Allogenic bone marrow-derived mesenchymal stromal cell-based therapy for patients with chronic low back pain: a prospective, multicentre, randomised placebo controlled trial (RESPINE study).

OBJECTIVES: To assess the efficacy of a single intradiscal injection of allogeneic bone marrow mesenchymal stromal cells (BM-MSCs) versus a sham placebo in patients with chronic low back pain (LBP). METHODS: Participants were randomised in a prospective, double-blind, controlled study to receive either sham injection or intradiscal injection of 20 million allogeneic BM-MSC, between April 2018 and December 2022. The first co-primary endpoint was the rate of responders defined by improvement of the Visual Analogue Scale (VAS) for pain of at least 20% and 20 mm, or improvement of the Oswestry Disability Index (ODI) of 20% between baseline and month 12. The secondary structural co-primary endpoint was assessed by the disc fluid content measured by quantitative MRI T2, between baseline and month 12. Secondary endpoints included pain VAS, ODI, the Short Form (SF)-36 and the minimal clinically important difference in all timepoints (1, 3, 6, 12 and 24 months). We determined the immune response associated with allogeneic cell injection between baseline and 6 months. Serious adverse events (SAEs) were recorded. RESULTS: 114 patients were randomised (n=58, BM-MSC group; n=56, sham placebo group). At 12 months, the primary outcome was not reached (74% in the BM-MSC group vs 69% in the placebo group; p=0.77). The groups did not differ in all secondary outcomes. No SAE related to the intervention occurred. CONCLUSIONS: While our study did not conclusively demonstrate the efficacy of allogeneic BM-MSCs for LBP, the procedure was safe. Long-term outcomes of MSC therapy for LBP are still being studied. TRIAL REGISTRATION NUMBER: EudraCT 2017-002092-25/ClinicalTrials.gov: NCT03737461.

Interventional treatments for low back pain due to sacroiliac joint dysfunction: a systematic review of the literature.

PURPOSE: This systematic review aimed to report the current evidence in the literature about the efficacy of interventional treatments in the management of low back pain (LBP) due to sacroiliac joint dysfunction. METHODS: A systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Medline, EMBASE, Scopus, CINAHL, Cochrane Library, and CENTRAL bibliographic databases were searched. The search was performed from October to December 2021, and articles from the inception of the database to December 2021 were searched. RESULTS: Fourteen studies were included for qualitative synthesis. Five studies used the traditional radiofrequency approach (tRF), five studies used cooled radiofrequency approach (cRF), one study used botulinum toxin (BT), two studies used steroid injection, triamcinolone (TA) and local anesthetics injections, and one study used pulsed radiofrequency (PRF) denervation. Two studies used sham as a comparator. CONCLUSIONS: Cooled radiofrequency seems to be the most effective treatment in improving pain and functionality, while intra-articular injections are helpful only as diagnostic tools. However, due to the lack of high-quality studies, it was not possible to draw significant conclusions.

Previous lumbar spine fusion increases the risk of dislocation following total hip arthroplasty in patients with hip-spine syndrome: a systematic review and meta-analysis.

BACKGROUND: With life expectancy on the rise, there has been an increase in patients with concomitant degenerative hip and spine pathology, defined as hip-spine syndrome (HSS). Patients affected by HSS may require both total hip arthroplasty (THA) and lumbar spinal fusion (LSF), although there is a paucity of data regarding how the sequential timing of these procedures may influence clinical outcomes. This study aims to compare complications and spinopelvic parameters in patients with HSS who underwent either LSF first or THA first. METHODS: A systematic search of PubMed and Scopus was conducted for randomized and nonrandomized studies investigating complications and spinopelvic parameters in patients with HSS who had undergone THA and LSF. The Methodological Index for Non-Randomized Studies (MINORS) tool was utilized to assess the risk of bias in included studies. Relevant outcomes were pooled for meta-analysis. RESULTS: Eleven articles were included in this study. There was a significantly higher THA dislocation rate in patients who had undergone LSF first compared to those who had THA first (OR: 3.17, 95% CI 1.23-8.15, P = 0.02). No significant difference was found in terms of THA aseptic loosening (OR: 0.86; 95% CI 0.32-2.32, p = 0.77) and revision rate (OR: 1.18, 95% CI: 0.53-2.62) between these two groups. Individuals who received THA only showed a significantly lower risk of hip dislocation (OR: 0.14, 95% CI: 0.08-0.25, P < 0.00001) and THA revision (OR: 0.22, 95% CI: 0.14-0.36, P < 0.00001) compared to patients with a previous LSF. CONCLUSIONS: In HSS patients who underwent both LSF and THA, those who received LSF first displayed an increased risk of hip dislocation after subsequent THA. Additionally, the relative risks of dislocation and revision rate appeared significantly lower in patients who had undergone THA only when compared to THA patients with a history of previous LSF. Due to the impact of LSF on spinopelvic biomechanics, caution must be exercised when performing THA in individuals with instrumented spines. PROSPERO ID: CRD42023412447. LEVEL OF EVIDENCE: LL.

Anterior Cruciate Ligament Repair Augmented With Dynamic Intraligamentary Stabilization Is Equivalent to Hamstring Autograft Reconstruction at Short- and Mid-Term Follow-Up: A Systematic Review.

PURPOSE: To compare clinical outcomes, knee stability and complications, failure, and revision rates after anterior cruciate ligament repair (ACLr) with dynamic intraligamentary stabilization (DIS) versus anterior cruciate ligament reconstruction (ACLR) with hamstring autograft for primary ACL ruptures at short and mid-term follow-up. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review of PubMed/MEDLINE and Scopus was performed. Studies that evaluated patients undergoing ACLr with DIS or ACLR with hamstring autograft were considered for inclusion. Studies were excluded if patients were affected by concomitant meniscal, ligamentous, or chondral injuries needing surgical treatment, because of their potential confounding effect on postoperative outcomes. The Risk of Bias-2 tool was used to assess the risk of bias in the included studies. The quality of available evidence was rated according to Grading of Recommendations Assessment, Development, and Evaluation recommendations. The study protocol was registered in the PROSPERO database (ID: CRD42023394558). RESULTS: Five randomized controlled trials comparing the outcomes of ACLr with DIS versus ACLR with hamstring autograft met the inclusion criteria. No major differences in terms of patient-reported outcomes (International Knee Documentation Committee subjective form, Lysholm score, Tegner activity scale, Knee injury and Osteoarthritis Outcome Score, visual analog scale satisfaction) or rates of complications, revisions, and failures were found in included studies at all time points. Repair showed greater International Knee Documentation Committee subjective form scores at 5 years in one study, whereas ACLR displayed significantly increased knee stability at 6 months and 5 years in 2 different studies, although the clinical relevance of these differences is doubtful. CONCLUSIONS: The results of this study suggest that ACLr with DIS is not inferior to ACLR with hamstring autograft in terms of rates of clinical outcomes, knee stability, risk of failure, complications, and revision surgery. Therefore, ACLr with DIS may be a viable alternative to ACLR with hamstring autograft in selected patients. LEVEL OF EVIDENCE: Level I, systematic review of Level I studies.

Improved cytocompatibility and antibacterial properties of zinc-substituted brushite bone cement based on ß-tricalcium phosphate.

For bone replacement materials, osteoconductive, osteoinductive, and osteogenic properties are desired. The bacterial resistance and the need for new antibacterial strategies stand among the most challenging tasks of the modern medicine. In this work, brushite cements based on powders of Zinc (Zn) (1.4 wt%) substituted tricalcium phosphate (ß-TCP) and non-substituted ß-TCP were prepared and investigated. Their initial and final phase composition, time of setting, morphology, pH evolution, and compressive strength are reported. After soaking for 60 days in physiological solution, the cements transformed into a mixture of brushite and hydroxyapatite. Antibacterial activity of the cements against Enterococcus faecium, Escherichia coli, and Pseudomonas aeruginosa bacteria strains was attested. The absence of cytotoxicity of cements was proved for murine fibroblast NCTC L929 cells. Moreover, the cell viability on the ß-TCP cement containing Zn2+ ions was 10% higher compared to the ß-TCP cement without zinc. The developed cements are perspective for applications in orthopedics and traumatology.

A Hyaluronan and Platelet-Rich Plasma Hydrogel for Mesenchymal Stem Cell Delivery in the Intervertebral Disc: An Organ Culture Study.

The purpose of the present pilot study was to evaluate the effect of a hydrogel composed of hyaluronic acid (HA) and platelet-rich plasma (PRP) as a carrier for human mesenchymal stem cells (hMSCs) for intervertebral disc (IVD) regeneration using a disc organ culture model. HA was mixed with batroxobin (BTX) and PRP to form a hydrogel encapsulating 1 × 106 or 2 × 106 hMSCs. Bovine IVDs were nucleotomized and filled with hMSCs suspended in ~200 µL of the PRP/HA/BTX hydrogel. IVDs collected at day 0 and nucleotomized IVDs with no hMSCs and/or hydrogel alone were used as controls. hMSCs encapsulated in the hydrogel were also cultured in well plates to evaluate the effect of the IVD environment on hMSCs. After 1 week, tissue structure, scaffold integration, hMSC viability and gene expression of matrix and nucleus pulposus (NP) cell markers were assessed. Histological analysis showed a better preservation of the viability of the IVD tissue adjacent to the gel in the presence of hMSCs (~70%) compared to the hydrogel without hMSCs. Furthermore, disc morphology was maintained, and the hydrogel showed signs of integration with the surrounding tissues. At the gene expression level, the hydrogel loaded with hMSCs preserved the normal metabolism of the tissue. The IVD environment promoted hMSC differentiation towards a NP cell phenotype by increasing cytokeratin-19 (KRT19) gene expression. This study demonstrated that the hydrogel composed of HA/PRP/BTX represents a valid carrier for hMSCs being able to maintain a good cell viability while stimulating cell activity and NP marker expression.

Prevalence of work related musculoskeletal disorders in Italian workers: is there an underestimation of the related occupational risk factors?

BACKGROUND: Work-related musculoskeletal disorders (WMSDs) represent an important socio-economic burden. The current risk assessment and management involved in the ethiopathogenesis of WMSDs is based on observational tools and checklists, which have some limitations in terms of accuracy and reliability. The aim of this study was to assess WMSD prevalence and identify possible correlations with several socio-demographic and work-related variables in a large cohort representative of Italian workers in order to improve our understanding of the WMSD phenomenon. METHODS: This study includes data from INSuLa, a cross-sectional nationally representative survey of health and safety at work, developed by the Italian Workers' Compensation Authority. A total of 8000 Italian workers were included. Multivariate logistic regression analyses were performed to evaluate the association of independent variables, such as workers' perceptions of exposure to biomechanical/ergonomic and video display unit (VDU) risks (Risk Perceived) and the actual risk exposure (Risk Detected) on Back, Lower and Upper limb pain. Socio-demographic, occupational and other health-related variables were included to investigate possible association with musculoskeletal disorders. RESULTS: Workers perceiving a significant exposure to biomechanical/ergonomic and VDU risks but not included in a health surveillance program for them (Risk Perceived/No Risk Detected) have had significantly higher odds of reporting musculoskeletal disorders. Regarding the biomechanical/ergonomic risk these workers are in the 19-24 age range (39.9%), transportation, warehousing/information and communication sectors (38.9%) and are employed in companies with more than 250 workers (35.8%). Regarding VDU risk, workers are in the 45-54 age range (24.5%), professional, financial and business services (38.0%) and come from companies with more than 250 employees (25.6%). CONCLUSIONS: Within the occupational safety and health management systems an appropriate assessment of occupational risk factors correlated to musculoskeletal disorders (mainly biomechanical/ergonomic and VDU) and the correct definition of their exposure levels is essential to adequately prevent the onset of WMSDs. In this regard, our findings provide useful information to design novel approaches, aimed at improving our understanding of emerging risks, identifying gaps in current risk assessment strategies and enhancing workplace interventions are mandatory to improve the occupational risk assessment and management process and therefore implement the subsequent health surveillance systems.

How to treat lumbar disc herniation in pregnancy? A systematic review on current standards.

PURPOSE: In this systematic review, we aim to illustrate the current and safe concepts in the assessment, diagnosis and management of herniated lumbar disc (HLD) during pregnancy. METHODS: A systematic review and reporting on the diagnosis, treatment and clinical results of HLD during pregnancy is performed. RESULTS: The MRI represents the first level and safest diagnostic tool for pregnant women affected by spinal problems allowing for a noninvasive and detailed radiological examination of the spine. The initial management of pregnant women affected by HLD is conservative, and primarily aimed to pain therapy. Whenever radicular pain and progressive neurological deficits unresponsive to medical management occur, surgery should be considered. Few case reports regarding the operative management of HLD in pregnant women have been published up to date. Laminectomy and/or microdiscectomy represent the classical and most commonly used techniques that can be safely performed without affecting pregnancy, delivery, or baby's health. Endoscopic discectomy may be an alternative. The most adequate timing and surgical position are chosen based on to the fetal gestational age and site of the pathology. CONCLUSIONS: Surgical treatments during pregnancy impose multiple medical and ethical problems. Timely diagnosis by MRI, careful clinical evaluation, and surgical treatment represent safe and effective procedures. Ongoing evolution of surgical, anesthesiological and obstetrical procedures results in favorable outcomes. However, interdisciplinary management and a wide knowledge of pregnancy-related pathologies are crucial for the best outcome for both mother and child.

Higher Accuracy and Better Clinical Outcomes in Navigated Thoraco-Lumbar Pedicle Screw Fixation Versus Conventional Techniques : A Systematic Review and Meta-Analysis.

STUDY DESIGN: A systematic review and meta-analysis. OBJECTIVE: This study aims to compare pedicle screw accuracy, clinical outcomes, and complications between navigated and conventional techniques. SUMMARY OF BACKGROUND DATA: In the last decades, intraoperative navigation has been introduced in spinal surgery to prevent risks and complications. MATERIALS AND METHODS: The search was executed on Cochrane Central Library, PubMed, and Scopus on April 30, 2023. Randomized controlled trials, prospective and retrospective studies that compared pedicle screw accuracy in the thoracic-lumbar-sacral segments, blood loss, operative time, hospital stay, intraoperative and postoperative revision of screws, neurological and systemic complications, Visual Analogue Scale (VAS), and Oswestry Disability Index (ODI) between navigated and freehand or fluoroscopy-assisted techniques were included in this study. The meta-analysis was performed using Review Manager software. Clinical outcomes were assessed as continuous outcomes with mean difference, while pedicle screw accuracy and complications were assessed as dichotomous outcomes with odds ratio, all with 95% CIs. The statistical significance of the results was fixed at P <0.05. RESULTS: This meta-analysis included 30 studies for a total of 17,911 patients and 24,600 pedicle screws. Statistically significant results in favor of the navigated technique were observed for the accuracy of pedicle screws ( P =0.0001), hospital stay ( P =0.0002), blood loss ( P <0.0001), postoperative revision of pedicle screws ( P <0.00001), and systemic complications ( P =0.0008). In particular, the positioning of the screws was clinically acceptable in 96.2% of the navigated group and 94.2% with traditional techniques. No significant differences were found in VAS, ODI, and operative time between the two groups. CONCLUSION: Navigated pedicle screw fixation has been demonstrated to be a safe and effective technique with high improvement in clinical outcomes and accuracy in patients undergoing spinal fusion compared with conventional techniques. LEVEL OF EVIDENCE: Level III.

How to Improve Meniscal Repair through Biological Augmentation: A Narrative Review.

Since the role of the menisci in knee stability, proprioception, and homeostasis has been well established, significant efforts have been made to repair meniscal tears, resulting in excellent clinical outcomes and a reduction in the progression of knee osteoarthritis (OA). However, varying failure rates have been reported, raising questions regarding the healing potential in cases of complex injuries, poorly vascularized and degenerated areas, and generally in the presence of unfavorable biological characteristics. Therefore, over the last few decades, different strategies have been described to increase the chances of meniscal healing. Biological augmentation of meniscal repair through various techniques represents a safe and effective strategy with proven clinical benefits. This approach could reduce the failure rate and expand the indications for meniscal repair. In the present study, we thoroughly reviewed the available evidence on meniscal repair surgery and summarized the main techniques that can be employed to enhance the biological healing potential of a meniscal lesion. Our aim was to provide an overview of the state of the art on meniscal repair and suggest the best techniques to reduce their failure rate.

Knee osteonecrosis after SARS-CoV-2 infection: a systematic case-based review.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for coronavirus disease 2019 (COVID-19). Patients with COVID-19 manifested symptoms mainly related to the respiratory system, but also the musculoskeletal system can be involved. COVID-19 has been described as a possible cause of knee osteonecrosis (ON). A systematic review was performed to investigate the hypothetical correlation between COVID-19 and knee ON. Methods: Inclusion criteria were all articles reporting cases of knee ON after a diagnosis of SARS-CoV-2 infection. Considering that COVID-19 is an emerging disease, all levels of evidence studies were included. Results: Finally, two case series and three case reports were included. We extracted data regarding demographic and clinical characteristics, details of magnetic resonance imaging (MRI), use of corticosteroids (CCS), temporal correlation between ON and COVID-19, treatment of the lesion and its outcomes. A total of seven cases of post-COVID knee ON have been described. Knee pain arose on average 11 weeks after the diagnosis of COVID-19. All patients had knee MRI showing ON. CCS were used to treat COVID-19-related symptoms in four cases. Conservative treatment was successful in five patients. Conclusions: The correlation between COVID-19 and ON remains unclear. Probably post-COVID-19 ON has a multifactorial origin in which factors related to the patient, consequences of COVID-19 and CCS therapy add up to cause a reduction of blood supply and bone vitality until ON is triggered. A greater number of patients is needed to clarify the role of COVID-19 in the etiopathogenesis of knee ON.

Threats and opportunities of using ChatGPT in scientific writing-The risk of getting spineless.

ChatGPT and AI chatbots are revolutionizing several science fields, including medical writing. However, the inadequate use of such advantageous tools can raise numerous methodological and ethical issues.

Importance of an Integrated Assessment of Functional Disability and Work Ability in Workers Affected by Low Back Pain.

Background: This study examines the relationship between functional disability and work ability in workers affected by low back pain (LBP) through an analysis of correlations between the Oswestry Disability Index (ODI) and Work Ability Index (WAI). The role of personal and work factors on functional disability/work ability levels has also been studied. LBP is the most common musculoskeletal problem and a major disabling health problem worldwide. Its etiology is multifactorial. Multidisciplinary approaches may help reduce the burden of pain and disability and improve job continuity and reintegration at work. Methods: A cohort of 264 patients affected by LBP from an Italian outpatient clinic were included in a clinical diagnostic/therapeutic trial aiming at rehabilitation and return to work through an integrated investigation protocol. Data were collected during the first medical examination using anamnestic and clinical tools. The final sample is composed of 252 patients, 57.1% man, 44.0 % blue collars, 46.4% with the high school degree, 45.6% married. Results: WAI and ODI reported a negative and fair correlation (r = -0.454; p = .000). Workers with acute LBP symptoms have a higher probability of severe disability than those with chronic LBP symptoms. White collars without depressive symptoms reported higher work ability - even in chronic disability conditions-than those with depressive symptoms. Conclusion: The study found that ODI and WAI have a convergent validity and this suggests that the two tools measure capture distinctive aspects of disability related to personal, environmental, and occupational characteristics. The most important and modifiable prognostic factors found for ODI and WAI were depressive symptoms, workday absence, and intensity of back pain. The study also found a mild association between age and ODI. The study's findings highlight the importance of using a multidisciplinary approach to manage and prevent disability due to LBP.

Rehabilitation of sick-listed LBP patients in occupational health with collaboration of the workplace.

The aim was to evaluate if rehabilitation procedures including occupational health (OH) and workplace participation increase return to work (RTW) rates among patients with subacute and chronic low back pain (LBP). A systematic review of randomized controlled trials was conducted using the PubMed and Cochrane databases. Main outcomes were RTW and days of sick leave. Interventions needed to be multidisciplinary including both OH and active workplace involvement in rehabilitation. Out of 1073 potentially eligible references, 8 met the inclusion criteria. Three studies had OH and 5 case managers involved in rehabilitation. Rehabilitation involving both OH and workplace improved RTW and decreased the number of sick leave days among LBP patients. Having case managers involved had no effect in RTW. In order to improve RTW, workplace visits and work ability meetings (WAMs) between OH and workplace are essential components in the rehabilitation process among patients with chronic LBP. Based on the study results, the authors suggest utilizing these co-operative interventions with workplaces in OH. High quality research investigating only the effect of WAMs in OH setting is needed in future. Int J Occup Med Environ Health. 2024;37(1):3-17.

Intraoperative Cone-Beam Computed Tomography Navigation Versus 2-Dimensional Fluoroscopy in Single-Level Lumbar Spinal Fusion: A Comparative Analysis.

OBJECTIVE: Several studies have advocated for the higher accuracy of transpedicular screw placement under cone-beam computed tomography (CBCT) compared to conventional 2-dimensional (2D) fluoroscopy. The superiority of navigation systems in perioperative and postoperative outcomes remains a topic of debate. This study aimed to compare operative time, screw placement time and accuracy, total radiation dose, perioperative and postoperative outcomes in patients who underwent transpedicular screw fixation for degenerative lumbar spondylolisthesis (DLS) using intraoperative CBCT navigation versus 2D fluoroscopy. METHODS: A retrospective analysis was conducted on patients affected by single-level DLS who underwent posterior lumbar instrumentation with transpedicular screw fixation using surgical CBCT navigation (NV group) or 2D fluoroscopy-assisted freehand technique (FH group). Demographics, screw placement time and accuracy, operative time, total radiation dose, intraoperative blood loss, screw revision rate, complications, and length of stay (LOS) were assessed. RESULTS: The study included a total of 30 patients (NV group: n = 15; FH group: n = 15). The mean screw placement time, operative time, and LOS were significantly reduced in the NV group compared to the FH group (p < 0.05). The total radiation dose was significantly higher in the NV group (p < 0.0001). No significant difference was found in terms of blood loss and postoperative complications. CONCLUSION: This study suggests that intraoperative CBCT-navigated single-level lumbar transpedicular screw fixation is superior in terms of mean screw placement time, operative time, and LOS compared to 2D fluoroscopy, despite a higher intraoperative radiation exposure.

Why clinical trials in disc regeneration strive to achieve completion: Insights from publication status and funding sources.

Background: Chronic discogenic low back pain (LBP) poses a significant global burden, yet effective therapeutic interventions directly targeting the underlying degenerative process remain elusive. After demonstrating promising results in preclinical studies, intradiscal injection of cell-based treatments has been increasingly investigated in the clinical setting. However, most clinical trials failed to reach publication, with the few available reports showing only minor improvements. The aim of this study was to analyze the prospective clinical trials registered on ClinicalTrials.gov investigating cell therapies for LBP, with a specific emphasis on identifying critical obstacles hindering study completion, including trial design and funding sources. Methods: A systematic search of prospective clinical trials investigating cell-based treatments for chronic LBP due to intervertebral disc degeneration was performed on ClinicalTrials.gov. Extracted data encompassed study design, recruitment, experimental treatment modalities, investigated outcomes, current status, completion date, publication status, and funding sources. Fisher's exact test assessed associations between categorical variables, while a multiple logistic regression model aimed to identify factors potentially linked to the publication status of the studies. Results: Our search identified 26 clinical trials. Among these, only 7 (26.9%) were published, and none of the other studies marked as completed reported any results on ClinicalTrials.gov. Fifty percent of included trials were funded by universities, whereas the rest was sponsored by industry (38.5%) or private institutions (11.5%). Experimental treatments primarily involved cell-based or cell-derived products of varying sources and concentrations. Products containing carriers, such as hyaluronic acid or fibrin, were more frequently funded by industry and private organizations (p = 0.0112). No significant differences emerged when comparing published and nonpublished studies based on funding, as well as between publication status and other variables. Conclusion: Most clinical trials exploring cell-based disc regenerative therapies for chronic LBP have never reached completion, with only a small fraction reporting preliminary data in publications.

Wharton's Jelly mesenchymal stromal cell-derived extracellular vesicles promote nucleus pulposus cell anabolism in an in vitro 3D alginate-bead culture model.

Background: Intradiscal transplantation of mesenchymal stromal cells (MSCs) has emerged as a promising therapy for intervertebral disc degeneration (IDD). However, the hostile microenvironment of the intervertebral disc (IVD) may compromise the survival of implanted cells. Interestingly, studies reported that paracrine factors, such as extracellular vesicles (EVs) released by MSCs, may regenerate the IVD. The aim of this study was to investigate the therapeutic effects of Wharton's Jelly MSC (WJ-MSC)-derived EVs on human nucleus pulposus cells (hNPCs) using an in vitro 3D alginate-bead culture model. Methods: After EV isolation and characterization, hNPCs isolated from surgical specimens were encapsulated in alginate beads and treated with 10, 50, and 100 µg/mL WJ-MSC-EVs. Cell proliferation and viability were assessed by flow cytometry and live/dead staining. Nitrite and glycosaminoglycan (GAG) content was evaluated through Griess and 1,9-dimethylmethylene blue assays. hNPCs in alginate beads were paraffin-embedded and stained for histological analysis (hematoxylin-eosin and Alcian blue) to assess extracellular matrix (ECM) composition. Gene expression levels of catabolic (MMP1, MMP13, ADAMTS5, IL6, NOS2), anabolic (ACAN), and hNPC marker (SOX9, KRT19) genes were analyzed through qPCR. Collagen type I and type II content was assessed with Western blot analysis. Results: Treatment with WJ-MSC-EVs resulted in an increase in cell content and a decrease in cell death in degenerated hNPCs. Nitrite production was drastically reduced by EV treatment compared to the control. Furthermore, proteoglycan content was enhanced and confirmed by Alcian blue histological staining. EV stimulation attenuated ECM degradation and inflammation by suppressing catabolic and inflammatory gene expression levels. Additionally, NPC phenotypic marker genes were also maintained by the EV treatment. Conclusions: WJ-MSC-derived EVs ameliorated hNPC growth and viability, and attenuated ECM degradation and oxidative stress, offering new opportunities for IVD regeneration as an attractive alternative strategy to cell therapy, which may be jeopardized by the harsh microenvironment of the IVD.

The importance of psoas muscle on low back pain: a single-center study on lumbar spine MRI.

Background: Low back pain (LBP) is the most frequent indication to magnetic resonance imaging (MRI) examinations of the lumbosacral spine. The individual role of soft tissues, including muscles, on LBP is not fully understood and the contribution of each MRI-derived parameter of soft tissues status on the intensity of LBP has not been investigated in detail. Methods: The study design was observational retrospective, single center carried out at a University Hospital. Images were acquired using a using a 1.5 Tesla scanner. Patients completed a symptom questionnaire and rated their pain intensity using the Visual Analogue Scale (VAS). The VAS scores ​​were categorized as mild, moderate, and severe using cutoff values of 3.8 and 5.7, based on the literature. Biometric data, including weight and height, were also recorded to calculate the body mass index (BMI). The ratios between intramuscular fat infiltration and net muscle area were also calculated. Patient sample included 94 patients with LBP underwent MRI of the lumbosacral spine. Results: The stepwise analysis revealed that increasing psoas net area was associated with lower VAS levels (odds ratio [OR]: 0.94: 95% confidence interval [CI]: 0.90-0.98; p=.005), and an increase of one square centimeter of total psoas area resulted in a greater probability of reporting a mild (+1.21%; 95% CI: 0.37, 2.05%) or a moderate VAS (+0.40%; 95% CI: -0.02, 0.82%), Furthermore, a more severe VAS was associated with a higher BMI (OR: 1.13; 95% CI: 1.00-1.27). Conclusion: Our study demonstrates a relationship between LBP and MRI parameters of paravertebral and psoas muscles status. The psoas muscle is extremely important for spine stabilization and is linked to clinical symptoms of patients affected by LBP. These findings could contribute to future studies and improve treatment options in patients with LBP, possibly reducing the impact on disability, quality of life and socioeconomical burden.

High-fiber diet reduces bone formation but does not affect bone microarchitecture in type 2 diabetes individuals.

Bone fragility is a recognized complication of type 2 diabetes mellitus (T2DM), increasing patient morbidity. Thus, the development of an effective intervention to prevent diabetic bone fragility is urgently needed. As lifestyle intervention represents an effective option for diabetes management, it may have an impact on bone health. While studies have shown a beneficial effect of dietary fiber in T2DM management, its effect on bone health is still unclear. Thus, we investigated the impact of a high-fiber diet on bone and glucose control in men and women with T2DM. Forty-five T2DM patients (HbA1c: 6.5% ± 0.49%, age: 74 ± 7.29 yr) scheduled for hip arthroplasty were randomly assigned to follow a high-fiber diet (38 g/day) or to make no diet changes for 12 wk. Interestingly, BMI decreased by 4% (p <.0001) and HbA1c by 3.4% (p <.0001) in the high-fiber diet group, but did not decrease in the control group. However, serum concentration of the bone formation marker procollagen type 1 amino-terminal propeptide (P1NP) decreased by 8.6 % in the high-fiber diet group (p =.0004), whereas it remained unchanged in the control group. In contrast, similar to the control group, serum concentration of the bone resorption marker C-terminal telopeptide of type I collagen (CTX) concentrations did not change in the high-fiber diet group. Bone microCT analysis revealed no changes in trabecular and cortical bone parameters between the high-fiber diet and control groups. Similarly, real-time (RT)-PCR analysis in bone tissue showed no changes in the gene expression of Wnt pathway-related genes (Sost, Dkk-1, Wnt10b, and Lef-1), bone formation markers (Runx2, Col1a1, and Ocn), and inflammatory cytokines (IL-6, IL-8, TNF-α, and IL-10) between the two groups. Our findings suggest that 12-wk high-fiber diet intervention improves metabolic outcomes in patients with T2DM. However, it may reduce bone formation without affecting bone microarchitecture or Wnt pathway regulation.

Exploring Borate-Modified Calcium Phosphate Ceramics: Antimicrobial Potential and Cytocompatibility Assessment.

Addressing periprosthetic infections, which present significant healing challenges that often require revision surgeries, necessitates the development of novel antibacterial materials and implants. Current research focuses on creating materials that hinder bacterial adhesion, colonization, and proliferation in surrounding tissues. Boron (B)-containing compounds are known for their antibacterial properties and potential in bone metabolism for regenerative medicine. In this study, we synthesized B-containing tricalcium phosphate (0.3B-TCP) with 1.1 wt.% B content via precipitation from aqueous solutions and sintering at 1100 °C. X-ray diffraction confirmed the ceramic's primary crystalline phase as ß-TCP, with B evenly distributed according to energy-dispersive spectroscopy data. Electron paramagnetic resonance (EPR) data verified stable paramagnetic borate anions, indicating successful BO33- substitution for phosphate groups. The microstructural properties of 0.3B-TCP ceramic were assessed before and after soaking in a saline solution. Its bending strength was approximately 30 MPa, and its porosity was about 33%. 0.3B-TCP ceramic demonstrated significant antimicrobial efficacy against various bacterial strains and a fungus. Cytotoxicity evaluation using equine adipose tissue-derived mesenchymal stem cells and osteogenic differentiation assessment were conducted. The combination of antibacterial efficacy and good cytocompatibility suggests 0.3B-TCP ceramic as a promising bone substitute material.