Journal of Investigative Medicine最新文献

{"title":"Early onset colorectal cancer, not just the age: Data from a large health organization.","authors":"Naim Abu-Freha, Amani Beshara, Jordan Winberg, Sarah Weissmann, Bracha Cohen, Yael Kopelman, Zlata Lerner, Michal Gordon","doi":"10.1177/10815589241296022","DOIUrl":"10.1177/10815589241296022","url":null,"abstract":"<p><p>Early onset colorectal cancer (EO-CRC) is increasing. We investigated the risk factors for ER-CRC compared to late onset colorectal cancer (LO-CRC). CRC patients between the years 1999 and 2021 were retrospectively evaluated. Data regarding demographics, comorbidities, malignancies, and mortality were collected. Data were retrieved using the MdClone platform from a large Health Maintenance Organization. The cohort was subdivided into EO-CRC (age ≤ 50 years) and LO-CRC (age ≥ 51 years) groups. 61,679 patients diagnosed with CRC were included in our analysis, 30,456 (49.4%) males, and 4891 (7.9%) Arabs, with an average age at diagnosis of 70.1 ± 13.1 years. 5561 (9%) patients were included in the EO-CRC group. Over the last decades, higher rates of EO-CRC were diagnosed compared to the previous decade, 9.8% vs 8.3%, p < 0.001. A higher percentage of EO-CRC patients were females (52.8% vs 50.4%), had a family history of CRC (9.9% vs 5.5%), were Arabs (18.7% vs 6.9%), and were smokers (32.7% vs 30.2%) compared to LO-CRC patients. Significantly lower rates of comorbidities such as ischemic heart disease, diabetes mellitus, hypertension, obesity, and iron deficiency anemia were found among EO-CRC patients, with a lower all-cause mortality (27.7% vs 63.1%, p < 0.001). 348 (6.3%) of the EO-CRC patients had another Lynch-related cancer until age 50 years compared to 45 (0.1%) at the LO-CRC. Young individuals with increased risk for CRC need special consideration and should be referred early for screening and endoscopic investigation, particularly those with a family history of CRC, smokers, and those of Arab ethnicity.</p>","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"261-267"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma from type 1 diabetes patients promotes pro-atherogenic cholesterol transport in human macrophages.","authors":"Siham Accacha, Iryna Voloshyna, Lora J Kasselman, Jorge Mejia-Corletto, Ankita Srivastava, Heather A Renna, Joshua De Leon, Robert L Levine, Allison B Reiss","doi":"10.1177/10815589241296025","DOIUrl":"10.1177/10815589241296025","url":null,"abstract":"<p><p>Hyperglycemia, one of the major risk factors for atherosclerosis, leads to the accumulation of advanced glycation end products (AGEs), contributing to cardiovascular complications. Such accumulation may accelerate the progression of vascular disease in patients with diabetes. Reverse cholesterol transport (RCT) protein, ATP-binding membrane cassette transporters A1 and G1 (ABCA1 and ABCG1) and cholesterol 27-hydroxylase facilitate cholesterol removal from macrophages. AGE inhibits RCT by reducing the expression of ABCA1 and ABCG1. This study aimed to evaluate whether plasma from poorly controlled adolescents with type 1 diabetes (T1D) disrupts cholesterol homeostasis in human monocytes/macrophages. Twenty healthy controls (HCs) and 20 patients with type 1 diabetes mellitus (T1DM), 10-19 years old, were enrolled. Naïve THP-1 macrophages were exposed to plasma from each HC and patient with T1D. Following incubation, mRNA for cholesterol efflux (ABCA1, ABCG1, and 27-hydroxylase) and cholesterol uptake (CD36, ScR-A1, lectin oxidized low-density lipoprotein (LOX)-1, and CXCL16) were isolated. Foam cell formation was quantified to confirm the pro-atherogenic effects of T1D plasma on macrophages. Results showed that T1D plasma had an elevated level of N-(carboxymethyl)-lysine-modified proteins and upregulated CXCL16 and, to a lesser degree, ScR-A1. This change in gene expression in the presence of T1D plasma is associated with increased lipid accumulation and foam cell formation by THP-1 macrophages. In our study, these cells' uptake of an AGE product occurred mainly through the SR-A1 and CXCL16 receptors, leading to increased intracellular oxidized low-density lipoprotein. We conclude that AGEs may contribute to accelerated atherosclerosis in diabetes through effects on both forward and reverse cholesterol movement.</p>","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"183-192"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of exposure to nonpersistent endocrine disruptors with sex hormones and metabolic health in US females.","authors":"Pallavi Dubey, Sireesha Y Reddy, Chinthana Thangavel, Ghislain Hardy, Alok Kumar Dwivedi","doi":"10.1177/10815589241297724","DOIUrl":"10.1177/10815589241297724","url":null,"abstract":"<p><p>Endocrine disruptive chemicals (EDCs) are considered as the potential attributes for the increasing trend in obesity and metabolic syndrome (MS) through disruption of sex hormones, particularly in women. We evaluated the association of understudied EDC compounds with total testosterone (TT), sex hormone-binding globulin (SHBG), obesity, and MS. A population-based cross-sectional study was conducted using the National Health and Nutrition Examination Survey datasets collected during the years 2013-2016. Women of age ≥15 years with urinary measurements of nonpersistent EDCs, including bisphenol, triclosan, triclocarban, dichlorophenol, and paraben compounds were included in this study. Data were analyzed using the modified Poisson models to estimate the adjusted relative risk (RR) and 95% confidence interval (CI). The associations were also validated by considering TT and SHBG concentrations as the outcomes. The study included 1974 women with 11% high TT, 10.5% low SHBG, 40% obesity, and 46.2% MS. A medium to high exposure to bisphenol-A (RR = 1.64; 95% CI: 1.14, 2.35, p = 0.009), bisphenol-F (RR = 1.83; 95% CI: 1.35, 2.49, p < 0.001), bisphenol-S (RR = 1.83; 95% CI: 1.35, 2.49, p = 0.041) and 2, 4- dichlorophenol (RR = 1.61; 95% CI: 1.06, 2.45, p = 0.026) were associated with low SHBG but not with high TT. In addition, high exposure to triclosan was also inversely associated with SHBG concentrations (regression coefficient = -0.09; 95% CI: -0.15, -0.02, p = 0.013). However, these EDCs were found to be associated with SHBG, obesity, and MS according to menopausal status. High exposure to certain nonpersistent EDCs was associated with low SHBG, obesity, and MS according to menopausal status.</p>","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"193-205"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined treatment with ruxolitinib and MK-2206 inhibits ERα activity by inhibiting MAPK signaling in BT474 breast cancer cells.","authors":"Esin Guvenir Celik, Onur Eroglu","doi":"10.1177/10815589241298184","DOIUrl":"10.1177/10815589241298184","url":null,"abstract":"<p><p>Triple-positive breast cancer (TPBC) is a type of breast cancer that overexpresses estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). Dysregulation of ER signaling has been implicated in the pathogenesis of breast cancer. ERα activation triggers the production of second messengers, including cAMP, leading to the activation of signals such as PI3K/AKT or Ras/MAPK. Ruxolitinib is a specific inhibitor of JAK1/JAK2. MK-2206 is an allosteric inhibitor of the Akt. The limitations of the use of ruxolitinib and MK-2206 as single agents necessitate the development of combination therapies with other drugs. This study is the first to investigate the effects of combining ruxolitinib with MK-2206 on MAPK and PI3K/AKT signaling in BT474 breast cancer cells. In addition, this work aimed to increase the anticancer effects of cotreatment with MK-2206 and ruxolitinib. Ruxolitinib, MK-2206, and their combination reduced cell viability in a dose- and time-dependent manner, as determined by MTT assays after 48 h of treatment. Colony formation and wound healing assays demonstrated that MK-2206 exhibited a synergistic anti-proliferative effect. The effects of ruxolitinib, MK-2206, and their combination on PI3K/AKT and MAPK signaling were assessed via western blotting. Ruxolitinib and MK-2206 combined treatment inhibit cell death in BT474 cells by downregulating ERα, Src-1, ERK1/2, SAPK/JNK, and c-Jun. Our results revealed the relationships among the ERα, PI3K/AKT, and MAPK signaling pathways in ER+ breast cancer cells. Understanding the interactions among ERα, PI3K-AKT-mTOR, and MAPK could lead to novel combination therapies.</p>","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"218-228"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Normal saline vs balanced intravenous fluids in acute ischemic stroke: A retrospective study.","authors":"Joshua J Davis","doi":"10.1177/10815589241300081","DOIUrl":"10.1177/10815589241300081","url":null,"abstract":"<p><p>While some studies have suggested better outcomes for critically ill patients with balanced solutions over normal saline, the best type of intravenous fluid to use for stroke patients remains unknown. Using a retrospective chart review of 2015-2019 Get with the Guidelines^® data at a single academic medical center, this study sought to determine whether balanced solutions or normal saline are associated with risk of hemorrhagic transformation or 90-day disability in patients with acute ischemic stroke treated with intravenous thrombolysis. Exposure was the type of intravenous fluid and outcomes were modified Rankin scale (mRS) ≤2 at 90 days and hemorrhagic transformation. Multivariate analysis controlled for age, demographics, medical history, time to tissue plasminogen activator (tPA), and admission stroke scale. We identified 302 patients who received thrombolysis, of which 166 patients had mRS data at 90 days. In univariate analysis, exposure to any balanced solution was associated with increased 90-day disability (odds ratio (OR) 4.3, 95% confidence interval (CI) 3.8-4.9) and hemorrhagic transformation (OR 2.0, 95% CI 1.3-2.2). In multivariate analysis, exposure to a balanced solution at any time was associated with increased 90-day disability (OR 6.3, 95% CI 2.4-17.0, <i>p</i> < 0.01), but not hemorrhagic transformation. Thus, this observational trial demonstrated that exposure to balanced solutions is associated with an increased risk of disability at 90 days and possibly hemorrhagic transformation in patients with acute ischemic stroke treated with intravenous thrombolysis. This data would suggest that normal saline is a preferred solution in these patients, though larger future trials are needed.</p>","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"257-260"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of stem cell therapy for male infertility restoration: A systematic review.","authors":"Mohammad Modanlou, Mahdi Mahdipour, Halimeh Mobarak","doi":"10.1177/10815589241305317","DOIUrl":"10.1177/10815589241305317","url":null,"abstract":"<p><p>Cell therapy has emerged as a prominent leader in regenerative medicine, offering potential solutions for various disorders, including infertility. Half of all infertility cases are related to male factors. The objective of this study is to systematically summarize the existing knowledge regarding studies on stem cell-based therapy for the regeneration of impaired spermatogenesis. Initial searching was performed through main databases (e.g., PubMed, Scopus, Cochrane Library, and Embase) until December 2023. Articles conducted on stem cell transplantation into the testis of infertile models were considered. The titles and abstracts of articles were carefully evaluated and screened by independent authors. Nonrelated articles were deleted. The desired outcomes of infertility treatment after stem cell transplantation were attentively evaluated in the final selected articles. In the primary search, 3237 published studies were identified. Finally, 39 studies were included based on the eligibility criteria. In all studies except for two articles, all the outcomes considered, including germ cells/spermatogonia stem cell differentiation, spermatogenesis restoration, defective testicular tissue regeneration, improved sperm quality parameters, and hormonal levels, as well as increased expression of fertility-related markers and fertility rate, were observed after stem cell transplantation. Transplantation of stem cells, especially MSCs could be a safe and effective method for the treatment of male infertility patients, such as azoospermic cases. Further research to investigate the efficiency of different stem cell sources, providing nutrient conditions for the isolation and differentiation of stem cells, and exploring the paracrine effects of MSCs in male infertility therapy, could be useful.</p>","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"229-252"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EXPRESS: Unlocking the Immune Puzzle: T Cell exhaustion in cirrhosis and implication for immunotherapy.","authors":"Geeta Yadav, Amit Goel, Manish Kumar, Hardeep Malhotra, Harshita Katiyar, Himanshu Dandu","doi":"10.1177/10815589251320368","DOIUrl":"https://doi.org/10.1177/10815589251320368","url":null,"abstract":"<p><strong>Background: </strong>Cirrhosis, an advanced stage of liver diseases, induces Cirrhosis-Associated Immune Dysfunction Syndrome (CAIDS) characterized by both innate and adaptive immune dysfunction. Inflammation triggered by factors such as alcohol, viruses, toxins, and cholesterol induce metabolic reprogramming of both innate and adaptive immune cells. Our study specifically sought to investigate the compromised adaptive immune response in cirrhosis by focusing on assessing T-cell exhaustion and activation markers on helper and cytotoxic T cells.</p><p><strong>Method: </strong>A prospective observational study involving 19 liver cirrhosis patients and 36 healthy controls was conducted. Hepatic decompensation degree was assessed using various parameters including serum bilirubin, albumin, international normalized ratio, ascites and hepatic encephalopathy. T cell activation (CD38, CD44, CD69, HLADR), and exhaustion markers (CTLA-4, PD-1, TIM-3, LAG-3) were assessed on helper and cytotoxic T cells by flow cytometry.</p><p><strong>Result: </strong>Cirrhosis patients showed reduced T cells with no alteration in CD4:CD8 T cell ratio. Among activation markers, HLADR showed increased expression on CD8+ T cells (P=0.031). Regarding exhaustion markers LAG-3 and TIM-3 exhibited increased expression in cirrhotic patients compared to controls in both CD4 and CD8 T cells (P=0.004, P=0.016, P=0.001, P=0.004, respectively). Neither cirrhotic nor healthy controls showed CTLA expression. PD-1 did not differ significantly between the two groups. Co-expression of PD-1/TIM-3 on CD8+ T cells was notably higher in cirrhotic patients (P<0.002).</p><p><strong>Conclusion: </strong>The observation of impaired adaptive immunity with notable T cell exhaustion and activation in cirrhosis underscores the potential relevance of immunotherapy.</p>","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"10815589251320368"},"PeriodicalIF":2.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms of ferroptosis in renal ischemia-reperfusion injury Investigated via bioinformatics analysis and animal experiments.","authors":"Haiming Wen, Jun Liu, Chaona Wang, Shu Yan, Zhaoyu Li, Wei Lan, Hongtao Liu, Shaopeng Ming","doi":"10.1177/10815589241288518","DOIUrl":"10.1177/10815589241288518","url":null,"abstract":"<p><p>Kidney transplantation is a pivotal treatment for end-stage renal disease. However, renal ischemia-reperfusion injury (IRI) during surgery significantly impacts graft function. Despite unclear molecular mechanisms, no specific therapies or preventative measures are available. Gene expression profiles from renal biopsies before and after IRI were downloaded from public databases. Differentially expressed genes were identified using the Wilcoxon rank-sum test and weighted gene co-expression network analysis. Ferroptosis-associated genes were screened using the FerrDb database. The genes with the highest connectivity were identified via the protein-protein interaction (PPI) network and upstream regulatory miRNAs were found through the gene-miRNA network. A mouse renal IRI model was constructed for transcriptome sequencing and quantitative real-time polymerase chain reaction (qRT-PCR) validation to elucidate the relationship between key ferroptosis genes and regulatory miRNAs in renal IRI. Differential analysis identified 15 ferroptosis-associated genes (<i>TNFAIP3</i>, <i>IL6</i>, <i>KLF2</i>, <i>EGR1</i>, <i>JUN</i>, <i>ZFP36</i>, <i>GDF15</i>, <i>CDKN1A</i>, <i>HSPB1</i>, <i>BRD2</i>, <i>PDK4</i>, <i>DUSP1</i>, <i>SLC2A3</i>, <i>DDIT3</i>, and <i>CXCL2</i>) involved in renal IRI regulation. In animal experiments, ferroptosis-related genes were also upregulated in the model group. Enrichment analysis and hematoxylin-eosin pathological staining suggested these genes are primarily involved in renal inflammatory responses. PPI network analysis revealed <i>IL6</i> as the gene with the highest connectivity, and the gene-miRNA network indicated <i>IL6</i> might be regulated by <i>miR-let-7a.</i> Animal experiments revealed decreased <i>miR-let-7a</i> and increased <i>IL6</i> levels in the model group, identifying potential therapeutic targets. <i>MiR-let-7a</i> regulates ferroptosis in renal IRI by targeting <i>IL6</i>, highlighting <i>IL6</i> as a crucial gene in the ferroptosis process of renal IRI.</p>","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"134-146"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted therapy of multiple myeloma by IL21-NKG2D CAR-T cells.","authors":"Kunkun Han, Xuan Wang, Guodong Chen, Wenyue Liu, Xiao Mei, Yili Yang, Xin Xu","doi":"10.1177/10815589241291846","DOIUrl":"10.1177/10815589241291846","url":null,"abstract":"<p><p>NKG2D chimeric antigen receptor (CAR)-modified T cells (NKG2D CAR-T cells) have been reported to be preclinically efficient in several tumors, but little is known whether NKG2D CAR-T cells co-expressing IL21 (IL21-NKG2D CAR-T cells) display greater antitumor activity in multiple myeloma (MM). In this study, the lentivirus has been produced for expression of the IL21 sequence linked to the extracellular NKG2D sequence with the signal peptide linked through the CD8α hinge-transmembrane domain to the 4-1BB molecule fused with the CD3-ζ chain signaling domain, and the engineered IL21-NKG2D CAR-T cells and NKG2D CAR-T cells were constructed. The CAR expression on CAR-T cells was assessed by flow cytometry, and the killing effects of CAR-T cells on MM were assessed by the cytotoxicity assay and ELISA assay. Moreover, xenograft models were also established to evaluate the ability of IL21-NKG2D-CAR-T cells to eliminate MM in vivo. Our results indicated that NKG2D CAR-T cells had dramatic cytotoxicity on MM cells in vitro, and co-expression of IL-21 significantly increased the cytotoxicity of NKG2D CAR-T cells on MM cells. Remarkably, we found that dexamethasone enhanced the cytotoxicity of IL21-NKG2D CAR-T cells on MM cells. Furthermore, IL21-NKG2D CAR-T cells also displayed significant anti-myeloma activity in vivo. In conclusion, IL21-NKG2D CAR-T cells had dramatic cytotoxicity on MM cells in vitro and in vivo, and a system to apply IL21-NKG2D CAR-T cells and low dosage of dexamethasone for the future study of the targeted therapy for MM has been established.</p>","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"45-53"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between acetaminophen and risk of mortality in patients with sepsis-associated acute kidney injury: A retrospective cohort study from the MIMIC-IV database.","authors":"Hui Yu, Ting Yang, Dongsong Liu","doi":"10.1177/10815589241290210","DOIUrl":"10.1177/10815589241290210","url":null,"abstract":"<p><p>The occurrence of sepsis-associated acute kidney injury (SA-AKI) predicts a worse prognosis. We aimed to assess the impact of acetaminophen use on short-term mortality in patients with SA-AKI. A total of 6563 patients diagnosed with SA-AKI from the 2008 to 2019 Medical Information Mart for Intensive Care IV (MIMIC-IV) database were enrolled in this retrospective cohort study. The Cox regression model was utilized to analyze the associations of acetaminophen with 30-day mortality and in-hospital mortality. Additional propensity score matching (PSM) analysis was performed regarding patients with acetaminophen use versus those without. Of these patients, 30-day mortality occurred in 1421 (21.65%) patients and in-hospital mortality in 1246 (18.99%) patients. Patients who used acetaminophen were associated with a reduced risk of 30-day mortality (hazard ratio (HR) = 0.80, 95% confidence interval (CI): 0.71-0.90) and in-hospital mortality (HR = 0.72, 95% CI: 0.63-0.82). The PSM analysis demonstrated that acetaminophen use was still related to a reduced risk of 30-day mortality and in-hospital mortality. Subgroup analysis showed that the relationships between acetaminophen and 30-day mortality and in-hospital mortality were consistent across subgroups (p < 0.05). The use of acetaminophen has an association with lower short-term mortality in patients with SA-AKI.</p>","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"125-133"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}