Clinical Manifestations Of Patients Research Articles

Heterozygous SERPINA1 Defects and Their Impact on Clinical Manifestations of Patients with Predominantly Antibody Deficiencies.

Patients with predominantly antibody deficiencies (PADs) display hypogammaglobulinemia with a high prevalence of infections, along with autoimmune manifestations, benign and malignant lymphoproliferation and granulomatous disease. It is noteworthy that PAD patients, even those with defects in the same causative genes, display a variable clinical phenotype, suggesting that additional genetic polymorphisms, located in either immune-related or non-immune-related genes, may affect their clinical and laboratory phenotype. In this context, we analyzed 80 PAD patients, including 70 with common variable immunodeficiency (CVID) for SERPINA1 defects, in order to investigate the possible contribution to PAD clinical phenotype. Ten CVID patients carried heterozygous pathogenic SERPINA1 defects with normal alpha-1 antitrypsin levels. Interestingly, the presence of the Z allele (rs28929474), which was found in three patients, was significantly associated with liver disease; hepatic complications were also observed in patients carrying the p.Leu23Gln (rs1379209512) and the p.Phe76del (rs775982338) alleles. Conversely, no correlation of SERPINA1 defective variants with respiratory complications was observed, although patients with pathogenic variants exhibit a reduced probability of developing autoimmune diseases. Therefore, we recommend SERPINA1 genetic analysis in PAD in order to identify patients with a higher risk for liver disease.

Effect of Novel Inflammatory Biomarkers on Adverse Outcomes in Patients with Interstitial Lung Disease and Pneumonia: A Multicenter Retrospective Cohort Study.

Interstitial lung disease frequently coincides with pneumonia in clinical settings, and both conditions are closely associated with immunoinflammation. The Systemic Immune Inflammatory Index (SII) is a recently identified marker, and its connection to the prognosis of individuals suffering from interstitial lung disease and concurrent pneumonia remains unclear. The objective of this study was to scrutinize the correlation between varying SII levels and unfavorable outcomes in patients grappling with interstitial lung disease complicated by pneumonia. This study encompassed a retrospective multicenter cohort of 324 patients diagnosed with interstitial lung disease and pneumonia, all receiving glucocorticoid treatment during their hospitalization. We initially conducted ROC analysis to determine the optimal SII threshold. Subsequently, we examined disparities in clinical symptoms, physical signs, clinical test data, and other clinical attributes among patients with differing SII levels. Later, we employed the Kaplan-Meier survival curve method to assess the association between distinct SII levels and the 30-day and 90-day mortality rates in patients dealing with interstitial lung disease complicated by pneumonia. Finally, a Cox regression model was employed to identify factors influencing adverse prognosis in these patients. The findings demonstrated that the optimal SII threshold for predicting 30-day mortality was 1416.97, with an AUC of 0.633 (95% CI: 0.559-0.708) and a P value of <0.001. For 90-day mortality, the optimal SII threshold was 994.59, yielding an AUC of 0.628 (95% CI: 0.56-0.697) and a P value of <0.001. Noteworthy statistical distinctions emerged in dyspnea, cyanosis, and oxygenation index among patients with varying SII levels. Additionally, invasive mechanical ventilation, non-invasive ventilation, and extended infection duration independently constituted 30-day and 90-day mortality risk factors. Elevated heart rate and higher SII levels emerged as independent risk factors for 90-day mortality. To some extent, SII levels exhibit correlations with the clinical manifestations in patients grappling with interstitial lung disease complicated by pneumonia. Notably, a high SII level is an independent predictor for an unfavorable prognosis in these patients. Nevertheless, these findings warrant further validation through prospective cohort studies.

Characteristics and Clinical Manifestations of Patients, Including Organ Transplant Patients, during the Surge of JN.1: Insights from Saudi Arabia

BackgroundAmidst the persistent global health threat posed by the evolving SARS-CoV-2 virus throughout the four-year-long COVID-19 pandemic, the focus has now turned to the Omicron variant and its subvariant, JN.1, which has rapidly disseminated worldwide. This study reports on the characteristics and clinical manifestations of patients during the surge of the JN.1 variant in Saudi Arabia; it also investigates the evolution of SARS-CoV-2 variants in organ transplant patients and identifies patient risk factors. MethodsA total of 151 nasopharyngeal samples from patients with PCR-confirmed SARS-CoV-2 infection were collected between September 2023 and January 2024. Demographic and clinical data of the patients were obtained from electronic health records. All confirmed positive samples underwent sequencing using Ion GeneStudio and the Ion AmpliSeq™ SARS-CoV-2 panel. ResultsDuring the surge of the JN.1 variant, the average age of the patients was 40 years, ranging from 3 to 93 years, and nearly 50% of the patients were male. Our investigation revealed that the J.N variant predominantly infected patients with comorbidities or organ transplant recipients (57.6%). Moreover, patients with comorbidities or organ transplants exhibited a higher number of mutations. In our organ transplant cohort, an increased total number of spike mutations was associated with a lower risk of developing severe disease (OR = 0.96, 95% CI: 0.93-0.98). ConclusionsAlthough JN.1 may not prove to be particularly harmful, it is crucial to recognize the persistent emergence of concerning variants, which create new pathways for the virus to evolve. The ongoing evolution of SARS-CoV-2 is evident in the continuous divergence of these variants from the original strain that marked the onset of the pandemic nearly four years ago.

Assessing the impact of repetitive transcranial magnetic stimulation on effective connectivity in autism spectrum disorder: An initial exploration using TMS-EEG analysis

Initial indications propose that repetitive transcranial magnetic stimulation (rTMS) could mitigate clinical manifestations in patients with autism spectrum disorder (ASD). Nevertheless, the precise mechanisms responsible for these therapeutic and behavioral outcomes remain elusive. We examined alterations in effective connectivity induced by rTMS using concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) in children with ASD. TMS-EEG data were acquired from 12 children diagnosed with ASD both before and following rTMS treatment. The rTMS intervention regimen included delivering 5-s trains at a frequency of 15 Hz, with 10-min intervals between trains, targeting the left parietal lobe. This was conducted on each consecutive weekday over 3 weeks, totaling 15 sessions. The dynamic EEG network analysis revealed that following the rTMS intervention, long-range feedback connections within the brains of ASD patients were strengthened (e.g., frontal to parietal regions, frontal to occipital regions, and frontal to posterior temporal regions), and short-range connections were weakened (e.g., between the bilateral occipital regions, and between the occipital and posterior temporal regions). In alignment with alterations in network connectivity, there was a corresponding amelioration in fundamental ASD symptoms, as assessed through clinical scales post-treatment. According to our findings, people with ASD may have increased long-range frontal-posterior feedback connection on application of rTMS to the parietal lobe.

Urinary PKM2, a marker predicating acute kidney injury in patients with sepsis.

Acute kidney injury (AKI) is a complication commonly occurred in patients with sepsis, and AKI has become the leading cause associated with mortality. PKM2, as a rate-limiting enzyme of glycolysis, was considered to be involved in AKI in vitro and animal models. However, there have been no studies reported on the expression of PKM2 in humans and its association with AKI. A retrospective study including 57 patients (35 males and 22 females) that were admitted into hospital in 2019 was carried out in our research. The basic characteristics and clinical parameters of each patient were collected from patients' medical records. We assessed changes in the expression of serum and urinary PKM2 using ELISA and its association with clinical manifestations in patients with sepsis through correlation analysis. Besides, ROC analysis was applied for evaluating the role of PKM2 in predicting AKI and death rate. Urinary PKM2 is obviously increased in patients with sepsis-associated AKI (P < 0.05), while no significant change was found in the expression of serum PKM2. Moreover, the expression of urinary PKM2 is positively correlated with serum creatinine (r=0.577, P < 0.01) and blood-urea-nitrogen (r=0.531, P<0.01). In addition, it is negatively correlated with glomerular filtration rate (r=-0.583, P<0.01). Besides, ROC analysis indicated that urinary PKM2 could be a predictor of AKI in patients with sepsis (AUC-ROC, 0.819; SE, 0.086, P = 0.004, 95% CI 0.651-0.986). Urinary PKM2 could be a marker predicting acute kidney injury in patients with sepsis.

The effects of IL-27 and IL-35 gene variation and expression levels on the susceptibility and clinical manifestations of pulmonary tuberculosis.

Inflammatory cytokines have crucial roles in the pathogenesis of tuberculosis (TB), and interleukin (IL)-27 and IL-35 have a pro-inflammatory and anti-inflammatory effect on many diseases, including infectious diseases. Therefore, we evaluated the relationship between IL-27 and IL-35 gene polymorphism, expression levels, and pulmonary TB (PTB) susceptibility. Nine single-nucleotide polymorphisms (SNPs) in the IL-27 gene (rs181206, rs153109, and rs17855750) and the IL-35 gene (rs4740, rs428253, rs9807813, rs2243123, rs2243135, and rs568408) were genotyped by the SNPscan technique in 497 patients with PTB and 501 controls. There was no significant difference regarding the genotype and allele frequencies of the above SNPs in the IL-27 and IL-35 genes between patients with PTB and controls. Haplotype analysis showed that the frequency of the GAC haplotype in the IL-35 gene was significantly decreased in patients with PTB when compared to controls (p = 0.036). Stratified analysis suggested that the frequency of the IL-27 rs17855750 GG genotype was significantly increased in patients with PTB with fever. Moreover, the lower frequency of the IL-35 rs568408 GA genotype was associated with drug-induced liver injury in patients with PTB. The IL-35 rs428253 GC genotype, as well as the rs4740 AA genotype and A allele, showed significant relationships with hypoproteinemia in patients with PTB. When compared with controls, the IL-27 level was significantly increased in patients with PTB. Taken together, IL-35 gene variation might contribute to a protective role on the susceptibility to PTB, and IL-27 and IL-35 gene polymorphisms were associated with several clinical manifestations of patients with PTB.

COVID-19 acts like a stress test, uncovering the vulnerable part of the human body: a retrospective study of 1640 cases in China.

Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exhibits multi-organ damage with diverse complications, the correlation between age, gender, medical history and clinical manifestations of novel coronavirus disease 2019 (COVID-19) patients was investigated. 1640 patients who were infected with SARS-CoV-2 and hospitalized at the First Affiliated Hospital of Ningbo University from 22 December 2022 to 1 March 2023 were categorized and analysed. Normal distribution test and variance homogeneity test were performed. Based on the test results, one-way analysis of variance, Pearson's chi-squared test and logistic regression analysis were conducted in the study. According to the ANOVA, there was a significant difference in the age distribution (P = .001) between different clinical presentations, while gender did not (P = .06). And regression analysis showed that age, hypertension, atherosclerosis and cancer were significant hazard factors for the development of predominant clinical manifestations in patients hospitalized with novel COVID-19. Additionally, infection with SARS-CoV-2 has the potential to exacerbate the burden on specific diseased or related organs. The elderly who are infected with SARS-CoV-2 ought to be treated with emphasis not only on antiviral therapy but also on individualized treatment that takes their medical history and comorbidities into account.

The Challenge for a Correct Diagnosis of Refractory Thrombocytopenia: ITP or MDS with Isolated Thrombocytopenia?

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by isolated thrombocytopenia. It is diagnosed in patients with a platelet count below 100,000 per cubic millimeter in whom other causes of thrombocytopenia have been ruled out, and its diagnosis is generally one of exclusion. Clinical manifestations of patients may vary from asymptomatic disease to mild mucocutaneous or life-threatening bleeding. Glucocorticoids are used as first-line treatment for ITP, while other second-line medications, mainly thrombopoietin-receptor agonists (TPO-RA) and rituximab, are given to patients in whom ITP does not remit, or relapses soon after glucocorticoid treatment. Refractoriness of ITP strongly questions its diagnosis and necessitates a thorough clinical and laboratory work-up to decide whether that is the case of refractory ITP or a misdiagnosis. The aim of this review is to summarize the conditions associated with isolated thrombocytopenia and highlight the characteristics of confusing cases. Even though the case of a myelodysplastic syndrome presented with isolated thrombocytopenia (MDS-IT) is relatively rare and not well-established in the literature, it constitutes one of the most predominant misdiagnoses of refractory ITP. MDS-IT patients are thought to present with multilineage dysplasia, normal karyotype and low risk prognostic score, based on IPSS-R. It has been shown that a significant proportion of MDS-IT patients are misdiagnosed as having the more common ITP. Therefore, it is crucial that in confusing cases of persistent thrombocytopenia a detailed diagnostic work-up is applied-including evaluation of peripheral-blood smear, bone marrow examination and cytogenetic testing-to avoid unnecessary therapy delay.

Abstract 2079: Tumor-derived fibrinogen promotes pancreatic ductal adenocarcinoma progression

Abstract Background: Hypercoagulability is a common clinical manifestation in patients with cancers, especially in pancreatic ductal adenocarcinoma (PDAC). Over 20% of PDAC patients with advanced-stage and worse prognosis undergo a venous thromboembolism (VTE) incidence. Fibrinogen (FG) may contribute to VTE due to its high expression in advanced PDAC tumors. Here, we set to determine the biological roles of tumor-derived FG in PDAC. In addition, our previous study showed that Von Willebrand Factor (VWF) A2 domain can effectively bind to FG and reduce platelet clot formation. Therefore, the functional roles of A2 on FG in PDAC were also studied. Methods: The correlation between survival rate and FG expression in PDAC was analyzed using RNAseq profiles of 149 PDAC patient samples from the TCGA database. PDAC subtyping of Baylor College of Medicine (BCM) PDAC patient-derived xenograft (PDX) cohort was performed using RNAseq data according to Moffitt’s criteria. The FG (three chains FGA, FGB, FGG) overexpression (OE) and knock-out (KO) PDAC cell lines were established. The gene expression and biological functions of FG were performed in PDX and cell lines using IHC and immunoblot assays. The FG effect on PDAC progression in vivo was studied in mouse models. Results: TCGA analysis showed that elevated tumor-derived FG gene expression is significantly correlated with worse overall survival and disease-free survival rates in PDAC patients. PDX lines RNAseq analysis clearly separated BCM PDAC PDXs into two subtypes: basal-like and classical PDACs. Basal-like PDXs showed significantly stronger FG staining than that in classical ones. Compared to the classical subtype, the basal-like subtype showed significantly upregulated genes that are associated with the epithelial-mesenchymal transition (EMT), IL6/JAK/STAT3, and TNFα signaling pathways. Accordingly, basal-like subtype PDAC exposed to IL6 or TNFα significantly increased FG and FG receptor expression with activated STAT3 and AKT pathways and elevated EMT markers, whereas classical subtype cells have minimal changes. In addition, we found that the FG-OE cells exhibit enhanced cell proliferation and migration properties whereas FG-KO cells reduced the effects. Consistent with in vitro data, FG-OE PDAC showed significantly higher tumor burdens than that of control PDAC in both orthotopic and subcutaneous PDAC mouse models. Furthermore, A2 protein treatment can effectively block the FG function and dramatically inactivate the FG-induced EMT process and AKT signaling pathway. Conclusions: Tumor-derived fibrinogen is upregulated in a basal-like subtype of PDAC cells and may contribute to tumor growth and metastasis by activating aberrant signaling pathways and promoting EMT. Our findings imply that elevated fibrinogen in PDAC could contribute to tumor progression and the A2 protein which target to fibrinogen may be a promising therapy for basal-like subtype PDAC. Citation Format: Dongliang Liu, Lisa Brubaker, Yichi Niu, Emily LaPlante, George Van Buren, Aleksandar Milosavljevic, Changyi Chen, Chenghang Zong, Miguel Cruz, Qizhi Yao. Tumor-derived fibrinogen promotes pancreatic ductal adenocarcinoma progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2079.

Efficacy of Nano-curcumin Supplementation on Depression, Anxiety, Stress and Clinical Symptoms in Migraine Patients: A Randomized Double-blind Clinical Trial

Background:: Migraine is a debilitating neuroinflammatory disorder. Patients with migraine often experience elevated levels of depression, anxiety, and stress, which are associated with the frequency and severity of migraine attacks. Curcumin has been shown to have regulatory effects on depression, anxiety, and stress, as well as analgesic properties through various mechanisms. The objective of this study was to assess the impact of nanocurcumin supplementation on depression, anxiety, stress, and clinical manifestations in patients with migraine. Methodology:: This study was conducted as a randomized, double-blind clinical trial. A total of forty-four patients with episodic migraines were recruited for the trial. Stratified randomization was employed to ensure a balanced distribution of participants based on BMI and sex. The patients were equally assigned to two groups using permuted block randomization: 1) the intervention group, which received 80 mg of nano-curcumin, and 2) the placebo (control) group, which received a paraffin-based placebo. The intervention and control periods lasted for 2 months. Anthropometric and demographic data, clinical signs and symptoms (including headache frequency, duration, and severity as reported by the patients), as well as stress, anxiety, and depression scores (using the Dass-21 questionnaire), were recorded before and after the study. The collected data were analyzed using SPSS 22. For normally distributed data, paired t-tests and independent t-tests were utilized. Non-normal data were analyzed using the Wilcoxon test and Mann-Whitney U test. The chi-squared test was employed for categorical variables. To account for confounding factors, the ANCOVA test was conducted. A p-value of ≤ 0.05 was considered statistically significant. The intention-to-treat method was applied to address outliers and missing data. Results:: Based on the findings, the current study demonstrates that supplementation with nano-curcumin can effectively mitigate symptoms of depression and anxiety (p &lt; 0.05). Regarding stress, a noticeable reduction within the nano-curcumin group was observed, although it did not reach statistical significance when compared between groups (p &gt; 0.05). Moreover, nano-curcumin exhibited a significant decrease in the frequency, duration, and severity of headaches (p &lt; 0.05). Conclusion:: Our research findings have shown that supplementation with nano-curcumin can effectively decrease the frequency, severity, and duration of headaches while also alleviating symptoms of depression and anxiety in comparison to the placebo group. Hence, curcumin exhibits significant potential as an adjuvant therapy to enhance the treatment of migraines.

Disturbance in the Composition of the Intestinal Microflora in the Mechanisms of the Formation of Clinical Manifestations in Patients with Chronic Pancreatitis

To determine the role of a violation of the composition of the intestinal microflora in the formation of clinical manifestations and in structural changes of COD in patients with CP and to evaluate the effect of therapy aimed at restoring intestinal microbiosenosis on the course of the disease

A Novel Splicing Mutation Leading to Wiskott-Aldrich Syndrome from a Family.

Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive genetic disease characterized by clinical symptoms such as eczema, thrombocytopenia with small platelets, immune deficiency, prone to autoimmune diseases, and malignant tumors. This disease is caused by mutations of the WAS gene encoding WASprotein (WASP). The locus and type of mutations of the WAS gene and the expression quantity of WASP were strongly correlated with the clinical manifestations of patients. We found a novel mutation in the WAS gene (c.931 + 5G > C), which affected splicing to produce three abnormal mRNA, resulting in an abnormally truncated WASP. This mutation led to a reduction but not the elimination of the normal WASP population, resulting in causes X-linked thrombocytopenia (XLT) with mild clinical manifestations. Our findings revealed the pathogenic mechanism of this mutation.

The association between vertebral artery hypoplasia and fetal-type variants of the posterior cerebral artery with imaging findings among patients with posterior circulation stroke: A single-center cross-sectional study.

The present study investigated the correlation between vertebral artery hypoplasia and fetal-type variations of posterior cerebral arteries with stroke patterns and imaging findings in individuals with posterior circulation ischemic stroke. In this cross-sectional study, patients with symptoms of acute ischemic stroke in the posterior circulation system referred to Ghaem Hospital in Mashhad between 2016 and 2022 were investigated. Demographic data, including age, gender, systemic diseases, history of previous stroke or transient ischemic attacks, and clinical manifestations of patients, were recorded using questionnaires and checklists from patient files. The results of imaging studies, including magnetic resonance imaging and computed tomography angiography, were also recorded. The obtained data were analyzed by SPSS statistical software. Among 974 patients suffering from posterior circulation ischemic stroke, 155 patients with an average age of 60.44 ± 13.95 years were included in the study, out of which 97 patients (62.6%) were male. Unilateral vertebral artery hypoplasia on the right, left, and bilateral hypoplasia was present in 67 (43.2%), 35 (22.6%), and 5 (3.2%) patients, respectively. There were complete unilateral fetal origin on the right in 38 (24.5%), complete unilateral on the left in 12 (7.7%), partial unilateral on the right in 12 (7.7%), partial unilateral on the left in 6 (3.9%), complete bilateral in 14 (9%), and partial bilateral in 8 (5.2%) patients. There was no significant relationship between vertebral artery hypoplasia and PCA fetal-type variants with different ischemia locations and infarct patterns (p > 0.05). Also, there was no significant relationship between the age and gender of patients with ischemia location and infarct pattern (p > 0.05). Despite previous evidence showing a relation between vertebral artery hypoplasia and PCA fetal-type variants as risk factors for PC stroke, the present study did not establish a significant correlation between these factors and the location of ischemia and infarct patterns.

Clinical characteristics and efficacy analysis of various treatments for spontaneous carotid artery dissection

Objective: To investigate the clinical features of spontaneous carotid artery dissection (SCAD) and the efficacy of different treatment methods. Methods: The clinical data of 164 patients with SCAD who were treated at the First Affiliated Hospital of Zhengzhou University from June 2018 to January 2023 were retrospectively analyzed. There were 127 males and 37 females, with a mean age of (49.5±11.1) years. They were divided into conservative treatment group (n=100) and surgical treatment group (n=64) according to whether they received surgical treatment. Patients were followed at 3, 6, and 12 months after discharge and annually thereafter through outpatient or inpatient visits. The incidence of cerebral ischemic events, cerebral hemorrhage events, and mortality rates during hospitalization and follow-up periods were analyzed in the two patient groups. To examine correlates of revascularization in SCAD, multifactorial logistic regression analysis was used. Results: Of the 164 patients, 18 patients had bilateral SCAD and a total of 182 carotid arteries were included in the study. Ischemic stroke (85 cases, 51.8%) and transient ischemic attack (31 cases, 18.9%) were the main clinical manifestations in SCAD patients. Hypertension (81 cases, 49.4%) and hyperlipidemia (39 cases, 23.8%) were the main comorbidities in SCAD patients. During hospitalization, 100 patients in the conservative treatment group received medication in 113 carotid arteries, no new cerebral ischemic events or symptomatic intracranial hemorrhage events occurred, and no death occurred. A total of 69 carotid arteries were surgically treated in 64 patients in the surgical treatment group. The success rate was 97.1% (67/69). In the surgical treatment group, the proportion of carotid stenosis degree≥90% was 47.8% (33/69), the proportion of type Ⅱ SCAD was 60.9% (42/69), and the proportion discharged from the hospital to receive antiplatelet therapy was 92.8% (64/69), which were higher than those in the conservative treatment group, which were 25.7% (29/113), 45.1% (51/113), and 73.5% (83/113), respectively (all P<0.05). The follow-up time [M(Q1, Q3)] in the conservative treatment group was 24 (13, 34) months, with an 8% (9/113) rate of ischemic events and a 7.1% (8/113) rate of readmission; in the surgical treatment group, the follow-up time was 24 (11, 38) months, and there were no new ischemic events or deaths. The results of multifactorial logistic regression analysis showed that the degree of true luminal stenosis<90% (OR=2.738, 95%CI: 1.067-7.026, P=0.036) and type Ⅰ dissections (OR=2.656, 95%CI: 1.189-5.935, P=0.017) were the correlates of complete revascularization. Conclusions: Ischemic stroke and transient ischemic attack are the main clinical manifestations in patients with SCAD. Pharmacological antithrombotic therapy remains the method of choice, and endovascular treatment after failure of conservative therapy reduces the risk of recurrent long-term cerebral ischemic events and the re-admission rate of patients.

Clinical and genetic characterization of patients with catecholaminergic polymorphic ventricular tachycardia: a case series

AIM: of the study was to evaluate the clinical and genetic characteristics, including the development of adverse events and outcomes in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT).&#x0D; MATERIALS AND METHODS: The clinical phenotype of eight patients with CPVT, two of whom were relatives of probands, was observed over 4 years. The clinical and instrumental study included ECG-12, 24-hour Holter ECG monitoring, genealogical history collection and family history of sudden cardiac death (SCD), transthoracic echocardiography and cardiac magnetic resonance imaging to detect structural myocardial changes, electrophysiologic study according to indications, and ICD monitoring. High-throughput sequencing (NGS) was utilized to search for mutations in genes linked to the onset of channelopathies and other inherited rhythm disorders.&#x0D; RESULTS: In 8 patients, nucleotide variants of pathogenicity classes III-V were identified according to the ACMG (2015) criteria in the RYR2 gene associated with CPVT. Pathogenic (IV-V class) and likely pathogenic (IV class) mutations in the RYR2 gene were found in 6 (75%) probands, variants with uncertain clinical significance (VUS, class III) were found in 2 patients. At the time of diagnosis, transient QTc interval prolongation of more than 480 ms was detected in 4 (50%) patients; bradycardia less than 54 beats/min — in 2 (25%) patients, sequences of supraventricular tachycardia and ventricular tachyarrhythmia — in 2 (25%) patients. The most severe form of the disease with marked clinical manifestations and an episode of clinical death with subsequent resuscitation, as well as a transient QTc interval prolongation exceeding 500 ms was observed in patients with mutations c.11814C A (p.Ser3938Arg, rs794728704); c.463G A (p.Gly155Arg) and c.14876G A (p.Arg4959Gln, rs794728811) in the RYR2 gene. Three (37.5%) patients underwent ICD implantation; one for primary SCD prevention and two for secondary prevention.&#x0D; CONCLUSION: In this study, the spectrum of clinical manifestations in patients with genetically confirmed CPVT was examined. The findings highlight transient QTc interval extensions, significant sinus bradycardia, and sequences of supraventricular tachyarrhythmias, which can escalate into life-threatening ventricular tachyarrhythmias in CPVT patients.

Diabetic peripheral neuropathy: pathogenetic mechanisms and treatment.

Diabetic peripheral neuropathy (DPN) refers to the development of peripheral nerve dysfunction in patients with diabetes when other causes are excluded. Diabetic distal symmetric polyneuropathy (DSPN) is the most representative form of DPN. As one of the most common complications of diabetes, its prevalence increases with the duration of diabetes. 10-15% of newly diagnosed T2DM patients have DSPN, and the prevalence can exceed 50% in patients with diabetes for more than 10 years. Bilateral limb pain, numbness, and paresthesia are the most common clinical manifestations in patients with DPN, and in severe cases, foot ulcers can occur, even leading to amputation. The etiology and pathogenesis of diabetic neuropathy are not yet completely clarified, but hyperglycemia, disorders of lipid metabolism, and abnormalities in insulin signaling pathways are currently considered to be the initiating factors for a range of pathophysiological changes in DPN. In the presence of abnormal metabolic factors, the normal structure and function of the entire peripheral nervous system are disrupted, including myelinated and unmyelinated nerve axons, perikaryon, neurovascular, and glial cells. In addition, abnormalities in the insulin signaling pathway will inhibit neural axon repair and promote apoptosis of damaged cells. Here, we will discuss recent advances in the study of DPN mechanisms, including oxidative stress pathways, mechanisms of microvascular damage, mechanisms of damage to insulin receptor signaling pathways, and other potential mechanisms associated with neuroinflammation, mitochondrial dysfunction, and cellular oxidative damage. Identifying the contributions from each pathway to neuropathy and the associations between them may help us to further explore more targeted screening and treatment interventions.

The Characteristics of Chest Pain in the Emergency Setting among Patients with Chronic Kidney Disease

Background: Chronic kidney disease (CKD) is considered a major public health issue, not only due to the possibility of progressing to end-stage renal disease but also because it is closely related to the development of acute coronary syndrome (ACS). It is still unclear in the literature whether individuals with renal dysfunction present particularities in the clinical manifestations during acute myocardial infarction, similar to individuals with diabetes. Aims: To evaluate the characteristics of clinical manifestations in patients with CKD and ACS. Methods: The Chi-square test and Student's t-test were used to analyze the profile of patients with coronary syndrome and renal disease who were admitted for chest pain at the analyzed hospital. Results: The majority of individuals with renal disfunction present highly suspicious characteristics, with statistical significance by presenting a p-value equal to 0.01 and a 95% confidence interval (0.04-0.14). Conclusion: Individuals with kidney disease predominantly exhibit highly suspicious clinical manifestations for acute coronay syndrome.

Оценка факторов риска развития интраоперационного синдрома девиации инфузионных потоков с учетом анатомо-топографических особенностей переднего отрезка

Relevance. Despite continuous improvement in cataract surgery technology, intraoperative fluid misdirection syndrome remains an underestimated problem. Purpose. To evaluate intraoperative fluid misdirection syndrome clinical manifestation in patients with pseudoexfoliation syndrome (PXS) and without it; to assess intraoperative fluid misdirection syndrome risk factors according to anatomical and topographical features of anterior segment. Material and methods. There were two groups of patients who underwent phacoemulsification in the prospective study. Study group (50 eyes) included patients with complicated cataract, PXS and drug-induced mydriasis less than 6 mm. Control group (50 eyes) included patients with senile cataract, no PXS and drug-induced mydriasis more than 6 mm were enrolled in the control group. Clinical examination of patients included optical biometry, pupillometry using rotational Scheimpflug imaging, ultrasound biomicroscopy for evaluation of iris thickness and sectional area of posterior chamber under drug-induced mydriasis. Results. The average pupil diameter in 1 hour after instillation of mydriatics was 5.46±0.46 mm in the study group and 6.6±0.43 mm in the control group. The sectional area of posterior chamber was 0.67±0.28 mm² and iris thickness – 0.53±0.05 mm in the study group. The sectional area of posterior chamber was 0.43±0.15 mm² and iris thickness – 0.64±0.07 mm in the control group. The results revealed positive correlation between pupil diameter and iris thickness, and negative correlation between pupil diameter, iris thickness and sectional area of posterior chamber. Lens floaters were determined after phacoemulsification in 9 eyes (18%) in the study group and in 3 eyes (6%) in the control group. The results showed statistically significant difference between groups (p≤0.05). Conclusion. Lens floaters in the retrolental space as one of the main manifestations of the intraoperative fluid misdirection syndrome were observed in 18% patients of study group and in 6% patients of control group (p≤0.05). Combination of PXS and drug-induced mydriasis less than 6 mm is considered to be the predictive factor of intraoperative fluid misdirection syndrome. Key words: intraoperative fluid misdirection syndrome, pseudoexfoliation syndrome, anterior vitreous face

Percutaneous coronary intervention in patients admitted with acute coronary syndrome within 6 months after COVID-19 (retrospective single-center study)

BACKGROUND: Assessing clinical manifestations in patients during the period of destabilization of the course of coronary artery disease after COVID-19 coronavirus infection remains a clinical problem. Identifying features of coronary artery lesions in such patients will help to prevent the development of complications and may influence the tactics of active dynamic monitoring.&#x0D; AIM: To evaluate the structure of coronary artery lesions and clinical manifestations in patients with acute coronary syndrome that developed within 6 months after COVID-19 new coronavirus infection.&#x0D; MATERIALS AND METHODS: A comparative analysis of the results of coronary artery stenting in 157 patients admitted with acute coronary syndrome has been carried out. The 1st group included 69 patients who had COVID-19 (vaccinated — 24.6%) during the 6 months preceding acute coronary syndrome; in the 2nd — 88 patients without a history of COVID-19 (vaccinated — 42%). All the patients had drug-eluting stents implanted in the infarct-related artery. Long-term results have been observed in 151 (96.2%) patients.&#x0D; RESULTS: Before the development of acute coronary syndrome, dispnoe was more often observed in patients of the 1st group (36; 52%) than in patients of the 2nd group (13; 14.8%). There were no focal neurological symptoms in the patients of both groups. Dizziness more often preceded acute coronary syndrome in the patients of the 1st group (26; 38.2%) compared to the control group (5; 5.7%). Decreased motivation and fatigue were detected in 27 (67.5%) patients in the 1st group, which was more common than in the 2nd group (13; 32.5%). Acute coronary syndrome with ST elevation was treated in 47 % and 38.6% of the patients in the 1st groups and the 2nd, respectively. The development of acute coronary syndrome with ST segment elevation with previous clinical manifestations of post-covid syndrome in the 1st group was observed in 95.8%, whereas in the absence of post-covid syndrome in 53.3%. The mean value of LVEF in patients who had COVID-19 was 55.9 ± 14%, which was significantly lower than in the patients in the control group (63.2 ± 5.5%; р 0.001). During the course of coronavirus infection in the patients in the first group, lung damage of degrees I–II according to CT scan data was observed in 76.8% of the patients and in 23.2% of degrees III–IV. The frequency of lesions of the circumflex branch in the 1st group was 15.9%, in the 2nd — 11.4% (р = 0.403); of the right coronary artery — 33.3%, and 22.7% (р = 0.41); of the diagonal branch — 5.8%, and 3.4% (р = 0.47); of the left main coronary artery — 5.8%, and 6.8% (р = 0.79), of the left anterior descending branch — 52.2%, and 35.2% (р = 0.033), respectively. The incidence of vasospastic angina in the 1st group was 53.6%, in the 2nd — 15.9% (р 0.0001). ST segment elevation in lead AVR as a manifestation of subendocardial ischemia was registered in the 1st group — 40.6%, the 2nd — 11.4% (р 0.0001). All the patients had drug-eluting stents implanted in the infarct-related artery. Overall survival (in-hospital and long-term) was 100% for the first group and 100 % for the second one.&#x0D; CONCLUSIONS: In the structure of coronary arteries lesions after COVID-19 new coronavirus infection in patients with acute coronary syndrome, damage to the anterior interventricular artery dominates (52.2%). The likelihood of having a left anterior descending lesion during the development of acute coronary syndrome with ST segment elevation in patients who have had COVID-19 is 1.5 times higher. The structure of clinical manifestations after COVID-19 in patients before the development of acute coronary syndrome is dominated by shortness of breath (52 %) and decreased motivation and fatigue (67.5 %).

Priority choice of topical antibacterial drugs in the commonly accepted paradigm of acute rhinosinusitis treatment

Introduction. In the complex therapy of acute rhinosinusitis, topical drugs with different mechanisms of action and influence on the main links in the pathogenesis of acute infectious lesions of the mucous membrane of the paranasal sinuses are widely used. Local drugs with antibacterial, as well as mucolytic and vasoconstrictor effects do not inhibit mucociliary clearance, have a convenient release form and ensure dosing accuracy with each use.Aim. Evaluation of the clinical effectiveness of the use in complex therapy of a topical antibiotic of the aminoglycoside group in combination with a drug having vasoconstrictive and mucolytic effects of domestic production in the treatment of acute bacterial rhinosinusitis.Materials and methods. The study involved 30 patients with a verified diagnosis of acute bacterial rhinosinusitis of moderate severity aged 18 to 68 years, who were divided into two groups. Patients of the first group (n = 15), in addition to complex treatment (antibacterial, antihistamine and unloading therapy, anti-inflammatory and puncture treatment), used a drug with a bactericidal effect from the group of aminoglycosides (Tramicent). Patients of the second group (n = 15) supplemented the same treatment with a drug with mucolytic and vasoconstrictive action (Rhinostein®). The effectiveness of therapy was evaluated based on the results of three visits to the doctor within two weeks.Results. The positive dynamics of the subjective and objective status of patients in both study groups was noted. By the 3rd visit (10–14 days), the severity of clinical manifestations in patients who used two drugs Tramicent and Rhinostein® as additional therapy was 2 times lower than at the first visit compared with the group of patients who used only Tramicent as additional therapy. The absence of complaints after treatment in the 2nd group was noted by 15% of the examined, in the 1st – 10%.Conclusions. Topical drug from the group of aminoglycosides containing the active substance framycetin sulfate (Tramicent) in the form of a spray is a safe and effective remedy in the complex therapy of bacterial rhinosinusitis, and its use in combination with the drug mucolytic and vasoconstrictive action (Rhinostein®) significantly reduces the duration of treatment and improves the quality of life of patients.