Chronic Disease Research Articles

Deep Learning Assisted Diagnosis of Chronic Obstructive Pulmonary Disease Based on a Local-to-Global Framework

To aid the diagnosis of chronic obstructive pulmonary disease (COPD), a local-to-global deep framework with group attentions and slice-aware loss is designed in this paper, which utilizes the chest CT sequences of the patients as the network input. To fully mine the medical hints submerged in the CT slices, two types of group attentions are designed to extract local–global features of the grouped slices. Specifically, in each group, a group local attention block (GLAB) and a group global attention block (GGAB) are designed to extract local features in the CT slices and long-range dependencies among the grouped slices. To alleviate the influence of different numbers of CT slices in the chest CT sequences for different patients, a slice-aware loss is proposed by incorporating a normalized coefficient into the cross-entropy loss. Experimental results indicate that the designed deep model performs a good COPD identification on a real COPD dataset with 96.08% accuracy, 94.12% sensitivity, 97.06% specificity, and 95.32% AUC, which is superior to some existing deep learning methods.

High Rates of Obesity and Chronic Diseases Among North Carolina United Methodist Clergy: An Updated Analysis

Background Varied demands and stressors experienced by clergy can contribute adversely to their overall well-being. Data from United Methodist Church (UMC) clergy in North Carolina in 2008 revealed that clergy had significantly higher non-communicable disease (NCD) rates than their fellow North Carolinians. Methods Using data from the Clergy Health Initiative and Behavioral Risk Factor Surveillance Survey, the present study provided an updated analysis of obesity and 6 other NCDs among North Carolina UMC clergy compared to the general North Carolina population. First, we described the prevalence of each health condition among North Carolina UMC clergy and the general North Carolina population across multiple waves from 2008 to 2021. Then, we compared the predicted probabilities of each health condition in 2021 using logistic regressions to adjust for age, sex, and race. Results Comparing the unadjusted prevalence of health conditions between 2008 and 2021, we found that North Carolina UMC clergy have higher rates of obesity, hypertension, hypercholesterolemia, diabetes, angina, arthritis, and asthma than North Carolinians overall. Adjusting for age, sex, and race, we found that significantly higher rates of obesity, severe obesity, hypercholesterolemia, and asthma persisted among UMC clergy in 2021 compared to all North Carolinians, with the higher rates of severe obesity being particularly concerning. Limitations While the current study is limited to an update of health prevalence among UMC clergy, pastors across denominations are influential leaders in their communities, shaping the physical and social health environments of their congregations. Conclusions Further research is needed to investigate risk factors, such as relocation and adverse childhood experiences, which may influence the higher prevalence of NCDs within and potentially beyond the UMC.

Adapting to Adulthood: A Review of Transition Strategies for Osteogenesis Imperfecta.

Osteogenesis Imperfecta (OI), known as "brittle bone disease," presents a rare genetic disorder characterized by bone fragility, often accompanied by skeletal deformities and extraskeletal complications. OI is primarily associated with collagen type I defects, responsible for the syndromic nature of the disease affecting a broad range of tissues. As such, its multisystemic complexity necessitates multidisciplinary care approaches in all patient life stages. OI treatment remains largely supportive, commonly including bisphosphonates and orthopedic surgeries, which show promise in children. Although rehabilitation programs for children exist, guidelines for adult care and especially the transition from pediatric to adult care, are lagging behind in OI care and research. The current systematic review summarizes the literature on OI patient pediatric to adult care transition experiences and compares OI transition approaches to other chronic diseases. The review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Systematic searches were conducted across multiple databases. Search terms encompassed synonyms and closely related phrases relevant to "OI" and "Transition to adult care". The initial screening involved the evaluation of article titles, followed by a thorough review of abstracts to assess relevance for the purpose of the current review. Programs aimed at easing the transition from pediatric to adult OI care necessitate a multifaceted approach. Collaborative efforts between different medical disciplines including pediatricians, endocrinologists, orthopedics, cardiology, pulmonology, ophthalmology, otolaryngologists, maxillofacial specialists, psychologists and medical genetics, are crucial for addressing the diverse needs of OI patients during this critical life phase. Comprehensive education, readiness assessments, personalized transition plans, and further follow-up are essential components of a structured transition framework. Further research is warranted to evaluate the feasibility and efficacy of sequential stepwise transition systems tailored to individuals with OI.

«I have ants in my pants»: Metaphorical Framing in Female’s Conversational Narratives of Osteoporosis

Some changes that humans undergo in their bodies as they grow older are accompanied by a decline in health. Exclusively from the patients’ perspective, this paper is based on narratives of lived experiences related to osteoporosis, one chronic disease that usually develops unnoticedly as age increases and that is more frequent in females than in males. The general aim is to delve into the linguistic expressions used by women suffering from osteoporosis to talk about their condition. More specifically, the study focuses on the metaphors that patients use to describe or share their real insights and experiences with the disease and how these contribute to project an image of women themselves, on the one hand, but also to provide peers with further information and support, help them improve their lives and understand the inherent complex changes, symptoms and difficulties that they, their bodies and bones (may) experiment, on the other. To fulfil these purposes, a sample of conversational voluntarily produced narratives of women diagnosed with osteoporosis has been compiled, where metaphors have been identified and analysed following the cognitive metaphor theory. The results reveal an alternance of positive empowering and negative metaphors, where women face the suffering and complexities of the disease, but they present and see themselves as brave and empowered patients with dreams and non-stigmatised lives.

Innovative Strategies in Regenerative Medicine: Bridging Science and Clinical Practice

Regenerative medicine is a rapidly advancing field to revolutionize healthcare by offering innovative solutions for repairing or replacing damaged tissues and organs. By addressing significant challenges associated with conventional therapies—such as the shortage of donor organs and complications related to immune rejection—regenerative medicine provides a hopeful alternative for patients suffering from chronic diseases and injuries. This review outlines the urgent need for regenerative medicine to tackle prevalent issues like chronic conditions, organ scarcity, and injury recovery through approaches like stem cell therapy and tissue engineering. Key therapies currently available in the market, such as Carticel and Celution, utilize both autologous and allogeneic cells to promote healing and tissue regeneration. Recent breakthroughs showcase the transformative potential of regenerative medicine, with notable successes including stem cell therapies for spinal cord injuries, 3D-printed skin grafts for burn victims, and the development of lab-grown organs. These advancements highlight regenerative medicine's capability to enhance patient outcomes significantly. Looking ahead, the future of regenerative medicine lies in the personalization of therapies, advanced biomaterials, and cutting-edge technologies like 3D bioprinting. These innovations will enable the creation of complex and functional tissues tailored to individual patients. As research continues to progress, regenerative medicine holds the promise of offering long-term, transformative solutions for a wide range of medical conditions..

Abstract A027: Systematic review of real-world adherence to blood-based laboratory tests for average-risk disease screening: potential implications for emerging colorectal cancer screening modalities

Abstract Introduction: Blood-based tests represent a compelling option for early detection and management of cancers and other chronic diseases. While blood-based tests may offer potential to increase patient engagement, the assumption of greater adherence in clinical practice requires further evaluation. This systematic review aimed to evaluate the real-world adherence to established blood-based tests for commonly recommended screening indications, to better inform expectations for proposed application to average-risk colorectal cancer (CRC) screening. Methods: A systematic search of PubMed, Embase, and citations was performed to identify literature published from 2010 to 2023. Studies examined adherence to routine blood-based laboratory tests with a Grade A or B recommendation per the United States Preventive Services Task Force (USPSTF) for diabetes, dyslipidemia, human immunodeficiency virus (HIV), and hepatitis C virus (HCV) in an average-risk patient population were included. In addition, prostate-specific antigen (PSA) testing adherence for prostate cancer screening (Grade-C USPSTF recommendation), the only commonly accessible blood-based single-cancer screening test for average-risk adults, was also included. Studies without venipuncture-derived blood were excluded. Results: Of 53,067 articles screened, 69 were included in the analysis. Overall, adherence rates of blood-based tests were highly variable, with median values (interquartile range, IQR) of 66.3% (11.8%), 67.8% (18.0%), 34% (28.7%), and 36.8% (30%) for diabetes, dyslipidemia, HCV, and HIV, respectively. PSA testing adherence was 37.2% (18.4%). Beyond disease type, adherence varied by study design, data source, patient characteristics, clinical setting, and study country. Information and selection bias were the most common risks of bias. Conclusions: Based on data from this comprehensive systematic review, real-world adherence to currently recommended, blood-based screening strategies is suboptimal. Future research is needed to identify the extent to which these data are generalizable to blood-based CRC screening, and to determine if/how this candidate strategy would impact clinical, economic, and health equity outcomes. Citation Format: Quang A. Le, Takako Kiener, Heather A. Johnson, Rukaiyya S. Khan, Joyce Kong, Kevin H. Li, Gina Thompson, A. Burak Ozbay, Mallik Greene, Paul J. Limburg, A. Mark Fendrick, John B. Kisiel, Derek W. Ebner. Systematic review of real-world adherence to blood-based laboratory tests for average-risk disease screening: potential implications for emerging colorectal cancer screening modalities [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A027.

Tirzepatide for Obesity Treatment and Diabetes Prevention.

Obesity is chronic disease and causal precursor to myriad other conditions, including type 2 diabetes. In an earlier analysis of the SURMOUNT-1 trial, tirzepatide was shown to provide substantial and sustained reductions in body weight in persons with obesity over a 72-week period. Here, we report the 3-year safety outcomes with tirzepatide and its efficacy in reducing weight and delaying progression to type 2 diabetes in persons with both obesity and prediabetes. We performed a phase 3, double-blind, randomized, controlled trial in which 2539 participants with obesity, of whom 1032 also had prediabetes, were assigned in a 1:1:1:1 ratio to receive tirzepatide at a once-weekly dose of 5 mg, 10 mg, or 15 mg or placebo. The current analysis involved the participants with both obesity and prediabetes, who received their assigned dose of tirzepatide or placebo for a total of 176 weeks, followed by a 17-week off-treatment period. The three key secondary end points, which were controlled for type I error, were the percent change in body weight from baseline to week 176 and onset of type 2 diabetes during the 176-week and 193-week periods. At 176 weeks, the mean percent change in body weight among the participants who received tirzepatide was -12.3% with the 5-mg dose, -18.7% with the 10-mg dose, and -19.7% with the 15-mg dose, as compared with -1.3% among those who received placebo (P<0.001 for all comparisons with placebo). Fewer participants received a diagnosis of type 2 diabetes in the tirzepatide groups than in the placebo group (1.3% vs. 13.3%; hazard ratio, 0.07; 95% confidence interval [CI], 0.0 to 0.1; P<0.001). After 17 weeks off treatment or placebo, 2.4% of the participants who received tirzepatide and 13.7% of those who received placebo had type 2 diabetes (hazard ratio, 0.12; 95% CI, 0.1 to 0.2; P<0.001). Other than coronavirus disease 2019, the most common adverse events were gastrointestinal, most of which were mild to moderate in severity and occurred primarily during the dose-escalation period in the first 20 weeks of the trial. No new safety signals were identified. Three years of treatment with tirzepatide in persons with obesity and prediabetes resulted in substantial and sustained weight reduction and a markedly lower risk of progression to type 2 diabetes than that with placebo. (Funded by Eli Lilly; SURMOUNT-1 ClinicalTrials.gov number, NCT04184622.).

Abstract A066: Could ancestry play a role in cancer development? Insights from a risk assessment and early detection test of naturally occurring cancers in companion dogs

Abstract Companion dogs have a lifetime cancer risk similar to that of humans. This excess risk, as compared to what is seen in other species, seems to be due to our recent success in outliving our evolutionarily adapted lifespan. For cancers to develop, a cancer-permissive environment must be present, which may exist months or even years before a tumor becomes detectable. We have developed the Shine On Suspicion (SOS) test; a flow cytometry based test to detect these changes that lead to a cancer-permissive environment. To make this test actionable, we combined it with eBAT, a novel bispecific ligand-targeted toxin that targets emerging cancer cells and the inflammatory niche to disrupt cancer formation. The Shine On Study used machine- learning algorithms to determine cancer risk based on a training set of 97 dogs with known conditions and a test set of 209 adult dogs with no evidence of cancer or other chronic diseases. Dogs assigned to the low-risk category had a less than 4% chance of developing cancer within 400 days after testing, whereas dogs assigned to the high-risk category had a nearly 25% chance of developing cancer in that timeframe. By 1,450 days, more than 50% of dogs assigned to the high-risk category developed cancer. Surprisingly, the SOS test’s specificity varied by breed. In Boxers and Portuguese Water Dogs the test accurately predicted the risk of hemangiosarcoma and other malignancies, whereas for Golden Retrievers, the test accurately predicted the risk for hemangiosarcoma, but no significant difference in the development of other cancers was observed between high-risk and low-risk groups. This suggests that the contribution of the cancer-permissive environment detected by the SOS test interacts with heritable factors, i.e., those defined by ancestry in creating the overall cancer risk state. To date, eBAT interception has been administered to 9 dogs, with only 1 potentially developing cancer 2 years after treatment. The drug is well-tolerated and shows promising outcomes. Future research aims to refine the SOS test, understand breed-specific responses, and explore the identity and function of niche- forming cells to improve cancer prevention strategies and their applicability to humans. Citation Format: Ashley J Schulte, Taylor A DePauw, Ali Khammanivong, Mitzi Lewellen, Lauren Burt, Rose Dicovitsky, Amber L Winter, Kathleen M Stuebner, Andrea Chehadeh, Sara Pracht, Christopher Ober, Kari L Anderson, Esther Nell, Antonella Borgatti, Michael S Henson, Erin B Dickerson, Aaron L Sarver, Daniel A Vallera, Gary R Cutter, Jaime F Modiano. Could ancestry play a role in cancer development? Insights from a risk assessment and early detection test of naturally occurring cancers in companion dogs [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A066.

Convergence of Alcohol Consumption and Dietary Quality in US Adults Who Currently Drink Alcohol: An Analysis of Two Core Risk Factors of Liver Disease

Background/Objectives: Alcohol consumption and poor dietary habits are on the rise in the United States, posing significant challenges to public health due to their contribution to chronic diseases such as liver failure. While associations between alcohol consumption patterns and diet quality have been explored, the relationship between specific alcoholic beverage types and diet quality remains underexamined. This study aims to compare diet quality among consumers of different alcoholic beverage types. Methods: We conducted a cross-sectional analysis of 1917 current alcohol drinkers from the National Health and Nutrition Examination Survey (NHANES) who completed a 24 h dietary recall survey. Diet quality was assessed using the Healthy Eating Index (HEI), with higher scores indicating superior diet quality. Multivariable logistic regression models were employed to assess differences in HEI between consumers of various alcoholic beverage types, using wine-only drinkers as the reference group and controlling for demographic, socioeconomic, lifestyle, and metabolic syndrome variables. Results: Beer-only drinkers were more likely to have lower income, higher rates of cigarette smoking, and insufficient physical activity compared to other alcohol consumers. In the fully adjusted multivariable model, beer-only drinkers had an HEI score that was 3.12 points lower than wine-only drinkers. In contrast, liquor/cocktail-only and multiple-type drinkers had similar HEI scores to wine-only drinkers. Conclusions: Beer-only consumption is associated with poorer diet quality among alcohol drinkers. Targeted patient education and public health campaigns may be effective in addressing the combined impact of alcohol consumption and poor diet quality on chronic disease risk.

Efficacy of levothyroxine monotherapy in achieving clinical euthyroidism and its impact on weight loss in women with hypothyroidism and obesity.

In light of research indicating that normal TSH levels do not necessarily reflect clinical euthyroidism in hypothyroid patients, and given the patient dissatisfaction with levothyroxine (LT4) monotherapy, we evaluate the response to weight loss treatment in patients with obesity and primary hypothyroidism who are euthyroid under LT4 therapy, with a focus on weight and metabolic parameters. The retrospective study included 138 subjects with obesity (BMI ≥ 30kg/m2), 69 women with hypothyroidism on levothyroxine, and 69 age- and BMI-matched women without thyroid disease. Secondary causes of obesity, medications that may affect thyroid functions and metabolic parameters, chronic and oncological disease, pregnancy, TSH outside the reference range, follow-up periods of less than one year, and bariatric surgery were the exclusion criteria. Patients' characteristics and metabolic responses to weight reduction treatment consisting of calorie restriction, moderate exercise, and metformin if needed were evaluated. TSH and fT4 levels were higher, and fT3 and T3/T4 ratios were lower all within the reference ranges in hypothyroid women. They were less insulin resistant. Both patient' groups experienced a significant decrease in body weight, BMI, and atherogenic index of plasma (AIP) during the follow-up (p = 0.001). Insulin resistance was not changed. The groups' body weight, BMI, HOMA-IR, and AIP changes were similar at the end of the study (p = 0.876, p = 0.850, p = 0.555, p = 0.293). The results suggest that achieving euthyroid status via levothyroxine monotherapy in hypothyroid women leads to weight loss responses comparable to those in women with normal thyroid. This supports the effectiveness of current hypothyroidism treatment strategies, emphasizing TSH level normalization, in achieving clinical euthyroidism concerning weight loss outcomes.

Lipoprotein-associated phospholipase A2 and its possible association with COPD development: a case-control study.

The association of lipoprotein-associated phospholipase A2 (Lp-PLA2) with various cardiovascular events has been well-established. However, the exploration of its potential involvement in Chronic obstructive pulmonary disease (COPD) is currently limited. Therefore, our study aims to examine the relationship between Lp-PLA2 and pulmonary conditions, including emphysema, obstructive ventilatory dysfunction as well as small airway dysfunction, to provide further evidence of a possible association with COPD development. Using data from the Southwest Hospital Health Management Center, spanning January 2013 to July 2024, we analyze relationship of serum Lp-PLA2 levels with diffuse pulmonary emphysema and pulmonary functions. In univariate analysis, group differences were assessed with t-tests for numerical variables and Chi-square tests for categorical data. Variables found to be statistically significant (two-sided P < 0.05) in univariate analysis were subsequently included as covariates in multivariate analysis, performed using a binary logistic regression model. Odds ratios and 95% confidence intervals were calculated to assess the differences. We established 2 case-control populations: the Imaging population (1056 subjects, mean age 57.666 ± 8.700 years old, 89.9% male) selected from 24,670 initial records, and the Pulmonary Function population (279 subjects, mean age 52.082 ± 11.473 years old, 71.4% male) selected from 1868 initial records. Univariate analysis revealed that serum Lp-PLA2 levels were significantly higher in patients with diffuse pulmonary emphysema, obstructive ventilatory dysfunction as well as small airway dysfunction compared to those without (454.682 ± 141.382U/L vs. 423.330 ± 140.658U/L, P < 0.001; 475.059 ± 157.181U/L vs. 420.824 ± 142.119U/L, P = 0.006; 475.31 ± 148.980U/L vs. 439.036 ± 157.977U/L, P = 0.049, respectively). Multivariate analysis further showed higher Lp-PLA2 levels were associated with increased risks of diffuse pulmonary emphysema, obstructive ventilatory dysfunction as well as small airway dysfunction. Using Lp-PLA2 ≤ 300 U/L as reference, odds ratios for the aforementioned conditions showed a gradually increasing trend with every 100U/L increase in Lp-PLA2 levels. Our preliminary study suggests that Lp-PLA2 is independently associated with diffuse pulmonary emphysema, obstructive ventilatory dysfunction as well as small airway dysfunction, which are commonly seen in COPD development. These findings indicated a possible association between Lp-PLA2 and COPD, though further validation is needed in a large cohort of COPD patients.

Design, Synthesis, and Biological Evaluation of New Selective PDE4 Inhibitors for Topical Treatment of Psoriasis.

Psoriasis is a complex and chronic inflammatory disease. Current drugs help control the symptoms of psoriasis but make no cure, urging discovery of novel drugs. We report in this paper the discovery of new phosphodiesterase 4 (PDE4) inhibitors for treatment of psoriasis. We designed and synthesized 45 new compounds, among which 14h exhibited IC50 of 0.57 nM for PDE4D and >4100-fold selectivity over other PDE families. Compound 14h inhibited release of inflammatory cytokines of TNF-α (IC50 = 34.2 μM) and IL-6 (IC50 = 40.9 μM) in Raw264.7 cells and reduced the expression of IL-1β and IL-17A in the skin of psoriasis mice. In addition, 14h alleviated IMQ-induced psoriasis in the mouse model and reduced the erythema level, scales, and thickness of the back skin of the mice. In short, our results suggested that PDE4 inhibitor 14h is a strong candidate for the topical treatment of psoriasis.

Enhanced Outcomes in Type 2 Diabetes Patients with Acute Kidney Disease Through Thiazolidinedione.

Patients with diabetes are prone to acute kidney injury with the potential transition to chronic kidney disease. Few studies have investigated the role of thiazolidinedione (TZD) in these patients under acute kidney disease (AKD) phase. We sought to examine whether using TZD during AKD could reduce the risk of future major adverse outcomes. We employed the TriNetX platform before September 30, 2022, for TZD administration to patients with type 2 diabetes mellitus (T2DM) within 90 days of an AKD diagnosis. Clinical endpoints include the risk of all-cause mortality, major adverse cardiovascular events (MACE), and major adverse kidney events (MAKE). Hazard ratios (HRs) and 95% confidence intervals were calculated with 1:1 ratio propensity score matching (PSM). Among the cohort of 263,101 patients with AKD and T2DM, we identified 2,723 individuals (1.03%) who were TZD users during the AKD period. After PSM, the final cohort of TZD users included 2,555 individuals, with 53.82% being male and a mean age of 64.0 ± 13.5 years. Over a median follow-up period of 1.5 years, the TZD group exhibited a lower risk across various outcomes, with hazard ratios (HR) of 0.68 (95% CI, 0.57-0.81) for all-cause mortality, 0.68 (95% CI, 0.58-0.80) for MACE, and 0.75 (95% CI, 0.66-0.86) for MAKE. TZD demonstrated a notable reduction in mortality, cardiovascular events, and kidney-related adverse events among T2DM patients with AKD. These findings suggest a potential benefit of TZD usage for managing cardiovascular events in T2DM patients with AKD.

Association between body roundness index and psoriasis among US adults: a nationwide population-based study.

In clinical practice, psoriasis is a prevalent chronic inflammatory cutaneous disease featured with the development of red plaque with silvery scales, which considerably affects cutaneous health and quality of life of those afflicted. This research aimed to examine the association between the body roundness index (BRI) and psoriasis, using data sourced from the National Health and Nutrition Examination Survey (NHANES). Our study used a cross-sectional design, including 8,479 adults, of whom 234 were diagnosed with psoriasis. Multivariable logistic regression was used to analyze the relationship between BRI and psoriasis, with stepwise adjustments for covariables. Results from multivariable logistic regression analyses indicated a significant positive relationship between BRI and the risk of developing psoriasis; specifically, after comprehensive adjustment for covariables, per 1 unit increase in BRI was linked to an 11% rise in psoriasis risk (OR = 1.11, 95% CI = 1.05-1.17). Furthermore, psoriasis patients exhibited higher average BRI compared to non-psoriasis patients and a greater prevalence of comorbidities such as hypertension and smoking. These findings suggest that higher BRI is positively correlated with the risk of psoriasis in the adult population in the US. BRI could potentially act as a practical anthropometric index for more accurately predicting the risk of developing psoriasis.

Depletion by Hemodialysis of the Antioxidant Ergothioneine

Background: Hemodialysis may excessively remove valuable solutes. Untargeted metabolomics data from a prior study suggested that ergothioneine was depleted in the plasma of hemodialysis subjects. Ergothioneine is a dietary-derived solute with antioxidant properties. The presence of a highly specific ergothioneine uptake transporter suggests that it is valuable. Ergothioneine levels are high in tissues susceptible to oxidative stress, particularly erythrocytes. We compared erythrocyte and plasma ergothioneine levels in subjects receiving hemodialysis to those in subjects with advanced chronic kidney disease (CKD) and subjects without known kidney disease (controls). We further examined the extent to which indiscriminate removal by hemodialysis could contribute to ergothioneine depletion. Methods: Liquid chromatography tandem mass spectrometry with stable isotope dilution was used to measure the erythrocyte and plasma levels of ergothioneine in 12 control, 12 CKD, and 11 hemodialysis subjects. We also measured the urinary excretion of ergothioneine in control and CKD subjects, and the dialytic removal of ergothioneine in hemodialysis subjects. Results: Erythrocyte ergothioneine levels were markedly reduced in CKD and hemodialysis subjects. Erythrocyte levels in CKD subjects were on average 24% of the levels in control subjects and were even lower in hemodialysis subjects, averaging 8% of control subjects. Plasma ergothioneine levels were also reduced in CKD and hemodialysis subjects but to a lesser extent than the erythrocyte levels. Kidney tubular reabsorption of ergothioneine was avid. In contrast, hemodialysis cleared ergothioneine at a rate of 146±36 ml/min so that removal of ergothioneine by hemodialysis greatly exceeded the amount excreted in the urine in both CKD and control subjects. Conclusions: Ergothioneine, a potentially valuable antioxidant, is severely depleted in people maintained on hemodialysis. Future studies are required to assess the consequences of ergothioneine depletion.

Vitamin D Status in Supplemented Hemodialysis Patients

Introduction: Chronic kidney disease (CKD) causes decreased activity of the enzyme 1-alpha-hydroxylase and calcitriol deficiency with mineral and bone metabolism disorders or secondary hyperparathyroidism. Anticipation of the occurrence of these complications implies the systematic supplementation of all hemodialysis patients, with monitoring of biological parameters. It is in this context that this study was carried out, the general objective of which was to establish the profile of vitamin D concentration in hemodialysis and Ivorian public sector supplemented patients in Abidjan. Patients and Methods: In a cross-sectional study conducted from September to December 2022, we included 89 patients with end-stage CKD treated with hemodialysis at the CNPTIR in Cocody. The collection of epidemio-clinical data was done on the basis of a questionnaire on the one hand and the patients' medical records on the other. The vitamin D concentration was determined by the ELFA immunoassay method on mini Vidas (BIOMERIEUX). Results: The mean age of the patients was 45 ± 13 and 65.17% of them were men. 55.06% of the patients had been treated with dialysis for at least 5 years. 48.31% of the patients had regular supplementation treatment. Of the two types of vitamin D supplementation, 94.38% of the study population was supplemented with cholecalciferol compared to 18% for alfacalcidol with 12% of patients included, using both types. From a biological point of view, it appears that the average concentration of vitamin D in the patients was 26.9 ng/mL, and only 16% have a concentration of less than 20 mg/mL, corresponding to an deficiency vitamin D status. Conclusion: At the end of this cross-sectional study, it emerged that the average in adult hemodialysis subjects followed at the CNPTIR in Cocody had an insufficient vitamin D status. And 37% of the study population with normal vitamin D status. However, these results could be improved by better accessibility to the products, and regular compliance with supplementation.

An Updated Review For Hyperuricemia and Gout Management; Special Focus on the Available Drug Delivery Systems and Clinical Trials.

Hyperuricemia belongs to metabolic syndromes where increased uric acid levels are identified in the blood serum. Such a syndrome could be responsible for kidney stone formation, gout, hypertension, and chronic kidney diseases. It has been reported that cardiovascular risks have been linked with hyperuricemia. Gout is of the most frequent manifestations due to hyperuricemia; its management involves various pharmacological available options and dietary changes. Throughout the literature, various dosage forms are studied as alternative options to the present drug delivery systems. To update and summarize the current information for gout and hyperuricemia management. Authors have performed a thorough literature research from 2010-2023 using keywords such as hyperuricemia, gout, diagnosis, guidelines, drug delivery and clinical trials. The databases used were PubMed, ScienceDirect. According to our inclusion criteria, all studies which include the previous terms, as well as drugs or other molecules that can be applied for gout and/or hyperuricemia management, were added. In this article, authors have summarized the pathogenesis, diagnosis and updated guidelines for gout and hyperuricemia management. Moreover, the authors have reviewed and discussed current drug delivery systems found in the literature, including drugs targeting the above disorders. Finally, the available clinical trials assessing the efficacy of newer drugs or combinations of the past ones, are being discussed. The available drugs and dosage forms are limited, and therefore, scientific society should focus on the development of more efficient drug delivery systems for hyperuricemia and gout management.

Protective effects of YCHD on the autoimmune hepatitis mice model induced by Ad-CYP2D6 through modulating the Th1/Treg ratio and intestinal flora

BackgroundAutoimmune hepatitis (AIH) is a chronic liver inflammatory disease mediated by autoimmune reactions, the pathogenesis of AIH is probably related to the imbalance of intestinal flora. Yinchenhao decoction (YCHD) has been used to relieve AIH. However, the mechanisms underpinning YCHD’s hepatoprotective effects with the gut microbito have not been fully revealed.ObjectiveTo explore the potential mechanism of YCHD in treating AIH based on changes in the intestinal flora and Th1/Treg ratio in the spleen and hepatic hilar lymph nodes.MethodsThe AIH mice model induced by the adenovirus vectors that overexpress human cytochrome P450 family 2 subfamily D member 6 (Ad-CYP2D6) was established (untreated group). One week after the Ad-CYP2D6 injection, the AIH model mice were treated by administering YCHD by gavage for 14 days (YCHD-treated group). The therapeutic efficacy of YCHD on AIH was evaluated by detecting the histopathological changes of the liver, serum transaminases (ALT and AST), inflammatory factors (TNF-α,IL-17 and IFN-γ), and autoantibodies (including LKM-1 and LC-1). The ratio of Th1 to Treg within the spleen and hepatic hilar lymph nodes of the mice was detected by flow cytometry. The changes in the species and abundance of intestinal flora and intestinal flora metabolites were analyzed via 16S rRNA gene sequencing and gas chromatography-mass spectrometry (GC/MS) to reveal the protective mechanism of YCHD on liver injury.ResultYCHD decreased the transaminase activity (AST and ALT), the content of autoantibodies (LC-1 and LKM-1), and the serum TNF-α, IL-12, and IL-17 levels in AIH mice. The degree of inflammatory infiltration in the YCHD-treated group was significantly less than that in the untreated group. YCHD can effectively reverse the abundance and diversity of intestinal flora in AIH mice and affect the release of short-chain fatty acids (SCFAs), especially butyric acid. Moreover, the flow cytometry results showed that YCHD could also decline the ratio of Th1/Treg, which probably be induced by SCFAs via the G protein-coupled receptor (GPR).ConclusionYCHD may affect the release of SCFAs by regulating the intestinal microbiota, thereby affecting the differentiation of Th1 and Treg, and achieving the effect of alleviating liver damage.

The Roles of Vitamin D Levels, Gla-Rich Protein (GRP) and Matrix Gla Protein (MGP), and Inflammatory Markers in Predicting Mortality in Intensive Care Patients: A New Biomarker Link?

Objectives: Identifying reliable biomarkers to predict mortality in critically ill patients is crucial for optimizing management in intensive care units (ICUs). Inflammatory and metabolic markers are increasingly recognized for their prognostic value. This study aims to evaluate the association of various inflammatory and metabolic markers with ICU mortality. Methods: This prospective observational study was conducted from January 2023 to January 2024 in the City Hospital’s ICU. A total of 160 critically ill patients were enrolled. Laboratory parameters, including white blood cell (WBC) count, red cell distribution width (RDW), platelet count, neutrophil count, mean platelet volume (MPV), monocyte count, lymphocyte count, procalcitonin (PCT), C-reactive protein (CRP), calcium (Ca++), and vitamin D levels, were analyzed. Additionally, ratios such as the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), systemic inflammatory index (SII), and pan-immune-inflammation value (PIV) were calculated. Plasma levels of Gla-rich protein (GRP) and dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP) were measured using ELISA. Results: The mean age of the patients included in the study was 60.5 ± 15.8 years. Cardiovascular disease was present in 72 patients (45%), respiratory system disease in 58 (36%), and chronic kidney disease (CKD) in 38 (24%). Additionally, 61 patients (38%) had diabetes, and 68 (42%) had hypertension. Inflammatory markers, including PLR, NLR, and PIV, were all significantly higher in non-survivors, while calcium and vitamin D levels were lower (p &lt; 0.05). Higher WBC, RDW, neutrophil count, PLR, NLR, PIV, CRP, procalcitonin, GRP, and dp-ucMGP levels were positively correlated with longer hospital stays and increased mortality. In contrast, platelet and lymphocyte counts were negatively correlated with both outcomes (p &lt; 0.05). Vitamin D levels showed an inverse relationship with both hospital stay and mortality, indicating that lower levels were associated with worse outcomes (p &lt; 0.05). In multiple logistic regression analysis, elevated WBC count (OR = 1.20, p = 0.02), RDW (OR = 1.35, p = 0.01), neutrophil count (OR = 1.25, p = 0.01), MPV (OR = 1.20, p = 0.02), PLR (OR = 1.30, p = 0.01), NLR (OR = 1.40, p = 0.001), PIV (OR = 1.50, p = 0.001), CRP (OR = 1.32, p = 0.01), procalcitonin (OR = 1.45, p = 0.001), GRP (OR = 1.40, p = 0.001), and dp-ucMGP (OR = 1.30, p = 0.001) levels were significantly associated with increased mortality. Conclusions: Inflammatory and metabolic markers, particularly NLR, PLR, PIV, GRP, and dp-ucMGP, are strong predictors of mortality in ICU patients. These markers provide valuable insights for risk stratification and early identification of high-risk patients, potentially guiding more targeted interventions to improve outcomes.

Features оf Changes in the Level of Neurotransmitters and Markers of Neurodegeneration in the Brain of Rats with Experimental Parkinson’s Disease Against the Background of Course Therapy with Steroid Glycoalkaloids

Parkinson’s disease is a chronic neurodegenerative disease, one of the pathobiochemical manifestations of which is an imbalance of neurotransmitters in the brain. The aim of this work is to study the effect of glycoalkaloids on changes in the level of neurotransmitters and markers of brain neurodegeneration in rats with experimental Parkinson’s disease. Parkinson’s disease was modeled in animals by intracerebral administration of rotenone. The studied glycoalkaloids were administered orally at a dose of 0.06 mg / kg, a course of 28 days after pathology modeling. The study found that the use of the analyzed glycoalkaloids did not affect the concentration of dopamine and serotonin, and also significantly (p 0.05) reduced the level of ACh by 35.9% and increased the level of GABA by 55.1%, reduced the concentration of S100β protein by 68.6% and increased the level of BDNF by 52.4%.