深部脑动静脉畸形的显微手术治疗

目的 探讨深部脑动静脉畸形(BAVM)的显微手术技巧及效果. 方法 吉林大学中日联谊医院自2001年1月至2008年6月对收治入院的70例深部BAVM患者采用显微手术治疗,其中70例患者脑部畸形血管团属小型(直径＜3 cm)31例,中型(直径3～6 cm)36例,巨大型(直径＞6 cm)3例;按Spetzler-Martin分级:Ⅰ级11例,Ⅱ级12例,Ⅲ级23例,Ⅳ级16例,Ⅴ级8例,对术中的显微手术技巧及术后疗效进行总结分析. 结果 70例患者深部畸形血管团术中均完整切除,27例复查MRI、8例复查DSA证实.1例Spetzler-MartinⅤ级患者术后发生正常灌注压突破.所有患者随访6个月～3年,均无复发及再次出血.8例术前脑疝患者术后3例重残,2例中残,3例生活能自理.10例癫痫患者术后服用抗癫痫药物症状得到控制.余患者术后未遗留明显神经功能障碍. 结论 深部BAVM血管构筑复杂,手术全切除最为彻底.高流量BAVM行术前栓塞及口服β受体阻滞剂,术中降低动脉压、延长麻醉苏醒时间,术后减少液体摄入及应用脱水疗法,可降低正常灌注压突破的发生率.     

中医药临床研究待“突破”

中医药临床研究开展如火如荼,但是由于诸多瓶颈制约,影响其质量的整体提升和研究水平的“突破”.从中医药临床研究的需求与目标、思路与方法、组织模式以及国际化等多角度展开论述,强调“分类开展”,做到三个“和谐统一”,加强组织分工,强化国际合作,冀望为中医药临床研究设计者及组织实施人员提供思路和借鉴。     

Effects of mifepristone on proliferation and apoptosis of human endometrium in new users of medroxyprogesterone acetate

BACKGROUND: Mifepristone has been demonstrated to decrease breakthrough bleeding (BTB) in users of progestin-only contraceptives. METHODS: Endometrial biopsies were collected from 50 normal cycling women who were new users of depot medroxyprogesterone acetate (DMPA) randomized to receive either mifepristone or placebo before, during and after treatment. Proliferation, apoptosis and sex steroid receptors were evaluated by either immunohistochemistry or TUNEL assay. RESULTS: Administration of mifepristone to DMPA-exposed endometrium for 1 week significantly increased endometrial expression of Ki-67 (MKI67), estrogen receptor (ER)alpha and progesterone receptors A and B (PRAB) and decreased the number of TUNEL-positive and caspase-3 (CASP3)-active cells in the endometrial stroma. However, after 10 weeks of mifepristone treatment, no significant difference in proliferation, apoptosis and the expression of ERalpha or PRAB could be detected between the endometrium treated with DMPA alone and endometrium treated with mifepristone and DMPA. CONCLUSIONS: Administration of mifepristone to DMPA users significantly increases endometrial proliferation and decreases endometrial stromal apoptosis in the short term. Prolonged exposure to mifepristone does not counteract the inhibitory effects of progestin therapy on endometrial proliferation. Estrogen and progesterone receptors may play an important role in these effects.     

Transmucosal fentanyl vs intravenous morphine in doses proportional to basal opioid regimen for episodic-breakthrough pain

The use of supplemental doses of opioids is commonly suggested to manage breakthrough pain. A comparative study of intravenous morphine (IV-MO) and oral transmucosal fentanyl citrate (OTFC) given in doses proportional to the basal opioid regimen was performed in 25 cancer patients receiving stable opioid doses. For each episode, when it occurred and 15 and 30 min after the treatment, pain intensity and opioid-related symptoms were recorded. Fifty-three couples of breakthrough events, each treated with IV-MO and OTFC, were recorded. In episodes treated with IV-MO, pain intensity decreased from a mean of 6.9 to 3.3 and to 1.7 at T1 and T2, respectively. In episodes treated with OTFC, pain intensity decreased from a mean of 6.9 to 4.1 and to 2.4 at T1 and T2, respectively. Statistical differences between the two treatments were found at T1 (P=0.013), but not at T2 (P=0.059). Adverse effects were comparable and were not significantly related with the IV-MO and OTFC doses. Intravenous morphine and OTFC in doses proportional to the scheduled daily dose of opioids were both safe and effective, IV-MO having a shorter onset than OTFC. Future comparative studies with appropriate design should compare titration methods and proportional methods of OTFC dosing.     

High rate of breakthrough invasive aspergillosis among patients receiving caspofungin for persistent fever and neutropenia

A number of agents are now available for empirical antifungal treatment (EAFT) of patients with persistent fever and neutropenia. We carried out a study of efficacy of antifungal drugs to prevent breakthrough invasive aspergillosis by reviewing the medical records of all consecutive patients who received EAFT from November 2005 to February 2006. Patients’ characteristics and the type, dose and duration of antifungal therapy were recorded. Breakthrough invasive fungal infections were documented according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) definition. Fifty-six episodes of persistent fever with neutropenia requiring EAFT were recorded among 49 patients. All patients received high-dose chemotherapy for acute myeloid leukaemia (51%), acute lymphoid leukaemia (12%), lymphoma (14%) or other haematologic conditions (22%). Fourteen (29%) and five (10%) patients were allogeneic and autologous haematopoietic stem cell transplant recipients, respectively. Caspofungin was prescribed initially in 40 episodes (71%), amphotericin B (AmB) desoxycholate and liposomal AmB being prescribed in six (10%) and ten (18%) episodes, respectively. Six patients were switched from liposomal AmB to caspofungin because of adverse events. The median duration of antifungal therapy was 9 days. During follow-up, six patients (12%) were diagnosed with invasive aspergillosis after a median of 8 days (range 3–16 days) of EAFT. Invasive aspergillosis breakthrough occurred in 6/46 (13%) caspofungin recipients and in 0/16 (0%) AmB recipients (OR 3.1, p 0.32). The observed high rate of invasive aspergillosis among caspofungin recipients requires further evaluation.     

Precore stop codon mutation of hepatitis B virus is associated with low breakthrough rate following long-term lamivudine therapy

BACKGROUND: Frequent viral breakthroughs limit the usefulness of lamivudine in the treatment of chronic hepatitis B (CHB). The purpose of the present study was to evaluate the effects of precore stop codon mutation (G to A mutation at nucleotide 1896; A(1896)) of hepatitis B virus (HBV) on the occurrence of viral breakthrough following lamivudine therapy. METHODS: Among 260 consecutive CHB patients treated with lamivudine for >12 months, 231 patients whose pretreatment sera were available were tested for A(1896) variant of HBV using direct sequencing. RESULTS: Between patients with A(1896) variant (n = 74) and those without it (n = 157), there was no difference in age, gender, serum alanine aminotransferase (ALT) level, the duration of therapy and prevalence of core promoter mutants. Serum hepatitis B e antigen (HBeAg) positivity and HBV-DNA level were lower (P = 0.00 and P = 0.01) and liver cirrhosis was more commonly associated in patients with A(1896) variant mutant compared with those without it. In univariate analysis, viral breakthrough was more frequent in HBeAg-positive patients (P = 0.03) and in those with high serum HBV-DNA level (P = 0.01) as well as in those without A(1896) variant (P = 0.01). However, in multivariate analysis, the absence of A(1896) variant (P = 0.02) and high serum HBV-DNA level (P = 0.03) were independent factors for viral breakthrough following lamivudine therapy. The cumulative viral breakthrough rates at 1 and 2 years were much lower in patients with A(1896) variant compared with those without it (P = 0.01). CONCLUSION: The stop codon mutation at the precore region of HBV in addition to low serum HBV-DNA level may be associated with low breakthrough rate following lamivudine therapy.     

Granisetron Extended-Release Subcutaneous Injection versus Palonosetron Infusion for CINV Prevention: Cost Comparison of Unscheduled Hydration

BackgroundGranisetron extended-release subcutaneous (SC) injection is a novel formulation of granisetron for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV). Palonosetron is administered intravenously and is indicated for CINV prevention in acute and delayed phases after the use of moderately emetogenic chemotherapy (MEC) and in the acute phase after highly emetogenic chemotherapy (HEC). No data are available regarding the impact of SC granisetron on the cost of unscheduled hydration compared with other antiemetic drugs, specifically the older-generation palonosetron.ObjectiveTo compare the costs of unscheduled hydration associated with breakthrough CINV after SC granisetron versus palonosetron administration in patients receiving MEC or HEC.MethodsThis retrospective analysis was based on electronic medical records data from a single multicenter, community-based practice involving patients receiving MEC or HEC with a 3-drug antiemetic regimen, including a neurokinin-1 receptor antagonist, dexamethasone, and either SC granisetron or palonosetron. A cost-of-care analysis for SC granisetron and palonosetron was based on the maximum per-unit Medicare reimbursement amounts for the use of unscheduled hydration, administration of rescue antiemetic drugs, laboratory tests, and patient office evaluations.ResultsA total of 182 patient records were evaluated, 91 for patients receiving SC granisetron and 91 receiving palonosetron. The mean per-patient cost of care related to unscheduled hydration in patients receiving HEC or MEC was significantly lower with SC granisetron ($296) than palonosetron ($837; P <.0001), including subset analysis of patients requiring additional care (SC granisetron [$691], N = 39; palonosetron [$1058], N = 72; P = .0260). The mean hydration costs per patient receiving HEC or MEC were lower with SC granisetron ($62) than with palonosetron ($253; P <.0001). The hydration costs per patient receiving only HEC were lower with SC granisetron ($66) than palonosetron ($280; P <.0001). The per-patient costs were lower when SC granisetron was administered than when palonosetron was administered as part of the antiemetic regimen, except for the cost of rescue antiemetic drug in patients receiving MEC. Fewer median unscheduled hydration therapies per patient were used with SC granisetron versus palonosetron (HEC, 3 vs 5; MEC, 2 vs 3).ConclusionThe use of SC granisetron reduced the total per-patient costs of care associated with unscheduled hydration compared with palonosetron in patients receiving HEC or MEC for breakthrough CINV events.     

Multistate Outbreak of SARS-CoV-2 Infections,Including Vaccine Breakthrough Infections,Associated with Large Public Gatherings,United States

During July 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.617.2 variant infections, including vaccine breakthrough infections, occurred after large public gatherings in Provincetown, Massachusetts, USA, prompting a multistate investigation. Public health departments identified primary and secondary cases by using coronavirus disease surveillance data, case investigations, and contact tracing. A primary case was defined as SARS-CoV-2 detected <14 days after travel to or residence in Provincetown during July 3–17. A secondary case was defined as SARS-CoV-2 detected <14 days after close contact with a person who had a primary case but without travel to or residence in Provincetown during July 3–August 10. We identified 1,098 primary cases and 30 secondary cases associated with 26 primary cases among fully and non–fully vaccinated persons. Large gatherings can have widespread effects on SARS-CoV-2 transmission, and fully vaccinated persons should take precautions, such as masking, to prevent SARS-CoV-2 transmission, particularly during substantial or high transmission.