Development of a Machine Learning-Based Model to Predict Timed-Up-and-Go Test in Older Adults.

INTRODUCTION: The measurement of physical frailty in elderly patients with orthopedic impairments remains a challenge due to its subjectivity, unreliability, time-consuming nature, and limited applicability to uninjured individuals. Our study aims to address this gap by developing objective, multifactorial machine models that do not rely on mobility data and subsequently validating their predictive capacity concerning the Timed-up-and-Go test (TUG test) in orthogeriatric patients. METHODS: We utilized 67 multifactorial non-mobility parameters in a pre-processing phase, employing six feature selection algorithms. Subsequently, these parameters were used to train four distinct machine learning algorithms, including a generalized linear model, a support vector machine, a random forest algorithm, and an extreme gradient boost algorithm. The primary goal was to predict the time required for the TUG test without relying on mobility data. RESULTS: The random forest algorithm yielded the most accurate estimations of the TUG test time. The best-performing algorithm demonstrated a mean absolute error of 2.7 s, while the worst-performing algorithm exhibited an error of 7.8 s. The methodology used for variable selection appeared to exert minimal influence on the overall performance. It is essential to highlight that all the employed algorithms tended to overestimate the time for quick patients and underestimate it for slower patients. CONCLUSION: Our findings demonstrate the feasibility of predicting the TUG test time using a machine learning model that does not depend on mobility data. This establishes a basis for identifying patients at risk automatically and objectively assessing the physical capacity of currently immobilized patients. Such advancements could significantly contribute to enhancing patient care and treatment planning in orthogeriatric settings.

Evaluation of a New Treatment Strategy for Geriatric Fragility Fractures of the Posterior Pelvic Ring Using Sensor-Supported Insoles: A Proof-of-Concept Study.

The incidence of fragility fractures of the pelvis (FFPs) is currently rising. Surgical treatment, which is performed using sacroiliac screws, is complicated by compromised bone quality, oftentimes resulting in implant failure. The iFuse implant system aims to improve attachment and durability with promising results for sacroiliac dysfunction, though data for its feasibility on FFPs are rare. Consequently, this study aims to evaluate the feasibility of the iFuse for FFPs. A total of 10 patients with FFPs were treated with the iFuse in this study. Pre- and postoperatively, both mobility using an established insole force sensor for an inpatient gait analysis and general well-being and pain using questionnaires were evaluated. When comparing pre- and postoperative findings, this study demonstrated a significant increase in the average (8.14%) and maximum (9.4%) loading (p < 0.001), a reduction in pain, as measured by the visual analog scale (VAS), from 4.60 to 2.80 at rest (p = 0.011) and from 7.00 to 4.40 during movement (p = 0.008), an increase in the Barthel Index by 20 points (p < 0.001) and an increase in the Parker Mobility Score by 2.00 points (p = 0.011). All this contributes to the possibility of early postoperative mobilization and improved general well-being, ultimately preventing the late consequences of postoperative immobilization and maintaining patients autonomy and contentment.

Predictive Value of Prognostic Nutritional Index for Early Postoperative Mobility in Elderly Patients with Pertrochanteric Fracture Treated with Intramedullary Nail Osteosynthesis.

BACKGROUND: Early postoperative mobilization is essential for orthogeriatric patients. The prognostic nutritional index (PNI) is widely used to evaluate nutritional status. This study sought to investigate the predictive value of PNI for early postoperative mobility in patients with pertrochanteric femur fractures. MATERIALS AND METHODS: This study included 156 geriatric patients with pertrochanteric femur fractures treated with TFN-Advance™ (DePuy Synthes, Raynham, MA, USA). Mobility was evaluated on the third postoperative day and by discharge. Stepwise logistic regression analyses were performed to evaluate the association significance of PNI with postoperative mobility together with comorbidities. The optimal PNI cut-off value for mobility was analyzed using the receiver operating characteristic (ROC) curve. RESULTS: Three days postoperatively, PNI was an independent predictor of mobility (OR: 1.14, 95% CI: 1.07-1.23, p < 0.01). By discharge, it was found that PNI (OR: 1.18, 95% CI: 1.08-1.30, p < 0.01) and dementia (OR: 0.17, 95% CI: 0.07-0.40, p < 0.001) were significant predictors. PNI correlated weakly with age (r = -0.27, p < 0.001). The PNI cut-off value for mobility on the third postoperative day was 38.1 (specificity = 78.5%, sensitivity = 63.6%). CONCLUSIONS: Our findings indicate that PNI is an independent predictor of early postoperative mobility in geriatric patients with pertrochanteric femur fractures treated with TFNA™.

Cell-Cell Signaling Proteobacterial LuxR Solos: a Treasure Trove of Subgroups Having Different Origins, Ligands, and Ecological Roles.

Many proteobacteria possess LuxR solos which are quorum sensing LuxR-type regulators that are not paired with a cognate LuxI-type synthase. LuxR solos have been implicated in intraspecies, interspecies, and interkingdom communication by sensing endogenous and exogenous acyl-homoserine lactones (AHLs) as well as non-AHL signals. LuxR solos are likely to play a major role in microbiome formation, shaping, and maintenance through many different cell-cell signaling mechanisms. This review intends to assess the different types and discuss the possible functional roles of the widespread family of LuxR solo regulators. In addition, an analysis of LuxR solo types and variability among the totality of publicly available proteobacterial genomes is presented. This highlights the importance of these proteins and will encourage scientists to mobilize and study them in order to increase our knowledge of novel cell-cell mechanisms that drive bacterial interactions in the context of complex bacterial communities.

Changing patterns in the epidemiology of tibial plateau fractures: a 10-year review at a level-I trauma center.

PURPOSE: Mobility patterns of western societies have been changing due to ongoing demographic change. Therefore, continuously updated epidemiological data on fracture morphology and treatment strategies are needed. METHODS: This retrospective single-center study included all tibial plateau fractures (TPF) between January 2011 and December 2020 in a level-I trauma center in Central Europe. Epidemiology, trauma mechanism and fracture morphology were analyzed. Age- and sex-specific differences regarding fracture classification (Schatzker, AO/OTA, Moore) and changes during the study period are highlighted. RESULTS: A total of 607 patients (55.2% women, 44.8% men, mean age 52.9 years (± 17.9)) were included in the study, 462 (76.1%) thereof having undergone surgical treatment. Over the decade, an increase in mean age (+ 7.4 years; p = 0.10), incidence (+ 68%; p < 0.05) and low-energy trauma was observed, with the highest peak in elderly women. Within classifications, AO/OTA 41-B3 (24.9%), Schatzker II (26.8%) and Moore V (46.6%) fractures were the most common. CONCLUSION: Incidence (+ 68%), mean age and fractures with signs of knee dislocation of tibial plateau fracture increased over the last decade and low-energy trauma mechanism are more frequent. As the increase in incidence is mainly seen in older women, the comorbidities and need for immediate postoperative full weight-bearing have to be considered in treatment strategies.

[Influence of the COVID-19 pandemic on fracture epidemiology exemplified by tibial plateau fractures]. / Einfluss der COVID-19-Pandemie auf die Frakturepidemiologie am Beispiel der Tibiaplateaufraktur.

BACKGROUND: During the COVID-19 pandemic interventions, such as contact restrictions, lockdowns and postponement of elective surgeries were taken to ease the burden on the healthcare system. Among the population, these interventions led to changes in recreational behavior as well as personal transportation. OBJECTIVE: This paper examines the epidemiological data of tibial plateau fractures (TPF) before and during the pandemic and to what extent pandemic control measures had an impact. MATERIAL AND METHODS: In this retrospective monocentric study of a German level 1 trauma center, the intra-articular tibial plateau fractures of the years 2019 and 2020 were compared regarding incidence, demographics, cause of the accident, and treatment strategy. Fracture classification was according to Schatzker, AO/OTA, and Moore. RESULTS: Incidence showed a decrease of -8.5% as well as a shift in the age incidence curves. There was a decrease in incidence during lockdown periods but also an increase in late summer 2020 compared to 2019. Tripping accidents (+12.4%) and bicycle accidents (+6.6%) increased in the pandemic year, whereas motorized traffic accidents (-7%) and skiing accidents (-10%) decreased. In terms of fracture morphology, 2020 showed an increase in impression fractures and a decrease in complex fractures. The number of surgically treated patients decreased by 7.3%. CONCLUSION: The 12 months of pandemic resulted in only a slight incidence decrease of intra-articular tibial plateau fractures. The pandemic control measures showed effects within the calendar year and led directly and indirectly to a change in incidence, cause of the accident, fracture entities and care strategy.

Reduced Awareness for Osteoporosis in Hip Fracture Patients Compared to Elderly Patients Undergoing Elective Hip Replacement.

Background: Osteoporotic fractures are associated with a loss of quality of life, but only few patients receive an appropriate therapy. Therefore, the present study aims to investigate the awareness of musculoskeletal patients to participate in osteoporosis assessment and to evaluate whether there are significant differences between acute care patients treated for major fractures of the hip compared to elective patients treated for hip joint replacement.; Methods: From May 2015 to December 2016 patients who were undergoing surgical treatment for proximal femur fracture or total hip replacement due to osteoarthritis and were at risk for an underlying osteoporosis (female > 60 and male > 70 years) were included in the study and asked to complete a questionnaire assessing the awareness for an underlying osteoporosis. ASA Score, FRAX Score, and demographic information have also been examined. Results: In total 268 patients (female = 194 (72.0%)/male = 74 (28%)), mean age 77.7 years (±7.7) undergoing hip surgery were included. Of these, 118 were treated for fracture-related etiology and 150 underwent total hip arthroplasty in an elective care setting. Patients were interviewed about their need for osteoporosis examination during hospitalization. Overall, 76 of 150 patients receiving elective care (50.7%) considered that an examination was necessary, whereas in proximal femur fracture patients the awareness was lower, and the disease osteoporosis was assessed as threatening by significantly fewer newly fractured patients. By comparison, patients undergoing trauma surgery had a considerably greater risk of developing another osteoporotic fracture than patients undergoing elective surgery determined by the FRAX® Score (p ≤ 0.001).; Conclusions: The patients' motivation to endure additional osteoporosis diagnostic testing is notoriously low and needs to be increased. Patients who underwent acute care surgery for a fragility proximal femur fracture, although acutely affected by the potential consequences of underlying osteoporosis, showed lower awareness than the elective comparison population that was also on average 6.1 years younger. Although elective patients were younger and at a lower risk, they seemed to be much more willing to undergo further osteoporosis assessment. In order to better identify and care for patients at risk, interventions such as effective screening, early initiation of osteoporosis therapy in the inpatient setting and a fracture liaison service are important measures.

Cardiac PI3K p110α attenuation delays aging and extends lifespan.

Phosphoinositide 3-kinase (PI3K) is a key component of the insulin signaling pathway that controls cellular me-tabolism and growth. Loss-of-function mutations in PI3K signaling and other downstream effectors of the insulin signaling pathway extend the lifespan of various model organisms. However, the pro-longevity effect appears to be sex-specific and young mice with reduced PI3K signaling have increased risk of cardiac disease. Hence, it remains elusive as to whether PI3K inhibition is a valid strategy to delay aging and extend healthspan in humans. We recently demonstrated that reduced PI3K activity in cardiomyocytes delays cardiac growth, causing subnormal contractility and cardiopulmonary functional capacity, as well as increased risk of mortality at young age. In stark contrast, in aged mice, experi-mental attenuation of PI3K signaling reduced the age-dependent decline in cardiac function and extended maximal lifespan, suggesting a biphasic effect of PI3K on cardiac health and survival. The cardiac anti-aging effects of reduced PI3K activity coincided with enhanced oxida-tive phosphorylation and required increased autophagic flux. In humans, explanted failing hearts showed in-creased PI3K signaling, as indicated by increased phos-phorylation of the serine/threonine-protein kinase AKT. Hence, late-life cardiac-specific targeting of PI3K might have a therapeutic potential in cardiac aging and related diseases.

Methanol utilizers of the rhizosphere and phyllosphere of a common grass and forb host species.

BACKGROUND: Managed grasslands are global sources of atmospheric methanol, which is one of the most abundant volatile organic compounds in the atmosphere and promotes oxidative capacity for tropospheric and stratospheric ozone depletion. The phyllosphere is a favoured habitat of plant-colonizing methanol-utilizing bacteria. These bacteria also occur in the rhizosphere, but their relevance for methanol consumption and ecosystem fluxes is unclear. Methanol utilizers of the plant-associated microbiota are key for the mitigation of methanol emission through consumption. However, information about grassland plant microbiota members, their biodiversity and metabolic traits, and thus key actors in the global methanol budget is largely lacking. RESULTS: We investigated the methanol utilization and consumption potentials of two common plant species (Festuca arundinacea and Taraxacum officinale) in a temperate grassland. The selected grassland exhibited methanol formation. The detection of 13C derived from 13C-methanol in 16S rRNA of the plant microbiota by stable isotope probing (SIP) revealed distinct methanol utilizer communities in the phyllosphere, roots and rhizosphere but not between plant host species. The phyllosphere was colonized by members of Gamma- and Betaproteobacteria. In the rhizosphere, 13C-labelled Bacteria were affiliated with Deltaproteobacteria, Gemmatimonadates, and Verrucomicrobiae. Less-abundant 13C-labelled Bacteria were affiliated with well-known methylotrophs of Alpha-, Gamma-, and Betaproteobacteria. Additional metagenome analyses of both plants were consistent with the SIP results and revealed Bacteria with methanol dehydrogenases (e.g., MxaF1 and XoxF1-5) of known but also unusual genera (i.e., Methylomirabilis, Methylooceanibacter, Gemmatimonas, Verminephrobacter). 14C-methanol tracing of alive plant material revealed divergent potential methanol consumption rates in both plant species but similarly high rates in the rhizosphere and phyllosphere. CONCLUSIONS: Our study revealed the rhizosphere as an overlooked hotspot for methanol consumption in temperate grasslands. We further identified unusual new but potentially relevant methanol utilizers besides well-known methylotrophs in the phyllosphere and rhizosphere. We did not observe a plant host-specific methanol utilizer community. Our results suggest that our approach using quantitative SIP and metagenomics may be useful in future field studies to link gross methanol consumption rates with the rhizosphere and phyllosphere microbiome.

Impact of keel saw blade design and thickness on the incidence of tibial plateau fracture and tibial implant-loosening in cementless medial UKR.

BACKGROUND: Tibial plateau fractures and tibial implant- loosening are severe complications in cementless unicompartmental knee replacement (UKR). The tibial keel preparation is particularly demanding and different saw blades can be used. It was hypothesized that different blade designs and thickness have an influence on the frequency of tibial plateau fractures and implant-loosening in cementless medial UKR. METHODS: 1258 patients with cementless medial UKR were included in this retrospective study between 2013 and 2020. The tibial keel cut was performed either with a double keel saw blade (DKS; 2.8 mm) and added hand guided pick or a mono reciprocating saw blade (RKB) of different thickness (2.5 mm; 2.65 mm; 2.75 mm). Tibial plateau fracture and loosening were demonstrated by standard two-plane radiographs. Tibial implant-loosening was defined as complete radiolucency and implant migration. Fracture and loosening were combined with pain and loss of function. RESULTS: In 126 patients (10%) the tibial keel was prepared with DKS, in 407 patients (32.4%) with RKB 2.5 mm, in 330 patients (26.2%) with RKB 2.65 mm and in 395 patients (31.4%) with 2.75 mm. In 4 patients (3.17%) with DKS tibial plateau fracture occurred, in 4 patients (0.99%) with 2.5 mm RKB, in 3 patients (0.92%) with 2.65 mm RKB and in 1 patient (0.25%) with 2.75 mm RKB. Significantly fewer fractures occurred with a RKB design (p = 0.007). A negative correlation between fracture incidence and RKB saw blade thickness was found (Spearman-r = - 0.93). No difference for tibial implant-loosening was shown (p = 0.51). CONCLUSION: Different blade designs and thickness have a significant influence on the incidence of tibial plateau fractures and aseptic tibial implant-loosening. The incidence of tibial plateau fractures in cementless medial UKR can be reduced by changing the design and thickness of the tibial keel saw blade. Greater thickness of RKB leads to significantly fewer tibial plateau fractures while the incidence of implant-loosening is not increasing. TRIAL REGISTRATION: This study was retrospectively registered and ethical approval was waived by the local ethical committee (No. 2020-1174).

Fine-Tuning Cardiac Insulin-Like Growth Factor 1 Receptor Signaling to Promote Health and Longevity.

BACKGROUND: The insulin-like growth factor 1 (IGF1) pathway is a key regulator of cellular metabolism and aging. Although its inhibition promotes longevity across species, the effect of attenuated IGF1 signaling on cardiac aging remains controversial. METHODS: We performed a lifelong study to assess cardiac health and lifespan in 2 cardiomyocyte-specific transgenic mouse models with enhanced versus reduced IGF1 receptor (IGF1R) signaling. Male mice with human IGF1R overexpression or dominant negative phosphoinositide 3-kinase mutation were examined at different life stages by echocardiography, invasive hemodynamics, and treadmill coupled to indirect calorimetry. In vitro assays included cardiac histology, mitochondrial respiration, ATP synthesis, autophagic flux, and targeted metabolome profiling, and immunoblots of key IGF1R downstream targets in mouse and human explanted failing and nonfailing hearts, as well. RESULTS: Young mice with increased IGF1R signaling exhibited superior cardiac function that progressively declined with aging in an accelerated fashion compared with wild-type animals, resulting in heart failure and a reduced lifespan. In contrast, mice with low cardiac IGF1R signaling exhibited inferior cardiac function early in life, but superior cardiac performance during aging, and increased maximum lifespan, as well. Mechanistically, the late-life detrimental effects of IGF1R activation correlated with suppressed autophagic flux and impaired oxidative phosphorylation in the heart. Low IGF1R activity consistently improved myocardial bioenergetics and function of the aging heart in an autophagy-dependent manner. In humans, failing hearts, but not those with compensated hypertrophy, displayed exaggerated IGF1R expression and signaling activity. CONCLUSIONS: Our findings indicate that the relationship between IGF1R signaling and cardiac health is not linear, but rather biphasic. Hence, pharmacological inhibitors of the IGF1 pathway, albeit unsuitable for young individuals, might be worth considering in older adults.

The grade of instability in fragility fractures of the pelvis correlates with impaired early mobilization.

PURPOSE: This study aimed to investigate whether gait patterns of patients with fragility fractures of the pelvis (FFP) comply with the grade of fracture instability, defined by radiological patterns. PATIENTS AND METHODS: This prospective, single-center, observational study included 39 patients with an FFP. Gait analysis was performed with a wearable insole force sensor (Loadsol® by Novel, Munich, Germany) 4-7 days after admission. Patients were divided in two groups: Group A included FFP type 1 fractures, which affect the anterior pelvic ring only, Group B contained FFP type 2-4 fractures with an involvement of the posterior pelvic ring. Primary outcome parameter was the FTI ratio (force-time integral (N*s)). RESULTS: The mean age was 85.08 years (SD ± 6.45), 94.9% (37/39) of the patients were female. The most common fracture type was an FFP 2b (64.1%, 25/39). Group A showed a significantly higher FTI ratio (45.12%, SD ± 4.19%) than Group B (38.45%, SD ± 5.97%, p = 0.002). Further, a significant correlation of the FTI ratio and the average (r = 0.570, p < 0.001) and maximum (r = 0.394, p = 0.013) peak force was observed. CONCLUSION: The gait pattern of patients with an FFP type 2-4 was more imbalanced than of patients with an FFP type 1 fracture. These findings match with the radiological classification of FFP, which indicates higher instability, when the posterior pelvis is affected. Gait analysis might offer earlier functional diagnostics and may accelerate the treatment decision with shorter periods of immobility in future. Especially in cross-border cases, early gait analysis could be beneficial to clarify the indication for or against surgery.

Prediction of Physical Frailty in Orthogeriatric Patients Using Sensor Insole-Based Gait Analysis and Machine Learning Algorithms: Cross-sectional Study.

BACKGROUND: Assessment of the physical frailty of older patients is of great importance in many medical disciplines to be able to implement individualized therapies. For physical tests, time is usually used as the only objective measure. To record other objective factors, modern wearables offer great potential for generating valid data and integrating the data into medical decision-making. OBJECTIVE: The aim of this study was to compare the predictive value of insole data, which were collected during the Timed-Up-and-Go (TUG) test, to the benchmark standard questionnaire for sarcopenia (SARC-F: strength, assistance with walking, rising from a chair, climbing stairs, and falls) and physical assessment (TUG test) for evaluating physical frailty, defined by the Short Physical Performance Battery (SPPB), using machine learning algorithms. METHODS: This cross-sectional study included patients aged >60 years with independent ambulation and no mental or neurological impairment. A comprehensive set of parameters associated with physical frailty were assessed, including body composition, questionnaires (European Quality of Life 5-dimension [EQ 5D 5L], SARC-F), and physical performance tests (SPPB, TUG), along with digital sensor insole gait parameters collected during the TUG test. Physical frailty was defined as an SPPB score≤8. Advanced statistics, including random forest (RF) feature selection and machine learning algorithms (K-nearest neighbor [KNN] and RF) were used to compare the diagnostic value of these parameters to identify patients with physical frailty. RESULTS: Classified by the SPPB, 23 of the 57 eligible patients were defined as having physical frailty. Several gait parameters were significantly different between the two groups (with and without physical frailty). The area under the receiver operating characteristic curve (AUROC) of the TUG test was superior to that of the SARC-F (0.862 vs 0.639). The recursive feature elimination algorithm identified 9 parameters, 8 of which were digital insole gait parameters. Both the KNN and RF algorithms trained with these parameters resulted in excellent results (AUROC of 0.801 and 0.919, respectively). CONCLUSIONS: A gait analysis based on machine learning algorithms using sensor soles is superior to the SARC-F and the TUG test to identify physical frailty in orthogeriatric patients.

A longitudinal and cross-sectional study of plasma neurofilament light chain concentration in Charcot-Marie-Tooth disease.

Advances in genetic technology and small molecule drug development have paved the way for clinical trials in Charcot-Marie-Tooth disease (CMT); however, the current FDA-approved clinical trial outcome measures are insensitive to detect a meaningful clinical response. There is, therefore, a need to identify sensitive outcome measures or clinically relevant biomarkers. The aim of this study was to further evaluate plasma neurofilament light chain (NFL) as a disease biomarker in CMT. Plasma NFL was measured using SIMOA technology in both a cross-sectional study of a US cohort of CMT patients and longitudinally over 6 years in a UK CMT cohort. In addition, plasma NFL was measured longitudinally in two mouse models of CMT2D. Plasma concentrations of NFL were increased in a US cohort of patients with CMT1B, CMT1X and CMT2A but not CMT2E compared with controls. In a separate UK cohort, over a 6-year interval, there was no significant change in plasma NFL concentration in CMT1A or HSN1, but a small but significant reduction in patients with CMT1X. Plasma NFL was increased in wild type compared to GARSC201R mice. There was no significant difference in plasma NFL in GARSP278KY compared to wild type mice. In patients with CMT1A, the small difference in cross-sectional NFL concentration vs healthy controls and the lack of change over time suggests that plasma NFL may lack sufficient sensitivity to detect a clinically meaningful treatment response in adulthood.

Patients with complex proximal tibial fractures overestimate the prognosis of their injury.

PURPOSE: To investigate, if patients with complex proximal tibial fracture have realistic expectations on open reduction and internal fixation. METHODS: 114 patients (mean 49 years, SD ± 13) with closed AO-type B and C proximal tibial fracture were grouped (group B, respectively C). Prior to surgery expectations concerning knee function, pain, return to work/sports, and the risk for osteoarthritis was assessed with the Hospital for Special Surgery-Knee Surgery Expectations Survey (HFSS-KSE) and a non-validated ten-item survey. RESULTS: 92% of patients expected at least an almost natural knee postoperatively. All items regarding restoring knee function were ranked to be at least important in both groups. 65% in group B and 47% in group C expected at most occasional pain. 83% in group B and 67% in group C expected full return to work without any limitations. Patients with low physical work intensity expected significantly shorter incapacity to work in both groups (7.8, respectively 8.9 weeks). 71% in group B and 60% in group C expected to return to sports with at most small limitations. 33% in group B and 22% in group C assumed risk for osteoarthritis will be prevented by surgery. CONCLUSION: Expectations on surgery for complex proximal tibial fracture are high regardless of fracture type. The prognosis of many health and lifestyle domains was overestimated. The risk for osteoarthritis was underestimated. This study should sensitize surgeons to discuss realistic expectations. This may help to improve patient comprehension what leads to sensible expectations, resulting in improved patients´ satisfaction. LEVEL OF EVIDENCE: IV. TRIAL REGISTRATION NUMBER: 14104, Date of registration: 06/2015.

How relevant is lumbar bone mineral density for the stability of symphyseal implants? A biomechanical cadaver study.

PURPOSE: Osteoporotic bone tissue appears to be an important risk factor for implant loosening, compromising the stability of surgical implants. However, it is unclear whether lumbar measured bone mineral density (BMD) is of any predictive value for stability of surgical implants at the pubic symphysis. This study examines the fixation strength of cortical screws in human cadaver specimens with different BMDs. METHODS: The lumbar BMD of ten human specimens was measured using quantitative computed tomography (qCT). A cut-off BMD was set at 120 mg Ca-Ha/mL, dividing the specimens into two groups. One cortical screw was drilled into each superior pubic ramus. The screw was withdrawn in an axial direction with a steady speed and considered failed when a force decrease was detected. Required force (N) and pull-out distance (mm) were constantly tracked. RESULTS: The median peak force of group 1 was 231.88 N and 228.08 N in group 2. While BMD values differed significantly (p < 0.01), a comparison of peak forces between both groups showed no significant difference (p = 0.481). CONCLUSION: Higher lumbar BMD did not result in significantly higher pull-out forces at the symphysis. The high proportion of cortical bone near the symphyseal joint allows an increased contact of pubic screws and could explain sufficient fixation. This condition is not reflected by a compromised lumbar BMD in a qCT scan. Therefore, site-specific BMD measurement could improve individual fracture management.

The TSC Complex-mTORC1 Axis: From Lysosomes to Stress Granules and Back.

The tuberous sclerosis protein complex (TSC complex) is a key integrator of metabolic signals and cellular stress. In response to nutrient shortage and stresses, the TSC complex inhibits the mechanistic target of rapamycin complex 1 (mTORC1) at the lysosomes. mTORC1 is also inhibited by stress granules (SGs), RNA-protein assemblies that dissociate mTORC1. The mechanisms of lysosome and SG recruitment of mTORC1 are well studied. In contrast, molecular details on lysosomal recruitment of the TSC complex have emerged only recently. The TSC complex subunit 1 (TSC1) binds lysosomes via phosphatidylinositol-3,5-bisphosphate [PI(3,5)P2]. The SG assembly factors 1 and 2 (G3BP1/2) have an unexpected lysosomal function in recruiting TSC2 when SGs are absent. In addition, high density lipoprotein binding protein (HDLBP, also named Vigilin) recruits TSC2 to SGs under stress. In this mini-review, we integrate the molecular mechanisms of lysosome and SG recruitment of the TSC complex. We discuss their interplay in the context of cell proliferation and migration in cancer and in the clinical manifestations of tuberous sclerosis complex disease (TSC) and lymphangioleiomyomatosis (LAM).