Variations in mortality in Medicare recipients on extracorporeal membrane oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a rescue modality against severe cardiac and pulmonary compromise. We sought to assess variation in mortality and associated environmental and infrastructural predictors among Medicare beneficiaries on ECMO. METHODS: We used Medicare claims data to evaluate hospitalizations between 2017 and 2019 during which beneficiaries required ECMO. The primary outcome of interest was mortality. We evaluated the influence on mortality of Medicare Case Mix Index (CMI), Medicare Wage Index, hospital size, ECMO cannulations, cardiology volume, region, and gender and modeled necessity and sufficiency relations involving ECMO volume, hospital size, cardiology volume, US region, and the mortality index through qualitative comparative analysis (QCA). RESULTS: 5368 ECMO cases were performed at 306 hospitals. Compared to institutions with a mortality index equal to or below 2, those above this threshold had statistically significant higher number of beds, cardiology volumes, and lower survival percentages (p < 0.05). Moreover, we observed a smaller proportion of institutions with an ECMO volume < 20 (78.3% vs 63.4%), which had mortality index > 2. The QCA analysis indicated that low cardiology volume and central/east location are necessary but not sufficient conditions for a mortality index above 2. CONCLUSION: Trends in mortality are influenced by prevailing socioeconomic, utilization, infrastructural characteristics, and volume. As such, ECMO mortality may be more accurately predicted by models that account for more factors than clinical parameters alone.

Incremental effect of complications on mortality and hospital costs in adult ECMO patients.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is a resource-intense modality whose usage is expanding rapidly. It is a costly endeavor and best conducted in a multidisciplinary setting. There is a growing impetus to mitigate the mortality and costs associated with ECMO. We sought to examine the impact of complications on mortality and hospital costs in patients on ECMO. METHODS: Using the NIS database, we performed multivariable logistic regression to assess the influence of complications on the primary outcome, in-hospital mortality. Similarly, we performed multivariable survey linear regression analysis to evaluate the effect of the complications on hospital costs. RESULTS: Of the 12,637 patients supported using ECMO between 2004 and 2013, 9836 (78%) developed at least one complication. The three most common complications were acute kidney injury (32.8%), bloodstream infection (31.8%), and bleeding (27.8%). An ECMO hospitalization with no complications was associated with median costs of $53,470, a single complication with costs of $97,560, two complications with costs of $139,035, and three complication with costs of $162,284. A single complication was associated with a 165% increase in odds of mortality. Two or three complications resulted in 375% or 627% higher odds of mortality, respectively. Having one, two, or three complications was associated with 24%, 38%, or 38% increase in median costs respectively (Figure 1). Complications associated with the highest median costs were central line-associated bloodstream infection $217,751; liver failure $176,201; bloodstream infection $169,529. CONCLUSION: In-hospital mortality and costs increase with each incremental complication in patients on ECMO. Accurate prediction and mitigation of complications is likely to improve outcomes and cost.

Contemporary look at extracorporeal membrane oxygenation as a bridge to reoperative lung transplantation in the United States - a retrospective study.

The purpose of this study was to examine the influence of extracorporeal membrane oxygenation (ECMO) as a bridge to reoperative lung transplantation (LT) on outcomes and survival. A total of 1960 LT recipients transplanted a second time between 2005 and 2017 were analyzed using the United Network for Organ Sharing (UNOS) Organ Procurement and Transplantation Network (OPTN). Of these recipients, 99 needed ECMO as a bridge to reoperative LT. Mean age was 50 ± 14 years, 47% were females, and the group with ECMO was younger [42 (30-59) vs. 55 (40-62) years]. In both univariate and multivariable analyses (adjusting for age and gender), the ECMO group had greater incidence of prolonged ventilation >48 h (83% vs. 40%, P < 0.001) and in-hospital dialysis (27% vs. 7%, P < 0.001). There were no differences in incidence of acute rejection (15% vs. 11%, P = 0.205), airway dehiscence (4% vs. 2%, P = 0.083), stroke (3% vs. 2%, P = 0.731), or reintubation (20% vs. 20%, P = 0.998). Kaplan-Meier survival analysis showed the ECMO group had reduced 1-year survival (66.6% vs. 83.0%, P < 0.001). After covariate adjustment, the ECMO group only had increased risk for 1-year mortality in the 2005-2011 era (HR = 2.57, 95% CI = 1.45-4.57, P = 0.001). For patients who require reoperative LT, bridging with ECMO was historically a significant predictor of poor outcome, but may be improving in recent years.

Selective bladder denervation for overactive bladder (OAB) syndrome: From concept to healing outcomes using the ovine model.

AIMS: We evaluated a Selective Bladder Denervation (SBD) device, which uses radiofrequency ablation, for the treatment of overactive bladder syndrome in terms of its nerve denervation, ablation characteristics, and post-treatment healing. METHODS: Using the SBD device, eight fresh extirpated ovine bladder trigones were treated (90°C set point for 60 s) and nitroblue tetrazolium viability stained to characterize the ablation. In addition, 12 trigones were treated in vivo with three adjacent ablations and divided into survival cohorts: Day 7, Day 30, and Day 90 to assess the ablations and their associated healing. RESULTS: The ex vivo single trigone ablations had a 7.9 ± 0.9 mm width and 5.7 ± 1.0 mm thickness that involved the submucosa, detrusor muscle, adventitia, and vagina. Microscopic viability staining confirmed complete nerve necrosis within the targeted tissue. The in vivo Day 7 trigones supported the ex vivo ablation characteristics and showed up to minimal inflammation, granulation tissue, and collagen fibrosis. Day 30 trigones had essentially absent inflammation and granulation tissue with evolving collagen fibrosis at the ablation's periphery. Day 90 trigones had essentially absent acute inflammation, minimal chronic inflammation, essentially absent granulation tissue, and up to mild collagen fibrosis. No ureteral/urethral alterations, vesico-vaginal fistulas, or other complications were identified. CONCLUSIONS: The SBD device provided a targeted trigone ablation with resultant denervation. The tissue healing timeline followed that expected for a hyperthermic ablation and was characterized by a fibroproliferative healing response with limited inflammation and granulation tissue. The ablations did not impact the overlying bladder mucosal surface.

LetsTalkShots: personalized vaccine risk communication.

Introduction: Vaccine hesitancy is a global health threat undermining control of many vaccine-preventable diseases. Patient-level education has largely been ineffective in reducing vaccine concerns and increasing vaccine uptake. We built and evaluated a personalized vaccine risk communication website called LetsTalkShots in English, Spanish and French (Canadian) for vaccines across the lifespan. LetsTalkShots tailors lived experiences, credible sources and informational animations to disseminate the right message from the right messenger to the right person, applying a broad range of behavioral theories. Methods: We used mixed-methods research to test our animation and some aspects of credible sources and personal narratives. We conducted 67 discussion groups (n = 325 persons), stratified by race/ethnicity (African American, Hispanic, and White people) and population (e.g., parents, pregnant women, adolescents, younger adults, and older adults). Using a large Ipsos survey among English-speaking respondents (n = 2,272), we tested animations aligned with vaccine concerns and specific to population (e.g., parents of children, parents of adolescents, younger adults, older adults). Results: Discussion groups provided robust feedback specific to each animation as well as areas for improvements across animations. Most respondents indicated that the information presented was interesting (85.5%), clear (96.0%), helpful (87.0%), and trustworthy (82.2%). Discussion: Tailored vaccine risk communication can assist decision makers as they consider vaccination for themselves, their families, and their communities. LetsTalkShots presents a model for personalized communication in other areas of medicine and public health.

Corrigendum: LetsTalkShots: personalized vaccine risk communication.

[This corrects the article DOI: 10.3389/fpubh.2023.1195751.].

Functional Hierarchy and Cooperation of EMT Master Transcription Factors in Breast Cancer Metastasis.

Several master transcription factors (TF) can activate the epithelial-to-mesenchymal transition (EMT). However, their individual and combinatorial contributions to EMT in breast cancer are not defined. We show that overexpression of EMT-TFs individually in epithelial cells upregulated endogenous SNAI2, ZEB1/2, TCF4, and TWIST1/2 as a result of positive feedback mediated in part by suppression of their negative regulator miRNAs miR200s/203/205. We identified TCF4 as a potential new target of miR200s. Expression of ZEB1/2 strongly correlated with the mesenchymal phenotype in breast cancer cells, with the CD24-/CD44+ stemness profile, and with lower expression of core epithelial genes in human breast tumors. Knockdown of EMT-TFs identified the key role of ZEB1 and its functional cooperation with other EMT-TFs in the maintenance of the mesenchymal state. Inducible ZEB1+2 knockdown in xenograft models inhibited pulmonary metastasis, emphasizing their critical role in dissemination from primary site and in extravasation. However, ZEB1+2 depletion one-week after intravenous injection did not inhibit lung colonization, suggesting that ZEB1/2 and EMT are not essential for macrometastatic outgrowth. These results provide strong evidence that EMT is orchestrated by coordinated expression of several EMT-TFs and establish ZEB1 as a key master regulator of EMT and metastasis in breast cancer. IMPLICATIONS: The EMT program is orchestrated by coordinated expression of multiple EMT transcription factors, whereas ZEB1 integrates the EMT master regulatory network and plays the major role in promoting EMT and metastasis.

Contemporary analysis of charges and mortality in the use of extracorporeal membrane oxygenation: A cautionary tale.

Objective: The use of extracorporeal membrane oxygenation (ECMO) has increased exponentially. Costs and outcomes, however, vary considerably by indication. We sought to elucidate and quantify these differences. Methods: Adult patients supported on ECMO between 2008 and 2016 were analyzed using the Nationwide Inpatient Sample. We divided the study period into an early (2008-2013) and late period (2013-2016). The primary outcome was hospital charges, and the secondary outcomes were mortality, length of stay (LOS), and duration of ECMO support. These were stratified by the 5 most common indications: postcardiotomy shock (PCS), cardiogenic shock (CS), severe acute respiratory failure (SARF), heart (HT), and lung transplantation (LT). Both patient and hospital characteristics were assessed. Charges were adjusted for inflation and analyzed using a generalized linear model with gamma distribution. Pairwise comparison with Bonferroni correction was used to evaluate the cost and multivariate logistic regression to assess the risk of mortality. Results: Data pertaining to 15,829 adult patients were evaluated. Mean age of the entire cohort was 52.8 years, 8895 (56%) were white, and 10,278 (65%) were male. PCS was the predominant indication for ECMO (39%), followed by CS (37%). SARF accounted for 15% and HT and LT accounted for 3.9% and 5.4%, respectively. Mean LOS and duration of ECMO support were 23.4 days and 5.3 days respectively. Mean hospital charges per hospitalization for the entire cohort were USD 731,914 per patient. Charges per patient pertaining to hospitalizations in which ECMO was used in transplant patients were the highest: USD 1,448,931 and USD 1,574,378 (P = .99) for HT and LT, respectively. Charges were lower for the other indications: PCS USD 798,909, CS USD 655,099, and SARF USD 824,852. Overall mortality for the entire cohort was 55%. PCS and CS (53% vs 58%, P = .34) had similar survival, whereas SARF was 45%, LT was 39% and HT 32%. There were no differences in survival in these latter indications (SARF, LT and HT). The cumulative charges (proportion × hospital charges) reveal that PCS and CS (39% and 37%) account for both the majority of charges as well as the greatest mortality. Conversely, SARF and transplantation accounted for the smaller proportion of charges and the lower mortality. Patients undergoing HT had the longest LOS (51.7 days) and duration on ECMO (15.9 days), followed by LT (35.4 and 8.8 days respectively), and patients with SARF (28.6 and 6.6 respectively). LOS and duration of ECMO for those with PCS were 18.7 days and 4.8 days, respectively. Those on ECMO for CS were hospitalized for 19.7 days and spent an average of 3.8 days on ECMO. Mortality decreased, whereas charges increased in the late era. Conclusions: The use of ECMO is associated with high hospital charges and a wide variation in outcomes. Hospitalizations, in which ECMO is used to support patients with cardiogenic shock (PCS and CS), are individually associated with lower LOS and charges. Cumulatively, however, these account for greater charges and greater mortality. Although mortality may be decreasing, overall charges are increasing with time. These variations may influence reimbursement decisions in value-based healthcare.

KAP1 promotes proliferation and metastatic progression of breast cancer cells.

KAP1 (TRIM28) is a transcriptional regulator in embryonic development that controls stem cell self-renewal, chromatin organization, and the DNA damage response, acting as an essential corepressor for KRAB family zinc finger proteins (KRAB-ZNF). To gain insight into the function of this large gene family, we developed an antibody that recognizes the conserved zinc fingers linker region (ZnFL) in multiple KRAB-ZNF. Here, we report that the expression of many KRAB-ZNF along with active SUMOlyated KAP1 is elevated widely in human breast cancers. KAP1 silencing in breast cancer cells reduced proliferation and inhibited the growth and metastasis of tumor xenografts. Conversely, KAP1 overexpression stimulated cell proliferation and tumor growth. In cells where KAP1 was silenced, we identified multiple downregulated genes linked to tumor progression and metastasis, including EREG/epiregulin, PTGS2/COX2, MMP1, MMP2, and CD44, along with downregulation of multiple KRAB-ZNF proteins. KAP1-dependent stabilization of KRAB-ZNF required direct interactions with KAP1. Together, our results show that KAP1-mediated stimulation of multiple KRAB-ZNF contributes to the growth and metastasis of breast cancer.