Manifestations Of Syndrome Research Articles

MAFLD in adults: non-invasive tests for diagnosis and monitoring of MAFLD.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the liver manifestation of a metabolic syndrome and is highly prevalent in the general population. There has been significant progress in non-invasive tests for MAFLD, from the diagnosis of fatty liver and monitoring of liver fat content in response to intervention, to evaluation of liver fibrosis and its change over time, and from risk stratification of patients within the context of clinical care pathways, to prognostication. Various non-invasive tests have also been developed to assess for fibrotic metabolic dysfunction-associated steatohepatitis, which has emerged as an important diagnostic goal, particularly in the context of clinical trials. Non-invasive tests can be used to diagnose clinically significant portal hypertension so that intervention can be administered to reduce the risk of decompensation. Furthermore, the use of risk stratification algorithms can identify at-risk patients for hepatocellular carcinoma surveillance. Beyond the liver, various tests that evaluate cardiovascular disease risk, assess sarcopenia and measure patient reported outcomes, can be utilized to improve the care of patients with MAFLD. This review provides an up-to-date overview of these non-invasive tests and the limitations of liver biopsy in the management of patients with MAFLD.

Role of gut-liver axis and glucagon-like peptide-1 receptor agonists in the treatment of metabolic dysfunction-associated fatty liver disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a hepatic manifestation of the metabolic syndrome. It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries. MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma. Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis. The mechanisms involved in maintaining gut-liver axis homeostasis are complex. One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gut-liver axis functionality. An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis. Moreover, alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of drugs developed for the treatment of type 2 diabetes mellitus. They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis. The mechanisms reported to be involved in this effect include an improved regulation of glycemia, reduced lipid synthesis, β-oxidation of free fatty acids, and induction of autophagy in hepatic cells. Recently, multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment. A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD. This review presents the current understanding of the role of the gut-liver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.

Treatment Options and Continuity of Care in Metabolic-associated Fatty Liver Disease: A Multidisciplinary Approach.

The terms non-alcoholic fatty liver disease and non-alcoholic steatohepatitis have some limitations as they use exclusionary confounder terms and the use of potentially stigmatising language. Recently, a study with content experts and patients has been set to change this nomenclature. The term chosen to replace non-alcoholic fatty liver disease was metabolic dysfunction-associated steatotic liver disease (MASLD), which avoids stigmatising and helps improve awareness and patient identification. MASLD is the most common cause of chronic liver disease with an increasing prevalence, accounting for 25% of the global population. It is considered the hepatic manifestation of the metabolic syndrome with lifestyle playing a fundamental role in its physiopathology. Diet change and physical activity are the cornerstones of treatment, encompassing weight loss and healthier behaviours and a holistic approach. In Europe, there is no approved drug for MASLD to date and there is a substantial unmet medical need for effective treatments for patients with MASLD. This review not only provides an update on advances in evidence for nutrition and physical activity interventions but also explores the different therapeutic options that are being investigated and whose development focuses on the restitution of metabolic derangements and halting inflammatory and fibrogenic pathways.

HGG-26. MLH1, MSH2, MSH6, AND PMS2 IMMUNOHISTOCHEMISTRY REPRESENTS A HIGHLY SENSITIVE SCREENING METHOD FOR MISMATCH REPAIR DEFICIENCY SYNDROMES IN PEDIATRIC HIGH-GRADE GLIOMA

Abstract BACKGROUND Pediatric central nervous system (CNS) tumors can occur as first manifestations of cancer predisposition syndromes (CPS) resulting from pathogenic variants in DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2. Early detection of MMR deficiencies (MMRD) may warrant the therapeutic use of checkpoint inhibitors and enable genetic consulting for the patient’s families. METHODS We prospectively screened 128 pediatric high-grade gliomas (pedHGG) for MMR protein expression by immunohistochemistry (IHC) as part of the HIT-HGG-2013 clinical trial. We compared IHC results to independently collected patient information on CPS including MMRD to test the method’s efficiency in screening for Lynch syndrome and Constitutional MMRD syndrome CMMRD. RESULTS From 128 successfully tested tumors, ten cases (10/128, 7.8%), showed loss of expression of at least one of the MMR proteins. In seven of the ten affected patients (7/128, 5.5%), genetic testing uncovered heterozygous (6/10) or homozygous (1/10) pathogenic germline variants in MMR genes (MLH1, MSH2 or MSH6) confirming the diagnosis of Lynch syndrome respectively CMMRD. In three cases (3/128 2.3%), MMR alterations were restricted to tumor tissue. The group of diffuse midline gliomas, H3 K27-altered, (67/128, 52.3%) did not show MMR alterations, while either somatic or germline MMR mutations were detected in two of eight patients with diffuse hemispheric glioma, H3 G34-mutant. In 88 patients (88/128, 68.8%) either clinical or molecular-genetic information on CPS could be provided. All ten patients with signs of MMRD were successfully detected by IHC from tumor tissue. CONCLUSIONS IHC for MMR proteins represents a highly sensitive screening method for MMRD in pedHGG. Considering the occurrence of at least 11.5% (7/61) of MMRD in pediatric patients with diffuse high-grade glioma excluding DMG, MMRD IHC should be part of routine diagnostics as cost-effective, broadly available and robust screening method.

Research progress on monogenic inherited glomerular diseases with central nervous system symptoms

To date, approximately 500 monogenic inherited kidney diseases have been reported, with more than 50 genes associated with the pathogenesis of monogenic isolated or syndromic nephrotic syndrome. Most of these genes are expressed in podocytes of the glomerulus. Neurological symptoms are common extrarenal manifestations of syndromic nephrotic syndrome, and various studies have found connections between podocytes and neurons in terms of morphology and function. This review summarizes the genetic and clinical characteristics of monogenic inherited diseases with concomitant glomerular and central nervous system lesions, aiming to enhance clinicians' understanding of such diseases, recognize the importance of genetic diagnostic techniques for comorbidity screening, and reduce the rates of missed diagnosis and misdiagnosis.

Monoclonal gammopathy of clinical signifi cance with osteosclerotic lesions - a case report and a literature review.

Multiple myeloma is a common plasma cell neoplasia usually accompanied by the formation of osteolytic foci, whereas osteosclerotic myeloma is a very rare form of plasma cell dyscrasia. When osteosclerotic myeloma is detected, osteosclerotic foci are usually part of the POEMS syndrome. Osteosclerotic myeloma without other manifestations of the POEMS syndrome is an unusual finding. In a 46-year-old woman, osteosclerotic changes of the temporoparietal region caused soft tissue induration over this lesion, which initiated further investigation. Imaging studies subsequently showed multiple osteosclerotic foci in the skull. Examination of blood proteins revealed 8 g/L of IgG-lambda monoclonal immunoglobulin, subclass IgG1. In search of the cause of the osteosclerotic changes, FDG-PET/CT was performed, which revealed no FDG accumulation, i.e., no other tumor (breast or stomach cancer). Low-dose CT showed irregular bone structure, but not significant osteolytic or osteosclerotic foci. To map the extent of osteosclerotic changes, NaF-PET/CT imagination followed, which revealed multiple spots with high fluoride accumulation. A parietal bone biopsy showed osteosclerosis with minor clonal plasma cell infiltration. Trepanobioptic bone marrow sampling revealed an infiltration of bone marrow with atypical plasma cells in 8%. Flow-cytometric examination of bone marrow showed 0,37% of plasma cells, however predominantly (91%) clonal with lambda expression. MRI of the brain identified asymptomatic meningeal thickening. There was no evidence of POEMS syndrome in the patient; thus, we concluded the diagnosis as monoclonal gammopathy of clinical significance with osteosclerosis which was previously termed osteosclerotic multiple myeloma. Monoclonal gammopathy of clinical significance (MGCS) with osteosclerotic skeletal changes, documented on CT and multiple foci with intensive osteoneogenesis, documented on NaF-PET/CT without evidence of POEMS syndrome, is an extremely rare form of plasma cell dyscrasia. This publication documents the unique clinical manifestations of IgG-lambda type plasma cell proliferation without signs of POEMS syndrome and the role of NaF-PET/CT imaging. Classification of this disease as MGSC with osteosclerotic manifestations is more consistent with the indolent nature of the disease with a significantly better prognosis, compared with multiple myeloma.

КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ УСПЕШНОГО ЛЕЧЕНИЯ СИНДРОМА КОРОТКОЙ КИШКИ У РЕБЕНКА С ИСПОЛЬЗОВАНИЕМ ПРЕПАРАТА ТЕДУГЛУТИД

Authors represent a clinical case of short bowel syndrome, pathological condition caused by a decrease in the absorptive surface of the small intestine, which arose in a child as a result of surgical interventions for small intestinal atresia type IV (multiple atresias). The use of the Teduglutide drug experience is described in a child with severe manifestations of short bowel syndrome.

Skin Manifestations of VEXAS Syndrome and Associated Genotypes

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly defined genetic disease with an estimated prevalence of 1 in 4269 men older than 50 years and is marked by systemic inflammation, progressive bone marrow failure, and inflammatory cutaneous manifestations. To define the spectrum of cutaneous manifestations in VEXAS syndrome and the association of these findings with clinical, genetic, and histological features. This observational cohort study included data from 112 patients who were diagnosed with VEXAS-defining genetic variants in UBA1 between 2019 and 2023. Data were collected from medical record review or from patients with VEXAS directly evaluated at the National Institutes of Health in Bethesda, Maryland. To define the spectrum of cutaneous manifestations in VEXAS in association with genetic, histological, and other clinical findings. A secondary outcome was cutaneous response to treatment in VEXAS. Among the 112 patients (median [range] age, 69 [39-79] years; 111 [99%] male), skin involvement was common (93 [83%]), and the most frequent presenting feature of disease (68 [61%]). Of 64 histopathologic reports available from 60 patients, predominant skin histopathologic findings were leukocytoclastic vasculitis (23 [36%]), neutrophilic dermatosis (22 [34%]), and perivascular dermatitis (19 [30%]). Distinct pathogenic genetic variants were associated with specific cutaneous manifestations. The p.Met41Leu variant was most frequently associated with neutrophilic dermal infiltrates (14 of 17 patients [82%]), often resembling histiocytoid Sweet syndrome. In contrast, the p.Met41Val variant was associated with vasculitic lesions (11 of 20 patients [55%]) with a mixed leukocytic infiltrate (17 of 20 patients [85%]). Oral prednisone improved skin manifestations in 67 of 73 patients (92%). Patients with VEXAS treated with anakinra frequently developed severe injection-site reactions (12 of 16 [75%]), including ulceration (2 of 12 [17%]) and abscess formation (1 of 12 [8%]). Results of this cohort study show that skin manifestations are a common and early manifestation of VEXAS syndrome. Genetic evaluation for VEXAS should be considered in older male patients with cutaneous vasculitis, neutrophilic dermatoses, or chondritis. Awareness of VEXAS among dermatologists is critical to facilitate early diagnosis.

Case Report of Gorlin-Goltz Syndrome

Gorlin-Goltz syndrome, also known as basal cell nevus syndrome. This condition is characterized by various clinical manifestations, including multiple cutaneous lesions and other systemic abnormalities. We present the case of a 32-year-old man with no significant medical history who was referred to our institution for evaluation of multiple budding lesions. Clinical examination revealed three lesions in the upper right nasolabial fold, one in the lower right cheek, one in the left nasolabial fold, and additional suspect lesions on the chin, right temple, and right cheek. This case underscores the importance of recognizing the diverse manifestations of Gorlin-Goltz syndrome, which can aid in early diagnosis and management of this inherited disorder. Further investigation and long-term follow-up are essential for understanding the progression and management of this condition.

Heterocyclic Amines Disrupt Lipid Homeostasis in Cryopreserved Human Hepatocytes.

Metabolic dysfunction associated-steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH) is the liver manifestation of metabolic syndrome, which is characterized by insulin resistance, hyperglycemia, hypertension, dyslipidemia, and/or obesity. Environmental pollutant exposure has been recently identified as a risk factor for developing MASH. Heterocyclic amines (HCAs) are mutagens generated when cooking meat at high temperatures or until well-done. Recent epidemiological studies reported that dietary HCA exposure may be linked to insulin resistance and type II diabetes, and we recently reported that HCAs induce insulin resistance and glucose production in human hepatocytes. However, no previous studies have examined the effects of HCAs on hepatic lipid homeostasis. In the present study, we assessed the effects of two common HCAs, MeIQx (2-amino-3, 8-dimethylimidazo [4, 5-f] quinoxaline) and PhIP (2-amino-1-methyl-6-phenylimidazo[4, 5-b] pyridine), on lipid homeostasis in cryopreserved human hepatocytes. Exposure to a single concentration of 25μM MeIQx or PhIP in human hepatocytes led to dysregulation of lipid homeostasis, typified by significant increases in lipid droplets and triglycerides. PhIP significantly increased expression of lipid droplet-associated genes, PNPLA3 and HSD17B13, and both HCAs significantly increased PLIN2. Exposure to MeIQx or PhIP also significantly increased expression of several key genes involved in lipid synthesis, transport and metabolism, including FASN, DGAT2, CPT1A, SCD, and CD36. Furthermore, both MeIQx and PhIP significantly increased intracellular cholesterol and decreased expression of PON1 which is involved in cholesterol efflux. Taken together, these results suggest that HCAs dysregulate lipid production, metabolism, and storage. The current study demonstrates, for the first time, that HCA exposure may lead to fat accumulation in hepatocytes, which may contribute to hepatic insulin resistance and MASH.

Esophageal Striae as a Possible Gastrointestinal Manifestation of Hypermobile Ehlers-Danlos Syndrome.

Esophageal Striae as a Possible Gastrointestinal Manifestation of Hypermobile Ehlers-Danlos Syndrome.

Effects of a multicomponent lifestyle modification intervention on liver function, lipid profile, and body composition in adults with elevated hepatic steatosis index

Parallel to the escalating burden of obesity is the steadily increasing prevalence of metabolic dysfunction associated steatotic liver diseases (MASLD), a chronic condition that progresses from simple steatosis to advanced stages of steatohepatitis, fibrosis, and cirrhosis (1-2). MASLD, regarded as the hepatic manifestation of metabolic syndrome is known to be exacerbated by unhealthy lifestyle choices and the presence of comorbidities such as diabetes, dyslipidemia, and obesity (3-4). Therefore, early identification of the general population at risk of MASLD and the development of multicomponent interventions that can prevent the progression of liver damage and mitigate associated adverse cardiometabolic health outcomes are important. Our study aimed to evaluate the effects of a lifestyle modification program on glucose levels, lipid profile, liver function, and body composition measures in community-living adults with elevated hepatic steatosis index in Mumbai, India.Adults (n= 231, mean age 46.1(13.7) years), 58.6% men) were screened for risk of MASLD using a non-invasive screening tool, Hepatic Steatosis Index (HSI) (calculated as (HSI)= 8 x (ALT/AST ratio) +BMI (+2, if female; +2, if diabetes mellitus) (5). Eligible participants with HSI >36 (predictive of the presence of MASLD) were randomized to receive either a multicomponent lifestyle intervention (experimental group, EG) comprising weekly sessions of individualized dietary counseling (Participants having BMI >23kg/m2 (n = 36) received hypocaloric diets with 40% carbohydrates, 40% fat and 30% proteins (WLD) and those having BMI <22.9kg/m2 (n= 22) received weight maintenance diet (WMD) plans including 55% carbohydrates, 15% protein and 30% fats) and fortnightly group sessions of structured exercise and nutrition education or a standard of care package (control group, CG, n= 43) including general healthy eating and activity guidelines for the 8- week study duration. Paired t test and independent sample t tests were used to determine within and between group changes in variables from baseline to endline.Trial Registration: This study is registered as CTRI/2022/05/042927.Overall, the prevalence of MASLD was 52.2%, 32.8% were hypertensive, and 26.7% and 15.4% had diabetes and hypertriglyceridemia respectively. The intervention (WLD) resulted in decreased weight (mean (M)= 3.4 kg, standard error (SE) = 1.88 k, p = 0.02), body fat percent (M = 2.2%, SE = 1.1%, p= 0.042), serum triglycerides (M=28.8mg/dL, SE 8.5mg/dL, p<0.001) and AST (M= 3.8 U/L, SE= 2.2U/L, p <0.05) values. The WMD group reported improvements in serum cholesterol levels, and ALT/ AST ratio as compared to CG (p <0.001). In WMD, HDL-C increased from 45.8 mg/dl to 47.2 mg/dl and the mean AST values reduced from 28.8 (10.6) U/L to 25.6 (9.9) U/L, but these changes were not statistically significant.Multicomponent lifestyle modification programs integrating diet, physical activity and education are effective strategies to improve liver outcomes and optimize cardiometabolic health in people with MASLD.

Intramyocardial edema as an atypical manifestation of capillary leak syndrome

Intramyocardial edema as an atypical manifestation of capillary leak syndrome

Establishment of a mouse model of yin deficiency syndrome by prednisolon

Background: We are conducting the project “Establishment of a mouse model of yin deficiency syndrome by prednisolone” due to the need to establish a mouse model to simulate yin deficiency syndrome and the actual situation of glucocorticoid abuse causing many complications, which, from the perspective of traditional medicine, are manifestations of yin deficiency syndrome. Materials and methods: In mice, establish a model of yin deficiency syndrome with prednisolone. Subjects and methods: We randomly divided four groups of healthy male Swiss albino mouse strains: a control group that drank distilled water, and three groups that took prednisolone doses of 0.5 mg/kg, 2.5 mg/kg, and 15 mg/kg from day 1 to day 14. After stopping the drug, we continued to monitor the mice for an additional seven days. We monitored some primary yin deficiency symptoms, such as weight loss, tidal fever, dry thirst, frequent urination, fatigue, and weakness, by recording data on body weight, food weight, water weight, urine weight, and rectal temperature measurements every day from day 0 to day 21. We also measured mouse activity on days 0, 7, and 14. Results: Taking 15 mg/kg and 2.5 mg/kg of prednisolone changed things like the ratio of food intake to body weight, the ratio of water intake to body weight, the ratio of urine weight to body weight, and the afternoon rectal temperature compared to the control group on days 4 and 9; mouse activity compared to the control group at day 7 and day 14. Taking 15 mg/kg of prednisolone also caused unstable yin deficiency symptoms, just like taking 2.5 mg/kg of prednisolone did with the same parameters. Conclusion: We recorded the onset of yin deficiency symptoms in Swiss albino white mice treated with 2.5 mg/kg of prednisolone on day nine, as well as the duration of symptom maintenance after stopping prednisolone for one day. Key words: Yin deficiency syndrome, mouse model, prednisolone

Objective Evaluation of Stellate Ganglion Block Effects Using Ultrasound Wave Intensity Technology: A Study on Hemodynamics.

Emerging evidence suggests that although Horner's syndrome manifests observable facial changes, it may not comprehensively evaluate the hemodynamic alterations associated with stellate ganglion block (SGB). This study endeavors to systematically evaluate the influence of SGB on the elasticity and flow velocity of the common carotid artery (CCA) and brachial artery utilizing ultrasound wave intensity analysis (usWIA). Particularly, it focuses on patients necessitating monitoring for its effects on specific organs or regions. Totally, we selected 33 patients, where only 31 patients (comprising 15 males and 16 females) were included between September 2020 to January 2022 after screening patients who require SGB treatment for painful disorders. The side on which the SGB was administered depended on the patient's painful side, 13 cases underwent left stellate ganglion block (LSGB), and 18 cases underwent right stellate ganglion block (RSGB). Wave intensity (WI) data were collected by usWIA on the CCA and brachial artery before the administration of SGB and after the manifestation of Horner's syndrome. We then compared the changes in these data pre- and post-SGB using SPSS 26.0. The results showed an increase in arterial compliance (AC) of the CCA and brachial artery on the blocked side after SGB (P < 0.05). In contrast, pressure-strain elastic modulus (EP) and arterial stiffness pulse wave velocity (PWVβ) decreased (for all P < 0.05). Furthermore, the minimum velocity (Vmin) of the CCA exhibited a significant increase (P < 0.01), while wave intensity pulse wave velocity (PWVwi) was significantly reduced (P < 0.01). In contrast, on the contralateral side of the CCA, EP and PWVβ increased after SGB (for all P < 0.05), while AC decreased (P < 0.05). SGB has been observed to enhance the elasticity and blood flow velocity of arteries within its innervated areas. In clinical practice, usWIA can serve as an objective measurement tool for assessing the impact of SGB on arterial elasticity and flow velocity in specific organs or regions. Furthermore, unilateral SGB has been noted to diminish the arterial elasticity of the CCA on the contralateral side.

Increased incidence and diverse manifestations of multiple evanescent white dot syndrome during the COVID-19 pandemic

The advent of coronavirus disease 2019 (COVID-19) pandemic has affected the incidence and course of various diseases and numerous studies have investigated ocular involvement associated with COVID-19 and corresponding vaccines. In this study, we compared the incidence of multiple evanescent white dot syndrome (MEWDS) before and during the COVID-19 pandemic at a single center in Korea and analyzed the demographic and clinical features of patients with MEWDS presenting during the COVID-19 pandemic. We categorized patients with MEWDS into two groups according to date of diagnosis. Pre-COVID19 group included patients diagnosed during the pre-pandemic period (between March 11, 2017, and March 10, 2020), whereas post-COVID19 group included patients diagnosed during the pandemic period (between March 11, 2020, and March 10, 2023). 6 and 12 patients were included in pre-COVID19 group and post-COVID19 group, respectively. Among all hospital visits during the pre-pandemic and pandemic periods, 0.011% and 0.030% were due to MEWDS, indicating a significant increase during the pandemic (p = 0.029, B = 2.756). The annual incidence of patients with MEWDS in 2017–2022 were 0.73, 0.75, 0.78, 1.32, 2.49, and 2.07 per 10,000 population, respectively, corresponding to a significant increase (p = 0.039, B = 1.316). Our results imply that the incidence and manifestation of MEWDS are likely to become more diverse in the COVID-19 pandemic era.

The Role of Curcumin in Oral Health and Diseases: A Systematic Review.

Curcumin (Curcumin) belongs to the polyphenol family. It is extracted by drying the root of a plant of Asian origin, belonging to the Zingiberaceae family. The best-known species is Curcumincuma Longa. Curcumin has been recognized as having great therapeutic powers since ancient times. Studies on curcumin have since confirmed its powerful antioxidant properties, preventing both the formation of free radicals and their neutralization, having anti-inflammatory, antibacterial, immunological, and neuroprotective properties, as well as being a regulator of the intestinal microbiota with beneficial effects on the clinical manifestations of metabolic syndrome. Our study aimed to highlight how all these therapeutic aspects could benefit oral health, both preventing and improving the course of pathological processes. The effect of mouthwashes, and curcumin-based gels on the regulation of bacterial plaque and in the control of gingivitis, was largely comparable to that of using 0.20% chlorhexidine, with fewer side effects. Being a highly hydrophobic substance, it has a high permeability to cross the cell membrane. Bioavailability increases when combined with liposoluble substances (e.g., olive oil) and piperine, which improves absorption. Curcumin also has a negligible degree of toxicity, making it an excellent alternative to the use of gold standard products for oral disinfection.

Ornithine aspartate effects on bacterial composition and metabolic pathways in a rat model of steatotic liver disease.

Metabolic-dysfunction associated steatotic liver disease (MASLD) is a hepatic manifestation of metabolic syndrome. Studies suggest ornithine aspartate (LOLA) as drug therapy. To analyze the influence of LOLA intake on gut microbiota using a nutritional model of MASLD. Adult male Sprague Dawley rats were randomized into three groups: Control (10 rats fed with a standard diet), MASLD (10 rats fed with a high-fat and choline-deficient diet), and LOLA (10 rats receiving 200 mg/kg/d LOLA, after the 16th week receiving high-fat and choline-deficient diet). After 28 wk of the experiment, animals were euthanized, and feces present in the intestine were collected. Following fecal DNA extraction, the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™ system. Alpha and beta diversity metrics were comparable between MASLD and LOLA. 3 OTUs were differentially abundant between MASLD and LOLA, which belong to the species Helicobacter rodentium, Parabacteroides goldsteinii, and Parabacteroides distasonis. The functional prediction provided two different metabolic profiles between MASLD and LOLA. The 9 pathways differentially abundant in MASLD are related to a change in energy source, adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides biosynthesis. The 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate, including tricarboxylic acid cycle pathways, purine/guanosine nucleotides biosynthesis, pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA biosynthesis. Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLD, it was associated with changes in specific gut microbes and their related metabolic pathways.

Evolving Concepts of the SCORE System: Subtracting Cholesterol from Risk Estimation: A Way for a Healthy Longevity?

The role of cholesterol, mainly low-density lipoproteins (LDL-C), as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) is now established and accepted by the international scientific community. Based on this evidence, the European and American guidelines recommend early risk stratification and "rapid" achievement of the suggested target according to the risk estimation to reduce the number of major cardiovascular events. Prolonged exposure over the years to high levels of LDL-C is one of the determining factors in the development and progression of atherosclerotic plaque, on which the action of conventional risk factors (cigarette smoking, excess weight, sedentary lifestyle, arterial hypertension, diabetes mellitus) as well as non-conventional risk factors (gut microbiota, hyperuricemia, inflammation), alone or in combination, favors the destabilization of the atherosclerotic lesion with rupture/fissuration/ulceration and consequent formation of intravascular thrombosis, which leads to the acute clinical manifestations of acute coronary syndromes. In the current clinical practice, there is a growing number of cases that, although extremely common, are emblematic of the concept of long-term exposure to the risk factor (LDL hypercholesterolemia), which, not adequately controlled and in combination with other risk factors, has favored the onset of major cardiovascular events. The triple concept of "go lower, start earlier and keep longer!" should be applied in current clinical practice at any level of prevention. In the present manuscript, we will review the current evidence and documents supporting the causal role of LDL-C in determining ASCVD and whether it is time to remove it from any score.

#844 Renal manifestations of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome: an updated systematic review

Abstract Background and Aims Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a systemic autoimmune genetic disorder caused by mutation of the forkhead box protein 3 (FOXP3) gene. We performed this study to analyze the clinical and demographic characteristics of renal involvement in IPEX patients, genotype-phenotype correlations and the effect of renal involvement on patient outcome. Method We performed a literature search (PubMed and EMBASE) to systematically investigate the case reports of IPEX with renal involvement which were published before Dec 21st, 2023. Results A total of 37 patients were identified. All IPEX patients included had FOXP3 mutations which were most frequently located in the forkhead domain. Among 25 patients in whom detailed information is available, 22 showed single presentation (6 proteinuria, 8 nephrotic syndrome (nephrotic range proteinuria), 3 acute glomerulonephritis, 5 renal insufficiency), 2 showed multiple presentations (1 nephrotic range proteinuria, microscopic hematuria and 1 nephrotic range proteinuria, microscopic hematuria, renal insufficiency). Renal biopsy was documented in 19 patients. Membranous nephropathy (n = 9) was most common, followed by Interstitial nephritis (n = 3), membranoproliferative nephropathy (n = 2), tubulopathy (n = 2), mesangial proliferative glomerulonephritis (n = 2), autoimmune nephritis (n = 1). Nephrotic syndrome was more frequent in patients with intron 6 mutation (p &amp;lt; 0.05). However, renal presentation of IPEX syndrome was not related to patient outcome (death). Conclusion We found renal involvement is one of the important manifestations of IPEX syndrome and membranous nephropathy was most common. Close renal monitoring is necessary to detect renal involvement of IPEX syndrome. Further studies are necessary to compare the course of glomerulonephritis between IPEX-related and IPEX-unrelated one. Response to treatment should also be elucidated in patients with IPEX in the future.