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OBJECTIVES: This study aimed to predict blood pressure during CPR using chest compression waveform information obtained from a CPR feedback device. METHODS: Quantitative data including chest compression waveforms from a CPR feedback device and the blood pressure measured by arterial cannulation in patients with cardiac arrest during CPR were used. Forty-one features to predict blood pressure were selected from chest compression waveform and demographic characteristics with neighborhood component analysis algorithm. Optimized Gaussian process regression was used as a machine learning algorithm. RESULTS: A total of 14,619 datasets from 19 patients with cardiac arrest (mean age: 66 ± 13 years, 14 men) were used in the analysis. The model could predict blood pressure with high precision and low bias for almost the whole range of systolic (SBP), diastolic (DBP), and mean arterial blood pressure (MAP). The correlation coefficients (r) between the predicted and actual values were 0.954 (95% confidence interval: 0.951-0.957, p < 0.001) for SBP, 0.926 (95% confidence interval: 0.921-0.931, p < 0.001) for DBP, and 0.958 (95% confidence interval: 0.955-0.961, p < 0.001) for MBP, which all indicated a very good agreement. CONCLUSIONS: Blood pressure generated by chest compressions can be predicted with high accuracy by a machine learning method using chest compression waveform information obtained from a CPR feedback device and the patient's demographic characteristics. Real-time provision of the predicted blood pressure can be used to monitor the quality and efficacy of CPR.
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INTRODUCTION: Distal femur fractures are difficult to successfully treat due to high rates of nonunion. Obesity is an independent prognostic risk factor for nonunion. Advances in finite element analyses (FEAs) have allowed researchers to better understand the performance and behavior of constructs at the bone-implant interface under a variety of conditions. The purpose of this study is to determine the impact of body weight on fracture strain in a lateral locking plate construct for supracondylar femur fractures and whether additional construct rigidity is beneficial to optimize fracture strain in high body mass patients. HYPOTHESIS: We hypothesized that increased loads would produce a higher interfragmentary strain (IFS), which could be decreased by shortening the working length of the construct. MATERIALS AND METHODS: A 3D finite element analysis was performed on two separate femur models with a comminuted supracondylar distal femur fracture fixed with a lateral distal femoral locking plate in bridging mode with Ansys software. Axial forces were varied to recreate the effect of load from normal and high body mass patients. Working length and screw density of the construct were varied for each condition. Measurements of interfragmentary strain and shear motion (SM) were compared. RESULTS: Doubling the axial load from 70kg (control) to 140kg (high body mass) increased the interfragmentary strain by an average of 76% for the three working lengths (3.38%±1.67% to 4.37%±0.88% at the baseline working length (BWL), 1.42%±1.00% to 2.87%±2.02% at the intermediate working length (IWL) and 0.62%±0.22% to 1.22%±0.42% at the short working length (SWL)). On average, decreasing the working length in the 140kg load reduced the mean IFS to within 15% of the mean IFS of the 70kg load at the longer working length (2.87%±2.02% at IWL 140kg versus 3.38%±1.67% at BWL 70kg and 1.22%±0.45% SWL 140kg versus 1.42±1.00% IWL 70kg). DISCUSSION: Increased axial load increases interfragmentary strain in an AO/OTA 33A distal femur fracture fixed with a lateral distal femoral locking plate. Decreasing the working length of the fixation construct in the high body mass model decreased interfragmentary strain. Higher loading conditions reflective of high body mass patients should be considered in studies investigating optimization of fracture strain. LEVEL OF PROOF: V; Finite Element Analysis (FEA).
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BACKGROUND: To increase skin permeability, various transdermal delivery techniques have been developed. However, due to the stratum corneum as a skin barrier, transdermal delivery remains limited. AIMS: In this study, we evaluated efficacy and safety of arc-poration as a novel technique disrupting the stratum corneum. RESULTS: Optical images and histological analysis using reconstituted human skin and porcine skin showed that the treatment of arc-poration created micropores with an average diameter of approximately 100 µm only to the depth of the stratum corneum, but not viable epidermis. In addition, the Franz diffusion cell experiment using reconstituted human skin showed a remarkable increase in permeability following pretreatment with arc-poration. Clinical results clearly demonstrated the enhancement of the skin-improving effect of cosmetics by pretreatment of arc-poration in terms of gloss, hydration, flakiness, texture, tone, tone evenness, and pigmentation of skin, without causing abnormal skin responses. The concentration of ozone and nitrogen oxides generated by arc-poration was below the permissible value for the human body. CONCLUSIONS: Arc-poration can increase skin permeability by creating stratum corneum-specific micropores, which can enhance the skin-improving effect of cosmetics without adverse responses.
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Administración Cutánea , Permeabilidad , Absorción Cutánea , Humanos , Porcinos , Absorción Cutánea/efectos de los fármacos , Animales , Adulto , Femenino , Piel/metabolismo , Piel/efectos de los fármacos , Epidermis/metabolismo , Epidermis/efectos de los fármacos , Cosméticos/administración & dosificación , Cosméticos/farmacocinética , Cosméticos/química , Adulto JovenRESUMEN
Primary graft dysfunction (PGD) is a leading cause of early morbidity and mortality following heart transplantation (HT). We sought to determine the association between pretransplant human leukocyte antigen (HLA) sensitization, as measured using the calculated panel reactive antibody (cPRA) value, and the risk of PGD. METHODS: Consecutive adult HT recipients (n = 596) from 1/2015 to 12/2019 at 2 US centers were included. Severity of PGD was based on the 2014 International Society for Heart and Lung Transplantation consensus statement. For each recipient, unacceptable HLA antigens were obtained and locus-specific cPRA (cPRA-LS) and pre-HT donor-specific antibodies (DSA) were assessed. RESULTS: Univariable logistic modeling showed that peak cPRA-LS for all loci and HLA-A was associated with increased severity of PGD as an ordinal variable (all loci: OR 1.78, 95% CI: 1.01-1.14, p = 0.025, HLA-A: OR 1.14, 95% CI: 1.03-1.26, p = 0.011). Multivariable analysis showed peak cPRA-LS for HLA-A, recipient beta-blocker use, total ischemic time, donor age, prior cardiac surgery, and United Network for Organ Sharing status 1 or 2 were associated with increased severity of PGD. The presence of DSA to HLA-B was associated with trend toward increased risk of mild-to-moderate PGD (OR 2.56, 95% CI: 0.99-6.63, p = 0.053), but DSA to other HLA loci was not associated with PGD. CONCLUSIONS: Sensitization for all HLA loci, and specifically HLA-A, is associated with an increased severity of PGD. These factors should be included in pre-HT risk stratification to minimize the risk of PGD.
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Trasplante de Corazón , Disfunción Primaria del Injerto , Adulto , Humanos , Disfunción Primaria del Injerto/epidemiología , Disfunción Primaria del Injerto/etiología , Trasplante de Corazón/efectos adversos , Antígenos HLA , Donantes de Tejidos , Anticuerpos , Antígenos HLA-A , Estudios RetrospectivosRESUMEN
Semiconductor nanocrystals are promising optoelectronic materials. Understanding their anisotropic photoluminescence is fundamental for developing quantum-dot-based devices such as light-emitting diodes, solar cells, and polarized single-photon sources. In this study, we experimentally and theoretically investigate the photoluminescence anisotropy of CdSe semiconductor nanocrystals with various shapes, including plates, rods, and spheres, with either wurtzite or zincblende structures. We use defocused wide-field microscopy to visualize the emission dipole orientation and find that spheres, rods, and plates exhibit the optical properties of 2D, 1D, and 2D emission dipoles, respectively. We rationalize the seemingly counterintuitive observation that despite having similar aspect ratios (width/length), rods and long nanoplatelets exhibit different defocused emission patterns by considering valence band structures calculated using multiband effective mass theory and the dielectric effect. The principles are extended to provide general relationships that can be used to tune the emission dipole orientation for different materials, crystalline structures, and shapes.
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BACKGROUND: We investigated associations between primary graft dysfunction (PGD) and development of acute cellular rejection (ACR), de novo donor-specific antibodies (DSAs), and cardiac allograft vasculopathy (CAV) after heart transplantation (HT). METHODS: A total of 381 consecutive adult HT patients from January 2015 to July 2020 at a single center were retrospectively analyzed. The primary outcome was incidence of treated ACR (International Society for Heart and Lung Transplantation grade 2R or 3R) and de novo DSA (mean fluorescence intensity >500) within 1 y post-HT. Secondary outcomes included median gene expression profiling score and donor-derived cell-free DNA level within 1 y and incidence of cardiac allograft vasculopathy (CAV) within 3 y post-HT. RESULTS: When adjusted for death as a competing risk, the estimated cumulative incidence of ACR (PGD 0.13 versus no PGD 0.21; P = 0.28), median gene expression profiling score (30 [interquartile range, 25-32] versus 30 [interquartile range, 25-33]; P = 0.34), and median donor-derived cell-free DNA levels was similar in patients with and without PGD. After adjusting for death as a competing risk, estimated cumulative incidence of de novo DSA within 1 y post-HT in patients with PGD was similar to those without PGD (0.29 versus 0.26; P = 0.10) with a similar DSA profile based on HLA loci. There was increased incidence of CAV in patients with PGD compared with patients without PGD (52.6% versus 24.8%; P = 0.01) within the first 3 y post-HT. CONCLUSIONS: During the first year after HT, patients with PGD had a similar incidence of ACR and development of de novo DSA, but a higher incidence of CAV when compared with patients without PGD.
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Cardiopatías , Trasplante de Corazón , Disfunción Primaria del Injerto , Adulto , Humanos , Estudios Retrospectivos , Disfunción Primaria del Injerto/diagnóstico , Disfunción Primaria del Injerto/epidemiología , Disfunción Primaria del Injerto/etiología , Antígenos HLA , Trasplante de Corazón/efectos adversos , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/epidemiología , AloinjertosRESUMEN
We report an unexpected enhancement of photoluminescence (PL) in CdSe-based core/shell nanoplatelets (NPLs) upon electrochemical hole injection. Moderate hole doping densities induce an enhancement of more than 50% in PL intensity. This is accompanied by a narrowing and blue-shift of the PL spectrum. Simultaneous, time-resolved PL experiments reveal a slower luminescence decay. Such hole-induced PL brightening in NPLs is in stark contrast to the usual observation of PL quenching of CdSe-based quantum dots following hole injection. We propose that hole injection removes surface traps responsible for the formation of negative trions, thereby blocking nonradiative Auger processes. Continuous photoexcitation causes the enhanced PL intensity to decrease back to its initial level, indicating that photocharging is a key step leading to loss of PL luminescence during normal aging. Modulating the potential can be used to reversibly enhance or quench the PL, which enables electro-optical switching.
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BACKGROUND: Primary graft dysfunction (PGD) is a major cause of early mortality following heart transplant (HT). Donor risk factors for the development of PGD are incompletely characterized. Donor management goals (DMG) are predefined critical care endpoints used to optimize donors. We evaluated the relationship between DMGs as well as non-DMG parameters, and the development of PGD after HT. METHODS: A cohort of HT recipients from 2 transplant centers between 1/1/12 and 12/31/19 was linked to their respective donors in the United Network for Organ Sharing (UNOS) DMG Registry (n = 1,079). PGD was defined according to modified ISHLT criteria. Variables were subject to univariate and multivariable multinomial modeling with development of mild/moderate or severe PGD as the outcome variable. A second multicenter cohort of 4,010 donors from the DMG Registry was used for validation. RESULTS: Mild/moderate and severe PGD occurred in 15% and 6% of the cohort. Multivariable modeling revealed 6 variables independently associated with mild/moderate and 6 associated with severe PGD, respectively. Recipient use of amiodarone plus beta-blocker, recipient mechanical circulatory support, donor age, donor fraction of inspired oxygen (FiO2), and donor creatinine increased risk whereas predicted heart mass ratio decreased risk of severe PGD. We found that donor age and FiO2 ≥ 40% were associated with an increased risk of death within 90 days post-transplant in a multicenter cohort. CONCLUSIONS: Donor hyperoxia at heart recovery is a novel risk factor for severe primary graft dysfunction and early recipient death. These results suggest that excessive oxygen supplementation should be minimized during donor management.
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Trasplante de Corazón , Hiperoxia , Disfunción Primaria del Injerto , Humanos , Disfunción Primaria del Injerto/epidemiología , Disfunción Primaria del Injerto/etiología , Hiperoxia/complicaciones , Factores de Riesgo , Trasplante de Corazón/efectos adversos , Donantes de Tejidos , Oxígeno , Estudios RetrospectivosRESUMEN
BACKGROUND: Donor-derived cell free DNA (dd-cfDNA) and gene expression profiling (GEP) offer noninvasive alternatives to rejection surveillance after heart transplantation; however, there is little evidence on the paired use of GEP and dd-cfDNA for rejection surveillance. METHODS: A single center, retrospective analysis of adult heart transplant recipients. A GEP cohort, transplanted from January 1, 2015 through December 31, 2017 and eligible for rejection surveillance with GEP was compared to a paired testing cohort, transplanted July 1, 2018 through June 30, 2020, with surveillance from both dd-cfDNA and GEP. The primary outcomes were survival and rejection-free survival at 1 year post-transplant. RESULTS: In total 159 patients were included, 95 in the GEP and 64 in the paired testing group. There were no differences in baseline characteristics, except for less use of induction in the paired testing group (65.6%) compared to the GEP group (98.9%), P < .01. At 1-year, there were no differences between the paired testing and GEP groups in survival (98.4% vs. 94.7%, P = .23) or rejection-free survival (81.3% vs. 73.7% P = .28). CONCLUSIONS: Compared to post-transplant rejection surveillance with GEP alone, pairing dd-cfDNA and GEP testing was associated with similar survival and rejection-free survival at 1 year while requiring significantly fewer biopsies.
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Ácidos Nucleicos Libres de Células , Trasplante de Corazón , Adulto , Humanos , Estudios Retrospectivos , Ácidos Nucleicos Libres de Células/genética , Trasplante de Corazón/efectos adversos , Perfilación de la Expresión Génica , Donantes de TejidosRESUMEN
Background: Emerging evidence is revealing the impact of the gut microbiome on hematopoietic and solid organ transplantation. Prior studies postulate that this influence is mediated by bioactive metabolites produced by gut-dwelling commensal bacteria. However, gut microbial metabolite production has not previously been measured among heart transplant (HT) recipients. Methods: In order to investigate the potential influence of the gut microbiome and its metabolites on HT, we analyzed the composition and metabolite production of the fecal microbiome among 48 HT recipients at the time of HT. Results: Compared to 20 healthy donors, HT recipients have significantly reduced alpha, i.e. within-sample, microbiota diversity, with significantly lower abundances of key anaerobic commensal bacteria and higher abundances of potentially pathogenic taxa that have been correlated with adverse outcomes in other forms of transplantation. HT recipients have a wide range of microbiota-derived fecal metabolite concentrations, with significantly reduced levels of immune modulatory metabolites such as short chain fatty acids and secondary bile acids compared to healthy donors. These differences were likely due to disease severity and prior antibiotic exposures but were not explained by other demographic or clinical factors. Conclusions: Key potentially immune modulatory gut microbial metabolites are quantifiable and significantly reduced among HT recipients compared to healthy donors. Further study is needed to understand whether this wide range of gut microbial dysbiosis and metabolite alterations impact clinical outcomes and if they can be used as predictive biomarkers or manipulated to improve transplant outcomes.
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BACKGROUND: We evaluated post-heart transplant (HTx) outcomes after use of higher-risk donor hearts for candidates supported with pre-HTx mechanical circulatory support (MCS). METHODS: In this retrospective analysis of the national United Network for Organ Sharing registry, a total of 9,915 adult candidates on MCS underwent HTx from January 1, 2010 to March 31, 2019. Multi-organ, re-transplant, and congenital heart disease patients were excluded. Higher-risk donor organs met at least one of the following criteria: left ventricular ejection fraction <50%, donor to recipient predicted heart mass ratio <0.86, donor age >55 years, or ischemic time >4 hours. Primary outcome was 1 year post-transplant survival. RESULTS: Among HTx recipients, 3688 (37.2%) received higher-risk donor hearts. Candidates supported with pre-HTx extracorporeal membrane oxygenation or biventricular assist device (n = 374, 3.8%) who received higher-risk donor hearts had comparable 1 year survival (HR: 1.14, 95% CI: [0.67-1.93], p = 0.64) to recipients of standard-risk donor hearts, when adjusted for recipient age and sex. In candidates supported with intra-aortic balloon pump (n = 1391, 14.6%), transplantation of higher-risk donor hearts did not adversely affect 1 year survival (HR: 0.80, 95% CI: [0.52-1.22], p = 0.30). Patients on durable left ventricular assist devices (LVAD) who received higher-risk donor hearts had comparable 1 year survival to continued LVAD support on the waitlist, but mortality was increased compared to those who received standard-risk donor hearts (HR: 1.37, 95% CI: [1.11-1.70], p = 0.004). CONCLUSIONS: Patients requiring pre-HTx temporary MCS who received higher-risk donor hearts had comparable 1 year post-transplant survival to those who received standard-risk donor hearts. Stable patients on durable LVADs may benefit from waiting for standard-risk donor hearts.
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Oxigenación por Membrana Extracorpórea/métodos , Insuficiencia Cardíaca/terapia , Trasplante de Corazón/métodos , Corazón Auxiliar , Contrapulsador Intraaórtico/métodos , Cuidados Preoperatorios/métodos , Donantes de Tejidos/estadística & datos numéricos , Adulto , Femenino , Supervivencia de Injerto , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Volumen Sistólico/fisiología , Factores de Tiempo , Estados Unidos/epidemiología , Función Ventricular Izquierda , Listas de Espera/mortalidadRESUMEN
PURPOSE: Diabetes mellitus (DM) is common among recipients of heart transplantation (HTx) but its impact on clinical outcomes is unclear. We evaluated the associations between pretransplant DM and posttransplant DM (PTDM) and outcomes among adults receiving HTx at a single center. METHODS: We performed a retrospective study (range 01/2008 - 07/2018), n = 244. The primary outcome was survival; secondary outcomes included acute rejection, cardiac allograft vasculopathy, infection requiring hospitalization, macrovascular events, and dialysis initiation post-transplant. Comparisons were performed using Kaplan-Meier and multivariable Cox regression analyses. RESULTS: Pretransplant DM was present in 75 (30.7%) patients and was associated with a higher risk for infection requiring hospitalization (p < 0.05), but not with survival or other outcomes. Among the 144 patients without pretransplant DM surviving to 1 year, 29 (20.1%) were diagnosed with PTDM at the 1-year follow-up. After multivariable adjustment, PTDM diagnosis at 1-year remained associated with worse subsequent survival (hazard ratio 2.72, 95% confidence interval 1.03-7.16). Predictors of PTDM at 1-year included cytomegalovirus seropositivity and higher prednisone dose (> 5 mg/day) at 1-year follow-up. CONCLUSIONS: Compared to HTx recipients without baseline DM, those with baseline DM have a higher risk for infections requiring hospitalization, and those who develop DM after HTx have worse survival.
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Diabetes Mellitus , Trasplante de Corazón , Trasplante de Riñón , Adulto , Diabetes Mellitus/etiología , Trasplante de Corazón/efectos adversos , Humanos , Complicaciones Posoperatorias , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Recent studies have shown an increased incidence of primary graft dysfunction (PGD) in patients treated with amiodarone prior to orthotopic heart transplant (OHT). We hypothesized that discontinuation of amiodarone before OHT may lower the incidence of severe PGD. METHODS: This was a single-center retrospective study of 381 adult OHT recipients between January 2010 and June 2017. Within 6 months prior to OHT, 197 did not receive amiodarone (Group 1), 142 continued amiodarone to OHT (Group 2), and 42 had amiodarone treatment discontinued before OHT (Group 3). RESULTS: 53 (13.9%) participants developed severe PGD, 13 (6.6%) of which were in Group 1, 36 (25.4%) were in Group 2, and 4 (9.5%) were in Group 3 (P < .001). Multivariable analysis revealed continued amiodarone treatment to OHT (Group 2; OR, 3.70; 95% CI, 1.26-10.88; P = .018) to be an independent risk factor for the development of severe PGD when Group 1 served as the reference group. Moreover, patients in Group 3 had no difference in the risk of severe PGD (OR = 0.416, 95% CI = 0.08-2.15; P = .296). CONCLUSION: We found that discontinuing amiodarone treatment prior to OHT resulted a lower incidence of severe PGD.
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Amiodarona , Trasplante de Corazón , Disfunción Primaria del Injerto , Adulto , Trasplante de Corazón/efectos adversos , Humanos , Incidencia , Disfunción Primaria del Injerto/tratamiento farmacológico , Disfunción Primaria del Injerto/epidemiología , Disfunción Primaria del Injerto/etiología , Estudios RetrospectivosRESUMEN
BACKGROUND: Although extremely high pulmonary vascular resistance (PVR) is a relative contraindication for heart transplantation (HTx), recent data with continuous-flow left ventricular assist devices (LVADs) indicate HTx outcomes may be different when high PVR is managed with an LVAD. This study clarifies the contemporary association between PVR at HTx and posttransplant survival in LVAD vs non-LVAD cohorts. METHODS: We reviewed the United Network for Organ Sharing registry for adults who received a transplant from 2008 to 2015. In those with continuous-flow LVADs and those with no VADs at HTx, (non-VAD), we grouped patients by low PVR (PVR <3), intermediate PVR (PVR 3 to <6), and high PVR (PVR ≥6) groups. Adjusted hazard ratios (aHRs) for death after HTx were calculated by Cox regression. RESULTS: The non-LVAD cohort included 6270 patients (4385 in low, 1643 in intermediate, and 242 in high PVR), and the LVAD cohort included 4111 patients (3227 in low, 798 in intermediate, and 86 in high PVR). The high PVR LVAD group had the worst survival, which was not significant, likely to low power (P = .300). The aHR for death in non-LVAD was 1.047 (95% confidence interval, 1.010-1.088) and in LVAD was 1.063 (95% confidence interval, 1.010-1.119). Cubic spline analysis demonstrated nonlinear associations between PVR and the aHR, especially in the LVAD cohort. CONCLUSIONS: There was no significant evidence to conclude the effect of pretransplant PVR on posttransplant survival is higher in LVAD vs non-LVAD patients, based on analysis of the United Network for Organ Sharing database. However, further investigations are indicated to clarify HTx candidacy in those with extremely high PVR even after LVAD.
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Insuficiencia Cardíaca/terapia , Trasplante de Corazón , Corazón Auxiliar , Hipertensión Pulmonar/complicaciones , Adulto , Estudios de Cohortes , Femenino , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/mortalidad , Humanos , Hipertensión Pulmonar/mortalidad , Hipertensión Pulmonar/terapia , Masculino , Persona de Mediana Edad , Selección de Paciente , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: The purpose of this study is to evaluate the utility of vasoactive-inotropic score (VIS) in predicting outcomes after left ventricular assist device (LVAD) implantation and explore possible mechanisms of post-operative hemodynamic instability. METHODS: Retrospective review was performed in 418 consecutive patients with LVAD implantation. VIS was calculated as dopamineâ¯+â¯dobutamineâ¯+â¯10â¯×â¯milrinoneâ¯+â¯100â¯×â¯epinephrineâ¯+â¯100â¯×â¯norepinephrine (all µg/kg/min)â¯+â¯10000â¯×â¯vasopressin (U/kg/min) after initial stabilization in the operating room and upon arrival at the intensive care unit. The primary outcome was in-hospital mortality. The secondary outcomes were a composite of in-hospital mortality, delayed right ventricular assist device (RVAD) implantation, and continuous renal replacement therapy. The pre-operative biomarkers of inflammation, oxidative stress, endotoxemia and gut-derived metabolite trimethylamine-N-oxide (TMAO) were measured in a subset of 61 patients. RESULTS: Median VIS was 20.0 (interquartile range 13.3-27.9). VIS was an independent predictor of in-hospital mortality (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.03-1.09, p < 0.001) and composite outcome (OR 1.03, 95% CI 1.01-1.06, pâ¯=â¯0.008). In-hospital mortality increased for each VIS quartile (0% vs 3.9% vs 7.6% vs 12.3%, pâ¯=â¯0.002). VIS was superior to other established LVAD risk models as a predictor of in-hospital mortality (area under the curve 0.73, 95% CI 0.64-0.82). The optimal cut-off point for VIS as a predictor of in-hospital mortality was 20. Pre-operative hemoglobin level was the only independent predictor of VIS ≥ 20 (pâ¯=â¯0.003). Patients with a high VIS were more likely to have elevated TMAO pre-operatively (53.6% vs 25.8%, pâ¯=â¯0.03). CONCLUSIONS: A high post-operative VIS is associated with adverse in-hospital outcomes and is a better predictor of in-hospital mortality compared with existing LVAD risk models. Whether early hemodynamic stabilization using RVAD may benefit patients with a high VIS remains to be investigated.
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Cardiotónicos/farmacología , Insuficiencia Cardíaca/cirugía , Corazón Auxiliar , Hemodinámica , Complicaciones Posoperatorias/diagnóstico , Vasoconstrictores/farmacología , Adulto , Anciano , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/fisiopatología , Valor Predictivo de las Pruebas , Pronóstico , Estudios RetrospectivosRESUMEN
Nuclear factor of activated T cells (NFATc1-c4), a family of transcription factors, is involved in many biological processes by regulating various downstream target genes. However, their role in cancer progression remains controversial. We here report that NFATc3 is the dominant isoform of NFAT in human oral epithelial cells, and its expression was increased in a stepwise manner during the progression of oral/oropharyngeal squamous cell carcinoma (OSCC). More importantly, NFATc3 was highly enriched in self-renewing cancer stem-like cells (CSCs) of OSCC. Increased expression of NFATc3 was required for the maintenance of CSC self-renewal, as NFATc3 inhibition suppressed tumor sphere formation in OSCC cells. Conversely, ectopic NFATc3 expression in non-tumorigenic immortalized oral epithelial cells resulted in the acquisition of self-renewal and increase in CSC phenotype, such as enhanced ALDH1HIGH cell population, mobility and drug resistance, indicating the functional role of NFATc3 in the maintenance of CSC phenotype. NFATc3 expression also converted the non-tumorigenic oral epithelial cells to malignant phenotypes. Mechanistic investigations further reveal that NFATc3 binds to the promoter of OCT4, a stemness transcription factor, for its activation, thereby promoting CSC phenotype. Moreover, suppression of OCT4 abrogated CSC phenotype in the cell with ectopic NFATc3 overexpression and OSCC, and ectopic OCT4 expression sufficiently induced CSC phenotype. Our study indicates that NFATc3 plays an important role in the maintenance of cancer stemness and OSCC progression via novel NFATc3-OCT4 axis, suggesting that this axis may be a potential therapeutic target for OSCC CSCs.
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BACKGROUND: Outcomes have improved in patients bridged to heart transplant on contemporary continuous-flow ventricular assist devices over the past decade. We evaluated mechanical circulatory support as a means to bridge patients to cardiac retransplantation. METHODS: We retrospectively reviewed 464 patients who underwent cardiac retransplant from the United Network for Organ Sharing database between January 2006 and November 2016. Pre- and post-transplant data were compared between patients bridged to retransplant with mechanical circulatory support (n = 81) and those without mechanical circulatory support (n = 383). RESULTS: The mean ages for the patients in the mechanical circulatory support and nonmechanical circulatory support cohorts were 41.2 ± 16 years and 42.1 ± 15.7 years, respectively (P = .64). Patients bridged with mechanical circulatory support were placed on extracorporeal membrane oxygenation (n = 29, 35.8%), a total artificial heart (n = 13, 16.0%), or a temporary or durable ventricular assist device (n = 39, 48.1%). Twelve patients (14.8%) were placed on a second device before retransplant. Thirty-nine percent of the mechanical circulatory support group were indicated for listing because of primary graft dysfunction or acute rejection versus 6% of the nonmechanical circulatory support group (P < .01). Likewise, 30% of patients in the mechanical circulatory support group were listed for cardiac allograft vasculopathy compared with 59% of the nonmechanical circulatory support group (P < .01). Thirty-day mortality was significantly higher in the mechanical circulatory support group (17.8% vs 4.8%, P < .01). However, patients who were bridged with a ventricular assist device or total artificial heart had comparable midterm outcomes to the nonmechanical circulatory support group. CONCLUSIONS: Patients who require mechanical circulatory support bridge to retransplantation belong to a high-risk cohort. Comparable midterm outcomes to the nonmechanical circulatory support cohort were demonstrated when patients' conditions allow for bridge with a ventricular assist device or total artificial heart. Bridging to retransplantation with extracorporeal membrane oxygenation remains a relative contraindication.