Total Group Of Patients Research Articles

Clinical Outcomes of Endonasal Dacryocystorhinostomy with Canalicular Trephination in Canalicular Obstruction

Purpose: To investigate the surgical outcomes of endonasal dacryocystorhinostomy with canalicular trephination in patients with canalicular obstruction.Methods: We retrospectively analyzed the medical records of 37 eyes from 32 patients who were diagnosed with canalicular obstruction between May 2010 and July 2022 and underwent endonasal dacryocystorhinostomy with canalicular trephination to evaluate the success rate and complications.Results: In the total patient group, 81.1% achieved complete success in which epiphora completely disappeared, 13.5% had partial success in which epiphora remained but improved, and 5.4% experienced failure in which tearing persisted or worsened. Complications included one case of dacryocystorhinostomy bony opening granuloma and one case of dacryocystorhinostomy bony opening inflammation.Conclusions: Endonasal dacryocystorhinosomy with canalicular trephination is an effective method for treating canalicular obstruction, offering a high success rate and few complications. It can be considered before resorting to conjunctivodacryocystorhinostomy, which is a more conventional treatment.

Blood Growth Factor Levels in Patients with Systemic Lupus Erythematosus: High Neuregulin-1 Is Associated with Comorbid Cardiovascular Pathology.

Patients with systemic lupus erythematosus (SLE) are known to frequently suffer from comorbid cardiovascular diseases (CVDs). There are abundant data on cytokine levels and their role in the pathogenesis of SLE, while growth factors have received much less attention. The aim of this study was to analyze growth factor levels in SLE patients and their association with the presence of comorbid CVDs. The serum concentrations for the granulocyte-macrophage colony-stimulating factor (GM-CSF), nerve growth factor β (NGFβ), glial cell line-derived neurotrophic factor (GDNF), and neuregulin-1 β (NRG-1β) were determined in the SLE patients (n = 35) and healthy individuals (n = 38) by a Luminex multiplex assay. The NGFβ and NRG-1β concentrations were shown to be significantly higher in the total group of SLE patients (median [Q1-Q3]: 3.6 [1.3-4.5] and 52.5 [8.5-148], respectively) compared with the healthy individuals (2.9 [1.3-3.4] and 13.7 [4.4-42] ng/mL, respectively). The GM-CSF and GDNF levels did not differ. Interestingly, elevated NRG-1β levels were associated with the presence of CVDs, as SLE patients with CVDs had significantly higher NRG-1β levels (99 [22-242]) compared with the controls (13.7 [4.4-42]) and patients without CVDs (19 [9-80] ng/mL). The model for the binary classification of SLE patients with and without CVDs based on the NRG-1β level had an average predictive ability (AUC = 0.67). Thus, altered levels of growth factors may be associated with comorbid CVDs in SLE patients.

Effect of consolidation radiation therapy on treatment outcomes of early-stage favorable Hodgkin lymphoma

Background. Early (stage I–II) classical Hodgkin lymphoma is a highly treatable malignant neoplasm. For many years, the standard treatment of early Hodgkin lymphoma has been combination therapy: polychemotherapy with subsequent consolidating radiation therapy. Aim. To retrospectively evaluate the results of treatment of stage I–II classical Hodgkin lymphoma in a favorable prognosis group using monotherapy and combination therapy (chemotherapy followed by consolidating radiotherapy). Materials and methods. The study included 58 patients aged 19–81 years (median age 36 years) diagnosed with stage I–II classical Hodgkin lymphoma with favorable prognosis; 23 (39.7 %) patients were men, 35 (60.3 %) were women. Depending on the treatment received, the patients were divided into two groups: 40 (69 %) patients received ABVD polychemotherapy, and 18 (31 %) patients received polychemotherapy followed by consolidating radiation therapy to the initial lesion zones with standard fractionation regimen (total dose 30 Gy). The Kaplan–Mayer method was used to evaluate overall, progression-free, recurrence-free, and event-free survival. Odds ratios and their 95 % confidence intervals were also calculated. The statistical significance of differences in survival was assessed using the log-rank test. The level of statistical significance was 0.05. Statistical data processing was carried out using the IBM SPSS Statistics 27 software and Microsoft Excel. Results. According to the results of our study, while in the total patient group a clear numerical advantage in survival (overall, progression-free, relapse-free and event-free survival) was observed in the combination therapy group compared to chemotherapy group (5.5, 13.2, 9.2 and 23.9 %, respectively), no preferred tactics were identified in the total patient group. However, considering a subgroup of patients with mediastinum involved in the tumor process, a statistically significant advantage of combined treatment over single-mode chemotherapy was determined for 2-year event-free survival (92.9 ± 6.9 % vs. 62.5 ± 9.9 %, respectively, p = 0.046). The risk of an adverse event is reduced by >80 % (odds ratio 0.197; 95 % confidence interval 0.036–0.977) when using consolidating radiation therapy after chemotherapy.

Basal FSH values are positively associated with aneuploidy incidence in pre-advanced maternal age (AMA) but not in AMA patients.

To assess the impact of maternal age on the association between maternal basal FSH and aneuploidy. A retrospective study including data from 1749 blastocysts diagnosed as euploid or aneuploid by PGT-A (preimplantation genetic testing for aneuploidy). Aneuploidy incidence was compared between embryos from mothers with high vs. low basal FSH levels (above and below the group median, respectively) in total, pre-AMA (advanced maternal age; < 35years, 198 embryos) and AMA (≥ 35years, 1551 embryos) patient groups, separately. To control for the interference of potentially confounding variables, the association between aneuploidy and high basal FSH levels was assessed by multivariate logistic analysis in overall, pre-AMA and AMA patient groups. Overall, aneuploidy rate was 9% higher (p = 0.02) in embryos from patients with high basal FSH (63.7%) compared to those with low basal FSH (58.4%). In the pre-AMA subgroup, aneuploidy incidence was 35% higher (p = 0.04) in embryos from patients with high basal FSH (53.5%) compared to those with low basal FSH (39.4%). Differently, aneuploidy occurrence did not vary between embryos from AMA patients with low (61.0%) and high (64.8%) basal FSH (p = 0.12). The multivariate analysis revealed that, in pre-AMA embryos, the association between aneuploidy occurrence and high basal FSH is independent of potential confounding variables (p = 0.04). Maternal basal FSH values are associated with embryo aneuploidy in pre-AMA but not in AMA patients. The present findings suggest that basal FSH is a useful parameter to assess aneuploidy risk in pre-AMA patients and reinforce the hypothesis that excessive FSH signalling can predispose to oocyte meiotic errors.

Selective opioid agonist Taphalgin® as a component of postoperative analgesia in various surgical areas: “NIKITA” observational multicenter study

Introduction. The role of peptides in antinociceptive system regulation has became a subject of interest for scientists worldwide. The first registered peptide analgesic tyrosyl-D-arginyl-phenylalanyl-glycinamide acetate which currently can be used in clinical practice was developed in Russia under the name Taphalgin® (PharmFirma “Sotex”, Russia). The effectiveness and safety of this pharmaceutical in postoperative pain management was evaluated in the all-Russia multicenter prospective observation program NICITA (Non-interventional Clinical Trial of Taphalgin ®).Aim. To analyze the effectiveness and safety of Taphalgin® in postoperative pain management in various surgical fields.Materials and methods. The observational program NICITA included 887 patients including patients with malignant tumors of various locations from 15 study centers in different Russian cities. All patients underwent surgical interventions in various anatomical areas under general, regional and combination anesthesia. The principal scheme of postoperative pain management was based on the multimodal approach which included peptide opioid agonist alongside acetaminophen, cyclooxygenase inhibitors in combination with regional anesthesia or without it. The study also included patients who underwent small-volume surgeries, and pain was managed through Taphalgin® monotherapy with subsequent switch to cyclooxygenase inhibitors. The primary endpoint of the NICITA observational program was response to therapy after the first Taphalgin® administration. Decreased pain syndrome per the numerical rating scale 15–60 min after subcutaneous injection and maintenance of analgesic effect 3 h later were considered treatment response. The secondary endpoints included mean time to analgesia start after administration of the 1st single drug dose (in min), duration of effect, types and frequency of adverse reactions including serious in the central nervous system, pulmonary system, gastrointestinal tract developed during the observational program, as well as patient and research physician satisfaction with pain management. To evaluate the significance of pain intensity change at rest and in motion in time, analysis of variance with repeat measurements was used; for pairwise comparison of two time periods, Student’s t-test for dependent samples was used. The differences were considered significant at p = 0.05.Results. Statistically significant decrease in pain intensity in the total patient group was observed 15 minutes after Taphalgin® administration; it reached its minimum 40 min after the injection (р &lt;0.05). The percentage of patients responding to analgesic therapy with Taphalgin® was 96.5 %. During administration of the drug, insignificant decrease (10–15 mmHg) in arterial blood pressure (1.7 % of cases) and vertigo (1 % of cases) were observed. In some patients, several adverse reactions were observed. Satisfaction with analgesic effect of Taphalgin® was relatively high both in patients and research physicians.Conclusion. Taphalgin® has pronounced analgesic effect and is effective for pain management after surgical interventions of various volumes and injury level. The use of this drug is associated with low rate of adverse reactions and absence of pulmonary depression characterizing opioid agonists. Therefore, Taphalgin® can be recommended for clinical use for postoperative pain management after various types of surgical interventions.

Influence of initial misdiagnosis on mortality in patients with bacteraemia: propensity score matching and propensity score weighting analyses

BackgroundThe diagnostic process is a key element of medicine but it is complex and prone to errors. Infectious diseases are one of the three categories of diseases in which diagnostic errors can be most harmful to patients. In this study we aimed to estimate the effect of initial misdiagnosis of the source of infection in patients with bacteraemia on 14 day mortality using propensity score methods to adjust for confounding.MethodsData from a previously described longitudinal cohort of patients diagnosed with monobacterial bloodstream infection (BSI) at the Leiden University Medical Centre (LUMC) between 2013 and 2015 were used. Propensity score matching and inversed probability of treatment weighting (IPTW) were applied to correct for confounding. The average treatment effect on the treated (ATT), which in this study was the average effect of initial misdiagnosis on the misdiagnosed (AEMM), was estimated. Methodological issues that were encountered when applying propensity score methods were addressed by performing additional sensitivity analyses. Sensitivity analyses consisted of varying caliper in propensity score matching and using different truncated weights in inversed probability of treatment weighting.ResultsData of 887 patients were included in the study. Propensity scores ranged between 0.015 and 0.999 and 80 patients (9.9%) had a propensity score > 0.95. In the matched analyses, 35 of the 171 misdiagnosed patients died within 14 days (20.5%), versus 10 of the 171 correctly diagnosed patients (5.8%), yielding a difference of 14.6% (7.6%; 21.6%). In the total group of patients, the observed percentage of patients with an incorrect initial diagnosis that died within 14 days was 19.8% while propensity score reweighting estimated that their probability of dying would have been 6.5%, if they had been correctly diagnosed (difference 13.3% (95% CI 6.9%;19.6%)). After adjustment for all variables that showed disbalance in the propensity score a difference of 13.7% (7.4%; 19.9%) was estimated. Sensitivity analyses yielded similar results. However, performing weighted analyses without truncation yielded unstable results.ConclusionThus, we observed a substantial increase of 14 day mortality in initially misdiagnosed patients. Furthermore, several patients received propensity scores extremely close to one and were almost sure to be initially misdiagnosed.

Cellular adhesion molecules in drug-naïve and previously medicated patients with schizophrenia-spectrum disorders

BackgroundEndothelial inflammation may be involved in the pathogenesis of schizophrenia, and cellular adhesion molecules (CAMs) on endothelial cells may facilitate leukocyte binding and transendothelial migration of cells and inflammatory factors. The aim of the present study was to assess levels of soluble cellular adhesion molecules, including intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, mucosal addressin cell adhesion molecule (MADCAM), junctional adhesion molecule (JAM-A) and neural cadherin (N-CAD) in patients with schizophrenia compared to healthy controls. MethodsThe study population consists of 138 patients with schizophrenia-spectrum disorder, of whom 54 were drug-naïve, compared to 317 general population controls. The potential confounders age, gender, smoking and body mass index (BMI) were adjusted for in linear regression models. ResultsThe total patient group showed significantly higher levels of ICAM-1 (p < 0.001) and VCAM-1 (p < 0.001) compared to controls. Previously medicated patients showed higher ICAM-1 levels compared to drug-naïve patients (p = 0.042) and controls (p < 0.001), and elevated VCAM-1 levels compared to controls (p < 0.001). Drug-naive patients had elevated levels of VCAM-1 (p = 0.031) compared to controls. ConclusionsIn our study, patients with schizophrenia – including the drug-naïve – have higher levels of soluble CAMs compared to healthy controls. These findings suggest activation of the endothelial system as in inflammation.

Retrospective Evaluation of Attacks, EDSS Scores, and MRI Changes Before the Start of Treatment and One Year After the Start of Treatment in Patients Followed by a Diagnosis of Multiple Sclerosis and Using Ocrelizumab in Our Clinic

Objective: Depletion of B cells by anti-CD20 monoclonal antibodies has been proven to reduce relapsing remitting multiple sclerosis (RRMS) activity and progression of primary progressive MS (PPMS). In our study, we aimed to retrospectively present our clinical experience and contribute to real-life data after the use of Ocrelizumab. Material and Methods: Patients aged 18-55 years using Ocrelizumab and diagnosed with MS by McDonald's 2017 criteria were included. Neurological examination findings and EDSS findings available in our file records were used to evaluate the level of disability. Patients with MRI lesions consistent with their clinical complaint lasting more than 24 hours were evaluated as an attack. Patients' ages, MS diagnosis times, and previous immune modulatory treatments were recorded. The number of T2, FLAIR sequence MRI lesions, EDSS before ocrelizumab, and the number of T2, FLAIR sequence MRI lesions 1 year after receiving ocrelizumab were recorded. After 1 year of follow-up, the absence of attacks, no increase in the number of lesions in MRI, and no progress in EDSS were accepted as NEDA 3. Results: Our cases in this study include 30 MS patients. Patients were 26.7% relapsing remitting MS (RRMS), 26.7% primary progressive MS (PPMS), and 46.7% secondary progressive MS (SPMS). There was no attack in 87.5% of the RRMS patient group. In the SPMS patient group, no attacks were observed after ocrelizumab in the cases with attacks. In our study, the rate of patients who did not develop new T2 lesions and whose lesions disappeared was 62.5% in the RRMS patient group, 78.5% in the SPMS patient group, and 75% in the PPMS patient group. In the total patient group, the rate of patients without EDSS increase was 93% (28 patients). Conclusion: In our study, it was determined that ocrelizumab was effective by reducing the attack rates, preserving the EDSS scores and preventing the increase in the lesion burden. Our findings are consistent with real-life data.

Biofeedback training for the analysis of gait stereotypes in patients with gonarthrosis

BACKGROUND: The justification of the treatment techniques for patients with gonarthrosis requires the use of modern methods for assessing walking stereotypes.&#x0D; AIM: This study aimed to evaluate the biomechanical and podometric gait parameters of patients with gonarthrosis using the C-Mill multifunctional complex with biofeedback.&#x0D; MATERIALS AND METHODS: The study included 55 patients who were divided into the following groups: main group (n=35) of patients who had gait disturbances, diagnosed with stage III–IV primary gonarthrosis with varus deformation of the limb axis according to ICD-10, and underwent total knee replacement and control group (n=20) of patients diagnosed with stage I primary gonarthrosis. The average age of patients was 58.7 years in the main group and 47.5 years in the control group.&#x0D; RESULTS: In the main group, the decrease in average walking speed was accompanied by decreases in stride length and step frequency (р 0.05). In the stance phase, which is characterized by the contact of the foot of the affected and contralateral lower extremities with the platform surface, the durations of the double stance phase of both extremities in the main group were longer than those in the control group (p 0.05), indicating gait asymmetry and redistribution of excess load on the contralateral lower extremity, which is clinically manifested by lameness. In the main group, gait was characterized by a decrease in voluntary speed, step frequency, and gait pattern changes in various planes, confirming severe clinical and functional disorders in the lower limbs.&#x0D; CONCLUSION: The study of the walking stereotype in patients using the C-Mill multifunctional complex with biofeedback can be used to substantiate treatment techniques, followed by drawing up an individual medical rehabilitation plan to restore lower limb functions in the postoperative period, fully monitor treatment dynamics, prevent falls, and improve the quality of life of patients.

Metastasis suppressor kisspeptin (KISS1) in serum of patients with renal cell carcinoma

Background. The most important problems in improvement of treatment outcomes in patients with renal cell carcinoma (RCC) are search and validation of molecular markers for its early diagnosis and prognosis. Genes suppressing distant metastasizing but not affecting the primary tumor are called metastasis suppressors. Study of these genes and their products not only improves understanding of the mechanisms of tumor progression, but has practical value for diagnosis, prognosis, and establishment of new molecular targets for antitumor therapy. One of such genes is KISS1 with its product kisspeptin (KISS1) protein.Aim: comparative evaluation of KISS1 concentration in blood serum of practically healthy persons and patients with renal cancer; analysis of correlations between the marker’s level and clinical and morphological characteristics of the disease.Materials and methods. 140 patients with RCC (88 men, 52 women) aged between 29 and 82 years were included in the study. Among them, clear cell RCC was diagnosed in 84 patients, papillary in 38, chromophobe in 18. The control group was comprised of 40 healthy persons of matched age and sex. Pre-treatment KISS1 concentration in blood serum was measured using a direct enzyme immunoassay kit (Kisspeptin 1 – KISS1, Cloud-Clone Corp., USA).Results. Median serum KISS1 concentration in the control group was 51.7 pg/mL which was significantly lower than in the total RCC patient group – 243.6 pg/mL (p &lt;0.0001). ROC analysis of diagnostic value of serum KISS1 level was performed both for the total RCC group and for each of its three histological types. In the total group the sensitivity of the test was 75 %, specificity – 80 % (AUC 0.877; 95 % confidence interval (CI) 0.827–0.927; optimal cut-off level 130.8 pg/mL; р &lt;0.0001). For clear cell RCC, both sensitivity and specificity were 85 % (AUC 0.941; 95 % CI 0.902– 0.979; cut-off 141.8 pg/mL; p &lt;0.0001). In non-clear cell RCC types, sensitivity of this marker was only 58 % while the specificity remained 80 % (for papillary RCC AUC 0.787; 95 % CI 0.684–0.889; cut-off level 135.5 pg/mL; p &lt;0.0001, and for chromophobe RCC AUC 0.774; 95 % CI 0.617–0.929; cut-off level 132.1 pg/mL; p &lt;0.001). KISS1 level increased with disease progression: it is significantly higher at more advanced stages above stage I, and in patients with distant metastases compared to those without metastases. Higher serum KISS1 level is also observed in patients with poorly differentiated high-grade (per Furhman) clear cell RCC and papillary RCC (G3–G4) than in those with well differentiated low-grade (G1–G2) tumors.Conclusion. KISS1 level is significantly increased in patients with RCC compared to healthy controls and is a stagedependent marker of this disease. It has relatively high diagnostic sensitivity and specificity (both 85 %) for the most frequent histological type of RCC – clear cell RCC. Thus, clinical significance of kisspeptin in RCC requires further investigation.

SEX AND ASA CLASSIFICATION, NOT FASTING TIME, ARE ASSOCIATED WITH THE LIKELIHOOD OF COMPLICATIONS IN THE POSTOPERATIVE PERIOD.

According to the literature, some factors are associated with the development of postoperative complications including surgical approach, smoking, comorbidities, nutritional status, classification of the American Society of Anesthesiologists (ASA), fasting time period, and others. In the case of surgical patients, some factors are important for the assessment of the outcomes. To investigate the factors associated with the likelihood of postoperative complications in surgical patients. A prospective observational study was conducted with patients who were admitted to hospital more than 24 h. The following variables were investigated: nutritional risk screening, body mass index, ASA classification, fasting time, length of hospital stay, and postoperative complications. For statistical analysis, the Chi-square, Fisher's exact, and Mann-Whitney tests were used. To investigate the risk factors associated with postoperative complications, simple and multiple Cox regression analyses were used. In the total group of patients, there was an association between postoperative complications and men (p=0.0197), surgical risk (ASA) (p=0.0397) and length of hospital stay (p<0001); men showed a risk 2.2 times greater than women for some kind of postoperative complication (p=0.0456; PR=2.167; 95%CI 1.015-4.624). In patients undergoing gastrointestinal surgery, there was an association between postoperative complications and length of hospital stay (p<0001). In patients undergoing other surgeries, there was an association between postoperative complications and length of hospital stay (p<0001) and ASA classification (p=0.0160); ASA classification was considered a factor associated with the probability of postoperative complications (p=0.0335; PR=4.125; 95%CI 1.117-15.237). Men in the total group of patients and the ASA 3 or 4 criteria in the group of patients undergoing other surgeries were considered factors associated with the occurrence of complications in the postoperative period.

Predictions of PD-L1 Expression Based on CT Imaging Features in Lung Squamous Cell Carcinoma.

To develop models to predict programmed death ligand 1 (PD-L1) expression in pulmonary squamous cell carcinoma (SCC) using CT. A total of 97 patients diagnosed with SCC who underwent PD-L1 expression assay were included in this study. We performed a CT analysis of the tumors using pretreatment CT images. Multiple logistic regression models were constructed to predict PD-L1 positivity in the total patient group and in the 40 advanced-stage (≥ stage IIIB) patients. The area under the receiver operating characteristic curve (AUC) was calculated for each model. For the total patient group, the AUC of the 'total significant features model' (tumor stage, tumor size, pleural nodularity, and lung metastasis) was 0.652, and that of the 'selected feature model' (pleural nodularity) was 0.556. For advanced-stage patients, the AUC of the 'selected feature model' (tumor size, pleural nodularity, pulmonary oligometastases, and absence of interstitial lung disease) was 0.897. Among these factors, pleural nodularity and pulmonary oligometastases had the highest odds ratios (8.78 and 16.35, respectively). Our model could predict PD-L1 expression in patients with lung SCC, and pleural nodularity and pulmonary oligometastases were notable predictive CT features of PD-L1.

An association between PPARα-L162V polymorphism and increased plasma LDL cholesterol levels after risperidone treatment

Peroxisome proliferator-activated receptor alpha (PPARα) and antipsychotic medications both influence polyunsaturated fatty acids (PUFA) homeostasis, and thus PPARα polymorphism may be linked to antipsychotic treatment response. Here we investigated whether the functional leucine 162 valine (L162V) polymorphism in PPARα influenced antipsychotic treatment in a group of psychosis patients (N = 186), as well as in a patient subgroup with risperidone, paliperidone, or combination treatment (N = 65). Antipsychotic-naïve first-episode patients and nonadherent chronic individuals were genotyped by polymerase chain reaction analysis. At baseline, and after 8 weeks of treatment with various antipsychotic medications, we assessed the patients’ Positive and Negative Syndrome Scale (PANSS) scores; PANSS factors; and metabolic syndrome-related parameters, including fasting plasma lipid and glucose levels, and body mass index. In the total patient group, PPARα polymorphism did not affect PANSS psychopathology or metabolic parameters. However, in the subgroup of patients with risperidone, paliperidone, or combination treatment, PPARα polymorphism influenced changes in plasma LDL cholesterol. Specifically, compared to PPARα-L162L homozygous patients, PPARα-L162V heterozygous individuals exhibited significantly higher increases of LDL cholesterol levels after antipsychotic treatment. The PPARα polymorphism had a strong effect size, but a relatively weak contribution to LDL cholesterol level variations (∼12.8 %).

Studying the activity of matrix metalloproteinases and antibodies to DNA in patients with autoimmune thyroiditis

Background. In autoimmune thyroiditis, in addition to impaired immunological tolerance, a significant role is played by biochemical markers such as matrix metalloproteinases and antibodies to deoxyribonucleic acid (DNA), which can contribute to the pathogenesis of the disease.&#x0D; Aim. Studying the activity of metalloproteinases-3, -7 and the level of antibodies to DNA in patients with autoimmune thyroiditis.&#x0D; Material and methods. In 2019–2021 a non-randomized study in the research laboratory at the Department of Biochemistry of the Azerbaijan Medical University, during which the blood serum of 170 patients with autoimmune thyroiditis, 64 (37.6%) men, average age 39.4±11.2 years and 106 (62.4%) women, average age 37.8±9.05 years, was conducted. Inclusion criteria: men and women aged 18 years and older with a primary diagnosis of “autoimmune thyroiditis” without concomitant allergic or other autoimmune diseases and severe somatic disorders. The control group consisted of 65 people (average age 38.7±10.8 years) without any thyroid disease or autoimmune pathology. Analysis of clinical and laboratory studies with determination of the level of thyroid-stimulating hormone, free thyroxine and free triiodothyronine made it possible to divide patients into two groups: the first group — 74 patients with a subclinical form of the disease; the second group — 96 patients with a manifest form of the disease. In all patients, the activity of metalloproteinases-3 and -7 in the blood serum was determined by enzyme-linked immunosorbent assay, and the content of antibodies to native and denatured DNA was determined by enzyme-linked immunosorbent assay. Intergroup comparisons on quantitative indicators were carried out using the nonparametric Mann–Whitney rank test, taking into account the difference in the distribution of the analyzed indicators from the normal one. Qualitative characteristics were assessed as percentages.&#x0D; Results. The median activity of metalloproteinases-3 and -7 in the total group of patients was 56 (51.0; 59.0) and 4.6 (4.3; 5.2) ng/ml, respectively, which was significantly higher than the control values — 23.0 (16.0; 26.0) and 3.6 (3.4; 4.1) ng/ml, respectively (p=0.0001252 and p=0.00054). There were no statistically significant differences in the level of metalloproteinase-7 in patients with subclinical and manifest thyroiditis (p=0.097), while the median activity of metalloproteinase-3 in the manifest group was 59.0 (56.0; 65.0) ng/ml and it was higher than in patients of the subclinical group by 13.2%. The content of antibodies to native DNA in patients was 4.4 (2.3; 9.9) units/ml, which was statistically significantly higher compared to the control group — 2.6 (1.5; 3.6) units/ml (p 0.001), while no significant differences were found in the levels of antibodies to denatured DNA in patients compared to control values.&#x0D; Conclusion. The worsening of the autoimmune process is accompanied by an increase in the activity of metalloproteinases and antinuclear antibodies.

Hormones, oxidized proteins, and lipids in alcoholism. Duration of remission

The instability of remission in alcohol dependence (AD) creates a need to search for criteria for predicting its duration. The aim of study was to determine the hormones, oxidized proteins, and lipids in patients with AD, and the possible relations between these parameters and the duration of remission. Blood samples were obtained from 49 male patients with AD after alcohol detoxification (Total group). Two groups of patients were formed: with unstable therapeutic remission up to 6 months (UTR-group); with stable therapeutic remission which lasted 12 months or longer (STR-group). The control group comprised men without AD. The levels of carbonylated proteins (CP), lipid peroxidation (TBA-RS) were determined in the blood plasma. The levels of cortisol, testosterone total, thyroid-stimulating hormone (TSH), triiodothyronine free (fT3), and thyroxine free (fT4) in the blood serum were measured. The Total group of patients showed an increase in CP, TBA-RS, Cortisol, cortisol/testosterone ratio, and a decrease in TSH, fT3, and fT3/fT4 levels. A set of parameters (T, fT3, fT4, cortisol/testosterone ratio) associated with unstable remission was identified.

Broadly Reactive SARS-CoV-2-Specific T-Cell Response and Participation of Memory B and T Cells in Patients with Omicron COVID-19 Infection.

January 2022 onward, India witnessed a sudden increase in Omicron COVID-19 infections, having a mild course that prompted us to identify the key host factors/immune molecules modulating disease course/outcomes. The current study evaluated the percentages of lymphocyte subsets by flowcytometry, SARS-CoV-2 specific T-cell immune response by ELISPOT, estimation of plasma cytokine/chemokine levels on a Bio-plex Multiplex Immunoassay System and anti-SARS-CoV-2 IgG levels by enzyme-linked immunosorbent assay in 19 mild Omicron infected patients, 45 mild SARS-CoV-2 (2020) patients and 36 uninfected controls from India. Natural killer cells, B and memory B cells were high in vaccinated and total Omicron-infected patients groups compared to the mild SARS-CoV-2 (2020) patient group, while CD8+ T cells were high in total Omicron-infected patients group compared to the uninfected control group (p < 0.05 each). Omicron-infected patients had T-cell response against SARS-CoV-2 whole virus, S1 proteins (wild type and delta variant) in 10 out of 17 (59%), 10 out of 17 (59%), and 8 out of 17 (47%), respectively. The current study of Omicron-infected patients elucidates broadly reactive antibody, T-cell response, and participation of memory B and T cells induced by vaccination/natural infection. The limited effect of Omicron's mutations on T-cell response is suggestive of protection from severity. Pro-inflammatory IL-6, IFN-γ, chemokines CCL-2, CCL-3, CCL-4, CCL-5, and IL-8 as potential biomarkers of Omicron infection may have future diagnostic importance. The cellular immune response data in Omicron-infected patients with parental Omicron lineage could serve as a starting point to define the readouts of protective immunity against circulating Omicron subvariants.

Efficacy and Safety of Intravenous Immunoglobulin Treatment in Selected Neurological Diseases-One Centre's Experience Based on the Therapy of 141 Patients.

Intravenous immunoglobulins (IVIg) are the first-choice drugs for the treatment of certain neuroimmune diseases. The aim of this study was to evaluate the efficacy and safety of IVIg in patients with selected nervous system diseases. The study enrolled patients who received IVIg in programmes financed by the National Health Fund in Poland. The status of patients upon inclusion and during treatment was assessed using scales dedicated to specific neurological diseases. The study enrolled 141 patients aged 56.28 ± 14.72 (51.77% female): 21 patients with myasthenia gravis (MG), 65 with chronic inflammatory demyelinating polyneuropathy (CIDP), 30 with Guillain-Barré syndrome (GBS), 12 with neuromyelitis optica spectrum disorder (NMOSD) and 13 patients with autoimmune encephalitis (AE). Neurological improvement was found in 14 (66.66%) MG patients (with a reduction of at least three points on the Quantitative Myasthenia Gravis Score (QMGS) within 14 days from the completion of the cycle), and in 34 (52.3%) GBS patients (with a reduction of at least one point on the Medical Research Council Scale within 14 days from the completion of the cycle). The parameters with the strongest effect on clinical improvement in MG patients were age [OR 1.033, CI 95% [0.09-1.09], p = 0.049] and baseline QMGS [OR 0.505; CI 95% [0.24-0.87], p = 0.038]. In the majority of CIDP patients (27, 97%) and NMOSD patients (6, 50%), neurological stabilisation was observed (without clinical improvement, defined for CIDP patients as an increase of at least two points on the Lovett Scale after three courses of IVIg were administered, and for NMOSD patients as an increase of at least one point on the Medical Research Council Scale and/or a shift of at least 0.3 logMAR after three courses of treatment). Deep-vein thrombosis was only one serious adverse event in the total group of patients treated with IVIg. The use of IVIg in patients with MG and GBS mostly results in neurological improvement, while in patients with NMOSD and CIDP, it mostly results in disease stabilisation. This could indicate the predominant anti-idiotypic antibody activity of IVIg in acute neuroimmune diseases or during exacerbations in chronic autoimmune diseases. The therapy of AE in comorbid neoplastic disease is burdened with an elevated risk of failure for IVIg. The results of our study confirm the improved safety of IVIg for selected neurological diseases.

BDNF and Cognitive Function in Chilean Schizophrenic Patients

Despite cognitive symptoms being very important in schizophrenia, not every schizophrenic patient has a significant cognitive deficit. The molecular mechanisms underlying the different degrees of cognitive functioning in schizophrenic patients are not sufficiently understood. We studied the relation between brain-derived neurotrophic factor (BDNF) and cognitive functioning in two groups of schizophrenic patients with different cognitive statuses. According to the Montreal Cognitive Assessment (MoCA) results, the schizophrenic patients were classified into two subgroups: normal cognition (26 or more) and cognitive deficit (25 or less). We measured their plasma BDNF levels using ELISAs. The statistical analyses were performed using Spearman’s Rho and Kruskal–Wallis tests. We found a statistically significant positive correlation between the plasma BDNF levels and MoCA score (p = 0.04) in the subgroup of schizophrenic patients with a cognitive deficit (n = 29). However, this correlation was not observed in the patients with normal cognition (n = 11) and was not observed in the total patient group (n = 40). These results support a significant role for BDNF in the cognitive functioning of schizophrenics with some degree of cognitive deficit, but suggest that BDNF may not be crucial in patients with a normal cognitive status. These findings provide information about the molecular basis underlying cognitive deficits in this illness.

Antibodies to cyclic citrullinated peptide and angiopoietin-like protein type 4 as markers of immune inflammation and osteoporotic processes in rheumatoid arthritis patients

Low-energy fractures in rheumatoid arthritis (RA) are more common in patients with high activity and long duration of disease, and with high titers of anti-citrullinated antibodies (ACPA). Increased expression of angiopoietin-like protein type 4 (ANGPTL4) in bone tissue has also been noted in inflammatory arthritis. The purpose of the present study was to analyze the effect of ACPA and ANGPTL4 on systemic bone mineral density in RA patients. Antibodies to ACPA and ANGPTL4 content were detected in blood serum of 96 RA patients (women, 91.7%) by enzyme immunoassay. Mineral density of the lumbar vertebrae (BMDL1-L4), hip neck, and entire femur (BMDtotal) was measured by dual-energy X-ray absorptiometry (DXA). In study group, the ACPA and ANGPTL4 tests were positive in 61.5% and 41.7% of patients, respectively. Negative correlations were shown between ACPA and BMDtotal, and of ANGPTL4 with BMDL1-L4 (p &lt; 0.05). Separation of the patients into groups with low (n = 34) and high (n = 62) DAS28 activity demonstrated a significant increase in ACPA with increasing RA activity (p = 0.042). ACPA and ANGPTL4 scores were also significantly higher in the group of 45 RA patients with osteoporosis (OP) compared to the RA group without OP (n = 51) showing significant difference at p = 0.002 and p = 0.028, respectively. Patients’ age, body mass index (BMI), duration and activity of the disease had no significant effect on ACPA in the general group of RA patients. However, the correlation between ACPA and DAS28 proved to be significant in the group of RA patients with OP (b = 0.31, p = 0.039). Among all presented variables, the disease duration was the only significant factor for ANGPTL4 in the total group of RA patients (b = 0.31, p = 0.039). In the regression model, BMDtotal showed similar correlations with patients’ age (b = -0.28), BMI (b = 0.25), and ACPA level (b = -0.26). A search for association between BMDL1-L4 and various RA characteristics demonstrated a strong correlation with ANGPTL4 only (b = -0.74; R2 = 0.57). The revealed correlation between ANGPTL4 and decreased BMD specifically in the spongy layer of bone allows us to identify the RA patients with high ANGPTL4 levels as a risk group specifically for spinal fractures thus considering ANGPTL4 as a potential target for treatment of osteoporotic disorders.

Role of consolidative thoracic and prophylactic cranial radiation in extensive stage small cell lung cancer in chemo-immunotherapy era.

8595 Background: The role of consolidative thoracic and prophylactic brain radiation in extensive stage small cell lung cancer patients is controversial. We investigated the factors associated with the use of any radiation therapy (RT) and whether Radiation has a benefit to overall survival (OS) in the total patient group and whether this benefit is the same if Chemotherapy (CT) only is used, or chemo-immunotherapy (CT-IO) is used. Methods: The NCDB database was queried from years 2017-2019. Patients receiving systemic therapy- STX (CT or CT-IO) had to have at least 6 months of follow-up and have no brain metastases at diagnosis. All RT patients had to receive upfront systemic therapy, were treated 2 to 6 months from diagnosis, and if treated to the brain received 25Gy in 10 fractions only. Multi-variate analyses (MVA) were used to determine factors associated with OS and selection for any radiation. Propensity matching for factors affecting OS were used to generate Kaplan-Meier OS curves. Log-rank tests were used to determine differences in Kaplan Meier survival curves for the effects of RT on OS. Results: The total number of patients receiving RT or systemic therapy alone as well as their median follow-ups(months(mn) were (981, 33.02mn) and (8909, 30.59mn). The median time to the start of STX and RT were 22days and 135 days respectively. MVA noted that RT had a greater effect on OS (Thoracic, Brain, Both – HRs = 0.78, 0.75, and 0.68) than other interventions including IO (HR 0.87) and palliative care without RT (HR 1.07). Selection for radiation depended significantly upon factors affecting OS(HR) including liver metastases (0.59), females (1.21), age/10yr(0.78) and Charlson co-morbidity index of &gt; 3(0.66), but did not depend upon insurance status, race, or county income/high school graduation rates. Propensity score matched OS curves noted the same effects of RT on OS whether CT or CT-IO was given. The lowest HRs were noted when both thoracic and brain RT were given (see table). Conclusions: The patient with extensive stage small cell lung cancer who reach candidacy and receive RT may have a significant improvement in OS compared to the patients treated only with CT or CT-IO. Combined thoracic and prophylactic brain RT seems to be better than either one alone. The impact of radiation whether given to one or two sites may be more beneficial than immunotherapy added to chemotherapy. [Table: see text]