ABO血型不合活体肾移植11例分析

目的  探讨ABO血型不合活体肾移植（ABOi-KT）的疗效和安全性。方法  回顾性分析11例ABOi-KT的供、受体临床资料。受体术前均经过脱敏治疗,术后监测ABOi-KT受体的肾功能和血型抗体滴度恢复情况,观察ABOi-KT术后受体的并发症发生情况及预后情况。结果  ABOi-KT术后11例受体血清肌酐（Scr）均恢复良好,未出现移植肾功能恢复延迟。其中2例受体分别在术后14、45 d出现Scr明显升高,1例受体术后出现临界性细胞性排斥反应,1例受体在术后33 d出现Scr升高,伴血型抗体滴度上升,经治疗后病情均平稳。其余7例受体术后移植肾功能正常,术后血型抗体滴度均无反弹。随访至2018年11月,未出现受体死亡和移植肾失功,受体及移植肾存活率均为100%。其中3例受体术后发生并发症,分别为肺部感染、BK病毒尿症和粒细胞缺乏症,经对症治疗后均痊愈。结论  ABOi-KT安全可行且长期疗效较好,可以增加活体供肾的来源,缓解供肾来源短缺。     

siRNA干扰SIRT1对辐射后IL-6表达的影响

目的 研究siRNA干扰沉默信息调节因子2相关酶1（SIRT1）对间充质干细胞（MSCs）电离辐射后诱导的炎性因子白细胞介素6（IL-6）的影响,探究SIRT1的辐射防护作用。 方法 使用0、2、4、8 Gy照射MSCs,分别在照后3、6、12、24 h提取总RNA和总蛋白,检测IL-6表达水平;将MSCs分为空白对照组、单纯照射组和SIRT1干扰联合照射组,使用Western blot、RT-PCR检测SIRT1和IL-6胞内表达。 结果 MSCs在电离照射后,IL-6的表达水平先升高后降低;在照后12 h达到最高,24 h恢复基准水平;而联合SIRT1干扰会引起IL-6水平进一步升高,加重MSCs电离辐射后的炎症反应。 结论 SIRT1可能通过抑制电离辐射诱导的炎性因子IL-6的表达,发挥辐射防护作用。     

GBZ 97-2017 《职业性放射性肿瘤判断规范》解析——放射性肿瘤病因概率方法的不确定性

放射性肿瘤病因概率（PC）方法具有先天的不确定性,这是我国国家标准中亟待加强的部分。笔者总结了放射性肿瘤PC方法不确定性的来源和主要内容,以及不确定性的分析和评估的研究现状,并介绍了降低PC方法不确定度的几种措施。     

Humoral response to vaccination against SARS-CoV-2 in patients undergoing dialysis

Patients undergoing maintenance dialysis have a higher mortality rate associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and response rates to vaccination against SARS-CoV-2 vary from 29.6% to 96.4% in such patients. This study aimed to assess the immunogenicity of SARS-CoV-2 vaccination in Korean patients undergoing dialysis. We enrolled 70 SARS-CoV-2-vaccinated patients undergoing dialysis, with 11 healthcare workers serving as healthy control subjects. Thirty-two patients had received a third vaccination, whereas 38 had received 2 vaccinations. The healthy control subjects completed the second vaccination. Immunoglobulin G (IgG) antibodies targeting the receptor-binding domain of the S1 subunit of the SARS-CoV-2 spike protein were measured The vaccination responder rates were 86% (37/43), 96% (26/27), and 91% (10/11) in the patients undergoing hemodialysis and peritoneal dialysis and healthy controls, respectively. IgG antibody levels were significantly higher when a third dose was administered, independent of the type of vaccine or the time interval between vaccination and the subsequent blood sampling date. When a third dose of vaccine was administered, there was no difference in IgG antibody levels between those receiving cross-vaccination or a single vaccine. There was no significant difference in IgG antibodies between healthy controls and patients undergoing dialysis. Patients on dialysis exhibited a sufficient antibody-related response to vaccination against SARS-CoV-2, even in those receiving cross-vaccination, and the antibody titer was higher after a third vaccination. Therefore, it is necessary to administer a third vaccine dose to Korean patients undergoing dialysis.     

A phase II randomized double blinded trial evaluating the efficacy of curcumin with pre-operative chemoradiation for rectal cancer

BackgroundIn vivo studies demonstrate that curcumin increases radioresponse of colorectal cancers. To demonstrate efficacy in humans, we performed a randomized double-blind study of locally advanced rectal cancer (LARC) patients receiving pre-operative chemoradiation therapy (CRT) ± curcumin. We used pathologic complete response (pCR) rate as a surrogate for clinical outcome.MethodsFrom 2008–2010, LARC patients were randomized to placebo/curcumin in a 1:2 ratio. Patients received CRT [50.4 gray in 28 fractions; capecitabine (825 mg/m² twice daily)] followed by surgery. Curcumin (4 grams orally, twice daily) or placebo was given throughout CRT and 6 weeks afterward. Toxicity was monitored weekly. Blood samples taken pre- and 1-hour post-ingestion and tissue biopsies (both collected at CRT week 2) were analyzed for pharmacokinetics. The primary outcome was surgical pCR rate.ResultsOf 22 enrolled patients, 15 received curcumin. Median age was 61 years and the majority were male (n=13; 59%). The median serum curcumin concentrations before (3.04 ng/mL; range, 1.24–18.88 ng/mL) and 1 hour after (3.32 ng/mL; range, 0.84–5.36 ng/mL) curcumin intake did not differ significantly (P=0.33). Serum curcumin concentrations both increased and decreased 1-hour post-administration (range as percentage of baseline: 8.8–258.1%). Twelve curcumin patient tissue biopsies had median curcumin concentration of 33.7 ng/mg tissue (range, 0.1–4,765.7 ng/mg). Two placebo and 1 curcumin patient achieved pCRs (P=0.18). One grade 3 toxicity (infection) was experienced.ConclusionsThe addition of curcumin to CRT did not increase pCR rates for LARC patients. The unpredictable bioavailability of curcumin contributes to continued uncertainties regarding curcumin efficacy.Trial RegistrationClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT00745134","term_id":"NCT00745134"}}NCT00745134.     

Prognostic implications of microRNA-21 overexpression in pancreatic ductal adenocarcinoma: an international multicenter study of 686 patients

Despite progress in genomic characterization, no single prognostic marker that can be evaluated using an easy-to-perform and relatively inexpensive method is available for pancreatic ductal adenocarcinoma (PDAC). MicroRNAs, which are stable, tumor- and tissue-specific molecules, are potentially ideal biomarkers, and we established an inter-laboratory validated method to investigate miR-21 as a prognostic biomarker in PDAC. The study samples of PDAC patients were recruited from a test cohort of Glasgow (n = 189) and three validation cohorts of Pisa (n = 69), Sydney (n = 249), and International Cancer Genome Consortium (ICGC) (n = 249). Tissue microarrays were used for miR-21 staining by chromogenic in situ hybridization (CISH). The patients were subdivided into no/low and high miR-21 staining groups using a specific histoscore. Furthermore, miR-21 staining was evaluated against clinicopathological variables and follow-up data by Fisher/log-rank test and Cox proportional models. The prognostic variables found to be significant in univariate analysis (P value < 0.10) were included in multivariate analysis in a backward-stepwise fashion. MiR-21 expression was cytoplasmic, with more consistent staining in the malignant ductal epithelium than in the stroma. The expression of miR-21 was significantly associated with tumor size and lymph node metastasis, whereas no association was observed with other clinicopathological variables. High miR-21 staining (histoscore ≥ 45 [median score]) was an independent predictor of survival in the Glasgow test cohort (HR 2.37, 95% CI: 1.42-3.96, P < 0.0001) and three validation cohorts (Pisa, HR 2.03, 95% CI: 1.21-3.39, P = 0.007; Sydney, HR 2.58, 95% CI (1.21-3.39), P < 0.0001; and ICGC, HR 3.34, 95% CI: 2.07-5.84, P = 0.002) when adjusted for clinical variables in a multivariate model. In comparison to the patients with low miR-21, the patients with high miR-21 expression had significant increase in OS as they benefit from gemcitabine-based adjuvant chemotherapy (Glasgow 16.5 months [with chemotherapy] vs 10.5 months [without chemotherapy]); Sydney 25.0 vs 10.6; ICGC 25.2 vs 11.9. These results indicated that miR-21 is a predictor of survival, prompting prospective trials. Evaluation of miR-21 offers new opportunities for the stratification of patients with PDAC and might facilitate the implementation of clinical management and therapeutic interventions for this devastating disease.     

The Effect of Cognitive Impairment on the Association Between Social Network Properties and Mortality Among Older Korean Adults

Objectives:This study investigated the effect of cognitive impairment on the association between social network properties and mortality among older Korean adults.Methods:This study used data from the Korean Social Life, Health, and Aging Project. It obtained 814 older adults’ complete network maps across an entire village in 2011-2012. Participants’ deaths until December 31, 2020 were confirmed by cause-of-death statistics. A Cox proportional hazards model was used to assess the risks of poor social network properties (low degree centrality, perceived loneliness, social non-participation, group-level segregation, and lack of support) on mortality according to cognitive impairment.Results:In total, 675 participants (5510.4 person-years) were analyzed, excluding those with missing data and those whose deaths could not be verified. Along with cognitive impairment, all social network properties except loneliness were independently associated with mortality. When stratified by cognitive function, some variables indicating poor social relations had higher risks among older adults with cognitive impairment, with adjusted hazard ratios (HRs) of 2.12 (95% confidence interval [CI], 1.34 to 3.35) for social non-participation, 1.58 (95% CI, 0.94 to 2.65) for group-level segregation, and 3.44 (95% CI, 1.55 to 7.60) for lack of support. On the contrary, these effects were not observed among those with normal cognition, with adjusted HRs of 0.73 (95% CI, 0.31 to 1.71), 0.96 (95% CI, 0.42 to 2.21), and 0.95 (95% CI, 0.23 to 3.96), respectively.Conclusions:The effect of social network properties was more critical among the elderly with cognitive impairment. Older adults with poor cognitive function are particularly encouraged to participate in social activities to reduce the risk of mortality.     

Promoting Informed Decisions About Colorectal Cancer Screening in Older Adults (PRIMED Study): a Physician Cluster Randomized Trial

BackgroundFor adults aged 76–85, guidelines recommend individualizing decision-making about whether to continue colorectal cancer (CRC) testing. These conversations can be challenging as they need to consider a patient’s CRC risk, life expectancy, and preferences.ObjectiveTo promote shared decision-making (SDM) for CRC testing decisions for older adults.DesignTwo-arm, multi-site cluster randomized trial, assigning physicians to Intervention and Comparator arms. Patients were surveyed shortly after the visit to assess outcomes. Analyses were intention-to-treat.Participants and SettingPrimary care physicians affiliated with 5 academic and community hospital networks and their patients aged 76–85 who were due for CRC testing and had a visit during the study period.InterventionsIntervention arm physicians completed a 2-h online course in SDM communication skills and received an electronic reminder of patients eligible for CRC testing shortly before the visit. Comparator arm received reminders only.Main MeasuresThe primary outcome was patient-reported SDM Process score (range 0–4 with higher scores indicating more SDM); secondary outcomes included patient-reported discussion of CRC screening, knowledge, intention, and satisfaction with the visit.Key ResultsSixty-seven physicians (Intervention n=34 and Comparator n=33) enrolled. Patient participants (n=466) were on average 79 years old, 50% with excellent or very good self-rated overall health, and 66% had one or more prior colonoscopies. Patients in the Intervention arm had higher SDM Process scores (adjusted mean difference 0.36 (95%CI (0.08, 0.64), p=0.01) than in the Comparator arm. More patients in the Intervention arm reported discussing CRC screening during the visit (72% vs. 60%, p=0.03) and had higher intention to follow through with their preferred approach (58.0% vs. 47.1, p=0.03). Knowledge scores and visit satisfaction did not differ significantly between arms.ConclusionPhysician training plus reminders were effective in increasing SDM and frequency of CRC testing discussions in an age group where SDM is essential.Trial RegistrationThe trial is registered on clinicaltrials.gov ({"type":"clinical-trial","attrs":{"text":"NCT03959696","term_id":"NCT03959696"}}NCT03959696).Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-022-07738-4.KEY WORDS: shared decision-making, colorectal cancer screening, patient preferences/patient engagement, online training