• 【转移至区域烧伤中心的患者的结果分析: 转移状态不影响生存率。】 复制标题 收藏 收藏
    DOI:10.1016/j.burns.2006.04.001 复制DOI
    作者列表:Klein MB,Nathens AB,Heimbach DM,Gibran NS
    BACKGROUND & AIMS: BACKGROUND:Optimal burn care is provided at specialized burn centers. Given the geographic location of these centers, many burn patients receive initial treatment at local emergency departments prior to transfer. The purpose of this study was to determine whether patients transferred from other facilities have worse outcomes than those admitted directly from the field. STUDY DESIGN:A retrospective cohort study was performed comparing the outcomes of patients admitted to our burn center directly from the field with patients requiring transfer from a preliminary care facility. The outcomes of interest were mortality, length of stay, length of stay/TBSA burned, number of operations and hospital charges. Poisson regression or Cox proportional hazards model was used to evaluate differences in outcomes after adjusting for potential confounders. RESULTS:From 2000 to 2003 a total of 1877 patients were admitted to our burn center and 953 (51%) were transferred from a preliminary care facility. No difference (p<0.05) was found in length of stay, number of operations, hospital charges and mortality between the two cohorts. CONCLUSIONS:This study demonstrates that patients transferred to a regional burn center from local hospitals have equivalent mortality, length of stay and hospital charges as those admitted directly from the field.
    背景与目标:
  • 【血液透析开始前进入的障碍: 单中心综述。】 复制标题 收藏 收藏
    DOI:10.1111/j.1542-4758.2007.00191.x 复制DOI
    作者列表:Bhan V,Soroka S,Constantine C,Kiberd BA
    BACKGROUND & AIMS: :Guidelines recommend that > or =50% of patients starting dialysis have a fistula. We reviewed our experience in consecutive incident patients over a 1-year period. Only 30 of the 93 patients starting hemodialysis had a fistula that was accessed. Late referral (nephrology contact <90 days) was a significant issue in 48% (30/63) of the patients without a fistula. Most (n=21) of the late referrals were acute disease; only 9 were late referrals of chronic disease. Nephrology follow-up exceeded 200 days in the remaining (33/63) without this access. In the cohort with sufficient nephrology referral, we explored variables associated with a fistula (n=30) compared with those without one (n=33). In multivariate logistic regression analysis, peripheral vascular disease (odds ratio [OR] 0.026, 95% confidence interval [CI] 0.002-0.286) and rapid loss of estimated glomerular filtration rate (eGFR) (OR 0.745 per mL/min/1.73 m(2)/year, 95% CI 0.625-0.888) in the year preceding dialysis were significant negative predictors for a fistula. Patients without access experienced faster declines in GFR in the year preceding dialysis (12.1+/-9.9 vs. 4.7+/-3.5 mL/min 1.73 m(2) with access, p<0.001). Glomerular filtration rate loss in the 2 years before starting dialysis was the same between the 2 groups (-0.54+/-10.4 vs. 1.42+/-3.9 mL/min 1.73 m(2)). Age, sex, diabetes, other comorbidity, length of nephrology follow-up, eGFR at dialysis start, hemoglobin, and albumin were not significant. At our center, rapid loss of renal function in otherwise stable chronic kidney disease (CKD) patients is more important than late referral of CKD for the lack of access. Improvements in rapid referral for access creation could help reduce this barrier.
    背景与目标: : 指南建议> 或> 50% 开始透析的患者有瘘管。我们回顾了我们在1年内连续事件患者中的经验。在开始进行血液透析的93例患者中,只有30例有瘘管。在48% (30/63) 无瘘管的患者中,晚期转诊 (肾脏病学接触 <90天) 是一个重要问题。大多数 (n = 21) 晚期转诊是急性病; 只有9例是慢性疾病的晚期转诊。在没有这种访问的情况下,肾脏病学随访超过200天 (33/63天)。在具有足够肾脏病转诊的队列中,我们探索了与瘘管相关的变量 (n = 30) 与没有瘘管的变量 (n = 33) 相比。在多变量logistic回归分析中,外周血管疾病 (优势比 [OR] 0.026,95% 置信区间 [CI] 0.002-0.286) 和估计肾小球滤过率 (eGFR) 的快速损失 (或0.745/mL/min/1.73 m(2)/年),透析前一年的95% CI 0.625-0.888) 是瘘管的显著阴性预测因子。没有通路的患者在透析前一年经历了更快的GFR下降 (12.1 +/-9.9 vs. 4.7 +/-3.5 mL/min 1.73 m(2),p<0.001)。开始透析前2年的肾小球滤过率损失在两组之间是相同的 (-0.54/-10.4对1.42/-3.9 mL/min 1.73 m(2))。年龄,性别,糖尿病,其他合并症,肾脏病随访时间,透析开始时的eGFR,血红蛋白和白蛋白均无显着性。在我们的中心,在其他稳定的慢性肾脏病 (CKD) 患者中,肾功能的快速丧失比由于缺乏进入而导致的CKD的晚期转诊更为重要。改善访问创建的快速转介可以帮助减少这一障碍。
  • 【极低体重婴儿的PBSC收集: 单中心体验。】 复制标题 收藏 收藏
    DOI:10.1080/14653240701320270 复制DOI
    作者列表:Sevilla J,Plaza SF,González-Vicent M,Lassaletta A,Ramírez M,Madero L,Díaz MA
    BACKGROUND & AIMS: BACKGROUND:Peripheral blood progenitor cell (PBPC) collection has become the main source of hematopoietic cells for high-dose chemotherapy with stem cell rescue and, in some protocols, for allogeneic hematopoietic transplantation. This procedure is complicated in the smallest children because of difficulties related to their weight, and there is little published experience. We have conducted a prospective study to analyze the incidence of adverse events during PBPC collection in the smallest children (< or = 10 kg). METHODS:From January 2000 to November 2005, 257 leukapheresis were performed in our unit, and 13 of them (5%) in 12 children weighing up to 10 kg (median 9 kg, range 5.8-10.9 kg). RESULTS:Most cases had hypovolemic signs during the procedure (usually tachycardia); six cases had hypotension, five of them with pallor and diaphoresis, and, of those, two also had nausea. In all these cases infusion of saline or plasma volume expanders resolved the clinical findings. In two cases the nausea related to hypocalcemia was resolved after calcium gluconate infusion. Changes in platelet counts were also remarkable, with a median platelet loss of 52%. DISCUSSION:Leukapheresis with continuous-flow cell separators has frequent complications related to volume shift in the smallest children. These adverse events are mild and easily resolved with standard measures for hypovolemia, as plasma expander or normal saline infusions. However, we recommend that the procedure should only be performed by teams with extensive experience in the field.
    背景与目标:
  • 【肾移植受者非椎骨骨折的患病率和危险因素-单中心回顾性分析。】 复制标题 收藏 收藏
    DOI:10.5414/CNP88FX23 复制DOI
    作者列表:Jerman A,Lindič J,Škoberne A,Borštnar Š,Martinuč Bergoč M,Godnov U,Kovač D
    BACKGROUND & AIMS: BACKGROUND:Complex and longstanding bone disease superimposed by harmful influences of immunosuppression is the reason for increased risk of bone fracture in kidney transplant recipients. The aim of our study was to analyze the incidence and prevalence of nonvertebral bone fractures and early (in the first post-transplant year) clinical and laboratory risk factors for suffering bone fracture in the long-term post-transplant period. METHODS:Clinical and laboratory data as well as bone mineral density (BMD) measurements of 507 first kidney transplant recipients who were transplanted in the period from 1976 to 2011 were analyzed. RESULTS:The mean age of included patients was 54.3 ± 12.0 years, there were 45% females, and mean time on renal replacement treatment prior to transplantation was 63.4 ± 43.6 months. The average observation time post-transplant was 9.7 years (1.4 - 36.3 years). Post-transplant, 64 (12.6%) patients suffered 89 nonvertebral fractures (44 patients suffered 1 fracture, 15 patients 2 fractures, and 5 patients 3 fractures). Patients with fractures had significantly lower late BMD of femoral neck in the period of 1 - 10 years post-transplant, had osteopenia and osteoporosis more frequently in the same time period, and higher serum alkaline phosphatase in the first year post-transplant. 13 patients (13/64, 20.3%) had major fractures. Patients with major fractures were significantly older than patients with no major fractures and had lower serum albumin. Frequency of treatment with bisphosphonate, calcium, or phosphate did not differ between the groups. Vitamin D supplement (active form in 98% of cases) was prescribed more frequently in the group without fractures, but this was not statistically significant. CONCLUSION:Fracture rate in our transplant patient population was comparable to that reported in the literature. Except for a higher level of serum total alkaline phosphatase in the fracture group, we found no other early laboratory risk factors for bone fractures. BMD at the femoral region 1 - 10 years after kidney transplantation but not BMD at the time of transplantation was a risk factor for nonvertebral fractures. Osteopenia and osteoporosis in the post-transplant period were found to be a fracture risk factor.
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    背景与目标:
  • 【长春瑞滨治疗晚期非小细胞肺癌: Fox Chase癌症中心经验的回顾性回顾和文献综述。】 复制标题 收藏 收藏
    DOI:10.3816/CLC.2007.n.011 复制DOI
    作者列表:Devlin JG,Langer CJ
    BACKGROUND & AIMS: BACKGROUND:Published phase III non-small-cell lung cancer (NSCLC) literature has demonstrated minimal activity for salvage vinorelbine (response rate [RR], 0.8% in 1 published study); however, our clinical experience has been discordant with such reports. PATIENTS AND METHODS:All patients with NSCLC who had received vinorelbine at Fox Chase Cancer Center from June 2002 to June 2005 were identified. Evaluable patients had biopsy-proven, measurable, recurrent or metastatic NSCLC, had full medical records and imaging available, and had received >or= 1 cycle of single-agent vinorelbine after first-line therapy. The primary endpoint was RR; secondary endpoints included safety, overall survival (OS), and time to progression. RESULTS:Of 52 patients, 39 were evaluable. Median age was 63 years and 59% of patients were women. The Eastern Cooperative Oncology Group performance status was 0 in 12.8% of patients, 1 in 53.8%, 2 in 25.6%, and 3 in 7.7%. Nearly 80% of patients underwent 2 lines of previnorelbine therapy; 38.4% underwent 3 lines, and 7.7% underwent 4 lines. Approximately, 28.2% had received previous epidermal growth factor receptor tyrosine kinase inhibitor therapy; 23% had brain metastases; and 84.6% had significant comorbidities. The most common dosing schedules were 25-30 mg/m(2) on days 1 and 8 every 3 weeks. The median number of vinorelbine cycles was 3. The partial RR was 7.7%; 25.6% had stable disease; 43.6% had disease progression, and 23.1% were not radiographically assessed for response (but were included in the OS analysis). Approximately, 20.5% required dose reductions, predominantly for hematologic toxicities; nonhematologic toxicities were generally mild, and there were no treatment-related deaths. Nearly 31% received subsequent therapy after vinorelbine. Median OS was 5 months (n = 39), median time to progression was 3 months (n = 30), 1-year OS was 25.6%, and 2-year OS was 7.7%. CONCLUSION:Salvage vinorelbine is active and well tolerated in patients with NSCLC. The RR exceeds that reported in the literature.
    背景与目标:
  • 【由滤泡辅助性T细胞IL-9驱动的记忆b细胞的生发中心发育。】 复制标题 收藏 收藏
    DOI:10.1038/ni.3788 复制DOI
    作者列表:Wang Y,Shi J,Yan J,Xiao Z,Hou X,Lu P,Hou S,Mao T,Liu W,Ma Y,Zhang L,Yang X,Qi H
    BACKGROUND & AIMS: :Germinal centers (GCs) support high-affinity, long-lived humoral immunity. How memory B cells develop in GCs is not clear. Through the use of a cell-cycle-reporting system, we identified GC-derived memory precursor cells (GC-MP cells) that had quit cycling and reached G0 phase while in the GC, exhibited memory-associated phenotypes with signs of affinity maturation and localized toward the GC border. After being transferred into adoptive hosts, GC-MP cells reconstituted a secondary response like genuine memory B cells. GC-MP cells expressed the interleukin 9 (IL-9) receptor and responded to IL-9. Acute treatment with IL-9 or antibody to IL-9 accelerated or retarded the positioning of GC-MP cells toward the GC edge and exit from the GC, and enhanced or inhibited the development of memory B cells, which required B cell-intrinsic responsiveness to IL-9. Follicular helper T cells (TFH cells) produced IL-9, and deletion of IL-9 from T cells or, more specifically, from GC TFH cells led to impaired memory formation of B cells. Therefore, the GC development of memory B cells is promoted by TFH cell-derived IL-9.
    背景与目标: : 生发中心 (GCs) 支持高亲和力、长寿的体液免疫。记忆b细胞如何在GCs中发育尚不清楚。通过使用细胞周期报告系统,我们确定了GC衍生的记忆前体细胞 (gc-mp细胞),这些细胞在GC中退出循环并达到G0期,表现出与记忆相关的表型,并具有亲和成熟的迹象,并定位于GC边界。转移到过继宿主后,gc-mp细胞像真正的记忆b细胞一样重建了次级反应。Gc-mp细胞表达白介素9 (IL-9) 受体并对IL-9产生反应。用IL-9或抗体IL-9的急性治疗加速或延迟了gc-mp细胞朝向GC边缘的定位并从GC退出,并增强或抑制了记忆b细胞的发育,这需要b细胞对IL-9的内在反应性。滤泡辅助性T细胞 (TFH细胞) 产生IL-9,T细胞或更具体地说,GC TFH细胞中IL-9的缺失导致b细胞的记忆形成受损。因此,TFH细胞衍生的IL-9促进了记忆b细胞的GC发育。
  • 【39例纯红细胞发育不全: 来自印度的单中心经验。】 复制标题 收藏 收藏
    DOI:10.1080/10245330701255056 复制DOI
    作者列表:Srinivas U,Mahapatra M,Saxena R,Pati HP
    BACKGROUND & AIMS: UNLABELLED:Pure red cell aplasia (PRCA) is an uncommon disorder, characterized by transfusion dependent anemia, reticulocytopenia with selective aplasia or paucity of erythroid cells in bone marrow. There are only a few large series of PRCA reported in literature. This is the largest single center series of PRCA from India. OBJECTIVE:To evaluate the utility of Immunohistochemistry with Glycophorin A on bone marrow biopsies in quantitating the cut-off percentage of erythroid blasts required for diagnosis, as the upper cut-off percentage of erythroblasts for establishing a diagnosis of PRCA is still not clear. METHODS:The clinical data were obtained from patients' case files. Immunohistochemistry with Glycophorin A was performed using an immunoperoxidase technique and percentage of Glycophorin A positive cells of all nucleated cells was calculated by two independent observers. RESULTS:In our study, bone marrow aspirates showed a variable percentage of erythroblasts ranging from 2 to 12% (mean 6.3%) in children and from 1 to 8% (mean 4.6%) in adults on Giemsa smears. Immunohistochemistry (IHC) with Glycophorin A showed a mean positive cell % of 8.2 (range 2-16%) and 6.8 (1-9%) in pediatric and adult respectively against a mean of 28% (range 21-39%) in idiopathic thrombocytopenia (ITP) cases. Treatment with prednisone showed good response in a majority of both adults and childhood PRCA. Cyclosporine was found to be a good alternative in prednisone non-responders. Thymectomy was beneficial in patients with thymoma. CONCLUSION:A higher percentage of erythroid cells (>5%) does not exclude a diagnosis of PRCA in an appropriate clinical setting and therefore can be managed as PRCA.
    背景与目标:
  • 【程序性死亡-1 (PD-1) 是生发中心相关T细胞和血管免疫母细胞性T细胞淋巴瘤的标志物。】 复制标题 收藏 收藏
    DOI:10.1097/01.pas.0000209855.28282.ce 复制DOI
    作者列表:Dorfman DM,Brown JA,Shahsafaei A,Freeman GJ
    BACKGROUND & AIMS: :Programmed death-1 (PD-1), a member of the CD28 costimulatory receptor family, is expressed by germinal center-associated T cells in reactive lymphoid tissue. In a study of a wide range of lymphoproliferative disorders, neoplastic T cells in 23 cases of angioimmunoblastic lymphoma were immunoreactive for PD-1, but other subtypes of T cell and B cell non-Hodgkin lymphoma, as well as classic Hodgkin lymphoma, did not express PD-1. The pattern of PD-1 immunostaining of neoplastic cells in angioimmunoblastic lymphoma was similar to that reported for CD10, a recently described marker of neoplastic T cells in angioimmunoblastic lymphoma. Tumor-associated follicular dendritic cells in cases of angioimmunoblastic lymphoma were found to express PD-L1, the PD-1 ligand. In addition, PD-1-positive reactive T cells formed rosettes around neoplastic L&H cells in 14 cases of nodular lymphocyte predominant Hodgkin lymphoma studied. These findings, along with data from previous studies, suggest that angioimmunoblastic lymphoma is a neoplasm of germinal center-associated T cells and that there is an association of germinal center-associated T cells and neoplastic cells in nodular lymphocyte predominant Hodgkin lymphoma. PD-1 is a useful new marker for angioimmunoblastic lymphoma and lends further support to a model of T-cell lymphomagenesis in which specific subtypes of T cells may undergo neoplastic transformation and result in specific, distinct histologic, immunophenotypic, and clinical subtypes of T-cell neoplasia.
    背景与目标: : 程序性死亡-1 (PD-1) 是CD28共刺激受体家族的成员,由反应性淋巴组织中的生发中心相关T细胞表达。在一项广泛的淋巴增生性疾病的研究中,23例血管免疫母细胞淋巴瘤的肿瘤性T细胞对PD-1具有免疫反应性,但其他亚型的T细胞和b细胞非霍奇金淋巴瘤以及经典的霍奇金淋巴瘤均不表达PD-1。血管免疫母细胞淋巴瘤中肿瘤细胞的PD-1免疫染色模式与CD10的报道相似,CD10是最近描述的血管免疫母细胞淋巴瘤中肿瘤T细胞的标志物。在血管免疫母细胞淋巴瘤病例中,发现肿瘤相关滤泡树突状细胞表达PD-L1,即PD-1配体。此外,在研究的14例结节淋巴细胞为主的霍奇金淋巴瘤中,PD-1-positive反应性T细胞在肿瘤性L & H细胞周围形成了玫瑰花结。这些发现以及先前研究的数据表明,血管免疫母细胞性淋巴瘤是与生发中心相关的T细胞的肿瘤,并且在结节性淋巴细胞为主的霍奇金淋巴瘤中,生发中心相关的T细胞和肿瘤细胞存在关联。PD-1是血管免疫母细胞淋巴瘤的有用的新标记物,并为T细胞淋巴瘤发生模型提供了进一步的支持,在该模型中,T细胞的特定亚型可能经历肿瘤转化并导致T细胞瘤形成的特定,独特的组织学,免疫表型和临床亚型。
  • 【骨科创伤室对一级创伤中心下班后手术的影响。】 复制标题 收藏 收藏
    DOI:10.1097/BOT.0b013e31816c748b 复制DOI
    作者列表:Wixted JJ,Reed M,Eskander MS,Millar B,Anderson RC,Bagchi K,Kaur S,Franklin P,Leclair W
    BACKGROUND & AIMS: PURPOSE:The purpose of this study is to examine the effect of establishing a dedicated operating room for unscheduled orthopedic cases and to evaluate a group of patients with isolated femur fractures. The frequency of after-hours surgery and the impact of patients who present with acute orthopedic injuries are reviewed. METHODS:A retrospective review of all orthopedic cases from the operating room scheduling system at a level-one trauma center was undertaken from October 2003 to September 2005. Before October 2004, unscheduled cases were placed on a shared add-on list, and no special priority was given to orthopedic cases. Additionally, a subset of adult patients with isolated femoral shaft fractures was identified to evaluate time from admission to surgery, operative time, frequency of transfer of care between surgeons, and total length of hospital stay. RESULTS:The number of orthopedic cases was 1799 in fiscal year 2004 (FY04) and 2046 in FY05, an increase of 14%. Overall, the hospital experienced an increase in level-one trauma activations from 1450 in FY04 to 1580 in FY05 (8.2%), and an increase in the number operative trauma cases from 447 to 494 (9.5%). Cases after 7:00 pm declined from 197 in FY04 to 165 in FY05, a decrease of 16%. Cases between midnight and 7:00 am declined from 63 in FY04 to 35 in FY05, a decrease of 44%. For the subset of femur fracture patients, transfer of care to another operating surgeon occurred 4.5 times more frequently. The median delay between admission and surgery increased from 5.7 hours to 10.9 hours. Median case duration increased from 106 to 127 minutes. CONCLUSIONS:It is possible to dramatically decrease the occurrence of after-hours orthopedic surgery in a level-one trauma center through the use of a dedicated room for unscheduled orthopedic trauma cases. Benefits include less frequent activation of after-hours operating room resources, fewer disruptions to the OR schedule and office hours, and more frequent fracture care by orthopedic traumatologists. The impact of a longer delay between admission and surgical treatment and more frequent transfer of care between surgeons deserves further evaluation.
    背景与目标:
  • 【用thoratec VAD装置移植的患者生存率的预测因素: 一项针对100多名患者的单中心回顾性研究。】 复制标题 收藏 收藏
    DOI:10.1016/s1053-2498(00)00174-1 复制DOI
    作者列表:El-Banayosy A,Arusoglu L,Kizner L,Tenderich G,Boethig D,Minami K,Körfer R
    BACKGROUND & AIMS: BACKGROUND:Careful patient selection markedly influences the outcome of patients who undergo mechanical circulatory support. Therefore, we tried to evaluate predictors of survival after implantation of the Thoratec ventricular assist device (VAD). METHODS:Between October 1992 and January 2000, 104 patients (86 men, 18 women, aged 11 to 69 years) received the Thoratec VAD as a bridge to transplant. A total of 51 patients required left ventricular support (LVAD), 50 patients required biventricular support (BVAD), and 3 patients required total artificial heart implantation. We performed univariate analysis of 25 parameters with regard to their effect on survival and then applied a multivariate analysis to evaluate those factors that turned out to be marginally significant. We performed all analysis for the total collective as well as for the LVAD and BVAD sub-group. RESULTS:The BVAD patients tended to have worse outcomes than did LVAD patients. We found no significant predictors of survival in either sub-group. In the total collective, however, we found the following pre-implant conditions were independent risk factors for survival after VAD implantation: patient age > 60 years (odds ratio [OR] 3.87, confidence interval [CI] 1.39 to 10.76), pre-implant ventilation (OR, 6.76; CI 2.42 to 18.84), and increased pre-implant total bilirubin (OR, 1.42; CL, 1.19 to 1.69). CONCLUSIONS:Transplant candidates on inotropic support should be considered for bridging to transplant as soon as bilirubin values start to increase or before respiratory function deteriorates and ventilation becomes necessary. In elderly patients, careful patient selection, particularly considering potential risk factors, might favorably affect their outcomes.
    背景与目标:
  • 【埃克替尼在具有EGFR不常见突变的亚洲晚期非小细胞肺癌中的现实疗效和耐药潜在机制: 一项多中心研究。】 复制标题 收藏 收藏
    DOI:10.1002/cam4.2652 复制DOI
    作者列表:Lei L,Wang WX,Zhu YC,Li JL,Fang Y,Wang H,Zhuang W,Zhang YB,Wang LP,Fang MY,Xu CW,Wang XJ,Lv TF,Song Y
    BACKGROUND & AIMS: :The response to icotinib in advanced non-small cell lung cancers (NSCLC) with EGFR uncommon mutation (EGFRum) is unclear. Here we reported the efficacy and potential resistance mechanism of icotinib in Chinese EGFRum NSCLC patients. Between July 2013 and November 2016, 3117 NSCLC patients were screened for EGFRum in a multi-center study in China. Circulating tumor DNA (ctDNA) was detected and analyzed using next-generation sequencing (NGS) after progression from icotinib. The efficacy, safety and the potential resistance mechanism of icotinib were explored. After a median follow-up of 6.2 months, 69 patients (70.41%) developed disease progression, the objective rate (ORR) and disease control rate (DCR) were 13.27% and 29.59% respectively, and the median progression-free survival (PFS) was 5.5 months (95% CI: 1.2-13.0 months). Both complex-pattern with EGFR classical mutations (EGFRcm) and single-pattern have better PFS than complex-pattern without EGFRcm (median PFS was 7.2 (95% CI: 4.65-9.75), 5.2 (95% CI: 3.24-7.16) and 3.2 (95% CI: 2.97-3.44) months, respectively, P < .05); patients harboring S768I mutation had the worst PFS than others (2.0 months, P < .05). Diarrhea was the most frequent side effect (42.9%). Forty-eight (69.6%) patients developed drug resistance after 3.0 months and 81.2% of them acquired T790M mutation. Better response was observed in complex-pattern with the EGFRcm group. S768I mutation carriers may not benefit from icotinib. Acquired T790M mutation was common in icotinib-resistant EGFRum NSCLC patients.
    背景与目标: : 埃克替尼在EGFR罕见突变 (EGFRum) 的晚期非小细胞肺癌 (NSCLC) 中的反应尚不清楚。本文报道了埃克替尼对中国EGFRum NSCLC患者的疗效和潜在耐药机制。在中国的一项多中心研究中,在2013年7月和2016年11月之间,对3117例NSCLC患者进行了EGFRum筛查。从埃克替尼进展后,使用下一代测序 (NGS) 检测并分析循环肿瘤DNA (ctDNA)。探讨了埃克替尼的有效性、安全性和潜在的耐药机制。中位随访6.2个月,69例患者 (70.41% 例) 出现疾病进展,客观率 (ORR) 和疾病控制率 (DCR) 分别为13.27% 和29.59%,中位无进展生存期 (PFS) 为5.5个月 (95% CI: 1.2-13.0个月)。具有EGFR经典突变的复杂模式 (EGFRcm) 和单模式均比没有EGFRcm的复杂模式具有更好的PFS (中位PFS为7.2 (95% CI: 4.65-9.75),5.2 (95% CI: 3.24-7.16) 和3.2 (95% CI: 2.97-3.44) 个月,分别为P <.05); 携带S768I突变的患者PFS最差 (2.0个月,P <.05)。腹泻是最常见的副作用 (42.9%)。48 (69.6%) 名患者在3.0个月后出现耐药性,其中81.2% 人获得了T790M突变。EGFRcm组在复杂模式下观察到更好的反应。S768I突变携带者可能无法从埃克替尼中受益。获得性T790M突变在埃克替尼耐药的EGFRum NSCLC患者中很常见。
  • 【新型冠状病毒肺炎爆发期间沉浸在急诊科分诊中心: 列日大学医院经历的第一份报告。】 复制标题 收藏 收藏
    DOI:10.1080/17843286.2020.1778348 复制DOI
    作者列表:Gilbert A,Brasseur E,Petit M,Donneau AF,Diep A,Hetzel Campbell S,Servotte JC,Piazza J,Ancion A,Gensburger M,D'Orio V,Ghuysen A
    BACKGROUND & AIMS: OBJECTIVES:Since the beginning of the novel coronavirus outbreak, different strategies have been explored to stem the spread of the disease and appropriately manage patient flow. Triage, an effective solution proposed in disaster medicine, also works well to manage Emergency Department (ED) flow. The aim of this study was to describe the role of an ED Triage Center for patients with suspected novel coronavirus disease (Covid-19) and characterize the patient flow. METHODS:In March 2020, we established a Covid-19 triage center close to the Liège University EDs. From March 2 to March 23, we planned to analyze the specific flow of patients admitted to this triage zone and their characteristics in terms of inner specificities, work-up and management. During this period, all patients presented to the ED with symptoms suggestive of Covid-19 were included in the study. RESULTS:A total amount of 1071 patients presented to the triage center during the study period. 41.50% of the patients presented with flu-like symptoms. In 82.00% of the cases, no risk factor of virus transmission was found. The SARS-Cov2 positive patients represented 29.26% of the screened patients. 83.00% of patients were discharged home while 17.00% were admitted to the hospital. CONCLUSION:Our experience suggests that triage centers for the assessment and management of Covid-19 suspected patients is an essential key strategy to prevent the spread of the disease among non-symptomatic patients who present to the EDs for care. This allows for a disease-centered work-up and safer diversion of Covid-19 patients to specific hospital units.
    背景与目标:
  • 【小鼠和单纯疱疹病毒核糖核苷酸还原酶中混合价二铁位点的EPR研究。酪酰基对二铁中心结构和反应性的影响。】 复制标题 收藏 收藏
    DOI:10.1021/bi9700375 复制DOI
    作者列表:Davydov RM,Davydov A,Ingemarson R,Thelander L,Ehrenberg A,Gräslund A
    BACKGROUND & AIMS: :Reduction of ribonucleotide reductase (EC 1.17.4.1) R2 proteins in a frozen glycerol-buffer solution at 77 K by mobile electrons generated by gamma-irradiation produces EPR-detectable iron sites in mixed-valent Fe(II)/Fe(III) states. The primary EPR signals give information about the ligand arrangement of the diferric form of the iron site, whereas secondary signals observed after annealing of the sample show the effects of structural relaxation. In recombinant metR2 proteins (without free radical) from mouse and herpes virus type 1, the mixed-valent sites trapped at 77 K give rise to axial S = 1/2 EPR spectra with g values in the range 1.79-1.94, observable at temperatures up to 110 K. The spectra are assigned to mu-oxo-bridged dinuclear iron sites. In mouse metR2, the primary EPR spectrum is a mixture of two components. Annealing the R2 samples to 160-170 K transforms the primary EPR signals into rhombic spectra, characterized by gav < 1.8, and observable only below 25 K. These spectra are assigned to partially relaxed forms with a mu-hydroxo bridge, formed by protonation of the oxo bridge. Further annealing at 220 K produces new rhombic EPR spectra, which are closely similar with those observed and found to be stable after chemical reduction at room temperature. The EPR signal of the primary mixed-valent iron site in active mouse R2 protein with a tyrosyl radical also has two components. Both are different from those observed in metR2. In herpes simplex virus type 1 protein R2, one primary mixed-valent component was observed for the met protein. The dose-yield curve for the mixed-valent state in active mouse R2 is sigmoidal in shape, indicating that the tyrosyl radical is reduced by mobile electrons before the iron site. Kinetic experiments on the reduction by dithionite on mouse R2 without and with radical show a significantly enhanced rate for reduction of the iron site in the protein without radical. The results suggest that in active mouse R2 only complete diferric sites with neighboring radicals give rise to the mixed-valent spectra, and that these sites may exist in two structurally distinct forms. The results on the mouse R2 proteins confirm and extend previous results obtained on the Escherichia coli protein R2 showing that the presence of the tyrosyl radical significantly affects not only the structure but also the reactivity of the iron site.
    背景与目标: : 通过伽马辐照产生的移动电子在77 K的冷冻甘油缓冲溶液中还原核糖核苷酸还原酶 (EC 1.17.4.1) R2蛋白,在混合价的Fe(II)/Fe(III) 状态下产生可检测到EPR的铁位点。初级EPR信号提供有关铁位点二铁形式的配体排列的信息,而样品退火后观察到的次级信号显示了结构弛豫的影响。在来自小鼠和1型疱疹病毒的重组metR2蛋白 (无自由基) 中,捕获在77 k的混合价位点产生轴向S = 1/2 EPR光谱,g值在1.79-1.94范围内,可在高达110 K的温度下观察到。光谱分配给mu-氧桥双核铁位点。在小鼠metR2中,主要EPR光谱是两种成分的混合物。将R2样品退火至160-170 K将初级EPR信号转换为菱形光谱,其特征在于gav <1.8,并且仅在25 k以下可观察到。这些光谱被分配为具有 μ-羟基桥的部分松弛形式,该形式是由氧桥的质子化形成的。在220 K下进一步退火产生新的菱形EPR光谱,该光谱与观察到的光谱非常相似,并且在室温下化学还原后被发现是稳定的。具有酪氨酰自由基的活性小鼠R2蛋白中初级混合价铁位点的EPR信号也有两个成分。两者都不同于在metr2中观察到的。在1型单纯疱疹病毒蛋白R2中,观察到met蛋白的一种主要混合价成分。活性小鼠R2中混合价态的剂量-产量曲线呈s形,表明酪氨酰自由基在铁位点之前被移动电子还原。在没有自由基的情况下,连二亚硫酸盐在小鼠R2上还原的动力学实验表明,没有自由基的蛋白质中铁位的还原速率显着提高。结果表明,在活性小鼠R2中,只有具有相邻自由基的完整二价位点会产生混合价光谱,并且这些位点可能以两种结构上不同的形式存在。小鼠R2蛋白的结果证实并扩展了先前在大肠杆菌蛋白R2上获得的结果,表明酪氨酰自由基的存在不仅显着影响铁位点的结构,而且还影响铁位点的反应性。
  • 【与男性发生性关系的黑人男性的HIV健康中心隶属网络: 解开分散的HIV预防服务利用模式。】 复制标题 收藏 收藏
    DOI:10.1097/OLQ.0b013e3182515cee 复制DOI
    作者列表:Schneider JA,Walsh T,Cornwell B,Ostrow D,Michaels S,Laumann EO
    BACKGROUND & AIMS: BACKGROUND:In the United States, black men who have sex with men (BMSM) are at highest risk for HIV infection and are at high risk for limited health service utilization. We describe HIV health center (HHC) affiliation network patterns and their potential determinants among urban BMSM. METHODS:The Men's Assessment of Social and Risk Network instrument was used to elicit HHC utilization, as reported by study respondents recruited through respondent-driven sampling. In 2010, 204 BMSM were systematically recruited from diverse venues in Chicago, IL. A 2-mode data set was constructed that included study participants and 9 diverse HHCs. Associations between individual-level characteristics and HHC utilization were analyzed using Multiple Regression Quadratic Assignment Procedure. Visualization analyses included computation of HHC centrality and faction membership. RESULTS:High utilization of HHCs (45.9%-70.3%) was evident among BMSM, 44.4% who were HIV infected. Multiple Regression Quadratic Assignment Procedure revealed that age, social network size, and HIV status were associated with HHC affiliation patterns (coeff., 0.13-0.27; all P < 0.05). With the exception of one HHC, HHCs offering HIV prevention services to HIV-infected participants occupied peripheral positions within the network of health centers. High-risk HIV-uninfected participants affiliated most with an HHC that offers only treatment services. CONCLUSIONS:Subcategories of BMSM in this sample affiliated with HHCs that may not provide appropriate HIV prevention services. Using 2-mode data, public health authorities may be better able to match prevention services to BMSM need; in particular, HIV prevention services for high-risk HIV-uninfected men and HIV "prevention for positives" services for HIV-infected men.
    背景与目标:
  • 【开始肾脏替代治疗时患者的特征-血液透析中心的经验。】 复制标题 收藏 收藏
    DOI:10.3892/etm.2020.8608 复制DOI
    作者列表:Timofte D,Dragos D,Balcangiu-Stroescu AE,Tanasescu MD,Gabriela Balan D,Raducu L,Jecan CR,Stiru O,Medrihan L,Ionescu D
    BACKGROUND & AIMS: :The monitoring and care of patients with chronic kidney disease (CKD) before the dialysis initiation contribute to a better survival rate and an improvement in quality of life. The patients who do not benefit from a good predialysis management have a worse short and long-term prognosis. A retrospective, unicentric study was performed to evaluate the status of patients with stage 5 CKD at the time of initiation of renal replacement treatment. A total of 109 patients were included in the study. The evaluation of the patients included the clinical manifestations leading to hemodialysis initiation, the clinical and laboratory data of the patients when the hemodialysis was started. Based on the obtained data, a statistical analysis was performed using the Chi-square test, Fisher's exact test, ANOVA, and Kruskal-Wallis H test. The mean age of the patients was 64.61±13.59 years. Of the patients 51.38% were women. Vascular nephropathies and diabetes mellitus dominated the etiology of CKD. The comorbidities were high blood pressure, ischemic heart disease, history of myocardial infarction, heart failure, history of stroke, peripheral artery disease or atrial fibrillation. Only 43 (39.45%) of our patients were monitored before the hemodialysis initiation. Hemodialysis was initiated on central venous catheter (in most cases non-tunneled) in 78.90% of the patients. Most of the patients had an altered general status, fatigue/tiredness with poor exercise capacity when hemodialysis was initiated. Most of the patients (98.17%) had anemia, the average level of hemoglobin being 8.69±1.85 g/dl. In conclusion, careful monitoring of patients in the early stages of CKD would result in lower morbidity and mortality. These objectives can be achieved by implementing screening programs and early interventions.
    背景与目标: : 透析开始前对慢性肾脏病 (CKD) 患者的监测和护理有助于提高生存率和改善生活质量。无法从良好的透析前管理中受益的患者的短期和长期预后较差。进行了一项回顾性,单中心研究,以评估开始肾脏替代治疗时5期CKD患者的状况。共有109名患者被纳入研究。对患者的评估包括导致血液透析开始的临床表现,开始血液透析时患者的临床和实验室数据。根据获得的数据,使用卡方检验,Fisher精确检验,ANOVA和Kruskal-Wallis H检验进行统计分析。患者的平均年龄为64.61 ± 13.59岁。51.38% 名患者是女性。血管性肾病和糖尿病是CKD的病因。共病为高血压、缺血性心脏病、心肌梗死史、心力衰竭、卒中史、外周动脉疾病或心房颤动。在开始血液透析之前,仅监测了43名 (39.45% 名) 患者。在78.90% 患者中,在中心静脉导管 (在大多数情况下,非隧道) 上开始血液透析。开始血液透析时,大多数患者的一般状态,乏力/疲劳以及运动能力差。大多数患者 (98.17%) 患有贫血,平均血红蛋白水平为8.69 ± 1.85g/dl。总之,对CKD早期患者的仔细监测将导致较低的发病率和死亡率。这些目标可以通过实施筛查计划和早期干预来实现。

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