Course Of Disease Research Articles

DARIER-ROUSSY SUBCUTANEOUS SARCOIDOSIS: A CASE-BASED REVIEW

Sarcoidosis is a systemic granulomatous inflammatory condition characterized by varied clinical manifestations, with a higher prevalence observed in individuals aged 25 to 40 and women over 50. Typical presentations involve symmetric involvement of hilar and mediastinal lymph nodes, followed by lung involvement. While initial stages are often asymptomatic, the disease can impact various organs. Cutaneous involvement, observed in up to a quarter of patients, includes lupus pernio, papules, plaques, erythema nodosum, and occasionally subcutaneous nodules. Subcutaneous sarcoidosis, once considered rare, is now increasingly recognized. We present a case of Darier-Roussy sarcoidosis in a middle-aged man, demonstrating multiple painless subcutaneous nodules confirmed through biopsy. Our findings suggest that Darier-Roussy sarcoidosis typically manifests early in the disease course, indicating non-severe systemic involvement. Additionally, our patient responded well to hydroxychloroquine treatment, suggesting a positive outcome.

Susceptibility-Weighted MRI for Predicting NF-2 Mutations and S100 Protein Expression in Meningiomas.

S100 protein expression levels and neurofibromatosis type 2 (NF-2) mutations result in different disease courses in meningiomas. This study aimed to investigate non-invasive biomarkers of NF-2 copy number loss and S100 protein expression in meningiomas using morphological, radiomics, and deep learning-based features of susceptibility-weighted MRI (SWI). This retrospective study included 99 patients with S100 protein expression data and 92 patients with NF-2 copy number loss information. Preoperative cranial MRI was conducted using a 3T clinical MR scanner. Tumor volumes were segmented on fluid-attenuated inversion recovery (FLAIR) and subsequent registration of FLAIR to high-resolution SWI was performed. First-order textural features of SWI were extracted and assessed using Pyradiomics. Morphological features, including the tumor growth pattern, peritumoral edema, sinus invasion, hyperostosis, bone destruction, and intratumoral calcification, were semi-quantitatively assessed. Mann-Whitney U tests were utilized to assess the differences in the SWI features of meningiomas with and without S100 protein expression or NF-2 copy number loss. A logistic regression analysis was used to examine the relationship between these features and the respective subgroups. Additionally, a convolutional neural network (CNN) was used to extract hierarchical features of SWI, which were subsequently employed in a light gradient boosting machine classifier to predict the NF-2 copy number loss and S100 protein expression. NF-2 copy number loss was associated with a higher risk of developing high-grade tumors. Additionally, elevated signal intensity and a decrease in entropy within the tumoral region on SWI were observed in meningiomas with S100 protein expression. On the other hand, NF-2 copy number loss was associated with lower SWI signal intensity, a growth pattern described as "en plaque", and the presence of calcification within the tumor. The logistic regression model achieved an accuracy of 0.59 for predicting NF-2 copy number loss and an accuracy of 0.70 for identifying S100 protein expression. Deep learning features demonstrated a strong predictive capability for S100 protein expression (AUC = 0.85 ± 0.06) and had reasonable success in identifying NF-2 copy number loss (AUC = 0.74 ± 0.05). In conclusion, SWI showed promise in identifying NF-2 copy number loss and S100 protein expression by revealing neovascularization and microcalcification characteristics in meningiomas.

Long-term effectiveness of zoledronic acid in patients with Paget's disease of bone - a retrospective cohort study.

The aims of the current study were to describe clinical and biochemical features of patients with Paget disease of bone (PDB) followed at our medical center, and to examine the long-term effectiveness of zoledronate. Retrospective cohort study included consecutive patients≥18 years with a diagnosis of PDB, followed in the Rabin Medical Center (RMC) Institute of Endocrinology from 1973 to 2023. The cohort comprised two groups: patients treated/not treated with zoledronic acid (ZOL/NZOL). The primary outcome was the percentage of patients who achieved a biochemical therapeutic response. Overall, 101 patients with PDB were included, 68 in the ZOL group and 33 in the NZOL group. The mean age was 65.2 ± 10.0 years, and 47% were female. Notably, 77% exhibited monostotic involvement, and only 3% had experienced fractures attributed to PDB. Mean ALP level at diagnosis was 160 ± 70.6 U/L. The median follow-up duration was 17 years since PDB diagnosis, comparable between the groups. Primary outcome was more prevalent in the ZOL compared to the NZOL group [42 patients (88%) VS 11 patients (52%) respectively, P = 0.004]. At the end of follow-up, mean ALP levels in the NZOL group were significantly higher than the levels in the ZOL group irrespective of the number of infusions received. The majority of patients with PDB experience a mild disease course, marked by monostotic involvement and a low prevalence of fractures. Zoledronic acid effectively manages PDB, providing sustained biochemical response. The necessity for multiple zoledronic acid injections remains questionable, often implemented due to osteoporosis.

Alterations in gamma frequency oscillations correlate with cortical tau deposition in Alzheimer’s disease

We assessed the relationship of gamma oscillations with tau deposition in Alzheimer’s disease (AD) and other cognitive diseases, as both are altered during the disease course and relate to neurodegeneration. We retrospectively analyzed data from 7 AD, tau positive patients and 9 tau negative patients, who underwent cerebral amyloid PET and tau PET, and EEG within 12 months. Relative gamma power was higher in tau positive (AD) patients than in tau negative patients (p < .05). In tau positive AD patients, tau burden was associated with a linear increase in gamma power (p < .05), while no association was present in the tau negative group nor with amyloid-β burden in either group. Thus, increase in the gamma power might represent a novel biomarker for tau driven neurodegeneration.

Real life experience of tafamidis for the treatment of Spanish patients with Val30Met transthyretin amyloidosis with polyneuropathy

IntroductionTafamidis is the only approved transthyretin stabiliser approved for the treatment of variant transthyretin amyloidosis (A-ATTRv) related polyneuropathy (PNP). The aim of this study is to analyse the effectiveness of tafamidis in a real-world setting in Spain. MethodsThis is a national multicenter study in which patients with V30M A-ATTR related PN treated with tafamidis for at least 1 year were included. Clinical, demographic, analytical and neurophysiological variables were analysed. Results100 patients were recruited. Overall, 47 patients (47%) were classified as complete responders, 32 (32%) as partial responders and 21 (21%) as non-responders. The median duration of treatment with tafamidis was 35 months. Better treatment response was shown in patients with in polyneuropathy disability score (PND) I, lower neuropathy impairment score (NIS), compound muscle action potential (CMAP) and Norfolk QoL questionnaire. Higher albumin levels and lower NTproBNP levels were also associated with better treatment response. A basal NIS≥15 predicts that the patient could be a non-responder with a 60% probability. ConclusionsOur results reinforce the tafamidis efficacy to treat A-ATTRv-PNP if started early in the disease course. Patients with the V30M variant, NIS<15 and PND I are the most appropriate subjects for this treatment.

Burden of Mental Health among Patients with Inflammatory Bowel Disease-A Cross-Sectional Study from a Tertiary IBD Center in Hungary.

Background: Inflammatory bowel diseases (IBDs) are chronic conditions that negatively affect the patient's quality of life. With the spread of the biopsychosocial model, the role of mental health in the activity and course of inflammatory bowel disease is becoming more and more recognized. Our study aimed to assess the prevalence of anxiety and depression in IBD patients in our tertiary referral center and determine the predictive factors of these mental conditions. Methods: A total of 117 patients were included consecutively between 1 December 2021 and 28 February 2022. We used a questionnaire to gather demographic information, disease course, and IBD-specific symptoms. We assessed anxiety symptoms using the GAD-7 and depressive complaints using the PHQ-9 questionnaire. We evaluated disease activity using CDAI and pMayo scores. Results: Of the 117 patients (male/female: 63/54), 88 suffered from Crohn's disease, and 29 were diagnosed with ulcerative colitis. Only 6 patients were taking medication for mood disorders, and 38 individuals sought mental support during their lifetime. A total of 15% of the population suffered from moderate-severe anxiety disorder, and 22% were affected by moderate-severe depression. The GAD-7 and PHQ9 values showed a significant correlation between the number of stools, bloody stools, abdominal pain, number of flare-ups, and CDAI scores. Conclusions: Our study confirmed that there is a high incidence of anxiety and depressive symptoms among IBD patients. Our results highlighted the symptoms that could be associated with mental disorders. It is important to assess the mental status of IBD patients to improve their quality of life.

Alterations in Cerebrospinal Fluid Urea Occur in Late Manifest Huntington's Disease.

Huntington's disease (HD) is a neurodegenerative disorder caused by expanded cytosine-adenine-guanine (CAG) repeats in the Huntingtin gene, resulting in the production of mutant huntingtin proteins (mHTT). Previous research has identified urea as a key metabolite elevated in HD animal models and postmortem tissues of HD patients. However, the relationship between disease course and urea elevations, along with the molecular mechanisms responsible for these disturbances remain unknown. To better understand the molecular disturbances and timing of urea cycle metabolism across different stages in HD. We completed a global metabolomic profile of cerebrospinal fluid (CSF) from individuals who were at several stages of disease: pre-manifest (PRE), manifest (MAN), and late manifest (LATE) HD participants, and compared to controls. Approximately 500 metabolites were significantly altered in PRE participants compared to controls, although no significant differences in CSF urea or urea metabolites were observed. CSF urea was significantly elevated in LATE participants only. There were no changes in the urea metabolites citrulline, ornithine, and arginine. Overall, our study confirms that CSF elevations occur late in the HD course, and these changes may reflect accumulating deficits in cellular energy metabolism.

Is Mean Platelet Volume a Predictive Marker for the Development of Thrombosis in Patients with COVID-19 Infection?

Mean platelet volume (MPV) can provide important information about the course and prognosis of many diseases. MPV is an early indicator of platelet activation, which has an important role in the pathogenesis of thrombosis. In this study, we aimed to investigate whether MPV was a predictive marker for the development of thrombosis in hospitalized patients with COVID-19 infection. Fifty-seven patients whose courses were followed after the diagnosis of COVID-19 infection using a polymerase chain reaction test during the pandemic were included in the study. Our results demonstrated that there was a negative correlation between platelet count and MPV (r=0.470, p≤ 0.01), and there was a positive correlation between Platelet Distribution Width (PDW) and MPV (r=0,933, p≤ 0.01), but no significant correlation was found between the other variables and MPV.

Comorbidity of periodontal diseases and atopic dermatitis

Summary. Currently, the relationship between periodontal diseases and somatic pathology has been proven. Studies on the relationship between periodontal diseases and atopic diseases are few, which determines the relevance of this study.&#x0D; Purpose of the study. To characterize the relationship between inflammatory periodontal diseases and atopic dermatitis.&#x0D; Methods. Using the citation-analytical databases PubMed, Google Scholar and eLibrary, 26,470 full-text publications on the research topic were found from 2016 to 2023.&#x0D; Results and discussion: An analysis of literature data was carried out to study the relationship between inflammatory periodontal diseases and atopic dermatitis. The presence of oral pathology in patients with atopic diseases can, on the one hand, lead to a worsening of the course of the atopic disease, and on the other hand, an atopic disease can contribute to the development of oral diseases. After conducting a literature search and applying the inclusion and exclusion criteria for the sample, complete overlap of the research topics was found in only 3 publications. The data obtained turned out to be contradictory, since two publications established a direct connection between periodontitis and atopic dermatitis, and one publication did not. In publications touching on the research topic on certain aspects, the possible mechanisms of comorbidity of periodontal diseases and atopic diseases are characterized and opinions are presented on the existence of a feedback or direct relationship between these pathologies.&#x0D; Conclusion: To date, the periodontal status of patients with atopic dermatitis remains poorly understood, and the evidence linking oral diseases to it is ambiguous. The presented studies partially confirmed the direct connection between periodontal diseases and atopic dermatitis, but the hygiene hypothesis, according to which there is an inverse relationship between periodontal diseases and atopic diseases, was not confirmed.

FEATURES OF THE COURSE OF STABLE CORONARY ARTERY DISEASE WITH BORDERLINE CORONARY ARTERY STENOSES DEPENDING ON THE EPICARDIAL FAT THICKNESS

HighlightsPatients with stable coronary artery disease, borderline coronary artery stenoses (BCAS) and increased thickness of epicardial adipose tissue (EAT) are characterized by development of cardiovascular diseases (CVD) at a younger age and higher levels of proinflammatory markers compared to patients without increased thickness of EAT (in case of comparable obesity class, diabetes type, angina grade and apolipoprotein B levels). Aim. To study the features of the course of stable coronary artery disease with borderline coronary artery stenoses (BCAS) depending on the epicardial fat thickness.Methods. 201 patients with stable angina of 1–3 grade with BCAS (50–70%) were included in the study. The 1st group consisted of 57 (28,4%) patients with high EAT levels, the 2nd group consisted of 144 (71,6%) patients without normal EAT levels. The results of biochemical blood tests and systemic inflammation markers (high-sensitivity C-reactive protein, IL 1, 6, 8, 10, TNF-a, cystatin С, MMP-9, NTproBNP) concentration were evaluated. The epicardial fat thickness was determined by echocardiography. All patients underwent coronary angiography.Results. The general EAT thickness was at 6.00 [5.00; 6.50] mm in the 1st group and at 3.00 [2.30; 4.00] mm in the 2nd group (p&lt;0.001). Hypertension (p&lt;0.001), CAD (p&lt;0.001), and myocardial infarction in particular (p = 0.003) were detected at a younger age in the 1st group. There were no significant differences in terms of prevalence of obesity, diabetes mellitus, angina grade and type of prescribed medication. Patients in the 1st group showed higher levels of NTproBNP (p = 0.002) and hsCRP (p = 0.027). Moreover, patients in the 1st group had a higher Apo-A1 levels (p = 0.023) and a lower Apo B/Apo-A1 ratio (p = 0.019). Proinflammatory cytokine levels were comparable, however anti-inflammatory cytokine IL-10 levels (р =0.005) and the frequency of elevated IL-10 levels (p&lt;0.001) were lower in the 1st group. Higher cystatin C levels and the frequency of elevated cystatin C levels (p&lt;0.001) were observed more often in patients with high EAT levels.Conclusion. Patients with stable CAD, borderline coronary artery stenoses and high EAT levels can be characterized by cardiovascular diseases detected at a younger age and higher levels of proinflammatory markers compared with patients with normal EAT levels in case of comparable obesity class, diabetes mellitus, angina grade, and Apo B levels.

Shifting our attention earlier in the multiple sclerosis disease course.

Revisions of multiple sclerosis (MS) diagnostic criteria enable clinicians to diagnose patients earlier in the biologic disease course. Prompt initiation of therapy correlates with improved clinical outcomes. This has led to increased attention on the earliest stages of MS, including the MS prodrome and radiologically isolated syndrome (RIS). Here, we review current understanding and approach to patients with preclinical MS. MS disease biology often begins well before the onset of typical MS symptoms, and we are increasingly able to recognize preclinical and prodromal stages of MS. RIS represents the best characterized aspect of preclinical MS, and its diagnostic criteria were recently revised to better capture patients at highest risk of conversion to clinical MS. The first two randomized control trials evaluating disease modifying therapy use in RIS also found that treatment could delay or prevent onset of clinical disease. Despite progress in our understanding of the earliest stages of the MS disease course, additional research is needed to systematically identify patients with preclinical MS as well as capture those at risk for developing clinical disease. Recent data suggests that preventive immunomodulatory therapies may be beneficial for high-risk patients with RIS; though management remains controversial.

Electrocardiographic signs of cardiovascular system dysfunction in the context of various courses of COVID-19 in young and middle-aged individuals

BACKGROUD: Intensive monitoring of patients with the coronavirus disease should include functional monitoring of the cardiovascular system. Physiologic methods can detect dysfunction of the cardiovascular system, however, it is not always possible to identify initial or hidden dysfunction. Therefore, clinical data should be complemented with results from instrumental methods, particularly electrocardiography. AIM: To identify preclinical electrocardiography signs of cardiovascular system dysfunction in the context of various courses of coronavirus disease in young and middle-aged individuals. MATERIALS AND METHODS: A retrospective analysis of 337 medical records of young and middle-aged individuals (40.0 ± 13.3 years old) was conducted. The analysis of the medical records included electrocardiograms in 12 leads with the assessment of standard parameters, results of laboratory and instrumental tests. In order to identify the main factors predicting an unfavorable course of the coronavirus disease, a factor analysis was conducted using electrocardiography parameters. Logistic regression analysis was used to develop a statistical model for predicting the likelihood of a severe course and fatal outcome of COVID-19, followed by assessing the diagnostic value of the prognostic model using the ROC curve and determining the area under the curve. RESULTS: The main factors predicting an unfavorable course of the new coronavirus disease in young and middle-aged individuals based on electrocardiography data include the α angle factor, the ventricular repolarization factor and the heart rate factor. In addition, as electrocardiography predictors, the elongation of the P wave and PQ interval, the amplitude of the R wave in lead one, the decrease in the T wave amplitude in the precordial leads, and the amplitude of the R wave in leads two and three can be considered. Based on the identified electrocardiography predictors, a mathematical model for predicting a severe course and fatal outcome of the new coronavirus disease was developed. CONCLUSIONS: Thus, electrocardiography is an indicative method that can be influenced by infectious process which is performed for all individuals upon admission to the hospital, allowing this examination to be considered the most accessible for detecting preclinical signs of an unfavorable course of COVID-19.

Pediatric Acute Mastoiditis in Saudi Arabia: Demographic Insights, Clinical Profiles, and Prognostic Factors.

Acute mastoiditis, a complication of otitis media, poses significant challenges in diagnosis and treatment, particularly in pediatric populations. This study aims to comprehensively evaluate the demographic characteristics, clinical features, and prognostic factors associated with acute mastoiditis in pediatric patients in Saudi Arabia. Analysis of a multicenter dataset was conducted to assess demographic variables, symptomatology, disease course, and predictors of acute mastoiditis in pediatric patients. Significant associations were found between demographic variables (age group, gender, nationality) and acute mastoiditis risk. Symptomatology analysis revealed consistent frequencies of otalgia across age groups and genders. Disease course analysis highlighted a mean duration from symptom onset to diagnosis of 14.11 days, with frequent complications like mastoid abscess and meningitis. Predictor identification identified symptoms (otalgia, fever, otorrhea), duration of illness, and complications as significant predictors of disease severity. These findings contribute valuable insights into the epidemiology and clinical management of acute mastoiditis, informing targeted interventions to improve patient outcomes.

ANALYTICAL REVIEW OF PUBLICATIONS ON MACHINE LEARNING METHODS IN ONCOLOGY AND APPROACH TO EVALUATING THEIR QUALITY

The work includes an analytical review of publications on machine learning methods in oncology and an approach to evaluating their quality. An analysis of publications by year was conducted in the Web of Science and Scopus bibliometric databases. The highest number of authors, the number of publications among universities, the number of countries, and publication categories in the Scopus bibliometric database on machine learning methods in oncology are presented. A multifactor regression prediction model for bone tissue density in oncological pathology predicting four severity grades of the studied disease course was proposed. This model included the following factors with corresponding weights: gender (2.1), age (0.06), stage (0.9), absence/presence of B-symptoms (A/B) (0.9), international prognostic index (IPI-NCCN) ( 1.1), body mass index (BMI) (-0.2), number of chemotherapy courses (0.9), Charlson comorbidity index (СCI) (0.3), bone mineral density after completion of chemotherapy (HU C) (-0.08), β-2-microglobulin (B2M) level (0.0007), lactate dehydrogenase (LDH) (0.006), body surface area (BSA) (-3.3). To assess the level of confidence in the proposed model for predicting bone density disorders in oncological pathology, ROC analysis was performed to obtain the corresponding curves and the area under them was estimated. A conclusion was made about the quality of the classification and the sensitivity, specificity, prognostic value of positive and negative results, the ratio of the probability of positive and negative results, as well as the accuracy of the classification were determined. For each of the four degrees of severity of violations (1C, 2C, 3C, 4C), it is necessary to carry out appropriate calculations, the matrices of inconsistencies for which are given in four tables. Sensitivity was calculated for 1C (98.8%), 2C (97.5%), 3C (95.2%) and 4C (98.5%); specificity for 1C (90.4%), 2C (83.3%), 3C (90.9%) and 4C (95%); predictive value of a positive result for 1C (97.6%), 2C (95.2%), 3C (97.5%) and 4C (97%); predictive value of a negative result for 1C (95%), 2C (90.9%), 3C (83.3%) and 4C (97.4%); accuracy for 1C (97.1%), 2C (97.1%), 3C (97.1%), and 4C (97.1%). According to the results of the analysis of ROC curves, a high level of classification of 1C (AUC=0.869), 3C (AUC=0.869) and 4C (AUC=0.869) was established. The average level of classification of bone density disorders according to 2C (AUC=0.758).

PULMONARY ARTERIAL HYPERTENSION ASSOCIATED WITH CONGENITAL HEART DISEASE: RATIONALE FOR MANAGEMENT ALGORITHM BASED ON A LITERATURE REVIEW

The substantial progress achieved in cardiology and paediatric cardiac surgery has led to a considerable increase of life expectancy of patients with congenital heart disease (CHD), and at the same time to growing number of adult patients developing pulmonary arterial hypertension (PAH) associated with congenital heart defects. Nowadays guidelines were developed and updated for PAH, but no expert recommendations exist for effective management of PAH associated with CHD. Thus, it is important to develop an algorithm for managing these patients, based on international standards and a comprehensive understanding of prognostic markers of worsening the course of pulmonary arterial hypertension (PAH), considering local cardiac tertiary hospitals' capabilities.&#x0D; The aim. To highlight the pathophysiology and clinical characteristics of PAH-CHD patients, identify prognostic markers for its onset and progression, and develop a management algorithm for patients.&#x0D; Results. The article presents the pathophysiology of PAH-CHD, the mechanisms of right ventricle adaptation to pressure overload, which determine the functional abilities of patients and prognosis, PAH formation, and progression after defects correction. The accurate identification of stages in PAH-CHD (volume overload, mixed, stage of pulmonary vascular disease) is essential for the timely determination of surgical intervention, selecting conservative treatment strategies, and predicting the outcomes of surgical defect correction. The type of defect, its size, and the volume of blood flow through the defect influence the onset and progression of PH-CHD. We review the pathophysiology and clinical features of PAH-CHD, as well as the reasons for the late diagnosis of heart failure at the stage of severe decompensation and irreversible remodelling of the lung vessels when diuretic therapy is not effective enough and inotropic support, circulatory mechanical support and heart / lung complex transplantation are required. The necessity of developing new scales for stratifying the risk of PAH-CHD is justified considering the particularities of the disease course and cardiac hemodynamic in different anatomical types of the defects. Based on this literature review, at the Municipal Enterprise «Dnipropetrovsk Regional Clinical Center for Diagnostics and Treatment» of the Dnipropetrovsk Regional Council» the algorithm for managing patients with PAH-CHD was devised and implemented into clinical practice.&#x0D; Conclusions. PAH is a common complication of CHD. The prevalence of PAH-CHD is substantial and it can manifest and progress even in patients with previously corrected heart defects. To effectively manage patients with PAH-CHD, an algorithm has been devised and implemented in clinical practice. It includes factors that have demonstrated associations with poor prognosis which are more than two hospitalizations for HF in the last year, pulmonary vascular resistance (PVR) (or index of PVR), mean pressure in the pulmonary artery, pulmonary capillary wedge pressure, left ventricular ejection fraction, heart failure with a reduced ejection fraction, right ventricle heart failure, NYHA FC, high risk of atrial fibrillation or flutter, 6-minute walking test distance, NTproBNP, highly sensitive C-reactive protein, B-lines on lung ultrasound, glomerular filtration rate, haemoglobin, platelet count, sodium, Model for End-Stage Liver Disease scale.

Brain microstructure is linked to cognitive fatigue in early multiple sclerosis.

Cognitive fatigue is a major symptom of Multiple Sclerosis (MS), from the early stages of the disease. This study aims to detect if brain microstructure is altered early in the disease course and is associated with cognitive fatigue in people with MS (pwMS) compared to matched healthy controls (HC). Recently diagnosed pwMS (N = 18, age < 45years old) with either a Relapsing-Remitting or a Clinically Isolated Syndrome course of the disease, and HC (N = 19) matched for sex, age and education were analyzed. Quantitative multiparameter maps (MTsat, PD, R1 and R2*) of pwMS and HC were calculated. Parameters were extracted within the normal appearing white matter, cortical grey matter and deep grey matter (NAWM, NACGM and NADGM, respectively). Bayesian T-test for independent samples assessed between-group differences in brain microstructure while associations between score at a cognitive fatigue scale and each parameter in each tissue class were investigated with Generalized Linear Mixed Models. Patients exhibited lower MTsat and R1 values within NAWM and NACGM, and higher R1 values in NADGM compared to HC. Cognitive fatigue was associated with PD measured in every tissue class and to MTsat in NAWM, regardless of group. Disease-specific negative correlations were found in pwMS in NAWM (R1, R2*) and NACGM (R1). These findings suggest that brain microstructure within normal appearing tissues is already altered in the very early stages of the disease. Moreover, additional microstructure alterations (e.g. diffuse and widespread demyelination or axonal degeneration) in pwMS may lead to disease-specific complaint of cognitive fatigue.

High frequencies of alpha common cold coronavirus/SARS-CoV-2 cross-reactive functional CD4+ and CD8+ memory T cells are associated with protection from symptomatic and fatal SARS-CoV-2 infections in unvaccinated COVID-19 patients.

Cross-reactive SARS-CoV-2-specific memory CD4+ and CD8+ T cells are present in up to 50% of unexposed, pre-pandemic, healthy individuals (UPPHIs). However, the characteristics of cross-reactive memory CD4+ and CD8+ T cells associated with subsequent protection of asymptomatic coronavirus disease 2019 (COVID-19) patients (i.e., unvaccinated individuals who never develop any COVID-19 symptoms despite being infected with SARS-CoV-2) remains to be fully elucidated. This study compares the antigen specificity, frequency, phenotype, and function of cross-reactive memory CD4+ and CD8+ T cells between common cold coronaviruses (CCCs) and SARS-CoV-2. T-cell responses against genome-wide conserved epitopes were studied early in the disease course in a cohort of 147 unvaccinated COVID-19 patients who were divided into six groups based on the severity of their symptoms. Compared to severely ill COVID-19 patients and patients with fatal COVID-19 outcomes, the asymptomatic COVID-19 patients displayed significantly: (i) higher rates of co-infection with the 229E alpha species of CCCs (α-CCC-229E); (ii) higher frequencies of cross-reactive functional CD134+CD137+CD4+ and CD134+CD137+CD8+ T cells that cross-recognized conserved epitopes from α-CCCs and SARS-CoV-2 structural, non-structural, and accessory proteins; and (iii) lower frequencies of CCCs/SARS-CoV-2 cross-reactive exhausted PD-1+TIM3+TIGIT+CTLA4+CD4+ and PD-1+TIM3+TIGIT+CTLA4+CD8+ T cells, detected both ex vivo and in vitro. These findings (i) support a crucial role of functional, poly-antigenic α-CCCs/SARS-CoV-2 cross-reactive memory CD4+ and CD8+ T cells, induced following previous CCCs seasonal exposures, in protection against subsequent severe COVID-19 disease and (ii) provide critical insights into developing broadly protective, multi-antigen, CD4+, and CD8+ T-cell-based, universal pan-Coronavirus vaccines capable of conferring cross-species protection.

Surgical management of pediatric Crohn's disease

Management of pediatric-onset Crohn's disease uniquely necessitates consideration of growth, pubertal development, psychosocial function and an increased risk for multiple future surgical interventions. Both medical and surgical management are rapidly advancing; therefore, it is increasingly important to define the role of surgery and the breadth of surgical options available for this complex patient population. Particularly, the introduction of biologics has altered the disease course; however, the ultimate need for surgical intervention has remained unchanged. This review defines and evaluates the surgical techniques available for management of the most common phenotypes of pediatric-onset Crohn's disease as well as identifies critical perioperative considerations for optimizing post-surgical outcomes.

MORPHO-FUNCTIONAL PROPERTIES OF ERYTHROCYTES AS A MARKER OF THE PROGRESS OF KIDNEY INJURIES IN PATIENTS WHO HAD CORONAVIRUS DISEASE

Pathology of the morpho-functional state of erythrocytes affects the rheological properties of blood and various regulatory processes that ensure microcirculation in the kidneys. Changes in the morpho-functional state of erythrocytes are the cause of pathological effects on the membranes and receptors of kidney cells. It leads to adverse disorders of vital activity and functioning of the kidneys.Aim. The paper aims to investigate the morpho-functional state of erythrocytes in patients with kidney damage who were sick with COVID-19. Material and methods. 75 patients aged 45-65 years with kidney damage who suffered from moderate COVID 8-12 months ago were examined. Research groups and control groups were formed (patients with appropriate nosology who did not suffer from COVID): I – glomerulonephritis; II – pyelonephritis; ІІІ – diabetic nephropathy of the 4th century. All patients had a protocol examination of nephrological patients, and we also examined the morpho-functional properties of erythrocytes (the deformability index of erythrocytes, peroxide hemolysis of erythrocytes and the relative viscosity of the erythrocyte suspension using filtration methods.Results. Changes in the morpho-functional properties of erythrocytes may indicate the progressive course of kidney diseases in patients who have undergone COVID. It manifested by a decrease in the deformability index of erythrocytes, by more than 40% in patients with glomerulonephritis and twice in patients with diabetic nephropathy, as well as a probable increase in the relative viscosity of the erythrocyte suspension, which was 2 times higher in the group with glomerulonephritis and 3 times higher in the group with diabetic nephropathy compared with pyelonephritis. An inverse correlation between daily proteinuria and the index of deformability of erythrocytes in patients with chronic kidney disease (CKD) after COVID (r=-0.59) (р=0.041), as well as a direct correlation between peroxide hemolysis of erythrocytes and daily proteinuria (r=0.68) ( p=0.038) and between the relative viscosity of the erythrocyte suspension with daily proteinuria (r=0.76) (p=0.035) were detected.Conclusions. Changes in the morpho-functional properties of erythrocytes were more profound in patients with diabetic nephropathy and glomerulonephritis after experiencing COVID than in patients with pyelonephritis. A correlation was found between indicators of morpho-functional properties of erythrocytes and daily proteinuria. Indicators of the morpho-functional properties of erythrocytes can be markers of the progression of CKD in patients who have experienced moderate COVID.

Matching proposed clinical and MRI criteria of aggressive multiple sclerosis to serum and cerebrospinal fluid markers of neuroaxonal and glial injury.

Definitions of aggressive MS employ clinical and MR imaging criteria to identify highly active, rapidly progressing disease courses. However, the degree of overlap between clinical and radiological parameters and biochemical markers of CNS injury is not fully understood. Aim of this cross-sectional study was to match clinical and MR imaging hallmarks of aggressive MS to serum/CSF markers of neuroaxonal and astroglial injury (neurofilament light chain (sNfL, cNfL), and glial fibrillary acidic protein (sGFAP, cGFAP)). We recruited 77 patients with relapsing-remitting MS (RRMS) and 22 patients with clinically isolated syndrome. NfL and GFAP levels in serum and CSF were assessed using a single-molecule-array HD-1-analyzer. A general linear model with each biomarker as a dependent variable was computed. Clinical and imaging criteria of aggressive MS, as recently proposed by the ECTRIMS Consensus Group, were modeled as independent variables. Other demographic, clinical or laboratory parameters, were modeled as covariates. Analyses were repeated in a homogenous subgroup, consisting only of newly diagnosed, treatment-naïve RRMS patients presenting with an acute relapse. After adjusting for covariates and multiplicity of testing, sNfL and cNfL concentrations were strongly associated with the presence of ≥2 gadolinium-enhancing lesions (psNfL = 0.00008; pcNfL = 0.004) as well as the presence of infratentorial lesions on MRI (psNfL = 0.0003; pcNfL < 0.004). No other clinical and imaging criteria of aggressive MS correlated significantly with NfL or GFAP in serum and CSF. In the more homogeneous subgroup, sNfL still was associated with the presence of ≥2 gadolinium-enhancing lesions (psNfL = 0.001), presence of more than 20 T2-lesions (psNfL = 0.049) as well as the presence of infratentorial lesions on MRI (psNfL = 0.034), while cNfL was associated with the presence of ≥2 gadolinium-enhancing lesions (psNfL = 0.011) and presence of more than 20 T2-lesions (psNfL = 0.029). Among proposed risk factors for an aggressive disease course, MRI findings but not clinical characteristics correlated with sNfL and cNfL as a marker of neuroaxonal injury and should be given appropriate weight considering MS prognosis and therapy. No significant correlation was detected for GFAP alone.