Search

Genotoxic bystander signals released from irradiated human mesenchymal stromal cells (MSC) may induce radiation-induced bystander effects (RIBEs) in human hematopoietic stem and progenitor cells (HSPC), potentially causing leukemic transformation. Although the source of bystander signals is evident, the identification and characterization of these signals is challenging. Here, RIBEs were analyzed in human CD34+ cells cultured in distinct molecular size fractions of medium, conditioned by 2 Gy irradiated human MSC. Specifically, γH2AX foci (as a marker of DNA double-strand breaks) and chromosomal instability were evaluated in CD34+ cells grown in approximate (I) < 10 kDa, (II) 10–100 kDa and (III) > 100 kDa fractions of MSC conditioned medium and un-/fractionated control medium, respectively. Hitherto, significantly increased numbers of γH2AX foci (p = 0.0286) and aberrant metaphases (p = 0.0022) were detected in CD34+ cells grown in the (II) 10–100 kDa fraction (0.67 ± 0.10 γH2AX foci per CD34+ cell ∨ 3.8 ± 0.3 aberrant metaphases per CD34+ cell sample; mean ± SEM) when compared to (I) < 10 kDa (0.19 ± 0.01 ∨ 0.3 ± 0.2) or (III) > 100 kDa fractions (0.23 ± 0.04 ∨ 0.4 ± 0.4) or un-/fractionated control medium (0.12 ± 0.01 ∨ 0.1 ± 0.1). Furthermore, RIBEs disappeared after heat inactivation of medium at 75 °C. Taken together, our data suggest that RIBEs are mainly mediated by the heat-sensitive (II) 10–100 kDa fraction of MSC conditioned medium. We postulate proteins as RIBE mediators and in-depth proteome analyses to identify key bystander signals, which define targets for the development of next-generation anti-leukemic drugs.

Purpose: Computed tomography (CT) scans are an important source of ionizing irradiation (IR) in medicine that can induce a variety of DNA damage in human tissues. With technological improvements CT scans at reduced absorbed doses became feasible presumably lowering genotoxic side effects. Materials and methods: For measuring DNA damage we performed γH2AX foci microscopy in peripheral blood mononuclear cells (PBMC) after exposure to reduced and conventional absorbed radiation doses using 3rd generation dual-source CT (DSCT) technology. Results: CT scans performed at reduced absorbed doses of 3 mGy induced significant lower levels (p

Zusammenfassung  Dislozierte Tuberkelfrakturen finden sich bei unfallchirurgischen Patienten häufig. Die Osteosynthese beinhaltet die Gefahr einer sekundären Dislokation oder eines sekundären Impingements. Wir stellen ein neues und einfach anwendbares Implantat zur Versorgung von v. a. multipel frakturierten Tuberkeln vor, eine Kalkaneustitanplatte (Litos®), aus welcher eine kleine 6(oder mehr)-Loch-Platte angefertigt wird. Die Technik erwies sich bei 10 Patienten als komplikationsfrei und einfach anwendbar. Die Patienten zeigten ein sehr gutes Ergebnis im Constant-Murley-Score ohne sekundäre Dislokation. Die Bamberger Platte mit der beschriebenen Operationstechnik stellt eine einfache, effektive und preisgünstige Methode zur operativen Fixation von Tuberculum-majus-Frakturen dar, die quasi keine Lernkurve beinhaltet. [ABSTRACT FROM AUTHOR]

Background: Displaced intra-articular calcaneal fractures are a complication-ridden injury to treat and there are various treatment techniques to address this injury. The aim of this study was to evaluate the mid-term outcome of a percutaneous two-point distractor technique in patients with displaced intra-articular calcaneal fractures., Methods: A retrospective data analysis of patients with intra-articular calcaneal fractures treated in a level 1 trauma center was conducted. The patients were subsequently invited for a follow-up visit to assess the mid-term outcome. The Böhler's and Gissane's angles, the American Orthopaedic Foot & Ankle Society hindfoot score, the Maryland foot score and a visual analog scale for pain were measured preoperatively and postoperatively and after at least 6 years to assess the radiological and functional outcome., Results: Of the patients 59 completed the study with a mean follow-up of 76 months after surgery. The mean American Orthopedic Foot and Ankle Society hindfoot score at the last follow-up visit was 81, the mean Maryland foot score was 78. There were three cases (5%) of superficial wound complications and secondary arthrodesis of the subtalar joint was performed in five patients (8%)., Conclusion: The low rates of postoperative infections and secondary arthrodesis in this study underline the good to excellent mid-term functional results for a minimally invasive technique., Competing Interests: Conflict of interest: M. Stark, D. Popp, L. Schmoelz, K. Doering, K. Stark and A. Nia declare that they have no competing interests., (© 2024. The Author(s).)

Objective: The main objective of this study was to examine the relationship between mobility patterns during the coronavirus disease 2019 (COVID-19) pandemic and orthopedic trauma patients in Austria. Utilizing global positioning system (GPS)-based mobility data, the attempt was to assess both the impact of COVID-19 lockdowns on reducing orthopedic trauma patients and the degree of compliance to the imposed movement restrictions., Methods: This retrospective analysis included all patients (283,501) treated at 3 major level I trauma centers in Austria. Analyzed time periods were 1 January 2019 to 8 February 2021. Freely available GPS-based mobility data from Google and Apple Inc. was gathered., Results: A moderate to strong correlation between the cumulative average outpatients and the assessed mobility index was observed for all cities (Google: r = 0.70 p < 0.001, 95% confidence interval, CI: 0.67-0.73; Apple: r = 0.64 p < 0.001, 95% CI: 0.61-0.67). A significant linear regression equation was found for Vienna (adjusted r 2  = 0.48; F(1, 350) = 328,05; p < 0.01). During the first lockdown there was a drastic decline in mobility (up to -75.36%) and in numbers of orthopedic trauma outpatients (up to -64%, from 153 patients/day 2019 to 55 patients/day 2020) in comparison to the prepandemic era. The decline diminished as time passed., Conclusion: Analyses of GPS-based mobility patterns show a correlation with trauma patient numbers. These findings can be used to develop prediction models, leading to better resource planning and public health policy, enhancing patient care and cost-effectiveness, especially in the event of future pandemics. Furthermore, the results suggest that compliance to mobility restrictions decreased over time during the COVID-19 pandemic, resulting in increased mobility and trauma patients., (© 2024. The Author(s).)

Introduction: Thiamine-responsive megaloblastic anemia syndrome (TRMA) is a rare autosomal recessive disease with a homozygous or compound-heterozygous mutation in the SLC19A2 gene characterized by megaloblastic anemia, diabetes mellitus (DM), and sensorineural hearing loss with onset in childhood. Folic acid and vitamin B12 in serum are normal with dysplastic erythropoiesis in the bone marrow often mimicking myelodysplastic neoplasms (MDS) as a potential differential diagnosis. Thiamine substitution leads to normalization of anemia, without effects on hearing loss or DM., Case Presentation: We report about a 38-year-old male patient, presented with a 12-year history of anemia, insulin dependent DM, optic neuropathy, and a cataract since early childhood. The laboratory showed megaloblastic anemia. Other values were normal. The bone marrow smear showed dysplastic erythropoiesis with megaloblastic changes, and normal findings in cytogenetic and molecular genetic examinations. Next-generation sequencing-based diagnostics revealed a heterozygous missense variant in the SLC19A2 gene on the maternal allele and a 3.4 Mb inversion in the chromosomal region 1q24.2 with breaking points in FAM78B and SLC19A2 on the paternal allele. Treatment with oral thiamine 100 mg daily was initiated, and 12 weeks later hemoglobin levels and bone marrow morphology had normalized., Conclusion: Late-onset TRMA should be considered in adult patients with indicative comorbidities and a typical phenotype, which may mimic features of MDS., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background/objectives: To assess magnetic resonance image (MRI) findings in children and adolescents with atraumatic non-overload ankle pain and to identify potential anatomic risk factors., Methods: In total, 310 MRIs of 6- to 20-year-old patients were evaluated regarding detectable ankle pathologies. A total of 147 patients (68 males; 79 females) suffered from atraumatic non-overload ankle pain. The findings were compared to a control group (163 patients: 89 males; 74 females), including patients with ankle trauma in the 4 weeks prior to MRI examination. A t -test for unpaired samples and a binary logistic regression model were used to identify significant differences between both groups and determine potential anatomic risk factors., Results: In the group with atraumatic ankle pain, 95 patients (64.6%) showed at least one pathology. Anterolateral impingement of the upper ankle joint was found in 29 patients (19.7%). Its occurrence was significantly higher in atraumatic non-overload patients than in the control group ( p = 0.043). Moreover, a significant correlation between anterolateral impingement of the upper ankle and the presence of hindfoot valgus malposition ( n = 25; 17.0%) could be proven in atraumatic non-overload patients ( p = 0.035)., Conclusions: Anterolateral impingement of the upper ankle joint is frequently observed in children and adolescents suffering from atraumatic non-overload ankle pain, whereby a hindfoot valgus malposition seems to present an anatomic risk factor.

Background: The actual significance of prehospital immobilization of the cervical spine in severely injured trauma patients remains unclear. In view of possible negative implications, such as an increase in intracranial pressure due to the application of a rigid cervical spine orthosis, the long-term use must be critically questioned. Further studies are required to justify the long-term use of a rigid cervical spine orthosis in the prehospital setting., Objective: Comparative measurements of the mobility of the cervical spine during immobilization using a vacuum mattress with or without the additional application of a rigid cervical spine orthosis after positioning on the stretcher were carried out., Material and Methods: Biomechanical measurements of the movement of the cervical spine were carried out by attaching inertial measurement units to a test person during the loading and unloading process in a modern ambulance and during the journey along a predefined parkour. The test person on whom the measurements were carried out was immobilized on a vacuum mattress with the option of lateral fixation of the head and chin and forehead strap on an electrohydraulic stretcher. The complete standard monitoring was set up to simulate as realistic a transport of a severely injured patient as possible. A total of 30 test runs were realized. In one half of the tests, the cervical spine was additionally immobilized using a rigid orthosis and in the other half a cervical spine orthosis was not used. For each of the 30 tests, the angles, axial rotation, lateral bending and flexion/extension as well as the first and second derivatives were considered for loading, transport and unloading and the parameters mean deviation from the zero position, size of the swept angle range and maximum were calculated for each test run., Results: Statistically significant differences were only found for some biomechanical parameters in the sagittal plane (flexion and extension). No significant differences were found for the measured parameters in the other directions of movement (axial rotation, lateral flexion). In general, only very small angular deflections were measured both in the tests with the cervical spine orthosis and without the cervical spine orthosis (on average in the range of 1-2° for axial rotation and flexion/extension and up to 3° for lateral flexion)., Conclusion: If immobilization is carried out correctly using a vacuum mattress with the option of lateral stabilization of the head and chin and a forehead strap on an electrohydraulic stretcher with a loading system, there are no relevant advantages with respect to the restriction of movement of the cervical spine by the additional use of a rigid cervical spine orthosis for the loading and unloading process or during the transport in a modern ambulance. It could therefore be advantageous to remove the rigid cervical spine orthosis initially applied for the rescue of the patient at the scene after the patient has been positioned on the vacuum mattress and stretcher to avoid potential negative effects of the rigid cervical spine orthosis for the period of transportation to the hospital., (© 2024. The Author(s).)

Multidisciplinary team (MDT) meetings have emerged as a promising approach for the treatment of cancer patients. These meetings involve a team of healthcare professionals from different disciplines working together to develop a holistic, patient-centered treatment. Although MDT meetings are well established in oncology, they play a minor role in other diseases. Recent evidence suggests that the implementation of MDT meetings can improve patient outcomes in musculoskeletal infections. The aim of this retrospective, observational study was to present the agenda of our multidisciplinary limb board including live microscopy with a special focus on the pathologist's role. The descriptive analysis of the limb board included 66 cases receiving live microscopy at the meeting and a total of 124 histopathological findings and 181 stainings. We could elucidate that pathologists seem to play an important role especially in clarifying the correct diagnosis. In 80.3 % of the findings, the pathologist specified the clinical diagnosis of the requesting physician leading to a consensus-based treatment plan for each patient. The implementation of MDT meetings including live microscopy in patients with musculoskeletal infections holds potential benefits, such as improved communication, scientific collaboration, and raising clinicians' awareness and understanding of histopathology findings. However, potential challenges, such as organizational effort and technical prerequisites should be considered., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

The introduction of three-dimensional (3D) printed anatomical models has garnered interest in pre-operative planning, especially in orthopedic and trauma surgery. Identifying potential error sources and quantifying their effect on the model dimensional accuracy are crucial for the applicability and reliability of such models. In this study, twenty radii were extracted from anatomic forearm specimens and subjected to osteotomy to simulate a defined fracture of the distal radius (Colles' fracture). Various factors, including two different computed tomography (CT) technologies (energy-integrating detector (EID) and photon-counting detector (PCD)), four different CT scanners, two scan protocols (i.e., routine and high dosage), two different scan orientations, as well as two segmentation algorithms were considered to determine their effect on 3D model accuracy. Ground truth was established using 3D reconstructions of surface scans of the physical specimens. Results indicated that all investigated variables significantly impacted the 3D model accuracy (p < 0.001). However, the mean absolute deviation fell within the range of 0.03 ± 0.20 to 0.32 ± 0.23 mm, well below the 0.5 mm threshold necessary for pre-operative planning. Intra- and inter-operator variability demonstrated fair to excellent agreement for 3D model accuracy, with an intra-class correlation (ICC) of 0.43 to 0.92. This systematic investigation displayed dimensional deviations in the magnitude of sub-voxel imaging resolution for all variables. Major pitfalls included missed or overestimated bone regions during the segmentation process, necessitating additional manual editing of 3D models. In conclusion, this study demonstrates that 3D bone fracture models can be obtained with clinical routine scanners and scan protocols, utilizing a simple global segmentation threshold, thereby providing an accurate and reliable tool for pre-operative planning., (© 2024. The Author(s).)

Background: Genetic variants that cause rare disorders may remain elusive even after expansive testing, such as exome sequencing. The diagnostic yield of genome sequencing, particularly after a negative evaluation, remains poorly defined., Methods: We sequenced and analyzed the genomes of families with diverse phenotypes who were suspected to have a rare monogenic disease and for whom genetic testing had not revealed a diagnosis, as well as the genomes of a replication cohort at an independent clinical center., Results: We sequenced the genomes of 822 families (744 in the initial cohort and 78 in the replication cohort) and made a molecular diagnosis in 218 of 744 families (29.3%). Of the 218 families, 61 (28.0%) - 8.2% of families in the initial cohort - had variants that required genome sequencing for identification, including coding variants, intronic variants, small structural variants, copy-neutral inversions, complex rearrangements, and tandem repeat expansions. Most families in which a molecular diagnosis was made after previous nondiagnostic exome sequencing (63.5%) had variants that could be detected by reanalysis of the exome-sequence data (53.4%) or by additional analytic methods, such as copy-number variant calling, to exome-sequence data (10.8%). We obtained similar results in the replication cohort: in 33% of the families in which a molecular diagnosis was made, or 8% of the cohort, genome sequencing was required, which showed the applicability of these findings to both research and clinical environments., Conclusions: The diagnostic yield of genome sequencing in a large, diverse research cohort and in a small clinical cohort of persons who had previously undergone genetic testing was approximately 8% and included several types of pathogenic variation that had not previously been detected by means of exome sequencing or other techniques. (Funded by the National Human Genome Research Institute and others.)., (Copyright © 2024 Massachusetts Medical Society.)

The introduction of photon-counting detector CT (PCD-CT) marks a remarkable leap in innovation in CT imaging. The new detector technology allows X-rays to be converted directly into an electrical signal without an intermediate step via a scintillation layer and allows the energy of individual photons to be measured. Initial data show high spatial resolution, complete elimination of electronic noise, and steady availability of spectral image data sets. In particular, the new technology shows promise with respect to the imaging of osseous structures. Recently, PCD-CT was implemented in the clinical routine. The aim of this review was to summarize recent studies and to show our first experiences with photon-counting detector technology in the field of musculoskeletal radiology.We performed a literature search using Medline and included a total of 90 articles and reviews that covered recent experimental and clinical experiences with the new technology.In this review, we focus on (1) spatial resolution and delineation of fine anatomic structures, (2) reduction of radiation dose, (3) electronic noise, (4) techniques for metal artifact reduction, and (5) possibilities of spectral imaging. This article provides insight into our first experiences with photon-counting detector technology and shows results and images from experimental and clinical studies. · This review summarizes recent experimental and clinical studies in the field of photon-counting detector CT and musculoskeletal radiology.. · The potential of photon-counting detector technology in the field of musculoskeletal radiology includes improved spatial resolution, reduction in radiation dose, metal artifact reduction, and spectral imaging.. · PCD-CT enables imaging at lower radiation doses while maintaining or even enhancing spatial resolution, crucial for reducing patient exposure, especially in repeated or prolonged imaging scenarios.. · It offers promising results in reducing metal artifacts commonly encountered in orthopedic or dental implants, enhancing the interpretability of adjacent structures in postoperative and follow-up imaging.. · With its ability to routinely acquire spectral data, PCD-CT scans allow for material classification, such as detecting urate crystals in suspected gout or visualizing bone marrow edema, potentially reducing reliance on MRI in certain cases.. Bette S, Risch F, Becker J et al. Photon-counting detector CT - first experiences in the field of musculoskeletal radiology. Fortschr Röntgenstr 2024; DOI 10.1055/a-2312-6914., Competing Interests: The Department of Radiology received research funding from Siemens Healthineers for research in the field of photon-counting CT., (Thieme. All rights reserved.)

The timely and accurate identification of causative agents is crucial for effectively managing fracture-related infections (FRIs). Among various diagnostic methods, the "time to positivity" (TTP) of cultures has emerged as a valuable predictive factor in infectious diseases. While sonication of implants and inoculation of blood culture bottles with sonication fluid have enhanced sensitivity, data on the TTP of this microbiological technique remain limited. Therefore, patients with ICM criteria for confirmed FRI treated at our institution between March 2019 and March 2023 were retrospectively identified and their microbiological records were analyzed. The primary outcome parameter was TTP for different microorganism species cultured in a liquid culture collected from patients with confirmed FRI. A total of 155 sonication fluid samples from 126 patients (average age 57.0 ± 17.4 years, 68.3% males) was analyzed. Positive bacterial detection was observed in 78.7% (122/155) of the liquid culture pairs infused with sonication fluid. Staphylococcus aureus was the most prevalent organism (42.6%). Streptococcus species exhibited the fastest TTP (median 11.9 h), followed by Staphylococcus aureus (median 12.1 h) and Gram-negative bacteria (median 12.5 h), all of which had a 100% detection rate within 48 h after inoculation. Since all Gram-negative pathogens yielded positive culture results within 24 h, it could be discussed if empirical antibiotic therapy could be de-escalated early and limited towards the Gram-positive germ spectrum if no Gram-negative pathogens are detected up to this time point in the context of antibiotic stewardship.

Background: Long-read technologies such as nanopore sequencing provide new opportunities to detect short tandem repeat expansions. Therefore, a DNA extraction method is necessary that minimizes DNA fragmentation and hence allows the identification of large repeat expansions. In this study, an automated magnetic bead-based DNA extraction method and the required EDTA blood storage conditions as well as DNA and sequencing quality were evaluated for their suitability for repeat expansion detection with nanopore sequencing., Methods: DNA was extracted from EDTA blood, and subsequently, its concentration, purity, and integrity were assessed. DNA was then subjected to nanopore sequencing, and quality metrics of the obtained sequencing data were evaluated., Results: DNA extracted from fresh EDTA blood as well as from cooled or frozen EDTA blood revealed high DNA integrity whereas storage at room temperature over 7 days had detrimental effects. After nanopore sequencing, the read length N50 values of approximately 9 kb were obtained, and based on adaptive sampling of samples with a known repeat expansion, repeat expansions up to 10 kb could be detected., Conclusion: The automated magnetic bead-based DNA extraction was sufficient to detect short tandem repeat expansions, omitting the need for high-molecular-weight DNA extraction methods. Therefore, DNA should be extracted either from fresh blood or from blood stored in cooled or frozen conditions. Consequently, this study may help other laboratories to evaluate their DNA extraction method regarding the suitability for detecting repeat expansions with nanopore sequencing., (© 2024 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Purpose: To evaluate magnetic resonance image (MRI) findings in children and adolescents suffering from knee pain without traumatic or physical overload history and to identify potential anatomic risk factors., Material and Methods: A total of 507 MRIs of 6- to 20-year-old patients (251 males; 256 females) were evaluated with regard to detectable pathologies of the knee. The results were compared to a control group without pain ( n = 73; 34 males; 39 females). A binary logistic regression model and t-tests for paired and unpaired samples were used to identify possible risk factors and significant anatomic differences of the study population., Results: In 348 patients (68.6%), at least one pathology was detected. The most commonly detected finding was chondromalacia of the patellofemoral (PF) joint (n = 205; 40.4%). Chondral lesions of the PF joint occurred significantly more often in knee pain patients than in the control group (40% vs. 11.0%; p = 0.001), especially in cases of a patella tilt angle > 5° ( p ≤ 0.001), a bony sulcus angle > 150° ( p = 0.002), a cartilaginous sulcus angle > 150° ( p = 0.012), a lateral trochlear inclination < 11° ( p ≤ 0.001), a lateralised patella ( p = 0.023) and a Wiberg type II or III patella shape ( p = 0.019). Moreover, a larger patella tilt angle ( p = 0.021), a greater bony sulcus angle ( p = 0.042), a larger cartilaginous sulcus angle ( p = 0.038) and a lower value of the lateral trochlear inclination ( p = 0.014) were detected in knee pain patients compared to the reference group., Conclusion: Chondromalacia of the PF joint is frequently observed in children and adolescents suffering from non-overload atraumatic knee pain, whereby a patella tilt angle > 5°, a bony sulcus angle > 150°, a cartilaginous sulcus angle > 150°, a lateral trochlear inclination < 11°, a lateralised patella and a Wiberg type II or III patella shape seem to represent anatomic risk factors.

Introduction: Pediatric polytrauma is a complex condition with unique characteristics and requirements for early clinical care. This study aimed to analyze the injury patterns, early clinical care, and outcomes of pediatric polytrauma patients in a Level I trauma center. The focus was on evaluation between different age groups and the recognition of injuries as potential factors influencing outcomes. Methods: A prospective cohort study model of pediatric polytrauma patients (ISS ≥ 16) was conducted over a 13-year period, stratified by age groups (Group A: 0-5 years; Group B: 6-10 years; Group C: 11-15 years; and Group D: 16-18 years). A comparison of the groups was conducted to examine variations in early clinical care, trauma mechanisms, distribution of affected body regions (as per AIS and ISS criteria), and trauma-related mortality. Additionally, factors contributing to mortality were evaluated. Results: The median age of patients was 16 years, with a male predominance (64.7%). The Injury Severity Score (ISS) varied across age groups, with no significant difference. The 30-day mortality rate was 19.0%, with no significant age-related differences. Trauma mechanisms varied across age groups, with motor vehicle accidents being the most common mechanism in all age groups except 0-5 years, where falls were prevalent. Analysis of injury patterns by AIS body regions indicated that head trauma was a significant predictor of mortality (Hazard Ratio 2.894, p < 0.001), while chest, abdominal, and extremity trauma showed no significant association with mortality. Multiple regression analysis identified the ISS and preclinical GCS as valid predictors of mortality ( p < 0.001 and p = 0.006, respectively). Conclusions: While age-related differences in injury severity and clinical interventions were limited, head trauma emerged as a critical predictor of mortality. Early recognition and management of head injuries are crucial in improving outcomes. Additionally, the ISS and preclinical GCS were identified as valid predictors of mortality, emphasizing the importance of early assessment and resuscitation. A tailored approach to pediatric polytrauma care, considering both age and injury patterns, might contribute to survival benefits in this vulnerable population.

Aims: This study aimed to evaluate the clinical application of the PJI-TNM classification for periprosthetic joint infection (PJI) by determining intraobserver and interobserver reliability. To facilitate its use in clinical practice, an educational app was subsequently developed and evaluated., Methods: A total of ten orthopaedic surgeons classified 20 cases of PJI based on the PJI-TNM classification. Subsequently, the classification was re-evaluated using the PJI-TNM app. Classification accuracy was calculated separately for each subcategory (reinfection, tissue and implant condition, non-human cells, and morbidity of the patient). Fleiss' kappa and Cohen's kappa were calculated for interobserver and intraobserver reliability, respectively., Results: Overall, interobserver and intraobserver agreements were substantial across the 20 classified cases. Analyses for the variable 'reinfection' revealed an almost perfect interobserver and intraobserver agreement with a classification accuracy of 94.8%. The category 'tissue and implant conditions' showed moderate interobserver and substantial intraobserver reliability, while the classification accuracy was 70.8%. For 'non-human cells,' accuracy was 81.0% and interobserver agreement was moderate with an almost perfect intraobserver reliability. The classification accuracy of the variable 'morbidity of the patient' reached 73.5% with a moderate interobserver agreement, whereas the intraobserver agreement was substantial. The application of the app yielded comparable results across all subgroups., Conclusion: The PJI-TNM classification system captures the heterogeneity of PJI and can be applied with substantial inter- and intraobserver reliability. The PJI-TNM educational app aims to facilitate application in clinical practice. A major limitation was the correct assessment of the implant situation. To eliminate this, a re-evaluation according to intraoperative findings is strongly recommended., Competing Interests: D. F. Amanatullah reports grants or contracts from NIH-KL2 and OREF, royalties or licenses from United and Exactech, consulting fees from Stryker, DePuy, Exactech, United, and Medacta, ayment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Medscape, payment for expert testimony from Expert Institute, patents with Arthrology Consulting, Knimble Designs, nSight Surgical, and Stanford University, and stock or stock options in Knimble Designs, nSight Surgical, Recoup Fitness, and Qt Ultrasound, all of which are unrelated to this study., (© 2024 Alt et al.)

Background: The COVID-19 pandemic has had a significant impact on the treatment protocols of orthopedic and trauma departments, but its specific effect on the mortality of hip fracture patients due to possible delays in surgery remains uncertain. This study aimed to investigate whether the COVID-19 pandemic worsened the mortality of patients with hip fractures., Materials and Methods: This study included 246 prospectively enrolled patients who suffered from hip fractures during the Austrian State of Emergency period between 1 March and 30 June 2020 and 2021 and were admitted to a tertiary care trauma center. This cohort was compared with a retrospective control group of 494 patients admitted for hip fractures during the same timeframe in 2017, 2018, and 2019. These groups were compared to a prospective recruited "post-COVID-19 collective consisting of the years 2022 and 2023 including 313 patients., Results: This study found a 22% reduction in admissions during the COVID-19 period compared to the pre-COVID period ( p = 0.018), as well as significant changes in gender ( p = 0.013) and place of accident ( p = 0.049). No other changes in demographic variables were observed. The 30-day mortality rate was 14.67% in the pre-COVID period, compared to 15.18% during the COVID-19 period ( p = 0.381). No differences were observed in surgical complication rates or in the relationship between comorbidity burden and survival., Conclusion: This study did not show a higher perioperative mortality rate due to COVID-19. However, under current circumstances, with potentially reduced surgical and hospital bed capacities, it is expected that this condition might require a high degree of resources in times when resources are potentially scarce, such as during an ongoing pandemic., Level of Evidence: Level III.

Tscherne was the first to define the term polytrauma in 1966 as "multiple injuries to different regions of the body sustained simultaneously, with at least one injury or the combination of these injuries being life-threatening". This definition highlights the essential pathophysiological paradigm of polytrauma, with the life-threating characteristics resulting from injuries to multiple organ systems. The treatment of polytrauma patients begins at the scene of the accident. Important life-saving initial interventions can already be carried out on site through targeted measures and expertise of the emergency medical service team, thus improving patient survival. The advanced trauma life support/prehospital trauma life support (ATLS/PHTLS) concept is the worldwide gold standard. As prehospital treatment of severely injured patients is not routine for most emergency teams, concepts and emergency interventions must be regularly trained. This is the prerequisite for safe and effective emergency treatment in this time-critical situation., (© 2023. The Author(s).)

Background: Various rescue techniques are used for the prehospital transport of trauma patients. This study compares different techniques in terms of immobilization of the cervical spine and the rescue time., Methods: A wireless motion capture system (Xsens Technologies, Enschede, The Netherlands) was used to record motion in three-dimensional space and the rescue time in a standardized environment. Immobilization was performed by applying different techniques through different teams of trained paramedics and physicians. All tests were performed on the set course, starting with the test person lying on the floor and ending with the test person lying on an ambulance cot ready to be loaded into an ambulance. Six different settings for rescue techniques were examined: rescue sheet with/without rigid cervical collar (P1S1, P1S0), vacuum mattress and scoop stretcher with/without rigid cervical collar (P2S1, P2S0), and long spinal board with/without rigid cervical collar (P3S1, P3S0). Four time intervals were defined: the time interval in which the rigid cervical collar is applied (T0), the time interval in which the test person is positioned on rescue sheet, vacuum mattress and scoop stretcher, or long spinal board (T1), the time interval in which the test person is carried to the ambulance cot (T2), and the time interval in which the ambulance cot is rolled to the ambulance (T3). An ANOVA was performed to compare the different techniques., Results: During the simulated extrication procedures, a rigid cervical collar provided biomechanical stability at all angles with hardly any loss of time (mean angle ranges during T1: axial rotation P1S0 vs P1S1 p<0.0001, P2S0 vs P2S1 p<0.0001, P3S0 vs P3S1 p<0.0001; lateral bending P1S0 vs P1S1 p = 0.0263, P2S0 vs P2S1 p<0.0001, P3S0 vs P3S1 p<0.0001; flexion/extension P1S0 vs P1S1 p = 0.0023, P2S0 vs P2S1 p<0.0001). Of the three techniques examined, the scoop stretcher and vacuum mattress were best for reducing lateral bending in the frontal plane (mean angle ranges during T1: P2S1 vs P3S1 p = 0.0333; P2S0 vs P3S0 p = 0.0123) as well as flexion and extension in the sagittal plane (mean angle ranges during T2: P1S1 vs P2S1 p<0.0001; P1S0 vs P2S0 p<0.0001). On the other hand, the rescue sheet was clearly superior in terms of time (total duration P1S0 vs P2S0 p<0.001, P1S1 vs P2S1 p<0.001, P1S0 vs P3S0 p<0.001, P1S1 vs P3S1 p<0.001) but was always associated with significantly larger angular ranges of the cervical spine during the procedure. Therefore, the choice of technique depends on various factors such as the rescue time, the available personnel, as well as the severity of the suspected instability., Competing Interests: Martin Kieninger serves as academic editor for PLOS ONE. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Morag et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Unsupervised domain adaptation (UDA) aims to mitigate the performance drop due to the distribution shift between the training and testing datasets. UDA methods have achieved performance gains for models trained on a source domain with labeled data to a target domain with only unlabeled data. The standard feature extraction method in domain adaptation has been convolutional neural networks (CNNs). Recently, attention-based transformer models have emerged as effective alternatives for computer vision tasks. In this paper, we benchmark three attention-based architectures, specifically vision transformer (ViT), shifted window transformer (SWIN), and dual attention vision transformer (DAViT), against convolutional architectures ResNet, HRNet and attention-based ConvNext, to assess the performance of different backbones for domain generalization and adaptation. We incorporate these backbone architectures as feature extractors in the source hypothesis transfer (SHOT) framework for UDA. SHOT leverages the knowledge learned in the source domain to align the image features of unlabeled target data in the absence of source domain data, using self-supervised deep feature clustering and self-training. We analyze the generalization and adaptation performance of these models on standard UDA datasets and aerial UDA datasets. In addition, we modernize the training procedure commonly seen in UDA tasks by adding image augmentation techniques to help models generate richer features. Our results show that ConvNext and SWIN offer the best performance, indicating that the attention mechanism is very beneficial for domain generalization and adaptation with both transformer and convolutional architectures. Our ablation study shows that our modernized training recipe, within the SHOT framework, significantly boosts performance on aerial datasets.

Objective: The aim of this study was to compare the effectiveness of common strategies for artifact reduction of dental material in photon-counting detector computed tomography data sets., Materials and Methods: Patients with dental material who underwent clinically indicated CT of the neck were enrolled. Image series were reconstructed using a standard and sharp kernel, with and without iterative metal artifact reduction (IMAR) (Qr40, Qr40 IMAR , Qr60, Qr60 IMAR ) at different virtual monoenergetic imaging (VMI) levels (40-190 keV). On representative slice positions with and without dental artifacts, mean and standard deviation of CT values were measured in all series at identical locations. The mean absolute error of CT values ( ) and the artifact index (AIX) were calculated and analyzed focusing on 3 main comparisons: ( a ) different VMI levels versus 70 keV, ( b ) standard versus sharp kernel, and ( c ) nonuse or use of IMAR reconstruction. The Wilcoxon test was used to assess differences for nonparametric data., Results: The final cohort comprised 50 patients. Artifact measures decreased for VMI levels >70 keV, yet only significantly so for reconstructions using IMAR (maximum reduction, 25%). The higher image noise of the sharp versus standard kernel is reflected in higher AIX values and is more pronounced in IMAR series (maximum increase, 38%). The most profound artifact reduction was observed for IMAR reconstructions (maximum reduction : 84%; AIX: 90%)., Conclusions: Metal artifacts caused by large amounts of dental material can be substantially reduced by IMAR, regardless of kernel choice or VMI settings. Increasing the keV level of VMI series, on the other hand, only slightly reduces dental artifacts; this effect, however, is additive to the benefit conferred by IMAR reconstructions., Competing Interests: Conflicts of interest and sources of funding: Thomas J. Kroencke has received institutional funding from Siemens Healthcare GmbH. Florian Schwarz has received speaker honoraria from Siemens Healthcare GmbH., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To correlate CT values of the blood pool on VNC series with serum hemoglobin values for the detection of anemia in oncologic patients undergoing contrast-enhanced PCD-CT scans., Methods: This prospective study (NCT04989192) included consecutive oncologic patients undergoing contrast-enhanced CT on a novel PCD-CT system between 08/2021 and 01/2022. The interval between complete blood count (CBC) and CT scan acquisition had to be no more than seven days. CT-values of the blood pool were measured on 70 keV VMI series (CT-values(BP) 70keV ) and on VNC series (CT-values(BP) VNC ) at five anatomic positions (left atrium, left ventricle, main pulmonary artery, ascending and descending aorta) and averaged per patient. Pearson correlation analyses and ROC analyses were performed to identify relations between CT-values(BP) VNC , CBC parameters, and degrees of anemia as defined by the WHO (no anemia, mild, moderate, severe anemia)., Results: A total of 329 patients (age 68 ± 12 years; 200 men) were included. CT-values(BP) VNC showed a strong linear correlation to serum hemoglobin (r 2  = 0.80, p <.001) and hematocrit (r 2  = 0.76, p <.001) and were significantly different between anemia subgroups in both women and men (ΔHU: 3.5-11.4; all p <.01). ROC analyses yielded high diagnostic performance for the identification of patients without anemia, patients without and with mild anemia, and patients with severe anemia using gender-specific cutoffs for CT-value(BP) VNC (all AUC's > 0.90)., Conclusions: The spectral information inherent in PCD-CT acquisitions allows the detection and quantification of anemia in contrast-enhanced CT acquisitions of oncologic patients with high diagnostic accuracy., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof. Kroencke discloses receives institutional research support from Siemens Healthineers and Dr. Schwarz has received speaker honoraria from Siemens Healthineers. All other authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

DExD/H-box RNA helicases (DDX/DHX) are encoded by a large paralogous gene family; in a subset of these human helicase genes, pathogenic variation causes neurodevelopmental disorder (NDD) traits and cancer. DHX9 encodes a BRCA1-interacting nuclear helicase regulating transcription, R-loops, and homologous recombination and exhibits the highest mutational constraint of all DDX/DHX paralogs but remains unassociated with disease traits in OMIM. Using exome sequencing and family-based rare-variant analyses, we identified 20 individuals with de novo, ultra-rare, heterozygous missense or loss-of-function (LoF) DHX9 variant alleles. Phenotypes ranged from NDDs to the distal symmetric polyneuropathy axonal Charcot-Marie-Tooth disease (CMT2). Quantitative Human Phenotype Ontology (HPO) analysis demonstrated genotype-phenotype correlations with LoF variants causing mild NDD phenotypes and nuclear localization signal (NLS) missense variants causing severe NDD. We investigated DHX9 variant-associated cellular phenotypes in human cell lines. Whereas wild-type DHX9 was restricted to the nucleus, NLS missense variants abnormally accumulated in the cytoplasm. Fibroblasts from an individual with an NLS variant also showed abnormal cytoplasmic DHX9 accumulation. CMT2-associated missense variants caused aberrant nucleolar DHX9 accumulation, a phenomenon previously associated with cellular stress. Two NDD-associated variants, p.Gly411Glu and p.Arg761Gln, altered DHX9 ATPase activity. The severe NDD-associated variant p.Arg141Gln did not affect DHX9 localization but instead increased R-loop levels and double-stranded DNA breaks. Dhx9 -/- mice exhibited hypoactivity in novel environments, tremor, and sensorineural hearing loss. All together, these results establish DHX9 as a critical regulator of mammalian neurodevelopment and neuronal homeostasis., Competing Interests: Declaration of interests J.R.L. has stock ownership in 23andMe, is a paid consultant for Genome International, and is a co-inventor on multiple US and European patents related to molecular diagnostics for inherited neuropathies, eye diseases, genomic disorders, and bacterial genomic fingerprinting. The Department of Molecular and Human Genetics at the Baylor College of Medicine receives revenue from clinical genetic testing conducted at Baylor Genetics (BG) Laboratories. F.M. and T.S.-S. are employees of GeneDx., (Copyright © 2023 American Society of Human Genetics. All rights reserved.)

Purpose: To investigate the usefulness of virtual monoenergetic image (VMI) reconstructions derived from scans on a novel photon-counting detector CT (PCD-CT) for artifact reduction in patients after posterior spinal fixation., Methods: This retrospective cohort study included 23 patients status post posterior spinal fixation. Subjects were scanned on a novel PCD-CT (NAEOTOM Alpha, Siemens Healthineers, Erlangen, Germany) as part of routine clinical care. 14 sets of VMI reconstructions were derived in 10 keV increments for the interval 60-190 keV. The mean and the standard deviation (SD) of CT-values in 12 defined locations around a pair of pedicle screws on one vertebral level and the SD of homogenous fat were measured and used to calculate an artifact index (AIx)., Results: Averaged over all regions, the lowest AIx was observed at VMI levels of 110 keV (32.5 (27.8-37.9)) which was significantly different from those of VMIs ≤ 90 keV (p < 0.001) or ≥160 keV (p < 0.015), respectively. Overall AIx values increased in both lower- and higher-keV levels. Regarding individual locations, either a monotonous AIx-decrease for increasing keV values or an AIx-minimum in intermediate-keV levels (100-140 keV) was found. In locations adjacent to larger metal parts, the increase of AIx values at the high-end of the keV spectrum was mainly explained by a reappearance of streak artifacts., Conclusion: Our findings suggest that 110 keV is the optimal VMI setting for overall artifact suppression. In specific anatomical regions, however, slight adjustments towards higher-keV levels may provide better results., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof. Kroencke discloses receives institutional research support from Siemens Healthineers AG. The University Hospital Augsburg and Dr. Schwarz have received speaker honoraria from Siemens Healthineers AG. All other authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Recently, promising results have been reported for detection of osteoporosis with use of an aluminum phantom. Therefore, the aim of this study was to evaluate the feasibility of radiography-based bone mineral density (BMD) measurement using a graded aluminum phantom. This study included 27 postmenopausal women with a distal radius fracture. Aluminum phantom radiography of the healthy radius was conducted as well as high-resolution peripheral quantitative computed tomography (HR-pQCT) measurement of the ultradistal radius and dual energy X-ray absorptiometry (DXA) of the radius, spine, and hip. A strong correlation was observed between aluminum phantom radiography-based mean gray value (mGV) and DXA-derived BMD, especially for the ultradistal radius (ρ = 0.75; p < 0.001). A moderate correlation for the femoral neck (ρ = 0.61 and p < 0.001) between modalities was found. Radius mGV and HR-pQCT-derived BMD only showed a moderate correlation (ρ = 0.48; p < 0.09). Aluminum phantom radiography might serve as a cost efficient, highly available, low-radiation dose screening, and diagnostic method for osteoporosis additively to DXA measurements. Especially, an application in areas with constrained DXA availability and such as preoperative trauma settings would be beneficial. However, further investigation and assessment of specificity and sensitivity is needed., (© 2023 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Background: Hip fractures are becoming a growing concern due to an aging population. The high costs to the healthcare system and far-reaching consequences for those affected, including a loss of independence and increased mortality rates, make this issue important. Poor nutritional status is a common problem among geriatric patients and is associated with a worse prognosis. Nutritional screening tools can help identify high-risk patients and enable individualized care to improve survival rates., Material and Methods: This retrospective study investigates four nutritional scores and laboratory parameters' predictive significance concerning postoperative mortality after surgical treatment of proximal femur fractures at 1, 3, 6, and 12 month/s for patients over 60 years using the chi-square test, Cox regression analysis, and receiver operating characteristics (ROC). The European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines were used as part of the screening of the respective nutritional status of the patients, in particular to filter out malnutrition., Results: A total of 1080 patients were included in this study, whereas 8.05% suffered from malnutrition, defined as a body mass index (BMI) below 18.5 kg/m 2 . The Mini Nutritional Assessment (MNA) screening tool identified the highest proportion of malnourished patients at 14.54%. A total of 36.39% of patients were at risk of malnutrition according to three nutrition scores, with MNA providing the most significant proportion at 41.20%. Patients identified as malnourished had a higher mortality rate, and MNA screening was the only tool to show a significant correlation with postoperative mortality in all survey intervals. The MNA presented the best predictive significance among the screening tools, with a maximum area under the curve (AUC) of 0.7 at 12 month postoperatively., Conclusions: MNA screening has a solid correlation and predictive significance regarding postoperative mortality-therefore routine implementation of this screening in orthopedic/traumatology wards is recommended. Moreover, nutritional substitution therapy can offer a relatively inexpensive and easy-to-implement measure. The Graz malnutrition screening (GMS) shows moderate predictive power and could be considered as an alternative for patients under 60 years of age. A higher albumin level is associated with improved survival probability, but cannot be indicative of nutritional status.

Xenobiotics often challenge the principle of microbial infallibility. One example is acesulfame introduced in the 1980s as zero-calorie sweetener, which was recalcitrant in wastewater treatment plants until the early 2010s. Then, efficient removal has been reported with increasing frequency. By studying acesulfame metabolism in alphaproteobacterial degraders of the genera Bosea and Chelatococcus , we experimentally confirmed the previously postulated route of two subsequent hydrolysis steps via acetoacetamide-N-sulfonate (ANSA) to acetoacetate and sulfamate. Genome comparison of wildtype Bosea sp. 100-5 and an acesulfame degradation-defective mutant revealed the involvement of two plasmid-borne gene clusters. The acesulfame-hydrolyzing sulfatase is strictly manganese-dependent and belongs to the metallo beta-lactamase family. In all degraders analyzed, it is encoded on a highly conserved gene cluster embedded in a composite transposon. The ANSA amidase, on the other hand, is an amidase signature domain enzyme encoded in another gene cluster showing variable length among degrading strains. Transposition of the sulfatase gene cluster between chromosome and plasmid explains how the two catabolic gene clusters recently combined for the degradation of acesulfame. Searching available genomes and metagenomes for the two hydrolases and associated genes indicates that the acesulfame plasmid evolved and spread worldwide in short time. While the sulfatase is unprecedented and unique for acesulfame degraders, the amidase occurs in different genetic environments and likely evolved for the degradation of other substrates. Evolution of the acesulfame degradation pathway might have been supported by the presence of structurally related natural and anthropogenic compounds, such as aminoacyl sulfamate ribonucleotide or sulfonamide antibiotics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bonatelli, Rohwerder, Popp, Liu, Akay, Schultz, Liao, Ding, Reemtsma, Adrian and Kleinsteuber.)

The palladium catalyzed cyclotrimerization of ortho-silylaryl triflates as aryne precursors is meanwhile an established method to synthesize polycyclic aromatic hydrocarbons (PAHs) with triphenylene cores. During the palladium-catalyzed reaction of a pyrene with an o-silylaryl triflate moiety in the K-region higher homologues with central eight- and ten-membered rings (the pyrenylenes) were found, besides the expected trimer and a protocol was developed to isolate all members of this series. This unprecedented new class of PAHs was fully investigated by all means, including X-ray diffraction of single-crystals, UV/Vis and fluorescence spectroscopy and theoretical calculations. Supported by density-functional theory (DFT) calculations, a mechanism of all higher cyclooligomers is proposed., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Analyzing microbial communities using metagenomes is a powerful approach to understand compositional structures and functional connections in anaerobic digestion (AD) microbiomes. Whereas short-read sequencing approaches based on the Illumina platform result in highly fragmented metagenomes, long-read sequencing leads to more contiguous assemblies. To evaluate the performance of a hybrid approach of these two sequencing approaches we compared the metagenome-assembled genomes (MAGs) resulting from five AD microbiome samples. The samples were taken from reactors fed with short-chain fatty acids at different feeding regimes (continuous and discontinuous) and organic loading rates (OLR). Methanothrix showed a high relative abundance at all feeding regimes but was strongly reduced in abundance at higher OLR, when Methanosarcina took over. The bacterial community composition differed strongly between reactors of different feeding regimes and OLRs. However, the functional potential was similar regardless of feeding regime and OLR. The hybrid sequencing approach using Nanopore long-reads and Illumina MiSeq reads improved assembly statistics, including an increase of the N50 value (on average from 32 to 1740 kbp) and an increased length of the longest contig (on average from 94 to 1898 kbp). The hybrid approach also led to a higher share of high-quality MAGs and generated five potentially circular genomes while none were generated using MiSeq-based contigs only. Finally, 27 hybrid MAGs were reconstructed of which 18 represent potentially new species-15 of them bacterial species. During pathway analysis, selected MAGs revealed similar gene patterns of butyrate degradation and might represent new butyrate-degrading bacteria. The demonstrated advantages of adding long reads to metagenomic analyses make the hybrid approach the preferable option when dealing with complex microbiomes.

Objectives: Fracture-related infection (FRI) is a major complication in orthopedic and trauma surgery. The management and choice of treatment can be difficult depending on multiple factors. Therefore, we implemented a weekly multidisciplinary team discussion to determine diagnostic and treatment strategies in FRI patients and aimed to analyze its effect on clinical outcomes., Methods: Clinical outcomes of FRI patients treated before and after implementation of a structured multidisciplinary treatment (MDT) approach with a weekly case discussion were compared at a follow-up of 12 months., Results: In total, n = 117 were eligible for enrolment, whereby n = 58 patients (72.4% male, mean age 56.7 ± 16.8 years) constituted the MDT group and n = 59 patients (72.9% male, mean age 55.0 ± 16.5 years) the control group. In the MDT group more cases were treated with local antibiotics (67.2% vs. 27.1%, p < 0.001) and significant less amputations (3.4% vs. 6.8%, p = 0.014), as well as less revision surgeries (1.5 ± 1.2 (0-5) vs. 2.2 ± 1.2 (0-7), p = 0.048) were performed. A trend towards less debridement, antibiotics and implant retention (DAIR) procedures, lower rates of recurrence of infection and less treatment failures in the MDT group was observable, even though not statistically significant., Conclusion: An MDT approach providing a patient tailored treatment concept in the treatment of FRI patients appears to be beneficial for the affected patients. Quality and efficacy of implemented MDT meetings should further be evaluated to provide sufficient evidence to further implement this valuable tool in clinical practice and decision making.

In 2016 and 2018, Chung, Jansen and others described a new syndrome caused by haploinsufficiency of PHIP (pleckstrin homology domain interacting protein, OMIM *612,870) and mainly characterized by developmental delay (DD), learning difficulties/intellectual disability (ID), behavioral abnormalities, facial dysmorphism and obesity (CHUJANS, OMIM #617991). So far, PHIP alterations appear to be a rare cause of DD/ID. "Omics" technologies such as exome sequencing or array analyses have led to the identification of distinct types of alterations of PHIP , including, truncating variants, missense substitutions, splice variants and large deletions encompassing portions of the gene or the entire gene as well as adjacent genomic regions. We collected clinical and genetic data of 23 individuals with PHIP -associated Chung-Jansen syndrome (CHUJANS) from all over Europe. Follow-up investigations (e.g. Sanger sequencing, qPCR or Fluorescence-in-situ-Hybridization) and segregation analysis showed either de novo occurrence or inheritance from an also (mildly) affected parent. In accordance with previously described patients, almost all individuals reported here show developmental delay (22/23), learning disability or ID (22/23), behavioral abnormalities (20/23), weight problems (13/23) and characteristic craniofacial features (i.e. large ears/earlobes, prominent eyebrows, anteverted nares and long philtrum (23/23)). To further investigate the facial gestalt of individuals with CHUJANS, we performed facial analysis using the GestaltMatcher approach. By this, we could establish that PHIP patients are indistinguishable based on the type of PHIP alteration (e.g. missense, loss-of-function, splice site) but show a significant difference to the average face of healthy individuals as well as to individuals with Prader-Willi syndrome (PWS, OMIM #176270) or with a CUL4B -alteration (Intellectual developmental disorder, X-linked, syndromic, Cabezas type, OMIM #300354). Our findings expand the mutational and clinical spectrum of CHUJANS. We discuss the molecular and clinical features in comparison to the published individuals. The fact that some variants were inherited from a mildly affected parent further illustrates the variability of the associated phenotype and outlines the importance of a thorough clinical evaluation combined with genetic analyses for accurate diagnosis and counselling., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kampmeier, Leitão, Parenti, Beygo, Depienne, Bramswig, Hsieh, Afenjar, Beck-Wödl, Grasshoff, Haack, Bijlsma, Ruivenkamp, Lausberg, Elbracht, Haanpää, Koillinen, Heinrich, Rost, Jamra, Popp, Koch-Hogrebe, Rostasy, López-González, Sanchez-Soler, Macedo, Schmetz, Steinborn, Weidensee, Lesmann, Marbach, Caro, Schaaf, Krawitz, Wieczorek, Kaiser and Kuechler.)

In 2020, the COVID-19 pandemic impacted global life and transitioned economies and societal perceptions of life as we knew it. Professional and social life mostly ground to a nadir during the first lockdown in Europe in March. As a consequence, measures aimed at preventing the spread of the virus were established in medical facilities also and elective plastic surgery procedures were temporarily suspended in our clinic and others. A majority of the population, including those potentially contemplating plastic surgery procedures, spent most of their time at home with ample time available to research information about surgical procedures and other topics online. This investigation analyzes the relevance of plastic surgery during the pandemic on the basis of online search behavior patterns. Online traffic data from the online platform http://www.mooci.org were extracted using Google Analytics over a period of 6 months. The parameters analyzed were: pageviews, session duration, and bounce rate. Additionally, differentiation by areas of interest has been obtained. The data were compared and analyzed before and after the beginning of the first hard lockdown in Austria, Germany, and Switzerland. There were no significant differences in regard to pageviews and session duration when comparing time points before and after the beginning of the hard lockdown. The bounce rate exhibited a significant decrease after the beginning of the lockdown, implying a more conscious search for information and greater absorption and retention. There was no difference that could conclusively be attributed to the pandemic in terms of specific areas of interest researched. Society's demand for information about plastic-surgical procedures continues to be steadily prevalent-despite, or even in particular, during a global pandemic. Providing reliable and readily available information about plastic surgery procedures is an important component of a functioning doctor-patient relationship and informed consent. This information may reflect society's increased interest in plastic surgery during the pandemic, or be simply reflective of more spare time at hand to allow for such research. Further studies should investigate the relevance of elective procedures over the entire course of the pandemic., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2023.)

Background: For the treatment of carpometacarpal arthritis of the thumb, various therapies are used. Infiltration therapy with autologous substances such as platelet-rich plasma and autologous fat have recently gained increasing attention because of beneficial pain-reducing effects in arthritis and the associated regenerative potential. However, the extent of clinical evidence in this area and how well autologous substances work in terms of pain reduction and improvements in hand function remain unclear., Methods: A systematic review and meta-analysis were conducted to evaluate the current evidence and to provide more insight into pain reduction and improvement in hand function after infiltration of autologous substances. The authors identified 11 clinical trials, of which we included eight in the meta-analysis., Results: Autologous substances achieved a good and long-lasting pain reduction, which may also be accompanied by corresponding improvement in hand function. Autologous substances appear to be more effective than corticoid infiltrations. The infiltration of autologous fat seems to be particularly promising in more advanced stages of carpometacarpal arthritis of the thumb. Our meta-analysis showed a mean pain reduction of 2.4 to 3 in visual analogue scale score and a reduction of 18 to 19 points in the Disabilities of the Arm, Shoulder, and Hand questionnaire after infiltration with autologous substances., Conclusion: Both platelet-rich plasma and autologous fat infiltration offer an efficient and long-lasting, minimally invasive therapy option in the treatment of carpometacarpal arthritis of the thumb., Competing Interests: Disclosure : The authors have no financial interests or conflicts of interest to declare. No funding was received for this research., (Copyright © 2022 by the American Society of Plastic Surgeons.)

The re-analysis of nondiagnostic exome sequencing (ES) has the potential to increase diagnostic yields in individuals with rare diseases, but its implementation in the daily routines of laboratories is limited due to restricted capacities. Here, we describe a systematic approach to re-analyse the ES data of a cohort consisting of 1040 diagnostic and nondiagnostic samples. We applied a strict filter cascade to reveal the most promising single-nucleotide variants (SNVs) of the whole cohort, which led to an average of 0.77 variants per individual that had to be manually evaluated. This variant set revealed seven novel diagnoses (0.8% of all nondiagnostic cases) and two secondary findings. Thirteen additional variants were identified by a scientific approach prior to this re-analysis and were also present in this variant set. This resulted in a total increase in the diagnostic yield of 2.3%. The filter cascade was optimised during the course of the study and finally resulted in sensitivity of 85%. After applying the filter cascade, our re-analysis took 20 h and enabled a workflow that can be used repeatedly. This work is intended to provide a practical recommendation for other laboratories wishing to introduce a resource-efficient re-analysis strategy into their clinical routine.

Background and Objective : Translational large animal models are inevitable to transfer cartilage repair methods into clinical practice. Guidelines for these trials have been published by guiding agencies (FDA, ASTM, EMEA) including recommendations for study descriptors and study outcomes. However, practical adherence to these recommendations is not achieved in all aspects. This study includes an assessment of the recommended aspects regarding practical relevance in large animal models for cartilage repair by professionals in the field. Materials and Methods : In an online based survey, 11 aspects regarding study design and 13 aspects regarding study outcome from previously published guidelines were evaluated (0-10 points, with 10 being most important) by study participants. Additionally, the survey contained questions related to professional experience (years), professional focus (preclinical, clinical, veterinarian, industry) and the preferred translational large animal model for cartilage repair. Results : The total number of survey participants was 37. Rated as most important for study design parameters was lesion size (9.54 pts., SD 0.80) followed by study duration (9.43 pts., SD 1.21); and method of scaffold fixation (9.08 pts., SD 1.30) as well as depth of the lesion (9.03 pts., SD 1.77). The most important aspects of study outcome were considered histology (9.41 pts., SD 0.86) and defect filling (8.97 pts., SD 1.21), while gene expression was judged as the least important (6.11 pts., SD 2.46) outcome. A total of 62.2% of all participants were researchers, 18.9% clinicians, 13.5% veterinarians and 5.4% industry employees. Conclusions : In translational research, recommendations published by guiding agencies receive broad theoretical consensus within the community, including both clinically and preclinically orientated scientists. However, implementation into practical research lacks in major aspects. Ongoing re-evaluation of the guidelines under involvement of all stakeholders and approaches to overcome financial and infrastructural limitations could support the acceptance of the guidance documents and contribute to standardization in the field.

See also the editorial by Dodd and MacDermott in this issue.

Purpose: Surgical simulations are becoming increasingly relevant in musculoskeletal training. They provide the opportunity to develop surgical skills in a controlled environment while reducing the risks for patients. For K-wire internal fixation in musculoskeletal surgery, a force feedback virtual reality (VR) simulator was developed. The aim of this study was to evaluate training results using this technology and compare the results with that of standard teaching on cadavers., Methods: Twenty participants attending an AO Trauma Course during 2020 were randomly allocated in 2 groups. On day 1, group A was trained by senior surgeons using a cadaver and group B was trained by the VR simulator for K-wire insertion in the distal radius. On day 2, all participants performed K-wire insertion on the cadaver model, without assistance, to validate the training effect., Results: On a surgical skills test, group B performed better than group A. In group B, the entry point of the first K-wire was closer to the targeted styloid process of the radius, and the protrusion of the K-wires into soft tissue was less than that in group A., Conclusions: Training with the VR simulator for K-wire insertion resulted in better surgical skills than training by a surgeon and cadaver model., Clinical Relevance: Training with the VR simulator provides the opportunity to improve and refine surgical skills without the risk of harming patients. It offers easier access, unlimited repetitions, and is more cost-effective compared with training sessions with cadavers., (Copyright © 2022 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Cyanobacteria are highly promising microorganisms in forthcoming biotechnologies. Besides the systematic development of molecular tools for genetic engineering, the design of chassis strains and novel reactor concepts are in focus. The latter includes capillary biofilm reactors (CBR), which offer a high surface area-to-volume ratio and very high cell densities. In this context, Tolypothrix sp. PCC 7712 was found to be highly suited for this reactor system due to maximal surface coverage, extraordinarily strong biofilm attachment, and high biomass formation. Here, we provide the genome sequence of Tolypothrix sp. PCC 7712 to potentially allow targeted strain engineering. Surprisingly, it was almost identical to an available incomplete genome draft of Tolypothrix sp. PCC 7601. Thus, we completely sequenced this strain as well and compared it in detail to strain PCC 7712. Comparative genome analysis revealed 257 and 80 unique protein-coding sequences for strains PCC 7601 and PCC 7712, respectively. Clustering genomes based on average nucleotide identity (ANI) and 16S rRNA homology showed 99.98% similarity and only minor distance, respectively, between the two strains in contrast to 21 other cyanobacterial genomes. Despite these high similarities, both strains differ in the ability to fix atmospheric nitrogen and show specific sequence variations, which are discussed in the paper., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bozan, Popp, Kallies, da Rocha, Klähn and Bühler.)

Background and Objectives: Abdominal trauma among severely injured patients with an injury severity score (ISS) of 16 and above can lead to potentially life-threatening injuries that might need immediate surgical intervention. Traumatic injuries to the diaphragm (TID) are a challenging condition often accompanied by other injuries in the thoracoabdominal region. Materials and Methods: We retrospectively analyzed the occurrence and clinical course of TID among severely injured patients treated at our center between 2008 and 2019 and compared them to other groups of severely injured patients without TID. Results: Thirty-five patients with TID and a median ISS of 41 were treated in the period mentioned above. They were predominantly middle-aged men and mostly victims of blunt trauma as a consequence of motor vehicle accidents. A total of 70.6% had left-sided TID, and in 69.6%, the size of defect was larger than 10 cm. The diagnosis was made with computed tomography (CT) in 68.6% of the cases, while in 25.8%, it was made intraoperatively or delayed by a false-negative initial CT scan, and in 5.7%, an intraoperative diagnosis was made without preoperative CT imaging. Surgical repair was mostly conducted via laparotomy, performing a direct closure with continuous suture. A comparison to 191 patients that required laparotomy for abdominal injuries other than TID revealed significantly higher rates of concomitant injuries to several abdominal organs among patients suffering from TID. Compared to all other severely injured patients treated in the same period ( n = 1377), patients suffering from TID had a significantly higher median ISS and a longer mean duration of hospital stay. Conclusions: Our findings show that TID can be seen as an indicator of particularly severe thoracoabdominal trauma that requires increased attention from the treatment team so as not to miss relevant concomitant injuries that require immediate intervention.

The present study was conducted under the hypothesis that, in field peas, type of plant material, stage of maturity, ensiling, silage additive, and aerobic stress affect the composition and diversity of epiphytic microbial communities. Epiphytic microbial composition and diversity of pea seeds, partial crop peas, and whole crop peas was analyzed at different stages of late maturity, before and after ensiling, and with or without the use of lactic acid bacteria (LAB) as inoculant. Suitable combinations among pea crop variants, maturity stages, and inoculant use for the production of stable silages with sufficient aerobic stability after opening and during feed-out were identified. Genomic DNA was extracted, and 16S and 18S rRNA gene amplicons were sequenced. To assess the quality of the various silages, nutrient concentration, pH value, concentration of lactic acid, short chain fatty acids, and alcohols, and aerobic stability were determined. Pea seeds were barely colonized by epiphytic microorganisms. In partial and whole crop peas, composition and α-diversity (Shannon index) of bacterial communities did not differ between crop variants but differed among maturity stages. Epiphytic eukaryotes were rarely found on partial and whole crop peas. Bacterial composition and α-diversity were affected by ensiling and subsequent aerobic storage. In partial and whole crop peas, plant maturation caused an increase of the relative abundance of naturally occurring LAB ( Weissella , Pediococcus , and Lactobacillus spp.). As a possible result, natural LAB support stable ensiling conditions even without the use of inoculants beginning with a maturity of 78 on the BBCH scale. This corresponded with a dry matter (DM) concentration of 341 and 363 g/kg in partial and whole crop peas, respectively. Addition of LAB inoculants, however, reduced ammonia, acetic acid, and butanol concentrations, and supported aerobic stability. Earlier stages of plant maturity (BBCH 76 and 77, 300 g DM/kg or less) were more prone to microbial spoilage. Stable pea seed silages can be produced at a maturity between BBCH 78 (427 g DM/kg) and 79 (549 g DM/kg), but they undoubtedly require LAB inoculation or application of other ensiling agents. IMPORTANCE Field peas are important protein suppliers for human and animal nutrition. They can be grown in many areas of the world, which may reduce imports of protein plants and has beneficial economic and ecological effects. Ensiling is a method of preserving feed that can be implemented easily and cost-effectively at the farm. Peas harvested as seeds, partial crop, or whole crop at different maturities enable a wide range of applications. The study characterized epiphytic microbial communities on peas in terms of composition and diversity depending on the maturity of the plants and feed conservation by ensiling as they play an essential role for the production of silages. Even if this study did not consider year, site, or cultivar effects, the results would show which part of the plant is probably well suited for the production of stable and high-quality silages and at which stage of maturity.

Chronic wounds are a challenging medical entity for patients, medical professionals and healthcare systems. Frequently, patients present themselves to wound specialists after months or even years of unsuccessful treatment. Recent developments have resulted in a multitude of different advanced wound dressings created to treat complex, chronic wounds, one of which is the polylactide dressing Suprathel. This study aimed at investigating the healing potential of Suprathel in chronic wounds and differentiating between old and "young", diabetic and non-diabetic chronic wounds. A prospective, multicentric, non-controlled intervention study was conducted, treating patients with chronic lower leg ulcers (>3 months) with Suprathel and assessing them weekly. Afterwards, a retrospective analysis was performed analysing the wound size initially, after 4 and after 8 weeks of treatment. Furthermore, a differentiation between diabetic and non-diabetic, and chronic wounds older and younger than 12 months, was assessed. A significant reduction in wound size was observed in the study population after 8 weeks of treatment. The effect size in the diabetic wound and the old chronic wound group even reached more than one, with the other groups still showing a large effect of the intervention. This study shows that Suprathel is a valuable tool in the armamentarium of a wound specialist. Not only could we show a positive effect on chronic wounds, we could even demonstrate a significant wound size reduction in chronic wounds of old and young, as well as diabetic wounds, with the treatment of older chronic and diabetic wounds yielding an even larger effect size. Further randomised, controlled studies are necessary to show the full potential of advanced wound dressing materials in large patient cohorts., (© 2021 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Background: Zosyn ® (piperacillin-tazobactam; Pfizer Medical, New York, NY), a valuable antibiotic against gram-negative bacteria, combined with vancomycin (Z+V) is known for its high incidence of acute kidney injury (AKI), particularly in the intensive care unit (ICU), leading to the frequent use of alternatives for gram-negative coverage (Alt+V). Because there are limited data describing AKI on these alternative antibiotic agents, a systematic review and meta-analysis was conducted to determine if these regimens were indeed associated with decreased rates of AKI. Patients and Methods: A literature review was performed electronically from its inception to November 1, 2018, screening for relevant literature by title, abstract and full text according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines within the following databases: PubMed/Medline, CINAHL, Scopus, and Cochrane Central Register of Controlled Trials. Studies were included if they contained adults who had been admitted to the ICU for treatment and had received a combination of intravenous Z + V or Alt+V as well as had AKI measured during administration of these antibiotic agents. Studies were excluded if they represented pediatric populations, did not receive care in an ICU during their hospital admission, only received monotherapy for antibiotic treatment or received antibiotic treatment for less than 48 hours. Independent extraction was performed by two reviewers. Risk of bias was assessed using the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) methodology for retrospective studies. Random-effects models were used to calculate any differences between rates of AKI after Z + V or Alt + V. Results: Fourteen articles (totaling 30,399 patients) were included. All studies available were retrospective in design. Compared with Alt + V, Z + V was associated with a higher risk ratio of AKI (1.79; 95% confidence interval [CI], 1.46-2.19; p < 0.001). Cefepime (C + V) was the most common alternative to Zosyn, and Z + V was associated with higher rates of kidney injury compared with C + V (1.70; 95% CI, 1.36-2.12; p < 0.00001). However, there was substantial heterogeneity in the data collected as well as high risk of bias. Conclusions: Zosyn plus vancomycin is associated with more risk of AKI compared with Alt+V coverage in ICU adult populations. However, the conclusions were limited by the retrospective nature of the studies, high bias of included articles, and heterogeneity of the included studies.

Introduction: Heading is an integral part of football and frequent media reports and previous studies about potential danger of heading and head trauma in football fuelled discussions. Epidemiological data and video analyses regarding headings situation and associated head injuries are still missing in male adult professional football., Methods: In a prospective cohort study in the male fourth German football league, 100 official matches of the 2015-2016 season were assessed by video analysis and a standardized protocol. Heading situations and concomitant circumstances as well as incidents with a propensity of injury (critical incidents) were analyzed. Critical incidents (CI) and seasonal reported head injuries were cross-referenced., Results: Overall, 11,514 headings were analysed in detail. Video analysis yielded a mean of 5.7 headings per player and match (SD: 1.2; range 0-15). Heading was predominantly performed with the frontal part of the head (76.8%), and nearly two thirds of all headings occurred during defending (65.8%). 71.0% of all headings occured during tacklings, of which 71.9% involved body contact with the opponent player. Video analysis yielded 31 CI on the head due to heading (incidence: 1.02 per 1000 h match exposure and player). 29 CI occurred during heading duels (odds ratio: 5.91), 30 CI with body contact (odds ratio: 28.8) and 6 CI with elbow contact (odds ratio: 6.13)., Conclusion: Heading frequency in male semi-professional football could be determined with a rate of 5.7 headings per match and field player. Cross referencing CI and seasonal reported head injuries revealed a very low number of reported head injuries., (© 2022. The Author(s).)

According to the General Data Protection Regulation (GDPR 05/2018), anonymized data sets with a sufficiently high data density are classified as traceable and require a declaration of consent if they are evaluated centrally for research or quality control purposes. Quality assurance and further increases in the quality of care are, however, only possible with a nearly complete survey of seriously injured persons in the sense of health services research. The more than 600 German clinics that take part in the TraumaRegistry DGU® try to obtain the declarations of consent from this special patient population. The study clinic evaluated the rate of consent and the reasons for rejection or failure to obtain consent over a 12-month period. While using a resource-intensive workflow especially for patient education and obtaining the consent, a patient consent rate of 64.5% and an error rate of 35.5% were recorded. Of the 276 potential TraumaRegistry DGU® data records 98 could not be entered and were therefore neither available for quality control nor for multiple trauma research. In order to guarantee the quality control and the further improvement of the quality of care, an approximate total recording of the patient population is necessary; however, this cannot be achieved by requiring a declaration of consent. We therefore advocate creating the possibility of collecting the TraumaRegistry data set without consent, as this ultimately represents a standard data set, comparable to the Hospital Remuneration Act (§21-KHEntgG) data set but pseudonymised., (© 2021. The Author(s).)

Background: As the cost of healthcare rises, it is imperative to assess value delivered to patients and impact on the economic viability of institutions. We aimed to characterize plastic surgery operative time management and identified areas for efficiency improvement., Methods: Procedures from a US academic plastic surgery division from September 2017 to August 2018 were reviewed. Times were categorized into preparation (patient in room to incision), procedure (incision to closure), exit (closure to patient exiting room), and turnover (patient out of room to next patient in room). Median and interquartile ranges were calculated. Procedures were classified by relative value units (RVUs) for comparison of procedure complexities and resources. Components were plotted against RVUs; r2 values were calculated., Results: We analyzed 522 cases; 69 were excluded for missing data, primary surgeon not a plastic surgeon, emergent cases, or burn procedures; a total of 453 cases were analyzed. Median and interquartile range (in minutes) for preparation was (34, 18 minutes; 23% of total), procedure (53, 75 minutes; 36% of total), exit (30, 27 minutes; 20% of total), and turnover (30, 26 minutes; 20% of total). Normalized to RVUs, preparation demonstrated the most variability (r2 = 0.19), followed by exit (r2 = 0.38), and procedure (r2 = 0.57). Average work RVUs per month was 678.1 ± 158.7. Average work RVUs per OR hour was 7.2., Conclusions: The largest component with greatest variability was preparation for surgery in the OR. Improved efficiency by decreasing variability increases the value of healthcare delivered to patients and OR throughput., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)