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BMC Nephrology May 2024Polypharmacy would increase the risk of adverse drug events and the burden of renal drug excretion among older people. Nevertheless, the association between the number...
BACKGROUND
Polypharmacy would increase the risk of adverse drug events and the burden of renal drug excretion among older people. Nevertheless, the association between the number of medication and the risk of chronic kidney disease (CKD) remains controversial. Therefore, this study aims to investigate the association between the number of medication and the incidence of CKD in older people.
METHODS
This study investigates the association between the number of medications and CKD in 2672 elderly people (≥ 65 years older) of the community health service center in southern China between 2019 and 2022. Logistic regression analysis was used to evaluate the relationship between polypharmacy and CKD.
RESULTS
At baseline, the average age of the study subjects was 71.86 ± 4.60, 61.2% were females, and 53 (2.0%) suffer from polypharmacy. During an average follow-up of 3 years, new-onset CKD developed in 413 (15.5%) participants. Logistic regression analysis revealed that taking a higher number of medications was associated with increase of CKD. Compared with people who didn't take medication, a higher risk of CKD was observed in the older people who taken more than five medications (OR 3.731, 95% CI 1.988, 7.003), followed by those who take four (OR 1.621, 95% CI 1.041, 2.525), three (OR 1.696, 95% CI 1.178, 2.441), two drugs (OR 1.585, 95% CI 1.167, 2.153), or one drug (OR 1.503, 95% CI 1.097, 2.053). Furthermore, age, systolic blood pressure (SBP), white blood cell (WBC), blood urea nitrogen (BUN) and triglyceride (TG) were also independent risk factors CKD (P < 0.05).
CONCLUSION
The number of medications was associated with CKD in older people. As the number of medications taken increased, the risk of CKD was increased.
Topics: Humans; Female; Male; Aged; Polypharmacy; Renal Insufficiency, Chronic; China; Longitudinal Studies; Independent Living; Incidence; Aged, 80 and over; Risk Factors
PubMed: 38760750
DOI: 10.1186/s12882-024-03606-x -
BMC Nephrology May 2024Recent studies have suggested that the N-terminal fragment of B-type natriuretic peptide (NT-proBNP) level serve as a significant risk factor for mortality in patients...
BACKGROUND
Recent studies have suggested that the N-terminal fragment of B-type natriuretic peptide (NT-proBNP) level serve as a significant risk factor for mortality in patients with end-stage renal disease. However, the relationship between NT-proBNP levels and technique failure in peritoneal dialysis-associated peritonitis (PDAP) remains unclear. This study investigated the relationship between NT-proBNP levels at the onset of PDAP and the risk of technique failure in patients with PDAP.
METHODS
A retrospective analysis was conducted on patients with PDAP from December 1, 2009, to December 31, 2021, at our peritoneal dialysis center. We recorded all demographic and baseline clinical data at the time of admission for each PDAP episode. Logistic and Cox regression analyses were performed to assess the association between NT-proBNP levels and technique failure.
RESULTS
Of 485 PDAP episodes included in this study, 130 episodes of technique failure were observed. Multivariate logistic analysis revealed that hospital stay, Na and NT-proBNP levels, and peritoneal dialysate white blood cell counts on days 3 and 5 were independently associated with technique failure. The receiver operating characteristic curve demonstrated that the NT-proBNP level was a better indicator than the other four variables in indicating technique failure. In the multivariate Cox regression analysis, after adjusting for confounding factors, higher NT-proBNP levels (HR of 3.020, 95% CI 1.771, 5.150, P < 0.001) were associated with PDAP technique failure.
CONCLUSIONS
This retrospective study identified the serum NT-proBNP level at the onset of PDAP as an independent risk factor for technique failure in these patients.
Topics: Humans; Natriuretic Peptide, Brain; Male; Female; Peritoneal Dialysis; Peptide Fragments; Middle Aged; Peritonitis; Retrospective Studies; Risk Factors; Kidney Failure, Chronic; Treatment Failure; Aged; Adult; Biomarkers
PubMed: 38760707
DOI: 10.1186/s12882-024-03603-0 -
Stem Cell Reports May 2024Lung alveolar structure and function are maintained by subsets of alveolar type II stem cells (AT2s), but there is a need for characterization of these subsets and their...
Lung alveolar structure and function are maintained by subsets of alveolar type II stem cells (AT2s), but there is a need for characterization of these subsets and their associated niches. Here, we report a CD44 subpopulation of AT2s characterized by increased expression of genes that regulate immune signaling even during steady-state homeostasis. Disruption of one of these immune regulatory transcription factor STAT1 impaired the stem cell function of AT2s. CD44 cells were preferentially located near macro- blood vessels and a supportive niche constituted by LYVE1 endothelial cells, adventitial fibroblasts, and accumulated hyaluronan. In this microenvironment, CD44 AT2 cells were more responsive to transformation by KRAS than general AT2 cells. Moreover, after bacterial lung injury, there was a significant increase of CD44 AT2s and niche components distributed throughout the lung parenchyma. Taken together, CD44 AT2 cells and their perivascular niche regulate tissue homeostasis and tumor formation.
PubMed: 38759645
DOI: 10.1016/j.stemcr.2024.04.009 -
Medicine May 2024Early identification of the sources of infection in emergency department (ED) patients of sepsis remains challenging. Computed tomography (CT) has the potential to... (Observational Study)
Observational Study
Early identification of the sources of infection in emergency department (ED) patients of sepsis remains challenging. Computed tomography (CT) has the potential to identify sources of infection. This retrospective study aimed to investigate the role of CT in identifying sources of infection in patients with sepsis without obvious infection foci in the ED. A retrospective chart review was conducted on patients with fever and sepsis visiting the ED of Linkou Chang Gung Memorial Hospital between July 1, 2020 and June 30, 2021. Data on patient demographics, vital signs, clinical symptoms, underlying medical conditions, laboratory results, administered interventions, length of hospital stay, and mortality outcomes were collected and analyzed. Of 218 patients included in the study, 139 (63.8%) had positive CT findings. The most common sources of infection detected by CT included liver abscesses, acute pyelonephritis, and cholangitis. Laboratory results showed that patients with positive CT findings had higher white blood cell and absolute neutrophil counts and lower hemoglobin levels. Positive blood culture results were more common in patients with positive CT findings. Additionally, the length of hospital stay was longer in the group with positive CT findings. Multivariate logistic regression analysis revealed that hemoglobin levels and positive blood culture results independently predicted positive CT findings in patients with fever or sepsis without an obvious source of infection. In patients with sepsis with an undetermined infection focus, those presenting with leukocytosis, anemia, and elevated absolute neutrophil counts tended to have positive findings on abdominal CT scans. These patients had high rates of bacteremia and longer lengths of stay. Abdominal CT remains a valuable diagnostic tool for identifying infection sources in carefully selected patients with sepsis of undetermined infection origins.
Topics: Humans; Male; Retrospective Studies; Female; Tomography, X-Ray Computed; Sepsis; Middle Aged; Aged; Length of Stay; Emergency Service, Hospital; Liver Abscess; Adult; Pyelonephritis; Cholangitis; Aged, 80 and over; Fever of Unknown Origin
PubMed: 38758906
DOI: 10.1097/MD.0000000000038114 -
Medicine May 2024Human immunodeficiency virus (HIV) infection continues to pose significant global health challenges, necessitating advancements in diagnostic and prognostic approaches... (Review)
Review
Human immunodeficiency virus (HIV) infection continues to pose significant global health challenges, necessitating advancements in diagnostic and prognostic approaches to optimize disease management. While primarily recognized for their roles in allergic responses, mast cells have emerged as potential markers with diagnostic and prognostic significance in the context of HIV/AIDS. This paper aims to synthesize current insights and delineate future directions regarding the utility of mast cell markers in diagnosing HIV infection, predicting disease progression, and guiding therapeutic strategies. Mast cells, equipped with distinct markers such as tryptase, chymase, carboxypeptidase A3, and c-kit/CD117 receptors, exhibit tissue-specific expression patterns that offer potential as diagnostic indicators for HIV infection. Understanding the dynamics of these markers in different tissues and body fluids holds promise for accurate HIV diagnosis, disease staging, and monitoring treatment responses. Moreover, the prognostic significance of mast cell markers in HIV/AIDS lies in their potential to predict disease progression, immune dysregulation, and clinical outcomes. The integration of mast cell markers into clinical applications offers promising avenues for refining diagnostic assays, patient monitoring protocols, and therapeutic strategies in HIV/AIDS. Future research directions involve the development of novel diagnostic tools and targeted therapies based on mast cell-specific markers, potentially revolutionizing clinical practice and enhancing patient care in the management of HIV/AIDS. Continued investigations into mast cell markers' diagnostic and prognostic implications hold immense potential to advance our understanding and improve outcomes in HIV/AIDS management.
Topics: Humans; Mast Cells; Biomarkers; Prognosis; HIV Infections; Tryptases; Disease Progression; Carboxypeptidases A; Chymases; Proto-Oncogene Proteins c-kit; Acquired Immunodeficiency Syndrome
PubMed: 38758896
DOI: 10.1097/MD.0000000000038117 -
Medicine May 2024Studies have suggested that Vitamin D deficiency is associated with the occurrence of both type 1 and type 2 diabetes, and that vitamin D-binding proteins (VDBP) are...
Studies have suggested that Vitamin D deficiency is associated with the occurrence of both type 1 and type 2 diabetes, and that vitamin D-binding proteins (VDBP) are necessary for metabolic stress in pancreatic α-cells. However, the causal relationship between serum 25-hydroxyvitamin D [25(OH)D] levels, VDBP, and the risk of diabetes mellitus (DM) remains unclear. Mendelian randomization (MR) was used to investigate the causal relationship between 25(OH)D, VDBP, and DM. Relevant recent data were downloaded from the NHGRI-EBI Catalog of published genome-wide association studies (GWAS) and filtered for single nucleotide polymorphisms (SNPs). We used multiple MR methods, including inverse variance weighting (IVW), and performed sensitivity analyses to detect whether pleiotropy or heterogeneity biased the results. There was a causal relationship between genetically predicted VDBP levels and serum 25(OH)D levels, and serum 25(OH)D levels increased with increasing VDBP levels (IVW: β = 0.111, OR = 1.117, 95% CI:1.076-1.162, P = 1.41 × 10-8). There was no causal relationship between the genetically predicted VDBP levels, serum 25(OH)D levels, and DM (VDBP: IVW β:0.001, OR:1.001, 95% CI:0.998-1.003, P > .05; 25(OH)D: IVW β: -0.009, OR:0.991, 95% CI:0.982-1.001, P = .068). Sensitivity analysis indicated that horizontal pleiotropy was unlikely to bias causality in this study. MR analysis results demonstrated a positive causal relationship between VDBP levels and serum 25(OH)D levels in the European population. The 25(OH)D and VDBP levels were not causally related to an increased risk of diabetes.
Topics: Humans; Mendelian Randomization Analysis; Vitamin D-Binding Protein; Vitamin D; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Diabetes Mellitus, Type 2; Vitamin D Deficiency
PubMed: 38758851
DOI: 10.1097/MD.0000000000038219 -
PloS One 2024Insulin resistance is a common pathophysiology in patients with type 2 diabetes mellitus, cardiovascular disease, and non-alcoholic fatty liver disease. Thus, screening...
Insulin resistance is a common pathophysiology in patients with type 2 diabetes mellitus, cardiovascular disease, and non-alcoholic fatty liver disease. Thus, screening for the risk of insulin resistance is important to prevent disease progression. We evaluated the alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio to predict insulin resistance in the general population, regardless of comorbidities. Datasets from the 2015, 2019, and 2020 Korea National Health and Nutrition Examination Surveys were used, and the following four indices were implemented to indicate insulin resistance: fasting serum glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), and β-cell function. We analyzed the degree of association between the liver enzyme profile and insulin resistance indices using Pearson's correlation coefficient and determined the associations using linear or logistic regression analysis. Accordingly, ALT levels in both sexes were positively and consistently correlated with the four aforementioned insulin resistance indices in stratification analyses based on diabetes, dyslipidemia, alcohol consumption, and obesity status. In multivariate linear regression, when comparing with ALT levels, the ALT/AST ratio exhibited superior predictive performance for fasting serum glucose and HOMA-β in Korean men and improved outcomes for all insulin resistance indices in Korean women. In this analysis that included a large community-based population, the ALT/AST ratio was a more useful predictive marker than the HOMA-IR. Regarding the predicted presence or absence of insulin resistance, the ALT/AST ratio could better predict HOMA-IR than the ALT level alone in Koreans. A simple, precise marker that represents the ALT/AST ratio could be a practical method to screen for insulin resistance in the general population, regardless of diabetes mellitus, alcohol intake, and sex.
Topics: Humans; Insulin Resistance; Male; Female; Republic of Korea; Alanine Transaminase; Middle Aged; Cross-Sectional Studies; Aspartate Aminotransferases; Adult; Blood Glucose; Diabetes Mellitus, Type 2; Nutrition Surveys; Cohort Studies; Aged
PubMed: 38758828
DOI: 10.1371/journal.pone.0303333 -
Science Advances May 2024Monocytes are immune regulators implicated in the pathogenesis of type 1 diabetes (T1D), an autoimmune disease that targets insulin-producing pancreatic β cells. We...
Monocytes are immune regulators implicated in the pathogenesis of type 1 diabetes (T1D), an autoimmune disease that targets insulin-producing pancreatic β cells. We determined that monocytes of recent onset (RO) T1D patients and their healthy siblings express proinflammatory/cytolytic transcriptomes and hypersecrete cytokines in response to lipopolysaccharide exposure compared to unrelated healthy controls (uHCs). Flow cytometry measured elevated circulating abundances of intermediate monocytes and >2-fold more CD14CD16HLADRKLRD1PRF1 NK-like monocytes among patients with ROT1D compared to uHC. The intermediate to nonclassical monocyte ratio among ROT1D patients correlated with the decline in functional β cell mass during the first 24 months after onset. Among sibling nonprogressors, temporal decreases were measured in the intermediate to nonclassical monocyte ratio and NK-like monocyte abundances; these changes coincided with increases in activated regulatory T cells. In contrast, these monocyte populations exhibited stability among T1D progressors. This study associates heightened monocyte proinflammatory/cytolytic activity with T1D susceptibility and progression and offers insight to the age-dependent decline in T1D susceptibility.
Topics: Humans; Diabetes Mellitus, Type 1; Monocytes; Male; Female; Disease Progression; Adolescent; Child; Adult; Cytokines; Insulin-Secreting Cells; Killer Cells, Natural; Young Adult; Case-Control Studies
PubMed: 38758799
DOI: 10.1126/sciadv.adn2136 -
Science Advances May 2024Trauma rapidly mobilizes the immune response of surrounding tissues and activates regeneration program. Manipulating immune response to promote tissue regeneration shows...
Trauma rapidly mobilizes the immune response of surrounding tissues and activates regeneration program. Manipulating immune response to promote tissue regeneration shows a broad application prospect. However, the understanding of bone healing dynamics at cellular level remains limited. Here, we characterize the landscape of immune cells after alveolar bone injury and reveal a pivotal role of infiltrating natural killer T (NKT) cells. We observe a rapid increase in NKT cells after injury, which inhibit osteogenic differentiation of mesenchymal stem cells (MSCs) and impair alveolar bone healing. is up-regulated in NKT cells after injury. Systemic administration of CXCL2-neutralizing antibody or genetic deletion of improves the bone healing process. In addition, we fabricate a gelatin-based porous hydrogel to deliver NK1.1 depletion antibody, which successfully promotes alveolar bone healing. In summary, our study highlights the importance of NKT cells in the early stage of bone healing and provides a potential therapeutic strategy for accelerating bone regeneration.
Topics: Bone Regeneration; Animals; Natural Killer T-Cells; Mice; Osteogenesis; Chemokine CXCL2; Mesenchymal Stem Cells; Cell Differentiation; Mice, Inbred C57BL
PubMed: 38758783
DOI: 10.1126/sciadv.adl6343 -
Science Advances May 2024Acetyl-CoA synthetase short-chain family member 1 (ACSS1) uses acetate to generate mitochondrial acetyl-CoA and is regulated by deacetylation by sirtuin 3. We generated...
Acetyl-CoA synthetase short-chain family member 1 (ACSS1) uses acetate to generate mitochondrial acetyl-CoA and is regulated by deacetylation by sirtuin 3. We generated an ACSS1-acetylation (Ac) mimic mouse, where lysine-635 was mutated to glutamine (K635Q). Male mice were smaller with higher metabolic rate and blood acetate and decreased liver/serum ATP and lactate levels. After a 48-hour fast, mice presented hypothermia and liver aberrations, including enlargement, discoloration, lipid droplet accumulation, and microsteatosis, consistent with nonalcoholic fatty liver disease (NAFLD). RNA sequencing analysis suggested dysregulation of fatty acid metabolism, cellular senescence, and hepatic steatosis networks, consistent with NAFLD. Fasted mouse livers showed increased fatty acid synthase (FASN) and stearoyl-CoA desaturase 1 (SCD1), both associated with NAFLD, and increased carbohydrate response element-binding protein binding to and enhancer regions. Last, liver lipidomics showed elevated ceramide, lysophosphatidylethanolamine, and lysophosphatidylcholine, all associated with NAFLD. Thus, we propose that ACSS1-K635-Ac dysregulation leads to aberrant lipid metabolism, cellular senescence, and NAFLD.
Topics: Animals; Non-alcoholic Fatty Liver Disease; Mice; Cellular Senescence; Acetylation; Mitochondria; Stearoyl-CoA Desaturase; Male; Acetate-CoA Ligase; Gene Knock-In Techniques; Liver; Lipid Metabolism; Sirtuin 3; Disease Models, Animal; Coenzyme A Ligases; Fatty Acid Synthase, Type I
PubMed: 38758779
DOI: 10.1126/sciadv.adj5942