The American Association for Thoracic Surgery (AATS) 2022 Expert Consensus Document: The use of mechanical circulatory support in lung transplantation

ObjectiveThe use of mechanical circulatory support (MCS) in lung transplantation has been steadily increasing over the prior decade, with evolving strategies for incorporating support in the preoperative, intraoperative, and postoperative settings. There is significant practice variability in the use of these techniques, however, and relatively limited data to help establish institutional protocols. The objective of the AATS Clinical Practice Standards Committee (CPSC) expert panel was to review the existing literature and establish recommendations about the use of MCS before, during, and after lung transplantation.MethodsThe AATS CPSC assembled an expert panel of 16 lung transplantation physicians who developed a consensus document of recommendations. The panel was broken into subgroups focused on preoperative, intraoperative, and postoperative support, and each subgroup performed a focused literature review. These subgroups formulated recommendation statements for each subtopic, which were evaluated by the entire group. The statements were then developed via discussion among the panel and refined until consensus was achieved on each statement.ResultsThe expert panel achieved consensus on 36 recommendations for how and when to use MCS in lung transplantation. These recommendations included the use of veno-venous extracorporeal membrane oxygenation (ECMO) as a bridging strategy in the preoperative setting, a preference for central veno-arterial ECMO over traditional cardiopulmonary bypass during the transplantation procedure, and the benefit of supporting selected patients with MCS postoperatively.ConclusionsAchieving optimal results in lung transplantation requires the use of a wide range of strategies. MCS provides an important mechanism for helping these critically ill patients through the peritransplantation period. Despite the complex nature of the decision making process in the treatment of these patients, the expert panel was able to achieve consensus on 36 recommendations. These recommendations should provide guidance for professionals involved in the care of end-stage lung disease patients considered for transplantation.     

HLA-B evolutionary divergence is associated with outcomes after SARS-CoV-2 infection

We examined the correlation between class I HLA evolutionary divergence (HED), a surrogate for the capacity to present different peptides, and the outcomes of 234 adult inpatients with confirmed SARS-CoV-2 infection. Genomic DNA was extracted from peripheral blood and genotyped by next-generation sequencing (NGS). HED scores for HLA class I (HLA-A, -B, and -C) genotypes were calculated using Grantham’s distance. Higher HED scores for HLA-B, but not HLA-A or -C, are significantly associated with a decreased probability of poor outcomes including ICU admission, mechanical ventilation, and death (OR = 0.93; P = 0.04) in the univariate analysis. In the multivariate analysis, increased HLA-B HED score, younger age, and no comorbidity were independently associated with favorable outcomes (P = 0.02, P = 0.01, and P = 0.05, respectively). This finding is consistent with the notion that broader peptide repertoires presented by class I HLA may be beneficial in infection control.     

Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials

Background

The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.

CD8+ T cells induced by adenovirus-vectored vaccine are capable of preventing establishment of latent murine γ-herpesvirus 68 infection

CD8+ T cells are known to control infections, but their role in preventing latent infection from establishing has not been thoroughly investigated.We hypothesized that a potent CD8+ T cell response patrolling the mucosal viral entry points could kill the first infected cells and thereby abrogate the infection before latency is established.To investigate this, replication deficient adenovirus serotype 5 vectors encoding murine γ-herpesvirus-68 CD8+ T cell epitopes linked to the T cell adjuvant Invariant chain, were developed. We show that intranasal vaccination of mice reduces the risk of establishment of latent infection from multiple intranasal ID50 challenges with murine γ-herpesvirus-68 by 81% per exposure at 14 days post vaccination. Protection waned over time, but immune responses were extended by heterologous prime-boost vaccination applied simultaneously intramuscularly and intranasally, and animals vaccinated 66 days prior to challenge showed a strong trend of long-term protection.Our data provides evidence that CD8+ T cells are able to protect against establishment of latent infection. Although the protective efficacy is difficult to maintain over time, this proof-of-concept study suggests a role for a CD8+ T cell arm in future vaccine strategies against latent human viral infections caused by pathogens such as HIV and multiple herpes virus.     

Evaluating Resource Utilization for In-Person and Virtual Joint Classes in Total Joint Arthroplasty: An Analysis of Attendance Patterns at a Large Metropolitan Health System

BackgroundProvider-run “joint classes” educate total joint arthroplasty (TJA) patients on how to best prepare for surgery and maximize recovery. There is no research on potential healthcare inequities in the context of joint classes or on the impact of the recent shift toward telehealth due to coronavirus disease 2019 (COVID-19). Using data from a large metropolitan health system, we aimed to (1) identify demographic patterns in prepandemic joint class attendance and (2) understand the impact of telehealth on attendance.MethodsWe included data on 3,090 TJA patients from three centers, each with a separately operated joint class. Attendance patterns were assessed prepandemic and after the resumption of elective surgeries when classes transitioned to telehealth. Statistical testing included standardized differences (SD > 0.1 indicates significance) and a multivariate linear regression.ResultsThe in-person and telehealth attendance rates were 69.9% and 69.2%, respectively. Joint class attendance was significantly higher for non-White, Hispanic, non-English primary language, Medicaid, and Medicare patients (all SD > 0.1). Age was a determinant of attendance for telehealth (SD > 0.1) but not for in-person (SD = 0.04). Contrastingly, physical distance from hospital was significant for in-person (SD > 0.1) but not for telehealth (SD = 0.06). On a multivariate analysis, distance from hospital (P < .05) and telehealth (P < .0001) were predictors of failed class attendance.ConclusionThis work highlights the relative importance of joint classes in specific subgroups of patients. Although telehealth attendance was lower, telehealth alleviated barriers to access related to physical distance but increased barriers for older patients. These results can guide providers on preoperative education and the implementation of telehealth.     

翻转课堂联合CBL教学在中医辨证见习中的应用

目的探讨翻转课堂联合CBL教学法应用于中医学辨证见习教学中的效果。方法将60名学生随机分为两组,每组30名,学生均来自于中南大学湘雅医学院临床医学专业2016级五年制本科。翻转课堂联合CBL教学法被应用于试验组,传统教学模式被应用于对照组,教学效果评价采用理论知识考核与学生满意度调查的双向评价模式。结果试验组的见习内容知识考核卷面成绩和满意度调查得分均高于对照组,差异均有统计学意义(P <0.05)。结论在中医学辨证见习课中,翻转课堂联合CBL教学法的教学效果优于传统教学模式。     

微型种植体支抗与口外弓支抗对安氏Ⅱ类1分类错牙合畸形患者的矫治效果对比分析

目的:分析比较微型种植体支抗与口外弓支抗对安氏Ⅱ类1分类错牙合畸形患者的矫治效果。方法:收集笔者医院95例安氏Ⅱ类1分类错牙合畸形患者临床资料,根据其治疗方法将之分为口外弓支抗(MIA组)46例和微型种植体支抗组(HGA组)49例,比较其矫正前后头影测量结果和模型测量结果,矫治时间和不良反应。结果:治疗后,MIA组牙合平面与SN平面夹角(OP-SN)、上颌中切牙牙长轴与SN平面夹角(U1-SN)、上唇突度、下唇突度、上唇最凸点至E线垂直距离(E line-UL)、下唇最凸点至E线垂直距离(E line-LL)、覆牙合(OB)、覆盖(OJ)均小于HGA组(P<0.05),矫治时间短于HGA组(P<0.05),总不良反应发生率与HGA组差异无统计学意义(P>0.05)。结论:对比HGA,MIA对安氏Ⅱ类1分类错牙合畸形患者的矫治效果更佳,且能够缩短矫治时间。     

Isolation and characterization of new human carrier peptides from two important vaccine immunogens

In the preparation of glycoconjugate vaccines in clinical practice, two highly immunogenic carrier proteins, CRM₁₉₇ and tetanus toxoid (TT), are predominantly conjugated with the capsular polysaccharides (CPSs) of bacterial pathogens. In addition, TT has long been used as an effective vaccine to prevent tetanus. While these carrier proteins play an important role in immunogenicity and vaccine design alike, their defined human major histocompatibility complex class II (MHCII) T cell epitopes are inadequately characterized. In this current work, we use mass spectrometry to identify the peptides from these carrier proteins that are naturally processed and presented by human B cells via MHCII pathway. The MHCII-presented peptides are screened for their T cell stimulation using primary CD4+ T cells from four healthy adult donors. These combined methods reveal a subset of eleven CD4+ T cell epitopes that proliferate and stimulate human T cells with diverse MHCII allelic repertoire. Six of these peptides stand out as potential immunodominant epitopes by responding in three or more donors. Additionally, we provide evidence of these natural epitopes eliciting more significant T cell responses in donors than previously published TT peptides selected from T cell epitope screening. This study serves toward understanding carrier protein immune responses and thus enables the use of these peptides in developing novel knowledge-based vaccines to combat persisting problems in glycoconjugate vaccine design.