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The association between exosomal proteins and the efficacy of thermoradiochemotherapy in overweight/obese rectal cancer patients: a pilot prospective cohort study 超重/肥胖直肠癌患者体内外泌体蛋白与热放射化学疗法疗效之间的关系:一项前瞻性队列试点研究
Pub Date : 2024-07-05 DOI: 10.18786/2072-0505-2024-52-013
N. Yunusova, D. Svarovsky, Artem I. Konovalov, D. Kostromitsky, I. V. Kondakova, A. Usova, I. Frolova, Evgeniya A. Sidenko, G. Kakurina, Lyubov V. Gerdt, A. Grigor’eva, Zhanna A. Startseva
Background: Overweight and especially obesity are associated with the risk of the development and progression of colorectal cancer. It can be assumed that there are multifaceted interactions between the tumor and adipose tissue during anti-tumor treatment. Cancer cells secrete exosomes, extracellular vesicles affecting the microenvironment of the tumor and promoting its progression or regression. The presence of transcription/translation/folding factors (heat shock proteins (HSPs), matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in exosomes secreted by irradiated cells and cells exposed to hyperthermia, indicates the cell adaptation to the thermal and radiation stress. Aim: To analyze the MMPs, TIMP1, and HSPs on CD9-positive (CD9+) exosomes, as well as on exosomes of adipocytic origin (FABP4+) in rectal cancer patients with overweight/obesity under thermoradiochemotherapy (TRCT) and their association with the immediate treatment efficacy. Methods: Since 2021, 20 patients (of those 8 men; median age 59.0 [52.0; 63.0] years, median body mass index 29.6 [28.5; 33.1] kg/m2) with morphologically verified rectal cancer (T3-4N0M0 and T3-4N1M0, differentiation grade G1–G3) have been participating in the study. They were treated with TRCT: external gamma therapy (2 Gy, 1 fraction/day, 5 days/week, total focal dose 54 Gy), chemotherapy with capecitabine (825 mg/m2 twice daily) combined with local hyperthermia (42–44 °C, 60 min, 3 times/week, 10 sessions). The TRCT efficacy was assessed by RECIST 1.1 and ESGAR criteria. Blood samples for exosomes were taken from the patients at baseline (point 1), in the middle of the treatment course (point 2), at 6 to 10 weeks after the end of TRCT (point 3), and at 6 months after point 1 (point 4). Small extracellular vesicles were isolated from plasma by ultrafiltration with double ultracentrifugation. The isolated exosomes were characterized by transmission electronic microscopy, flow cytometry and nanoparticle trajectory analysis (NTA). Results: TRCT resulted in complete tumor regression in 13/20 of the rectal cancer patients and partial regression or stabilization in 7/20. Four subpopulations of CD9+ and FABP4+ exosomes associated with the TRCT efficacy were identified (CD9+MMP2+, СD9+MMP2+9+TIMP1+, СD9+MMP2+9+TIMP1-, and FABP4+MMP2+9-TIMP1+). Compared to the CD9+ exosomes, the adipocytic vesicles had higher MMP2 expression (p = 0.026); however, the adipocyte vesicles subpopulation were virtually free of vesicles with combined MMP2 and MMP9 gelatinase expression. The HSPs expression by circulating exosomes at various TRCT steps was associated neither with direct treatment efficacy nor with the vesicle type. Conclusion: The expression of MMPs and TIMP1 on CD9+ and FABP4+ exosomes is associated with TRCT efficacy. In the future, vesicular markers could be used to build prognostic models, to identify patient groups with an unfavorable prognosis, and to personalize treatment and follow-up.
背景:超重尤其是肥胖与结直肠癌的发生和发展风险有关。可以认为,在抗肿瘤治疗过程中,肿瘤与脂肪组织之间存在着多方面的相互作用。癌细胞会分泌外泌体,这种细胞外囊泡会影响肿瘤的微环境,促进肿瘤的发展或消退。辐照细胞和暴露于高热的细胞分泌的外泌体中存在转录/翻译/折叠因子(热休克蛋白(HSPs)、基质金属蛋白酶(MMPs)及其组织抑制剂(TIMPs)),表明细胞对热和辐射应激的适应。目的:分析接受热放射化学治疗(TRCT)的超重/肥胖直肠癌患者 CD9 阳性(CD9+)外泌体以及脂肪细胞来源(FABP4+)外泌体上的 MMPs、TIMP1 和 HSPs 及其与即时疗效的关系。研究方法自 2021 年以来,共有 20 名形态学确诊为直肠癌(T3-4N0M0 和 T3-4N1M0,分化等级 G1-G3)的患者(其中 8 名男性,中位年龄 59.0 [52.0; 63.0] 岁,中位体重指数 29.6 [28.5; 33.1] kg/m2)参与了研究。他们接受了TRCT治疗:体外伽马治疗(2 Gy,1次/天,5天/周,病灶总剂量54 Gy)、卡培他滨化疗(825 mg/m2,每天2次)和局部热疗(42-44 °C,60分钟,3次/周,10次疗程)。TRCT 疗效根据 RECIST 1.1 和 ESGAR 标准进行评估。分别在基线(第1点)、疗程中期(第2点)、TRCT结束后6至10周(第3点)和第1点后6个月(第4点)抽取患者血液样本检测外泌体。通过超滤和双重超速离心从血浆中分离出小细胞外囊泡。通过透射电子显微镜、流式细胞术和纳米粒子轨迹分析(NTA)对分离出的外泌体进行表征。结果显示13/20的直肠癌患者通过TRCT治疗后肿瘤完全消退,7/20的患者肿瘤部分消退或稳定。发现了与 TRCT 疗效相关的 CD9+ 和 FABP4+ 外泌体的四个亚群(CD9+MMP2+、СD9+MMP2+9+TIMP1+、СD9+MMP2+9+TIMP1- 和 FABP4+MMP2+9-TIMP1+)。与 CD9+ 外泌体相比,脂肪细胞囊泡的 MMP2 表达更高(p = 0.026);然而,脂肪细胞囊泡亚群中几乎不存在同时表达 MMP2 和 MMP9 明胶酶的囊泡。循环外泌体在不同 TRCT 阶段的 HSPs 表达既与直接治疗效果无关,也与囊泡类型无关。结论CD9+和FABP4+外泌体上MMPs和TIMP1的表达与TRCT疗效有关。未来,囊泡标记物可用于建立预后模型,识别预后不良的患者群体,并进行个性化治疗和随访。
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引用次数: 0
Del Nido versus cold crystalloid cardioplegia for myocardial protection during ventricular septal defect repair in children under one year of age: a prospective randomized trial 在一岁以下儿童室间隔缺损修补术中使用德尔尼多与冷晶体液心脏麻痹术保护心肌:一项前瞻性随机试验
Pub Date : 2024-02-28 DOI: 10.18786/2072-0505-2024-52-001
P. V. Lazarkov, Ekaterina N. Orekhova, O. Khlynova
Rationale: The choice of strategy for myocardial protection during procedures with cardiopulmonary bypass and cardioplegic arrest in children is not regulated by clinical guidelines due to insufficient data from clinical studies. The issue of methods to assess myocardial injury remains unresolved. Aim: To assess the frequency and specifics of the development of intraoperative myocardial injury syndrome in children of the first year of life with ventricular septal defect depending on the strategy for cardioplegia. Materials and methods: In a single center, prospective, randomized controlled trial we compared two cardioplegia strategies during surgical closure of ventricular septal defect in infants aged from 1 to 12 months: del Nido blood cardioplegia (n = 102) and cold crystalloid cardioplegia with Custodiol solution (n = 102). The primary endpoint was a persistent over 10-fold increase above the upper limit of the normal in the plasma concentration of high-sensitivity troponin I at 6 hours after surgery persisting after 24 hours. The secondary combined endpoint was myocardial damage verified by persistent increase in troponin I level more than 10-fold above the upper limit of the normal, persisting at 6 and 24 hours, accompanied by new pathological Q waves, acute complete left bundle branch block, abnormalities of the end part of the ventricular complex on the electrocardiography (ST segment elevation 1 mm or ST depression of 1 mm in more than 2 adjacent leads), and a decrease in the global longitudinal strain of the left ventricle by 50% from the initial value at 6 hours after surgery. Results: In 53/204 (26%) patients, the increase in troponin I persisted at 24 hours after the surgery and was associated with electrocardiography abnormalities, changes in the parameters of left ventricle longitudinal mechanics, and in some cases required greater inotropic support. By the end of the 1st postoperative 24 hours, the longitudinal strain of the left ventricle showed more negative changes over time in the Custodiol group compared to that in the del Nido group (-10 [-14.1; -6.27] versus -14.8 [- 16.5; -10]%; p 0.0001). The same was true for the left ventricle global strain rate (-0.71 [-0.9; -0.52] s-1 in the del Nido group and -0.57 [-0.760; - 0.44] s-1 in the Custodiol group; p = 0.0049). The primary endpoint was achieved by 21 (20.6%) and 55 (53.9%) patients in the del Nido and Custodiol groups, respectively (p = 0.032). The combined endpoint in the Custodiol group was achieved by 34 (33.3%) versus 19 (18.6%) patients in the del Nido group (p = 0.049, χ2 = 3.875, DF = 1, φ = 0.191). Conclusion: Del Nido blood cardioplegia compared to cold crystalloid cardioplegia with Custodiol has advantages in terms of preventing intraoperative myocardial damage and minimizing its severity. When assessing myocardial damage, such indicators as left ventricle global longitudinal strain and left ventricle global strain rate are informative, along with an increase
理由:由于临床研究数据不足,在对儿童进行心肺旁路和心脏麻痹停跳手术时,心肌保护策略的选择并没有得到临床指南的规范。评估心肌损伤的方法问题仍未解决。目的:评估室间隔缺损患儿术中发生心肌损伤综合征的频率和具体情况,这取决于心脏麻痹的策略。材料和方法:在一项单中心、前瞻性、随机对照试验中,我们比较了 1 到 12 个月大婴儿室间隔缺损手术封堵术中的两种心脏麻痹策略:Del Nido 血液心脏麻痹(102 人)和 Custodiol 溶液冷晶体液心脏麻痹(102 人)。主要终点是术后 6 小时血浆中高敏肌钙蛋白 I 的浓度比正常值上限持续增加 10 倍以上,且在 24 小时后仍持续增加。次要合并终点为心肌损伤,即肌钙蛋白 I 水平持续升高,超过正常值上限 10 倍以上,且在 6 小时和 24 小时内持续存在,同时伴有新的病理性 Q 波、急性完全性左束支传导阻滞、心电图上心室复极末端异常(ST 段抬高 1 毫米或相邻 2 个以上导联的 ST 段压低 1 毫米),以及左心室整体纵向应变比术后 6 小时的初始值降低 50%。结果:在 53/204 例(26%)患者中,肌钙蛋白 I 的升高在术后 24 小时仍持续存在,并且与心电图异常、左室纵向力学参数变化有关,在某些情况下需要更多的肌力支持。在术后 24 小时内,Custodiol 组的左心室纵向应变与 del Nido 组相比出现了更多的负变化(-10 [-14.1; -6.27] 对 -14.8 [-16.5; -10]%;P 0.0001)。左心室整体应变率也是如此(del Nido 组为 -0.71 [-0.9; -0.52] s-1,Custodiol 组为 -0.57 [-0.760; - 0.44] s-1;P = 0.0049)。德尔尼多组和 Custodiol 组分别有 21 名(20.6%)和 55 名(53.9%)患者达到主要终点(p = 0.032)。Custodiol 组有 34 名(33.3%)患者达到了综合终点,而 del Nido 组只有 19 名(18.6%)患者达到了综合终点(p = 0.049,χ2 = 3.875,DF = 1,φ = 0.191)。结论德尔尼多血液心脏麻痹与使用 Custodiol 的低温晶体液心脏麻痹相比,在预防术中心肌损伤和减轻损伤严重程度方面具有优势。在评估心肌损伤时,左心室整体纵向应变和左心室整体应变率等指标以及肌钙蛋白 I 水平的升高都具有参考价值。
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引用次数: 0
Efficacy and safety of negative wound pressure in the treatment of surgical complications after radical cystectomy: a retrospective cohort study 伤口负压治疗根治性膀胱切除术后手术并发症的有效性和安全性:一项回顾性队列研究
Pub Date : 2023-12-28 DOI: 10.18786/2072-0505-2023-51-039
Mariya V. Berkut, A. M. Belyaev, Nikolay F. Krotov, Marina E. Karaseva, Aleksander K. Nosov
Background: Negative pressure wound treatment (NPWT) is a relatively new, but promising method for management of surgical site infection (SSI). The literature data on the use of NPWT for complications in oncology surgery, and after radical cystectomy (RC) in particular, is scarce. Aim: To evaluate the short-term results of NPWT dressings in the management of SSI after RC. Materials and methods: We retrospectively analyzed data from 446 patients who had RC with various uroderivation types in the Department of Oncourology of the N. N. Petrov National Medical Research Center of Oncology from January 2012 to December 2021. A total of 62 cases of SSI emerging up to day 30 after RC were identified with complete data. Thirty six (36) cases of SSI were managed according to standard procedures, and 26 patients with SSI were treated with NPWT (VivanoTec® S 042) at constant negative pressure mode. The physical condition of the patients before RC was assessed according to the American Society of Anesthesiology (ASA) classification, and the severity of the patient's condition at SSI diagnosis within APACHE II scale. The following parameters were also analyzed: body mass index, median number of days in the hospital, number of program wound sanitations (surgical debridement) or frequency of changing NPWT dressings, changes over time in C-reactive protein and leukocyte index of intoxication, and events of clinical interest (intestinal fistulas and lateralization of the median wound margins, hernias). Results: Most cases of post-RC SSIs were identified in men (57/62, 91.93%). The standard management and NPWT study groups were well balanced for age, body mass index, and ASA physical status. The median time from the first surgical debridement of the wound to its closure was significantly shorter in the standard surgical management group: 4 days (0; 8.75) versus 8.5 days (3.25; 12.0) in the NPWT group (p = 0.026). However, this did not negatively affect the length of hospitalization (28.08 ± 12.80 and 30.03 ± 16.27 days, respectively, p = 0.599). The 30-day mortality rates were not significantly different between the groups (p = 0.137). In our series with NPWT dressings, there were no cases of intestinal fistulas in the early and late postoperative periods. Conclusion: Negative pressure wound treatment is a safe and effective method of SSI management. It is not inferior to the generally accepted treatment standard with surgical wound debridement, staged sanitations or dressings. NPWT dressings allow for early primary muscular-fascial closure of the abdominal cavity and does not increase the duration of hospital stay, postoperative death rates and the risk of intestinal fistulas.
背景:伤口负压疗法(NPWT)是一种相对较新但很有前景的治疗手术部位感染(SSI)的方法。有关使用 NPWT 治疗肿瘤手术并发症,尤其是根治性膀胱切除术(RC)后并发症的文献资料很少。 目的:评估 NPWT 敷料治疗 RC 术后 SSI 的短期效果。 材料与方法:我们回顾性分析了 2012 年 1 月至 2021 年 12 月期间在 N. N. 彼得罗夫国立肿瘤医学研究中心肿瘤科接受各种尿道憩室手术的 446 例患者的数据。共有 62 例在 RC 术后第 30 天内出现的 SSI 病例被确认并提供了完整的数据。36例SSI患者按照标准程序进行了处理,26例SSI患者在恒定负压模式下接受了NPWT(VivanoTec® S 042)治疗。根据美国麻醉学会(ASA)的分类评估了患者在进行 RC 之前的身体状况,并根据 APACHE II 分级评估了患者在确诊 SSI 时的病情严重程度。此外,还分析了以下参数:体重指数、住院天数中位数、伤口清创次数(手术清创)或更换 NPWT 敷料的频率、C 反应蛋白和白细胞中毒指数随时间的变化,以及临床关注的事件(肠瘘、伤口正中边缘侧移、疝气)。 结果:大多数 RC 术后 SSI 病例为男性(57/62,91.93%)。标准管理组和 NPWT 研究组在年龄、体重指数和 ASA 身体状况方面非常均衡。标准手术治疗组从首次手术清创到伤口闭合的中位时间明显更短:4 天(0;8.75),而 NPWT 组为 8.5 天(3.25;12.0)(P = 0.026)。然而,这并没有对住院时间产生负面影响(分别为 28.08 ± 12.80 天和 30.03 ± 16.27 天,p = 0.599)。两组的 30 天死亡率无明显差异(p = 0.137)。在我们使用 NPWT 敷料的系列中,术后早期和晚期均未出现肠瘘病例。 结论负压伤口治疗是一种安全有效的 SSI 治疗方法。它并不比外科伤口清创、分阶段消毒或敷料等公认的治疗标准逊色。负压伤口敷料可使腹腔的肌肉筋膜尽早闭合,不会延长住院时间、增加术后死亡率和肠瘘风险。
{"title":"Efficacy and safety of negative wound pressure in the treatment of surgical complications after radical cystectomy: a retrospective cohort study","authors":"Mariya V. Berkut, A. M. Belyaev, Nikolay F. Krotov, Marina E. Karaseva, Aleksander K. Nosov","doi":"10.18786/2072-0505-2023-51-039","DOIUrl":"https://doi.org/10.18786/2072-0505-2023-51-039","url":null,"abstract":"Background: Negative pressure wound treatment (NPWT) is a relatively new, but promising method for management of surgical site infection (SSI). The literature data on the use of NPWT for complications in oncology surgery, and after radical cystectomy (RC) in particular, is scarce. Aim: To evaluate the short-term results of NPWT dressings in the management of SSI after RC. Materials and methods: We retrospectively analyzed data from 446 patients who had RC with various uroderivation types in the Department of Oncourology of the N. N. Petrov National Medical Research Center of Oncology from January 2012 to December 2021. A total of 62 cases of SSI emerging up to day 30 after RC were identified with complete data. Thirty six (36) cases of SSI were managed according to standard procedures, and 26 patients with SSI were treated with NPWT (VivanoTec® S 042) at constant negative pressure mode. The physical condition of the patients before RC was assessed according to the American Society of Anesthesiology (ASA) classification, and the severity of the patient's condition at SSI diagnosis within APACHE II scale. The following parameters were also analyzed: body mass index, median number of days in the hospital, number of program wound sanitations (surgical debridement) or frequency of changing NPWT dressings, changes over time in C-reactive protein and leukocyte index of intoxication, and events of clinical interest (intestinal fistulas and lateralization of the median wound margins, hernias). Results: Most cases of post-RC SSIs were identified in men (57/62, 91.93%). The standard management and NPWT study groups were well balanced for age, body mass index, and ASA physical status. The median time from the first surgical debridement of the wound to its closure was significantly shorter in the standard surgical management group: 4 days (0; 8.75) versus 8.5 days (3.25; 12.0) in the NPWT group (p = 0.026). However, this did not negatively affect the length of hospitalization (28.08 ± 12.80 and 30.03 ± 16.27 days, respectively, p = 0.599). The 30-day mortality rates were not significantly different between the groups (p = 0.137). In our series with NPWT dressings, there were no cases of intestinal fistulas in the early and late postoperative periods. Conclusion: Negative pressure wound treatment is a safe and effective method of SSI management. It is not inferior to the generally accepted treatment standard with surgical wound debridement, staged sanitations or dressings. NPWT dressings allow for early primary muscular-fascial closure of the abdominal cavity and does not increase the duration of hospital stay, postoperative death rates and the risk of intestinal fistulas.","PeriodicalId":7638,"journal":{"name":"Almanac of Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139152358","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
Resistance to dopamine agonists in the treatment of prolactinomas: diagnostic criteria, mechanisms and ways to overcome it 多巴胺受体激动剂治疗泌乳素瘤的抗药性:诊断标准、机制和克服方法
Pub Date : 2023-12-26 DOI: 10.18786/2072-0505-2023-51-040
Irena A. Ilovayskaya, G. R. Vagapova
The priority treatment approach for prolactinomas is therapy with dopamine agonists, which allows for elimination of clinical symptoms, normalization of prolactin levels, reduction of the adenoma size and prevention of metabolic abnormalities in the majority of patients. Nevertheless, 10 to 20% of patients are resistant to dopamine agonists. The aim of this review is to analyze literature data on the source mechanisms and potential ways to overcome the resistance of prolactinomas to dopamine agonists. The criteria of a prolactinoma's resistance to dopamine agonists are as follows: 1) no normalization of serum prolactin levels and/or 2) no reduction of the adenoma volume by at least 50% after treatment of bromocriptine at a dose of ≤ 15 mg/day or cabergoline at a dose of ≤ 3 mg/week for at least 6 months. Full resistance is characterized by both no biochemical and no anti-tumor effects, whereas in partial resistance, prolactin levels can be decreased but not normalized, or the adenoma size can be reduced by less than 50% of the initial. The clinical and morphological predictors of prolactinoma resistance to dopamine agonists are male gender, young age, big size of the adenoma and its invasion into the sinus cavernosus, hypointensive and/or heterogeneous MRI signal on Т2 weighed images, and cystic components within the tumor. The main molecular genetic markers are: decreased expression of dopamine and estrogen receptors, higher proliferation index Ki-67 ≤ 3%, as well as the MENIN, AIP, SF3B1, PRDM2 gene mutations. In case of resistance to bromocriptine, it is recommended to switch the patient to cabergoline. In partial resistance to standard doses of cabergoline, it is possible to increase the dose up to a maximally tolerated. Neurosurgery and/or radiation surgery is recommended in cases of full resistance to dopamine agonists or an aggressive tumor. For very aggressive/malignant tumors, or in the event of their extended growth after surgery, temozolomide is recommended as adjuvant therapy.
多巴胺受体激动剂是治疗泌乳素瘤的首选方法,它可以消除大多数患者的临床症状,使泌乳素水平恢复正常,缩小腺瘤体积,防止代谢异常。尽管如此,仍有 10% 至 20% 的患者对多巴胺受体激动剂产生耐药性。本综述旨在分析有关催乳素瘤对多巴胺激动剂耐药的来源机制和潜在克服方法的文献资料。泌乳素瘤对多巴胺激动剂耐药的标准如下:1)血清泌乳素水平未恢复正常,和/或2)使用溴隐亭(剂量≤15 毫克/天)或卡麦角林(剂量≤3 毫克/周)治疗至少 6 个月后,腺瘤体积未缩小至少 50%。完全耐药的特点是没有生化和抗肿瘤作用,而部分耐药的特点是泌乳素水平可以下降但不能恢复正常,或者腺瘤的大小可以缩小到初始的 50%以下。泌乳素瘤对多巴胺受体激动剂耐药的临床和形态学预测因素包括:男性、年轻、腺瘤体积大且侵犯海绵窦、Т2 称重图像上的低密度和/或异质 MRI 信号以及肿瘤内的囊性成分。主要的分子遗传标记有:多巴胺和雌激素受体表达减少,增殖指数Ki-67≤3%,以及MENIN、AIP、SF3B1和PRDM2基因突变。如果患者对溴隐亭产生耐药性,建议改用卡麦角林。如果患者对标准剂量的卡麦角林产生部分耐药性,可以将剂量增加到最大耐受量。如果对多巴胺受体激动剂完全耐药或肿瘤具有侵袭性,建议进行神经外科和/或放射外科手术。对于侵袭性极强/恶性的肿瘤,或手术后肿瘤继续生长的情况,建议使用替莫唑胺作为辅助治疗。
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引用次数: 0
The clinical case of a combination of ankylosing spondylitis, ulcerative colitis and rheumatoid arthritis in one patient: where is the intersection point? 一名患者同时患有强直性脊柱炎、溃疡性结肠炎和类风湿性关节炎的临床病例:交点在哪里?
Pub Date : 2023-12-15 DOI: 10.18786/2072-0505-2023-51-043
O. Georginova, E. A. Makarov, Anton A. Budko, Vladimir G. Avdeev, Roman M. Gorbunov, M. Plotnikova, T. N. Krasnova
We describe a clinical observation of a 64-year old Caucasian patient with a longstanding ankylosing spondylitis, who was admitted to the clinic for diarrhea and joint syndrome. Physical and X-ray examination showed that his musculoskeletal system disorder was represented by ankylosing spondylitis, symmetrical erosive polyarthritis of the metacarpophalangeal joints, and wrist joint ankylosis. Laboratory work-up identified that the patient was HLA-B27 positive, had high rheumatoid factor and anti-citrulline antibodies levels. At colonoscopy, there were signs of ulcerative colitis. After the differential diagnosis procedures, we were able to conclude that the patient had a combination of rheumatoid arthritis, ankylosing spondylitis, and ulcerative colitis as three independent but associated disorders. The first description of these three autoimmune diseases in one patient can be of interest for clinicians.
我们描述了对一名 64 岁白种人患者的临床观察,该患者患有长期的强直性脊柱炎,因腹泻和关节综合征而入院。体格检查和 X 光检查显示,他的肌肉骨骼系统疾病表现为强直性脊柱炎、掌指关节对称性侵蚀性多关节炎和腕关节强直。实验室检查发现,患者的 HLA-B27 阳性,类风湿因子和抗瓜氨酸抗体水平较高。在结肠镜检查中,有溃疡性结肠炎的迹象。经过鉴别诊断程序后,我们得出结论,患者合并有类风湿性关节炎、强直性脊柱炎和溃疡性结肠炎三种独立但相关的疾病。这是首次在一名患者身上描述这三种自身免疫性疾病,值得临床医生关注。
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引用次数: 0
Lichenoid and psoriasiform drug induced rush during imatinib therapy: a clinical case 伊马替尼治疗期间药物诱发的苔藓样和银屑病样急疹:一个临床病例
Pub Date : 2023-12-09 DOI: 10.18786/2072-0505-2023-51-042
A. Khlebnikova, V. Shikina, G. E. Bagramova
Tyrosine kinase inhibitor imatinib is a standard agent for treatment of gastrointestinal stromal tumors (GIST). Treatment courses are quite long and are usually well tolerated. However, skin rash can occur on treatment, with a prevalence of 7 to 88.9%. We describe a clinical case of a patient with GIST, who has been on treatment with imatinib at daily dose of 400 mg for one year. Several weeks from the treatment initiation, she had facial edema, and 4 months thereafter psoriasiform rash appeared which was initially considered to be psoriatic. After 8 months, the patient had lichenoid rash on the inguinal skin and oral, tongue and vulvar mucosae. Clinically, the lichenoid rash was similar with lichen ruber planus. To confirm the diagnosis, we performed biopsy of psoriasiform and lichenoid foci. Histological examination verified the drug-induced rash. Topical treatment of psoriasiform rash with glucocorticosteroids resulted in regression of some plaques, although a proportion of them persisted. Inguinal and vulvar lichenoid rashes completely regressed and numbers of oral and tongue foci decreased after a 6-week daily application of the 0.1% tacrolimus cream. Treatment with imatinib 400 mg daily was not interrupted. The clinical observation illustrates the possibility of skin and mucosal lichenoid and psoriasiform rash simultaneously during treatment with imatinib and demonstrates the first successful experience in the treatment of lichenoid rashes with 0.1% tacrolimus cream.
酪氨酸激酶抑制剂伊马替尼是治疗胃肠道间质瘤(GIST)的标准药物。治疗过程相当长,通常耐受性良好。然而,治疗后可出现皮疹,患病率为7%至88.9%。我们描述了一个临床病例的胃肠道间质瘤患者,谁已经在治疗伊马替尼在每日剂量400mg一年。开始治疗数周后,患者出现面部水肿,4个月后出现牛皮癣样皮疹,最初认为是银屑病。8个月后,患者在腹股沟皮肤及口腔、舌、外阴粘膜出现地衣样疹。临床表现为类地衣皮疹与扁平橡皮地衣相似。为了确认诊断,我们对牛皮癣状和地衣样病灶进行了活检。组织学检查证实为药物性皮疹。局部治疗银屑病样皮疹与糖皮质激素导致一些斑块消退,尽管他们的一部分持续存在。每天使用0.1%他克莫司乳膏6周后,腹股沟和外阴地衣样疹完全消退,口腔和舌头病灶数量减少。伊马替尼每日400mg治疗未中断。临床观察表明伊马替尼治疗期间皮肤及粘膜地衣样疹和银屑病样疹同时发生的可能性,并首次成功应用0.1%他克莫司乳膏治疗地衣样疹。
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引用次数: 0
Diabetes mellitus in acromegaly: prevalence, pathophysiological particulars and treatment strategies 肢端肥大症糖尿病:发病率、病理生理学特点和治疗策略
Pub Date : 2023-12-09 DOI: 10.18786/2072-0505-2023-51-037
Irena A. Ilovayskaya, G. Galstyan
The prevalence of diabetes mellitus in acromegaly is significantly higher than that in the general population. Carbohydrate metabolism abnormalities often precede other phenotypic manifestations of acromegaly. The review presents data on the prevalence of carbohydrate metabolism disorders in acromegaly and describes their pathophysiological characteristics and approaches to treatment. Growth hormone (GH) excess is recognized as a key factor of glucose homeostasis abnormalities due to decreased insulin sensitivity (resulting from active lipolysis) and direct stimulation of insulin secretion. Insulin-like growth factor 1 (IGF1) improves insulin sensitivity; however, the GH diabetogenic effects prevail over the insulin-sensitizing impact of IGF1. Surgical and radiation treatment for somatotropinoma may indirectly improve carbohydrate metabolism, because they decrease the GH levels. Treatment with first generation somatostatin analogues can both improve glycemic control due to decreased GH levels and worsen it due to deterioration of postprandial insulin release, especially in patients with already manifest carbohydrate metabolism disorders. The GH receptor antagonist pegvisomant blocks the effects of excess GH on the target tissues without suppressing insulin secretion, which results in better glucose control; treatment with this agent can be preferred in patients with acromegaly and diabetes mellitus. Management of carbohydrate metabolism disorders in acromegaly is done in accordance with general treatment principles for type 2 diabetes mellitus.
肢端肥大症患者糖尿病患病率明显高于普通人群。碳水化合物代谢异常通常先于肢端肥大症的其他表型表现。这篇综述介绍了肢端肥大症中碳水化合物代谢紊乱的患病率,并描述了它们的病理生理特征和治疗方法。生长激素(GH)过量被认为是葡萄糖稳态异常的关键因素,这是由于胰岛素敏感性降低(由活跃的脂肪分解引起)和直接刺激胰岛素分泌引起的。胰岛素样生长因子1 (IGF1)改善胰岛素敏感性;然而,生长激素对糖尿病的影响优于IGF1对胰岛素增敏的影响。生长激素瘤的手术和放射治疗可以间接改善碳水化合物代谢,因为它们可以降低生长激素水平。用第一代生长抑素类似物治疗既可以由于生长激素水平下降而改善血糖控制,也可以由于餐后胰岛素释放恶化而使血糖控制恶化,特别是在已经出现碳水化合物代谢紊乱的患者中。生长激素受体拮抗剂pegvisomant阻断过量生长激素对靶组织的影响,而不抑制胰岛素分泌,从而更好地控制血糖;此药可用于肢端肥大症和糖尿病患者。肢端肥大症患者碳水化合物代谢紊乱的治疗应遵循2型糖尿病的一般治疗原则。
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引用次数: 0
Association of VEGFA gene rs2010963 polymorphism with cervical cancer and its progression VEGFA 基因 rs2010963 多态性与宫颈癌及其进展的关系
Pub Date : 2023-12-07 DOI: 10.18786/2072-0505-2023-51-041
Artem V. Rogalev, Maria S. Kishenya, Svetlana V. Pishchulina, E. V. Khomutov
Background: Cervical cancer is the most common type of female genital malignancies. In Russia, its incidence is 17 to 19 cases per 100,000 of female population. Cervical cancer is characterized by high activity, rapid development of radio/chemoresistance and unfavorable prognosis. To assess the risk of recurrence, metastasis and choice of the optimal treatment strategy, factors related to the disease progression are under study. Vascular endothelial growth factor (VEGF) overexpression is related to tumor angiogenesis and poor outcome in various cancer types, including cervical cancer. Aim: To study an association between the rs2010963 polymorphism of the VEGFA gene and risk of development and progression of cervical cancer. Materials and methods: This case-control study included 120 women (aged 49 [42; 65] years) with cervical cancer stage I-II and 112 women without cervical or other types of cancer. Based on the results of histological examination, two subgroups were formed: the one with tumor emboli (TE+) in the tumor vasculature and surrounding tissues (n = 41, 34.17%) and the other without tumor emboli (TE-) (n = 79, 65.83%). The polymorphic DNA loci of the rs2010963 VEGFA gene were analyzed by real time polymerase chain reaction. Results: In the patients, cervical cancer has associated with the VEGFA gene allelic polymorphism rs2010963 (χ2 = 5.47; p = 0.021). The minor C allele increased risk of cervical cancer by 1.6-fold (odds ratio (ОR) 1.58, 95% confidence interval (CI) 1.08-2.31), and the ancestral G allele reduced the cervical cancer probability (ОR 0.63, 95% CI 0.43-0.93). The genotypes distribution in the dominant model (GG and GC + CC) confirmed the association of the rs2010963 VEGFA gene polymorphism with cervical cancer (χ2 = 4.73; p = 0.031), specifically, if there was a minor C allele in the genotype (GC + CC). We found that the association of the rs2010963 VEGFA gene polymorphism with TE in the tumor vessels and surrounding tissues was a predictor of unfavorable progression and metastasis of cervical cancer (χ2 = 3.94; р = 0.049). The minor C allele increased the risk of TE by 1.7-fold (ОR 1.72, 95% CI 1.004-2.98), whereas the ancestral G allele reduced this chance (ОR 0.58, 95% CI 0.34-0.996). Conclusion: The C allele of the rs2010963 polymorphism of the VEGFA gene is a risk factor for cervical cancer, as well as a risk factor for the development of tumor emboli.
背景:宫颈癌是女性生殖器官最常见的恶性肿瘤。在俄罗斯,每10万女性人口中有17至19例。宫颈癌具有活动性高、放射/化疗耐药发展快、预后不良的特点。为了评估复发、转移的风险和最佳治疗策略的选择,与疾病进展相关的因素正在研究中。血管内皮生长因子(VEGF)过表达与包括宫颈癌在内的多种癌症类型的肿瘤血管生成和预后不良有关。目的:探讨VEGFA基因rs2010963多态性与宫颈癌发生发展风险的关系。材料和方法:本病例对照研究纳入120名女性(49岁[42;[65]年)和112名没有宫颈癌或其他类型癌症的女性。根据组织学检查结果分为肿瘤血管及周围组织有肿瘤栓塞(TE+)组(n = 41, 34.17%)和无肿瘤栓塞(TE-)组(n = 79, 65.83%)。采用实时聚合酶链反应分析rs2010963 VEGFA基因的多态性位点。结果:宫颈癌患者中存在VEGFA基因等位基因多态性rs2010963相关(χ2 = 5.47;P = 0.021)。次要的C等位基因使子宫颈癌的发生几率增加1.6倍(优势比(ОR) 1.58, 95%可信区间(CI) 1.08 ~ 2.31),祖传的G等位基因使子宫颈癌发生几率降低(ОR 0.63, 95% CI 0.43 ~ 0.93)。优势模型(GG和GC + CC)的基因型分布证实了rs2010963 VEGFA基因多态性与宫颈癌的相关性(χ2 = 4.73;p = 0.031),特别是在基因型(GC + CC)中存在少量C等位基因时。我们发现rs2010963 VEGFA基因多态性与肿瘤血管及周围组织TE的相关性是宫颈癌不良进展和转移的预测因子(χ2 = 3.94;= 0.049)。较小的C等位基因使TE的风险增加了1.7倍(ОR 1.72, 95% CI 1.004-2.98),而祖先的G等位基因降低了这一机会(ОR 0.58, 95% CI 0.34-0.996)。结论:VEGFA基因rs2010963多态性的C等位基因是宫颈癌的危险因素,也是肿瘤栓塞发生的危险因素。
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引用次数: 0
Ischemic injury of colon mucosa as a first manifestation of Takayasu arteritis in a young female patient: challenges in the differential diagnosis 结肠粘膜缺血性损伤是一名年轻女性患者高安动脉炎的首发症状:鉴别诊断中的难题
Pub Date : 2023-12-07 DOI: 10.18786/2072-0505-2023-51-038
Maina E. Akhmedova, Nina A. Fadeeva, Diana S. Filina, I. D. Loranskaya
Takayasu arteritis (TA) is a type of chronic large vessel vasculitis, which most often affects the aorta and its main branches as a kind of destructive-productive segmental aortitis and subaortic panarteritis, with possible obliteration of their orifices. Clinical picture of TA may be different depending on the nature and localization of the pathological process. We present a clinical case of ischemic injury of the colon mucosa in TA in a young (21 year old) female patient after she had a novel coronavirus infection (COVID-19). Due to ineffectiveness of out-patient treatment of ulcerative colitis, as well as complaints that were not meeting the diagnosis of ulcerative colitis, the patient was referred for additional examination and treatment modification in inpatient settings. Taking into account her diarrheal syndrome at the disease onset, the ileocolonoscopy results (rectal and colonic erosions), the results of histological examination (diffuse leukocytic infiltration of the mucosa, lymphoid infiltration of submucosa of the colon), elevation of proinflammatory markers, involvement of the inferior mesenteric artery at ultrasound dopplerography, the differential diagnosis was made between the TA overlap syndrome with inflammatory bowel diseases and TA-associated ischemic colitis. The assessment results made it possible to exclude inflammatory bowel diseases, to establish the diagnosis of TA and to consider colonic mucosa abnormalities as ischemic with underlying disease. The clinical case described is a rare event of intestinal ischemia as a first TA manifestation. Given the increasing worldwide prevalence of TA, especially after the new coronavirus infection pandemic, it is necessary to include this rare cause of gastrointestinal vasculitis to the differential diagnostic search, since mesenteric ischemia is one of the main causes of death in AT patients.
高松动脉炎(Takayasu arteritis, TA)是一种慢性大血管炎,主要影响主动脉及其主要分支,是一种破坏性节段性主动脉炎和主动脉下旁动脉炎,可导致其孔口闭塞。TA的临床表现可能因病理过程的性质和局部而异。我们报告一位年轻(21岁)女性患者在新型冠状病毒感染(COVID-19)后,TA结肠粘膜缺血性损伤的临床病例。由于溃疡性结肠炎的门诊治疗无效,以及不符合溃疡性结肠炎诊断的投诉,患者被转介到住院进行额外检查和治疗修改。考虑到她发病时的腹泻综合征,回肠结肠镜检查结果(直肠和结肠糜烂),组织学检查结果(粘膜弥漫性白细胞浸润,结肠粘膜下层淋巴浸润),促炎标志物升高,超声多普勒检查累及肠系膜下动脉,鉴别诊断为TA重叠综合征合并炎症性肠病和TA相关性缺血性结肠炎。评估结果可以排除炎症性肠病,建立TA的诊断,并考虑结肠黏膜异常为缺血性伴基础疾病。本文所描述的临床病例是一个罕见的以肠缺血为首发TA表现的事件。鉴于TA在全球范围内的患病率不断上升,特别是在新型冠状病毒感染大流行之后,有必要将这种罕见的胃肠道血管炎病因纳入鉴别诊断,因为肠系膜缺血是AT患者死亡的主要原因之一。
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引用次数: 0
Laboratory evaluation of the hormonal agents effects on the plasma hemostasis system in women of reproductive age 实验室评估荷尔蒙制剂对育龄妇女血浆止血系统的影响
Pub Date : 2023-11-29 DOI: 10.18786/2072-0505-2023-51-036
O. N. Startseva, N. N. Zybina, Elena Y. Zharova, T. Vavilova
Background: With the evolution of hormonal contraception, such as implementation of low dose agents, new regiments and administration routes of contraceptives, the risk of thrombotic complications persists, although is decreasing. The search for an available test for hemostasis assessment, which would allow for the prediction of thrombotic complications in high risk patients, remains relevant. Global tests for hemostasis assessment, such as thrombin generation test and thrombodynamics test, are attracting the specialists' attention due to the possibility of a quick integrative assessment of plasma hemostasis, especially during choice and tailoring of an optimal version of hormonal therapy. Aim: To assess the value of the integral thrombodynamics test in the multifactorial assessment of hemostasis system in women of reproductive age using hormonal contraceptives. Materials and methods: This observational prospective comparative study included 408 women aged 18 to 49 years followed from 2018 to 2022 in The Nikiforov Russian Center of Emergency and Radiation Medicine and Centre of Miscarriage Prevention and Treatment of the Maternity Hospital No. 1, St. Petersburg. From these, 208 women (mean age, 38.0 ± 7.0 years) were taking hormonal contraceptives (HC+ group), and 200 women (mean age, 37.5 ± 9.2 years) were in the control group (HC-). In the HC+ group, 163 women were taking combination oral contraceptives, 24 had an intrauterine levonorgestrel-releasing system, 8 used vaginal rings, and 13 were using progestin only oral contraceptives. Multifactorial clinical and laboratory assessment included taking past history, measurement of pro- and anticoagulation blood parameters, fibrinolysis, and endothelial function parameters (automatic coagulometer ACL TOP 500, Instrumentation Laboratory, USA). The integral assessment of the hemostasis system was performed with Thrombodynamics Registrator T-2 (Hemacor, Russia). Results: The groups were similar as per their age, chronic venous insufficiency and smoking. The HC+ group had significantly higher proportion of women with cardiovascular disorders (p = 0.0037), obesity (p = 0.0004), and headache (p 0.0001), compared to the HC- group. The thrombodynamics test showed a significantly higher rate of clot formation in the women taking hormonal contraception, compared to that in the HC- group (36.2 [30.1; 43.6] and 30.3 [28.0; 33.6] mcm/min, respectively, р 0.001). Hypercoagulation identified by the thrombodynamics test was associated with slowing down of XIIа-dependent fibrinolysis (6 [5; 8] min in the HC- and 12.8 [8; 16] min in the HC+ group, p 0,001) and higher levels of endothelial dysfunction markers (FVIII, 113 [85; 156] and 150 [107; 180]%, p = 0.015; vFW, 98 [85; 133] and 146 [95; 168]%, respectively, p = 0.003). The analysis of plasma hemostasis parameters depending on the presence of thromboembolic risk factors has shown that higher number of the risk factors is associated with higher velocity paramet
背景:随着激素避孕的发展,如低剂量药剂的使用、新的避孕方法和给药途径,血栓并发症的风险虽然在降低,但仍然存在。因此,寻找一种可用的止血评估检测方法,以预测高风险患者的血栓并发症,仍然具有现实意义。全球止血评估测试,如凝血酶生成测试和血栓动力学测试,正吸引着专家们的注意力,因为这些测试可以快速综合评估血浆止血情况,尤其是在选择和定制最佳激素治疗方案时。 目的:评估血栓动力学综合测试在使用激素避孕药的育龄妇女止血系统多因素评估中的价值。 材料和方法:这项观察性前瞻性比较研究纳入了圣彼得堡第一妇产医院尼基福罗夫俄罗斯急诊与放射医学中心和流产预防与治疗中心在 2018 年至 2022 年期间随访的 408 名 18 至 49 岁女性。其中,208 名妇女(平均年龄为 38.0 ± 7.0 岁)服用激素避孕药(HC+ 组),200 名妇女(平均年龄为 37.5 ± 9.2 岁)服用激素避孕药(HC- 组)。在 HC+ 组中,163 名妇女服用复方口服避孕药,24 名妇女使用宫内左炔诺孕酮释放系统,8 名妇女使用阴道环,13 名妇女仅使用孕激素口服避孕药。多因素临床和实验室评估包括询问既往史、测量促凝和抗凝血参数、纤溶和内皮功能参数(自动凝血仪 ACL TOP 500,美国仪器实验室)。止血系统的综合评估由血栓动力学注册仪 T-2 (Hemacor,俄罗斯)完成。 结果两组患者的年龄、慢性静脉功能不全和吸烟情况相似。与 HC- 组相比,HC+ 组中患有心血管疾病(p = 0.0037)、肥胖(p = 0.0004)和头痛(p 0.0001)的女性比例明显更高。血栓动力学测试显示,与 HC 组相比,服用激素避孕药的妇女血栓形成率明显更高(分别为 36.2 [30.1; 43.6] mcm/min 和 30.3 [28.0; 33.6] mcm/min,р 0.001)。血栓动力学试验确定的高凝与 XIIа依赖性纤溶减慢有关(HC 组为 6 [5; 8] 分钟,HC 组为 12.8;16] 分钟,p 0.001)和更高水平的内皮功能障碍标志物(FVIII,分别为 113 [85;156] 和 150 [107;180]%,p = 0.015;vFW,分别为 98 [85;133] 和 146 [95;168]%,p = 0.003)。根据血栓栓塞风险因素对血浆止血参数进行的分析表明,在慢性高凝范围内,风险因素越多,血栓动力学测试的速度参数越高。 结论用于评估血浆止血功能的血栓动力学综合测试可用于识别服用激素避孕药的妇女的止血功能障碍。为了预防血栓栓塞并发症的风险,最好在服用激素类药物前评估血液凝固系统参数。
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Almanac of Clinical Medicine
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