Journal of investigative medicine : the official publication of the American Federation for Clinical Research最新文献

{"title":"Immune checkpoint inhibitor-induced hypophysitis: lessons learnt from a large cancer cohort.","authors":"Anupam Kotwal,&nbsp;Samuel G Rouleau,&nbsp;Surendra Dasari,&nbsp;Lisa Kottschade,&nbsp;Mabel Ryder,&nbsp;Yogish C Kudva,&nbsp;Svetomir Markovic,&nbsp;Dana Erickson","doi":"10.1136/jim-2021-002099","DOIUrl":"https://doi.org/10.1136/jim-2021-002099","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) can cause pituitary dysfunction due to hypophysitis. We aimed to characterize ICI-induced hypophysitis and examine its association with overall survival in this single-center retrospective cohort study of adult patients with cancer who received an ICI from January 1, 2012 through December 31, 2016. A total of 896 patients were identified who received ipilimumab alone (n=120); ipilimumab and nivolumab (n=50); ipilimumab before or after pembrolizumab (n=70); pembrolizumab alone (n=406); and nivolumab alone (n=250). Twenty-six patients (2.9%) developed hypophysitis after a median of 2.3 months. Median age at the start of ICI was 57.9 years and 54% were men. Hypophysitis occurred in 7.9% of patients receiving ipilimumab alone or in combination or sequence with a programmed cell death protein 1 inhibitor; 1.7% after pembrolizumab alone, never after nivolumab alone. Secondary adrenal insufficiency occurred in all hypophysitis cases. Use of ipilimumab alone or in combination was associated with pituitary enlargement on imaging and mass effects more frequently than pembrolizumab alone. Occurrence of hypophysitis was associated with improved overall survival by univariate analysis (median 50.7 vs 16.5 months; p=0.015) but this association was not observed in multivariable landmark survival analysis (HR for mortality 0.75; 95% CI 0.38 to 1.30; p=0.34) after adjusting for age, sex and malignancy type. To conclude, hypophysitis occurred most frequently after ipilimumab and manifested as anterior hypopituitarism affecting the corticotrophs more commonly than thyrotrophs and gonadotrophs. Mass effects and pituitary enlargement occurred more frequently in ipilimumab-induced hypophysitis. The association of hypophysitis with overall survival needs further investigation.</p>","PeriodicalId":520677,"journal":{"name":"Journal of investigative medicine : the official publication of the American Federation for Clinical Research","volume":" ","pages":"939-946"},"PeriodicalIF":2.6,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39774197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between genetic variant rs2267716 of <i>CRHR2</i> gene with colorectal cancer.","authors":"Angélica Araceli Ramírez-Guerrero,&nbsp;Christian Octavio González-Villaseñor,&nbsp;Evelia Leal-Ugarte,&nbsp;Melva Gutiérrez-Angulo,&nbsp;Mario Ramírez-Flores,&nbsp;Iván Delgado-Enciso,&nbsp;Nelly Margarita Macías-Gómez","doi":"10.1136/jim-2021-002047","DOIUrl":"https://doi.org/10.1136/jim-2021-002047","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is the third most common cancer and one of the main causes of death around the world. Multiple lines of evidence have suggested the role of the corticotropin-releasing hormone (CRH) family in CRC induction, including the low expression of corticotropin-releasing hormone receptor 2 (<i>CRHR2</i>), which is an angiogenesis inhibitor and inflammatory modulator. Previous research suggests that CRHR2 expression in colonic intestinal cells can regulate migration, proliferation and apoptosis through the modulation of several pathways. The aim of this study was to analyze the association of the rs10250835, rs2267716 and rs2267717 variants of <i>CRHR2</i> gene with CRC in the Mexican population in order to consider its predictive value in CRC. This cross-sectional study included a group of 187 unrelated patients with sporadic CRC and a control group of 191 healthy blood donors. DNA extraction from peripheral blood was carried out using the Miller method. Identification of the rs10250835 variant was performed using PCR-restriction fragment length polymorphism (RFLP) and the rs2267716 and rs2267717 variants using TaqMan allelic discrimination assay. The minor allele homozygous CC of the rs2267716 variant of <i>CRHR2</i> showed significant difference between CRC and control group (p=0.025), as well as the GCA haplotype (p=0.007), corresponding to the rs10250835, rs2267716 and rs2267717 variants, respectively. Our results suggest that the rs2267716 variant and GCA haplotype of <i>CRHR2</i> represent a risk factor for CRC development in Mexican patients.</p>","PeriodicalId":520677,"journal":{"name":"Journal of investigative medicine : the official publication of the American Federation for Clinical Research","volume":" ","pages":"947-952"},"PeriodicalIF":2.6,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39774406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic derangement in patients with vitiligo: a cross-sectional study.","authors":"Zeinab Aryanian,&nbsp;Azar Shirzadian,&nbsp;Sepideh Farzaneh,&nbsp;Azadeh Goodarzi,&nbsp;Arghavan Azizpour,&nbsp;Parvaneh Hatami","doi":"10.1136/jim-2021-002062","DOIUrl":"https://doi.org/10.1136/jim-2021-002062","url":null,"abstract":"<p><p>Vitiligo is a pigmentary disorder resulting from progressive destruction of melanocytes in the skin. There is a growing body of evidence about higher risk of metabolic syndrome and dyslipidemia in some dermatoses including vitiligo. We aimed to evaluate lipid profile, leptin and C reactive protein (CRP) status among Iranian patients with vitiligo, compared with healthy controls and perused the relationship between abnormal values of these parameters with disease duration and physical characteristics of patients. 40 patients with vitiligo and 40 age-matched and sex-matched healthy controls were enrolled in the study. Data on weight, height, lipid profile, leptin and CRP values were recorded and compared. The mean values for nearly all study parameters (except for high-density lipoprotein) were significantly higher in patients with vitiligo, compared with healthy controls, irrespective of age and sex. We could not find any correlation between vitiligo and study parameters, regarding disease severity and extension of lesions; but in patients who have been suffering from vitiligo for more than 5 years, systolic blood pressure, diastolic blood pressure and CRP values were noted to be significantly higher (p<0.001, p=0.003 and p=0.03, respectively). In conclusion, screening of patients with vitiligo in regard to their lipid profile as well as blood pressure should be considered, especially in patients with longer disease duration or those who have other cardiovascular risk factors to prevent morbidity and mortality as a result of developing cardiovascular events.</p>","PeriodicalId":520677,"journal":{"name":"Journal of investigative medicine : the official publication of the American Federation for Clinical Research","volume":" ","pages":"963-966"},"PeriodicalIF":2.6,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f3/9a/jim-2021-002062.PMC9016231.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39803165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to: Correspondence on 'Prospective predictive performance comparison between clinical gestalt and validated COVID-19 mortality scores' by Meza-Comparán.","authors":"Adrian Soto-Mota,&nbsp;Braulio Alejandro Marfil-Garza","doi":"10.1136/jim-2021-002316","DOIUrl":"https://doi.org/10.1136/jim-2021-002316","url":null,"abstract":"© American Federation for Medical Research 2022. Reuse permitted under CC BYNC. No commercial reuse. Published by BMJ. We would like to thank Héctor David MezaComparán for their interest in our work and their insightful comments on our study published in the Journal of Investigative Medicine. Here we address the issues raised in it. As correctly pointed out, ‘clinical gestalt’ refers to ‘a physician’s unstructured estimate’ or an ‘overall clinical impression’. No formal definition was provided because it is a widespread term with a consistent connotation in the literature. On the other hand, as was emphasized in our introduction and in our discussion section, the main objective of our work was to make the point that the current validity of all mortality scores is likely impaired by the change in the pandemic context. Therefore, being thorough and including all Mexican COVID19 mortality scores was beyond the purpose of our work. Regarding the differences in years of experience between residents, we respectfully disagree. While it is true that senior residents are more likely to be confident than junior residents, this confidence applies most likely to the late clinical scenarios where senior residents have more experience (ie, nosocomial pneumonia, acute respiratory distress syndrome or pulmonary embolism) and not at hospital admission (before these complications occur). Nonetheless, because the admission process to the Internal Medicine residency program in our hospital is the most competitive in the country, the students in the top percentiles of each generation are the ones that usually conform to every resident’s cohort and their graduation years tend to be quite homogenous. With regard to the issues raised about our sample size, we would like to point out that, as was specified in our Methods section, we did not use the default input parameters of easyROC but those necessary for using Obuchowski’s method which considers allocation ratio and levels of observer variability. Arguably, and without the intention of falling into a semantic discussion about what it means to be noninferior in terms of area under the curve (AUC), for any diagnostic or classification tool it is reasonable to deem relevant any discrepancy beyond the original CI. Since the originally documented AUC of the LOWHARM score was 0.96 (95% CI 0.94 to 0.98), as detailed in our Methods section, detecting a 0.05 AUC difference with a case allocation ratio of 0.7 (because the mortality at our center is ~0.3) with a power of 0.8 and a significance cutoff level of 0.05 would require 159 patients. Since we included 166 patients and since the discrepancies with the original AUC of all scores were so large, we think it is unlikely our results are due to low statistical power. In summary, we think that despite its inherent limitations, our work strongly suggests that the clinical utility and predictive performance of most COVID19 mortality scores (and of many other clinical scenarios as ","PeriodicalId":520677,"journal":{"name":"Journal of investigative medicine : the official publication of the American Federation for Clinical Research","volume":" ","pages":"975-976"},"PeriodicalIF":2.6,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a1/23/jim-2021-002316.PMC9016235.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39865506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of atrial fibrillation on in-hospital outcomes among hospitalizations for cardiac surgery: an analysis of the National Inpatient Sample.","authors":"Kanishk Agnihotri,&nbsp;Paris Charilaou,&nbsp;Dinesh Voruganti,&nbsp;Kulothungan Gunasekaran,&nbsp;Jawahar Mehta,&nbsp;Hakan Paydak,&nbsp;Alexandros Briasoulis","doi":"10.1136/jim-2021-001864","DOIUrl":"https://doi.org/10.1136/jim-2021-001864","url":null,"abstract":"<p><p>The short-term impact of atrial fibrillation (AF) on cardiac surgery hospitalizations has been previously reported in cohorts of various sizes, but results have been variable. Using the 2005-2014 National Inpatient Sample, we identified all adult hospitalizations for cardiac surgery using the International Classification of Diseases, Ninth Revision, Clinical Modification as any procedure code and AF as any diagnosis code. We estimated the impact of AF on inpatient mortality, length of stay (LOS), and cost of hospitalization using survey-weighted, multivariable logistic, accelerated failure-time log-normal, and log-transformed linear regressions, respectively. Additionally, we exact-matched AF to non-AF hospitalizations on various confounders for the same outcomes. A total of 1,269,414 hospitalizations were noted for cardiac surgery during the study period. Coexistent AF was found in 44.9% of these hospitalizations. Overall mean age was 65.6 years, 40.9% were female, mean LOS was 11.6 days, and inpatient mortality was 4.5%. Stroke rate was lower in AF hospitalizations (1.8% vs 2.1%, p<0.001). Mortality was lower in the AF (3.9%) versus the non-AF (5%) group (exact-matched OR or emOR=0.48, 95% CI 0.29 to 0.80, p<0.001; 987 matched pairs, n=2423), with similar results after procedural stratification: isolated valve replacement/repair (emOR=0.38, p<0.001), isolated coronary artery bypass graft (CABG) (emOR=0.33, p<0.001), and CABG with valve replacement/repair (emOR=0.55, p<0.001). A 12% increase was seen in LOS in the AF subgroup (exact-matched time ratio=1.12, 95% CI 1.10 to 1.14, p<0.001) among hospitalizations which underwent valve replacement/repair with or without CABG. Hospitalizations for cardiac surgery which had coexistent AF were found to have lower inpatient mortality risk and stroke prevalence but higher LOS and hospitalization costs compared with hospitalizations without AF.</p>","PeriodicalId":520677,"journal":{"name":"Journal of investigative medicine : the official publication of the American Federation for Clinical Research","volume":" ","pages":"899-906"},"PeriodicalIF":2.6,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39876506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correspondence on 'Prospective predictive performance comparison between clinical gestalt and validated COVID-19 mortality scores' by Soto-Mota <i>et al</i>.","authors":"Héctor David Meza-Comparán","doi":"10.1136/jim-2021-002243","DOIUrl":"https://doi.org/10.1136/jim-2021-002243","url":null,"abstract":"© American Federation for Medical Research 2021. No commercial reuse. See rights and permissions. Published by BMJ. Dear Editor, I read the article ‘Prospective predictive performance comparison between clinical gestalt and validated COVID19 mortality scores’ with great interest. The authors compared various COVID19 mortality prediction models validated in Mexican patients — LOWHARM, MSLCOVID19, NutriCoV, and neutrophiltolymphocyte ratio (NLR) —, qSOFA, and NEWS2 against clinical gestalt to predict mortality among COVID19 patients admitted to a tertiary hospital, concluding that clinical gestalt was noninferior. I would like to comment on some issues with this article. It is unclear what “clinical gestalt” meant in the study since no formal definition was provided by the authors other than study procedures. Others have defined clinical gestalt as “a physician’s unstructured estimate” or an “overall clinical impression”. Additionally, it is not clear how the authors selected the prediction models to be evaluated. They mentioned that three models validated in datasets including Mexican patients were included; however, in the absence of clear inclusion criteria, other models validated in Mexican patients could have been left out. Thus, I performed a systematic search within","PeriodicalId":520677,"journal":{"name":"Journal of investigative medicine : the official publication of the American Federation for Clinical Research","volume":" ","pages":"972-974"},"PeriodicalIF":2.6,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39876507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosis of coronary artery rethrombosis after effective systemic thrombolytic therapy in patients with ST-segment elevation myocardial infarction.","authors":"Valentin E Oleynikov,&nbsp;Simon Matskeplishvili,&nbsp;Ekaterina Shigotarova,&nbsp;Alexey Kulyutsin,&nbsp;Nadezhda Burko","doi":"10.1136/jim-2021-001945","DOIUrl":"https://doi.org/10.1136/jim-2021-001945","url":null,"abstract":"<p><p>The aim of the study was to evaluate the diagnostic significance of ST-segment re-elevation episodes registered with telemetric ECG monitoring in patients with ST-segment elevation myocardial infarction (STEMI) treated with thrombolytic therapy (TLT). The study included 117 patients with STEMI following effective TLT. The elective coronary angiography followed by percutaneous coronary interventions was performed in the interval from 3 to 24 hours after a successful systemic TLT. Before and after cardiac catheterization, the telemetric ECG monitoring was performed using AstroCard Telemetry system (Meditec, Russia). During the study, two groups of patients were formed. Group 1 included 85 patients (72.6%) without new ST-segment deviations on telemetry. 77 patients (90.6%) had no recurrent coronary artery thrombosis at angiography. Eight patients (9.4%) from group 1 were diagnosed with thrombosis of the infarct-related coronary artery. Group 2 included 32 patients (27.4%) who underwent TLT and then had ST-segment re-elevation episodes of 1 mV or more in the infarct-related leads, lasting for at least 1 minute. In group 2, in 27 of 32 patients (84.4%), thrombosis of the infarct-related coronary artery was confirmed (p<0.01 compared with group 1). In 71.9% cases, the recurrent ischemic episodes were asymptomatic ('painless myocardial ischemia') (p<0.01). Thus, in patients with STEMI and successful TLT, re-elevation of ST-segment during remote ECG monitoring is strongly related to angiographically documented coronary artery thrombotic reocclusion. The absence of chest pain during recurrent myocardial ischemia requires continuous ECG telemetry to select patients for the rescue percutaneous coronary interventions at an earlier stage.</p>","PeriodicalId":520677,"journal":{"name":"Journal of investigative medicine : the official publication of the American Federation for Clinical Research","volume":" ","pages":"892-898"},"PeriodicalIF":2.6,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39832995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Latin Americans and US Hispanics show differences in IBD phenotype: a systematic review with meta-analysis.","authors":"Danny Juan Avalos,&nbsp;Jinendra Satiya,&nbsp;Alberto Contreras,&nbsp;Shivani Trivedi,&nbsp;Luis Alvarado,&nbsp;Christopher Dodoo,&nbsp;Alok Kumar Dwivedi,&nbsp;Marc J Zuckerman","doi":"10.1136/jim-2021-001846","DOIUrl":"https://doi.org/10.1136/jim-2021-001846","url":null,"abstract":"<p><p>Latin America has experienced a rise in the prevalence and incidence of inflammatory bowel disease (IBD). Differences in IBD phenotype between Hispanics in Latin America and those in the USA have not been described. We conducted a systematic review with meta-analysis of population-based and cohort studies comparing the phenotype of ulcerative colitis (UC) and Crohn's disease (CD) in Latin Americans and US Hispanics. A systematic search was conducted up to March 2019 using MEDLINE, EMBASE and Google Scholar. Inclusion criterion includes studies describing IBD phenotype in Latin Americans or in US Hispanics. Exclusion criterion includes prevalence or incidence studies not describing phenotype. A random effects model was chosen \"a priori\" for analysis of pooled proportions. A total of 46 studies were included from Latin America and 7 studies from the USA. The predominant IBD subtype in Latin America was UC with a more balanced UC:CD ratio noted in Puerto Rico (0.53) and Brazil (0.56). UC-related extensive colitis was more common in US Hispanics (0.64) than in Latin Americans (0.38), p<0.001. CD phenotype was similar between US Hispanics and Latin Americans. UC is the predominant IBD subtype in Latin America, with the exception of Puerto Rico and Brazil which demonstrate a more balanced UC:CD ratio. In UC, extensive colitis was more frequently seen in US Hispanics than in Latin Americans. CD phenotype was similar in both US Hispanics and Latin Americans.</p>","PeriodicalId":520677,"journal":{"name":"Journal of investigative medicine : the official publication of the American Federation for Clinical Research","volume":" ","pages":"919-933"},"PeriodicalIF":2.6,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39858259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Basic fibroblast growth factor inhibits aortic valvular interstitial cells calcification via Notch1 pathway.","authors":"Yuan Gao,&nbsp;Ning Li,&nbsp;Qing Xue,&nbsp;Xinli Fan,&nbsp;Xiaohong Liu,&nbsp;Lin Han","doi":"10.1136/jim-2021-002132","DOIUrl":"https://doi.org/10.1136/jim-2021-002132","url":null,"abstract":"<p><p>Calcific aortic valve disease (CAVD) is an active pathological process mediated by abnormal activation and transdifferentiation of valvular interstitial cells (VICs). The present study aims to investigate the function and underlying mechanism of the basic fibroblast growth factor (BFGF) on osteogenic differentiation of VICs. Porcine VICs cultured with osteogenic induction medium are supplemented with or without BFGF. Morphology of VICs is identified by fluorescein isothiocyanate-labeled phalloidin, the cell viability is assessed by the cell counting kit-8 method, and protein and mRNA expression level of osteogenic differentiation markers, including Runx2, osteopontin, and Sp7, are verified by western blot analysis and quantitative real-time PCR, respectively. RNA sequencing is used to identify changes in gene profiles. Alizarin Red S staining is used to measure calcium deposition. The results demonstrate that the content of calcium deposition and the expression level of osteogenic markers are downregulated by supplementing BFGF. Notch1 signaling pathway is extracted as a candidate target after bioinformatics analysis by RNA sequencing. The transfection of si-Notch1 abolishes the calcification inhibitory effect of BFGF. Taken together, our findings shed the light on the mechanism and potential therapeutics of BFGF for CAVD.</p>","PeriodicalId":520677,"journal":{"name":"Journal of investigative medicine : the official publication of the American Federation for Clinical Research","volume":" ","pages":"907-913"},"PeriodicalIF":2.6,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39946099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deferasirox combination with eltrombopag shows anti-myelodysplastic syndrome effects by enhancing iron deprivation-related apoptosis.","authors":"Lei Huang,&nbsp;Mengyue Tian,&nbsp;Zhaoyun Liu,&nbsp;Chunyan Liu,&nbsp;Rong Fu","doi":"10.1136/jim-2021-002147","DOIUrl":"https://doi.org/10.1136/jim-2021-002147","url":null,"abstract":"<p><p>Iron overload (IO) affected the survival of patients with myelodysplastic syndrome (MDS). Deferasirox (DFX) is widely used in patients with MDS for iron chelation therapy, but is not suitable for MDS patients with severe thrombocytopenia. Eltrombopag (ELT) is a type of thrombopoietin receptor (TPOR) analog used in the treatment of thrombocytopenia. Therefore, we sought to explore the synergistic effects and possible mechanisms of DFX combination with ELT in MDS cells. In our study, the combination of DFX with ELT synergistically inhibited proliferation, induced apoptosis and arrested cell cycle of MDS cells. Through the RNA-sequence and gene set enrichment analysis (GSEA), iron metabolism-related pathway played important roles in apoptosis of SKM-1 cells treated with DFX plus ELT. Transferrin receptor (TFRC) was significantly highly expressed in combination group than that in single agent groups, without affecting TPOR. Furthermore, the apoptosis of the combination group MDS cells could be partially reversed by ferric ammonium citrate (FAC), accompanied with decreased expression of TFRC. These results suggested that the combination of DFX and ELT synergistically induced apoptosis of MDS cells by enhancing iron deprivation-related pathway.</p>","PeriodicalId":520677,"journal":{"name":"Journal of investigative medicine : the official publication of the American Federation for Clinical Research","volume":" ","pages":"953-962"},"PeriodicalIF":2.6,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39824105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}