Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies treated with anticancer therapy

Hepatitis due to hepatitis B virus(HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximabcontaining therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBs Ag) and antibody to hepatitis B core antigen(antiHBc). Patients found to be positive for HBs Ag should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving highrisk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBs Ag-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.     

Validation of a prognostic scoring system for locally recurrent nasopharyngeal carcinoma treated by stereotactic radiosurgery

Background  

Selection of patients with local failure of nasopharyngeal carcinoma (NPC) for appropriate type of salvage treatment can be difficult due to the lack of data on comparative efficacy of different salvage treatments. The purpose of the present study was to validate a previously published prognostic scoring system for local failures of NPC treated by radiosurgery based on reported results in the literature.     

顺-3-甲基芬太尼的4-N-丙酰基结构类似物的合成与镇痛活性及构效关系的研究

以不同电性的基团取代顺-3-甲基芬太尼中4-N-丙酰基上的乙基,合成某些顺-3-甲基芬太尼的结构类似物。药理试验结果表明,所合成的化合物均有典型的吗啡样作用。化合物3的镇痛活性略强于顺-3-甲基芬太尼。应用半经验的INDO方法对4个代表化合物进行了量子化学计算,讨论了电子结构与镇痛活性间的关系,化合物3由于氯乙烯基的引入具有与顺-3-甲基芬太尼不同的电子结构特征,氯乙烯基可能作为电子接受体参与了与受体的作用。     

Cholesterol efflux capacity of high‐density lipoprotein was not associated with cognitive decline and brain structures in older people with diabetes mellitus

Aims/IntroductionTo examine the association between cholesterol efflux capacity (CEC) of serum high‐density lipoprotein (HDL) and cognitive function and brain structures in older people with diabetes mellitus.Materials and MethodsParticipants of a randomized placebo‐controlled trial of 27‐month vitamin B₁₂ supplementation in older people with diabetes mellitus, which showed no effect on cognition, were further followed up at month 72. Cognitive tests included the Clinical Dementia Rating scale, Neuropsychological Test Battery in memory, executive function and psychomotor speed. Brain magnetic resonance imaging scans were carried out in a subset at baseline, month 27 and month 45. Fasting serum at baseline, month 9, month 27 and month 72 were analyzed for adenosine triphosphate‐binding cassette transporter A1‐mediated CEC of HDL and apolipoprotein A1 (ApoA1).ResultsSerum HDL cholesterol at baseline was associated with better executive and memory function at follow up. Serum ApoA1 was associated with a better memory Z‐score at month 18. Serum CEC and ApoA1 were not associated with Clinical Dementia Rating scale, Neuropsychological Test Battery, hippocampal volume and white matter disease on magnetic resonance imaging at baseline and whole brain atrophy rates. They were also not associated with cognitive function at month 27 and 72 on multilevel modeling. CEC and ApoA1 decreased significantly from baseline to month 27. Faster decliners in CEC had a greater increase in brain peak width of skeletonized mean diffusivity.ConclusionsHigher serum HDL cholesterol was associated with more favorable changes in memory and executive function in older people with diabetes mellitus. However, this was not due to CEC or ApoA1. A decline in CEC was associated with small vessel disease in the brain.     

Nitrogen-Containing Bisphosphonates Are Associated With Reduced Risk of Pneumonia in Patients With Hip Fracture

The objective of this work was to study the risk of pneumonia and pneumonia mortality among patients receiving nitrogen-containing bisphosphonates (N-BPs), non-N-BP anti-osteoporosis medications, and no anti-osteoporosis medications after hip fracture. We studied a historical cohort using a population-wide database. Patients with first hip fracture during 2005–2015 were identified and matched by time-dependent propensity score. The cohort was followed until December 31, 2016, to capture any pneumonia and pneumonia mortality. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox-proportional hazards regression. Absolute risk difference (ARD) and number needed to treat (NNT) were calculated. We identified 54,047 patients with hip fracture. Of these, 4041 patients who received N-BPs and 11,802 without anti-osteoporosis medication were propensity score–matched. N-BPs were associated with a significantly lower risk of pneumonia compared with no treatment (6.9 versus 9.0 per 100 person-years; HR 0.76; 95% CI, 0.70 to 0.83), resulting in an ARD of 0.02 and NNT of 46. A similar association was observed with pneumonia mortality (HR 0.65; 95% CI, 0.56 to 0.75). When N-BPs were compared with non-N-BP anti-osteoporosis medications, the association remained significant. N-BPs were associated with lower risks of pneumonia and pneumonia mortality. Randomized controlled trials are now required to determine whether N-BPs, non–vaccine-based medications, can reduce pneumonia incidence in high risk groups. © 2020 American Society for Bone and Mineral Research.     

样品固相净化及反相高效液相色谱法测定血浆中茶碱

本文用氧化铝固相净化血样以消除血中杂质及某些合并用药的干扰,用Zorbax-C18柱及甲醇-(0.05 mol/L)醋酸钠缓冲液(50:50)为流动相,254 nm波长检测,咖啡因为内标测定了茶碱人体血浆浓度的变化。该法样品处理简便、快速,净化回收率好(80～86%)茶碱的检测限为0.2ng(信噪比3),在血浆中的最低检测浓度为20 ng/ml。标准曲线r为0.9995,日内变异系数1.89%,日间变异系数为2.41%,方法平均回收率为98.44±0.89%。     

对青少年特发性脊柱侧弯患者的体感诱发电位检查

本体感觉神经传导异常被认为与青少年特发性脊柱侧弯有关。用体感诱发电位检查在青少年特发性脊柱侧弯患者中是否合并存在本体感觉传导通道的功能异常。研究包括147例青少年特发性脊柱侧弯患者及31位同年龄分布正常对照。对每一位受试者检查胜后神经体感皮质诱发电位，电信号缺失、传导时间延长或双侧传导时间不对称为本体感觉传导通道结构性异常诊断指标。在脊柱侧弯患者中有7人电信号单或双侧缺失，其余140例脊柱侧弯患者中10例传导时间延长，其中4例双侧延长，6例单侧延长。结果证实，部分青少年特发性脊柱侧弯患者同时有本体感觉传导异常，提示青少年特发性脊柱侧弯可进一步分为有本体感觉传导异常及无异常两组。     

N-(4-乙氧羰基-4-取代丁酰基)-N-取代甘氨酸的合成

本文报道9个估计具有血管紧张素转化酶抑制活性的N-(4-乙氧羰基-4-取代丁酰基)-N-取代甘氨酸及其相应叔丁酯的合成和鉴定。药理初试结果,化合物Ⅶ₇和Ⅶ₉显示明显降压活性。     

Rp－HPLC法测定血清中的抗生育甾体药物利洛司酮

以ＲＵ４８６为内标，建立了血清样品中新型抗孕激素甾体药物利洛司酮（ｌｉｌｏｐｒｉｓｔｏｎｅ）的反相高效液相色谱法。色谱分析条件为μＢｏｎｄａｐａｋＣ１８柱１０μｍ，３００ｍｍ×３．９ｍｍＩＤ；流动相为甲醇－二氯甲烷－１０ｍｍｏｌ·Ｌ－１磷酸盐缓冲液（ｐＨ４．０）（６７：５：２８ｖ／ｖ）；紫外检测波长为３０２ｎｍ。利洛司酮的检测限为１ｎｇ（Ｓ／Ｎ≥４：１）。血清样品经二次液一液超声振荡萃取后，得到了较好的净化。血清样品中利洛司酮的方法回收率为１０３．３％，日内精密度及日间精密度平均ＲＳＤ为３．５１％及２．９２％。在浓度为１０～１０００ｎｇ·ｍｌ－１血清范围内呈线性关系。