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2.  Thyroid hormones increase collagen I and cartilage oligomeric matrix protein (COMP) expression in vitro human tenocytes 
we previously demonstrated the presence of high levels of thyroid hormones (THs) receptors isoforms in healthy tendons, their protective action during tenocyte apoptosis, and the capability to enhance tenocyte proliferation in vitro. In the present study we tested the ability of THs to influence ECM protein tenocyte secretion in an in vitro system.
primary tenocyte-like cells were cultivated for 1, 7 and 14 days in the presence of T3 or T4 individually or in combination with ascorbic acid (AA).
THs (T3 or T4) in synergism with AA increase significantly the total collagen production after 14 days. THs in synergism with AA increase significantly the expression of collagen I,biglycan and COMP, after some days.
THs play a role on the extra cellular matrix of tendons, enhancing in vitro the production of several proteins such as collagen I, biglycan and COMP. THs receptors are active on human tenocytes, and can play a role in tendon ailments.
PMCID: PMC4241417  PMID: 25489544
ascorbic acid; collagen I; COMP; tenocytes; thyroid hormones; tendons
3.  Epidemiology of the rotator cuff tears: a new incidence related to thyroid disease 
in the last years the incidence of rotator cuff tears increased and one main cause still waiting to be clarified. Receptors for thyroid hormones in rotator cuff tendons suggest possible effects on tendons metabolism and status. We undertook a retrospective, observational cohort study of 441 patients who underwent arthroscopic and mini-open repair for non traumatic degenerative rotator cuff tears.
all the patients, predominantly females (63%), were interview to assess the relationship (frequency for class age “20 yrs” and factor analysis) between lesions of the rotator cuff with the following variables: gender, thyroid disease, smoker, taking medications for diabetes, hypertension or high cholesterol; presence of associated conditions (diabetes, hypertension, hypercholesterolemia).
thyroid disease is highly frequently (until 63% for 60<80 yrs) in females group independent to the age. Conversely, males showed a high frequency for smoker 37<62% until 80 yrs and 50% hypercholesterolemia over 80 yrs for the clinical variable studied.
this is the first clinical report that shown a relationship between thyroid pathologies and non-traumatic rotator cuff tear as increased risk factors.
PMCID: PMC4241421  PMID: 25489548
age-group; clinical field; epidemiology; gender; healthcare; musculoskeletal disorders; rotator cuff tears; tendons; thyroid hormones; upper extremity
4.  A comparison of thought and perception disorders in borderline personality disorder and schizophrenia: psychotic experiences as a reaction to impaired social functioning 
BMC Psychiatry  2014;14(1):239.
Although previous studies suggest a high frequency of psychotic symptoms in DSM-IV Borderline Personality Disorder (BPD) there is currently no consensus on their prevalence and characteristics (type, frequency, duration, location etc.). Similarly, there are few papers addressing psychotic reactivity, the crucial aspect of BPD included in the ninth criterion for DSM-IV BPD, which remained unchanged in DSM-IV-TR and DSM-5. The purposes of the present study were to compare thought and perception disorders in patients with DSM-IV BPD and schizophrenia (SC), investigating their relationship with social functioning.
Thought and perception disorders and social functioning over the previous two years were assessed by the Diagnostic Interview for Borderline Revised (DIB-R) and Personal and Social Performance scale (PSP) respectively in outpatients with DSM-IV BPD (n = 28) or DSM-IV SC (n = 28).
Quasi-psychotic thought (i.e. transient, circumscribed and atypical psychotic experiences) was more frequent in BPD (BPD = 82.1%, SC = 50%, p = 0.024); whereas true psychotic thought (i.e. Schneiderian first-rank, prolonged, widespread and bizarre psychotic symptoms) was more frequent in SC (SC = 100%, BPD = 46.4%, p < 0.001). However both types of psychotic features were prevalent in both groups. Non-delusional paranoia (e.g. undue suspiciousness and ideas of references) was ubiquitous but was more severe in BPD than SC patients (U(54) = 203.5, p = 0.001). In the BPD group there was a strong negative correlation between personal and social functioning and non-delusional paranoia (τ(28) = 0.544, p = 0.002) and level of personal and social functioning was a significant predictor of the severity of non-delusional paranoia only in the BPD group (β = −0.16, t(23) = 2.90, p = 0.008).
BPD patients reported less severe psychotic experiences with more frequent quasi-psychotic thought, less frequent true psychotic thought and more severe non-delusional paranoia than SC patients. Interpersonal functioning seems to predict non-delusional paranoia in BPD, which would validate the “stress-related paranoid ideation”, included in the ninth diagnostic criterion for DSM-IV and DSM-5 BPD. PBD patients had higher scores on the psychotic experiences subscale that support the use of a dimensional assessment of the severity of thought and perception disorders, for example the Clinician-Rated Dimensions of Psychosis Symptom Severity introduced in DSM-5, Section III.
PMCID: PMC4219117  PMID: 25277100
Borderline personality disorder; Schizophrenia; Thought disorder; Perception disorder; Psychotic-like symptoms; Quasi-psychotic symptoms; Social functioning; Non-delusional paranoia; DSM
5.  Pseudoaneurysm of peroneal artery after ankle arthroscopy 
ankle arthroscopy increased its role in the diagnosis and treatment of pathology of the ankle since 1970s. Although the benefits are well established, ankle arthroscopy is associated with a definite risk of complications, especially neurological. The incidence rate of vascular complication after anterior ankle arthroscopy has been reported.
we review the literature on vascular complications after anterior ankle arthroscopy especially pseudoaneurysm and a case report of a peronal artery pseudoaneurysm was reported.
vascular complications after an anterior ankle arthroscopy are extremely rare but orthopaedic surgeons should be wary of this chance. Among vascular complications after an anterior ankle arthroscopy, peroneal artery pseudoaneurysm to our knowledge never has been described until now.
PMCID: PMC4187590  PMID: 25332946
ankle arthroscopy; peroneal artery; pseudoaneurysm
6.  Bovine xenograft locking Puddu plate versus tricalcium phosphate spacer non-locking Puddu plate in opening-wedge high tibial osteotomy: a prospective double-cohort study 
International Orthopaedics  2013;37(5):819-826.
The aim of the study was to compare clinical and radiographic outcomes of opening-wedge high tibial osteotomy (HTO) augmented with either xenograft or tricalcium phosphate spacer for the management of medial compartment osteoarthritis (OA) with genu varum.
Between 2004 and 2007, we prospectively enrolled 52 patients with medial compartment knee OA who underwent opening-wedge HTO fixed with locking Puddu plate and xenograft (n = 26) or non-locking Puddu plate and tricalcium phosphate spacer (n = 26). The alignment of the lower limb was assessed by measuring the hip-knee-ankle (HKA) angle. Clinical outcomes were assessed with the Knee Society Score, Western Ontario and McMaster Universities Osteoarthritis Index, SF-36 and European Quality of Life-5 Dimensions scale. All patients were followed up at six weeks and at three, six, 12 and 24 months post-operatively. Clinical outcomes were assessed preoperatively and at 24 months post-operatively.
All clinical scores improved significantly in both groups after surgery, without any significant difference between the two groups. Immediately after surgery, the HKA angle went from 9.1 ± 5.2° in varus to 3.1 ± 4.8° in valgus (P = 0.01) in the xenograft group, and from 8.5 ± 5.9° in varus to 3.4 ± 4.2° in valgus (P = 0.01) in the tricalcium phosphate group. At the last follow-up, the tricalcium phosphate group showed a significant loss of correction (P = 0.03).
HTO performed with xenograft locking plate and tricalcium phosphate non-locking plate constructs showed good clinical outcomes. However, the xenograft locking plate construct is superior to the tricalcium phosphate spacer non-locking plate to prevent the loss of correction in the middle term.
PMCID: PMC3631487  PMID: 23412369
7.  ISMuLT Guidelines for muscle injuries 
Muscle injuries are frequent in high demand sports. No guidelines are available in the scientific literature. ISMuLT, the “Italian Society of Muscles, Ligaments and Tendons”, in line with its multidisciplinary mission, is proud to cover this gap.
PMCID: PMC3940495  PMID: 24596685
muscles injuries; classification; guidelines
8.  Muscle, Ligaments and Tendons Journal. Basic principles and recommendations in clinical and field science research 
The design, implementation, evaluation, interpretation and report of research is a key important for the science. The research required minimize the uncertainty, therefore we encourage all authors of respect how much can possible the contents in this official editorial also in order to stimulate interest and debate about constructive change in the use of statistics in our disciplines1,2. Authors are required to confirm that these standards and laws have been adhered to by formally citing this editorial within the methods section of their own manuscript.
PMCID: PMC3940496  PMID: 24596686
statistical analysis; case report; experimental approach; design; ethical standard; best practice; sample size; performance indicators; reliability of the measures
9.  Surgical repair of muscle laceration: biomechanical properties at 6 years follow-up 
Muscle injuries are challenging problems for surgeons. Muscle trauma is commonly treated conservatively with excellent outcome results while surgical repair is advocated for larger tears/lacerations, where the optimal goal is restore of function. Repair of muscle belly lacerations is technically demanding because the sutures pull out and the likelihood of clinical failure is high. Different suture techniques have been described but still the best suture is debated. We show a case of a pure vastus medialis muscle laceration surgically repaired at 6 years of follow-up.
PMCID: PMC3940505  PMID: 24596695
muscle belly lesion; skeletal muscle laceration; muscle repair; epimysium; fibrous scar
11.  Thyroid hormones and tendon: current views and future perspectives. Concise review 
Thyroid hormones (THs) T3 and T4, play an essential role in the development and metabolism of many tissues and organs, and have profound metabolic effects in adult life. THs action is mediated mainly by the thyroid hormone receptor (TRs) which seem to be ubiquitous. To-date thyroid-associated disease are not thought to be related in tendinopathies and tendons tears. Recent study demonstrated the presence of TRs in tendons and their possible role in the proliferation and apoptosis of human tenocyte isolated from tendon. We review new discovery that revisit our current thinking on the tendon biology focusing on thyroid hormones (THs) T3 and T4, and their possible role on human tenocyte.
PMCID: PMC3838329  PMID: 24367780
thyroid hormones; T3; T4; tenocytes; rotator cuff tendons; tendon tears
13.  Clinical and biological aspects of rotator cuff tears 
Rotator cuff tears are common and are a frequent source of shoulder pain and disability. A wide variation in the prevalence of rotator cuff tears has been reported. The etiology of rotator cuff tear remains multifactorial and attempts to unify intrinsic and extrinsic theories tried to explain the etiopathogenesis of rotator cuff tears. Knowledge of the etiopathogenesis of rotator cuff tears is important to improve our therapies, surgical techniques and promote tendon repair. Several strategies have been proposed to enhance tendon healing and recently research has focused on regenerative therapies, such as Growth Factors (GFs) and Plasma Rich Platelet (PRP), with high expectations of success.
PMCID: PMC3711705  PMID: 23888289
rotator cuff tears; shoulder; growth factors; platelet rich plasma
14.  All is around ECM of tendons!? 
PMCID: PMC3676158  PMID: 23885338
15.  Tendon’s ultrastructure 
The structure of a tendon is an important example of complexity of ECM three-dimensional organization. The extracellular matrix (ECM) is a macromolecular network with both structural and regulatory functions. ECM components belong to four major types of macromolecules: the collagens, elastin, proteoglycans, and noncollagenous glycoproteins. Tendons are made by a fibrous, compact connective tissue that connect muscle to bone designed to transmit forces and withstand tension during muscle contraction. Here we show the ultrastructural features of tendon’s components.
PMCID: PMC3676160  PMID: 23885339
tendon; collagen; ultrastructure; extra-cellular matrix
16.  Metalloproteases and tendinopathy 
Matrix metalloproteinases (MMP) are involved in the development of tendinopathy. These potent enzymes completely degrade all components of the connective tissue, modify the extracellular matrix (ECM), and mediate the development of painful tendinopathy. To control the local activity of activated proteinases, the same cells produce tissue inhibitors of metalloproteinases (TIMP). These latter bind to the enzyme and prevent degradation. The balance between the activities of MMPs and TIMPs regulates tendon remodeling, whereas an imbalance produces a collagen dis-regulation and disturbances in tendons. ADAMs (a disintegrin and metalloproteinase) are cell membrane-linked enzymes with proteolytic and cell signaling functions.
ADAMTSs (ADAM with thrombospondin motifs) are secreted into the circulation and constitute a heterogenous family of proteases with both anabolic and catabolic functions. Further studies are needed to better define the mechanism of action, and whether these new strategies are safe and effective in larger models.
PMCID: PMC3676164  PMID: 23885345
metalloproteases; tendinopathy; tendon healing
17.  Biological properties of mesenchymal Stem Cells from different sources 
Mesenchymal stem cells (MSCs) are adult, nonhematopoietic, stem cells that were initially isolated from bone marrow. Now they can be isolated from almost every tissue of the body. They have the ability to self-renew and differentiate into multiple cell lineage, including bone, chondrocytes, adipocytes, tenocytes and cardiomyocytes, and it makes them an attractive cell source for a new generation of cell-based regenerative therapies. In this review we try to summarize data on sources and the biological properties of MSCs.
PMCID: PMC3666517  PMID: 23738292
bone marrow; mesenchymal stem cells; stromal cells; tissue engineering
19.  Treatment of adhesive capsulitis: a review 
Adhesive capsulitis is a condition “difficult to define, difficult to treat and difficult to explain from the point of view of pathology”. This Codman’s assertion is still actual because of a variable nomenclature, an inconsistent reporting of disease staging and many types of treatment. There is no consensus on how the best way best to manage patients with this condition, so we want to provide an evidence-based overview regarding the effectiveness of conservative and surgical interventions to treat adhesive capsulitis.
PMCID: PMC3666515  PMID: 23738277
adhesive capsulitis; frozen shoulder; review; conservative treatment
20.  Physiopathology of intratendinous calcific deposition 
BMC Medicine  2012;10:95.
In calcific tendinopathy (CT), calcium deposits in the substance of the tendon, with chronic activity-related pain, tenderness, localized edema and various degrees of decreased range of motion. CT is particularly common in the rotator cuff, and supraspinatus, Achilles and patellar tendons. The presence of calcific deposits may worsen the clinical manifestations of tendinopathy with an increase in rupture rate, slower recovery times and a higher frequency of post-operative complications. The aetiopathogenesis of CT is still controversial, but seems to be the result of an active cell-mediated process and a localized attempt of the tendon to compensate the original decreased stiffness. Tendon healing includes many sequential processes, and disturbances at different stages of healing may lead to different combinations of histopathological changes, diverting the normal healing processes to an abnormal pathway. In this review, we discuss the theories of pathogenesis behind CT. Better understanding of the pathogenesis is essential for development of effective treatment modalities and for improvement of clinical outcomes.
PMCID: PMC3482552  PMID: 22917025
Calcific Tendinopathy; Calcific Deposits; Tendons; Review
21.  Achilles tendinopathy in amateur runners: role of adiposity (Tendinopathies and obesity) 
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 over-weight 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 over-weight 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.
PMCID: PMC3666497  PMID: 23738273
Achilles tendon; obesity; running; tendinopathy; ultrasound
23.  Short-term effectiveness of bi-phase oscillatory waves versus hyperthermia for isolated long head biceps tendinopathy 
Long head biceps (LHB) tendinopathy is a common cause of anterior shoulder pain. Isolated LHB pathology is most common among younger people who practise overhead sports. The authors conducted a short-term prospective randomised study to test the effectiveness of two different methods for the treatment of isolated LHB tendinopathy: biphasic oscillatory waves and hyperthermia.
Study design:
The study is a prospective randomised study (Level II).
Material and methods:
The authors identified 20 patients who had clinical and ultrasound (US) evidence of LHB tendinopathy. No patient was a high-level athlete. The patients were randomly assigned to two groups. Group A (10 patients) was treated with bi-phasic oscillatory waves, while Group B received hyperthermia. During the treatment period, no other electromedical therapy, injections with corticosteroids, oral analgesics or nonsteroidal anti-inflammatory drugs were allowed. All the patients were assessed at baseline (T0), immediately after the end of the treatment period (T1) and 6 months after the end of treatment (T2) using a visual analogic scale (VAS) and Constant-Murley Score (CMS). Furthermore, all patients underwent US examinations at T0 and at T1. All the US examinations were performed by the same radiologist.
The VAS scores showed a highly statistically significant reduction of pain at T1 both in Group A (65%; p=0,004) and in Group B (50%; p=0,0002). The CMS also showed a statistically significant improvement between the pre-intervention, the post-treatment and the short-term follow-up in both groups. In addition, the peritendinous fluid evident on US examination at T0 was no longer present in all cases at T1.
These findings suggest that both bi-phasic oscillatory waves and hyperthermia are able to relieve pain in patients with isolated LHB tendinopathy. This is a Class II level of evidence.
PMCID: PMC3666475  PMID: 23738257
biphasic oscillatory waves; InterX; hyperthermia; long head biceps; rehabilitation; tendinopathy
25.  Single injection of platelet-rich plasma in a rat Achilles tendon tear model 
The purpose of this study was to determine the efficacy of platelet-rich plasma (PRP) 1-injection during an Achilles tendon rat tear model. 80 male adult imbreded rats (Wistar Kyoto), underwent under surgical tendon rupture. 40 Animal (PRP group rats) were given a local injection with 0,25 mL of PRP, and 40 animal (control group) were given the same quantity of control solution. The rats were sacrified at 1, 2, 4 and 6 weeks (each time point, 20 rats of the each group) after surgical tear and tendon tissue was analysed by macroscopic aspect, histology, immunostaining and Real Time (RT)-PCR to evaluate tissue repair. PRP improved tendon remodelling by better coordination of the reconstructive process with earlier formation of tendon-like continuity only in the first week after surgery. However, after 2,4 and 6 weeks, Achilles tendons in the PRP group had no difference compared to the control group. Immunostaining and RT-PCR did not show any difference between PRP treated and untreated group. Based on these findings a single injection of PRP appear not useful for Achilles rat tendon tear.
PMCID: PMC3666471  PMID: 23738245
growth factors; Achilles tendon tear; PRP; tendon repair

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