New Translational Trends in Personalized Medicine: Autologous Peripheral Blood Stem Cells and Plasma for COVID-19 Patient

The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), still remains a severe threat. At the time of writing this paper, the second infectious wave has caused more than 280,000 deaths all over the world. Italy was one of the first countries involved, with more than 200,000 people reported as infected and 30,000 deaths. There are no specific treatments for COVID-19 and the vaccine still remains somehow inconclusive. The world health community is trying to define and share therapeutic protocols in early and advanced clinical stages. However, numbers remain critical with a serious disease rate of 14%, ending with sepsis, acute respiratory distress syndrome (ARDS), multiple organ failure (MOF) and vascular and thromboembolic findings. The mortality rate was estimated within 2–3%, and more than double that for individuals over 65 years old; almost one patient in three dies in the Intensive Care Unit (ICU). Efforts for effective solutions are underway with multiple lines of investigations, and health authorities have reported success treating infected patients with donated plasma from survivors of the illness, the proposed benefit being protective antibodies formed by the survivors. Plasma transfusion, blood and stem cells, either autologous or allograft transplantation, are not novel therapies, and in this short paper, we propose therapeutic autologous plasma and peripheral blood stem cells as a possible treatment for fulminant COVID-19 infection.

Longitudinal characterisation of phagocytic and neutralisation functions of anti-Spike antibodies in plasma of patients after SARS-CoV-2 infection.

Phagocytic responses by effector cells to antibody or complement-opsonised viruses have been recognized to play a key role in anti-viral immunity. These include antibody dependent cellular phagocytosis mediated via Fc-receptors, phagocytosis mediated by classically activated complement-fixing IgM or IgG1 antibodies and antibody independent phagocytosis mediated via direct opsonisation of viruses by complement products activated via the mannose-binding lectin pathway. Limited data suggest these phagocytic responses by effector cells may contribute to the immunological and inflammatory responses in SARS-CoV-2 infection, however, their development and clinical significance remain to be fully elucidated. In this cohort of 62 patients, acutely ill individuals were shown to mount phagocytic responses to autologous plasma-opsonised SARS-CoV-2 Spike protein-coated microbeads as early as 10 days post symptom onset. Heat inactivation of the plasma prior to use as an opsonin caused 77-95% abrogation of the phagocytic response, and pre-blocking of Fc-receptors on the effector cells showed only 18-60% inhibition. These results suggest that SARS-CoV-2 can provoke early phagocytosis, which is primarily driven by heat labile components, likely activated complements, with variable contribution from anti-Spike antibodies. During convalescence, phagocytic responses correlated significantly with anti-Spike IgG titers. Older patients and patients with severe disease had significantly higher phagocytosis and neutralisation functions when compared to younger patients or patients with asymptomatic, mild, or moderate disease. A longitudinal study of a subset of these patients over 12 months showed preservation of phagocytic and neutralisation functions in all patients, despite a drop in the endpoint antibody titers by more than 90%. Interestingly, surface plasmon resonance showed a significant increase in the affinity of the anti-Spike antibodies over time correlating with the maintenance of both the phagocytic and neutralisation functions suggesting that improvement in the antibody quality over the 12 months contributed to the retention of effector functions.

THE USE OF A DIODE LASER IN THE TREATMENT OF DRUG-ASSOCIATED OSTEONECROSIS OF THE JAW (CLINICAL CASE)

Object of research. Drug-associated osteonecrosis of the jaw is a complication of therapy with osteo-modifying agents. Several theories of its pathogenesis have been deduced, but there is no uniform treatment plan that would reduce the risk of relapse and allow timely prevention. The research aims to demonstrate the effectiveness of the intraoperative use of a diode laser in the treatment of drug-associated osteonecrosis of the jaw. Methodology. The article presents the case of treatment of 60-year-old patient with drug-associated osteonecrosis of the jaw. The underlying medical condition is Bence-Jones myeloma, Stage III on the Durie-Salmone Staging System, with the Th1 – Th12, L1 – L5 involvement. A laser surgical device with a diode laser with a wavelength of 980 nm, power of 0.1-20 W, with a continuous pulse type was used intraoperatively for ablation of residual granulations. An APRF clot was placed at the bottom of the wound. On the 5th and 10th days, autologous plasma injections were performed in the area of surgical treatment. Results. Low pain syndrome during the postoperative period, immediate agglutination, no relapse a month after surgery, closure of the cortical plates according to the control CT scan results. Conclusion. Thus, the first case of clinical use of a diode laser in the treatment of drug-associated osteonecrosis of the jaw has demonstrated its effectiveness. It cannot completely replace the traditional methods, but diode laser is an important auxiliary instrument which contributes to the rehabilitation of the focus of infection, stimulates reparative processes both in the mucous membrane and in the bone. Its future application in the treatment of drug-associated osteonecrosis of the jaw is promising and might prove its effectiveness in reducing the frequency of relapses.

A multidisciplinary approach to the comprehensive treatment of edentulous patients with perioral wrinkles of the skin

Objectives: The purpose of this study was to comparative analysis of effectiveness of isolated use of intradermal injections of modified hyaluronic acid (Hyalorepair 04) and its combination with platelet-rich autologous plasma in edentulous patients with perioral wrinkles of the skin. Materials and Methods: A total of 56 patient’s presence of perioral wrinkles of the skin participate in the study after dental implant prosthodontics rehabilitations. They were randomly divided into 2 groups in accordance with the applied therapy method (29 isolated implementation of modified hyaluronic acid bio-repairing and 27 bio-repairing combined with autologic plasmotherapy). Treatment included implant-prosthetic rehabilitation followed by hyaluronic acid injections in order to correct cheek-zygomatic sulcus, nasolabial folds and marionette wrinkles. Preparations in an amount from 1 to 4 ml were injected into the face area, depending on the zones to be corrected at the request of the patients. Results: The complex treatment restored the aesthetic profile of the face and oral cavity and increased the effectiveness of the chewing function. On M03 and M05, 2/3 of patients had significant improvement as assessed by physician and patient according to GAIS. Most of the patients also showed significant improvement at visit M12. Conclusion: A multidisciplinary approach to the treatment of edentulous patients with perioral wrinkles increases the functional and aesthetic effect of the treatment. Implementation of combined of bioreparation and autologous plasmotherapy is significantly more effective comparatively to the isolated implementation of modified hyaluronic acid. Keywords: Facial Esthetic; Implant-Prosthetic Rehabilitation; Hyaluronic Acid

Evaluation and Implementation of Biocompatible Methods for the Cross-linking of Plasma Proteins

Autologous plasma proteins can be used to fabricate patient specific cardiovascular implants but need to be cross-linked to increase their mechanical strength and reduce water solubility. Glutaraldehyde is the state-of-the-art solution but its reaction products have been shown to be cytotoxic and pro-inflammatory. In this work, it has been shown, that cross-linking of plasma proteins with biocompatible alternatives to glutaraldehyde is possible. This was achieved by identifying four candidate substances (thrombin, transglutaminase, genipin, EDC) from current literature and investigating their ability to cross-link porcine plasma proteins in vitro. The degree of crosslinking was examined using calorimetric (DSC) and spectroscopic (FTIR, Raman) methods, mapping the influence of cross-linking on the denaturation temperature and primary amino-group content of the proteins. It could be shown that thrombin, genipin and EDC are able to cross-link plasma proteins to a satisfactory degree and thus represent useful alternatives to glutaraldehyde. Transglutaminase, on the other hand, could not sufficiently cross-link the plasma proteins and was therefore ruled out as an alternative.

VAGINAL PLATELET-RICH PLASMA ADMINISTRATION TO IMPROVE FEMALE SEXUAL SATISFACTION

Objective:To investigate the effect of platelet-rich plasma (PRP) injection to the lower one-third of the anterior vaginal wall on sexual function, orgasm, in women with sexual dysfunction by scoring with FSFI. Materials and Methods:Three sessions of PRP (platelet rich human autologous plasma) were administered to the anterior vaginal wall of fiftyfemale patients with sexual dysfunctiondiagnosed by FSFI scoring card obtained in JAM clinic in Benha city Egypt and orgasmic disorder. Female Sexual Function Index (FSFI) total score ≤26 orgasmic subdomain score ≤3.75 were considered having sexual dysfunction and recruited in the study. Results:Following the application of the PRP, the total FSFI score was observed as 27.7±4.5 and the total score was 26 and above in patients having sexual dysfunction (p<0.001). Orgasm subdomain scores were found as 2.2±1.2 before the PRP treatment and 4.4±1.06 at the third dose after (p<0.001). Conclusion:PRP administration to the distal anterior vaginal wall improved female sexuality with high satisfaction by using multiple sessions (three month).

Effects of trypsin on aggregation, disaggregation and aggregate morphology of red blood cells in autologous plasma and serum

We study the influence of trypsin on aggregation, disaggregation, and aggregate morphology of RBCs in autologous plasma and serum. The effect of trypsin on the surface charge of red blood cells and the aggregation of glutaraldehyde fixed cells after treatment with the enzyme was also studied. RBC aggregation was studied by means of an aggregometer and microscopic observations. The results obtained in this study indicate that trypsin treatment increases RBCs aggregation in autologous plasma and serum. The disaggregation of erythrocytes after trypsin treatment considerably decreased in autologous plasma and serum. Increase in the strength of red blood cell aggregates was observed in autologous plasma and serum. The microscopic images of RBCs aggregates indicate the formation of globular (pathologic) structures of aggregates in autologous plasma and serum. Trypsin decrease the surface charge of RBCs. In autologous plasma and serum, the cup shapes of RBCs appear. The control RBCs fixed with glutaraldehyde were not aggregated after their placement in autologous plasma. At the same time, red blood cells pretreated with trypsin and fixed with glutaraldehyde interact with each other in autologous plasma. The physiological significance of glycoproteins of erythrocyte surface for RBCs aggregation was discussed.

Efficacy of autologous plasma microneedling with cells in patients with post-acne atrophic scars

Objective: to studythe effectiveness of autologous plasma-cell microneedling in patients with different phenotypes of post-acne atrophic scars. Group 1A (n = 32) included patients with post – acne atrophic scars: ice pick – 12 patients; boxcar – 11; rolling – 9 patients. Group 1B consisted of 34 patients with scars ice pick – 12; boxcar – 12; rolling – 10 patients. In group 1A, patients underwent a microneedling procedure. In group 1B, microneedling was performed with autologous plasma with cells. To evaluate the effectiveness of the therapy methods, we used the IGA (Investigators Global Assessment) scale modified for post-acne scars, adapted for post-acne scars by the Assessment of the Psychological and Social Effects of Acne (APSEA). Special methods included ultrasound examination using an ultrasound scanner IU 22. The end result for different post-acne scar phenotypes showed the advantages of the developed complex for boxcar and rolling AR and slightly lower for ice pick. The recommended course of therapy is three procedures performed once in 4 weeks.