Clinical Manifestations Of Disease Research Articles

2-Butoxytetrahydrofuran, Isolated from Holothuria scabra, Attenuates Aggregative and Oxidative Properties of α-Synuclein and Alleviates Its Toxicity in a Transgenic Caenorhabditis elegans Model of Parkinson's Disease.

Aggregative α-synuclein and incurring oxidative stress are pivotal cascading events, leading to dopaminergic (DAergic) neuronal loss and contributing to clinical manifestations of Parkinson's disease (PD). Our previous study demonstrated that 2-butoxytetrahydrofuran (2-BTHF), isolated from Holothuria scabra (H. scabra), could inhibit amyloid-β aggregation and its ensuing toxicity, which leads to Alzheimer's disease. In the present study, we found that 2-BTHF also attenuated the aggregative and oxidative activities of α-synuclein and lessened its toxicity in a transgenic Caenorhabditis elegans (C. elegans) PD model. Such worms treated with 100 μM of 2-BTHF showed substantial reductions in α-synuclein accumulation and DAergic neurodegeneration. Mechanistically, 2-BTHF, at this concentration, significantly decreased aggregation of monomeric α-synuclein and restored locomotion and dopamine-dependent behaviors. Molecular docking exhibited potential bindings of 2-BTHF to HSF-1 and DAF-16 transcription factors. Additionally, 2-BTHF significantly increased the mRNA transcripts of genes encoding proteins involved in proteostasis, including the molecular chaperones hsp-16.2 and hsp-16.49, the ubiquitination/SUMOylation-related ubc-9 gene, and the autophagy-related genes atg-7 and lgg-1. Transcriptomic profiling revealed an additional mechanism of 2-BTHF in α-synuclein-expressing worms, which showed upregulation of PPAR signaling cascades that mediated fatty acid metabolism. 2-BTHF significantly restored lipid deposition, upregulated the fat-7 gene, and enhanced gcs-1-mediated glutathione synthesis in the C. elegans PD model. Taken together, this study demonstrated that 2-BTHF could abrogate aggregative and oxidative properties of α-synuclein and attenuate its toxicity, thus providing a possible therapeutic application for the treatment of α-synuclein-induced PD.

Inhibition of interferon gamma impairs induction of experimental epidermolysis bullosa acquisita

Epidermolysis bullosa acquisita (EBA) is a muco-cutaneous autoimmune disease characterized and caused by autoantibodies targeting type VII collagen (COL7). The treatment of EBA is notoriously difficult, with a median time to remission of 9 months. In preclinical EBA models, we previously discovered that depletion of regulatory T cells (Treg) enhances autoantibody-induced, neutrophil-mediated inflammation and blistering. Increased EBA severity in Treg-depleted mice was accompanied by an increased cutaneous expression of interferon gamma (IFN-γ). The functional relevance of IFN-γ in EBA pathogenesis had been unknown. Given that emapalumab, an anti-IFN-γ antibody, is approved for primary hemophagocytic lymphohistiocytosis patients, we sought to assess the therapeutic potential of IFN-γ inhibition in EBA. Specifically, we evaluated if IFN-γ inhibition has modulatory effects on skin inflammation in a pre-clinical EBA model, based on the transfer of COL7 antibodies into mice. Compared to isotype control antibody, anti-IFN-γ treatment significantly reduced clinical disease manifestation in experimental EBA. Clinical improvement was associated with a reduced dermal infiltrate, especially Ly6G+ neutrophils. On the molecular level, we noted few changes. Apart from reduced CXCL1 serum concentrations, which has been demonstrated to promote skin inflammation in EBA, the expression of cytokines was unaltered in the serum and skin following IFN-γ blockade. This validates IFN-γ as a potential therapeutic target in EBA, and possibly other diseases with a similar pathogenesis, such as bullous pemphigoid and mucous membrane pemphigoid.

Observational and cross-sectional study on clinical profile of nontuberculous mycobacterial (NTM) disease in patients at tertiary care hospital of central India

Background Nontuberculous Mycobacterial (NTM) diseases present unique clinical challenges and are increasingly recognised as significant contributors to respiratory and extrapulmonary morbidity. This study protocol outlines an observational and cross-sectional investigation aiming to comprehensively understand the clinical profile of NTM disease, including its prevalence, risk factors, and clinical features, in patients at a tertiary care hospital in central India. Methods Over two years, from July 2022 to June 2024, a convenience sample size will be recruited from TB suspects meeting inclusion criteria. Comprehensive data collection will be conducted, including demographic information, clinical history, radiological findings, microbiological test results, and risk factor assessments. Statistical methods will be applied to the collected data, including descriptive statistics, comparative analysis, risk factor assessments, and multivariate analyses. Expected Results The study aims to provide valuable insights into the prevalence and clinical manifestations of NTM disease, shedding light on the risk factors contributing to its occurrence. The statistical analyses will identify key factors associated with NTM disease and characterise its clinical and radiological features.

A Nationwide Study of the Delayed Diagnosis and the Clinical Manifestations of Predominantly Antibody Deficiencies and CTLA4-Mediated Immune Dysregulation Syndrome in Greece

Predominantly antibody deficiencies (PAD) represent the most common type of primary immunodeficiencies in humans, characterized by a wide variation in disease onset, clinical manifestations, and outcome. Considering that the prevalence of PAD in Greece is unknown, and there is limited knowledge on the clinical and laboratory characteristics of affected patients, we conducted a nationwide study including 153 patients (male/female: 66/87; median age: 43.0 years; range: 7.0–77.0) diagnosed, and followed-up between August 1979 to September 2023. Furthermore, we classified our cohort into five groups according to their medical history, immunoglobulin levels, and CTLA4-mutational status: 123 had common variable immunodeficiency (CVID), 12 patients with “secondary” hypogammaglobulinemia due to a previous B-cell depletion immunotherapy for autoimmune or malignant disease several years ago (median: 9 years, range 6–14) displaying a typical CVID phenotype, 7 with combined IgA and IgG subclass deficiencies, 5 patients with CVID-like disease due to CTLA4-mediated immune dysregulation syndrome, and 6 patients with unclassified hypogammaglobulinemia. We demonstrated a remarkable delay in PAD diagnosis, several years after the onset of related symptoms (median: 9.0 years, range: 0–43.0). A family history of PAD was only present in 11.8%, with the majority of patients considered sporadic cases. Most patients were diagnosed in the context of a diagnostic work-up for recurrent infections, or recurrent/resistant autoimmune cytopenias. Interestingly, 10 patients (5.6%) had no history of infection, diagnosed due to either recurrent/resistant autoimmunity, or during a work-up of their medical/family history. Remarkable findings included an increased prevalence of lymphoproliferation (60.1%), while 39 patients (25.5%) developed bronchiectasis, and 16 (10.5%) granulomatous disease. Cancer was a common complication in our cohort (25 patients, 16.3%), with B-cell malignancies representing the most common neoplasms (56.7%). Our findings indicate the necessity of awareness about PAD and their complications, aiming for early diagnosis and the appropriate management of affected patients.

African ancestry-derived APOL1 risk genotypes show proximal epigenetic associations

Apolipoprotein L1 (APOL1) coding variants, termed G1 and G2, are established genetic risk factors for a growing spectrum of diseases, including kidney disease, in individuals of African ancestry. Evidence suggests that the risk variants, which show a recessive mode of inheritance, lead to toxic gain-of-function changes of the APOL1 protein. Disease occurrence and presentation vary, likely due to modifiers or second hits. To understand the role of the epigenetic landscape in relation to APOL1 risk variants, we performed methylation quantitative trait locus (meQTL) analysis to identify differentially methylated CpGs influenced by APOL1 risk variants in 611 African American individuals. We identified five CpGs that were significantly associated with APOL1 risk alleles in discovery and replication studies, and one CpG-APOL1 association was independent of other genomic variants. Our study highlights proximal DNA methylation alterations that may help explain the variable disease risk and clinical manifestation of APOL1 variants.

Abstract PO5-19-12: Innovative Trial Design: ARTIDIS Nanomechanical Generated Measurements for Early Breast Lesions (ANGEL) - Multicentre Study

Abstract Background: The diagnosis of breast cancer based on histopathology of core needle biopsies and the delineation into breast cancer subtypes to drive clinical treatment decisions can be time consuming and cause patient (and clinician) anxiety. Alternative, near patient, approaches to conventional diagnostic pathways would be desirable to drive diagnostic and therapeutic planning. This study harnesses the novel concept of evaluating diagnostic cores for nanomechanical features at the time of core biopsy. Clinical manifestations of disease are often accompanied by biomechanical alterations at sub-/cellular, extracellular, tissue and organ level. Mechanical properties of cancer cells and their microenvironment play a critical role in cancer invasion, progression, and immune cell infiltration. Ultrastructural (sub-) cellular alterations (nanoscale level), including the remodulation and alteration of cellular cytoskeleton dynamics, contribute to altered mechanical state of cancer cells, and lead to increased deformability and motility of soft cancer cells to overcome stromal barrier, and spread into the adjacent tissues and distant sites in the body. This results in a direct mechanistic correlation between nanomechanical properties and clinical outcome in cancer tissues. The ARTIDIS Nanomechanical Generated measurements for Early Lesions (ANGEL) Study will prospectively evaluate the efficacy of the ARTIDIS system as an aid to diagnosis, as well as subtyping breast cancer and predicting clinical outcomes based on tissue nanomechanics, particularly in the context of neoadjuvant therapy (NAT). Methods: The study seeks to validate the predictive power of the nanomechanical signature, a unique tissue biomarker reflecting the tissue phenotype, by comparing it to standard histological assessment. A projected cohort of 2,705 patients will be enrolled, from diverse ethnic and socioeconomic backgrounds, with benign or malignant breast conditions undergoing diagnostic core biopsy. A single core biopsy (gauge agnostic) is placed in a cassette and subjected to thousands of mechanical measurements at the “nano” scale over a period of 1-3 hours. The ARTIDIS technology builds upon the Atomic Force Microscopy platform to non-disruptively detect up to 17 different nanomechanical parameters in soft tissues with a subcellular resolution. The same core biopsy can then undergo fixation and conventional histopathological analyses for comparison with the final pathology. The primary aim is to confirm the potential of the ARTIDIS system in diagnosis (benign vs malignant) and secondarily address whether the nanomechanical signature can differentiate subtypes of breast cancer, associate with clinical outcome, and guide treatment decisions. Particularly, we will investigate ARTIDIS potential as a predictor of treatment response for patients receiving NAT. Results: The multicenter ANGEL study is a prospective investigation that builds upon previous clinical data from the NANO study at the University Hospital Basel (Switzerland) and is designed to demonstrate the power of using a nanomechanical signature to evaluate breast biopsies within a routine clinical setting in a multicenter setting. The data will be used to develop ARTIDIS as an aid to diagnosis, as well as NEO Match test applications to predict and guide response to NAT. Conclusion: This study presents the first of its kind as a direct prospective, multi-center based clinical translation of the Physics of Cancer findings into clinical settings. This innovative trial design allows the prospective development of ARTIDIS as an aid to diagnosis and NAT outcome prediction and therapy guidance applications. Citation Format: Karla Sepulveda, Ashley Roark, Sagar Dhamne, Chandandeep Nagi, Ivan Marin, Iqbal Tabish, Susanne G. Hilsenbeck Hilsenbeck, Sara Nizzero, Mariam Gachechiladze, Tobias A Appenzeller, Marko Loparic, Marija Plodinec, Alastair Thompson. Innovative Trial Design: ARTIDIS Nanomechanical Generated Measurements for Early Breast Lesions (ANGEL) - Multicentre Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-19-12.

Extreme elevations of donor-derived cell-free DNA increases the risk of chronic lung allograft dysfunction and death, even without clinical manifestations of disease.

Lung transplant recipients are traditionally monitored with pulmonary function testing (PFT) and lung biopsy to detect post-transplant complications and guide treatment. Plasma donor-derived cell free DNA (dd-cfDNA) is a novel molecular approach of assessing allograft injury, including subclinical allograft dysfunction. The aim of this study was to determine if episodes of extreme molecular injury (EMI) in lung transplant recipients increases the risk of CLAD or death. This multicenter prospective cohort study included 238 lung transplant recipients. Serial plasma samples were collected for dd-cfDNA measurement by shotgun sequencing. EMI was defined as a dd-cfDNA above the third quartile of levels observed for acute rejection (dd-cfDNA level of ≥ 5% occurring after 45 days post-transplant). EMI was categorized as Secondary if associated with co-existing acute rejection, infection or PFT decline; or Primary if not associated to these conditions. EMI developed in 16% of patients at a median 343.5 (IQR: 177.3-535.5) days post-transplant. Over 50% of EMI episodes were classified as Primary. EMI was associated with an increased risk of severe CLAD or death (HR: 2.52, 95% CI: 1.10 - 3.82, p= 0.024). The risk remained consistent for Primary EMI (HR: 2.34, 95% CI 1.18-4.85, p=0.015). Time to first EMI episode was a significant predictor of the likelihood of developing CLAD or death (AUC=0.856, 95% CI =.805-908, p<.001). Episodes of EMI in lung transplant recipients are often isolated and not detectable with traditional clinical monitoring approaches. EMI is associated with an increased risk of severe CLAD or death, independent of concomitant transplant complications.

Denile

A 51-year-old man presented with decreased vision, fever, confusion, headaches, agitation, nausea, vomiting and diarrhea. Magnetic resonance imaging of the brain demonstrated bilateral T2 hyperintense lesions in the region of the mesial temporal lobe and optic radiations. There was a predominantly polymorphonuclear leukocyte pleocytosis in the cerebrospinal fluid (CSF) with hyperproteinorachia. A meningoencephalitis was diagnosed. Intravenous fluorescein angiography demonstrated a multifocal chorioretinitis that was in a linear pattern in the left eye. CSF enzyme-linked immunosorbent assay was positive for West Nile virus (WNV) IgM. We review the clinical manifestations of WNV disease and highlight the diagnostic value of IVFA in determining the diagnosis.

Prevalence of GIT symptoms in patients of COVID 19 and role of rectal PCR in detecting COVID 19 with GIT symptoms

BackgroundIn December 2019, a cluster of patients with pneumonia of undetermined etiology was recognized in Wuhan, Hubei, China. Subsequently, a novel coronavirus (Severe Acute Respiratory Distress Syndrome- related Coronavirus) (SARS-CoV-2) was identified from lower respiratory tract samples obtained from affected patients. The clinical manifestation of Coronavirus disease 2019 (COVID 19) is broad and ranges from asymptomatic and mild upper respiratory tract symptoms to severe illnesses with multi-organ failure and death. Furthermore, it is challenging to predict the clinical course or determine patients at risk of deterioration.Aim of the workThe aim of our study is to assess prevalence of gastrointestinal tract (GIT) symptoms in COVID 19 infected patients and to assess significance of rectal PCR in detecting COVID 19 patients with gastrointestinal symptoms.Patients and methodsThis study was conducted on 100 adult COVID 19 patients recently diagnosed by polymerase chain reaction (PCR). All patients were submitted to clinical examination, laboratory testing for Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein,(CRP), Complete Blood Count (CBC), and D-dimer. Radiological investigations in the form of Computed Tomography Chest were reported by radiologist for all patients (High resolution computed tomography). Nasopharyngeal, oropharyngeal and rectal swabs were collected for COVID-19 (PCR) test. All patients received COVID-19 treatment according to protocols of World Health Organization (WHO) and Ministry of Health and Population, Egypt.ResultsWe found that GI symptoms are prevalent among COVID-19 Egyptian patients (64%). The most common GIT symptoms were Nausea, vomiting and diarrhea. We observed that 25 patients (25%) had positive viral RiboNucleic Acid (RNA) in rectal swab. Nausea was manifested in 38 patients (38%), Vomiting was manifested in 24 patients (24%), diarrhea was manifested in 21 patients (21%), pain was manifested in 22 patients (22%), hematemesis was manifested in 3 patients (3%) and melena was manifested in 2 patients (2%).ConclusionThe results of current study demonstrated that GIT symptoms are prevalent among COVID-19 Egyptian patients (64%) with Nausea, vomiting and diarrhea to be most common symptoms. Rectal PCR was found in 25 patients, all of them had GIT symptoms but it was statistically non-significant result when compared to the overall number of COVID-19 infected patients. Severe COVID-19 was more frequent in older age.

MASLD/MASH and type 2 diabetes: two sides of the same coin? From single PPAR to pan-PPAR agonists

Type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD), mainly related to nutrition and lack of physical activity, are both very common conditions, share several disease pathways and clinical manifestations, and increasingly co-occur with disease progression. Insulin resistance is an upstream node in the biology of both conditions and triggers liver parenchymal injury, inflammation and fibrosis. Peroxisome proliferator-activated receptor (PPAR) nuclear transcription factors are master regulators of energy homeostasis - insulin signaling in liver, adipose and skeletal muscle tissue - and affect immune and fibrogenesis pathways. Among distinct yet overlapping effects, PPARα regulates lipid metabolism and energy expenditure, PPAR β/δ has anti-inflammatory effects and increases glucose uptake by skeletal muscle, while PPARγ improves insulin sensitivity and exerts direct antifibrotic effects on hepatic stellate cells. Together PPARs thus represent pharmacological targets across the entire biology of MASH. Single PPAR agonists are approved for hypertriglyceridemia (PPARα) and T2D (PPARγ), but these, as well as dual PPAR agonists, have shown mixed results as anti-MASH treatments in clinical trials. Agonists of all three PPAR isoforms have the potential to improve the full disease spectrum from insulin resistance to fibrosis, and correspondingly to improve cardiometabolic and hepatic health, as has been shown (phase II data) with the pan-PPAR agonist lanifibranor.

Graves Disease Presenting Psychosis: a Case Report

Introductions: Graves’ disease is the most common cause of hyperthyroidism. Neuropsychiatric manifestations may occur in thyroid disease. As the premier clinical manifestation of Graves disease, psychosis is highly uncommon; it was reported in 1% of cases. The major neuropsychiatric manifestations of hyperthyroidism are acute psychosis, dementia, apathy, agitation, mania, delusional behavior, and hallucinations, especially in older people. Psychosis is highly rare as the first clinical symptom of a grave disease. Case: A 48-year-old female with grave disease symptoms had been taken to the emergency department with psychotic manifestations. She had a three-month history of increasing irritability, increasing irrational talking, staying awake most of the night, muttering, night-time wandering, and poor personal hygiene. She was admitted to the hospital, and the laboratory investigations showed an elevated FT4 and a decreased thyroid-stimulating hormone (TSH). The patient was started on propanolol 3 x 10 mg, propylthiouracil 3 x 50 mg tab, risperidone 2x2mg, trihexylphenidil 2x2mg, lorazepam 1x2mg, and Zyprexa injection once, which showed improvement in psychotic symptoms. Conclusion: Graves’ disease can present with neuropsychiatric manifestations such as psychosis, mania, or a combination of both. A detailed medical history and physical and psychiatric evaluation are necessary for diagnosing and giving adequate treatment. A detailed clinical evaluation, including thyroid function tests, could be recommended for all patients who showed psychotic symptoms. More research is needed to comprehend the pathophysiology underlying psychosis due to Graves’ disease, so that it is expected that the management can be carried out properly.

ELECTRONEUROMYOGRAPHY AS ONE OF THE METHODS OF DIAGNOSTICS OF PATHOLOGIES OF DIFFERENT GENESIS (LITERATURE REVIEW)

Modern possibilities of using the auxiliary method of electroneuromyography (ENMG) research by narrow specialists are multifaceted. This is primarily due to the safety and wide range of its use in clinical practice. Thus, diagnostics of the speed and time of the nerve impulse to organs and tissues, as well as the ability of the muscular apparatus to respond to stimulation of nerve endings is increasingly used in neurological, coloproctological, urological, surgical, endocrinological, pediatric specialties, in occupational medicine. The heterogeneity of the use of electroneuromyography in clinical medicine allows to identify functional and organic pathologies of the nervous and muscular apparatus, the causes of their occurrence and further development, the extent of the spread of the pathological process, as well as to establish the stages of the detected violation and assess possible risks for the subsequent life of patients. This is achieved by determining the main parameters of individual motor units that are functional elements of each skeletal muscle: shape, amplitude, duration, latent period of evoked potentials and analysis of spontaneous activity of the muscle fiber. Interpretation of the data obtained together with clinical manifestations of neuromotor diseases and with the results of additional research methods allow clinicians to make the correct diagnosis and choose the necessary tactics for managing patients with neuromuscular pathology.

Open-label observational study of effectiveness and tolerability of ipidacrine in treatment of patients with diabetic polyneuropathy (DIAMANT study)

Diabetic polyneuropathy (DPN) is one of the most common complications of diabetes mellitus, leading to the development of flaccid paresis, neuropathic pain syndrome, sensitive ataxia, as well as trophic disorders in the distal parts of the lower extremities.The purpose of the randomized, open-label, comparative, prospective study was to evaluate the effectiveness and tolerability of ipidacrine in the complex treatment of patients with DPN.Materials and methods. Patients with DPN (n = 60) were randomized into 2 groups. Both groups received basic therapy (alpha-lipoic acid, B vitamins, gabapentin); in the treatment of patients of the main group (n = 30), in addition, ipidacrine was used (Ipidacrine-SZ, North Star Co., Russia). We have analyzed the intensity of pain syndrome (VAS-P), the average daily dosage of gabapentin, and the results of the neuropathic dysfunctional scale (modified version, NDSm), Pittsburgh Sleep Quality Index, PSQI), Global Rating of Change Scale (GROC), the results of electroneuromyography (ENMG). The total duration of the observation and treatment period was 2 months.Results. After 2 months of therapy in the main group of patients, compared with the control group, there was significantly more complete pain control (VAS-P: 3.0 ± 0.9 vs 3.6 ± 0.8), a decrease in the average daily dosage of gabapentin (390 vs 500 mg/day), reduction in the severity of clinical manifestations of polyneuropathic syndrome (NDSm: 4.4 ± 1.0 vs 4.9 ± 1.0 points) and improvement in sleep quality (PSQI: 6.8 ± 1.3 vs 7.9 ± 1.7). According to ENMG data, patients in the main group showed a significant improvement in the neurophysiological parameters of both motor and sensory fibers, which was significantly more pronounced compared to the control group. A significantly larger proportion of patients in the main group assessed the improvement from the therapy as ‘pronounced’ (GROC: 10/33.3 % vs 6/20.0 %).Conclusions. The use of ipidacrine in complex therapy of patients with DPN can significantly reduce the clinical manifestations of disease and improve the neurophysiological parameters of the peripheral nerves of the lower extremities. Ipidacrine can be considered as a basic drug for the treatment of patients with neurological complications of diabetes mellitus.

Post-COVID Trajectory of Pentraxin 3 Plasma Levels Over 6 Months and Their Association with the Risk of Developing Post-Acute Depression and Anxiety.

Clinical manifestations of coronavirus disease 2019 (COVID-19) often persist after acute disease resolution. Underlying molecular mechanisms are unclear. The objective of this original article was to longitudinally measure plasma levels of markers of the innate immune response to investigate whether they associate with and predict post-COVID symptomatology. Adult patients with previous severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during the first pandemic wave who underwent the 6-month multidisciplinary follow-up were included. Plasma levels of pentraxin 3 (PTX3), the complement components C3a and C5a, and chitinase-3 like-protein-1 (CHI3L1) were measured at hospital admission during acute disease (baseline) and at 1 and 6 months after hospital discharge. Associations with post-COVID-19 sequelae at 6 months were investigated using descriptive statistic and multiple regression models. Ninety-four COVID-19 patients were included. Baseline PTX3, C5a, C3a, and CHI3L1 did not predict post-COVID-19 sequelae. The extent of the reduction of PTX3 over time (delta PTX3) was associated with lower depressive and anxiety symptoms at 6 months (both p < 0.05). When entering sex, age, need for intensive care unit or non-invasive ventilation during hospital stay, psychiatric history, and baseline PTX3 as nuisance covariates into a generalized linear model (GLM), the difference between baseline and 6-month PTX3 levels (delta PTX3) significantly predicted depression (χ2 = 4.66, p = 0.031) and anxiety (χ2 = 4.68, p = 0.031) at 6 months. No differences in PTX3 levels or PTX3 delta were found in patients with or without persistent or new-onset other COVID-19 symptoms or signs at 6 months. Plasma levels of C3a, C5a, and CHI3L1 did not correlate with PTX3 levels at either time point and failed to associate with residual or de novo respiratory or systemic clinical manifestations of the disease at 6 months. A lower reduction of plasma PTX3 after acute COVID-19 associates with the presence of depression and anxiety, suggesting an involvement of inflammation in post-COVID-19 psychopathology and a potential role of PTX3 as a biomarker.

E064 Identifying patients with pulmonary disease in a mixed connective tissue disease cohort

Abstract Background/Aims Respiratory involvement specifically interstitial lung disease (ILD) is a recognised complication of mixed connective tissue disease (MCTD), with a reported prevalence ranging from 40-78%. Surveillance for ILD in other connective tissue diseases such as systemic sclerosis is established clinical practice. Using guidelines recently published by the American College of Rheumatology (2023) we undertook a service evaluation to evaluate current practice for patients in our centre. Methods Electronic case notes were searched using key terms ‘mixed connective tissue disease’, ‘MCTD’ and ‘anti-RNP positive’ to identify patients seen between January 2021-2023. Patients identified were then compared against three MCTD classification criteria (Sharp et al, Alarcon-Sergovia et al and Kasukawa et al). To ensure a robust diagnosis, only those meeting the classification threshold on two or more criterion were included. Results 56 patients were identified however only 44 met two classification criteria and were subsequently included. Mean age was 47.3 years with 40/44 (91%) female. 28/44 (64%) had previous CT chest imaging. In the remaining 16/44 (46%), none had reported symptoms suggestive of ILD in preceding two years. 34/44 (77%) patients had previous pulmonary function testing. In those without, 1/10 had recently reported dyspnoea. 9/44 (20%) had identified MCTD-ILD of which 7/9 (30%) were on immunosuppression, 3/9 for predominant lung disease. Of those with ILD, 7/9 (78%) had had PFTs in the last year. No patients with ILD had undergone assessment for ambulatory desaturation. 7/9 (78%) patients with ILD had received specialist respiratory input, 1 had been seen in a general respiratory clinic, and in 1 case it was unknown. All patients with identified ILD who met established criteria for treatment were receiving immunosuppression. No patient met criteria for progressive fibrotic ILD. No specific disease characteristics (utilising clinical criterion from classification criteria) were demonstrated to have association with ILD (statistical analysis performed using the chi-squared test). No association was demonstrated in patients displaying anti- Ro52 and Ro60 positivity and ILD. Conclusion This evaluation has highlighted that patients with identified MCTD-ILD are being treated and monitored well. However further surveillance for pulmonary involvement both at baseline and then subsequent interval pulmonary function testing needs to improve. This may account for the lower prevalence of ILD in our MCTD cohort in comparison to the literature. Surveillance of pulmonary involvement should take place regardless of clinical disease manifestations displayed. We need to establish feasibility for ambulatory desaturation testing in those with ILD within our outpatient setting. With increasing immunomodulatory treatment available identifying patients with MCTD-ILD is imperative. Disclosure R. Benson: None. K. Mashida: None. M. Ahmad: None. L.G. Spencer: None. Z. McLaren: None. T. Barnes: None.

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.

Hormones and B-cell development in health and autoimmunity.

The development of B cells into antibody-secreting plasma cells is central to the adaptive immune system as they induce protective and specific antibody responses against invading pathogens. Various studies have shown that, during this process, hormones can play important roles in the lymphopoiesis, activation, proliferation, and differentiation of B cells, and depending on the signal given by the receptor of each hormone, they can have a positive or negative effect. In autoimmune diseases, hormonal deregulation has been reported to be related to the survival, activation and/or differentiation of autoreactive clones of B cells, thus promoting the development of autoimmunity. Clinical manifestations of autoimmune diseases have been associated with estrogens, prolactin (PRL), and growth hormone (GH) levels. However, androgens, such as testosterone and progesterone (P4), could have a protective effect. The objective of this review is to highlight the links between different hormones and the immune response mediated by B cells in the etiopathogenesis of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS). The data collected provide insights into the role of hormones in the cellular, molecular and/or epigenetic mechanisms that modulate the B-cell response in health and disease.

New insights into Trypanosoma cruzi genetic diversity, and its influence on parasite biology and clinical outcomes.

Chagas disease, caused by Trypanosoma cruzi, remains a serious public health problem worldwide. The parasite was subdivided into six distinct genetic groups, called "discrete typing units" (DTUs), from TcI to TcVI. Several studies have indicated that the heterogeneity of T. cruzi species directly affects the diversity of clinical manifestations of Chagas disease, control, diagnosis performance, and susceptibility to treatment. Thus, this review aims to describe how T. cruzi genetic diversity influences the biology of the parasite and/or clinical parameters in humans. Regarding the geographic dispersion of T. cruzi, evident differences were observed in the distribution of DTUs in distinct areas. For example, TcII is the main DTU detected in Brazilian patients from the central and southeastern regions, where there are also registers of TcVI as a secondary T. cruzi DTU. An important aspect observed in previous studies is that the genetic variability of T. cruzi can impact parasite infectivity, reproduction, and differentiation in the vectors. It has been proposed that T. cruzi DTU influences the host immune response and affects disease progression. Genetic aspects of the parasite play an important role in determining which host tissues will be infected, thus heavily influencing Chagas disease's pathogenesis. Several teams have investigated the correlation between T. cruzi DTU and the reactivation of Chagas disease. In agreement with these data, it is reasonable to suppose that the immunological condition of the patient, whether or not associated with the reactivation of the T. cruzi infection and the parasite strain, may have an important role in the pathogenesis of Chagas disease. In this context, understanding the genetics of T. cruzi and its biological and clinical implications will provide new knowledge that may contribute to additional strategies in the diagnosis and clinical outcome follow-up of patients with Chagas disease, in addition to the reactivation of immunocompromised patients infected with T. cruzi.

Development of a Composite Score for the Clinical Assessment of Anti-IgLON5 Disease.

To develop a composite score to assess the severity of the multiple symptoms present in anti-IgLON5 disease. The anti-IgLON5 disease composite score (ICS) was designed to evaluate 17 symptoms divided into 5 clinical domains (bulbar, sleep, movement disorders, cognition, and others). Each symptom was scored from 0 (absent/normal) to 3 or 6 (severe) depending on the contribution of the symptom to neurologic disability with a maximum ICS of 69. The ICS was tested in patients from 2 cohorts (Barcelona, Spain, and GENERATE, Germany) that included cases personally seen by the authors (internal) and patients whose ICS was obtained from information of questionnaires completed by the referring neurologists (external). Test-retest and interrater reliabilities of the ICS were assessed by the intraclass coefficient (ICC) and the correlation between the ICS and modified Rankin scale (mRS) with the nonparametric Spearman rank coefficient. The Wilcoxon signed rank test was used to compare the ICS at diagnosis of anti-IgLON5 disease and follow-up in a subset of patients with available clinical information. A total of 86 patients (46 from Barcelona cohort; 40 from GENERATE cohort) were included. The median ICS was 15 (range 2-31). The ICS was higher in the Barcelona cohort than in the German cohort (18 vs 12, p < 0.001), due to higher partial scores in sleep and movement disorder domains. There were no significant differences in the ICS between internal and external patients (15 vs 14, p = 0.96). The ICS correlated with the mRS score (r = 0.429, p < 0.001). Test-retest and interrater reliabilities were excellent with an ICC of 0.997 (95% CI 0.992-0.999) and 0.973 (95% CI 0.925-0.990), respectively. ICS was retested during follow-up in 27 patients, and it was similar to that at diagnosis in 10 clinically stable patients (median ICS at diagnosis 11.5 vs 11.5 at follow-up; p = 1), higher in 8 patients who worsened (12.5 vs 18; p = 0.012), and lower in 9 patients who improved after immunotherapy (14 vs 10; p = 0.007). The ICS is a valid method to assess the extension and severity of the different clinical manifestations of anti-IgLON5 disease.

HIV/AIDS and its marker diseases-manifestations

An objective confirmation of the seriousness of the human community’s understanding of the global significance of such a «relatively young» infection as HIV/AIDS is the extensive discussions — the discussion of this seemingly purely medical problem at several meetings of the UN General Assembly, as well as the creation of a specialized UNAIDS program (of the United Nations AIDS Program) which this year published a final report entitled «In danger». It assessed the current situation with this infectious disease as an absolute threat to the entire modern human society. Objective — to conduct an analysis of professional publications of recent years regarding the modern clinical and epidemiological features of the clinical course of HIV-infection/AIDS and to determine organizational measures to ensure at least partial well-being of the public health of the population of Ukraine in wartime conditions and the conduct of active hostilities. It is important to emphasize to primary care physicians not only the significant variety of clinical manifestations of various forms of this acutely contagious viral pathology, but also the real possibility of visually diagnosing it — suspecting it at a daily outpatient polyclinic appointment, based on the clinical manifestations of numerous marker diseases already present on the skin and mucous membranes. Materials and methods. Official documents and scientific publications related to public health policy, approaches to overcoming the HIV/AIDS epidemic, dynamics of morbidity and specific manifestations and clinical course of certain marker dermatological manifestations of this viral pathology in Ukraine were analyzed. Results and discusion. The content of the analyzed professional publications indisputably shows that the problem of HIV/AIDS has gone far beyond the scope of the purely medical field and has acquired the status of national significance. A modern approach to improving the state of public health requires constant coordination of the efforts of different people, who at the same time have a wide range of professional skills in many different disciplines, as well as the ability to collaborate fruitfully with others in joint multiprofessional teams to achieve the common goal of overcoming this viral epidemic. Conclusions. The analysis of scientific publications of recent years on the problem of HIV/AIDS indicates an urgent need to consider this disease in the state public health system as a socially significant infectious disease of the whole organism, in which early visual identification on the skin of clinical manifestations of a number of marker dermatoses allows prompt suspicion, and then and to quickly confirm both the fact of HIV infection and to start a course of ART. This requires an interdisciplinary approach and systematic methodological cooperation of primary care physicians, dermatovenerologists, infectious disease specialists, and pathologists in the aspect of timely (early) diagnosis and complex therapy of this viral infectious pathology.