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Spontaneous rupture of the digital extensor tendons of the hand has been reported after Kienbocks disease, rheumatoid arthritis, Vaughan-Jackson syndrome, distal radial fracture. Rupture may also occur as a consequence of unrecognized carpal lunate fracture. We present a case report of a man affected with spontaneous rupture of the digital extensor tendons secondary to unrecognized carpal lunate fracture with partial dorsal dislocation. The edges of the tendon were debrided and sutured using a locked modified Kessler suture. A dynamic splinting cast was applied in moderate extension of the wrist. The aim of this case report is to highlight that in absence of a clear etiology for rupture of the extensor tendons of the hand, carpal lunate fracture, though rare, is an important cause of spontaneous extensor tendons rupture.La ruptura espontánea de tendones extensores digitales de la mano ha sido reportado después de la enfermedad de Kienböck, artritis reumatoide, síndrome de Jackson Vaughan, fractura del radio distal. La lesión del tendón también puede ocurrir como consecuencia de la fractura no reconocida de carpal semilunar. En este artículo, se presenta un caso de un hombre que sufre de rotura espontánea del tendón extensor digital secundaria a fractura semilunar no reconocida de los huesos del carpo con luxación dorsal del fragmento parcial. Los bordes del tendón se han limpiado y se sutura usando una sutura de Kessler. Un refuerzo dinámico se aplicó en extensión moderada de la muñeca. El propósito de este caso clínico es poner de relieve que, en ausencia de una etiología clara de la ruptura de los tendones extensores de la mano, una fractura de los huesos del carpo semilunar puede ser una causa importante de la ruptura espontánea de los tendones extensores de la mano.

Increasing evidence indicates that local neurogenic inflammation, possibly in response to different stimuli, may be involved in sensory nerve sensitization, migraine generation and some other precipitating events leading to neuronal dysfunction in the brain. In addition, mast cells generate eicosanoids that are linked to asthma and other inflammatory diseases. Regulated upon activation, normal T-cell expressed and secreted (RANTES) is a small protein and a prototype member of the CC chemokine-beta subfamily with chemoattractant and inflammatory properties. In this study we used the RBL-2H3 cell line to determine whether or not these cells generate prostaglandin D2 (PGD2) after treatment with RANTES. After 4 hours of incubation, RBL-2H3 cells cultured with RANTES at 20 ng/mL released large amounts of PGD2 in a dose-response manner compared to control. Moreover, RBL-treated RANTES generated a large quantity of histamine. Our study confirms once again the proinflammatory action of RANTES, in this case acting on the stimulation of the arachidonic acid cascade product PGD2.

Due to a growing numbers of lateral fragility fractures of the femur and their high social costs the need to work out an effective strategy in order to find a better solution for these patients is warranted. From January 2010 to July 2011, we carried out a prospective randomized clinical study comparing the results of patients with femoral lateral fractures treated by nail and cephalic hydroxyapatite coated screws (study group including 27 patients) compared to the patients with the same fractures treated with nail and head standard screws (control group including 27 patients). We defined the two parts of the femoral neck as ROI 1 (under the head screw) and ROI 2 (above the femoral screw) on the AP view. The bone density of the two areas was calculated using DEXA at T0 (1st day post-surgery), at T1 (40th day post-surgery), at T2 (3 months later), at T3 (1 year later). The clinical-radiography evaluations were based on the Harris Hip Score (HHS), ADL test and x-ray views of the hip. As far as the bone mineral density average of ROI 1 and ROI 2 is concerned, we found a significant statistical increase at T1 and T3 in the study group, while it was not significant in the control group. We could account for this data through the higher mechanical stability of hydroxyapatite coated screws than standard screws. In fact, this material was responsible for improved implant osteointegration. Thanks to a 1 year follow-up we were able to demonstrate the implant utility associated with augmentation and the importance of densitometry exams such as easily repeatable and low cost diagnostics to prevent the onset of complications linked to screw loosening.

Background In spite of the proven efficacy of pharmacological prophylaxis of heterotopic ossification followingtotal hip arthroplasty, its routine use is still debated, and nodata are available regarding the adherence to its administration in clinical practice.Materials and methods In this prospective, observational,multicenter study, 480 consecutive patients operated on forprimary total hip arthroplasty during the year 2009 werefollowed radiographically for 12 months after surgery inorder to assess the incidence of periprosthetic heterotopicossification. Surgeons were free to choose whether toadminister pharmacological prophylaxis, and were asked tokeep a record of the duration of the prophylaxis (if used) orthe reasons for not using it. To facilitate the statisticalanalysis, all of the participating centers agreed to use onlyone drug (celecoxib) that had already proven to be effective.Results 368 patients were administered celecoxib and112 patients did not receive any prophylaxis. Reportedreasons for not administering celecoxib prophylaxis werethe surgeon’s opinion that prophylaxis was not needed on aroutine basis (84/112 patients, 75%), previous history ofgastrointestinal bleeding (17.8%), and concomitant cardiorenal pathologies (7.1%). The overall incidence of heterotopic ossification in the celecoxib-treated patients was23% (no cases of Brooker grade 3 or 4 ossifications),compared to 55% in the untreated patients (Brooker grade3 and 4: 8.9%). Multivariate analysis showed that celecoxib prophylaxis was the single most important variablewhen predicting the occurrence of heterotopic ossification.Conclusions This study confirms the efficacy and tolerability of celecoxib for the prophylaxis of heterotopicossification after total hip arthroplasty, and shows how thesurgeon’s belief that routine prevention is not required still plays an important role in the determination of this complication, together with the fear of possible unwanted sideeffects

IL-18 is produced by many cell types, such as Kupffer cells, keratinocytes, macrophages, dendritic cells, and activated T cells stimulated by LPS. It is an important regulator of both innate and acquired immune responses. IL-18 plays a central role in rheumatoid arthritis since the T cells and macrophages that invade the synovial. These finding support a role for IL-18 in inflammation, allergy and immune diseases.

Interleukin-36 (IL-36) is a pro-inflammatory cytokine which plays an important role in innate and adaptive immunity. IL-36 activates MAPK and NF-kB pathways and is produced by many different cells. This cytokine is a family member of interleukin-1 (IL-1) and plays an important role in the pathophysiology of several diseases. Here we summarise and review the new aspects of this important pro-inflammatory cytokine.

Chemokines are small proteins (8-12 kD polypeptides) secreted by the cells of innate and adaptive immunity that mediate many of the functions of these cells, including recruitment of other cells. They are classified into families: CC, CXC and CX3C. CXC chemoattract mainly on neutrophils and CC act mainly on monocytes, eosinophils and mast cells. Mast cells are important cells in the modulation of allergic and inflammatory diseases. Activation of mast cells with specific IgE antibody and antigens or other active compounds such as Substance P and corticotrophin releasing hormone causes transcription and translation of several different cytokines/chemokines such as tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-1 (MIP-1) and GM-CSF, RANTES, MCP-1, CXCL8, along with other proinflammatory compounds, proteases (chymase and tryptase), histamine, leukotrienes and prostaglandin D2. Neutralization of chemokines may reduce inflammatory cell accumulation and may protect against allergy, toxic shock syndrome and inflammatory diseases.

Adult acquired flatfoot deformity is generally associated with a collapsing medial longitudinal arch and a progressive loss of strength of the posterior tibial tendon (PTT). This condition is commonly associated with PTT dysfunction or rupture, which can have an arthritic or a traumatic etiology. Several causes have been proposed to explain the clinical evidence of tendon degeneration observed at the time of surgery including trauma, anatomical, mechanical, inflammatory and ischemic factors.In this review, we analyzed anatomy, pathophysiology and existing classifications of posterior tibial tendon dysfunction.Anatomical features, and in particular vascularization, expose PTT to major degenerative disorders until rupture. A literature overview showed that a low blood supply of the gliding part of the tendon is linked to a dysfunction and/or a rupture of the PTT in the region located behind the medial malleolus.PTT low blood supply causes a dysfunction resulting in an abnormal loading of the foot's medial structures. This may be the reason why PTT dysfunction leads to an acquired flatfoot deformity. Conversely, flatfoot deformity may be a predisposing factor for the onset of PTT dysfunction.

Mast cells are granulated hematopoietic cells derived from stem cells that reside in nearly all tissues and are involved in protection of a host from bacterial infection with a protective and pathogenic activity. Mast cells are important for both innate and adaptive immunity in tissues which are in close contact with the environment. These cells express proinflammatory cytokines such as IL-1, IL-6, IL-8 and tumor necrosis factor which are necessary for innate immunity. Mast cells also produce interleukin-9 and enhance mast cell expression of several cytokines including IL-1beta, IL-5, IL-6, IL-9 and IL-13. In addition, IL-9 can induce mast cell production of TGF-beta which can have proinflammatory downstream effects. IL-9 can function as either a positive or a negative regulator of immune responses and can have a detrimental role in allergy and autoimmunity. Furthermore, IL-9 contributes to disease by promoting mast cell expansion and production of IL-13 which in turn contributes to airway hyperresponsiveness. Here, in this editorial we review the interrelationship between IL-9 and mast cells.

OBJECTIVE:Skeletal diseases, both degenerative and secondary to trauma, infections or tumors, represent an ideal target for regenerative medicine and in the last years, stem cells have been considered as good candidates for in vitro and in vivo bone regeneration. To date, several stem cell sources, such as adult mesenchymal stem cells, embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have shown significant osteogenic potential.MATERIALS AND METHODS:In this narrative review, we analyze the possible advantages of the use of AFSCs in the treatment of skeletal diseases, especially through the application of tissue engineering and biomaterials.RESULTS:Among the different sources of stem cells, great attention has been recently devoted to amniotic fluid-derived stem cells (AFSC) characterized by high renewal capacity and ability to differentiate along several different lineages.CONCLUSIONS:Due to these features, AFSCs represent an interesting model for regenerative medicine, also considering their low immunogenicity and the absence of tumor formation after transplantation in nude mice.

The present study was aimed at identifying a new scaffold/stem cell combination useful to treat large bone defects. Human amniotic fluid stem cells (AFSCs) were expanded in vitro, labeled with a fluorescent cell-permeable dye (PKH26) and transplanted in vivo in a femoral injured rat model. The femoral defect was left untreated (control rats) or filled with hydroxyapatite (HA; natural nanocrystalline carbonated hydroxyapatite-Orthoss®) scaffold alone or loaded with PKH26-labeled AFSCs. All animals were killed 3 weeks after implantation. Both gross anatomy and histological observations revealed a major bone regenerative response in rat specimens treated with HA scaffold, alone or supplemented with AFSCs. Samples injected with HA plus AFSCs displayed the presence of abundant fibrotic tissue, the formation of periosteal woven bone, and an increased presence of blood vessels in the bone marrow, with still fluorescent AFSCs in close proximity. These observations provide evidence that natural HA plus AFSCs represents a promising alternative therapeutic strategy to autologous bone grafting procedures.

The efficacy of platelet-rich plasma in the treatment for Achilles tendinopathy is debated. Therefore, it is important to know which factors, related to the subjects and/or the disease, are associated with positive or negative outcomes. Aim of this study was to evaluate in a large cohort of patients with Achilles mid-portion tendinopathy which variables were independently associated with a positive outcome after platelet-rich plasma treatment. Eighty-four subjects with Achilles tendinopathy were evaluated by means of VISA-A score and ultrasound and treated with a single platelet-rich plasma injection once a week for 3 weeks. Afterward, a rehabilitation program, based on eccentric training, was implemented. At 3 and 6 months, the relationship between the mean VISA-A score and the following putative predictors was evaluated: sex, age, physical activity, sport, smoking, metabolic risk factors, BMI, symptoms duration, tendon damage, neovessels, adherence to eccentric training. Finally, the percentage of clinically evident positive outcomes (defined as an increase in VISA-A score ≥ 20 points) related to each variable was computed. At final follow-up, using the General Linear Model for Repeated Measures procedure, male sex (0.02), age ≤ 40 (0.05) and adequate eccentric training (0.02) were found to be independently associated with a significant increase in the mean VISA-A score. Moreover, the clinically evident positive outcomes, as previously defined, were significantly associated with male sex (0.01), age ≤ 40 (0.000), BMI ≤ 25 (0.001), symptoms duration ≤ 12 months (0.02) and good adherence to eccentric training (0.004). Younger age, male sex and good adherence to eccentric training can be considered predictors of better results after platelet-rich plasma therapy in Achilles tendinopathy

Background Patients affected by coxarthrosis may be treated surgically with total hip arthroplasty (THA). During the surgical intervention, the hip joint capsule can be completely removed, performing a capsulectomy. Otherwise it's possible to perform a capsulotomy, which allows for capsular conservation. Since there is no scientific evidence demonstrating the superiority of one method over the other, the choice whether to remove or conserve the capsule is at the surgeon's discretion and both procedures are actually accepted. The purpose of our study is to evaluate the differences in functional activities and proprioception in patients who underwent THA and capsulotomy with capsular conservation versus patients who underwent THA with capsulectomy. Methods In order to compare the two surgical techniques of capsulotomy with capsular conservation and capsulectomy, we created a randomized, controlled, double-blind, single-centre, non-pharmacological, interventional, superiority, parallel-group trial. The primary outcome of our study is evaluated using the HOOS scale (Hip disability and Osteoarthritis Outcome Score). Secondary outcomes are: the proprioceptive sensitivity, the postoperative bleeding, the surgical time, the active range of motion, and the ability to walk, sit and stand. The proprioception study is carried out through active and passive repositioning tests. THA is performed through the minimally invasive direct anterior approach. The evaluation tests are carried out in the 15 days preceding the intervention (T0), at 50-day post-operative (T1), and finally at three months after surgery (T2). Discussion Considering that the hip joint capsule is innervated by proprioceptive nerve endings, while the psuedocapsule that replaces the native capsule following a THA with capsulectomy doesn't have any active neurophysiological role, we hypothesize that capsulotomy with capsular conservation at the time of primary THA may lead to better proprioception and therefore better functional recovery. Trial registration ClinicalTrials.gov identifier: NCT02749058. Date of registration: 04/21/2016.

Introduction: Running is a very popular modality of physical activity, which may help to lose weight and normalize pathological values of blood parameters in subjects suffering from metabolic disorders. Given that both overuse and metabolic pathologies are responsible for the onset of tendon damage, aim of the present study was to evaluate whether the first group of pathogenetic factors or the latter was more responsible for mid-portion Achilles tendinopathy. Method: Thirty-six and 28 subjects with and without mid-portion Achilles tendinopathy, who were regular runners and started running for metabolic disorders, were enrolled, respectively. Information about body weight and blood parameters at baseline was collected. The characteristics of running practice, dietary habits and anthropometric measures were registered. An ultrasound evaluation of the tendon was performed, and the blood metabolic parameters were evaluated. Results: The amount of running years and mileage was equivalent in both groups. A similar weight loss was observed; the subjects with mid-portion Achilles tendinopathy showed a worse metabolic profile (Hb1aC%, p = 0.008; total cholesterol, p = 0.04; HDL cholesterol, p = 0.003; triglycerides, p = 0.009). Conclusions: These findings suggest that the subjects with less evident positive effects of running on metabolism are more exposed to the onset of mid-portion Achilles tendinopathy.

Objectives: The efficacy of platelet rich plasma in the treatment of Achilles tendinopathy is controversial. Despite positive results observed in open studies, randomized controlled trials failed to show difference against saline or rehabilitation. Aims of this retrospective observational study were to compare the efficacy of platelet-rich plasma and dry needling and to assess possible differences age and sex-related. Methods: Groups of 46 and 38 patients with non-insertional Achilles tendinopathy were treated with platelet-rich plasma and dry needling (once a week for 3weeks), respectively. At baseline, 3 and 6months, pain and function scores and the percentage of satisfactory outcomes were evaluated. Sub-group analyses were performed according to age and sex. Results: At 3 and 6months no differences in terms of pain and function between groups were observed, but the percentage of subjects reporting satisfactory results, at 6months, was higher in platelet rich plasma group. Better results were observed in younger subjects, with a greater reduction of pain, improvement of function, and accordingly of the percentage of positive outcomes. A trend toward better results was also observed in males. Conclusion: Beneficial effects of platelet rich plasma and dry needling in non-insertional Achilles tendinopathy have been observed only in some subjects, but not in others; platelet rich plasma shows a slight superiority against dry needling, mainly in younger persons; finally, a gender difference in the therapeutic response can be hypothesized.

Background The aim of this retrospective study was to evaluate the outcome of patients with intra-articular calcaneal fractures treated using a minimally invasive locking nail (Calcanail®). Methods Between January 2016 and April 2017, 15 patients (9 men and 6 women) with a calcaneal fracture were consecutively treated with Calcanail®. The Bohler angle was recorded on standard X-rays pre- and post-operatively. The articular reduction of the posterior facet was evaluated with the Goldzak index in a CT scan 3 months post-operatively. The mean age of the patients was 53 years (range, 24–78). Mean final follow-up was 18 months (range, 12–24). Results Six fractures were classified as Sanders II, 7 as Sanders III and 2 as Sanders IV. In 13 out of the 15 patients treated, the post-operative Bohler angle was of more than 20°. Goldzak index was deemed as excellent in 73.5% of the cases (11 patients), good in 20% of cases (3 patients), and poor in 6.5% (1 patient). Post-operative mean AOFAS score was 85 (range, 60–96). Conclusions The Calcanail® provides good restoration of the subtalar joint and the calcaneal angles with the advantages of a minimally invasive approach. It was effectively used in Sanders types II and III, even in the presence of poor cutaneous conditions.

Background Chronic ankle instability is defined by an instability lasting more than 6 months, in those cases where a comprehensive conservative treatment fails a surgical stabilization is required. Several surgical techniques have been proposed for the management of the chronic lateral instability of the ankle and even after 50 years, the Brostrom–Gould technique is still considered the gold standard for the treatment of this pathology. Recently, many authors have developed completely arthroscopic lateral ligament repair and the use of these procedures is rapidly increasing. The aim of this review is to provide an updated overview of open and new arthroscopic lateral ligament repair techniques in order to summarize and compare the effectiveness of these strategies. Methods A systematic literature review using PubMed/Medline databases was performed (July 1972–July 2015). Clinical results, satisfaction rate and complications of both patient populations were recorded and statistically analyzed. Results The total ankles treated with an open Brostrom ATFL repair in the 13 studies was 505 with a mean follow up of 73.4 months (range 9 months–27.9 years). Postoperative AOFAS score was reported in 11 studies, with a mean value of 90.1 (range, 60–100), patient's satisfaction rate was 91.7%. Surgery-related complications occurred in 40 (7.92%) out of 505 treated ankles. The total number of ankles treated within the 6 arthroscopic studies was 216 with a mean follow up of 37.2 months (range 6 months–14 years). Five studies reported a mean postoperative AOFAS score of 92.48 (range, 44–100) with a patient's satisfaction rate of 96.4%. Surgery-related complications were observed in 33 (15.27%) cases. Conclusions The results of this review show the excellent efficacy of open and arthroscopic surgical procedures in the treatment of the chronic ankle instability. The higher complication rate of arthroscopic procedures respect to the open ones represents the major issue: however, this does not seem to affect the patient's satisfaction. Because of statistical heterogeneity observed no definitive conclusions can be statistically drawn. Finally, to definitively validate the effectiveness of arthroscopic procedures prospective and comparative studies are needed.

Distal humerus fractures are uncommon injuries requiring specific clinical and radiographic analysis in order to plan the optimal therapeutic strategy. In particular, bicolumnar distal humerus fractures (Type A2, A3 and C) are complex fractures. In the last years, double plating fixation became the standard treatment: this procedure helped surgeons to obtain a stable and anatomical fixation and an early mobilization, which is the main outcome for obtaining valuable functional results. In this retrospective study, we evaluated the use of open bicolumnar 90-90 plating for fixation of acute fragility fractures of the distal humerus in elderly patients, using the olecranon osteotomy as surgical approach.

OBJECTIVE: Rotator cuff tendon tears increase with age, but no study has specifically addressed prevalence changes in women from premenopause to postmenopause. The aims of this study were to evaluate the prevalence of rotator cuff asymptomatic tears in postmenopausal women and to study their relationship with anthropometric and metabolic measures. METHODS: Premenopausal and postmenopausal women who were free from shoulder pain/functional impairment were enrolled. Body mass index (BMI), fasting glucose, triglycerides, total cholesterol, and high-density lipoprotein (HDL) cholesterol were evaluated. Both shoulders were examined by ultrasound imaging. For the purposes of this study, only full-thickness tears (classified as small, large, or massive) were taken into account. RESULTS: The prevalence of full-thickness tears (mainly localized in the supraspinatus tendon of the dominant side) was significantly higher in the postmenopausal group (8.9\% vs 3.1\%), with small, medium, and large tears in 60\%, 20\%, and 20\% of cases, respectively. In women with tears, intragroup comparison showed significantly higher values for BMI and fasting glucose, and lower levels of HDL cholesterol; no difference was found for triglycerides and total cholesterol in premenopausal and postmenopausal women, respectively. On multiple logistic regression analysis, the probability of detecting a tear in both groups was positively related to high values of BMI and lower levels of HDL cholesterol. CONCLUSIONS: The prevalence of asymptomatic full-thickness tears is increased in the postmenopausal period, and there is an association between tears and metabolic disorders. Because asymptomatic tears have a great potential to evolve into symptomatic painful shoulder, a precocious discovery of this pathology may allow the planning of preventive and therapeutic measures.

Previous research has shown that plantar fascia and Achilles tendon thickness is increased in diabetes. The aims of present study were to assess whether tendon changes can occur in the early stages of the disease and to evaluate the extent of the influence of body mass index (BMI). The study population included 51 recent-onset type II diabetic subjects, who were free from diabetic complications, divided according to BMI into three groups (normal weight, overweight, and obese). Eighteen non-diabetic, normal-weight subjects served as controls. Plantar fascia and Achilles tendon thickness was measured by means of sonography. The groups were well balanced for age and sex. In all the diabetic subjects, plantar fascia and Achilles tendon thickness was increased compared to the controls (p < 0.001, p = 0.01, p = 0.003, respectively). A significant relationship was found between plantar fascia thickness and BMI values (r = 0.749, p < 0.0001), while the correlation between BMI and Achilles tendon was weaker (r = 0.399, p = 0.004). This study shows that plantar fascia and Achilles tendon thickness is increased in the early stages of type II diabetes and that BMI is related more to plantar fascia than Achilles tendon thickness. Further longitudinal studies are needed to evaluate whether these early changes can overload the metatarsal heads and increase the stress transmitted to plantar soft tissues, thus representing an additional risk factor for foot ulcer development.

LJM is frequently observed in young subjects with insulin-dependent diabetes mellitus (IDDM). Aim of this study was to evaluate whether non-insulin-dependent diabetes mellitus (NIDDM) increases the risk of LJM in elderly subjects. Thirty patients (15 males, 15 females, mean age 73.93 ± 12.72 years) with NIDDM in good glycemic control were compared with thirty non-diabetic elderly, well matched for sex and age (15 males, 15 females, mean age 74.3 ± 4.24 years), and with ten young normal subjects (5 males, 5 females, mean age 26.3 ± 1.56 years). In these subjects, the range of motion (ROM) of ankle, knee, hip, elbow and shoulder were measured with a double-armed goniometer. Moreover, abnormalities of supraspinatus, patellar and Achilles tendons were evaluated with a standardized ultrasound (US) procedure. A significant reduction in the mobility of all joints was found in elderly subjects, compared to younger ones, with exception for the knee and elbow flexion. Elderly patients with diabetes, compared with their age-matched counterpart, showed LJM for ankle dorso- and plantar flexion, hip flexion and adduction, shoulder abduction and flexion. Moreover, tendons sonographic abnormalities were more frequently observed in diabetics. Our data confirm that diabetes worsens the LJM in the elderly, increasing the cross-linking of collagen by the non-enzymatic advanced glycation end products formation.

Rare side-effects of fluoroquinolone therapy are tendinitis and tendon rupture. Many reports have demonstrated that the concomitant use of corticosteroids, in patients aged 60 years or older, increase the risk substantially. We present a case of spontaneous bilateral Achilles tendon rupture induced by ciprofloxacin and methylprednisolone. A 61-year-old woman was diagnosed with Bronchiolitis Obliterans with Organizing Pneumonia (BOOP) and was started on oral ciprofloxacin 500 mg twice daily for 3 weeks and on oral methylprednisolone 16 mg twice daily for 2 weeks. The diagnosis was made after doctors, rather than stop drug therapy and advise complete rest, had mistakenly prescribed for the woman to undergo physiotherapy and local NSAIDs, thus favoring the onset of tendon ruptures and resulting in surgical and legal implications. Inspired by this case, we also submit a brief review on professional liability in Orthopaedics. Copyright © by BIOLIFE, s.a.s.

Relapses are frequently observed in subjects with chronic tendinopathies. Corticosteroid injections are usually performed with positive results, but are uncomfortable for the patient and not free from side effects. The aim of this pilot study is to evaluate the short-term efficacy and tolerability of an occlusive Betamethasone Valerate medicated Plaster (BMVP). Fifteen subjects with relapses of chronic tendinopathies (clinical and ultrasound diagnosis) were enrolled, and treated according to RICE (Rest - Ice - Compression - Elevation) protocol. An BMVP plaster was also applied on the affected tendon. Clinical examination, at baseline and after 7, 14, 21 and 28 days, included pain (VAS at rest and during activities) and functional evaluation. Local side effects on the area and drop-outs were also recorded. Pain, both at rest and during activities, significantly decreased at 28 days (from 3.7 ± 2.7 to 1.1 ± 1.7 [p < 0.01], and from 7.3 ± 1.7 to 3.3 ± 1.4 [p < 0.0000], respectively). Moreover, the patients reported a significant improvement in the functional limitation. Five subjects dropped out of the study. No side effects were reported. The release of the steroid in pharmacologically-active concentrations over 12–24 hours and the good penetration of the drug in subcutaneous tissues explain the positive results. BMVP application may be considered a reliable first therapeutic approach in relapses of chronic tendinopathies.

The need for bone grafting procedures to replace skeletal defects has become more considerable because of increased opportunities to save major bone loss. We report our experience and a critical analysis about the role of bone grafts and bone graft substitutes in prosthetic hip surgery replacement.

The aim of this study is to assess the biocompatibility of two types of Poly-L-lactic acid (PLLA) screws (with either hydroxiapatite (HA) or β-tricalcium phosphate (β-TCP)) implanted in the left femur of four sheep euthanized at 42, 50, 57 and 84 days after surgery. Titanium screws were also implanted for comparison purposes. No signs of inflammation were seen in the 240 specimens. A rating of “+/-”for macrophages and “-”for neutrophils was assigned to all specimens. All specimens were assigned a rating which ranged from “+/-” to “+++” for fibroblasts and osteoblasts. The presence of macrophages, neutrophils and fibroblasts/osteoblasts was not statistically different for the four implantation periods. PLLA implants with β-TCP have a biocompatibility comparable to PLLA implants with HA.

RANTES (regulated on activation, normal T cell-expressed and secreted) is a CC chemokine appearing to be involved in the recruitment of leukocytes at inflammation sites. RANTES is produced by CD8+ T cells, epithelial cells, fibroblasts, and platelets. It acts in vitro in leukocyte activation and human immunodeficiency virus suppression, but its role in vivo is still uncertain. In our study, we established the involvement of RANTES in an in vivo model of chronic inflammation induced by potassium permanganate, leading to calcified granulomas. In our rat model, RANTES expression (mRNA and protein) was significantly upregulated in granulomatous tissue; RANTES expression was further increased upon i.p. injection of lipopolysaccharide (LPS), while it was kept at basal levels by dexamethasone (Dex) given 18 hours before sacrifice. LPS and Dex increased and decreased, respectively, the recruitment of mononuclear cells in granulomatous tissue compared with control granulomas from phosphate-buffered saline (PBS)-treated animals. In granuloma tissue, levels of RANTES were higher in LPS-treated rats and lower in the Dex group compared to controls. RANTES was also found in the conditioned medium of granuloma tissue from treated (LPS or Dex) and untreated (PBS) rats. When LPS was added in vitro for 18 hours, RANTES was further increased, except in the Dex group (P > 0.05). On serum analysis, RANTES levels were higher in the LPS group and lower in the Dex group compared to controls. This study shows for the first time that RANTES is produced in vivo in chronic, experimental inflammatory states, an effect increased by LPS and inhibited by Dex.

The authors compared postural changes produced in 20 Caucasian female children treated with the Frankel Functional Regulator appliance (FR-2) (Frankel Industries, Morangis Cedex, France) using cephalometric tracings and comparing the tracings to 20 untreated Class II controls from the University of Chieti. Each patient in the study group was treated for exactly two years by the same operator using the FR-2 appliance and a standardized design and clinical technique, including prefunctional orthodontics where indicated. The average starting age was 8.4 yrs. (SD+/-2.1). At the end of the therapy, the average age was 10.3 yrs. (SD+/-2.4). Two teleradiographs were made of each patient: the first one at the beginning of treatment and the second one after six months. The radiographs were taken with the subjects standing in the ortho-position with no ear rods in the cephalostat; mirror position was carried out. In order to detect errors due to landmark identification, duplicate measurements were made using ten radiographs, and the error variance was calculated using Dahlberg's formula. Thirty-seven variables were studied. The cervical lordosis angle (CVT/EVT) was significantly higher in the study group as compared to the control group (p

Limited joint mobility is frequently observed in elderly people and in patients suffering from diabetes, who represent a growing segment of the population of western countries. Our review wishes to offer the “state of art” about this interesting topic, which may have important clinical implications, leading to impairment of both basic and instrumental activities of daily living. The main causes of a reduced range of motion are degenerative joint diseases and increased stiffness of collagen tissue. The main biochemical abnormality, common to aging and diabetes, is the non-enzymatic glycosilation of collagen, with advanced glycation end product (AGE) formation, which in turn leads to an increase of collagen cross-links. The most extensive accumulation of AGEs occurs in tissues that contain proteins with low turnover, such as the collagen in the extracellular matrix of articular capsule, ligaments and muscle-tendon units. The increase in collagen cross-linking alters the mechanical properties of these tissues with a decrease in elasticity and tensile strength, and an increase in mechanical stiffness. Besides this, AGEs react with specific cell surface receptors (RAGEs). The engagement of the ligand by RAGEs triggers cell-specific signalling, resulting in enhanced generation of reactive oxygen species and sustained up-regulation of pro-inflammatory mediators and adhesion molecules. An appropriate control of the glucose levels and a diet rich in antioxidant agents are recommended in patients with diabetes. Stretching and strengthening programmes are widely used, in order to prevent and to reduce joint stiffness, but the improvements with physiotherapy are little and short-lasting. Several drugs, which can interfere with AGE formation and removal, or with the cellular effects of AGEs, are under study (among them pyridoxamine, an active form of Vitamin B6, AGE-breaker compounds, glucosamine, rutin and derivatives, soluble RAGE isoforms, and statins). In experimental animal models, these drugs are effective in reducing diabetic complications due to AGE formation; however, further study is necessary before their extensive use in the clinical setting.

Chemokines are cytokines with chemotactic properties on inflammatory cells and other cell types. Chemokine (C-C motif) ligand 2 (CCL2), which is also called monocyte chemotactic protein 1 (MCP-1), is a potent chemotactic molecule that attracts lymphocytes, monocytes, mast cells, and memory T cells, but not neutrophils. CCL2/MCP-1 represents a link between the activation of monocytes, lymphocytes, basophils, mast cells, and eosinophils in inflammatory disorders, such as the late-phase allergic reaction. This C-C chemokine also plays a role in regulating Th-cell cytokine production and leukocyte trafficking. Laboratory of allergic diseases (LAD) cells is the first reported human mast cell line that closely resembles a primary culture of CD34+-derived human mast cells. These cells were cultured in vitro and treated with different concentrations of substance P (SP) for the production of CCL2/MCP-1. We used calcium ionophore as a positive control for stimulating transcription and translation of CCL2/MCP-1. The stimulation of SP on CCL2/MCP-1 was statistically significant (P0.05) compared with the control (untreated cells). In this study, we determined the expression and secretion of CCL2/MCP-1 from SP-activated LAD2 human mast cells in vitro. The levels of CCL2/MCP-1 from SP-activated LAD2 human mast cells were higher at 10 microM and at 18 h incubation compared with controls. This effect was also revealed on CCL2/MCP-1 messenger RNA (mRNA) expression, as determined by reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Our data suggest that SP is an important neurotransmitter that can stimulate the chemokine CCL2, which plays a fundamental role in inflammation by recruiting inflammatory cells to specific cites.

Background: Viscosupplementation (VS) with hyaluronic acid (HA) is largely used for knee osteoarthritis therapy, but the evidences for its usefulness in hip osteoarthritis (OA) are limited. Methods: In this review, an extensive search of published trials on VS in hip OA was performed. From the selected papers the following data were extracted: sample size, inclusion / exclusion criteria, treatment procedures, evaluation methods, follow-up duration and clinical outcomes. Results: The level of evidence was low in quite all the trials (no placebo controlled groups). A reduction of pain and an improvement of function after 3 months, persistent in the long term (12 - 18 months), was observed. Patients with mild morphological alterations responded better to therapy. Side effects were negligible, and were limited to pain and a sensation of heaviness in the injection site. No clear differences among Low (LMW) and High Molecular Weight (HMW) HA preparations were found in the clinical outcomes. However, for HMW-HA preparations, a lower number of injections was, in general, necessary in order to reach the therapeutic effect. Conclusions: Despite the initial promising results, some questions still remain open : 1) the characteristics of responders must be more precisely defined; 2) the treatment schedules, at present mainly based on the individual clinical experience, need a proper and accepted standardization. Finally, larger and placebo controlled trials are necessary to confirm the efficacy of VS in hip OA.

Purpose: Mast cells play an important role in innate and acquired immunity and are thought to be the cellular origin of most proteases and cytokines. Substance P (SP) and its receptor, NK-1R, play critical roles in immune regulation in human and animal models of inflammation. Methods: We used mature human cord blood mast cells (HCBMC) differentiated from cord blood CD34+ precursor activated with SP in culture. Results: Our data indicate that Substance P strongly activates mature HCBMC in releasing CXCL8 expression and secretion (Control: 1.200 ± 1.0; SP: 4.10 ± 0.90; P < 0.01). Moreover, in a RT-PCR, HCBMC expressed CXCL8 mRNA after Substance P activation. Since calcium ionophore A23187 is a pharmacological activator that raises cytosolic free calcium ion concentraion and stimulates mast cells in the production and secretion of proinflammatory compounds, it was used as positive control. In addition, we found that HCBMCs generate the transcription of histidine decarboxylase (HDC), the enzyme responsible for the generation of histamine from histidine, after SP treatment. Since CXCL8 is a member of the CXC chemokine subfamily with potent chemotactic activity and is a primary inflammatory cytokine we conclude that our results, obtained from HCBMC cultures, a good and valid model in vitro, support the concept that the neurogenic system modulates inflammatory events by Substance P-mediated HCBMC chemokine CXCL8 release. Conclusion: The expression, synthesis and release of CXCL8 suggest an increase of inflammatory process in vivo mediated by the recruitment and infiltration of inflammatory cells in inflamed tissues.

Obesity is an important risk factor for Achilles tendinopathy, and running is usually carried out to reduce excess body weight. Aim of this study was to evaluate the prevalence of Achilles tendinopathy in young overweight amateur runners. Male runners and non runners were recruited and, in each category, divided in two groups: normal weight, and overweight. Data about Achilles tendon thickness, vascularisation and structural abnormalities were collected using a Power Doppler Ultrasonography device. Achilles tendon thickness was greater in both normal weight or overweight runners, but the difference was significant only in normal weight subjects. In non - runners, thickness was significantly higher only in overweight subjects. Sonographic abnormalities were significantly prevalent in overweight runners. Running is associated to a physiologic hypertrophy of Achilles tendon in normal weight subjects. Overweight runners may precociously develop tendon abnormalities, due to the increased stress and the unfavourable milieu of repair. © CIC Edizioni Internazionali.

Cytokines are important proteins that modulate immunity and inflammation. Vitamins are also involved in immunity and inflammation. They are found to restore the ability of some cells to produce certain cytokines. Vitamin deficiency appears to affect the mechanism of immune cells, though the impact of reduced cytokine response in vitamin malnutrition is not clear. Vitamin D is involved in many medical conditions, such as infections and inflammation, and mediates innate immunity. Deficiency of vitamin D increases the risk of infectious and inflammatory diseases. In addition, this vitamin modulates Treg function and IL-10 production which is important for therapeutic treatment. Vitamin A increases inflammatory response and is involved in tissue damage; moreover, vitamin A is a key modulator of TGFbeta which can suppress several cytokines. Vitamin E, an anti-ageing compound, is associated with a defect of naive T cells and may inhibit some inflammatory compounds such as prostaglandin generation.

The aim of the study was to evaluate the effects that an anterior cruciate ligament (ACL) injury of the knee has on postural control and activity of neck, head and trunk muscles in order to investigate the existence of connections between the masticatory system and body posture.Surface electromyographic (sEMG) activity of the muscles and their asymmetry index, at mandibular rest position, and during maximal voluntary clenching (MVC), and posturometric and stabilometric measurements of 25 patients (mean age 28+/-9 years) having undergone ACL injury of the left knee were compared with a control non-pathologic group.At rest, the patients showed a higher sEMG activity of the anterior temporalis, masseter, sternocleidomastoid and lower trapezius, compared with the control subjects (P0.05). At MVC, the patients showed a lower sEMG activity of the right anterior temporalis and masseter and a higher sEMG activity of the lower trapezius, compared with the control subjects. For the stabilometric measurements, all the subjects showed a significant reduction in the Center of Pressure (CoP) path length during the test with eyes open and cotton rolls, compared with the test with eyes closed and mandibular rest position (P0.05). In addition, the patients showed a significant displacement of the CoP in a forward direction (P0.05) and to the righ side (P0.05), compared with the control-subjects during each test.ACL injury appears to be associated to a change in the sEMG activity of head, neck and trunk muscles and to a change in the position of the CoP of the body. Cotton rolls seem to improve the stability of the subject.

In this study we investigated the in vitro behaviour, morphostructure and extracellular matrix synthesis of human dental follicular stem cells (hDFSCs) isolated from human dental bud, which resulted to be positive for mesenchymal markers (CD29, CD90, CD146 and CD166) by FACS analysis. Cells were analysed by light and electronic microscopy to evaluate their biological response either at week 1, that is before differentiation, or at weeks 3–6, when they had been cultured in osteogenic medium onto a highly porous natural scaffold material (Bio-Oss®). Microscopy analysis of primary culture cells showed they had a mesenchymal stem cell-like morphostructure, spindle shaped, similar to the culture of mesenchymal stem cells derived from adult bone marrow. Also, after osteogenic differentiation, these analyses indicate typical osteoblast morphostructure and reveale a tri-dimensional organization of the cells and deposition of extracellular matrix (ECM) in close contact with biomaterial. This approach would allow to personalize the scaffold for bone tissue engineering in order to accelerate the process of osteogenesis.

The intrinsic pathogenetic mechanisms of tendinopathies are largely unknown and whether inflammation or degeneration has the prominent role is still a matter of debate. Assuming that there is a continuum from physiology to pathology, overuse may be considered as the initial disease factor; in this context, microruptures of tendon fibers occur and several molecules are expressed, some of which promote the healing process, while others, including inflammatory cytokines, act as disease mediators. Neural in-growth that accompanies the neovessels explains the occurrence of pain and triggers neurogenic-mediated inflammation. It is conceivable that inflammation and degeneration are not mutually exclusive, but work together in the pathogenesis of tendinopathies.