Pregnancy induced TMA in severe preeclampsia results from complement-mediated thromboinflammation

Preeclampsia is a multifactorial vascular disease unique to human pregnancy. While genetic and antiangiogenic factors are important contributors to preeclampsia susceptibility, recent studies have shown that dysregulation and/or over-activation of the complement system has an integral role in disease etiology. Furthermore, the role of the coagulation cascade may be underappreciated in the development of the disease. Traditionally, for research purposes, the pool of preeclampsia cases has been divided into non-severe and severe disease depending on the onset and severity of the symptoms. However, of particular interest are a small but important minority of cases that present with symptoms likening to those of hemolysis, elevated liver enzymes and low platelets syndrome, atypical hemolytic uremic syndrome, or thrombotic thrombocytopenic purpura, all thrombotic microangiopathy (TMA) diseases, with the hallmark mechanisms of endothelial dysfunction and aberrant activation of complement and coagulation cascades. We therefore propose a third class, severe TMA-like preeclampsia to be included in the categorization of preeclampsia patients. Identifying these patients would target research, diagnostic differentiation, and novel treatment options to the subclass of patients with life-threatening disease that are most likely to benefit from next-generation drug development.     

The personal limitations checklist: human factors insights from air accidents to reduce intraoperative harm

High Reliability Organisations (HRO), including healthcare and aviation, have a common focus on risk management. The human element is a ‘weak link’ which may result in accidents or adverse events taking place. Surgeons and other healthcare professionals can learn from aviation's rigorous approach to the role of human factors (HF) in such events, and how we can minimise them. Air Accident Investigation Branch (AAIB) reports show that fatal accidents are frequently caused by pilots flying outside their own personal limits, those of the aircraft or environment. Similarly, patient morbidity or mortality may occur if surgeons work outside personal their capability, with poor procedure selection and patient optimisation, or with a team or theatre environment not suited to the procedure. We introduce the personal limitations checklist – a tool adapted from aviation that allows surgeons to define their limits in advance of any decision to operate, and develop critical self-reflection. It also allows management of patient expectations, shared decision making, and flattening of team hierarchy. The minimum skills, patient characteristics, team and theatre resources for any given procedure to proceed are defined. If the surgeon is ‘out of limits’, redressing these factors, seeking additional assistance, or thorough patient consenting may be required for the safe conduct of the procedure. We explore external pressures that could cause a surgeon to exceed both personal and organisational limits.     

Primary vaccination in adult patients after allogeneic hematopoietic stem cell transplantation – A single center retrospective efficacy analysis

Allogeneic hematopoietic stem cell transplantation (alloHSCT) results in a loss of humoral immunity and subsequent risk for severe infections. Thus, re-vaccination is required but may fail due to incomplete immune reconstitution. We retrospectively analyzed predictors of immune response to primary vaccination applied according to the EBMT (European Blood and Marrow Transplantation Group) recommendations. Serologic response to vaccination against diphtheria (D), tetanus (T), Bordetella pertussis (aP) and Haemophilus influenzae (Hib) (administrated as combined DTaP-Hib-IPV vaccination) was studied in 84 alloHSCT patients transplanted between 2008 and 2015 (age at alloHSCT: 18.6–70.6 years). All patients with a relapse-free survival of ≥9 months, at least 3 consecutive vaccinations and absence of intravenous immunoglobulin administration within 3 months before and after vaccination met the primary inclusion criteria. Additionally, immunological response to a pneumococcal conjugate vaccine was analyzed in a subgroup of 67 patients. Patients’ characteristics at the time of first vaccination were recorded. Responses were measured as vaccine-specific antibody titers. Regarding DTaP-Hib-IPV vaccination, 89.3% (n = 75) of all patients achieved protective titers to at least 3 of the 4 vaccine components and were thus considered responders. 10.7% (n = 9) of the patients were classified as non-responders with positive immune response to less than 3 components. Highest response was observed for Hib (97.4%), tetanus (95.2%) and pneumococcal vaccination (83.6%) while only 68.3% responded to vaccination against Bordetella pertussis. Significant risk factors for failure of vaccination response included low B cell counts (p < 0.001; cut-off: 0.05 B cells/nl) and low IgG levels (p = 0.026; mean IgG of responders 816 mg/dl vs. 475 mg/dl of non-responders). Further, a trend was observed that prior cGvHD impairs vaccination response as 88.9% of the non-responders but only 54.7% of the responders had prior cGvHD (p = 0.073). The results demonstrate, that the currently proposed vaccination strategy leads to seroprotection in the majority of alloHSCT patients.     

Neuromodulation in Psychiatric disorders: Experimental and Clinical evidence for reward and motivation network Deep Brain Stimulation: Focus on the medial forebrain bundle

Deep brain stimulation (DBS) in psychiatric illnesses has been clinically tested over the past 20 years. The clinical application of DBS to the superolateral branch of the medial forebrain bundle in treatment‐resistant depressed patients—one of several targets under investigation—has shown to be promising in a number of uncontrolled open label trials. However, there are remain numerous questions that need to be investigated to understand and optimize the clinical use of DBS in depression, including, for example, the relationship between the symptoms, the biological substrates/projections and the stimulation itself. In the context of precision and customized medicine, the current paper focuses on clinical and experimental research of medial forebrain bundle DBS in depression or in animal models of depression, demonstrating how clinical and scientific progress can work in tandem to test the therapeutic value and investigate the mechanisms of this experimental treatment. As one of the hypotheses is that depression engenders changes in the reward and motivational networks, the review looks at how stimulation of the medial forebrain bundle impacts the dopaminergic system.     

结核性脑膜炎临床诊断评分体系的建立及评价研究

背景 结核性脑膜炎（TM）是临床常见的中枢性感染的一种，其起病较慢，症状不典型，病原学诊断困难，误诊率高。目前有效的TM诊断工具较少。利用常见的临床症状、检查指标等建立诊断评分系体可提高诊断准确率，减少误诊。 目的 建立TM临床诊断评分体系（TMCDS），并对其应用价值进行初步评价。 方法 选取2011年11月至2021年9月在柳州市人民医院感染病科住院并诊断为脑膜炎的患者187例为研究对象，采用SPSS 21.0统计软件将患者随机分成建模组（147例）和验模组（40例）。根据是否为TM将建模组分为非TM亚组（76例）和TM亚组（71例）。收集患者的一般资料，主要包括性别、年龄、临床症状（发热、头痛、意识障碍、颈抵抗），实验室及影像学检查结果，包括人类免疫缺陷病毒（HIV）感染情况、CD4+ T淋巴细胞计数、C反应蛋白、颅内压、脑脊液常规生化检查（糖、氯、蛋白、细胞数）。建模组采用多因素Logistic回归分析探讨TM的影响因素；根据每个因素的β值所占比重设立相应分值，建立TMCDS；采用受试者工作特征曲线（ROC曲线）分析TMCDS诊断TM的价值。 结果 两亚组头痛、HIV感染、CD4+ T淋巴细胞计数<200/μl、C反应蛋白升高、颅内压>200 mm H2O（1 mm H2O=0.009 8 kPa）、脑脊液糖降低、脑脊液氯降低、脑脊液蛋白升高、脑脊液单核细胞升高情况比较，差异有统计学意义（P<0.05）。多因素Logistic回归分析结果显示，头痛、CD4+ T淋巴细胞<200/μl、C反应蛋白升高、脑脊液糖降低、脑脊液蛋白升高均是TM的影响因素（P<0.05）。将以上5个影响因素同时结合临床经验纳入脑脊液氯、脑脊液细胞数再次进行多因素Logistic回归分析，结果显示，头痛、CD4+ T淋巴细胞<200/μl、C反应蛋白升高、脑脊液糖降低、脑脊液蛋白升高均是TM的影响因素（P<0.05）。根据上述7个因素β值建立评分系统，将脑脊液氯降低β值设定为1分，其他因素β值与其的倍数即为该因素所对应的分值，因2个影响因素评分为负值，为方便临床，每个因素对应分值增加2.5分，最终建立TMCDS。TMCDS诊断建模组TM的ROC曲线下面积（AUC）为0.807〔95%CI（0.735，0.879），标准误=0.037，P<0.001〕，最佳诊断界值为21.50分。TMCDS诊断验模组TM的AUC为0.766〔95%CI（0.610，0.921），标准误=0.079，P=0.004〕，灵敏度为0.789，特异度为0.667。 结论 通过7个变量建立的TMCDS简单易行，对于早期TM具有较高的临床诊断价值。     

2型糖尿病患者扫描式葡萄糖监测系统指标与尿白蛋白/肌酐比值的相关性研究

背景 随着血糖监测技术的发展，近些年来人们开始使用扫描式葡萄糖监测系统（FGMS）"全景式"地观察2型糖尿病（T2DM）患者的血糖水平，明确FGMS指标与T2DM并发症之间的关系有助于提高其临床应用价值，但目前相关研究较少。 目的 探究佩戴FGMS的T2DM患者葡萄糖在目标范围内时间（TIR）等指标与尿白蛋白/肌酐比值（UACR）的相关性。 方法 选取2019年1月至2021年10月于北京大学人民医院老年科就诊并佩戴FGMS的T2DM患者79例，以尿液检查中UACR是否<30 mg/g将患者分为无白蛋白尿组（n=50）和白蛋白尿组（n=29）。比较两组患者的临床特征、实验室检查指标及FGMS指标等。采用Pearson相关、Spearman秩相关分析探讨TIR、高血糖时间（TAR）与糖化血红蛋白（HbA1c）的相关性。分别采用Pearson相关、Spearman秩相关、偏相关分析探讨FGMS指标与lnUACR的相关性。使用多因素Logistic回归分析探究T2DM患者发生白蛋白尿的影响因素，采用受试者工作特征（ROC）曲线评估TIR对白蛋白尿的预测价值。 结果 白蛋白尿组T2DM病程长于无白蛋白尿组，三酰甘油（TG）、HbA1c、平均血糖（MBG）、TAR、平均血糖标准差（SDBG）、最大葡萄糖波动幅度（LAGE）、平均葡萄糖波动幅度（MAGE）、连续每隔2 h血糖净作用（CONGA2）高于无白蛋白尿组，TIR低于无白蛋白尿组（P<0.05）。Pearson相关、Spearman秩相关分析结果显示，TIR与HbA1c呈负相关（P<0.001），TAR与HbA1c呈正相关（P<0.001）。Pearson相关、Spearman秩相关、偏相关分析结果均表明，TIR与lnUACR呈负相关（P<0.001），MBG、TAR、SDBG、LAGE、MAGE、CONGA2与lnUACR呈正相关（P<0.001）。多因素Logistic回归分析结果显示，TIR>70%〔OR=0.038，95%CI（0.003，0.467）〕是T2DM患者出现白蛋白尿的保护因素（P<0.05），TAR升高〔OR=1.046，95%CI（1.000，1.094）〕是T2DM患者出现白蛋白尿的危险因素（P<0.05）。TIR预测T2DM患者出现白蛋白尿的ROC曲线下面积（AUC）为0.784〔95%CI（0.674，0.894）〕（P=0.003），灵敏度为78%，特异度为83%，最佳切点为69.71%。 结论 在FGMS指标中，TIR>70%是T2DM患者出现白蛋白尿的保护因素，TAR升高是T2DM患者出现白蛋白尿的危险因素。同时，SDBG、LAGE、MAGE、CONGA2等多种反映血糖波动的指标也与UACR密切相关。对TIR水平较低及TAR、SDBG、LAGE、MAGE、CONGA2水平较高的T2DM患者进行FGMS筛查有助于早期识别及预防白蛋白尿的发生、发展。     

发达国家医学生器官捐献意愿研究现状的范围综述

目的了解发达国家医学生器官捐献意愿研究的目的、结果、障碍因素和解决对策。 方法以主题词和自由词联合的方式对PubMed、Web of Science、Ovid MEDLINE、Ovid EMBASE(Excerpta Medica)、EBSCOhost Complete和Cochrane Library等已发表文献数据库，以及灰色文献数据库York Centre for Reviews and Dissemination、Open Grey、ProQuest Dissertation and Theses和Mednar进行系统、全面地检索，并采用Arksey和O′Malley提出的范围综述框架进行文献资料整合。 结果共纳入17项发达国家医学生器官捐献意愿研究。研究背景主要为医学生未来对于公众器官捐献有着重要影响。研究结果表明，大多数医学生器官捐献意愿性良好，但不同亚组的研究结果不一；其最主要的障碍因素为医学生器官捐献相关知识的缺乏；解决对策主要为施予系统化、结构化和可评价的教育课程。 结论21世纪以来发达国家医学生器官捐献意愿研究方兴未艾，其研究的多层面、多角度以及揭示的问题、寻求的解决对策，可对我国现阶段医学生器官捐献的研究提供一定参考。     

Applications of geospatial analyses in health research among homeless people: A systematic scoping review of available evidence

BackgroundUnequal housing access resulted in more than 150 million homeless people worldwide, with millions more expected to be added every year due to the ongoing climate-related crises. Homeless population has a counterproductive effect on the social, psychological integration efforts by the community and exposure to other severe health-related issues. Geographic Information Systems (GIS) have long been applied in urban planning and policy, housing and homelessness, and health-related research.MethodsWe used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method to systematically review 24 articles collected from multiple databases (n = 10) that focused on health-related issues among homeless people and used geospatial analysis techniques in their research.ResultsOur findings indicated a geographic clustering of case study locations– 26 out of the 31 case study sites are from the USA and Canada. Studies used spatial analysis techniques to identify hotspots, clusters and patterns of patient location and population distribution. Studies also reported relationships among the location of homeless shelters and substance use, discarded needles, different infectious and non-infectious disease clusters.ConclusionMost studies were restricted in analyzing and visualizing the patterns and disease clusters; however, geospatial analyses techniques are useful and offer diverse techniques for a more sophisticated understanding of the spatial characteristics of the health issues among homeless people. Better integration of GIS in health research among the homeless would help formulate sensible policies to counter health inequities among this vulnerable population group.     

Medical error disclosure in the Italian healthcare context: A delicate balance between ethical obligations and the principle of non-self-incrimination

Surprisingly, Italian legal doctrine and jurisprudence never systematically address the medical error disclosure issue. The topic of medical error communication represents a non-negligible profile of interest, relating to the possible detrimental effects on doctors who accuse themselves of conduct that does not comply with the lex artis. The effects of error disclosure on the effectiveness of insurance guarantees in civil and administrative liability are particularly relevant, as are the implications for ethical liability. Although the burden of reporting an error falls within the wide range of informative duties doctors hold, it still seems far from having found a factual statement in clinical practice, especially in Italy. This applies whether the error has a marginal or significant impact on the patient’s health. The reasons lay in a very contradictory legal framework. Doctors tend with increasing ease not to comply with their information obligation – especially in cases where fulfilling this duty means admitting a personal, professional error – to preserve the integrity of their professional images. This article aims to offer a brief overview of that topic in the context of Italian healthcare.