Allogeneic platelet-derived growth factors local injection in treatment of tennis elbow: a prospective randomized controlled study

Purpose The purpose of this study aimed to evaluate the efficacy of local injection of allogeneic platelet-derived growth factors in treatment of patients with tennis elbow. Patients and methods This study included 120 tennis elbow patients randomly divided into two groups. The patients were locally injected with allogeneic growth factors (treatment group) or with normal saline (control group). The outcomes were assessed using Patient-Related Tennis Elbow Evaluation (PRTEE) and quick Disabilities of the Arm, Shoulder and Hand (qDASH) scales. The clinical outcomes were accordingly classified as excellent, good and poor. The patient’s satisfaction and adverse effects were also recorded. Results There was no statistically significant difference between the two groups regarding the age, gender, dominant arm or the pre-injection scores. At three month follow-up, the reductions in the mean PRTEE and qDASH scores were 88.7% and 70.6% in the treatment group versus 21.8% and 14.9% in the control group, respectively. At the last follow-up, the outcomes in the treatment group were excellent in 85% of patients and good in 15%, versus 8% and 32% in the control group. Overall, 95% were satisfied in the treatment group compared to 25% in control group. Forty patients in the treatment group experienced mild transient post-injection pain. Conclusion This study strongly suggests that local injection of allogeneic platelet-derived growth factors could be a promising safe treatment option for tennis elbow with significant pain relief, functional improvement and patient’s satisfaction. Yet, additional larger studies are needed to assess the durability of these outcomes.

Stroke - shoulder pain and upper limb function

Introduction: Stroke causes disability and pain, especially shoulder pain. Often, shoulder pain, has a not completely known mechanism and evolution.1,2 Objectives: Assess shoulder pain and its impact in upper limb function, in patients who had suffered a stroke within 6 months. Methods: Observational study. Included patients at discharge from an inpatient rehabilitation centre, from November 2019 until February 2020. Assessment was done using validated Portuguese versions of the Brief Pain Inventory (BPI) and Fugl Meyer Assessment Scale (FMAS). Results: Of 32 patients screened, 26 fulfilled the inclusion criteria, 7 were females (26,9 %), with mean age of 60,7±10 years. Mean values of BPI Severity and Interference were 3,2±1,6 and 2,4±1,8, respectively. The mean values of the FMAS Motor Function and Passive Articular Movement were 38,8±23,2 and 20,3±2,3, respectively. Analysing the association between both subscales of BPI and both Subscales of FMAS negative correlations were found to be statistically significant with a confidence interval of 95% but there was no correlation between BPI Severity and FMAS motor function. Six patients (23%) received a local injection for shoulder pain. Analysing both groups, BPI Severity and both subscales of FMAS showed a statistically significant difference (p values of 0,0083, 0,0031 and 0,0056, respectively) for a Wilcoxon/Kruskal-Wallis test with a confidence interval of 95%. Discussion/Conclusions: Patients with voluntary upper limb movements after a stroke tend to have less shoulder pain. Local injection was an effective intervention for shoulder pain. The greatest limitation of this study is the small sample size.

Results of use of polyacrylamide gel Noltrexsin in patients with different grades of gonarthrosis in outpatient practice

Introduction. Osteoarthritis of the knee joints is the most common joint disease affecting more than 80% of people over 55 years of age. The priority method for the treatment of gonarthrosis is the use of local injection therapy with the introduction of synovial fluid endoprostheses based on hyaluronic acid, included in the Second Step of the ESCEO 2019 algorithm. Viscoelastic polyacrylamide gels for intra-articular administration since 2003 have also shown their high effciency in the symptomatic OA treatment. Since 2018, the new 3rd generation PAAG endoprosthesis of synovial fluid, Noltrexsin, has been actively used.Objective. To compare the efficacy and safety of Noltrexsin viscoprosthesis use with oral NSAIDs in patients with grade I-III of gonarthrosis.Materials and methods. 40 patients with gonarthrosis participated in a comparative study of the effcacy and safety of injection therapy Noltrexsin 4.0 ml No. 2 (study group, А) and oral administration of NSAIDs 200 mg per day (comparison group, В). NSAIDs were taken in groups A and B, the duration of therapy in both groups was 1 month. The results were evaluated by standard examination methods, including measuring the range of motion in the joint and scoring of physical signs, tests with walking up the stairs and at a distance, VAS, WOMAC, Lequesne Index.Results. In group А, a more signifcant reduction in pain according to VAS was revealed to 15–20 mm at the grade I–II of gonarthrosis and up to 25–30 mm in the grade III, a decrease in the Lequesne index to 1–2 and 3–4 points, respectively. In group В with a standard therapy, and then on-demand within 6 months, a decrease in VAS was revealed on the 8–9th day, and after 6 months the level of pain at the grade I–II did not exceed 20–25 mm, at the grade 3 it did not decrease below 40–45 mm. The Lequesne Index decreased to 2 points at the grade I–II and to 6–7 points at the grade III. Changes of WOMAC index correlated with VAS.Conclusions. 1. Noltrexsin can be used as a safe endoprosthesis of synovial fluid in the form of local injection therapy in patients with insufficient effect of chondroprotectors and NSAIDs. 2. Noltrexsin is recommended for use at all stages of arthrosis, as well as in comorbid patients.

Intrapleural Injection of Anti-PD1 Antibody: A Novel Management of Malignant Pleural Effusion

BackgroundMalignant tumors accompanied with malignant pleural effusion (MPE) often indicate poor prognosis. The therapeutic effect and mechanism of intrapleural injection of anti-programmed cell death protein 1 (PD1) on MPE need to be explored.MethodsA preclinical MPE mouse model and a small clinical study were used to evaluate the effect of intrapleural injection of anti-PD1 antibody. The role of immune cells was observed via flow cytometry, RNA-sequencing, quantitative PCR, western blot, immunohistochemistry, and other experimental methods.ResultsIntrathoracic injection of anti-PD1 monoclonal antibody (mAb) has significantly prolonged the survival time of mice (P = 0.0098) and reduced the amount of effusion (P = 0.003) and the number of cancer nodules (P = 0.0043). Local CD8+ T cells participated in intrapleural administration of anti-PD1 mAb. The proportion of CD69+, IFN-γ+, and granzyme B+ CD8+ T cells in the pleural cavity was increased, and the expression of TNF-α and IL-1β in MPE also developed significantly after injection. Local injection promoted activation of the CCL20/CCR6 pathway in the tumor microenvironment and further elevated the expression of several molecules related to lymphocyte activation. Clinically, the control rate of intrathoracic injection of sintilimab (a human anti-PD1 mAb) for 10 weeks in NSCLC patients with MPE was 66.7%. Local injection improved the activity and function of patients’ local cytotoxic T cells (CTLs).ConclusionsIntrapleural injection of anti-PD1 mAb could control malignant pleural effusion and the growth of cancer, which may be achieved by enhancing local CTL activity and cytotoxicity.

Electron microscopic and pathological changes of lung cancer after intratumoral injection of sodium bicarbonate

Background: Lung cancer can be treated with surgery, chemotherapy, radiation therapy, targeted therapy and palliative care. Palliative therapy is applied for inoperable lung cancer as it induces tumour necrosis. PH of tumour tissue is acidic; application of sodium bicarbonate (SB) into lung cancer locally via bronchoscopy can change its core pH, which may lead to tumour destruction. We aimed to study the ultrastructural characteristics of lung cancer and to assess the destructive effects of sodium bicarbonate 8.4% local injection on tumour tissue integrity by light and electron microscopies. Methods: This study was conducted on 21 patients with central bronchial carcinoma diagnosed according to WHO classification 2015. Three bronchoscopic biopsies were taken; two biopsies before and one after injection of sodium bicarbonate 8.4% solution of 20 ml via transbronchial needle. All biopsies were examined by both light and electron microscopes. The first biopsy was examined to diagnose the tumour morphologically with and without immunostaining. Second and third biopsies were taken before and after SB 8.4% injection to compare pathological changes in tumour tissue integrity as well as cellular ultra-structures. Different lung cancer pathological types were included in the study. Results: Tumour tissue integrity and pathological changes were examined in biopsies before and after injection of sodium bicarbonate 8.4%. Extensive necrosis in all cell types of lung cancer was seen after injection of SB; this important finding was delineated by both light and electron microscopies. Conclusion: Preliminary ultrastructural study of small biopsy of lung tumor has a complementary role to both morphological and immunohistochemical studies. Local injection of sodium bicarbonate into lung cancer induces extensive necrosis that may reflect its important therapeutic role in lung cancer.

All-viral tracing of monosynaptic inputs to single birthdate-defined neurons in the intact brain

Neuronal firing patterns are the result of inputs converging onto single cells. Identifying these inputs, anatomically and functionally, is essential to understand how neurons integrate information. Single-cell electroporation of helper genes and subsequent local injection of recombinant rabies viruses enable precise mapping of inputs to individual cells in superficial layers of the intact cortex. However, access to neurons in deeper structures requires more invasive procedures, including removal of overlying tissue. We have developed a method that through a combination of virus injections allows us to target ≤4 hippocampal cells 48% of the time and a single cell 16% of the time in wildtype mice without the use of electroporation or tissue aspiration. We identify local and distant monosynaptic inputs that can be functionally characterised in vivo. By expanding the toolbox for monosynaptic circuit tracing, this method will help further our understanding of neuronal integration at the level of single cells.

Mesenchymal Stem Cells and NF-κB Sensing Interleukin-4 Over-Expressing Mesenchymal Stem Cells Are Equally Effective in Mitigating Particle-Associated Chronic Inflammatory Bone Loss in Mice

Wear particles from total joint arthroplasties (TJAs) induce chronic inflammation, macrophage infiltration and lead to bone loss by promoting bone destruction and inhibiting bone formation. Inhibition of particle-associated chronic inflammation and the associated bone loss is critical to the success and survivorship of TJAs. The purpose of this study is to test the hypothesis that polyethylene particle induced chronic inflammatory bone loss could be suppressed by local injection of NF-κB sensing Interleukin-4 (IL-4) over-expressing MSCs using the murine continuous polyethylene particle infusion model. The animal model was generated with continuous infusion of polyethylene particles into the intramedullary space of the femur for 6 weeks. Cells were locally injected into the intramedullary space 3 weeks after the primary surgery. Femurs were collected 6 weeks after the primary surgery. Micro-computational tomography (μCT), histochemical and immunohistochemical analyses were performed. Particle-infusion resulted in a prolonged pro-inflammatory M1 macrophage dominated phenotype and a decrease of the anti-inflammatory M2 macrophage phenotype, an increase in TRAP positive osteoclasts, and lower alkaline phosphatase staining area and bone mineral density, indicating chronic particle-associated inflammatory bone loss. Local injection of MSCs or NF-κB sensing IL-4 over-expressing MSCs reversed the particle-associated chronic inflammatory bone loss and facilitated bone healing. These results demonstrated that local inflammatory bone loss can be effectively modulated via MSC-based treatments, which could be an efficacious therapeutic strategy for periprosthetic osteolysis.