A Combined Cyto- and Histopathological Diagnostic Approach Reduces Time to Diagnosis and Time to Therapy in First Manifestation of Metastatic Spinal Disease: A Cohort Study.

Malignant spinal lesions (MSLs) are frequently the first manifestation of malignant disease. Spinal care, diagnostic evaluation, and the initiation of systemic therapy are crucial for outcomes in patients (pts) with advanced cancer. However, histopathology (HP) may be time consuming. The additional evaluation of spinal lesions using cytopathology (CP) has the potential to reduce the time to diagnosis (TTD) and time to therapy (TTT). CP and HP specimens from spinal lesions were evaluated in parallel in 61 pts (CP/HP group). Furthermore, 139 pts in whom only HP was performed were analyzed (HP group). We analyzed the TTD of CP and HP within the CP/HP group. Furthermore, we compared the TTD and TTT between the groups. The mean TTD in CP was 1.7 ± 1.7 days (d) and 8.4 ± 3.6 d in HP (p < 0.001). In 13 pts in the CP/HP group (24.1%), specific therapy was initiated based on the CP findings in combination with imaging and biomarker results before completion of HP. The mean TTT in the CP/HP group was 21.0 ± 15.8 d and was significantly shorter compared to the HP group (28.6 ± 23.3 d) (p = 0.034). Concurrent CP for MSLs significantly reduces the TTD and TTT. As a result, incorporating concurrent CP for analyzing spinal lesions suspected of malignancy might have the potential to enhance pts' quality of life and prognosis in advanced cancer. Therefore, we recommend implementing CP as a standard procedure for the evaluation of MSLs.

Are Synovial Inflammatory Markers Increased in Patients Who Have Aseptic Total Hip Arthroplasty Dislocation Indicated for Revision?

BACKGROUND: Previous studies have speculated on elevated synovial inflammatory markers in patients undergoing surgical revision for total hip arthroplasty (THA) dislocation. However, this assumption is based on small patient series and a full investigation according to International Consensus Meeting (ICM) criteria has not yet been performed. METHODS: Patients who had aseptic THA dislocation indicated for revision surgery were identified retrospectively. Only patients who had available diagnostic workup according to ICM 2018 criteria, including preoperative and intraoperative parameters, were included. For comparison, we analyzed a matched cohort of patients indicated for aseptic THA revision for other conditions. The 2 cohorts each consisted of 55 patients and were not different regarding age, sex, BMI, or implant fixation. RESULTS: There was no difference in synovial white blood cell count (2,238 ± 2,544 versus 2,533 ± 3,448 c/µL; P = .601), alpha-defensin quotient (0.14 ± 0.11 versus 0.19 ± 0.28; P = .207), or polymorphonuclear neutrophil percentage (% PMN) (36.7 ± 22.6 versus 31.3 ± 24.5%; P = .312) between the groups. In the dislocation cohort, 20% of patients had a synovial white blood cell count of 3,000 c/µL or higher, compared with 18% in the control cohort. However, all patients in the dislocation cohort were below the cutoff for alpha-defensin or % PMN. CONCLUSION: In patients who have aseptic THA dislocation, synovial inflammatory markers are not elevated compared with patients undergoing aseptic revision for other complications. A detailed preoperative analysis of synovial inflammatory markers using ICM criteria appears critical in patients who have a THA dislocation to exclude periprosthetic joint infection. LEVEL OF EVIDENCE: Level III, retrospective, comparative study.

Influence of health literacy on health-related quality of life after total hip arthroplasty.

INTRODUCTION: Personal knowledge about the own disease, a key component of health literacy (HL), may have a considerable impact on treatment outcomes. The purpose of this study was to investigate whether the patients' knowledge about the surgical procedure, risks, and aftercare, as well as the satisfaction with the preoperative level of information, has an influence on the health-related quality of life (HRQoL) after primary total hip arthroplasty (THA). MATERIALS AND METHODS: A total of 176 patients (68.3 ± 10.3 years, 60.8% female) were evaluated. HRQoL was assessed prior to surgery as well as one and twelve months after THA using the 12-item Short Form Questionnaire. Following standardized surgical informed consent, HL was assessed preoperatively using a self-constructed quiz score, while information satisfaction was measured with a single-item rating scale. Sociodemographic and clinical characteristics, including pain (VAS), functionality (WOMAC), and psychological distress (PHQ-4), were also assessed at baseline. Multiple linear regression analyses were performed to examine whether HL, satisfaction with information, age, social class, WOMAC, VAS, and PHQ-4 predict HRQoL at one and twelve months post-surgery. RESULTS: The average HL quiz score was 23 ± 5.1 out of a possible 33 points. Social class index significantly influenced HL (p < 0.001). A weak correlation between HL and age (r = 0.23, p = 0.01) and no correlation between HL and psychological distress (p = 0.868) were observed. One month after THA, physical HRQoL was significantly predicted by the WOMAC index (p = 0.031) and subjective satisfaction with information (p = 0.022), but not by HL. After twelve months, only the WOMAC was a significant predictor (p < 0.001) of physical HRQoL. CONCLUSION: Although subjective satisfaction with the patient's preoperative level of information had a significant effect on the physical HRQoL at one month after THA, the influence of osteoarthritis severity outweighed this effect after twelve months. HL had no direct influence on HRQoL. These results suggest that patient satisfaction, rather than knowledge, predicts HRQoL.

Macromolecular condensation buffers intracellular water potential.

Optimum protein function and biochemical activity critically depends on water availability because solvent thermodynamics drive protein folding and macromolecular interactions1. Reciprocally, macromolecules restrict the movement of 'structured' water molecules within their hydration layers, reducing the available 'free' bulk solvent and therefore the total thermodynamic potential energy of water, or water potential. Here, within concentrated macromolecular solutions such as the cytosol, we found that modest changes in temperature greatly affect the water potential, and are counteracted by opposing changes in osmotic strength. This duality of temperature and osmotic strength enables simple manipulations of solvent thermodynamics to prevent cell death after extreme cold or heat shock. Physiologically, cells must sustain their activity against fluctuating temperature, pressure and osmotic strength, which impact water availability within seconds. Yet, established mechanisms of water homeostasis act over much slower timescales2,3; we therefore postulated the existence of a rapid compensatory response. We find that this function is performed by water potential-driven changes in macromolecular assembly, particularly biomolecular condensation of intrinsically disordered proteins. The formation and dissolution of biomolecular condensates liberates and captures free water, respectively, quickly counteracting thermal or osmotic perturbations of water potential, which is consequently robustly buffered in the cytoplasm. Our results indicate that biomolecular condensation constitutes an intrinsic biophysical feedback response that rapidly compensates for intracellular osmotic and thermal fluctuations. We suggest that preserving water availability within the concentrated cytosol is an overlooked evolutionary driver of protein (dis)order and function.

Synthetic Par polarity induces cytoskeleton asymmetry in unpolarized mammalian cells.

Polarized cells rely on a polarized cytoskeleton to function. Yet, how cortical polarity cues induce cytoskeleton polarization remains elusive. Here, we capitalized on recently established designed 2D protein arrays to ectopically engineer cortical polarity of virtually any protein of interest during mitosis in various cell types. This enables direct manipulation of polarity signaling and the identification of the cortical cues sufficient for cytoskeleton polarization. Using this assay, we dissected the logic of the Par complex pathway, a key regulator of cytoskeleton polarity during asymmetric cell division. We show that cortical clustering of any Par complex subunit is sufficient to trigger complex assembly and that the primary kinetic barrier to complex assembly is the relief of Par6 autoinhibition. Further, we found that inducing cortical Par complex polarity induces two hallmarks of asymmetric cell division in unpolarized mammalian cells: spindle orientation, occurring via Par3, and central spindle asymmetry, depending on aPKC activity.

The Use of Intraoperative Cell Salvage in Two-Stage Revision of Septic Hip Arthroplasties: A Double-Center Retrospective Study.

(1) Background: intraoperative cell salvage (ICS) devices can provide a valuable contribution to patient blood management. An infection of the surgical site presents a formal contraindication to the use of ICS. To date, there is no recommendation for the use of ICS in the context of reimplantation in two-stage septic exchange arthroplasty. (2) Methods: at two hospitals of maximum endoprosthetic care, a retrospective evaluation of patients who had received ICS blood during reimplantation of hip arthroplasties was performed. Patients' and surgical characteristics, intraoperative cultures, and the occurrence of septic complications in the short- and long-term follow-up were recorded. (3) Results: 144 patients were included. Detection of positive cultures during reimplantation occurred in 13 cases. A total of 127 patients showed no complication, 8 patients showed a non-specific septic complication, 6 patients a local persistence of infection, and 3 patients a possible bloodstream-associated infection. No significant correlation was found between the occurrence of complications and the detection of positive intraoperative cultures. (4) Conclusions: no clustering of septic complications due to the use of ICS during reimplantation was found. In the risk-benefit analysis, we considered the use of ICS during reimplantation to be indicated in terms of patient blood management, while the safety of the procedure during septic first-stage resection arthroplasty or septic one-stage exchange arthroplasty was not investigated. Given the paucity of comparative literature, further studies are needed on ideal patient blood management in the setting of septic revision arthroplasty.

Double level osteotomy for medial osteoarthritis and bifocal varus malalignment has excellent short-term results while maintaining physiologic radiographic joint parameters.

PURPOSE: The purpose of this study was to prospectively evaluate the clinical and radiological results of double level osteotomy (distal femoral lateral closed wedge and proximal tibial medial open wedge) in medial osteoarthritis and varus malalignment due to bifocal deformity of femur and tibia. METHODS: From 2017 to 2019 all cases of DLO in osteoarthritic varus malaligned knees with bifocal deformity (femoral and tibial deformity) were prospectively enrolled into this observational therapeutic study. Evaluation was performed preoperatively, at six, twelve, 18 and 24 months with regard to survival (not requiring arthroplasty), functional outcome [subjective International Knee Documentation Committee score (IKDC), Oxford Knee Score (OKS), Knee Injury and Osteoarthritis Outcome score (KOOS) and Tegner Activity Scale], pain level (numeric rating scale), subjective satisfaction (rating 1-5), radiographic parameters on a pre-and postoperative full leg x-rays (mechanical axis, mechanical proximal tibial and distal femoral angles) and complications. For statistical evaluation student's t test, Mann-Whitney U test and Wilcoxon-signed-rank test were used. RESULTS: Fifty-two consecutive cases in 48 patients were enrolled in the study. Three cases were excluded, resulting in a follow-up rate of 94%. No arthroplasties were performed within follow-up. All functional outcome scores substantially and significantly increased as early as six months after the index procedure and further increased until final follow-up (p < 0.001). Pain level significantly decreased (p < 0.001). At final follow-up all patients stated that they would retrospectively undergo the operation again, and rated the result with 4.5 ± 0.6 out of 5 (3-5). Radiographic parameters were within physiological limits postoperatively. No severe complications occurred. CONCLUSIONS: Double level osteotomy has excellent short-term results while maintaining physiological radiographic parameters. Therefore, it should be an integral part and standard procedure in realignment surgery for monocompartimental osteoarthritis. LEVEL OF EVIDENCE: IV (prospective observational therapeutic study).

Reliability, validity and clinical applicability of the German version of the European Foot and Ankle Society Score.

BACKGROUND: Purpose of this study was an external evaluation of the recently developed European Foot and Ankle Society (EFAS) Score. METHODS: From July 2021 to January 2022, all consecutive patients with foot and ankle disorders were asked to complete three validated questionnaires prior to the medical examination. Validity was evaluated with correlations between the EFAS Score, Manchester-Oxford Foot Questionnaire (MOxFQ) and Foot and Ankle Outcome Score (FAOS). Cronbach's alpha, floor and ceiling effects and the minimal important difference (MID) were determined. RESULTS: In a total of 161 included patients, the EFAS Score demonstrated a very good correlation with the MOxFQ index score (r = 0.76, p < 0.001). There were no floor or ceiling effects. Cronbach's alpha was 0.863, and the MID amounts 3 points and 7 points for significant changes respectively. CONCLUSION: In terms of reliability and validity, the EFAS Score demonstrated good to excellent psychometric values. A change of 7 points or more in the EFAS Score in longitudinal examinations is clinically highly relevant.

Self-efficacy in relation to the use of complementary and alternative medicine, lifestyle choices and cancer aetiology.

PURPOSE: This survey assesses cancer patients' etiological concepts, lifestyle choices, use of complementary and alternative medicine (CAM), and self-efficacy, as well as associations between those. It aims to find patterns which may facilitate communication and understanding between patients and physicians. METHODS: 353 oncological patients attending lectures on CAM answered a questionnaire. Correlations were examined and an exploratory factor analysis conducted to identify comprehensive lay-etiological concepts among a list of potential carcinogenic factors. RESULTS: Patients considered scientifically proven agents as well as other non-carcinogenic influences to be responsible for their disease. An exploratory factor analysis yielded vague indications of possible underlying concepts but factors tend to include items that do not fit the pattern in terms of content. Higher self-efficacy correlated with healthy diet and sports, but not with use of CAM. No conclusive correlations emerged between lay-aetiological concepts and most other variables, but we found a tendency for higher self-efficacy among patients who assigned higher carcinogenic effects to tobacco and lower carcinogenic effects to fasting and physical trauma. CONCLUSION: Interest in CAM can arise for many reasons that are not necessarily related to self-efficacy. Lay-aetiological concepts of cancer differ significantly from scientific ones. They are complex and presumably highly individualistic. Their connection to use of CAM methods, lifestyle choices and self-efficacy should be explored in more detail. Patient information and communication with clinicians need to address cancer patients' individual aetiological concepts to further patient's understanding not only of their diagnosis but also of the treatment as well.

Transcription-wide mapping of dihydrouridine reveals that mRNA dihydrouridylation is required for meiotic chromosome segregation.

The epitranscriptome has emerged as a new fundamental layer of control of gene expression. Nevertheless, the determination of the transcriptome-wide occupancy and function of RNA modifications remains challenging. Here we have developed Rho-seq, an integrated pipeline detecting a range of modifications through differential modification-dependent rhodamine labeling. Using Rho-seq, we confirm that the reduction of uridine to dihydrouridine (D) by the Dus reductase enzymes targets tRNAs in E. coli and fission yeast. We find that the D modification is also present on fission yeast mRNAs, particularly those encoding cytoskeleton-related proteins, which is supported by large-scale proteome analyses and ribosome profiling. We show that the α-tubulin encoding mRNA nda2 undergoes Dus3-dependent dihydrouridylation, which affects its translation. The absence of the modification on nda2 mRNA strongly impacts meiotic chromosome segregation, resulting in low gamete viability. Applying Rho-seq to human cells revealed that tubulin mRNA dihydrouridylation is evolutionarily conserved.

Kinesin-6 Klp9 orchestrates spindle elongation by regulating microtubule sliding and growth.

Mitotic spindle function depends on the precise regulation of microtubule dynamics and microtubule sliding. Throughout mitosis, both processes have to be orchestrated to establish and maintain spindle stability. We show that during anaphase B spindle elongation in Schizosaccharomyces pombe, the sliding motor Klp9 (kinesin-6) also promotes microtubule growth in vivo. In vitro, Klp9 can enhance and dampen microtubule growth, depending on the tubulin concentration. This indicates that the motor is able to promote and block tubulin subunit incorporation into the microtubule lattice in order to set a well-defined microtubule growth velocity. Moreover, Klp9 recruitment to spindle microtubules is dependent on its dephosphorylation mediated by XMAP215/Dis1, a microtubule polymerase, creating a link between the regulation of spindle length and spindle elongation velocity. Collectively, we unravel the mechanism of anaphase B, from Klp9 recruitment to the motors dual-function in regulating microtubule sliding and microtubule growth, allowing an inherent coordination of both processes.

[Difficulties in diagnosing an osteoid osteoma of the big toe : A case report with review of the literature]. / Erschwerte Diagnosestellung eines Osteoidosteoms der Großzehe : Fallbericht mit Review der Literatur.

BACKGROUND: Osteoid osteomas belong to the benign osseous neoplasia and can occur on the entire skeleton. The prolonged diagnosis of an osteoid osteoma of the great toe prompted us to prepare a case report with a literature review to identify possible sources of error and to contribute to a more expeditious diagnosis and therapy. LITERATURE: Currently, only two case reports on osteoid osteomas of the toes are known in the German literature. Internationally, however, a large number of cases have been described, which, when viewed as a whole, present a homogeneous picture. A very clear accumulation of osteoid osteomas at the distal phalanx of the great toe suggests a possible post-traumatic aetiology. The typical NSAID-sensitive night pain is clinically unambiguous and should make one think of an osteoid osteoma at any site on the body. The symptom of macrodactyly, which is unique to the toes, is striking and may provide a helpful clue to establishing the diagnosis. The median time from symptom onset to correct diagnosis was 12 months. One possible reason for this prolonged diagnosis is the often atypical and ambiguous imaging. Surgical therapy is the method of choice for osteoid osteomas of the toes and should always be supplemented by histopathologic examination.

[Injuries in German Paralympic alpine skiing over 25 years]. / Verletzungen im deutschen paralympischen Ski Alpin über einen 25-jährigen Zeitraum.

INTRODUCTION: Despite the size of the Paralympic Games and the large number of people with disabilities, there is a lack of studies on (high-performance) Paralympic sports. Major injuries in the German Paralympic Alpine Skiing Team have been recorded and presented in this retrospective cohort study. PATIENTS AND METHODS: All major injuries in competition and training of the German Paralympic Ski Team were recorded over 25 years. A descriptive statistic evaluation was performed. RESULTS: Major injuries were sustained by 22 of 94 athletes (23 %). These included 12 (55 %) "sitting" athletes, 9 (41 %) "standing" athletes and one "visually impaired" athlete (5 %). The most common injuries were upper extremity injuries (n = 9, 41 %), especially of the shoulder (n = 8, 36 %). Seated athletes were particularly prone to shoulder injuries. The most dangerous disciplines by far were the speed disciplines Downhill and Super-G (n = 17, 77 %). The average injury rate was 7 % of the athletes per year. In our cohort, the highest absolute number of athletes got injured during the 1998 Paralympic Games in Nagano (n = 4). The highest injury rate, however, was observed during the Sotchi 2014 Paralympic Games (33 %). DISCUSSION: The current literature indicates that, contrary to previous assumptions, the risk of sustaining an injury seems to be higher in Paralympic athletes compared with Olympic athletes. Sitting athletes, in particular, have an increased risk of injury. They should be given special consideration when implementing preventive measures. An intensified training of the core muscles seems to be essential. Technical equipment such as the mono-ski bob deserves special attention to ensure safe usage. Shoulder injuries are particularly frequent and, at the same time, particularly debilitating for seated athletes. Careful strength training of the shoulder seems to be indispensable. In order to reduce the frequency and severity of injuries, the further development of preventive measures is essential. We think that the Paralympic sport should be further professionalized. CONCLUSIONS: Sitting athletes show an increased injury rate and tend to have shoulder injuries, which often have a debilitating effect on an athlete's everyday life. We consider the further development of preventive measures to be essential for the future of Paralympic sport.

Spindle scaling mechanisms.

The mitotic spindle robustly scales with cell size in a plethora of different organisms. During development and throughout evolution, the spindle adjusts to cell size in metazoans and yeast in order to ensure faithful chromosome separation. Spindle adjustment to cell size occurs by the scaling of spindle length, spindle shape and the velocity of spindle assembly and elongation. Different mechanisms, depending on spindle structure and organism, account for these scaling relationships. The limited availability of critical spindle components, protein gradients, sequestration of spindle components, or post-translational modification and differential expression levels have been implicated in the regulation of spindle length and the spindle assembly/elongation velocity in a cell size-dependent manner. In this review, we will discuss the phenomenon and mechanisms of spindle length, spindle shape and spindle elongation velocity scaling with cell size.

Kinesin-6 regulates cell-size-dependent spindle elongation velocity to keep mitosis duration constant in fission yeast.

The length of the mitotic spindle scales with cell size in a wide range of organisms during embryonic development. Interestingly, in C. elegans embryos, this goes along with temporal regulation: larger cells speed up spindle assembly and elongation. We demonstrate that, similarly in fission yeast, spindle length and spindle dynamics adjust to cell size, which allows to keep mitosis duration constant. Since prolongation of mitosis was shown to affect cell viability, this may resemble a mechanism to regulate mitosis duration. We further reveal how the velocity of spindle elongation is regulated: coupled to cell size, the amount of kinesin-6 Klp9 molecules increases, resulting in an acceleration of spindle elongation in anaphase B. In addition, the number of Klp9 binding sites to microtubules increases overproportionally to Klp9 molecules, suggesting that molecular crowding inversely correlates to cell size and might have an impact on spindle elongation velocity control.

Assessing the risk for major injuries in equestrian sports.

BACKGROUND/AIM: Horse riding is a popular sport, which bears the risk of serious injuries. This study aims to assess whether individual factors influence the risk to sustain major injuries. METHODS: Retrospective data were collected from all equine-related accidents at a German Level I Trauma Centre between 2004 and 2014. Logistic regression was used to identify the risk factors for major injures. RESULTS: 770 patients were included (87.9% females). Falling off the horse (67.7%) and being kicked by the horse (16.5%) were the two main injury mechanisms. Men and individuals of higher age showed higher odds for all tested parameters of serious injury. Patients falling off a horse had higher odds for being treated as inpatients, whereas patients who were kicked had higher odds for a surgical therapy (OR 1.7) and intensive care unit/intermediate care unit (ICU/IMC) treatment (OR 1.2). The head was the body region most often injured (32.6%) and operated (32.9%). Patients with head injuries had the highest odds for being hospitalised (OR 6.13). Head or trunk injuries lead to the highest odds for an ICU/IMC treatment (head: OR 4.37; trunk: OR 2.47). Upper and lower limb injuries showed the highest odds for a surgical therapy (upper limb: OR 2.61; lower limb: OR 1.7). CONCLUSION: Risk prevention programmes should include older individuals and males as target groups. Thus a rethinking of the overall risk assessment is necessary. Not only horseback riding itself, but also handling a horse bears a relevant risk for major injuries. Serious head injures remain frequent, serious and an important issue to be handled in equestrians sports.

Waterpipe and Cigarette Smoking among University Students in the Western Cape, South Africa.

OBJECTIVE: Cigarette smoking in South Africa decreased sharply since the early 1990s. Waterpipe smoking increased, especially among students. We estimate the prevalence of waterpipe and cigarette smoking and associated characteristics among university students in the Western Cape. METHODS: An anonymous self-administered online questionnaire was sent to all registered students at 4 public Western Cape universities. The 4578 valid responses were weighted to represent the Western Cape's university student population. We present descriptive statistics and logistic regressions. RESULTS: We found that 63% of Western Cape university students ever smoked waterpipe, 9.9% of students smoked waterpipe in the past 30 days and 17.7% of students smoked cigarettes in the past 30 days. Waterpipe smoking has a strong socialization aspect. Controlling for confounders, current waterpipe smoking is associated with alcohol consumption (positively), age (negatively), population group (mixed-race and Indian students smoke more), religion (Muslims smoke more), faculty (medical students smoke less), and spending money (positively). Current cigarette smoking is associated with similar covariates, but not with age. CONCLUSION: Waterpipe smoking in the Western Cape is widespread, but less than cigarette smoking. Because all tobacco products are harmful, the government has an obligation to impose appropriate regulatory measures to reduce waterpipe consumption.