Protocol for a systematic review of guidelines for rigour in the design, conduct and analysis of biomedical experiments involving laboratory animals

Objective: Within the last years, there has been growing awareness of the negative repercussions of unstandardized planning, conduct and reporting of preclinical and biomedical research. Several initiatives have set the aim of increasing validity and reliability in reporting of studies and publications, and publishers have formed similar groups. Additionally, several groups of experts across the biomedical spectrum have published experience and opinion-based guidelines and guidance on potential standardized reporting. While all these guidelines cover reporting of experiments, an important step prior to this should be rigours planning and conduction of studies. The aim of this systematic review is to identify and harmonize existing experimental design, conduct and analysis guidelines relating to internal validity and reproducibility of preclinical animal research. The review will also identify literature describing risks of bias pertaining to the design, conduct and analysis of preclinical biomedical research. Search strategy: PubMed, Embase and Web of Science will be searched systematically to identify guidelines published in English language in peer-reviewed journals before January 2018 (box 1). All articles or systematic reviews in English language that describe or review guidelines on the internal validity and reproducibility of animal studies will be included. Google search for guidelines published on the websites of major funders and professional organisations can be found in (Box 2). Screening and annotation: Unique references will be screened in two phases: screening for eligibility based on title and abstract, followed by screening for definitive inclusion based on full text. Screening will be performed in SyRF (http://syrf.org.uk). Each reference will be randomly presented to two independent reviewers. Disagreements between reviewers will be resolved by additional screening of the reference by a third, senior researcher. Data management and reporting: All data, including extracted text and guidelines, will be stored in the SyRF platform. Elements of the included guidelines will be identified using a standardized extraction form. Reporting will follow the PRISMA guidelines as far as applicable

Use of cell-free collagen type I matrix implants for the treatment of small cartilage defects in the knee: clinical and magnetic resonance imaging evaluation

Abstract Purpose Articular cartilage defects of the knee are a common condition for which several repair techniques have been described. The aim of the present study was to assess medium-term results of a one-step procedure using a cell-free collagen type I matrix. Methods Fifteen patients with articular cartilage defects of the knee were treated with an 11-mm-diameter cell-free collagen type 1 matrix implant. The matrices were implanted in a press-fit manner into the defect after careful debridement down to the subchondral bone but without penetration of this margin. Follow-up examinations were carried out at 6 weeks, 6 months, and at 12, 24, 36, and 48 months after implantation. Clinical assessment included the visual analogue scale (VAS), the Tegner activity scale, and the International Knee Documentation Committee (IKDC) score. Radiological assessment for graft attachment and tissue regeneration was performed using the magnetic observation of cartilage repair tissue (MOCART) score. Results A total of 15 patients (males: n = 6 and females: n = 9) with a mean age of 26.4 years (range 19-40) were treated. The mean VAS improved significantly when compared to the preoperative values (P \ 0.05). Six weeks after implantation, IKDC values were slightly lower than the preoperative values (n.s.), but increased significantly at final follow-up (P \ 0.05). At 24 months, there were no significant differences in the median Tegner score between the post-operative values and the preoperative values (n.s.). However, after 36 months, a significant improvement was noted that lasted at least up to 48 months (P \ 0.05). The MOCART score improved consistently up to 4 years after implantation, with significant improvements already observed after 12 months (P \ 0.05). No correlation between the clinical scores and the MOCART score could be perceived. Conclusion The present study showed that the use of cellfree collagen type I matrix implants led to a significant and durable improvement in all the clinical and imaging scores investigated 4 years after implantation. Level of evidence IV

Functionalised High-Performance Oxide Ceramics with Bone Morphogenic Protein 2 (BMP-2) Induced Ossification: An In Vivo Study

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

Histomorphometry of Ossification in Functionalised Ceramics with Tripeptide Arg-Gly-Asp (RGD): An In Vivo Study

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

Arthroscopic versus mini-open rotator cuff repair: A meta-analysis

BackgroundAn 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 methodsThe 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.ResultsA 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).ConclusionArthroscopic 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

Patellar fixation graft via suture anchors versus tunnel techniques during isolated MPFL reconstruction for recurrent patellofemoral instability: a systematic review of the literature

Introduction!#!There is still a lack of evidence concerning the patellar fixation of the medial patellofemoral ligament (MPFL) graft in selected patient with recurrent instability. The purpose of the present study was to investigate and compare clinical outcomes and further complications of isolated MPFL reconstruction via suture anchors versus tunnel techniques for recurrent patellofemoral instability.!##!Materials and methods!#!This systematic review of the literature was conducted according to the PRISMA guidelines. In September 2019, the main databases were accessed. All the clinical trials performing isolated MPFL reconstruction in patients with recurrent patellofemoral instability were included in the present study. Only articles fixing the MPFL graft through suture anchors and/ or patellar tunnel techniques were included in the analysis.!##!Results!#!Data from 46 papers (1712 patients) were recorded. The mean follow-up was 40 ± 18 months. No differences were found in Kujala, Lysholm and Tegner score, International Knee Documentation Committee, visual analogic scale, range of motion and re-dislocation rate. The suture anchors fixation group detected reduced rate of apprehension test (OR: 0.6; p = 0.03), revision surgeries (OR: 0.4; p = 0.02) and anterior knee pain (OR: 0.05; p < 0.0001) and reduced not-classified complications (OR: 0.18; p < 0.0001).!##!Conclusion!#!Both the suture anchors and the bone-tunnels are a feasible option for isolated MPFL reconstruction in patients with recurrent patellofemoral instability. Patellar fixation via suture anchors evidenced a reduced rate of anterior knee pain, revision surgeries, apprehension test and an overall reduced complication compared to the bone-tunnel technique

Osteointegration of functionalised high-performance oxide ceramics: imaging from micro-computed tomography

BackgroundThis 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.Methods36 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.ResultsBV/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.ConclusionSinalised 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

Silica coated high performance oxide ceramics promote greater ossification than titanium implants: an in vivo study

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 < 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

Is ROTEM Diagnostic in Trauma Care Associated with Lower Mortality Rates in Bleeding Patients?—A Retrospective Analysis of 7461 Patients Derived from the TraumaRegister DGU^®

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