Time-dependent mortality risk of lung transplantation compared with remaining on the waitlist

Human leukocyte antigen (HLA)-G is a non-classical HLA that inhibits immune responses. Its expression is modified by single nucleotide polymorphisms (SNPs), which are associated with transplant outcomes. Our aim was to investigate the association of donor and recipient HLA-G SNPs with chronic lung allograft dysfunction (CLAD) and mortality after lung transplantation.In this single-centre study, we examined 11 HLA-G SNPs in 345 consecutive recipients and 297 donors of a first bilateral lung transplant. A multivariable Cox proportional hazards model assessed associations of SNPs with death and CLAD. Transbronchial biopsies (TBBx) and bronchoalveolar lavage (BAL) samples were examined using quantitative PCR, ELISA and immunofluorescence.Over a median of 4.75 years, 142 patients (41%) developed CLAD; 170 (49%) died. Multivariable analysis revealed donor SNP +3142 (GG+CG versus CC) was associated with increased mortality (hazard ratio 1.78, 95% CI 1.12–2.84; p=0.015). In contrast, five donor SNPs, -201(CC), -716(TT), -56(CC), G*01:03(AA) and 14 bp INDEL, conferred reduced mortality risk. Specific donor–recipient SNP pairings reduced CLAD risk. Predominantly epithelial HLA-G expression was observed on TBBx without rejection. Soluble HLA-G was present in higher concentrations in the BAL samples of patients who later developed CLAD.Specific donor SNPs were associated with mortality risk after lung transplantation, while certain donor–recipient SNP pairings modulated CLAD risk. TBBx demonstrated predominantly epithelial, and therefore presumably donor-derived, HLA-G expression in keeping with these observations. This study is the first to demonstrate an effect of donor HLA-G SNPs on lung transplantation outcome.

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IgM Enriched Human Immunoglobulins and Rituximab Nullify the Mortality Risk Associated with Early Donor Specific Antibodies After Lung Transplantation

The Journal of Heart and Lung Transplantation ◽

10.1016/j.healun.2016.01.471 ◽

2016 ◽

Vol 35 (4) ◽

pp. S169

Author(s):

F. Ius ◽

W. Sommer ◽

M. Verboom ◽

C. Erdfelder ◽

I. Tudorache ◽

...

Keyword(s):

Lung Transplantation ◽

Mortality Risk ◽

Specific Antibodies ◽

Human Immunoglobulins ◽

Donor Specific Antibodies

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Is Overtriage Associated With Increased Mortality? Insights From a Simulation Model of Mass Casualty Trauma Care

Disaster Medicine and Public Health Preparedness ◽

10.1097/dmp.0b013e31814cfa54 ◽

2007 ◽

Vol 1 (S1) ◽

pp. S14-S24 ◽

Cited By ~ 32

Author(s):

Nathaniel Hupert ◽

Eric Hollingsworth ◽

Wei Xiong

Keyword(s):

Simulation Model ◽

Discrete Event ◽

Trauma System ◽

Mass Casualty ◽

Time Dependent ◽

Patient Treatment ◽

System Response ◽

Critical Patients ◽

Injured Patients ◽

Dependent Mortality

ABSTRACTPurpose: To examine the relationship between overtriage and critical mortality after a mass casualty incident (MCI) using a simulation model of trauma system response.Methods: We created a discrete event simulation model of trauma system management of MCIs involving individual patient triage and treatment. Model variables include triage performance, treatment capability, treatment time, and time-dependent mortality of critically injured patients. We model triage as a variable selection process applied to a hypothetical population of critically and noncritically injured patients. Treatment capability is represented by staffed emergency department trauma bays with associated staffed operating rooms that are recycled after each use. We estimated critical and noncritical patient treatment times and time-dependent mortality rates from the trauma literature.Results: In this simulation model, overtriage, the proportion of noncritical patients among all of those labeled as critical, has a positive, negative, or variable association with critical mortality depending on its etiology (ie, related to changes in triage sensitivity or to changes in the prevalence and total number of critical patients). In all of the modeled scenarios, the ratio of critical patients to treatment capability has a greater impact on critical mortality than overtriage level or time-dependent mortality assumption.Conclusions: Increasing overtriage may have positive, negative, or mixed effects on critical mortality in this trauma system simulation model. These results, which contrast with prior analyses describing a positive linear relationship between overtriage and mortality, highlight the need for alternative metrics to describe trauma system response after MCIs. We explore using the relative number of critical patients to available and staffed treatment units, or the critical surge to capability ratio, which exhibits a consistent and nonlinear association with critical mortality in this model. (Disaster Med Public Health Preparedness. 2007;1(Suppl 1):S14–S24)

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