Role of macrophages in peripheral nerve injury and repair

Resident and inflammatory macrophages are essential effectors of the innate immune system. These cells provide innate immune defenses and regulate tissue and organ homeostasis. In addition to their roles in diseases such as cancer, obesity and osteoarthritis, they play vital roles in tissue repair and disease rehabilitation. Macrophages and other inflammatory cells are recruited to tissue injury sites where they promote changes in the microenvironment. Among the inflammatory cell types, only macrophages have both pro-inflammatory(M1) and anti-inflammatory(M2) actions, and M2 macrophages have four subtypes. The co-action of M1 and M2 subtypes can create a favorable microenvironment, releasing cytokines for damaged tissue repair. In this review, we discuss the activation of macrophages and their roles in severe peripheral nerve injury. We also describe the therapeutic potential of macrophages in nerve tissue engineering treatment and highlight approaches for enhancing M2 cell-mediated nerve repair and regeneration.     

中华传统文化视角下疾病终末期患者尊严模型解析

目的:解析加拿大Chochinov疾病终末期患者尊严模型在中华文化情境下的适用性,并基于此对模型进行调适。方法:采用内容分析法,按照选定分析范围、抽取样本、确定分析单位和分析框架、资料分析四步完成。首先检索中、英文数据库中以中华文化背景下临终尊严为主题的文献,然后以尊严模型为框架对文献内容进行编码、归纳和分析。结果:尊严模型包含的多数主题符合我国临终患者的认知,如身体功能、医疗不确定性、死亡焦虑、隐私界限、照护要旨、他人负担、后事担忧等。但也出现了矛盾的主题,如忍受痛苦、自主性等,以及新的主题,包括家庭支持、病耻感和财务担忧。结论:加拿大版疾病终末期患者尊严模型并不完全符合中国文化,调适后的尊严模型更具我国文化特色,但仍需实证研究对模型进行验证。     

Peripheral whole blood FOXP3 TSDR methylation: a potential marker in severity assessment of autoimmune diseases and chronic infections

Immune dysregulation is a cardinal feature of autoimmune diseases and chronic microbial infections. In particular, regulatory T cells are downregulated in autoimmune diseases while upregulated in chronic microbial infections. FOXP3 is the master regulator of Treg development. Treg-specific demethylated region (TSDR) is a highly conserved locus on the FOXP3 gene that is fully demethylated in natural Tregs but methylated in effector T cells. In our study, we used high resolution melt-polymerase chain reaction (HRM-PCR) to determine the FOXP3 TSDR methylation status in autoimmune diseases and chronic microbial infections. We found that FOXP3 TSDR to have the highest mean melting temperature (highly methylated) in active SLE patients compared to all the other groups (p?<?0.001). The psoriasis group also had a significantly high mean melting temperature (78.62?±?0.20) when compared with the inactive SLE group (78.49?±?0.29, p?<?0.05) and control group (78.44?±?0.25, p?<?0.01). There was no significant difference in melting temperature between inactive SLE and healthy controls. Disease activity in SLE was directly associated with methylation of the FOXP3 TSDR. On the other hand, patients with chronic microbial infections had significantly lower FOXP3 TSDR mean melting temperature (demethylated) when compared with healthy controls (78.28?±?0.21 vs 78.44?±?0.25, p?<?0.05). Our results suggest that the use of HRM-PCR to detect FOXP3 TSDR methylation status is a reliable and easy method to predict natural regulatory T cell levels in peripheral blood in different disease conditions. Determining FOXP3 TSDR methylation status can be a useful tool in diagnosis, and monitoring the severity of autoimmune diseases and chronic microbial infections.     

Mortality,length of stay and costs associated with acute graft-versus-host disease during hospitalization for allogeneic hematopoietic stem cell transplantation

Objective: Acute graft-versus-host disease (aGVHD) is a common and life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The extent to which aGVHD increases inpatient costs associated with allo-HSCT has not been thoroughly evaluated. In this analysis, mortality, hospital length of stay (LOS) and costs associated with aGVHD during allo-HSCT admissions are evaluated.

Methods: This is a retrospective analysis of discharge records from the National Inpatient Sample database for patients receiving allo-HSCT between 1 January 2009 and 31 December 2013. Allo-HSCT discharges with an aGVHD diagnosis were included in the aGVHD group and those without any graft-versus-host disease (GVHD) diagnosis comprised the non-GVHD group. Mortality, LOS and costs were compared between the two groups, as well as within subgroups, including age (<18 vs. ≥18 years) and survival status (alive vs. deceased) at discharge.

Results: Overall, mortality (16.2% vs. 5.3%; p?<?.01), median hospital LOS (42.0 vs. 26.0 days; p?<?.01) and median total costs ($173,144 vs. $98,982; p?<?.01) were significantly increased in patients with aGVHD versus those without GVHD during hospitalizations for allo-HSCT, irrespective of age group. Patients with aGVHD who were <18 years of age had a lower mortality rate but greater hospital LOS and total costs versus patients aged ≥18 years. Patients who died during allo-HSCT hospitalization had longer LOS and incurred greater costs than those who survived in both the aGVHD and non-GVHD groups.

Conclusion: Occurrence of aGVHD during allo-HSCT admissions resulted in a tripling of the mortality rate and a near doubling of hospital LOS and total costs. In addition, death during allo-HSCT hospitalizations was associated with greater healthcare utilization and costs. Effectively mitigating aGVHD may improve survival and substantially reduce hospital LOS and costs for allo-HSCT.     

Cefoperazone-sulbactam and risk of coagulation disorders or bleeding: a retrospective cohort study

ABSTRACT

Objectives: Limited evidence has suggested that cefoperazone-sulbactam causes coagulation disorders and bleeding.

Methods: The authors conducted a retrospective study to compare patients receiving cefoperazone-sulbactam versus those treated with cefoperazone-tazobactam or ceftazidime. Propensity-score matching was used to explore whether treatment with cefoperazone-sulbactam increased the risk of prothrombin time (PT) prolongation, coagulation disorders, and bleeding, or decreased platelets (PLT).

Results: The cohort included 23,242 patients. Among patients receiving cefoperazone-sulbactam, the risk of PT prolongation, coagulation disorders, decreased PLT, and bleeding was 5.3%, 9.2%, 15.7%, and 4.2%, respectively. Propensity-score matching analyses suggested that cefoperazone-sulbactam increased the risk of PT prolongation (aOR 2.26, 95% CI 1.61–3.18), coagulation disorders (aOR 1.81, 95% CI 1.43–2.30), and decreased PLT (aOR 1.46, 95% CI 1.25–1.72), but not increase bleeding (aOR 1.05, 95% CI 0.79–1.40) compared with ceftazidime. Patients receiving cefoperazone-sulbactam had higher risk of PT prolongation (aOR 1.53, 95% CI 1.11–2.10), coagulation disorders (aOR 1.53, 95% CI 1.21–1.95), but not decreased PLT (aOR 0.93, 95% CI 0.81–1.07) or bleeding (aOR 1.11, 95% CI 0.87–1.42), compared with those receiving cefoperazone-tazobactam.

Conclusion: Cefoperazone-sulbactam may be associated with a higher risk of PT prolongation and coagulation disorders compared with cefoperazone-tazobactam and ceftazidime.