Paraneoplastic Syndromes

副肿瘤综合征
  • 文章类型: Journal Article
    背景:很少有研究分析住院肿瘤患者高钙血症的特征。我们的目的是描述副肿瘤性高钙血症住院患者的临床特征,并确定死亡率的预后变量。
    方法:这是一个观察性的,纵向,回顾性,和双中心研究。其中包括马拉加两家医院收治的成年患者,西班牙(2014-2018)。最短随访期为2年或直至死亡。
    结果:共纳入154例患者;大多数(71.4%)进入内科。中位随访时间为3.5周(四分位距[IQR]1.1-11.5)。平均(标准差)年龄为67.6(12.3)岁,以男性为主(58.4%)。入院时血清钙中位数(IQR)为13.2(11.8-14.6)mg/dl。最常见的肿瘤是肺(27.3%),血液学(23.4%),泌尿外科(13%),和乳房(12.3%)。此外,56.5%的病例在诊断时具有已知的肿瘤病史。甲状旁腺激素(PTH)水平测定为24%;其中,10.8%的水平升高。总之,95.5%的患者在随访期间死亡。中位生存期为3.4周(95%置信区间2.6-4.3)。与较高死亡率相关的因素是年龄,入院时血清钙,以前的肿瘤病史,多发性骨髓瘤以外的病因,和未纠正高钙血症。
    结论:在住院患者中,副肿瘤性高钙血症与高短期死亡率相关.在这些患者中发现了与预后较差相关的几个因素。
    BACKGROUND: There are few studies that have analyzed the characteristics of hypercalcemia in hospitalized oncological patients. Our objectives were to describe the clinical characteristics of hospitalized patients with paraneoplastic hypercalcemia and to identify prognostic variables for mortality.
    METHODS: This was an observational, longitudinal, retrospective, and bicentric study. It included adult patients admitted to two hospitals in Málaga, Spain (2014-2018). The minimum follow-up period was 2 years or until death.
    RESULTS: A total of 154 patients were included; the majority (71.4%) were admitted to the internal medicine department. The median follow-up was 3.5 weeks (interquartile range [IQR] 1.1-11.5). The mean (standard deviation) age was 67.6 (12.3) years, with a predominance of males (58.4%). The median (IQR) serum calcium at admission was 13.2 (11.8-14.6) mg/dl. The most common neoplasms were pulmonary (27.3%), hematologic (23.4%), urological (13%), and breast (12.3%). Furthermore, 56.5% of cases had a known history of neoplasia at the time of diagnosis. The parathyroid hormone (PTH) level was determined in 24%; of these, 10.8% had elevated levels. In all, 95.5% of patients died during follow-up. The median survival was 3.4 weeks (95% confidence interval 2.6-4.3). Factors associated with higher mortality were age, serum calcium at admission, previous history of neoplasia, etiology other than multiple myeloma, and noncorrection of hypercalcemia.
    CONCLUSIONS: In hospitalized patients, paraneoplastic hypercalcemia was associated with high short-term mortality. Several factors associated with a worse prognosis were identified in these patients.
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  • 文章类型: Letter
    暂无摘要。
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  • 文章类型: Journal Article
    背景和目的:肝癌对全球健康构成重大威胁,在癌症相关死亡的三大原因中排名。肝细胞癌(HCC)患者通常表现为与肿瘤相关的症状或不寻常的临床特征,如副肿瘤综合征(PNS),包括低血糖,高胆固醇血症,血小板增多症,和红细胞增多症。我们的研究旨在调查患病率,临床特征,和生存结果与PNS相关的HCC患者,并评估每个PNS对患者生存的影响。材料和方法:我们进行了PNS临床特征和生存的连续HCC患者在我们部门诊断超过7年的回顾性分析。将它们与没有PNS的HCC患者进行比较。该研究涉及2016年1月至2023年10月期间诊断为HCC的378例患者的回顾性数据评估。结果:我们获得了25.7%的PNS患病率,副肿瘤性高胆固醇血症为10.9%,低血糖6.9%,红细胞增多率为4.5%,和3.4%的血小板增多。PNS患者倾向于年轻且主要为男性。多因素分析显示PNS与甲胎蛋白水平和肿瘤大小之间有很强的相关性,与糖尿病也显示出显着的统计关联(p<0.05)。基于特定副肿瘤综合征的亚组分析显示,PNS患者的生存期较短,尽管没有显著的统计差异,除了低血糖(p<0.0001)。匹配分析表明PNS患者的生存率较短,尽管没有观察到显著的统计学差异。结论:PNS在HCC病例中经常观察到,并且由于与肿瘤负担增加有关,因此与预后不良和生存率降低有关。然而,他们不能独立预测不良的生存。个体PNS对HCC预后的影响各不相同。
    Background and Objectives: Liver cancer poses a significant global health threat, ranking among the top three causes of cancer-related deaths. Patients with hepatocellular carcinoma (HCC) often present with symptoms associated with neoplasms or unusual clinical features such as paraneoplastic syndromes (PNS), including hypoglycemia, hypercholesterolemia, thrombocytosis, and erythrocytosis. Our study aimed to investigate the prevalence, clinical characteristics, and survival outcomes associated with PNS in HCC patients and assess each PNS\'s impact on patient survival. Materials and Methods: We conducted a retrospective analysis of PNS clinical features and survival among consecutive HCC patients diagnosed at our department over seven years, comparing them with HCC patients without PNS. The study involved a retrospective data evaluation from 378 patients diagnosed with HCC between January 2016 and October 2023. Results: We obtained a PNS prevalence of 25.7%, with paraneoplastic hypercholesterolemia at 10.9%, hypoglycemia at 6.9%, erythrocytosis at 4.5%, and thrombocytosis at 3.4%. Patients with PNS tended to be younger and predominantly male. Multivariate analysis revealed a strong correlation between PNS and levels of alpha-fetoprotein and tumor size, with diabetes also showing a significant statistical association (p < 0.05). Subgroup analysis based on specific paraneoplastic syndromes demonstrated shorter survival in patients with PNS, albeit without significant statistical differences, except for hypoglycemia (p < 0.0001). Matched analysis indicated a shorter survival rate for patients with PNS, although no significant statistical differences were observed. Conclusions: PNS are frequently observed in HCC cases and are associated with unfavorable prognoses and decreased survival rates due to their correlation with increased tumor burdens. However, they do not independently predict poor survival. The impact of individual PNS on HCC prognosis varies.
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  • 文章类型: Journal Article
    背景:线性IgA大疱性皮肤病(LABD)是一种罕见的自身免疫性大疱性疾病,可能是药物诱发或副肿瘤。我们的目标是表征LABD的特征,并确定特发性,药物诱导,或恶性肿瘤相关疾病。
    方法:我们在大型三级转诊中心对成人线性IgA大疱性皮肤病患者进行了单中心回顾性图表回顾,并对成人线性IgA大疱性皮肤病进行了文献回顾。
    结果:本研究纳入了81例患者。10例(12.3%)患有恶性肿瘤,9例(11.1%)患有炎症性肠病。两种药物诱导的中位疾病持续时间均显着缩短(1.2vs.48.8个月;P<0.001)和恶性肿瘤相关(1.7与48.8个月;P<0.001)LABD与特发性LABD相比。与药物诱发的患者相比,特发性LABD的复发发作频率明显更高(76.1vs.11.5%;P<0.001)或恶性肿瘤相关疾病(76.1vs.33.3%;P=0.019)。药物诱导的诊断时间明显缩短(0.2vs.5.4个月;P<0.001)和恶性肿瘤相关组(0.7vs.5.4个月;P=0.049)与特发性相比;同样,两种药物诱导的改善时间均显著缩短(0.4vs.3.0个月;P<0.001)和恶性肿瘤相关疾病(1.1vs.3.0个月;P=0.016)。两组之间的临床形态难以区分。限制包括回顾性数据收集,来自三级转诊中心的数据,有限的种族和民族多样性。
    结论:筛查潜在的恶性肿瘤,以及易感药物或可能的炎症性肠病,LABD患者可能是可取的,尤其是新诊断的时候。
    BACKGROUND: Linear IgA bullous dermatosis (LABD) is a rare autoimmune blistering disorder that may be drug-induced or paraneoplastic. We aim to characterize features of LABD and determine differentiating factors among idiopathic, drug-induced, or malignancy-associated diseases.
    METHODS: We conducted a single-center retrospective chart review of adult patients with linear IgA bullous dermatosis at a large tertiary referral center and a literature review of adult linear IgA bullous dermatosis.
    RESULTS: Eighty-one patients were included in the study. Ten patients (12.3%) had comorbid malignancy and nine (11.1%) had inflammatory bowel disease. Median disease duration was significantly shorter in both drug-induced (1.2 vs. 48.8 months; P < 0.001) and malignancy-associated (1.7 vs. 48.8 months; P < 0.001) LABD compared with idiopathic LABD. Recurrent episodes occurred significantly more often in idiopathic LABD compared to those with drug-induced (76.1 vs. 11.5%; P < 0.001) or malignancy-associated disease (76.1 vs. 33.3%; P = 0.019). Time to diagnosis was significantly shorter in the drug-induced (0.2 vs. 5.4 months; P < 0.001) and malignancy-associated groups (0.7 vs. 5.4 months; P = 0.049) compared with idiopathic; similarly, time to improvement was significantly shorter in both drug-induced (0.4 vs. 3.0 months; P < 0.001) and malignancy-associated disease (1.1 vs. 3.0 months; P = 0.016). Clinical morphology was indistinguishable between groups. Limitations included retrospective data collection, data from tertiary referral centers, and limited racial and ethnic diversity.
    CONCLUSIONS: Screening for underlying malignancy, as well as for a predisposing medication or possibly inflammatory bowel disease, may be advisable in patients with LABD, particularly when it is newly diagnosed.
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  • 文章类型: Journal Article
    对自身免疫性脑炎(AIE)的病例进行成像可能具有挑战性,因为潜在的肿瘤可能是隐匿的。这项基于病例的回顾性研究的目的是评估全身MRI/正电子发射断层扫描(PET)在AIE检查中的作用。标准化全身MRI/PET协议,与血清学和磁共振/PET(MR/PET)交叉模式产生,最后突出了混合MR/PET的优势。我们提供了2016年1月至2019年12月的回顾性回顾数据,涉及疑似AIE/副肿瘤综合征的全身MR/PET,根据共识标准,在一个单一的三级中心治疗。分析是根据肿瘤学的转诊方式进行的,免疫或神经精神疾病。在我们的MR/PET方案和优势系列中,以表格形式提供了具有敏感性和特异性的详细结果,并进行了基于病例的审查。在总共600例MR/PET病例中,227例被怀疑患有AIE/副肿瘤综合征,并被转诊进行全身成像。第1组分布已知肿瘤学组(n=10),第2组非肿瘤性系统性疾病组(n=174)和第3组原发性神经精神疾病(n=43),第2组最大。性别分布相似,平均年龄为42岁。血清阴性病例(n=130)大于血清阳性病例(n=97)。血清阳性按照以下顺序:自身免疫>副肿瘤>肌炎组。全身MRPET在9%的病例中产生隐匿性恶性肿瘤,在88%的病例中产生影像学异常。全身MR/PET在AIE的检查中具有重要作用。选择适当的协议很重要,尤其是当病史和体格检查是非特异性时。
    Imaging a case of autoimmune encephalitis (AIE) can be challenging as the underlying tumor may be occult. The aim of this retrospective case-based study is to evaluate role of whole-body MRI/Positron emission tomography (PET) in workup of AIE. Standardizing the whole-body MRI/PET protocol, Cross modality yield with serology and magnetic resonance/PET (MR/PET) and finally highlight the advantage of hybrid MR/PET. We present the retrospective review data from January 2016 to December 2019 referred for whole body MR/PET with suspected AIE/Paraneoplastic syndrome, per consensus criteria, treated at a single tertiary center. Analysis is done group wise based on referral being for oncological, immunological or neuropsychiatric condition. Detailed results with sensitivity and specificity are presented in tabular format with case-based review in our series for protocols and advantages of MR/PET. Among total of 600 MR/PET cases, 227 were suspected of AIE/paraneoplastic syndrome and were referred for whole body imaging. Distribution of Group 1 Known oncology group (n = 10), Group 2 Non oncological systemic illness group (n = 174) and group 3 the primary neuropsychiatric illness (n = 43) with Group 2 being largest. The gender distribution was similar and mean age was 42 years. Seronegative cases (n = 130) were greater than seropositive cases (n = 97). Seropositivity was in the following order Autoimmune > Paraneoplastic > Myositis panel. Whole body MRPET yielded occult malignancy in 9% and imaging abnormality in 88% of cases. Whole body MR/PET has an important role in workup of AIE. Selection of the appropriate protocol is important, especially when history and physical examination are nonspecific.
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  • 文章类型: Multicenter Study
    目的:分析住院患者高钙血症的研究有限。我们的目标是描述高钙血症住院患者的临床特征,估计其在医院环境中的患病率,分析高钙血症的纠正率,并确定预后变量。
    方法:观察性,纵向,回顾性,和双中心研究。纳入了马拉加两家医院(2014-2018年)诊断为高钙血症的成年患者。最低随访时间为2年或直至死亡。
    结果:共纳入205例高钙血症患者(发生率:0.13%)。平均年龄(SD)为68.2(13.1)岁,以男性为主(55.1%)。入院时血清钙中位数(IQR)为13.1(11.8-14.6)mg/dl。最常见的病因是肿瘤(75.1%),原发性甲状旁腺功能亢进,和药物(均为8.8%)。中位(IQR)随访期为5.1(1.7-60.3)周。最常用的治疗方法是液体疗法(86.8%),loop利尿剂(70.9%),双膦酸盐(60.7%),和糖皮质激素(46.2%)。高钙血症的纠正率为65.2%,中位数(IQR)为6(3-10)天。死亡率为81.5%。中位生存期(95%CI)为5.1(3-7.3)周。与较高死亡率相关的因素是高龄,肿瘤病因学,入院时血清钙,未能纠正高钙血症。
    结论:住院患者的高钙血症主要是由于肿瘤形成过程,并与高死亡率相关。我们观察到对高钙血症治疗建议的依从性较低。
    There are limited studies analyzing hypercalcemia in hospitalized patients. Our objectives were to describe the clinical characteristics of hospitalized patients with hypercalcemia, estimate its prevalence in the hospital setting, analyze the rate of correction of hypercalcemia, and identify prognostic variables.
    Observational, longitudinal, retrospective, and bicentric study. Adult patients admitted to two hospitals in Málaga (2014-2018) with a diagnosis of hypercalcemia were included. The minimum follow-up was 2 years or until death.
    A total of 205 patients with hypercalcemia were included (incidence: 0.13%). The mean age (SD) was 68.2 (13.1) years, with a predominance of males (55.1%). The median (IQR) serum calcium at admission was 13.1 (11.8-14.6) mg/dl. The most common etiologies were neoplasms (75.1%), primary hyperparathyroidism, and medications (both 8.8%). The median (IQR) follow-up period was 5.1 (1.7-60.3) weeks. The most commonly used treatments were fluid therapy (86.8%), loop diuretics (70.9%), bisphosphonates (60.7%), and glucocorticoids (46.2%). The rate of correction of hypercalcemia was 65.2%, with a median (IQR) of 6 (3-10) days. The mortality rate was 81.5%. The median (95% CI) survival was 5.1 (3-7.3) weeks. Factors associated with higher mortality were advanced age, neoplastic etiology, serum calcium at admission, and failure to correct hypercalcemia.
    Hypercalcemia in hospitalized patients is mainly due to neoplastic processes and is associated with high mortality. We observed a low rate of adherence to recommendations for the management of hypercalcemia.
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  • 文章类型: Journal Article
    背景:自身免疫性脑炎(AIE)和副肿瘤综合征(PNS)都是罕见的神经系统疾病,难以诊断。
    目的:我们的目的是确定脑炎这两种病因的共同和不同方面以及我们患者组的特征。
    方法:我们分别分析了患者的记录,包括症状,人口特征,神经系统检查,头颅磁共振成像(MRI),脑电图(EEG)的发现,脑脊液结果(CSF)发现。血液和/或CSF中的自身免疫/副肿瘤自身抗体全部被记录。
    结果:46例患者符合诊断标准。其中38人被诊断患有AIE,其中8人被诊断为PNS。PNS组的非惊厥性癫痫持续状态高于AIE(2/8vs0/38;p=0.027)。PNS患者在随访中被诊断为恶性肿瘤的患者多于AIE组[4/38vs8/8](p<0.001)。当在AIE组中比较抗体阳性和阴性患者的症状时,无抗体患者(n:15)的意识/记忆问题发生率(13/15vs11/23;p=0.020)和言语障碍发生率(8/15vs2/23;p=0.004)显著高于抗体阳性患者(n:23).在抗体阴性组中,与抗体阳性组(1/23vs5/15;p=0.027)相比,神经系统检查中的记忆问题发生率(13/15vs12/23,p=0.028)和脑电图上的时间点表现更为显著.抗体阳性患者中具有小脑体征的患者数量较高(6/23vs0/15;p=0.038)。
    结论:尽管自身抗体的阳性在AIE和PNS的诊断中至关重要,即使患者的临床和实验室检查结果的微小差异也有助于诊断,尤其是自身抗体阴性的患者。将数据与其他人群研究进行比较表明,几种遗传和环境因素可能有助于AIE和PNS的病理生理学,以及临床和实验室的差异。
    BACKGROUND: Autoimmune encephalitis (AIE) and paraneoplastic syndromes (PNS) are both rare groups of neurological diseases that are difficult to diagnose.
    OBJECTIVE: We aimed to determine the common and distinct aspects of these two aetiologies of encephalitis as well as the characteristics of our patient group.
    METHODS: We respectively analysed the records of the patients including symptoms, demographic features, neurological examination, cranial-magnetic-resonance-imaging (MRI), electroencephalography (EEG) findings, cerebrospinal fluid results (CSF) findings. Autoimmune/paraneoplastic autoantibodies in blood and/or CSF were all documented.
    RESULTS: Forty-six patients fulfilled the diagnostic criteria. Thirty-eight of them were diagnosed with AIE, and 8 of them were diagnosed with PNS. The PNS group had higher nonconvulsive status epilepticus than the AIE (2/8 vs 0/38; p=0.027). PNS patients were diagnosed with a malignancy in their follow-ups more than those in the AIE group [4/38 vs 8/8] (p<0.001). When the symptoms of antibody-positive and negative patients were compared in the AIE group, the rates of consciousness/memory problems (13/15 vs 11/23; p=0.020) and speech impairment (8/15 vs 2/23; p=0.004) were significantly higher in patients without antibodies (n: 15) than in antibody-positive patients (n: 23). In antibody-negative groups, the rates of memory problems in neurological examination (13/15 vs 12/23 p=0.028) and temporal findings on electroencephalography were more prominent than antibody-positive groups (1/23 vs 5/15; p=0.027). The number of patients with cerebellar signs was higher in antibody-positive patients (6/23 vs 0/15; p=0.038).
    CONCLUSIONS: Although the positivity of autoantibodies is critical in the diagnosis of AIE and PNS, even minor differences in clinical and laboratory findings of patients are helpful in the diagnosis, especially in the autoantibody-negative patients. Comparing the data with other population studies has shown that several inherited and environmental factors may contribute to the pathophysiology of AIE and PNS, as well as clinical and laboratory differences.
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  • 文章类型: Case Reports
    一名有疑似肿瘤诱导的骨软化病史的74岁女性接受了99mTc-HYNIC-TOC闪烁显像以寻找潜在的罪魁祸首肿瘤。图像显示左股骨中轴有一个,随后的SPECT/CT图像的CT部分没有相应的形态变化。患者拒绝对左股骨进行手术探查。另一个活动是在右乳房,切除后病理证实为乳腺癌。手术后,患者的症状没有改善。四年后,重复的99mTc-HYNIC-TOC闪烁显像显示,在相应的CT图像上,左股骨活动更为明显,异常异常。
    UNASSIGNED: A 74-year-old woman with a history of suspected tumor-induced osteomalacia underwent 99mTc-HYNIC-TOC scintigraphy to search potential culprit tumor. The images showed one in the middle shaft of left femur without corresponding morphology change on the CT portion of the subsequent SPECT/CT images. The patient declined surgical exploration of the left femur. Another activity was in the right breast, which was resected and pathologically confirmed as breast carcinoma. Postsurgically, the patient\'s symptoms were not improved. Four years later, a repeat 99mTc-HYNIC-TOC scintigraphy showed more prominent activity in the left femur with gross abnormality on the corresponding CT images.
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  • 文章类型: Clinical Trial, Phase II
    Patients with tumor-induced osteomalacia (TIO), an acquired paraneoplastic condition characterized by osteomalacia due to hypophosphatemia, exhibit a similar clinical picture to those with X-linked hypophosphatemic rickets/osteomalacia (XLH). The human monoclonal anti-fibroblast growth factor 23 (FGF23) antibody burosumab (KRN23) increases serum phosphate and improves bone turnover, fracture healing, pain, and physical function in XLH patients by inhibiting circulating FGF23; thus, burosumab is expected to be an effective treatment for TIO. We report here an interim analysis of a multicenter, open-label, intraindividual dose-adjustment study of burosumab (0.3 to 2.0 mg/kg every 4 weeks) in Japanese and Korean TIO patients. The primary endpoint was the fasting serum phosphate level at each visit. Key secondary endpoints were changes over time in bone biomarkers, pharmacodynamic markers, bone histomorphometric parameters, motor function, and patient-reported outcomes. Safety was assessed based on treatment-emergent adverse events (TEAEs). Thirteen patients received burosumab treatment, of whom 4 underwent bone biopsy. The mean dose after week 112 was approximately 1.0 mg/kg. After the first burosumab administration, mean serum phosphate levels increased and remained above the lower limit of normal and in the normal range from weeks 14 to 112. Bone biomarkers initially increased, reaching maximum values at week 16 or 24, and then gradually decreased. After burosumab treatment, patients were able to walk further (evaluated by the 6-minute walk test), reported decreased pain levels, and showed a tendency toward healing of baseline fractures and pseudofractures. Two patients discontinued, one each due to disease progression and consent withdrawal. Burosumab was generally well tolerated, with no treatment-related TEAEs of grade ≥3 and no treatment-related serious AEs. In conclusion, the interim results of this first study of burosumab to treat TIO patients indicate that this drug has the potential to provide clinical benefit for patients with unresectable tumors. The full study results are eagerly anticipated. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..
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  • 文章类型: Journal Article
    BACKGROUND: Paraneoplastic neurological syndromes (PNS) are immune-mediated diseases that occur in patients with tumors and can be associated with onconeural antibodies. Our aim was to describe our cohort of patients with PNS.
    METHODS: Retrospective analysis of a cohort of patients followed in a Portuguese tertiary center, with autoantibodies against intracellular antigens from our PNS panel, between 2012 and 2017.
    RESULTS: Among the 882 patients with suspected PNS (1029 samples), 37 (4.2%) had positive and 27 (3.1%) weak positive antibodies. A total of 17 (29.3%) PNS were diagnosed, 5 were classic syndromes. Autoantibodies found were anti-Yo, anti-Hu, anti-titin, anti-Ma2, anti-SOX1, anti-Ri and anti-CV2/CRMP5. They were associated with thymoma, breast, colon, parotid gland and lung (small-cell, neuroendocrine or carcinoid) cancer. Among the 17 PNS patients, no tumor was found in 4 (mean follow-up of 46 months); no patients improved with tumor treatment, while 8 improved with immunotherapy; ten patients (59%) died during follow-up. Twenty (60.6%) patients with positive antibodies and 21 (84.0%) with weak positive were not diagnosed with a PNS.
    CONCLUSIONS: PNS had highly heterogenous clinical presentations. Response to tumor treatment was overall poor, with an unfavorable prognosis. In our cohort, only 29.3% of the patients with positive antibodies were diagnosed with a PNS.
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