Search

AimTo assess the efficacy and safety of latanoprostene bunod (LBN) compared with latanoprost 0.005%, and to determine the optimum drug concentration(s) of LBN in reducing intraocular pressure (IOP) in subjects with open angle glaucoma or ocular hypertension.MethodsRandomised, investigator-masked, parallel-group, dose-ranging study. Subjects instilled one drop of study medication in the study eye once daily each evening for 28 days and completed five study visits. The primary efficacy endpoint was the reduction in mean diurnal IOP at Day 28.ResultsOf the 413 subjects randomised (LBN 0.006%, n=82; LBN 0.012%, n=85; LBN 0.024%, n=83; LBN 0.040%, n=81; latanoprost, n=82), 396 subjects completed the study. Efficacy for LBN was dose-dependent reaching a plateau at 0.024%-0.040%. LBN 0.024% led to significantly greater reductions in diurnal IOP compared with latanoprost at the primary endpoint, Day 28 (p=0.005), as well as Days 7 (p=0.033) and 14 (p=0.015). The incidence of adverse events, mostly mild and transient, was numerically higher in the LBN treatment groups compared with the latanoprost group. Hyperaemia was similar across treatments.ConclusionsLBN 0.024% dosed once daily was the lower of the two most effective concentrations evaluated, with significantly greater IOP lowering and comparable side effects relative to latanoprost 0.005%. LBN dosed once daily for 28 days was well tolerated.Clinical trial numberNCT01223378.

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 < 0.0001), and RGD (P < 0.0001) groups. At 12 weeks, the BMP-2 groups demonstrated greater ossification in the RGD (P < 0.0001) and silanised (P = 0.008) groups. Trabecular thickness increased significantly from 6 to 12 weeks (P < 0.0001). At 12 weeks, BMP-2 promoted greater trabecular thickness compared to the silanised group (P = 0.07), although no difference was found with the RGD (P = 0.1) group., Conclusion: Sinalised HPOC in isolation or functionalised with BMP-2 or RGD promotes in vivo osteointegration. The sinalised HOPC functionalised with BMP-2 demonstrated the greatest osseointegration., (© 2024. The Author(s).)

Background: The risk of developing late radiotoxicity after radiotherapy in patients with high chromosomal radiosensitivity after radiotherapy could potentially be higher compared to the risk in patients with average radiosensitivity. In case of extremely high radiosensitivity, dose reduction may be appropriate. Some rheumatic diseases (RhD), including connective tissue diseases (CTDs) appear to be associated with higher radiosensitivity. The question arises as to whether patients with rheumatoid arthritis (RA) also generally have a higher radiosensitivity and whether certain parameters could indicate clues to high radiosensitivity in RA patients which would then need to be further assessed before radiotherapy., Methods: Radiosensitivity was determined in 136 oncological patients with RhD, 44 of whom were RA patients, and additionally in 34 non-oncological RA patients by three-colour fluorescence in situ hybridization (FiSH), in which lymphocyte chromosomes isolated from peripheral blood are analysed for their chromosomal aberrations of an unirradiated and an with 2 Gy irradiated blood sample. The chromosomal radiosensitivity was determined by the average number of breaks per metaphase. In addition, correlations between certain RA- or RhD-relevant disease parameters or clinical features such as the disease activity score 28 and radiosensitivity were assessed., Results: Some oncological patients with RhD, especially those with connective tissue diseases have significantly higher radiosensitivity compared with oncology patients without RhD. In contrast, the mean radiosensitivity of the oncological patients with RA and other RhD and the non-oncological RA did not differ. 14 of the 44 examined oncological RA-patients (31.8%) had a high radiosensitivity which is defined as ≥ 0.5 breaks per metaphase. No correlation of laboratory parameters with radiosensitivity could be established., Conclusions: It would be recommended to perform radiosensitivity testing in patients with connective tissue diseases in general. We did not find a higher radiosensitivity in RA patients. In the group of RA patients with an oncological disease, a higher percentage of patients showed higher radiosensitivity, although the average radiosensitivity was not high., (© 2023. The Author(s).)

Background: An all-arthroscopic rotator cuff repair (ASR) may result in less postoperative pain and better functional outcomes than the mini-open (MOR) approach. This meta-analysis provides an updated assessment of the current literature which compares the clinical outcomes of mini-open versus all arthroscopic rotator cuff repair techniques., Material and Methods: The main online databases were accessed in October 2021. All the trials directly comparing primary ASR versus MOR for rotator cuff rupture were accessed. Studies concerning revision settings were not eligible, nor where those combining the surgical procedures with other adjuvants., Results: A total of 21 articles were retrieved. Data from 1644 procedures (ASR = 995, MOR = 649) were collected. The mean follow-up was 26.7 (6.0-56.4) months. Comparability was found between ASR and MOR groups at baseline with regards to age (P = 0.3), gender (P = 0.7) and mean duration of the follow-up (P = 0.7). No difference was found between ASR and MOR with regard to surgical duration (P = 0.05), Constant score (P = 0.2), University of California at Los Angeles Shoulder (P = 0.3), American Shoulder and Elbow Surgeons Shoulder (P = 0.5), VAS (P = 0.2), forward flexion (P = 0.3), abduction (P = 0.3), external rotation (P = 0.2), internal rotation (P = 0.7), re-tear (P = 0.9), adhesive capsulitis (P = 0.5)., Conclusion: Arthroscopic and mini-open rotator cuff repair result in similar clinical outcomes. Male gender and older age lead to greater rates of rotator cuff re-tears, while longer surgical duration was associated with a greater rate of adhesive capsulitis., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

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 < 0.0001). The overall OIC of the ceramic group was greater at 6 weeks compared to the titanium implants (P = 0.003). The other endpoints of interest were similar between the two implants at all follow-up points. No difference was found in BIC at 6- and 12-weeks follow-up. No bone necrosis, resorption, or inflammation were observed., Conclusion: HPOC implants demonstrated a greater osteoid implant contact at 6 weeks compared to the titanium implants, with no difference found at 12 weeks. The percentage of bone implant contact of HPOC implants was similar to that promoted by titanium implants., (© 2023. The Author(s).)

Purpose: This study investigated the impact of the Covid-19 pandemic in Europe on consultations, surgeries, and traumas in the field of orthopaedic and trauma surgery. Strategies to resume the clinical activities were also discussed., Methods: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the 2020 PRISMA statement. All the comparative studies reporting data on the impact of Covid-19 in the field of orthopaedic and trauma surgery in Europe were accessed. Only comparative clinical studies which investigated the year 2020 versus 2019 were eligible., Results: 57 clinical investigations were included in the present study. Eight studies reported a reduction of the orthopaedic consultations, which decreased between 20.9 and 90.1%. Seven studies reported the number of emergency and trauma consultations, which were decreased between 37.7 and 74.2%. Fifteen studies reported information with regard to the reasons for orthopaedic and trauma admissions. The number of polytraumas decreased between 5.6 and 77.1%, fractures between 3.9 and 63.1%. Traffic accidents admissions dropped by up to 88.9%, and sports-related injuries dropped in a range of 59.3% to 100%. The overall reduction of the surgical interventions ranged from 5.4 to 88.8%., Conclusion: The overall trend of consultations, surgeries, and rate of traumas and fragility fractures appear to decrease during the 2020 European COVID pandemic compared to the pre-pandemic era. Given the heterogeneities in the clinical evidence, results from the present study should be considered carefully., Level of Evidence: Level IV, systematic review., (© 2022. The Author(s).)

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 < 0.001), 6 (P < 0.001), and 8 (P < 0.001). No difference was found at week 1, 2, and 3. The group without fibrin glue demonstrated greater proliferation of B-MSCs within the membrane. These differences were significant at week 1 (P = 0.02), 2 (P = 0.008), 3 (P = 0.0009), 4 (P < 0.0001), 6 (P < 0.0001), 8 (P < 0.0001). Concluding, in the present setting, the use of fibrin in a collagenic biomembrane impairs B-MSCs proliferation and migration in vitro., (© 2022. The Author(s).)

Introduction: Death from uncontrolled trauma haemorrhage and subsequent trauma-induced coagulopathy (TIC) is potentially preventable. Point-of-care devices such as rotational thromboelastometry (ROTEM ® ) are advocated to detect haemostatic derangements more rapidly than conventional laboratory diagnostics. Regarding reductions in RBC transfusion, the use of ROTEM has been described as being efficient and associated with positive outcomes in several studies., Objective: The effect of ROTEM use was assessed on three different outcome variables: (i) administration of haemostatics, (ii) rate of RBC transfusions and (iii) mortality in severely injured patients., Methods and Material: A retrospective analysis of a large data set of severely injured patients collected into the TraumaRegister DGU ® between 2009 and 2016 was conducted. The data of 7461 patients corresponded to the inclusion criteria and were subdivided into ROTEM-using and ROTEM-non-using groups. Both groups were analysed regarding (i) administration of haemostatics, (ii) rate of RBC transfusions and (iii) mortality., Results: A lower mortality rate in ROTEM-using groups was observed ( p = 0.043). Furthermore, more patients received haemostatic medication when ROTEM was used. In ROTEM-using groups, there was a statistically relevant higher application of massive transfusion., Conclusions: In this retrospective study, the use of ROTEM was associated with reduced mortality and an increased application of haemostatics and RBC transfusions. Prospective evidence is needed for further evidence-based recommendations.

Background: It is unclear whether the results of osteochondral transplant using autografts or allografts for talar osteochondral defect are equivalent., Purpose: A systematic review of the literature was conducted to compare allografts and autografts in terms of patient-reported outcome measures (PROMs), MRI findings, and complications., Study Design: Systematic review; Level of evidence, 4., Methods: This study was conducted according to the PRISMA guidelines. The literature search was conducted in February 2021. All studies investigating the outcomes of allograft and/or autograft osteochondral transplant as management for osteochondral defects of the talus were accessed. The outcomes of interest were visual analog scale (VAS) score for pain, American Orthopaedic Foot and Ankle Society (AOFAS) score, and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. Data concerning the rates of failure and revision surgery were also collected. Continuous data were analyzed using the mean difference (MD), whereas binary data were evaluated with the odds ratio (OR) effect measure., Results: Data from 40 studies (1174 procedures) with a mean follow-up of 46.5 ± 25 months were retrieved. There was comparability concerning the length of follow-up, male to female ratio, mean age, body mass index, defect size, VAS score, and AOFAS score ( P > .1) between the groups at baseline. At the last follow-up, the MOCART (MD, 10.5; P = .04) and AOFAS (MD, 4.8; P = .04) scores were better in the autograft group. The VAS score was similar between the 2 groups ( P = .4). At the last follow-up, autografts demonstrated lower rate of revision surgery (OR, 7.2; P < .0001) and failure (OR, 5.1; P < .0001)., Conclusion: Based on the main findings of the present systematic review, talar osteochondral transplant using allografts was associated with higher rates of failure and revision compared with autografts at midterm follow-up.

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/m 2 . The mean defect surface area was 2.8 ± 1.9 cm 2 . 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., (© 2022. The Author(s).)

Background: No consensus has been reached regarding the optimal surgical treatment for focal chondral defects of the talus., Purpose: A Bayesian network meta-analysis was conducted to compare the clinical scores and complications of mosaicplasty, osteochondral auto- and allograft transplant, microfracture, matrix-assisted autologous chondrocyte transplant, and autologous matrix-induced chondrogenesis (AMIC) for chondral defects of the talus at midterm follow-up., Study Design: Bayesian network meta-analysis; Level of evidence, 4., Methods: This Bayesian network meta-analysis followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions. PubMed, Embase, Google Scholar, and Scopus databases were accessed in February 2021. All clinical trials comparing 2 or more surgical interventions for the management of chondral defects of the talus were accessed. The outcomes of interest were visual analog scale (VAS) score, American Orthopaedic Foot and Ankle Society (AOFAS) score, rate of failure, and rate of revision surgery. The network meta-analysis were performed through the routine for Bayesian hierarchical random-effects model analysis. The log odds ratio (LOR) effect measure was used for dichotomous variables, and the standardized mean difference (SMD) was used for continuous variables., Results: Data from 13 articles (521 procedures) were retrieved. The median length of the follow-up was 47.8 months (range, 31.7-66.8 months). Analysis of variance revealed no difference between the treatment groups at baseline in terms of age, sex, body mass index, AOFAS score, VAS score, and mean number of defects. AMIC demonstrated the greatest AOFAS score (SMD, 11.27) and lowest VAS score (SMD, -2.26) as well as the lowest rates of failure (LOR, 0.94) and revision (LOR, 0.94). The test for overall inconsistency was not significant., Conclusion: At approximately 4 years of follow-up, the AMIC procedure for management of focal chondral defects of the talus produced the best outcome.

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 < 0.001), 2 (P = 0.004), and 3 (P = 0.03). No difference was found at week 3, 6, and 8. The no-fibrin group demonstrated greater proliferation of the chondrocytes within the membrane. These differences were significant at week 4 (P < 0.0001), 6 (P < 0.0001), 8 (P < 0.0001)., Conclusion: The use of fibrin glue over a resorbable membrane leads to lower in vitro proliferation and migration of chondrocytes., (© 2022. The Author(s).)