Direct anterior approach with conventional instruments versus robotic posterolateral approach in elective total hip replacement for primary osteoarthritis: a case-control study.

BACKGROUND: The purpose of this study is to compare peri-operative and short-term outcomes in patients who underwent elective total hip replacement (THA) for primary osteoarthritis (OA) with direct anterior approach (DAA) versus a pair-matched cohort of patients who underwent robotic-assisted THA with posterolateral approach. MATERIALS AND METHODS: Data from consecutive patients who underwent elective hip replacement from 2021 to 2023 for primary OA were retrospectively retrieved and divided into two groups: the DAA group, who underwent THA with the DAA approach using conventional instruments, and the robotic posterolateral (R-PL group), who underwent robot arm-assisted THA with the posterolateral approach. Comparative assessed outcomes were: operative time, radiographical implant positioning, intake of rescue analgesics, blood loss, transfusion rate, leg length discrepancy and functional outcomes (Harris hip score and forgotten joint score). RESULTS: A total of 100 pair-matched patients were retrieved with a mean age of 66.7 ± 10.7 (range: 32-85) years and a mean follow-up of 12.8 ± 3.6 (range: 7-24) months. No differences in patients' characteristics were detected. Patients in the R-PL group required less rescue tramadol (p > 0.001), ketorolac (p = 0.028) and acetaminophen (p < 0.001). There was no significant difference in the operative time between (MD = 5.0 min; p = 0.071). Patients in the DAA group had significantly lower Hb levels at day 1 (p = 0.002) without significant differences in transfusion rate (p = 0.283). Patients in the R-PL group had shorter length of stay (LOS) with a mean difference of 1.8 days [p < 0.001; 95% confidence interval (CI) 1.4-2.3]. No difference in clinical outcomes was found [leg length discrepancy (LLD), p = 0.572; HHS, p = 0.558; forgotten joint score (FJS), p = 0.629]. No radiographical differences were measured in cup inclination (MD = 2.0°, p = 0.069), malpositioning [odd ratio (OR) = 0.2; p = 0.141], stem alignment (OR = 0.3; p = 0.485) and stem sizing (OR = 1.5; p = 1.000). There was no difference in complication rate except for lateral femoral cutaneous nerve damage, which was higher in DAA group (p < 0.001). CONCLUSIONS: R-PL and DAA THA had comparable short-term clinical and radiological outcomes along with similar complication rates. The R-PL group showed significantly lower Hb drop, rescue analgesic consumption and shorter LOS. This is a preliminary study and no strong recommendation can be provided. Further prospective randomized trials are requested to further investigate the cost-effectiveness of robotic surgery in THA. LEVEL OF EVIDENCE: Level IV, case-control study.

Isolated adductor longus avulsion in a young semi-professional football player: Imaging contribution and therapeutic considerations.

Adductor longus injuries are usually observed at the proximal musculo-tendinous junction, but isolated tendinous ruptures (i.e., avulsion) at the origin on the pubic bone are uncommon. In this article, we report a new case of isolated adductor longus avulsion that occurred in a young athlete and was treated with conservative therapy. An 18 years old semi-professional football player, in the attempt to reach the ball with his right leg, reported acute pain and functional limitation in his left adductor area. Clinical examination showed tenderness on palpation associated with mild swelling. Manual strength testing of adductor muscles showed weakness and elicited moderate pain in the proximal groin region near the pubic bone. The diagnostic evaluations (ultrasound [3-14 MHz linear probe] and magnetic resonance imaging [1.5 Tesla magnetic field]), performed a few days after the event, showed a complete isolated avulsion of the proximal adductor longus tendon associated with a fluid collection, with a gap of about 9.5 mm from its insertion on the pubic bone. Degenerative alterations (sub-chondral sclerosis, bone edema, erosions, cortical irregularities, calcifications) were found. These findings were crucial in the treatment choice because conservative management is suggested when the gap is below 1 cm and when no important displacement of proximal torn tendon's end at dynamic ultrasound is appreciated. A structured rehabilitation protocol was implemented, allowing the player to come back to his full athletic activity after 146 days. Return to play was allowed when several subjective and objective parameters were fully satisfied (full hip range of motion, pain-free football-specific activities, less than a 5%-10% difference in hip adduction strength between the injured and uninjured legs, advanced anatomical healing of the adductor longus tendon seen on diagnostic exams, and Hip And Groin Outcome Score [HAGOS] scores similar to baseline data). This case report emphasizes the importance of diagnostic imaging and clinical assessments in the management of an adductor longus avulsion with short retraction (about 1 cm). Both imaging techniques are non-invasive and without risks, allow contra-lateral examination and may guide in the treatment choice; moreover, they significantly influence the post-care approach by enabling to fine-tune a safe return to full athletic activity with minor re-injury rate. While US can be used as primary imaging modality, MRI offers a higher level of accuracy.

Surgical treatment of critical size bone defects with Masquelet technique versus bone transport: a systematic review and meta-analysis of comparative studies.

INTRODUCTION: To date, the management of critical-sized bone defects lacks a universally accepted approach among orthopedic surgeons. Currently, the main options to treat severe bone loss include autologous grafting, free vascularized bone transfer, bone transport and induced-membrane technique. The purpose of this study is to critically compare the outcomes of Masquelet technique and bone transport to provide a higher level of evidence regarding the indexed techniques. MATERIAL AND METHODS: The authors conducted a systematic search on several databases according to the PRISMA guidelines. English-written reports comparing outcomes of the Masquelet technique versus the bone transport technique in patients with critical-sized defects in lower extremities were included. RESULTS: Six observational studies involving 364 patients were included. The systematic review and meta-analysis of pooled data showed no significant difference in most outcomes, except for ASAMI bone outcomes and residual deformity, which showed better results in the bone transport group. The 64% of patients treated with Masquelet technique obtained excellent/good bone ASAMI results compared to 82.8% with bone transport (p = 0.01). Post-operative residual deformity was 1.9% with the bone transport method versus 9.7% with the Masquelet technique (p = 0.02). CONCLUSIONS: Both the Masquelet technique and bone transport showed comparable results for the management of critical-sized bone defects of the lower limb. However, these findings must be carefully interpreted due to the high risk of bias. Further prospective randomized controlled trials are necessary to better clarify the strengths and limitations of these two techniques and to identify the variables affecting the outcomes.

Oxidative Stress, Testosterone, Cortisol, and Vitamin D: Differences in Professional Soccer Players of African and Caucasian Origin.

BACKGROUND: Under conditions of intense exercise, the production of free radicals and cortisol increases, whereas blood levels of testosterone and vitamin D decrease. The aim of the study was to evaluate the behavior of these parameters, ethnic differences, and their relationships with overtraining. MATERIALS AND METHODS: Fifty professional soccer players were studied. Oxidative stress, testosterone, cortisol, and vitamin D were collected in pre- and mid-competitive season, and their differences in Africans and Caucasians were evaluated. RESULTS: An increase in oxidative stress was observed in mid-season in both groups, but this was more significant in Africans (386 ± 162.6 vs. 277.8 ± 106.9 UCarr, p = 0.005; 2,965.4 ± 815.8 vs. 2,560.6 ± 608.1 BAP, p = 0.035). Levels of testosterone and vitamin D were higher in August compared to February in all participants; in both months, testosterone levels were higher in Africans (11.5 ± 2.4 vs. 9.1 ± 2.6, p = 0.004; 10.3 ± 1.6 vs. 7.7 ± 2.3, p = 0.000), whereas vitamin D levels were higher in Caucasians (39.4 ± 11.1 vs. 33.4 ± 9.7, p = 0.048; 31.8 ± 9.7 vs. 27.4 ± 9.4, in August and February, respectively). Insufficient/deficient levels of vitamin D were more frequently observed in Africans, but the difference was close to significance only in August. CONCLUSIONS: Although lower levels of vitamin D and higher levels of cortisol and oxidative stress in mid-season in Africans could have a negative influence on performance, no symptoms of overtraining were observed, probably due to higher levels of testosterone which enable homeostatic balance.

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.

Rat bone healing induced by natural nanocrystalline carbonated hydroxyapatite in combination with human amniotic fluid stem cells (AFSCs).

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.

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.

Surgical treatment of displaced intraarticular calcaneal fractures by a minimally invasive technique using a locking nail: A preliminary study.

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 Böhler 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 Böhler 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.

Mid-portion Achilles tendinopathy in runners with metabolic disorders.

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.

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.

Open and arthroscopic lateral ligament repair for treatment of chronic ankle instability: A systematic review.

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 Broström-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 Broström 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.

Achilles tendinopathy in elderly subjects with type II diabetes: the role of sport activities.

BACKGROUND: Exercise is an important therapeutic tool in the management of diabetes in older people. Aim of this study was to assess the relationship among type II diabetes, sport, overweight, and symptomatic Achilles tendinopathy in elderly subjects. METHODS: Thirty-eight patients suffering from Achilles tendinopathy and thirty-eight controls were enrolled. The prevalence of diabetes and sport practice as well as BMI and Glycated Hemoglobin (HbA1c) values were registered. An ultrasound evaluation of Achilles tendon was performed. RESULTS: Patients showed an increased prevalence of diabetes (42 vs. 13.1 %, p = 0.004), and practice of sport (60.5 vs. 28.9 %, p = 0.0001), and higher BMI values (26.8 ± 3 vs. 24.8 ± 2.3, p = 0.001). Sonographic abnormalities, being diagnostic criteria, were present in all the patients with Achilles tendinopathy, but signs of degeneration were also found in 36.8 % of asymptomatic controls. Symptomatic subjects with diabetes, compared to those without, showed a higher prevalence of severe degeneration (75 vs. 36.3 %, p = 0.01). HbA1c values were significantly lower in sport practitioners, both diabetics and non-diabetics. Moreover, patients practicing sport showed a trend towards lower BMI values, compared to the sedentary counterpart. CONCLUSIONS: Sport practice in elderly diabetics provides relevant metabolic advantages, reducing HbA1c and BMI. However, some sport activities (e.g., speed walking, jogging or tennis) can expose to the risk of Achilles tendinopathy. So, sport practice should be encouraged, but practitioners should follow individual training programs and be submitted to periodic sonographic controls.

Tendons Involvement in Congenital Metabolic Disorders.

Congenital metabolic disorders are consequence of defects involving single genes that code for enzymes. Blocking metabolic pathways, the defect leads to the shortage of essential compounds, and/or to the accumulation of huge quantities of precursors, which interfere with normal functions. Only few of these diseases are characterized by a clinically significant tendon involvement.Heterozygous Familial Hypercholesterolaemia results from the inheritance of a mutant low-density lipoprotein receptor gene; patients show high cholesterol levels, precocious coronary artery disease, and may develop tendon xanthomata (mainly in Achilles tendon). The detection of xanthomata is important, because it allows an early diagnosis and treatment of the disorder. Cerebrotendinous Xanthomatosis is a rare genetic metabolic disorder of cholesterol and bile acid metabolism, characterized by accumulation of cholestanol in brain and tendons. Tendon abnormalities are similar to those reported in Heterozygous Familial Hypercholesterolaemia. Alkaptonuria is caused by a deficiency of the enzyme homogentisic acid oxidase. Due to the accumulation of the homogentisic acid, tendons and ligaments are characterized by a typical ochre/yellow pigmentation (ochronosis), with ensuing inflammation, calcification and rupture. In Congenital Hypergalactosemia an increased tendon collagen cross-linking by non-enzymatic galactosylation can be observed. Finally, Congenital Hypophosphatasia may be associated to deposition of hydroxyapatite crystals in rotator cuff, elbow, and Achilles tendons.

How Obesity Affects Tendons?

Several epidemiological and clinical observations have definitely demonstrated that obesity has harmful effects on tendons. The pathogenesis of tendon damage is multi-factorial. In addition to overload, attributable to the increased body weight, which significantly affects load-bearing tendons, systemic factors play a relevant role. Several bioactive peptides (chemerin, leptin, adiponectin and others) are released by adipocytes, and influence tendon structure by means of negative activities on mesenchymal cells. The ensuing systemic state of chronic, sub-clinic, low-grade inflammation can damage tendon structure. Metabolic disorders (diabetes, impaired glucose tolerance, and dislipidemia), frequently associated with visceral adiposity, are concurrent pathogenetic factors. Indeed, high glucose levels increase the formation of Advanced Glycation End-products, which in turn form stable covalent cross-links within collagen fibers, modifying their structure and functionality.Sport activities, so useful for preventing important cardiovascular complications, may be detrimental for tendons if they are submitted to intense acute or chronic overload. Therefore, two caution rules are mandatory: first, to engage in personalized soft training program, and secondly to follow regular check-up for tendon pathology.

Intraforaminal ozone therapy and particular side effects: preliminary results and early warning.

BACKGROUND: The term "low back pain syndrome" represents a complex nosological entity. The therapeutic approach is often only symptomatic and not etiologic. METHODS: Since 2013, 186 patients (97 males and 89 females, mean age 59.8 years) have undergone microsurgery for lumbar disc hernia or lumbar segmental stenosis. Among these patients, 23 had been previously treated with ozone therapy by the intraforaminal approach and 28 by intraforaminal steroid injections in other hospitals between 12 and 24 months before our clinical evaluation. These patients received 16 applications in an 8-week period (standard therapy). RESULTS: During the surgery, many hard adhesions between the soft tissues and bony structures were unexpectedly discovered. In particular, it was noted that the root contracted and had firm adhesions to the dural sac and/or fragmented disc, which were difficult to resolve. These specific pathological patterns were observed only in the patients who received ozone injections by the intraforaminal approach. We did not find any pathological abnormalities in the patients who did not receive any injections or who received intraforaminal steroid injections. Thus, we could exclude that the tissue damage was due to the mechanical action of the needle. CONCLUSION: It is important to assert that ozone therapy procedures can be associated with several major complications. Therefore, performing a revision of the guidelines and protocols for ozone therapy application is indispensable.

Amniotic Fluid Stem Cells: A Novel Source for Modeling of Human Genetic Diseases.

In recent years, great interest has been devoted to the use of Induced Pluripotent Stem cells (iPS) for modeling of human genetic diseases, due to the possibility of reprogramming somatic cells of affected patients into pluripotent cells, enabling differentiation into several cell types, and allowing investigations into the molecular mechanisms of the disease. However, the protocol of iPS generation still suffers from technical limitations, showing low efficiency, being expensive and time consuming. Amniotic Fluid Stem cells (AFS) represent a potential alternative novel source of stem cells for modeling of human genetic diseases. In fact, by means of prenatal diagnosis, a number of fetuses affected by chromosomal or Mendelian diseases can be identified, and the amniotic fluid collected for genetic testing can be used, after diagnosis, for the isolation, culture and differentiation of AFS cells. This can provide a useful stem cell model for the investigation of the molecular basis of the diagnosed disease without the necessity of producing iPS, since AFS cells show some features of pluripotency and are able to differentiate in cells derived from all three germ layers "in vitro". In this article, we describe the potential benefits provided by using AFS cells in the modeling of human genetic diseases.

Zoledronic acid at subtoxic dose extends osteoblastic stage span of primary human osteoblasts.

OBJECTIVE: This study aimed to check the effect of zoledronic acid (ZA) at subtoxic dose on human osteoblasts (HOs) in terms of cell viability, apoptosis occurrence, and differentiation induction. ZA belongs to the family of bisphosphonates (BPs), largely used in the clinical practice for the treatment of bone diseases, often associated with jaw osteonecrosis onset. Their pharmacological action consists in the direct block of the osteoclast-mediated bone resorption along with indirect action on osteoblasts. MATERIALS AND METHODS: HOs were treated choosing the highest limit concentration (10(-5) M) which does not induce toxic effects. Live/dead staining, flow cytometry, mitochondrial membrane potential assay, osteocalcin western blotting, gp38 RT-PCR, collagen type I, PGE2, and IL-6 ELISA assays were performed. RESULTS: Similar viability level between control and ZA-treated samples is found along with no significant increase of apoptotic and necrotic cells in ZA-treated sample. To establish if an early apoptotic pathway was triggered, Bax expression and mitochondrial membrane potential were evaluated finding a higher protein expression in control sample and a good integrity of mitochondrial membrane in both experimental points. Type I collagen secretion and alkaline phosphatase (ALP) activity appear increased in ZA-treated sample, osteocalcin expression level is reduced in ZA-treated cells, whereas no modifications of gp38 mRNA level are evidenced. No statistical differences are identified in PGE2 secretion level whereas IL-6 secretion is lower in ZA-treated HOs with respect to control ones. CONCLUSIONS: These results highlight that ZA, delaying the osteoblastic differentiation process versus the osteocytic lineage, strengthens its pharmacological activity enhancing bone density. CLINICAL RELEVANCE: The knowledge of ZA effects on osteoblasts at subtoxic dose allows to improve therapeutic protocols in order to strengthen drug pharmacological activity through a combined action on both osteoclastic and osteoblastic cells.

In Vitro Behavior of Primary Human Osteoblasts Onto Microrough Titanium Surface.

OBJECTIVE: The aim of this study was to evaluate in vitro the behavior and the biocompatibility of primary human osteoblasts (HOs) grown onto different implant surface. METHODS AND MATERIALS: HOs were cultured onto sandblasted/acid-etched (control group) and sandblasted/acid-etched followed by coating with inorganic ions (test group) experimental titanium discs. At established times, SEM analysis, LDH assay, MTT assay, and enzyme-linked immunosorbent assay for type 1 collagen, interleukin (IL)-6, and PGE2 secretion were performed. RESULTS: Both surfaces promote HOs adhesion and proliferation. After 21 days, cells on test surfaces are well spread, flattened, and attached by cellular extensions, whereas cells on control discs appear mainly elongated. Lower LDH levels and higher values of MTT assay are recorded for cells on test respect to control surfaces at each experimental time. Type 1 collagen release increases until 14 days, significantly decreasing at day 21 in cells grown on both surfaces. IL-6 and PGE2 secretion shows a peak in control group samples at day 7, whereas their levels do not significantly modify in both groups at days 14 and 21. CONCLUSION: Results indicate that the test group surface is more biocompatible, well tolerated, and suitable for supporting osteoblasts growth and proliferation.

Usefulness of rehabilitation in patients with rotator cuff calcific tendinopathy after ultrasound-guided percutaneous treatment.

OBJECTIVE: To evaluate the efficacy of a specific rehabilitation program for patients in whom ultrasound-guided percutaneous treatment (UGPT) was performed for rotator cuff calcific tendinopathy (RCCT). SUBJECTS AND METHODS: In this prospective observational study, 86 patients (22 males and 64 females) with shoulder calcific tendinopathy treated with UGPT were enrolled. At the end of the procedure, a corticosteroid injection into the subacromial-subdeltoid bursa was performed. The patients were then asked to follow a specific rehabilitation protocol (2 times/week for 5 weeks) that focused on mobility, strength and function. At baseline and after 6 weeks, clinical parameters, visual analog scale (VAS) and Constant-Murley scale (CMS) scores and ultrasound (US) features were collected. RESULTS: The mean age of the patients was 48.9 ± 8.4 years and their mean BMI was 22.7 ± 2.1. Considering the whole cohort, the treatment was effective, with a significant decrease in the VAS score and an improvement in the CMS score. Thereafter, on the basis of the compliance to the rehabilitation program (by self-report), 53 and 33 patients were included in the rehabilitation group (Rehab group; performed exercises ≥2 times/week) and the No Rehab group (performed exercises <2 times/week), respectively. The comparison between the groups showed that the subjects who performed the exercises regularly had better results in terms of pain and functional recovery, and less associated diseases (e.g. adhesive bursitis and tenosynovitis of the long head of the biceps) than those who were less compliant with the program. CONCLUSIONS: UGPT, followed by a specific postprocedure rehabilitation program, was an effective treatment for RCCT.