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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-1β, 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-1β 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.

The human meniscus plays a crucial role for transmission and distribution of load across the knee, as well as shock absorption, joint stability, lubrication, and congruity. The aim of this study was to compare the complex geometry, and unique ultrastructure and tissue composition of the meniscus in healthy (control) and pathological conditions to provide understanding of structural changes that could be helpful in the future design of targetted therapies and improvement of treatment indications. We analyzed meniscus samples collected from 3 healthy multi-organ donors (median age, 66 years), 5 patients with traumatic meniscal tear (median age, 41 years) and 3 patients undergoing total knee replacement (TKR) for end-stage osteoarthritis (OA) (median age, 72 years). We evaluated the extracellular matrix (ECM) organization, the appearance and distribution of areas of calcification, and modifications of cellular organization and structure by electron microscopy and histology. The ECM structure was similar in specimens from traumatic meniscus tears compared to those from patients with late-stage OA, showing disorganization of collagen fibers and increased proteoglycan content. Cells of healthy menisci showed mainly diffuse chromatin and well preserved organelles. Both in traumatic and in OA menisci, we observed increased chromatin condensation, organelle degeneration, and cytoplasmic vacuolization, a portion of which contained markers of autophagic vacuoles. Areas of calcification were also observed in both traumatic and OA menisci, as well as apoptotic-like features that were particularly prominent in traumatic meniscal tear samples. We conclude that meniscal tissue from patients with traumatic meniscal injury demonstrate pathological alterations characteristic of tissue from older patients undergoing TKR, suggesting that they have high susceptibility to develop OA.

The aim of this study was to analyze the magnetic resonance imaging (MRI) volumetric and morphometric characteristics of the infrapatellar fat pad (IFP) and the suprapatellar fat pad (SFP) in normal controls, moderate and end-stage osteoarthritis (OA) patients. Forty-four MRI images of the three groups were collected: a) 17 patients undergoing meniscectomy with Outerbridge score 0 (control group); b) 15 patients undergoing meniscectomy with Outerbridge score 3/4 (moderate OA group); and c) 12 patients undergoing total knee replacement (end-stage OA group). Volume, depth, femoral and tibial arch lengths of IFP were quantified. The hypointense IFP signals were also scored. The SFP volume, oblique, antero-posterior and cranio-caudal lengths were determined. IFP and SFP characteristics were compared between groups. A decrease of IFP volume, depth, femoral, and tibial arch lengths in moderate and end-stage OA compared to controls were observed. A difference in IFP hypointense signal was found between groups. No differences were found in SFP characteristics between the groups. In controls and moderate OA patients, correlations were found among the different MRI characteristics of both IFP and SFP, while in the end-stage OA group correlations were found only in SFP. We evidenced differences of the IFP MRI morphometric characteristics between the groups analyzed, supporting an important role of IFP in OA pathology and progression. On the contrary, no differences were highlighted in SFP analysis suggesting that this fat pad is not clearly involved in OA, probably due to its peculiar localization and different function., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

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.

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.

Background: The aim of this study was to assess the reliability of the videotape scoring system collected during knee arthroscopy for meniscal tears, and to test the consistency with intra-operative findings., Methods: Fifty-seven patients undergoing arthroscopic treatment of meniscal tears were included in the analysis. The cartilage damage was assessed intra-operatively, at six sites, using the Outerbridge scoring system. The meniscal tears were graded according to the International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine (ISAKOS) classification. The presence of synovial inflammation was scored, at four different sites, according to the macro-score method. The total cartilage, meniscal and synovial scores were calculated for each knee by the sum of the maximum grade of the lesions at each anatomic site. In order to assess the reliability of the arthroscopic scoring system, the videotapes recorded during the arthroscopy were reviewed by two independent observers one year after the surgery and compared with the scores completed by the surgeon during the operation., Results: The total cartilage score showed substantial inter-rater and intra-rater reliability, and moderate consistency with the intra-operative score provided by the surgeon. The total meniscal score showed substantial inter-rater and intra-rater reliability, and good consistency with the intra-operative findings. The total synovial score showed substantial inter-rater agreement, substantial intra-rater reliability, and moderate consistency with intra-operative findings., Conclusions: The videotape scoring system provided a reliable and reproducible system for recording the intra-operative state of the whole joint pathology in patients undergoing arthroscopic treatment of meniscal tears., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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.

Background: Nonunion is a rare but severe complication following forearm fracture in skeletally immature patients. The purpose of this study is to describe a case series of pediatric forearm nonunions treated at our Institute., Materials and Method: We retrospectively reviewed medical charts and radiographs of healthy children affected by post-traumatic nonunion of the forearm, from April 1992 to July 2015. An overall series of 15 cases was included in the study. Nonunion developed at ulna in 5 cases and at radius in 10 cases, at a mean time of 9 months (range 6-12) from fracture. Surgical treatment was performed in 14 cases out of 15. Stabilization of the nonunion was achieved with Kirschner wires (5 cases), plates (4 cases), rush rods (2 cases) and unilateral external fixator (3 cases). Iliac crest bone autograft was used in 11 cases, strut cortical bone allograft was used in 2 cases while in one case no bone graft was applied. In 2 cases an additional shortening osteotomy of the ulnar shaft was necessary to obtain adequate compression of the bone fragments. Cast immobilization was maintained for 6 to 8 weeks after surgery, then a brace was applied for further 8 to 12 weeks., Results: The average follow-up was 54 months (range 12-129); nonunion healed in 14 cases (93%) at an average time of 4 months (range 2-8). One case of nonunion did not heal 12 months after surgery; other complications included: radio-ulnar fusion and radial nerve palsy (1 case), myositis ossificans at the ulna (1 case), olecranon bursitis with residual elbow stiffness (1 case). One case was treated conservatively and healed after 18 months with residual malalignment., Conclusions: The present study describes the largest series of pediatric forearm nonunions in the current literature. Whether the surgical management of pediatric forearm nonunion provides satisfactory results in terms of bone healing, it may be accompanied by several complications, permanent sequelae and residual functional impairment. Any effort must be undertaken to avoid this serious complication., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Introduction: Idiopathic posttraumatic nonunion is a rare condition in children; the treatment of this complication is still controversial in this peculiar population., Case Report: We report a case of a subcapital type II femoral neck fracture, in a 12-year-old boy, which was initially treated by internal fixation and subsequently went on to a nonunion at the femoral neck, in absence of infection or other disease.1 year after index surgery we performed surgical debridement and refixation with plate and bone allograft, added with autologous bone marrow aspiration concentrate (BMAC) and platelet-rich fibrin (PRF).After 3 months the nonunion healed and the boy was allowed full weight-bearing., Conclusions: Combined surgery and adjuvant cell therapy can be considered an option of treatment in nonunion of the femoral neck in the paediatric population.

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.

Introduction: Recent evidence suggests that GSK3 activity is chondroprotective in osteoarthritis (OA), but at the same time, its inactivation has been proposed as an anti-inflammatory therapeutic option. Here we evaluated the extent of GSK3β inactivation in vivo in OA knee cartilage and the molecular events downstream GSK3β inactivation in vitro to assess their contribution to cell senescence and hypertrophy., Methods: In vivo level of phosphorylated GSK3β was analyzed in cartilage and oxidative damage was assessed by 8-oxo-deoxyguanosine staining. The in vitro effects of GSK3β inactivation (using either LiCl or SB216763) were evaluated on proliferating primary human chondrocytes by combined confocal microscopy analysis of Mitotracker staining and reactive oxygen species (ROS) production (2',7'-dichlorofluorescin diacetate staining). Downstream effects on DNA damage and senescence were investigated by western blot (γH2AX, GADD45β and p21), flow cytometric analysis of cell cycle and light scattering properties, quantitative assessment of senescence associated β galactosidase activity, and PAS staining., Results: In vivo chondrocytes from obese OA patients showed higher levels of phosphorylated GSK3β, oxidative damage and expression of GADD45β and p21, in comparison with chondrocytes of nonobese OA patients. LiCl mediated GSK3β inactivation in vitro resulted in increased mitochondrial ROS production, responsible for reduced cell proliferation, S phase transient arrest, and increase in cell senescence, size and granularity. Collectively, western blot data supported the occurrence of a DNA damage response leading to cellular senescence with increase in γH2AX, GADD45β and p21. Moreover, LiCl boosted 8-oxo-dG staining, expression of IKKα and MMP-10., Conclusions: In articular chondrocytes, GSK3β activity is required for the maintenance of proliferative potential and phenotype. Conversely, GSK3β inactivation, although preserving chondrocyte survival, results in functional impairment via induction of hypertrophy and senescence. Indeed, GSK3β inactivation is responsible for ROS production, triggering oxidative stress and DNA damage response.

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.

Background: In osteoarthritis (OA), an inflammatory environment is responsible for the imbalance between the anabolic and catabolic activity of chondrocytes and, thus, for articular cartilage derangement. This study was aimed at providing further insight into the impairment of the anabolic cytokine IL-4 and its receptors in human OA cartilage, as well as the potential ability of IL-4 to antagonize the catabolic phenotype induced by IL-1β., Methodology/principal Findings: The in vivo expression of IL-4 and IL-4 receptor subunits (IL-4R, IL-2Rγ, IL-13Rα1) was investigated on full thickness OA or normal knee cartilage. IL-4 expression was found to be significantly lower in OA, both in terms of the percentage of positive cells and the amount of signal per cell. IL-4 receptor type I and II were mostly expressed in mid-deep cartilage layers. No significant difference for each IL-4 receptor subunit was noted. IL-4 anti-inflammatory and anti-catabolic activity was assessed in vitro in the presence of IL-1β and/or IL-4 for 24 hours using differentiated high density primary OA chondrocyte also exhibiting the three IL-4 R subunits found in vivo. Chemokines, extracellular matrix degrading enzymes and their inhibitors were evaluated at mRNA (real time PCR) and protein (ELISA or western blot) levels. IL-4 did not affect IL-1β-induced mRNA expression of GRO-α/CXCL1, IL-8/CXCL8, ADAMTS-5, TIMP-1 or TIMP-3. Conversely, IL-4 significantly inhibited RANTES/CCL5, MIP-1α/CCL3, MIP-1β/CCL4, MMP-13 and ADAMTS-4. These results were confirmed at protein level for RANTES/CCL5 and MMP-13., Conclusions/significance: Our results indicate for the first time that OA cartilage has a significantly lower expression of IL-4. Furthermore, we found differences in the spectrum of biological effects of IL-4. The findings that IL-4 has the ability to hamper the IL-1β-induced release of both MMP-13 and CCL5/RANTES, both markers of OA chondrocytes, strongly indicates IL-4 as a pivotal anabolic cytokine in cartilage whose impairment impacts on OA pathogenesis.

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.

Human aging is associated with a progressive loss of muscle mass and strength and a concomitant fat accumulation in form of inter-muscular adipose tissue, causing skeletal muscle function decline and immobilization. Fat accumulation can also occur as intra-muscular triglycerides (IMTG) deposition in lipid droplets, which are associated with perilipin proteins, such as Perilipin2 (Plin2). It is not known whether Plin2 expression changes with age and if this has consequences on muscle mass and strength. We studied the expression of Plin2 in the vastus lateralis (VL) muscle of both healthy subjects and patients affected by lower limb mobility limitation of different age. We found that Plin2 expression increases with age, this phenomenon being particularly evident in patients. Moreover, Plin2 expression is inversely correlated with quadriceps strength and VL thickness. To investigate the molecular mechanisms underpinning this phenomenon, we focused on IGF-1/p53 network/signalling pathway, involved in muscle physiology. We found that Plin2 expression strongly correlates with increased p53 activation and reduced IGF-1 expression. To confirm these observations made on humans, we studied mice overexpressing muscle-specific IGF-1, which are protected from sarcopenia. These mice resulted almost negative for the expression of Plin2 and p53 at two years of age. We conclude that fat deposition within skeletal muscle in form of Plin2-coated lipid droplets increases with age and is associated with decreased muscle strength and thickness, likely through an IGF-1- and p53-dependent mechanism. The data also suggest that excessive intramuscular fat accumulation could be the initial trigger for p53 activation and consequent loss of muscle mass and strength.

The molecular mechanisms underlying spermine osteo-inductive activity on human adipose-derived stem cells (ASCs) grown in 3-dimensional (3D) cultures were investigated. Spermine belongs to the polyamine family, naturally occurring, positively charged polycations that are able to control several cellular processes. Spermine was used at a concentration close to that found in platelet-rich plasma (PRP), an autologous blood product containing growth and differentiation factors, which has recently become popular in in vitro and in vivo bone healing and engineering. Adipose tissue was surgically obtained from the hypodermis of patients undergoing hip arthroplasty. Patient age negatively affected both ASC yield and ASC ability to form 3D constructs. ASC 3D cultures were seeded in either non differentiating or chondrogenic conditions, with or without the addition of 5 μM spermine to evaluate its osteogenic potential across 1, 2, and 3 weeks of maturation. Osteogenic medium was used as a reference. The effects of the addition of spermine on molecular markers of osteogenesis, at both gene and protein level, and mineralization were evaluated. The effects of spermine were temporally defined and responsible for the progression from the early to the mature osteoblast differentiation phases. Spermine initially promoted gene and protein expression of Runx-2, an early marker of the osteoblast lineage; then, it increased β-catenin expression and activation, which led to the induction of Osterix gene expression, the mature osteoblast commitment factor. The finding that spermine induces ASC to differentiate toward mature osteoblasts supports the use of these easily accessible mesenchymal stem cells coupled with PRP for orthopedic applications.

Sensitivity to implant materials is an unpredictable event, which may contribute to the process leading to the failure of the total hip replacement (THR). The aim of the current study was to investigate the informative power of skin testing in detecting the sensitization to the implant components in patients undergoing THR. A consecutive series of 223 patients was enrolled in the study, including 66 candidates to THR, 53 with stable implant, and 104 with THR loosening. The patch testing was performed by using the most relevant components of cobalt-based alloys (CoCrMo), Ti-based alloys (TiAlV), and bone cements. The frequency of positive patch testing in preimplant patients did not differ from that observed after THR. Patients with CoCrMo-failed implant showed a significant low frequency of nickel-positive skin reaction, while patients with TiAlV-THR had a high incidence of vanadium-positive patch testing. The panel of haptens showed a good performance in the identification of patients known to have a contact dermatitis. With regard to the THR outcome, patch testing was not able to discriminate between stable and failed implant. Sensitivity to at least one hapten, namely bone cement, as well as the positive medical history of hypersensitivity, influenced negatively the THR survival. Our results show the reliability of patch testing for investigating the sensitivity to implant components. The cause-effect relationship between sensitization and negative outcome cannot be established, but the shorter lifespan of THR in patients who have a positive patch testing supports the significant role of this event in contributing to the implant failure., ((c) 2005 Wiley Periodicals, Inc.)

Unlabelled: In a population of 417 hospitalized patients, the efficacy and safety of different drug regimens administered to convert atrial fibrillation (AF) of recent onset (< or = 7 days duration) to sinus rhythm were evaluated. All patients were in NYHA Class < or = 2, and free of heart failure. They were randomly allocated to treatment with placebo in 121 patients; i.v. amiodarone, 5 mg/kg bolus, followed by 1.8 g/24 hours in 51 patients; i.v. propafenone, 2 mg/kg bolus, followed by 0.0078 mg/kg/min in 57 patients; p.o. propafenone, 600 mg p.o. in a single dose in 119 patients; and p.o. flecainide, 300 mg p.o. in a single dose in 69 patients. All patients were continuously monitored by Holter ECG, and the number of conversions to sinus rhythm was measured at 1, 3, and 8 hours., Results: (1) I.v. propafenone resulted in a higher conversion rate within 1 hour compared with the oral loading regimens of propafenone or flecainide, but the conversion rates at 3 and 8 hours were comparable, approximately 75% at 8 hours; 2) i.v. amiodarone was not different from placebo until 8 hours when it was associated with 57% of conversions; (3) conversion to sinus rhythm at 8 hours was observed in 37% of the placebo treated patients. Serious adverse effects occurred in few patients: two patients treated with flecainide and one treated with i.v. propafenone experienced left ventricular decompensation; one patient treated with placebo and two treated with flecainide had atrial flutter with rapid ventricular response. In conclusion, single-dose, oral loading with propafenone or flecainide are acceptable alternatives to conventional drug regimens in selected hospitalized patients. In addition, the measure of a placebo effect is mandatory in studies of recent-onset AF.

Sixty-two patients with recent-onset (less than or equal to 1 week) atrial fibrillation (New York Heart Association functional class 1 and 2) were randomized in a single-blind study to 1 of the following treatment groups: (1) flecainide (300 mg) as a single oral loading dose; or (2) amiodarone (5 mg/kg) as an intravenous bolus, followed by 1.8 g/day; or (3) placebo for the first 8 hours. Twenty-four-hour Holter recording was performed, and conversion to sinus rhythm at 3, 8, 12 and 24 hours was considered as the criterion of efficacy. Conversion to sinus rhythm was achieved within 8 hours (placebo-controlled period) in 20 of 22 patients (91%) treated with flecainide, 7 of 19 (37%) treated with amiodarone (p less than 0.001 vs flecainide), and 10 of 21 (48%) treated with placebo (p less than 0.01 vs flecainide). Resumption of sinus rhythm within 24 hours occurred in 21 of 22 patients (95%) with flecainide and in 17 of 19 (89%) with amiodarone (p = not significant). Mean conversion times were shorter for flecainide (190 +/- 147 minutes) than for amiodarone (705 +/- 418; p less than 0.001). No major side effects occurred. At Holter monitoring, a pause of 9.3 seconds was observed in 1 asymptomatic patient treated with flecainide. Phases of atrial flutter with a ventricular rate less than or equal to 150 beats/min were detected before sinus conversion in 1 patient receiving placebo and in 2 receiving flecainide.(ABSTRACT TRUNCATED AT 250 WORDS)