Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 Among Residents and Employees in a Veterans Affairs Community Living Center: A 42-Month Prospective Cohort Study.

Background: Understanding routes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in long-term care facilities is essential for the development of effective control measures. Methods: Between March 1, 2020, and August 31, 2023, we identified coronavirus disease 2019 (COVID-19) cases among residents and employees in a Veterans Affairs community living center that conducted routine screening for asymptomatic COVID-19. Contact tracing was conducted to identify suspected transmission events, and whole genome sequencing was performed to determine the relatedness of SARS-CoV-2 samples. Results: During the 42-month study period, 269 cases of COVID-19 were diagnosed, including 199 employees and 70 residents. A total of 48 (24.1%) employees and 30 (42.9%) residents were asymptomatic. Sequencing analysis provided support for multiple events in which employees transmitted SARS-CoV-2 to co-workers and residents. There was 1 episode of likely transmission of SARS-CoV-2 from one resident to another resident, but no documented transmissions from residents to employees. Conclusions: Transmission of SARS-CoV-2 in the community living center predominantly involved transmission from employees to co-workers and residents. There is a need for improved measures to prevent transmission of SARS-CoV-2 by healthcare personnel.

Performance status at the time of lung retransplant predicts long-term function.

BACKGROUND: Lung retransplantation is offered to select patients with chronic allograft dysfunction. Given the increased risk of morbidity and mortality conferred by retransplantation, post-transplant function should be considered in the decision of who and when to list. The aim of this study is to identify predictors of post-operative disability in patients undergoing lung retransplantation. METHODS: Data were collected from the UNOS national dataset and included all patients who underwent lung retransplant from May 2005-March 2023. Pre- and post-operative function was reported by the Karnofsky Performance Status (KPS) and patients were stratified based on their needs. Cumulative link mixed effects models identified associations between pre-transplant variables and post-transplant function. RESULTS: A total of 1275 lung retransplant patients were included. After adjusting for between-group differences, pre-operative functional status was predictive of post-transplant function; patients requiring Total Assistance ( n = 740) were 74% more likely than No/Some Assistance patients (n = 535) to require more assistance in follow-up (OR 1.74, 95% CI 1.13-2.68, p = .012). Estimated one year survival of Total Assistance patients is lower than No/Some Assistance Recipients (72% vs. 82%, CI 69%-75%; 79%-86%) but similar to overall re-transplant survival (76%, CI 74%-79%). CONCLUSION: Both survival and regain of function in patients requiring Total Assistance prior to retransplant may be higher than previously reported. Pre-operative functional status is predictive of post-operative function and should weigh in the selection, timing and post-operative care of patients considered for lung retransplantation.

Comprehensive Proteomic Analysis of the Differential Expression of 83 Proteins Following Intracortical Microelectrode Implantation.

Intracortical microelectrodes (IMEs) are devices designed to be implanted into the cerebral cortex for various neuroscience and neuro-engineering applications. A critical feature of these devices is their ability to detect neural activity from individual neurons. Currently, IMEs are limited by chronic failure, largely considered to be caused by the prolonged neuroinflammatory response to the implanted devices. Over the decades, characterization of the neuroinflammatory response has grown in sophistication, with the most recent advances including advanced genomics and spatially resolved transcriptomics. While gene expression studies increase our broad understanding of the relationship between IMEs and cortical tissue, advanced proteomic techniques have not been reported. Proteomic evaluation is necessary to describe the diverse changes in protein expression specific to neuroinflammation, neurodegeneration, or tissue and cellular viability, which could lead to the development of more targeted intervention strategies designed to improve IME function. In this study, we have characterized the expression of 83 proteins within 180 µm of the IME implant site at 4-, 8-, and 16-weeks post-implantation. We identified potential targets for immunotherapies, as well as key pathways and functions that contribute to neuronal dieback around the IME implant.

Outcomes following minimally invasive approaches vs. open extended lobectomy for non-small cell lung cancer: a propensity-matched analysis of the National Cancer Database.

Background: Traditional thoracotomy, an invasive surgical procedure, has been the standard approach for extended lobectomy in treating non-small cell lung cancer (NSCLC). However, minimally invasive surgery (MIS) has gained traction with advancements in surgical techniques. Despite this, the outcomes of extended lobectomy via a minimally invasive approach remain largely uncharted. Using the comprehensive National Cancer Database (NCDB), our research aimed to clarify the safety, feasibility, and efficacy of minimally invasive extended lobectomy in patients diagnosed with NSCLC. Methods: Our study encompassed a selection of patients with NSCLC who underwent extended lobectomy (defined as lobectomy or bilobectomy with chest wall, diaphragm or pericardial resection) between 2010 and 2014. Through propensity score matching (PSM), we ensured a balanced comparison between patients who underwent MIS and those who opted for the traditional open extended lobectomy. Both univariate and multivariate analyses were employed to discern whether the surgical approach had any significant impact on the prognosis of patients undergoing this specific procedure. Results: Before PSM, our dataset included 3,934 patients. After 1:2 PSM, the MIS group included 683 cases, while the open group included 1,317 cases. One notable finding was the reduced average postoperative hospital stay for the MIS group at 7.15 days compared to the open group at 8.40 days (P<0.001). Furthermore, the 5-year survival rate was similar, with the MIS group at 53.1% and the open group at 51.3% (P=0.683). Conclusions: The results of our study suggest that MIS for extended lobectomy not only is safe and feasible but also is oncologically effective. However, it is imperative to note that these encouraging findings necessitate further validation through prospective studies to ascertain the full scope of benefits and potential risks associated with MIS.

IL-17-producing cells in ankylosing spondylitis patients show gender-based differences in gene expression.

OBJECTIVES: Gender has been shown to impact disease expression in ankylosing spondylitis (AS) and Th17 cells play a key role in AS pathogenesis. To better understand what Th17-associated immune pathways are different between men and women, we compared the transcriptome of IL-17-enriched peripheral blood mononuclear cells (PBMCs) in male and female AS patients, with a particular focus on inflammatory cytokine genes. METHODS: PBMCs were collected from 10 female and 11 male AS patients at the Clinical Research Unit of MetroHealth Medical Center. IL-17-enriched PBMCs were isolated and stimulated with CytoStim. RNA-sequencing (RNA-seq) was performed on the samples, and the data were analysed using iPathwayGuide. Inflammatory markers and genes related to Th17 differentiation and function were identified based on previous studies. RESULTS: RNA-seq identified 12,893 genes with 2,851 genes with p-values <0.05 with distinct patterns of gene expression between male and female AS patients. TGF-ß, PGE2, and S100 proteins were significantly upregulated in males. Levels of IL-12B, a Th17 inducer, were lower in males compared to females. Additionally, receptors of IL-6, 12, 23, TGF-ß, and PGE2 were downregulated in males, except for IL-17RC, which was upregulated. Genes involved in Th17 differentiation showed differential expression between genders, with elevated expression of BATF, SOCS1, NKD2, and ARID5A in men and decreased expression of FOXO1. CONCLUSIONS: Transcriptomic analysis revealed that male AS patients exhibit distinct expression patterns of IL-17 pro-inflammatory genes, which may contribute to the phenotypic differences observed between genders in AS.

Lung transplantation in HIV seropositive recipients: An analysis of the UNOS registry.

BACKGROUND: Experience with lung transplantation (LT) in patients with human immunodeficiency virus (HIV) is limited. Many studies have demonstrated the success of kidney and liver transplantation in HIV-seropositive (HIV+) patients. Our objective was to conduct a national registry analysis comparing LT outcomes in HIV+ to HIV-seronegative (HIV-) recipients. METHODS: The United Network for Organ Sharing database was queried to identify LTs performed in adult HIV+ patients between 2016 and 2023. Patients with unknown HIV status, multiorgan transplants, and redo transplants were excluded. The primary endpoints were mortality and graft rejection. Survival time was analyzed using Kaplan-Meier analysis. RESULTS: The study included 17 487 patients, 67 of whom were HIV+. HIV+ recipients were younger (59 vs. 62 years, p = .02), had higher pulmonary arterial pressure (28 vs. 25 mm Hg, p = .04), and higher lung allocation scores (47 vs. 41, p = .01) relative to HIV- recipients. There were no differences in graft/recipient survival time between groups. HIV+ recipients had higher rates of post-transplant dialysis (18% vs. 8.4%, p = .01), but otherwise had similar post-transplant outcomes to HIV-recipients. CONCLUSIONS: This national registry analysis suggests LT outcomes in HIV+ patients are not inferior to outcomes in HIV- patients and that well-selected HIV+ recipients can achieve comparable patient and graft survival rates relative to HIV- recipients.

Immediate Postoperative COVID-19 Infection after Lung Transplantation: A Systematic Review and Case Series.

BACKGROUND: With new variants challenging the effectiveness of preventive measures, we are beginning to recognize the reality that COVID-19 will continue to pose an endemic threat. The manifestations of COVID-19 in lung transplant recipients during index admission are poorly understood with very few cases reported in recent lung transplant recipients. Optimal management of immunosuppression and antiviral therapy in recent transplant recipients is challenging. METHODS: We performed a retrospective analysis identifying lung transplant recipients at our institution who contracted COVID-19 in the immediate postoperative period (within index admission). In addition, we performed a systematic review from January 2020 to August 2023 identifying all publications on the PUBMED database regarding COVID-19 infection in lung transplant recipients during index admission. RESULTS: We report four cases of COVID-19 pneumonia in lung transplant recipients in the immediate postoperative period and we describe the clinical course, treatment options, and immunosuppression changes to manage this unique clinical problem. All patients made a full recovery and were eventually discharged home. Within our review of the literature, the most prevalent presenting symptoms were cough, dyspnea, and fatigue. Six (75%) patients decreased or held their antimetabolite. The two most common treatments were monoclonal antibodies (38%) and remdesivir (63%). CONCLUSION: Although previous literature demonstrates that COVID-19 can be deadly in recent lung transplant recipients, rapid treatment with anti-viral therapy/immunotherapy, deescalating immunosuppression, and treatment of respiratory decompensation with Decadron was effective in our patients.

Genomic Biomarkers Can Provide a Deeper Understanding of Recurrent Pressure Injuries.

OBJECTIVE: To identify genetic biomarkers predisposing individuals with spinal cord injury (SCI) to recurrent pressure injuries (PIs). METHODS: Repeated measures of the transcriptome profile of veterans with SCI at three Veterans Spinal Cord Injuries and Disorders Centers. Exclusion criteria included having significant active systemic disease at time of enrollment. Researchers obtained comprehensive profiles of clinical and health factors and demographic information relevant to PI history at enrollment and at each follow-up visit by reviewing patients' medical charts. Whole blood samples were collected at 6- to 12-month intervals for 2 to 4 years. In addition to DNA profiling with whole genome sequencing of the patients, RNA sequencing was performed to assess pathways associated with PI risk. RESULTS: Whole genome sequencing analysis identified 260 genes that showed increased prevalence of single-nucleotide variations in exonic regions with high (>20) combined annotation-dependent depletion scores between persons with high versus low intramuscular adipose tissue levels when cross-referenced with persons who had recurrent PIs. Gene set enrichment analysis using Hallmark and KEGG (Kyoto Encyclopedia of Genes and Genomes) gene sets of these candidate genes revealed enrichment in genes encoding proteins involved in fatty acid metabolism (P < .01). Further, RNA sequencing revealed upregulated activity in biological senescence pathways and downregulated activity in antimicrobial protection pathways. CONCLUSIONS: Genomic biomarkers may complement electronic health records to support management of complex interactive health issues such as risk of recurrent PIs in people with SCI. These findings may also be leveraged for homogeneous phenotypic grouping of higher-risk individuals.

Impact of gastro-jejunostomy tube in lung transplant patients: a propensity-matched analysis.

OBJECTIVES: During the postoperative phase of lung transplantation, the surgical creation of a gastro-jejunostomy (GJ) may be deemed necessary for patients with severe oesophageal dysmotility, prolonged oral intake difficulties stemming from use of a ventilator or marked malnutrition. We explored the effects of postoperative GJ tube on survival and bronchiolitis obliterans syndrome in lung transplant recipients. METHODS: We retrospectively reviewed all lung transplants performed at our institution between 2011 and 2022. Propensity score matching was performed to match patients who required a GJ tube with control patients on a 1:1 ratio. The preoperative, operative and postoperative outcomes of the patients were evaluated. RESULTS: After propensity score matching, 193 patients with GJ were compared to 193 patients without GJ. Patients with GJ had significantly higher rates of delayed chest closure (P = 0.007), and postoperative dialysis (P = 0.016), longer intensive care unit stays (P < 0.001), longer ventilator duration (P < 0.001), higher rates of pneumonia (P = 0.035) and higher rates of being treated for acute cellular rejection within 1 year of transplant (P = 0.008). Overall survival and freedom from bronchiolitis obliterans syndrome were not found to be significantly different between the matched groups (P = 0.09 and P = 0.3). CONCLUSIONS: GJ tube placement during the postoperative phase of lung transplantation did not compromise patient survival or freedom from bronchiolitis obliterans syndrome although the results reflect more difficult and complicated cases. This study indicates that the GJ tube may be a useful option for enteral feeding.

A novel scoring system to predict survival in cirrhotic patients undergoing isolated lung transplantation: The PENS-CEPT score.

Cirrhosis is usually regarded as a contraindication to isolated lung transplantation (ILT). We sought to determine which patients with cirrhosis could safely undergo ILT. Based on a retrospective analysis of patients with cirrhosis who underwent ILT at our center between 2007 and 2020, we developed an exclusionary algorithm (PENS-CEPT: Pittsburgh ExclusioN Score in Cirrhotics Evaluated for Pulmonary Transplant) to help determine which patients can undergo ILT with minimal incurred risk from their underlying liver disease. The score utilizes a combination of readily available clinical data and the presence (or absence) of spontaneous portosystemic shunts on preoperative cross-sectional imaging. Sixteen patients underwent ILT with a diagnosis of cirrhosis: nine with cystic fibrosis. On univariate analysis, only our model was able to predict 1 year survival. Of the nine patients that would have been approved using our model, there was only one short term death. Of the seven patients that would have been rejected by the model, all but one died within the first year with six dying of complications from liver failure. We are proposing a simple score utilizing routine clinical parameters and pre-operative imaging to determine the safety of ILT in cirrhotic patients. Further studies are required to validate this scoring system with the goal of safely increasing the opportunity for cirrhotic patients who would otherwise be rejected for ILT.

Pharmacogenomic variation in the Malagasy population: implications for the antimalarial drug primaquine metabolism.

Aim: Antimalarial primaquine (PQ) eliminates liver hypnozoites of Plasmodium vivax. CYP2D6 gene variation contributes to PQ therapeutic failure. Additional gene variation may contribute to PQ efficacy. Information on pharmacogenomic variation in Madagascar, with vivax malaria and a unique population admixture, is scanty. Methods: The authors performed genome-wide genotyping of 55 Malagasy samples and analyzed data with a focus on a set of 28 pharmacogenes most relevant to PQ. Results: Mainly, the study identified 110 coding or splicing variants, including those that, based on previous studies in other populations, may be implicated in PQ response and copy number variation, specifically in chromosomal regions that contain pharmacogenes. Conclusion: With this pilot information, larger genome-wide association analyses with PQ metabolism and response are substantially more feasible.

Lung Transplantation Outcomes in Recipients Aged 70 Years or Older and the Impact of Center Volume.

OBJECTIVE: To evaluate trends and outcomes of lung transplants (LTx) in recipients ≥ 70 years. METHODS: We performed a retrospective analysis of the UNOS database identifying all patients undergoing LTx (May 2005-December 2022). Baseline characteristics and postoperative outcomes were compared by age (<70 years, ≥70 years) and center volume. Kaplan-Meier analyses were performed with pairwise comparisons between subgroups. RESULTS: 34,957 patients underwent LTx, of which 3236 (9.3%) were ≥70 years. The rate of LTx in recipients ≥ 70 has increased over time, particularly in low-volume centers (LVCs); consequently, high-volume centers (HVCs) and LVCs perform similar rates of LTx for recipients ≥ 70. Recipients ≥ 70 had higher rates of receiving from donor after circulatory death lungs and of extended donor criteria. Recipients ≥ 70 were more likely to die of cardiovascular diseases or malignancy, while recipients < 70 of chronic primary graft failure. Survival time was shorter for recipients ≥ 70 compared to recipients < 70 old (hazard ratio (HR): 1.36, 95% confidence interval (CI): 1.28-1.44, p < 0.001). HVCs were associated with a survival advantage in recipients < 70 (HR: 0.91, 95% CI: 0.88-0.94, p < 0.001); however, in recipients ≥ 70, survival was similar between HVCs and LVCs (HR: 1.11, 95% CI: 0.99-1.25, p < 0.08). HVCs were more likely to perform a bilateral LTx (BLT) for obstructive lung diseases compared to LVCs, but there was no difference in BLT and single LTx likelihood for restrictive lung diseases. CONCLUSIONS: Careful consideration is needed for recipient ≥ 70 selection, donor assessment, and post-transplant care to improve outcomes. Further research should explore strategies that advance perioperative care in centers with low long-term survival for recipients ≥ 70.

Postoperative Acute Kidney Injury and Long-Term Outcomes After Lung Transplantation.

BACKGROUND: This study sought to characterize perioperative risk factors of acute kidney injury (AKI) and report outcomes associated with its development in the immediate postoperative setting after lung transplantation. METHODS: Study investigator performed a retrospective analysis of all adult patients undergoing primary lung transplantation at a single institution from January 1, 2011 to December 31, 2021 AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria after lung transplantation and was stratified on the basis of whether patients required renal replacement therapy (RRT; AKI-no RRT vs AKI-RRT). RESULTS: Of the 754 patients included, 369 (48.9%) any AKI developed in the postoperative period (252 AKI-no RRT vs 117 AKI-RRT). Risk factors for postoperative AKI included higher preoperative creatinine levels (odds ratio [OR], 5.15; P < .001), lower preoperative estimated glomerular filtration rate (OR, 0.99; P < 0.018), delayed chest closure (OR, 2.72; P < .001), and higher volumes of postoperative blood products (OR, 1.09; P < .001) in the multivariable analysis. On univariate analysis, both AKI groups were also associated with higher rates of pneumonia (P < .001), reintubation (P < .001), mortality on index admission (P < 0.001), longer ventilator duration (P < .001), longer intensive care unit length of stay (P < .001), and longer hospital length of stay (P < .001), with the highest rates in the AKI-RRT group. In a multivariable survival analysis, postoperative AKI-no RRT (hazard ratio [HR], 1.50; P = .006) and AKI-RRT (HR, 2.70; P < .001) were associated with significantly worse survival independent of severe grade 3 primary graft dysfunction at 72 hours (HR, 1.45; P = .038). CONCLUSIONS: The development of postoperative AKI was associated with numerous preoperative and intraoperative factors. Postoperative AKI remained significantly associated with poorer posttransplantation survival. Severe cases of AKI necessitating RRT portended the worst survival after lung transplantation.

A core NRF2 gene set defined through comprehensive transcriptomic analysis predicts selective drug resistance and poor multi-cancer prognosis.

The NRF2-KEAP1 pathway plays an important role in the cellular response to oxidative stress but may also contribute to metabolic changes and drug resistance in cancer. We investigated the activation of NRF2 in human cancers and fibroblast cells through KEAP1 inhibition and cancer associated KEAP1/NRF2 mutations. We define a core set of 14 upregulated NRF2 target genes from seven RNA-Sequencing databases that we generated and analyzed, which we validated this gene set through analyses of published databases and gene sets. An NRF2 activity score based on expression of these core target genes correlates with resistance to drugs such as PX-12 and necrosulfonamide but not to paclitaxel or bardoxolone methyl. We validated these findings and also found NRF2 activation led to radioresistance in cancer cell lines. Finally, our NRF2 score is prognostic for cancer survival and validated in additional independent cohorts for novel cancers types not associated with NRF2-KEAP1 mutations. These analyses define a core NRF2 gene set that is robust, versatile, and useful as a NRF2 biomarker and for predicting drug resistance and cancer prognosis.

Waitlist Mortality and Extracorporeal Membrane Oxygenation Bridge to Lung Transplant.

BACKGROUND: Use of extracorporeal membrane oxygenation (ECMO) as bridge to lung transplant has increased. However, little is known about patients placed on ECMO who die while on the waiting list. Using a national lung transplant data set, we investigated variables associated with waitlist mortality of patients bridged to lung transplant. METHODS: All patients supported on ECMO at time of listing were identified using the United Network for Organ Sharing database. Univariable analyses were performed using bias-reduced logistic regression. Cause-specific hazard models were used to determine the effect of variables of interest on hazard of outcomes. RESULTS: From April 2016 to December 2021, 634 patients met inclusion criteria. Of these, 445 (70%) were successfully bridged to transplant, 148 (23%) died on the waitlist, and 41 (6.5%) were removed for other reasons. Univariable analysis found associations between waitlist mortality and blood group, age, body mass index, serum creatinine, lung allocation score, days on waitlist, United Network for Organ Sharing region, and being listed at a lower-volume center. Cause-specific hazard models demonstrated that patients at high-volume centers were 24% more likely to survive to transplant and 44% less likely to die on the waitlist. Among patients who were successfully bridged to transplant, there was no difference in survival between low- and high-volume centers. CONCLUSIONS: ECMO is an appropriate strategy to bridge selected high-risk patients to lung transplant. Of those placed on ECMO with intent to transplant, about one quarter may not survive to transplantation. High-risk patients requiring advanced support strategies may be more likely to survive to transplant when bridged at a high-volume center.

The WAVE2/miR-29/Integrin-ß1 Oncogenic Signaling Axis Promotes Tumor Growth and Metastasis in Triple-negative Breast Cancer.

Breast cancer is the most frequently diagnosed malignancy in women and the major cause of death because of its invasion, metastasis, and resistance to therapies capabilities. The most aggressive subtype of breast cancer is triple-negative breast cancer (TNBC) due to invasive and metastatic properties along with early age of diagnosis and poor prognosis. TNBC tumors do not express estrogen, progesterone, and HER2 receptors, which limits their treatment with targeted therapies. Cancer invasiveness and metastasis are known to be promoted by increased cell motility and upregulation of the WAVE proteins. While the contribution of WAVE2 to cancer progression is well documented, the WAVE2-mediated regulation of TNBC oncogenic properties is still under investigated, as does the molecular mechanisms by which WAVE2 regulates such oncogenic pathways. In this study, we show that WAVE2 plays a significant role in TNBC development, progression, and metastasis, through the regulation of miR-29 expression, which in turn targets Integrin-ß1 (ITGB1) and its downstream oncogenic activities. Conversely, we found WAVE2 expression to be regulated by miR-29 in a negative regulatory feedback loop. Reexpression of exogenous WAVE2 in the WAVE2-deficient TNBC cells resulted in reactivation of ITGB1 expression and activity, further confirming the specificity of WAVE2 in regulating Integrin-ß1. Together, our data identify a novel WAVE2/miR-29/ITGB1 signaling axis, which is essential for the regulation of the invasion-metastasis cascade in TNBC. Our findings offer new therapeutic strategies for the treatment of TNBC by targeting WAVE2 and/or its downstream effectors. Significance: Identification of a novel WAVE2/miR-29/ITGB1 signaling axis may provide new insights on how WAVE2 regulates the invasion-metastasis cascade of TNBC tumors through the modulation of ITGB1 and miR-29.

Risk Factors and Outcomes of Postoperative Hepatic Dysfunction After Lung Transplantation.

BACKGROUND: Hepatic dysfunction is a morbid complication of lung transplantation. Little is known about risk factors for postoperative hepatic dysfunction or its impact on survival after lung transplantation. METHODS: This retrospective analysis of 1406 adult lung transplant recipients was performed at the University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania between January 1, 2007 and December 1, 2019. Patients were excluded for redo lung transplantation, concomitant cardiac surgery, or concurrent solid organ transplantation. Postoperative liver dysfunction was classified as either ischemic liver injury or nonischemic dysfunction (transaminitis, hyperbilirubinemia). RESULTS: Among the 1155 primary lung transplant recipients included, postoperative hepatic dysfunction developed in 96 (8.3%) after lung transplantation. A history of liver disease was the greatest predictor of postoperative hepatic dysfunction (odds ratio, 6.19; CI, 2.13-17.4; P < .001). Patients with postoperative hepatic dysfunction had a greater need for intraoperative blood products (ischemic, 12 U [range, 6-21 U]; nonischemic, 10 U [range, 4-28 U]; vs none, 4 U [range, 1-12 U]; P < .001) and an increased need for postoperative circulatory support (ischemic, 16 [76%]; nonischemic, 25 [33%]; none, 117 [11%]; P < .001). Both ischemic liver injury and nonischemic dysfunction were associated with diminished 1-, 3-, and 5-year term survival (ischemic, 27.5%, 16.5%, and 0%, respectively; nonischemic, 60%, 49.6%, and 46.9%, respectively; none, 87.3%, 72.3%, and 59.5%, respectively; P < .001). CONCLUSIONS: Hepatic dysfunction after lung transplantation is associated with significant morbidity and mortality. A history of liver disease was the best positive predictor for postoperative dysfunction. Additional studies are necessary to identify the best treatment algorithm to avoid hepatic dysfunction more effectively in the postoperative setting after lung transplantation.

Utilization of machine learning to model the effect of blood product transfusion on short-term lung transplant outcomes.

The objective of this study was to identify the relationship between blood product transfusion and short-term morbidity and mortality following lung transplantation utilizing machine learning. Preoperative recipient characterstics, procedural variables, perioperative blood product transfusions, and donor charactersitics were included in the model. The primary composite outcome was occurrence on any of the following six endpoints: mortality during index hospitalization; primary graft dysfunction at 72 h post-transplant or the need for postoperative circulatory support; neurological complications (seizure, stroke, or major encephalopathy); perioperative acute coronary syndrome or cardiac arrest; and renal dysfunction requiring renal replacement therapy. The cohort included 369 patients, with the composite outcome occurring in 125 cases (33.9%). Elastic net regression analysis identified 11 significant predictors of composite morbidity: higher packed red blood cell, platelet, cryoprecipitate and plasma volume from the critical period, preoperative functional dependence, any preoperative blood transfusion, VV ECMO bridge to transplant, and antifibrinolytic therapy were associated with higher risk of morbidity. Preoperative steroids, taller height, and primary chest closure were protective against composite morbidity.

Intraoperative Red Blood Cell Transfusion and Primary Graft Dysfunction After Lung Transplantation.

BACKGROUND: In this international, multicenter study of patients undergoing lung transplantation (LT), we explored the association between the amount of intraoperative packed red blood cell (PRBC) transfusion and occurrence of primary graft dysfunction (PGD) and associated outcomes. METHODS: The Extracorporeal Life Support in LT Registry includes data on LT recipients from 9 high-volume (>40 transplants/y) transplant centers (2 from Europe, 7 from the United States). Adult patients who underwent bilateral orthotopic lung transplant from January 2016 to January 2020 were included. The primary outcome of interest was the occurrence of grade 3 PGD in the first 72 h after LT. RESULTS: We included 729 patients who underwent bilateral orthotopic lung transplant between January 2016 and November 2020. LT recipient population tertiles based on the amount of intraoperative PRBC transfusion (0, 1-4, and >4 units) were significantly different in terms of diagnosis, age, gender, body mass index, mean pulmonary artery pressure, lung allocation score, hemoglobin, prior chest surgery, preoperative hospitalization, and extracorporeal membrane oxygenation requirement. Inverse probability treatment weighting logistic regression showed that intraoperative PRBC transfusion of >4 units was significantly ( P < 0.001) associated with grade 3 PGD within 72 h (odds ratio [95% confidence interval], 2.2 [1.6-3.1]). Inverse probability treatment weighting analysis excluding patients with extracorporeal membrane oxygenation support produced similar findings (odds ratio [95% confidence interval], 2.4 [1.7-3.4], P < 0.001). CONCLUSIONS: In this multicenter, international registry study of LT patients, intraoperative transfusion of >4 units of PRBCs was associated with an increased risk of grade 3 PGD within 72 h. Efforts to improve post-LT outcomes should include perioperative blood conservation measures.