TNFα-Induced Inflammation Model-Evaluation of Concentration and Passage-Dependent Effects on Bovine Chondrocytes.

Inflammation models are widely used in the in vitro investigation of new therapeutic approaches for osteoarthritis. TNFα (tumor necrosis factor alpha) plays an important role in the inflammatory process. Current inflammation models lack uniformity and make comparisons difficult. Therefore, this study aimed to systematically investigate whether the effects of TNFα are concentration-dependent and whether chondrocyte expansion has an effect on the inflammatory model. Bovine chondrocytes were enzymatically isolated, expanded to passages 1-3, and transferred into a 3D pellet culture. Chondrocyte pellets were stimulated with recombinant bovine TNFα at different concentrations for 48 h to induce inflammation. Gene expression of anabolic (collagen 2, aggrecan, cartilage oligomeric protein (COMP)), catabolic (matrix metalloproteinases (MMP3, MMP13)), dedifferentiation (collagen 1) markers, inflammation markers (interleukin-6 (IL-6), nuclear factor kappa B (NFkB), cyclooxygenase-2 (COX), prostaglandin-E-synthase-2 (PTGES2)), and the apoptosis marker caspase 3 was determined. At the protein level, concentrations of IL-6, nitric oxide (NO), and sulfated glycosaminoglycans (GAG) were evaluated. Statistical analysis was performed using the independent t-test, and significance was defined as p < 0.05. In general, TNFα caused a decrease in anabolic markers and an increase in the expression of catabolic and inflammatory markers. There was a concentration-dependent threshold of 10 ng/mL to induce significant inflammatory effects. Most of the markers analyzed showed TNFα concentration-dependent effects (COMP, PRG4, AGN, Col1, MMP3, and NFkB). There was a statistical influence of selected gene expression markers from different passages on the TNFα chondrocyte inflammation model, including Col2, MMP13, IL-6, NFkB, COX2, and PTGES2. Considering the expression of collagen 2 and MMP3, passage 3 chondrocytes showed a higher sensitivity to TNFα stimulation compared to passages 1 and 2. On the other hand, MMP13, IL-6, NFkB, and caspase 3 gene expression were lower in P3 chondrocytes compared to the other passages. On the protein level, inflammatory effects showed a similar pattern, with cytokine effects starting at 10 ng/mL and differences between the passages. TNFα had a detrimental effect on cartilage, with a clear threshold observed at 10 ng/mL. Although TNFα effects showed concentration-dependent patterns, this was not consistent for all markers. The selected passage showed a clear influence, especially on inflammation markers. Further experiments were warranted to explore the effects of TNFα concentration and passage in long-term stimulation.

One Year of Experience in the Orthopaedic and Trauma Surgical Care of War Refugees and Soldiers from Ukraine in a Maximum Care Trauma Centre. / Herausforderungen bei der orthopädisch-unfallchirurgischen Versorgung von Kriegsflüchtlingen und Soldaten aus der Ukraine in einem Trauma Zentrum der Maximalversorgung.

According to the United Nations, around 8,400 people have been injured and over 5,800 killed on the Ukrainian side in the Ukraine war, which has been going on for over 14 months. Extensive humanitarian aid operations were carried out to support Ukraine, so that war-wounded people from Ukraine were also cared for in Germany. In a retrospective cohort study, 10 patients were examined who were treated in the department between February 24th 2022 and February 24th 2023, using the cloverleaf system from Ukraine.The average duration of inpatient treatment was 53.10 days. The average ISS was 23.7. The patients were operated on an average of 3.3 times in our institution. All patients received consultative psychological care. All patients were initially put into protective isolation until the results of a corona test and microbiological swabs were available. After preliminary protective isolation, further isolation had to be carried out in 5 cases due to germs requiring isolation. Eight patients were released to state accommodation. Three patients were transferred back to Ukraine at their own request.The treatment of war-injured patients from Ukraine represents a particular challenge. It absolutely requires an interdisciplinary treatment concept that, in addition to special trauma surgery and orthopaedic expertise, also requires plastic-reconstructive, microbiological and, last but not least, psychological care. Due to the high rate of infections requiring isolation, long, costly therapy with multiple revision operations is often necessary.

Osteomyelitis is associated with increased anti-inflammatory response and immune exhaustion.

Introduction: Osteomyelitis (OMS) is a bone infection causing bone pain and severe complications. A balanced immune response is critical to eradicate infection without harming the host, yet pathogens manipulate immunity to establish a chronic infection. Understanding OMS-driven inflammation is essential for disease management, but comprehensive data on immune profiles and immune cell activation during OMS are lacking. Methods: Using high-dimensional flow cytometry, we investigated the detailed innate and adaptive systemic immune cell populations in OMS and age- and sex-matched controls. Results: Our study revealed that OMS is associated with increased levels of immune regulatory cells, namely T regulatory cells, B regulatory cells, and T follicular regulatory cells. In addition, the expression of immune activation markers HLA-DR and CD86 was decreased in OMS, while the expression of immune exhaustion markers TIM-3, PD-1, PD-L1, and VISTA was increased. Members of the T follicular helper (Tfh) cell family as well as classical and typical memory B cells were significantly increased in OMS individuals. We also found a strong correlation between memory B cells and Tfh cells. Discussion: We conclude that OMS skews the host immune system towards the immunomodulatory arm and that the Tfh memory B cell axis is evident in OMS. Therefore, immune-directed therapies may be a promising alternative for eradication and recurrence of infection in OMS, particularly in individuals and areas where antibiotic resistance is a major concern.

An Updated Overview of Risk Factors for Shoulder Stiffness. / Risikofaktoren für die Entstehung der primären Schultersteife: ein aktueller Überblick.

A painful reduction in shoulder mobility, known as "shoulder stiffness", can occur both as a primary idiopathic condition and as a secondary condition, for example, following surgical procedures. Various factors can contribute to the development of primary shoulder stiffness. In this review we summarize the pathophysiological mechanisms, genetic influences, endocrine disorders, metabolic conditions, as well as other diseases and medical-therapeutic approaches that might have an impact on the development of primary shoulder stiffness.

Comparison of Minced Cartilage Implantation with Autologous Chondrocyte Transplantation in an In Vitro Inflammation Model.

The current gold standard to treat large cartilage defects is autologous chondrocyte transplantation (ACT). As a new surgical method of cartilage regeneration, minced cartilage implantation (MCI) is increasingly coming into focus. The aim of this study is to investigate the influence of chondrogenesis between isolated and cultured chondrocytes compared to cartilage chips in a standardized inflammation model with the proinflammatory cytokine TNFα. Articular chondrocytes from bovine cartilage were cultured according to the ACT method to passage 3 and transferred to spheroid culture. At the same time, cartilage was fragmented (<1 mm3) to produce cartilage chips. TNFα (20 ng/mL) was supplemented to simulate an inflammatory process. TNFα had a stronger influence on the passaged chondrocytes compared to the non-passaged ones, affecting gene expression profiles differently between isolated chondrocytes and cartilage chips. MCI showed less susceptibility to TNFα, with reduced IL-6 release and less impact on inflammation markers. Biochemical and histological analyses supported these findings, showing a greater negative influence of TNFα on the passaged pellet cultures compared to the unpassaged cells and MCI constructs. This study demonstrated the negative influence of TNFα on chondrogenesis in a chondrocyte spheroid culture and cartilage fragment model. Passaged chondrocytes are more sensitive to cytokine influences compared to non-passaged cells and chondrons. This suggests that MCI may have superior regeneration potential in osteoarthritic conditions compared to ACT. Further investigations are necessary for the translation of these findings into clinical practice.

Effects of single and repeated shock wave application on the osteogenic differentiation potential of human primary mesenchymal stromal cells and the osteoblastic cell line MG63 in vitro.

Introduction: Extracorporeal shock wave therapy is a non-invasive and effective option for treating various musculoskeletal disorders. Recent literature indicates that the parameters for extracorporeal shock wave therapy, such as the optimal intensity, treatment frequency, and localization, are yet to be determined. Studies reporting on the effects of shock wave application on primary mesenchymal stromal cells (MSCs) as well as osteoblastic cell lines in vitro are barely available and not standardized. Methods: In this study, we designed a special setup to precisely expose primary MSCs and the osteoblastic cell line MG63 to shock waves and subsequently analyzed the resulting cellular responses using standardized protocols to investigate their viability, proliferation behavior, cytokine secretion, and osteogenic differentiation potential in vitro. The shock wave transducer was coupled to a specifically designed water bath containing a 5 mL tube holder. Primary human MSCs and MG63 cells were trypsinated and centrifuged in a 5 mL tube and exposed to single and repeated shock wave application using different intensities and numbers of pulses. Results: Single treatment of MSCs using intensities 5, 10, 15, and 20 and pulse numbers 100, 250, 500, 750, and 1,000 at a constant pulse repetition frequency of 1 Hz resulted in a decreased viability and proliferation of both cell types with an increase in the intensity and number of pulses compared to controls. No significant difference in the osteogenic differentiation was observed at different time intervals in both cell types when a single shock wave application was performed. However, repeated shock wave sessions over three consecutive days of primary MSCs using low intensity levels 0.1 and 1 showed significant osteogenic differentiation 4-fold higher than that of the extracted Alizarin Red S at day 14, whereas MG63 cells showed no significant osteogenic differentiation compared to their corresponding controls. More specifically, repeated shock wave application triggered a significant downregulation of COL1A1, upregulation of RUNX2, and sustained increase of OCN in primary MSCs but not in the cell line MG63 when induced toward the osteogenic differentiation. Discussion: The effects of shock wave application on MSCs make it an effective therapy in regenerative medicine. We established a protocol to analyze a standardized shock wave application on MSCs and were able to determine conditions that enhance the osteogenic differentiation of MSCs in vitro.

The Influence of Sagittal Pin Angulation on the Stiffness and Pull-Out Strength of a Monolateral Fixator Construct.

Monolateral pin-to-bar-clamp fixators are commonly used to stabilize acute extremity injuries. Certain rules regarding frame geometry have been established that affect construct stability. The influence of sagittal pin angulation on construct stiffness and strength has not been investigated. The purpose of this biomechanical study was to demonstrate the effect of a pin angulation in the monolateral fixator using a composite cylinder model. Three groups of composite cylinder models with a fracture gap were loaded with different mounting variants of monolateral pin-to-bar-clamp fixators. In the first group, the pins were set parallel to each other and perpendicular to the specimen. In the second group, both pins were set convergent each in an angle of 15° to the specimen. In the third group, the pins were set each 15° divergent. The strength of the constructions was tested using a mechanical testing machine. This was followed by a cyclic loading test to produce pin loosening. A pull-out test was then performed to evaluate the strength of each construct at the pin-bone interface. Initial stiffness analyses showed that the converging configuration was the stiffest, while the diverging configuration was the least stiff. The parallel mounting showed an intermediate stiffness. There was a significantly higher resistance to pull-out force in the diverging pin configuration compared to the converging pin configuration. There was no significant difference in the pull-out strength of the parallel pins compared to the angled pin pairs. Convergent mounting of pin pairs increases the stiffness of a monolateral fixator, whereas a divergent mounting weakens it. Regarding the strength of the pin-bone interface, the divergent pin configuration appears to provide greater resistance to pull-out force than the convergent one. The results of this pilot study should be important for the doctrine of fixator mounting as well as for fixator component design.

A Worldwide Analysis of Adipose-Derived Stem Cells and Stromal Vascular Fraction in Orthopedics: Current Evidence and Applications.

The biological enhancement of tissue regeneration and healing is an appealing perspective in orthopedics. We aimed to conduct a systematic review to describe the global distribution of studies investigating the use of adipose tissue derivates in orthopedics and to provide information on their quality and on the products available. The quality of the included studies was assessed using the modified Coleman Methodology Score (mCMS) and the Cochrane risk-of-bias tool for randomized trials. Eighty-two studies were included, with a total of 3594 patients treated. In total, 70% of the studies investigated the treatment of knee disorders, predominantly osteoarthritis; 26% of all studies dealt with expanded adipose-derived stem/stromal cells (ADSCs), 72% of which had stromal vascular fraction (SVF); 70% described the injection of adipose tissue derivates into the affected site; and 24% described arthroscopies with the addition of adipose tissue derivates. The mean mCMS for all studies was 51.7 ± 21.4 points, with a significantly higher score for the studies dealing with expanded ADSCs compared to those dealing with SVF (p = 0.0027). Our analysis shows high heterogeneity in terms of the types of performed procedures as well as the choice and processing of adipose tissue derivates.

COVID-19 measures as an opportunity to reduce the environmental footprint in orthopaedic and trauma surgery.

Background: Climate change and its consequences on our everyday life have also tremendous impacts on public health and the health of each individual. The healthcare sector currently accounts for 4.4% of global greenhouse gas emissions. The share of the emissions in the health care system caused by the transportation sector is 7%. The study analyses the effect of video consultation on the CO2 emissions during the Covid-19 pandemic in an outpatient clinic of the department of orthopaedics and traumatology surgery at a German university hospital. Methods: The study participants were patients who obtained a video consultation in the period from June to December 2020 and voluntarily completed a questionnaire after the consultation. The type of transport, travel time and waiting time as well as patient satisfaction were recorded by questionnaire. Results: The study comprised 51 consultations. About 70% of respondents would have travelled to the clinic by car. The reduction in greenhouse gas emissions of video consultations compared to a face-to-face presentation was 97% in our model investigation. Conclusion: The video consultation can be a very important part of the reduction of greenhouse gas emissions in the health care system. It also saves time for the doctor and patient and can form an essential part of individual patient care.

Agonistic and antagonistic targeting of immune checkpoint molecules differentially regulate osteoclastogenesis.

Introduction: Immune checkpoint inhibitors are used in the treatment of various cancers and have been extensively researched with regard to inflammatory and autoimmune diseases. However, this revolutionary therapeutic strategy often provokes critical auto-inflammatory adverse events, such as inflammatory reactions affecting the cardiovascular, gastrointestinal, nervous, and skeletal systems. Because the function of these immunomodulatory co-receptors is highly cell-type specific and the role of macrophages as osteoclast precursors is widely published, we aimed to analyze the effect of immune checkpoint inhibitors on these bone-resorbing cells. Methods: We established an in vitro model of osteoclastogenesis using human peripheral blood mononuclear cells, to which various immune checkpoints and corresponding antagonistic antibodies were administered. Formation of osteoclasts was quantified and cell morphology was analyzed via immunofluorescence staining, cell size measurements, and calculation of cell numbers in a multitude of samples. Results: These methodical approaches for osteoclast research achieved objective, comparable, and reproducible results despite the great heterogeneity in the form, size, and number of osteoclasts. In addition to the standardization of experimental analyses involving osteoclasts, our study has revealed the substantial effects of agonistic and antagonistic checkpoint modulation on osteoclastogenesis, confirming the importance of immune checkpoints in bone homeostasis. Discussion: Our work will enable more robust and reproducible investigations into the use of immune checkpoint inhibitors in conditions with diminished bone density such as osteoporosis, aseptic loosening of endoprostheses, cancer, as well as the side effects of cancer therapy, and might even pave the way for novel individualized diagnostic and therapeutic strategies.

Epidemiology and specific features of shoulder injuries in patients affected by epileptic seizures.

PURPOSE: Epileptic seizures can cause multiple shoulder injuries, the most common of which are dislocations, recurrent instability, fractures, and isolated lesions of the rotator cuff. Currently, only limited literature exists which describes the frequency and types of lesions in cohorts of epileptic patients and the corresponding treatment outcome. This study aims to document the occurrence of shoulder lesions in patients affected by seizures and to provide detailed information on trauma dynamics, specific lesion characteristics and treatment complications. METHODS: All patients referring to a tertiary epilepsy center were screened for shoulder injuries and the clinical records of those sustaining them during a seizure were reviewed. Demographic information, lesions' characteristics and trauma dynamics were analysed, as wells as-when carried out-the type of surgical intervention and any postoperative complications. RESULTS: The average age at the time of injury of 106 included patients was 39.7 ± 17.5 years and a male predominance was recorded (65%). Bilateral injuries occurred in 29 patients, simultaneously in 17 cases. A younger age, bilateral shoulder injuries and shoulder dislocations were significantly associated with the occurrence of a shoulder injury solely by muscular activation (p = 0.0054, p = 0.011, p < 0.0001). The complication rate in 57 surgically treated patients with follow-up data was 38.7%, with recurring instability being the most frequently reported complication (62.5%). CONCLUSIONS: Uncontrolled muscle activation during a seizure is a distinctive but not exclusive dynamic of injury in epileptic patients, accounting for more than the half of all shoulder lesions, especially in the younger. This can lead both to anterior and posterior dislocations or fracture-dislocations and is frequently cause of bilateral lesions and of instability recurrence after surgery. The high complication rates after surgical treatment in this selected subgroup of patients require that appropriate preventative measures are taken to increase the probability of treatment success. LEVEL OF EVIDENCE: Cohort study, level III.

The German version of the Nottingham Clavicle Score is a reliable and valid patient-reported outcome measure to evaluate patients with clavicle and acromioclavicular pathologies.

PURPOSE: The Nottingham Clavicle Score (NCS) is a patient-reported outcome measure developed to evaluate treatment results of clavicle, acromioclavicular and sternoclavicular joint pathologies. Valid, reliable and user-friendly translations of outcome measure instruments are needed to allow comparisons of international results. The aim of this cross-sectional study was to translate and adapt the NCS into German and evaluate the psychometric properties of the German version. METHODS: The translation and cross-cultural adaptation of the NCS were completed using a 'translation-back translation" method and the final version was administered to 105 German-speaking patients. The psychometric properties of this version (NCS-G) were evaluated in terms of feasibility, reliability, validity and sensitivity to change. RESULTS: No major differences occurred between the NCS translations into German and back into English, and no content- or linguistic-related difficulties were reported. The Cronbach's alpha for the NCS-G was 0.885, showing optimal internal consistency. The Intraclass Correlation Coefficient for test-retest reliability was 0.907 (95% CI 0.844-0.945), with a standard error of measurement of 5.59 points and a minimal detectable change of 15.50 points. The NCS-G showed moderate to strong correlation with all other investigated scales (Spearman correlation coefficient: qDASH: ρ = - 0.751; OSS: ρ = 0.728; Imatani Score: ρ = 0.646; CMS: ρ = 0.621; VAS: ρ = - 0.709). Good sensitivity to change was confirmed by an effect size of 1.17 (95% CI 0.89-1.47) and a standardized response mean of 1.23 (95% CI 0.98-1.45). CONCLUSIONS: This study demonstrated that NCS-G is reliable, valid, reproducible and well accepted by patients, showing analogous psychometric properties to the original English version. LEVEL OF EVIDENCE: Level III.

Video Based Assessment of Treatment Urgency in Outpatient Orthopaedic and Trauma Patients - a Pilot Trial. / Videobasierte Einschätzung der Behandlungsdringlichkeit - eine Pilotstudie für ambulante Patienten in der Orthopädie und Unfallchirurgie.

INTRODUCTION: When consulting a specialist in orthopaedics and trauma surgery, personal assessment and manual clinical examination by the doctor on site are essential. Nevertheless, implementation of video consultation hours has been made legally easier in Germany. The present pilot study examines the possibility of video-based assessment of the urgency of treatment in outpatient orthopaedic and trauma patients. MATERIALS AND METHODS: Within an ex ante study design, 40 patients with an orthopaedic clinical picture for trauma surgery with elective, urgent or emergency indication were selected from consultation hours. A short questionnaire was filled in based on the information provided and a medical colleague simulated a movement sequence based on the patient information. After modification to the "red flags" and "yellow flags" established in spinal orthopaedics, nine short questions were recorded, which inquire about the urgency of a medical consultation. The video-based movement sequence is based on a 60 s long instruction video in which motor tests and movement sequences are demonstrated: Cervical spine movement in all levels, elevation of the upper extremity, test of the finger-floor distance when "bending forward over-bending", possibility of crouching from standing and getting up again, standing on heels and toes. RESULTS: In 91.1% (n = 328) of the cases, the diagnosis was associated with the same joint or the same pathological entity. In 37.5% (n = 135) of the cases an emergency indication was seen, in 10.8% (n = 39) of the cases an urgent indication and in 51.6% (n = 186) of the cases it was seen to offer an elective indication. 12.5% (n = 45) of the cases were evaluated as "false positives" with regard to an emergency or urgent presentation. This means that the test persons were classified as "emergency" or "urgent", although there was no preventable dangerous course or medical emergency. 18 cases (5%) were evaluated as "false negative". DISCUSSION: The screening questionnaire presented and the short video assessment are technically feasible and practicable method for the initial evaluation in video-based online medical consultation. In addition, the questionnaire presented in combination with the short video assessment was suitable as an instrument for assessing the urgency of the consultation and selecting preventable dangerous processes and acute emergencies. CONCLUSION: The questionnaire, in combination with the short video assessment, is a suitable method for the social distancing requirements during limited accessibility of the medical system. Nevertheless, a false negative rate of 5% is too high to implement the questionnaire presented into daily clinics without further optimisation.

Practicability of a Virtual Consultation to Evaluate the Shoulder Joint. / Durchführbarkeit einer digitalen Sprechstunde zur Untersuchung des Schultergelenkes.

OBJECTIVE: In the course of the corona pandemic, resource conservation and the protection of further infections have made it necessary to break new ground in the organisation of orthopaedic and trauma surgery consultations. One solution is consistent digitisation and the offer of video consultation hours. In this study, non-contact examination of patients with shoulder disorders is described and critically examined. METHODS: Thirty patients who presented with pathologies of the shoulder joint in a university outpatient clinic were subjected to a physical examination in a conventional and contactless manner. The data obtained on mobility, function and provocation test of both examinations were compared to draw conclusions about the virtual feasibility. RESULTS: 46% of the patients suffered from a traumatic shoulder lesion, and 54% showed degenerative lesions. The assessment of mobility showed a high correlation of 70 - 90% between the two examinations. Common tests to evaluate the supraspinatus, infraspinatus, subscapularis and the long head of the biceps could be adequately performed in a contactless version by more than three quarters of the patients, but with low-to-moderate performance values. CONCLUSION: Contact-less examination is particularly disadvantageous when evaluating stability criteria. For the medical history and functional test, there were no significant differences between the classic consultation and contactless consultation. Although virtual consultation is a widespread and valuable addition in pandemic times, it cannot replace a safe assessment and indication by personal examination.

Proximal Femur Fractures - How Decisive are Reduction and the Chosen Implant? / Osteosynthese bei proximalen Femurfrakturen ­ Wie entscheidend sind Reposition und die Wahl des Implantats?

Proximal femoral fractures are frequent and complex injuries requiring prompt and targeted care. Numerous treatment strategies have been described, some of which have been assessed and clinically implemented clinically. The aim of surgical is always the restoration of a pain-free and stable extremity. Mostly elderly patients are affected and treatment is associated with high postoperative complications and mortality rates. With increasing numbers of patients, the topic is of great medical and economic relevance. In this work, the choice of implants for the osteosynthesis of proximal femoral fractures - as depending on the fracture type - will be examined, as based on a review of current literature. Standard care includes cannulated screws, sliding hips screws and cephalomedullary nails. In addition, the influence of implant positioning, fracture reduction and additional measures such as cement augmentation are evaluated and discussed. Careful fracture reduction and the quality of implant positioning are paramount in order to avoid complications.

Economic Effects of the SARS-CoV-2 Pandemic in 2020. / Wirtschaftliche Auswirkungen der SARS-CoV-2-Pandemie im Jahr 2020.

INTRODUCTION: In 2020, the SARS-CoV-2 pandemic necessitated an adjustment to the care structure in all medical facilities in Germany. In this study we analysed the effects of the SARS-CoV-2 pandemic using the data from the annual balance sheet of a university department and maximum care provider for orthopaedics and trauma surgery. METHODS: Data analysis was performed on the clinic's performance parameters from 2019 and 2020. The analysis included 52943 outpatient and 7980 inpatient cases, together with the Case Mix Index (CMI), and the costs and revenues. RESULTS: As a result of the reduction in scheduled surgeries, the mean number of inpatients in March and April 2020 decreased by 10.4% (p = 0.004). Due to the focus on complex cases, the CMI increased by 29.5% (p = 0.007). The number of outpatient surgical procedures increased by 16.9% (n = 84). Rising costs of consumables due to the purchase of protective equipment were offset by a reduced need for orthopaedic implants. CONCLUSION: By reducing the number of elective inpatient surgical treatments, the focus was shifted to treating complex cases; this is reflected in the increased CMI. Due to internal compensation mechanisms, the clinic was able to conserve intensive care capacities while still achieving an increase in revenue.

The Role of Immune Checkpoint Molecules on Macrophages in Cancer, Infection, and Autoimmune Pathologies.

Immune checkpoint inhibitors have revolutionized immunotherapy against various cancers over the last decade. The use of checkpoint inhibitors results in remarkable re-activation of patients' immune system, but is also associated with significant adverse events. In this review, we emphasize the importance of cell-type specificity in the context of immune checkpoint-based interventions and particularly focus on the relevance of macrophages. Immune checkpoint blockade alters the dynamic macrophage phenotypes and thereby substantially manipulates therapeutical outcome. Considering the macrophage-specific immune checkpoint biology, it seems feasible to ameliorate the situation of patients with severe side effects and even increase the probability of survival for non-responders to checkpoint inhibition. Apart from malignancies, investigating immune checkpoint molecules on macrophages has stimulated their fundamental characterization and use in other diseases as well, such as acute and chronic infections and autoimmune pathologies. Although the macrophage-specific effect of checkpoint molecules has been less studied so far, the current literature shows that a macrophage-centered blockade of immune checkpoints as well as a stimulation of their expression represents promising therapeutic avenues. Ultimately, the therapeutic potential of a macrophage-focused checkpoint therapy might be maximized by diagnostically assessing individual checkpoint expression levels on macrophages, thereby personalizing an effective treatment approach for each patient having cancer, infection, or autoimmune diseases.

[Climate change: how surgery contributes to global warming]. / Klimawandel: Wie die Chirurgie zur Erderwärmung beiträgt.

BACKGROUND: Surgery as an important part of the healthcare sector contributes to environmental pollution and therefore to the climate crisis. The aim of this review is to create an overview of the current data situation and possibilities for improvement. METHODS: A literature search was performed in PubMed/MEDLINE using the following five terms: "carbon footprint and surgery", "climate change and surgery", "waste and surgery" and "greening the operating room" focusing on energy, waste, water and anesthesia. RESULTS: The greatest part of emissions in surgery is generated by the use of energy. The operating rooms (OR) need 3-6 times more energy than the other hospital rooms. Of the total hospital waste 20-30% is produced during operations, which is particularly due to the increasing use of disposable articles and 50-90% of waste classified as hazardous is incorrectly sorted. The disposal of this waste is not only more environmentally harmful but also much more expensive. The processing of surgical items by autoclaving consumes large amounts of water. Modern sterilization methods, for example using plasma could be future alternatives. Up to 20% of volatile nonmetabolized anesthetic agents are vented into the stratosphere and destroy the ozone layer. Intravenous anesthetic drugs should be used whenever possible instead. The choice of operating method can also contribute to the environmental impact of an operation. CONCLUSION: The surgical disciplines are a relevant producer of environmental pollutants. Through diverse interdisciplinary approaches surgery can also contribute to protecting the environment.

The base of coracoid process as a reference for glenoid reconstruction in primary or revision reverse shoulder arthroplasty: CT-based anatomical study.

INTRODUCTION: Joint replacement surgery as a treatment for glenohumeral arthritis with glenoid bone loss is challenging. The aim of this study is to offer an anatomical orientation for glenoid reconstruction. METHODS: In this study, we measured size, inclination and version of the glenoid surface, as well as the distance between the articular line of the glenoid, base of the coracoid process, and acromion using computer tomographic (CT) imaging of 131 study participants aged 19-88 years in the period of 2010-2013. RESULTS: We measured a mean distance of 6.5 ± 0.2 mm from the glenoid articular line to the base of the coracoid process in the transverse CT plane. Body height has shown no significant impact on the glenoid morphology. We observed significant differences between males and females: The glenoid appeared to be located 5.2 ± 0.9 mm higher and the humeral head was 4.5 ± 0.7 mm larger in male subjects compared with females (r = .699; p < .01). CONCLUSION: In our study, the base of the coracoid offers an anatomical reference during reconstruction of the glenoid in primary and revision shoulder arthroplasty. As only 2D-CT imaging allows for accurate assessment of glenoid bone defects, we consider conventional X-ray imaging insufficient for proper preoperative planning before shoulder arthroplasty. LEVEL OF EVIDENCE: III.

A Feasibility Pilot Study on the Use of Telemedicine for the Examination of the Knee Joint. / Eine Pilotuntersuchung zur Machbarkeit der Videosprechstunde bei muskuloskelettalen Beschwerden des Kniegelenks.

BACKGROUND: In times of a pandemic threat, such as COVID-19, and the need for reduced direct doctor-patient contact, internet-based telemedicine has attracted more and more attention as a surrogate service. Suspending the diagnosis and treatment of non-virus related diseases for longer periods of time is not a viable option since this would only exacerbate problems on the patient and national level. The need for alternative treatment modalities increased rather quickly. So far, telemedical applications have mainly focused on teleradiological diagnosis, follow-up and monitoring of psychiatric and internal diseases, as well as geriatric patient care. As far as these authors are aware, orthopaedic physical examination of the knee joint, including trauma work-up, has not been the subject of any studies to date. This feasibility study explores how video consultation can be designed and implemented in the context of history taking and physical examination in knee joint complaints. MATERIAL AND METHOD: 21 patient actors (PA) with simulated complaints of the knee joint were examined individually for each diagnosis, first via video consultation and then directly by a specialist (SP). One PA group has a medical background, the other was made up of laypersons. The time was measured for both types of consultation. The physician documented the detected symptoms, the quality of implementation of the self-examination steps, and the derived diagnosis on an assessment form. After completion of both consultation sessions, the PAs were handed a questionnaire on the respective examination modality. RESULTS: With the video consultation the examination lasted 8.63 (± 2.5) minutes on average and with the regular consultation in person 5.63 (± 1.7) minutes (p < 0.001). For the group with medical background the examination lasted 7.67 (± 1.4) minutes on average, while for the lay group the video consultation took 9.7 (± 3.1) minutes (p = 0.049). With increased age, the video consultation was prolonged (p = 0.032; r = 0.47). The mean value for self-examination of leg axis, gait pattern and degrees of freedom was 9.32 (± 0.4) of 10 points. The following functional tests resulted in lower mean values (points): Payr 7.2 (± 2.3), Merke 5.9 (± 2.8), no-touch Lachmann 6.4 (± 2.7), gravity sign-recurvatum 6.7 (± 2.4). The mean grade by the PAs for the feasibility of self-examination was 2.43 (± 0.98) out of 5 points. CONCLUSION: The video consultation for musculoskeletal complaints of the knee joint allows exploratory remote examination and helps to minimise the number of patients in hospitals and practices. It takes longer for the physician to perform and does not permit functional testing for ligament injuries of the knee joint. In its present form, telemedical examination is not able to fully replace personal consultation.