absolute neutrophil count

中性粒细胞绝对计数
  • 文章类型: Journal Article
    背景:骨髓性,大剂量化疗后再进行自体外周血干细胞移植(PBSCT)可改善儿童和青少年一些高危恶性实体瘤和淋巴瘤的预后.
    方法:我们于2015年8月至2020年12月对12名患有高危恶性实体瘤或难治性/复发性霍奇金淋巴瘤的儿童和2名年轻成人患者进行了16次外周血干细胞(PBSC)采集。在我们的化疗动员方案中,我们使用化疗后最低点后中性粒细胞绝对计数(ANC)>1×109/L作为进行单采的标准.
    结果:33种单采药物每千克体重的CD34+细胞计数中位数为4.92×106细胞/千克(范围,0.34-22.53×106细胞/kg)。14例患者中有13例(93%)成功收集了PBSC,达到了PBSCT的目标。由于移植前疾病进展,三名患者未接受PBSCT。其余11例17例PBSCT患者均发生了及时的植入。
    结论:我们的数据表明,当外周血CD34+计数不可用时,ANC可以作为临床决策的替代参数。
    BACKGROUND: Myeloablative, high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) improves outcome in some high-risk malignant solid tumors and lymphomas in children and young adults.
    METHODS: We performed 16 peripheral blood stem cell (PBSC) harvests in 12 children and 2 young adult patients with a high-risk malignant solid tumor or refractory/relapsed Hodgkin\'s lymphoma from August 2015 to December 2020. In our chemotherapy mobilization protocol, we used an absolute neutrophil count (ANC) of >1 × 109/L following the nadir after chemotherapy as the criterion for undertaking the apheresis.
    RESULTS: The median CD34+ cell count per kg body weight of the 33 apheresis products was 4.92 × 106 cells/kg (range, 0.34-22.53 × 106 cells/kg). Thirteen of the 14 patients (93%) had successful PBSC collections that met their goals for PBSCT. Three patients did not receive PBSCT due to disease progression prior to transplantation. Prompt engraftment occurred in all the remaining 11 patients with 17 PBSCTs.
    CONCLUSIONS: Our data suggest that ANC can be helpful as a surrogate parameter in clinical decision-making when the peripheral blood CD34+ count is unavailable.
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  • 文章类型: Journal Article
    该研究的目的是调查基线炎症,在COVID-19住院患者中,止血指标和新发深静脉血栓形成(DVT)与死亡风险有关。在这项单中心研究中,共有401名COVID-19患者在邵逸夫医院住院,浙江大学医学院于2022年12月1日至2023年1月31日入学。基本信息,第一次实验室检查结果,影像学检查,比较中度和重度亚组患者的结局相关指标。我们发现,在重症COVID-19住院患者中,基线D-二聚体和基线中性粒细胞绝对计数(ANC)水平与新发DVT和死亡相关。基线D-二聚体和基线ANC与死亡率的比值比(OR)为1.18(95%置信区间[CI],1.08-1.28;P<.001)和1.13(95%CI,1.06-1.21;P<.001)。基线ANC与重症住院COVID-19患者的死亡风险相关,无论DVT状态如何。此外,在患有DVT的严重COVID-19住院患者或住院期间死亡患者中,观察到血清中性粒细胞活性显著升高.新发DVT部分介导基线D-二聚体之间的关联(间接效应:0.011,估计介导比例:67.0%),基线ANC(间接效应:0.006,估计中介比例:48.7%),严重COVID-19住院患者的死亡率。总之,在重症COVID-19住院患者,尤其是DVT住院患者中,基线D-二聚体和基线中性粒细胞绝对计数(ANC)水平与死亡率相关.新发DVT部分介导了基线D-二聚体之间的关联,基线ANC,严重COVID-19住院患者的死亡率。
    The purpose of the study was to investigate baseline inflammatory, hemostatic indicators and new-onset deep vein thrombosis (DVT) with the risk of mortality in COVID-19 inpatients. In this single-center study, a total of 401 COVID-19 patients hospitalized in Sir Run Run Shaw Hospital, Zhejiang University School of Medicine were enrolled from December 1, 2022 to January 31, 2023. The basic information, first laboratory examination results, imaging examination, and outcome-related indicators were compared between patients in the moderate and severe subgroups. We found that baseline D-dimer and baseline absolute neutrophil count (ANC) levels were associated with new-onset DVT and death in severe hospitalized patients with COVID-19. The odds ratio (OR) of baseline D-dimer and baseline ANC with mortality was 1.18 (95% confidence interval [CI], 1.08-1.28; P < .001) and 1.13 (95% CI, 1.06-1.21; P < .001). Baseline ANC was associated with the risk of death in severe hospitalized COVID-19 patients, irrespective of the DVT status. In addition, a significantly higher serum neutrophil activity was observed in severe COVID-19 inpatients with DVT or those deceased during hospital stay. New-onset DVT partially mediated the association between baseline D-dimer (indirect effect: 0.011, estimated mediating proportion: 67.0%), baseline ANC (indirect effect: 0.006, estimated mediating proportion: 48.7%), and mortality in severe hospitalized patients with COVID-19. In summary, baseline D-dimer and baseline absolute neutrophil count (ANC) levels were associated with the mortality in severe hospitalized patients with COVID-19, especially DVT inpatients. New-onset DVT partially mediated the association between baseline D-dimer, baseline ANC, and mortality in severe hospitalized patients with COVID-19.
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  • 文章类型: Journal Article
    异基因造血干细胞移植(HSCT)前中性粒细胞绝对计数(ANC)对再生障碍性贫血(AA)患者预后的影响尚不清楚。我们回顾性评估了移植前ANC与患者预后之间的关系,涉及883名日本成年AA患者,他们在2008年至2020年间首次接受同种异体HSCT移植。根据ANC将患者分为三组:0/µL(n=116);1-199(n=210);和≥200(n=557)。在低ANC组(ANC<200)中,患者年龄较高,以前的抗胸腺细胞球蛋白(ATG)治疗很少,从诊断到移植的持续时间较短,造血细胞移植合并症指数(HCT-CI)较高,基于ATG的调理很少使用,并且经常使用来自相关供体和脐带血的外周血干细胞。在多变量分析中,患者年龄,以前的ATG治疗,HCT-CI,干细胞来源,移植前ANC与5年总生存率(OS)显着相关(“ANC≥200”:80.3%vs.“ANC1-199”:71.7%vs.“ANC0”:64.4%)。细菌感染的累积发生率,侵袭性真菌病,在低ANC组中,植入前的早期死亡明显更高。在移植前ANC为零的患者中,患者年龄较小,从诊断到移植的持续时间较短,0的HCT-CI和来自相关供者的骨髓作为干细胞来源与较好的OS显著相关。因此,发现同种异体HSCT之前的ANC是成年AA患者的重要预后因素。医师在移植前应注意ANC。
    The impact of absolute neutrophil count (ANC) before allogenic hematopoietic stem cell transplantation (HSCT) on the outcomes for patients with aplastic anemia (AA) remains unclear. We retrospectively evaluated the relationship between ANC before transplantation and patient outcomes, involving 883 adult Japanese patients with AA who underwent allogeneic HSCT as their first transplantation between 2008 and 2020. Patients were divided into three groups based on ANC: 0/µL (n = 116); 1-199 (n = 210); and ≥ 200 (n = 557). In the low ANC groups (ANC < 200), patient age was higher, previous anti-thymocyte globulin (ATG) treatments were infrequent, duration from diagnosis to transplantation was shorter, hematopoietic cell transplantation-comorbidity index (HCT-CI) was higher, ATG-based conditioning was used infrequently, and peripheral blood stem cell from related donor and cord blood were used frequently. In multivariate analysis, patient age, previous ATG treatment, HCT-CI, stem cell source, and ANC before transplantation were significantly associated with 5-year overall survival (OS) (\"ANC ≥ 200\": 80.3% vs. \"ANC 1-199\": 71.7% vs. \"ANC 0\": 64.4%). The cumulative incidence of bacterial infection, invasive fungal disease, and early death before engraftment were significantly higher in the low ANC groups. Among patients with ANC of zero before transplantation, younger patient age, shorter duration from diagnosis to transplantation, HCT-CI of 0, and bone marrow from related donor as stem cell source were significantly associated with better OS. Consequently, ANC before allogeneic HSCT was found to be a significant prognostic factor in adult patients with AA. Physicians should pay attention to ANC before transplantation.
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  • 文章类型: Journal Article
    癌症是全球第二大常见死亡原因。中性粒细胞-淋巴细胞比率(NLR)和血小板-淋巴细胞比率(PLR)是包括头颈癌在内的各种癌症中炎症和肿瘤发生的重要标志物。治疗前血小板-淋巴细胞比率可用作死亡率的独立预测因子,而中性粒细胞-淋巴细胞比率是复发的独立预测因子。这项研究的主要目的是比较头颈部恶性肿瘤患者与对照组的治疗前中性粒细胞淋巴细胞比率和血小板淋巴细胞比率。
    100例经组织学诊断为头颈部恶性肿瘤的患者。年龄和性别匹配的健康受试者参加耳鼻咽喉科门诊治疗任何其他投诉(100名对照受试者)。完成血细胞计数以计算绝对中性粒细胞计数和绝对淋巴细胞计数。
    研究组受试者的平均年龄为55.73±11.56岁。在对照组中,平均年龄组为54.11±10.46岁.病例中NLR和PLR显著高于对照组。与T级相关的NLR,组织学类型和组织学分级,但不涉及部位和淋巴结。与T级相关的PLR,转移,但与组织学分级无关,组织学类型,现场和节点参与。
    从这项研究来看,我们得出的结论是,治疗前NLR和PLR与头颈部恶性肿瘤患者的原发肿瘤大小和恶性疾病分期密切相关.
    UNASSIGNED: Carcinoma is the second most common cause of death worldwide. The neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) are essential markers of inflammation and tumorigenesis in various cancers including head and neck cancers. Pretreatment platelet- lymphocytic ratio can be used as an independent predictor of mortality whereas neutrophil- lymphocytic ratio is an independent predictor of recurrence. The main aim of this study is to compare the pre-treatment neutrophil lymphocyte ratio and platelet-lymphocyte ratio in the patients of head and neck malignancies with those of the control group.
    UNASSIGNED: 100 patients with histologically diagnosed cases of head and neck malignancies. Age and sex matched healthy subjects attending Otorhinolaryngology out-patient department for any other complaints (100 control subjects). Complete blood count had been done to calculate absolute neutrophil count and absolute lymphocyte count.
    UNASSIGNED: The mean age of the subjects in the study group was 55.73 ± 11.56 years. In control group, the mean age group was 54.11 ± 10.46 years. NLR and PLR significantly increased in cases than controls. NLR associated with T stage, histological type and histological grade but not with site and nodal involvement. PLR associated with T stage, metastasis but not with the histological grade, histological type, site and nodal involvement.
    UNASSIGNED: From this study, we conclude that pre-treatment NLR and PLR were closely associated both with the size of primary tumor and also with the stage of malignant disease in patients of head and neck malignancies.
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  • 文章类型: Clinical Trial, Phase II
    正常绝对中性粒细胞计数(ANC)变化,如Duffy-null相关中性粒细胞计数(DANC)所示,没有计入审判资格,这可能会导致种族入学差异。我们使用ClinicalTrials.gov.根据2010年至2023年的主要赞助,描述了ANC对儿科肿瘤I/II期临床试验的资格。在438项试验中,20%是行业赞助的。总共17%的试验需要ANC≥1500个细胞/μL进行登记;然而,行业赞助的试验比非行业赞助的试验更可能需要ANC≥1500个细胞/μL(比值比2.53,95%置信区间:1.39-4.62;p<.001).这些数据表明实验室排除标准是儿科临床试验登记差异的一种可能机制。
    Normal absolute neutrophil count (ANC) variations, as seen with Duffy-null associated neutrophil count (DANC), are not accounted for in trial eligibility, which may contribute to racial enrollment disparities. We describe ANC eligibility for pediatric oncology phase I/II clinical trials according to primary sponsorship from 2010 to 2023 using ClinicalTrials.gov. Out of 438 trials, 20% were industry-sponsored. Total 17% of trials required ANC ≥1500 cells/μL for enrollment; however, industry-sponsored trials were significantly more likely to require ANC ≥1500 cells/μL than non-industry-sponsored trials (odds ratio 2.53, 95% confidence interval: 1.39-4.62; p < .001). These data suggest laboratory exclusion criteria are one possible mechanism for pediatric clinical trial enrollment disparities.
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  • 文章类型: Journal Article
    背景:巯基嘌呤是急性淋巴细胞白血病(ALL)和淋巴瘤(LLy)维持治疗的重要组成部分。6-硫代鸟嘌呤核苷(6-TGN)被认为是骨髓抑制和免疫抑制作用的主要贡献者。而6-甲基巯基嘌呤(6-MMPN)被认为是负责几种毒性,包括肝毒性,胰腺炎,和低血糖。以前的报道表明,加入别嘌呤醇可能会降低这些毒性。
    目的:评估别嘌呤醇在小儿ALL和LLy患者维持治疗期间的安全性和有效性。次要目标包括评估患者的耐受性和偏态代谢。此外,我们还分析了别嘌呤醇开始时的巯基嘌呤日剂量减少。
    结果:主要终点是在别嘌呤醇开始之前和之后在目标ANC内的时间。次要终点包括;选择性毒性的改善(肝毒性,胰腺炎,和低血糖)以及别嘌呤醇开始之前和之后的6-MMPN与6-TGN的比率。此外,纳入了一项探索性终点,该终点评估了别嘌呤醇开始前和开始后巯基嘌呤的每日剂量减少.16例患者符合纳入标准,其中15例(94%)纳入本研究。在开始别嘌醇之前和之后,目标ANC内维持天数的中位数百分比分别为27.8(IQR22.6-44.9)和41.6(IQR20.2-58.2)。所有患者都经历了选择性毒性;15(100%)肝毒性,1(7%)胰腺炎,和3(20%)低血糖。毒性改善见于13/15(87%),1/1(100%)和2/3(67%)。别嘌呤醇引发之前的平均6-MMPN:6-TGN比率为304:1,别嘌呤醇引发改善至15:1,导致95%的减少。别嘌呤醇引发之前和之后的平均巯基嘌呤剂量减少了约56%(63至28mg/m2/天)。
    结论:结果表明,ALL和LLy患儿在维持治疗期间使用别嘌呤醇既安全又有效。
    Mercaptopurine is an important component of acute lymphoblastic leukemia (ALL) and lymphoma (LLy) maintenance therapy. The 6-thioguanine nucleosides (6-TGN) are believed to be the primary contributor to myelosuppression and immunosuppressive effects, while 6-methylmercaptopurine (6-MMPN) is believed to be responsible for several toxicities including hepatotoxicity, pancreatitis, and hypoglycemia. Previous reports suggest the addition of allopurinol may reduce these toxicities.
    To assess the use of allopurinol to improve both safety and efficacy of mercaptopurine in pediatric patients with ALL and LLy during maintenance therapy. Secondary objectives included evaluating patient tolerability and skewed metabolism. In addition, we also analyzed mercaptopurine daily dose reduction upon allopurinol initiation.
    The primary endpoint was time within goal ANC prior to and after initiation of allopurinol. Secondary endpoints included; improvement in selective toxicities (hepatotoxicity, pancreatitis, and hypoglycemia) and 6-MMPN to 6-TGN ratio prior to and after allopurinol initiation. In addition, an exploratory endpoint assessing mercaptopurine daily dose reduction prior to and after allopurinol initiation was included. Sixteen patients met inclusion criteria and 15 (94%) of which were included in this study. Median percent of maintenance days within goal ANC prior to and after initiation of allopurinol was 27.8 (IQR 22.6-44.9) and 41.6 (IQR 20.2-58.2) respectively. All patients experienced selective toxicities; 15 (100%) hepatotoxicity, 1 (7%) pancreatitis, and 3 (20%) hypoglycemia. Improvement of toxicities was seen in 13/15 (87%), 1/1 (100%), and 2/3 (67%) respectively. Average 6-MMPN:6-TGN ratio prior to allopurinol initiation was 304:1 and after, allopurinol initiation improved to 15:1, resulting in a 95% reduction. Average mercaptopurine dose prior to and after allopurinol initiation decreased by about 56% (63 to 28 mg/m2 /day).
    Results suggest that the use of allopurinol in pediatric patients with ALL and LLy receiving mercaptopurine during maintenance therapy is both safe and effective.
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    文章类型: Journal Article
    中性粒细胞是循环中最常见的细胞类型,被认为是免疫系统抵抗微生物的第一道防线。这项研究旨在调查沙特阿拉伯中部地区健康个体中孤立的良性中性粒细胞减少症(IBN)的发生。
    这项回顾性研究分析了2022年4月至9月期间作为慢性健康状况常规检查的一部分的全血细胞计数检查。随机选择10,442名参与者,并审查他们的病历中的中性粒细胞减少症,并计算平均绝对中性粒细胞计数(ANC)。描述性分析用于评估IBN在各种人口统计学因素中的患病率,比如年龄,性别,和国籍。
    在整个参与者队列中,沙特阿拉伯中部地区的IBN患病率为2.82%。所有参与者的平均ANC为4.55×109/L。男性参与者中性粒细胞减少症的患病率高于女性。男性中性粒细胞减少症的平均ANC低于女性;然而,差异无统计学意义(P>0.05)。与非沙特人相比,沙特参与者的中性粒细胞减少症患病率较低。而与非沙特参与者相比,沙特人的平均非国大更低。然而,差异无统计学意义(P>0.05)。
    这是沙特阿拉伯中部地区的第一项研究,该研究确定了健康个体中慢性良性中性粒细胞减少症的患病率。发现IBN的患病率相对较低。此外,男性中性粒细胞减少症发生率高于女性.此外,男性中性粒细胞减少个体的ANC较低。
    UNASSIGNED: Neutrophils are the most common cell types in circulation and are considered the first line of defense in the immune system against microorganisms. This study was undertaken to investigate the occurrence of isolated benign neutropenia (IBN) among healthy individuals in the central region of Saudi Arabia.
    UNASSIGNED: This retrospective study analyzed complete blood count tests as part of routine checkups for chronic health conditions from April to September 2022. The 10,442 participants were randomly selected and their medical records were reviewed for neutropenia and mean absolute neutrophil counts (ANCs) were calculated. Descriptive analysis was employed to assess the prevalence of IBN across various demographic factors, such as age, gender, and nationality.
    UNASSIGNED: The prevalence of IBN in the central region of Saudi Arabia was found to be 2.82% across the entire cohort of participants. The mean ANC among all participants was 4.55 × 109/L. The prevalence of neutropenia was higher in male participants compared with female. Male neutropenic had a lower mean ANC than female; however, the differences were not statistically different (P > 0.05). The prevalence of neutropenia was lower in Saudi participants compared with non-Saudis. While the mean ANC was lower among Saudis as compared with non-Saudi participants. However, the differences were not statistically different (P > 0.05).
    UNASSIGNED: This is the first study from the central region of Saudi Arabia that determined the prevalence of chronic benign neutropenia among healthy individuals. The prevalence of IBN was found to be relatively low. Furthermore, neutropenia was more frequent in males than females. Moreover, male neutropenic individuals have a lower ANC.
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  • 文章类型: Journal Article
    背景:即使是最有经验的骨科医生,诊断假体周围感染(PJI)也是一项艰巨的任务,因为目前没有可用的测试可以提供绝对的准确性。利用已建立的滑膜指标来检测PJI而不产生额外的成本或资源将是预测感染存在的最佳解决方案。因此,我们假设滑膜中性粒细胞绝对计数(ANC)可以提高慢性膝和髋部PJI的诊断准确性.
    方法:纳入所有有慢性症状并入住我们机构的患者进行审查。这包括260名患者(134名男性和126名女性,平均年龄70岁(范围,26至89),在术前检查中进行了抽吸。其中,109例(41.9%)被诊断为慢性PJI(50膝,59臀部),151例患者(58.1%)被诊断为无菌(94膝,57臀部)。从所有患者获得的数据包括年龄,性别,手术类型(全髋关节或全膝关节置换术),操作侧,滑膜白细胞(WBC)计数(细胞/μL),滑膜多形核细胞百分比(PMN%),从电子病历中检索入院时的滑膜α-防御素(AD)免疫测定值。
    结果:滑膜ANC的最佳阈值为1,415.5细胞/μL,与慢性膝关节PJI诊断的曲线下面积(AUC)为0.930相关。敏感性和特异性分别为90%和93%,分别。2,247细胞/μL的滑膜ANC的计算最佳阈值与用于慢性髋关节PJI诊断的0.905的AUC相关。敏感性和特异性分别为86.4和89.4%,分别。
    结论:本研究已得出结论,滑膜ANC在PJI的复杂诊断中具有重要的价值。应利用这种高效的方法通过标准测试获得更多信息,从而排除了PJI的可能性。
    BACKGROUND: Diagnosing periprosthetic joint infection (PJI) is a daunting task for even the most experienced orthopedic surgeons, as there is currently no test available that can provide absolute accuracy. Utilizing an established synovial indicator for detecting PJI without incurring additional costs or resources would be the optimal solution for predicting the presence of infection. Therefore, we hypothesized that synovial absolute neutrophil count (ANC) would improve the diagnostic accuracy of chronic knee and hip PJI.
    METHODS: The study included 260 patients (134 men and 126 women, mean age of 70 years [range, 26 to 89]) who underwent aspiration during preoperative workup. Of these, 109 patients (41.9%) were diagnosed with chronic PJI (50 knees, 59 hips), and 151 patients (58.1%) were diagnosed as aseptic (94 knees, 57 hips). Data obtained from all patients included age, sex, procedure type (total hip or total knee arthroplasty), operation side, synovial white blood cell count (cells/μL), synovial polymorphonuclear cells percentage, and synovial α-defensin immunoassay value at the admission were retrieved from the electronic medical record.
    RESULTS: The calculated optimal threshold for synovial ANC of 1,415.5 cells/μL was associated with an area under the receiver operating characteristic curve (AUC) of 0.930 for chronic knee PJI diagnosis. The calculated optimal threshold for synovial ANC of 2,247 cells/μL was associated with an AUC of 0.905 for chronic hip PJI diagnosis.
    CONCLUSIONS: This study has conclusively shown that the synovial ANC serves as a valuable marker in the complicated diagnosis of PJI. This highly effective and efficient approach should be utilized for obtaining further information through standard tests, thereby ruling out the possibility of PJI.
    METHODS: III.
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  • 文章类型: Journal Article
    背景:我们旨在评估术前中性粒细胞与白蛋白比值(NAR)在口腔鳞状细胞癌(OSCC)中的预后意义。
    方法:共纳入622例经手术治疗的OSCC患者。NAR定义为根治性手术前中性粒细胞绝对计数除以外周血中的血清白蛋白水平。Cox比例风险模型用于发现生存结果相关因素。
    结果:确定预测总生存期(OS)的NAR的最佳截止值为0.1。在Cox模型中,高NAR被确定为OS的独立阴性预测因子,癌症特异性生存率,和无复发生存率(校正后的风险比分别为:1.503,1.958和1.727;所有p<0.05)。基于NAR的列线图准确预测了OS(一致性指数:0.750)。
    结论:我们的研究表明,术前NAR是OSCC的方便和有效的预后指标,基于NAR的列线图在临床上可能是一个有前途的预后工具。
    We aimed to evaluate the prognostic significance of preoperative neutrophil-to-albumin ratio (NAR) in oral squamous cell carcinoma (OSCC).
    A total of 622 patients with surgically treated OSCC were enrolled. NAR was defined as the absolute neutrophil count divided by the serum albumin level in peripheral blood before the radical surgery. Cox proportional hazards model were used to discover survival outcome-associated factors.
    The optimal cut-off of NAR to predict overall survival (OS) was determined to be 0.1. In Cox model, high NAR was identified as an independent negative prognosticator of OS, cancer-specific survival, and recurrence-free survival (adjusted hazard ratio: 1.503, 1.958, and 1.727, respectively; all p < 0.05). The NAR-based nomogram accurately predicted OS (concordance index: 0.750).
    Our study suggests that preoperative NAR is a convenient and effective prognostic marker for OSCC and NAR-based nomogram can be a promising prognostic tool in clinical setting.
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  • 文章类型: Journal Article
    背景:氯氮平是治疗难治性精神分裂症最有效的抗精神病药物,但是它明显没有得到充分利用,特别是在美国黑人人口中,部分原因是对氯氮平相关中性粒细胞绝对计数(ANC)偏低的担忧.非洲人后裔的ANC规范范围低于白人,与ACKR1基因上的特定“ACKR1-null”(“Duffynull”)CC基因型(SNPrs2814778)相关,称为良性种族中性粒细胞减少症(BEN)。尚未在BEN患者中确定氯氮平的ANC变异性和安全性的范围,也未在非洲裔人群中进行前瞻性检查。
    方法:我们完成了多站点,6个月,prospective,氯氮平治疗非洲裔精神分裂症谱系障碍患者的开放标签临床试验,有或没有ACKR1空基因型。我们检查了氯氮平治疗期间的氯氮平安全性和每周ANC,并通过ACKR1-null基因型评估了ANC变异性,性别,研究地点,和氯氮平给药使用重复测量协方差分析。使用TaqMan®技术测定基因型。
    结果:我们招募了274名参与者,其中227人(82.8%)完成了6个月的氯氮平治疗。有一例严重的中性粒细胞减少症(<500细胞/mm3)(0.36%)超过1467.6人-月的氯氮平暴露。该参与者在停用氯氮平后恢复无后遗症。在249名具有已知基因型的参与者中,199(79.9%)具有ACKR1无效基因型。中性粒细胞减少症(<1500个细胞/mm3)在ACKR1-null组中(33%[65/199])的发生率明显高于T等位基因组(6%(3/50);p<0.001)。14名(5%)患者因不良事件停药。感染和发烧的发生率很低,流涕是最常见的副作用(N=187,68%)。
    结论:据我们所知,这是针对非洲人后裔的最大的前瞻性氯氮平试验.严重的中性粒细胞减少症很罕见,尽管ACKR1-null基因型的患病率很高(80%)。我们的研究结果表明,氯氮平可以安全地用于Black患者,包括BEN患者。
    BACKGROUND: Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, but it is markedly underutilized, particularly in the US Black population, partly because of concern over clozapine-associated low absolute neutrophil count (ANC). People of African descent have a lower normative ANC range than the White population, which is associated with a specific \"ACKR1-null\" (\"Duffy null\") CC genotype (SNP rs2814778) on the ACKR1 gene, termed benign ethnic neutropenia (BEN). The range of ANC variability and safety of clozapine have not been established in people with BEN or examined prospectively in people of African descent.
    METHODS: We completed a multisite, 6-month, prospective, open-label clinical trial of clozapine treatment in people of African descent with schizophrenia spectrum disorders for whom clozapine was clinically indicated, with or without the ACKR1-null genotype. We examined clozapine safety and weekly ANC during clozapine treatment and evaluated ANC variability by ACKR1-null genotype, sex, study site, and clozapine dosing using repeated measures analysis of covariance. Genotype was assayed using TaqMan® technology.
    RESULTS: We enrolled 274 participants, of whom 227 (82.8 %) completed 6 months of clozapine treatment. There was one case of severe neutropenia (<500 cells/mm3) (0.36 %) over 1467.6 person-months of clozapine exposure. This participant recovered without sequelae after discontinuation of clozapine. Of the 249 participants with known genotypes, 199 (79.9 %) had the ACKR1-null genotype. Neutropenia (<1500 cells/mm3) occurred significantly more often in the ACKR1-null group (33 % [65/199]) than in those with the T allele (6 % (3/50); p < 0.001). Fourteen (5 %) patients discontinued due to adverse events. Rates of infection and fever were low and sialorrhea was the commonest side effect (N = 187, 68 %).
    CONCLUSIONS: To our knowledge, this is the largest prospective clozapine trial in people of African descent. Severe neutropenia was rare, despite the high prevalence (80 %) of the ACKR1-null genotype. Our findings suggest that clozapine can be used safely in Black patients including those with BEN.
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