Testosterone, cortisol, vitamin D and oxidative stress and their relationships in professional soccer players.

BACKGROUND: The testosterone/cortisol ratio has been used in sport physiology to evaluate the balance between anabolism and catabolism; its decrease below 30% has been considered a marker of overtraining. In this framework recent studies in soccer players have investigated the relationships between testosterone, cortisol, vitamin D and reactive oxygen species, but with unconvincing results. The aim of the present study was to evaluate the behavior of such biological parameters and their relationships both in winter (the season of championship) and in summer (off-competition season), characterized by different homeostatic situations. METHODS: Twenty-seven professional male football players (Second Italian Division), were studied. Blood levels of free testosterone, cortisol, vitamin D and reactive oxygen species were evaluated in August (pre-season training) and in February, in the midseason. A comparison between these two periods was performed and for each of them the relationships between the biological parameters were evaluated. RESULTS: Blood levels of testosterone were higher during summer whereas those of cortisol were higher in winter. Vitamin D levels were higher in summer; in this season a positive significant relationship between vitamin D and testosterone was observed (P=0.001), but not in winter (P=0.592). Reactive oxygen species were higher in winter; in this season a significant positive relationship between these substances and cortisol was observed (0.000), but not in summer (P=0.325). CONCLUSIONS: In professional soccer players it was found a positive relationship between vitamin D and testosterone in summer and between reactive oxygen species and cortisol in winter. However, the question whether such results are genuine cause-effect relationships or mere casual or spurious statistical correlations is still unsolved. As matter of fact, such results could be dependent from other determinants which might drive the aforementioned biological parameters in the same direction. These conclusions must be considered valid only in relation to the experimental conditions (training workload, diet and sun exposure) of the present study.

Oxidative Stress and Abnormal Tendon Sonographic Features in Elite Soccer Players (A Pilot Study).

Objective Sound experimental data suggest that oxidative stress plays an important role in the pathogenesis of tendinopathies. However, this hypothesis in humans remains speculative given that clinical data are lacking to confirm it. Recently, a new methodology has allowed to quantify the oxidative stress in vivo by measuring the concentration of hydroperoxides of organic compounds, which have been utilized as an oxidative stress-related marker in several pathologic and physiologic conditions. Given the reliability of this test and the lack of information in subjects with tendinopathies, the aim of the present study was to assess the oxidative stress status in elite professional soccer players with and without ultrasonographic features of tendon damage. Methods In 73 elite players, blood metabolic parameters were evaluated and oxidative stress was measured by means of a specific test (expressed as U-Carr units). Therefore, an ultrasonographic evaluation of the Achilles and patellar tendons was performed. Results No significant relationships were observed between metabolic parameters and oxidative stress biomarkers. The Achilles and patellar tendons showed a normal echographic pattern in 58 athletes, and sonographic abnormalities in 15. The athletes with ultrasonographic alterations, compared to those with normal US picture, showed significantly higher U-Carr levels ( p = 0.000), body mass index (BMI) values ( p = 0.03) and were older ( p = 0.005). The difference in U-Carr values among the subjects remained significant also after adjustment for age and BMI. Conclusion The results of the present study support the hypothesis that oxidative substances, also increased at systemic and not only at local level, may favor tendon damage. Level of Evidence IV (pilot study).

Baker's Cyst with Knee Osteoarthritis: Clinical and Therapeutic Implications.

OBJECTIVE: Several symptoms are common to knee osteoarthritis and Baker's cyst. To what extent each condition contributes to the patient's discomfort is still a matter of debate. The aim of the present study was twofold: first, to compare the burden of symptoms in patients with isolated knee osteoarthritis and patients with knee osteoarthritis associated with Baker's cyst; second, to assess the outcomes after conservative treatments. SUBJECT AND METHODS: Patients suffering from monolateral idiopathic knee osteoarthritis were enrolled. Demographic, anthropometric and clinical data (KOOS scale) were collected. Ultrasound evaluation was performed according to standard protocols. On the basis of the clinical presentation different therapeutic options were used (fluid withdrawal, hyaluronic acid and/or steroids injections). RESULTS: One-hundred and thirty patients were included in the study (97 with isolated knee osteoarthritis, 33 with knee osteoarthritis and Baker's cyst). In basal conditions, lower scores in KOOS sub-scales were observed in patients with knee osteoarthritis associated with Baker's cyst and in patients with effusion compared with patients without effusion. At 3 months after therapy significant higher scores were observed in both groups. At 6 months the scores were unchanged in the patients without Baker's cyst, but worsened in those with Baker's cyst. CONCLUSIONS: The study shows that Baker's cysts associated with knee osteoarthritis contribute to the burden of symptoms. The conservative treatment of both conditions allows significant improvements, but in the medium term (6 months) the efficacy of the therapy declines in patients with knee osteoarthritis associated with Baker's cyst.

To evaluate the outcomes of PRP treatment in Achilles tendinopathy: An intriguing methodological problem.

INTRODUCTION: Assessing the outcomes of Platelet Rich Plasma (PRP) treatment in Achilles Tendinopathy (AT) may prove difficult due to several methodological reasons. For example, given that the simple mean of VISA-A score is just the result of positive, negative or null values, this may provide incomplete information, and therefore the size of individual changes can remain unknown. On the contrary, calculating the score changes in each subject after treatment would allow a more appropriate evaluation of the clinical results. However, this method has been applied only to few small-scale studies. Therefore we performed a retrospective study aiming to determine: (1) are the percentages of positive outcomes of the present research comparable to those of previous studies performed in different settings? (2) Is there a relationship between the size of increase of the clinical score and the patient satisfaction? HYPOTHESES: The percentages of positive outcomes of the present research are comparable to those of previous studies performed in different settings. MATERIAL AND METHODS: This is a retrospective observational study. Eighty-four patients submitted to PRP treatment for mid-portion AT were enrolled. Pain and function were evaluated by means of VISA-A scale. Besides the mean, in each subject the pre- and post-treatment difference of VISA-A score was computed and the outcome was defined clinically no detectable, detectable and evident according to the increasing values of the score (0 to 9 points, 10 to 19, and≥20 points change, respectively). The Likert's scale for the patients satisfaction was also used. RESULTS: The mean VISA-A increased significantly after treatment (from 50.1±9.1 at baseline to 63.7±13.8 at 3 months (p=0.00001) and 67.2±14.1 at 6 months (p=0.00001)). At 3 and 6 months the subjects belonging to the prefixed categories were 15, 45, 24 and 19, 36, 29, respectively. Moreover, large discrepancies were observed between the size of increase of the clinical score and patients satisfaction, mainly for intermediate increases of the score. DISCUSSION: The percentages of positive outcomes found in this study are slightly lower than those reported in literature. The different patients expectations about the efficacy of the therapy can explain the discrepancies between the size of increase of the clinical score and the individual satisfaction. In comparison to the simple mean, the individual changes of VISA-A score allow a proper evaluation of the outcomes. The research shows that discrepancies can be present in the percentage of positive clinical outcomes between different studies. The size of increase of the clinical score does not always match patient satisfaction. LEVEL OF PROOF: IV retrospective study without control group.

Factors associated with positive outcomes of platelet-rich plasma therapy in Achilles tendinopathy.

BACKGROUND: 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. MATERIAL AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Platelet-Rich Plasma Diffusion in Achilles Tendon: Relationship with Therapeutic Outcomes.

OBJECTIVE: The therapeutic efficacy of platelet-rich plasma in the treatment of Achilles tendinopathy is controversial. Among the variables which can explain the discrepant results, little attention has been paid to the distribution of platelet-rich plasma inside the tendon. The aim of the present study was to evaluate whether this factor is related to the clinical outcome of treatment. SUBJECTS AND METHODS: Forty patients suffering from mid-portion Achilles tendinopathy were studied. At baseline, pain and function were measured by means of a visual analogue scale and the Victorian Institute of Sport Assessment-Achilles questionnaire. Thereafter, an ultrasound examination was performed, and platelet-rich plasma was injected. Immediately after injection, the plasma distribution was assessed visualizing the material in the tendon. The patients were re-evaluated at 3 and 6 months, computing pain and function values and the percentage of satisfactory outcomes in relation to the distance reached by the plasma from the point of injection. RESULTS: The diffusion inside the tendon was longitudinal in all cases and cross-sectional only in 9. The mean distance from the tip of the needle increased significantly according to the severity of tendon damage. At follow-up, no relationship was found between plasma diffusion and clinical outcomes. CONCLUSIONS: Platelet-rich plasma diffusion has no effect on clinical outcome, which mainly depends on the metabolic activation of the whole structure of the tendon.

Platelet rich plasma compared to dry needling in the treatment of non-insertional 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 3 weeks), respectively. At baseline, 3 and 6 months, 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 6 months no differences in terms of pain and function between groups were observed, but the percentage of subjects reporting satisfactory results, at 6 months, 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.

Synergistic activity of platelet rich plasma and high volume image guided injection for patellar tendinopathy.

PURPOSE: Platelet rich plasma and high volume image guided injections of saline have been used in the treatment of patellar tendinopathy with positive results. As the different mechanisms of action do not interfere each other, it can be hypothesized that they can be used in combination. Aim of this study was twofold: first, to evaluate the efficacy of these two treatments in the management of patellar tendinopathy; second, to verify whether the combination of these therapies could provide further advantages. METHODS: Fifty-four patients suffering from patellar tendinopathy were enrolled. After clinical (VAS and VISA-P) and sonographic evaluation, two ultrasound guided injections (2 weeks apart) of platelet rich plasma, high-volume image-guided injections of saline, or both in association were performed. The VAS and VISA-P scores obtained from the three treatments groups (18 patients in each group) were compared across the different follow-up times (3 and 6 months). RESULTS: In the short term both treatments showed comparable efficacy, whereas in the medium term the positive effects of high-volume image-guided injections gradually diminished and platelet rich plasma showed greater efficacy. Better results (reduced pain, improved function and increased number of subjects who exhibited optimal recovery [> 20 points in VISA-P score]) were observed when both procedures were associated. CONCLUSIONS: The contemporaneous administration of platelet rich plasma and high volume image guided injections of saline treatments, which influence tendon repair by means of different mechanisms, grants a greater improvement for patellar tendinopathy. This finding has clinical relevance, given that this condition has a substantial impact on sports and work performance. LEVEL OF EVIDENCE: III.

Metabolic syndrome associated to non-inflammatory Achilles enthesopathy.

Enthesopathies are frequently found in rheumatic inflammatory diseases, but can be observed also in absence of systemic inflammation. Aging, overuse, and microtraumas can be responsible for enthesis-degenerative phenomena. Despite that Achilles enthesis is the more frequently affected, no systematic study on the risk factors associated to this enthesopathy has been yet performed. The aim of this paper was to assess whether the metabolic syndrome could be associated to entheseal lesions. Forty-five subjects with symptomatic non-inflammatory Achilles enthesopathy were compared to 45 asymptomatic controls. An ultrasound study of the Achilles enthesis was carried out, and the presence/absence of lesions (morphologic abnormalities, calcific deposits, enthesophytes, cortical abnormalities, and adjacent bursitis) was assessed. On the basis of history, comorbidities (osteoarthritis, diabetes, and hypertension) were recorded. In each subject, body mass index (BMI), glucose, total, and HDL cholesterol were also evaluated. All symptomatic subjects showed at ultrasound evaluation at least one structural entheseal alteration; pathologic features in asymptomatic subjects were found in 6/45 (13.3 %) of cases. Higher values of BMI and glucose were found in subjects with symptomatic enthesopathy. At multiple logistic regression analysis, the presence of high values of BMI and glucose was related to a higher probability to detect entheseal lesions. Metabolic syndrome and overweight may have a role in the pathogenesis of Achilles enthesopathy due to their synergistic worsening effect on other pathogenetic factors of tendon degeneration, such age and overuse. Therefore, subjects with metabolic syndrome practicing sports and other activities stressing the Achilles tendon should receive advice for more frequent controls.

Prevalence of and risk factors for asymptomatic rotator cuff tears in postmenopausal women.

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.

Non-invasive in vivo detection of peripheral limb ischemia improvement in the rat after adipose tissue-derived stromal cell transplantation.

BACKGROUND: Adipose tissue-derived stromal cells (ADSCs) might help repair ischemic cardiovascular tissue. Their in vivo effects on the bioenergetics and microcirculation of ischemic muscle through a variety of non-invasive techniques was examined. METHODS AND RESULTS: Unilateral hindlimb ischemia was induced in 42 rats. One day after femoral artery ligation, 6 rats per group were randomly injected with intramuscularly allogeneic ADSCs (10(6)-10(7)-10(8) cells/ml), conditioned media from ADSC cultures (conditioned media [CM], control), saline (control), allogeneic fibroblasts (10(7) cells/ml, control) or a non-conditioned medium (control). Rats underwent magnetic resonance angiography (MRA), short-time inversion recovery (STIR) edema-weighed imaging, proton MR spectroscopy ((1)H-MRS), thermal infrared imaging (IRI), immunoblotting and immunofluorescence analysis on both hindlimbs for 4 weeks. MRA and STIR documented arterial occlusion and ischemia, respectively. Muscle (1)H-MRS and IRI showed reductions of total creatine (tCr)/water and skin temperature in occluded hind limbs, respectively. At 4 weeks, the ADSC and CM groups had greater recovery of skin temperature and tCr/water in ischemic limbs compared with controls (P<0.01), with increased expression of α-sarcomeric actinin and vascular growth factors, such as hepatocyte growth factor (HGF), increased vessel density (capillaries, arterioles and venules) and less type III collagen. CONCLUSIONS: Allogeneic ADSCs improve ischemic muscle metabolism, increase neovasculogenesis and decrease fibrosis, largely through a paracrine mechanism. (1)H-MRS and IRI are useful tools to monitor attempts at salvaging the ischemic tissues with cell-derived novel therapies.

Achilles tendon and plantar fascia in recently diagnosed type II diabetes: role of body mass index.

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.

Scrotal thermoregulatory model and assessment of the impairment of scrotal temperature control in varicocele.

Varicocele is defined as the pathological dilatation of the pampiniform plexus and scrotal veins with venous blood reflux. Varicocele may impair scrotal thermoregulation and spermatogenesis, even when present in asymptomatic forms. In this study, we use the control system theory to model scrotal thermoregulation in response to a standardized cold challenge in order to study the functional thermal impairment secondary to varicocele. The proposed model is based on a homeostatic negative feedback loop, characterized by four distinct parameters, which describe how the control mechanisms are activated and maintained. Thermal infrared images series from 49 young patients suffering from left varicocele and 17 healthy controls were processed. With respect to healthy controls, left varicocele patients presented higher basal scrotal temperature and faster recovery of the left hemiscrotum. The model indicated that varicocele alters local heat exchange processes among cutaneous layers and inner structures. The estimated model parameters help in the assessment of the scrotal thermoregulatory impairment secondary to the disease.