Experimental evidence for Parthanatos-like mode of cell death of heat-damaged human skin fibroblasts in a cell culture-based in vitro burn model.

The cellular mechanisms of burn conversion of heat damaged tissue are center of many studies. Even if the molecular mechanisms of heat-induced cell death are controversially discussed in the current literature, it is widely accepted that caspase-mediated apoptosis plays a central role. In the current study we wanted to develop further information on the nature of the mechanism of heat-induced cell death of fibroblasts in vitro. We found that heating of human fibroblast cultures (a 10 s rise from 37 °C to 67 °C followed by a 13 s cool down to 37 °C) resulted in the death of about 50% of the cells. However, the increase in cell death started with a delay, about one hour after exposure to heat, and reached the maximum after about five hours. The lack of clear evidence for an active involvement of effector caspase in the observed cell death mechanism and the lack of observation of the occurrence of hypodiploid nuclei contradict heat-induced cell death by caspase-mediated apoptosis. Moreover, a dominant heat-induced increase in PARP1 protein expression, which correlated with a time-delayed ATP synthesis inhibition, appearance of double-strand breaks and secondary necrosis, indicate a different type of cell death than apoptosis. Indeed, increased translocation of Apoptosis Inducing Factor (AIF) and Macrophage Migration Inhibitory Factor (MIF) into cell nuclei, which correlates with the mentioned enhanced PARP1 protein expression, indicate PARP1-induced, AIF-mediated and MIF-activated cell death. With regard to the molecular actors involved, the cellular processes and temporal sequences, the mode of cell death observed in our model is very similar to the cell death mechanism via Parthanatos described in the literature.

Navigation versus fluoroscopy in minimalinvasive iliosacral screw placement.

INTRODUCTION: When needed operative treatment of sacral fractures is mostly performed with percutaneous iliosacral screw fixation. The advantage of navigation in insertion of pedicle screws already could be shown by former investigations. The aim of this investigation was now to analyze which influence iliosacral screw placement guided by navigation has on duration of surgery, radiation exposure and accuracy of screw placement compared to the technique guided by fluoroscopy. METHODS: 68 Consecutive patients with sacral fractures who have been treated by iliosacral screws were inclouded. Overall, 85 screws have been implanted in these patients. Beside of demographic data the duration of surgery, duration of radiation, dose of radiation and accuracy of screw placement were analyzed. RESULTS: When iliosacral screw placement was guided by navigation instead of fluoroscopy the dose of radiation per inserted screw (155.0 cGy*cm2 vs. 469.4 cGy*cm2 p < 0.0001) as well as the duration of radiation use (84.8 s vs. 147.5 s p < 0.0001) were significantly lower. The use of navigation lead to a significant reduction of duration of surgery (39.0 min vs. 60.1 min p < 0.01). The placement of the screws showed a significantly higher accuracy when performed by navigation (0 misplaced screws vs 6 misplaced screws-p < 0.0001). CONCLUSION: Based on these results minimal invasive iliosacral screw placement guided by navigation seems to be a safe procedure, which leads to a reduced exposure to radiation for the patient and the surgeon, a reduced duration of surgery as well as a higher accuracy of screw placement.

Efficacy of lysostaphin-coated titanium plates on implant-associated MRSA osteitis in minipigs.

PURPOSE: The growing incidence of implant-associated infections (IAIs) caused by biofilm-forming Staphylococcus aureus in combination with an increasing resistance to antibiotics requires new therapeutic strategies. Lysostaphin has been shown to eliminate this biofilm. Own studies confirm the effectiveness in a murine model. The current study characterizes the effects of lysostaphin-coated plates in an IAI minipig model. METHODS: The femur of 30 minipigs was stabilized with a five-hole plate, a bone defect was created, and in 20 cases methicillin-resistant Staphylococcus aureus was applied. Ten animals served as control group. After 14 days, local debridement, lavage, and plate exchange (seven-hole plate) were performed. Ten of the infected minipigs received an uncoated plate and 10 a lysostaphin-coated plate. On day 84, the minipigs were again lavaged, followed by euthanasia. Bacterial load was quantified by colony-forming units (CFU). Immunological response was determined by neutrophils, as well as interleukins. Fracture healing was assessed radiologically. RESULTS: CFU showed significant difference between infected minipigs with an uncoated plate and minipigs with a lysostaphin-coated plate (p = 0.0411). The infection-related excessive callus formation and calcification was significantly greater in the infected animals with an uncoated plate than in animals with a lysostaphin-coated plate (p = 0.0164/p = 0.0033). The analysis of polymorphonuclear neutrophils and interleukins did not reveal any pioneering findings. CONCLUSION: This study confirms the minipig model for examining IAI. Furthermore, coating of plates using lysostaphin could be a promising tool in the therapeutic strategies of IAI. Future studies should focus on coating technology of implants and on translation into a clinical model.

Epidemiology of distal radius fractures in Germany - incidence rates and trends based on inpatient and outpatient data.

We examined incidence rates (IR) for all distal radius fracture (DRF) events based on inpatient and outpatient data from a large statutory health insurance in Germany. Of all DRF, 56% were treated as inpatients, and thus, 44% treated as outpatients. IR were higher in women than in men. PURPOSE: Although a distal radius fracture (DRF) is one of the most common fractures in the elderly population, epidemiological data are limited. Many studies examine only hospitalized patients, do not analyze time trends, or include only small populations. In this retrospective population-based observational study, routine data on inpatient and outpatient care of persons aged ≥ 60 years insured by a large statutory health insurance in Germany were analyzed from 2014 to 2018. METHODS: DRF were identified by ICD-10 codes. All DRF events of an individual were considered with a corresponding individual washout period. Incidence rates (IR) and time trends were estimated assuming a Poisson distribution per 100,000 person-years, with 95% confidence intervals [95% CI] and age-sex standardization to the German population in 2018. Associations of calendar year, age, sex, and comorbidity with IR were examined using Poisson regression estimating incidence rate ratios (IRR) with CI. RESULTS: The study population consists of 974,332 insured individuals, with 16,557 experiencing one or more DRF events during the observation period. A total of 17,705 DRF events occurred, of which 9961 (56.3%) were hospitalized. Standardized IR were 439 [424-453] (inpatient: 240 [230-251], outpatient: 199 [189-209]) in 2014 and 438 [423-452] (inpatient: 238 [227-249], outpatient: 200 [190-210]) in 2018. Female sex, older age, and comorbidity were associated with higher IR and adjusted Poisson regression showed no significant time trend (IRR overall 0.994 [0.983-1.006]). CONCLUSION: A relevant proportion of DRF were treated in outpatient settings, so both inpatient and outpatient data are necessary for a valid estimate.

Establishing regions of interest of the lower leg and ankle for perioperative volumetric assessment with a portable 3D scanner in orthopedic and trauma surgery - a pilot study.

BACKGROUND: Soft tissue swelling assessment benefits from a reproducible and easy to use measurement method. Monitoring of the injured lower extremity is of clinical import during staged soft tissue management. Portable 3D scanners offer a novel and precise option to quantify and contrast the shapes and volumes of the injured and contralateral uninjured limbs. This study determined three regions of interest (ROI) within the lower extremity (lower leg, ankle and foot), that can be used to evaluate 3D volumetric assessment for staged soft tissue management in orthopedic and trauma surgery. METHODS: Twelve healthy volunteers (24 legs) were included in this cohort study. Scans of all three ROI were recorded with a portable 3D scanner (Artec, 3D scanner EVA) and compared between the right and left leg using the software Artec Studio (Arctec Group, Luxemburg). RESULTS: Mean volume of the right leg was 1926.64 ± 308.84 ml (mean ± SD). ROI: lower leg: 931.86 ± 236.15 ml; ankle: 201.56 ± 27.88 ml; foot: 793.21 ± 112.28 ml. Mean volume of the left leg was 1937.73 ± 329.51 ml. ROI: lower leg: 933.59 ± 251.12 ml; ankle: 201.53 ± 25.54 ml; foot: 802.62 ± 124.83 ml. There was no significant difference of the overall volume between right and left leg (p > 0.05; overall volume: △ difference: 29.5 ± 7.29 ml, p = 0.8; lower leg: △ difference: 21.5 ± 6.39 ml, p = 0.8; ankle: △ difference: 5.3 ± 2.11 ml, p = 0.4; △ difference: 16.33 ± 4.45 ml, p = 0.8. CONCLUSION: This pilot study defines three regions of interest of the lower leg and demonstrates no difference between the right and left side. Based on these ROI, further studies are needed to evaluate the clinical applicability of the scanner.

Comparison of compositional MRI techniques to quantify the regenerative potential of articular cartilage: a preclinical minipig model after osteochondral defect treatments with autologous mesenchymal stromal cells and unseeded scaffolds.

Background: The field of orthopedics seeks effective, safer methods for evaluating articular cartilage regeneration. Despite various treatment innovations, non-invasive, contrast-free full quantitative assessments of hyaline articular cartilage's regenerative potential using compositional magnetic resonance (MR) sequences remain challenging. In this context, our aim was to investigate the effectiveness of different MR sequences for quantitative assessment of cartilage and to compare them with the current gold standard delayed gadolinium-enhanced MR imaging of cartilage (dGEMRIC) measurements. Methods: We employed ex vivo imaging in a preclinical minipig model to assess knee cartilage regeneration. Standardized osteochondral defects were drilled in the proximal femur of the specimens (n=14), which were divided into four groups. Porcine collagen scaffolds seeded with autologous adipose-derived stromal cells (ASC), autologous bone marrow stromal cells (BMSC), and unseeded scaffolds (US) were implanted in femoral defects. Furthermore, there was a defect group which received no treatment. After 6 months, the specimens were examined using different compositional MR methods, including the gold standard dGEMRIC as well as T1, T2, T2*, and T1ρ techniques. The statistical evaluation involved comparing the defect region with the uninjured tibia and femur cartilage layers and all measurements were performed on a clinical 3T MR Scanner. Results: In the untreated defect group, we observed significant differences in the defect region, with dGEMRIC values significantly lower (404.86±64.2 ms, P=0.018) and T2 times significantly higher (44.24±2.75 ms, P<0.001). Contrastingly, in all three treatment groups (ASC, BMSC, US), there were no significant differences among the three regions in the dGEMRIC sequence, suggesting successful cartilage regeneration. However, T1, T2*, and T1ρ sequences failed to detect such differences, highlighting their lower sensitivity for cartilage regeneration. Conclusions: As expected, dGEMRIC is well suited for monitoring cartilage regeneration. Interestingly, T2 imaging also proved to be a reliable cartilage imaging technique and thus offers a contrast agent-free alternative to the former gold standard for subsequent in vivo studies investigating the cartilage regeneration potential of different treatment modalities.

Tumorigenic effects of human mesenchymal stromal cells and fibroblasts on bladder cancer cells.

Background: Patients with muscle-invasive bladder cancer face a poor prognosis due to rapid disease progression and chemoresistance. Thus, there is an urgent need for a new therapeutic treatment. The tumor microenvironment (TME) has crucial roles in tumor development, growth, progression, and therapy resistance. TME cells may also survive standard treatment of care and fire up disease recurrence. However, whether specific TME components have tumor-promoting or tumor-inhibitory properties depends on cell type and cancer entity. Thus, a deeper understanding of the interaction mechanisms between the TME and cancer cells is needed to develop new cancer treatment approaches that overcome therapy resistance. Little is known about the function and interaction between mesenchymal stromal cells (MSC) or fibroblasts (FB) as TME components and bladder cancer cells. Methods: We investigated the functional impact of conditioned media (CM) from primary cultures of different donors of MSC or FB on urothelial carcinoma cell lines (UCC) representing advanced disease stages, namely, BFTC-905, VMCUB-1, and UMUC-3. Underlying mechanisms were identified by RNA sequencing and protein analyses of cancer cells and of conditioned media by oncoarrays. Results: Both FB- and MSC-CM had tumor-promoting effects on UCC. In some experiments, the impact of MSC-CM was more pronounced. CM augmented the aggressive phenotype of UCC, particularly of those with epithelial phenotype. Proliferation and migratory and invasive capacity were significantly increased; cisplatin sensitivity was reduced. RNA sequencing identified underlying mechanisms and molecules contributing to the observed phenotype changes. NRF2 and NF-κB signaling was affected, contributing to improved cisplatin detoxification. Likewise, interferon type I signaling was downregulated and regulators of epithelial mesenchymal transition (EMT) were increased. Altered protein abundance of CXCR4, hyaluronan receptor CD44, or TGFß-signaling was induced by CM in cancer cells and may contribute to phenotypical changes. CM contained high levels of CCL2/MCP-1, MMPs, and interleukins which are well known for their impact on other cancer entities. Conclusions: The CM of two different TME components had overlapping tumor-promoting effects and increased chemoresistance. We identified underlying mechanisms and molecules contributing to the aggressiveness of bladder cancer cells. These need to be further investigated for targeting the TME to improve cancer therapy.

Dupuytren's Disease Is Mediated by Insufficient TGF-ß1 Release and Degradation.

Dupuytren's disease (DD) is a fibroproliferative disorder affecting the palmar fascia, causing functional restrictions of the hand and thereby limiting patients' daily lives. The disturbed and excessive myofibroblastogenesis, causing DD, is mainly induced by transforming growth factor (TGF)-ß1. But, the extent to which impaired TGF-ß1 release or TGF-ß signal degradation is involved in pathologically altered myofibroblastogenesis in DD has been barely examined. Therefore, the complex in which TGF-ß1 is secreted in the extracellular matrix to elicit its biological activity, and proteins such as plasmin, integrins, and matrix metalloproteinases (MMPs), which are involved in the TGF-ß1 activation, were herein analyzed in DD-fibroblasts (DD-FBs). Additionally, TGF-ß signal degradation via caveolin-1 was examined with 5-fluoruracil (5-FU) in detail. Gene expression analysis was performed via Western blot, PCR, and immunofluorescence analyses. As a surrogate parameter for disturbed myofibroblastogenesis, 𝛼-smooth-muscle-actin (𝛼-SMA) expression was evaluated. It was demonstrated that latency-associated peptide (LAP)-TGF-ß and latent TGF-ß-binding protein (LTBP)-1 involved in TGF-ß-complex building were significantly upregulated in DD. Plasmin a serinprotease responsible for the TGF-ß release was significantly downregulated. The application of exogenous plasmin was able to inhibit disturbed myofibroblastogenesis, as measured via 𝛼-SMA expression. Furthermore, a reduced TGF-ß1 degradation was also involved in the pathological phenotype of DD, because caveolin-1 expression was significantly downregulated, and if rescued, myofibroblastogenesis was also inhibited. Therefore, our study demonstrates that a deficient release and degradation of TGF-ß1 are important players in the pathological phenotype of DD and should be addressed in future research studies to improve DD therapy or other related fibrotic conditions.

[Scaphoid fractures : Current diagnostic and treatment concepts]. / Skaphoidfrakturen : Aktuelle diagnostische und therapeutische Konzepte.

Scaphoid fractures are by far the most frequent fractures of the carpal bones of the hand and often lead to problematic healing processes if the diagnostics and treatment are inadequate. The main complication of a scaphoid fracture is pseudarthrosis, which leads to carpal collapse and degenerative arthritis of the wrist if left untreated. Early diagnosis and individualized differentiated treatment aim to achieve bony healing with restoration of the scaphoid shape and preservation of the function of the wrist. The anatomical and biomechanical characteristics of the scaphoid can impede bony healing after a fracture and, in contrast to the diagnostics and treatment, cannot be influenced. A history of trauma and typical clinical signs of a scaphoid fracture should lead to systematic imaging diagnostics with obligatory computed tomography. Only by determining the exact fracture morphology can an appropriate treatment concept be established. Conservative treatment should be restricted to stable fractures without relevant displacement. Fractures of the proximal scaphoid pole are considered unstable even if they are not displaced. Operative treatment is indicated for all unstable fractures. The favored surgical procedure is osteosynthesis with a cannulated double-threaded screw, which can be used in a retrograde or antegrade manner and in a minimally invasive or open technique, depending on the fracture type. Surgical treatment results in earlier bony healing and quicker restoration of function but can be associated with a higher complication rate. Posttraumatic osteoarthritis after healing in malalignment is usually asymptomatic.

Outcome of Targeted vs Empiric Antibiotic Therapy in the Treatment of Spondylodiscitis: A Retrospective Analysis of 201 Patients.

BACKGROUND: Antibiotic treatment of spondylodiscitis is influenced by antibiotic stewardship; specifically, empirical antibiotic therapy is avoided in favor of-delayed-targeted antibiotic therapy after microbiological diagnosis. Only patients with neurological deficits or clinical signs of sepsis should be treated by empirical antibiotic therapy. However, the level of evidence for this treatment concept is weak. PURPOSE: The aim of this study was to investigate whether patients who were treated with a nontargeted antibiotic therapy show a worse outcome than patients who were exclusively treated with targeted antibiotic therapy. STUDY DESIGN/SETTING: A retrospective single-center data analysis. PATIENT SAMPLE: We included 201 patients with spondylodiscitis who were treated at the authors' institution between 2013 and 2020. OUTCOME MEASURES: Mortality rate, time in hospital, development of laboratory parameters, and development of pain (visual analog scale). METHODS: We performed a retrospective data analysis of patients who were treated for spondylodiscitis from January 2013 to March 2020. Clinical and demographic data as well as outcome and complications were recorded and analyzed. We investigated whether patients who were treated by a nontargeted antibiotic therapy had a worse outcome than patients who were exclusively treated by targeted antibiotic therapy and which other clinical factors had an impact on clinical outcome. RESULTS: A total of 201 patients were included, 37 of whom developed sepsis during their hospital stay, and 14 of these 37 patients died. The 14 patients who died represented (10.0%) of the subgroup who received an empirical antibiotic treatment before the targeted antibiotic therapy (n = 141). There were 0 deaths in the subgroup who did not receive an empirical antibiotic treatment (P < 0.05). The time to diagnosis since admission to the hospital was 10.5 (2.2) days in patients with sepsis; in patients without sepsis, it was 5.2 (0.9) days (P < 0.05). CONCLUSIONS: Based on the results of this investigation, the authors recommend delaying antibiotic therapy until targeted antibiotic therapy is possible. Furthermore, early diagnosis of spondylodiscitis and prevention and early detection of sepsis are essential to reduce the mortality rate of patients with spondylodiscitis.

May bending radiographs be replaced by magnetic resonance imaging in patients with adolescent idiopathic scoliosis?

PURPOSE: There is no data that shows if it is possible to determine if a curve is structural or non-structural or to assess flexibility of an adolescent idiopathic scoliosis (AIS) by magnetic resonance imaging (MRI) instead of bending radiographs (BR). We investigated if the results of BR may be compared to those of MRI. METHODS: We retrospectively analyzed prospectively collected data of patients with AIS in whom a selective spinal fusion was performed and in whom a MRI, BR and full-spine X-rays were obtained preoperatively. We measured the Cobb angles of the main and of the minor curve in full-spine X-ray (FSR), BR and MRI and analyzed the degree of the intervertebral disk degeneration in the MRI. RESULTS: After applying inclusion and exclusion criteria, 25 patients were included. We found a significant correlation (p < 0.05, Corr Coeff = 0.41) between the Cobb angle of the main curve in FSR and the Cobb angle of the main curve in the MRI and between the Cobb angle of the minor curve in FSR and the Cobb angle of the minor curve in the MRI (p < 0.001, Corr Coeff = 0.04). All patients with a minor curve of less than 25° in the BR had a Cobb angle of less than 30° in the MRI. CONCLUSION: Spinal curves showed a significant correlation between bending radiographs and recumbent images (MRI). In our group of patients, a Cobb angle of the minor curve of less than 30° in the MRI indicated that this minor curve was non-structural according to the classification of Lenke.

Enrichment of Bone Tissue with Antibacterially Effective Amounts of Nitric Oxide Derivatives by Treatment with Dielectric Barrier Discharge Plasmas Optimized for Nitrogen Oxide Chemistry.

Cold atmospheric plasmas (CAPs) generated by dielectric barrier discharge (DBD), particularly those containing higher amounts of nitric oxide (NO) or NO derivates (NOD), are attracting increasing interest in medical fields. In the present study, we, for the first time, evaluated DBD-CAP-induced NOD accumulation and therapeutically relevant NO release in calcified bone tissue. This knowledge is of great importance for the development of new therapies against bacterial-infectious complications during bone healing, such as osteitis or osteomyelitis. We found that by modulating the power dissipation in the discharge, it is possible (1) to significantly increase the uptake of NODs in bone tissue, even into deeper regions, (2) to significantly decrease the pH in CAP-exposed bone tissue, (3) to induce a long-lasting and modulable NO production in the bone samples as well as (4) to significantly protect the treated bone tissue against bacterial contaminations, and to induce a strong bactericidal effect in bacterially infected bone samples. Our results strongly suggest that the current DBD technology opens up effective NO-based therapy options in the treatment of local bacterial infections of the bone tissue through the possibility of a targeted modulation of the NOD content in the generated CAPs.

Surgical Site Infection After Posterior Stabilization of the Spine - When do we Have to Remove the Implants?

STUDY DESIGN: Retrospective data analysis. OBJECTION: The primary objective of this investigation was to analyze if treatment of Postoperative surgical site infections (PSSI) after posterior stabilization of the spine (PS) without radiological signs of screw loosening (RSL) shows a sufficient success rate without implant removal and if there was any difference between early and late PSSI. SUMMARY OF BACKGROUND DATA: PSSI after PS are usually treated by implant removal and reinstrumentation if loosening of one of more screws is detected. There is presently no conclusive data that shows the success rate of the treatment of PSSI after PS without implant removal if no RSL are perceived. MATERIALS AND METHODS: All patients who were treated for a PSSI after PS without RSL in a single spine center from 12/2009 to 03/2020 were enrolled in a retrospective analysis. Patients were treated by revision surgery with debridement and irrigation and subsequent antibiotic therapy. Implant removal was performed if the initial treatment did not lead to an improvement in wound healing and normalization of laboratory values. Statistical analysis was performed by Statistical Package for the Social Sciences 25. Descriptive data are given as mean and standard error of mean, a χ 2 test was performed. RESULTS: Of the 32 enrolled patients, 17 had an early PSSI, 15 a late PSSI. In 71.9% (23/32), the PSSI was treated without implant removal: 12/17 in early PSSI, 11/15 in late PSSI. The difference was not significant ( P >0.05). One patient died, all other patients were discharged from the hospital with no remaining laboratory signs of the infection and with closed soft tissues. CONCLUSIONS: In our group of patients, the success rate of irrigation and debridement without implant removal was 71.9%. In the light of this data, performing at least two irrigations and debridement before implant removal seems to be a valid treatment option in PSSI after PS if there are no RSL in early and late PSSI.

Comparative Study of the Osteogenic Differentiation Potential of Adipose Tissue-Derived Stromal Cells and Dedifferentiated Adipose Cells of the Same Tissue Origin under Pro and Antioxidant Conditions.

Adipose tissue-derived stromal cells (ASCs) play an important role in various therapeutic approaches to bone regeneration. However, such applications become challenging when the obtained cells show a functional disorder, e.g., an impaired osteogenic differentiation potential (ODP). In addition to ASCs, human adipose tissue is also a source for another cell type with therapeutic potential, the dedifferentiated fat cells (DFATs), which can be obtained from mature adipocytes. Here, we for the first time compared the ODPs of each donors ASC and DFAT obtained from the same adipose tissue sample as well as the role of oxidative stress or antioxidative catalase on their osteogenic outcome. Osteogenic potential of ASC and DFAT from nine human donors were compared in vitro. Flow cytometry, staining for calcium accumulation with alizarin red, alkaline phosphatase assay and Western blots were used over an osteogenic induction period of up to 14 days. H2O2 was used to induce oxidative stress and catalase was used as an antioxidative measure. We have found that ASC and DFAT cultures' ODPs are nearly identical. If ASCs from an adipose tissue sample showed good or bad ODP, so did the corresponding DFAT cultures. The inter-individual variability of the donor ODPs was immense with a maximum factor of about 20 and correlated neither with the age nor the sex of the donors of the adipose tissue. Oxidative stress in the form of exogenously added H2O2 led to a significant ODP decrease in both cell types, with this ODP decrease being significantly lower in DFAT cultures than in the corresponding ASC cultures. Regardless of the individual cell culture-specific ODP, however, exogenously applied catalase led to an approx. 2.5-fold increase in osteogenesis in the ASC and DFAT cultures. Catalase appears to be a potent pro-osteogenic factor, at least in vitro. A new finding that points to innovative strategies and therapeutic approaches in bone regeneration. Furthermore, our results show that DFATs behave similarly to ASCs of the same adipose tissue sample with respect to ODPs and could therefore be a very attractive and readily available source of multipotent stem cells in bone regenerative therapies.

Volumetry of Hand and Forearm: A 3D Volumetric Approach.

BACKGROUND: Swelling and edema of the hand and forearm may occur in various traumatic and degenerative diseases. So far, no precise measurement protocol exists. The objective of this study was to evaluate an examination protocol with relevant regions of interest (ROIs) measured by a 3-dimensional (3D) scanner to achieve precise, reproducible, and objective measurements for an optimized detection of volumes of the hand and forearm. METHODS: A 3D scan protocol was developed using an Artec, 3D scanner EVA to measure discrete hand volumes of healthy volunteers. Five areas were defined as ROIs, representing volumes of the finger, metacarpus, wrist, hand, and distal forearm. Contralateral limbs were used for volume comparisons and calculation of volume differences. RESULTS: For this study, 12 individuals (58.3% women, 24 hands and forearms) with a mean age of 27.1 ± 3 years were included. Mean volume values for left and right ROIs correlated with each other, with slightly higher volumes for the right upper extremity. Volume differences showed statistically significant results for the finger region (ROI I; P = .009), the metacarpal region (ROI II; P < .001), hand region (ROI IV; P = .001), and forearm region (ROI V; P = .006), with the exception of the wrist region (ROI III; P = .722). CONCLUSIONS: Our results demonstrate that this 3D volumetric approach is a reliable and objective tool for measuring volumes and circumferences in hand and forearm. Based on our determined ROIs, further studies are needed to explore the significance for clinical applications.

Influence of the COVID-19 pandemic on causes for the development of carbon monoxide intoxications.

Introduction: Several causes can lead to carbon monoxide (CO) intoxication. A first-line treatment option for such intoxications is hyperbaric oxygenation (HBO2) therapy. The COVID-19 pandemic has been changing everyday life in Germany since March 2020, mainly caused by statutory provisions. Our aim was to review whether these changes have an influence on the causes and frequency for the development of CO intoxication. Methods: We retrospectively analyzed the data of patients who were treated for CO intoxication in our institution between April 2019 and March 2021. Besides demographic data, we compared the overall number and documented causes for each CO intoxication in the period of April 2020 to March 2021 with the period between April 2019 and March 2020. Results: After applying inclusion and exclusion criteria, 139 patients were included. We found a significant decrease in the overall number of patients who needed treatment since the beginning of the COVID-19 pandemic. However, the share of CO intoxication caused by the indoor use of coal stoves, coal barbecue, or suicide attempts increased. In contrast, the share of cases caused by apartment or house fire, smoking waterpipe, or gas stoves decreased. Conclusion: The COVID-19 pandemic and the associated restrictions lead to a significant reduction in the number of patients in need for HBO2 therapy due to CO-Intoxication. The causes leading to CO intoxication also changed since the beginning of the COVID-19 pandemic. We observed a shift toward causes related to the indoor use of coal-fired stoves and barbecues as well as suicide attempts.

Enhancement of human bladder carcinoma cell chemosensitivity to Mitomycin C through quasi-monochromatic blue light (λ = 453 ± 10 nm).

Human urothelial bladder carcinoma (uBC) is the second most tumor entity of the urogenital tract. As far as possible, therapy for non-muscle invasive uBC takes place as resection of the tumor tissue, followed by intravesical chemotherapy or immunotherapy. Because of the high recurrence rate of uBC, there is a need for improved efficiency in the treatment. In the present in vitro study we have evaluated a new approach to enhance the cytotoxic efficiency of Mitomycin C (MMC), which is commonly used for intravesical treatment of uBC on the relevant urothelial cancer cell line RT112. For that we used quasi-monochromatic blue light (453 ± 10 nm) at its non-toxic dose of 110 J/cm2 as an additive stimulus to enhance the therapeutic efficiency of MMC (10 µg/ml). We found, that blue light exposure of RT112 cells led to a very strong increase in intracellular production of reactive oxygen species (ROS) and to a significant reduction (p < 0.05) of all function parameters of mitochondrial respiration, including basal activity and ATP production. Although not being toxic when used as a single impact, together with MMC blue light strongly enhanced the therapeutic efficiency of MMC in the form of significantly enhanced cytotoxicity via apoptosis and secondary necrosis. Our results clearly show that blue light, most likely due to its ability to increase intracellular ROS production and reduce mitochondrial respiration, increased the cytotoxic efficiency of MMC and therefore might represent an effective, low-side-effect, and success-enhancing therapy option in the local treatment of bladder cancer.

Screw fixation in the treatment of displaced intra-articular calcaneus fractures: a systematic review protocol.

BACKGROUND: The Calcaneus is the largest bone of the foot and the most frequent tarsal bone to be fractured. Overall, it causes round about 10 cases per 100,000 residents per year mainly in men. Especially displaced intra-articular calcaneus fractures often have early and late complications and its associated disability. There are various strategies for the treatment of displaced intra-articular calcaneus fractures, but the gold standard is still subject of a long-standing controversy. Minimally invasive procedures became more common in an attempt to reduce the high rate of complications associated with open reduction and internal fixation. With the increase in minimally invasive techniques, screw fixation also gained in significance. The current literature does not sufficiently elucidate whether the screw fixation is superior to other treatment options especially in relation to adverse events, health-related quality of life and postoperative pain. This study aims to investigate benefits and harms of treating displaced intra-articular calcaneus fractures (types II, III and IV according to Sanders) with screw fixation in adults. METHODS: A systematic review will be conducted based on the principles described in the Cochrane Handbook. We will include adults with displaced intra-articular calcaneus fractures of Sanders type II, III and IV. The surgical method of screw fixation shall be compared to other surgical interventions to stabilise calcaneus fractures. Primary outcomes are serious adverse events, health-related quality of life and postoperative pain level. MEDLINE, CENTRAL, CINAHL, Web of Science and bibnet.org, ClinicalTrial.gov and the World Health Organization International Clinical Trials Registry Platform (ICTR) will be searched. Screening and data extraction will be performed by two authors independently. A third author will arbitrate disputes. Risk of Bias will be assessed with the Cochrane tool. Meta-analysis will be performed if participants, interventions, comparisons and outcomes are sufficiently similar to ensure a result that is clinically meaningful. DISCUSSION: Due to the increasing use of minimally invasive techniques and the increasing use of screw fixation instead of open reduction and plate fixation, it is important to analyse the benefits and harms of screw fixation for calcaneus fractures. Screw fixation could, in the future, help to operate in a less invasive and tissue preserving manner while still achieving an adequate functional result for the patient SYSTEMATIC REVIEW REGISTRATION: CRD42021244695.