Vascular Endothelial Growth Factor as Potential Biomarker for COVID-19 Severity.

INTRODUCTION: COVID-19 is characterized by immunological responses to viral replication and coherent with endothelitis, microvascular disturbance of lung vasculature and coagulopathy. Vascular Endothelial Growth Factor (VEGF) is a proangiogenic mediator regulating endothelial changes. It is induced by proinflammatory signaling and hypoxia. We sought to determine whether VEGF levels differ between SARS-CoV-2-positive patients of different disease severity and whether VEGF might be useful in risk stratification. METHODS: After retrospective screening of all SARS-CoV-2-positive patients treated in Unfallkrankenhaus Berlin in 2020, we included those with documented VEGF measurement. We extracted laboratory values and clinical parameters. An exploratory data analysis was performed to detect possible relations between VEGF level and clinical disease features. RESULTS: We included 167 SARS-CoV-2-positive patients of which 139 suffered from COVID-19. Seventy-one of the COVID-19 patients had to be treated in the intensive care unit (ICU), those patients exhibited higher VEGF levels than those being admitted to normal wards (535 vs 279 pg/L, P < .001). APACHE-2 (Acute Physiology And Chronic Health Evaluation Score) correlated with mortality and patients with high values showed higher VEGF concentrations on admission (456 vs 875 pg/L, p = 0.006). Receiver operating characteristic analytic revealed that the occurrence of organ dysfunctions like acute respiratory distress syndrome (ARDS), shock, or acute kidney injury could be predicted by VEGF. It was significantly higher in patients who later died compared to survivors (637 vs 389 pg/mL, P = 0.041) and predicted mortality with same accuracy as established markers. In our cohort, association of VEGF above 277 pg/L on admission with risk of ARDS could be confirmed in logistic regression adjusting for possible confounding factors (odds ratio 3.1, 95% confidence interval: 1.34-7.7). DISCUSSION: Even though there are several limitations to this retrospective study it revealed that in COVID-19 patients VEGF can contribute to the prediction of necessity of ICU, mortality and the prediction of ARDS, kidney injury or shock. Its use in risk stratification and potential pathogenetic involvement should be further investigated.

Inhibition of Angiogenesis by Treatment with Cold Atmospheric Plasma as a Promising Therapeutic Approach in Oncology.

BACKGROUND: Cold atmospheric plasma (CAP) is increasingly used in the field of oncology. Many of the mechanisms of action of CAP, such as inhibiting proliferation, DNA breakage, or the destruction of cell membrane integrity, have been investigated in many different types of tumors. In this regard, data are available from both in vivo and in vitro studies. Not only the direct treatment of a tumor but also the influence on its blood supply play a decisive role in the success of the therapy and the patient's further prognosis. Whether the CAP influences this process is unknown, and the first indications in this regard are addressed in this study. METHODS: Two different devices, kINPen and MiniJet, were used as CAP sources. Human endothelial cell line HDMEC were treated directly and indirectly with CAP, and growth kinetics were performed. To indicate apoptotic processes, caspase-3/7 assay and TUNEL assay were used. The influence of CAP on cellular metabolism was examined using the MTT and glucose assay. After CAP exposure, tube formation assay was performed to examine the capillary tube formation abilities of HDMEC and their migration was messured in separate assays. To investigate in a possible mutagenic effect of CAP treatment, a hypoxanthine-guanine-phosphoribosyl-transferase assay with non malignant cell (CCL-93) line was performed. RESULTS: The direct CAP treatment of the HDMEC showed a robust growth-inhibiting effect, but the indirect one did not. The MMT assay showed an apparent reduction in cell metabolism in the first 24 h after CAP treatment, which appeared to normalize 48 h and 72 h after CAP application. These results were also confirmed by the glucose assay. The caspase 3/7 assay and TUNEL assay showed a significant increase in apoptotic processes in the HDMEC after CAP treatment. These results were independent of the CAP device. Both the migration and tube formation of HDMEC were significant inhibited after CAP-treatment. No malignant effects could be demonstrated by the CAP treatment on a non-malignant cell line.

The neck-shaft angle: an update on reference values and associated factors.

Background and purpose - The neck-shaft angle (NSA) is valuable for diagnostics and therapy of the hip, but current reference values derive mostly from studies on anatomic specimens, small cohorts, or are hospital-based. Moreover, associated factors such as age, sex, or anthropometric data have rarely been considered. Therefore, we determined associated factors for NSA and reassessed the historical reference values in a general adult population.Methods - NSAs on both sides of 3,226 volunteers from the population-based Study of Health in Pomerania (SHIP) were measured with MRI. SHIP drew a representative sample of the population of Pomerania (northeastern Germany). NSAs were compared with sex, age, and anthropometric data by bivariable linear regression models. Reference values were assessed by quantile regressions for 2.5th and 97.5th percentiles.Results - The mean NSA was 127° (SD 7), while men had a lower NSA than women (95% confidence interval [CI] 0.4°-1.4°). The reference range was 114°-140°. Age was inversely associated with NSA (CI -0.2 to -0.1). Body height was positively associated with the NSA, while BMI and waist circumference showed a negative association. There was no association between body weight and NSA.Interpretation - The historical lower limit of 120° might be too high, so the radiological prevalence of hip pathology might have been overestimated. The previously reported influence of age, sex, and body height on the NSA has been confirmed.

Duration of antibiotic treatment and risk of recurrence after surgical management of orthopaedic device infections: a multicenter case-control study.

BACKGROUND: Device-related infections in orthopaedic and trauma surgery are a devastating complication with substantial impact on morbidity and mortality. Systemic suppressive antibiotic treatment is regarded an integral part of any surgical protocol intended to eradicate the infection. The optimal duration of antimicrobial treatment, however, remains unclear. In a multicenter case-control study, we aimed at analyzing the influence of the duration of antibiotic exposure on reinfection rates 1 year after curative surgery. METHODS: This investigation was part of a federally funded multidisciplinary network project aiming at reducing the spread of multi-resistant bacteria in the German Baltic region of Pomerania. We herein used hospital chart data from patients treated for infections of total joint arthroplasties or internal fracture fixation devices at three academic referral institutions. Subjects with recurrence of an implant-related infection within 1 year after the last surgical procedure were defined as case group, and patients without recurrence of an implant-related infection as control group. We placed a distinct focus on infection of open reduction and internal fixation (ORIF) constructs. Uni- and multivariate logistic regression analyses were employed for data modelling. RESULTS: Of 1279 potentially eligible patients, 269 were included in the overall analysis group, and 84 contributed to an extramedullary fracture-fixation-device sample. By multivariate analysis, male sex (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.08 to 3.94, p = 0.029) and facture fixation device infections (OR 2.05, 95% CI 1.05 to 4.02, p = 0.036) remained independent predictors of reinfection. In the subgroup of infected ORIF constructs, univariate point estimates suggested a nearly 60% reduced odds of reinfection with systemic fluoroquinolones (OR 0.42, 95% CI 0.04 to 2.46) or rifampicin treatment (OR 0.41, 95% CI 0.08 to 2.12) for up to 31 days, although the width of confidence intervals prohibited robust statistical and clinical inferences. CONCLUSION: The optimal duration of systemic antibiotic treatment with surgical concepts of curing wound and device-related orthopaedic infections is still unclear. The risk of reinfection in case of infected extramedullary fracture-fxation devices may be reduced with up to 31 days of systemic fluoroquinolones and rifampicin, although scientific proof needs a randomized trial with about 1400 subjects per group. Concerted efforts are needed to determine which antibiotics must be applied for how long after radical surgical sanitation to guarantee sustainable treatment success.

What Are the Reference Values and Associated Factors for Center-edge Angle and Alpha Angle? A Population-based Study.

BACKGROUND: The available evidence regarding normal ranges for the center-edge angle and the alpha angle derives from a few small studies, and associated factors such as sex and anthropometric factors have not been well evaluated. Knowing more about normal values for these parameters is critical, because this can inform decisions about when to perform elective hip preservation surgery. Population-level studies would provide considerable clarity on these issues, but to our knowledge, no such studies are available. QUESTIONS/PURPOSES: The purposes of this study were (1) to use MRI in patients of a population-based study to establish normal values for the alpha and center-edge angles in the normal adult hip; and (2) to determine whether age, sex, or anthropometric variables were associated with differences in these values. METHODS: We used MRI images (1.5 T) of 3226 participants of the Study of Health in Pomerania (SHIP). SHIP is a population-based study that started with 4308 participants in 1997. Participants were recruited randomly from official inhabitant data files as a stratified cluster sample of the population from a defined region in northeastern Germany. To ensure a representative epidemiologic cohort, stratification variables were sex, age, and city of residence. Between 2008 and 2012, 1094 of these participants underwent whole-body MRI with pelvic sequences in the second followup. In parallel, the next cohort, SHIP-Trend, started with the same protocol in which 2132 participants underwent MRI examination. Reference values were calculated by quantile regressions for the 2.5 and 97.5 percentiles. Associations with the demographic features sex, age, weight, height, body mass index (BMI), and waist circumference were analyzed by bivariate linear regression models. RESULTS: The mean center-edge angle was 31° (± 7°) with a corresponding calculated normal range of 17° to 45°. The mean alpha angle was 55° (± 8°) with a corresponding calculated normal range between 39° and 71°. Men (30° ± 7°) had a lower center-edge angle than women (32° ± 8°) (p < 0.001, ß = 1.4°; 95% confidence interval [CI], 0.9°-1.9°) and a higher alpha angle (57° ± 8° versus 52° ± 7°, p < 0.001, ß = 5.7°; 95% CI, 5.2°-6.3°). Moreover, a higher center-edge angle for the left side was found (33° ± 8° versus 30° ± 8°, p < 0.001, ß =3.2°; 95% CI, 3.0°-3.4°). In addition to sex, we found that age, height, waist circumference, and BMI affected both center-edge angle and alpha angle. Weight was associated with the alpha angle as well. Because of these associations, age- and sex-adjusted reference values with belonging formulas were calculated. CONCLUSIONS: The range of normal center-edge and alpha angles is quite wide. Therefore, only markedly abnormal angles may be associated with pathology. Moreover, center-edge angle and alpha angle are associated with age, sex, and anthropometric factors, which have to be taken into account for better interpretation. CLINICAL RELEVANCE: The association of abnormal radiographic values with true clinical hip pathology is tenuous at best. Assuming that a patient with an abnormal radiograph requires treatment is unwise. The clinical picture has to be substantial for therapeutic decisions.

A Neutrophil Proteomic Signature in Surgical Trauma Wounds.

Non-healing wounds continue to be a clinical challenge for patients and medical staff. These wounds have a heterogeneous etiology, including diabetes and surgical trauma wounds. It is therefore important to decipher molecular signatures that reflect the macroscopic process of wound healing. To this end, we collected wound sponge dressings routinely used in vacuum assisted therapy after surgical trauma to generate wound-derived protein profiles via global mass spectrometry. We confidently identified 311 proteins in exudates. Among them were expected targets belonging to the immunoglobulin superfamily, complement, and skin-derived proteins, such as keratins. Next to several S100 proteins, chaperones, heat shock proteins, and immune modulators, the exudates presented a number of redox proteins as well as a discrete neutrophil proteomic signature, including for example cathepsin G, elastase, myeloperoxidase, CD66c, and lipocalin 2. We mapped over 200 post-translational modifications (PTMs; cysteine/methionine oxidation, tyrosine nitration, cysteine trioxidation) to the proteomic profile, for example, in peroxiredoxin 1. Investigating manually collected exudates, we confirmed presence of neutrophils and their products, such as microparticles and fragments containing myeloperoxidase and DNA. These data confirmed known and identified less known wound proteins and their PTMs, which may serve as resource for future studies on human wound healing.

Cold Atmospheric Plasma in the Treatment of Osteosarcoma.

Human osteosarcoma (OS) is the most common primary malignant bone tumor occurring most commonly in adolescents and young adults. Major improvements in disease-free survival have been achieved by implementing a combination therapy consisting of radical surgical resection of the tumor and systemic multi-agent chemotherapy. However, long-term survival remains poor, so novel targeted therapies to improve outcomes for patients with osteosarcoma remains an area of active research. This includes immunotherapy, photodynamic therapy, or treatment with nanoparticles. Cold atmospheric plasma (CAP), a highly reactive (partially) ionized physical state, has been shown to inherit a significant anticancer capacity, leading to a new field in medicine called "plasma oncology." The current article summarizes the potential of CAP in the treatment of human OS and reviews the underlying molecular mode of action.

In vitro susceptibility of methicillin-resistant and methicillin-susceptible strains of Staphylococcus aureus to two different cold atmospheric plasma sources.

BACKGROUND: Staphylococcus aureus may be the most important wound pathogen and causative for most of surgical site infections. As many anti-staphylococcal drugs are useless because of resistance, novel antimicrobial strategies are strongly needed and may be provided by cold atmospheric plasma (CP), which is being currently investigated for antiseptic efficacy. METHODS: To test the antimicrobial properties of CP against Staphylococcus aureus, 168 methicillin-susceptible isolates (MSSA) and 50 methicillin-resistant isolates (MRSA) were treated with two technically different plasma sources [an atmospheric pressure plasma jet (APPJ) and a dielectric barrier discharge plasma (DBD)] in vitro. RESULTS: CP treatment allowed a reproducible and significant growth reduction of MRSA and MSSA. However, MRSA was significantly less susceptible to treatment with DBD than was MSSA, while no difference between MRSA and MSSA was found using APPJ. CONCLUSIONS: As the initial physical antiseptic on skin, CP may be suitable for rapid decolonization of microbial pathogens in vivo. Each device must undergo validated efficacy testing prior to clinical application, as device related differences may occur.

Current management of open fractures: results from an online survey.

BACKGROUND: Open fractures are orthopaedic emergencies that carry a high risk for infection, non-union and soft tissue complications. Evidence-based treatment is impeded by the lack of high-quality evidence-based studies. The aim of this investigation was to elucidate the current practice of open fracture management in Germany and to determine major differences in treatment. METHODS: Surgeons were asked to complete an online questionnaire consisting of 45 items developed by an expert consensus. The first part covered questions on general principles of open fracture management. The second part included questions on soft tissue management, the preferred method of initial surgical stabilisation, microbiological testing, employment of pulsatile lavage and local antibiotics, antibiotic regimen, second-look operations, and blood testing. RESULTS: Of 653 respondents, 364 (65 %) completed the first part and 314 (48 %) completed the second part of the online survey. 55 % answered that a standard operating procedure for the diagnosis and treatment of patients with open fractures exists in their hospital. Only 25 % leave pre-hospitalisation applied dressings intact until arrival of the patient in the operating room, and 40 % make this decision depending on information provided by pre-hospitalisation emergency personnel. 84 % participants exclude the use of antibiotic-coated implants in the treatment of open fractures. The favoured stabilisation method in Gustilo type I fractures is definitive internal osteosynthesis and primary wound closure for 61 % of respondents. In Gustilo type II (74 %) and type III fractures (93 %), temporary external fixation is preferred. High-pressure pulsatile lavage is used by 22 % responding surgeons in Gustilo type I fractures, 53 % for type II fractures and 67 % for type III fractures. CONCLUSIONS: Open fracture management differs considerably among surgeons in Germany. Further studies are needed to deliver high-quality evidence concerning primary fracture stabilisation, soft tissue management and second-look operations. Existing evidence-based recommendations for general treatment, antibiotic prophylaxis and soft tissue management should be followed more strictly in clinical practice.

Retrospektive Analyse von56 Weichteildefekten nach einzeitiger Rekonstruktion unter Verwendung von Dermisersatzpräparaten.

HINTERGRUND: Der Verschluss von Wunden mit ausgeprägtem Weichteilschaden stellt eine chirurgische Herausforderung dar und erfordert häufig umfangreiche plastische Operationen sowie freie Lappenplastiken. Die Kombination von Dermisersatzpräparaten und Spalthauttransplantationen ist eine innovative Methode die zur Versorgung von komplexen Verletzungen der Extremitäten angewandt werden kann. Wir haben diese Technik in das Standard-Handwerkszeug bei komplexen Verletzungen der Extremitäten aufgenommen. Die klinischen Ergebnisse von 56 behandelten Patienten werden vorgestellt. PATIENTEN UND METHODEN: In 44 Fällen (78,6 %) wurde die beschriebene Methode an Defekten der unteren Extremitäten verwendet, einschließlich sieben Personen (12,5 %), die sich einer Stumpfdeckung nach Amputation unterzogen. Zwölf Defekte (21,4 %) befanden sich an den oberen Extremitäten. In zwei Fällen (3,6 %) wurde die Matriderm(®) -Matrix verwendet, um Nerven von unmittelbar angrenzenden chirurgischen Implantaten zu schützen. ERGEBNISSE: Bei 41 Patienten (73,2 %) kam es zur Einheilung des Transplantats ohne Komplikationen. Fünfzehn Patienten (26,8 %) zeigten eine gestörte Wundheilung nach Defektverschluss, die unter konservativer Therapie zur Ausheilung gebracht werden konnte. Ein Patient (1,8 %) zeigte ein Transplantatversagen, was eine Revisionsoperation erforderlich machte. Umfangreiche plastische Rekonstruktionen mussten bei keinem Patienten angewandt werden. SCHLUSSFOLGERUNGEN: Bei Fällen, in denen ausgedehnte plastische Operationen nicht möglich oder nicht erwünscht sind, ist die Verwendung von Dermisersatzpräparaten in Kombination mit Spalthauttransplantationen eine vielversprechende Alternative zum Wundverschluss bei ausgedehnten Weichteilschäden.

Retrospective analysis of 56 soft tissue defects treated with one-stage reconstruction using dermal skin substitutes.

BACKGROUND: The closure of wounds associated with soft tissue defects is surgically challenging, frequently requiring extensive plastic surgery and free flaps. The combination of dermal skin substitutes and split-thickness skin grafting is an innovative method used to cover such wounds. We incorporated this technique into the standard therapeutic armamentarium for complex injuries to the extremities. Clinical results of 56 patients thus treated are presented. PATIENTS AND METHODS: In 44 (78.6 %) cases, the method described was used for defects on the lower extremities, including seven (12.5 %) individuals undergoing amputation stump coverage. Twelve (21.4 %) defects were located on the upper extremities. In two (3.6 %) cases, Matriderm(®) matrix was used to protect nerves from adjacent surgical implants. RESULTS: In 41 (73.2 %) patients, the graft healed without any complication. Fifteen (26.8 %) patients displayed impaired wound healing following defect closure and were subsequently managed conservatively. One patient (1.8 %) showed graft failure, leading to revision surgery. None of the patients required extensive plastic surgery. CONCLUSIONS: In cases where plastic surgery is unavailable or undesirable, the use of dermal skin substitutes in combination with split-thickness skin grafting represents a promising alternative for covering wounds associated with soft tissue defects.

Antimicrobial Efficacy of a Historical High-Frequency Plasma Apparatus in Comparison With 2 Modern, Cold Atmospheric Pressure Plasma Devices.

BACKGROUND: Today, highly sophisticated devices deliver cold atmospheric pressure plasma (CAPP) with a multitude of bioactive properties, opening the window to a new medical field: plasma medicine. Different techniques to create the optimal plasma device for different medical indications are currently being explored. However, even a 100 years ago, CAPP was briefly used in the related form of high-frequency therapy. The objective of our study was to compare historic with modern techniques regarding antimicrobial efficacy. METHODS: First, 26 different clinical isolates of relevant wound pathogens were treated in vitro with a historic violet wand (VW) and 2 modern plasma sources (kINPen 09 and dielectric barrier discharge [DBD]) and the obtained inhibition areas (IAs) were compared. Second, a biofilm model was used to compare biofilm inactivation by VW, DBD, ethanol, and polyhexanide treatment. RESULTS: DBD with the largest electrode produced the largest IAs. VW showed results similar to 2 different modes of the kINPen 09. IAs of VW were enlargeable by attaching a larger electrode. Against biofilms, VW was less effective than DBD but more effective than ethanol 70% and polyhexanide. CONCLUSION: The proven antimicrobial efficacy of VW may encourage the development of new, potent plasma devices based on the very simple and inexpensive technique of the historic high-frequency apparatus.

Influencing factors for delayed diagnosed injuries in multiple trauma patients - introducing the 'Risk for Delayed Diagnoses Score' (RIDD-Score).

PURPOSE: Delayed diagnosed injuries (DDI) in severely injured patients are an essential problem faced by emergency staff. Aim of the current study was to analyse incidence and type of DDI in a large trauma cohort. Furthermore, factors predicting DDI were investigated to create a score to identify patients at risk for DDI. METHODS: Multiply injured patients admitted between 2011 and 2020 and documented in the TraumaRegister DGU® were analysed. Primary admitted patients with severe injuries and/or intensive care who survived at least 24 h were included. The prevalence, type and severity of DDI were described. Through multivariate logistic regression analysis, risk factors for DDI were identified. Results were used to create a 'Risk for Delayed Diagnoses' (RIDD) score. RESULTS: Of 99,754 multiply injured patients, 9,175 (9.2%) had 13,226 injuries first diagnosed on ICU. Most common DDI were head injuries (35.8%), extremity injuries (33.3%) and thoracic injuries (19.7%). Patients with DDI had a higher ISS, were more frequently unconscious, in shock, required more blood transfusions, and stayed longer on ICU and in hospital. Multivariate analysis identified seven factors indicating a higher risk for DDI (OR from 1.2 to 1.9). The sum of these factors gives the RIDD score, which expresses the individual risk for a DDI ranging from 3.6% (0 points) to 24.8% (6 + points). CONCLUSION: DDI are present in a sounding number of trauma patients. The reported results highlight the importance of a highly suspicious and thorough physical examination in the trauma room. The introduced RIDD score might help to identify patients at high risk for DDI. A tertiary survey should be implemented to minimise delayed diagnosed or even missed injuries.

Full-body MR imaging: a retrospective study on a novel diagnostic approach for children sustaining high-energy trauma.

PURPOSE: Severe accidents are the leading cause of long-term impairment and death in children. A common diagnostic procedure for children exposed to high-injury trauma is full-body contrast-enhanced CT (fbCT). However, the number of fbCT without detected injuries is relevant. In 2007, full-body MRI (fbMRI) was implemented as a diagnostic approach for children sustaining high-energy trauma. The aim of this cross-sectional retrospective study was to analyze fbMRI as a diagnostic tool for children after high-energy trauma focusing on feasibility, radiological findings, and limitations. METHODS: Diagnostics using fbMRI (from apex of the head to the pelvis) was performed if a child was stable and suffered a high-energy trauma in a Level I Trauma Center in Germany. 105 fbMRIs in patients exposed to high-energy trauma aged ≤ 16 years were performed between January 2007 and December 2018. Four fbMRIs were excluded as conducted for reasons other than trauma. Time between arrival in the emergency department and fbMRI, additional diagnostic procedures, injuries, and non-trauma related pathologies were analyzed. RESULTS: Mean time between arrival in the emergency department and fbMRI was 71 min (± SD 132 min). Two scans were discontinued and changed to a faster diagnostic procedure. 45% of children had additional X-rays and 11% CT scans. The MRIs showed intracranial abnormalities in 27%, extremities injuries in 26%, spinal injuries in 18%, pelvic, and thoracic injuries in 7% of the cases. CONCLUSION: Overall fbMRI is a diagnostic alternative for hemodynamically stable, conscious children after high-energy trauma with the advantages of a radiation-free technique. However, MRI diagnostics take longer than CT scans. Prospective studies will be needed to identify the limiting factors of fbMRIs as primary diagnostic procedure compared to CT scans. TRIAL REGISTRATION: German Clinical Trials Register (DRKS; DRKS00017015). LEVEL OF EVIDENCE: Case series, level of evidence V.

Quality and quantity of serious violent suicide attempts during the COVID-19 pandemic.

Background: While repeated shutdown and lockdown measures helped contain the spread of SARS-CoV-2 during the COVID-19 pandemic, social distancing and self-isolation negatively impacted global mental health in 2020 and 2021. Although suicide rates did reportedly not increase during the first months of the pandemic, long-term data, and data on the quality of serious violent suicide attempts (SVSAs) are not available to date. Materials and methods: Orthopaedic trauma patient visits to the emergency department (ED), ED trauma team activations, and SVSAs were retrospectively evaluated from January 2019 until May 2021 in four Level-I Trauma Centers in Berlin, Germany. SVSAs were assessed for suicide method, injury pattern and severity, type of treatment, and length of hospital stay. Results: Significantly fewer orthopaedic trauma patients presented to EDs during the pandemic (n = 70,271) compared to the control (n = 84,864) period (p = 0.0017). ED trauma team activation numbers remained unchanged. SVSAs (corrected for seasonality) also remained unchanged during control (n = 138) and pandemic (n = 129) periods, and no differences were observed for suicide methods, injury patterns, or length of hospital stay. Conclusion: Our data emphasize that a previously reported rise in psychological stress during the COVID-19 pandemic does not coincide with increased SVSA rates or changes in quality of SVSAs.

Soluble CD40 ligand impairs the function of peripheral blood angiogenic outgrowth cells and increases neointimal formation after arterial injury.

BACKGROUND: Recent work has revealed an essential involvement of soluble CD40 ligand (sCD40L) in inflammation and atherosclerosis. We investigated whether sCD40L functionally affects peripheral blood-derived angiogenic early outgrowth cells (EOCs) and neointimal remodeling after arterial injury. METHODS AND RESULTS: Besides myeloid and endothelial markers, cultured human EOCs strongly expressed CD40 mRNA and protein. EOC adhesion to fibronectin, fibrinogen, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 under flow conditions, as well as their transmigration toward stromal cell-derived factor-1alpha, was dose-dependently reduced after preincubation with recombinant human sCD40L for 24 hours. Integrin expression was unaffected by sCD40L, implying that integrin adhesiveness was attenuated. Surface-immobilized CD40L supported much lower adhesion of EOCs than fibronectin. Treatment of EOCs with sCD40L increased superoxide anion production and decreased viability and proliferation. Notably, CD40(-/-) mice displayed reduced neointima and improved re-endothelialization after carotid wire injury compared with wild-type mice, and therapeutic infusion of control EOCs but not EOCs pretreated with sCD40L attenuated neointimal growth after wire injury in nude mice. Furthermore, neointimal growth was more markedly diminished by infusion of spleen-derived CD40(-/-) mouse EOCs than by that of wild-type EOCs. Preincubation of wild-type EOCs but not CD40(-/-) EOCs with sCD40L before their infusion markedly aggravated neointimal formation. Treatment with sCD40L attenuated luminal incorporation of EOCs and accelerated neointimal progression. CONCLUSIONS: Endothelial dysfunction due to persistently elevated plasma levels of sCD40L may be attributable to an impairment of EOC function. Hence, in the context of arterial injury, therapeutic blockade of sCD40L may provide a novel strategy for accelerating endothelial regeneration and attenuating neointimal remodeling.

Quality indicators in the treatment of geriatric hip fractures: literature review and expert consensus.

PURPOSE: Even though hip fracture care pathways have evolved, mortality rates have not improved during the last 20 years. This finding together with the increased frailty of hip fracture patients turned hip fractures into a major public health concern. The corresponding development of an indicator labyrinth for hip fractures and the ongoing practice variance in Europe call for a list of benchmarking indicators that allow for quality improvement initiatives for the rapid recovery of fragile hip fractures (RR-FHF). The purpose of this study was to identify quality indicators that assess the quality of in-hospital care for rapid recovery of fragile hip fracture (RR-FHF). METHODS: A literature search and guideline selection was conducted to identify recommendations for RR-FHF. Recommendations were categorized as potential structure, process, and outcome QIs and subdivided in-hospital care treatment topics. A list of structure and process recommendations that belongs to care treatment topics relevant for RR-FHF was used to facilitate extraction of recommendations during a 2-day consensus meeting with experts (n = 15) in hip fracture care across Europe. Participants were instructed to select 5 key recommendations relevant for RR-FHF for each part of the in-hospital care pathway: pre-, intra-, and postoperative care. RESULTS: In total, 37 potential QIs for RR-FHF were selected based on a methodology using the combination of high levels of evidence and expert opinion. The set consists of 14 process, 13 structure, and 10 outcome indicators that cover the whole perioperative process of fragile hip fracture care. CONCLUSION: We suggest the QIs for RR-FHF to be practice tested and adapted to allow for intra-hospital longitudinal follow-up of the quality of care and for inter-hospital and cross-country benchmarking and quality improvement initiatives.

A mass casualty incident of infectious diseases at the port of Hamburg: an analysis of organizational structures and emergency concepts.

BACKGROUND: The project "ARMIHN" (Adaptive Resiliency Management in Port) focuses on strengthening the capability to act in a mass casualty incident (MCI) due to an outbreak of infectious diseases (MCI-ID). In addition to the current threat from the COVID-19 pandemic and associated outbreaks on cruise ships, previous MCI-ID were especially caused by pathogens such as Influenza virus or Norovirus. The first step was, to get an overview of processes and resources using the example of the Port of Hamburg, and to show the associated interaction of involved parties. This will serve as a basis for developing an operational strategy and offers the opportunity to optimize current work processes. METHODS: A selective literature research using specified key words was performed and existing MCI concepts were received from local authorities. Identified structures and processes were analyzed in a multiple step process and also brought together through discussions in workshops with involved organizations and other experts. Additionally, the distances between the nearest rescue stations and selected hospitals from the Port of Hamburg were analyzed. RESULTS: The current available concepts are proven, but an adaptation to an MCI-ID shows opportunities for a further cross-organizational development. The organizational structure of an MCI-ID in the Port of Hamburg was described, including a large number of involved organizations (n = 18). There are 17 involved fire and rescue stations and the port can be reached from these locations within 6 to 35 min. Based on their specialist expertise, 14 of the 31 listed clinics were selected. CONCLUSION: The purpose of the study was to provide an analysis of the current situation and show how involved parties would cope an MCI. A description of processes and resources at the Port of Hamburg will be used when designing a management plan for responding to an MCI-ID.

Acromioclavicular and sternoclavicular joint dislocations indicate severe concomitant thoracic and upper extremity injuries in severely injured patients.

Preliminary studies show that clavicle fractures (CF) are known as an indicator in the severely injured for overall injury severity that are associated with relevant concomitant injuries in the thorax and upper extremity. In this regard, little data is available for the rarer injuries of the sternoclavicular and acromioclavicular joints (SCJ and ACJ, respectively). Our study will answer whether clavicular joint injuries (CJI), by analogy, have a similar relevance for the severely injured. We performed an analysis from the TraumaRegister DGU (TR-DGU). The inclusion criterion was an Injury Severity Score (ISS) of at least 16. In the TR-DGU, the CJI were registered as one entity. The CJI group was compared with the CF and control groups (those without any clavicular injuries). Concomitant injuries were distinguished using the Abbreviated Injury Scale according to their severity. The inclusion criteria were met by n = 114,595 patients. In the case of CJI, n = 1228 patients (1.1%) were found to be less severely injured than the controls in terms of overall injury severity. Compared to the CF group (n = 12,030; 10.5%) with higher ISS than the controls, CJI cannot be assumed as an indicator for a more severe trauma; however, CF can. Concomitant injuries were more common for severe thoracic and moderate upper extremity injuries than other body parts for CJI. This finding confirms our hypothesis that CJI could be an indicator of further specific severe concomitant injuries. Despite the rather lower relevance of the CJI in the cohort of severely injured with regard to the overall injury severity, these injuries have their importance in relation to the indicator effect for thoracic concomitant injuries and concomitant injuries of the upper extremity. A limitation is the collective registration of SCJ and ACJ injuries as one entity in the TR-DGU. A distorted picture of the CJI in favor of ACJ injuries could arise from the significantly higher incidence of the ACJ dislocation compared to the SCJ. Therefore, these two injury entities should be recorded separately in the future, and prospective studies should be carried out in order to derive a standardized treatment strategy for the care of severely injured with the respective CJI.

Digital versus analogue record systems for mass casualty incidents at sea-Results from an exploratory study.

OBJECTIVE: Mis-triage may have serious consequences for patients in mass casualty incidents (MCI) at sea. The purpose of this study was to assess outcome, reliability and validity of an analogue and a digital recording system for triage of a MCI at sea. METHODS: The study based on a triage exercise conducted with a cross-over-design. Forty-eight volunteers were presented a fictional MCI with 50 cases. The volunteers were randomly assigned to start with the analogue (Group A, starting with the analogue followed by the digital system) or digital system (Group B, starting with the digital followed by the analogue system). Triage score distribution and agreement between the triage methods and a predefined standard were reported. Reliability was analysed using Cronbach's Alpha and Cohen's Kappa. Validity was measured through sensitivity, specificity and predictive value. Treatment, period and carry-over-effects were analysed using a linear mixed-effects model. RESULTS: The number of patients triaged (total: n = 3545) with the analogue system (n = 1914; 79.75%) was significantly higher (p = 0.001) than with the digital system (n = 1631; 67.96%). A trend towards a higher percentage of correct triages with the digital system was observed (p = 0.282). Ratio of under-triage was significantly smaller with the digital system (p = 0.001). Validity measured with Cronbach's Alpha and Cohen's Kappa was higher with the digital system. So was sensitivity (category; green: 80.67%, yellow: 73.24%, red: 83.54%; analogue: green: 93.28%, yellow: 82.36%, red: 94.04%) and specificity of the digital system (green: 78.07%, yellow: 63.75%, red: 66.25%; analogue: green: 85.50%, yellow: 79.88%, red: 91.50%). Comparing the predictive values and accuracy, the digital system showed higher scores than the analogue system. No significant patterns of carry-over-effects were observed. CONCLUSIONS: Significant differences were found for the number of triages comparing the analogue and digital recording system. The digital system has a slightly higher reliability and validity than the analogue triage system.