The Masquelet technique is used to treat large bone defects; it is a two-stage procedure based on an induced membrane. To improve the induced membrane process, demineralized bone matrix in granular (GDBM) and fibrous form (f-DBM) was tested with and without bone marrow mononuclear cells (BMC) as filling of the membrane against the gold standard filling with syngeneic cancellous bone (SCB). A total of 65 male Sprague–Dawley rats obtained a 5 mm femoral defect. These defects were treated with the induced membrane technique and filled with SCB, GDBM, or f-DBM, with or without BMC. After a healing period of eight weeks, the femurs were harvested and submitted for histological, radiological, and biomechanical analyses. The fracture load in the defect zone was lower compared to SCB in all groups. However, histological analysis showed comparable new bone formation, bone mineral density, and cartilage proportions and vascularization. The results suggest that f-DBM in combination with BMC and the induced membrane technique cannot reproduce the very good results of this material in large, non-membrane coated bone defects, nevertheless it supports the maturation of new bone tissue locally. It can be concluded that BMC should be applied in lower doses and inflammatory cells should be removed from the cell preparation before implantation.

Introduction: The non-invasive assessment of disease severity remains pivotal in patients with chronic liver disease (CLD) as it has wide implications in predicting liver-related complications or death. Shear-wave elastography (SWE) is an emerging ultrasound-based method to non-invasively measure liver stiffness. The aim of our study was to evaluate two-dimensional (2D) and point (p) SWE to predict the presence of esophageal varices (EV) or clinically significant portal hypertension (CSPH). Methods: This was a retrospective analysis of a prospectively performed cohort study of patients with CLD treated in the outpatient clinic of the Frankfurt University Hospital. PSWE using the Hitachi HI Vision ASCENDUS system and the Siemens ACUSON S2000^TM system or 2D-SWE using the Toshiba APLIO500 system were analyzed at baseline and during follow-up to predict EV or surrogate parameters of CSPH. ROC curves were calculated for pooled liver stiffness measurements (LSMs) using a bootstrap approach. A combined model of SWE and platelet count was created and a mixed-effect logistic regression analysis using log-transformed values was performed. Results: Overall, 511 patients with CLD and 919 consecutive LSMs were included and 315 patients (61.6%) had signs of CSPH. 2D-SWE performed best to predict EV and CSPH, and the addition of platelet count to the predictive model significantly increased test results for EV (AUC 0.83, 95%-CI: 0.76–0.89; difference in AUC 0.11, 95%-CI: 0.03–0.19, p = 0.004), but only marginally for CSPH (AUC 0.75, 95%-CI: 0.64–0.85; difference in AUC 0.06, 95%-CI: 0.02–0.14, p = 0.150). LSM > 18.5 and >20 kPa were indicative of CSPH and EV, while LSM < 10 kPa and <11 kPa ruled out CSPH and EV, respectively. Conclusions: Our study found that 2D-SWE in combination with platelet count performed best (in comparison to the other SWE methods) to predict EV or CSPH in patients with CLD. Future prospective trials are needed to validate our results.

The classic two-stage masquelet technique is an effective procedure for the treatment of large bone defects. Our group recently showed that one surgery could be saved by using a decellularized dermis membrane (DCD, Epiflex, DIZG). In addition, studies with bone substitute materials for defect filling show that it also appears possible to dispense with the removal of syngeneic cancellous bone (SCB), which is fraught with complications. The focus of this work was to clarify whether the SCB can be replaced by the granular demineralized bone matrix (g-DBM) or fibrous demineralized bone matrix (f-DBM) demineralized bone matrix and whether the colonization of the DCD and/or the DBM defect filling with bone marrow mononuclear cells (BMC) can lead to improved bone healing. In 100 Sprague Dawley rats, a critical femoral bone defect 5 mm in length was stabilized with a plate and then encased in DCD. Subsequently, the defect was filled with SCB (control), g-DBM, or f-DBM, with or without BMC. After 8 weeks, the femurs were harvested and subjected to histological, radiological, and biomechanical analysis. The analyses showed the incipient bony bridging of the defect zone in both groups for g-DBM and f-DBM. Stability and bone formation were not affected compared to the control group. The addition of BMCs showed no further improvement in bone healing. In conclusion, DBM offers a new perspective on defect filling; however, the addition of BMC did not lead to better results.

Background: A variety of endoscopic techniques are available for the closure of esophageal defects, each offering distinct advantages. Endoscopic vacuum therapy (EVT) has emerged as a highly effective approach. Alternatively, fully covered self-expanding metal stents (SEMS) can be placed intraluminally until defect closure is achieved. For smaller defects, over-the-scope clips (OTSC®) provide a viable option. However, comparative data remain limited and reported closure rates vary widely across the literature. This study aimed to evaluate and compare closure rates of postoperative anastomotic leaks treated with EVT, SEMS, and OTSC® at two specialized centers in Germany. Methods: This retrospective study included all patients treated endoscopically for anastomotic leakage at two tertiary gastroenterological centers between May 2007 and February 2023. The primary endpoint was successful endoscopic defect closure. Secondary endpoints included in-hospital mortality, need for revision surgery, duration of therapy, hospital stay length, time to treatment initiation, and procedure-related complications. Results: A total of 59 patients (71% male, mean age 64 years) were included. In 94.9% of cases, surgery was performed for oncologic indications; 46% had received neoadjuvant therapy. The most common procedure was Ivor Lewis esophagectomy (89.8%). EVT was used in 24 patients, SEMS in 32, and OTSC® in 14. The overall closure rate was 78.0%. Patients with successful closure had a significantly lower ASA score (p = 0.039), smaller defects (≤ 1 cm: 57.8% vs. 15.4%, p = 0.007), lower in-hospital mortality (2.2% vs. 38.5%, p < 0.001), and reduced need for revision surgery (0% vs. 61.5%, p < 0.001). Conclusions: The success of endoscopic therapy is closely linked to patient health status and defect size. Notably, esophageal defects ≤ 1 cm can almost always be closed successfully using endoscopic methods. Graphical

Background: Infections caused by multidrug-resistant organisms (MDROs) are a growing concern in patients with advanced chronic liver disease and acute-on-chronic liver failure, worsening clinical outcomes. Although prior antibiotic exposure is associated with resistance, prospectively defined, clinically actionable exposure thresholds in this population are lacking. We aimed to quantify cumulative-exposure thresholds for de novo MDRO acquisition and assess the prognostic impact of MDRO emergence on survival. Methods: We prospectively enrolled 256 consecutive adults with advanced chronic liver disease at the University Hospital Frankfurt (2020–2023). Antibiotic exposure was quantified using defined daily doses (DDD) and antibiotic use density; MDRO colonization and infection were captured by systematic microbiological surveillance. Time-to-death was analyzed in a competing-risk framework with liver transplantation as a competing event. Results: Among 246 patients without MDRO at the first admission swab, de novo acquisition of vancomycin-resistant enterococci (VRE) or Gram-negative MDR was strongly associated with cumulative antibiotic exposure (P < .001). The 20% probability threshold for VRE was reached at 9.6 cumulative DDDs of any antibiotic, with substantially lower thresholds for β-lactam/β-lactamase inhibitor combinations, carbapenems, and glycopeptides. De novo MDRO detection during follow-up, but not at baseline, was independently associated with increased 180-day mortality (HR 2.15, 95% CI 1.27–3.64; P = .004). Conclusions: In advanced cirrhosis, MDRO emergence is associated with cumulative antibiotic exposure beyond distinct, class-specific thresholds and carries excess mortality. These prospective findings identify cumulative antibiotic burden as a modifiable risk factor and support an exposure-aware approach to antimicrobial stewardship in this population.

Background/Aims: Endoscopic therapy for neoplastic Barrett’s esophagus (BE) has become the standard of care over the past two decades. In clinical practice, we regularly encounter patients who fail to achieve complete squamous epithelialization of the esophagus. Although the therapeutic strategies in the individual stages of BE, dysplasia, and esophageal adenocarcinoma are well studied and largely standardized, the problem of inadequate healing after endoscopic therapy is only marginally considered. This study aimed to shed light on the variables influencing inadequate wound healing after endoscopic therapy and the effect of bile acid sequestrants (BAS) on healing.Methods: Retrospective analysis of endoscopically treated neoplastic BE in a single referral center.Results: In 12.1% out of 627 patients, insufficient healing was present 8 to 12 weeks after previous endoscopic therapy. The average follow-up duration was 38.8±18.4 months. Complete healing was achieved in 13 patients already after intensifying proton pump inhibitor therapy. Out of 48 patients under BAS, 29 patients (60.4%) showed complete healing. An additional eight patients (16.7%) improved, but only partial healing was achieved. Eleven (22.9%) patients showed no response to BAS augmented therapy.Conclusions: In cases of insufficient healing even under exhaustion of proton pump inhibitors, treatment with BAS can be an option as an ultimate healing attempt.