A novel surgical technique for revision anterior cruciate ligament reconstruction using an isolated rectus femoris tendon autograft.

INTRODUCTION: Only a few anatomic studies have described an isolated rectus femoris tendon autograft for anterior cruciate ligament (ACL) reconstruction. This study aims to demonstrate a new surgical technique utilising the rectus femoris tendon for ACL reconstruction. This study hypothesises that the rectus tendon autograft will yield satisfying postoperative outcomes in terms of stability, with minimal complications at the harvest site. METHODS: This retrospective study investigated the outcomes of 28 revision ACL reconstructions using a rectus tendon autograft with a mean follow-up of 41.7 (range, 24.0-64.8) months. A 3 cm longitudinal incision was used to harvest the rectus tendon with an open tendon stripper. Intraoperative collected data included the length of the tendon and thickness of a 4-fold graft. Further outcome parameters include anterior cruciate ligament stability and range of motion. Additionally, postoperative complications, especially donor site morbidity, were documented in type and frequency. RESULTS: The mean tendon length measured 32.4 cm (range, 30-35 cm). After preparing a 4-fold graft, the mean diameter was 9.2 mm (range, 8.0-10 mm) at the tibial and 9.0 mm (range, 7.5-10 mm) at the femoral end. Stability evaluated by the Lachman test improved significantly from 2 (Interquartile range (IQR), 2-3) preoperatively to 0 (IQR, 0-1) postoperatively (p < .001). Rerupture of the anterior cruciate ligament graft was observed in 2 patients (7.1%). Four patients showed a persistent extension deficit of about 5 degrees postoperatively. Two of them underwent revision surgery due to a Cyclops lesion. Only one patient complained of prolonged pain at the harvest site (3.6%). CONCLUSION: The 4-fold rectus tendon represents a novel autograft technique in revision ACL reconstruction. This study provides evidence of appropriate graft dimensions and satisfying postoperative outcomes regarding stability. The technique is associated with a low complication rate at the harvest site. STUDY DESIGN: Case series; Level of evidence, IV.

Gait symmetry - A valid parameter for pre and post planning for total knee arthroplasty.

OBJECTIVES: We aimed to determine whether GS can help to plan and rearrange the treated side by using IMUs to measure the joint angle of the hip, knee, and ankle. We hypothesized that the kinematics in healthy individuals for both sides are approximately equal during walking. METHODS: IMUs were used to measure the joint angles of 25 healthy participants during walking. The participants performed the 10-meter walk test. The normalized symmetry index (SInorm) was used to calculate the symmetry of joint angles for the hip, knee, and ankle throughout the gait cycle. RESULTS: The SInorm demonstrated high symmetry between both legs; and the ranges were -1.5% and 1.1% for the hip, -3.0% and 3.1% for the knee, and -12% and 9.2% for the ankle joint angle throughout the gait cycle. CONCLUSION: The SInorm provides strong information that can be helpful in the planning process for the surgeries. Further, the IMUs system gives the possibility to measure the patients before their surgeries and use their data to plan and rearrange for the operated side.

Single- versus double-bundle patellar graft insertion for isolated MPFL reconstruction in patients with patellofemoral instability: a systematic review of the literature.

INTRODUCTION: The MPFL reconstruction is performed either via a single-bundle (SB) or double-bundle (DB) procedure. The purpose of this study is to perform a systematic review comparing SB versus DB graft for recurrent patellofemoral instability, to summarize current evidence, and to clarify the role of both techniques. We focused on clinical scores, physical examination, complications, revision surgeries, and failures. MATERIAL AND METHODS: In May of 2019 the main online databases were accessed. All the clinical studies treating isolated MPFL reconstruction for patellofemoral instability through a single and/or double-bundle graft were enrolled in the present systematic review. Only articles reporting primary isolated MPFL reconstruction, reporting a minimum of 12-months follow-up were considered for inclusion. RESULTS: The scores of interest were in favour of the DB cohort: Kujala (+ 3.2, P = 0.03), Lysholm (+ 5.1, P = 0.001), Tegner (+ 0.3, P = 0.2), IKDC (+ 5.4, P = 0.01), VAS (+ 0.8, P = 0.3), ROM (+ 9.96, P = 0.04). In the DB graft, a reduction of overall complications (OR 0.59; P = 0.1), further surgeries (OR 0.64; P = 0.12) and re-dislocations (OR 0.61; P = 0.16) was observed. The SB group reported a reduction in the post-operative apprehension test (OR 2.42; P = 0.24). CONCLUSION: Current study support the use of double-bundle tendon graft for isolated MPFL reconstruction in selected patients with recurrent patellofemoral instability.

Implant positioning among the surgical approaches for total hip arthroplasty: a Bayesian network meta-analysis.

INTRODUCTION: Although there is anatomical individuality among patients, some standardized requirements for component orientation for total hip arthroplasty (THA) exist. To date, no study has compared implant positioning using a network meta-analysis (NMA). Hence, the purpose of this study was to perform a NMA comparing implant positioning among the various approaches for THA. METHODS: This study was conducted according to the PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions. All randomized (RCT) and non-randomized (nRCT) clinical trials comparing two or more different approaches for THA were considered for inclusion. For the statistical analysis, the STATA Software/ MP, Version 14.1 (Stata Corporation, College Station, Texas, USA) was used. The NMA was performed through a Stata routine for Bayesian hierarchical random-effects model analysis. RESULTS: We enrolled in the present study, a total of 4060 patients, with a mean of 17.84 ± 16.41 months follow-up. The patient baseline data were very homogeneous across the groups concerning age (P = 0.91), sex (P = 0.52), and BMI (P = 0.83). Concerning the cup anteversion, the anterolateral approach reported the value closest to the reference value. The test for overall inconsistency, however, was not statistically significant (P = 0.30). Concerning cup inclination, the lateral approach reported the value closest to the reference value. The test for overall inconsistency was statistically significant (P = 0.01). CONCLUSION: The anterolateral approach for total hip arthroplasty detected the best femoral stem alignment and cup anteversion. Data concerning cup inclination detected no sufficient transitivity to draw consistent conclusions.

Improved outcomes after mesenchymal stem cells injections for knee osteoarthritis: results at 12-months follow-up: a systematic review of the literature.

PURPOSE: According to the World Health organization (WHO), more than 10% in people older than 60 years suffer from osteoarthritis (OA). Over the last years, there has been an increased interest around regenerative medicine, especially regarding stem cell treatments and related applications. We hypothesize that stem cell therapies can represent a feasible option for idiopathic knee OA, delaying or even avoiding the joint replacement. To emphasize the potential of percutaneous injections of mesenchymal stem cells for knee OA, a comprehensive systematic review of the literature was conducted. MATERIAL AND METHODS: Two independent authors (FM, GC) performed the literature search. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). The main databases were accessed: Pubmed, Embase, Google Scholar, Cochrane Systematic Reviews, Scopus, AMED. For this systematic review, all articles treating percutaneous injections of mesenchymal stem cells for knee OA were considered. Because of the rapid advancements promoted by the scientific progress on stem cell expansion and processing, only articles published within the last five years were included. Solely articles reporting the outcomes of interest across 6- and 12-month follow-up were recruited for eligibility. We included only studies reporting quantitative data under the outcomes of interest. We referred for the quality assessment to the Coleman Methodology Score (CMS). The statistical analysis was performed with Review Manager Software 5.3 (The Nordic Cochrane Centre, Copenhagen). RESULTS: A total of 18 studies were enrolled in the present study, comprising 1069 treated knees. The mean age of the samples was 57.39 ± 7.37 years. 72% of the included studies harvested the stem cells from the iliac crest (bone marrow-derived MSCs), the remaining 28% from the adipose tissue (adipose-derived MSCs). The mean visual analogic scale improved from 18.37 to 30.98 and 36.91 at 6- and 12-month follow-up, respectively. The mean WOMAC score improved from 25.66 to 25.23 and 15.60 at 6- and 12-month follow-up, respectively. The mean walking distance improved from 71.90 to 152.22 and 316.72 at 6- and 12-month follow-up, respectively. The mean Lequesne scale improved from 33.76 to 12.90 at 12-month follow-up. The KOOS score improved from 41.07 to 8.47% and 18.94 at 6- and 12-month follow-up. All the KOOS subscales improved significantly from the baseline. A total of 136 (12.7%) local complications were detected. CONCLUSION: According to the current evidences and the main findings of this systematic review, we reported that MSC infiltrations for knee OA can represent a feasible option, leading to an overall remarkable improvement of all clinical and functional considered outcomes, regardless of the cell source. Patients treated at earlier-degeneration stages reported statistically significant greater outcomes. The pain and function scores were improved considerably, thus, leading to a significant improvement of patient participation in recreational activities and quality of life.

Total hip arthroplasty: minimally invasive surgery or not? Meta-analysis of clinical trials.

BACKGROUND: There exist a relevant number of clinical trials comparing the minimally invasive surgery to the standard-invasive approach in total hip arthroplasty (THA). Up to date, there are still debates concerning the most effective approach in THA. AIM: The purpose of this study is to compare the clinical outcomes concerning patients undergoing primary THA performed via the minimally invasive versus standard-invasive surgery incision. MATERIAL AND METHODS: The search was performed in the main databases, evaluating both quantitative and qualitative results. All the randomised controlled trials (RCTs) and non-randomised controlled trials (nRCTs) comparing the minimally invasive versus the standard-invasive approach were enrolled in this study. We focused on the clinical and radiological outcomes and on the complication rate. Study methodological quality was assessed performing the PEDro critical appraisal scale. All meta-analyses were performed using the Review Manager software. To analyse the publication's bias, we performed the Funnel plot. RESULT: We enrolled in our study 4761 patients, undergoing to 4842 total hip arthroplasties. The mean follow-up was 22.26 months. In favour of the minimally invasive group, we reported less total estimated blood loss, shorter surgical duration, and a shorter length of stay. In favour of the standard-invasive group, we reported a higher value of the Harris hip score. Concerning the radiological outcomes, we did not report substantial differences across the two exposures. No difference was observed regarding the risk of femoral fractures, dislocation, and revision rates. We evidenced an increasing risk occurred in an iatrogenic nerve palsy during the minimally invasive approach. CONCLUSION: Based on currently available evidences concerning the outcomes following THA and the analysis of our results, we stated no remarkable benefits of the minimally invasive compared to the standard-invasive surgery.

Autogenic mesenchymal stem cells for intervertebral disc regeneration.

PURPOSE: A systematic review of the literature was conducted to clarify the outcomes of autologous mesenchymal stem cells (MSC) injections for the regeneration of the intervertebral disc (IVD). METHODS: The following databases were accessed: PubMed, Medline, CINAHL, Cochrane, Embase and Google Scholar bibliographic databases. Articles including previous or planned surgical interventions were excluded. Only articles reporting percutaneous autologous MSC injection to regenerate IVD in humans were included. We referred to the Coleman Methodology Score for the methodological quality assessment. The statistical analysis was performed using Review Manager Software 5.3. RESULTS: After the databases search and cross-references of the bibliographies, seven studies were included in the present work. The funnel plot detected low risk of publication bias. The Coleman Methodology Score reported a good result, scoring 61.07 points. A total of 98 patients were enrolled, with 122 treated levels. All the patients underwent conservative therapies prior to injection. A remarkable improvement in the quality of life were reported after the treatment. The average Oswestry Disability Index (ODI) improved from "severe disability" to "minimal disability" at one year follow-up. The visual analogue scale (VAS) showed an improvement of ca. 30% at one year follow-up. Only one case of herniated nucleus pulposus was reported. No other adverse events at the aspiration or injection site were observed. CONCLUSIONS: This systematic review of the literature proved MSC injection to be a safe and feasible option for intervertebral disc regeneration in the early-degeneration stage patients. Irrespective of the source of the MSCs, an overall clinical and radiological improvement of the patients has been evidenced, as indeed a very low complication rate during the follow-up.

Better outcomes with patellar resurfacing during primary total knee arthroplasty: a meta-analysis study.

BACKGROUND: Total knee arthroplasty (TKA) is a feasible and cost-effective procedure. However, resurfacing of the patella sparks a heated debate. Anterior knee pain after TKA was supposed to be correlated to the patellofemoral joint, and the resurface of the patella was believed to be effective to avoid this complication. AIM: A meta-analysis was performed to update current evidence concerning the outcomes of patellar resurfacing versus retaining for total knee arthroplasty. The first outcomes of interest were to compare the rate of anterior knee pain and revision surgeries. MATERIAL AND METHODS: This study was conducted according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA). A comprehensive review of the literature was conducted accessing the main databases: Embase, Google Scholar, PubMed, Scopus. All the prospective clinical trials comparing the outcomes between patellar resurfacing versus retaining were included in this study. Only articles classified as level of evidence I to II were considered for inclusion. Only studies reporting a minimum 24 months follow-up were included. The following data were extracted: demographic baseline, anterior knee pain, reoperations, clinical scores (HSS, KSS and related subscales) and range of motion (ROM). Studies solely reporting quantitative data under the outcomes of interest were included. RESULTS: In favor of the resurfacing group, we observed a statistically significant reduced rate of anterior knee pain (odd ratio 1.73) and reoperation (odd ratio 3.24). In the resurfacing group, a prevalence of anterior knee pain of 11.15% was detected, whereas in the retaining group it amounted to 17.39%. Furthermore, a greater KSS pain (+ 0.97%), KSS clinical (+ 0.23%), KSS functional (+ 2.44%), KSS overall (+ 2.47%) and HSS (+ 5.64%) were reported. In the retaining group, we found a better range of motion (+ 3.09°). CONCLUSION: Based on the main findings of this meta-analysis, patellar resurfaced TKA was demonstrated to have performed superior overall. Patellar resurfacing detected a lower rate of postoperative anterior knee pain and reoperation. Moreover, the resurfacing group showed greater value of the HSS, KSS and related subscales. In favor of the retaining group, a slightly better ROM was evidenced. LEVEL OF EVIDENCE: Level II, meta-analysis of prospective clinical trials.

Distal alignment procedures for patellofemoral instability: comprehensive review of the literature.

Patellofemoral disorders are a common cause of complaint in adolescent patients. Several distal realignment procedures performed in isolation or combination with proximal alignment have been described. To clarify the role of distal alignment for patellofemoral instability, a systematic review of the literature was conducted. Two independent reviewers accessed the following databases: PubMed, Medline, CINAHL, Cochrane, EMBASE and Google Scholar. A total of 1478 patients with a mean age of 22.78 years were included. The mean follow-up was 86.53 months. The average Kujala score improved from 57.66 to 82.73. The average Lysholm score improved from 63.25 to 87.87, and the average Tegner score from 3 to 4.16. VAS score improved from an average 8 to 2.56. We account a total of 46 major complications, 45 minor complications and 95 recurrences. The risk of a recurrence is 6.42%. A total of 122 additional surgeries were performed during the follow-up. This systematic review of literature suggests the importance to identify the pathological background that predisposes patients for developing patellofemoral instability and its implications for the decision-making process. The optimal treatment for patellofemoral instability should be individualized to address the specific anatomical abnormalities that contribute to patellofemoral dislocations. Distal alignments are a feasible solution to restore correct patellar biomechanics and tracking, leading to an improvement of patients' quality of life.

Posterior-stabilized versus cruciate-retained implants for total knee arthroplasty: a meta-analysis of clinical trials.

AIM: A meta-analysis comparing the outcomes of patients undergoing cruciate retaining (CR) versus posterior stabilized (PS) in primary total knee arthroplasty was performed. The outcomes of interest were the Knee Society Rating System, clinical (KSCS) and functional (KSFS) subscales, joint range of motion (ROM), surgical duration and further complications (anterior knee pain, instability and revision rate). MATERIALS AND METHODS: The search was conducted in July 2018, accessing the following databases: Cochrane Systematic Reviews, Scopus, PubMed, EMBASE, CINAHL, AMED and Google Scholar. We included only clinical trials level of evidence I and II. During the statistical analysis, we excluded all the studies that affect negatively the I2 test, in order to achieve more reliable results. For the methodological quality assessment we referred to the PEDro score. The risk of publication's bias was evaluated by the funnel plots across all the comparisons. RESULTS: The PEDro score reported a good methodological quality assessment. The funnel plot detected a very low risk of publication's bias. We included in this study 36 articles, counting a total of 4052 patients and 4884 procedures. The mean follow-up term for both groups was 3.39 years. The ROM resulted in an overall estimate effect of 2.18° in favor of the PS group. The overall WOMAC showed a result in favor of the PS group. The overall estimate effect of the KSCS was 0.02% higher in the CR group. The KSFS showed an overall estimate effect of 2.09% in favor of the PS group. Concerning the surgical duration, the estimate effect resulted in 6.87 min shorter in the CR group. No differences were reported across the two groups regarding anterior knee pain, knee joint instability or revision rate. CONCLUSION: Both the prosthetic implants provided to be a safety and feasible solution to treat end-stage knee joint degeneration. The PS implants reported improvements in the knee range of motion and a prolongation of the surgical time. No clinically relevant dissimilarities concerning the analyzed scores were evidenced. No statistically significant relevant differences in complications were detected.

Unicompartmental versus total knee arthroplasty for knee osteoarthritis.

PURPOSE: In the last couple of years, a significant amount of studies comparing the UKA and TKA for unicompartmental knee osteoarthritis have been published. However, there is a lack of recent meta-analysis comparing the two implants. Since the number of performed UKAs is currently increasing and the indications are obsolete, it becomes important to update current evidences and outcomes. With these premises, a meta-analysis of clinical trials comparing UKA versus TKA was conducted. METHODS: In October 2018, the following databases were accessed: Cochrane Systematic Reviews, Scopus, PubMed and Google Scholar. According to the Oxford Center of Evidence-based Medicine, level of evidence articles I to III were included. Only studies reporting quantitative data concerning the outcomes of interest were included. For the statistical analysis and the methodological quality assessment, we referred to the Review Manager Software 5.3. Dichotomous data were analyzed through the Mantel-Haenszel statistical method with the odd ratio effect measure. For continuous data, the inverse variance statistical method was used with the mean difference effect measure. A confidence interval of 95% was considered for analysis. To evaluate study heterogeneity, both Chi-square and Higgins tests were performed. Values of P < 0.05 were considered statistically significant. RESULTS: The overall methodological quality assessment was moderate. The risk of publication's bias was moderate. We enrolled in this study a total of 13,789 patients. The mean follow-up was 42.69 months. The UKA evidenced increased risk of revision's surgeries (OR 2.16, P > 0.0001). All the other scores of interest were in favor of the UKA: Oxford Knee Score, KSS Clinical, WOMAC overall and related subscales. The UKA also reported better functional outcomes: KSS Function, longer walking distance, improvement of the joint flexion and ROM. Moreover, in the UKA group have been reported a shorter length of stay, reduced estimated total blood loss and shorter surgical duration. CONCLUSION: The main findings of this meta-analysis are that UKA reported a reduced survivorship but better clinical and functional performances compared to TKA. Furthermore, shorter surgical duration, lower total estimated blood loss and quicker hospitalization length were observed in the UKA cohort.

Surgical management for recurrent patellar dislocations in skeletally immature patients.

BACKGROUND: Due to his multifactorial aetiology, treating patellofemoral instability can be a challenge for the orthopaedic surgeon. The incidence of patellofemoral instability shows a peak during adolescence, especially from 11 to 14 years old. AIM: Several clinical studies focusing on recurrent patellar dislocations in skeletally immature patients have been published, reporting inconsistent or controversial results. Currently, there is a lack of consensus regarding the surgical management of these patients. The purpose of this study is to update current evidence and systematically review indications, treatments, and outcomes of surgical management for recurrent patellar dislocations in skeletally immature patients. METHODS: A comprehensive review of the literature was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis, the PRISMA Statement. The following electronic databases were accessed in February 2019: PubMed, Scopus, Google Scholar, CINAHL, EMBASE. All the articles treating surgical management for recurrent patellar dislocations in skeletally immature patients were considered for inclusion. For the methodological quality assessment, we referred to the Coleman Methodology Score (CMS). For the statistical analysis, we referred to the unpaired t-test to establish whether the results are statistically significant. RESULT: The overall CMS resulted in 52.78 points, attesting a satisfactory methodological quality assessment to this systematic review. A total of 21 articles including 623 patients (577 knees) were evaluated. The overall mean age was 13.02 years. The mean follow-up was 46.61 months. The mean Kujala score improved from 58.94 ± 10.38 to 87.07 ± 7.68 points. The Lysholm score reported a pre- and post-operative mean values of 49.54 ± 14.20 and 88.32 ± 8.80, respectively. The mean Tegner Activity Scale scored 4.28 ± 1.22 at baseline, improving to 5.26 ± 0.83 post-operatively. A total of 4.19% of patients incurred into a major complication, while 9.6% sustained a minor one. We observed a total of 89 re-dislocations above 692 treated knees (12%). CONCLUSION: The main findings of this study are that surgical procedures for skeletally immature patients affected by recurrent patellar dislocations are feasible and effective. Complications and re-dislocations occurred infrequently. It is of fundamental importance to treat precociously these patients in order to reduce the risk of further recurrences, to increase the level of sporting activity and improving the quality of life.

The lncRNA HOTAIR impacts on mesenchymal stem cells via triple helix formation.

There is a growing perception that long non-coding RNAs (lncRNAs) modulate cellular function. In this study, we analyzed the role of the lncRNA HOTAIR in mesenchymal stem cells (MSCs) with particular focus on senescence-associated changes in gene expression and DNA-methylation (DNAm). HOTAIR binding sites were enriched at genomic regions that become hypermethylated with increasing cell culture passage. Overexpression and knockdown of HOTAIR inhibited or stimulated adipogenic differentiation of MSCs, respectively. Modification of HOTAIR expression evoked only very moderate effects on gene expression, particularly of polycomb group target genes. Furthermore, overexpression and knockdown of HOTAIR resulted in DNAm changes at HOTAIR binding sites. Five potential triple helix forming domains were predicted within the HOTAIR sequence based on reverse Hoogsteen hydrogen bonds. Notably, the predicted triple helix target sites for these HOTAIR domains were also enriched in differentially expressed genes and close to DNAm changes upon modulation of HOTAIR Electrophoretic mobility shift assays provided further evidence that HOTAIR domains form RNA-DNA-DNA triplexes with predicted target sites. Our results demonstrate that HOTAIR impacts on differentiation of MSCs and that it is associated with senescence-associated DNAm. Targeting of epigenetic modifiers to relevant loci in the genome may involve triple helix formation with HOTAIR.

Functional MR Imaging Mapping of Human Articular Cartilage Response to Loading.

Purpose To determine if multiparametric magnetic resonance (MR) imaging mapping can be used to quantify the response to loading of histologically intact human knee cartilage. Materials and Methods Institutional review board approval and written informed consent were obtained. Twenty macroscopically intact cartilage-bone samples were obtained from the central lateral femoral condyles in 11 patients undergoing total knee replacement. A clinical 3.0-T MR imaging system was used to generate T1, T1ρ, T2, and T2* maps with inversion recovery, spin-lock multiple gradient-echo, multiple spin-echo, and multiple gradient-echo sequences. Serial mapping was performed at three defined strain levels (strain 0 [δ0], 0%; strain 1 [δ1/2], 19.8% ± 4.6 [standard deviation]; strain 2 [δ1], 39.5% ± 9.3) by using displacement-controlled static indentation loading. The entire sample and specific cartilage zones (superficial zone [SZ], transitional zone [TZ], and deep zone [DZ]) and regions (subpistonal area [SPA] and peripistonal area [PPA]) were defined as regions of interest. Upon log transformation, repeated measures analysis of variance was used to detect groupwise regional and zonal differences. Load-induced relative changes were determined and analyzed by using paired Student t test and Spearman correlation. Biomechanical testing (unconfined compression) and histologic assessment (Mankin score) served as the reference standard. Results All samples were histologically intact. Strain-related decreases were found at the SZ and TZ for T1 and T2*; for T1ρ, increases were seen in all zones; and for T2, increases were seen at the SZ and PPA only. Significant parameter changes in the entire sample depth of SPA versus PPA were found for δ1/2 (T1ρ, 14% ± 12 vs 6% ± 9) and δ1 (T1, -4% ± 5 vs -1% ± 3; T1ρ, 13% ± 12 vs 7% ± 7; T2*, -9% ± 12 vs -2% ± 8). SPA versus PPA changes were significant at the SZ and TZ (T1), TZ and DZ (T1ρ), and SZ (T2*). No significant correlations were found between relative changes and biomechanical or histologic parameters. Conclusion Serial multiparametric MR imaging mapping can be used to evaluate cartilage beyond mere static analysis and may provide the basis for more refined graduation strategies of cartilage degeneration. © RSNA, 2016 Online supplemental material is available for this article.

Feedback signals in myelodysplastic syndromes: increased self-renewal of the malignant clone suppresses normal hematopoiesis.

Myelodysplastic syndromes (MDS) are triggered by an aberrant hematopoietic stem cell (HSC). It is, however, unclear how this clone interferes with physiologic blood formation. In this study, we followed the hypothesis that the MDS clone impinges on feedback signals for self-renewal and differentiation and thereby suppresses normal hematopoiesis. Based on the theory that the MDS clone affects feedback signals for self-renewal and differentiation and hence suppresses normal hematopoiesis, we have developed a mathematical model to simulate different modifications in MDS-initiating cells and systemic feedback signals during disease development. These simulations revealed that the disease initiating cells must have higher self-renewal rates than normal HSCs to outcompete normal hematopoiesis. We assumed that self-renewal is the default pathway of stem and progenitor cells which is down-regulated by an increasing number of primitive cells in the bone marrow niche--including the premature MDS cells. Furthermore, the proliferative signal is up-regulated by cytopenia. Overall, our model is compatible with clinically observed MDS development, even though a single mutation scenario is unlikely for real disease progression which is usually associated with complex clonal hierarchy. For experimental validation of systemic feedback signals, we analyzed the impact of MDS patient derived serum on hematopoietic progenitor cells in vitro: in fact, MDS serum slightly increased proliferation, whereas maintenance of primitive phenotype was reduced. However, MDS serum did not significantly affect colony forming unit (CFU) frequencies indicating that regulation of self-renewal may involve local signals from the niche. Taken together, we suggest that initial mutations in MDS particularly favor aberrant high self-renewal rates. Accumulation of primitive MDS cells in the bone marrow then interferes with feedback signals for normal hematopoiesis--which then results in cytopenia.

Abrasion arthroplasty increases mesenchymal stem cell content of postoperative joint effusions.

BACKGROUND: Abrasion arthroplasty (AAP) is a procedure by which intrinsic cartilage healing is believed to be stimulated. Although clinically accepted for degenerative and traumatic cartilage lesions scientific evidence at a molecular level that proves the effect of AAP is scarce. METHOD: Mononuclear cells were extracted from postoperative joint effusions 21.5 h post AAP and simple debridement of cartilage lesions. Luminex, ELISA and FACS experiments were performed. Immunohistochemical stainings of cell cultures for cartilage markers were used to confirm the findings. RESULTS: Postoperative joint effusions after AAP showed increased contents of Mononuclear cells compared to Arthroscopic Chondroplasty (ACP). BMP-4 and IGF were increased in AAP as complared to ACP. Mononuclear cells isolated after AAP express the MSC markers CD 73, CD 105, CD 90, CD 44 and are CD34 negative. Chondrogenic differentiation was demonstrated by positive staining for Sox9, collagen II, proteoglycan, chondroitin-4-sulfate. CONCLUSION: Our results support the clinical application of AAP as a procedure that enhances cartilage repair as an alternative to far more complex procedures that have gained popularity. Furthermore the data presented supports clinical investigations that recommend not to use suction drainage as by this procedure a considerable amount of the regeneratory potential of postoperative joint effusions might be extracted.

Effects of athletic training on the spinal curvature in child athletes.

The purpose of this study was to examine the spinal posture in young athletes depending on training intensity. The spinal curvature of 245 children, age 8 to 12 years, was evaluated using rasterstereography. According to their weekly training time group 1 (mean age: 9.54 ± 1.18) did 2-6, group 2 (mean age: 9.49 ± 0.87) did 6-15 and group 3 (mean age: 9.68 ± 0.87) did over 15 hours of training. Group 1 had a significantly higher weight (p = 0.028) (33.86 ± 7. kg) than those of the more active groups (30.67 ± 6.49 kg and 29.46 ± 4.33 kg). The mean kyphotic angle decreased significantly (p < 0.001) with the amount of training per week from 46.86 ± 8.2° in group 1 to 40.08 ± 8° in group 3. We also found a significant decrease (p = 0.047) in lateral deviation with training from group 1 with 5.3 ± 3 mm to group 2 with 4.1 ± 1.6 mm. The results of our study suggest that higher training time can be associated with lower weight and decreases in thoracic kyphosis and lateral deviation of the spine.

Sex-Specific Size Analysis of Carpal Bones: Implications for Orthopedic Biomedical Device Design and Therapy Planning.

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.

Eliminating the need of serum testing using low serum culture conditions for human bone marrow-derived mesenchymal stromal cell expansion.

BACKGROUND: The conventional expansion of human mesenchymal stromal cells (hMSC) for tissue engineering or (pre-) clinical investigation includes the use of 10% fetal bovine serum (FBS). However, there exists immense lot-to-lot variability in FBS samples and time consuming as well as cost intensive lot pre-testing is essential to guarantee optimal hMSC proliferation and stem cells characteristics maintenance. Furthermore, lot-to-lot variability impedes the long-term consistency of research and comparability between research groups. Therefore, we investigated the use of defined, invariable, non-synthetic FBS in low serum culture conditions for isolation and expansion of hMSC. METHODS: hMSC were isolated from bone marrow in Panserin 401 supplemented with growth factors and 2% MSC-tested or non-tested, defined, invariable, non-synthetic FBS and further cultivated in vitro. The surface marker expression, differentiation capacity as well as cell proliferation and cytotoxicity was analyzed and compared between serum samples. RESULTS: Cells isolated and cultivated with low concentrations of MSC-tested or non-tested FBS demonstrated no differences in surface marker expression or differentiation capacity. Proliferation of hMSC was equal in medium supplemented with either serum with no indication of cell death. CONCLUSIONS: The low serum concentration in Panserin 401 supplemented with growth factors enables the use of defined, invariable, non-synthetic FBS for the isolation and expansion of hMSC. The required hMSC characteristics like surface marker expression and differentiation capacity are maintained. Importantly, no differences in the cell proliferation could be detected. Therefore, using these low-serum culture conditions, the need for lot-to-lot pre-testing of FBS usually needed for optimal hMSC expansion is abolished leading to long-term consistency and comparability of results.