Platelet lysate for the treatment of osteoarthritis: a systematic review of preclinical and clinical studies.

Intra-articular injection-based therapy is often used aside conservative treatment and lifestyle modifications to manage knee osteoarthritis (KO) patients. Conventional injections contain steroids and hyaluronic acid, while more recently multipotential adult stem cell, platelet-rich plasma (PRP), and platelet lysate (PL) injections have been used to promote cartilage regeneration or repair. The aim of the current study is to analyse current evidence on PL injections for the treatment of KO and to determine if these are effective and how these perform compared to other injection regimens. The databases of Scopus, Embase, PubMed, Web of Science, and Cochrane Library were searched on 30 June 2023. Risk of bias was assessed using the SYRCLE tool for animal studies and Cochrane RoB 2 as well as ROBINS-I tool for human studies. Studies were included if these were in English, any year, and regarded animals with osteoarthritis (OA) or human adult patients with OA. In vitro trials and non-adult human studies were excluded. Results on OA symptom stage and severity, and pain were recorded. The research retrieved three human studies (n = 48, n = 25, n = 58) and four animal studies: one rabbit, two studies, and one rat study. PL was found to decrease KO symptoms at follow-up ≤ 1 year with respect to baseline levels and when compared to hyaluronic acid or platelet-rich plasma. Symptoms returned 6 months-1 year after the final administration, with studies showing peak efficacy at approximately 6 months. Animal studies showed clinical improvements, reduction of lameness, and partial effect on the cartilage regeneration of the seven studies, two had a high risk of bias, four were associated to some concerns, and one had low risk. A major source of bias in these studies was the use of questionnaires and scoring that could be subject to interpretation. Overall, PL was well-tolerated and showed efficacy comparable to PRP; when pain control was assessed, it showed similar efficacy compared to hyaluronic acid. These findings may support its use in clinical trials to confirm these initial findings; future research should also focus on the comparison with other non-surgical treatments, on a more detail of the potential regenerative properties, and to optimise the treatment schedule.

Infrapatellar branch of the saphenous nerve lesion following tibial nailing: it is possible to avoid it?

BACKGROUND: Iatrogenic injury to the infrapatellar branches of saphenous nerve is a common complication following tibial nailing. This lesion seems to be directly related to the surgical approach adopted for nail insertion. The aim of the present study was to systematically review the current literature in order to assess the eventual superiority of one surgical approach for tibial nailing over the others in limiting the neurological impairment related to infrapatellar branch injury. MATERIALS AND METHODS: The available literature was systematically screened searching papers dealing with iatrogenic injury to the infrapatellar branch of saphenous nerve after intramedullary tibial nailing. The terms "Saphenous" and "Infrapatellar branch" were used in combination with "intramedullary nailing" and "tibial fractures", supplying no limits regarding the publication year. Only publications in English were considered. Case reports, technical notes, instructional course, literature reviews, biomechanical and/ or in vitro studies were all excluded. Coleman methodological score was performed in all the retained articles. RESULTS: Four articles matched the inclusion criteria. There were one original article and three retrospective study. Hypoesthesia and a larger extension of the area of sensory-loss were more frequently observed after vertical incision approach in three out of four articles. A trend towards a lower rate of iatrogenic nerve damage using a transverse incision was found in the remaining one, without any statistical significance. CONCLUSIONS: In order to avoid infrapatellar nerve lesion, horizontal or oblique incisions or percutaneous approaches should be favored, although in some cases a longitudinal incision is required. Limited-extension incisions could minimize the risk and the incidence of this complication.

Age, Blasts, Performance Status and Lenalidomide Therapy Influence the Outcome of Myelodysplastic Syndrome With Isolated Del(5q): A Study of 58 South American Patients.

BACKGROUND: Myelodysplastic Syndrome (MDS) with isolated deletion 5q is associated with a low risk to leukemic evolution and long overall survival (OS); it comprises 3%-4.5% of MDS cases in Latin America classified according to the World Health Organization 2008. This study aims to describe clinical, laboratory and the outcome of patients according to the newest World Health Organization 2016 proposal. METHODS: We retrospectively reviewed patients from four Brazilian (BR) and four Argentinean (AR) centers diagnosed between 1999 and 2019. RESULTS: The 58 patients (16-AR and 42-BR) presented a median age of 67 (IQR 61-75) years old, women predominance (70.7%) and transfusion dependency (62.5%) at diagnosis. Median hemoglobin level was 8.1g/dL, 27.5% and 44.4% presented thrombocytosis and neutropenia, respectively. Bone marrow (BM) was predominantly hypercellular (43.1%) with 66% showing dysplasia >1 lineage and 37.9% with >2% of blasts. Deletion 5q was mostly isolated (79.3%) and a variety of abnormalities were observed in remaining cases. Most patients were treated with erythropoietin-stimulating agents (ESA), 18 with lenalidomide and 15 with thalidomide. Median follow-up was 7.6 years, with a median OS of 3.5 years and an 8-years leukemic evolution rate of 18.4%. Multivariate analysis showed that age >75 years (HR 2.19), ECOG ≥2 (HR 5.76), BM blasts >2% (HR 2.92) and lenalidomide treatment (HR 0.25) independently influenced the OS. CONCLUSION: Older age, worse performance status and higher percentage of blasts, that can be easily assessed, were associated to a worse prognosis. Also, our results corroborate the protective influence of lenalidomide in terms of OS in this South American series.

Total hip arthroplasty and sexual activity: a systematic review.

Hip discomfort due to degenerative pathologies causes limitations in the everyday activities of patients, including sexual activity. To address such limitations, patients are usually treated with total hip arthroplasty (THA). The aim of this systematic review was to investigate the success of this surgical procedure to ameliorate sexual activity of patients. We performed a comprehensive research of four electronic databases for articles pertaining to the benefits of THA on sexual activity. Exclusion criteria included articles not in English. The search initially yielded 34 articles. Two authors subsequently read all abstracts and excluded all studies unrelated to the topic, leaving 16 articles for further evaluation. Sixteen articles filtered by orthopaedic departments were included in this review. A total of 2391 patients were considered. Pre- and postoperative reports on sexual concerns have been evaluated and compared. The current literature suggests that sexual life is improved after THA. Patient education regarding postoperative expectations and resumption of sexual activity is severely lacking and the majority of surgeons offer little or no information on the subject. Specifically designed studies on the subject are required to evaluate the effects of surgery and approaches on postoperative restrictions.

How to prevent dislocation after revision total hip arthroplasty: a systematic review of the risk factors and a focus on treatment options.

BACKGROUND: Dislocation represents the most common complication after revision total hip arthroplasty (rTHA). Understanding risk factors for dislocation has a great clinical relevance for every hip surgeon in order to consider all surgical options for effective planning. The aim of this systematic review was to answer two main questions-(1) what are the risk factors for instability after rTHA? and (2) what are the best preoperative assessments and surgical options to avoid dislocation after rTHA? MATERIALS AND METHODS: Scientific databases were accessed to identify papers dealing with prevention and treatment of dislocation after rTHA. We performed a search using the keywords 'revision hip arthroplasty' and 'dislocation', 'instability', 'outcome', 'failure', 'treatment'. After removal of duplicates and exclusion of works published in different languages, 33 articles were reviewed completely. RESULTS: Risk factors were analysed in order to establish the most relevant and evidence-based treatments available in the current literature. CONCLUSIONS: The risk of dislocation after rTHA can be reduced using some precautions inferred from the literature. The use of a larger femoral and acetabular component, elevated rim liner and dual mobility implants can significantly reduce the risk of dislocation after rTHA. However, care must be taken regarding patient-related risk factors since these cannot be addressed and modified. Hence, a complete evaluation of risk factors should be performed for each patient and procedure before starting rTHA.

Increased levels of cyclin D1 negatively impacts on acute lymphoblastic leukemia overall survival

Background: Cyclin D1 is a protein essential for transition from G1 to S phase during cell cycle progression, which has an oncogenic potential and is highly expressed in several human malignancies. However, in view of the heterogeneity of the findings in the literature, the prognostic value of cyclin D1 expression still needs to be validated in different cohorts of adult acute lymphoblastic leukemia (ALL) patients. Methods: Bone marrow samples from 13 healthy donors and 45 adult patients with acute lymphoblastic leukemia were included. Cyclin D1 gene expression was evaluated by quantitative PCR. For statistical analysis, Mann­Whitney test, Fisher's exact test, Chi-squared test and Cox regression were used, as appropriate. All p values were two-sided with a significance level of 5%. Results: Cyclin D1 mRNA levels were similar between primary cells from ALL patients and healthy donors. In ALL patients, high cyclin D1 expression was associated with older age at the diagnosis, presence of BCR-ABL1, and lower white blood cell counts. Importantly, increased cyclin D1 expression was an independent factor that predicted worse overall survival in our adult ALL cohort. Conclusion: Increased levels of cyclin D1 negatively impacted on ALL survival outcome, suggesting that this gene is involved in the malignant phenotype of ALL.

Scanning electron, 3D-confocal and stereotactic microscopies morpho-structural analysis of antibiotic-loaded cement porosity in three different formulations.

Chronic osteoarticular infections such as osteomyelitis or periprosthetic joint infection (PJI) have become a growing problem over the years. The "gold standard" in local antibiotic administration is still the antibiotic-loaded acrylic bone cement (ALABC) which is used in both prophylaxis, because it has been shown it can reduce the risk of infection and used in therapy during a "two-stage surgery" in PJI or in chronic osteomyelitis. We performed morphological analysis of three different formulations of antibiotic-loaded cement (ALABC) using techniques of light microscopy, scanning electron microscopy (SEM) and 3D immunofluorescence, in order to explain how the morphological aspects of cement could influence and modulate antibiotic elution.

Saphenous nerve injury during hamstring tendons harvest: Does the incision matter? A systematic review.

PURPOSE: Infrapatellar branch of saphenous nerve injury is a common complication following hamstring graft harvest during anterior cruciate ligament reconstruction. The direction of skin incision performed at proximal tibial metaphysis may affect the rate of iatrogenic nerve damage. Aim of the present systematic review was to evaluate evidence that would substantiate the adoption of one incision over another for hamstring graft harvesting. METHODS: The available literature was systematically screened searching studies dealing with iatrogenic injury to the saphenous nerve after anterior cruciate ligament reconstruction using hamstring tendons. A search was performed using the keywords "Saphenous" and "Infrapatellar branch" in combination with "Anterior cruciate ligament", "arthroscopy" and "hamstrings", supplying no limits regard the publication year. Coleman methodological score was performed in all the retained articles. RESULTS: Five articles matched the inclusion criteria. There were two randomized controlled trials, one prospective comparative study and two retrospective comparative series. Poor methodological quality was found overall. A vertical incision was found to significantly affect the presence of hypoesthesia and the extent of the area of sensory loss in three articles; no difference was registered in one, and a trend towards a lower rate of iatrogenic nerve damage using an oblique incision was found in the remaining one, without any statistical significance. CONCLUSION: Although the low methodological quality of the analysed studies does not permit to draw definitive conclusions, the anatomical course of the nerve along with the results obtained in the available studies seems to suggest lower rate of neurological impairment adopting an oblique incision. This kind of incision may therefore be preferred in the routine clinical practice. LEVEL OF EVIDENCE: Systematic review, Level II.

Surgical treatment of insertional Achilles tendinopathy: a systematic review.

Insertional Achilles tendinopathy is a frequent cause of pain and performance impairment of the ankle. It is more common in runners, but may also affect general population. Conservative treatment is the gold standard in the early phases but 10% to 30% of patients require surgery. The aim of this study is to review the current literature in order to evaluate current surgical strategies for Insertional Achilles tendinopathy and to analyze the effectiveness of the available techniques. We performed a systematic review of the literature, to identify studies reporting clinical outcome after surgical treatment for Insertional Achilles tendinopathy in any population group with at least 6 months follow-up. The quality of the articles included was evaluated by the Coleman Methodology Score and correlated with the reported outcome and year of publication. We identified 16 studies reporting on 465 surgically treated Insertional Achilles tendinopathy with a mean follow-up of 29.8 months. Average age at the time of surgery was 53 years. Two different categories of surgical treatment were distinct: debridement alone or debridement with augmentation in case of excessive tendon loss. Results were excellent or good in 89.6% of cases and fair or poor in 10.4%. Average complications rate was 18.3%, with 15.7% of minor and 2.6% of major complications with no difference in the two groups. Negative correlation was found between Coleman Methodology Score and the reported outcome and positive correlation was found between Coleman Methodology Score and year of publication. Good or excellent outcome can be expected after surgical treatment for Insertional Achilles tendinopathy whatever the adopted procedure, but there is no specific evidence regarding which surgical technique provides a better outcome or a lower rate of complications. Research with higher levels of evidence and methodology that is more rigorous are needed in order to evaluate the optimal surgical strategy for patients with IAT.

Is a minimally invasive anterior approach effective in old patients? A pilot study.

Minimally invasive approach to the hip is a blood preserving surgery, with rapid rehabilitation, and low dislocation rate. Intuitively, these characteristics render this approach extremely suitable in the elderly patient. The aim of this study was to analyze the early clinical and radiographic results in the first 30 consecutive patients above 70 years of age undergoing THR through a minimally invasive anterior approach. Clinical evaluations showed an improvement of the Harris Hip Score and WOMAC score after surgery. Radiographic assessment showed cup orientation averaging 47° (range 40°–59°) and no valgus stem aligned. Allogeneic blood transfusion was required in only 6 patients (19.8%). One patient experienced an intraoperative fracture of the greater trochanter. No early implant dislocation was observed in the study population. In conclusion we advise a minimally invasive anterior approach for THR in older patients when a careful patient selection has been done.

Congenital forward shoulder with clavicle hypoplasia: surgical lengthening by intercalary graft positioning and plate fixation.

BACKGROUND: Congenital forward shoulder with clavicular hypoplasia is a rare disease which can be caused by an alteration of clavicular development in such a way that the clavicles are short. Symptoms are often absent; in most cases the main problem is represented by the cosmetic implications. There is no general consensus about the correct management, and surgery is the only way to correct the deformity. MATERIALS AND METHODS: The aim of the study is to describe a new surgical treatment in patients with congenital forward shoulder and clavicular hypoplasia. In 2010, three patients suffering from bilateral congenital forward shoulder were managed surgically by a intercalary graft positioning with plate fixation aimed at the elongation of the clavicles. RESULTS: Patients were followed by up to 2 years. All the patients treated were satisfied with the results, regarding the resolution of mild pain, but especially from the cosmetic point of view. CONCLUSION: The intercalary graft positioning was found to be easy to perform and allowed an elongation of the clavicles with immediate stability.

Surgical treatment of neglected congenital idiopathic talipes equinovarus after walking age in Eritrea: an Italo-Eritrean cooperation.

An Italian team of orthopaedic surgeons joined Eritrean colleagues to perform a clinical study in ambulating children affected by neglected idiopathic congenital talipes equinovarus (clubfoot). This study reports the surgical strategy as well as clinical outcomes, early complications and relapse at a mid-term follow-up. Four expeditions of 7 days were organized between 2012 and 2015 from Italy to the Halibet Hospital of Asmara in Eritrea. In each expedition were included two experienced surgeons, two assistants and one anaesthesiologist. During these expeditions, a total of 468 patients were evaluated together with Eritrean colleagues and 45 cases of neglected talipes equinovarus in ambulating children were diagnosed and selected for surgery. Follow-up range was 1-3 years. During the four expeditions, the Eritrean team of orthopaedic surgeons learned to manage most cases of neglected talipes equinovarus. No major complications were reported. Sixteen feet were considered excellent, 25 good and four poor. No overcorrections were observed. Neglected congenital talipes equinovarus is the result of delayed treatment of congenital deformity in developing countries, and its treatment often requires extensive surgery. Collaboration with foreign expert surgeons may help local doctors to learn how to treat this disease. The current study demonstrates that surgical expeditions in developing countries, when organized in collaboration with local doctors, help to manage on site this severe deformity.

Marchetti Vicenzi elastic retrograde nail in the treatment of humeral shaft fractures: review of the current literature.

Shoulder impairment following anterograde intramedullary nailing for humeral shaft fractures represents a challenging problem for the orthopedic surgeon. Traditional retrograde nailing lowers the rates of shoulder impairment although exposing the surgeons to severe technical issues related to the proximal interlocking. The Marchetti Vicenzi nail (MVN) permits a retrograde insertion along with a self-locking mechanism that lowers the risk of iatrogenic damage during proximal interlocking. Aim of this literature review was to evaluate all the case series dealing with MVN and the obtained results in terms of union rates, complications, and functional outcomes in order to evaluate evidence that would substantiate the adoption of MVN in the treatment of humeral shaft fractures. A search was performed using the keywords "humeral shaft fracture nail," "humeral retrograde nail," "humeral elastic nail," "Marchetti Vicenzi nail," "Marchetti nail," "Vicenzi nail." After accurate revision 13 articles found to be relevant with a total of 532 humeral fractures (traumatic and pathologic) and non-unions treated with MVN. The cumulative healing rate reported is 93.7 % with 6.3 % of non-unions. Despite the fact that obtained results compare favorably to the published data on the outcome of anterograde nailing, the evaluated studies presented a huge number of methodological flaws, thus making it difficult to recommend the adoption of MVN in preference of other better-validated forms of treatment.

Preservation of hamstring tibial insertion in anterior cruciate ligament reconstruction: a review of the current literature.

Hamstring graft (HG) used in anterior cruciate ligament (ACL) reconstruction undergoes a biological modification process called "ligamentization" in the early postoperative period that proceeds through three different phases: an early graft-healing phase with central graft necrosis, a phase of proliferation, and finally, a ligamentization phase toward the properties of the intact ACL. The fastening of this process could result in more aggressive rehabilitation protocols as well as faster sport resumption. A recent literature supports the preservation of HG tibial attachment in order to enhance "ligamentization" process. Aim of this literature review is to describe all the techniques described that spare HG tibial insertion and the obtained results in order to evaluate evidence that would substantiate the maintenance of HG tibial insertion in ACL reconstruction. A search was performed using the following keywords "ACL reconstruction" in combination with "hamstrings," "hamstrings insertion," "tibial insertion," "ligamentization," and "over the top"; 18 articles were found to be relevant. Among these, eight randomized clinical trials (RCTs) were found. The RCT analyzed presented a high number of biases regarding the analyzed topic, thus making impossible to draw definitive evidences to validate HG tibial insertion sparing in ACL reconstruction. Despite the satisfactory results in many clinical series and the promising results in anatomic and animal studies, well-designed prospective clinical trials with large cohort of patients associated with MRI evaluation are mandatory to assess the beneficial effects of HG attachment preservation in ACL reconstruction.

Minimally invasive technique for curettage of chondroblastoma using endoscopic technique.

Chondroblastoma is a rare benign bone tumor. The treatment for chondroblastoma usually consists of curettage of the lesion and packing the tumor cavity with bone grafts or bone cement. However, chondroblastomas are known to recur in 10% to 20% of cases after excision, possibly because the incomplete removal of pathological tissue at surgery. We present a case of chondroblastoma in the distal femur treated by endoscopic curettage, which allowed a complete resection of tumor tissue and a minimal damage of the bone. The patient had relief of symptoms, rapid function restoration and no local recurrence. Endoscopic curettage is a promising new treatment for chondroblastoma. In fact, the extra-articular technique enters the tumor cavity via a tunnel drilled through the medullary canal, allowing to visualize possible residual tumor tissue or defects of the articular surface, without violating the joint and without taking away a much bigger cortical window.

Impact of molecular mutations on treatment response to DNMT inhibitors in myelodysplasia and related neoplasms.

We hypothesized that specific molecular mutations are important biomarkers for response to DNA methyltransferase inhibitors (DNMT inhibitors) and may have prognostic value in patients with myelodysplastic syndromes (MDS). Mutational analysis was performed in 92 patients with MDS and related disorders who received 5-azacytidine (n=55), decitabine (n=26) or both (n=11). Mutational status was correlated with overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) by univariate and multivariate analysis. Risk stratification models were created. TET2, DNMT3A, IDH1/IDH2, ASXL1, CBL, RAS and SF3B1 mutations were found in 18, 9, 8, 26, 3, 2 and 13% of patients, respectively. In multivariate analysis, TET2(MUT) and/or DNMT3A(MUT) (P=0.03), platelets > or = 100 × 10(9)/l (P=0.007) and WBC<3.0 × 10(9)/l (P=0.03) were independent predictors of better response. TET2(MUT) and/or DNMT3A(MUT) (P=0.04) status was also independently prognostic for improved PFS, as were good or intermediate cytogenetic risk (P<0.0001), age<60 (P=0.0001), treatment with both 5-azacytidine and decitabine (P=0.02) and hemoglobin > or = 10 g/dl (P=0.01). Better OS was associated with ASXL1(WT) (P=0.008) and SF3B1(MUT) (P=0.01), and, similar to PFS, cytogenetic risk (P=0.0002), age (P=0.02) and hemoglobin (P=0.04). These data support the role of molecular mutations as predictive biomarkers for response and survival in MDS patients treated with DNMT inhibitors.

Lack of association between MDM2 SNP309 and TP53 Arg72Pro polymorphisms with clinical outcomes in myelodysplastic syndrome.

MDM2/p53 pathway plays an important role in the control of apoptotic and proliferation mechanisms, and alterations in this pathway have been described in myelodysplastic syndromes (MDS). We investigated the frequency of MDM2 SNP309, TP53 Arg72Pro polymorphisms in de novo MDS and the association of these polymorphisms with clinical characteristics. Our results showed that the frequencies of genotypes for MDM2 SNP309 and TP53 Arg72Pro did not differ between MDS and healthy controls and that these polymorphisms were not associated with clinical and laboratory parameters, disease progression and overall survival, suggesting that MDM2 and TP53 polymorphisms are not involved in risk for MDS, or in the clinical and laboratory characteristics of the disease.

Alumina-on-alumina hip implants: A wear study of retrieved components.

Alumina-alumina bearings are among the most resistant to wear in total hip replacement. Examination of their surfaces is one way of comparing damage caused by wear of hip joints simulated in vitro to that seen in explanted bearings. The aim of this study was to determine whether second-generation ceramic bearings exhibited a better pattern of wear than those reported in the literature for first-generation bearings. We considered both macro- and microscopic findings. We found that long-term alumina wear in association with a loose acetabular component could be categorised into three groups. Of 20 specimens, four had 'low wear', eight 'crescent wear' and eight 'severe wear', which was characterised by a change in the physical shape of the bearing and a loss of volume. This suggests that the wear in alumina-alumina bearings in association with a loose acetabular component may be variable in pattern, and may explain, in part, why the wear of a ceramic head in vivo may be greater than that seen after in vitro testing.

The impact of several phenotypic features at diagnosis on survival of patients with myelodysplastic syndromes.

Multiparametric flow cytometry is a useful co-criterion for diagnostic confirmation of MDS in patients with peripheral cytopenias and a normal karyotype. We examined the impact on patients' survival of several phenotypic aberrancies detected by a small 4-color panel of monoclonal antibodies (MoAbs). Diagnosis of the patients (54) was made by WHO criteria using peripheral blood counts, bone marrow (BM) morphology and karyotype. Flow cytometry was performed at diagnosis, and features obtained were compared to normal BM (24). We could detect 16 alterations: 4 in granulocytic precursors, 4 in monocytes, 6 in CD34+ cells, beside changes in plasmacytoid dendritic cells and basophil precursors. The total number of changes in RAEB was higher (median 8) than in cases with of abnormalities) were independent risk factors for a shorter survival. Our panel was sufficient to confirm the diagnosis of MDS and permitted to detect independent prognostic features.