World's First Experience of the Low-Dose Radionuclide Inhalation Therapy in the Treatment of COVID-19-Associated Viral Pneumonia: Phase 1/2 Clinical Trial.

OBJECTIVE: Previously, low-dose radiation therapy was used for pneumonia treatment. We aimed to investigate the safety and effectiveness of carbon nanoparticles labeled with Technetium isotope (99mTc) in a form of ultradispersed aerosol in combination with standard COVID-19 therapy. The study was a randomized phase 1 and phase 2 clinical trial of low-dose radionuclide inhalation therapy for patients with COVID-19 related pneumonia. METHODS: We enrolled 47 patients with confirmed COVID-19 infection and early laboratory signs of cytokine storm and randomized them into the Treatment and Control groups. We analyzed blood parameters reflecting the COVID-19 severity and inflammatory response. RESULTS: Low-dose 99mTc-labeled inhalation showed a minimal accumulation of radionuclide in lungs in healthy volunteers. We observed no significant differences between the groups before treatment in WBC-count, D-dimer, CRP, Ferritin or LDH levels. We found that Ferritin and LDH levels significantly raised after the 7th day follow-up only in the Control group (p < 0.0001 and p = 0.0005, respectively), while mean values of the same indicators did not change in patients in the Treatment group after the radionuclide treatment. D-dimer values also lowered in the radionuclide treated group, however, this effect was not statistically significant. Furthermore, we observed a significant decrease in CD19+ cell counts in patients of the radionuclide-treated group. CONCLUSION: Inhalation low-dose radionuclide therapy of 99mTc aerosol affects the major prognostic indicators of COVID-19- related pneumonia restraining inflammatory response. Overall, we identified no evidence of major adverse events in the group receiving radionuclide.

Ultra early molecular biologic diagnosis of malignant and neurodegenerative diseases by the immunospecific profiles of the proteins markers of the surface of the mobilized autologous hematopoietic stem cells.

The comparative study of the protein markers of the membrane surface of the autologous hematopoietic stem cells (СD34+ СD45+) was performed to detect the patterns of the proteomic profiles, if any. The study included five groups. The subpopulations of the hematopoietic stem cells were studied in 569 samples of the mobilized peripheral blood mononuclear cells from adult cancer cases (group 1), 557 samples from children cancer cases (group 2), 66 samples from amyotrophic lateral sclerosis cases (group 3), 5 samples from other neurodegenerative diseases cases (supplementary group 4) and 61 samples isolated from healthy donors (control group 5). The protein markers of the membrane surface of the autologous hematopoietic stem cells were mapped and profiled with flow cytometry. The specific patterns of the proteomic profiles characteristic for cancer and neurodegenerative disease and different from those of healthy donors were identified. The authors suppose that as far as the HSC is the parent cell of the immune system cells, the modification of its proteomic profile speaks of specific immune insufficiency that not only accompanies the disease but presents the key cause for its onset and precedes its clinical manifestation. Thus, the evaluation of the protein markers of the membrane surface of hematopoietic stem cells can be used for ultra early diagnosis of these diseases.

Azoximer Bromide: Mystery, Serendipity, and Promise.

Azoximer bromide (AZB) was identified as an immunomodulator, and was initially developed and currently successfully indicated as one of several natural polyelectrolytes, a vaccine adjuvant, and an effective agent for the treatment of infectious and inflammatory diseases of viral, bacterial, and fungal origin. AZB has the potential to increase an individual's resistance to local and general infection and is indicated for the treatment of viral infections, and has also demonstrated clinical efficacy in the treatment of a variety of secondary immunodeficiencies. However, AZB may offer long-term promise beyond use against infection. Multiple clinical trials and research studies in cancer patients have reported favourable outcomes with AZB as well as an optimal safety and tolerability profile. The findings raise the possibility of direct antitumor properties. This literature review analyses the novel mechanisms that mediate the AZB direct anticancer effects. Overall, the evidence suggests that AZB has the hallmark of an agent that could be used to support existing cancer treatments at different stages of disease.

Is the ALS a motor neuron disease or a hematopoietic stem cell disease?

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is also known as motor neuron disease (MND) or Lou Gehrig's disease. It is a fatal neurodegenerative disease the cause of which is not clear. The effective therapy is absent. ALS is diagnosed through clinical examination and neurophysiologic tests. Clinically, the symptoms manifest when about 80% of motor neurons are dead. MATERIALS AND METHODS: The hematopoietic stem cells are isolated through administration of the granulocyte colony-stimulating factor from three groups: group 1 of 62 ALS cases, group 2 of 54 ALS-free healthy donors and group 3 of 6 ALS-free ALS-family members. The expression of HLA-DR, CD38, CD117, CD13, CD33, CD56, Thy-1, CD45, СD10, CD71 was assessed in 86 samples of HSCs in ALS group, 61 samples of HSCs in healthy group and 6 samples from ALS-free ALS-family members by the multiparameter flow cytometry. RESULTS: The obtained immunophenotypic profiles of HSCs membrane antigens of the ALS group significantly differ from the ALS-free group, while the immunophenotypic profiles of HSCs membrane antigens of the ALS-family members group are close to the ALS group. DISCUSSION: We suppose that the ALS onset as the disease of HSCs and manifests in the genome and proteome of the HSCs. Such immunophenotypic profiling might permit identification of ALS-specific immune insufficiency and become a tool for early diagnostics of the ALS before clinical manifestation of the disease. New options of the updated therapy of ALS might be developed or corrected considering this new evidence. CONCLUSION: Further research with larger samples and deeper examination is required.