The currently available osteoarthritis (OA) treatments offer symptoms\' relief without disease-modifying effects. Increasing evidence supports the role of human mesenchymal stem cells (MSCs) to drive beneficial effects provided by their secretome and extracellular vesicles (EVs), which includes trophic and biologically active factors. Aim of this study was to evaluate the in vitro literature to understand the potential of human secretome and EVs for OA treatment and identify trends, gaps, and potential translational challenges. A systematic review was performed on PubMed, Embase, and Web-of-Science, identifying 58 studies. The effects of secretome and EVs were analysed on osteoarthritic cells regarding anabolic, anti-apoptotic/anti-inflammatory and catabolic/pro-inflammatory/degenerative activity, chondroinduction, and immunomodulation. The results showed that MSC-derived EVs elicit an increase in proliferation and migration, reduction of cell death and inflammation, downregulation of catabolic pathways, regulation of immunomodulation, and promotion of anabolic processes in arthritic cells. However, a high heterogeneity in several technical or more applicative aspects emerged. In conclusion, the use of human secretome and EVs as strategy to address OA processes has overall positive effects and disease-modifying potential. However, it is crucial to reduce protocol variability and strive toward a higher standardization, which will be essential for the translation of this promising OA treatment from the in vitro research setting to the clinical practice.

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OBJECTIVE: To investigate symptom trajectories in chiropractic patients with lumbar spinal stenosis (LSS).
METHODS: Patients diagnosed with LSS were recruited from chiropractic clinics and self-reported questionnaires were collected at baseline and 1-year follow-up. Patients received weekly text messages about low back pain (LBP) and leg symptoms for 1 year. Group-based trajectory modelling was performed to identify symptom trajectory groups. The groups were compared based on patient characteristics, LBP and leg pain intensity, Oswestry Disability Index (ODI) and Zurich Claudication Questionnaire (ZCQ).
RESULTS: A total of 90 patients were included in the analysis. A three-group trajectory model was chosen: \'improving\' (16%), \'fluctuating/improving\' (30%), and \'persistent\' (54%). The \'persistent\' group had a higher proportion of women [71% (95% CI 57-82%)] than the \'improving\' group 29% (95% CI 11-56%), and a higher ODI score at both baseline [34.2 (95% CI 29.7-38.8) vs. 22.8 (16.4-29.1)] and 1-year follow-up [28.1 (95% CI 23.2-33.0) vs. 4.8 (0.1-9.4)]. Similar differences were observed for ZCQ symptom and function scores.
CONCLUSIONS: Pain symptoms in people with LSS followed distinctly different trajectories. Half of the sample had a pattern of consistently severe symptoms over a year, while the other half either improved rapidly or experienced fluctuating symptoms with some improvement.

BACKGROUND: Compartment syndrome is a well-known phenomenon that is most commonly reported in the extremities. However, paralumbar compartment syndrome is rarely described in available literature. The authors present a case of paralumbar compartment syndrome after high intensity deadlifting.
METHODS: 53-year-old male who presented with progressively worsening low back pain and paresthesias one day after high-intensity deadlifting. Laboratory testing found the patient to be in rhabdomyolysis; he was admitted for intravenous fluid resuscitation and pain control. Orthopedics was consulted, and Magnetic Resonance Imaging revealed significant paravertebral edema and loss of muscle striation. Given the patient\'s lack of improvement with intravenous and oral pain control, clinical and radiographic findings, there was significant concern for acute paralumbar compartment syndrome. The patient subsequently underwent urgent fasciotomy of bilateral paralumbar musculature with delayed closure.
CONCLUSIONS: Given the paucity of literature on paralumbar compartment syndrome, the authors\' goal is to promote awareness of the diagnosis, as it should be included in the differential diagnosis of intractable back pain after high exertional exercise. The current literature suggests that operative cases of paralumbar compartment syndromes have a higher rate of return to pre-operative function compared to those treated non-operatively. This case report further supports this notion. The authors recommend further study into this phenomenon, given its potential to result in persistent chronic exertional pain and irreversible tissue damage.

BACKGROUND: Basicervical femoral neck fracture is a rare proximal femur fracture with a high implant failure rate. Biomechanical comparisons between cephalomedullary nails (CMNs) and dynamic hip screws (DHSs) under torsion loading are lacking. This study compared the biomechanical performance of three fixations for basicervical femoral neck fractures under torsion load during early ambulation.
METHODS: The biomechanical study models used three fixations: a DHS, a DHS with an anti-rotation screw, and a short CMN. Finite element analysis was used to simulate hip rotation with muscle forces related to leg swing applied to the femur. The equivalent von Mises stress (EQV) on fixation, fragment displacement, and strain energy density at the proximal cancellous bone were monitored for fixation stability.
RESULTS: The EQV of the short CMN construct (304.63 MPa) was comparable to that of the titanium DHS construct (293.39 MPa) and greater than that of the titanium DHS with an anti-rotation screw construct (200.94 MPa). The proximal fragment displacement in the short CMN construct was approximately 0.13 mm, the greatest among the constructs. The risk of screw cutout for the lag screw in short CMNs was 3.1-5.8 times greater than that for DHSs and DHSs with anti-rotation screw constructs.
CONCLUSIONS: Titanium DHS combined with an anti-rotation screw provided lower fragment displacement, stress, and strain energy density in the femoral head than the other fixations under torsion load. Basicervical femoral neck fracture treated with CMNs may increase the risk of lag screw cutout.

BACKGROUND: A growing body of evidence has highlighted the interactions of lipids metabolism and immune regulation. Nevertheless, there is still a lack of evidence regarding the causality between lipids and autoimmune diseases (ADs), as well as their possibility as drug targets for ADs.
OBJECTIVE: This study was conducted to comprehensively understand the casual associations between lipid traits and ADs, and evaluate the therapeutic possibility of lipid-lowering drug targets on ADs.
METHODS: Genetic variants for lipid traits and variants encoding targets of various lipid-lowering drugs were derived from Global Lipid Genetics Consortium (GLGC) and verified in Drug Bank. Summary data of ADs were obtained from MRC Integrative Epidemiology Unit (MER-IEU) database and FinnGen consortium, respectively. The causal inferences between lipid traits/genetic agents of lipid-lowering targets and ADs were evaluated by Mendelian randomization (MR), summary data-based MR (SMR), and multivariable MR (MVMR) analyses. Enrichment analysis and protein interaction network were employed to reveal the functional characteristics and biological relevance of potential therapeutic lipid-lowering targets.
RESULTS: There was no evidence of causal effects regarding 5 lipid traits and 9 lipid-lowering drug targets on ADs. Genetically proxied 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) inhibition was associated with a reduced risk of rheumatoid arthritis (RA) in both discovery (OR [odds ratio] = 0.45, 95%CI: 0.32, 0.63, P = 6.79 × 10- 06) and replicate datasets (OR = 0.37, 95%CI: 0.23, 0.61, P = 7.81 × 10- 05). SMR analyses supported that genetically proxied HMGCR inhibition had causal effects on RA in whole blood (OR = 0.48, 95%CI: 0.29, 0.82, P = 6.86 × 10- 03) and skeletal muscle sites (OR = 0.75, 95%CI: 0.56, 0.99, P = 4.48 × 10- 02). After controlling for blood pressure, body mass index (BMI), smoking and drinking alchohol, HMGCR suppression showed a direct causal effect on a lower risk of RA (OR = 0.33, 95%CI: 0.40, 0.96, P = 0.042).
CONCLUSIONS: Our study reveals causal links of genetically proxied HMGCR inhibition (lipid-lowering drug targets) and HMGCR expression inhibition with a decreased risk of RA, suggesting that HMGCR may serve as candidate drug targets for the treatment and prevention of RA.

BACKGROUND: The accelerated growth of older individuals worldwide has increased the number of patients presenting with fragility hip fractures. Having a hip fracture can cause excess mortality, and patients with hip fracture have a higher risk of death than those without hip fracture. Most studies have treated hip fracture as a single, homogeneous condition, but hip fracture includes two major anatomic types: intertrochanteric fracture and femoral neck fracture. Few studies have specifically evaluated 1-year mortality risk in older individuals with femoral intertrochanteric fracture. The aim of this study was to evaluate 1-year mortality and factors associated with mortality in older individuals with femoral intertrochanteric fracture.
METHODS: A retrospective review was conducted of 563 patients ≥ 65 years old who underwent surgery for femoral intertrochanteric fractures at our institution between January 2010 and August 2018. Patient demographics, comorbidities, and treatment were collected by retrospective chart review. Age, sex, Body Mass Index (BMI), American Society of Anesthesiologists (ASA) classification, Charlson comorbidity index (CCI), Arbeitsgemeinschaft Für Osteosynthesefragen (AO) fracture classification, haemoglobin value at admission, time to surgery, operation time, and intraoperative blood loss were risk factors to be tested. Multivariable logistic regression was used to evaluate associations between variables and death.
RESULTS: Among the 563 patients, 49 died within 1 year after surgery, and the 1-year mortality rate was 8.7%. Multivariate analysis identified age > 80 years (OR = 4.038, P = 0.011), haemoglobin < 100 g/l (OR = 2.732, P = 0.002), ASA score ≥ 3 (OR = 2.551, P = 0.005), CCI ≥ 3 (OR = 18.412, P = 0.018) and time to surgery > 14 d (OR = 3.907, P = 0.030) as independent risk factors for 1-year mortality. Comorbidities such as myocardial infarction and chronic pulmonary disease were associated with 1-year mortality after adjusting for age > 80 years and time to surgery > 14 days.
CONCLUSIONS: Patients over 80 years old with haemoglobin < 100 g/l, ASA score ≥ 3, CCI ≥ 3, and multiple comorbidities, especially myocardial infarction and chronic pulmonary disease before surgery, are at a higher risk of 1-year mortality. Doctors should pay more attention to these vulnerable patients, and a surgical delay greater than 14 days should be avoided.

BACKGROUND: The disability and significant economic costs accredited to Low back pain (LBP) are likely to rise which is an essential problem in low and middle-income countries like Pakistan. The associated factors of LBP are age, sex, and race including physical activity, high spinal load, lifting, bending, and twisting occupations. The literature highlighted there is substantial differences in associated factors of LBP within available studies in developing countries. The objective is to investigate the association of demographic factors and lumbar range of motion with disability in patients with chronic low back.
METHODS: A baseline data analysis was performed as an analytical cross-sectional study among 150 patients with chronic low back in a randomized controlled trial with a duration from March 2020 and January 2021. After recording demographics, Modified-Modified Schober\'s test was used to measure lumbar flexion and extension and Oswestry disability index for disability. After the descriptive analysis the continuous variables, age and pain were analyzed with Spearman\'s correlation. Variables that were significant in bivariate analysis were then fitted in a multivariable linear regression. The Kruskal-Wallis test was used to analyze variations of disability in gender, marital status, work status, education level, and duration of pain. The p-value of 0.05 was significant.
RESULTS: The results showed a significant correlation between age and pain in sitting (rh=-0.189, p = 0.021 and rh = 0.788, p < 0.001) with the disability but no significant effects of age and pain in sitting (B=-0.124, p = 0.212 and B = 1.128, p = 0.082) on disability were found. The decrease in lumbar flexion and extension was found to increase disability (B=-6.018 and - 4.032 respectively with p < 0.001). Female gender (x2(1) = 15.477, p = < 0.001) and unmarried marital status (x2(1) = 4.539, p = 0.033) had more disability than male gender and married marital status, respectively. There was a significance between groups of the duration of pain regarding disability (x2 (2) = 70.905, p < 0.001). Age, education level, and work status showed no significance (p > 0.05).
CONCLUSIONS: The female gender and unmarried marital status are associated with functional disability. Decreased lumbar range of motion accompanies more disability, while age, education level, and work status do not effect on disability.

BACKGROUND: Increased intake of specific vitamins has been linked to a decreased prevalence of osteoporosis. However, the association between dietary folate intake and the risk of osteoporosis in the general population remains incompletely understood. Therefore, we aimed to determine the association between dietary folate intake and the risk of osteoporosis in the general population of the USA.
METHODS: In this cross-sectional study, data from the National Health and Nutrition Examination Survey (2017-2020) were collected. Osteoporosis was considered to be indicated by a bone mineral density greater than 2.5 standard deviations below the mean of the young adult reference group. Dietary folate intake was measured by a 24-hour dietary recall. Multivariate logistic regression models and restricted cubic spline models were used.
RESULTS: The study included 2297 participants (mean age: 63.69 ± 0.35 years), 49.92% of whom were female. In the general population, increased dietary folate intake was directly associated with a decreased risk of osteoporosis (P for trend = 0.005). In the age > 60 years and female subgroups, folate intake was inversely associated with the risk of osteoporosis (P for trend < 0.001). The dose‒response curve suggested that this association was nonlinear (P for nonlinearity = 0.015).
CONCLUSIONS: Our cross-sectional study provides initial insights into the inverse association between dietary folate intake and the risk of osteoporosis in the general U.S.
METHODS: Further research is needed to confirm these associations.

BACKGROUND: After spinal cord injury (SCI), a large number of survivors suffer from severe motor dysfunction (MD). Although the injury site is in the spinal cord, excitability significantly decreases in the primary motor cortex (M1), especially in the lower extremity (LE) area. Unfortunately, M1 LE area-targeted repetitive transcranial magnetic stimulation (rTMS) has not achieved significant motor improvement in individuals with SCI. A recent study reported that the M1 hand area in individuals with SCl contains a compositional code (the movement-coding component of neural activity) that links matching movements from the upper extremities (UE) and the LE. However, the correlation between bilateral M1 hand area excitability and overall functional recovery is unknown.
OBJECTIVE: To clarify the changes in the excitability of the bilateral M1 hand area after SCI and its correlation with motor recovery, we aim to specify the therapeutic parameters of rTMS for SCI motor rehabilitation.
METHODS: This study is a 12-month prospective cohort study. The neurophysiological and overall functional status of the participants will be assessed. The primary outcomes included single-pulse and paired-pulse TMS. The second outcome included functional near-infrared spectroscopy (fNIRS) measurements. Overall functional status included total motor score, modified Ashworth scale score, ASIA Impairment Scale grade, spinal cord independence measure and modified Barthel index. The data will be recorded for individuals with SCI at disease durations of 1 month, 2 months, 4 months, 6 months and 12 months. The matched healthy controls will be measured during the same period of time after recruitment.
CONCLUSIONS: The present study is the first to analyze the role of bilateral M1 hand area excitability changes in the evaluation and prediction of overall functional recovery (including motor function and activities of daily living) after SCI, which will further expand the traditional theory of the predominant role of M1, optimize the current rTMS treatment, and explore the brain-computer interface design for individuals with SCI.
BACKGROUND: ChiCTR2300068831.