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Abstract Chronic hepatitis B virus (HBV) infection may follow four different consecutive phases, which are defined by virology as well as biochemical markers and differ in terms of prognosis and need for antiviral treatment. Currently, host responses reflected by immune markers are not considered in this definition. We aimed to study soluble immune markers and their distribution in different phases of chronic HBV infection. In this cross-sectional retrospective study, we investigated a panel of 14 soluble immune markers (SIM) including CXCL10 in 333 patients with chronic HBV infection. In a small cohort of HBeAg positive patients we analyzed SIM before and after HBeAg seroconversion and compared seroconverters to patients with unknown outcome. Significant differences were documented in the levels of several SIM between the four phases of chronic HBV infection. The most pronounced difference among all investigated SIM was observed for CXCL10 concentrations with highest levels in patients with hepatitis. TGF-β and IL-17 revealed different levels between HBeAg negative patients. HBeAg positive patients with HBeAg seroconversion presented higher amounts of IL-12 before seroconversion compared to HBeAg positive patients with unknown follow up. SIM such as CXCL10 but also IL-12, TGF-β and IL-17 may be useful markers to further characterize the phase of chronic HBV infection.

Abstract Lesion verification and quantification is traditionally done via histological examination of sectioned brains, a time-consuming process that relies heavily on manual estimation. Such methods are particularly problematic in posterior cortical regions (e.g. visual cortex), where sectioning leads to significant damage and distortion of tissue. Even more challenging is the post hoc localization of micro-electrodes, which relies on the same techniques, suffers from similar drawbacks and requires even higher precision. Here, we propose a new, simple method for quantitative lesion characterization and electrode localization that is less labor-intensive and yields more detailed results than conventional methods. We leverage staining techniques standard in electron microscopy with the use of commodity micro-CT imaging. We stain whole rat and zebra finch brains in osmium tetroxide, embed these in resin and scan entire brains in a micro-CT machine. The scans result in 3D reconstructions of the brains with section thickness dependent on sample size (12–15 and 5–6 microns for rat and zebra finch respectively) that can be segmented manually or automatically. Because the method captures the entire intact brain volume, comparisons within and across studies are more tractable, and the extent of lesions and electrodes may be studied with higher accuracy than with current methods.

Abstract Seasonal Malaria Chemoprevention consisting of monthly administration of amodiaquine/sulfadoxine-pyrimethamine to children aged 3–59 months during the transmission season could promote SP-resistance. Mutations in dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes were assessed before and after SMC adoption in Burkina Faso. A total of 769 dried blood spots were selected from studies conducted in Nanoro, Burkina Faso, between 2010 and 2020. Of those, 299 were pre-SMC (2010–2012) and 470 were post-SMC-samples. Pfdhps and Pfdhfr genes were PCR-amplified and sequenced. A systematic review/meta-analysis of published studies conducted in Burkina Faso (2009–2023) was additionally performed. In Nanoro, the prevalence of Pfdhfr triple mutations (CIRNI) rose from 43.6% pre-SMC to 89.4% post-SMC (p

Abstract Cardiac magnetic resonance (CMR) imaging allows precise non-invasive quantification of cardiac function. It requires reliable image segmentation for myocardial tissue. Clinically used software usually offers automatic approaches for this step. These are, however, designed for segmentation of human images obtained at clinical field strengths. They reach their limits when applied to preclinical data and ultrahigh field strength (such as CMR of pigs at 7 T). In our study, eleven animals (seven with myocardial infarction) underwent four CMR scans each. Short-axis cine stacks were acquired and used for functional cardiac analysis. End-systolic and end-diastolic images were labelled manually by two observers and inter- and intra-observer variability were assessed. Aiming to make the functional analysis faster and more reproducible, an established deep learning (DL) model for myocardial segmentation in humans was re-trained using our preclinical 7 T data (n = 772 images and labels). We then tested the model on n = 288 images. Excellent agreement in parameters of cardiac function was found between manual and DL segmentation: For ejection fraction (EF) we achieved a Pearson’s r of 0.95, an Intraclass correlation coefficient (ICC) of 0.97, and a Coefficient of variability (CoV) of 6.6%. Dice scores were 0.88 for the left ventricle and 0.84 for the myocardium.

Abstract Osteoporosis is underdiagnosed in patients undergoing total hip arthroplasty (THA). Bone mineral density measurement by dual-energy X-ray absorptiometry (DXA) is the gold standard, but indices on plain hip radiographs also seemed to be reliable screening tools in female or Asian ethnicities in previous studies. Given the lack of knowledge about male patients and Caucasian ethnicities, this study was conducted to evaluate plane hip radiographic indices as a screening tool for osteopenia and osteoporosis in Caucasian female and also male patients before undergoing THA. A retrospective analysis of 216 elderly patients with pre-existing DXA before hip arthroplasty was performed and four indices were calculated on plain hip radiographs: Canal-Flare-Index (CFI), Canal-Calcar-Ratio (CCR), Canal-Bone-Ratio (CBR) 7 and 10 cm below the lesser trochanter. They were correlated with femoral neck DXA T-scores by Pearson’s correlation and intraclass correlation coefficient, and a ROC analysis was performed. A total of 216 patients (49.5% male) were included. CBR-7 and -10 were highly correlated (p

Abstract Periprosthetic infections (PPIs) are a serious concern in total knee and hip arthroplasty, and they have an increasing incidence. To prevent PPI, preoperative skin disinfection, as a key element of antisepsis, represents an important part of infection prevention. However, no specific antiseptic agent is endorsed by the relevant guidelines. The purpose of this retrospective, not randomized study was to investigate the difference in the residual bacteria load between an approved antiseptic with an alcohol-based solution with additional benzalkonium chloride (BAC) and an alcohol-based solution with additional octenidine dihydrochloride (OCT) at two different time periods. In 200 consecutive patients with total knee or hip arthroplasty, skin samples from the surgical sites were collected after skin disinfection with BAC (100 g solution contain: propan-2-ol 63.0 g, benzalkonium chloride 0.025 g) or OCT (100 g solution contain: octenidine dihydrochloride 0.1 g, propan-1-ol, 30.0 g, propan-2-ol 45.0 g) (100 patients per group). Following the separation of cutis and subcutis and its processing, culture was performed on different agar plates in aerobic and anaerobic environments. In the case of bacteria detection, the microbial identification was determined by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS), and the number of contaminated samples was compared between the groups. Additionally, multiple regression analysis was performed to examine the effect of the type of disinfectant, BMI, age, sex, rheumatoid arthritis, diabetes mellitus, skin disorders, smoking status, and localization of skin samples on positive bacteria detection. A total of 34 samples were positive for bacteria in the BAC group, while only 17 samples were positive in the OCT group (p = 0.005). Disinfectant type was the only significant parameter in the multiple regression analysis (p = 0.006). A significantly higher contamination rate of the subcutis was shown in the BAC group compared to the OCT group (19 vs. 9, p = 0,003). After the change from BAC to OCT in preoperative skin cleansing in the hip and knee areas, the number of positive cultures decreased by 50%, which might have been caused by a higher microbicidal activity of OCT. Therefore, the use of OCT in preoperative cleansing may reduce the risk of PPI in hip and knee surgery. Randomized controlled trials are required to confirm the effect and to evaluate if it reduces the risk of PPI.

Abstract Acetabular defects are a challenging condition for surgeons in revision THA. A crucial aim is an anatomical restoration of the centre of rotation (COR) through grafts. The aim of this study was to determine the cup survival after biological restoration of acetabular defects in THA and the effect of Paprosky classification, age, BMI, and number of previous operations on cup survival. Retrospectively patients with a cup exchange and an impaction of cortico-cancellous or bulk grafts between 2009 and 2012 were included with a follow up with a minimum of 5 year. Implant failure was defined as radiographic loosening or explantation of the cup. The acetabular defect situation was classified to Paprosky. 82 patients (58 female 70.7%) were included. 26 patients were not available to contact. 56 patients (40 female 71.4%) remained for survival analysis with mean age of 75.6 ± 8 years. Survival of the cup after 5 years was 90% and after 7.8 years 88%. There was no difference in survival concerning defect classification, type of implant or graft, age, BMI, and number of previous operations. Patients on the follow up reached an HHS of 67.4 ± 19, a WOMAC Score of 33.4 ± 25.4 points and an unsatisfactory result in the SF-36. Impaction bone grafting of acetabular defects is a good option with satisfactory biomechanical results and survival for small defects. Predictive factors for cup survival could not be clarified in our study. So, the correct indication, knowing the limits of the methods and the correct choice of implant allow a defect-oriented approach and are decisive for the success of the operation.

Abstract Patients developing perioperative myocardial infarction/injury (PMI) have a high mortality. PMI work-up and therapy remain poorly defined. This prospective multicenter study included high-risk patients undergoing major non-cardiac surgery within a systematic PMI screening and clinical response program. The frequency of cardiovascular imaging during PMI work-up and its yield for possible type 1 myocardial infarction (T1MI) was assessed. Automated PMI detection triggered evaluation by the treating physician/cardiologist, who determined selection/timing of cardiovascular imaging. T1M1 was considered with the presence of a new wall motion abnormality within 30 days in transthoracic echocardiography (TTE), a new scar or ischemia within 90 days in myocardial perfusion imaging (MPI), and Ambrose-Type II or complex lesions within 7 days of PMI in coronary angiography (CA). In patients with PMI, 21% (268/1269) underwent at least one cardiac imaging modality. TTE was used in 13% (163/1269), MPI in 3% (37/1269), and CA in 5% (68/1269). Cardiology consultation was associated with higher use of cardiovascular imaging (27% versus 13%). Signs indicative of T1MI were found in 8% of TTE, 46% of MPI, and 63% of CA. Most patients with PMI did not undergo any cardiovascular imaging within their PMI work-up. If performed, MPI and CA showed high yield for signs indicative of T1MI. Trial registration: https://clinicaltrials.gov/ct2/show/NCT02573532 .

Abstract Sustained forms of atrial fibrillation (AF) may be associated with a higher risk of adverse outcomes, but few if any long-term studies took into account changes of AF type and co-morbidities over time. We prospectively followed 3843 AF patients and collected information on AF type and co-morbidities during yearly follow-ups. The primary outcome was a composite of stroke or systemic embolism (SE). Secondary outcomes included myocardial infarction, hospitalization for congestive heart failure (CHF), bleeding and all-cause mortality. Multivariable adjusted Cox proportional hazards models with time-varying covariates were used to compare hazard ratios (HR) according to AF type. At baseline 1895 (49%), 1046 (27%) and 902 (24%) patients had paroxysmal, persistent and permanent AF and 3234 (84%) were anticoagulated. After a median (IQR) follow-up of 3.0 (1.9; 4.2) years, the incidence of stroke/SE was 1.0 per 100 patient-years. The incidence of myocardial infarction, CHF, bleeding and all-cause mortality was 0.7, 3.0, 2.9 and 2.7 per 100 patient-years, respectively. The multivariable adjusted (a) HRs (95% confidence interval) for stroke/SE were 1.13 (0.69; 1.85) and 1.27 (0.83; 1.95) for time-updated persistent and permanent AF, respectively. The corresponding aHRs were 1.23 (0.89, 1.69) and 1.45 (1.12; 1.87) for all-cause mortality, 1.34 (1.00; 1.80) and 1.30 (1.01; 1.67) for CHF, 0.91 (0.48; 1.72) and 0.95 (0.56; 1.59) for myocardial infarction, and 0.89 (0.70; 1.14) and 1.00 (0.81; 1.24) for bleeding. In this large prospective cohort of AF patients, time-updated AF type was not associated with incident stroke/SE.

Abstract Biomarkers may help to improve our knowledge about the complex pathophysiology of atrial fibrillation (AF). In this study we sought to identify significant changes in biomarkers and clinical measures in patients with and without AF recurrence after electrical cardioversion. We measured 21 conventional and new biomarkers before and 30 days after electrical cardioversion and assessed the associations of changes in biomarker levels with rhythm status at follow-up. Significant between-group changes were observed for bone morphogenetic protein 10 (BMP10), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and total bilirubin. Their respective changes were − 10.4%, − 62.0% and − 25.6% in patients with sinus rhythm, and 3.1%, 1.1% and − 9.4% in patients with recurrent AF, for a between-group difference of − 13.5% (95% confidence interval [CI] − 19.3% to − 7.6%; P

Abstract Dalbavancin is a novel glycopeptide antibiotic approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). It is characterized by a potent activity against numerous Gram-positive pathogens, a long elimination half-life and a favorable safety profile. Most recently, its application for the treatment of periprosthetic joint infections (PJIs) was introduced. The aim of this study was to proof our hypothesis, that dalbavancin shows superior efficacy against staphylococcal biofilms on polyethylene (PE) disk devices compared with vancomycin and additive behavior in combination with rifampicin. Staphylococcus aureus biofilms were formed on PE disk devices for 96 h and subsequently treated with dalbavancin, vancomycin, rifampicin and dalbavancin-rifampicin combination at different concentrations. Quantification of antibacterial activity was determined by counting colony forming units (CFU/ml) after sonification of the PE, serial dilution of the bacterial suspension and plating on agar-plates. Biofilms were additionally life/dead-stained and visualized using fluorescence microscopy. Dalbavancin presented superior anti-biofilm activity compared to vancomycin. Additive effects of the combination dalbavancin and rifampicin were registered. Dalbavancin combined with rifampicin presents promising anti-biofilm activity characteristics in vitro. Further in vivo studies are necessary to establish recommendations for the general use of dalbavancin in the treatment of PJIs.

Abstract Diagnosis of pheochromocytomas and paragangliomas in patients receiving hemodialysis is troublesome. The aim of the study was to establish optimal conditions for blood sampling for mass spectrometric measurements of normetanephrine, metanephrine and 3-methoxytyramine in patients on hemodialysis and specific reference intervals for plasma metanephrines under the most optimal sampling conditions. Blood was sampled before and near the end of dialysis, including different sampling sites in 170 patients on hemodialysis. Plasma normetanephrine concentrations were lower (P

The description of physical processes with many-particle systems is a key approach to the modeling of numerous physical systems. For example in storage rings, where ultrarelativistic particles are agglomerated in dense bunches, the modeling and measurement of their phase-space distribution is of paramount importance: at any time the phase-space distribution not only determines the complete space-time evolution but also provides fundamental performance characteristics for storage ring operation. Here, we demonstrate a non-destructive tomographic imaging technique for the 2D longitudinal phase-space distribution of ultrarelativistic electron bunches. For this purpose, we utilize a unique setup, which streams turn-by-turn near-field measurements of bunch profiles at MHz repetition rates. To demonstrate the feasibility of our method, we induce a non-equilibrium state and show that the phase-space distribution microstructuring as well as the phase-space distribution dynamics can be observed in great detail. Our approach offers a pathway to control ultrashort bunches and supports, as one example, the development of compact accelerators with low energy footprints., (© 2023. The Author(s).)