{"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<sup>®</sup> 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}
Mohammad Modanlou, Mahdi Mahdipour, Halimeh Mobarak
{"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}
Jillian E Nickerson, Alexandra Rucker, Molly Walker, Christopher Gable, Tanika Jones, Theresa Ryan Schultz, Shireen Atabaki
{"title":"EXPRESS: Implementation of telepsychiatry in an urban pediatric satellite emergency department (ED).","authors":"Jillian E Nickerson, Alexandra Rucker, Molly Walker, Christopher Gable, Tanika Jones, Theresa Ryan Schultz, Shireen Atabaki","doi":"10.1177/10815589251318621","DOIUrl":"https://doi.org/10.1177/10815589251318621","url":null,"abstract":"<p><p>While pediatric mental health emergencies are increasing in frequency and severity, psychiatric resources remain concentrated in tertiary care facilities. Telepsychiatry has successfully mitigated these challenges in rural emergency departments (EDs), suggesting potential benefits for urban EDs that lack psychiatric resources. We implemented telepsychiatry in an urban ED to reduce ED length of stay and the need for transferring pediatric patients with mental and behavioral health complaints. We conducted a retrospective review of patients aged 0-17 presenting from July 1, 2018 to May 31, 2020 (PRE-intervention) and from June 1, 2020 to June 30, 2023 (POST-intervention) for psychiatric evaluation, suicidal ideation, homicidal ideation, behavioral issues, intentional ingestion, or altered mental status. Our outcomes of interest were ED length-of-stay (LOS), proportion transferred, and proportion with a repeat visit within 30 days for a mental health complaint. There were 199 patients; 74 PRE and 125 POST. Post-intervention, 91% (114 patients) were evaluated completely via telepsychiatry; thus only 11 (9%) required transfer. The median age was 14 years (range 8-17). The most common complaints were suicidal ideation, intentional ingestion, and behavioral problems. Seventy-four percent of patients (n=84) evaluated by telepsychiatry were discharged from the satellite ED. The median length of stay decreased significantly from 473 minutes (95% CI=431-733) to 275 min (95% CI=316-462) after implementation. Repeat visits for mental health complaints within 30 days decreased from 23% to 10%. Implementing a telepsychiatry evaluation program in an urban pediatric satellite ED reduced transfers and decreased patient length of stay.</p>","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"10815589251318621"},"PeriodicalIF":2.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065850","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":"Fluorouracil enhances the anti-pancreatic cancer effect of anti-PD-L1 antibodies via up-regulating the expression of PD-L1 in cancer cells.","authors":"Wei Wang, Sujing Zhang, Cong Wang, Siming Gao, Lingling Zhang, Changwang Zhang, Zheng Zheng, Jiancong Zhang, Hui Xu, Changwen Bo, Na Li","doi":"10.1177/10815589251314192","DOIUrl":"10.1177/10815589251314192","url":null,"abstract":"<p><p>Pancreatic cancer is characterized by occult onset, low early diagnosis rate, rapid progress, and poor prognosis. Due to the low response rate and low programmed cell death ligand 1 (PD-L1) expression in pancreatic cancer, the therapeutic application of PL-L1 inhibitors in pancreatic cancer is greatly limited. In vitro studies showed that the expression of PD-L1 increased in pancreatic cancer cells stimulated by fluorouracil (5-FU). We aim to explore the combined effect of 5-FU and anti-PD-L1 antibodies and to provide a reference for the clinical application of PD-L1 antibodies in pancreatic cancer. In the current study, male BALB/c mice were adopted to construct a tumor-bearing model of pancreatic cancer cells. 5-FU and anti-mouse PD-L1 antibodies were combined and administered to evaluate their synergistic effects. The enhancing immune cytotoxicity effect of 5-FU sensitizing the anti-PD-L1 antibody in vivo and in vitro was analyzed by immunohistochemistry and western blot assays. Results showed that 5-FU and anti-PD-L1 antibody combination increased the expression of PD-L1 and IFN-γ, and infiltration of CD8<sup>+</sup> T lymphocytes in pancreatic xenograft tumor tissues, which was proven by immunohistochemistry and western analysis. Moreover, the combination with the 5-FU remarkably enhanced the immune cytotoxicity of anti-PD-L1 antibodies in mice. In vitro analysis demonstrates that 5-FU increases the expression of PD-L1 on the surface of pancreatic cancer cell lines via up-regulating nuclear factor kappa B (NF-κB) and Protein kinase B (AKT) pathways. This synergistic effect could be abolished by NF-κB and AKT inhibitors.</p>","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"10815589251314192"},"PeriodicalIF":2.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931958","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":"Synergistic efficacy of orthokeratology and 0.01% atropine in controlling pediatric myopia progression: A retrospective analysis.","authors":"Yingying Yang, Zhigang Xiao, Jing Ouyang, Yan Guo","doi":"10.1177/10815589241308819","DOIUrl":"10.1177/10815589241308819","url":null,"abstract":"<p><p>This study investigates the combined efficacy of orthokeratology lenses and 0.01% atropine in controlling the progression of pediatric progressive myopia. The study, conducted retrospectively on 33 children aged 8-14, measured key parameters, including axial length growth, uncorrected visual acuity (UCVA), intraocular pressure (IOP), tear film breakup time (TBUT), and pupil diameter. The results revealed a significant reduction in axial length growth with the combined treatment compared to orthokeratology alone, while UCVA and IOP remained stable. TBUT decreased, and pupil diameter increased post-treatment. The findings suggest that combining orthokeratology with low-dose atropine offers a safe and effective strategy for managing pediatric myopia, particularly in younger patients.</p>","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"10815589241308819"},"PeriodicalIF":2.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828769","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":"Investigation of the synergic effect of mocetinostat and capecitabine in a triple-negative breast neoplasms mouse model.","authors":"Hacer Kaya Çakir, Onur Eroğlu","doi":"10.1177/10815589241309603","DOIUrl":"10.1177/10815589241309603","url":null,"abstract":"<p><p>Combined administration of two or more drugs is emerging as a new strategy in triple-negative breast neoplasms. This is the first study to investigate the combination of the histone deacetylase inhibitor mocetinostat and the antimetabolite drug capecitabine in triple-negative mammary neoplasms in a preclinical mouse model. Thirty-five female mice were grouped into the control group, capecitabine group, mocetinostat group, and combined drugs group. At the end of the experimental period, body weight, and tumor weight were measured and tumor tissue and lung tissue were histologically examined. The results showed that the body weight of mice in the drug-treated groups was reduced by about 18%. Tumor weights were also reduced by 21% in the mocetinostat group, 27.5% in the capecitabine group, and 45% in the combined group. The combination of mocetinostat and capecitabine decreased the formation of tumors and metastases in lung tissue. In summary, the combination of mocetinostat and capecitabine was more effective than either drug alone in reducing the size of triple-negative breast neoplasms in a mouse model.</p>","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"10815589241309603"},"PeriodicalIF":2.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846751","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":"Screening for presence of primary Sjogren's syndrome in patients with autoimmune thyroid diseases.","authors":"Manar Elgebaly, Wael Farrag, Khaled Shalaby, Hesham Elserougy, Manal Saad Negm","doi":"10.1177/10815589241308573","DOIUrl":"10.1177/10815589241308573","url":null,"abstract":"<p><p>Autoimmune thyroid disorders (AITD) are the most common autoimmune human disorders as the thyroid gland is a main target for autoimmunity. The association between rheumatologic and thyroid disorders has long been known, the most common being the association with rheumatoid arthritis. Our study was conducted to screen for the presence of symptoms, signs, and immune markers suggesting the presence of Sjogren's syndrome among patients with autoimmune thyroid disorders. Eighty AITD patients (46 patients with Hashimoto's thyroiditis and 34 patients with Graves' disease) were included in the study and 40 healthy subjects matched age and sex as a control group. The two groups were compared according to 2002 the American-European Consensus Group (AECG) criteria for diagnosis of primary Sjogren's syndrome. 12.5% of AITD patients (n = 10 patients) were diagnosed with Sjogren's syndrome (AITD-SS). Eight out of ten of AITD-SS had Hashimoto's disease while only two had Grave's disease. Anti-Ro was detected in serum of seven patients of the AITD patients with Sjogren syndrome while anti-La was detected in serum of eight patients. The most independent predictors of Sjogren's syndrome in AITD patients are anti-La, ESR, and salivary gland sonographic change. Sjogren's syndrome has been found in patients with AITD, and also patients with AITD have symptoms that mimic sicca disease despite not fulfilling the criteria for diagnosis.</p>","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"10815589241308573"},"PeriodicalIF":2.5,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837184","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}
Haiming Wen, Jun Liu, Chaona Wang, Shu Yan, Zhaoyu Li, Wei Lan, Hongtao Liu, Shaopeng Ming
{"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}