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.

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.

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.

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.

Getting to the Core: Exploring the Embryonic Development from Notochord to Nucleus Pulposus.

The intervertebral disc (IVD) is the largest avascular organ of the human body and plays a fundamental role in providing the spine with its unique structural and biomechanical functions. The inner part of the IVD contains the nucleus pulposus (NP), a gel-like tissue characterized by a high content of type II collagen and proteoglycans, which is crucial for the disc's load-bearing and shock-absorbing properties. With aging and IVD degeneration (IDD), the NP gradually loses its physiological characteristics, leading to low back pain and additional sequelae. In contrast to surrounding spinal tissues, the NP presents a distinctive embryonic development since it directly derives from the notochord. This review aims to explore the embryology of the NP, emphasizing the pivotal roles of key transcription factors, which guide the differentiation and maintenance of the NP cellular components from the notochord and surrounding sclerotome. Through an understanding of NP development, we sought to investigate the implications of the critical developmental aspects in IVD-related pathologies, such as IDD and the rare malignant chordomas. Moreover, this review discusses the therapeutic strategies targeting these pathways, including the novel regenerative approaches leveraging insights from NP development and embryology to potentially guide future treatments.

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.

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.

Bone canonical Wnt signaling is downregulated in type 2 diabetes and associates with higher advanced glycation end-products (AGEs) content and reduced bone strength.

Type 2 diabetes (T2D) is associated with higher fracture risk, despite normal or high bone mineral density. We reported that bone formation genes (SOST and RUNX2) and advanced glycation end-products (AGEs) were impaired in T2D. We investigated Wnt signaling regulation and its association with AGEs accumulation and bone strength in T2D from bone tissue of 15 T2D and 21 non-diabetic postmenopausal women undergoing hip arthroplasty. Bone histomorphometry revealed a trend of low mineralized volume in T2D (T2D 0.249% [0.156-0.366]) vs non-diabetic subjects 0.352% [0.269-0.454]; p=0.053, as well as reduced bone strength (T2D 21.60 MPa [13.46-30.10] vs non-diabetic subjects 76.24 MPa [26.81-132.9]; p=0.002). We also showed that gene expression of Wnt agonists LEF-1 (p=0.0136) and WNT10B (p=0.0302) were lower in T2D. Conversely, gene expression of WNT5A (p=0.0232), SOST (p<0.0001), and GSK3B (p=0.0456) were higher, while collagen (COL1A1) was lower in T2D (p=0.0482). AGEs content was associated with SOST and WNT5A (r=0.9231, p<0.0001; r=0.6751, p=0.0322), but inversely correlated with LEF-1 and COL1A1 (r=-0.7500, p=0.0255; r=-0.9762, p=0.0004). SOST was associated with glycemic control and disease duration (r=0.4846, p=0.0043; r=0.7107, p=0.00174), whereas WNT5A and GSK3B were only correlated with glycemic control (r=0.5589, p=0.0037; r=0.4901, p=0.0051). Finally, Young's modulus was negatively correlated with SOST (r=-0.5675, p=0.0011), AXIN2 (r=-0.5523, p=0.0042), and SFRP5 (r=-0.4442, p=0.0437), while positively correlated with LEF-1 (r=0.4116, p=0.0295) and WNT10B (r=0.6697, p=0.0001). These findings suggest that Wnt signaling and AGEs could be the main determinants of bone fragility in T2D.

Type 2 diabetes is a long-term metabolic disease characterised by chronic high blood sugar levels. This in turn has a negative impact on the health of other tissues and organs, including bones. Type 2 diabetes patients have an increased risk of fracturing bones compared to non-diabetics. This is particularly true for fragility fractures, which are fractures caused by falls from a short height (i.e., standing height or less), often affecting hips or wrists. Usually, a lower bone density is associated with higher risk of fractures. However, patients with type 2 diabetes have increased bone fragility despite normal or higher bone density. One reason for this could be the chronically high levels of blood sugar in type 2 diabetes, which alter the properties of proteins in the body. It has been shown that the excess sugar molecules effectively 'react' with many different proteins, producing harmful compounds in the process, called Advanced Glycation End-products, or AGEs. AGEs are ­ in turn ­thought to affect the structure of collagen proteins, which help hold our tissues together and decrease bone strength. However, the signalling pathways underlying this process are still unclear. To find out more, Leanza et al. studied a signalling molecule, called sclerostin, which inhibits a signalling pathway that regulates bone formation, known as Wnt signaling. The researchers compared bone samples from both diabetic and non-diabetic patients, who had undergone hip replacement surgery. Analyses of the samples, using a technique called real-time-PCR, revealed that gene expression of sclerostin was increased in samples of type 2 diabetes patients, which led to a downregulation of Wnt signaling related genes. Moreover, the downregulation of Wnt genes was correlated with lower bone strength (which was measured by compressing the bone tissue). Further biochemical analysis of the samples revealed that higher sclerostin activity was also associated with higher levels of AGEs. These results provide a clearer understanding of the biological mechanisms behind compromised bone strength in diabetes. In the future, Leanza et al. hope that this knowledge will help us develop treatments to reduce the risk of bone complications for type 2 diabetes patients.

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.

Surgeon Preference Regarding Wound Dressing Management in Lumbar Fusion Surgery: An AO Spine Global Cross-Sectional Study.

OBJECTIVE: To evaluate the global practice pattern of wound dressing use after lumbar fusion for degenerative conditions. METHODS: A survey issued by AO Spine Knowledge Forums Deformity and Degenerative was sent out to AO Spine members. The type of postoperative dressing employed, timing of initial dressing removal, and type of subsequent dressing applied were investigated. Differences in the type of surgery and regional distribution of surgeons' preferences were analyzed. RESULTS: Right following surgery, 60.6% utilized a dry dressing, 23.2% a plastic occlusive dressing, 5.7% glue, 6% a combination of glue and polyester mesh, 2.6% a wound vacuum, and 1.2% other dressings. The initial dressing was removed on postoperative day 1 (11.6%), 2 (39.2%), 3 (20.3%), 4 (1.7%), 5 (4.3%), 6 (0.4%), 7 or later (12.5%), or depending on drain removal (9.9%). Following initial dressing removal, 75.9% applied a dry dressing, 17.7% a plastic occlusive dressing, and 1.3% glue, while 12.1% used no dressing. The use of no additional coverage after initial dressing removal was significantly associated with a later dressing change (p < 0.001). Significant differences emerged after comparing dressing management among different AO Spine regions (p < 0.001). CONCLUSION: Most spine surgeons utilized a dry or plastic occlusive dressing initially applied after surgery. The first dressing was more frequently changed during the first 3 postoperative days and replaced with the same type of dressing. While dressing policies tended not to vary according to the type of surgery, regional differences suggest that actual practice may be based on personal experience rather than available evidence.

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.

ISSLS PRIZE in Basic Science 2024: superiority of nucleus pulposus cell- versus mesenchymal stromal cell-derived extracellular vesicles in attenuating disc degeneration and alleviating pain.

PURPOSE: To investigate the therapeutic potential of extracellular vesicles (EVs) derived from human nucleus pulposus cells (NPCs), with a specific emphasis on Tie2-enhanced NPCs, compared to EVs derived from human bone marrow-derived mesenchymal stromal cells (BM-MSCs) in a coccygeal intervertebral disc degeneration (IDD) rat model. METHODS: EVs were isolated from healthy human NPCs cultured under standard (NPCSTD-EVs) and Tie2-enhancing (NPCTie2+-EVs) conditions. EVs were characterized, and their potential was assessed in vitro on degenerative NPCs in terms of cell proliferation and senescence, with or without 10 ng/mL interleukin (IL)-1ß. Thereafter, 16 Sprague-Dawley rats underwent annular puncture of three contiguous coccygeal discs to develop IDD. Phosphate-buffered saline, NPCSTD-EVs, NPCTie2+-EVs, or BM-MSC-derived EVs were injected into injured discs, and animals were followed for 12 weeks until sacrifice. Behavioral tests, radiographic disc height index (DHI) measurements, evaluation of pain biomarkers, and histological analyses were performed to assess the outcomes of injected EVs. RESULTS: NPC-derived EVs exhibited the typical exosomal morphology and were efficiently internalized by degenerative NPCs, enhancing cell proliferation, and reducing senescence. In vivo, a single injection of NPC-derived EVs preserved DHI, attenuated degenerative changes, and notably reduced mechanical hypersensitivity. MSC-derived EVs showed marginal improvements over sham controls across all measured outcomes. CONCLUSION: Our results underscore the regenerative potential of young NPC-derived EVs, particularly NPCTie2+-EVs, surpassing MSC-derived counterparts. These findings raise questions about the validity of MSCs as both EV sources and cellular therapeutics against IDD. The study emphasizes the critical influence of cell type, source, and culture conditions in EV-based therapeutics.

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.

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.

The Role of Osteobiologics in Augmenting Spine Fusion in Unplated Anterior Cervical Discectomy and Fusion Compared to Plated Constructs: A Systematic Review and Meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To compare clinical and radiographic outcomes as well as complications of unplated vs plated anterior cervical discectomy and fusion (ACDF) surgery considering the role of osteobiologics in single- and multi-level procedures. METHODS: A systematic search of PubMed/MEDLINE, Scopus, CINAHL, EMBASE, CENTRAL, Cochrane and ClinicalTrials.gov databases was performed. Briefly, we sought to identify studies comparing unplated vs. plated ACDF for cervical degenerative disc disease reporting the use of osteobiologics in terms of clinical outcomes, radiographic fusion, and complications. Data on study population, follow-up time, type of cage and plate used, type of osteobiologic employed, number of levels treated, patient-reported outcomes (PROs), radiographic outcomes and complications were collected and compared. Relevant information was pooled for meta-analyses. RESULTS: Thirty-eight studies met the inclusion criteria. No significant difference was found in terms of clinical outcomes between groups. Unplated ACDF was characterized by reduced blood loss, operation time and length of hospital stay. Fusion was achieved by the majority of patients in both groups, with no evidence of any specific contribution depending on the osteobiologics used. Dysphagia was more commonly associated with anterior plating, while cage subsidence prevailed in the unplated group. CONCLUSION: Unplated and plated ACDF seem to provide similar outcomes irrespective of the osteobiologic used, with minor differences with doubtful clinical significance. However, the heterogeneity and high risk of bias affecting included studies markedly prevent significant conclusions.

AO Spine Guideline for the Use of Osteobiologics (AOGO) in Anterior Cervical Discectomy and Fusion for Spinal Degenerative Cases.

STUDY DESIGN: Guideline. OBJECTIVES: To develop an international guideline (AOGO) about the use of osteobiologics in anterior cervical discectomy and fusion (ACDF) for treating degenerative spine conditions. METHODS: The guideline development process was guided by AO Spine Knowledge Forum Degenerative (KF Degen) and followed the Guideline International Network McMaster Guideline Development Checklist. The process involved 73 participants with expertise in degenerative spine diseases and surgery from 22 countries. Fifteen systematic reviews were conducted addressing respective key topics and evidence was collected. The methodologist compiled the evidence into GRADE Evidence-to-Decision frameworks. Guideline panel members judged the outcomes and other criteria and made the final recommendations through consensus. RESULTS: Five conditional recommendations were created. A conditional recommendation is about the use of allograft, autograft or a cage with an osteobiologic in primary ACDF surgery. Other conditional recommendations are about the use of osteobiologic for single- or multi-level ACDF, and for hybrid construct surgery. It is suggested that surgeons use other osteobiologics rather than human bone morphogenetic protein-2 (BMP-2) in common clinical situations. Surgeons are recommended to choose 1 graft over another or 1 osteobiologic over another primarily based on clinical situation, and the costs and availability of the materials. CONCLUSION: This AOGO guideline is the first to provide recommendations for the use of osteobiologics in ACDF. Despite the comprehensive searches for evidence, there were few studies completed with small sample sizes and primarily as case series with inherent risks of bias. Therefore, high-quality clinical evidence is demanded to improve the guideline.

Complications With Demineralized Bone Matrix, Hydroxyapatite and Beta-Tricalcium Phosphate in Single and Two-Level Anterior Cervical Discectomy and Fusion Surgery.

STUDY DESIGN: Systematic literature review. OBJECTIVES: To analyze the evidence available reporting complications in single or two-level anterior cervical discectomy and fusion (ACDF) using a demineralized bone matrix (DBM), hydroxyapatite (HA), or beta-tricalcium phosphate (ß-TCP). METHODS: A systematic review of the literature using PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov databases was performed in August 2020 to identify studies reporting complications in one or two-level ACDF surgery using DBM, HA, or ß-TCP. The study was reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. RESULTS: A total of 1857 patients were included, 981 male and 876 female, across 17 articles; 5 prospective, and 12 retrospectives. We noted heterogeneity among the included studies concerning the study design and combination of graft materials utilized in them. However, we noted a higher incidence of adjacent segment disease (17.7%) and pseudoarthrosis (9.3%) in fusion constructs using DBM. Studies using ß-TCP reported a higher incidence of pseudoarthrosis (28.2%) and implant failures (17.9%). CONCLUSIONS: Degenerative cervical conditions treated with one or two-level ACDF surgery using DBM, HA, or ß-TCP with or without cervical plating are associated with complications such as adjacent segment disease, dysphagia, and pseudarthrosis. However, consequent to the study designs and clinical heterogeneity of the studies, it is not possible to correlate these complications accurately with any specific graft material employed. Further well-designed prospective studies are needed to correctly know the related morbidity of each graft used for achieving fusion in ACDF.

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.