Search

Space radiation is a notable hazard for long-duration human spaceflight1. Associated risks include cancer, cataracts, degenerative diseases2 and tissue reactions from large, acute exposures3. Space radiation originates from diverse sources, including galactic cosmic rays4, trapped-particle (Van Allen) belts5 and solar-particle events6. Previous radiation data are from the International Space Station and the Space Shuttle in low-Earth orbit protected by heavy shielding and Earth’s magnetic field7,8 and lightly shielded interplanetary robotic probes such as Mars Science Laboratory and Lunar Reconnaissance Orbiter9,10. Limited data from the Apollo missions11–13 and ground measurements with substantial caveats are also available14. Here we report radiation measurements from the heavily shielded Orion spacecraft on the uncrewed Artemis I lunar mission. At differing shielding locations inside the vehicle, a fourfold difference in dose rates was observed during proton-belt passes that are similar to large, reference solar-particle events. Interplanetary cosmic-ray dose equivalent rates in Orion were as much as 60% lower than previous observations9. Furthermore, a change in orientation of the spacecraft during the proton-belt transit resulted in a reduction of radiation dose rates of around 50%. These measurements validate the Orion for future crewed exploration and inform future human spaceflight mission design.Measurements from the heavily shielded Orion spacecraft during the uncrewed Artemis I mission show dose-rate reductions due to shielding and orientation for Van Allen belt crossings and quantify the interplanetary cosmic-ray radiation in a human-rated spacecraft. [ABSTRACT FROM AUTHOR]

Purpose and objective: To develop expert consensus statements on multiparametric dose prescriptions for stereotactic body radiotherapy (SBRT) aligning with ICRU report 91. These statements serve as a foundational step towards harmonizing current SBRT practices and refining dose prescription and documentation requirements for clinical trial designs. Materials and methods: Based on the results of a literature review by the working group, a two-tier Delphi consensus process was conducted among 24 physicians and physics experts from three European countries. The degree of consensus was predefined for overarching (OA) and organ-specific (OS) statements (≥ 80%, 60–79%, < 60% for high, intermediate, and poor consensus, respectively). Post-first round statements were refined in a live discussion for the second round of the Delphi process. Results: Experts consented on a total of 14 OA and 17 OS statements regarding SBRT of primary and secondary lung, liver, pancreatic, adrenal, and kidney tumors regarding dose prescription, target coverage, and organ at risk dose limitations. Degree of consent was ≥ 80% in 79% and 41% of OA and OS statements, respectively, with higher consensus for lung compared to the upper abdomen. In round 2, the degree of consent was ≥ 80 to 100% for OA and 88% in OS statements. No consensus was reached for dose escalation to liver metastases after chemotherapy (47%) or single-fraction SBRT for kidney primaries (13%). In round 2, no statement had 60–79% consensus. Conclusion: In 29 of 31 statements a high consensus was achieved after a two-tier Delphi process and one statement (kidney) was clearly refused. The Delphi process was able to achieve a high degree of consensus for SBRT dose prescription. In summary, clear recommendations for both OA and OS could be defined. This contributes significantly to harmonization of SBRT practice and facilitates dose prescription and reporting in clinical trials investigating SBRT. [ABSTRACT FROM AUTHOR]

Complex algorithms and enormous data sets require parallel execution of programs to attain results in a reasonable amount of time. Both aspects are combined in the domain of three-dimensional stencil operations, for example, computational fluid dynamics. This work contributes to the research on high-level parallel programming by discussing the generalizable implementation of a three-dimensional stencil skeleton that works in heterogeneous computing environments. Two exemplary programs, a gas simulation with the Lattice Boltzmann method, and a mean blur, are executed in a multi-node multi-graphics processing units environment, proving the runtime improvements in heterogeneous computing environments compared to a sequential program. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether strength training or tai ji quan can reduce frailty in older, postmenopausal women treated with chemotherapy for cancer. Methods: We conducted a secondary data analysis from a 3-arm, single-blind, randomized controlled trial where older (50–75 years), postmenopausal women cancer survivors were randomized to supervised group exercise programs: tai ji quan, strength training, or stretching control for 6 months. We assessed frailty using a 4-criteria model consisting of weakness, fatigue, inactivity, and slowness. Using logistic regression, we determined whether the frailty phenotype (pre-frailty or frailty) decreased post-intervention, how many and which frailty criteria decreased, and what characteristics identified women most likely to reduce frailty. Results: Data from 386 women who completed baseline and 6-month testing were used (mean age of 62.0 ± 6.4 years). The odds of reducing overall frailty over 6 months were significantly higher in the strength training group compared to controls (OR [95%CI] 1.86 [1.09, 3.17]) but not for tai ji quan (1.44 [0.84, 2.50]). Both strength training (OR 1.99 [1.10, 3.65]) and tai ji quan (OR 2.10 [1.16, 3.84]) led to significantly higher odds of reducing ≥ 1 frailty criterion compared to controls. Strength training led to a three-fold reduction in inactivity (p < 0.01) and tai ji quan to a two-fold reduction in fatigue (p = 0.08) versus control. Higher baseline BMI, comorbidity score, and frailty status characterized women were more likely to reduce frailty than other women. Conclusions: Strength training appears superior to tai ji quan and stretching with respect to reducing overall frailty phenotype among postmenopausal women treated with chemotherapy for cancer, but tai ji quan favorably reduced the number of frailty criteria. Trial registration: ClinicalTrials.gov identifier: GET FIT was registered as a clinical trial in clinicaltrials.gov: NCT01635413. Implications for Cancer Survivors: Supervised, group exercise training that emphasizes strength training and/or tai ji quan may help combat accelerated aging and reduce frailty after cancer treatment. [ABSTRACT FROM AUTHOR]

Summary: Since 1979 Austrian children and adolescents with acute lymphoblastic leukemia (ALL) have been treated according to protocols of the Berlin-Frankfurt-Münster (BFM) study group. The Associazione Italiana di Ematologia e Oncologia Pediatrica and BFM (AIEOP-BFM) ALL 2000 study was designed to prospectively study patient stratification into three risk groups using minimal residual disease (MRD) on two time points during the patient's early disease course. The MRD levels were monitored by detection of clone-specific rearrangements of the immunoglobulin and T‑cell receptor genes applying a quantitative polymerase chain reaction-based technique. The 7‑year event-free survival (EFS) and overall survival rates for all 608 Austrian patients treated between June 1999 and December 2009 within the AIEOP-BFM 2000 study were 84 ± 2% and 91 ± 1%, respectively, with a median observation time of 6.58 years. Event-free survival for patients with precursor B‑cell and T‑cell ALL were 84 ± 2% (n = 521) and 84 ± 4% (n = 87; p = 0.460), respectively. The MRD assessment was feasible in 94% of the patients and allowed the definition of precursor B‑cell ALL patients with a low, intermediate or high risk of relapse even on top of clinically relevant subgroups. A similar finding with respect to MRD relevance in T‑ALL patients was not possible due to the small number of patients and events. Since this pivotal international AIEOP-BFM ALL 2000 trial, molecular response to treatment has been continuously used with additional refinements to stratify patients into different risk groups in all successive trials of the AIEOP-BFM ALL study group. [ABSTRACT FROM AUTHOR]

Purpose: Lung cancer is a disease with high mortality and morbidity, impacting both the patient and their closest contact, referred to in this paper as their care partner. There is limited evidence on how to support mental health and quality of life (QOL) for patient-care partner dyads during cancer treatment. This pilot study examines yoga as an intervention to improve well-being for the dyad. Methods: A single-group, 12-week pilot trial of yoga for patients and their care partners recruited from two hospitals during cancer treatment (N = 23 patient-partner dyads or 46 individuals). Most care partners were spouses (70%), with the remainder being adult children (22%), a sibling (4%), or a friend (4%). Descriptive statistics, Cohen’s d effect sizes, and paired t-tests for validated psychosocial measures were calculated at baseline and 12 weeks. Results: Sixty-five percent of dyads (N = 13) completed the study, with withdrawals mostly due to disease progression. Among care partners, there was a decrease in depression symptomology on the PHQ-8 (p = 0.015, Cohen’s d = 0.96) and improvement in QOL on the Caregiver QOL-Cancer scale (p = 0.001, Cohen’s d = 0.61). Fifty percent of dyads experienced concordant improvement in depressive symptoms and 77% in QOL. Conclusion: Patient-partner yoga is a promising intervention for improving mental health and QOL for patient-partner dyads among lung cancer survivors. This study demonstrates yoga to be acceptable, feasible, and with high concordance within patient-partner dyads for improvements in QOL. Yoga shows promise for patients and care partners to alleviate the negative psychosocial impacts of lung cancer, though more research is needed to confirm effects. Trial registration: ClinicalTrials.gov, NCT03649737, 12/9/2020. [ABSTRACT FROM AUTHOR]

Tuberculosis remains a large global disease burden for which treatment regimens are protracted and monitoring of disease activity difficult. Existing detection methods rely almost exclusively on bacterial culture from sputum which limits sampling to organisms on the pulmonary surface. Advances in monitoring tuberculous lesions have utilized the common glucoside [18F]FDG, yet lack specificity to the causative pathogen Mycobacterium tuberculosis (Mtb) and so do not directly correlate with pathogen viability. Here we show that a close mimic that is also positron-emitting of the non-mammalian Mtb disaccharide trehalose – 2-[18F]fluoro-2-deoxytrehalose ([18F]FDT) – is a mechanism-based reporter of Mycobacteria-selective enzyme activity in vivo. Use of [18F]FDT in the imaging of Mtb in diverse models of disease, including non-human primates, successfully co-opts Mtb-mediated processing of trehalose to allow the specific imaging of TB-associated lesions and to monitor the effects of treatment. A pyrogen-free, direct enzyme-catalyzed process for its radiochemical synthesis allows the ready production of [18F]FDT from the most globally-abundant organic 18F-containing molecule, [18F]FDG. The full, pre-clinical validation of both production method and [18F]FDT now creates a new, bacterium-selective candidate for clinical evaluation. We anticipate that this distributable technology to generate clinical-grade [18F]FDT directly from the widely-available clinical reagent [18F]FDG, without need for either custom-made radioisotope generation or specialist chemical methods and/or facilities, could now usher in global, democratized access to a TB-specific PET tracer. Current methods for detection of tuberculosis rely mostly on bacterial culture from sputum. Here, the authors provide preclinical evidence that a positron-emitting mimic of the disaccharide trehalose ([18F]FDT) can be used as a radiotracer for the imaging of tuberculosis-associated lesions and monitoring the effects of treatment. [ABSTRACT FROM AUTHOR]

A nonlinear integral equation arising from a parametric closure of the third spatial moment in the single-species model of logistic dynamics of U. Dieckmann and R. Law is analyzed. The case of piecewise constant kernels is studied, which is important for further computer modeling. Sufficient conditions are found that guarantee the existence of a nontrivial solution to the equilibrium equation. The use of constant kernels makes it possible to obtain more accurate results compared to earlier works, in particular, more accurate estimates for the L1 norm of the solution and for the closure parameter are obtained. [ABSTRACT FROM AUTHOR]

Cope's rule posits that evolution gradually increases the body size in lineages. Over the last decades, two schools of thought have fueled a debate on the applicability of Cope's rule by reporting empirical evidence, respectively, for and against Cope's rule. The apparent contradictions thus documented highlight the need for a comprehensive process-based synthesis through which both positions of this debate can be understood and reconciled. Here, we use a process-based community-evolution model to investigate the eco-evolutionary emergence of Cope's rule. We report three characteristic macroevolutionary patterns, of which only two are consistent with Cope's rule. First, we find that Cope's rule applies when species interactions solely depend on relative differences in body size and the risk of lineage extinction is low. Second, in environments with higher risk of lineage extinction, the recurrent evolutionary elimination of top predators induces cyclic evolution toward larger body sizes, according to a macroevolutionary pattern we call the recurrent Cope's rule. Third, when interactions between species are determined not only by their body sizes but also by their ecological niches, the recurrent Cope's rule may get inverted, leading to cyclic evolution toward smaller body sizes. This recurrent inverse Cope's rule is characterized by highly dynamic community evolution, involving the diversification of species with large body sizes and the extinction of species with small body sizes. To our knowledge, these results provide the first theoretical foundation for reconciling the contrasting empirical evidence reported on body-size evolution. The processes underlying Cope's rule of increasing body size in animal lineages are investigated using computational models. Varied levels of extinction risk may alter the conformity of a lineage to Cope's rule. [ABSTRACT FROM AUTHOR]

Biological sex is a key variable influencing many physiological systems. Disease prevalence as well as treatment success can be modified by sex. Differences emerge already early in life and include pregnancy complications and adverse birth outcomes. The placenta is a critical organ for fetal development and shows sex-based differences in the expression of hormones and cytokines. Epigenetic regulation, such as DNA methylation (DNAm), may underlie the previously reported placental sexual dimorphism. We associated placental DNAm with fetal sex in three cohorts. Individual cohort results were meta-analyzed with random-effects modelling. CpG-sites differentially methylated with sex were further investigated regarding pathway enrichment, overlap with methylation quantitative trait loci (meQTLs), and hits from phenome-wide association studies (PheWAS). We evaluated the consistency of findings across tissues (CVS, i.e. chorionic villus sampling from early placenta, and cord blood) as well as with gene expression. We identified 10,320 epigenome-wide significant sex-differentially methylated probes (DMPs) spread throughout the epigenome of the placenta at birth. Most DMPs presented with lower DNAm levels in females. DMPs mapped to genes upregulated in brain, were enriched for neurodevelopmental pathways and significantly overlapped with meQTLs and PheWAS hits. Effect sizes were moderately correlated between CVS and placenta at birth, but only weakly correlated between birth placenta and cord blood. Sex differential gene expression in birth placenta was less pronounced and implicated genetic regions only marginally overlapped with those associated with differential DNAm. Our study provides an integrative perspective on sex-differential DNAm in perinatal tissues underscoring the possible link between placenta and brain. [ABSTRACT FROM AUTHOR]

Purpose: Tumor boards serve as established platforms for interdisciplinary expert discussions and therapeutic recommendations tailored to individual patient characteristics. Despite their significance, medical students often lack exposure to such interdisciplinary discussions as tumor boards are currently not integrated into medical curricula. To address this, we aimed to enhance future physicians' interdisciplinary communication skills and subject-specific knowledge by introducing an interactive series of five linked tumor board seminars within the domain of neuro-oncology. Methods: We developed a neuro-oncological student tumor board using a flipped-classroom format. The primary objectives of this case-centered approach included fostering an understanding of the tumor board process, active participation in multidisciplinary case discussions, honing appropriate communication strategies, and creating personalized therapy plans that consider inputs from all relevant disciplines, individual patient factors, and ethical considerations. To gauge the effectiveness of the seminar series, we administered structured pre- and post-course questionnaires. Results: Fourteen medical students in third to fifth year participated in the pilot series. Despite its organizational complexity, the interdisciplinary seminars were feasible. Students demonstrated significant growth in competence, aligned with predefined learning objectives. Notably, they appreciated the supportive learning environment and interactive teaching format, which kindled their interest in interdisciplinary oncology. Conclusion: Active participation in a student tumor board can empower students to tackle the diverse challenges of caring for cancer patients within an interdisciplinary team during the early stages of their careers. The student tumor board represents an innovative, learner-centered approach to teach interdisciplinary cancer treatment, communication strategies, and ethical aspects of medical practice. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate interobserver agreement (IOA) on target volume definition for pancreatic cancer (PACA) within the Radiosurgery and Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (DEGRO) and to identify the influence of imaging modalities on the definition of the target volumes. Methods: Two cases of locally advanced PACA and one local recurrence were selected from a large SBRT database. Delineation was based on either a planning 4D CT with or without (w/wo) IV contrast, w/wo PET/CT, and w/wo diagnostic MRI. Novel compared to other studies, a combination of four metrics was used to integrate several aspects of target volume segmentation: the Dice coefficient (DSC), the Hausdorff distance (HD), the probabilistic distance (PBD), and the volumetric similarity (VS). Results: For all three GTVs, the median DSC was 0.75 (range 0.17–0.95), the median HD 15 (range 3.22–67.11) mm, the median PBD 0.33 (range 0.06–4.86), and the median VS was 0.88 (range 0.31–1). For ITVs and PTVs the results were similar. When comparing the imaging modalities for delineation, the best agreement for the GTV was achieved using PET/CT, and for the ITV and PTV using 4D PET/CT, in treatment position with abdominal compression. Conclusion: Overall, there was good GTV agreement (DSC). Combined metrics appeared to allow a more valid detection of interobserver variation. For SBRT, either 4D PET/CT or 3D PET/CT in treatment position with abdominal compression leads to better agreement and should be considered as a very useful imaging modality for the definition of treatment volumes in pancreatic SBRT. Contouring does not appear to be the weakest link in the treatment planning chain of SBRT for PACA. [ABSTRACT FROM AUTHOR]

Preoperative homeostasis of sex hormones in testicular germ cell tumor (TGCT) patients is scarcely characterized. We aimed to explore regulation of sex hormones and their implications for histopathological parameters and prognosis in TGCT using a data-driven explorative approach. Pre-surgery serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estradiol (E2) and prolactin were measured in a retrospective multicenter TGCT cohort (n = 518). Clusters of patients were defined by latent class analysis. Clinical, pathologic and survival parameters were compared between the clusters by statistical hypothesis testing, Random Forest modeling and Peto-Peto test. Cancer tissue expression of sex hormone-related genes was explored in the publicly available TCGA cohort (n = 149). We included 354 patients with pure seminoma and 164 patients with non-seminomatous germ cell tumors (NSGCT), with a median age of 36 years. Three hormonal clusters were defined: 'neutral' (n = 228) with normal sex hormone homeostasis, 'testicle' (n = 91) with elevated T and E2, low pituitary hormones, and finally 'pituitary' subset (n = 103) with increased FSH and LH paralleled by low-to-normal levels of the gonadal hormones. Relapse-free survival in the hormonal subsets was comparable (p = 0.64). Cancer tissue expression of luteinizing hormone- and follicle-stimulating hormone-coding genes was significantly higher in seminomas, while genes of T and E2 biosynthesis enzymes were strongly upregulated in NSGCT. Substantial percentages of TGCT patients are at increased risk of sex hormone dysfunction at primary diagnosis before orchiectomy. TGCT may directly influence systemic hormonal homeostasis by in-situ synthesis of sex hormones. [ABSTRACT FROM AUTHOR]

Purpose: In testicular neoplasms, the interrelationship of elevations of the novel serum tumor marker microRNA-371a-3p (M371) and traditional markers with other clinical features is still incompletely understood. The present study evaluated marker expression rates in relation to various other clinical parameters. Methods: The following data were retrospectively registered from 641 consecutive patients with testicular neoplasms: histology, such as seminoma (n = 365), nonseminoma (n = 179), benign tumor (n = 79), other malignant tumor (n = 18); patients age (years); clinical stage (CS1, CS2a/b, CS2c, CS3); and preoperative elevation of beta HCG, AFP, LDH, M371 (yes/no). Descriptive statistical methods were employed with comparisons of various subgroups to disclose associations of marker expression rates with age, histology and CS, and of age with histology. Results: The histologic subgroups revealed significantly different expression rates of tumor markers. M371 performed best with expression rates of 82.69% and 93.58% in seminoma and in nonseminoma, respectively. In germ cell tumors, all markers had significantly higher expression rates in metastasized stages than in localized disease. All markers except LDH have significantly higher expression rates in younger than in older patients. Nonseminoma is most prevalent in the youngest age category, seminoma predominates in patients > 40 years, other malignancies were restricted to patients > 50 years. Conclusion: The study documented significant associations of serum marker expression rates with histology, age and clinical staging, with highest rates in nonseminomas, young age and advanced clinical stages. M371 showed significantly higher expression rates than other markers suggesting its superior clinical usefulness. [ABSTRACT FROM AUTHOR]

Summary: Among married couples living with breast and prostate cancer, positive perceptions of relationship quality by both survivors and their spouses were associated with lower inflammation or insulin resistance in their partner. Our data support evidence that health within couples is both interdependent and transactional and suggests that one member's perception of the relationship is associated with biologic changes in one's partner, leading to better physical health of the couple. These findings may provide a biologic underpinning to observations of an inverse relationship between relational satisfaction and overall mortality and underscore the need for a dyadic approach to health. Purpose: Couples' health and health behaviors are intertwined, where the health of one partner can influence the health of the other but the biologic underpinnings are not known. We examined the associations between relational health and markers of inflammation and insulin resistance in couples coping with breast or prostate cancer. Methods: Participants (90 cancer survivor-spouse dyads) completed self-report measures of relational health including Dyadic Adjustment Scale-7 (relationship quality), Dyadic Coping Inventory (communication), and shared physical activity, as well as Community Health Activities Model Program for Seniors (individual physical activity). Inflammation (C-reactive protein (CRP)) and homeostasis model assessment of insulin resistance (HOMA-IR) were measured in serum samples. Structural equation modeling including demographic and clinical covariate controls was used to estimate separate actor and partner effects of relationship quality, communication, and physical activity on CRP and HOMA-IR. Results: Participants were aged 63.1 ± 10.4 years with an average relationship duration of 30.0 ± 1.1 years. Higher survivor perceived relationship quality was associated with lower spouse CRP (b = − 0.07; 95%CI: − 0.13, − 0.01), whereas higher spouse perceived relationship quality was associated with lower survivor HOMA-IR (b = − 0.07; 95%CI: − 0.13, − 0.03). There were no other significant actor or partner effects observed. Conclusions: Among cancer survivor-spouse dyads, how one member of the couple perceives the quality of the relationship impacts disease biomarkers in the other, providing preliminary evidence for biological linkage between relational health and chronic disease risk. Implications for Cancer Survivors: Relationship quality may positively influence biomarkers of inflammation and insulin resistance in couples coping with breast and prostate cancer. Dyadic approaches to optimize survivorship health may be warranted. Trial registration: ClinicalTrials.gov NCT03630354, 08/14/2018; Open Science Framework (https://bit.ly/3S4rUtJ). [ABSTRACT FROM AUTHOR]

Malaria results in more than 500,000 deaths per year and the causative Plasmodium parasites continue to develop resistance to all known agents, including different antimalarial combinations. The class XIV myosin motor PfMyoA is part of a core macromolecular complex called the glideosome, essential for Plasmodium parasite mobility and therefore an attractive drug target. Here, we characterize the interaction of a small molecule (KNX-002) with PfMyoA. KNX-002 inhibits PfMyoA ATPase activity in vitro and blocks asexual blood stage growth of merozoites, one of three motile Plasmodium life-cycle stages. Combining biochemical assays and X-ray crystallography, we demonstrate that KNX-002 inhibits PfMyoA using a previously undescribed binding mode, sequestering it in a post-rigor state detached from actin. KNX-002 binding prevents efficient ATP hydrolysis and priming of the lever arm, thus inhibiting motor activity. This small-molecule inhibitor of PfMyoA paves the way for the development of alternative antimalarial treatments. Myosin A (PfMyoA) is essential for the pathogenesis of Plasmodium falciparum, the causative agent of malaria. Here we decipher the mechanism by which a small molecule inhibitor (KNX-002) of PfMyoA impedes its motor activity. [ABSTRACT FROM AUTHOR]

Brain metastases (BM) in patients with thyroid cancer (TC) are rare with an incidence of 1% for papillary and follicular, 3% for medullary and up to 10% for anaplastic TC (PTC, FTC, MTC and ATC). Little is known about the characteristics and management of BM from TC. Thus, we retrospectively analyzed patients with histologically verified TC and radiologically verified BM identified from the Vienna Brain Metastasis Registry. A total of 20/6074 patients included in the database since 1986 had BM from TC and 13/20 were female. Ten patients had FTC, 8 PTC, one MTC and one ATC. The median age at diagnosis of BM was 68 years. All but one had symptomatic BM and 13/20 patients had a singular BM. Synchronous BM at primary diagnosis were found in 6 patients, while the median time to BM diagnosis was 13 years for PTC (range 1.9–24), 4 years for FTC (range 2.1–41) and 22 years for the MTC patient. The overall survival from diagnosis of BM was 13 months for PTC (range 1.8–57), 26 months for FTC (range 3.9–188), 12 years for the MTC and 3 months for the ATC patient. In conclusion, development of BM from TC is exceedingly rare and the most common presentation is a symptomatic single lesion. While BM generally constitute a poor prognostic factor, individual patients experience long-term survival following local therapy. [ABSTRACT FROM AUTHOR]

Purpose: Germ cell neoplasia in situ (GCNis), the precursor of adult testicular germ cell tumours (GCTs), is found in 5–6% of contralateral testicles in patients with testicular GCT and in the tumour-surrounding tissue of > 90% of testes undergoing testis-sparing surgery (TSS) for GCT. Local radiotherapy to the testis with 18–20 Gy eradicates GCNis while preserving Leydig cells. The frequency of treatment failures is so far unknown. Methods: A 22-year-old patient with right-sided seminoma clinical stage I and contralateral GCNis received radiotherapy with 18 Gy to his left testicle. Fifteen years later he underwent orchiectomy of the irradiated testis for seminoma with adjacent GCNis. The patient is well 1 year postoperatively while on testosterone-replacement therapy. The literature was searched for further cases with GCTs arising despite local radiotherapy. Results: Six failures of radiotherapy have been reported previously. An estimated total number of 200 and 100 radiotherapeutic regimens with 18–20 Gy applied to cases with contralateral GCNis and with TSS, respectively, are documented in the literature. Conclusion: Cumulative experience suggests that radiotherapy with 18–20 Gy to the testis may fail with an estimated frequency of around 1%. Reasons for failure are elusive. A primary radioresistant subfraction of GCNis is hypothesized as well as technical failures regarding application of the radiotherapeutic dose volume in small and mobile testes. Caregivers of patients with TSS and contralateral GCNis should be aware of local relapses occurring after intervals of > 10 years. [ABSTRACT FROM AUTHOR]

Abstract Amoeba use phagocytosis to internalize bacteria as a source of nutrients, whereas multicellular organisms utilize this process as a defense mechanism to kill microbes and, in vertebrates, initiate a sustained immune response. By using a large‐scale approach to identify and compare the proteome and phosphoproteome of phagosomes isolated from distant organisms, and by comparative analysis over 39 taxa, we identified an ‘ancient’ core of phagosomal proteins around which the immune functions of this organelle have likely organized. Our data indicate that a larger proportion of the phagosome proteome, compared with the whole cell proteome, has been acquired through gene duplication at a period coinciding with the emergence of innate and adaptive immunity. Our study also characterizes in detail the acquisition of novel proteins and the significant remodeling of the phagosome phosphoproteome that contributed to modify the core constituents of this organelle in evolution. Our work thus provides the first thorough analysis of the changes that enabled the transformation of the phagosome from a phagotrophic compartment into an organelle fully competent for antigen presentation.

Purpose: Testicular germ cell tumours (GCTs) represent the most common malignancy in young adult males with two thirds of all cases presenting with clinical stage I (CSI). Active surveillance is the management modality mostly favoured by current guidelines. This systematic review assesses the treatment results in CSI patients concerning recurrence rate and overall survival in non-seminoma (NS) and pure seminoma (SE) resulting from surveillance in comparison to adjuvant strategies. Methods/systematic review: We performed a systematic literature review confining the search to most recent studies published 2010–2021 that reported direct comparisons of surveillance to adjuvant management. We searched Medline and the Cochrane Library with additional hand-searching of reference lists to identify relevant studies. Data extraction and quality assessment of included studies were performed with stratification for histology (NS vs. SE) and treatment modalities. The results were tabulated and evaluated with descriptive statistical methods. Results: Thirty-four studies met the inclusion criteria. In NS patients relapse rates were 12 to 37%, 0 to 10%, and 0 to 11.8% for surveillance, chemotherapy and for retroperitoneal lymph node dissection (RPLND) while overall survival rates were 90.7−100%, 91.7−100%, and 97−99.1%, respectively. In SE CSI, relapse rates were 0−22.3%, 0−5%, and 0−12.5% for surveillance, radiotherapy, chemotherapy, while overall survival rates were 84.1−98.7%, 83.5−100%, and 92.3−100%, respectively. Conclusion: In both histologic subgroups, active surveillance offers almost identical overall survival as adjuvant management strategies, however, at the expense of higher relapse rates. Each of the management strategies in CSI GCT patients have specific merits and shared-decision-making is advised to tailor treatment. [ABSTRACT FROM AUTHOR]

In this paper, we analyze a system of nonlinear integral equations resulting from the three-parameter closure of the third spatial moments in the logistic dynamics model of U. Dieckmann and R. Law in the multi-species case. Specifically, the conditions under which the solution of this system is stable with respect to the closure parameters are investigated. To do this, the initial system of equations is represented as a single operator equation in a special Banach space, after which the generalized fixed point principle is applied. [ABSTRACT FROM AUTHOR]

Copyright of Best Practice Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Unfallchirurg is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The paper deals with the analysis of a system of nonlinear integral equations resulting from the three-parameter closure of the third spatial moment in the Dieckmann–Law model in the case of an -species community in an -dimensional space. For the analysis of its solvability, this system is represented as an operator equation in a Banach space of a special form. Sufficient conditions for the existence of a nontrivial solution are stated using a generalized fixed point principle. [ABSTRACT FROM AUTHOR]

Background: Important non-technical skills enable operating teams to establish shared mental models (SMMs). The importance of SMMs in regards to surgical performance and peri-operative outcomes remains to be investigated. The aim of this study was to explore whether shared mental models (SMMs) of team resources and the current situation, respectively, were predictive of technical skills, duration of surgery, and amount of intra-operative bleeding in video-assisted thoracoscopic surgery (VATS). Methods: A prospective multi-center observational study was conducted at four tertiary academic hospitals during VATS lobectomy procedures. Data included pre-operative and post-operative questionnaires answered by each of the six team members to measure the SMMs; thoracoscopic video recordings assessed using the previously validated VATS lobectomy Assessment Tool (VATSAT); surgery-related time stamps; and amount (volume) of intra-operative bleeding. Linear regression analyses were conducted to adjust for confounders. Results: Fifty-eight lobectomy procedures were included. Median (interquartile range) VATSAT score was 33.3 (scale 8–40) duration of surgery 101 min (88–123), and amount of intra-operative bleeding 100 ml (20–150). The mean (± SD) of teams' SMMs of the current situation was 20 (± 5). They were not predictive of the surgeons' technical skills, but every one point increase in SMM score significantly predicted a 1 min 52 s decrease in duration of surgery and an 11% decrease in amount of bleeding. The SMMs of team resources were not predictive of any outcomes. Conclusion: VATS teams' superior SMMs of the current situation related to significantly shorter duration of surgery and decreased intra-operative bleeding, indicating an effect on team performance and patient care. Trial registration: NCT02999113 at http://www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Introduction: Dry eye disease is characterized by a persistently unstable or deficient tear film causing discomfort or visual impairment. Varenicline is a small-molecule nicotinic acetylcholine receptor agonist recently approved for use as a preservative-free nasal spray (OC-01 [varenicline solution] nasal spray [OC-01 VNS]) to treat signs and symptoms of dry eye disease, but its effect on conjunctival goblet cells has not been studied. Methods: In this phase 2, single-center, vehicle-controlled study, patients aged 18 years or more with a diagnosis of dry eye disease and Ocular Surface Disease Index© score of at least 23 were randomized 2:1 to receive a 50-µL single dose of OC-01 0.06 mg VNS or vehicle nasal spray in each nostril. Image assessments for area and perimeter were performed pre and 10 min post treatment for goblet cells by in vivo confocal microscopy and for meibomian glands by infrared meibography. Non-parametric Wilcoxon signed-rank test compared pre- and post-treatment measurements for each treatment group. Treatment-emergent adverse events (TEAEs) were assessed. Results: The study randomized 18 patients (mean age 61 years); 6 received vehicle (3/6 [50%] female) and 12 patients received OC-01 VNS (11/12 [92%] female). OC-01 VNS treatment decreased mean goblet cell area (pre-treatment, 106.4 µm2; post-treatment, 67.6 µm2; p = 0.02) and perimeter (pre-treatment, 38.9 µm; post-treatment, 31.2 µm; p = 0.03) but not vehicle did not (p = 0.25). There were no significant changes in mean meibomian gland area with either treatment (p ≥ 0.05). All TEAEs were non-ocular, non-serious, and mild. Conclusions: This study demonstrated that a single administration of OC-01 0.06 mg VNS in patients with dry eye disease reduced conjunctival goblet cell area and perimeter, suggesting goblet cell degranulation and associated release of lubricating mucin. By activating the natural tear film, OC-01 VNS may provide benefits over topical medications. Trial Registration: ClinicalTrials.gov, NCT03688802. [ABSTRACT FROM AUTHOR]

Research regarding daily acute pain and its correlates has primarily been conducted with adolescents who have had major surgery or musculoskeletal pain, restraining efforts towards adapting interventions for adolescents with other sources of acute pain. We explored the trajectories and correlates of pain intensity. Adolescents with an opioid prescription to treat acute pain (N = 157) completed demographic questions, and the PROMIS pediatric depression and anxiety subscales. A 10-day daily diary assessed pain intensity, pain interference, sleep quality, and opioid use. Three trajectories of pain intensity emerged: (1) slow decreases in pain, (2) rapid decreases in pain, and (3) stable or slight increases in pain. Teens with stable pain demonstrated the greatest anxiety levels. Higher sleep quality predicted lower next day pain intensity and pain interference, when controlling for opioid use. Future research should employ intensive longitudinal methodology to further guide intervention development and prevent the transition to chronic pain. [ABSTRACT FROM AUTHOR]

Background: Studies assessing multiple symptoms and the distress of these symptoms in decompensated cirrhosis are lacking. Aims: The aims of this study were to assess symptom prevalence and distress among patients with decompensated cirrhosis and to describe medical management of the most prevalent symptoms. Methods: Patients were recruited from hepatology clinics within two health-care systems. Eligibility criteria included a model for end-stage liver disease (MELD-Na) score ≥15. Patients completed the Condensed Memorial Symptom Assessment Scale and Patient Health Questionnaire. Comparative statistics were used to analyze the cross-sectional survey data. Results: Of the sample (n = 146), most patients were Child-Turcotte-Pugh (CTP) class B (49.7%) and C (46.2%). Mean age was 56.5 years, 65.1% were male, and 88.4% were white. Average MELD-Na score was 19.1 ± 4.5. The most prevalent symptoms were lack of energy and feeling drowsy while the most distressing were lack of energy and difficulty sleeping. Only 24 patients (16.4%) were treated for their difficulty sleeping with sleep medication. Importantly, those prescribed sleep medications had similar distress (3.9 ± 1.2 vs. 3.5 ± 1.2, p = 0.229) compared with patients not prescribed sleep medications. Opioids were prescribed to 57 (39.0%) patients; antidepressants to 34 (23.3%). Forty patients (27.4%) who reported moderate or greater depression were not prescribed an antidepressant. Conclusions: The study highlights the multiple symptoms and distress experienced by patients with decompensated cirrhosis, and the need for improved medical management by health-care providers through enhanced awareness and attention to these complex symptoms. Future research should focus on improvements in symptom management. [ABSTRACT FROM AUTHOR]

Self-assembly and fibril formation play important roles in protein behaviour. Amyloid fibril formation is well-studied due to its role in neurodegenerative diseases and characterized by refolding of the protein into predominantly β-sheet form. However, much less is known about the assembly of proteins into other types of supramolecular structures. Using cryo-electron microscopy at a resolution of 1.97 Å, we show that a triple-mutant of the anti-microbial peptide plectasin, PPI42, assembles into helical non-amyloid fibrils. The in vitro anti-microbial activity was determined and shown to be enhanced compared to the wildtype. Plectasin contains a cysteine-stabilised α-helix-β-sheet structure, which remains intact upon fibril formation. Two protofilaments form a right-handed protein fibril. The fibril formation is reversible and follows sigmoidal kinetics with a pH- and concentration dependent equilibrium between soluble monomer and protein fibril. This high-resolution structure reveals that α/β proteins can natively assemble into fibrils. Here the authors report the cryo-EM structure of a triple-mutant of the anti-microbial peptide plectasin, PPI42, assembling in a pH- and concentration dependent manner into helical non-amyloid fibrils. The fibrils formation is reversible, and follows a sigmoidal kinetics. The fibrils adopt a right-handed helical superstructure composed by two protofilaments, stabilized by an outer hydrophobic ring and an inner hydrophobic centre. These findings reveal that α/β proteins can natively assemble into fibrils. [ABSTRACT FROM AUTHOR]

We prove a version of the Ambrosio–Figalli–Trevisan superposition principle for a restricted subclass of solutions to the Fokker–Planck–Kolmogorov equation that is valid on separable infinite-dimensional Hilbert spaces. Furthermore, we transfer this restricted superposition principle into a nonlinear setting. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Rheumatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In this work we examine how small hydrophobic molecules such as inert gases interact with membrane proteins (MPs) at a molecular level. High pressure atmospheres of argon and krypton were used to produce noble gas derivatives of crystals of three well studied MPs (two different proton pumps and a sodium light-driven ion pump). The structures obtained using X-ray crystallography showed that the vast majority of argon and krypton binding sites were located on the outer hydrophobic surface of the MPs – a surface usually accommodating hydrophobic chains of annular lipids (which are known structural and functional determinants for MPs). In conformity with these results, supplementary in silico molecular dynamics (MD) analysis predicted even greater numbers of argon and krypton binding positions on MP surface within the bilayer. These results indicate a potential importance of such interactions, particularly as related to the phenomenon of noble gas-induced anaesthesia. Noble gases are known to interact with proteins and can be good anaesthetics in hyperbaric conditions. This study identifies argon and krypton binding sites on membrane proteins and proposes as a hypothesis that noble gases, by altering protein/lipid contacts, may affect protein function. [ABSTRACT FROM AUTHOR]

Introduction: Adult brainstem gliomas (BSGs) are rare central nervous system tumours characterized by a highly heterogeneous clinical course. Median survival times range from 11 to 84 months. Beyond surgery, no treatment standard has been established. We investigated clinical and radiological data to assess prognostic features providing support for treatment decisions. Methods: 34 BSG patients treated between 2000 and 2019 and aged ≥ 18 years at the time of diagnosis were retrospectively identified from the databases of the two largest Austrian Neuro-Oncology centres. Clinical data including baseline characteristics, clinical disease course, applied therapies, the outcome as well as neuroradiological and neuropathological findings were gathered and analysed. The tumour apparent diffusion coefficient (ADC), volumetry of contrast-enhancing and non-contrast-enhancing lesions were determined on magnetic resonance imaging scans performed at diagnosis. Results: The median age at diagnosis was 38.5 years (range 18–71 years). Tumour progression occurred in 26/34 (76.5%) patients after a median follow up time of 19 months (range 0.9–236.2). Median overall survival (OS) and progression-free survival (PFS) was 24.1 months (range 0.9–236.2; 95% CI 18.1–30.1) and 14.5 months (range 0.7–178.5; 95% CI 5.1–23.9), respectively. Low-performance status, high body mass index (BMI) at diagnosis and WHO grading were associated with shorter PFS and OS at univariate analysis (p < 0.05, log rank test, respectively). ADC values below the median were significantly associated with shorter OS (14.9 vs 44.2 months, p = 0.018). Conclusion: ECOG, BMI, WHO grade and ADC values were associated with the survival prognosis of BSG patients and should be included in the prognostic assessment. [ABSTRACT FROM AUTHOR]

Purpose: In Germany, Austria, and Switzerland, pretreatment radiotherapy quality control (RT-QC) for tumor bed boost (TB) in non-metastatic medulloblastoma (MB) was not mandatory but was recommended for patients enrolled in the SIOP PNET5 MB trial between 2014 and 2018. This individual case review (ICR) analysis aimed to evaluate types of deviations in the initial plan proposals and develop uniform review criteria for TB boost. Patients and methods: A total of 78 patients were registered in this trial, of whom a subgroup of 65 patients were available for evaluation of the TB treatment plans. Dose uniformity was evaluated according to the definitions of the protocol. Additional RT-QC criteria for standardized review of target contours were elaborated and data evaluated accordingly. Results: Of 65 initial TB plan proposals, 27 (41.5%) revealed deviations of target volume delineation. Deviations according to the dose uniformity criteria were present in 14 (21.5%) TB plans. In 25 (38.5%) cases a modification of the RT plan was recommended. Rejection of the TB plans was rather related to unacceptable target volume delineation than to insufficient dose uniformity. Conclusion: In this analysis of pretreatment RT-QC, protocol deviations were present in a high proportion of initial TB plan proposals. These findings emphasize the importance of pretreatment RT-QC in clinical trials for MB. Based on these data, a proposal for RT-QC criteria for tumor bed boost in non-metastatic MB was developed. [ABSTRACT FROM AUTHOR]

Purpose: Megaprosthetic distal femoral reconstruction (DFR) is a limb-salvage procedure to address bone loss following two-stage revision for periprosthetic knee joint infection (PJI). The purpose of this study was to analyze the survival of DFR compared to hinged total knee arthroplasty (TKA). It was hypothesized that DFR was associated with a poorer survival. Methods: In this retrospective single-center study, 97 subjects who underwent two-stage revision of chronic knee PJI were included. Among these, 41 were DFR. The diagnosis of PJI was established using the Musculoskeletal Infection Society (MSIS) criteria. Implant survival was calculated using Kaplan–Meier method and compared with the log-rank test as well as multivariate Cox regression at a minimum follow-up period of 24 months. Results: The median follow-up period was 59 (interquartile range (IQR) 45–78) months. Overall, 24% (23/97) of patients required revision surgery for infection. The infection-free survival of rotating hinge revision TKA was 93% (95% Confidence Interval (CI) 86–100%) at five years compared to 50% (95% CI 34–66%) for DFR. In multivariate analysis, the risk factors for reinfection were DFR reconstruction (HR 4.7 (95% CI 1–22), p = 0.048), length of megaprosthesis (HR 1.006 (95% CI 1.001–1.012), p = 0.032) and higher BMI (HR 1.066, 95% CI 1.018–1.116), p = 0.007). 10% (4/41) of patients undergoing DFR underwent amputation to treat recurrent infection. Conclusion: Megaprosthetic DFR as part of a two-stage exchange for PJI is a salvage treatment that has a high risk for reinfection compared to non-megaprosthetic TKA. Patients must therefore be counseled accordingly. Level of evidence: Retrospective observational study, Level IV. [ABSTRACT FROM AUTHOR]

The placenta is a central organ during early development, influencing trajectories of health and disease. DNA methylation (DNAm) studies of human placenta improve our understanding of how its function relates to disease risk. However, DNAm studies can be biased by cell type heterogeneity, so it is essential to control for this in order to reduce confounding and increase precision. Computational cell type deconvolution approaches have proven to be very useful for this purpose. For human placenta, however, an assessment of the performance of these estimation methods is still lacking. Here, we examine the performance of a newly available reference-based cell type estimation approach and compare it to an often-used reference-free cell type estimation approach, namely RefFreeEWAS, in placental genome-wide DNAm samples taken at birth and from chorionic villus biopsies early in pregnancy using three independent studies comprising over 1000 samples. We found both reference-free and reference-based estimated cell type proportions to have predictive value for DNAm, however, reference-based cell type estimation outperformed reference-free estimation for the majority of data sets. Reference-based cell type estimations mirror previous histological knowledge on changes in cell type proportions through gestation. Further, CpGs whose variation in DNAm was largely explained by reference-based estimated cell type proportions were in the proximity of genes that are highly tissue-specific for placenta. This was not the case for reference-free estimated cell type proportions. We provide a list of these CpGs as a resource to help researchers to interpret results of existing studies and improve future DNAm studies of human placenta. [ABSTRACT FROM AUTHOR]

Purpose: Lymphovascular invasion (LV1) and presence of > 50% embryonal carcinoma (> 50% EC) represent risk factors for progression in patients with clinical stage 1 (CS1) nonseminomatous (NS) testicular germ cell tumours. As serum levels of microRNA-371a-3p (M371) are capable of detecting small amounts of GCT, we evaluated if LV1 and > 50% EC are associated with M371 levels. Methods: M371 serum levels were measured postoperatively in 153 NS CS1 patients and both pre- and postoperatively in 131 patients. We registered the following factors: age, tumour size, LV status, > 50% EC, teratoma in primary, preoperative elevation of classical tumour markers. M371 expression was compared among subgroups. The ability of M371 to predict LV1 was calculated by receiver operating characteristics (ROC) curves. Multiple regression analysis was used to look for associations of M371 levels with other factors. Results: Postoperatively elevated M371 levels were found in 29.4% of the patients, but were neither associated with LV status nor with > 50% EC. Likewise, relative decrease of M371 was not associated. ROC analysis of postoperative M371 levels revealed an AUC of 0.5 for the ability to predict LV1 while preoperative M371 had an AUC of 0.732. Multiple regression analysis revealed significant associations of preoperative M371 levels with LV status (p = 0.003), tumour size (p = 0.001), > 50% EC (p = 0.004), and teratoma component (p = 0.045). Conclusion: Postoperatively elevated M371 levels are not associated with risk factors for progression in NS CS1 patients. However, the significant association of preoperative M371 expression with LV1 deserves further evaluation. [ABSTRACT FROM AUTHOR]

Purpose: Clinical stage I (CSI) testicular germ cell tumors (TGCT) represents disease confined to the testis without metastasis and CSIS is defined as persistently elevated tumor markers (TM) after orchiectomy, indicating subclinical metastatic disease. This study aims at assessing clinical characteristics and oncological outcome in CSIS. Methods: Data from five tertiary referring centers in Germany were screened. We defined correct classification of CSIS according to EAU guidelines. TM levels, treatment and relapse-free survival were assessed and differences between predefined groups (chemotherapy, correct/incorrect CSIS) were analyzed with Fisher's exact and Chi-square test. Results: Out of 2616 TGCT patients, 43 (1.6%) were CSIS. Thereof, 27 were correctly classified (cCSIS, 1.03%) and 16 incorrectly classified (iCSIS). TMs that defined cCSIS were in 12 (44.4%), 10 (37%), 3 (11.1%) and 2 (7.4%) patients AFP, ß-HCG, AFP plus ß-HCG and LDH, respectively. In the cCSIS group, six patients were seminoma and 21 non-seminoma. Treatment consisted of active surveillance, carboplatin-mono AUC7 and BEP (bleomycin, etoposide and cisplatin). No difference between cCSIS and iCSIS with respect to applied chemotherapy was found (p = 0.830). 5-year relapse-free survival was 88.9% and three patients (11%) in the cCSIS group relapsed. All underwent salvage treatment (3xBEP) with no documented death. Conclusion: Around 1% of all TGCT were classified as cCSIS patients. Identification of cCSIS is of critical importance to avoid disease progression and relapses by adequate treatment. We report a high heterogeneity of treatment patterns, associated with excellent long-term survival irrespective of the initial treatment approach. [ABSTRACT FROM AUTHOR]

Purpose: One of the main issues in testicular germ cell tumors (TGCTs) management is to reduce the necessary amount of treatment to achieve cure. Excess treatment burden may arise from late diagnosis of the primary as well as from false positive or negative staging results. Correct imaging is of paramount importance for successful management of TGCT. The aim of this review is to point out the current state of the art as well as innovative developments in TGCT imaging on the basis of three common challenging clinical situations. Methods: A selective literature search was performed in PubMed, Medline as well as in recent conference proceedings. Results: Regarding small testicular lesions, recent studies using elastography, contrast-enhanced ultrasound or magnetic resonance imaging (MRI) showed promising data for differentiation between benign and malignant histology. For borderline enlarged lymph nodes FDG-PET-CT performance is unsatisfactory, promising new techniques as lymphotropic nanoparticle-enhanced MRI is the subject of research in this field. Regarding the assessment of postchemotherapeutic residual masses, the use of conventional computerized tomography (CT) together with serum tumor markers is still the standard of care. To avoid overtreatment in this setting, new imaging modalities like diffusion-weighted MRI and radiomics are currently under investigation. For follow-up of clinical stage I TGCTs, the use of MRI is non-inferior to CT while omitting radiation exposure. Conclusion: Further efforts should be made to refine imaging for TGCT patients, which is of high relevance for the guidance of treatment decisions as well as the associated treatment burdens and oncological outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Arthrogryposis multiplex congenita (AMC) is a rare congenital condition that leads to severe joint contractures and deformities. As painful joint dysplasia and degeneration might develop over time, total joint replacement (TJR) can be a potential treatment option for these patients. The aim of this study is to investigate functional results, implant survivorship and potential complications in patients with AMC who undergo hip or knee arthroplasty. Materials and methods: We retrospectively identified six TJR in three patients at a single centre performed between 2006 and 2019. The median patient age at surgery was 23 years and the median follow-up period was 69 (IQR 55–99) months. We analysed surgical technique, implant survivorship and complications as well as functional outcome determined by pain reported on the Numerical Rating Scale (NRS), patient-reported outcome scores [Oxford Hip Score (OHS), Harris Hip score (HHS), Oxford Knee Score (OKS)], range of motion and ambulatory status. Depending on data distribution means with ranges and median with interquartile range were compared with the Wilcoxon signed rank test or Student's t test. The level of significance was defined at < 0.05. Results: In hips, the mean range of motion in flexion/extension (52° vs. 85°, p = 0.014) and in rotation (28° vs. 68°, p = 0.02) as well as mean pain score on the NRS (8.5 vs. 0, p = 0.001), OHS (9 vs. 26, p = 0.031) and HHS (17 vs. 52, p = 0.007) significantly improved. In knees, mean range of motion (55° vs. 93°, p = 0.403), mean pain score on the NRS (0 vs. 7) and the OKS (2 vs. 21) also improved. While the ambulatory status did not change, the patients who were wheelchair dependent reported less problems with transfers to a bed or chair and the patient who ambulated reported an improved walking distance. One total knee arthroplasty (TKA) underwent revision for an acute, late infection 155 months following the initial surgery. Conclusions: TJR is a safe procedure in patients with AMC that effectively improves function and reduces pain irrespective of preoperative ambulatory status. [ABSTRACT FROM AUTHOR]