Development and Validation of a Laboratory Risk Score (LabScore) to Predict Outcomes after Resection for Intrahepatic Cholangiocarcinoma

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Impact of antimicrobial stewardship with the Xpert MRSA/SA BC assay at a tertiary hospital in Japan

IntroductionGenetic testing is gaining increasing importance as a part of antimicrobial stewardship (AS). Rapid identification and determination of methicillin susceptibility using the Xpert MRSA/SA BC assay can improve the management of Staphylococcus aureus bacteremia (SAB) and reduce inappropriate antibiotic use. However, few reports have described the effectiveness of this approach.MethodsThe present study aimed to assess the influence of AS using the Xpert MRSA/SA BC assay. Cases were classified into the pre-intervention group (n = 98 patients), in which SAB was identified by traditional culture (November 2017 to November 2019), and the post-intervention group (n = 97 patients), in which the Xpert MRSA/SA BC assay was performed when necessary (December 2019 to December 2021).ResultsPatient characteristics, prognosis, duration of antimicrobial use, and length of hospital stay were compared between the groups. The Xpert assay was performed in 66 patients in the post-intervention group (68.0%). The two groups showed no significant differences in severity and mortality. The rate of cases treated with anti-MRSA agents reduced following the intervention (65.3% vs. 40.4%, p = 0.008). The number of cases involving definitive therapy within 24 h was higher in the post-intervention group (9.2% vs. 24.7%, p = 0.007). The hospitalization rate at >60 days was lower in Xpert implementation cases among MRSA bacteremia cases (28.6% vs. 0%, p = 0.01).ConclusionsThus, the Xpert MRSA/SA BC assay has potential as an AS tool, especially for early definitive treatment to SAB and reduction of long-term hospitalization in MRSA bacteremia cases.     

Endoprosthetics for bleeding esophageal varices

Refractory esophageal hemorrhage and early rebleeding following endoscopic therapy remain challenging conditions to treat and are associated with a high mortality. Techniques such as balloon tamponade (BT) and transjugular intrahepatic portosystemic shunt (TIPS) are highly effective at controlling refractory bleeding, but they can be associated with a high rate of complications and, in the case of TIPS, may not be immediately available outside specialist centers. Recently, removable self-expanding metal stents (SEMSs) have been introduced in clinical practice for the management of esophageal variceal bleeding. SEMSs control bleeding by tamponade of varices in the distal esophagus and can remain in situ for a number of days, thus preventing early rebleeding. The use of SEMSs does not require the transfer of the patient to a specialist center, and unlike TIPS, it is not associated with deterioration in liver function. The use of SEMSs has been described in small series of patients with refractory bleeding. These series report high rates of hemostasis with low complication rates, suggesting that SEMSs may have an important role in the management of refractory bleeding either as an alternative to BT or where TIPS is contraindicated. SEMSs may also have a role in treating complications of therapy for bleeding esophageal varices, such as postbanding ulceration and BT-induced esophageal tears. The aim of this review is to summarize the published data on the efficacy of SEMSs and suggest future studies that may clarify its role in the management of esophageal variceal hemorrhage.     

应用三维斑点追踪技术评价2型糖尿病患者左心室收缩功能

目的 应用三维斑点追踪技术(3D-STE)检测2型糖尿病(T2DM)患者左心室收缩功能。 方法 收集T2DM患者55例,分为单纯糖尿病组31例和糖尿病合并微血管病变组24例;另选择健康人31名作为对照组。常规采集各切面图像和左心室全容积图像,将全容积图像输入TomTec 4D LV analysis软件,计算16节段心肌三维应变(3DS)、纵向应变(LS)、圆周应变(CS)值,并与左心室射血分数(LVEF)行相关性分析。 结果 与对照组比较,单纯糖尿病组和糖尿病合并微血管病变组中间部和心尖部的前间隔、侧壁,基底部和中间部后壁,心尖部下壁的3DS均显著减低(P均<0.05);中间部前间隔、前壁、后壁,心尖部后间隔 LS均减低(P均<0.05);基底部、中间部及心尖部侧壁,基底部和中间部后壁CS明显减低(P均<0.05);3DS与LVEF呈正相关(r=0.75,P<0.01)。 结论 3D-STE对评价糖尿病左心室动力学具有较高的应用价值;3DS可较CS、LS更全面、客观地评价糖尿病心肌病左心室心肌收缩功能受损情况。     

High-dose dexamethasone plus recombinant human thrombopoietin vs high-dose dexamethasone alone as frontline treatment for newly diagnosed adult primary immune thrombocytopenia: A prospective,multicenter, randomized trial

We conducted a prospective, multicenter, randomized, controlled clinical trial to compare the efficacy and safety of high-dose dexamethasone (HD-DXM) plus recombinant human thrombopoietin (rhTPO), vs HD-DXM alone in newly diagnosed adult immune thrombocytopenia (ITP) patients. Enrolled patients were randomly assigned to receive DXM plus rhTPO or DXM monotherapy. Another 4-day course of DXM was repeated if response was not achieved by day 10 in both arms. One hundred patients in the HD-DXM plus rhTPO arm and 96 patients in the HD-DXM monotherapy arm were included in the full analysis set. So, HD-DXM plus rhTPO resulted in a higher incidence of initial response (89.0% vs 66.7%, P < .001) and complete response (CR, 75.0% vs 42.7%, P < .001) compared with HD-DXM monotherapy. Response rate at 6 months was also higher in the HD-DXM plus rhTPO arm than that in the HD-DXM monotherapy arm (51.0% vs 36.5%, P = .02; sustained CR: 46.0% vs 32.3%, P = .043). Throughout the follow-up period, the overall duration of response was greater in the HD-DXM plus rhTPO arm compared to the HD-DXM monotherapy arm (P = .04), as estimated by the Kaplan-Meier analysis. The study drugs were generally well tolerated. In conclusion, the combination of HD-DXM with rhTPO significantly improved the initial response and yielded favorable SR in newly diagnosed ITP patients, thus could be further validated as a frontline treatment for ITP. This study is registered as clinicaltrials.gov identifier: NCT01734044.     

HDAC2 was involved in placental P-glycoprotein regulation both in vitro and vivo

IntroductionPlacental P-glycoprotein (P-gp) plays a significant role in regulating drugs' transplacental transfer rates. Investigations on placental P-gp regulation could provide more therapeutic targets for individualized and safe pharmacotherapy during pregnancy. Currently, the epigenetic regulation of placental P-gp is rare. Our previous study has demonstrated that HDACs inhibition could up-regulate placental P-gp and HDAC1/2/3 might be involved in this process. The present study was carried out to further explore whether HDAC1/2/3 were indeed involved in the regulation of placental P-gp or not and screen out the subtype engaged in this process.MethodsBeWo and JAR cells were transfected with HDAC1/2/3 specific siRNA. After 48 h of transfection, cells were harvested for real-time quantitative PCR (qRT-PCR), Western blot, immunofluorescence and fluorescent dye efflux assay to evaluate P-gp expression, localization, and efflux activity, respectively. Hdac2 siRNA was intraperitoneally injected to pregnant mice every 48 h from E7.5 to E15.5 and digoxin was administered by gavages 1 h prior to euthanasia at E16.5. Placental Hdac1/2/3 and P-gp expression were determined by qRT-PCR and Western blot. Maternal plasma and fetal-unit digoxin concentrations were detected by enzyme-multiplied immunoassay.ResultsIn vitro, HDAC2 inhibition could significantly elevate P-gp expression and reduce intracellular accumulation of P-gp substrates (DiOC₂ (3) and Rh 123) both in BeWo and JAR, while knockdown of HDAC1/3 had no influence on P-gp expression and its efflux activity. Additionally, in vivo, Hdac2 silencing in pregnant mice also elevated placental P-gp expression and decreased digoxin transplacental transfer rate.ConclusionHDAC2 inhibition could result in induction of placental P-gp expression and functionality both in vitro and in vivo.     

创伤骨科患者围术期下肢静脉血栓形成诊断及防治专家共识(2022年)

下肢深静脉血栓形成(DVT)是创伤骨科患者的主要并发症之一,严重DVT甚至会影响动脉供血,出现相应肢体供血不足。若发生血栓脱落可并发肺栓塞,病死率较高。临床上下肢骨折患者DVT的治疗和康复策略均有其特殊性。创伤骨科患者并发DVT已经引起广泛的关注与研究,预防和治疗DVT的最佳措施也在不断发展。近年来国内外陆续更新了一系列血栓防治指南,但临床上对于不同创伤骨折患者DVT的防治方式仍有不少疑惑。因此,笔者在总结国内外最新的循证医学证据和广大专家的临床经验基础上,针对创伤骨科患者DVT的临床诊疗和预防方案进行总结,就下肢DVT的诊断、评估、治疗及预防措施等方面制订本共识,为创伤骨科患者下肢DVT的处理提供一套适合我国国情且简便易行的方案,以期改善患者预后,提高其生活质量。     

多发性骨髓瘤伴髓外病变研究进展

多发性骨髓瘤（MM）是一种以分泌单克隆免疫球蛋白或其片段（M蛋白）为特征的恶性浆细胞疾病。一般情况下,骨髓瘤细胞局限于髓内,但在初诊或疾病进展过程中均可出现髓外病变（EM）,伴EM的MM患者预后较差。根据EM的发生方式可将其分为单纯骨相关髓外病变（EM-b）和软组织相关髓外病变（EM—s）。EM—b为骨髓瘤细胞突破骨皮质累及周围连续性软组织的病变;EM-s为通过血源播散到髓外的软组织或其他器官的病变。研究发现不论是初诊MM还是疾病进展过程中发生的EM-s,其预后都比EM-b差。因此,文章主要综述EM-b和EM-S的区别,包括两者的发病率、生物学特征、临床表现、治疗及预后。