Human Acellular Collagen Matrices-Clinical Opportunities in Tissue Replacement.

The field of regenerative medicine is increasingly in need of effective and biocompatible materials for tissue engineering. Human acellular dermal matrix (hADM)-derived collagen matrices stand out as a particularly promising candidate. Their ability to preserve structural integrity, coupled with exceptional biocompatibility, positions them as a viable choice for tissue replacement. However, their clinical application has been largely confined to serving as scaffolds. This study aims to expand the horizon of clinical uses for collagen sheets by exploring the diverse cutting-edge clinical demands. This review illustrates the clinical utilizations of collagen sheets beyond traditional roles, such as covering skin defects or acting solely as scaffolds. In particular, the potential of Epiflex®, a commercially available and immediately clinically usable allogeneic membrane, will be evaluated. Collagen sheets have demonstrated efficacy in bone reconstruction, where they can substitute the induced Masquelet membrane in a single-stage procedure, proving to be clinically effective and safe. The application of these membranes allow the reconstruction of substantial tissue defects, without requiring extensive plastic reconstructive surgery. Additionally, they are found to be apt for addressing osteochondritis dissecans lesions and for ligament reconstruction in the carpus. The compelling clinical examples showcased in this study affirm that the applications of human ADM extend significantly beyond its initial use for skin defect treatments. hADM has proven to be highly successful and well-tolerated in managing various etiologies of bone and soft tissue defects, enhancing patient care outcomes. In particular, the application from the shelf reduces the need for additional surgery or donor site defects.

Early spontaneous breathing for acute respiratory distress syndrome in individuals with COVID-19.

BACKGROUND: Acute respiratory distress syndrome (ARDS) represents the most severe course of COVID-19 (caused by the SARS-CoV-2 virus), usually resulting in a prolonged stay in an intensive care unit (ICU) and high mortality rates. Despite the fact that most affected individuals need invasive mechanical ventilation (IMV), evidence on specific ventilation strategies for ARDS caused by COVID-19 is scarce. Spontaneous breathing during IMV is part of a therapeutic concept comprising light levels of sedation and the avoidance of neuromuscular blocking agents (NMBA). This approach is potentially associated with both advantages (e.g. a preserved diaphragmatic motility and an optimised ventilation-perfusion ratio of the ventilated lung), as well as risks (e.g. a higher rate of ventilator-induced lung injury or a worsening of pulmonary oedema due to increases in transpulmonary pressure). As a consequence, spontaneous breathing in people with COVID-19-ARDS who are receiving IMV is subject to an ongoing debate amongst intensivists. OBJECTIVES: To assess the benefits and harms of early spontaneous breathing activity in invasively ventilated people with COVID-19 with ARDS compared to ventilation strategies that avoid spontaneous breathing. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register (which includes CENTRAL, PubMed, Embase, Clinical Trials.gov WHO ICTRP, and medRxiv) and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies from their inception to 2 March 2022. SELECTION CRITERIA: Eligible study designs comprised randomised controlled trials (RCTs) that evaluated spontaneous breathing in participants with COVID-19-related ARDS compared to ventilation strategies that avoided spontaneous breathing (e.g. using NMBA or deep sedation levels). Additionally, we considered controlled before-after studies, interrupted time series with comparison group, prospective cohort studies and retrospective cohort studies. For these non-RCT studies, we considered a minimum total number of 50 participants to be compared as necessary for inclusion. Prioritised outcomes were all-cause mortality, clinical improvement or worsening, quality of life, rate of (serious) adverse events and rate of pneumothorax. Additional outcomes were need for tracheostomy, duration of ICU length of stay and duration of hospitalisation. DATA COLLECTION AND ANALYSIS: We followed the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions. Two review authors independently screened all studies at the title/abstract and full-text screening stage. We also planned to conduct data extraction and risk of bias assessment in duplicate. We planned to conduct meta-analysis for each prioritised outcome, as well as subgroup analyses of mortality regarding severity of oxygenation impairment and duration of ARDS. In addition, we planned to perform sensitivity analyses for studies at high risk of bias, studies using NMBA in addition to deep sedation level to avoid spontaneous breathing and a comparison of preprints versus peer-reviewed articles. We planned to assess the certainty of evidence using the GRADE approach. MAIN RESULTS: We identified no eligible studies for this review. AUTHORS' CONCLUSIONS: We found no direct evidence on whether early spontaneous breathing in SARS-CoV-2-induced ARDS is beneficial or detrimental to this particular group of patients.  RCTs comparing early spontaneous breathing with ventilatory strategies not allowing for spontaneous breathing in SARS-CoV-2-induced ARDS are necessary to determine its value within the treatment of severely ill people with COVID-19. Additionally, studies should aim to clarify whether treatment effects differ between people with SARS-CoV-2-induced ARDS and people with non-SARS-CoV-2-induced ARDS.

Epidemiology of complete knee dislocations: an updated classification system.

INTRODUCTION: Current classifications of complete knee dislocations do not capture the extent of the complex concomitant ligamentous and bony injuries, which may have an impact on future outcomes. The purpose of this retrospective study was to evaluate the epidemiology of complete knee dislocations as well as to present an updated classification system based on the author's experience at a Level-I trauma center. MATERIALS AND METHODS: Only patients with complete loss of contact of the articulating bones and ≥ 18 years of age who admitted in our level-I trauma center between 2002 and 2019 were included. Patients were identified using a retrospective systematical query in the Hospital Information System (HIS) using the International Statistical Classification of Diseases and Related Health Problems Version10 (ICD-10) codes of the German Diagnosis Related Groups (G-DRG). RESULTS: Final data included 80 patients, with the majority of patients being male (n = 64; 80.0%). Mean age was 34.9 years (range: 18-70 years). External protective fixation was applied in 32 patients (40.0%). Reconstruction of the posterior cruciate ligament and the anterior cruciate ligament were performed in 56.3% (n = 45) and 55.0% (n = 44) of cases, respectively. The lateral collateral ligament complex was surgically addressed in 47.5% (n = 38), while the medial collateral ligament complex was reconstructed in 40% (n = 32). Surgery of the lateral meniscus and the medial meniscus was needed in 31.1% (n = 25) and 30.0% (n = 24). Neurovascular surgery occurred in 13.8% (n = 11). From the characteristic injury-patterns the authors of this study present a new classification system that ranks the injuries from Grade-A to Grade-D according to their severity. CONCLUSION: This retrospective study demonstrates that the historically used classification systems for dislocations of the knee are insufficient for these severe injuries. Concomitant ligamentous, neurovascular, bony, and meniscal injuries were frequent, and required several staged procedures. Consequently, an updated classification system is proposed.

11,12 Epoxyeicosatrienoic Acid Rescues Deteriorated Wound Healing in Diabetes.

Epoxyeicosatrienoic acids (EET) facilitate regeneration in different tissues, and their benefit in dermal wound healing has been proven under normal conditions. In this study, we investigated the effect of 11,12 EET on dermal wound healing in diabetes. We induced diabetes by i.p. injection of streptozotocin 2 weeks prior to wound creation on the dorsal side of the mouse ear. 11,12 EET was applied every second day on the wound, whereas the control groups received only solvent. Epithelialization was monitored every second day intravitally up to wound closure. Wounds were stained for VEGF, CD31, TGF-ß, TNF-α, SDF-1α, NF-κB, and Ki-67, and fibroblasts were counted after hematoxylin-eosin stain on days 3, 6, 9, and 16 after wounding. After induction of diabetes, wounds closed on day 13.00 ± 2.20 standard deviation (SD). Local 11,12 ETT application improved wound closure significantly to day 8.40 ± 1.39 SD. EET treatment enhanced VEGF and CD31 expression in wounds on day 3. It also seemed to raise TNF-α level on all days investigated as well as TGF-ß level on days 3 and 6. A decrease in NF-κB could be observed on days 9 and 16 after EET application. The latter findings were not significant. SDF-1α expression was not influenced by EET application, and Ki-67 was significantly less in the EET group on day 9 after EET application. The number of fibroblasts was significantly increased on day 9 after the 11,12 EET application. 11,12 EET improve deteriorated wound healing in diabetes by enhancing neoangiogenesis, especially in the early phase of wound healing. Furthermore, they contribute to the dissolution of the initial inflammatory reaction, allowing the crucial transition from the inflammatory to proliferative phase in wound healing.

Bipolar Corona Discharge-Based Charge Equilibration for Nano Electrospray Gas-Phase Electrophoretic Mobility Molecular Analysis of Bio- and Polymer Nanoparticles.

Separation of polydisperse, single-charged analytes in the nanometer size range in a high laminar sheath flow of particle-free ambient air and a tunable electric field based on the respective particle electrophoretic mobility diameter (EMD) can be achieved via gas-phase electrophoresis. In order to transfer analytes from a volatile electrolyte solution to the gas-phase as a single-charged species, a nano electrospray (nES) process followed by drying of nanodroplets and charge conditioning reaching Boltzmann charge equilibrium is a necessary prerequisite. In the case of a so-called nES gas-phase electrophoretic mobility molecular analyzer (nES GEMMA, also known as nES differential mobility analyzer, nES DMA), charge equilibration is based on bionanoparticle interaction with a bipolar atmosphere induced, e.g., by a radioactive α-particle emitter like 210Po. It was the aim of our investigation to examine whether such a radioactive source can be easily replaced in the same nES housing by a nonradioactive one, i.e., by an AC corona discharge unit. The latter would be significantly easier to handle when compared to radioactive material in laboratory day-to-day business, waste disposal, as well as regulatory confinements. Indeed, we were able to combine a standard nES unit of our nES GEMMA instrument with a commercially available AC corona discharge device in a novel setup via an adapter. Our results show that this replacement yields very good results for a number of chemically different nanoparticles, an exemplary protein, a noncovalent protein complex, a virus-like particle, a polymer, and a liposome sample, when compared to a 210Po based bipolar charge equilibration device.

[Modified arthroscopic technique to replace the posterior cruciate ligament in multiligament knee injuries : Results compared to open tibial inlay technique]. / Modifizierte arthroskopische Technik zum Ersatz des hinteren Kreuzbands bei multiligamentären Kniegelenkverletzungen : Ergebnisse im Vergleich zur offenen "Tibial-inlay"-Technik.

BACKGROUND: There is no standard procedure regarding surgical treatment of multiligament knee injuries involving rupture of the posterior cruciate ligament. OBJECTIVE: Does the modified and purely arthroscopic operation technique show similarly good results compared to the familiar open tibial inlay technique? METHODS: A total of four patients were surgically treated using the open tibial inlay technique (group A) and seven using the modified arthroscopic approach (group B). The prospectively designed follow-up examination comprised the Lysholm score, the subjective questionnaire of the International Knee Documentation Committee (IKDC) score as well as the specifically extended Orthopedic Working Group Knee (OAK) score for clinical assessment. Tests on translational movability of the knee joint were performed with the Rolimeter®. The level of statistical significance alpha was set at 5%. RESULTS: The follow-up examination took place on average 28.5 ± 19.60 months and 30.6 ± 26.26 months postoperatively in groups A and B, respectively. Groups A and B recorded mean 70.3 ± 5.32 and 69.6 ± 19.82 points in the Lysholm score, respectively. In the subjective IKDC score group A showed 67.3 ± 7.76 points and group B 65.9 ± 12.35 points. The OAK score was 77.5 ± 6.10 points in group A and 75.3 ± 11.31 points in group B. The side difference in the posterior drawer test was 1.75 ± 1.192 mm in group A and 2.50 ± 2.160 mm in group B. In the reverse Lachman test differences of 2.37 ± 2.175 mm and 3.22 ± 2.059 mm were measured in groups A and B, respectively. All values showed no significant differences between the two evaluated groups. CONCLUSION: The results of the two operation techniques were not significantly different. The arthroscopic approach is therefore regarded as the preferred method in this institute.

Trunk muscle strength and lumbo-pelvic kinematics in adolescent athletes: Effects of age and sex.

Considering their potential relevance for low-back pain, we investigated trunk muscle strength, sagittal lumbo-pelvic alignment while standing and lumbo-pelvic ratio during trunk flexion in adolescent athletes with regard to the effects of age and sex. Twenty-two early adolescent (EA: 13-15 years, 10 females) and 28 late adolescent (LA: 16-19 years, 14 females) high-level athletes (training duration more than 12 hours per week) participated in the study. We measured trunk extension and trunk flexion moments during maximum voluntary isometric contractions using a dynamometer. Further, we examined lumbo-pelvic kinematics in the upright standing position and during forward trunk bending using two 3-dimensional accelerometers. Using a lineal regression model in which the flexion moment from each participant was used as predictor for the corresponding extension moment, we found higher residuals (P < 0.001) in the EA compared to LA, indicating greater imbalances in the trunk muscle strength in EA. We found a higher lordosis in the upright position, greater pelvic rotation, and greater lordotic posture during the forward bending in females (P < 0.01). These age-related imbalances and sex-related characteristics in lumbo-pelvic kinematics might affect the neuromuscular control of trunk stability and the magnitude of spine loading. We recommend the implementation of specific coordination and stabilization programs for muscle groups that contribute to lumbo-pelvic kinematics and training routines that support a balanced strength development within the trunk muscles in adolescent athletes.

Treatment of infection following intramedullary nailing of tibial shaft fractures-results of the ORS/ISFR expert group survey.

OBJECTIVE: The lack of universally accepted treatment principles and protocols to manage infected intramedullary (IM) nails following tibial fractures continues to challenge us, eliciting a demand for clear guidelines. Our response to this problem was to create an ORS/ISFR taskforce to identify potential solutions and trends based on published evidence and practices globally. MATERIALS AND METHODS: A questionnaire of reported treatment methods was created based on a published meta-analysis on the topic. Treatment methods were divided in two groups: A (retained nail) and B (nail removed). Experts scored the questionnaire items on a scale of 1-4 twice, before and after revealing the success rates for each stage of infection. Inter- and intra-observer variability analysis among experts' personal scores and between experts' scores was performed. An agreement mean and correlation degree between experts' scores was calculated. Finally, a success rate report between groups was performed. RESULTS: Experts underestimated success rate of an individual treatment method compared to published data. The mean difference between experts' scores and published results was + 26.3 ± 46 percentage points. Inter-observer agreement mean was poor (< 0.2) for both rounds. Intra-observer agreement mean across different treatment methods showed a wide variability (18.3 to 64.8%). Experts agree more with published results for nail removal on stage 2 and 3 infections. CONCLUSIONS: Experts' and published data strongly agree to retain the implant for stage 1 infections. A more aggressive approach (nail removal) favoured for infection stages 2 and 3. However, literature supports both treatment strategies. EVIDENCE: Clinical Question.

A laser desorption ionization/matrix-assisted laser desorption ionization target system applicable for three distinct types of instruments (LinTOF/curved field RTOF, LinTOF/RTOF and QqRTOF) with different performance characteristics from three vendors.

RATIONALE: We have developed a target system which enables the use of only one target (i.e. target preparation set) for three different laser desorption ionization (LDI)/matrix-assisted laser desorption ionization (MALDI) mass spectrometric instruments. The focus was on analysing small biomolecules with LDI for future use of the system for the study of meteorite samples (carbonaceous chondrites) using devices with different mass spectrometric performance characteristics. METHODS: Three compounds were selected due to their potential presence in meteoritic chondrites: tryptophan, 2-deoxy-d-ribose and triphenylene. They were prepared (with and without MALDI matrix, i.e. MALDI and LDI) and analysed with three different mass spectrometers (LinTOF/curved field RTOF, LinTOF/RTOF and QqRTOF). The ion sources of two of the instruments were run at high vacuum, and one at intermediate pressure. Two devices used a laser wavelength of 355 nm and one a wavelength of 337 nm. RESULTS: The developed target system operated smoothly with all devices. Tryptophan, 2-deoxy-d-ribose and triphenylene showed similar desorption/ionization behaviour for all instruments using the LDI mode. Interestingly, protonated tryptophan could be observed only with the LinTOF/curved field RTOF device in LDI and MALDI mode, while sodiated molecules were observed with all three instruments (in both ion modes). Deprotonated tryptophan was almost completely obscured by matrix ions in the MALDI mode whereas LDI yielded abundant deprotonated molecules. CONCLUSIONS: The presented target system allowed successful analyses of the three compounds using instruments from different vendors with only one preparation showing different analyser performance characteristics. The elemental composition with the QqRTOF analyser and the high-energy 20 keV collision-induced dissociation fragmentation will be important in identifying unknown compounds in chondrites.

Shear-Dependent Interactions of von Willebrand Factor with Factor VIII and Protease ADAMTS 13 Demonstrated at a Single Molecule Level by Atomic Force Microscopy.

Vital functions of mammals are only possible due to the behavior of blood to coagulate most efficiently in vessels with particularly high wall shear rates. This is caused by the functional changes of the von Willebrand Factor (VWF), which mediates coagulation of blood platelets (primary hemostasis) especially when it is stretched under shear stress. Our data show that shear stretching also affects other functions of VWF: Using a customized device to simulate shear conditions and to conserve the VWF molecules in their unstable, elongated conformation, we visualize at single molecule level by AFM that VWF is preferentially cleaved by the protease ADAMTS13 at higher shear rates. In contrast to this high shear-rate-selective behavior, VWF binds FVIII more effectively only below a critical shear rate of ∼30.000 s(-1), indicating that under harsh shear conditions FVIII is released from its carrier protein. This may be required to facilitate delivery of FVIII locally to promote secondary hemostasis.

Dehydration of corneal anterior donor tissue with polyethylene glycol (PEG)-enriched media.

Anterior donor grafts (including scleral rim, without Descemet membrane) increase in thickness and become hazy upon storage in organ culture (OC) medium. Transfer of these grafts to standard dehydration media just before transplantation does not reduce their thickness to normal. Therefore, we assessed the efficacy of different media enriched with polyethylene glycol (PEG) as dehydrating agents for organ-cultured anterior donor grafts. Grafts were harvested and stored in the commercial OC medium 'Max' (without dextran) for 1 week, and subsequently dehydrated in the standard commercial dehydration medium 'Jet' (with dextran) supplemented with 4-20% PEG3350, or 'Max' supplemented with 20% PEG6000 and PEG20.000, or 5-20% PEG35.000. Central corneal thickness (CCT), as assessed by anterior segment-optical coherence tomography, and transparency were evaluated before, and at 1, 4 and 7 days of dehydration. Transfer of grafts after 1 week of OC (average 1,200 µm) to 'Jet' supplemented with PEG3350 revealed a concentration-dependent effect of dehydration; CCT was restored to normal (500-600 µm) when 10% PEG3350 was added. However, transparency was only temporarily restored; after 1 day, the grafts turned hazy. In contrast, grafts transferred to 'Max' supplemented with 20% PEG35.000 were transparent throughout the evaluation period, but were dehydrated to beyond normal levels (average 300 µm). 'Max' supplemented with 5% PEG35.000 dehydrated grafts to normal values and restored transparency throughout. Thus, dehydration of anterior donor grafts prior to surgery in dextran-free OC medium supplemented with 5% PEG35.000 reduces graft thickness to normal and may facilitate anterior keratoplasty procedures.

[Large Language Models for Rapid Simplification of Quality Assurance Data Input: Field Trial with Real Data in the Context of Tumour Documentation in Urology]. / Large Language Modelle zur schnellen Vereinfachung der Eingabe von Qualitätssicherungsdaten: Performance-Test mit Echtdaten am Beispiel der Tumordokumentation in der Urologie.

INTRODUCTION: Large Language Models (LLMs) such as ChatGPT have rapidly brought the application of artificial intelligence into widespread use. Among many different use cases for text generation and processing, one application is the extraction of data from existing documents and conversations for simplified and automated form-filling. OBJECTIVE: In the field of quality assurance and documentation of cancer diseases, there is currently a significant workload involved in transferring data under various aspects into slightly varying formats and applying interpretations such as the TNM classification of tumours. However, there is a lack of trials with real data to assess the applicability of LLM-supported processes in this area, which would enable an evaluation of efficiency and practicality. This study aims to implement and assess such a trial. METHODOLOGY: A trial was conducted with N=153 privacy-compliant and ethics committee-cleared medical reports from 25 patients. Using the publicly available version of ChatGPT 4.0, an automated script was used to extract the date of initial diagnosis and common tumor classifications. The results were then individually checked for accuracy. Based on this, the utility of a simple system for guided support in tasks related to tumour documentation was assessed. Additionally, the approach was evaluated in terms of operational costs for the model and its applicability. RESULTS: In summary, the study concludes that the use of generative AI in this field is promising and suitable as a tool even in an untrained state. In a simplified calculation, costs of 35 cents are offset by a value creation of 61,54 euros. However, it also becomes clear that AI can only act in a supportive role, and the correct integration with pre-made specific prompts and tools into the workflow is crucial for a relevant performance. CONCLUSION: The use of generative AI in the context of search, transfer, and interpretation tasks in the creation of tumor documentation is a promising approach. However, its implementation in practical applications must be closely monitored, and the optimal interaction between man and machine should continue to be evaluated and must be accompanied by tools and task-specific prompts.

Cell-Based Therapy by Autologous Bone Marrow-Derived Mononuclear Cells for Bone Augmentation of Plate-Stabilized Proximal Humeral Fractures: A Multicentric, Randomized, Open Phase IIa study.

Proximal humerus fractures are common in an aging population. The standard operative treatment is open reduction internal fixation (ORIF) using an angular stable plate. However, this procedure has complications such as a relatively high rate of secondary dislocation, humeral head necrosis or nonunion caused by delayed bony consolidation. Autologous bone marrow mononuclear cells (BMC) combined with a ß-TCP scaffold could support bone healing and is considered clinically safe. This multicentric, randomized, open phase IIa clinical trial (Clinical Trials. Gov Identifier: NCT02803177, Eudra CT No: 2015-001820-51) evaluated whether autologous BMC with ß-TCP in addition to ORIF reduces the incidence of secondary dislocations in patients with proximal humerus fracture. Ninty-four patients equally divided between verum group (BMC+ß-TCP) and control group (ß-TCP only) were targeted and calculated. At the time of planned interim evaluation, ie, enrolment of 56 patients, no statistical difference in secondary dislocations or complications was demonstrated in either group after an observation period of 12 weeks. Radiographic bone healing and DASH score to determine shoulder function were comparable between both groups. Bone marrow harvest and BMC transplantation did not result in any severe adverse events. Therefore, the study was terminated after the interim analysis, as no other result could be expected. From the study results, it can be concluded that the application of autologous BMC is well tolerated, and bone healing can be achieved. Augmentation of bone defects with ß-TCP could be shown to be feasible and might be considered in other clinical situations.

Using Rapid Prototyping to Develop a Cell-Based Platform with Electrical Impedance Sensor Membranes for In Vitro RPMI2650 Nasal Nanotoxicology Monitoring.

Due to advances in additive manufacturing and prototyping, affordable and rapid microfluidic sensor-integrated assays can be fabricated using additive manufacturing, xurography and electrode shadow masking to create versatile platform technologies aimed toward qualitative assessment of acute cytotoxic or cytolytic events using stand-alone biochip platforms in the context of environmental risk assessment. In the current study, we established a nasal mucosa biosensing platform using RPMI2650 mucosa cells inside a membrane-integrated impedance-sensing biochip using exclusively rapid prototyping technologies. In a final proof-of-concept, we applied this biosensing platform to create human cell models of nasal mucosa for monitoring the acute cytotoxic effect of zinc oxide reference nanoparticles. Our data generated with the biochip platform successfully monitored the acute toxicity and cytolytic activity of 6 mM zinc oxide nanoparticles, which was non-invasively monitored as a negative impedance slope on nasal epithelial models, demonstrating the feasibility of rapid prototyping technologies such as additive manufacturing and xurography for cell-based platform development.

Blood Pressure Variability and Plasma Biomarkers of Neuronal Injury and Alzheimer's Disease: A Clinic-Based Study of Patients with Diseases Along the Heart-Brain Axis.

 Higher blood pressure variability (BPV) predisposes to cognitive decline. To investigate underlying mechanisms, we measured 24-h ambulatory BPV, nocturnal dipping and orthostatic hypotension in 518 participants with vascular cognitive impairment, carotid occlusive disease, heart failure, or reference participants. We determined cross-sectional associations between BPV indices and plasma biomarkers of neuronal injury (neurofilament light chain) and Alzheimer's disease (phosphorylated-tau-181 and Aß42/Aß40). None of the BPV indices were significantly associated with any of the biomarkers. Hence, in patients with diseases along the heart-brain axis, we found no evidence for an association between BPV and selected markers of neuronal injury or Alzheimer's disease.

Routine 6-Week Outpatient Radiography and Visit in Patients with Conservatively Treated Multiple Rib Fractures: Valuable or a Waste of Resources?

Background: This study investigated the incidence and clinical consequences of abnormal radiological and clinical findings during routinely performed 6-week outpatient visits in patients treated conservatively for multiple (3 or more) rib fractures. Methods: A retrospective analysis was conducted among patients with multiple rib fractures treated conservatively between 2018 and 2021 (Opvent database). The primary outcome was the incidence of abnormalities on chest X-ray (CXR) and their clinical consequences, which were categorized as requiring intervention or additional clinical/radiological examination. The secondary focus was the incidence of deviation from standard treatment in response to the findings (clinical or radiological) at the routine 6-week outpatient visit. Results: In total, 364 patients were included, of whom 246 had a 6-week visit with CXR. The median age was 57 years (interquartile range, 46-70 years) and the median Injury Severity Score was 17 (interquartile range, 13-22). Forty-six abnormalities (18.7%) were found on CXR. These abnormalities resulted in additional outpatient visits in 4 patients (1.5%) and in chest drain insertion in 2 (0.8%). Only 2 patients (0.8%) with an abnormality on CXR presented without symptoms. None of the 118 patients who had visits without CXR experienced problems. Conclusion: Routine 6-week outpatient visits for patients with conservatively treated multiple rib fractures infrequently revealed abnormalities requiring treatment modifications. It may be questioned whether the 6-week outpatient visit is even necessary. Instead, a more targeted approach could be adopted, providing follow-up to high-risk or high-demand patients only, or offering guidance on recognizing warning signs and providing aftercare through a smartphone application.

Does plate position influence the outcome in midshaft clavicular fractures? A multicenter analysis.

PURPOSE: To date, it remains unclear whether superior or anterior plating is the best option for treating midshaft clavicular fractures. The aim of this study was to compare both techniques with regard to the incidence of implant removal due to implant irritation, risk of complications, time to union, and function. METHODS: In this retrospective cohort study, all midshaft clavicular fractures treated operatively between 2017 and 2020 in two hospitals in Switzerland were analyzed. The participating hospitals differed with regard to their standard practice; one offered superior plating only, while the other predominantly employed an anterior plate. The primary outcome was the incidence of implant removal for irritation. Secondary outcomes were time to union, complications, re-interventions, and range of motion during the follow-up period of at least 6 months. RESULTS: In total, 168 patients were included in the study of which 81 (48%) received anterior plating and 87 (52%) superior plating. The overall mean age was 45 years (SD 16). There was no significant difference between anterior and superior plating with regard to implant removal (58.5% versus 57.1%, p = 0.887), infection (5.7% versus 1.8%, p = 0.071), and time to union (median 48 weeks versus 52 weeks, p = 0.643). Data on range of motion were available in 71 patients. There was no significant difference in anteflexion (median 180 degrees anterior versus 180 degrees superior) and abduction (median 180 degrees anterior versus 180 degrees superior) between the two groups. CONCLUSION: This retrospective cohort study did not find sufficient evidence to recommend one implant position over the other for midshaft clavicular fractures with regard to removal due to irritation. Time to union was similar and Infections were equally rare in both groups. Notably, a considerable number of patients in both groups had their implants removed due to irritation. Larger prospective studies are needed to determine how much plate position contributes to the occurrence of irritation and whether other patient or implant-related factors might play a role. Until this is clarified, implant position should be based on surgeons preference and experience.

Soluble epoxide hydrolase disruption as therapeutic target for wound healing.

BACKGROUND: Cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) possess angiogenic effects. However, the effect of CYP-derived EETs and soluble epoxide hydrolase (sEH) deletion on wound healing in vivo has not been rigorously investigated. In this study, we measured the effect of exogenous CYP-derived EETs and targeted disruption of sEH in an in vivo wound model. MATERIALS AND METHODS: Standardized full-thickness dermal wounds were created on the dorsum of mouse ears. Wound epithelialization was directly viewed and measured using intravital microscopy and computerized planimetry every second day until healing was complete. Wound sections were analyzed by immunostaining for metalloproteinase (MMP) 2, MMP7, MMP9, tissue inhibitor of metalloproteinases (TIMP) 1, and tumor necrosis factor (TNF) α on days 2, 4, and 12. RESULTS: Treatment with 11,12-EETs, 14,15-EETs, and sEH deletion significantly accelerated wound closure. This effect was attenuated by the EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE) in sEH(-/-) mice. Neither 11,12- nor 14,15-EETs caused significant alterations in MMP9 expression in wounds. In contrast, MMP2 and MMP7 were significantly upregulated in the EET-treated groups, whereas TIMP1 and TNF-α were downregulated. CONCLUSIONS: Collectively, these data demonstrated that potentiation of the CYP epoxy-genase pathway by either exogenous CYP-derived EETs or sEH deletion significantly accelerated wound epithelialization in vivo. This beneficial effect might be due to downregulation of TNF-α production and, to a lesser degree, to the release of MMPs and could be used as a viable angiogenic therapeutic strategy.

Human endothelial-like differentiated precursor cells maintain their endothelial characteristics when cocultured with mesenchymal stem cell and seeded onto human cancellous bone.

INTRODUCTION: Cancellous bone is frequently used for filling bone defects in a clinical setting. It provides favourable conditions for regenerative cells such as MSC and early EPC. The combination of MSC and EPC results in superior bone healing in experimental bone healing models. MATERIALS AND METHODS: We investigated the influence of osteogenic culture conditions on the endothelial properties of early EPC and the osteogenic properties of MSC when cocultured on cancellous bone. Additionally, cell adhesion, metabolic activity, and differentiation were assessed 2, 6, and 10 days after seeding. RESULTS: The number of adhering EPC and MSC decreased over time; however the cells remained metabolically active over the 10-day measurement period. In spite of a decline of lineage specific markers, cells maintained their differentiation to a reduced level. Osteogenic stimulation of EPC caused a decline but not abolishment of endothelial characteristics and did not induce osteogenic gene expression. Osteogenic stimulation of MSC significantly increased their metabolic activity whereas collagen-1α and alkaline phosphatase gene expressions declined. When cocultured with EPC, MSC's collagen-1α gene expression increased significantly. CONCLUSION: EPC and MSC can be cocultured in vitro on cancellous bone under osteogenic conditions, and coculturing EPC with MSC stabilizes the latter's collagen-1α gene expression.