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In previous studies, lower functional status measured by Karnofsky Performance Status (KPS) correlated with worse survival after redo lung transplant. We hypothesize that combining reduced functional status and time from primary lung transplant will correlate with the etiology of lung allograft failure after primary lung transplant and more accurately predict survival after redo lung transplant.This retrospective study was approved by University of Minnesota Institutional Review Board. From the Scientific Registry of Transplant Recipients (SRTR) database, 739 patients underwent redo lung transplant (01/01/2005-8/30/2019). Pre-lung transplant characteristics, KPS, time between primary and redo lung transplant, outcomes, overall survival were evaluated. Paired comparisons were used to compare pre-transplant variables. A Cox regression model was fit to examine re-transplant survival. Due to non-proportional hazards, time between transplants was split into1-yearAfter KPS grouping (10-40%, 50-70%, 80-100%), KPS 10-40% were less likely to be discharged after primary transplant and more likely required mechanical ventilation or extracorporeal membrane oxygenation (ECMO) bridging (P0.001). Redo lung transplant survival was worse in the KPS 10-40% group who more likely underwent lung transplant1 year after primary lung transplant. Mortality was significantly higher for patients who underwent redo lung transplant within one year of primary transplant when KPS was 10-40% (P0.001). These patients were more likely to require redo lung transplant due to primary graft failure or acute cellular rejection.Functional status and time from primary lung transplant are strong predictors of outcome after redo lung transplant. We categorized redo lung transplant recipients in two distinct groups. One group has early allograft failure and poor functional status with a very poor prognosis after redo lung transplant. The other group has chronic allograft failure and overall better functional status with relatively better survival after redo lung transplant. Salvage redo lung transplant for primary allograft failure or acute rejection is associated with low one year survival.

Prior coronary artery bypass grafting (CABG) has been considered a relative contraindication to lung transplantation due to the atherosclerotic disease burden and technical challenges. We hypothesized that lung transplant recipients with prior CABG have increased mortality compared to recipients without prior CABG. Further, the causes of death are different for lung transplant recipients with prior CABG vs without CABG. The Scientific Registry of Transplant Recipients database was queried to define the survival and causes of death of lung transplant recipients with or without CABG during the Lung Allocation Score era from May 5, 2005 to December 31, 2015. The primary end-points were all-cause mortality at 1 year and 5 years, as well as mortality due to major causes of death. This retrospective study cohort included a total of 13,064 lung transplant recipients, of whom 319 patients had previously undergone CABG, representing 2.4% of all transplants. Patients without prior CABG were more likely to have undergone bilateral lung transplantation compared to those with prior CABG (61.2 % vs 15.7%, P0.001). Among patients with prior CABG, single right lung transplant was most common. Overall patient survival at 1 year was 76.8% for lung transplant recipients with prior CABG and 85.4% for patients without prior CABG. Freedom from death due to graft failure at 1 and 5 years in patients with a prior CABG was 93.1% and 76.2% respectively, cardiac and/or cerebrovascular disease 96.2% and 88.5% respectively, and hemorrhage 97.9% and 97.5% respectively. In a multivariate Cox regression model utilizing time-dependent coefficients for recipient age, prior CABG, among several other risk factors, was associated with increased mortality within 1 year. Prior CABG is associated with short- and long-term mortality in lung transplant recipients with history of CABG despite the majority of these patients undergoing single lung transplantation vs bilateral lung transplantation. Graft failure and/or pulmonary causes are the most common cause of death regardless of whether or not the lung transplant recipient had prior CABG, but patients with prior CABG are at increased risk of death due to graft failure, cardiac or cerebrovascular disease, and hemorrhage.

Objective The purpose of this study was to determine the relationship between blood product transfusion, with or without recombinant human activated factor VIIa, and survival after lung transplantation. Design Retrospective analysis of a single center with follow-up out to 6 years post-transplantation. Setting Single-center academic lung transplantation program. Participants The study comprised 265 adult patients who underwent single or bilateral sequential lung transplantation from March 2011 to June 2017. Interventions Overall survival using Kaplan-Meier curves was compared among the following 3 cohorts: those not transfused with blood products, those transfused with blood products, and those given blood products and recombinant human activated factor VIIa. Cox proportional hazards regression was used to estimate hazard ratios (HRs), confidence intervals (CIs), and p values. Measurements and Main Results Seventy-eight patients received no packed red blood cell transfusions, 149 received packed red blood cell transfusions, and 38 received both packed red blood cell transfusions and recombinant human activated factor VII. Packed red blood cell transfusion was associated with an increased risk of mortality that did not reach statistical significance (HR 2.168, CI 0.978-4.805; p = 0.057). Additional packed red blood cells beyond 15 U were associated with worsened survival (HR 1.363, CI 1.137-1.633; p = 0.001), but recombinant human activated factor VIIa did not increase the risk of mortality. Conclusion Blood product transfusion during and after lung transplantation is associated with decreased survival, especially with large-volume transfusions. Survival is not worse with recombinant human activated factor VIIa administration, but additional studies are needed to determine whether recombinant human activated factor VIIa administration reduces the need for blood product transfusions.

Purpose Survival is worse after redo lung transplant (LTx) compared to primary LTx. We hypothesize that functional status and time since primary LTx predict survival after redo LTx. Methods From the Scientific Registry of Transplant Recipients (SRTR) database, 681 adult and pediatric patients underwent primary LTx before redo LTx from 01/01/2005-9/1/2018. Pre-LTx characteristics, Karnofsky Performance Status (KPS), time between primary and redo LTx, intra-operative variables, LTx complications, and survival were evaluated. Those with en bloc, lobar, multivisceral or heart-lung transplants, or without preoperative KPS were excluded. Paired comparisons were used to compare pre-transplant variables. Survival analysis was used to examine mortality after redo LTx, and risk factors for survival within a Cox PH regression model including recipient center as a random effect, while time between transplants was considered using time-dependent coefficients at follow-up times of 3, 6, and 12 months. All analysis was performed in R (ver. 3.6.0) Results KPS was grouped into 3 categories:10-40%, 50-60%, 70-100%. Compared to their first transplant, KPS prior to redo LTx was significantly worse (37% vs 64% with a KPS of 10-40%). Prior to their redo LTx, patients were more likely to require ventilation support (9% vs 37%) and ICU admission (13% vs 37%). Following redo LTx, survival was worse in the KPS 10-40% group, compared to the 50-60% and 70-100% groups (Figure 1, log-rank p=0.017). This effect was lessened in the multivariate model, but survival for the 70-100% group was still better than for KPS 10-40%. The effect of decreased time between transplants is most prominent in the early postoperative period. Conclusion Higher functional status and increased time between the primary and redo LTx predict improved survival after redo LTx. Increased mortality risk with early redo LTx is most dramatic in the early postoperative period after redo LTx.

BACKGROUND Tracheostomy is an important adjunct for lung transplant patients requiring prolonged ventilation. We explored the effects of post-transplant tracheostomy on survival and bronchiolitis obliterans syndrome after lung transplant. METHODS A retrospective, single center analysis was performed on all lung transplant recipients during the Lung Allocation Score (LAS) era. Risk factors for post-transplant tracheostomy or death within 30 days were assessed. Kaplan-Meier estimates and Cox proportional hazards models were used to examine the association between tracheostomy within 30 days after transplant and survival at 1 and 3 years. A total of 403 patients underwent single or bilateral lung transplant between May 2005 and February 2016 with complete data for 352 cases, and 35 patients (9.9%) underwent tracheostomy or died (N = 10, 2.8%) within 30 days. RESULTS In adjusted analyses, primary graft dysfunction grade 3 (PGD3) was associated with a composite end point of tracheostomy or death within 30 days (HR 3.11 (1.69, 5.71), P-value

Purpose Donor cardiac death (DCD) donors could expand the field of lung donors, but the acceptably safe time interval between the onset of agonal phase and application of the pulmonary artery clamp is controversial. The purpose of this study was to determine if the time from the beginning of the agonal phase to placement of the pulmonary artery cross clamp in DCD donors is associated with worse recipient lung function or long-term survival. Methods The Scientific Registry for Transplant Research database (2008-2019) was queried for lung transplants performed from DCD donors (N=227) excluding pediatric, multi-organ, and redo lung transplants. Time from the beginning of agonal phase to the time of pulmonary artery cross clamp placement was determined, and donor and recipient characteristics and outcomes were examined for 3 groups: 0-30 minutes (N=178), 30-45 minutes (N=25), and over 45 minutes (N=21). Eight DCD donor lungs had an agonal phase to pulmonary artery cross clamp time between 75 and 120 minutes. The primary endpoints were forced expiratory volume in 1 second (FEV1) at 1 and 2 years and overall survival using Kaplan Meier analysis. Results There were no significant differences in donor age, gender or body mass index between the three groups. Recipient characteristics were comparable between the three groups, and there was no difference in recipient FEV1 at 1 (80.47+/-22.45%, 79.81+/-16.60%, and 76.67+/-13.30%, p=0.840) and 2 years (76.23+/-27.13%, 76.11+/-24.31%, 82.17+/-17.58%, p=0.868) for the three groups (0-30 minutes, 30-45 minutes, and over 45 minutes, respectively) . There was no difference in long term survival out to 10 years between the three groups using Kaplan Meier analysis. Conclusion Lung transplant recipient lung function and survival is similar for recipients of DCD donor lungs regardless of the time from start of the agonal phase to application of the pulmonary artery transplant out to and beyond 45 minutes.

White matter disruption has been repeatedly documented in schizophrenia consistent with microstructural disorganization (reduced fractional anisotropy (FA)) and axonal dysfunction (reduced N-acetylaspartate NAAc). However, the clinical significance of these abnormalities is poorly understood. Diffusion tensor and proton spectroscopic imaging where used to assess FA, axial diffusivity and radial diffusivity (RD), and supra-ventricular white matter NAAc, respectively, in 64 schizophrenia and 64 healthy subjects. Schizophrenia patients had reduced FA across several regions, with additional regions where FA correlated positively with positive symptoms severity. These regions included genu, body and splenium of corpus callosum, anterior and superior corona radiata, superior longitudinal and inferior fronto-occipital fasciculi, and internal capsule. The FA/symptoms relationships corresponded with opposite correlations between RD and positive symptoms. The schizophrenia group (SP group) had progressively reduced NAAc with age, and NAAc correlated negatively with positive symptoms. Cognition correlated positively with both FA and NAAc in controls, whereas in the SP group it had a negative correlation with NAAc and no significant relationship with FA. Antipsychotic dose did not account for the results. Correlates of psychosis, cognitive and negative symptoms can be found in white matter. The significant correlations between positive symptoms in schizophrenia and diffusion and NAAc measures suggest decreased axonal density with increased glial cells and higher myelination in this subpopulation. A separate set of abnormal relationships between cognition and FA/RD, as well as with NAAc, converge to suggest that in schizophrenia, white matter microstructure supports the two core illness domains: psychosis and cognitive/negative symptoms.

Glutamine plus glutamate (Glx), as well as N-acetylaspartate compounds (NAAc, N-acetylaspartate plus N-acetyl-aspartyl-glutamate), a marker of neuronal viability, can be quantified with proton magnetic resonance spectroscopy (1H-MRS). We used 1H-MRS imaging to assess Glx and NAAc, as well as total-choline (glycerophospho-choline plus phospho-choline), myo-inositol and total-creatine (creatine plus phosphocreatine) from an axial supraventricular slab of gray matter (GM, medial-frontal and medial-parietal) and white matter (WM, bilateral-frontal and bilateral-parietal) voxels. Schizophrenia subjects (N = 104) and healthy controls (N = 97) with a broad age range (16 to 65) were studied. In schizophrenia, Glx was increased in GM (P < .001) and WM (P = .01), regardless of age. However, with greater age, NAAc increased in GM (P < .001) but decreased in WM (P < .001) in schizophrenia. In patients, total creatine decreased with age in WM (P < .001). Finally, overall cognitive score correlated positively with WM neurometabolites in controls but negatively in the schizophrenia group (NAAc, P < .001; and creatine [only younger], P < .001). We speculate the results support an ongoing process of increased glutamate metabolism in schizophrenia. Later in the illness, disease progression is suggested by increased cortical compaction without neuronal loss (elevated NAAc) and reduced axonal integrity (lower NAAc). Furthermore, this process is associated with fundamentally altered relationships between neurometabolite concentrations and cognitive function in schizophrenia.

Importance The N -methyl-d-aspartic acid receptor hypofunction model of schizophrenia predicts a paradoxical increase in synaptic glutamate release. In vivo measurement of glutamatergic neurotransmission in humans is challenging, but glutamine, the principal metabolite of synaptic glutamate, can be quantified with proton magnetic resonance spectroscopy ( 1 H-MRS). Although a few studies have measured glutamate, glutamine, and glutamine to glutamate ratio, it is not clear which of these 1 H-MRS indices of glutamatergic neurotransmission is altered in schizophrenia. Objective To examine glutamine, glutamate, and glutamine to glutamate ratio in the dorsal anterior cingulate, as well as their relationships with symptoms and cognition in schizophrenia. Design, Setting, and Participants Cross-sectional design using 3-T 1 H-MRS in participants recruited from university-based psychiatric outpatient clinics who underwent neuroimaging at an affiliated research facility. Participants were 84 patients with a DSM-IV-TR diagnosis of schizophrenia and 81 psychiatrically healthy volunteers, matched in age, sex, ethnicity, and occupational level to the head of household of family of origin. Main Outcomes and Measures Glutamine, glutamate, and glutamine to glutamate ratio. Also symptoms and cognition. Results Glutamine was increased in the schizophrenia group ( P = .01) as well as the glutamine to glutamate ratio ( P = .007) but not glutamate ( P = .89). Glutamine levels were positively correlated with severity of psychotic symptoms ( P = .02). Choline was also increased in schizophrenia ( P = .002). Conclusions and Relevance Elevated glutamine, which was directly related to psychotic symptoms, is consistent with increased glutamatergic synaptic release in schizophrenia, as predicted by the N -methyl-d-aspartic acid receptor hypofunction model. Further understanding the underlying mechanism of glutamatergic dysfunction in schizophrenia may lead to new pharmacological strategies to treat psychosis.

Electroconvulsive therapy (ECT) is the most effective treatment for a depressive episode but the mechanism of action and neural correlates of response are poorly understood. Different theories have suggested that anticonvulsant properties or neurotrophic effects are related to the unique mechanism of action of ECT. This review assessed longitudinal imaging investigations (both structural and functional) associated with ECT response published from 2002 to August 2013. We identified 26 investigations that used a variety of different imaging modalities and data analysis methods. Despite these methodological differences, we summarized the major findings of each investigation and identified common patterns that exist across multiple investigations. The ECT response is associated with decreased frontal perfusion, metabolism, and functional connectivity and increased volume and neuronal chemical metabolites. The general collective of longitudinal neuroimaging investigations support both the anticonvulsant and the neurotrophic effects of ECT. We propose a conceptual framework that integrates these seemingly contradictory hypotheses.