clinical research, practice

  • 文章类型: Journal Article
    在肺移植(LT)的背景下,由于诊断困难,抗体介导的排斥反应(AMR)仍然是一个有争议的问题。我们回顾性分析了Foch医院的LT队列,以证明AMR对LT预后的影响。AMR诊断需要临床症状的关联,供体特异性抗体(DSA),和C4d(+)染色和/或组织学模式与AMR一致。前瞻性分类将患者分为四组:(i)DSA阳性,AMR阳性(DSA(pos)AMR(pos));(ii)DSA阳性,AMR阴性(DSA(pos)AMR(neg));(iii)DSA有限,AMR阴性(DSA(Lim);等于一种特异性,平均荧光强度为500-1000次);(iv)DSA阴性,AMR阴性(DSA(neg))。AMR治疗包括血浆置换的组合,静脉注射免疫球蛋白和利妥昔单抗。在206名移植患者中,10.7%为DSA(pos)AMR(pos)(n=22),40.3%为DSA(pos)AMR(neg)(n=84),6%为DSA(Lim)(n=13),43%为DSA(neg)(n=88)。第12个月的急性细胞排斥分析显示,DSA(pos)AMR(pos)组(2.1±1.7)与DSA(pos)AMR(neg)(1±1.2)相比,DSA(Lim)(0.75±1),DSA(neg)(0.7±1.23)组。多变量分析表明,AMR是DSA(pos)AMR(pos)患者的慢性同种异体肺移植功能障碍(风险比[HR]8.7)和移植物丢失(HR7.56)的危险因素。我们的结果表明AMR对LT临床过程有负面影响,并主张采用早期积极的诊断方法和评估治疗策略以改善预后。
    In the context of lung transplant (LT), because of diagnostic difficulties, antibody-mediated rejection (AMR) remains a matter of debate. We retrospectively analyzed an LT cohort at Foch Hospital to demonstrate the impact of AMR on LT prognosis. AMR diagnosis requires association of clinical symptoms, donor-specific antibodies (DSAs), and C4d(+) staining and/or histological patterns consistent with AMR. Prospective categorization split patients into four groups: (i) DSA positive, AMR positive (DSA(pos) AMR(pos) ); (ii) DSA positive, AMR negative (DSA(pos) AMR(neg) ); (iii) DSA limited, AMR negative (DSA(Lim) ; equal to one specificity, with mean fluorescence intensity of 500-1000 once); and (iv) DSA negative, AMR negative (DSA(neg) ). AMR treatment consisted of a combination of plasmapheresis, intravenous immunoglobulin and rituximab. Among 206 transplanted patients, 10.7% were DSA(pos) AMR(pos) (n = 22), 40.3% were DSA(pos) AMR(neg) (n = 84), 6% were DSA(Lim) (n = 13) and 43% were DSA(neg) (n = 88). Analysis of acute cellular rejection at month 12 showed higher cumulative numbers (mean plus or minus standard deviation) in the DSA(pos) AMR(pos) group (2.1 ± 1.7) compared with DSA(pos) AMR(neg) (1 ± 1.2), DSA(Lim) (0.75 ± 1), and DSA(neg) (0.7 ± 1.23) groups. Multivariate analysis demonstrated AMR as a risk factor for chronic lung allograft dysfunction (hazard ratio [HR] 8.7) and graft loss (HR 7.56) for DSA(pos) AMR(pos) patients. Our results show a negative impact of AMR on LT clinical course and advocate for an early active diagnostic approach and evaluation of therapeutic strategies to improve prognosis.
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  • 文章类型: Comparative Study
    器官移植受者(OTR)的鳞状细胞皮肤癌(SCSC)的风险显着升高,主要归因于用于预防移植物排斥的免疫抑制药物,尽管支持新药在SCSC风险中的作用的数据很少.我们在SCOT队列研究中调查了心脏和肾脏移植受者中免疫抑制药物与SCSC风险之间的关系。在皮肤活检自我报告后,通过病历审查确定事件病例(n=170)。没有SCSC的对照(n=324)与性别病例相匹配,年龄,种族,移植年,医院,供体类型,器官移植,以及移植和面谈之间的时间。使用条件逻辑回归来评估特定药物与SCSC之间的关联。使用抗代谢物硫唑嘌呤的患者发生SCSC的可能性是后者的两倍多(比值比[OR]=2.67,95%置信区间[CI]1.23-5.76)。相比之下,较新的抗代谢制剂(即,霉酚酸[MPA])与较低的SCSC风险相关(OR=0.45,95%CI0.29-0.69)。在没有硫唑嘌呤使用史的OTR中,MPA和SCSC之间的这种负相关仍然存在,即使同时使用钙调神经磷酸酶抑制剂他克莫司进行了调整(OR=0.52,95%CI0.32-0.84).我们的数据表明,与硫唑嘌呤相关的SCSC增加的风险在OTRs处方较新的方案中未见到。包括MPA和他克莫司。
    Organ transplant recipients (OTRs) have a substantially elevated risk of squamous cell skin carcinoma (SCSC), largely attributed to immunosuppressive medications used to prevent graft rejection, although data to support the role of newer drugs in SCSC risk are sparse. We investigated the association between immunosuppressive medications and SCSC risk among cardiac and renal transplant recipients in the SCOT cohort study. Incident cases were ascertained through medical record review after self-report of skin biopsy (n = 170). Controls without SCSC (n = 324) were matched to cases on sex, age, race, transplant year, hospital, donor type, organ transplanted, and time between transplantation and interview. Conditional logistic regression was used to evaluate the association between specific medications and SCSC. Users of the antimetabolite azathioprine were more than twice as likely to develop SCSC (odds ratio [OR] = 2.67, 95% confidence interval [CI] 1.23-5.76). In contrast, the newer antimetabolite preparations (i.e., mycophenolic acid [MPA]) were associated with lower SCSC risk (OR = 0.45, 95% CI 0.29-0.69). This inverse association between MPA and SCSC persisted among OTRs with no history of azathioprine use, even after adjustment for simultaneous use of the calcineurin inhibitor tacrolimus (OR = 0.52, 95% CI 0.32-0.84). Our data suggest that the increased risk of SCSC historically associated with azathioprine is not seen in OTRs prescribed newer regimens, including MPA and tacrolimus.
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  • 文章类型: Journal Article
    实体器官移植的进步每年成功地延长了数千名患者的生命。器官管理的宗旨是防止死亡风险高的患者人群中稀缺的供体器官的徒劳支出。不利于预期寿命更长的潜在接受者。移植后皮肤癌的发展预示着巨大的发病率,对许多移植受者的生活质量产生不利影响。这篇特别的文章,由国际移植皮肤癌合作组织(ITSCC)成员提供,将为移植专业人员提供一致的意见和建议,以便为有皮肤鳞状细胞癌病史的移植候选人提供适当的等待期,恶性黑色素瘤,或者默克尔细胞癌。
    Advancements in solid organ transplantation successfully extend the lives of thousands of patients annually. The tenet of organ stewardship aims to prevent the futile expenditure of scarce donor organs in patient populations with high mortality risk, to the detriment of potential recipients with greater predicted life expectancy. The development of skin cancer posttransplantation portends tremendous morbidity, adversely affecting quality of life for many transplant recipients. This special article, provided by of members of the International Transplant Skin Cancer Collaborative (ITSCC), will provide the transplant professional with a consensus opinion and recommendations as to an appropriate wait period pretransplantation for transplant candidates with a history of either cutaneous squamous cell carcinoma, malignant melanoma, or Merkel cell carcinoma.
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  • 文章类型: Journal Article
    影响原发性胆汁性肝硬化(PBC)活体肝移植(LDLT)后长期结局的因素尚不清楚。与死者移植相比,LDLT具有增加的相关供体的可能性和减少的人白细胞抗原(HLA)错配的数量。为了阐明供者亲缘关系和HLA错配对LDLT后结局的影响,我们回顾性分析了444例日本患者.捐献者是332名患者的血亲,105人的配偶,7人的“其他”。HLAA-B-DR错配的数量在141例中为2,在123例中为3,在106例患者中为4至6。15年生存率为52.6%,65例患者PBC复发。收件人61岁或以上,HLA不匹配四个或更多(最多六个),移植物:受体体重比小于0.8,丈夫供体是患者生存的不利指标。IgM554mg/dL或更高,供体-受体性别不匹配,和环孢素的初始免疫抑制是PBC复发的显著风险,这并不影响患者的生存。在亚组分析中,1年内他克莫司转用环孢素可减少复发.需要进行前瞻性研究以确定妊娠相关致敏的影响,并建立LDLT患者的最佳免疫抑制方案。
    The factors that influence long-term outcomes after living-donor liver transplantation (LDLT) for primary biliary cirrhosis (PBC) are not well known. Compared with deceased-donor transplantation, LDLT has an increased likelihood of a related donor and a decreased number of human leukocyte antigen (HLA) mismatches. To clarify the effects of donor relatedness and HLA mismatch on the outcomes after LDLT, we retrospectively analyzed 444 Japanese patients. Donors were blood relatives for 332 patients, spouses for 105, and \"other\" for 7. The number of HLA A-B-DR mismatches was none to two in 141, three in 123, and four to six in 106 patients. The 15-year survival rate was 52.6%, and PBC recurred in 65 patients. Recipient aged 61 years or older, HLA mismatches of four or more (maximum of six), graft:recipient weight ratio less than 0.8, and husband donor were adverse indicators of patient survival. IgM 554 mg/dL or greater, donor-recipient sex mismatch, and initial immunosuppression with cyclosporine were significant risks for PBC recurrence, which did not affect patient survival. In subgroup analysis, conversion to cyclosporine from tacrolimus within 1 year diminished recurrence. Prospective studies are needed to determine the influence of pregnancy-associated sensitization and to establish an optimal immunosuppressive regimen in LDLT patients.
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