Chronic Syndrome Research Articles

SMARTSeiz: Deep Learning With Attention Mechanism for Accurate Seizure Recognition in IoT Healthcare Devices.

The Internet of Things (IoT) is capable of controlling the healthcare monitoring system for remote-based patients. Epilepsy, a chronic brain syndrome characterized by recurrent, unpredictable attacks, affects individuals of all ages. IoT-based seizure monitoring can greatly enhance seizure patients' quality of life. IoT device acquires patient data and transmits it to a computer program so that doctors can examine it. Currently, doctors invest significant manual effort in inspecting Electroencephalograph (EEG) signals to identify seizure activity. However, EEG-based seizure detection algorithms face challenges in real-world scenarios due to non-stationary EEG data and variable seizure patterns among patients and recording sessions. Therefore, a sophisticated computer-based approach is necessary to analyze complex EEG records. In this work, the authors proposed a hybrid approach by combining traditional convolution neural (CN) and recurrent neural networks (RNN) along with an attention mechanism for the automatic recognition of epileptic seizures through EEG signal analysis. This attention mechanism focuses on significant subsets of EEG data for class recognition, resulting in improved model performance. The proposed methods are evaluated using a publicly available UCI epileptic seizure recognition dataset, which consists of five classes: four normal conditions and one abnormal seizure condition. Experimental results demonstrate that the suggested approach achieves an overall accuracy of 97.05% for the five-class EEG recognition data, with an accuracy of 99.52% for binary classification distinguishing seizure cases from normal instances. Furthermore, the proposed intelligent seizure recognition model is compatible with an IoMT (Internet of Medical Things) cloud-based smart healthcare framework.

Hépatocarcinomes liés à l’infection par le VHB et potentielles nouvelles stratégies thérapeutiques

AbstractHepatocellular carcinomas (HCC) are the most common primary liver tumours. They are the second leading cause of cancer-related mortality worldwide. The main etiological factors include viral hepatitis B and C, chronic alcohol intake and metabolic syndromes. We will focus this review on the impact of hepatitis B virus (HBV) infection and the progression of liver damage to HCC. Both direct and indirect mechanisms of HBV infection contribute to the emergence of HCC. We will address these two types of mechanisms by focusing on direct viral effects, explored in numerous in vivo and in vitro studies. Published results can sometimes be contradictory. They vary depending on the study model, the viral sequence, the level of HBV expression, the type of viral genome transferred (partial or complete), the transfer method, generating a stable or transient expression, and many other parameters. Nevertheless, the knowledge acquired recently on the viral cycle, and in particular on the nature of the hepatocyte receptor of HBV, allows today to reproduce in vitro a complete viral cycle in different experimental models and thus, to better appreciate the pro-tumor activities of HBV infection.This review is obviously not exhaustive and the knowledge, particularly on the clinical and therapeutic management of HCC, whether associated with the presence of HBV or not, is currently evolving with the rise of combined immunotherapies.

Monoclonal antibody therapy for refractory chronic migraine-like headache related Lyme disease: a case report

IntroductionLyme disease, caused by Borrelia burgdorferi, can lead to diverse neurological manifestations, including headache. While most Lyme-associated headaches resolve with antibiotics, some may evolve into a refractory chronic migraine-like syndrome. We present a case of post-Lyme chronic migraine-like headache responsive to galcanezumab, a calcitonin gene-related peptide (CGRP) monoclonal antibody.Case ReportA 42-year-old woman developed chronic migraine-like headaches following treatment for Lyme neuroborreliosis. The headaches were refractory to standard preventive therapies and only partially responsive to onabotulinumtoxinA. Administration of galcanezumab resulted in significant reduction of headache frequency, intensity, and impact on daily activities.CommentThis case highlights the potential of CGRP-targeted therapies for persistent migraine-like headaches following Lyme neuroborreliosis. The favorable response to galcanezumab suggests a role for CGRP in the pathophysiology of post-Lyme headache. While further research is needed to establish efficacy and safety, clinicians should consider CGRP monoclonal antibodies for chronic migraine-like headaches refractory to standard treatments in the post-infectious phase of Lyme disease. The emergence of chronic migraine-like headaches following Lyme neuroborreliosis and the response to a CGRP monoclonal antibody in this case underscore the importance of considering targeted migraine therapies in the management of persistent headaches after antibiotic treatment. This report contributes to the understanding of Lyme disease sequelae and potential treatment options, warranting further investigation into the utility of CGRP-targeted therapies in this context.

Study of the Relationship between the Polymorphic Genes of Metaloproteinases MMP9 (A-8202G) rs11697325 and the Level of Cystatin C in Children with Chronic Nephritic Syndrome

Study of the Relationship between the Polymorphic Genes of Metaloproteinases MMP9 (A-8202G) rs11697325 and the Level of Cystatin C in Children with Chronic Nephritic Syndrome

Surface-Enhanced Raman Spectroscopy Combined with Multivariate Analysis for Fingerprinting Clinically Similar Fibromyalgia and Long COVID Syndromes.

Fibromyalgia (FM) is a chronic central sensitivity syndrome characterized by augmented pain processing at diffuse body sites and presents as a multimorbid clinical condition. Long COVID (LC) is a heterogenous clinical syndrome that affects 10-20% of individuals following COVID-19 infection. FM and LC share similarities with regard to the pain and other clinical symptoms experienced, thereby posing a challenge for accurate diagnosis. This research explores the feasibility of using surface-enhanced Raman spectroscopy (SERS) combined with soft independent modelling of class analogies (SIMCAs) to develop classification models differentiating LC and FM. Venous blood samples were collected using two supports, dried bloodspot cards (DBS, n = 48 FM and n = 46 LC) and volumetric absorptive micro-sampling tips (VAMS, n = 39 FM and n = 39 LC). A semi-permeable membrane (10 kDa) was used to extract low molecular fraction (LMF) from the blood samples, and Raman spectra were acquired using SERS with gold nanoparticles (AuNPs). Soft independent modelling of class analogy (SIMCA) models developed with spectral data of blood samples collected in VAMS tips showed superior performance with a validation performance of 100% accuracy, sensitivity, and specificity, achieving an excellent classification accuracy of 0.86 area under the curve (AUC). Amide groups, aromatic and acidic amino acids were responsible for the discrimination patterns among FM and LC syndromes, emphasizing the findings from our previous studies. Overall, our results demonstrate the ability of AuNP SERS to identify unique metabolites that can be potentially used as spectral biomarkers to differentiate FM and LC.

Vildagliptin ameliorates intrapulmonary vasodilatation and angiogenesis in chronic common bile duct ligation-induced hepatopulmonary syndrome in rat

IntroductionExperimental hepatopulmonary syndrome (HPS) is best reproduced in the rat common bile duct ligation (CBDL) model. Vildagliptin (Vild) is an anti-hyperglycemic drug that exerts beneficial anti-inflammatory, anti-oxidant and anti-fibrotic effects. Therefore, the present search aimed to explore the possible effectiveness of Vild in CBDL-induced HPS model. MethodsFour groups of male Wistar rats which weigh 220–270 g were used, including the normal control group, the sham control group, the CBDL group and CBDL+Vild group. The first three groups received i.p. saline, while the last group was treated with i.p. Vild (10 mg/kg/day) from the 15th to 28th day of the experiment. ResultsCBDL decreased the survivability and body weight of rats, increased diameter of the pulmonary vessels, and altered the arterial blood gases and the liver function parameters. Additionally, it increased the pulmonary expressions of endothelin-1 (ET-1) and tumor necrosis factor-α (TNF-α) mRNA as well as endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor-A (VEGF-A) proteins. The CBDL rats also exhibited elevation of the pulmonary interleukin-6 (IL-6), dipeptidyl peptidase-4 (DPP-4) and nitric oxide (NO) levels along with reduction of the pulmonary total anti-oxidant capacity and glucagon-like peptide-1 (GLP-1) levels. Vild mitigated these alterations and improved the histopathological abnormalities caused by CBDL. ConclusionVild effectively attenuated CBDL-induced HPS through its anti-oxidant and anti-inflammatory effects along with its modulatory effects on ET-1/NOS/NO and TNF-α/IL-6/VEGF-A signaling implicated in the regulation of intrapulmonary vasodilatation and angiogenesis, respectively.

Lid Margin Microbiome in Stevens-Johnson Syndrome Patients With Lid Margin Keratinization and Severe Dry Eye Disease.

The current study evaluated the lid margin microbiome of keratinized lid margins of patients with chronic Stevens-Johnson syndrome (SJS) and compared it with healthy controls and historically reported lid margin microbiome of patients with meibomian gland dysfunction (MGD). Eyelid margin swabs of 20 asymptomatic adults (mean age = 29 ± 12years) and 10 patients with chronic SJS (mean age = 31.2 ± 14years) with lid margin keratinization were sequenced using next generation of 16S rDNA V3 to V4 variable region. Within SJS, the keratinized lid margin microbiome was compared with adjacent eyelid skin. All patients had obstructive MGD, and mean Schirmer I value was 2.8 ± 1.9 mm. The phyla were similar in two groups, whereas at the genera level, an increase in the relative abundance of Corynebacterium, Haemophilus, Azotobacter, and Afipia and a decrease of Acinetobacter was noted in SJS compared to healthy lid margins. SJS-associated microbiota displayed lesser diversity and more heterogeneity than healthy controls. The Principal Components Analysis (PCA) plot revealed wide separation in the SJS and the control groups. Correlational network analysis revealed Corynebacterium and Sphingomonas forming a major hub of negative interactions with other bacterial genera in the SJS group. Significant differences exist in the prevalent genera between keratinized lid margins and historically reported meibum microbiome of patients with MGD. In addition, the eyelid skin of patients with SJS had predominant Staphylococcus, whereas Corynebacterium and Pseudomonas were more in the keratinized lid margins compared to the eyelid skin microbiome. Lid margin microbiome is significantly altered in the keratinized lid margins of patients with SJS compared to the eyelid skin of patients with SJS, normal lid margins, and patients with MGD.

Multimodal benefits of hypnosis on pain, mental health, sleep, and quality of life in patients with chronic pain related to fibromyalgia: A randomized, controlled, blindly-evaluated trial

Background and purposeFibromyalgia is a chronic syndrome marked by intense musculoskeletal pain often refractory to pharmacological treatment. Although studies have shown that hypnosis improves fibromyalgia pain, gaps in experimental design limit their reliability. This work aimed to evaluate the effects of hypnosis on pain, mental health, sleep, and quality of life in participants with fibromyalgia chronic pain. MethodsIn this prospective, parallel, randomized, controlled, blindly-evaluated trial, participants of both sexes (n = 49) diagnosed with fibromyalgia and with moderate to severe chronic pain attended 8 weekly 1-h sessions with a hypnotherapist. For the hypnosis group (n = 24), sessions consisted in induction of hypnotic trance followed by suggestions to promote analgesia. For the control group (n = 25), sessions consisted in casual unscripted conversation. Participants were assessed at baseline (7 days before), post-intervention (7 days after), and follow-up (3 months after). The primary outcome was pain intensity. The secondary outcomes were the sensory and affective dimensions of pain; pain unpleasantness; pain catastrophizing; anxiety and depression; sleep quality; fibromyalgia impact; and quality of life. ResultsHypnosis significantly reduced pain scores both at post-intervention and follow-up in comparison with baseline. The analgesic effect of hypnosis combined with pharmacological treatment lasted for at least 3 months and was superior to analgesia promoted by first- and second-line pharmacological treatment alone. Hypnosis significantly improved all parameters evaluated as secondary outcomes both at post-intervention and follow-up without inducing adverse events. ConclusionOur results corroborate that clinical hypnosis is an effective and feasible tool for managing chronic pain and other symptoms of fibromyalgia.

Risk of Cardiovascular Events Associated with Chronic Obstructive Pulmonary Disease and/or Metabolic Syndrome: A Large-Scale Nationwide Population-Based Cohort Study.

Chronic obstructive pulmonary disease (COPD) and metabolic syndrome (MetS) are among the most prevalent conditions that might predispose individuals to life-threatening events. We aimed to examine their associations with cardiovascular (CV) events and mortality using a large-scale population dataset from the National Health Information Database in Korea. This population-based cohort study enrolled adults aged ≥40 years who had undergone more than two health examinations between 2009 and 2011. They were divided into four groups based on the presence of COPD and MetS. Analysis of the outcomes and CV events or deaths was performed from 2014 to 2019. We compared CV event incidence and mortality rates using a multivariate Cox proportional hazards model and Kaplan-Meier curves. Totally, 5,101,810 individuals were included, among whom 3,738,458 (73.3%) had neither COPD nor MetS, 1,193,014 (23.4%) had only MetS, 125,976 (2.5%) had only COPD, and 44,362 (0.9%) had both. The risk of CV events was significantly higher in individuals with both COPD and MetS than in those with either COPD or MetS alone (HRs: 2.4 vs 1.6 and 1.8, respectively; all P <0.001). Similarly, among those with both COPD and MetS, all-cause and CV mortality risks were also elevated (HRs, 2.9 and 3.0, respectively) compared to the risks in those with either COPD (HRs, 2.6 and 2.1, respectively) or MetS (HRs, 1.7 and 2.1, respectively; all P <0.001). The comorbidity of MetS in patients with COPD increases the incidence of CV events and all-cause and cardiovascular mortality rates.

A Comprehensive Study of Deep Learning Techniques to Predict Dissimilar Diseases in Diabetes Mellitus Using IoT

Abstract: India has evaluated 77 million people with diabetes, which makes it the second most elaborated disease in the world. Diabetes is a chronic syndrome that occurs with increased sugar levels in the blood cells. Once diabetes is diagnosed and untreated by physicians, it may affect the internal organs slowly, so there is a necessity for early prediction. Popular Machine Learning (ML) techniques existed for the early prediction of diabetes mellitus. A significant perspective is to be considered in total management by machine learning algorithms, but it is not a good enough model to predict DMT2. Therefore, Deep learning (DL) models are utilized to produce enhanced prediction accuracy. The ML methods are evaluated and analyzed distinctly on the inconspicuous test information. DL is a subpart of ML with many data sets recurrently used to train the system. IoT was another emerging technology-based Healthcare Monitoring System (HMS) built to support the vision of patients and doctors in the healthcare domain. This paper aims to survey ML and DL techniques relevant to Dissimilar Disease prediction in Diabetes Mellitus. Finally, by doing a study on it, deep learning methods performed well in predicting the dissimilar diseases related to diabetes and also other disease predictions using m-IoT devices. This study will contribute to future deep-learning ideas that will assist in detecting diabetic-related illnesses with greater accuracy.

Exploring the Experiential Journey of Women with PCOS Across the Lifespan: A Qualitative Inquiry.

Peri-postmenopausal women with the chronic condition polycystic ovary syndrome (PCOS) remain at cardiometabolic risk and/or subsist with established comorbidity while continuing to manage persistent PCOS signs and symptoms, such as hirsutism. Thus, PCOS transcends the reproductive years, yet there is sparse scientific literature on the peri-postmenopausal years of women with PCOS. To explore how peri-postmenopausal women's perceptions about PCOS have changed over the lifespan since their PCOS diagnosis. A cross-sectional survey with one qualitative question was conducted via Research Electronic Data Capture (REDCap) among women with PCOS aged ≥43 years, who were all recruited from PCOS-specific Facebook pages. Of the 107 women completing the survey, 72 substantively answered the qualitative question. The qualitative responses were analyzed using the steps of reflexive thematic analysis. Themes were interpreted and discussed through the lens of the bioecological conceptual model. Respondents were 47.6 (±4.1) years of age, primarily White (87.5%), employed full time (65.3%), and married (75%) with children (68%). Four overall themes were identified: 1) dismissal 2) information desert, 3) PCOS experience over the lifespan, and 4) mindset. The study findings illustrated the unique healthcare needs among peri-postmenopausal women with PCOS. Further research is needed to further explore their healthcare concerns and psychosocial needs followed by studies that develop and assess interventions that promote symptom and adaptive coping strategies across their lifespan.

Home non-invasive ventilation: An observational study of aetiology, chronic respiratory failure of multiple aetiologies, survival and treatment adherence

Home non-invasive ventilation (NIV) is used to treat patients with chronic respiratory failure (CRF). However, knowledge on the prevalence and impact of multimorbid aetiology of CRF, patterns of NIV use, and survival of these patients is limited. Our aim was to analyse the multiple aetiologies of CRF, patterns of NIV use and the outcome of those patients.We conducted a retrospective analysis of 1,281 patients treated with home-NIV between 2004 and 2014 in Turku University Hospital, Finland. The patients were divided into nine disease categories: obstructive airways disease (16 %); obesity hypoventilation syndrome (11 %); neuromuscular disease (10 %); chest wall diseases (4 %); sleep apnoea (26 %); interstitial lung diseases (3 %); malignancy (2 %); other (3 %) and acute (8 %), which refers to the patients who did not fulfil criteria of CRF. In addition, multiple aetiologies of CRF were found in 17 %. Mean adherence to home-NIV was 6.0 ± 4.4 h/d and median treatment duration 410 (120–1021) days. Adherence, treatment duration or survival did not significantly differ between patients with either single or multiple causative diseases leading to CRF. Median survival was 4.5 years (95 % CI 3.6 to 5.4). The main reasons for discontinuing NIV were death (56 %) and lack of motivation (19 %).We conclude that home-NIV is used in a variety of diseases. CRF of multiple aetiologies is prevalent and not limited to chronic obstructive lung disease and obstructive sleep apnoea overlap syndrome. However, the adherence to home-NIV or survival did not differ between patients with a single or multiple diseases causing CRF, but the survival of the home-NIV patients differed according to the underlying aetiology of CRF.

Corrigendum to: EACTS/STS Guidelines for diagnosing and treating acute and chronic syndromes of the aortic organ

Corrigendum to: EACTS/STS Guidelines for diagnosing and treating acute and chronic syndromes of the aortic organ

PREVALENCE AND CORRELATION OF METABOLIC SYNDROME IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

Background: Chronic obstructive pulmonary disease (COPD) and metabolic syndrome (MetS) are prevalent chronic conditions with significant impacts on public health. Despite evidence suggesting a bidirectional relationship between COPD and MetS, data on the prevalence and correlation of MetS in COPD patients remain limited.This cross-sectional study aimed to investigate the prevalence of MetS in COPD patients admitted at Rural Medical College Loni and explore its correlation. Methods: A total of 50 COPD patients aged 40 years and above were recruited. Demographic and clinical data were collected through face-to-face interviews and medical record review. Diagnosis ofMetS was done based on the International Diabetes Federation criteria. Logistic regression analysis was performed to identify factors associated with MetS in COPD patients. Results: The mean age of the study population was 60.92 ± 8.97 years, with 76% being male. The prevalence of MetS among COPD patients was42%. The majority of patients with MetS exhibited grade 3 dyspnea based on modified medical research council grading (MMRC). MetS was most prevalent among patients with GOLD stage III disease. Conclusion: Metabolic syndrome is highly prevalent among COPD patientsadmitted at Rural Medical College Loni andpatients with MetS present with more severe disease and frequent exacerbations. Identification of MetS in COPD patients is crucial for comprehensive disease management and warrants integrated care approaches targeting both respiratory and metabolic health. Further research is needed to elucidate the underlying mechanisms linking COPD and MetS and develop tailored interventions to improve outcomes in this population.

Nocturia, nocturnal polyuria, and nocturnal enuresis in adults: What we know and what we do not know.

Nocturia is defined as the nocturnal frequency of one or more voiding episodes per night. It increases with aging and has an impact on sleep quality and the risks of falling and mortality. Nocturia disorder involves nighttime frequency, nocturnal polyuria, and nocturnal enuresis. In older adults with nocturia disorder, multiple factors could contribute to nocturia severity and characteristics, including poor sleep quality, lower urinary tract dysfunction, and excessive fluid output. Several nonurological medical diseases have been found to result in nocturia, such as hypertension, congestive heart failure, chronic kidney disease, chronic obstructive pulmonary disease, metabolic syndrome, and diabetes. Urological and medical assessments should be performed to diagnose nocturia disorder. A frequency volume chart to evaluate the nocturnal polyuria index, functional bladder capacity, and urodynamic study can reveal the presence of nocturnal polyuria and lower urinary tract dysfunction. Treatment should be based on multiple nocturia etiologies, and a combination of multiple therapies for individual pathophysiology will achieve a better treatment outcome.

Long-COVID autonomic syndrome in working age and work ability impairment

Long-COVID19 has been recently associated with long-sick leave and unemployment. The autonomic nervous system functioning may be also affected by SARS-CoV-2, leading to a chronic autonomic syndrome. This latter remains widely unrecognized in clinical practice. In the present study, we assessed the occurrence of Long-COVID19 Autonomic Syndrome in a group of active workers as well as the relationships between their autonomic dysfunction and work ability. This prospective observational study was conducted during the 2nd wave of the pandemic in Italy. Forty-five patients (53.6 ± 8.4 years; 32 M) hospitalized for COVID19, were consecutively enrolled at the time of their hospital discharge (T0) and followed-up for 6 months. Autonomic symptoms and work ability were assessed by COMPASS31 and Work Ability Index questionnaires at T0, one (T1), three and six (T6) months after hospital discharge and compared to those retrospectively collected for a period preceding SARS-CoV-2 infection. Clinical examination and standing test were also performed at T1 and T6. One in three working-age people developed a new autonomic syndrome that was still evident 6 months after the acute infection resolution. This was associated with a significant reduction in the work ability. Recognition of Long-COVID19 Autonomic Syndrome may promote early intervention to facilitate return to work and prevent unemployment.

#234 Clinical spectrum and genetic variants of Alport syndrome and thin basement membrane nephropathy—single center experience

Abstract Background and aims Alport syndrome (AS) and thin basement membrane nephropathy (TBMN) are genetically heterogeneous kidney diseases that manifest with kidney involvement, AS also with hearing and visual impairment. Electron microscopic examination shows characteristic ultrastructural changes in the glomerular basement membrane (GBM) in AS and TBMN, but cannot reliably distinguish between the two entities. Therefore, molecular genetic studies and the identification of individual pathogenic variants in the target genes are crucial to confirm the diagnosis. The aim of our study is to determine the significance of the genetic variants associated with the ultrastructural changes of GBM found in the renal biopsy. Method We retrospectively analyzed records of patients from the University Medical Centre Ljubljana in which ultrastructural GBM changes characteristic for AS and TBMN were found in the renal biopsy, including their clinical, laboratory and histological features. Molecular genetic investigations were made using the new generation sequencing method (NGS) to determine germline pathogenic variants in genes directly related to AS and TBMN (COL4A3, COL4A4 and COL4A5) and in genes that are important in syndromes with a related clinical picture (COL4A6, CD151, LMX1B, MYH9, FN1 and MYO1E). The pathogenicity of variants was determined according to the Clinical Molecular Genetic Society best practice guidelines. Results The study included 73 patients with ultrastructurally confirmed thin GBM. Indications for kidney biopsy were chronic nephritis syndrome in 33 patients (45%), acute worsening of renal function in 16 (22%), nephrotic syndrome in 9 (12%), nephrotic proteinuria and chronic kidney disease in 6 (8%), isolated proteinuria in 5 (7%) and suspected vasculitis in 4 patients (6%). At the time of kidney biopsy average age was 50 ± 16 years, average creatinine 112 ± 70 µmol/L and average estimated glomerular filtration rate (eGFR) 65 ± 24 ml/min/1.73 m2, 7 patients had eGFR below 30 ml/min/1.73 m2. Average daily proteinuria was 2.4 ± 3.3 gr and 88% of patients had hematuria. 38% of them have hearing impairment and 43% had positive familiar history of kidney disease. We recorded 33 patients (45%) with genetic variants associated with AS or TBMN: 22 patients (67%) with pathogenic variants, 2 patients (6%) with likely pathogenic and 9 patients (27%) with variants of uncertain significance. The presence of a positive genetic analysis was associated with a higher level of hematuria (p = 0.003), a lower level of proteinuria (p = 0.004) and a positive family history of kidney disease (p &amp;lt; 0.001). It was also associated with hearing loss, but the association was not statistically significant (p = 0.099). Patients with genetic variants had similar eGFR to those with negative genetics (63.9 ml/min/1.73 m2 (58.3-69.4) vs 66.2 ml/min/1.73 m2 (60.0-72.3)), p = 0.698. We also found no differences in GBM thickness in patients without compared to those with identified gene variants (213 nm (160-315) vs. 209 nm (140-410)), p = 0.761. 32 patients (44%) had only focal chronic changes and ultrastructural changes of thin GBM present on kidney biopsy and 41 patients (56%) had also been diagnosed with other renal pathology. When comparing these two groups, patients without associated pathology had lower daily proteinuria (p = 0.048), higher level of hematuria (p = 0.021), frequent hearing impairment (p = 0.008) and also positive genetics analysis (p = 0.016). Conclusion We have shown that in patients with proven ultrastructural alterations in GBM, the presence of so far recognized genetic variants associated with AS and TBMN is 45%, and corresponds to the frequency of other phenotypic characteristics of AS, including hearing impairment and positive family history. In the future, additional clinical tools will be required to accurately determine the role of coexistent thin GBM on the prognosis of patients with other relevant kidney pathology and other genetic tools beyond NGS should be employed to explore other pathologic genetic variants associated with the AS spectrum.

#1961 Cardiovascular-kidney-metabolic syndrome components and cardio-vascular disease mortality based on half-a-million Asian adults

Abstract Background and Aims The American Heart Association (AHA) has recently issued guidelines addressing the “Cardiovascular-Kidney-Metabolic (CKM) Syndrome” to mitigate cardiovascular diseases. In parallel, European healthcare entities have established the CaReMe (CArdioRenal and MEtabolic) Partnership, emphasizing interdisciplinary health concepts. This study aims to evaluate CKM prevalence and its associated components in a substantial Asian cohort, along with the risk of cardiovascular mortality. Method The investigation focused on a cohort of 565 940 participants aged 20 years and above enrolled in a health screening program in Taiwan spanning from 1994 to 2017. The study assessed cardiovascular disease (CVD) and cause-specific mortality related to CKM stages and its components—hypertension, diabetes, chronic kidney disease, metabolic syndrome, and hyperlipidemia. Multivariable Cox proportional hazards models were employed to calculate hazard ratios (HRs). Results In this cohort with more than half-a-million Asian adults, approximately 74.3% exhibit CKM syndrome, distributed as 28.1% in Stage 1, 38.9% in Stage 2, 4.9% in Stage 3, and 2.4% in Stage 4. Among individuals aged 50 and above, almost 90% had CKM. The CKM components—hypertension (20.5%), chronic kidney disease (CKD) (11.1%), hyperlipidemia (28.4%), metabolic syndrome (13.1%), and diabetes (5.5%)—display diverse prevalence rates. We identified 13,449 participants who had CVD mortality, and the median follow-up was 15 years. CKM predicts CVD mortality with a dose-response relationship: Hazard Ratios (HRs) for Stage 2 is 2.34 (95% confidence interval (CI): 2.06, 2.65); HR for Stage 3 is 2.69 (95% CI: 2.36, 3.07), and HR for Stage 4 is 4.70 (95% CI: 4.11, 5.39). Within CKM, 43.3% have two or more components, 20.4% have three or more, and 7.3% have four or more. In those aged 65 and above, 66.6% have two or more components, 37.9% have three or more, and 17.8% have four or more. Participants with two or more components exhibit a higher CVD mortality risk than those with a single CKM component. Conclusion The prevalence rates of CKM and its components vary, contributing to distinct risks of cardiovascular disease mortality. A clustering phenomenon exists among different components, where an increased number of clustered factors corresponds to a higher risk of cardiovascular disease mortality.

Apelin and Copeptin Levels in Patients With Chronic SIAD Treated With Empagliflozin.

Empagliflozin increases sodium levels in patients with a chronic syndrome of inappropriate antidiuresis (SIAD), and dapagliflozin increases apelin levels in patients with diabetes mellitus. Exogenous apelin increases sodium levels in rats with SIAD. We aimed to investigate whether an increase in plasma apelin concentration may contribute to the efficacy of empagliflozin in SIAD. Post hoc secondary analysis of a double-blind, crossover, placebo-controlled trial performed from December 2017 to August 2021 at the University Hospital Basel, Switzerland, investigating the effect of 4-week treatment with empagliflozin 25 mg/day as compared to placebo in 14 outpatients with chronic SIAD (NCT03202667). The objective was to investigate the effect of empagliflozin on plasma apelin and copeptin concentrations and their ratio. Fourteen patients, 50% female, with a median [interquartile range] age of 72 years [65-77] were analyzed. Median apelin concentration was 956 pmol/L [853, 1038] at baseline. Median [interquartile range] apelin relative changes were +11% [0.7, 21] and +8% [-5, 25] (P = .672) at the end of the placebo and empagliflozin phases, respectively. Median copeptin concentration was 2.6 [2.2, 4.5] pmol/L at baseline and had a relative change of +5 [-2. 11]% and +25% [10, 28] (P = .047) over the placebo and empagliflozin phases, respectively. Empagliflozin did not lead to significant changes in apelin or the apelin/copeptin ratio in patients with chronic SIAD but led to an increase in copeptin. This suggests that the efficacy of empagliflozin in SIAD is independent of apelin and is not blunted by the adaptative increase in copeptin.

A novel transmembrane CXCR4 variant that expands the WHIM genotype-phenotype paradigm

Warts, Hypogammglobulinemia, Infections, Myelokathexis (WHIM) syndrome is a rare immunodeficiency disease that results from impaired leukocyte trafficking (myelokathexis) predominately caused by gain-of-function variants in C-X-C chemokine receptor type 4 (CXCR4). Clinical manifestations of WHIM syndrome can differ in familial forms or in people harboring identical CXCR4 variants. All known pathogenic CXCR4 variants associated with WHIM syndrome (CXCR4WHIM) to date are localized in the intracellular C-terminus of CXCR4. We identified 4 unrelated patients with variable WHIM-like clinical presentations harboring a novel heterozygous CXCR4 variant (c.250G>C; p.D84H) localized at a highly conserved position in the transmembrane domain of the receptor outside the C-terminus. Functional characterization of the CXCR4D84Hvariant (CXCR4D84H) using patient-derived peripheral blood mononuclear cells and in vitro cellular assaysshow decreased CXCR4 internalization and increased chemotaxis in response to CXCL12, similar to known CXCR4WHIM, but also revealed unique features of CXCR4D84H signaling to cAMP, Ca2+ mobilization and AKT/ERK pathways. These findings are consistent with molecular dynamics simulations that show disruption of the Na+ binding pocket by D84H, resulting in collapse of the hydrophobic gate above and destabilization of the inactive state of CXCR4. Mavorixafor, a CXCR4 antagonist being evaluated in clinical trials for chronic neutropenia and WHIM syndrome, normalized CXCL12-mediated chemotaxis of CXCR4D84H patient lymphocytes ex vivo and improved WBC and subset counts in 1 patient with CXCR4D84H enrolled in the chronic neutropenia phase 1b clinical trial (NCT04154488). The present study expands the current understanding of CXCR4 function and genotype-phenotype correlations in WHIM syndrome and in people with WHIM-like phenotypes.