Health-related quality of life and associated risk factors in patients with Multiple Osteochondromas: a cross-sectional study.

PURPOSE: To evaluate the health-related quality of life and associated risk factors for Multiple Osteochondromas patients. METHODS: A cross-sectional, observational study was conducted from May to December 2022 during the routine visit to the referral center for rare skeletal disorders. All patients with Multiple Osteochondromas aged ≥ 3 years were included. EuroQol 5-dimension questionnaires, and demographic, clinical, and surgical history data were collected. Descriptive statistics, Fisher's exact test, One-sample t-test, Spearman's correlation, and multiple linear and logistic regression were performed to analyze the data. Results are reported following STROBE guidelines. RESULTS: A total of 128 patients were included in the study, with a mean age of 14 [SD, 10] years. The mean EQ-5D Index Value was 0.863 [SD, 0.200] and the EQ-VAS was 84 [SD, 19] with a positive correlation between two scores [r = 0.541, p < 0.001]. Patients frequently referred problems in pain/discomfort [78.8%], anxiety/depression [50%], and usual activities [38.8%] dimensions. Increasing age was the common risk factor for health-related quality of life [p < 0.000], as well as Index Value and VAS scores were significantly lower in surgical patients [p = 0.001 and p < 0.001, respectively]. CONCLUSION: Increasing age and surgical procedures were found highly associated with reduced health-related quality of life in Multiple Osteochondromas patients. Our findings provide relevant information to support the establishment of patient-centered healthcare pathways and pave the way for further research into medical and non-medical therapeutic strategies for these patients.

Hip Labral Morphological Changes in Patients with Femoroacetabular Impingement Speed Up the Onset of Early Osteoarthritis.

Over the last decade, evidence has mounted for a prominent etiologic role of femoroacetabular impingement (FAI) in the development of early hip osteoarthritis (OA). The aim of this study was to compare the ultrastructure and tissue composition of the hip labrum in healthy and pathological conditions, as FAI and OA, to provide understanding of structural changes which might be helpful in the future to design targeted therapies and improve treatment indications. We analyzed labral tissue samples from five healthy multi-organ donors (MCDs) (median age, 38 years), five FAI patients (median age, 37 years) and five late-stage OA patients undergoing total hip replacement (median age, 56 years). We evaluated morpho-functional by histology and transmission electron microscopy. Extracellular matrix (ECM) structure changes were similar in specimens from FAI compared to those from patients with OA (more severe in the latter) showing disorganization of collagen fibers and increased proteoglycan content. In FAI and in OA nuclei the chromatin was condensed, organelle degenerated and cytoplasm vacuolized. Areas of calcification were mainly observed in FAI and OA labrum, as well as apoptotic-like features. We showed that labral tissue of patients with FAI had similar pathological alterations of tissue obtained from OA patients, suggesting that FAI patients might have high susceptibility to develop OA.

High recall bias in retrospective assessment of the pediatric International Knee Documentation Committee Questionnaire (Pedi-IKDC) in children with knee pathologies.

PURPOSE: The increasing incidence of knee injuries among children is well known by sports physicians. Papers dealing with this topic have often collected patient-reported outcomes measures (PROMs) in a retrospective manner; this limitation could lead to a misinterpretation of the results, because pediatric patients might not remember their preoperative conditions adequately. This study aims to evaluate the reliability and the reproducibility of the IKDC pediatric score when administered retrospectively at a 12-month follow-up. METHODS: From September 2018 and June 2019, all patients aged 7-18 scheduled for surgery due to different knee pathologies in a single center were considered eligible. Parents were contacted by phone for consent. An open-source platform was implemented to collect the responses: two surveys were created (Q1, Q2). They included general information and the Pedi-IKDC score. Q1 was completed prospectively, while Q2 was completed 12 months after surgery. The two questionnaires were identical, and patients were carefully advised to complete Q2 recalling their health status before surgery. ICC and the concordance correlation coefficient (ρc) were used to assess the reproducibility between the prospective and recalled scores. RESULTS: Sixty-six patients responded to Q1 and Q2, and the mean age was 12.9 ± 2.2 years at Q1 and 14.1 ± 2.2 years at Q2. The mean time between Q1 and Q2 was 14.1 ± 2.1 months. Between prospective-IKDC and recall-IKDC, the ICC coefficient was "poor" at 0.32 (CI 0.09 to 0.5) and the ρc was "poor" at 0.4 (CI 0.29 to 0.51). Mean prospective-IKDC was 76.8 ± 23.52 mean recalled-IKDC was 60.4 ± 11.5 (P < 0.0001), while mean difference was -16.3 ± 2.09. Simple linear regression models showed that Δ-IKDC is independently associated with age at Q1 (R2 = 0.2676; P0.0001) and prospective-IKDC (R2 = 0.653; P < 0.0001). CONCLUSIONS: Retrospective collection of the Pedi-IKDC score is not reliable and has high recall bias. This should be avoided in children with knee conditions. LEVEL OF EVIDENCE: III.

Do Synovial Inflammation and Meniscal Degeneration Impact Clinical Outcomes of Patients Undergoing Arthroscopic Partial Meniscectomy? A Histological Study.

The menisci exert a prominent role in joint stabilization and in the distribution of mechanical loading. Meniscal damage is associated with increased risk of knee OA. The aim of this study was to characterize the synovial membrane and meniscal tissues in patients undergoing arthroscopic partial meniscectomy for meniscal tear and to evaluate association with clinical outcomes. A total of 109 patients were recruited. Demographic and clinical data were collected. Visual Analogic Scale (VAS) measuring pain and Knee injury and Osteoarthritis Outcome Score (KOOS) were recorded at baseline and at 2-years follow-up. Histological and immunohistochemical characterizations were performed on synovial membranes and meniscal tissues. More than half of the patients demonstrated synovial mononuclear cell infiltration and hyperplasia. Synovial fibrosis was present in most of the patients; marked vascularity and CD68 positivity were observed. Inflammation had an impact on both pain and knee symptoms. Patients with synovial inflammation had higher values of pre-operative VAS and inflammation. Higher pre-operative pain was observed in patients with meniscal MMP-13 production. In conclusion, multivariate analysis showed that synovial inflammation was associated with pre-operative total KOOS scores, knee symptoms, and pain. Moreover, meniscal MMP-13 expression was found to be associated with pre-operative pain in multivariate analysis. Thus, targeting inflammation of the synovial membrane and meniscus might reduce clinical symptoms and dysfunction at the time of surgery.

The Rizzoli Multiple Osteochondromas Classification revised: describing the phenotype to improve clinical practice.

Multiple osteochondromas (MO) is a rare disorder, characterized by benign osteocartilaginous tumors (osteochondromas), arising from the perichondrium of bones. The osteochondromas increase during growth, frequently causing deformities and limitations. Our study aims to analyze the data captured by the Registry of Multiple Osteochondromas, to refine Istituto Ortopedico Rizzoli (IOR) Classification, providing a representative picture of the phenotypic manifestations throughout the lifespan. We conducted a single-institution cross-sectional study. Patients were categorized according to IOR Classification, which identifies three patients' classes on the presence/absence of deformities and/or limitations. The present dataset was compared with our previously published data, to refine the classification. Nine hundred sixty-eight patients were included: 243 children (<10 years), 136 adolescents (10-15 years), and 589 adults. Of the entire population, half patients presented at least one deformity, and one quarter reported at least one limitation. Compared with our previous study, the amount of children was more than doubled and the percentage of mild/moderate cases was notably increased, giving a better disease overview throughout the lifespan and suggesting a different cut-off for dividing Class II in subclasses. We confirmed that MO is characterized by phenotypic heterogeneity, suggesting that an early classification of the disease may offer a useful tool to follow disease pattern and evolution, to support clinical practice, and to propose timely interventions.

Imaging of Congenital Skeletal Disorders.

Osteochondrodysplasias are the result of the expression of gene mutations. The phenotypes in osteochondrodysplasias evolve through life, with the possibility that previously unaffected bones may be involved at later stages of growth. Due to the variable time of onset, the diagnosis may be made prenatally, at birth, or later. Certainty in the diagnosis is sometimes only achieved as the patient matures and the disease evolves. Radiographic evaluation is a fundamental part of the diagnostic work-up of congenital skeletal disorders and in most cases the first tool used to arrive at a diagnosis. This review describes the imaging characteristics, specific signs, and evolution of several skeletal dysplasias in which diagnosis may be directly or indirectly suggested by radiologic findings. A definitive accurate diagnosis of a congenital skeletal abnormality is necessary to help provide a prognosis of expected outcomes and to counsel parents and patients.

Anatomical Considerations of Embryology and Development of the Musculoskeletal System: Basic Notions for Musculoskeletal Radiologists.

The musculoskeletal (MSK) system begins to form in the third week of intrauterine development. Multiple genes are involved in the complex different processes to form the skeleton, muscles and joints. The embryonic period, from the third to the eighth week of development, is critical for normal development and therefore the time when most structural defects are induced. Many of these defects have a genetic origin, but environmental factors may also play a very important role. This review summarizes the embryology of the different components of the MSK system and their configuration as an organ-system, analyzes the clinical implications resulting from failures in the process of organogenesis, and describes the first approach to diagnosis of skeletal abnormalities using prenatal ultrasound.

Operative versus nonoperative treatment in children with painful rigid flatfoot and talocalcaneal coalition.

BACKGROUND: The management of painful rigid flatfoot (RFF) with talocalcaneal coalition (TCC) is controversial. We aimed to compare operative and nonoperative treatment in children with RFF and TCC. METHODS: We retrospectively reviewed medical records and radiographs of children with RFF and TTC treated between 2005 and 2015. The nonoperative treatment consisted of manipulation under anesthesia, cast immobilization and shoe insert after cast removal. The operative treatment consisted of combined TCC resection, graft interposition and subtalar arthroereisis. RESULTS: Thirty-four children (47 ft) in the nonoperative group and twenty-one children (34 ft) in the operative group were included. No differences were found between groups, concerning baseline characteristics. The mean age at treatment was 11.8 years (9-17): 11.6 (9-17) for the nonoperative group, 12.2 (10-15) for the operative group. The mean follow-up averaged 6.6 (3-12) years and was significantly longer in the nonoperative group (7.8 versus 4.7 years; p < 0.0005), since the operative procedure was increasingly practiced in the latest years. There were no complications in either groups, but 6 patients (7 ft) in the nonoperative group were unsatisfied and required surgery. At the latest follow-up, the AOFAS-AHS improved in both groups, although the operative group showed significantly better improvement. The operative group reported also significantly better FADI score, after adjustment for follow-up and baseline variables. CONCLUSION: The operative treatment showed better results compared to the nonoperative treatment. Symptomatic RFF with TCC in children can be effectively treated in one step with resection, graft interposition and subtalar arthroereisis. Further prospective randomized studies are needed to confirm our findings and to identify the best operative strategy in this condition.

Deformity progression in congenital posteromedial bowing of the tibia: a report of 44 cases.

BACKGROUND: congenital posteromedial bowing of tibia (CPMBT) is a very rare birth defect, characterized by shortened bowed leg and ankle deformity. We described a single institution experience in the management of CPMBT. METHODS: we identified 44 CPMBT in 44 children. The age at presentation was 5.5 ± 5.6 years and the mean age at the final review was 10.1 ± 4.8 years. Radiographic evaluation included the antero-posterior and lateral inter-physeal angle (AP-IPA and L-IPA), the limb length discrepancy (LLD), the morphology of the distal tibia and the lateral distal tibial angle (LDTA). During the study period, 26 children underwent surgical treatment. RESULTS: the estimated curves showed a progressive spontaneous correction of both AP-IPA and L-IPA during growth, but a progressive increase of the LLD. The L-IPA showed a more predictable behaviour while the AP-IPA showed a scattered correction, with a wider variation of the estimated final angle. The final LDTA was 85.3° ± 4.2° and was correlated with the L-IPA (r = 0.5; p = 0.02). Among the 26 children who underwent surgical treatment, 23 cases had limb lengthening, 1 case had contralateral epiphysiodesis, 1 child underwent tibial osteotomy, 1 patient was treated by hemiepiphysiodesis of the distal tibia to correct ankle valgus deformity. CONCLUSIONS: our study described the largest case series of CPMBT. A combination of surgical treatments, in a staged surgical process, should be tailored to the developmental characteristics of this abnormality. An experience-based algorithm of treatment is also proposed. Further studies are needed to understand which is the best strategy to correct this deformity during childhood. LEVEL OF EVIDENCE: level IV prognostic study.

The Italian cross-cultural adaptations of the paediatric International Knee Documentation Committee Score and the Hospital for Special Surgery Paediatric Functional Activity Brief Scale are reliable instruments in paediatric population.

PURPOSE: The aim of the present study was to translate, cross-culturally adapt, and assess the psychometric properties of the Pedi-IKDC and Pedi-FABS scores in the Italian paediatric population with various knee pathologies. METHODS: In accordance with the Paediatric Anterior Cruciate Ligament Monitoring Initiative (PAMI) research protocol, the original English versions of the questionnaires were translated into Italian. All patients aged 8-16 and scheduled for knee surgery were considered eligible in the study. An open-source platform was implemented to collect responses to the surveys which included general patient information, the questionnaires Pedi-IKDC, and Pedi-FABS. Two surveys were sent under stable clinical conditions before surgery (Q1 and Q2); a third survey was sent 3-4 months after surgery (Q3). The following properties were calculated: reliability, internal consistency, criterion validity, responsiveness, and floor/ceiling effects. RESULTS: Eighty-nine patients completed Q1, 81 patients completed Q2, and 49 patients completed Q3. Both questionnaires demonstrated acceptable properties. Pedi-IKDC: standard error of measurement (SEM) = 4.4, smallest detectable change (SDC) = 12.3, interclass correlation coefficient (ICC) = 0.96, Cronbach alpha (α) = 0.92, moderate-to-low correlation to Pedi-FABS, effect size (ES) = 0.79, standardized response mean (SRM) = 0.86, floor = 0%, ceiling = 22%. Pedi-FABS: SEM = 2.1, SDC = 5.8, ICC = 0.94, Cronback alpha (α) = 0.93, moderate-to-low correlation to Pedi-IKDK, ES = 0.60, SRM = 0.51, floor = 19%, ceiling = 0%. CONCLUSIONS: The Italian version of Pedi-IKDC and Pedi-FABS is valuable tools for patient assessment, by demonstrating good psychometric properties. In clinical setting, these questionnaires can be used to properly evaluate outcomes in Italian pediatric patients with knee pathologies. LEVEL OF EVIDENCE: II.

Inflammatory molecules produced by meniscus and synovium in early and end-stage osteoarthritis: a coculture study.

The aim of this study was to identify the molecules and pathways involved in the cross-talk between meniscus and synovium that may play a critical role in osteoarthritis (OA) pathophysiology. Samples of synovium and meniscus were collected from patients with early and end-stage OA and cultured alone or cocultured. Cytokines, chemokines, metalloproteases, and their inhibitors were evaluated at the gene and protein levels. The extracellular matrix (ECM) changes were also investigated. In early OA cultures, higher levels of interleukin-6 (IL-6) and IL-8 messenger RNA were expressed by synovium and meniscus in coculture compared with meniscus cultured alone. RANTES release was significantly increased when the two tissues were cocultured compared with meniscus cultured alone. Increased levels of matrix metalloproteinase-3 (MMP-3) and MMP-10 proteins, as well as increased release of glycosaminoglycans and aggrecan CS846 epitope, were observed when synovium was cocultured with meniscus. In end-stage OA cultures, increased levels of IL-8 and monocyte chemoattractant protein-1 (MCP-1) proteins were released in cocultures compared with cultures of meniscus alone. Chemokine (C-C motif) ligand 21 (CCL21) protein release was higher in meniscus cultured alone and in coculture compared with synovium cultured alone. Increased levels of MMP-3 and 10 proteins were observed when tissues were cocultured compared with meniscus cultured alone. Aggrecan CS846 epitope release was increased in cocultures compared with cultures of either tissue cultured alone. Our study showed the production of inflammatory molecules by synovium and meniscus which could trigger inflammatory signals in early OA patients, and induce ECM loss in the progressive and final stages of OA pathology.

Conditioned media from human osteoarthritic synovium induces inflammation in a synoviocyte cell line.

AIM: Osteoarthritis (OA) is a whole joint pathology involving cartilage, synovial membrane, meniscus, subchondral bone, and infrapatellar fat pad (IFP). Synovitis has been widely documented in OA suggesting its important role in pathogenesis. The aim of this study was to investigate the role of different joint tissues in promoting synovitis. MATERIALS AND METHODS: Conditioned media (CM) from cartilage, synovial membrane, meniscus, and IFP were generated from tissues of five patients undergoing total knee replacement and used to stimulate a human fibroblast-like synoviocytes cell line (K4IM). Cytokines, chemokines, and metalloproteases release was analyzed in all CM by Bio-Plex Assay and sulfated glycosaminoglycan (GAG) content by dimethylmethylene blue assay. Gene expression of several markers was evaluated by real-time PCR in K4IM cells stimulated with the CM obtained from joint tissues. RESULTS: CM from all tissues produced high levels of IL-6, IL-8, and CCL2. CCL21, MMP-3, and -13 levels were detected in all CM except IFP. MMP-10 was present only in CM of cartilage and synovial tissues. IL-1ß, IL-15, TNF-α, CCL5, and CCL19 were undetectable. However, only K4IM cells stimulated by the CM from OA synovium showed an increase of IL-6, CXCL-8, CCL21, MMP10, and IL-1ß expression. CONCLUSION: Our study showed that K4IM might be a suitable in vitro model for evaluating different cellular pathways in OA studies. Importantly, we demonstrated that in OA, all joint tissues might be involved in the progression of synovitis with a predominant role of synovial membrane itself compared to the other joint tissues.

Comparison of Dimeglio and Pirani score in predicting number of casts and need for tenotomy in clubfoot correction using the Ponseti method.

PURPOSE: The Dimeglio and the Pirani scores are largely used to rate clubfoot at presentation and monitor correction. To date, the accuracy of these scores in predicting appropriate treatment is controversial. The aim of this study was to investigate the accuracy of Dimeglio and Pirani scores in predicting the number of casts and the need for tenotomy in clubfoot correction using the Ponseti method. METHODS: Ninety-one consecutive feet (54 patients; mean age at presentation: 28 ± 15 days) undergoing clubfoot correction using the Ponseti method were prospectively followed from first casting to correction. All feet were scored according to the Dimeglio and Pirani score. The relationships between the two scores, the number of casts and the need for tenotomy were analysed. RESULTS: Initial correction was achieved in all feet. Both Dimeglio (r = .73; p value < .0005) and Pirani scores (r = .56; p value < .000) showed good association with the number of casts. Multiple linear regression showed a high collinearity of the two scores but a more significant contribution of the Dimeglio score. Among subcomponents, hindfoot score, midfoot score, varus and muscular abnormality were independent predictors of the number of casts. Both Dimeglio and Pirani scores were significantly associated with the need for tenotomy (p value = .0000), and odds ratios and cut-off points were calculated. The receiving operator curve (ROC) analysis showed slightly better performance of the Dimeglio in comparison with the Pirani score in predicting the need for tenotomy, but the difference between the two areas under the curve (AUC) was not significant (p = .48). CONCLUSIONS: A quite accurate prediction of the number of casts and the need for tenotomy can be performed in most cases. The Dimeglio score showed slightly better accuracy in predicting both steps of Ponseti treatment.

Comparison between modified Dunn procedure and in situ fixation for severe stable slipped capital femoral epiphysis.

Background and purpose - The best treatment option for severe slipped capital femoral epiphysis (SCFE) is still controversial. We compared clinical and radiographic outcomes of modified Dunn procedure (D) and in situ fixation (S) in severe SCFE. Patients and methods - We retrospectively compared D and S, used for severe stable SCFE (posterior sloping angle (PSA) > 50°) in 29 patients (15 D; 14 S). Propensity analysis and inverse probability of treatment weights (IPTW) to adjust for baseline differences were performed. Patients were followed for 2-7 years. Results - Avascular necrosis (AVN) occurred in 3 patients out of 15, after D, causing conversion to total hip replacement (THR) in 2 cases. In S, 1 hip developed chondrolysis, requiring THR 3 years after surgery. 3 symptomatic femoroacetabular impingements (FAI) occurred after S, requiring corrective osteotomy in 1 hip, and osteochondroplasty in another case. The risk of early re-operation was similar between the groups. The slippage was corrected more accurately and reliably by D. The Nonarthritic Hip Score was similar between groups, after adjusting for preoperative and postoperative variables. Interpretation - Although D was superior to S in restoring the proximal femoral anatomy, without increasing the risk of early re-operation, some concern remains regarding the potential risk of AVN in group D.

Congenital pseudarthrosis of the clavicle: a report on 27 cases.

HYPOTHESIS: We aimed to report our experience in treating congenital pseudarthrosis of the clavicle (CPC). MATERIALS AND METHODS: A retrospective search of the archive of our institute was performed; 27 cases (12 male and 15 female patients) affected by CPC were recorded. Among these patients, 19 underwent surgical intervention for cosmetic appearance between 1960 and 2015. Of 19 patients, 18 were treated by pseudarthrosis resection and stabilization with a Kirschner wire, whereas in 1 case, the osteosynthesis was performed with a plate. Iliac crest bone autograft was used in 15 patients, whereas 4 patients were treated with a fibular allograft. RESULTS: The mean follow-up period was 36.3 ± 49.1 months. Bone healing was achieved in 14 of 19 operated cases (74%); none of the patients had complaints regarding cosmetic abnormalities or unesthetic appearance. All the operated patients were pain free, range of motion was complete, and no other subjective anomalies were found. No vascular or neurologic complications were observed. However, the use of allograft was associated with high rates of nonunion in this case series (P = .037). CONCLUSION: CPC can be satisfactorily treated by K-wire fixation and autologous iliac crest bone grafting, which showed better results in terms of functional and cosmetic outcome.

Long-term Results of Combined Epiphysiodesis and Imhauser Intertrochanteric Osteotomy in SCFE: A Retrospective Study on 53 Hips.

BACKGROUND: The management of moderate and severe slipped capital femoral epiphysis is still an issue. The main concern is represented by the choice of an intra-articular or an extra-articular osteotomy to correct the deformity. Theoretically, the intra-articular osteotomy allows the best correction, but it is technically demanding and involves a higher risk of avascular necrosis (AVN); conversely, an extra-articular intertrochanteric osteotomy (ITO) is easier and involves a lower risk of early complications, but may lead to femoroacetabular impingement, resulting in early osteoarthritis and the need for total hip replacement (THR).The aim of this study was to analyze the long-term survivorship free from THR after combined epiphysiodesis and Imhauser ITO. METHODS: From 1975 to 2000, 45 patients (53 hips) underwent a combined epiphysiodesis and Imhauser ITO. There were 27 male and 18 female patients with an average age of 12.8±1.9 years. All cases showed a posterior sloping angle >40 degrees (mean, 69±16 degrees). The cumulative survivorship was determined according to Kaplan and Meier, with the end point defined as conversion to THR. RESULTS: A total of 6 patients (6 hips; 11%) had a follow-up <2 years. Among them, no postoperative complications occurred. For the remaining 39 patients (47 hips, 89%), the mean follow-up was 21±11 years. Four early postoperative complications were reported (2 AVN, 2 chondrolysis). The cumulative 39 years' survivorship free from THR was 68.5% (95% confidence interval, 42.4%-84.7%). The age at surgery (hazard ratio=1.849 per year older, P=0.017) and the postoperative onset of AVN or chondrolysis (hazard ratio=10.146, P=0.010) affected the long-term prognosis significantly. CONCLUSIONS: The combined epiphysiodesis and Imhauser ITO is a valid surgical option in moderate to severe slipped capital femoral epiphysis, preserving the natural hip for at least 39 years in the majority of the patients. Care must be taken to avoid AVN or chondrolysis. The age at surgery affects the prognosis negatively. LEVEL OF EVIDENCE: Level III-a retrospective study.

Evolution of clubfoot deformity and muscle abnormality in the Ponseti method: evaluation with the Dimeglio score.

PURPOSE: The modality of progression of the correction along casting sessions of Ponseti method has been poorly investigated and information regarding evolution of muscular abnormalities is missing. The aim of the study was to investigate dynamics of correction of the different components of clubfoot deformity in a clinical setting. METHODS: In a prospective study, 124 clubfeet consecutively treated by a single orthopaedic surgeon were evaluated with the Dimeglio system at each casting session and score progression was determined. RESULTS: For each component a typical pattern was recorded. Cavus and medial crease showed a rapid correction. Rotation, adduction and varus corrected gradually and simultaneously. The posterior crease usually persisted until final cast was discontinued. Equinus improved progressively after each cast and then to a larger extent with Achilles tenotomy. The parameter describing poor muscular condition, reported at presentation in 39 feet (31.5%), was the only item showing extremely different dynamics of correction (from rapid and complete resolution to persistence at last cast removal), which could be explained by the large diversity of entities included (hypertonia, imbalance, fatty infiltration, fibrosis, aplasia). CONCLUSIONS: This study confirmed that dynamics of correction in clinical setting correspond essentially to theoretical principles of Ponseti method. Muscle abnormalities are not uncommon in clubfeet and have great influence on the progression of correction. If abnormalities are recorded, their evolution along the treatment should be monitored. A more objective evaluation would be required.

Differential expression of perilipin 2 and 5 in human skeletal muscle during aging and their association with atrophy-related genes.

Sarcopenia, the progressive loss of muscle mass and strength, is a phenomenon characterizing human aging whose etiology is still not clear. While there is increasing evidence for the influence of inter-muscular adipose tissue infiltration in the development of sarcopenia, much less is known about a possible role for intra-muscular triglycerides (IMTG). IMTG accumulate in form of lipid droplets decorated by proteins such as Perilipins (Plins). In skeletal muscle the most abundant are Plin2 and Plin5. In this study we compared the expression of these two Plins in Vastus lateralis muscle samples of subjects of different age, both healthy donors (HD) and patients with limited lower limb mobility (LLMI). These latter are characterized by a condition of chronic physical inactivity. Plin2 expression resulted higher in old age for both HD and LLMI patients, while Plin5 slightly decreased only in LLMI patients. Moreover, in these patients, only Plin2 was associated with the decrease of muscle strength and the expression of factors related to muscle atrophy (MuRF1, Atrogin and p53). An increase in Plin2 and a concomitant decrease of Plin5 was also observed when we considered animal model of disuse-induced muscle atrophy. As a whole, these data indicate that Plin2 and Plin5 have a different expression pattern during muscle aging and inactivity, and only Plin2 appears to be associated with functional alterations of the muscle.

Polyamine delivery as a tool to modulate stem cell differentiation in skeletal tissue engineering.

The first step in skeleton development is the condensation of mesenchymal precursors followed by any of two different types of ossification, depending on the type of bone segment: in intramembranous ossification, the bone is deposed directly in the mesenchymal anlagen, whereas in endochondral ossification, the bone is deposed onto a template of cartilage that is subsequently substituted by bone. Polyamines and polyamine-related enzymes have been implicated in bone development as global regulators of the transcriptional and translational activity of stem cells and pivotal transcription factors. Therefore, it is tempting to investigate their use as a tool to improve regenerative medicine strategies in orthopedics. Growing evidence in vitro suggests a role for polyamines in enhancing differentiation in both adult stem cells and differentiated chondrocytes. Adipose-derived stem cells have recently proved to be a convenient alternative to bone marrow stromal cells, due to their easy accessibility and the high frequency of stem cell precursors per volume unit. State-of-the-art "prolotherapy" approaches for skeleton regeneration include the use of adipose-derived stem cells and platelet concentrates, such as platelet-rich plasma (PRP). Besides several growth factors, PRP also contains polyamines in the micromolar range, which may also exert an anti-apoptotic effect, thus helping to explain the efficacy of PRP in enhancing osteogenesis in vitro and in vivo. On the other hand, spermidine and spermine are both able to enhance hypertrophy and terminal differentiation of chondrocytes and therefore appear to be inducers of endochondral ossification. Finally, the peculiar activity of spermidine as an inducer of autophagy suggests the possibility of exploiting its use to enhance this cytoprotective mechanism to counteract the degenerative changes underlying either the aging or degenerative diseases that affect bone or cartilage.

High-Temperature Polylactic Acid Proves Reliable and Safe for Manufacturing 3D-Printed Patient-Specific Instruments in Pediatric Orthopedics-Results from over 80 Personalized Devices Employed in 47 Surgeries.

(1) Background: Orthopedic surgery has been transformed by 3D-printed personalized instruments (3DP-PSIs), which enhance precision and reduce complications. Hospitals are adopting in-house 3D printing facilities, using cost-effective methods like Fused Deposition Modeling (FDM) with materials like Polylactic acid (PLA) to create 3DP-PSI. PLA's temperature limitations can be overcome by annealing High-Temperature PLA (ann-HTPLA), enabling steam sterilization without compromising properties. Our study examines the in vivo efficacy of ann-HTPLA 3DP-PSI in pediatric orthopedic surgery. (2) Methods: we investigated safety and efficacy using ann-HTPLA 3DP-PSI produced at an "in-office" 3D-printing Point-of-Care (3DP-PoC) aimed at correcting limb deformities in pediatric patients. Data on 3DP-PSI dimensions and printing parameters were collected, along with usability and complications. (3) Results: Eighty-three ann-HTPLA 3DP-PSIs were utilized in 33 patients (47 bone segments). The smallest guide used measured 3.8 cm3, and the largest measured 58.8 cm3. Seventy-nine PSIs (95.2%; 95% C.I.: 88.1-98.7%) demonstrated effective use without issues. Out of 47 procedures, 11 had complications, including 2 infections (4.3%; 95% CI: 0.5-14.5%). Intraoperative use of 3DP-PSIs did not significantly increase infection rates or other complications. (4) Conclusions: ann-HTPLA has proven satisfactory usability and safety as a suitable material for producing 3DP-PSI in an "in-office" 3DP-PoC.