Accessibility and quality of medical care for patients with chronic noncommunicable diseases during COVID-19 pandemic.

The purpose of this study is to conduct a comparative analysis of the impact of the accessibility and quality of medical care provided to patients with chronic noncommunicable diseases (CNCDs) during COVID-19 pandemic on the course and outcome of COVID-19 infection. The study included 132 patients hospitalized with a diagnosis of COVID-19 and having one or more concomitant CNCDs. The patients were divided into two groups based on the quality of the initial CNCD therapy they received. Group 1 involved 58 patients (42%) who received treatment according to clinical guidelines and had a compensated CNCD. Group 2 consisted of 76 patients (58%) who received treatment that was not in line with modern clinical guidelines and/or had a decompensated CNCD. All 'red zone' hospitalized patients were surveyed. In particular, they were asked questions related to the quality and accessibility of medical care during COVID-19 pandemic and their satisfaction with the medical care received during the pandemic. Reduced access to medical care (the failure to have the therapy received timely evaluated and adjusted) during COVID-19 pandemic affects the quality of the therapy received by patients with CNCDs. Generally, an unfavorable course and outcome of COVID-19 infection are typical for patients receiving a non-optimal CNCD therapy as compared to patients receiving a therapy that meets current clinical guidelines.

Personalized Prescription of Chemotherapy Based on Assessment of mRNA Expression of BRCA1, RRM1, ERCC1, TOP1, TOP2α, TUBß3, TYMS, and GSTP1 Genes in Tumors Compared to Standard Chemotherapy in the Treatment of Non-Small-Cell Lung Cancer

Objectives: A growing body of evidence suggests the important role of chemosensitive gene expression in the prognosis of patients with lung cancer. However, studies on combined gene expression assessments for personalized prescriptions of chemotherapy regimens in patients have not yet been conducted. The aim of this work was to conduct a prospective study on the appointment of personalized chemotherapy in patients with non-small-cell lung cancer. Materials and methods: The present study analyzed 85 patients with lung cancer (stage IIB-IIIB). Within this group, 48 patients received individualized chemotherapy, and 37 patients received classical chemotherapy. In the individualized chemotherapy group, the mRNA expression levels of ERCC1, RRM1, TUBB3, TYMS, TOP1, TOP2α, BRCA1, and GSTP1 in lung tissues were measured by quantitative real-time PCR (qPCR), and an individual chemotherapy regimen was developed for each patient according to the results. Patients in the classical chemotherapy group received the vinorelbine/carboplatin regimen. Survival analyses were performed using the Kaplan−Meier method. Prognostic factors of metastasis-free survival (MFS) and overall survival (OS) of patients were identified via Cox's proportional hazards regression model. Results: MFS and OS were significantly better in the personalized chemotherapy group compared to the classic chemotherapy group (MFS, 46.22 vs. 22.9 months, p = 0.05; OS, 58.6 vs. 26.9 months, p < 0.0001). Importantly, the best metastasis-free survival rates in the group with personalized ACT were achieved in patients treated with the paclitaxel/carboplatin regimen. Based on an assessment of chemosensitivity gene expression in the tumors, the classical chemotherapy strategy also increased the risk of death (HR = 14.82; 95% CI: 3.33−65.86; p < 0.000) but not metastasis (HR = 1.95; 95% CI: 0.96−3.98; p = 0.06) compared to the group of patients with chemotherapy. Conclusions: The use of combined ERCC1, RRM1, TUBB3, TYMS, TOP1, TOP2α, BRCA1, and GSTP1 gene expression results for personalized chemotherapy can improve treatment efficacy and reduce unnecessary toxicity.

Distribution of virulence genes and capsule types in Klebsiella pneumoniae among bloodstream isolates from patients with hematological malignancies.

The hypervirulent Klebsiella pneumoniae (hv-K. pneumoniae) pathotype has been spreading over during the last years. We evaluated the distribution of virulence genes (iucA, rmpA or rmpA2) and capsule types in K. pneumoniae isolates. A total of 572 K. pneumoniae were evaluated; of those 114 (20%) were carbapenemase-producing K. pneumoniae (CP-K.pneumoniae); 285 (49.8%) - extended-spectrum ß-lactamase-producing K. pneumoniae (ESBL-K. pneumoniae); and 173 (30.2%) - non-CP- and non-ESBL. Among CP-K. pneumoniae the prevalent sequence type was ST395 (37.7%), followed by ST23 (16.7%). A total of 138 (24.1%) hv-K. pneumoniae were detected. The rate of hv-K. pneumoniae (55.3%) was higher among CP-K. pneumoniae compared to ESBL-K. pneumoniae (17.3%) and non-CP- and non-ESBL (15.8%).The iucA and rmpA2 genes were detected in 89.5% of ST23 and 58.1% of ST395. The K57 capsule type was detected in all ST23; K2 was found in 55.8% of ST395. The hv-K. pneumoniae were common in bloodstream isolates, with a significantly higher rate among CP-K. pneumoniae. Most of them belonged to ST23/K57 and ST395/K2.

Amplifications of Stemness Gene Loci-New Markers for the Determination of the Need for Neoadjuvant Chemotherapy for Patients with Breast Cancer. A Prospective Study.

In this prospective study, a new strategy for the prescription of neoadjuvant chemotherapy (NAC) was prospectively tested and depended on the presence of stemness gene amplifications in the tumor before treatment, which in our early studies showed a connection with metastasis. The study included 92 patients with grade IIA-IIIB luminal B breast cancer. Patients underwent a biopsy before treatment, and with the use of a CytoScan HD Array microarray (Affymetrix, Santa Clara, CA, USA), the presence of stemness gene amplifications (3q, 5p, 6p, 7q, 8q, 13q, 9p, 9q, 10p, 10q21.1, 16p, 18chr, 19p) in the tumor was determined. In group 1 (n = 41), in the presence of two or more amplifications, patients were prescribed a personalized NAC regimen. In group 2 (n = 21), if there was no amplification of stemness genes in the tumor, then patients were not prescribed NAC, and treatment began with surgery. Group 3 (n = 30) served as a historical control. The frequency of an objective response to NAC in groups 1 and 3 was 79%. Nonmetastatic survival was found in 100% of patients in group 2, who did not undergo NAC. In patients in group 1, the frequency of metastasis was 10% (4/41). At the same time, in patients in group 3, who received NAC, the rate of metastasis was 47% (14/30). The differences between group 1 and group 3 and between group 2 and group 3 were statistically significant, both by Fisher's criterion and a log-rank test. The appointment of NAC was most feasible in patients with clones with stemness gene amplifications in the primary tumor, while in the absence of amplifications, preoperative chemotherapy led to a sharp decrease in metastasis-free survival. This strategy of NAC prescription allowed us to achieve 93% metastatic survival in patients with breast cancer.

Novel Cationic Meso-Arylporphyrins and Their Antiviral Activity against HSV-1.

This work is devoted to the search for new antiherpes simplex virus type 1 (HSV-1) drugs among synthetic tetrapyrroles and to an investigation of their antiviral properties under nonphotodynamic conditions. In this study, novel amphiphilic 5,10,15,20-tetrakis(4-(3-pyridyl-n-propanoyl)oxyphenyl)porphyrin tetrabromide (3a), 5,10,15,20-tetrakis(4-(6-pyridyl-n-hexanoyl)oxyphenyl)porphyrin tetrabromide (3b) and known 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin tetraiodide (TMePyP) were synthesized, and their dark antiviral activity in vitro against HSV-1 was studied. The influence of porphyrin's nanosized delivery vehicles based on Pluronic F127 on anti-HSV-1 activity was estimated. All the received compounds 3a, 3b and TMePyP showed virucidal efficiency and had an effect on viral replication stages. The new compound 3b showed the highest antiviral activity, close to 100%, with the lowest concentration, while the maximum TMePyP activity was observed with a high concentration; porphyrin 3a was the least active. The inclusion of the synthesized compounds in Pluronic F-127 polymeric micelles had a noticeable effect on antiviral activity only at higher porphyrin concentrations. Action of the received compounds differs by influence on the early or later reproduction stages. While 3a and TMePyP acted on all stages of the viral replication cycle, porphyrin 3b inhibited viral replication during the early stages of infection. The resulting compounds are promising for the development of utilitarian antiviral agents and, possibly, medical antiviral drugs.

Prognostic significance of ERCC1, RRM1, TOP1, TOP2A, TYMS, TUBB3, GSTP1 AND BRCA1 mRNA expressions in patients with non-small-cell lung cancer receiving a platinum-based chemotherapy.

PURPOSE: Currently, more researchers are attracted by the possibility of assessing the sensitivity of a lung tumor to certain chemotherapy drugs and their personalized choice based on an assessment of this sensitivity. The purpose of this study was to explore the prognostic significance of the level of 8 chemosensitivity genes' expression in patients with non-small cell lung cancer (NSCLC). METHODS: The study included 59 patients with NSCLC IIB-IIIA stage. RNA was isolated from the surgical material of the tumor and normal lung tissue. The expression level of 8 chemosensitivity genes BRCA1, RRM1, ERCC1, TOP1, TOP2a, TUBB3, TYMS, GSTP1 was evaluated using RT-PCR. RESULTS: Cases with higher metastasis-free survival rates showed a significantly low level of expression of the ERCC1, BRCA1, GSTP1 genes (p=0.0004, p=0.01, p=0.01). In addition, analysis of the overall survival revealed that the highest rates were achieved in patients with overexpression of the ERCC1 gene. The overall survival in these patients was 86%, versus 55% in the other group and the differences were statistically significant (p=0.002). No statistically significant differences were found for the remaining genes. CONCLUSION: Thus, a comprehensive assessment of the chemosensitivity genes expression is important not only from the point of view of understanding the heterogeneity and complexity in the field of molecular biology of NSCLC, but also for a more accurate prognosis and course of the disease.

Expression of M2 macrophage markers YKL-39 and CCL18 in breast cancer is associated with the effect of neoadjuvant chemotherapy.

PURPOSE: High activity of enzyme TOP2a in tumor cells is known to be associated with sensitivity to anthracycline chemotherapy, but 20% of such patients do not show clinical response. Tumor microenvironment, including tumor-associated macrophages (TAM), is an essential factor defining the efficiency of chemotherapy. In the present study, we analyzed the expression of M2 macrophage markers, YKL-39 and CCL18, in tumors of breast cancer patients received anthracycline-based NAC. METHODS: Patients were divided into two groups according to the level of doxorubicin sensitivity marker TOP2a: DOX-Sense and DOX-Res groups. Expression levels of TOR2a, CD68, YKL-39 and CCL18 genes were analyzed by qPCR, the amplification of TOR2a gene locus was assessed by the microarray assay. Clinical and pathological responses to neoadjuvant chemotherapy were assessed. RESULTS: We found that the average level of TOP2a expression in patients of DOX-Sense group was almost 10 times higher than in patients of DOX-Res group, and the expression of CD68 was 3 times higher in the DOX-Sense group compared to DOX-Res group. We demonstrated that expression levels of M2-derived cytokines but not the amount of TAM is indicative for clinical and pathological chemotherapy efficacy in breast cancer patients. Out of 8 patients from DOX-Sense group who did not respond to neoadjuvant chemotherapy (NAC), 7 patients had M2+ macrophage phenotype (YKL-39+CCL18- or YKL-39-CCL18+) and only one patient had M2- macrophage phenotype (YKL-39-CCL18-). In DOX-Res group, out of 14 patients who clinically responded to NAC 9 patients had M2- phenotype and only 5 patients had M2+ macrophage phenotype. Among pathological non-responders in DOX-Sense group, 19 (82%) patients had M2+ tumor phenotype and only 4 (18%) patients had M2- phenotype. In DOX-Res group, all 5 patients who pathologically responded to NAC had M2 phenotype (YKL-39-CCL18-). Unlike the clinical response to NAC, the differences in the frequency of M2+ and M2- phenotypes between pathologically responding and non-responding patients within DOX-Sense and DOX-Res groups were statistically significant. CONCLUSIONS: Thus, we showed that in patients with breast cancer who received anthracycline-containing NAC the absence of clinical response is associated with the presence of M2+ macrophage phenotype (YKL-39-CCL18 + or YKL-39 + CCL18-) based on TOP2a overexpression data.