University Hospital Regensburg

Implant-associated-infections against the background of multi-drug-resistance cause severe complications in orthopedic and trauma surgery and burden global healthcare. Equipment of implants with antibacterial coatings loaded by lytic bacteriophages (PHAG) are seen promising in this respect. Here, we report antibacterial polyelectrolyte multilayer (PEM) coatings functionalized by PHAG, which were deposited at model substrates and metallic implants by consecutive adsorption from solutions of poly-l-lactide-modified hyaluronic acid (DAC), ethylenediamino-cellulose (EDAC) or poly(ethyleneimine) (PEI) according to layer-by-layer technique. PHAG against Staphylococcus aureus (S. aureus) bacteria were bound at five- and six-layered PEM coatings of PEI/DAC or EDAC/DAC, respectively. PEM deposition and PHAG interaction were studied by FTIR and SFM. In-vivo antibacterial properties of PHAG/PEM coatings against S. aureus bacteria were evaluated using Galleria mellonella (G. mellonella) larvae infection model. PEM coatings of EDAC/DAC revealed far higher deposited polymer amounts compared to PEI/DAC and far more PHAG were bound at thicker EDAC/DAC compared to thinner PEI/DAC coatings. Higher relative released PHAG amount (40-80%) was found for thinner PEI/DAC coatings, while lower one (10-20%) for thicker EDAC/DAC coatings. In-vivo studies revealed survival rates >80% of uninfected G. mellonella larvae treated with uncoated and PEM/PHAG coated metallic implants, indicating biocompatibility of the used materials. Infected G. mellonella larvae showed survival rates of 33%-43% for metallic implants with PEM/PHAG coatings of EDAC/DAC, which were higher with statistical significance compared to uncoated controls (13%), indicating excellent antibacterial properties.

Plastic and reconstructive surgery (PRS) encompasses a wide range of procedures, and postoperative complications remain a persistentchallenge. While preoperative laboratory values (PLVs) are routinely assessed, their predictive value for postoperative outcomes inPRS is unclear. This study evaluates the association between PLVs and postoperative morbidity to enhance risk stratification. The ACS-NSQIP database (2008-2022) was analyzed for PRS patients. PLVs included sodium, blood urea nitrogen, creatinine, albumin, bilirubin, SGOT, alkaline phosphatase, white blood cell count, hematocrit, platelets, partial thromboplastin time, international normalized ratio, and prothrombin time (PT). Multivariate logistic regression identified independent predictors of complications, while decision tree analysis established risk thresholds, validated through cross-validation. A total of 200,015 patients with a mean age of 50.3±14.5 years and a mean BMI of 29.1±6.8 kg/m2 were included in this study. Albumin levels emerged as the strongest predictor for the occurrence of any complications. Patients with albumin ≤ 3.3 g/dL had a 36.5% risk for the occurrence of any complication compared to 10.4% in those with higher levels. In the high-risk group, prolonged PT (> 16.2s) further increased risk for the occurrence of any complications. Also, in the lower-risk group (albumin > 3.3 g/dL), prolonged PT (> 13.7 s) were found to significantly influence complication occurrence. Further, multivariate analysis confirmed reduced albumin (OR 0.460) as the strongest independent predictors for any complication occurrence. Albumin and PT are key predictors of 30-day postoperativecomplications in PRS. Preoperative optimization of these values can enhance patient safety and surgical outcomes. Findings support integrating targeted preoperative evaluations into clinical practice. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Short tandem repeats (STRs) are low-entropy regions in the genome, consisting of a short (1-6 bp) unit that is consecutively repeated multiple times. They are known for high mutational instability, due to so-called stutter-mutations, in which the number of units in the run increases or descreases. In particular, STRs with repeat unit length of 1-2 bp are prone to mutate even within several cell divisions. The extremely rapid accumulation of variation makes them interesting phylogenetic markers for retrospective single-cell lineage reconstruction. Here we model their mutational dynamics at the level of individual repeat unit type and then aggregate length variations over many STR loci with the aim of obtaining a very fast ``molecular clock''. We calibrate our model based on several datasets with known lineage structure prepared from cultured cells. We find that the mutational dynamics of STRs are reasonably consistent for a given cell line, but vary among different ones. This suggests that the dynamics are not entirely explained by mutations in caretaker genes, rather, various other factors play a role -- possibly tissue origin and differentiation state. Further data and research is necessary to asses their relative effects.

In trauma, even therapeutic apixaban levels can significantly exacerbate bleeding. In cases of overdose, the risk of prolonged, life-threatening hemorrhage increases substantially, necessitating targeted interventions, such as pharmacological reversal agents. Rapid identification of elevated anticoagulant levels is crucial to initiate specific countermeasures and limit blood loss, and point-of-care testing may facilitate timely treatment. In our case of an extreme overdose of apixaban (max 5664.24 ng/mL, first report of such high amount) has resulted in serious and life-threatening clinical symptoms due to sustained multiple injuries. It is still a debate which therapies prove the most efficacious, whereby the vast surplus of apixaban and the short half-life of andexanet alfa must be considered. This case, in which high apixaban concentration persisted, might help to shed light on these issues.

A consensus exists among vascular surgery societies that blunt thoracic aortic injury (BTAI) should be treated with thoracic endovascular aortic repair (TEVAR) in patients with favorable aortic anatomy. However, selecting the correct landing zones and endograft sizing remains challenging in patients with BTAI. To overcome these limitations, conformable endografts are often used for TEVAR, even in patients with BTAI. This study aimed to analyze the outcomes of these patients with respect to anatomical and technical factors. This retrospective study included all patients with BTAI who underwent TEVAR at a tertiary vascular center. The primary endpoint was aortic-related reintervention-free survival. Secondary endpoints were 30-day in-hospital mortality, postoperative complications, and radiological findings. Patients were divided into 2 groups: group 1, patients with a conformable endograft (cTAG Gore), and group 2, patients with a nonconformable endograft. Between June 2001 and May 2019, 57 patients (50 men; mean age, 37.3 years) with BTAI received 30 (52.6%) conformable (Gore cTAG) and 27 (47.4%) nonconformable endografts. The 1-, 3-, and 5-year aortic-related reintervention-free survival was 100%, 100%, and 96.7% in group 1 and 81.4%, 81.4%, and 77.7% in group 2, respectively (p=0.03). Two postoperative type Ia endoleaks and 3 postoperative type II endoleaks were observed in group 2. The bird beak sign was noted more often in group 2 (70.4% vs 53.3, p=0.32). This study, in a small cohort of patients, demonstrated that the Gore cTAG, when properly selected according to the patient's anatomy, appears to provide better outcomes after TEVAR for patients with BTAI than nonconformable devices. A bird beak sign occurred frequently in both groups and were not associated with poor outcomes. Further studies are required to confirm these findings.Clinical ImpactThis study in a small cohort of patients demonstrated that the Gore cTAG endoprosthesis, when properly selected to match the patient's anatomy, appears to result in better outcomes after TEVAR in patients with BTAI than nonconformable devices. In addition, the BBS was common in both groups of patients and was not associated with a worse outcome.

Colorectal cancer (CRC) exhibits increased levels of arachidonic acid-derived pro-inflammatory derivatives indicating an uptake of dietary polyunsaturated fatty acids (PUFAs). We aimed to investigate uptake of extrinsic fatty acids (FAs) in tumours and their relevance for CRC lipid metabolism and progression. Total FAs were quantified using gas chromatography-mass spectrometry in non-diseased mucosa and tumour tissue from patients with CRC of a discovery cohort (n=152), validated in an independent cohort (n=28) and associated with clinical, genomic and microbiome data. The genetic mouse tumour model Apc1638N was used to track the flux of stable isotope-labelled FAs in tumours from the intestinal lumen. The relationship between FA uptake and tumour progression was investigated in 2D and 3D cell models. Extrinsic long chain PUFAs, including arachidonic acid, accumulate in CRC, particularly in right-sided tumours, and in tumours of Apc1638N mice. The CRC-specific FA profiles were independent of sex, molecular subtypes, early-disease or late-disease onset. The absorption of FAs from the intestinal lumen in tumours was confirmed in specific pathogen-free Apc1638N mice. In the absence of the microbiome, in germ-free Apc1638N mice, fewer tumours were developed, and survival was increased. Inhibition of FA import or β-oxidation reduces cancer cell proliferation. Extrinsic FAs accumulate in CRC, verifying a central role of arachidonic acid-derived inflammatory mediators, but also suggesting a relevance of dietary FAs for cancer cell proliferation. It will be intriguing to explore to what extent targeting this flux pathway together with the interrelated microbiome opens new therapeutic avenues for CRC in humans.

Haemorrhage and blood product usage are common in venoarterial extracorporeal membrane oxygenation (VA ECMO) and associated with increased mortality. A prospective, investigator-initiated, longitudinal observational cohort study on major haemorrhagic events in 12 ECMO centres from 3 continents for three predefined subgroups (VA ECMO initiated during cardio-pulmonary resuscitation (ECPR), after cardiothoracic surgery (CTS), for cardiogenic shock (CS)). The aim was to describe haemorrhagic complications as well as transfusion practice and anticoagulation for the whole population as well as the subgroups. In addition, independent baseline predictors for red blood cell (RBC) transfusions were evaluated. 545 prospective patients were included between 2019 and 2022 (ECPR 149, CTS 169, CS 227). Hospital mortality was 46%. Over 2796 days 406 major haemorrhage events in 286 (52%) patients were recorded. CTS and ECPR patients had more frequent events occurring earlier in their course. 88% received RBC transfusions (1.27 (95%CI 1.22 – 1.31) units/day) with significantly more transfusions for CTS and ECPR patients. Platelet transfusion rates were highest in the CTS group (0.58 (95%CI 0.53–0.64) units/day). Haemoglobin and platelet count prior to transfusion were independent of subgroups and averaged (78 g/L (IQR 73, 84), 58 × 10^9/L (IQR 37, 85), respectively). However, platelet count prior transfusion was only marginally higher on days with major haemorrhage (74 × 10^9/L (IQR 50, 104). Systemic anticoagulation was started within the first 24 h in 83% (95% CI 80–87%) of patients, most frequently in CS patients (90%, CI 85–95%). Independent baseline predictors for RBC transfusion were ECPR (IRR 1.50, 95%CI 1.19–1.89) and prior use of antiplatelets (IRR: 1.43, 95%CI 1.13–1.80). Myocarditis and pulmonary embolism were associated with a lower rate of transfusion when compared to myocardial infarct (IRR: 0.57 (0.37–0.89), IRR: 0.67 (0.45–1.00, respectively). Haemorrhagic complications differ in clinical subgroups and RBC transfusion exposure is by far higher than in other critically unwell populations. We identified ECPR and antiplatelet therapy as additional predictors. Transfusion practice for RBC and platelets is variable and does not always follow international guidelines.

Abstract Background: Bone metabolism in children who have undergone pediatric liver transplantation (pLT) can be negatively affected, particularly in the presence of cholestasis. Pediatric bone status is a critical determinant of bone health through adulthood. The aim of this study was to evaluate bone age (BA), a marker of skeletal maturity, and bone health index (BHI), a surrogate marker of bone density, in pLT recipients. Methods: A total of 449 left hand radiographs of 207 patients [median age at LT: 1.1 years (IQR: 0.43; 6.8 years); female = 50.2%], all entered in the local pLT register, were evaluated in this retrospective, IRB-approved single-center exploratory study. Fully automated determination of BA-standard deviation score (BA SDS) and BHI SDS was performed using a commercial, CE-marked AI tool and relationships with age, sex, underlying disease (biliary atresia vs. non-biliary atresia), height percentile and plasma parathyroid hormone (PTH) were assessed using t-tests, permutation tests, and Pearson correlation in both the whole cohort and the subgroup with biliary complications. Results: Mean BA SDS pre-LT was 0.03 ± 1.50, 0.03 ± 1.70 at year 1, -0.07 ± 1.62 at year 3 and − 0.21 ± 1.63 at year 5. Mean BHI SDS pre-LT was − 1.8 ± 1.20, -1.6 ± 1.20 at year 1, -2.0 ± 1.10 year 3 and − 2.2 ± 1.3 at year 5. A significant positive correlation was observed between BA SDS and height percentiles at all timepoints. PTH showed a significant inverse correlation with BA SDS at years 3 and 5 and with BHI SDS at year 5. No significant differences in mean BA SDS or BHI SDS were observed between groups with or without biliary complications or PTCD/ERCP at any timepoint. Conclusions: While mean BA SDS remained stable around zero post-LT, mean BHI SDS was consistently reduced and declined progressively until year 5, indicating decreased bone mineral density. Further prospective studies with larger cohorts are needed to determine the utility of automated BA and BHI assessment following pLT.

In Germany, the German Cancer Society (Deutsche Krebsgesellschaft [DKG]) accredits hospitals to ensure high-quality cancer treatment through adherence to clinical guidelines and a multidisciplinary approach. Evidence suggests certified hospitals (CHs) achieve better clinical outcomes and prognoses than non-certified hospitals (NCHs). However, additional services required for certification incur substantial, unreimbursed costs, necessitating a focused cost-effectiveness evaluation. This retrospective cohort study utilized anonymized administrative routine healthcare data from Allgemeine Ortskrankenkasse, Germany's largest statutory health insurance. The study sample comprised 143,720 incident breast cancer (BC) patients treated between 2009 and 2017 across both CHs and NCHs. A health system perspective was used in this cost-effectiveness analysis. Direct medical costs (inpatient, outpatient, medication, and certification) were compared between CHs and NCHs. Life-years gained (LYG) were calculated from 5-year restricted mean survival time. The incremental cost-effectiveness ratio (ICER), quantified as cost per LYG, served as the primary outcome measure, reported in 2024 euro. Treatment in CHs significantly improved breast cancer survival, yielding 201 LYG per 1000 patients (95% confidence interval: 185-216). Accounting for €1.5 M in certification-related costs and marginal direct medical costs, the total incremental cost was €1.81 M per 1000 patients. This resulted in an ICER of €9036 per LYG. Despite the financial investment required for DKG certification, BC treatment in CHs provided significant survival benefits at a reasonable incremental cost, reinforcing the clinical and economic value. These findings offer critical insights for hospital authorities and healthcare policymakers, supporting the continued investment in certification.