Immunisation with the BCG and DTPw vaccines induces different programs of trained immunity in mice

In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings. The NSEs associated with BCG have been attributed, in part, to the induction of trained immunity, an epigenetic and metabolic reprograming of innate immune cells, increasing their responsiveness to subsequent microbial encounters. Whether non-live vaccines such as DTPw induce trained immunity is currently poorly understood. Here, we report that immunisation of mice with DTPw induced a unique program of trained immunity in comparison to BCG immunised mice. Altered monocyte and DC cytokine responses were evident in DTPw immunised mice even months after vaccination. Furthermore, splenic cDCs from DTPw immunised mice had altered chromatin accessibility at loci involved in immunity and metabolism, suggesting that these changes were epigenetically mediated. Interestingly, changing the order in which the BCG and DTPw vaccines were co-administered to mice altered subsequent trained immune responses. Given these differences in trained immunity, we also assessed whether administration of these vaccines altered susceptibility to sepsis in two different mouse models. Immunisation with either BCG or a DTPw-containing vaccine prior to the induction of sepsis did not significantly alter survival. Further studies are now needed to more fully investigate the potential consequences of DTPw induced trained immunity in different contexts and to assess whether other non-live vaccines also induce similar changes.     

Advancing primary and community care for persons with spinal cord injury: Key findings from a Canadian summit

Context: Persons with spinal cord injury (SCI) experience significant challenges when they access primary care and community services.

Design: A provincial summit was held to direct research, education, and innovation for primary and community care for SCI.

Setting: Toronto, Ontario, Canada.

Participants: Key stakeholders (N?=?95) including persons with SCI and caregivers, clinicians from primary care, rehabilitation, and specialized care, researchers, advocacy groups, and policy makers.

Methods: A one-day facilitated meeting that included guest speakers, panel discussions and small group discussions was held to generate potential solutions to current issues related to SCI care and to foster collaborative relationships to advance care for SCI. Perspectives on SCI management were shared by primary care, neurosurgery, rehabilitation, and members of the SCI community

Outcome Measures: Discussions were focused on five domains: knowledge translation and dissemination, application of best practices, communication, research, and patient service accessibility.

Results: Summit participants identified issues and prioritized solutions to improve primary and community care including the creation of a network of key stakeholders to enable knowledge creation and dissemination; an online repository of SCI resources, integrated health records, and a clinical network for SCI care; development and implementation of strategies to improve care transitions across sectors; implementation of effective care models and improved access to services; and utilization of empowerment frameworks to support self-management.

Conclusions: This summit identified priorities for further collaborative efforts to advance SCI primary and community care and will inform the development of a provincial SCI strategy aimed at improving the system of care for SCI.     

膀胱肿瘤切除术后尿路感染病原学和危险因素

目的观察膀胱肿瘤切除术后患者尿路感染发生情况与病原学特征,分析诱发尿路感染的危险因素,并提出合理且具备针对性的冲洗对策,为未来膀胱肿瘤切除术后尿路感染的预防提供合理参考。方法回顾性分析连云港市第一人民医院2016年1月-2019年1月接受经尿道膀胱肿瘤切除术治疗的451例膀胱肿瘤患者的临床资料,收集患者病例资料,全部患者术后均定期取尿液标本进行细菌培养,参照相关标准判定患者尿路感染情况,记录患者一般情况,包括一般人口学资料(性别、年龄、体质量、受教育程度等),同时记录患者糖尿病的疾病合并情况,将术后尿路感染可能的危险因素纳入初步分析,Logistic多因素回归分析膀胱肿瘤切除术后发生尿路感染的危险因素。结果451例膀胱肿瘤切除术患者术后第3天尿液中细菌培养阳性例数为80例,阳性率为17.74%,在使用抗菌药物后,患者尿液中细菌培养阳性率逐渐降低,各时点尿液细菌阳性培养率比较,差异有统计学意义(P<0.05);经多因素Logistic回归分析检验证实,高龄、血糖水平控制不佳、术前留置导尿管、多发肿瘤是膀胱肿瘤切除术后尿路感染的危险因素(OR>1,P<0.05);80例术后尿液细菌培养阳性患者共分离出87株菌株,其中革兰阴性菌66株占75.86%,革兰阳性球菌21株占24.14%。结论膀胱肿瘤切除术后患者有较高的尿路感染风险,革兰阴性菌是主要的感染病原菌,年龄、基础疾病、肿瘤位点、术前导尿管留置等是影响因素,这类患者应引起临床高度重视。     

Simeprevir added to peginterferon and ribavirin lessens time with fatigue,depressive symptoms and functional limitations in patients with chronic hepatitis C compared with peginterferon and ribavirin: results from 1161 patients in the QUEST‐1, QUEST‐2 and PROMISE studies

The value of adding simeprevir (SMV) vs placebo (PBO) to peginterferon and ribavirin (PR) for treatment of chronic hepatitis C virus infection was examined using patient‐reported outcomes (PROs); further, concordance of PROs with virology endpoints and adverse events (AEs) was explored. Patients (n = 768 SMV/PR, n = 393 PBO/PR) rated fatigue (FSS), depressive symptoms (CES‐D) and functional impairment (WPAI: Hepatitis C Productivity, Daily Activity and Absenteeism) at baseline and throughout treatment in three randomised, double‐blind trials comparing the addition of SMV or PBO during initial 12 weeks of PR. PR was administered for 48 weeks (PBO group) and 24/48 weeks (SMV group) using a response‐guided therapy (RGT) approach. Mean PRO scores (except Absenteeism) worsened from baseline to Week 4 to the same extent in both groups but reverted after Week 24 for SMV/PR and only after Week 48 for PBO/PR. Accordingly, there was a significantly lower area under the curve (baseline–Week 60, AUC₆₀) and fewer weeks with clinically important worsening of scores in the SMV/PR group at any time point. Incidences of patients with fatigue and anaemia AEs were similar in both groups, but FSS scores showed that clinically important increases in fatigue lasted a mean of 6.9 weeks longer with PBO/PR (P < 0.001). PRO score subgroup analysis indicated better outcomes for patients who met the criteria for RGT or achieved sustained virological response 12 weeks post‐treatment (SVR12); differences in mean PRO scores associated with fibrosis level were only observed with PBO/PR. Greater efficacy of SMV/PR enabled reduced treatment duration and reduced time with PR‐related AEs without adding to AE severity.     

Severe lumbar spinal stenosis combined with Guillain-Barré syndrome: A case report

BACKGROUNDGuillain-Barré syndrome (GBS) is a rare disorder that typically presents with ascending weakness, pain, paraesthesias, and numbness, which mimic the findings in lumbar spinal stenosis. Here, we report a case of severe lumbar spinal stenosis combined with GBS.CASE SUMMARYA 70-year-old man with a history of lumbar spinal stenosis presented to our emergency department with severe lower back pain and lower extremity numbness. Magnetic resonance imaging confirmed the diagnosis of severe lumbar spinal stenosis. However, his symptoms did not improve postoperatively and he developed dysphagia and upper extremity numbness. An electromyogram was performed. Based on his symptoms, physical examination, and electromyogram, he was diagnosed with GBS. After 5 d of intravenous immunoglobulin (0.4 g/kg/d for 5 d) therapy, he gained 4/5 of strength in his upper and lower extremities and denied paraesthesias. He had regained 5/5 of strength in his extremities when he was discharged and had no symptoms during follow-up.CONCLUSIONGBS should be considered in the differential diagnosis of spinal disorder, even though magnetic resonance imaging shows severe lumbar spinal stenosis. This case highlights the importance of a careful diagnosis when a patient has a history of a disease and comes to the hospital with the same or similar symptoms.     

Prostatic Artery Embolization—Anatomic Predictors of Technical Outcomes

PurposeTo determine if cone-beam CT and digital subtraction angiography analysis of pelvic arterial anatomy has predictive value for radiation exposure and technical success of prostatic artery embolization (PAE).Materials and MethodsThis prospective, nonrandomized, single-center study included 104 consecutive patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia. Cone-beam CT was performed in 160/208 (76.9%) hemipelves to determine prostatic artery (PA) origin. Classification of pelvic arterial tortuosity was possible in 73/104 (70.2%) patients. Learning curves of 2 interventionalists who performed 86.5% of PAEs were analyzed.ResultsTortuosity of pelvic arteries was classified as mild in 25 (34.2%) patients median age 64 years, moderate in 40 (54.8%) patients median age 69 years, and severe in 8 (11.0%) patients median age 70 years (mild vs moderate, P = .002; mild vs severe, P = .019); median fluoroscopy times were 24, 36, and 46 minutes (P = .008, P = .023); median contrast volumes were 105, 122.5, and 142 mL (P = .029, P = .064); and bilateral PAE rates were 84.0%, 77.5%, and 62.5% (P = .437), respectively. PA origin from superior vesical artery was most frequent (27.5%) and showed higher dose area product (median 402.4 vs 218 Gy ∙ cm², P = .033) and fluoroscopy time (median 42.5 vs 27 min, P = .01) compared with PA origin from obturator artery, which was least frequent. Interventionalist experience revealed significant impact on procedure times (median 159 vs 130 min, P = .006).ConclusionsTortuosity of pelvic arteries was more frequent in older patients and predicted worse technical outcomes of PAE. PA origin from obturator artery was associated with lower dose area product and fluoroscopy time, especially compared with PA origin from superior vesical artery. Interventionalist experience showed significant influence on technical outcome.     

科研评价导向的改变对中文科技期刊的机遇与挑战

【目的】 值此《中国科技期刊研究》创刊30周年之际,思考科研评价体系的改变给中文科技期刊带来的影响,为中文期刊探寻发展路径。【方法】 结合对中文科技期刊困境的研究,提出应对策略。【结果】 近期国家陆续出台的纠偏评价导向的政策文件,为中文科技期刊既带来了发展机遇,也提出了挑战。【结论】 在重构符合中文科技期刊发展特点的评价体系的基础上,中文科技期刊应明确目标定位,面向国家需求,提升知识服务能力,建立品牌特色。