passive ultrasonic irrigation (PUI) in the removal of dentinal debris from simulated irregularities in root canals with different apical sizes. Methodology Thirty extracted human pre-molars were randomly divided into three groups ( n = 10) followed by root canal preparation with rotary FlexMaster® NiTi instruments (VDW, Munich, Germany) to size 30, 0.02 taper (group 1), size 40, 0.02 taper (group 2) or size 50, 0.02 taper (group 3). The teeth were split longitudinally, and a standard groove and three hemispherical-shaped cavities were cut into the root canal halves. Grooves and cavities were filled with dentinal debris before each irrigation procedure and the root halves were reassembled. In all groups three different irrigation procedures were performed with 30 mL NaOCl (1%) and (i) syringe, (ii) RinsEndo® and (iii) PUI. The amount of remaining debris was evaluated under a microscope with 30× magnification and a four score system. The data were analysed with a non-parametric analysis of covariance and multiple comparisons using the Tukey adjustment ( P = 0.05). Results Passive ultrasonic irrigation removed debris significantly better from the artificial canal irregularities than RinsEndo® and syringe irrigation irrespective of the root canal diameter. Only in group 1 (30, 0.02 taper) the difference between PUI and RinsEndo® was not statistically significant ( P = 0.99). RinsEndo® demonstrated significantly better results than syringe irrigation in all groups ( P < 0.001). Conclusions Ultrasonic irrigation is more effective than syringe irrigation or RinsEndo® in removing debris from artificial extensions in straight root canals. [ABSTRACT FROM AUTHOR]

Background: Advances in CT technology from single to multi-detector row CT (MDCT) permit a high resolution and volumetric presentation of pulmonary lesions. This implicates emerging measurement techniques that need to be contrasted with established methods. Purpose: To compare bidimensional, unidimensional, and volumetric methods for evaluation of treatment response in patients with lung lesions. Material and Methods: This study comprised 68 patients with pulmonary lesions who underwent a total of 276 64-MDCTs of chest at baseline and follow-up. RECIST and WHO criteria were used for unidimensional and bidimensional methods and region growing (RG) for volumetry. Patients were classified into four response categories. Respectively, two measurement techniques were contrasted and the kappa index was calculated. For intra-observer reproducibility the relative measurement error (RME) and kappa index with regard to agreement of response categories were evaluated. Results: Comparison of WHO und RECIST criteria achieves high correlation with kappa indices of 0.76 and 0.82. In particular, lesions with moderate increase of size in the range of 25-44% for bidimensional and 12-29% for unidimensional measurement result in different response categories when applying WHO and RECIST criteria. WHO criteria delivered PD more often than RECIST. kappa indices of 0.79 and 0.87 were attained in comparison of RECIST and RG, and 0.83 and 0.84 for WHO and RG. RME was 2.82% for RECIST, 7.53% for WHO, and 8.97% for RG. Intra-observer reproducibility was 95% for RECIST, 95% for WHO, and 96% for RG. Conclusion: The comparison of all methods resulted in no statistically significant differences. WHO criteria seemed to diverge the most, they declared several lesions prematurely as progression, and showed no benefit in comparison to RECIST. RG showed the best reproducibility, considered irregular lesions, was slightly superior to RECIST, and could be applied uniformly. Unidimensional measurement represents an adequate alternative with the advantage of better clinical work flow. [ABSTRACT FROM AUTHOR]

Aims: Timely referrals for transplantation and left ventricular assist device (LVAD) play a key role in favourable outcomes in patients with advanced heart failure (HF). Cardiovascular mortality, driven by sudden cardiac death, is the main reason for dying while waiting for heart transplantation (HTx). The purpose of the Preventive Catheter Ablation for ventricular arrhythmiaS in patients with end-sTage heart faiLure rEferred for heart transplantation eValuaTion (CASTLE-VT) trial is to test the hypothesis that prophylactic catheter ablation of arrhythmogenic ventricular scar tissue will reduce mortality, need for LVAD implantation, and urgent HTx in patients with end-stage HF related to ischaemic cardiomyopathy (ICM)., Methods: CASTLE-VT is a randomized evaluation of prophylactic ablative treatment of arrhythmogenic ventricular scar in patients referred for HTx evaluation and diagnosed with ICM. Ablation will be performed with the use of a substrate-based approach in which the myocardial scar is mapped and ablated while the heart remains predominantly in sinus rhythm. The primary endpoint is the composite of all-cause mortality, worsening of HF requiring prioritized transplantation or LVAD implantation. The main secondary study endpoints are all-cause mortality, cardiovascular mortality, incidence of implantable cardioverter-defibrillator (ICD) therapy, hospitalizations, quality of life, time to first ICD therapy, number of device-detected ventricular tachycardia/ventricular fibrillation episodes, left ventricular function, and exercise tolerance. CASTLE-VT will randomize 160 patients with a follow-up period of 2 years., Conclusion: CASTLE-VT will determine whether prophylactic catheter ablation of arrhythmogenic ventricular scar tissue reduces mortality in patients with end-stage HF who are referred for HTx evaluation., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

In many trials and experiments, subjects are not only observed once but multiple times, resulting in a cluster of possibly correlated observations (e.g., brain regions per patient). Observations often do not fulfill model assumptions of mixed models and require the use of nonparametric methods. In this article, we develop and present a purely nonparametric rank-based procedure that flexibly allows the unbiased and consistent estimation of the Wilcoxon-Mann-Whitney effect P ( X < Y ) + 1 2 P ( X = Y ) $$ P\left(X

Aims: The CASTLE-HTx trial showed the benefit of atrial fibrillation (AF) ablation compared to medical therapy in decreasing mortality, need for left ventricular assist device implantation or heart transplantation (HTx) in patients with end-stage heart failure (HF). Herein we describe the effects of catheter ablation on AF burden, arrhythmia recurrences, and ventricular function in end-stage HF., Methods and Results: The CASTLE-HTx protocol randomized 194 patients in end-stage HF with AF to catheter ablation and medical therapy or medical therapy alone. AF burden, left ventricular ejection fraction (LVEF), and type of AF were assessed at baseline and at each follow-up visit. Overall, 97 patients received ablation; 66 patients (68%) underwent pulmonary vein isolation (PVI) and 31 patients (32%) were treated with PVI and additional ablation. Electroanatomic mapping showed the extent of left atrial low voltage (cardiomyopathy) >10% in 31 (31.9%) patients. At 12 months post-ablation, persistent AF was present in 31/89 patients (34.8%), which was significantly less frequent compared to baseline (p = 0.0001). Median AF burden reduction was 36.3 (interquartile range 13.6-63.3) percentage points at 12 months and LVEF improved from 29.2 ± 6.2% to 39.1 ± 8.3% (p < 0.001) following ablation. AF burden reduction <50% was significantly associated with LVEF improvement ≥5% at 12 months after ablation (p = 0.017)., Conclusion: Atrial fibrillation ablation in end-stage HF leads to a substantial decrease in AF burden, a regression from persistent to paroxysmal AF and notably improved LVEF. Favourable ablation outcomes were observed in patients regardless of the presence or absence of signs indicating left atrial cardiomyopathy., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Interventional valve implantation into the inferior vena cava (CAVI) lowers venous congestion in patients with tricuspid regurgitation (TR). We evaluated the impact of a reduction of abdominal venous congestion following CAVI on circulating immune cells and inflammatory mediators., Methods: Patients with severe TR were randomized to optimal medical therapy (OMT) + CAVI (n = 8) or OMT (n = 10). In the OMT + CAVI group, an Edwards Sapien XT valve was implanted into the inferior vena cava. Immune cells and inflammatory mediators were measured in the peripheral blood at baseline and three-month follow-up., Results: Leukocytes, monocytes, basophils, eosinophils, neutrophils, lymphocytes, B, T and natural killer cells and inflammatory markers (C-reactive protein, interferon-gamma, interleukin-2, -4, -5, -10, and tumor necrosis factor-alpha) did not change substantially between baseline and three-month follow-up within the OMT + CAVI and OMT group., Conclusion: The present data suggest that reduction of venous congestion following OMT + CAVI may not lead to substantial changes in systemic inflammation within a short-term follow-up., Clinical Trial Registration: NCT02387697., (© 2024. The Author(s).)

Background: The CASTLE-HTx trial demonstrated the benefit of atrial fibrillation (AF) ablation compared with medical therapy in decreasing mortality, need for left ventricular assist device implantation, or heart transplantation (HTx) in patients with end-stage heart failure (HF)., Objective: This analysis aimed to identify risk factors related to adverse outcomes in patients with end-stage HF and to assess the impact of ablation., Methods: The CASTLE-HTx protocol randomized 194 patients with end-stage HF and AF to ablation vs medical therapy. We identified left ventricular ejection fraction <30%, New York Heart Association class ≥III, and AF burden >50% as predictors for the primary end point. The CASTLE-HTx risk score assigned weights to these risk factors. Patients with a risk score ≥3 were identified as high risk., Results: The patients were assigned to low-risk (89 [45.9%]) and high-risk (105 [54.1%]) groups. After a median follow-up of 18 months, a primary end point event occurred in 6 and 31 patients of the low- and high-risk groups (hazard ratio, 4.98; 95% confidence interval, 2.08-11.9). The incidence rate (IR) difference between ablation and medical therapy was much larger in high-risk patients (8/49 [IR, 11.4] vs 23/56 [IR, 36.1]) compared with low-risk patients (2/48 [IR, 2.6] vs 4/41 [IR, 6.3]). The IR difference for ablation was significantly higher in high-risk patients (24.69) compared with low-risk patients (3.70)., Conclusion: The absolute benefit of ablation is more pronounced in high-risk patients, but low-risk patients may also benefit. The CASTLE-HTx risk score identifies patients with end-stage HF who will particularly benefit from ablation., Competing Interests: Disclosures Dr Sohns received research support and lecture fees from Medtronic, Abbott, Boston Scientific, and Biosense Webster; is a consultant for Medtronic, Boston Scientific, and Biosense Webster; has received grant support from the Else Kröner-Fresenius-Stiftung and Deutsche Herzstiftung. Dr Sommer is member of the Advisory Board for Abbott, Biosense Webster, Boston Scientific, and Medtronic. Dr Crijns reports support from The Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation, CVON 2014-9: reappraisal of atrial fibrillation: interaction between hypercoagulability, electrical remodelling, and vascular destabilization in the progression of AF (RACE V), outside this work. Dr Sossalla received speaker fees from AstraZeneca and Boehringer Ingelheim. Dr Marrouche has received grant support and consulting fees from Abbott, Wavelet Health, Medtronic, Vytronus, Biosense Webster, Boston Scientific, GE HealthCare, and Siemens; has received consulting fees from Preventice; and holds equity in Marrek and Cardiac Design. Dr Rudolph has received grant support from Abbott Vascular and Edwards Lifesciences. All other authors have nothing to declare., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

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., (© 2024 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.)

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., (© 2024 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Importance: Sex differences in head and neck cancer (HNC) incidence suggest a potential contribution of sex hormones., Objective: To assess the role of exogenous estrogen exposure in the development of HNC in female patients., Design, Settings, and Participants: This large multicenter cohort study using clinical records from the TriNetX real-world database included 20 years of data (through May 31, 2023) from 87 health care organizations. The TriNetX database was searched for medical records for female patients with and without exogenous estrogen exposure according to their chronological age. Cohort 1 included 731 366 female patients aged 18 to 45 years old with regular oral contraceptive (OC) intake and cohort 2 included 3 886 568 patients in the same age group who did not use OC. Cohort 3 comprised 135 875 female patients at least 50 years old receiving hormone replacement therapy (HRT), whereas cohort 4 included 5 875 270 patients at least 50 years old without HRT. Propensity score matching was performed for the confounders age, alcohol dependence, and nicotine dependence. Data analyses were performed in May 2023., Main Outcome and Measures: Diagnosis of HNC (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision: C00-C14), and after propensity score matching (1:1 nearest-neighbor greedy matching), a risk analysis to investigate risk differences and risk ratios (RRs) with a 95% CI., Results: Among the 718 101 female patients in each of cohorts 1 and 2 (mean [SD] age at diagnosis, 25.9 [6.7] years), those with OC intake had a higher risk of an HNC diagnosis (RR, 1.47; 95% CI, 1.21-1.78) than those without OC use. Among the 131 835 female patients in each of cohorts 3 and 4 (mean [SD] age, 67.9 [12.0] years), those with postmenopausal HRT intake had a lower risk of an HNC diagnosis (RR, 0.77; 95% CI, 0.64-0.92) than those without HRT use., Conclusions and Relevance: The findings of this cohort study illustrate a positive association between OC and a negative association between HRT and the development of HNC in female patients. Given the limitations of the TriNetX database, future research should include detailed information on the intake of OC and HRT and reproductive health information (eg, age at menarche/menopause, number of pregnancies) to more accurately define the strength and direction of the possible association between exogeneous estrogen exposure and the development of HNC in female patients.

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., (© 2024 The Authors. Biometrical Journal published by Wiley‐VCH GmbH.)

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., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. FundingThe author(s) received no financial support for the research, authorship, and/or publication of this article.

Background: Secondary central nervous system lymphoma (SCNSL) confers a dismal prognosis and treatment advances are constrained by the lack of prospective studies and real-world treatment evidence., Methods: Patients with SCNSL of all entities were included at first diagnosis and patient characteristics, treatment data, and outcomes were prospectively collected in the Secondary CNS Lymphoma Registry (SCNSL-R) (NCT05114330)., Findings: 279 patients from 47 institutions were enrolled from 2011 to 2022 and 243 patients (median age: 66 years; range: 23-86) were available for analysis. Of those, 49 (20 %) patients presented with synchronous (cohort I) and 194 (80 %) with metachronous SCNSL (cohort II). The predominant histology was diffuse large B-cell lymphoma (DLBCL, 68 %). Median overall survival (OS) from diagnosis of CNS involvement was 17·2 months (95 % CI 12-27·5), with longer OS in cohort I (60·6 months, 95 % CI 45·5-not estimable (NE)) than cohort II (11·4 months, 95 % CI 7·8-17·7, log-rank test p < 0.0001). Predominant induction regimens included R-CHOP/high-dose MTX (cohort I) and high-dose MTX/cytarabine (cohort II). Rituximab was used in 166 (68 %) of B-cell lymphoma. Undergoing consolidating high-dose therapy and autologous hematopoietic stem cell transplantation (HDT-ASCT) in partial response (PR) or better was associated with longer OS (HR adjusted 0·47 (95 % CI 0·25-0·89), p = 0·0197)., Interpretation: This study is the largest prospective cohort of SCNSL patients providing a comprehensive overview of an international real-world treatment landscape and outcomes. Prognosis was better in patients with SCNSL involvement at initial diagnosis (cohort I) and consolidating HDT-ASCT was associated with favorable outcome in patients with PR or better., Competing Interests: Declaration of Competing Interest U.Ke. served in an advisory role for BMS/ Celgene, Takeda, Janssen, Gilead/ Kite, Roche, Abbvie, AstraZeneca, Novartis, Lilly, Pentixapharm and received travel support from BMS/ Celgene, Takeda, Janssen, Roche, Abbvie, Gilead/ Kite, AstraZeneca, Novartis, Lilly, Pentixapharm. S.H. served in an advisory role for Pentixapharm. Ro.S. served in an advisory role for BMS/ Celgene, Janssen, Gilead/ Kite, and Novartis. M.S-H. has an advisory role for Celgene GmbH, Amgen GmbH, Gilead/ Kite, Sanofi-Aventis, Glaxo Smith Kline, Bristol Myers Squibb, Shionogi and received financial support from Janssen-Cilag, Takeda, Novartis, Pfizer, Roche, Vifor Pharma, Celgene. P.L.R. received payment from Novartis, MSD, Abbvie, Roche, Incyte, Janssen-Cilag and travel support from Abbvie, Novartis, BMS, Janssen-Cilag and Roche. K.J. received royalties from Elsevier and Wolters Kluwer, obtained consulting fees and honoraria from Amgen, art tempi, Astra Zeneca, BD Solutions, Helsinn, Hexal, Karyopharm med update GmbH, MSD, Mundipharma, onkowissen, Riemser, Roche, Shire (Takeda), Vifor Pharma and Voluntis, B.C. received research grants from Gilead, received honoraria from BMS, Astra Zeneca, Gilead, Roche, Sandoz, Incyte, Abbvie and received travel support from Roche and Gilead. St. S. received research grants from Protherics Medicines Development Ltd., served in an advisory role for AMGEN, Gilead Sciences, Pfizer, SERB SAS, received honoraria from Akademie für Infektionsmedizin e.V., AMGEN, AVIR Pharma, CSi Hamburg GmbH, Gilead Sciences, Labor28, Novartis, Persberg Group GmbH/DGIM e.V., Pfizer, Vivantes GmbH and received travel support from Gilead Sciences and Novartis. A.K. Received financial support from Riemser. All remaining authors have declared no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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., (© 2023 The Authors. Biometrical Journal published by Wiley-VCH GmbH.)

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.)., (Copyright © 2023 Massachusetts Medical Society.)

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Patients undergoing high-risk surgery show haemodynamic instability and an increased risk of morbidity. However, most of the available data concentrate on the intraoperative period. This study aims to characterise patients with advanced haemodynamic monitoring throughout the whole perioperative period using electrical cardiometry., Methods: In a prospective, observational, monocentric pilot study, electrical cardiometry measurements were obtained using an Osypka ICON™ monitor before surgery, during surgery, and repeatedly throughout the hospital stay for 30 patients with primary ovarian cancer undergoing multivisceral cytoreductive surgery. Severe postoperative complications according to the Clavien-Dindo classification were used as a grouping criterion., Results: The relative change from the baseline to the first intraoperative timepoint showed a reduced heart rate (HR, median - 19 [25-quartile - 26%; 75-quartile - 10%]%, p < 0.0001), stroke volume index (SVI, - 9.5 [- 15.3; 3.2]%, p = 0.0038), cardiac index (CI, - 24.5 [- 32; - 13]%, p < 0.0001) and index of contractility (- 17.5 [- 35.3; - 0.8]%, p < 0.0001). Throughout the perioperative course, patients had intraoperatively a reduced HR and CI (both p < 0.0001) and postoperatively an increased HR (p < 0.0001) and CI (p = 0.016), whereas SVI was unchanged. Thoracic fluid volume increased continuously versus preoperative values and did not normalise up to the day of discharge. Patients having postoperative complications showed a lower index of contractility (p = 0.0435) and a higher systolic time ratio (p = 0.0008) over the perioperative course in comparison to patients without complications, whereas the CI (p = 0.3337) was comparable between groups. One patient had to be excluded from data analysis for not receiving the planned surgery., Conclusions: Substantial decreases in HR, SVI, CI, and index of contractility occurred from the day before surgery to the first intraoperative timepoint. HR and CI were altered throughout the perioperative course. Patients with postoperative complications differed from patients without complications in the markers of cardiac function, a lower index of contractility and a lower SVI. The analyses of trends over the whole perioperative time course by using non-invasive technologies like EC seem to be useful to identify patients with altered haemodynamic parameters and therefore at an increased risk for postoperative complications after major surgery., (© 2023. European Society of Intensive Care Medicine and Springer Nature Switzerland AG.)