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Abstract Background Unicompartmental knee arthroplasty (UKA) is a surgical procedure for managing osteoarthritis of one joint compartment, most commonly the medial side. This systematic review investigates the causes of UKA revision. The outcomes of interest were establishing the revision rate, time to revision, and the most common causes of revision in the long- and midterm follow-up. Methods This study was conducted according to the 2020 PRISMA statement. In October 2024, the following databases were accessed: PubMed, Web of Science, Google Scholar, and Embase. All the clinical studies investigating the rate and causes of revision in UKA were accessed. Only studies with a minimum of 10 years of follow-up were considered. Results Data from 56 studies (13,540 patients) were collected. Of them, 65.6% were women. The mean length of the follow-up was 13.1 ± 3.0 years. The mean age of the patients was 65.6 ± 5.6 years, and the mean BMI was 28.5 ± 2.2 kg/m2. Revisions were performed in 8.8% (2641 of 30,140) of implanted UKAs. The mean time to revision was 6.5 ± 2.6 (range, 2.5 to 13.0) years. Conclusion 8.8% (2641 of 30,140) of UKAs were revised at a mean time of 6.5 ± 2.6 years. Level of evidence Level IV, systematic review.

Abstract Superior mesenteric artery syndrome (SMAS) is a rare and unpredictable complication after correction spine surgery for adolescent idiopathic scoliosis (AIS). The management of this condition is poorly investigated, with controversial outcomes. This investigation systematically reviewed current evidence on pathogenesis, risk factors, management, and outcomes of SMAS following correction spine surgery for AIS. The present systematic review was conducted according to the 2020 PRISMA statement. All the included investigations reported SMAS presentation following scoliosis correction surgery in AIS. 29 articles with 61 eligible patients were included in this review. The mean age of the patients was 15.8 ± 7.2 years. The mean weight was 45.3 ± 8.0 kg, the mean height 159.6 ± 13.6 cm, and the mean BMI 16.5 ± 2.9 kg/m2. The mean duration of the treatment for SMAS was 21.6 ± 10.3 days. The mean interval between spine surgery and symptoms of SAMS was 69 days, with high between-studies variability (3 days to 4 years). Prompt identification of risk factors and an early diagnosis are necessary to manage SMAS and reduce the risk of complications. Additional investigations are required to establish risk factors and diagnostic criteria. Level of evidence Level IV, systematic review.

Abstract Background This study evaluated the osseointegration potential of functionalised high-performance oxide ceramics (HPOC) in isolation or coated with BMP-2 or RGD peptides in 36 New Zeeland female rabbits using micro-computed tomography (micro CT). The primary outcomes of interest were to assess the amount of ossification evaluating the improvement in the bone volume/ total volume (BV/TV) ratio and trabecular thickness at 6 and 12 weeks. The second outcome of interest was to investigate possible differences in osteointegration between the functionalised silanised HPOC in isolation or coated with Bone Morphogenetic Protein 2 (BMP-2) or RGD peptides. Methods 36 adult female New Zealand white rabbits with a minimum weight of three kg were used. One-third of HPOCs were functionalised with silicon suboxide (SiOx), a third with BMP-2 (sHPOC-BMP2), and another third with RGD (sHPOC-RGD). All samples were scanned with a high-resolution micro CT (U-CTHR, MILabs B.V., Houten, The Netherlands) with a reconstructed voxel resolution of 10 µm. MicroCT scans were reconstructed in three planes and processed using Imalytics Preclinical version 2.1 (Gremse-IT GmbH, Aachen, Germany) software. The total volume (TV), bone volume (BV) and ratio BV/TV were calculated within the coating area. Results BV/TV increased significantly from 6 to 12 weeks in all HPOCs: silanised (P = 0.01), BMP-2 (P

Osteoarthritis (OA) is a prevalent disease among the elderly population, necessitating effective treatment options. Total joint arthroplasty (TJA) is a reliable surgical procedure that has shown good long-term clinical outcomes for OA. However, certain challenges, such as implant failure caused by particle-induced aseptic loosening or hypersensitivity to metal ions, remain unresolved in TJA. High-performance ceramic implants have emerged as a promising solution to address these persistent implant-related issues. This review article provides an overview of the composition and characteristics of ceramics used in TJA, highlighting their potential advantages and associated risks. While ceramic implants have demonstrated excellent performance in vivo for hip and knee arthroplasty, their bioinert behaviour is still considered a crucial factor regarding cementless options. Therefore, novel methods are investigated that seem to be able to combine the benefits of ceramic materials with an excellent osseointegration behaviour, which makes ceramics as implant materials an even stronger option for future applications.

Abstract Background Anterior cruciate ligament (ACL) tears in skeletally immature patients are increasingly common. Evidence comparing the outcomes of all-epiphyseal versus trans-epiphyseal ACL reconstruction in skeletally immature patients is limited, and the current literature could benefit from a comprehensive systematic review. The present study compared all-epiphyseal versus trans-epiphyseal ACL reconstruction in skeletally immature patients. The outcomes of interest were to compare joint laxity, patient-reported outcome measures (PROMs), return to sport, and complications. Methods This study was conducted according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. In November 2023, the following databases were accessed: PubMed, Web of Science, Google Scholar, and Embase. No additional filters were used in the database search. All the clinical studies investigating ACL reconstruction in skeletally immature patients were accessed. Only articles that clearly stated the surgical technique (all- or trans-epiphyseal) were eligible. Only articles with a minimum of 6 months of follow-up were included. Only articles that clearly stated that surgeries were conducted in children with open physis were eligible. Results Data from 1489 patients (1493 procedures) were collected, of which 32% (490 of 1489 patients) were female. The mean length of follow-up was 46.6 months. The mean age of the patients was 12.7 years. No difference was found in joint laxity (Table 3): positive pivot shift (P = 0.4), positive Lachman test (P = 0.3), and mean arthrometer laxity (P = 0.1). No difference was found in PROMs (Table 4): International Knee Documentation Committee (IKDC) (P = 0.3), Lysholm (P = 0.4), and Tegner (P = 0.7). The trans-epiphyseal technique was associated with a greater rate of patients unable to return to sports (1% versus 7%, P = 0.0001) and with a longer time to return to sports (7.7 versus 8.6 months, P = 0.01). Though the trans-epiphyseal technique was associated with a lower rate of return to sport, this difference was not statistically significant (P = 0.8). No difference was evidenced in the rate of patients who had reduced their league or level of sports activity (P = 0.6) or in the rate of patients who had returned to their previous league or level of sports activity (P = 0.7). No difference was found in the rate of complication: re-tear (P = 0.8), reoperation (P = 0.7), increased laxity (P = 0.9), and persistent instability sensation (P = 0.3). Conclusion Trans-epiphyseal ACL reconstruction was associated with a greater rate of patients unable to return to sport and with a longer time to return to sport compared with the all-epiphyseal technique in skeletally immature patients. Level of evidence Level III, systematic review.

Abstract Background Neurological gait disorders are mainly classified based on clinical observation, and therefore difficult to objectify or quantify. Movement analysis systems provide objective parameters, which may increase diagnostic accuracy and may aid in monitoring the disease course. Despite the increasing wealth of kinematic movement and balance parameter data, the discriminative value for the differentiation of neurological gait disorders is still unclear. We hypothesized that kinematic motion and balance parameter metrics would be differently altered across neurological gait disorders when compared to healthy controls. Methods Thirty one patients (9 normal pressure hydrocephalus , 16 cervical myelopathy , 6 lumbar stenosis ) and 14 healthy participants were investigated preoperatively in an outpatient setting using an inertial measurement system (MyoMotion) during 3 different walking tasks (normal walking, dual-task walking with simultaneous backward counting, fast walking). In addition, the natural postural sway of participants was measured by pedobarography, with the eyes opened and closed. The range of motion (ROM) in different joint angles, stride time, as well as sway were compared between different groups (between-subject factor), and different task conditions (within-subject factor) by a mixed model ANOVA. Results Kinematic metrics and balance parameters were differently altered across different gait disorders compared to healthy controls. Overall, NPH patients significantly differed from controls in all movement parameters except for stride time, while they differed in balance parameters only with regard to AP movement. LST patients had significantly reduced ROMs of the shoulders, hips, and ankles, with significantly altered balance parameters regarding AP movement and passed center-of-pressure (COP) distance. CM patients differed from controls only in the ROM of the hip and ankle, but were affected in nearly all balance parameters, except for force distribution. Conclusion The application of inertial measurement systems and pedobarography is feasible in an outpatient setting in patients with different neurological gait disorders. Rather than defining singular discriminative values, kinematic gait and balance metrics may provide characteristic profiles of movement parameter alterations in the sense of specific ´gait signatures´ for different pathologies, which could improve diagnostic accuracy by defining objective and quantifiable measures for the discrimination of different neurological gait disorders. Trial registration The study was retrospectively registered on the 27th of March 2023 in the ‘Deutsches Register für Klinische Studien’ under the number DRKS00031555.

Abstract Background Several clinical investigations have compared different pharmacologic agents for the prophylaxis of venous thromboembolism (VTE). However, no consensus has been reached. The present investigation compared enoxaparin, fondaparinux, aspirin and non-vitamin K antagonist oral anticoagulants (NOACs) commonly used as prophylaxis following total hip arthroplasty (THA). A Bayesian network meta-analysis was performed, setting as outcomes of interest the rate of deep venous thrombosis (DVT), pulmonary embolism (PE) and major and minor haemorrhages. Methods This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension statement for reporting systematic reviews incorporating network meta-analyses of healthcare interventions. All randomised controlled trials (RCTs) comparing two or more drugs used for the prophylaxis of VTE following THA were accessed. PubMed, Web of Science and Google Scholar databases were accessed in March 2023 with no time constraint. Results Data from 31,705 patients were extracted. Of these, 62% (19,824) were women, with age, sex ratio, and body mass index (BMI) being comparable at baseline. Apixaban 5 mg, fondaparinux, and rivaroxaban 60 mg were the most effective in reducing the rate of DVT. Dabigatran 220 mg, apixaban 5 mg, and aspirin 100 mg were the most effective in reducing the rate of PE. Apixaban 5 mg, ximelagatran 2 mg and aspirin 100 mg were associated with the lowest rate of major haemorrhages, while rivaroxaban 2.5 mg, apixaban 5 mg and enoxaparin 40 mg were associated with the lowest rate of minor haemorrhages. Conclusion Administration of apixaban 5 mg demonstrated the best balance between VTE prevention and haemorrhage control following THA. Level of evidence Level I, network meta-analysis of RCTs.

Abstract Extracellular vesicles (EVs) mediate cell-to-cell communication by horizontally transferring biological materials from host cells to target cells. During exposure to pathogens, pathogen-associated molecular patterns (e.g., lipopolysaccharide, LPS) get in contact with endothelial cells and stimulate the secretion of endothelial cell-derived EVs (E-EVs). The triggered EVs secretion is known to have a modulating influence on the EVs-receiving cells. Macrophages, a major component of innate immunity, are polarized upon receiving external inflammatory stimuli, in which toll-like receptor4 (TLR4)—nuclear factor kappa B (NFκB) pathway plays a key role. However, the functions of LPS-induced E-EVs (ELPS-EVs) in modulating macrophage phenotype and activation remain elusive. We collected the EVs from quiescent endothelial cells (ENor-EVs) and ELPS-EVs to detect their stimulatory role on NR8383 macrophages. Isolated EVs were characterized by transmission electron microscopy (TEM), western blot assay, and nanoparticle tracking analysis (NTA). NR8383 macrophages were stimulated with ELPS-EVs, ENor-EVs, or PBS for 24 h. Hereafter, the uptake of EVs by the macrophages was investigated. Upon EVs stimulation, cellular viability was determined by MTT assay, while macrophage phenotype was analyzed by flow cytometry and immunofluorescence analysis. Furthermore, a western blot assay was conducted to evaluate the potentially involved TLR4–NFκB pathway. Interestingly, upon exposure to LPS, endothelial cells secreted significantly higher amounts of EVs (i.e., ELPS-EVs) when compared to quiescent cells or cells in PBS. The ELPS-EVs were also better internalized by NR8383 macrophages than ENor-EVs. The cellular viability of ELPS-EVs-treated macrophages was 1.2 times higher than those in the ENor-EVs and PBS groups. In addition, ELPS-EVs modulated NR8383 macrophages towards a proinflammatory macrophage M1-like phenotype. This was indicated by the significantly upregulated expressions of proinflammatory macrophage biomarkers CD86 and inducible nitric oxide synthase (iNOS) observed in ELPS-EVs-treated macrophages. The TLR4–NFκB signaling pathway was substantially activated in ELPS-EVs-treated macrophages, indicated by the elevated expressions of makers TLR4 and phosphorylated form of nuclear factor kappa B p65 subunit (p-NFκBp65). Overall, our results indicate that E-EVs play a crucial role in macrophage phenotype modulation under inflammatory conditions.

Abstract Total hip arthroplasty (THA) is a common procedure for patients suffering from hip pain e.g. from osteoarthritis, osteonecrosis, or hip fractures. The satisfaction of patients undergoing THA is influenced by the choice of implant type and material, with one key factor being the selection of the appropriate material combination for the bearing surface. In this Bayesian network meta-analysis, we investigated the impact of material combinations for the bearing surface on the longevity of hip implants. The wear penetration rate per year and the total wear penetration in the liner resulting from different material combinations, as well as the survival rate at last follow-up, were examined. We analyzed a total of 663,038 THAs, with 55% of patients being women. Mean patient age was 59.0 ± 8.1 years and mean BMI 27.6 ± 2.6 kg/m2. The combination of an aluminium oxide (Al2O3) head and an Al2O3 liner demonstrated the lowest wear penetration at last follow-up and the lowest rate of wear penetration per year. Additionally, the combination of a crosslinked polyethylene (XLPE) liner and a zircon oxide (ZrO2) head demonstrated the lowest rate of revision at last follow-up. These findings underscore the importance of careful material selection for hip implant bearing surfaces to optimize their longevity and patient satisfaction after THA.

Abstract The prophylactic action of non-steroidal anti-inflammatory drugs (NSAIDs) in heterotopic ossification (HO) was first described following analgesic therapy with indomethacin. Following that evidence, several compounds have been successfully used for prophylaxes of HO. Ibuprofen has been also proposed for the prevention of HO following THA. The present study compared the administration of ibuprofen for three weeks versus indomethacin as prophylaxis for HO following primary THA. In all THA procedures, pre- and post-operative protocols were conducted in a highly standardized fashion. The type of HO prophylaxis (indomethacin 100 mg/daily or ibuprofen 100 mg/daily) was chosen according to a chronological criterion: from 2017 to 2019 indomethacin was used, whereas from 2019 to 2022 ibuprofen was administered. In case of allergy or intolerance to NSAIDs, no prophylaxis was performed, and patients were included as a control group. All patients who underwent an anteroposterior radiography of the pelvis at a minimum of 12 months following THA were considered for inclusion. On admission, the age and sex of the patients were recorded. Moreover, the causes of osteoarthritis and the date of surgery were recorded. The grade of HO was assigned by a blinded assessor who was not involved in the clinical management of the patients. The modified Brooker Staging System was used to rate the efficacy of the interventions. Data from 1248 patients were collected. 62% (767 of 1248 patients) were women. The mean age was 67.0 ± 2.9 years. The mean follow-up was 21.1 ± 10.8 months. In the ibuprofen group, 73% of patients evidenced Brooker 0, 17% Brooker I, and 10% Brooker II. In the indomethacin group, 77% of patients evidenced Brooker 0, 16% Brooker I, 6% Brooker II. No patient in the ibuprofen and indomethacin group developed Brooker III or IV. In the control group, 64% of patients evidenced Brooker 0, 21% Brooker I, 3% Brooker II, and 12% Brooker III. No patient in the control group developed Brooker IV HO. Concluding, three weeks of administration of ibuprofen demonstrated similar efficacy to indomethacin in preventing HO following primary THA. The prophylaxis with ibuprofen or indomethacin was more effective in preventing HO compared to a control group who did not receive any pharmacological prophylaxis.

Abstract Tears of the anterior cruciate ligament (ACL) negatively impact the stability and kinematics of the knee. Interference screws (ISs) are used for graft fixation in ACL reconstruction and provide sufficient fixation strength to withstand the patients' activities during the graft-to-bone integration process. Magnesium is a novel material used to manufacture IS given its strength and bioabsorbability. In previous studies, the selected magnesium IS design showed a better fixation performance in comparison to the conventional IS design due to its shape design and surface condition. In this study, bioabsorbable magnesium ISs were tested for their insertion (insertion torque and a number of turns to implement the IS) and fixation performance (pull-out and dynamic test). To obtain a reliable initial assessment of IS performance, ISs were implanted in 15 per cubic foot (PCF) Sawbones polyurethane foam blocks, Sawbones biomechanical tibia models with 17 PCF foam cores, and human cadaveric tibiae. Porcine tendons were used in the foam block pull-out test, and nylon ropes were used in all other test setups to prevent influences of the ligament graft material itself. In the pull-out test, the graft was subjected to tensile stress at a rate of 6 mm/min. For the dynamic test, 1000 cycles between 0 and 200 N were performed, followed by a final pull-out test. After each test, the tunnel widening pattern was observed by measuring the aspect ratio of the tunnel at the insertion site. The insertion torque lies within the normal insertion torque of the ISs as well as the average ligament tension before the insertion. In the foam block setup, the nylon rope showed a higher pull-out force than the porcine tendon. The comparison of each setup using nylon rope for both pull-out and pull-out after the dynamic test showed no significant difference between the foam block and cadaver setup. However, all tibia model setup shows unexpectedly high pull-out force due to the influence of its cortical layer. There were no statistically significant differences in tunnel widening between foam block-porcine tendon and foam block-nylon rope constructs. The pull-out resistance of magnesium ISs falls within the typical ACL tension range during daily activities. Even though the test results of the magnesium ISs are different in each bone material, the magnesium IS shows adequate fixation ability and workability during insertion without material failure.

Abstract Introduction The optimal dose of duloxetine in the management of fibromyalgia remains still controversial. Therefore, a systematic review and meta-analysis to investigate efficacy and safety of duloxetine was conducted. The outcomes of interests were to assess changes in Fibromyalgia Impact Questionnaire (FIQ), Brief Pain Inventory (BPI), and Clinical Global Impression (CGI). The rate of of adverse events and those leading to therapy discontinuation were also investigated. Material and methods This study followed the 2020 PRISMA guidelines. The literature search started in December 2022 accessing PubMed, Google scholar, Embase, and Scopus databases. All the RCTs investigating the efficacy and safety of daily administration of duloxetine for fibromyalgia were accessed. Studies reporting quantitative data under the outcomes of interest, and including a minimum of 10 patients who completed a minimum of 4 weeks follow-up, were included. Studies on combined pharmacological and non-pharmacological managements for fibromyalgia were not considered. Results Data from 3432 patients (11 RCTs) were included. The mean age of the patients was 46.4 ± 10.7 years old, and the mean BMI 25.3 ± 3.2 kg/m2. 90% (3089 of 3432 patients) were women. The 60 mg/daily cohort reported the higher FIQ, followed by the 30, 30–60, 120 mg/daily, and placebo groups, while the 60–120 mg /daily group performed the worst results. Concerning the CGI severity scale, placebo resulted in the lowest improvement, and no differences were found in the other groups. Concerning the BPI interference and severity pain scores, the 30–60 mg/daily group reported the worst result, along with the placebo group. The rate of adverse events leading to study discontinuation were lower in the 60–120 group, followed by the 30–60 and 30 mag/daily groups. Duloxetine was superior in all the comparisons to placebo, irrespective of the doses, in all endpoints analysed. Conclusions Duloxetine could help in improving symptoms of fibromyalgia. The dose of duloxetine should be customised according to individual patients. Irrespective of the doses, duloxetine was more effective than placebo in the management of fibromyalgia. The dose of duloxetine must be customised according to individual patients. Level of evidence I Meta-analysis of double-blind RCTs.

Abstract Bone-patellar tendon-bone (BPTB), two- and four-strand hamstring tendon (4SHT and 2SHT, respectively) are the most common autografts used for anterior cruciate ligament (ACL) reconstruction. The present study compared BPTB, 2SHT, and 4SHT for ACL reconstruction in terms of joint laxity, patient reported outcome measures (PROMs), rate of failure and anterior knee pain (AKP). The time to return to sport and the peak torque between the autografts were also compared. Finally, prognostic factors leading to worse outcomes were also investigated. It was hypothesized that all grafts yield similar proprieties in terms of joint laxity, patient reported outcome measures (PROMs) and rate of failure, but that the BPTB autograft causes a greater rate of anterior knee pain (AKP). The literature search was conducted. All clinical trials comparing BTPB and/or 2SHT, and/or 4SHT were accessed. Grafts other than BTPB and/or 4SHT and/or 2SHT were not considered. Articles reporting outcomes of allografts or synthetic grafts were not eligible, nor were those concerning revision settings. Articles reporting ACL reconstruction in patients with multi-ligament damage were also not eligible. Data from 95,575 procedures were retrieved. The median length of follow-up was 36 months. The median age of the patients was 27.5 years. With regard to joint laxity, similarity was found in terms of Lachman and Pivot shift tests between all three autografts. The BPTB demonstrated the greatest stability in terms of instrumental laxity. BPTB demonstrated the greatest PROMs. BPTB demonstrated the greatest rate of AKP, while AKP in 2SHT and 4SHT was similar. Concerning failure, statistically significant inconsistency was found (P = 0.008). The 4SHT demonstrated the quickest return to sport, followed by BPTB, and 2SHT. There was evidence of a negative association between the time span between injury to surgery, Lysholm score (P = 0.04), and Tegner scale (P = 0.04). Furthermore, there was evidence of a weak positive association between the time span between injury to surgery and return to sport (P = 0.01). BPTB may result in lower joint laxity, greater PROMs, and greater peak flexion torque compared to 2SHT and 4SHT autografts. On the other hand, BPTB reported the lowest peak extension torque and the greatest rate of AKP. Finally, a longer time span between injury and surgery negatively influences outcome.

Electrical stimulation (ES) is a widely discussed topic in the field of cartilage tissue engineering due to its ability to induce chondrogenic differentiation (CD) and proliferation. It shows promise as a potential therapy for osteoarthritis (OA). In this study, we stimulated mesenchymal stem cells (MSCs) incorporated into collagen hydrogel (CH) scaffolds, consisting of approximately 500,000 cells each, for 1 h per day using a 2.5 Vpp (119 mV/mm) 8 Hz sinusoidal signal. We compared the cell count, morphology, and CD on days 4, 7, and 10. The results indicate proliferation, with an increase ranging from 1.86 to 9.5-fold, particularly on day 7. Additionally, signs of CD were observed. The stimulated cells had a higher volume, while the stimulated scaffolds showed shrinkage. In the ES groups, up-regulation of collagen type 2 and aggrecan was found. In contrast, SOX9 was up-regulated in the control group, and MMP13 showed a strong up-regulation, indicating cell stress. In addition to lower stress levels, the control groups also showed a more spheroidic shape. Overall, scaffold-based ES has the potential to achieve multiple outcomes. However, finding the appropriate stimulation pattern is crucial for achieving successful chondrogenesis.

Abstract Background Immune-mediated conditions associated to Corona Virus Disease-19 (COVID-19) have been reported, including vasculitis, antiphospholipid antibody syndrome, myositis, and lupus. Emerging studies have reported the potential occurrence of reactive arthritis in patients previously infected with COVID-19. This systematic review summarised the current evidence on the occurrence of reactive arthritis in patients previously infected by COVID-19. Methods This study was conducted according to the 2020 PRISMA guidelines. All the clinical investigations describing the occurrence of reactive arthritis following COVID-19 were accessed. In September 2022, the following databases were accessed: PubMed, Web of Science, Google Scholar, Embase. The generalities of the study were extracted: author, year and journal of publication, country of the main author, study design, sample size, mean age, number of women, main results of the study. The following data on COVID-19 severity and management were retrieved: type of treatment, hospitalization regimes (inpatient or outpatient), admission to the intensive care unit, need of mechanical ventilation, pharmacological management. The following data on reactive arthritis were collected: time elapsed between COVID-19 infection to the onset of reactive arthritis symptoms (days), pharmacological management, type of arthritis (mono- or bilateral, mono- or polyarticular), extra-articular manifestations, presence of tenosynovitis or enthesitis, synovial examination at microscopic polarised light, imaging (radiography, magnetic resonance, sonography), clinical examination, laboratory findings. Results Data from 27 case reports (54 patients) were retrieved, with a mean age of 49.8 ± 14.5 years. 54% (29 of 54 patients) were women. The mean time span between COVID-19 infection and the occurrence of reactive arthritis symptoms was 22.3 ± 10.7 days. Between studies diagnosis and management of reactive arthritis were heterogeneous. Symptoms resolved within few days in all studies considered. At last follow-up, all patients were minimally symptomatic or asymptomatic, and no additional therapy or attentions were required by any patient. Conclusion Poor evidence suggests that COVID-19 could target the musculoskeletal system causing reactive arthritis at its post infectious stage. COVID-19 can act as a causative agent or as a trigger for development of reactive arthritis even without presence of antibodies of rheumatological disorders. Treating physicians should have a high index of suspicion while treating post infectious COVID-19 patient with arthralgia. Level of evidence Level IV, systematic review.

Abstract Background Following anterior cruciate ligament (ACL) tears, both repair and reconstruction may be performed to restore joint biomechanics and proprioception. The present study compared joint laxity, patient-reported outcome measures (PROMs), and rate of failure following primary repair versus reconstruction for ACL ruptures. Methods This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pubmed, Google scholar, Embase, and Web of Science were accessed in September 2022. All the clinical investigations comparing repair versus reconstruction for primary ACL tears were accessed. Studies reporting data on multiple ligament injuries settings were not eligible. Results Data from eight articles (708 procedures) were collected. The mean length of the follow-up was 67.3 ± 119.4 months. The mean age of the patients was 27.1 ± 5.7 years. Thirty-six percent (255 of 708 patients) were women. The mean body mass index (BMI) was 24.3 ± 1.1 kg/m2. The mean time span from injury to surgery was 36.2 ± 32.3 months. There was comparability at baseline with regards to instrumental laxity, Lachman test, International Knee Document Committee (IKDC), and Tegner Scale (P > 0.1). Similarity between ACL reconstruction and repair was found in IKDC (P = 0.2) and visual analog scale (VAS) satisfaction (P = 0.7). The repair group demonstrated greater mean laxity (P = 0.0005) and greater rate of failure (P = 0.004). Conclusion ACL reconstruction may yield greater joint stability and lower rate of failure compared with surgical repair. Similarity was found in PROMs. Level of evidence: III

Abstract Background This in vitro study investigated the osseointegration and implant integration of high performance oxide ceramics (HPOC) compared to titanium implants in rabbits. Methods Histomorphometry was conducted around the distal, proximal, medial, and lateral aspects of the HPOC to quantify the amount of mature and immature ossification within the bone interface. Histomorphometry was conducted by a trained musculoskeletal pathologist. The region of interest (ROI) represented the percentage of surrounding area of the implant. The percentage of ROI covered by osteoid implant contact (OIC) and mature bone implant contact (BIC) were assessed. The surrounding presence of bone resorption, necrosis, and/or inflammation were quantitatively investigated. Results All 34 rabbits survived the 6- and 12-week experimental period. All HPOC implants remained in situ. The mean weight difference from baseline was + 647.7 mg (P

Abstract During Autologous Matrix-Induced Chondrogenesis (AMIC), the membrane is often glued into the chondral defect. However, whether fibrin glue influences cells proliferation and migration remain unclear. This study evaluated the impact of fibrin glue addition to biologic membranes loaded with bone marrow-derived mesenchymal stem cells (B-MSCs). A porcine derived collagen membrane (Cartimaix, Matricel GmbH, Germany) was used. B-MSCs were harvested from three different unrelated donors. The membranes were embedded in mounting medium with DAPI (ABCAM, Cambridge, UK) and analysed at 1-, 2-, 3-, 4-, 6-, and at 8-week follow-up. The DAPI ties the DNA of the cell nucleus, emitting blue fluorescence. DAPI/nuclei signals were analysed with fluorescence microscopy at 100-fold magnification. The group without fibrin glue demonstrated greater migration of the B-MSCs within the membrane at week 4 (P

Abstract Introduction Potential advantages of the Extreme Lateral Interbody Fusion (XLIF) approach are smaller incisions, preserving anterior and posterior longitudinal ligaments, lower blood loss, shorter operative time, avoiding vascular and visceral complications, and shorter length of stay. We hypothesize that not every patient can be safely treated at the L4/5 level using the XLIF approach. The objective of this study was to radiographically (CT-scan) evaluate the accessibility of the L4/5 level using a lateral approach, considering defined safe working zones and taking into account the anatomy of the superior iliac crest. Methods Hundred CT examinations of 34 female and 66 male patients were retrospectively evaluated. Disc height, lower vertebral endplate (sagittal and transversal), and psoas muscle diameter were quantified. Accessibility to intervertebral space L4/5 was investigated by simulating instrumentation in the transverse and sagittal planes using defined safe zones. Results The endplate L5 in the frontal plane considering defined safe zones in the sagittal and transverse plane (Zone IV) could be reached in 85 patients from the right and in 83 from the left side. Through psoas split, the safe zone could be reached through psoas zone II in 82 patients from the right and 91 patients from the left side. Access through psoas zone III could be performed in 28 patients from the right and 32 patients from the left side. Safe access and sufficient instrumentation of L4/5 through an extreme lateral approach could be performed in 76 patients of patients from the right and 70 patients from the left side. Conclusion XLIF is not possible and safe in every patient at the L4/5 level. The angle of access for instrumentation, access of the intervertebral disc space, and accessibility of the safe zone should be taken into account. Preoperative imaging planning is important to identify patients who are not suitable for this procedure.

Abstract Background Corrective osteotomies of the upper extremities with patient-specific instruments (PSIs) are increasingly used. In this context, the concordance between planning and postoperative 3D radiographs as well as the association between 3D accuracy and clinical outcome has rarely been evaluated. In this pilot study, we aimed to investigate our clinical mid-term outcome and 3D accuracy as well as their possible correlation, including identifying aspects critical to reaching optimal correction results. Methods From October 2018 to January 2020, we used PSIs for 12 corrective osteotomies of the upper extremity in 11 bones of 8 patients (congenital or posttraumatic deformities in 2 elbows, 3 forearms, 3 distal radii). In follow-up examination (10–25 months postoperatively), patient satisfaction, grip strength, ROM, VAS, and DASH were evaluated. Three-dimensional radiological accuracy was determined with 3D-reconstructed postoperative CT scans. With the software tool “Part Comparison” of Mimics® Innovation Suite Software/Materialise, surface differences of pre-planned and postoperative 3D models were compared. Results Compared to the preoperative situation pain and function were better at follow-up: The average VAS score significantly decreased from 6.5 ± 4.1 cm preoperatively to 2.3 ± 2.6 cm at the follow-up time point (p = 0.008). The average DASH score significantly improved, from 48.4 ± 30.9 to 27.0 ± 25.2 (p = 0.015). In the part comparison analysis “planned vs postoperative comparison”, significantly more points in percent (= 3D accuracy) were in a −3 mm to 3 mm interval than in the “preoperative vs planned comparison” (87.3 ± 13.8% vs 48.9 ± 16.6%, p = 0.004). After surgery, the maximum deviation value over all cases was 4.5 ± 1.1 mm, and the minimum deviation value was − 4.5 ± 1.2 mm vs preoperatively 12.9 ± 6.2 mm (p = 0.004) and − 7.2 ± 2.1 mm (p = 0.02), respectively. Clinically, in all cases with higher accuracy (> 90%), an improvement of either DASH or VAS or both of > 60% to the preoperative values occurred. There was a significant correlation between accuracy (%) and ΔVAS (p = 0.004). There were no method-related complications. Conclusions Our data after PSI-based corrective osteotomy in complex deformities of the upper extremity in a limited number of cases indicate a positive correlation between 3D accuracy and clinical outcomes. Examination of 3D accuracy to analyse sources of error in the hole procedure from initial CT scan to end of surgery even in patients with not fully satisfactory clinical results is required for further development of the method to achieve optimal correction results with nearly 100% congruence between the planned and postoperative 3D bone position. Trial registration This retrospective study was registered in the Center for Translational & Clinical Research Aachen (CTC-A) with the number 20-514 on November 20, 2021

Consideration of the individual carpal bone characteristics of the wrist plays a key role in well-functioning biomedical devices and successful surgical procedures. Although geometric differences and individual bone sizes have been analyzed in the literature, detailed morphologic descriptions and correlations covering the entire wrist reported in a clinical context are lacking. This study aimed to perform a comprehensive and automatic analysis of the wrist morphology using the freely available “Open Source Carpal Database” (OSCD). We quantified the size of each of the individual carpal bones and their combination. These sizes were extracted in n = 117 datasets of the wrist of the OSCD in anatomical directions and analyzed using descriptive statics and correlation analysis to investigate the morphological characteristics under sex-specific aspects and to provide regression plots and equations to predict individual carpal bone sizes from the proximal and distal row dimensions. The correlations in the proximal row were higher compared to the distal row. We established comprehensive size correlations and size rations and found that there exist statistical differences between sex, particularly of the scaphoid. The regression plots and equations we provided will assist surgeons in a more accurate preoperative morphological evaluation for therapy planning and may be used for future anatomically inspired orthopedic biomedical device designs.

Abstract Background The efficacy and safety profile of mesenchymal stem cells (MSCs) augmentation in chondral procedures are controversial. This systematic review updated the current evidence on MSCs augmentation for chondral procedures in patients with symptomatic chondral defects of the knee. Methods This study followed the PRISMA guidelines. The literature search was updated in August 2022. Two independent authors accessed PubMed, Google scholar, Embase, and Scopus. No additional filters or time constrains were used for the search. A cross reference of the bibliographies was also performed. All the clinical studies investigating surgical procedures for chondral defects of the knee augmented with MSCs were accessed. Defects of both tibiofemoral and patellofemoral joints were included. The following patient reported outcomes measures (PROMs) were retrieved at baseline and last follow-up: Visual Analogic Scale (VAS), Tegner Activity Scale, Lysholm Knee Scoring System, International Knee Documentation Committee (IKDC). Return to daily activities and data on hypertrophy, failure, revision surgery were also collected. Failures were defined as the recurrence of symptoms attributable to the index procedure. Revisions were defined as any reoperation at the site of the index procedure. Results A total of 15 clinical studies (411 procedures) were included. Patients returned to their prior sport activity at 2.8 ± 0.4 months. All the PROMs improved at last follow-up: Tegner (P = 0.0002), Lysholm (P

Abstract Autologous matrix induced chondrogenesis (AMIC) is a bone marrow stimulating technique used for the surgical management of chondral defects of the talus. The present study evaluated the clinical outcomes and imaging of AMIC as revision procedure for failed AMIC surgery for osteochondral defects of the talus. Forty-eight patients with symptomatic osteochondral defects who received a revision AMIC were evaluated after a minimum of two years follow-up. Patients with previous procedures rather than AMIC, those who required additional surgical procedures (e.g. ligament repair or deformity correction), or those who had evidence of kissing, bilateral, or multiple lesions were excluded. Outcome parameters included the Visual Analogic Scale (VAS), Tegner Activity Scale, the American Orthopedic Foot and Ankle Score (AOFAS), and the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. All patients were followed by an assessor who was not involved in the clinical management. 27 patients were enrolled in the present study. The mean age of the patient was 34.9 ± 3.1 years, and the mean BMI 27.2 ± 5.1 kg/m2. The mean defect surface area was 2.8 ± 1.9 cm2. The mean follow-up was 44.3 ± 21.4 months. The mean hospital length of stay was 4.4 ± 1.4 days. At final follow-up, the mean VAS score was 4.1 ± 3.1, the mean Tegner 3.5 ± 1.6, the mean AOFAS 58.8 ± 20.6. The preoperative MOCART score was 22.1 ± 13.7 points, the postoperative MOCART score was 42.3 ± 27.9 points (+ 20.2%; P = 0.04), respectively. 30% (8 of 27 patients) experienced persistent pain and underwent a further chondral procedure. Concluding, AMIC could be a viable option as revision procedure for failed AMIC in recurrent symptomatic osteochondral defects of the talus. The PROMs indicated that patients were moderately satisfied with the procedure, and the MOCART score demonstrated a significant improvement from baseline to the last follow-up. A deeper understanding in prognostic factors and patient selection is critical to prevent failures.

Abstract Background This systematic review investigates the role of synthetic graft for primary medial patellofemoral ligament (MPFL) reconstruction in patients with recurrent patellofemoral instability, focusing on clinical scores and the rate of complications. Methods This systematic review was conducted according to the PRISMA statement. The main online databases were accessed in January 2022 without time constraints. All clinical studies investigating the use of synthetic grafts for MPFL reconstruction were accessed. Revision settings were not considered. Only articles reporting data on patients with recurrent patellofemoral instability were eligible. Studies regarding congenital or acute patellofemoral dislocation were excluded. Only studies performing a follow-up longer than 24 months were considered. Results Data on 199 patients [mean age 22.3 (range 19.0–28.0) years] were collected. The mean follow-up was 60.5 (39.0–142.8) months. All the scores of interest improved at last follow-up: Kujala (+ 24.8; P = 0.0002), Lysholm (+ 42.0; P = 0.02), Tegner (+ 1.2; P = 0.03), IKDC (+ 20.9; P = 0.02). Post-operatively, a positive apprehension test was detected in 6.1% (7/115) of patients, and a sensation of instability was reported by 1.5% (3/199) of patients. The rate of re-dislocations was 2.5% (5 of 199 patients), and revision procedures were performed in less than 1% (1 of 199) of patients. Conclusion Synthetic graft may be reliable and feasible for primary MPFL reconstruction in patients with recurrent patellofemoral instability.

Abstract Background This systematic review investigated the efficacy and safety of surgical procedures augmented with cell therapies for chondral defects of the talus. Methods The present systematic review was conducted according to the 2020 PRISMA guidelines. PubMed, Google scholar, Embase, and Scopus databases were accessed in March 2022. All the clinical trials investigating surgical procedures for talar chondral defects augmented with cell therapies were accessed. The outcomes of interest were to investigate whether surgical procedures augmented with cell therapies promoted improvement in patients reported outcomes measures (PROMs) with a tolerable rate of complications. Results Data from 477 procedures were retrieved. At a mean follow-up of 34.8 ± 9.7 months, the Visual Analogic Scale (VAS) improved of 4.4/10 (P = 0.002) and the American Orthopaedic Foot and Ankle Score (AOFAS) of 31.1/100 (P = 0.0001) points. No improvement was found in Tegner score (P = 0.4). Few articles reported data on complications. At last follow-up, the rate of reoperation and failure were 0.06% and 0.03%, respectively. No graft delamination or hypertrophy was observed. Conclusion The current evidence suggests that cell therapies may be effective and safe to enhance surgical procedures for chondral defects of the talus. These results should be considered within the limitations of the present study. The current literature should be enriched with randomized controlled clinical trials with larger population size and longer follow-up.

Abstract Background Some authors secured the membrane during matrix-induced autologous chondrocyte implantation (mACI) with fibrin glue or did not use a formal fixation. The real impact of fibrin glue addition on chondrocytes migration and proliferation has not yet been clarified. This study evaluated the impact of fibrin glue on a chondrocyte loaded collagenic membrane. Methods A resorbable collagen I/III porcine derived membrane commonly employed in AMIC was used for all experiments. Chondrocytes from three difference donors were used. At 1-, 2-, 3-, 4-, 6-, and at 8-week the membranes were embedded in Mounting Medium with Dapi (ABCAM, Cambridge, UK). The Dapi contained in the mounting medium ties the DNA of the cell nucleus and emits a blue fluorescence. In this way, the spreading of the cells in the membrane can be easily monitored. The outcomes of interest were to evaluate (1) cell migration and (2) cell proliferation within the porous membrane layer. DAPI/nuclei signals were analysed with fluorescence microscope under a magnification of 100-fold. Results The no-fibrin group demonstrated greater migration of the cells within the membrane. Although migration resulted higher in the no-fibrin group at every follow-up, this difference was significant only at week 1 (P

Abstract Background This Bayesian network meta-analysis investigated the available randomized control trials (RCTs) to point out which acupuncture protocol is the most effective for chronic aspecific low back pain (LBP). Efficacy was measured in terms of pain (Visual Analogic Scale, VAS) and disability (Roland Morris Disability Questionnaire, RMQ), Transcutaneous Electrical Nerve Stimulation (TENS). Methods PubMed, Google scholar, Embase, and Scopus were accessed in March 2022. All the RCTs comparing two or more acupuncture modalities for aspecific chronic LBP were accessed. Only studies which investigated the efficacy of acupuncture on patients with symptoms lasting a minimum of 1.5 months, or with at least three episodes in the previous 12 months, were considered eligible. The Review Manager Software (The Nordic Cochrane Collaboration, Copenhagen) was used for the methodological quality assessment. The STATA Software/MP, Version 14.1 (StataCorporation, College Station, Texas, USA), was used for the statistical analyses. The NMA was performed through the STATA routine for Bayesian hierarchical random-effects model analysis. Results Data from 44 RCTs (8338 procedures) were retrieved. 56% of patients were women. The mean age of the patients was 48 ± 10.6 years. The mean BMI was 26.3 ± 2.2 kg/m2. The individual group (95% confidence interval (CI) 2.02, 7.98) and the standard combined with TENS (95% CI 2.03, 7.97) demonstrated the highest improvement of the RMQ. The VAS score was lower in the standard combined with TENS group (95% CI 3.28, 4.56). Considering the standard acupuncture group, different studies used similar protocols and acupuncture points and the results could thus be compared. The equation for global linearity did not find any statistically significant inconsistency in any of the network comparison. Conclusion Verum acupuncture is more effective than sham treatment for the non-pharmacological management of LBP. Among the verum protocols, individualized acupuncture and standard acupuncture with TENS were the protocols that resulted in the highest improvement in pain and quality of life. Level of Evidence Level I, Bayesian network meta-analysis of RCTs.

Purpose: The present study aimed to systematically review and compare 2 femoral autograft fixation techniques, namely, interference screws and suture anchors, for isolated medial patellofemoral ligament reconstruction in patients with recurrent patellofemoral instability at mid- to long-term follow-up. Methods: A literature search was performed in September 2020. All studies reporting the outcomes of primary isolated medial patellofemoral ligament reconstruction for recurrent patellofemoral instability were considered for inclusion. Only studies reporting the type of femoral autograft fixation under examination were considered. Studies reporting data from patients with elevated tibial tuberosity-tibial groove, patella alta, and/or Dejour's trochlear dysplasia types C and D, were not included. Only articles reporting data with a minimum follow-up period of 18 months were considered. Results: Data from 19 studies (615 patients) were retrieved. The overall age was 24.4 ± 6.7 years (mean ± SD). The mean follow-up was 46.5 ± 20.9 months. There were 76 patients in the anchor group and 539 in the screw group. Comparability was found with regard to age and follow-up duration between the 2 study groups. There was comparability between the Kujala, Lysholm, and Tegner scores at baseline. At the last follow-up, no worthy differences were found in terms of mean Kujala (+2.1%; p = 0.04), Lysholm (+1.7%; p = 0.05), and Tegner (+15.8%; p = 0.05) scores. Although complications occurred almost exclusively in the screw cohort, no statistically significant difference was found. Conclusion: Femoral autograft fixation through interference screws or suture anchors report similar clinical scores and rate of apprehension test, persistent joint instability, re-dislocations, and revisions. These results must be interpreted within the limitations of the present study.

Abstract Background Patellar dislocations in patients presenting with recurrent patellofemoral instability can damage the surrounding structures, limiting patient’s participation to recreational activities and quality of life. This study evaluated frequency, location, and extent of associated injuries in patients with recurrent patellar dislocation. Methods This systematic review was conducted according to the PRISMA checklist. PubMed, Google scholar, Embase, and Web of Science databases were accessed in July 2021. All the published clinical studies reporting frequency, location, and extent of soft tissue lesions in patients with recurrent patellar dislocations were accessed. Results Data from 9 articles (232 patients) were retrieved. The mean age of the included patients was 21.2 ± 5.6 years. 84.8% of patients suffering from recurrent patellar dislocations demonstrated patellar chondral defects: medial facet (34.9%), while patellar crest (34.8%) and lateral facet (17%). 27.8% of patients demonstrated trochlear chondral injuries. Conclusion Chondral defects of the medial facet and the crest of the patella are the most common in patients with recurrent patellofemoral instability.

Abstract Background Symmetry is a sign of physiological and healthy movements, as pathologies are often described by increased asymmetries. Nevertheless, based on precisely measured data, even healthy individuals will show small asymmetries in their movements. However, so far there do not exist commonly accepted methods and reference values for gait symmetry in a healthy collective. Therefore, a comparison and presentation of reference values calculated by 3 different methods of symmetry indices for lower limb joint angles during walking, ascending, and descending stairs were shown. Methods Thirty-five healthy participants were analyzed during walking, ascending, and descending stairs with the help of the inertial measurement system MyoMotion. Using the normalized symmetry index (SInorm), the symmetry index (SI) as the integral of the symmetry function, and another normalized symmetry index (NSI), the symmetry of joint angles was evaluated. For statistical evaluation of differences, repeated measurement models and Bland–Altman-Plots were used. Results Apart from a bias between the symmetry indices, they were comparable in the predefined limits of 5%. For all parameters, significantly higher asymmetry was found for ankle dorsi/-plantarflexion, compared with the hip and knee flexion. Moreover, the interaction effect of the joint and movement factors was significant, with an increased asymmetry of the hip and knee during descending stairs greater than while ascending stairs or walking, but a reduced symmetry of the ankle during walking when compared to descending. The movement only showed significant effects when analyzing the SInorm . Conclusion Even for healthy individuals, small asymmetries of movements were found and presented as reference values using 3 different symmetry indices for dynamic lower limb joint angles during 3 different movements. For the quantification of symmetrical movements differences between the joints, movements, and especially their interaction, are necessary to be taken into account. Moreover, a bias between the methods should be noted. The potential for each presented symmetry index to identify pathological movements or track a rehabilitation process was shown but has to be proven in further research. Trial registration: DRKS00025878.

Abstract Background The present systematic review analysed the available literature to assess reliability of the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score in the evaluation of knee and ankle osteochondral lesions. Methods All the studies using the MOCART score for knee and/or talus chondral defects were accessed in March 2021. A multivariate analysis was performed to assess associations between the MOCART score at last follow-up and data of patients at baseline, clinical scores and complications. A multiple linear model regression analysis was used. Results The MOCART score evidenced no association with patient age (P = 0.6), sex (P = 0.1), body mass index (P = 0.06), defect size (P = 0.9), prior length of symptoms (P = 0.9) or visual analogue scale (P = 0.07). For chondral defects of the knee, no statistically significant association was found between the MOCART score and the International Knee Documentation Committee (P = 0.9) and with the Lysholm Knee Scoring Scales (P = 0.2), Tegner Activity Scale (P = 0.2), visual analogue scale P = 0.07), rate of failure (P = 0.2) and revision (P = 0.9). For chondral defect of the talus, no statistically significant associations were found between the MOCART score and the American Orthopedic Foot and Ankle Score (P = 0.3), Tegner Activity Scale (P = 0.4), visual analogue scale (P = 0.1), rate of failure (P = 0.1) and revision (P = 0.7). Conclusion The MOCART score demonstrated no association with patient characteristics and with the surgical outcome in patients who underwent surgical management for knee and talus chondral defects. Level of evidence Level IV.

Abstract Background Focal chondral defects of the knee are common. Several surgical techniques have been proposed for the management of chondral defects: microfractures (MFX), osteochondral autograft transplantation (OAT), autologous matrix-induced chondrogenesis (AMIC) and autologous chondrocyte implantation (ACI)—first generation (pACI), second generation (cACI) and third generation (mACI). A Bayesian network meta-analysis was conducted to compare these surgical strategies for chondral defects in knee at midterm follow-up. Methods This Bayesian network meta-analysis was conducted according to the PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions. PubMed, Google Scholar, Embase and Scopus databases were accessed in July 2021. All the prospective comparative clinical trials investigating two or more surgical interventions for chondral defects of the knee were accessed. The network meta-analyses were performed through a Bayesian hierarchical random-effects model analysis. The log odds ratio (LOR) effect measures were used for dichotomic variables, while the standardized mean difference (SMD) for the continuous variables. Results Data from 2220 procedures (36 articles) were retrieved. The median follow-up was 36 (24 to 60) months. The ANOVA test found good baseline comparability between symptoms duration, age, sex and body mass index. AMIC resulted in higher Lysholm score (SMD 3.97) and Tegner score (SMD 2.10). AMIC demonstrated the lowest rate of failures (LOR −0.22) and the lowest rate of revisions (LOR 0.89). As expected, MFX reported the lower rate of hypertrophy (LOR −0.17) followed by AMIC (LOR 0.21). No statistically significant inconsistency was found in the comparisons. Conclusion AMIC procedure for focal chondral defects of the knee performed better overall at approximately 3 years’ follow-up.

Abstract Background Osteoporosis affects mostly postmenopausal women, leading to deterioration of the microarchitectural bone structure and low bone mass, with an increased fracture risk with associated disability, morbidity and mortality. This Bayesian network meta-analysis compared the effects of current anti-osteoporosis drugs on bone mineral density. Methods The present systematic review and network meta-analysis follows the PRISMA extension statement to report systematic reviews incorporating network meta-analyses of health care interventions. The literature search was performed in June 2021. All randomised clinical trials that have investigated the effects of two or more drug treatments on BMD for postmenopausal osteoporosis were accessed. The network comparisons were performed through the STATA Software/MP routine for Bayesian hierarchical random-effects model analysis. The inverse variance method with standardised mean difference (SMD) was used for analysis. Results Data from 64 RCTs involving 82,732 patients were retrieved. The mean follow-up was 29.7 ± 19.6 months. Denosumab resulted in a higher spine BMD (SMD −0.220; SE 3.379), followed by pamidronate (SMD −5.662; SE 2.635) and zoledronate (SMD −10.701; SE 2.871). Denosumab resulted in a higher hip BMD (SMD −0.256; SE 3.184), followed by alendronate (SMD −17.032; SE 3.191) and ibandronate (SMD −17.250; SE 2.264). Denosumab resulted in a higher femur BMD (SMD 0.097; SE 2.091), followed by alendronate (SMD −16.030; SE 1.702) and ibandronate (SMD −17.000; SE 1.679). Conclusion Denosumab results in higher spine BMD in selected women with postmenopausal osteoporosis. Denosumab had the highest influence on hip and femur BMD. Level of evidence Level I, Bayesian network meta-analysis of RCTs

Abstract Background Matrix-induced autologous chondrocyte implantation (mACI) can be performed in a full arthroscopic or mini-open fashion. A systematic review was conducted to investigate whether arthroscopy provides better surgical outcomes compared with the mini-open approach for mACI in the knee at midterm follow-up. Methods This systematic review was conducted following the PRISMA guidelines. The literature search was performed in May 2021. All the prospective studies reporting outcomes after mACI chondral defects of the knee were accessed. Only studies that clearly stated the surgical approach (arthroscopic or mini-open) were included. Only studies reporting a follow-up longer than 12 months were eligible. Studies reporting data from combined surgeries were not eligible, nor were those combining mACI with less committed cells (e.g., mesenchymal stem cells). Results Sixteen studies were included, and 770 patients were retrieved: 421 in the arthroscopy group, 349 in the mini-open. The mean follow-up was 44.3 (12–60) months. No difference between the two groups was found in terms of mean duration of symptoms, age, body mass index (BMI), gender, defect size (P > 0.1). No difference was found in terms of Tegner Score (P = 0.3), Lysholm Score (P = 0.2), and International Knee Documentation Committee (IKDC) Score (P = 0.1). No difference was found in the rate of failures (P = 0.2) and revisions (P = 0.06). Conclusion Arthroscopy and mini-arthrotomy approaches for mACI in knee achieve similar outcomes at midterm follow-up. Level of evidence II, systematic review of prospective studies.

Abstract Background The differentiation of bone marrow mesenchymal stem cells is a complex and dynamic process. The gene expression pattern and mechanism of different periods of adipogenic and osteogenic differentiation remain unclear. Additionally, the interaction between these two lineage determination requires further exploration. Results Five modules that were most significantly associated with osteogenic or adipogenic differentiation of BMSCs were selected for further investigation. Biological terms (e.g. ribosome biogenesis, TNF-α signalling pathway, glucose import and fatty acid metabolism) along with hub transcription factors (e.g. PPARG and YY1) and hub miRNAs (e.g. hsa-mir-26b-5p) were enriched in different modules. The expression pattern of 6 hub genes, ADIPOQ, FABP4, SLC7A5, SELPLG, BIRC3, and KLHL30 was validated by RT-qPCR. Finally, cell staining experiments extended the findings of bioinformatics analysis. Conclusion This study identified the key genes, biological functions, and regulators of each time point of adipogenic and osteogenic differentiation of BMSCs and provided novel evidence and ideas for further research on the differentiation of BMSCs.

Abstract Background The medial patellofemoral ligament (MPFL) is always damaged after patellar dislocation. In selected patients, MPFL reconstruction is necessary to restore a correct patellar tracking. Despite the large number of different techniques reported to reconstruct the MPFL, there is no consensus concerning the optimal procedure, and debates is still ongoing. The present study analysed the results after isolated MPFL reconstruction in patients with patellofemoral instability. Furthermore, a subgroup analysis of patients presenting pathoanatomical risk factors was made. Methods In November 2020, the main electronic databases were accessed. All articles reporting the results of primary isolated MPFL reconstruction for recurrent patellofemoral instability were considered for inclusion. Only articles reporting a minimum 12-month follow-up were eligible. Results Data from a total of 1777 knees were collected. The mean age of the patients involved was 22.8 ± 3.4 years. The mean follow-up was 40.7 ± 25.8 months. Overall, the range of motion (+ 27.74; P < 0.0001) and all the other scores of interests improved at last follow-up: Kujala (+ 12.76; P = 0.0003), Lysholm (+ 15.69; P < 0.0001), Tegner score (+ 2.86; P = 0.006). Seventy-three of 1780 patients (4.1%) showed a positive apprehension test. Thirty of 1765 patients (1.7%) experienced re-dislocations, while 56 of 1778 patients (3.2%) showed persisting joint instability. Twenty-five of 1786 patients (1.4%) underwent revision surgeries. Conclusion Isolated MPFL reconstruction for recurrent patellofemoral instability provides reliable surgical outcomes. Patients with pathoanatomical predisposing factors reported worse surgical outcomes.

The rise in the occurrence of musculoskeletal disorders, such as thoracic hyperkyphosis (THK) or lumbar hypolordosis (LHL), is a result of demographic changes. Exercise therapy is an effective approach that can reduce related disabilities and costs. To ensure successful therapy, an individualized exercise program adapted to the severity of the disorder is expedient. Nevertheless, appropriate classification systems are scarce. This project aimed to develop and evaluate a severity classification focused on exercise therapy for patients with THK or LHL. A multilevel severity classification was developed and evaluated by means of an online survey. Reference limits of spinal shape angles were established by data from video rasterstereography of 201 healthy participants. A mean kyphosis angle of 50.03° and an average lordosis angle of 40.72° were calculated as healthy references. The strength of the multilevel classification consisting of the combination of subjective pain and objective spinal shape factors was confirmed by the survey (70% agreement). In particular, the included pain parameters were considered relevant by 78% of the experts. Even though the results of the survey provide important evidence for further analyses and optimization options of the classification system, the current version is still acceptable as therapeutic support.

Abstract Background A novel implant for occipitocervical fusion consisting of a median plate with an additional hook inserting in the foramen magnum was tested. Aim of this study was to test the stability of a new implant for occipitocervical fusion against the already available and employed median plate implant without hook. Material and method 36 rigid polyurethane foams occipital artificial bones were used. The two occipital implants, namely the occipital plate with hook (Group 1) and the one without hook (Group 2), were applied to the artificial occiput trough three occipital screws and ensured into the experimental setup trough a crossbar. The test parameters were set using the testing machine software as follows: (1) test speed: 10 mm/ min, with 25 mm/ min maximum; (2) preload: 5 N; (3) force switch-off threshold: 90% force drop from F_max. Failure force and path were recorded. Failure force is defined as the maximum reaction force under which failure occurs (F_max), while failure path is the travel path during which failure occurs (dL). Results Group 1 (plate with hook) showed a mean failure force of 459.3 ± 35.9 N and a mean failure path of 5.8 ± 0.3 mm Group 2 (plate without hook) showed a mean failure force of 323.9 ± 20.2 N and a mean failure path of 7.2 ± 0.4 mm. The Shapiro-Wilk test score was not significant (P > 0.1), assuming that data were normally distributed. Group 1 had a statistically significant greater F_max (+ 135.37; P > 0.0001) and less dL (− 1.52; P > 0.0001) compared to group 2. Conclusions Medial plates with foramen magnum hooks showed to be more stable that plates without a hook. These new implants may represent a new tool in OCJ fixation, but further studies are required to investigate their behavior in an anatomical setting.

Abstract Background Leg length inequalities (LLI) are a common condition that can be associated with detrimental effects like low back pain and osteoarthritis. Inertial measurement units (IMUs) offer the chance to analyze daily activities outside a laboratory. Analyzing the kinematic effects of (simulated) LLI on the musculoskeletal apparatus using IMUs will show their potentiality to improve the comprehension of LLI. Methods Twenty healthy participants with simulated LLI of 0-4 cm were analyzed while walking with an inertial sensor system (MyoMotion). Statistical evaluation of the peak anatomical angles of the spine and legs were performed using repeated measurement (RM) ANOVA or their non-parametric test versions (Friedman test). Results Lumbar lateral flexion and pelvic obliquity increased during the stance phase of the elongated leg and decreased during its swing phase. The longer limb was functionally shortened by higher hip and knee flexion, higher hip adduction, dorsiflexion, and lower ankle adduction. Finally, the shorter leg was lengthened by higher hip and knee extension, hip abduction, ankle plantarflexion, and decreased hip adduction. Conclusion We found differing compensation strategies between the different joints, movement planes, gait phases, and amounts of inequality. Overall the shorter leg is lengthened and the longer leg is shortened during walking, to retain the upright posture of the trunk. IMUs were helpful and precise in the detection of anatomical joint angles and for the analysis of the effects of LLI.

Abstract Background Until recently, rasterstereographic analysis of the spine was limited to static measurements. However, understanding and evaluating the motion of the spine under dynamic conditions is an important factor in the diagnosis and treatment of spinal pathologies. The aim of this study was to study the spinal posture and pelvic position under dynamic conditions and compare it to static measurements using a dynamic rasterstereographic system. Methods A total of 121 healthy volunteers (56 females; 65 males) were included in this observational study. The parameters trunk inclination, trunk imbalance, pelvic obliquity, kyphotic angle, lordotic angle, surface rotation, and lateral deviation were studied and compared under static and dynamic (1, 2, 4, 5 km/h) conditions using the system “Formetric 4D Motion®“ (DIERS International GmbH, Germany). Results Female volunteers had a higher lordotic angle than males under static conditions (p < 0.001). Trunk inclination (5.31° vs. 6.74°), vertebral kyphotic angle (42.53° vs. 39, 59°), and surface rotation (3.35° vs. 3.81°) increase under dynamic conditions (p < 0.001). Trunk inclination and lordotic angle both show significant changes during walking compared to static conditions (p < 0.001). Conclusion The spinal posture differs between females and males during standing and during walking. Rasterstereography is a valuable tool for the dynamic evaluation of spinal posture and pelvic position, which can also be used to quantify motion in the spine and therefore it has the potential to improve the understanding and treatment of spinal pathologies. Trial registration Retrospectively registered

An anterior cruciate ligament (ACL) reconstruction is a common treatment for patients with ACL rupture that aims to regain pre-injury knee stability and kinematics. During the ACL reconstruction, one method to fix the graft is the use of an interference screw (IS). The IS should provide initial stability and secure the graft during the healing period. In recent years, magnesium has emerged as an alternative material to permanent metal and polymer ISs. In addition, differences in designs, such as the shape of the IS, can influence the fixation performance of the IS. Therefore, in this biomechanical experiment, two different screw designs with two ligament materials were compared in an insertion and a pull-out test at a rate of 1 mm/s. The screw designs were a conventional polymer screw and a magnesium screw. Porcine tendon and nylon rope were used as ligament materials. All tests were performed in polyurethane foam blocks with 15 PCF density (Synbone AG, Switzerland). As a result, both screw designs required an insertion torque of less than 3 Nm. There was a significant difference between the porcine and nylon rope in pull-out tests for each screw design. The magnesium screw had the highest pull-out force at 412.14 ± 50.00 N for porcine tendon and 707.38 ± 21.81 N for nylon rope. There were no significant differences in tunnel widening (narrow–wide ratio) between each ligament material. The magnesium screw showed the lowest narrow–wide tunnel ratio, implying a better ability to compress the graft to the tunnel. In conclusion, a more optimized magnesium IS design resulted in better graft fixation and an improved ACL reconstruction outcome.

The wrist joint plays a vital role in activities of daily living. Clinical applications, e.g., therapeutic planning, prosthesis design, and wrist biomechanical analysis, require a detailed understanding of wrist maneuvers and motion. The lack of soft tissue information, motion analysis on limited carpal bones, etc., restrain the investigation of wrist kinematics. In this study, we established 3D models of carpal bones with their cartilages, and revealed the helical axes (HA) of all eight carpal bones for the first time. Both left and right hands at different positions of flexion-extension (FE) and radial-ulnar deviation (RUD) from five subjects were in-vivo imaged through a magnetic resonance imaging device. We segmented all of the bones, including cartilage information in the wrist joint, after which we explored the kinematics of all carpal bones with the HA method. The results showed that the HA of all carpal bones for FE bounded tightly and was mainly located slightly above the radius. During the RUD, carpal bones in the distal row rotated along with wrist movement while the scaphoid, lunate, and triquetrum primarily flexed and extended. Further results reported that the carpal bones translated greater in RUD than in FE. With the generation of more delicate wrist models and thorough investigations of carpal motion, a better understanding of wrist kinematics was obtained for further pathologic assessment and surgical treatment.

Pantelis Nikolaidis and Jose Afonso published a letter [...]

Background and Objectives: Starting in early December 2019, the novel Coronavirus Disease (COVID-19) from infection with COVID-19 has caused a global pandemic. Many aspects of its pathogenesis and related clinical consequences are still unclear. Early diagnosis and dynamic monitoring of prognostic factors are essential to improve the ability to manage COVID-19 infection. This study aimed to provide an account of the role played by vitamins C and D on the onset, progression and severity of COVID-19. Clinical features and infection-related risk factors are also briefly discussed. Material and Methods: In March 2022, the main online databases were accessed. All the articles that investigate the possible role of vitamins C and D on COVID-19 susceptibility, severity and progression were considered. Results: The current evidence on vitamin C and D supplementation in patients with COVID-19 infection is inconsistent and controversial. In some studies, vitamins were used as coadjuvant of a formal experimental therapy, while in others as main treatment. Ethnicity and hospital setting (inpatient/outpatient) were also variable. Moreover, there was no consensus between studies in administration protocol: high heterogeneity in dosage, administration, and duration of the treatment were evident. Finally, some studies administered vitamins pre- and/or during COVID infection, in patients with different risk factors and infection severity. Conclusions: While waiting to develop a targeted, safe and effective therapy, it is important to investigate individual predisposition and proper disease management. Concluding, available data on the use of nutraceuticals in COVID-19 are inconsistent. However, there is a lack of evidence-based guidelines which recommend vitamin C and D supplementation in patients with COVID-19, and results from high quality randomised controlled trials (RCTs) are inconsistent. Current investigations so far are mostly observational, and include a relatively small sample size which can lead to biased results. Large-scale multicentre studies are therefore needed.

Objective: To investigate the effectiveness of modified rehabilitation programmes in comparison with standard rehabilitation programmes after total knee arthroplasty through randomized controlled trials. Data sources: A search was conducted in PubMed, PubMed Central (PMC) and Cochrane Library databases in December 2020. Study selection: Randomized controlled trials were reviewed if they compared a physiotherapy exercise intervention with usual or standard physiotherapy care, or if they compared 2 types of exercise physiotherapy interventions meeting the review criteria, after total knee arthroplasty for osteoarthritis. A total of 18 randomized controlled trials were included at the end of the screening process. Data extraction: Two authors independently screened the literature, extracted data, and assessed the quality of included studies. The outcomes were knee extension, knee flexion, pain visual analogue scale, overall Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), 6-minute walking test, and Timed Up and Go test. Data synthesis: There was no clear pattern regarding which combination of starting time-point and duration of the rehabilitation programme after total knee arthroplasty significantly improves the clinical outcome when comparing modified rehabilitation programmes with standard programmes. Moreover, no particular modification to the modified programmes could be solely attributed to the improved clinical outcome in the 2 studies that showed significant improvement. Conclusion: Modified rehabilitation programmes do not result in systematic improvement in clinical outcome over one-size-fits-all-approaches after total knee arthroplasty.

This study investigated the in vivo osseointegration potential of high-performance oxide ceramics (HPOCs) with peptide bone morphogenic protein 2 (BMP-2), comparing them with titanium implants. Histomorphometry was conducted around the distal, proximal, medial, and lateral sides of the implants to quantify the amount of mature and immature ossification within the bone interface. We hypothesised that HPOCs functionalised with BMP-2 promote ossification. HPOCs functionalised with BMP-2 were manufactured at the Department of Dental Materials Science and Biomaterial Research of the RWTH University Aachen, Germany. Histomorphometry was conducted by a professional pathologist in all samples. The region of interest (ROI) represented the percentage of the surrounding area of the implant. The percentages of ROI covered by osteoid implant contact (OIC) and mature bone–implant contact (BIC) were assessed. The surrounding presence of bone resorption, necrosis, and/or inflammation was quantitatively investigated. A total of 36 rabbits were used for the experiments. No bone resorption, necrosis, or inflammation was found in any sample. At the 12-week follow-up, the overall BIC was significantly increased (p < 0.0001). No improvement was evidenced in OIC (p = 0.6). At the 6-week follow-up, the overall OIC was greater in the BMP-2 compared to the titanium group (p = 0.002). The other endpoints of interest evidenced similarity between the two implants at various follow-up time points (p > 0.05). In conclusion, alumina HPOCs functionalised with peptide BMP-2 promote in vivo ossification in a similar fashion to titanium implants.

The present study investigated the osseointegration promoted by functionalised ceramics with peptide Arg-Gly-Asp (RGD) in a rabbit model in vivo. Histomorphometry of the RGD functionalised ceramic implants was conducted by a trained pathologist to quantify the amount of mature and immature ossification at the bone interface, and then compared to titanium alloy implants. The region of interest was the area surrounding the implant. The percentage of ROI covered by osteoid implant contact and mature bone implant contact were assessed. The presence of bone resorption, necrosis, and/or inflammation in the areas around the implant were quantitatively investigated. All 36 rabbits survived the experimental period of 6 and 12 weeks. All implants remained in situ. No necrosis, bone resorption, or inflammation were identified. At 12 weeks follow-up, the overall mean bone implant contact (p = 0.003) and immature osteoid contact (p = 0.03) were improved compared to the mean values evidenced at 6 weeks. At 6 weeks follow-up, the overall osteoid implant contact was greater in the RGD enhanced group compared to the titanium implant (p = 0.01). The other endpoints of interest were similar between the two implants at all follow-up points (p ≥ 0.05). Functionalised ceramics with peptide RGD promoted ossification in vivo. The overall osteoid and bone implant contact improved significantly from 6 to 12 weeks. Finally, RGD enhanced ceramic promoted faster osteoid implant contact in vivo than titanium implants. Overall, the amount of ossification at 12 weeks is comparable with the titanium implants. No necrosis, bone resorption, or inflammation were observed in any sample.

The carpal bones are eight small bones with irregularities and high curvature on their surfaces. The 3D model of the carpal bone serves as the foundation of further clinical applications, e.g., wrist kinematic behavior. However, due to the limitation of the Magnetic Resonance Imaging (MRI) technique, reconstructed carpal bone models are discretely undersampled, which has dramatic stair-step effects and leads to abnormal meshes on edges or surfaces, etc. Our study focuses on determining the viability of various smoothing techniques for a carpal model reconstructed by in vivo gathered MR images. Five algorithms, namely the Laplacian smoothing algorithm, the Laplacian smoothing algorithm with pre-dilation, the scale-dependent Laplacian algorithm, the curvature flow algorithm, and the inverse distance algorithm, were chosen for evaluation. The assessment took into account the Relative Volume Difference and the Hausdorff Distance as well as the surface quality and the preservation of morphological and morphometric properties. For the five algorithms, we analyzed the Relative Volume Difference and the Hausdorff Distance for all eight carpal bones. Among all the algorithms, the scale-dependent Laplacian method processed the best result regarding surface quality and the preservation of morphological and morphometric properties. Based on our extensive examinations, the scale-dependent Laplacian algorithm is suitable for the undersampled carpal bone model with small volume and large curvature.