嗜肺军团菌血清10型致军团病爆发流行并分离培养成功

１９９２年２～３月，北京市郊某宾馆发生了一起上呼吸道感染流行。流行病学调查及细菌学检查证明，这是一起嗜肺军团菌血清１０型（Ｌｐ１０）引起的宾馆军团病爆发流行，感染率为２４．３２入（９／３７），患病率为１３．５１％（５／３７）。由Ｌｐ１０引起的军团病爆发流行在世界上属首次报道，而Ｌｐ１０分离培养成功在国内尚属首次。     

Delayed graft function requiring more than one‐time dialysis treatment is associated with inferior clinical outcomes

Delayed graft function (DGF) is a common complication of deceased donor kidney transplantation with negative impact on clinical outcomes. In a single‐center retrospective analysis, we compared patient and kidney survival, early renal function, and the incidence of acute rejection during the first year among all adult deceased donor kidney transplant patients without DGF, with DGF requiring one‐time and/or more than one‐time dialysis treatment between January 1, 2000, and December 31, 2008. Of 831 adult kidney transplant patients, 74 (8.9%) required one‐time and 134 (16.1%) more than one‐time dialysis treatment post‐transplantation, respectively. While DGF patients with one‐time dialysis treatment had comparable clinical outcomes to that of patients without DGF, patients with DGF requiring more than one‐time dialysis treatment had a 45% increased risk for death (HR 1.45, 95% CI 1.02, 2.05, p = 0.04) after adjustment for the differences in demographic and baseline characteristics. Furthermore, DGF patients with more than one‐time dialysis requirement displayed significantly lower renal function after recovery (OR 0.32, 95% CI 0.21, 0.49, p < 0.001, for eGFR ≥ 60 mL/min) and higher incidence of acute rejection during the first year (OR 1.66, 95% CI 1.11, 2.49, p = 0.015). Additional studies of therapeutic approaches to manage patients with prolonged DGF are needed.     

The role of CD14 and Toll-like receptor 4 of Kupffer cells in hepatic ischemia-reperfusion injury in rats

Objective

The objective of this study was to study the role of CD14 and Toll-like receptor 4 (TLR4) in Kupffer cells (KCs) on ischemia reperfusion injury (IRI) in rat liver grafts.

Methods

Isolated KCs were obtained from control, IRI, and IRI plus anti-CD14 antibody groups. We measured messenger RNA (mRNA) and protein expression of the lipopolysaccharide receptor CD14 and TLR4, nuclear factor kappa B (NF-κβ) activity, and TNF-α levels.

Results

mRNA and protein expressions of CD14 and TLR4 were significantly higher in the IRI than in the control group, as were protein expressions of CD14 and TLR4 by flow cytometry and by Western blots. NF-κβ activity and tumor necrosis factor-α level in the IRI group were significantly higher than in the control group (3.17 ± 0.21 and 0.28 ± 0.03 vs 654.2 ± 3.6 pg/mL and 147.4 ± 1.1 pg/mL; t value = 4.11 and 4.29 for each; P < .01). Compared with the IRI group they were greatly decreased after anti-CD14 antibody treatment: 2.14 ± 0.17 vs 3.17 ± 0.21, 298.7 ± 1.8 pg/mL vs 654.2 ± 3.6 pg/mL (t value = 2.52 and 2.92 for each; P < .05). They were still significantly higher than the control group (t values of 3.01 and 3.27 for each; P < .01).

Conclusion

IRI up-regulated CD14 and TLR4 gene expression in KCs, and subsequently activated NF-κβ to produce cytokines.     

Dynamic changes of indoleamine 2,3-dioxygenase of Kupffer cells in rat liver transplant rejection and tolerance

Aims

To study the dynamic changes and the immunologic role of indoleamine 2, 3-dioxygenase (IDO) in Kupffer cells (KCs) after rat liver transplantation.

Methods

Animals were randomly divided into two groups: a rejection group (REJ; LEW to BN) and a tolerance group (TOL; BN to LEW). Liver morphological changes were observed optically with hematoxylin/eosin staining. KCs were isolated from recipients. mRNA and protein expressions of IDO were detected by real-time polymerase chain reaction and Western blotting at 1, 3, 5, and 7 days after transplantation.

Results

The levels of IDO mRNA and protein in KCs of TOL groups were similar to those in REJ groups at day 1 posttransplantation. However, the expression of IDO mRNA and protein time-dependently increased to much higher levels in the TOL than the in REJ groups at 3, 5, and 7 days posttransplantation (P < .05). The peak was observed at 7 days.

Conclusions

The IDO level of KCs was closely associated with immune tolerance induction. IDO-mediated immune modulation appears to be an attractive means to assess transplant tolerance induction.     

云南白药外敷治疗静脉穿刺致皮下淤血

目的 探讨云南白药外敷治疗静脉穿刺致皮下淤血的效果.方法 将94例静脉穿刺后引起皮下淤血的患者随机分成观察组(48例)和对照组(46例),观察组采用乙醇调制的云南白药外敷,对照组进行热敷治疗,观察患者淤血消退时间.结果 观察组淤血消退时间显著短于对照组(P＜0.01).结论 云南白药外敷治疗静脉穿刺引起的皮下淤血效果优于传统方法.     

Mesenchymal stem cell‐conditioned medium accelerates wound healing with fewer scars

Mesenchymal stem cells (MSCs) derived from umbilical cord s (UC‐MSCs) have been shown to enhance cutaneous wound healing by means of the paracrine activity. Fibroblasts are the primary cells involved in wound repair. The paracrine effects of UC‐MSCs on dermal fibroblasts have not been fully explored in vitro or in vivo. Dermal fibroblasts were treated with conditioned media from UC‐MSCs (UC‐MSC‐CM). In this model, UC‐MSC‐CM increased the proliferation and migration of dermal fibroblasts. Moreover, adult dermal fibroblasts transitioned into a phenotype with a low myofibroblast formation capacity, a decreased ratio of transforming growth factor‐β1,3 (TGF‐β1/3) and an increased ratio of matrix metalloproteinase/tissue inhibitor of metalloproteinases (MMP/TIMP). Additionally, UC‐MSC‐CM‐treated wounds showed accelerated healing with fewer scars compared with control groups. These observations suggest that UC‐MSC‐CM may be a feasible strategy to promote cutaneous repair and a potential means to realise scarless healing.     

Efficacy and Safety of Everolimus Plus Low‐Dose Tacrolimus Versus Mycophenolate Mofetil Plus Standard‐Dose Tacrolimus in De Novo Renal Transplant Recipients: 12‐Month Data

In this 12‐month, multicenter, randomized, open‐label, noninferiority study, de novo renal transplant recipients (RTxRs) were randomized (1:1) to receive everolimus plus low‐dose tacrolimus (EVR+LTac) or mycophenolate mofetil plus standard‐dose Tac (MMF+STac) with induction therapy (basiliximab or rabbit anti‐thymocyte globulin). Noninferiority of composite efficacy failure rate (treated biopsy‐proven acute rejection [tBPAR]/graft loss/death/loss to follow‐up) in EVR+LTac versus MMF+STac was missed by 1.4%, considering the noninferiority margin of 10% (24.6% vs. 20.4%; 4.2% [?3.0, 11.4]). Incidence of tBPAR (19.1% vs. 11.2%; p < 0.05) was significantly higher, while graft loss (1.3% vs. 3.9%; p < 0.05) and composite of graft loss/death/lost to follow‐up (6.1% vs. 10.5%, p = 0.05) were significantly lower in EVR+LTac versus MMF+STac groups, respectively. Mean estimated glomerular filtration rate was similar between EVR+LTac and MMF+STac groups (63.1 [22.0] vs. 63.1 [19.5] mL/min/1.73 m²) and safety was comparable. In conclusion, EVR+LTac missed noninferiority versus MMF+STac based on the 10% noninferiority margin. Further studies evaluating optimal immunosuppression for improved efficacy will guide appropriate dosing and target levels of EVR and LTac in RTxRs.     

Six-Month Prophylaxis Is Cost Effective in Transplant Patients at High Risk for Cytomegalovirus Infection

The risk of late-onset cytomegalovirus (CMV) infection remains a concern in seronegative kidney and/or pancreas transplant recipients of seropositive organs despite the use of antiviral prophylaxis. The optimal duration of prophylaxis is unknown. We studied the cost effectiveness of 6- versus 3-mo prophylaxis with valganciclovir. A total of 222 seronegative recipients of seropositive kidney and/or pancreas transplants received valganciclovir prophylaxis for either 3 or 6 mo during two consecutive time periods. We assessed the incidence of CMV infection and disease 12 mo after completion of prophylaxis and performed cost-effectiveness analyses. The overall incidence of CMV infection and disease was 26.7% and 24.4% in the 3-mo group and 20.9% and 12.1% in the 6-mo group, respectively. Six-month prophylaxis was associated with a statistically significant reduction in risk for CMV disease (HR, 0.35; 95% CI, 0.17 to 0.72), but not infection (HR, 0.65; 95% CI, 0.37 to 1.14). Cost-effectiveness analyses showed that 6-mo prophylaxis combined with a one-time viremia determination at the end of the prophylaxis period incurred an incremental cost of $34,362 and $16,215 per case of infection and disease avoided, respectively, and $8,304 per one quality adjusted life-year gained. Sensitivity analyses supported the cost effectiveness of 6-mo prophylaxis over a wide range of valganciclovir and hospital costs, as well as variation in the incidence of CMV disease. In summary, 6-mo prophylaxis with valganciclovir combined with a one-time determination of viremia is cost effective in reducing CMV infection and disease in seronegative recipients of seropositive kidney and/or pancreas transplants.Cytomegalovirus (CMV) infection remains one of most common opportunistic infections in solid organ transplant patients despite availability of specific and efficacious anti-viral drugs.^1,2 Solid organ transplant patients who have a negative CMV serology and receive an organ from a positive CMV serologic donor (D+/R−) have the highest incidence of CMV disease with and without prophylaxis.^2–5 Although the risk for CMV disease persists for life, the majority of cases occur shortly after completion of prophylaxis, often within the first year after transplant.⁶ CMV disease causes significant morbidity, increases mortality, and is associated with inferior transplant outcomes, particularly in the case of kidney transplantation.^7–10 Furthermore, the presence of CMV disease is one of the most frequent infectious causes of hospitalization early after transplantation, increasing the total cost of kidney transplantation and reducing its overall effectiveness.^7,11–13Valganciclovir (VGCV) is an effective anti-CMV agent for prophylaxis and treatment of CMV disease that is widely used in transplantation.^2,14–16 Although the recommended dose for CMV prophylaxis is 900 mg daily adjusted for renal function, a recent study showed that VGCV at 450 mg daily provides similar drug exposure compared with oral ganciclovir (GCV) at 1000 mg three times daily in kidney transplant patients, a dose similarly effective for CMV prophylaxis.^2,17 In most studies, VGCV prophylaxis consisted of 100 d after transplant, after which time the risk of CMV infection and disease increased.^2,18,19 Extending the duration of VGCV prophylaxis beyond the early post-transplant period may abrogate this transient increase in the risk of infection and disease.^20,21 In this regard, the optimal duration of prophylaxis for CMV D+/R− patients has not been determined and is the subject of ongoing study.²² Cost, efficacy, and safety are important factors in determining the optimal duration of VGCV prophylaxis. Over the past two decades, various strategies have been used including pre-emptive versus universal prophylaxis and shorter versus longer period of prophylaxis.^20,21,23,24 Although several clinical studies comparing universal prophylaxis versus pre-emptive anti-viral therapy have found similar efficacy and cost in managing CMV infection across various combinations of donor and recipient CMV serologic status, two meta-analyses did find that the use of universal prophylaxis was associated with reduced risk for CMV disease and death.^23–26This study is based on a single center experience comparing two CMV prophylaxis strategies. We report here the clinical outcome and cost-effectiveness analyses of 6- versus 3-mo VGCV prophylaxis in CMV D+/R− de novo kidney and/or pancreas transplant patients.     

239例小儿室间隔缺损修补术后残余分流的近中期随访

目的:探讨小儿室间隔缺损(ventricular septal defect,VSD)修补术后残余分流的发生原因、常见部位、预后、影响预后的因素及干预时机。方法:回顾性分析2013年1月至2017年1月重庆医科大学附属儿童医院行VSD修补术后239例残余分流患者的临床资料,包括患者性别、手术年龄、体质量、术前左右心室压差、术前VSD分流方向、补片材料、体外循环时间、残余分流的大小及部位、残余分流的血流速度,运用单因素及多因素Cox回归分析患者预后的影响因素。结果:239例残余分流患者均未再次干预,155例(64.85%)残余分流自行愈合;84例(35.15%)未愈合。小于4 mm残余分流219例,153例(69.86%)自愈;大于4 mm残余分流20例,2例(10%)自愈(P<0.005)。单因素Cox分析结果表明,术前左右心室压差(P=0.028)、体外循环时间(P=0.006)、残余分流大小(P=0.003)、残余分流血流速度(P=0.00)是影响患者预后的因素(P<0.05);而多因素Cox回归分析显示体外循环时间(P=0.017)、残余分流血流速度(P=0.019)...