Synergistic effect of umbilical cord extracellular vesicles and rhBMP-2 to enhance the regeneration of a metaphyseal femoral defect in osteoporotic rats.

BACKGROUND: The aim of this study was to evaluate potential synergistic effects of a single, local application of human umbilical cord MSC-derived sEVs in combination with a low dose of recombinant human rhBMP-2 to promote the regeneration of a metaphyseal femoral defect in an osteoporotic rat model. METHODS: 6 weeks after induction of osteoporosis by bilateral ventral ovariectomy and administration of a special diet, a total of 64 rats underwent a distal femoral metaphyseal osteotomy using a manual Gigli wire saw. Defects were stabilized with an adapted Y-shaped mini-locking plate and were subsequently treated with alginate only, or alginate loaded with hUC-MSC-sEVs (2 × 109), rhBMP-2 (1.5 µg), or a combination of sEVs and rhBMP-2 (n = 16 for each group). 6 weeks post-surgery, femora were evaluated by µCT, descriptive histology, and biomechanical testing. RESULTS: Native radiographs and µCT analysis confirmed superior bony union with callus formation after treatment with hUC-MSC-sEVs in combination with a low dose of rhBMP-2. This finding was further substantiated by histology, showing robust defect consolidation 6 weeks after treatment. Torsion testing of the explanted femora revealed increased stiffness after application of both, rhBMP-2 alone, or in combination with sEVs, whereas torque was only significantly increased after treatment with rhBMP-2 together with sEVs. CONCLUSION: The present study demonstrates that the co-application of hUC-MSC-sEVs can improve the efficacy of rhBMP-2 to promote the regeneration of osteoporotic bone defects.

Enhancing Cranio-Maxillofacial Fracture Care in Low- and Middle-Income Countries: A Systematic Review.

Background: Cranio-maxillofacial (CMF) injuries represent a significant challenge in low- and middle-income countries (LMICs), exacerbated by inadequate infrastructure, resources, and training. This systematic review aims to evaluate the current strategies and solutions proposed in the literature to improve CMF fracture care in LMICs, focusing on education, patient transfer, and off-label solutions. Methods: A comprehensive literature search was conducted using PubMed/Medline from January 2000 to June 2023. Studies were selected based on the Preferred Reporting Items for Systematic Review and Meta-analysis Statement (PRISMA). Solutions were categorized into three main areas: education (digital and on-site teaching, fellowships abroad), patient transfer to specialized clinics, and off-label/non-operative solutions. Results: Twenty-three articles were included in the review, revealing a consensus on the necessity for enhanced education and training for local surgeons as the cornerstone for sustainable improvements in CMF care in LMICs. Digital platforms and on-site teaching were identified as key methods for delivering educational content. Furthermore, patient transfer to specialized national clinics and innovative off-label techniques were discussed as immediate solutions to provide quality care despite resource constraints. Conclusions: Effective CMF fracture care in LMICs requires a multifaceted approach, prioritizing the education and training of local healthcare professionals, facilitated patient transfer to specialized centers, and the adoption of off-label solutions to leverage available resources. Collaborative efforts between international organizations, local healthcare providers, and educational institutions are essential to implement these solutions effectively and improve patient outcomes in LMICs.

Functional Outcome and Safety of Endoscopic Treatment Options for Benign Prostatic Obstruction (BPO) in Patients ≥ 75 Years of Age.

Background: The selection of suitable patients for the surgical treatment of benign prostatic obstruction (BPO) is a challenge in persons ≥75 years of age. Methods: After a systematic literature search of PubMed, 22 articles were included in this review. Clinical and functional parameters were evaluated statistically. Results: The mean age of the patients was ≥79 years. The mean duration of postoperative catheterization ranged between 2 (d) (ThuLEP, thulium laser enucleation of the prostate) and 4.4 days (TURP, transurethral resection of the prostate). Complication rates ranged between 6% (HoLAP, holmium laser ablation of the prostate) and 34% (PVP, photoselective vaporization of the prostate); the maximum rate of severe complications was 4% (TURP). The mean postoperative maximal urinary flow (Qmax) in mL/sec. ranged between 12.9 mL/sec. (HoLAP) and 19.8 mL/sec (Hol-TUIP, holmium laser transurethral incision of the prostate). The mean quality of life (QoL) score fell from 4.7 ± 0.9 to 1.8 ± 0.7 (HoLEP), from 4.1 ± 0.4 to 1.9 ± 0.8 (PVP), from 5.1 ± 0.2 to 2.1 ± 0.2 (TURP), and from 4 to 1 (ThuVEP, thulium laser vapoenucleation of the prostate). Pearson's correlation coefficient (r) revealed a positive linear correlation between age and inferior functional outcome (higher postoperative International Prostate Symptom Score (IPSS) [r = 0.4175]), higher overall complication rates (r = 0.5432), and blood transfusions (r = 0.4474) across all surgical techniques. Conclusions: This meta-analysis provides the summary estimates for perioperative and postoperative functional outcome and safety of endoscopic treatment options for BPO in patients ≥ 75 years of age. Of particular importance is that all surgical techniques significantly improve the postoperative quality of life of patients in this age group compared to their preoperative quality of life.

Off-Label Use of an External Hand Fixator for Craniomaxillofacial Fractures-An Anatomical Feasibility Study.

BACKGROUND: The lack of resources limits the treatment of craniomaxillofacial fractures (CMF) in low-income countries (LIC). Therefore, Barton bandages and/or interdental wiring are considered in these regions. Fracture reduction is maintained by permanent occlusion for 6 weeks, which often leads to limited compliance and dissatisfying results. The aim of this cadaver-based study is to evaluate the feasibility of the use of an external face fixator (EFF) for the treatment of CMF, its biomechanical values and to define the optimal pin insertion points and angles. MATERIALS AND METHODS: An AO hand fixator was used. CMF of types Le Fort 1-3 with split fractures of the hard palate were treated with EFF on 13 anatomical specimens. Fractures were created using a chisel, and pins were placed in specific anatomical regions. The maximal pull-out force [N] of pins was analysed by a tensile force gauge, and Fmax of the mandibular pins was evaluated. Computer tomography scans were performed on the healthy, fractured and EFF-treated skulls. RESULTS: The pull-out forces for the single pins were mandibular pins (n = 15, median 488.0 N), supraorbital pins (n = 15, median 455.0 N), zygomatic pins (n = 14, median 269.1 N), medial hard palate pins (n = 12, median 208.4 N) and lateral hard palate pins (n = 8, median 49.6 N). CONCLUSIONS: The results indicate that the operation technique is feasible, and the stability of the EFF is sufficient for maintaining the reduction. The required pins can safely be inserted into the described areas with good reduction results. Using EFF offers a feasible alternative to the non-surgical treatment of CMF in LIC.

[Prehospital management in trauma patients and the increasing number of helicopter EMS transportations : An epidemiological study of the TraumaRegister DGU®]. / Präklinisches Management bei Traumapatienten und die zunehmende Zahl von Helikopter-Rettungstransporten : Eine epidemiologische Studie des TraumaRegister DGU®.

BACKGROUND/OBJECTIVE: To compare the prehospital treatment modalities and intervention regimens for major trauma patients with comparable injury patterns between Austria and Germany. PATIENTS AND METHODS: This analysis is based on data retrieved from the TraumaRegister DGU®. Data included severely injured trauma patients with an injury severity score (ISS) ≥ 16, an age ≥ 16 years, and who were primarily admitted to an Austrian (n = 4186) or German (n = 41,484) level I trauma center (TC) from 2008 to 2017. Investigated endpoints included prehospital times and interventions performed until final hospital admission. RESULTS: The cumulative time for transportation from the site of the accident to the hospital did not significantly differ between the countries (62 min in Austria, 65 min in Germany). Overall, 53% of all trauma patients in Austria were transported to the hospital with a helicopter compared to 37% in Germany (p < 0.001). The rate of intubation was 48% in both countries, the number of chest tubes placed (5.7% Germany, 4.9% Austria), and the frequency of administered catecholamines (13.4% Germany, 12.3% Austria) were comparable (Φ = 0.00). Hemodynamic instability (systolic blood pressure, BP ≤ 90 mmHg) upon arrival in the TC was higher in Austria (20.6% vs. 14.7% in Germany; p < 0.001). A median of 500 mL of fluid was administered in Austria, whereas in Germany 1000 mL was infused (p < 0.001). Patient demographics did not reveal a relationship (Φ = 0.00) between both countries, and the majority of patients sustained a blunt trauma (96%). The observed ASA score of 3-4 was 16.8% in Germany versus 11.9% in Austria. CONCLUSION: Significantly more helicopter EMS transportations (HEMS) were carried out in Austria. The authors suggest implementing international guidelines to explicitly use the HEMS system for trauma patients only a) for the rescue/care of people who have had an accident or are in life-threatening situations, b) for the transport of emergency patients with ISS > 16, c) for transportation of rescue or recovery personnel to hard to reach regions or, d) for the transport of medicinal products, especially blood products, organ transplants or medical devices.

Renal Arteriovenous (AV) Fistula after High-Grade Blunt Renal Trauma Caused by Traffic Accidents.

PURPOSE: To report a series of three patients with traumatic renal AV fistulas after blunt renal laceration. METHODS: We retrospectively analyzed the renal trauma cases treated in the Department of Urology of Salzburg University Clinic during a time period of 10 years concerning traumatic AV fistula formation and other clinical parameters. RESULTS: In total, 3 cases of traumatic AV fistula formation were identified in 106 blunt renal trauma patients (2.8%), with a mean age of 39 (17-56) years. All renal traumas were classified as American Association for the Surgery of Trauma (AAST) grade IV. Two patients were primarily treated with ureteral stent; one was managed conservatively. All AV fistulas were diagnosed after a mean time of 7 (1-13) days. Two patients were symptomatic with gross hematuria, and the mean time between trauma and onset of symptoms was 11 (9-13) days. All cases were managed via coil embolization after a mean of 10 (8-13) days. Two patients received a second intervention after a mean of 18 (11-25) days. The mean AV fistula size was 18.7 (12-24) mm. Mean hemoglobin loss was 3.6 g/dL. One patient received one erythrocyte concentrate. Discharge was after a mean time of 13.3 (7-12) days, with the mean time of intensive care treatment being 2.3 (1-3) days. CONCLUSIONS: Traumatic renal AV fistula is a rare but severe complication associated with higher-grade renal trauma. It can become evident through hematuria or blood loss several days after the initial trauma. The availability of coil embolization in a trauma center can help kidney preservation management.

Minimally invasive plate osteosynthesis (MIPO) for distal humeral fractures: a cadaveric study and first clinical application.

BACKGROUND: The indication for minimally invasive plate osteosynthesis (MIPO) may include articular fractures depending on the fracture pattern. The goal of this study was to evaluate the feasibility of the MIPO technique for extra- and intra-articular distal humeral fractures. METHODS: The feasibility of the MIPO technique was assessed on 8 cadaveric elbows and 2 clinical cases. The four surgical approaches tested included a 20-mm ulnar incision, a 20-mm dorsoradial incision, and two incisions for olecranon osteotomy (A and B). Surgical incision A was 40 mm on the osteotomy level of the olecranon, and surgical incision B was an extension of the radial incision toward the osteotomy of the olecranon (80 mm). The four approaches were tested on 4 extra-articular (AO 13 A3) fractures and 4 intra-articular (AO 13 C3) fractures. RESULTS: Reduction and plate fixation of all distal humeral fractures (8 cadaveric) with and without osteotomy was feasible. However, when using approach B, the soft tissue tension is reduced due to the wider incision. Nevertheless, both approaches A and B showed the same adequate intra-articular fracture control and reduction. CONCLUSION: The MIPO technique for reduction and plate fixation in distal humeral fractures is feasible. LEVEL OF EVIDENCE: As a feasibility study, this study cannot be clearly classified into a level of evidence. It corresponds most closely to level IV.

Development of a Metaphyseal Non-Union Model in the Osteoporotic Rat Femur.

The aim of this current study was to establish a metaphyseal femoral non-union model in osteoporotic rats by comparing a power tool versus a manual tool for fracture creation. Twelve adult female Sprague Dawley rats were ovariectomized (OVX) and received a special diet for 6 weeks. Biweekly pQCT measurements confirmed a significant reduction in the cancellous and total bone mineral density in OVX rats compared to control (CTRL) animals. After 6 weeks, OVX rats underwent surgery creating a distal metaphyseal osteotomy, either using a piezoelectric- (n = 6) or a manual Gigli wire (n = 6) saw. Fractures were stabilized with a Y-shaped mini-locking plate. Within each group, three rats received Alginate directly into the fracture gap. OVX animals gained more weight over 8 weeks compared to CTRL animals. pQCT analysis showed a significant difference in the volumetric cancellous bone mineral density between OVX and CTRL rats. A histological examination of the osteoporotic phenotype was completed. Radiographic evaluation and Masson-Goldner trichrome staining with the piezoelectric saw failed to demonstrate bony bridging or a callus formation. New bone formation and complete healing were seen after 6 weeks in the Gigli group. For the creation of a metaphyseal atrophic non-union in the osteoporotic bone, a piezoelectric saw should be used.

Comparison of Epidemiological Data of Complex Regional Pain Syndrome (CRPS) Patients in Relation to Disease Severity-A Retrospective Single-Center Study.

A retrospective data analysis of 159 complex regional pain syndrome (CRPS) patients (n = 116 women, 73.0%, mean age 60.9 ± 14.4 years; n = 43 men, 27.0%, mean age 52.3 ± 16.7 years) was performed from 2009 to 2020. The right side was affected in 74 patients (46.5%), the left in 84 patients (52.8%), and 1 patient (0.7%) developed a bilateral CRPS. Data were analyzed for the frequency and distribution of symptoms. The number of reduction maneuvers and the number of Budapest criteria were compared in relation to the severity of CRPS. Hand and wrist (n = 107, 67.3%), followed by foot and ankle (n = 36, 22.6%) and other locations (n = 16, 10.1%) were mainly affected by CRPS. The main causes included direct trauma (n = 120, 75.5%), surgery without previous trauma (n = 25, 15.7%), other causes (n = 9, 5.7%), and spontaneous development (n = 3, 1.9%); there was also missing documentation (n = 2, 1.3%). The most common symptoms were difference in temperature (n = 156, 98.1%), limitation of movement (n = 149, 93.7%), and swelling (n = 146, 91.8%). There was no correlation between the number of reduction maneuvers and the number of Budapest criteria. In summary, patients with the following constellation are at increased risk of CRPS: a female, over 60 years old, who has fallen and has sustained a fracture in the hand or wrist with persistent pain and has been immobilized with a cast for approx. 4 weeks.

The FRISK (Fracture Risk)-A New Tool to Indicate the Probability of Fractures.

Increasing patient inflow into the emergency department makes it necessary to optimize triage management. The scope of this work was to determine simple factors that could detect fractures in patients without the need for specialized personnel. Between 2014 and 2015, 798 patients were admitted to an orthopedic emergency department and prospectively included in the study. The patients received a questionnaire before contacting the doctor. Objective and subjective data were evaluated to determine fracture risk for the upper and lower extremities. The highest risk for fractures in one region was the hip (73.21%; n = 56), followed by the wrist (60.32%; n = 63) and the femoral shaft (4 of 7, 57.14%; n = 7). The regions with the lowest risk were the knee (8.41%; n = 107), the ankle (18.29%; n = 164), and the forearm shaft (30.00%; n = 10). Age was a predictor for fracture: patients older than 59 years had a risk greater than 59.26%, and patients older than 90 years had a risk greater than 83.33%. The functional questions could exclude fractures. Three factors seem to be able to predict fracture risk: the injured region, the patient's age, and a functional question. They can be used for a probatory heuristic that needs to be proven in a prospective way.

The Antimicrobial Resistance (AMR) Rates of Uropathogens in a Rural Western African Area-A Retrospective Single-Center Study from Kpando, Ghana.

Little is known about the antimicrobial resistance (AMR) status of uropathogens in Western Africa. We performed a retrospective evaluation of urine cultures collected from the rural Margret Marquart Catholic Hospital, Kpando, Ghana during the time period from October 2019−December 2021. Urine samples from 348 patients (median age 40 years, 52.6% male) were examined. Of these, 125 (35.9%) showed either fungal or bacterial growth, including Escherichia coli in 48 (38.4%), Candida species (spp.) in 29 (23.2%), Klebsiella spp. in 27 (21.6%), Proteus spp. in 12 (9.6%), Citrobacter spp. in 10 (8.0%), Salmonella spp. in 4 (3.2%), Staphylococcus spp. in 3 (2.4%), and Pseudomonas spp. in 2 (1.6%) cases. Two bacterial spp. were detected in 7 samples (5.6%). Antibiotic susceptibility testing showed resistance to a mean 8.6 out of 11 tested antibiotics per patient. Significant predictors (p < 0.05) of bacterial growth were age (OR 1.03), female sex (OR 3.84), and the number of pus cells (OR 1.05) and epithelial cells (OR 1.07) in urine microscopy. We observed an alarmingly high AMR rate among the uropathogens detected, even to reserve antibiotics. A similar resistance profile can be expected in West African patients living in high-income countries. These observations warrant the implementation of restrictive antibiotic protocols, together with the expansion of urine culture testing capacities, improvement of documentation and reporting of AMR rates, and continued research and development of new antibiotic therapies in order to stem the progression of AMR in this West African region.

Follow-Up Chest X-rays in Minor Chest Trauma with Fewer Than Three Rib Fractures: A Justifiable, Habitual Re-Imaging Industry?

Objective: We evaluated the necessity of follow-up chest X-rays (CXRs) to exclude a pneumothorax after 1 week of initial hospital presentation in patients with no signs of respiratory distress and fewer than three rib fractures. Materials and Methods: Adult patients with fewer than three fractured ribs who presented at our Level I trauma center between 2015 and 2017 were evaluated retrospectively. Patients with sternal fractures, who had suffered a polytrauma, or were primarily treated with a chest tube were excluded. The patients' and fractures' characteristics, trauma mechanism, median follow-up time, and the number of required secondary interventions were recorded. Results: This study included 249 patients, 137 (55.0%) of whom were male, with a median age of 64.34 years. In 150 patients (60.2%) one rib was affected, in 99 patients (39.8%) two ribs were affected, with the fractured ribs being true ribs (1-7) in 72 cases (28.9%), false ribs (8-12) in 151 cases (60.6%), and both in 26 cases (10.4%). The affected thorax half was the left side in 124 cases (49.8%) and both thorax halves in 4 cases (1.6%). The median follow-up time was 9 ± 4 days. In the follow-up CXRs, six patients (1.6%) required delayed intervention (tube thoracostomy): one case of hemopneumothorax and five cases of pneumothorax. All of the patients fully recovered. Conclusions: Planned CXR follow-ups revealed only a small number of complications that needed intervention and therefore seem not to be necessary. Symptom-triggered reappearance seems to be more sufficient and economical compared to habitual reimaging.

The Diagnostic Value of the Added MR Imaging of the Scrotum in the Preoperative Workup of Sonographically Indeterminate Testicular Lesions-A Retrospective Multicenter Analysis.

BACKGROUND: The purpose of this study was to retrospectively analyze the diagnostic accuracy of magnetic resonance imaging (MRI) examinations of the scrotum in comparison with standard ultrasound (US) and histopathology. METHODS: A retrospective multi-center analysis of MRI examinations of the scrotum performed between 06/2008 and 04/2021 was conducted. RESULTS: A total of n = 113 patients were included. A total of 53 histopathologies were available, with 52.8% malignant and 50.9% benign findings. Related to histopathology, imaging was true negative, false negative, false positive, and true positive in 4.1%, 2.1%, 25.0% and 37.5% for standard ultrasound (US) and 9.1%, 1.8%, 25.5% and 43.6% for MRI. Sensitivity, specificity, positive predictive value and negative predictive value were 94.7%, 20.0%, 36.0% and 88.9% for US and 85.7%, 72.8%, 52.1% and 93.7% for MRI, respectively. Benign lesions were significantly smaller than malignant ones in standard US (p = 0.001), histopathology (p = 0.001) and MRI (p = 0.004). The size of malignant tumors did not differ significantly between histopathology and standard US (0.72) and between histopathology and MRI (p = 0.88). CONCLUSIONS: MRI shows good sensitivity and specificity for the estimation of testicular tumors in this collective. Benign lesions are significantly smaller than malignant ones. Both MRI and US can estimate the size of malignant tumors adequately.

Reevaluation of a classification system: stable and unstable odontoid fractures in geriatric patients-a radiological outcome measurement.

OBJECTIVES: We carried out a retrospective cohort study to differentiate geriatric odontoid fractures into stable and unstable and correlated it with fracture fusion rates. Results are based on the literature and on our own experience. The authors propose that the simple Anderson and D'Alonzo classification may not be sufficient for geriatric patients. METHODS: There were 89 patients ≥ 65 years who presented at our institution with type II and III odontoid fractures from 2003 until 2017 and were included in this study. Each patient was categorized with CT scans to evaluate the type of fracture, fracture gap (mm), fracture angulation (°), fracture displacement (mm) and direction (ventral, dorsal). Fractures were categorized as stable [SF] or unstable [UF] distinguished by the parameters of its angulation (< / > 11°) and displacement (< / > 5 mm) with a follow-up time of 6 months. SFs were treated with a semi-rigid immobilization for 6 weeks, UFs surgically-preferably with a C1-C2 posterior fusion. RESULTS: The classification into SFs and UFs was significant for its angulation (P = 0.0006) and displacement (P < 0.0001). SF group (n = 57): A primary stable union was observed in 35, a stable non-union in 10, and an unstable non-union in 8 patients of which 4 were treated with a C1/2 fixation. The overall consolidation rate was 79%. UF group (n = 32): A posterior C1-C2 fusion was carried out in 23 patients, a C0 onto C4 stabilization in 7 and an anterior odontoid screw fixation in 2. The union rate was 100%. Twenty-one type II SFs (91%) consolidated with a nonoperative management (P < 0.001). A primary non-union occurred more often in type II than in type III fractures (P = 0.0023). There was no significant difference in the 30-day overall case fatality (P = 0.3786). CONCLUSION: To separate dens fractures into SFs and UFs is feasible. For SFs, semi-rigid immobilization provides a high consolidation rate. Stable non-unions are acceptable, and the authors suggest a posterior transarticular C1-C2 fixation as the preferred surgical treatment for UFs. LEVEL OF EVIDENCE: Level III.

Off-Label Treatment for Severe Craniomaxillofacial Fractures in Low-Income Countries-A Novel Operation Method with the External Face Fixator.

INTRODUCTION: Craniomaxillofacial fractures (CMF) are common in low-income countries (LIC). Due to limited resources, treatment of these fractures usually consists of interdental wiring or immobilization with a Barton bandage to maintain the reduction by permanent occlusion. These non-surgical treatment methods often lead to unsatisfactory results, such as a disturbed dental occlusion and lockjaw. The aim of this study is to present an off-label treatment option for CMF by applying a hand fixator as external face fixator (EFF) and to demonstrate the surgical method in detail. MATERIALS AND METHODS: The feasibility and postoperative outcomes of this new off-label operation technique were evaluated by analyzing patients with CMF (n = 13) treated at an NGO hospital in Sierra Leone between 2015 and 2019. RESULTS: The application of the EFF was feasible. The biggest advantage compared to the conventional non-operative methods was, that a dynamic occlusion was still possible during the 6 weeks healing period. Hence, patients could eat and drink almost normally and perform dental hygiene with the EFF in place. We did not discover pintrack infections or other complications. Three patients developed an oronasal fistula due to traumatic a palatal bone loss of about 7-8 mm which was treated by a palatal mucoperiosteal flap 15-20 days after the first operation. DISCUSSION AND CONCLUSIONS: In LIC, where plate osteosynthesis for CMF cannot be performed due to limited resources the application of an EFF is a promising alternative for a better outcome and an improved quality of life for the patients.

From Interferon to Checkpoint Inhibition Therapy-A Systematic Review of New Immune-Modulating Agents in Bacillus Calmette-Guérin (BCG) Refractory Non-Muscle-Invasive Bladder Cancer (NMIBC).

BACKGROUND: In Bacillus Calmette-Guérin (BCG) refractory non-muscle-invasive bladder cancer (NMIBC), radical cystectomy is the gold standard. The advent of immune checkpoint inhibitors (CPIs) has permanently changed the therapy landscape of bladder cancer (BC). This article presents a systematic review of immune-modulating (IM) therapies (CPIs and others) in BCG-refractory NMIBC. METHODS: In total, 406 articles were identified through data bank research in PubMed/Medline, with data cutoff in October 2021. Four full-text articles and four additional congress abstracts were included in the review. RESULTS: Durvalumab plus Oportuzumab monatox, Pembrolizumab, and Nadofaragene firadenovec (NF) show complete response (CR) rates of 41.6%, 40.6%, and 59.6% after 3 months, with a long-lasting effect, especially for NF (12-month CR rate of 30.5%). Instillations with oncolytic viruses such as NF and CG0070 show good efficacy without triggering significant immune-mediated systemic adverse events. Recombinant BCG VPM1002BC could prove to be valid as an alternative to BCG in the future. The recombinant pox-viral vector vaccine PANVAC™ is not convincing in combination with BCG. Interleukin mediating therapies, such as ALT-803, are currently being studied. CONCLUSION: CPIs and other IM agents now offer an increasing opportunity for bladder-preserving strategies. Studies on different substances are ongoing and will yield new findings.

On the black slope: analysis of the course of a blunt renal trauma collective in a winter sports region.

PURPOSE: The aim of this study was to analyze the injury patterns and clinical course of a winter sport dominated by blunt renal trauma collective. METHODS: Blunt renal trauma cases (N = 106) treated in a Level 1 Trauma Center in Austria were analyzed. RESULTS: We encountered 12.3% grade 1, 10.4% grade 2, 32.1% grade 3, 38.7% grade 4 and 6.6% grade 5 renal traumata classified according to the American Association for the Surgery of Trauma (AAST). The mechanisms of injury (MOI) did not have an influence on the frequency of HG trauma (i.e., grade 4 and 5). No concomitant injuries (CIs) were found in 57.9% of patients. The number of patients without CIs was significantly higher in the sports associated trauma group compared to other MOIs (p < 0.01). In 94.3% the primary treatment was a non-operative management (NOM) including 56.6% conservative, 34.0% endourological, and 3.8% interventional therapies. A follow-up computed tomography (FU-CT) was performed in 81.1%, 3.3 days after trauma. After FU-CT, the primary therapy was changed in 11.4% of cases (grade ≥ 3). Comparing the Hb loss between the patients with grade 3 and 4 kidney trauma with and without revision surgery, we find a significantly increased Hb loss within the first 96 h after the trauma in the group with a needed change of therapy (p < 0.0001). The overall rate of nephrectomy (primary or secondary) was 9.4%. Independent predictors of nephrectomy were HG trauma (p < 0.01), age (p < 0.05), and sex (p < 0.05). The probability of nephrectomy was lower with (winter) sports-associated trauma (p < 0.1). CONCLUSIONS: Sports-associated blunt renal trauma is more likely to occur isolated, and has a lower risk of severe outcomes, compared to other trauma mechanisms. NOM can successfully be performed in over 90% of all trauma grades.

Mild Traumatic Brain Injury in Older Adults: Are Routine Second cCT Scans Necessary?

Fall-related hospitalizations among older adults have been increasing in recent decades. One of the most common reasons for this is minimal or mild traumatic brain injury (mTBI) in older individuals taking anticoagulant medication. In this study, we analyzed all inpatient stays from January 2017 to December 2019 of patients aged > 75 years with a mTBI on anticoagulant therapy who received at least two cranial computer tomography (cCT) scans. Of 1477 inpatient stays, 39 had primary cranial bleeding, and in 1438 the results of initial scans were negative for cranial bleeding. Of these 1438 cases, 6 suffered secondary bleeding from the control cCT scan. There was no significance for bleeding related to the type of anticoagulation. We conclude that geriatric patients under anticoagulant medication don't need a second cCT scan if the primary cCT was negative for intracranial bleeding and the patient shows no clinical signs of bleeding. These patients can be dismissed but require an evaluation for need of home care or protective measures to prevent recurrent falls. The type of anticoagulant medication does not affect the risk of bleeding.

Enhanced BMP-2-Mediated Bone Repair Using an Anisotropic Silk Fibroin Scaffold Coated with Bone-like Apatite.

The repair of large bone defects remains challenging and often requires graft material due to limited availability of autologous bone. In clinical settings, collagen sponges loaded with excessive amounts of bone morphogenetic protein 2 (rhBMP-2) are occasionally used for the treatment of bone non-unions, increasing the risk of adverse events. Therefore, strategies to reduce rhBMP-2 dosage are desirable. Silk scaffolds show great promise due to their favorable biocompatibility and their utility for various biofabrication methods. For this study, we generated silk scaffolds with axially aligned pores, which were subsequently treated with 10× simulated body fluid (SBF) to generate an apatitic calcium phosphate coating. Using a rat femoral critical sized defect model (CSD) we evaluated if the resulting scaffold allows the reduction of BMP-2 dosage to promote efficient bone repair by providing appropriate guidance cues. Highly porous, anisotropic silk scaffolds were produced, demonstrating good cytocompatibility in vitro and treatment with 10× SBF resulted in efficient surface coating. In vivo, the coated silk scaffolds loaded with a low dose of rhBMP-2 demonstrated significantly improved bone regeneration when compared to the unmineralized scaffold. Overall, our findings show that this simple and cost-efficient technique yields scaffolds that enhance rhBMP-2 mediated bone healing.

Tenophages: a novel macrophage-like tendon cell population expressing CX3CL1 and CX3CR1.

Tendon disorders frequently occur and recent evidence has clearly implicated the presence of immune cells and inflammatory events during early tendinopathy. However, the origin and properties of these cells remain poorly defined. Therefore, the aim of this study was to determine the presence of cells in healthy rodent and human tendon tissue fulfilling macrophage-like functions. Using various transgenic reporter mouse models, we demonstrate the presence of tendon-resident cells in the dense matrix of the tendon core expressing the fractalkine (Fkn) receptor CX3CR1 and its cognate ligand CX3CL1/Fkn. Pro-inflammatory stimulation of 3D tendon-like constructs in vitro resulted in a significant increase in the expression of IL-1ß, IL-6, Mmp3, Mmp9, CX3CL1 and epiregulin, which has been reported to contribute to inflammation, wound healing and tissue repair. Furthermore, we demonstrate that inhibition of the Fkn receptor blocked tendon cell migration in vitro, and show the presence of CX3CL1/CX3CR1/EREG-expressing cells in healthy human tendons. Taken together, we demonstrate the presence of CX3CL1+/CX3CR1+ 'tenophages' within the healthy tendon proper, which potentially fulfill surveillance functions in tendons.This article has an associated First Person interview with the first author of the paper.