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Biological drugs, including monoclonal antibodies, represent a revolutionary strategy in all fields of medicine, offering promising results even in the treatment of osteoarthritis (OA). However, their safety and efficacy have not been fully validated, highlighting the need for in-depth studies. Therefore, we provided a comprehensive systematic review of the intra-articular use of monoclonal antibodies for the treatment of OA in animal models, reflecting ongoing efforts to advance therapeutic strategies and improve patient outcomes. A systematic literature search was conducted in December 2023 following the PRISMA guidelines, using the Web of Science, Google Scholar, and PUBMED databases. Out of a total of 456, 10 articles were included in the study analyzing intra-articular antibodies and focusing on various targets, including vascular endothelial growth factor (VEGF), nerve growth factor (NGF), interleukin 4-10 (IL4-10), tumor necrosis factor α (TNF-α), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), and matrix metalloproteinase 13 (MMP-13). Most studies administered the antibodies weekly, ranging from 1 to 10 injections. Animal models varied, with mean follow-up periods of 8.9 ± 4.1 weeks. The methods of assessing outcomes, including pain and morpho-functional changes, varied. Some studies reported only morphological and immunohistochemical data, while others included a quantitative analysis of protein expression. In conclusion, monoclonal antibodies represent a promising avenue in the treatment of OA, offering targeted approaches to modulate disease pathways. Further research and clinical trials are needed to validate their safety and efficacy, with the potential to revolutionize the management of OA and reduce reliance on prosthetic interventions. [ABSTRACT FROM AUTHOR]

Background: Pelvic insufficiency fractures (PIF) are typical in geriatric populations with reduced bone quality, most commonly in elderly postmenopausal women. These fractures are usually caused by low-energy forces over the bones during ordinary life and cause disabling pain. Treatment options range from conservative to operative. The aim of this study is to assess the outcomes of treatments for pelvic insufficiency fractures, determining optimal approaches between surgical intervention and conservative management. Methods: This literature review systematically examines articles focusing on patients with PIF, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and using PubMed, Medline, and the Cochrane Library database. We took into account only full-text articles in indexed journals with available English abstracts, considering data about patient demographics, surgery, and outcomes. Results: After screening 128 articles, this study reviewed 20 manuscripts involving 1499 patients, mostly elderly females and focusing on sacrum fractures. Common treatments included conservative methods and sacroplasty, with a few complications reported. Osteoporosis was the prevalent comorbidity, and the survival rate post-treatment was high at 92.3%. Mobility outcomes varied, with some patients experiencing significant autonomy loss. The average follow-up period was over 17 months. Conclusions: This study found a cautious approach to surgery (timing of three weeks), which is reserved only for specific patterns, and it leads to increased autonomy and a lower risk of mortality. Due to the lack of pre- and postoperative scores as well as conflicting results, it is imperative to undertake further studies and research to be able to compare the alternative treatments efficiently. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) stands as a prevalent global health concern, and mineral and bone disease are among the most impactful consequences. A severe complication arising from mineral and bone disease is the occurrence of fragility fractures, which disproportionately affect individuals with CKD compared to the general population. The prevalence of these fractures impacts both survival rates and quality of life. The aims of this study are analyzing and identifying (i) patient-related risk factors and (ii) CKD-related risk factors to contribute to the development of preventive measures for fragility fractures for this population. Methods: A retrospective, single-center observational study was conducted, encompassing patient data from the years 2021 to 2023. Registry data were recorded, including patient-related and CKD-related data. Patients were interviewed about traumatological history, and their answers were recorded. Logistic regression analysis was employed to investigate the association between independent variables and dependent variables. Results: Eighty-four patients, with a mean age of 64.3 ± 15.2 years and a male percentage of 58.3%, were included in this study. Among them, 19.5% exhibited smoking habits. The mean Charlson Comorbidity Index was 3.06 ± 1.21. All patients were diagnosed with end-stage chronic kidney disease, with mean durations of 208 months from the diagnosis and 84.5 months from the beginning of dialysis. The logistic regression analysis, adjusted for age, sex, and CCI, revealed that smoking habits play a significant role as a risk factor for fragility fractures in lower limbs (p: 0.011 *). The incidence of fragility fractures increases directly proportionally to the time since diagnosis (p-value: 0.021 *) and the beginning of dialysis treatment (p-value: 0.001 *). Conclusions: Among patient-related factors, smoking habits seem to significantly affect lower-limb fracture rates (p < 0.05), whereas among CKD-related factors, time since CKD diagnosis and time since the beginning of dialysis treatment are directly related to higher risks of fragility fractures. No relevant correlations emerged in the studied treatments, except for a reduction in proximal femur fracture occurrence when patients underwent a combined treatment of a calcimimetic and a vitamin D analog. [ABSTRACT FROM AUTHOR]

Introduction: Minimally invasive spine surgery became the gold standard for the treatment of many spinal diseases. Only a few comparative studies were performed regarding the superiority of robotic-assisted (RA) surgery over fluoroscopic guidance (FG) surgery during percutaneous pedicle screws placement. Therefore, the aim of the present study was to conduct a systematic literature review and meta-analysis to evaluate the accuracy and potential advantages of RA compared with FG. Material and Methods: This study is a systematic literature review conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The review questions were formulated following the PICO scheme. Measured outcomes were presented using Forest plots. Heterogeneity among the included studies was assessed using the Χ² test, and the I² statistic was utilized to estimate the proportion of total variation among the studies. A value exceeding 50% was considered indicative of substantial heterogeneity. Results: Seven studies that met inclusion criteria were finally included in this meta-analysis. These seven studies include: 447 patients, 228 patients (931 screws) treated with robotic guide, and 219 patients (767 pedicle screws) using fluoroscopic guide, with a mean age of 55.2. The percentages of clinically acceptable screws were 94.3% in the robot-assisted group and 89% in the fluoroscopic guided group. The percentages of non-acceptable screws were 5.7% in the robot-assisted group and 11% in the fluoroscopic-guided group. Discussion: Significant differences were observed between the two groups in terms of radiographic and clinical outcomes, with the robotic-assisted pedicle screw group exhibiting longer operative times. Robot technology serves as a valuable tool for assisting surgeons in challenging scenarios such as anatomical variants or patients with spinal deformities, ensuring accurate screw placement. Conclusion: The accuracy of pedicle screw placement with robotic technology is higher than with FG. In fact, the robotic approach allows significantly lower complication rates, fewer cases of violation of the proximal articular facet, less intraoperative exposure to radiation, even if it requires longer surgical times than the FG technique. [ABSTRACT FROM AUTHOR]

Intestinal fibrosis, the most common complication of inflammatory bowel disease (IBD), is characterized by an uncontrolled deposition of extracellular matrix proteins leading to complications resolvable only with surgery. Transforming growth factor is the key player in the epithelial-mesenchymal transition (EMT) and fibrogenesis process, and some molecules modulating its activity, including peroxisome proliferator-activated receptor (PPAR)-γ and its agonists, exert a promising antifibrotic action. The purpose of this study is to evaluate the contribution of signaling other than EMT, such as the AGE/RAGE (advanced glycation end products/receptor of AGEs) and the senescence pathways, in the etiopathogenesis of IBD. We used human biopsies from control and IBD patients, and we used a mouse model of colitis induced by dextran-sodium-sulfate (DSS), without/with treatments with GED (PPAR-gamma-agonist), or 5-aminosalicylic acid (5-ASA), a reference drug for IBD treatment. In patients, we found an increase in EMT markers, AGE/RAGE, and senescence signaling activation compared to controls. Consistently, we found the overexpression of the same pathways in DSS-treated mice. Surprisingly, the GED reduced all the pro-fibrotic pathways, in some circumstances more efficiently than 5-ASA. Results suggest that IBD patients could benefit from a combined pharmacological treatment targeting simultaneously different pathways involved in pro-fibrotic signals. In this scenario, PPAR-gamma activation could be a suitable strategy to alleviate the signs and symptoms of IBD and also its progression. [ABSTRACT FROM AUTHOR]

Background: The posterior wall fracture is the most frequent pattern of acetabular fractures. Many techniques of fixation have been described in the literature and involve plates, screws, or a combination of both. This study aims to investigate the clinical and radiological outcomes of spring plates in the treatment of comminuted posterior wall acetabular fractures. (2) Methods: A retrospective multicenter (four level I trauma centers) observational study was performed. Patients with a comminuted posterior wall acetabular fracture treated with a spring plate (DePuy Synthes, West Chester, PA) were included. Diagnosis was made according to the Judet and Letournel classification. Diagnosis was confirmed with plain radiographs in an antero-posterior view and Judet views, iliac and obturator oblique views, and thin-slice CT with multiplanar reconstructions. (3) Results: Forty-six patients (34 males and 12 females) with a mean age of 51.7 years (range 19–73) were included. The most common mechanism of injury was motor vehicle accident (34 cases). In all cases, spring plates were placed under an overlapping reconstruction plate. The mean follow-up was 33.4 months (range 24–48). The mean period without weight-bearing was 4.9 weeks (range 4–7), and full weight-bearing was allowed at an average of 8.2 weeks (range 7–11) after surgery. (4) Conclusions: According to the present data, spring plates can be considered a viable additional fixation of the posterior wall acetabular fractures. [ABSTRACT FROM AUTHOR]

Deep periprosthetic infection after total knee arthroplasty is a serious and challenging complication for the orthopedic surgeon. Muscular flaps may represent a valid treatment option for the treatment of this condition. We present a systematic literature review about the use of muscular flaps for the treatment of knee prosthetic joint infection. The review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. 70 articles, out of 589 titles, were considered eligible for the full-text analysis. Finally, 27 studies that met inclusion criteria were included in this review. Overall, 345 patients (139 males, 206 females) suffering from TKA infection treated with muscular flaps were collected. The mean age was 57.3 years. Mean follow-up, reported in all studies, was 30.1 months. The results presented by the different authors, highlight the effectiveness of muscular flaps for the treatment of periprosthetic infection, in terms of function, limb salvage, prevention of recurrences, cost-effectiveness, and quality of life postoperatively. Muscle flaps provide an excellent management option for patients with persistent infection after total knee arthroplasty. [ABSTRACT FROM AUTHOR]

Background: Surgical palliative treatment of spinal metastases (SM) could influence the quality of life (QoL) in cancer patients, since the spine represents the most common site of secondary bony localization. Traditional open posterior instrumented fusion (OPIF) and Percutaneous pedicle screw fixation (PPSF) became the main surgical treatment alternatives for SM, but in Literature there is no evidence that describes the absolute superiority of one treatment over the other. Materials and Methods: This is a systematic review and meta-analysis of comparative studies on PPSF versus OPIF in patients with SM, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The outcomes of interest were: complications, blood loss, infections, mortality, pain and also the Quality of Life (QoL). Results: There were a total of 8 studies with 448 patients included in the meta-analyses. Postoperative complications were more frequent in OPIF (odds ratio of 0.48. 95% CI, 0.27 to 0.83; p= 0.01), PPFS was associated with blood loss (odds ratio -585.70. 95% IC, -848.28 to -323.13.69; p< 0.0001) and a mean hospital stay (odds ratio -3.77. 95% IC, -5.92 to -1.61; p= 0.0006) decrease. The rate of infections was minor in PPFS (odds ratio of 0.31. 95% CI, 0.12 to 0.81; p= 0.02) whereas the occurrence of reinterventions (0.76. 95% CI, 0.25 to 2.27; p= 0.62) and the mortality rate was similar in both groups (odds ratio of 0.79. 95% CI, 0.40 to 1.58; p= 0.51). Finally, we also evaluated pre and post-operative VAS and the meta-analysis suggested that both techniques have a similar effect on pain. Discussion and Conclusion: The PPSF treatment is related with less complications, a lower rate of infections, a reduction in intraoperative blood loss and a shorter hospital stay compared to the OPIF treatment. However, further randomized clinical trials could confirm the results of this meta-analysis and provide a superior quality of scientific evidence. [ABSTRACT FROM AUTHOR]

Intestinal fibrosis is characterized by an abnormal deposition of Extracellular Matrix (ECM) produced by activated myofibroblats. Despite many biological mediators are implicated in ECM proteins accumulation, a pivotal role is certainly played by TGF-β that acts mainly through Smad proteins (1). Recently, it has been thought that different molecules could be involved in TGFβ-dependent fibrotic signaling (2) and for this reason, aim of this study was to evaluate the involvement of Sphingosine kinase/Sphingosine 1 phosphate in an experimental mice model of intestinal fibrosis induced by oral administration of DSS. 20 mice were divided into 2 groups: control (H2O) n=5 and DSS n=15. Histological and immunohistochemical evaluation using TGF-β, p-Smad3, Collagen I-III, α-SMA, SPHK1, RhoA, PI3K, Akt, p-Akt and p-mTOR were performed. In DSS mice histological analysis assessed in H&E and Masson's Trichrome showed marked signs of inflammation and fibrosis. Immunopositivity for canonical TGF-β/Smads pathway molecules TGF-β, p-Smad3, Collagen I-III and α-SMA resulted mild expressed in control mice, while there was a significant increase in DSS group. Immunohistochemical analysis for non-Smad TGF-β pathway proteins SPHK1, RhoA, PI3K, Akt, p-Akt and p-mTOR showed a high positivity in DSS mice compared to untreated group. These preliminary results demonstrated the hypothesis that the development of intestinal fibrosis could be influenced not only by TGFβ/Smad pathway but also by a crosstalk between TGFβ/SPHK1/S1P signaling that could represent a new crucial driver in colonic fibrosis. Development of molecules able to control the synthesis of S1P, through the regulation of its kinase SPHK1, could provide a novel attractive therapeutic target to control fibrogenic process. [ABSTRACT FROM AUTHOR]

Collagen and MMPs play a pivotal role in the pathophysiology of the Pelvic Organ Prolapse (1). In POP samples a switch between type I and type III collagen together with a simultaneous activation of MMPs have been observed and the main consequence of these changes is the loss of mechanical support in the vaginal wall (2). Aim of this study was to prove that AGEs induces the activation of MMPs through ERK1/2 and synchronically stimulates changes in collagen composition directly through Smads. The case group consisted of 20 patients suffering from stage III genital prolapse undergoing colpohysterectomy and anterior and posterior plastic vaginal surgery and 10 control patients treated with laparohysterectomy for uterine fibromatosis. Histological and Immunohistochemical analysis using AGE, RAGE, ERK 1/2, Smads 2-3, Smad 7, MMP-3 and collagen I-III were performed. AGE and ERK 1/2 were also evaluated using Western-Blot analysis. POP samples from anterior vaginal wall showed disorganization and a distortion of the normal muscularis architecture. In POP samples AGE, ERK 1/2, Smad 2-3, MMP-3 and collagen III were upregulated in muscularis whereas in controls Smad 7 and collagen I were increased in the same layer. RAGE was mild or absent both in controls and prolapse. In summary we suggest the possible role of these new markers in the pathogenesis of POP but further studies are required to elucidate if the change of these molecules is the reason or the result of POP disease. [ABSTRACT FROM AUTHOR]

Aim To evaluate the case series of the patients operated with percutaneous fixation by the navigation system based on 3D fluoroscopic images, to assess the precision of a surgical implant and functional outcome of patients. Methods A retrospective study of pelvic ring fractures in a 2-year period included those treated with the use of the O-Arm 2 in combination with the Stealth Station 8. Pelvic fractures were classified according to the Tile and the Young-Burgess classification. All patients were examined before surgery, with X-rays and CT scans, and three days after surgery with additional CT scan. The positioning of the screws was evaluated according to the Smith score, the outcome with the SF-36. Results Among 24 patients 18 were with B and six with C type fracture according to Tile, while eight were with APC, 10 LC, and six with VS type according to Young-Burgess classification. All patients were treated in the supine position, except two. A total of 41 iliosacral or transsacral screws and five anterior pelvic ring screws were implanted. The medium surgical time per screw was 41 minutes. There was a perfect correspondence of screw scores value from post-operative CT and intraoperative fluoroscopy. The mean screw score value was 0.92. There were no cases of poor positioning. The median follow-up was 17.5 months. The patients were satisfied with their health condition on SF-36. Conclusion The use of the O-arm guarantees great precision in the positioning of the screws and reduced surgical times with excellent clinical results in patients. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this prospective and randomized study is to analyze and compare the outcomes of two surgical techniques for trapeziometacarpal joint osteoarthritis (Eaton-Littler grade III and IV)., Materials and Methods: 52 consecutive patients underwent surgical intervention by two different surgical techniques and checked for subjective outcomes (DASH, NPRS), objective outcomes (ROM, opposition test, grinding test, pulp pinch, hand grip) and radiographic outcomes. Surgical time was calculated., Results: 26 patients underwent suspension arthroplasty using abductor pollicis longus tendon interposition (Ceruso procedure) and 26 patients underwent arthroplasty using suspension tenoplasty of the flexor radialis carpi (Altissimi procedure). Both techniques were performed by a single surgeon and showed good and satisfactory results, with best outcome reported in Altissimi procedure regarding DASH and ROM (p = 0.011 and p = 0.012, respectively), with reduced surgical time (about 6 min less, p = 0.03). The proximal shift between scaphoid and the base of first metacarpal did not influence the final results of the cases treated., Conclusion: This study provides evidence that trapeziectomy in combination with both tendon suspension arthroplasty and tendon interposition are two surgical procedures useful to solve advanced basal joint arthritis. Patients who underwent suspension tenoplasty without tendon interposition seemed to be generally more satisfied with significantly better symptomatic and functional outcomes., (© 2023 The Authors.)

An 80-year-old male patient affected by Charcot-Marie-Tooth (CMT) disease came to our attention in July 2020, for the occurrence of low back pain and lower limb weakness, and also saddle anesthesia, urinary and faecal retention were referred. His diagnosis of CMT is dated back to 1955 and through the years, the clinical picture slowly worsened but never got particularly severe. The quick symptoms outbreak and the presence of urinary disturbances were red flags, which lead us to direct the diagnostic orientation elsewhere. A Magnetic Resonance Imaging of the thoraco-lumbar spinal cord was then performed and it was suggestive for synovial cyst at T10-T11. The patient underwent a decompression with laminectomy and then stabilized through arthrodesis. In the very next days after the surgery, the patient showed a sudden and significant improvement of his condition. At the last visit, he showed a remarkable relief of the symptoms, walking by himself.

Background and Aim: Sacral fractures with concomitant unstable pelvic ring injuries are severe conditions which occur in patients involved in high-energy trauma. When operative treatment is required, high surgical experience on the field is mandatory, especially in a sub-polpulation of obese patients which have increased risk of complications. The aim of this multicentric retroscpective study was to describe and analyze clinical and radiological outcomes of sacral vertical fractures in obese patients with a minimum of 2 years follow-up.   Methods: A total of 121 pelvic fractures admitted to Emergency Departments of three II level trauma centres from April 2015 to April 2021 were retrospectively reviewed. Demographics, injury mechanism, surgical data and complications were collected. The quality of life and the pelvic function were respectively measured by SF-12 questionnaires, Denis Work Scale and Majeed Score. The inter-rater agreement between the clinical scores and the Denis Work Scale was assessed.   Results: A total of 19 patients were included in the study. The average follow up was 41.16 months. The average BMI was 38.63 and the mean abdominal circumference was 128.10 cm. The average Majeed and SF-12 scores were respectively 66.47 and 74.32. Five patients were able to return to their previous employment. The post traumatic life's quality and related dysfunctions are influenced by the high BMI.   Conclusions: Faster recovery and early weight-bearing should be persued in order to minimize complications, expecially in obese patients. In these sample of patients, "triangular osteosynthesis" was the best treatment choice for sacral vertical fractures.

Objective: In recent years, Candida spondylodiscitis has represented an increasingly emerging disease in clinical practice. This condition requires long-term antibiotic therapy and sometimes surgical treatments. The main purpose of this study is to investigate the epidemiology, clinical and radiological aspects, treatment protocols, and outcomes of Candida-mediated vertebral osteomyelitis., Methods: A systematic review of the English literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.The research was conducted on Medline, Cochrane library, PubMed, and Scopus using as search terms "vertebral"; "spinal"; "infection"; "spondylodiscitis"; "discitis"; "osteomyelitis"; "Candida"; and "Candidosis." A case of vertebral candidiasis that was surgically managed was also reported., Results: In total, 88 articles were included in our systematic review. Including the reported case, our analysis covered 113 cases of vertebral candidiasis. Candida albicans was isolated in 64 cases (56.1%), Candida tropicalis in 21 (18.4%), Candida glabrata in 14 (12.3%), and Candida parapsilosis in five (4.4%). The mean duration of the follow-up was 395 days. Finally, 87 (82%) patients completely recovered, ten (9.4%) died, and nine (8.5%) reported sequelae., Conclusion: This systematic review summarized the state of the art on vertebral candidiasis, describing data on its clinical features, diagnostic criteria and current limitations, and treatment alternatives and their outcomes., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Introductionː Cervical disk arthroplasty is a potential alternative procedure to anterior cervical decompression and fusion for the treatment of cervical disk disease. The aim of the study was to perform a systematic literature review on long-term clinical and radiological outcomes after Bryan cervical disk arthroplasty.Material and Methodsː A systematic literature review was performed according to PRISMA guidelines via PubMed and Embase, Scopus, and the Cochrane Library database by using the following keywords: "Bryan prosthesis"; "cervical disk arthroplasty"; "outcomes"; and "long-term follow-up." Eight articles with at least 10 years of follow-up were considered for eligibility.Resultsː In total, 481 patients were enrolled in the studies. Because of the occurrence of multiple treated levels, 588 arthroplasties were performed, divided as follows: 12 C3/4 cervical disk arthroplasties (2.01%), 63 C4/5 (10.71%), 325 C5/6 (55.27%), and 188 C6/7 (31.97%). The mean preoperative cervical lordosis was 13.6 ± 9.3°, whereas the last follow-up value was 12.8 ± 8.7°. In the last follow-up, the mean segmental range of motion was 8.2 ± 3.3°.Discussion: Recent studies have suggested that cervical disk arthroplasty should be safely performed in healthy young patients with disk degeneration who may need future revision surgery. The results suggest that this procedure preserves native cervical spinal biomechanics at long-term follow-up with acceptable adjacent segments disease and periprosthetic ossifications.Conclusionsː Cervical disk arthroplasty has good long-term device survival, motility, adjacent segment degeneration, and clinical outcomes. Therefore, it represents a valid alternative for the treatment of cervical spine degenerative pathologies, especially in young patients., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Fracture non-union is a challenging orthopaedic issue and a socio-economic global burden. Several biological therapies have been introduced to improve traditional surgical approaches. Among these, the latest research has been focusing on adipose tissue as a powerful source of mesenchymal stromal cells, namely, adipose-derived stem cells (ADSCs). ADSC are commonly isolated from the stromal vascular fraction (SVF) of liposuctioned hypodermal adipose tissue, and their applications have been widely investigated in many fields, including non-union fractures among musculoskeletal disorders. This review aims at providing a comprehensive update of the literature on clinical application of ADSCs for the treatment of non-unions in humans. The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Only three articles met our inclusion criteria, with a total of 12 cases analyzed for demographics and harvesting, potential manufacturing and implantation of ADSCs. The review of the literature suggests that adipose derived cell therapy can represent a promising alternative in bone regenerative medicine for the enhancement of non-unions and bone defects. The low number of manuscripts reporting ADSC-based therapies for long bone fracture healing suggests some critical issues that are discussed in this review. Nevertheless, further investigations on human ADSC therapies are needed to improve the knowledge on their translational potential and to possibly achieve a consensus on their use for such applications.