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Electrocardiogram abnormalities in patients with hematological malignancies before and after high dose chemotherapy and autologous hematopoietic stem cell transplantation 大剂量化疗和自体造血干细胞移植前后血液恶性肿瘤患者的心电图异常
Pub Date : 2024-06-03 DOI: 10.18786/2072-0505-2024-52-010
N. Potemkina, M. G. Glezer, P. Chomakhidze, P. A. Zeynalova, G. Petrova, A. I. Novikova, Artur N. Gasymov, Maria G. Poltavskaya
Rationale: Electrocardiography (ECG) is an objective and widely available method for the diagnosis of cardiovascular disorders recommended for identification of abnormalities, including those in patients with malignancies. A few studies have been published on the assessment of changes in ECG over time in patients with hemoblastoses under high-dose chemotherapy (HDCT) with subsequent transplantation of autologous hematopoietic stem cells (autoHSCT). Aim: To study ECG abnormalities before HDCT with autoHSCT and after treatment and their association with cardiac dysfunction in patients with hematological malignancies. Materials and methods: This prospective cohort observational study included 71 patients with confirmed hemoblastoses. Before HDCT with autoHSCT and at the average of 20 weeks thereafter, a 12-lead standard ECG, echocardiography, and measurement of cardiac biomarkers (troponin T [TnT] and N-terminal pro-peptide of brain natriuretic peptide (NT-proBNP) were performed. We assessed P wave abnormalities, PQ duration, QRS, ST segment, and T wave. The following cut-off values were considered abnormal: duration of P wave above 110 ms, of PQ interval above 210 ms, of QRS above 110 ms. The QTc intervals were calculated according to Bazett and Fridericia. QTc above 450 ms in men and above 460 in women was considered as prolonged. Results: After HDCT with autoHSCT, increased left ventricular myocardial mass index (LVMMI) was more commonly found in the patients with prolonged P wave ( 110 ms) at baseline (χ2 = 7.214; odds ratio (OR) 4.179; 95% confidence interval [CI] 1.425–12.250; p = 0.015), and increased left atrial volume index (LAVI) was more common for those with initially two-humped P wave (χ2 = 11.169; OR 19.231; 95% CI 2.064–179.212; p = 0.004). Before HDCT with autoHSCT, flattened T wave was present in 14 (19.7%) of the study patients. After the treatment, 8 (11.3%) of the patients demonstrated a new T wave abnormalities, associated with more frequent new TnT increase ( 14 pg/mL) (χ2 = 7.945; p = 0.025), as well as with increased LAVI (p = 0.018) and LVMMI (p = 0.018). Before HDCT with autoHSCT, 10 (14.1%) of the study patients had a prolonged QTc interval, which correlated to the increased NT-proBNP level ( 125 pg/mL) (r = 0.247; p = 0.038). The assessment of the QTc length after HDCT with autoHSCT showed, that the increase of NT-proBNP levels by 1 pg/mL was associated with an increase of the QTc duration by 0.003 mc(p = 0.027). Conclusion: In patients with hematological malignancies, baseline P wave abnormalities are the risk factor for increased LVMMI and LAVI after HDCT with autoHSCT. New T wave abnormalities and QTc prolongation after HDCT with autoHSCT are associated with the signs of myocadial injury and dysfunction.
理由:心电图(ECG)是诊断心血管疾病的一种客观且广泛使用的方法,建议用于识别异常,包括恶性肿瘤患者的异常。关于评估接受大剂量化疗(HDCT)并随后进行自体造血干细胞移植(autoHSCT)的血细胞病患者心电图随时间推移而发生的变化,目前已发表的研究不多。目的:研究血液恶性肿瘤患者在接受高剂量化疗(HDCT)和自体造血干细胞移植(autoHSCT)治疗前和治疗后的心电图异常及其与心脏功能障碍的关系。材料与方法:这项前瞻性队列观察研究纳入了 71 名确诊为血液母细胞瘤的患者。在进行自体供血干细胞移植(HDCT)前及其后平均 20 周,我们对患者进行了 12 导联标准心电图、超声心动图和心脏生物标志物(肌钙蛋白 T [TnT] 和脑钠肽 N 端前肽(NT-proBNP))测量。我们评估了 P 波异常、PQ 持续时间、QRS、ST 段和 T 波。以下截断值被视为异常:P 波持续时间超过 110 毫秒,PQ 间期超过 210 毫秒,QRS 超过 110 毫秒。QTc 间期根据 Bazett 和 Fridericia 的方法计算。男性 QTc 超过 450 毫秒,女性 QTc 超过 460 毫秒,即被视为 QTc 间期延长。结果HDCT联合autoHSCT治疗后,基线P波延长(110 ms)的患者左心室心肌质量指数(LVMMI)升高更为常见(χ2 = 7.214; odds ratio (OR) 4.179;95% 置信区间 [CI] 1.425-12.250;P = 0.015),左心房容积指数(LAVI)升高在初始 P 波为双驼峰的患者中更为常见(χ2 = 11.169;OR 19.231;95% CI 2.064-179.212;P = 0.004)。在使用自体血细胞移植进行 HDCT 之前,14 名(19.7%)研究患者出现了 T 波变平。治疗后,8 名患者(11.3%)出现了新的 T 波异常,与更频繁的新 TnT 升高(14 pg/mL)(χ2 = 7.945;p = 0.025)、LAVI 升高(p = 0.018)和 LVMMI 升高(p = 0.018)有关。在进行自体血细胞移植的 HDCT 前,10 名(14.1%)研究患者的 QTc 间期延长,这与 NT-proBNP 水平(125 pg/mL)的升高相关(r = 0.247;p = 0.038)。使用自体血细胞移植进行 HDCT 后的 QTc 时长评估显示,NT-proBNP 水平每增加 1 pg/mL,QTc 时长就会增加 0.003 mc(p = 0.027)。结论在血液恶性肿瘤患者中,基线 P 波异常是自体血细胞移植 HDCT 后 LVMMI 和 LAVI 增加的危险因素。接受自体血细胞介导的 HDCT 后出现新的 T 波异常和 QTc 延长与心肌损伤和功能障碍相关。
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引用次数: 0
Mild hyperprolactinemia in clinical practice: the diagnostic “traps” and treatment strategy 临床实践中的轻度高催乳素血症:诊断 "陷阱 "与治疗策略
Pub Date : 2024-04-22 DOI: 10.18786/2072-0505-2024-52-009
Irena A. Ilovayskaya, E. Kruchinina
Real world clinical practice frequently poses the question on the advisability of diagnostic and/or treatment interventions for increased prolactin levels of below 2500 mU/mL (100 ng/mL), which is commonly considered as mild and not unequivocally indicating a prolactinoma. The aim of the review is to critically analyze the body of literature within the last 10 years on clinical and biochemical particulars of patients with mildly increased prolactin levels. We performed the search in Pubmed and RISC (Russian Index of Science Citation) databases with the keywords of “mild hyperprolactinemia” and “women” (or their Russian equivalents). After exclusion of the studies in patients with primary hypothyroidism or treatment with agents inducing prolactin secretion, as well as of clinical case descriptions, we selected 21 original papers with clinical and biochemical data of female patients with mild hyperprolactinemia (prolactin levels of less than 2500 mU/mL or less than 100 ng/mL). Symptoms of mild hyperprolactinemia include menstrual cycle disorders, anovulatory infertility and/or early pregnancy losses, breast disorders, psychoemotional and sexual disorders, and metabolic abnormalities. Repeated testing of prolactin levels to exclude potential stress related to the vein puncture allows for exclusion of 27% to 28% of the patients from further diagnostic work up. Confirmation of persistently increased prolactin levels warrants a magnetic resonance imaging study of the pituitary. Most patients with persistently increased prolactin levels by repeated tests would have pituitary abnormalities (in most cases, pituitary microadenoma). Taking into account the data on negative effects of even mildly increased prolactin levels on reproductive and metabolic health, it is reasonable to administer a first line agent cabergoline at doses ensuring normoprolactinemia. The results of studies indicate that treatment with cabergoline at doses necessary to normalize prolactin levels would lead to regression of menstrual dysfunction, decrease the probability of early pregnancy losses, improve metabolic parameters, promotes restoration of the sexual function, and diminishes the level of depression. This is especially important when planning pregnancy in patients with menstrual cycle disorders, infertility and/or early pregnancy losses.
在现实的临床实践中,经常会遇到泌乳素水平升高低于 2500 mU/mL(100 ng/mL)时是否应该进行诊断和/或治疗干预的问题,这种情况通常被认为是轻度的,并不能明确表明患有泌乳素瘤。本综述旨在批判性地分析过去 10 年中有关泌乳素水平轻度增高患者的临床和生化细节的文献。我们在 Pubmed 和 RISC(俄罗斯科学引文索引)数据库中以 "轻度高泌乳素血症 "和 "女性"(或其俄语对应词)为关键词进行了检索。在排除了对原发性甲状腺功能减退症患者或接受催乳素分泌诱导剂治疗的患者的研究以及临床病例描述后,我们选择了 21 篇原创论文,这些论文提供了轻度高催乳素血症(催乳素水平低于 2500 mU/mL 或低于 100 ng/mL)女性患者的临床和生化数据。轻度高催乳素血症的症状包括月经周期紊乱、无排卵性不孕和/或早孕反应、乳腺疾病、精神情绪和性功能紊乱以及代谢异常。重复检测催乳素水平以排除与静脉穿刺有关的潜在压力,可使 27% 至 28% 的患者免于进一步诊断。如果确认泌乳素水平持续升高,则需要进行垂体磁共振成像检查。通过反复检查,大多数催乳素水平持续升高的患者都有垂体异常(大多数情况下是垂体微腺瘤)。考虑到即使泌乳素水平轻度升高也会对生殖和代谢健康产生负面影响的数据,使用卡贝戈林作为一线药物,其剂量确保正常泌乳素血症是合理的。研究结果表明,使用卡贝戈林治疗时,如果剂量能够使泌乳素水平恢复正常,就能缓解月经失调,降低早孕损失的概率,改善代谢指标,促进性功能恢复,并减轻抑郁程度。这对于月经周期紊乱、不孕和/或早孕失败的患者计划怀孕时尤为重要。
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引用次数: 0
Biomarkers for assessment of the polychemotherapy results in patients with adrenocortical cancer based on gas chromatography-mass spectrometry studies of urine steroid profiles 基于气相色谱-质谱尿液类固醇谱研究的肾上腺皮质癌患者多化疗效果评估生物标志物
Pub Date : 2024-04-12 DOI: 10.18786/2072-0505-2024-52-008
L. Velikanova, Natalia V. Vorokhobina, V. Kalugina, Zulfiya R. Shafigullina, E. Malevanaya, E. Strelnikova, V. Y. Bokhyan
Background: The effectiveness of polychemotherapy (PCT) for adrenocortical cancer (ACC) is assessed by imaging tests with the RECIST 1.1 criteria. However, the presence of subclinical tumor foci does not allow for an objective measurement of the true tumor burden. As shown previously, postoperative assessment of the steroid metabolome by gas chromatography-mass spectrometry (GCMS) in ACC patients makes it possible to identify early signs of adrenal steroidogenesis abnormalities and of the recurrence of adrenocortical carcinoma. Aim: To identify biomarkers of response to PCT by GCMS study of the urine steroid profile in ACC patients after surgical resection of the tumor. Materials and methods: Urine steroid profiles were studied by GCMS (Shimadzu GCMS-TQ8050 gas chromatography-mass spectrometer) in 30 ACC patients (stages II, III and IV) after surgery and first line (combination of etoposide, doxorubicin and cisplatin with daily mitotane) and second line (gemcitabine combined with capecitabine and mitotane) PCT. The control group included 25 patients with hormonally inactive adenomas. Results: The response to PCT according to RECIST 1.1 criteria was obtained in 23 patients (Group 1, responders) and in 7 patients ACC progressed under PCT (Group 2, non-responders). In the responders, the urinary excretion of etiocholanolone, pregnanediol and pregnanetriol was lower than in the control group. The non-responders had higher urinary excretion of androgens, progestogens and tetrahydro-11-deoxycortisol (THS), compared to the responders and the control group. The patients with ACC progression under PCT had an increase in 3β,16,20-pregnenetriol (3β,16,20-dP3) levels and a decrease of the 3α,16,20-dP3/3β,16,20-dP3 ratio, compared to those in the PCT responders. The threshold values for urinary excretion of dehydroepiandrosterone (DHEA, ≤ 469 mcg/24h; AUC = 1.0), THS (≤ 223 mcg/24h; AUC = 1.0), and 3β,16,20-dP3 (≤ 130 mcg/24h; AUC = 0.986), as well as the 3α,16,20-dP3/3β,16,20-dP3 ratio (≥ 2.13; AUC = 1.0) had 100% sensitivity and specificity for the assessment of the PCT effectiveness. Conclusion: Different urine steroid profiles were obtained by GCMS in the ACC patients after PCT with and without treatment response. The 100% sensitivity and specificity of the threshold values for urinary excretion of DHEA, THS, 3β,16,20-dP3 and the 3α,16,20-dP3/3β,16,20-dP3 ratio for the assessment of PCT results indicate the potential to use these parameters as biomarkers of response or progression of the disease in the monitoring of PCT effects in ACC patients.
背景:肾上腺皮质癌(ACC)的多化疗(PCT)效果是根据 RECIST 1.1 标准通过影像学检查来评估的。然而,亚临床肿瘤灶的存在无法客观测量真实的肿瘤负荷。如前文所示,通过气相色谱-质谱法(GCMS)对 ACC 患者术后类固醇代谢组进行评估,可以发现肾上腺类固醇生成异常的早期迹象和肾上腺皮质癌复发的早期迹象。目的:通过对 ACC 患者手术切除肿瘤后的尿液类固醇谱进行 GCMS 研究,确定对 PCT 反应的生物标志物。材料和方法:采用 GCMS(岛津 GCMS-TQ8050 气相色谱-质谱联用仪)研究了 30 名 ACC 患者(II、III 和 IV 期)在手术和一线(依托泊苷、多柔比星和顺铂联合用药,每日米托坦)及二线(吉西他滨联合卡培他滨和米托坦)PCT 后的尿液类固醇谱。对照组包括 25 名激素不活跃腺瘤患者。研究结果根据 RECIST 1.1 标准,23 名患者对 PCT 有反应(第一组,有反应者),7 名 ACC 患者在 PCT 治疗下病情进展(第二组,无反应者)。与对照组相比,应答者尿中乙酰胆碱酮、孕烷二醇和孕烷三醇的排泄量较低。与有反应者和对照组相比,无反应者尿液中雄激素、孕激素和四氢-11-脱氧皮质醇(THS)的排泄量较高。与 PCT 反应者相比,PCT 下 ACC 进展患者的 3β,16,20-孕三醇(3β,16,20-dP3)水平升高,3α,16,20-dP3/3β,16,20-dP3 比率降低。脱氢表雄酮(DHEA,≤ 469 mcg/24h;AUC = 1.0)、THS(≤ 223 mcg/24h;AUC = 1.0)和 3β,16,20-dP3(≤ 130 mcg/24h;AUC = 0.986)以及 3α,16,20-dP3/3β,16,20-dP3 比率(≥ 2.13;AUC = 1.0)对评估 PCT 有效性的敏感性和特异性均为 100%。结论通过 GCMS 对有治疗反应和无治疗反应的 PCT 治疗后的 ACC 患者进行尿液类固醇谱分析。尿液中 DHEA、THS、3β,16,20-dP3 和 3α,16,20-dP3/3β,16,20-dP3 比率的阈值对评估 PCT 结果的敏感性和特异性均为 100%,这表明在监测 ACC 患者的 PCT 效果时,有可能将这些参数用作疾病反应或进展的生物标志物。
{"title":"Biomarkers for assessment of the polychemotherapy results in patients with adrenocortical cancer based on gas chromatography-mass spectrometry studies of urine steroid profiles","authors":"L. Velikanova, Natalia V. Vorokhobina, V. Kalugina, Zulfiya R. Shafigullina, E. Malevanaya, E. Strelnikova, V. Y. Bokhyan","doi":"10.18786/2072-0505-2024-52-008","DOIUrl":"https://doi.org/10.18786/2072-0505-2024-52-008","url":null,"abstract":"Background: The effectiveness of polychemotherapy (PCT) for adrenocortical cancer (ACC) is assessed by imaging tests with the RECIST 1.1 criteria. However, the presence of subclinical tumor foci does not allow for an objective measurement of the true tumor burden. As shown previously, postoperative assessment of the steroid metabolome by gas chromatography-mass spectrometry (GCMS) in ACC patients makes it possible to identify early signs of adrenal steroidogenesis abnormalities and of the recurrence of adrenocortical carcinoma. \u0000Aim: To identify biomarkers of response to PCT by GCMS study of the urine steroid profile in ACC patients after surgical resection of the tumor. \u0000Materials and methods: Urine steroid profiles were studied by GCMS (Shimadzu GCMS-TQ8050 gas chromatography-mass spectrometer) in 30 ACC patients (stages II, III and IV) after surgery and first line (combination of etoposide, doxorubicin and cisplatin with daily mitotane) and second line (gemcitabine combined with capecitabine and mitotane) PCT. The control group included 25 patients with hormonally inactive adenomas. \u0000Results: The response to PCT according to RECIST 1.1 criteria was obtained in 23 patients (Group 1, responders) and in 7 patients ACC progressed under PCT (Group 2, non-responders). In the responders, the urinary excretion of etiocholanolone, pregnanediol and pregnanetriol was lower than in the control group. The non-responders had higher urinary excretion of androgens, progestogens and tetrahydro-11-deoxycortisol (THS), compared to the responders and the control group. The patients with ACC progression under PCT had an increase in 3β,16,20-pregnenetriol (3β,16,20-dP3) levels and a decrease of the 3α,16,20-dP3/3β,16,20-dP3 ratio, compared to those in the PCT responders. The threshold values for urinary excretion of dehydroepiandrosterone (DHEA, ≤ 469 mcg/24h; AUC = 1.0), THS (≤ 223 mcg/24h; AUC = 1.0), and 3β,16,20-dP3 (≤ 130 mcg/24h; AUC = 0.986), as well as the 3α,16,20-dP3/3β,16,20-dP3 ratio (≥ 2.13; AUC = 1.0) had 100% sensitivity and specificity for the assessment of the PCT effectiveness. \u0000Conclusion: Different urine steroid profiles were obtained by GCMS in the ACC patients after PCT with and without treatment response. The 100% sensitivity and specificity of the threshold values for urinary excretion of DHEA, THS, 3β,16,20-dP3 and the 3α,16,20-dP3/3β,16,20-dP3 ratio for the assessment of PCT results indicate the potential to use these parameters as biomarkers of response or progression of the disease in the monitoring of PCT effects in ACC patients.","PeriodicalId":502611,"journal":{"name":"Almanac of Clinical Medicine","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140708982","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}
引用次数: 0
The texture analysis of computed tomography studies in clear cell renal cell carcinoma: reproducibility of 2D and 3D segmentation 透明细胞肾细胞癌计算机断层扫描研究的纹理分析:二维和三维分割的再现性
Pub Date : 2024-04-11 DOI: 10.18786/2072-0505-2024-52-007
S. V. Khromova, G. G. Karmazanovsky, Natalia A. Karelskaya, I. Gruzdev
Background: Differentiation of tumor grade at the preoperative stage is of utmost importance for the modification of the treatment strategy and the extent of operation. However, the routine analysis of computed tomography (CT) data in clear cell renal cell carcinoma (ccRCC) does not allow for reliable determination of the tumor grade. Aim: To assess the reproducibility of the results of 2D and 3D segmentation of a kidney tumor in the cortico-medullary and nephrographic phases of CT studies, as well as the reproducibility of the first order texture parameters for 2D and 3D tumor segmentation in patients with verified ccRCC. Materials and methods: This retrospective study included the CT data of 50 patients with morphologically verified ccRCC obtained before their surgical treatment. The first patient group included the patients with the renal tumor size in the axial plane of ≥ 4 cm (28 patients, 29 CT studies), and the second patient group included those with the renal tumor size in axial plane of 4 cm (22 patients, 23 CT studies). Two radiologists independently performed segmentation of the renal tumor in the cortico-medullary and nephrographic phases of CT procedures done under a standard protocol with the bolus intravenous contrast enhancement. A two-dimensional region of interest (2D ROI) was selected by the investigators on a subjectively selected axial slice, where the tumor had the largest size. When forming a three-dimensional region of interest (3D ROI), the entire tumor volume was segmented. Next, the statistical analysis of the segmentation results and the results of calculation of the first order texture indices was performed with calculation of the intra-class correlation coefficient (ICC) to assess the strength of the data correlation. The ICC of ≥ 0.75 demonstrated the reproducibility of the segmentation results and the first order texture indices. Results: The 3D segmentation method for ccRCC demonstrated the best ROI reproducibility results, regardless of the tumor size and the phase of contrast enhancement, with the ICC values of 0.961 (95% confidence interval: 0.946–0.971) for the cortico-medullary phase and 0.969 (95% CI: 0.958–0.977) for the nephrographic phase. The 2D tumor segmentation method showed unsatisfactory ROI reproducibility, with the ICC values of ≤ 0.058; however, the unsatisfactory reproducibility of the segmentation results in the patients with ccRCC tumor size of ≥ 4 cm did not significantly affect the reproducibility of the Entropy and Energy texture indices (good to excellent correlation). With the 3D segmentation of ccRCC, most first-order texture metrics were reproducible, with the exception of the Kurtosis parameter. The Entropy and Energy scores in both patient groups demonstrated a high degree of reproducibility. In the 2D tumor segmentation, high reproducibility of the first order texture metrics was obtained for the Entropy and Energy indices. Conclusion: The 3D segmentation of the CT data for ccRC
背景:在术前阶段区分肿瘤分级对治疗策略和手术范围的调整至关重要。然而,对透明细胞肾细胞癌(ccRCC)的计算机断层扫描(CT)数据进行常规分析并不能可靠地确定肿瘤分级。目的:评估 CT 研究中肾肿瘤皮质髓质期和肾造影期二维和三维分割结果的可重复性,以及已验证 ccRCC 患者二维和三维肿瘤分割一阶纹理参数的可重复性。材料和方法:这项回顾性研究收集了 50 名形态学已证实的 ccRCC 患者在手术治疗前获得的 CT 数据。第一组患者包括肾脏肿瘤轴平面大小≥4厘米的患者(28例患者,29次CT检查),第二组患者包括肾脏肿瘤轴平面大小为4厘米的患者(22例患者,23次CT检查)。两名放射科医生按照标准方案,在静脉注射对比剂增强的情况下,独立完成了肾肿瘤的皮质髓质期和肾造影期的 CT 图像分割。研究人员在主观选定的轴切片上选择肿瘤最大的二维感兴趣区(2D ROI)。在形成三维感兴趣区(3D ROI)时,对整个肿瘤体积进行分割。接下来,对分割结果和一阶纹理指数的计算结果进行统计分析,计算类内相关系数(ICC),以评估数据相关性的强度。ICC ≥ 0.75 表明分割结果和一阶纹理指数具有可重复性。结果ccRCC的三维分割方法显示出最佳的ROI重现性结果,与肿瘤大小和对比度增强阶段无关,皮质髓质阶段的ICC值为0.961(95%置信区间:0.946-0.971),肾图阶段的ICC值为0.969(95% CI:0.958-0.977)。二维肿瘤分割方法的ROI再现性不尽人意,ICC值≤0.058;但是,ccRCC肿瘤大小≥4厘米的患者的分割结果再现性不尽人意,并没有明显影响熵和能量纹理指数的再现性(相关性良好至极佳)。在对 ccRCC 进行三维分割时,除峰度参数外,大多数一阶纹理指标都具有可重复性。两组患者的熵和能量评分均显示出高度的可重复性。在二维肿瘤分割中,熵指数和能量指数的一阶纹理指标具有很高的可重复性。结论ccRCC的CT数据三维分割具有很高的重现性,在三维分割时,大多数一阶纹理特征都具有很好的重现性。ccRCC的二维CT数据分割方法可重复性较低;不过,一些一阶纹理指数具有可重复性。这两种分割方法都可用于 CT 图像的纹理分析。
{"title":"The texture analysis of computed tomography studies in clear cell renal cell carcinoma: reproducibility of 2D and 3D segmentation","authors":"S. V. Khromova, G. G. Karmazanovsky, Natalia A. Karelskaya, I. Gruzdev","doi":"10.18786/2072-0505-2024-52-007","DOIUrl":"https://doi.org/10.18786/2072-0505-2024-52-007","url":null,"abstract":"Background: Differentiation of tumor grade at the preoperative stage is of utmost importance for the modification of the treatment strategy and the extent of operation. However, the routine analysis of computed tomography (CT) data in clear cell renal cell carcinoma (ccRCC) does not allow for reliable determination of the tumor grade. \u0000Aim: To assess the reproducibility of the results of 2D and 3D segmentation of a kidney tumor in the cortico-medullary and nephrographic phases of CT studies, as well as the reproducibility of the first order texture parameters for 2D and 3D tumor segmentation in patients with verified ccRCC. \u0000Materials and methods: This retrospective study included the CT data of 50 patients with morphologically verified ccRCC obtained before their surgical treatment. The first patient group included the patients with the renal tumor size in the axial plane of ≥ 4 cm (28 patients, 29 CT studies), and the second patient group included those with the renal tumor size in axial plane of 4 cm (22 patients, 23 CT studies). Two radiologists independently performed segmentation of the renal tumor in the cortico-medullary and nephrographic phases of CT procedures done under a standard protocol with the bolus intravenous contrast enhancement. A two-dimensional region of interest (2D ROI) was selected by the investigators on a subjectively selected axial slice, where the tumor had the largest size. When forming a three-dimensional region of interest (3D ROI), the entire tumor volume was segmented. Next, the statistical analysis of the segmentation results and the results of calculation of the first order texture indices was performed with calculation of the intra-class correlation coefficient (ICC) to assess the strength of the data correlation. The ICC of ≥ 0.75 demonstrated the reproducibility of the segmentation results and the first order texture indices. \u0000Results: The 3D segmentation method for ccRCC demonstrated the best ROI reproducibility results, regardless of the tumor size and the phase of contrast enhancement, with the ICC values of 0.961 (95% confidence interval: 0.946–0.971) for the cortico-medullary phase and 0.969 (95% CI: 0.958–0.977) for the nephrographic phase. The 2D tumor segmentation method showed unsatisfactory ROI reproducibility, with the ICC values of ≤ 0.058; however, the unsatisfactory reproducibility of the segmentation results in the patients with ccRCC tumor size of ≥ 4 cm did not significantly affect the reproducibility of the Entropy and Energy texture indices (good to excellent correlation). With the 3D segmentation of ccRCC, most first-order texture metrics were reproducible, with the exception of the Kurtosis parameter. The Entropy and Energy scores in both patient groups demonstrated a high degree of reproducibility. In the 2D tumor segmentation, high reproducibility of the first order texture metrics was obtained for the Entropy and Energy indices. \u0000Conclusion: The 3D segmentation of the CT data for ccRC","PeriodicalId":502611,"journal":{"name":"Almanac of Clinical Medicine","volume":"12 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140715718","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}
引用次数: 0
The LGALS1 gene polymorphism is not associated with galectin-1 levels in tumor tissue and blood of colon cancer patients LGALS1 基因多态性与结肠癌患者肿瘤组织和血液中的 galectin-1 水平无关
Pub Date : 2024-04-10 DOI: 10.18786/2072-0505-2024-52-006
O. Urazova, G. V. Reyngardt, Yuliya V. Kolobovnikova, A. V. Kurnosenko, V. S. Poletika, Olga A. Vasil'yeva, A. Avgustinovich
Background: Galectin-1 plays an important role in the pathogenesis of colorectal cancer (CRC). The blood and tumoral levels of galectin-1 could be dependent on the polymorphism of the promotor region of LGALS1 gene. Aim: To analyze an association between galectin-1 levels in tumor tissue and plasma and the genotype of the rs4820293 and rs4820294 polymorphisms of the LGALS1 gene in CRC patients. Materials and methods: The study included a total of 70 inpatients with pathologically verified CRC (International Classification of Diseases 10th Revision codes C18-C20, 39 men and 31 women, mean age 65.4 ± 5.7 years), who were receiving treatment in the Tomsk Regional Oncology Center and Cancer Research Institute of the Tomsk National Research Medical Center from 2020 to 2022. The control group consisted of 70 healthy volunteers (34 men and 36 women, mean age 62.3 ± 7.2 years). Venous blood samples were taken from all study participants and tumor tissue samples were obtained from the CRC patients. Galectin-1 expression in the tumor tissue was assessed by immunohistochemistry and plasma galectin-1 levels by enzyme-linked immunosorbent assay. The LGALS1 gene polymorphisms rs4820293 and rs4820294 were identified by restriction fragment length polymorphism analysis. Results: The distributions of genotype and allele frequencies of polymorphic variants rs4820293 and rs4820294 of the LGALS1 gene in the CRC patients and in the healthy donors were comparable (p 0.05). Calculation of odds ratios did not confirm any association between LGALS1 gene polymorphisms and CRC. However, the rs4820294 polymorphism had a strong association with regional metastasis and tumor differentiation grade (Cramer's V above 0.4, p 0.001). The plasma galectin-1 levels in the CRC patients with the AA genotype of the rs4820294 polymorphism were higher than in the healthy carriers (17.42 versus 12.92 ng/ml, p = 0.040). However, there were no significant differences in the content of galectin-1+ cells in the tumor and galectin-1 in plasma of the CRC patients depending on the genotype of the LGALS1 gene polymorphisms (p 0.05). Conclusion: The LGALS1 gene polymorphism is not associated with CRC, but in the carriers of the rs4820294 variant is related to clinical and morphological parameters of the tumor process. The intratumoral expression and blood levels of galectin-1 in CRC patients are not dependent on the genotype of rs4820293 and rs4820294 polymorphisms of the LGALS1 gene.
背景:Galectin-1 在结直肠癌(CRC)的发病机制中发挥着重要作用。血液和肿瘤中 galectin-1 的水平可能取决于 LGALS1 基因启动子区的多态性。目的:分析 CRC 患者肿瘤组织和血浆中 galectin-1 水平与 LGALS1 基因 rs4820293 和 rs4820294 多态性基因型之间的关联。材料和方法:研究对象包括 2020 年至 2022 年期间在托木斯克地区肿瘤中心和托木斯克国家研究医疗中心癌症研究所接受治疗的 70 名经病理证实的 CRC 住院患者(国际疾病分类第 10 次修订代码 C18-C20,男性 39 人,女性 31 人,平均年龄 65.4 ± 5.7 岁)。对照组包括 70 名健康志愿者(34 名男性和 36 名女性,平均年龄为 62.3 ± 7.2 岁)。研究人员采集了所有参与者的静脉血样本,并从 CRC 患者身上采集了肿瘤组织样本。肿瘤组织中 Galectin-1 的表达通过免疫组化法进行评估,血浆中 galectin-1 的水平通过酶联免疫吸附法进行评估。通过限制性片段长度多态性分析确定了 LGALS1 基因多态性 rs4820293 和 rs4820294。结果显示LGALS1基因多态性变异rs4820293和rs4820294在CRC患者和健康供体中的基因型和等位基因频率分布相当(P 0.05)。计算几率比值并未证实 LGALS1 基因多态性与 CRC 之间存在任何关联。然而,rs4820294 多态性与区域转移和肿瘤分化等级有密切关系(Cramer's V 高于 0.4,P 0.001)。具有 rs4820294 多态性 AA 基因型的 CRC 患者的血浆 galectin-1 水平高于健康携带者(17.42 对 12.92 ng/ml,P = 0.040)。然而,根据 LGALS1 基因多态性基因型的不同,肿瘤中 galectin-1+ 细胞的含量和 CRC 患者血浆中 galectin-1 的含量没有明显差异(P 0.05)。结论LGALS1基因多态性与CRC无关,但rs4820294变异携带者的LGALS1基因多态性与肿瘤过程的临床和形态学参数有关。CRC 患者瘤内 galectin-1 的表达和血液水平与 LGALS1 基因 rs4820293 和 rs4820294 多态性的基因型无关。
{"title":"The LGALS1 gene polymorphism is not associated with galectin-1 levels in tumor tissue and blood of colon cancer patients","authors":"O. Urazova, G. V. Reyngardt, Yuliya V. Kolobovnikova, A. V. Kurnosenko, V. S. Poletika, Olga A. Vasil'yeva, A. Avgustinovich","doi":"10.18786/2072-0505-2024-52-006","DOIUrl":"https://doi.org/10.18786/2072-0505-2024-52-006","url":null,"abstract":"Background: Galectin-1 plays an important role in the pathogenesis of colorectal cancer (CRC). The blood and tumoral levels of galectin-1 could be dependent on the polymorphism of the promotor region of LGALS1 gene. \u0000Aim: To analyze an association between galectin-1 levels in tumor tissue and plasma and the genotype of the rs4820293 and rs4820294 polymorphisms of the LGALS1 gene in CRC patients. \u0000Materials and methods: The study included a total of 70 inpatients with pathologically verified CRC (International Classification of Diseases 10th Revision codes C18-C20, 39 men and 31 women, mean age 65.4 ± 5.7 years), who were receiving treatment in the Tomsk Regional Oncology Center and Cancer Research Institute of the Tomsk National Research Medical Center from 2020 to 2022. The control group consisted of 70 healthy volunteers (34 men and 36 women, mean age 62.3 ± 7.2 years). Venous blood samples were taken from all study participants and tumor tissue samples were obtained from the CRC patients. Galectin-1 expression in the tumor tissue was assessed by immunohistochemistry and plasma galectin-1 levels by enzyme-linked immunosorbent assay. The LGALS1 gene polymorphisms rs4820293 and rs4820294 were identified by restriction fragment length polymorphism analysis. \u0000Results: The distributions of genotype and allele frequencies of polymorphic variants rs4820293 and rs4820294 of the LGALS1 gene in the CRC patients and in the healthy donors were comparable (p 0.05). Calculation of odds ratios did not confirm any association between LGALS1 gene polymorphisms and CRC. However, the rs4820294 polymorphism had a strong association with regional metastasis and tumor differentiation grade (Cramer's V above 0.4, p 0.001). The plasma galectin-1 levels in the CRC patients with the AA genotype of the rs4820294 polymorphism were higher than in the healthy carriers (17.42 versus 12.92 ng/ml, p = 0.040). However, there were no significant differences in the content of galectin-1+ cells in the tumor and galectin-1 in plasma of the CRC patients depending on the genotype of the LGALS1 gene polymorphisms (p 0.05). \u0000Conclusion: The LGALS1 gene polymorphism is not associated with CRC, but in the carriers of the rs4820294 variant is related to clinical and morphological parameters of the tumor process. The intratumoral expression and blood levels of galectin-1 in CRC patients are not dependent on the genotype of rs4820293 and rs4820294 polymorphisms of the LGALS1 gene.","PeriodicalId":502611,"journal":{"name":"Almanac of Clinical Medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140718361","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}
引用次数: 0
The content of soluble forms of galectins -1, -3, -4, -7, -9 in patients with renal cell cancer of various morphological types 不同形态的肾细胞癌患者体内可溶形式的加列汀-1、-3、-4、-7、-9的含量
Pub Date : 2024-04-10 DOI: 10.18786/2072-0505-2024-52-005
N. E. Kushlinskii, O. Kovaleva, Arseniy G. Basov, Yu. B. Kuzmin, Aleksandr A. Alferov, S. Bezhanova, Aleksey V. Kolpashchikov, I. A. Klimanov, Alexey N. Grachev, N. N. Zybina, V. Matveev, O. Yanushevich, I. Stilidi
Background: Galectins are a family of β-galactoside binding proteins that regulate the vast majority of cellular functions, including proliferation, migration, adhesion, and phagocytosis in both health and disease. More and more experimental and clinical evidence indicates that galectins are involved in many stages of carcinogenesis, including patients with renal cell carcinoma (RCC). Aim: To analyze the clinical significance of soluble forms of galectins -1, -3, -4, -7, -9 in patients with various histological RCC types. Materials and methods: We performed a retrospective analysis of the clinical significance of galectins -1, -3, -4, -7, -9 in the serum of 140 RCC patients (84 with clear cell RCC (ccRCC), 38 with papillary (papRCC), 18 with chromophobe (chrRCC)) and in 73 healthy donors (control group), who were examined and treated from 2019 to 2023 in the N. N. Blokhin National Medical Research Center of Oncology. Galectin levels were measured in serum (obtained according to standard methods before the initiation of specific treatment) with an enzyme-linked immunosorbent assay. Results: There was a significant increase in serum galectin -1, -3, -9 levels in the whole RCC patient group, compared to the healthy donor control group; no increase was found for galectins -4 and -7. Serum galectin-1 levels in the ccRCC and papRCC patients were significantly higher than those in the controls (p = 0.0003 and p = 0.0135, respectively). No association between the serum galectins -1 and -7 and the clinical and morphological characteristics of RCC was found; however, serum galectin-7 levels in the papRCC patients correlated with the grade of tumor differentiation (r = -0.592; p = 0.001). The area under the ROC curve (AUC) for galectin-1 in ccRCC was 0.721 (p 0.0001), in papRCC 0.673 (p = 0.0086), and in chrRCC 0.576 (p = 0.355). For galectin-7, the ROC AUC values were 0.527 (p = 0.634) in ccRCC, 0.513 (p = 0.845) in papRCC, and 0.566 (p = 0.425) in chrRCC. In all histological types of RCC, there was a significant increase in serum galectin-3 compared to the controls (ccRCC, p = 0.0208; papRCC, p = 0.0014; chrRCC, p = 0.0041). The ROC analysis for galectin-3 in patients with RCC of various histological types showed AUC = 0.721 (p 0.0001) for ccRCC, 0.673 (p = 0.0086) for papRCC, and 0.576 (p = 0.355) for chrRCC. Galectin-9 levels was directly and significantly associated with the tumor size, as well as with regional metastases (r = 0.251, p = 0.021; r = 0.239, p = 0.028, respectively). The AUC values for galectin-4 were 0.619 (p = 0.021) in ccRCC, 0.577 (p = 0.214) in papRCC, and 0.534 (p = 0.666) for chrRCC. For galectin-9, they were 0.649 (p = 0.0075), 0.613 (p = 0.087), and 0.539 (p = 0.637), respectively. Conclusion: The study has demonstrated a certain association between serum galectin -1, -3, -4, -7, and -9 in the patients with RCC of various histological types. Although the results of the ROC analysis indicated average quality of the model, whic
背景:半整联蛋白是β-半乳糖苷结合蛋白的一个家族,可调节绝大多数细胞功能,包括健康和疾病中的增殖、迁移、粘附和吞噬作用。越来越多的实验和临床证据表明,半连接蛋白参与了许多阶段的癌变,包括肾细胞癌(RCC)患者。目的:分析在不同组织学类型的 RCC 患者中可溶性形式的半凝集素-1、-3、-4、-7、-9 的临床意义。材料与方法:我们对 140 名 RCC 患者(84 名透明细胞 RCC (ccRCC)、38 名乳头状 RCC (papRCC)、18 名嗜铬细胞 RCC (chrRCC))和 73 名健康供体(对照组)血清中的高连蛋白-1、-3、-4、-7、-9 的临床意义进行了回顾性分析,这些患者于 2019 年至 2023 年期间在 N. N. Blokhin 国立肿瘤医学研究中心接受了检查和治疗。使用酶联免疫吸附测定法测量了血清中的伽连蛋白水平(根据标准方法在开始特定治疗前获得)。结果显示ccRCC和papRCC患者血清中的galectin-1水平明显高于对照组(分别为p = 0.0003和p = 0.0135)。血清中的 galectin-1 和 galectin-7 与 RCC 的临床和形态特征之间没有关联;但是,papRCC 患者血清中的 galectin-7 水平与肿瘤分化等级相关(r = -0.592;p = 0.001)。在ccRCC中,galectin-1的ROC曲线下面积(AUC)为0.721(p 0.0001),在papRCC中为0.673(p = 0.0086),在chrRCC中为0.576(p = 0.355)。对于 galectin-7,ccRCC 的 ROC AUC 值为 0.527(p = 0.634),papRCC 为 0.513(p = 0.845),chrRCC 为 0.566(p = 0.425)。与对照组相比,所有组织学类型的 RCC 患者血清中的 galectin-3 均显著增加(ccRCC,p = 0.0208;papRCC,p = 0.0014;chrRCC,p = 0.0041)。对不同组织学类型的RCC患者的Galectin-3的ROC分析显示,ccRCC的AUC = 0.721 (p 0.0001),papRCC的AUC = 0.673 (p = 0.0086),chrRCC的AUC = 0.576 (p = 0.355)。Galectin-9水平与肿瘤大小和区域转移直接且显著相关(分别为r = 0.251,p = 0.021;r = 0.239,p = 0.028)。在ccRCC中,galectin-4的AUC值为0.619(p = 0.021),在papRCC中为0.577(p = 0.214),在chrRCC中为0.534(p = 0.666)。至于 galectin-9,它们分别为 0.649 (p = 0.0075)、0.613 (p = 0.087) 和 0.539 (p = 0.637)。结论研究表明,不同组织学类型的 RCC 患者血清中的 galectin-1、-3、-4、-7 和 -9 之间存在一定的关联。虽然 ROC 分析结果表明模型质量一般,无法将获得的数据用于诊断目的,但在将基于 galectin 的治疗药物引入临床实践用于治疗 RCC 之前,有必要继续开展研究,以便更好地了解 galectin 的作用机制。
{"title":"The content of soluble forms of galectins -1, -3, -4, -7, -9 in patients with renal cell cancer of various morphological types","authors":"N. E. Kushlinskii, O. Kovaleva, Arseniy G. Basov, Yu. B. Kuzmin, Aleksandr A. Alferov, S. Bezhanova, Aleksey V. Kolpashchikov, I. A. Klimanov, Alexey N. Grachev, N. N. Zybina, V. Matveev, O. Yanushevich, I. Stilidi","doi":"10.18786/2072-0505-2024-52-005","DOIUrl":"https://doi.org/10.18786/2072-0505-2024-52-005","url":null,"abstract":"Background: Galectins are a family of β-galactoside binding proteins that regulate the vast majority of cellular functions, including proliferation, migration, adhesion, and phagocytosis in both health and disease. More and more experimental and clinical evidence indicates that galectins are involved in many stages of carcinogenesis, including patients with renal cell carcinoma (RCC). \u0000Aim: To analyze the clinical significance of soluble forms of galectins -1, -3, -4, -7, -9 in patients with various histological RCC types. \u0000Materials and methods: We performed a retrospective analysis of the clinical significance of galectins -1, -3, -4, -7, -9 in the serum of 140 RCC patients (84 with clear cell RCC (ccRCC), 38 with papillary (papRCC), 18 with chromophobe (chrRCC)) and in 73 healthy donors (control group), who were examined and treated from 2019 to 2023 in the N. N. Blokhin National Medical Research Center of Oncology. Galectin levels were measured in serum (obtained according to standard methods before the initiation of specific treatment) with an enzyme-linked immunosorbent assay. \u0000Results: There was a significant increase in serum galectin -1, -3, -9 levels in the whole RCC patient group, compared to the healthy donor control group; no increase was found for galectins -4 and -7. Serum galectin-1 levels in the ccRCC and papRCC patients were significantly higher than those in the controls (p = 0.0003 and p = 0.0135, respectively). No association between the serum galectins -1 and -7 and the clinical and morphological characteristics of RCC was found; however, serum galectin-7 levels in the papRCC patients correlated with the grade of tumor differentiation (r = -0.592; p = 0.001). The area under the ROC curve (AUC) for galectin-1 in ccRCC was 0.721 (p 0.0001), in papRCC 0.673 (p = 0.0086), and in chrRCC 0.576 (p = 0.355). For galectin-7, the ROC AUC values were 0.527 (p = 0.634) in ccRCC, 0.513 (p = 0.845) in papRCC, and 0.566 (p = 0.425) in chrRCC. In all histological types of RCC, there was a significant increase in serum galectin-3 compared to the controls (ccRCC, p = 0.0208; papRCC, p = 0.0014; chrRCC, p = 0.0041). The ROC analysis for galectin-3 in patients with RCC of various histological types showed AUC = 0.721 (p 0.0001) for ccRCC, 0.673 (p = 0.0086) for papRCC, and 0.576 (p = 0.355) for chrRCC. Galectin-9 levels was directly and significantly associated with the tumor size, as well as with regional metastases (r = 0.251, p = 0.021; r = 0.239, p = 0.028, respectively). The AUC values for galectin-4 were 0.619 (p = 0.021) in ccRCC, 0.577 (p = 0.214) in papRCC, and 0.534 (p = 0.666) for chrRCC. For galectin-9, they were 0.649 (p = 0.0075), 0.613 (p = 0.087), and 0.539 (p = 0.637), respectively. \u0000Conclusion: The study has demonstrated a certain association between serum galectin -1, -3, -4, -7, and -9 in the patients with RCC of various histological types. Although the results of the ROC analysis indicated average quality of the model, whic","PeriodicalId":502611,"journal":{"name":"Almanac of Clinical Medicine","volume":"169 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140719903","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}
引用次数: 0
Association between full blood count and urine steroid metabolome in patients with adrenal masses 肾上腺肿块患者全血细胞计数与尿液类固醇代谢组之间的关系
Pub Date : 2024-04-09 DOI: 10.18786/2072-0505-2024-52-004
Natalia V. Vorokhobina, V. Kalugina, L. Velikanova, Zulfiya R. Shafigullina, Ekaterina V. Malevanaya, A. A. Lisitsyn
Background: Endogenous hypercortisolism of adrenal origin is commonly associated with immune suppression. However, these patients also have signs characteristic of chronic inflammatory diseases. Better understanding of the mechanisms that alter the functioning of the immune system would allow for the development of a patient-centered approach to the treatment of corticotropin-independent endogenous Cushing's syndrome (CS). Aim: To assess the association between full blood count and gas chromatography-mass spectrometry-based urinary steroid excretion in patients with adrenal masses depending on malignancy grade and presence of hypercortisolism. Materials and methods: We retrospectively analyzed data from 42 patients with adrenal masses who had not received chemotherapy. The median age of the patients was 54 [Q25; Q75: 37; 63] years, and 76% of them were female. Preoperatively, all patients had hematology tests with differential leukocyte count. Steroid metabolome was assessed with Shimadzu GCMS-TQ8050 gas chromatography-mass spectrometer. Results: Twelve (12) patients had adrenocortical cancer (ACC) and CS, 9 patients had ACC without CS, 11 had adrenocortical adenomas (ACA) and CS, and 10 patients had ACA without CS. ACC patients had a higher neutrophil-to-lymphocyte ratio (NLR) than those with ACA: 3.35 [2.5; 6.3] vs 1.99 [1.41; 2.65] (р = 0.001). There was a linear correlation between NLR and serum cortisol levels after the 1 mg overnight dexamethasone suppression test (r = 0.41, p = 0.01), urinary excretion of 5β-tetrahydrocortisol (5β-THF) (r = 0.71, p 0.001) and 11β-hydroxyandrosterone (11β-OH-An) (r = 0.74, p 0.001). The ACC patients without CS had lower 5β-THF urinary excretion values, compared to ACA with CS patients: 931 [616; 1610] and 3139 [1480; 4375] mcg/24h, respectively (р = 0.007). 11β-OH-An urinary excretion in ACC patients without CS was higher than in ACA patients with CS: 1170 [806; 1266] и 602 [320; 739] mcg/24h (р = 0.007). The NLR cut-off value for adrenal mass malignancy in patients with CS exceeded 2.72 (sensitivity 90.0%, specificity 80.0%), and for the patients without hypercortisolism was above 1.92 (sensitivity 71.4%, specificity 100.0%). Conclusion: This is the first association identification between NLR, which is the marker of systemic inflammation, inflammation, and urinary excretion of 11β-OH-An, a metabolite of 11-hydroxyandrostenedione (a member of 11-oxygenated androgen family). This extends our understanding of the impact of hormonal activity of adrenal mass cells on the immune system.
背景:内源性肾上腺皮质醇分泌过多通常与免疫抑制有关。然而,这些患者也有慢性炎症性疾病的特征。如果能更好地了解改变免疫系统功能的机制,就能开发出一种以患者为中心的方法来治疗促肾上腺皮质激素依赖性内源性库欣综合征(CS)。目的:评估肾上腺肿块患者全血细胞计数与基于气相色谱-质谱法的尿液类固醇排泄量之间的关系,具体取决于恶性程度和是否存在高皮质醇血症。材料和方法:我们回顾性分析了 42 名未接受化疗的肾上腺肿块患者的数据。患者的中位年龄为 54 [Q25; Q75: 37; 63]岁,其中 76% 为女性。术前,所有患者都进行了血液学检查和白细胞计数鉴别。岛津 GCMS-TQ8050 气相色谱-质谱仪对类固醇代谢组进行了评估。结果显示12例患者患有肾上腺皮质癌(ACC)和CS,9例患者患有ACC但无CS,11例患者患有肾上腺皮质腺瘤(ACA)和CS,10例患者患有ACA但无CS。ACC患者的中性粒细胞与淋巴细胞比率(NLR)高于ACA患者:3.35 [2.5; 6.3] vs 1.99 [1.41; 2.65] (р = 0.001)。NLR 与 1 毫克过夜地塞米松抑制试验后的血清皮质醇水平(r = 0.41,p = 0.01)、5β-四氢皮质醇(5β-THF)尿排泄量(r = 0.71,p 0.001)和 11β- 羟基雄酮(11β-OH-An)(r = 0.74,p 0.001)之间存在线性相关。与患有 CS 的 ACA 患者相比,未患有 CS 的 ACC 患者的 5β-THF 尿排泄值更低:分别为 931 [616; 1610] 和 3139 [1480; 4375] mcg/24h(р = 0.007)。未患 CS 的 ACC 患者的 11β-OH-An 尿排泄量高于患 CS 的 ACA 患者:1170 [806; 1266] и 602 [320; 739] mcg/24h(р = 0.007)。CS患者肾上腺肿块恶性肿瘤的NLR临界值超过2.72(敏感性90.0%,特异性80.0%),而无高皮质醇症患者的NLR临界值超过1.92(敏感性71.4%,特异性100.0%)。结论这是首次鉴定 NLR(全身炎症、炎症的标志物)与尿液中 11β-OH-An(11-羟基雄烯二酮(11-氧代雄激素家族成员之一)的代谢产物)排泄量之间的关联。这扩展了我们对肾上腺肿块细胞激素活动对免疫系统影响的认识。
{"title":"Association between full blood count and urine steroid metabolome in patients with adrenal masses","authors":"Natalia V. Vorokhobina, V. Kalugina, L. Velikanova, Zulfiya R. Shafigullina, Ekaterina V. Malevanaya, A. A. Lisitsyn","doi":"10.18786/2072-0505-2024-52-004","DOIUrl":"https://doi.org/10.18786/2072-0505-2024-52-004","url":null,"abstract":"Background: Endogenous hypercortisolism of adrenal origin is commonly associated with immune suppression. However, these patients also have signs characteristic of chronic inflammatory diseases. Better understanding of the mechanisms that alter the functioning of the immune system would allow for the development of a patient-centered approach to the treatment of corticotropin-independent endogenous Cushing's syndrome (CS). \u0000Aim: To assess the association between full blood count and gas chromatography-mass spectrometry-based urinary steroid excretion in patients with adrenal masses depending on malignancy grade and presence of hypercortisolism. \u0000Materials and methods: We retrospectively analyzed data from 42 patients with adrenal masses who had not received chemotherapy. The median age of the patients was 54 [Q25; Q75: 37; 63] years, and 76% of them were female. Preoperatively, all patients had hematology tests with differential leukocyte count. Steroid metabolome was assessed with Shimadzu GCMS-TQ8050 gas chromatography-mass spectrometer. \u0000Results: Twelve (12) patients had adrenocortical cancer (ACC) and CS, 9 patients had ACC without CS, 11 had adrenocortical adenomas (ACA) and CS, and 10 patients had ACA without CS. ACC patients had a higher neutrophil-to-lymphocyte ratio (NLR) than those with ACA: 3.35 [2.5; 6.3] vs 1.99 [1.41; 2.65] (р = 0.001). There was a linear correlation between NLR and serum cortisol levels after the 1 mg overnight dexamethasone suppression test (r = 0.41, p = 0.01), urinary excretion of 5β-tetrahydrocortisol (5β-THF) (r = 0.71, p 0.001) and 11β-hydroxyandrosterone (11β-OH-An) (r = 0.74, p 0.001). The ACC patients without CS had lower 5β-THF urinary excretion values, compared to ACA with CS patients: 931 [616; 1610] and 3139 [1480; 4375] mcg/24h, respectively (р = 0.007). 11β-OH-An urinary excretion in ACC patients without CS was higher than in ACA patients with CS: 1170 [806; 1266] и 602 [320; 739] mcg/24h (р = 0.007). The NLR cut-off value for adrenal mass malignancy in patients with CS exceeded 2.72 (sensitivity 90.0%, specificity 80.0%), and for the patients without hypercortisolism was above 1.92 (sensitivity 71.4%, specificity 100.0%). \u0000Conclusion: This is the first association identification between NLR, which is the marker of systemic inflammation, inflammation, and urinary excretion of 11β-OH-An, a metabolite of 11-hydroxyandrostenedione (a member of 11-oxygenated androgen family). This extends our understanding of the impact of hormonal activity of adrenal mass cells on the immune system.","PeriodicalId":502611,"journal":{"name":"Almanac of Clinical Medicine","volume":"37 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140724268","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}
引用次数: 0
Clinical markers of cognitive impairment in patients with chronic heart failure of ischemic origin during out-patient regular follow-up: a cross-sectional study 缺血性慢性心力衰竭患者在门诊定期随访期间认知障碍的临床指标:一项横断面研究
Pub Date : 2024-04-01 DOI: 10.18786/2072-0505-2024-52-003
O. Efremova, O. V. Dudchenko, L. A. Kamyshnikova, T. N. Proskokova, O. A. Bolkhovitina, Ekaterina V. Lysenko
Background: Cognitive impairment (CI) is present in 25–50% of chronic heart failure (CHF) patients. Doctors who monitor patients with cardiovascular disorders do not have clearly set criteria for their referral to a neurologist in case of suspected CI. Therefore, CHF patients do not receive treatment for CI on time. Aim: To identify significant clinical markers of CI in patients with CHF of ischemic origin. Materials and methods: This cross-sectional cohort study included 134 patients with CHF of ischemic origin (mean age 63.36 ± 10.63 years; men, 76.12%), who were regularly monitored in a municipal polyclinic. All patients were tested for CI with the Montreal Cognitive Assessment Scale (MoCA); basic hemodynamic parameters, lipid profile, brain natriuretic peptide (NT-proBNP) were assessed, and triglyceride-glucose index (TyG) and body mass index (BMI) were calculated. Cardio-ankle vascular index (CAVI) was measured, echocardiography and a 6-minute walk test (SMWТ) were performed and past history of CHF, arterial hypertension (AH) and diabetes mellitus (DM) was collected. Results: CI (MoCA score ≤ 25) was detected in 85 (63.43%) outpatients with CHF of ischemic origin; the group without CI (MoCA score 26) included 49 (36.67%) patients. There were significant correlations between MoCA and CAVI scores (partial correlation coefficient, r = -0.802, p 0.001; adjusted squared multiple correlation coefficient (adj. R2) = 0.881, p 0.001), MoCA and TyG (r = -0.357, p = 0.029; adj. R2 = 0.363, p 0.001), MoCA and SMWТ (r = -0.211, p = 0.037; adj. R2 = 0.696, p 0.001). The multivariate test for significance of planned comparisons between CAVI and MoCA scores (Wilks' lambda) was 0.005 (F = 4.74; p 0.001). Conclusion: CAVI, TyG and SMWТ values are the clinical markers of CI in patients with CHF of ischemic origin. There is a direct association between increased CAVI and the presence of CI, regardless of age, lipid metabolism parameters, structural and functional heart parameters, CHF duration, AH and DM. Identification of these markers could be an indication for an in-depth assessment of CHF patients by a neurologist.
背景:25%-50%的慢性心力衰竭(CHF)患者存在认知障碍(CI)。监测心血管疾病患者的医生并没有明确的标准,要求他们在怀疑出现 CI 时将患者转介给神经科医生。因此,CHF 患者无法及时接受 CI 治疗。目的:确定缺血性 CHF 患者 CI 的重要临床指标。材料和方法:这项横断面队列研究纳入了 134 名缺血性慢性心力衰竭患者(平均年龄为 63.36 ± 10.63 岁;男性占 76.12%),他们在一家市级综合医院接受定期监测。所有患者都接受了蒙特利尔认知评估量表(MoCA)的 CI 测试;评估了基本血液动力学参数、血脂状况、脑钠肽(NT-proBNP),并计算了甘油三酯-葡萄糖指数(TyG)和体重指数(BMI)。测量了心踝关节血管指数(CAVI),进行了超声心动图检查和 6 分钟步行测试(SMWТ),并收集了慢性心力衰竭、动脉高血压(AH)和糖尿病(DM)的既往史。结果显示85例(63.43%)缺血性CHF门诊患者检测到CI(MoCA评分≤25分);无CI(MoCA评分26分)组包括49例(36.67%)患者。MoCA 评分与 CAVI 评分之间存在明显的相关性(部分相关系数 r = -0.802,P 0.001;调整后的平方多重相关系数 (adj. R2) = 0.881)。R2)= 0.881,p 0.001)、MoCA 和 TyG(r = -0.357,p = 0.029;adj. R2 = 0.363,p 0.001)、MoCA 和 SMWТ(r = -0.211,p = 0.037;adj. R2 = 0.696,p 0.001)。CAVI 和 MoCA 评分之间计划比较的多变量显著性检验(Wilks' lambda)为 0.005 (F = 4.74; p 0.001)。结论CAVI、TyG和SMWТ值是缺血性CHF患者CI的临床标志。无论年龄、脂代谢参数、心脏结构和功能参数、CHF 持续时间、AH 和 DM 如何,CAVI 升高与 CI 存在直接关联。这些标志物的识别可作为神经科医生对 CHF 患者进行深入评估的指征。
{"title":"Clinical markers of cognitive impairment in patients with chronic heart failure of ischemic origin during out-patient regular follow-up: a cross-sectional study","authors":"O. Efremova, O. V. Dudchenko, L. A. Kamyshnikova, T. N. Proskokova, O. A. Bolkhovitina, Ekaterina V. Lysenko","doi":"10.18786/2072-0505-2024-52-003","DOIUrl":"https://doi.org/10.18786/2072-0505-2024-52-003","url":null,"abstract":"Background: Cognitive impairment (CI) is present in 25–50% of chronic heart failure (CHF) patients. Doctors who monitor patients with cardiovascular disorders do not have clearly set criteria for their referral to a neurologist in case of suspected CI. Therefore, CHF patients do not receive treatment for CI on time. \u0000Aim: To identify significant clinical markers of CI in patients with CHF of ischemic origin. \u0000Materials and methods: This cross-sectional cohort study included 134 patients with CHF of ischemic origin (mean age 63.36 ± 10.63 years; men, 76.12%), who were regularly monitored in a municipal polyclinic. All patients were tested for CI with the Montreal Cognitive Assessment Scale (MoCA); basic hemodynamic parameters, lipid profile, brain natriuretic peptide (NT-proBNP) were assessed, and triglyceride-glucose index (TyG) and body mass index (BMI) were calculated. Cardio-ankle vascular index (CAVI) was measured, echocardiography and a 6-minute walk test (SMWТ) were performed and past history of CHF, arterial hypertension (AH) and diabetes mellitus (DM) was collected. \u0000Results: CI (MoCA score ≤ 25) was detected in 85 (63.43%) outpatients with CHF of ischemic origin; the group without CI (MoCA score 26) included 49 (36.67%) patients. There were significant correlations between MoCA and CAVI scores (partial correlation coefficient, r = -0.802, p 0.001; adjusted squared multiple correlation coefficient (adj. R2) = 0.881, p 0.001), MoCA and TyG (r = -0.357, p = 0.029; adj. R2 = 0.363, p 0.001), MoCA and SMWТ (r = -0.211, p = 0.037; adj. R2 = 0.696, p 0.001). The multivariate test for significance of planned comparisons between CAVI and MoCA scores (Wilks' lambda) was 0.005 (F = 4.74; p 0.001). \u0000Conclusion: CAVI, TyG and SMWТ values are the clinical markers of CI in patients with CHF of ischemic origin. There is a direct association between increased CAVI and the presence of CI, regardless of age, lipid metabolism parameters, structural and functional heart parameters, CHF duration, AH and DM. Identification of these markers could be an indication for an in-depth assessment of CHF patients by a neurologist.","PeriodicalId":502611,"journal":{"name":"Almanac of Clinical Medicine","volume":"356 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140779512","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}
引用次数: 0
Shear wave elastography values of thrombus in patients with lower extremity deep vein thrombosis for pulmonary embolism detection: the ROC analysis 用于肺栓塞检测的下肢深静脉血栓患者血栓剪切波弹性成像值:ROC 分析
Pub Date : 2024-03-18 DOI: 10.18786/2072-0505-2024-52-002
E. G. Akramova, Ekaterina P. Kapustina
Rationale: Thrombosis of the iliac (IV) and femoral veins (FV) is one of the most common causes of pulmonary embolism (PE). Modern ultrasound scanners are equipped with the technology of shear wave elastography, which gives a quantitative assessment of thrombus stiffness by Young's modulus reconstruction. However, the lack of convincing data on the role of thrombus stiffness for clinical manifestations of PE hinders the active use of shear wave elastography to diagnose the risk of embolism. Aim: To determine the threshold values of the venous thrombus Young’s modulus for deep venous thrombosis (DVT) of the lower extremities complicated by massive PE and/or PE with acute cor pulmonale (ACP). Materials and methods: This was a single center cross-sectional study in 101 patients who were hospitalized with the diagnosis of acute (duration of less than 2 weeks) or subacute (from 2 weeks to 3 months) IV and FV thrombosis. Doppler ultrasound of the lower extremity veins and echocardiography were done in all patients. Forty eight patients with clinical signs of PE had chest computed tomography. The venous thrombus stiffness was assessed by shear wave elastography with the Young's modulus reconstruction. We performed the ROC analysis for mean values of the Young's modulus for proximal segments of IV and FV thrombi in patients with DVT and massive PE and ACP. Results: PE was diagnosed in 40.6% (26/64) of the patients hospitalized with acute DVT and in 54.1% (20/37) of those with subacute DVT. Echocardiographic signs of ACP in massive PE were found in 47.4% (9/19) of the patients, in submassive and minor PE in 55.6% (15/27). In DVT complicated with PE, the ROC analysis of the shear wave elastography results gave the following threshold values of the mean Young’s modulus for the proximal thrombus segment: for acute IV thrombosis + PE and ACP, ≤ 16.7 kPa (AUC 0.714, sensitivity 100%, specificity 42.1%), in subacute IV thrombosis + PE and APC, ≤ 23.7 kPa (0.939, 100 and 90.9%, respectively), in acute FV thrombosis + massive PE, ≥ 9.5 kPa (0.706, 100 and 50%, respectively), in subacute FV thrombosis + massive PE, ≥ 24.4 kPa (0.550, 60.0 and 68.8%, respectively). Conclusion: Shear wave elastography of deep vein thrombi of the lower extremities makes it possible to identify patients with PE and ACP during acute and subacute IV thrombosis and to determine massive PE in acute FV thrombosis.
原理:髂静脉(IV)和股静脉(FV)血栓形成是肺栓塞(PE)最常见的原因之一。现代超声扫描仪配备了剪切波弹性成像技术,可通过杨氏模量重建对血栓的硬度进行定量评估。然而,由于缺乏关于血栓僵硬度对 PE 临床表现的作用的令人信服的数据,因此无法积极使用剪切波弹性成像来诊断栓塞风险。目的:确定下肢深静脉血栓形成(DVT)并发大面积 PE 和/或 PE 并发急性肺栓塞(ACP)时静脉血栓杨氏模量的阈值。材料和方法:这是一项单中心横断面研究,研究对象为 101 名被诊断为急性(病程少于 2 周)或亚急性(2 周至 3 个月)静脉血栓和深静脉血栓的住院患者。所有患者均接受了下肢静脉多普勒超声检查和超声心动图检查。48名有 PE 临床症状的患者接受了胸部计算机断层扫描。通过杨氏模量重建剪切波弹性成像技术评估了静脉血栓的硬度。我们对深静脉血栓、大面积 PE 和 ACP 患者 IV 和 FV 血栓近段的杨氏模量平均值进行了 ROC 分析。结果显示急性深静脉血栓形成住院患者中有 40.6%(26/64)被诊断为 PE,亚急性深静脉血栓形成住院患者中有 54.1%(20/37)被诊断为 PE。47.4% 的患者(9/19)在大面积 PE 中发现了 ACP 超声心动图征象,55.6% 的患者(15/27)在亚大面积和轻微 PE 中发现了 ACP 超声心动图征象。在伴有 PE 的深静脉血栓中,剪切波弹性成像结果的 ROC 分析得出了血栓近端段平均杨氏模量的以下阈值:急性静脉血栓 + PE 和 ACP,≤ 16.7 kPa(AUC 0.714,敏感性 100%,特异性 42.1%),亚急性静脉血栓 + PE 和 APC,≤ 23.7 kPa(分别为 0.939、100 和 90.9%),急性 FV 血栓 + 大量 PE,≥ 9.5 kPa(分别为 0.706、100 和 50%),亚急性 FV 血栓 + 大量 PE,≥ 24.4 kPa(分别为 0.550、60.0 和 68.8%)。结论对下肢深静脉血栓进行剪切波弹性成像可识别急性和亚急性静脉血栓形成时的 PE 和 ACP 患者,并确定急性静脉血栓形成时的大面积 PE。
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引用次数: 0
Neutrophil extracellular traps: molecular and cellular mechanisms of formation, role in the development of placental disorders and preeclampsia 中性粒细胞胞外捕获物:形成的分子和细胞机制,在胎盘疾病和子痫前期发病中的作用
Pub Date : 2024-02-11 DOI: 10.18786/2072-0505-2023-51-050
S. A. Gasparyan, A. G. Topuzov, I. A. Orfanova, S. M. Akhmedova
The review summarizes current understanding of neutrophil extracellular traps (NETs) and their role in the development of inflammation and thrombus formation during physiological and complicated pregnancy. The main initiation factors and molecular and cellular reactions leading to the generation of NETs are described. During gestation, various pregnancy-associated triggers (cytokines, hormones, colony-stimulating factors, etc.) contribute to increased activity of innate immune factors associated with the processes of neutrophil migration into gestational tissues, adhesion, degranulation, phagocytosis and release of extracellular neutrophil traps. It has been established that the uncontrolled aberrant generation of NETs, as well as their products, including reactive oxygen species, can exert a cytotoxic effect on maternal cells and tissues, adverse fetal effects and contribute to placental damage, resulting in such pregnancy complications as placental disorders, immunothrombosis and preeclampsia. The emergence of new data on the morphological and functional characteristics of the cellular component of innate immunity necessitates their advanced research with consideration of the functional potential and conditions for NETs formation, clarification and determination of their pathophysiological significance in normal and complicated pregnancy. It seems promising to study the possibility of assessment of the DNA traps levels for early diagnosis and prognosis of gestational complications, as well as for the development of new treatment strategies including targeted therapy.
这篇综述总结了目前对中性粒细胞胞外捕获物(NETs)及其在生理性妊娠和复杂妊娠期间炎症发展和血栓形成过程中作用的认识。文中描述了导致 NETs 生成的主要启动因子以及分子和细胞反应。在妊娠期间,各种与妊娠相关的诱发因素(细胞因子、激素、集落刺激因子等)会增加与中性粒细胞迁移到妊娠组织、粘附、脱颗粒、吞噬和释放细胞外中性粒细胞捕获物等过程相关的先天性免疫因子的活性。已经证实,不受控制的嗜中性粒细胞的异常生成及其产物,包括活性氧,可对母体细胞和组织产生细胞毒性作用,对胎儿产生不利影响,并造成胎盘损伤,导致胎盘功能紊乱、免疫血栓和子痫前期等妊娠并发症。有关先天性免疫细胞成分的形态和功能特征的新数据的出现,要求对其进行深入研究,考虑 NETs 的功能潜力和形成条件,阐明并确定其在正常妊娠和复杂妊娠中的病理生理意义。研究对 DNA 陷阱水平进行评估的可能性似乎很有希望,以用于妊娠并发症的早期诊断和预后,以及开发新的治疗策略,包括靶向治疗。
{"title":"Neutrophil extracellular traps: molecular and cellular mechanisms of formation, role in the development of placental disorders and preeclampsia","authors":"S. A. Gasparyan, A. G. Topuzov, I. A. Orfanova, S. M. Akhmedova","doi":"10.18786/2072-0505-2023-51-050","DOIUrl":"https://doi.org/10.18786/2072-0505-2023-51-050","url":null,"abstract":"The review summarizes current understanding of neutrophil extracellular traps (NETs) and their role in the development of inflammation and thrombus formation during physiological and complicated pregnancy. The main initiation factors and molecular and cellular reactions leading to the generation of NETs are described. During gestation, various pregnancy-associated triggers (cytokines, hormones, colony-stimulating factors, etc.) contribute to increased activity of innate immune factors associated with the processes of neutrophil migration into gestational tissues, adhesion, degranulation, phagocytosis and release of extracellular neutrophil traps. It has been established that the uncontrolled aberrant generation of NETs, as well as their products, including reactive oxygen species, can exert a cytotoxic effect on maternal cells and tissues, adverse fetal effects and contribute to placental damage, resulting in such pregnancy complications as placental disorders, immunothrombosis and preeclampsia. The emergence of new data on the morphological and functional characteristics of the cellular component of innate immunity necessitates their advanced research with consideration of the functional potential and conditions for NETs formation, clarification and determination of their pathophysiological significance in normal and complicated pregnancy. It seems promising to study the possibility of assessment of the DNA traps levels for early diagnosis and prognosis of gestational complications, as well as for the development of new treatment strategies including targeted therapy.","PeriodicalId":502611,"journal":{"name":"Almanac of Clinical Medicine","volume":"44 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139845396","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}
引用次数: 0
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Almanac of Clinical Medicine
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