Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 19 de 19
Filtrar
1.
Ann Surg ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38994583

RESUMO

OBJECTIVE: This study aimed to evaluate the association of surgeon self-reported gender on clinical outcomes in contemporary U.S. surgical practice. SUMMARY BACKGROUND DATA: Previous research has suggested that there are potentially improved surgical outcomes for female surgeons, yet the underlying causal path for this association remains unclear. METHODS: Using the Vizient® Clinical Database(2016-2021), 39 operations categorized by the CDC's National Healthcare Safety Network were analyzed. Surgeon self-reported gender was the primary exposure. The primary outcome was a composite of in-hospital death, complications, and/or 30-day readmission. Multivariable logistic regression and propensity score matching was used for risk adjustment. RESULTS: The analysis included 4,882,784 patients operated on by 11,955 female surgeons(33% of surgeons, performing 21% of procedures) and 23,799 male surgeons(67% of surgeons, performing 79% of procedures). Female surgeons were younger(45±9 vs. males-53±11 y;P<0.0001) and had lower operative volumes. Unadjusted incidence of the primary outcome was 13.6%(10.7%-female surgeons, 14.3%-male surgeons;P<0.0001). After propensity matching, the primary outcome occurred in 13.0% of patients(12.9%-female, 13.0%-male; OR[M vs. F]=1.02, 95%CI 1.01-1.03;P=.001), with female surgeons having small statistical associations with lower mortality and complication rates but not readmissions. Procedure-specific analyses revealed inconsistent or no surgeon-gender associations. CONCLUSIONS: In the largest analysis to date, surgeon self-reported gender had a small statistical, clinically marginal correlation with postoperative outcomes. The variation across surgical specialties and procedures suggests that the association with surgeon gender is unlikely causal for the observed differences in outcomes. Patients should be reassured that surgeon gender alone does not have a clinically meaningful impact on their outcome.

2.
J Vasc Surg ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38851467

RESUMO

BACKGROUND: Machine learning techniques have shown excellent performance in three-dimensional medical image analysis, but have not been applied to acute uncomplicated type B aortic dissection (auTBAD) using Society for Vascular Surgery (SVS) and Society of Thoracic Surgeons (STS)-defined aortic zones. The purpose of this study was to establish a trained, automatic machine learning aortic zone segmentation model to facilitate performance of an aortic zone volumetric comparison between patients with auTBAD based on the rate of aortic growth. METHODS: Patients with auTBAD and serial imaging were identified. For each patient, imaging characteristics from two computed tomography (CT) scans were analyzed: (1) the baseline CT angiography (CTA) at the index admission and (2) either the most recent surveillance CTA or the most recent CTA before an aortic intervention. Patients were stratified into two comparative groups based on aortic growth: rapid growth (diameter increase of ≥5 mm/year) and no or slow growth (diameter increase of <5 mm/year). Deidentified images were imported into an open source software package for medical image analysis and images were annotated based on SVS/STS criteria for aortic zones. Our model was trained using four-fold cross-validation. The segmentation output was used to calculate aortic zone volumes from each imaging study. RESULTS: Of 59 patients identified for inclusion, rapid growth was observed in 33 patients (56%) and no or slow growth was observed in 26 patients (44%). There were no differences in baseline demographics, comorbidities, admission mean arterial pressure, number of discharge antihypertensives, or high-risk imaging characteristics between groups (P > .05 for all). Median duration between baseline and interval CT was 1.07 years (interquartile range [IQR], 0.38-2.57). Postdischarge aortic intervention was performed in 13 patients (22%) at a mean of 1.5 ± 1.2 years, with no difference between the groups (P > .05). Among all patients, the largest relative percent increases in zone volumes over time were found in zone 4 (13.9%; IQR, -6.82 to 35.1) and zone 5 (13.4%; IQR, -7.78 to 37.9). There were no differences in baseline zone volumes between groups (P > .05 for all). The average Dice coefficient, a performance measure of the model output, was 0.73. Performance was best in zone 5 (0.84) and zone 9 (0.91). CONCLUSIONS: We describe an automatic deep learning segmentation model incorporating SVS-defined aortic zones. The open source, trained model demonstrates concordance to the manually segmented aortas with the strongest performance in zones 5 and 9, providing a framework for further clinical applications. In our limited sample, there were no differences in baseline aortic zone volumes between patients with rapid growth and patients with no or slow growth.

3.
J Vasc Surg ; 80(2): 413-421.e3, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38552885

RESUMO

INTRODUCTION: Clinical practice guidelines have recommended an endovascular-first approach (ENDO) for the management of patients with chronic mesenteric ischemia (CMI), whereas an open mesenteric bypass (OMB) is proposed for subjects deemed to be poor ENDO candidates. However, the impact of a previous failed endovascular or open mesenteric reconstruction on a subsequent OMB is unknown. Accordingly, this study was designed to examine the results of a remedial OMB (R-OMB) after a failed ENDO or a primary OMB (P-OMB) for patients with recurrent CMI. METHODS: All patients who underwent an OMB from 2002 to 2022 at the University of Florida were reviewed. Outcomes after an R-OMB (ie, history of a failed ENDO or P-OMB) and P-OMB were compared. The primary end point was 30-day mortality, whereas secondary outcomes included complications, reintervention, and survival. The Kaplan-Meier methodology was used to estimate freedom from reintervention and all-cause mortality, whereas multivariable Cox proportional hazards modeling identified predictors of death. RESULTS: A total of 145 OMB procedures (R-OMB, n = 48 [33%]; P-OMB, n = 97 [67%]) were analyzed. A majority of R-OMB operations were performed for a failed stent (prior ENDO, n = 39 [81%]; prior OMB, n = 9 [19%]). R-OMB patients were generally younger (66 ± 9 years vs P-OMB, 69 ± 11 years; P = .09) and had lower incidence of smoking exposure (29% vs P-OMB, 48%; P = .07); however, there were no other differences in demographics or comorbidities. R-OMB was associated with less intraoperative transfusion (0.6 units vs P-OMB, 1.4 units; P = .01), but there were no differences in conduit choice or bypass configuration.The overall 30-day mortality and complication rates were 7% (n = 10/145) and 53% (n = 77/145), respectively, with no difference between the groups. Notably, R-OMB had decreased cardiac (6% vs P-OMB, 21%; P < .01) and bleeding complication rates (2% vs P-OMB, 15%; P = .01). The freedom from reintervention (1 and 5 years: R-OMB: 95% ± 4%, 83% ± 9% vs P-OMB: 97% ± 2%, 93% ± 5%, respectively; log-rank P = .21) and survival (1 and 5 years: R-OMB: 82% ± 6%, 68% ± 9% vs P-OMB: 84% ± 4%, 66% ± 7%; P = .91) were similar. Independent predictors of all-cause mortality included new postoperative hemodialysis requirement (hazard ratio [HR], 7.4, 95% confidence interval [CI], 3.1-17.3; P < .001), pulmonary (HR, 2.7, 95% CI, 1.4-5.3; P = .004) and cardiac (HR, 2.4, 95% CI, 1.1-5.1; P = .04) complications, and female sex (HR, 2.1, 95% CI, 1.03-4.8; P = .04). Notably, R-OMB was not a predictor of death. CONCLUSIONS: The perioperative and longer-term outcomes for a remedial OMB after a failed intraluminal stent or previous open bypass appear to be comparable to a P-OMB. These findings support the recently updated clinical practice guideline recommendations for an endovascular-first approach to treating recurrent CMI due to the significant perioperative complication risk of OMB. However, among the subset of patients deemed ineligible for endoluminal reconstruction after failed mesenteric revascularization, R-OMB results appear to be acceptable and highlight the utility of this strategy in selected patients.


Assuntos
Procedimentos Endovasculares , Isquemia Mesentérica , Falha de Tratamento , Humanos , Masculino , Feminino , Isquemia Mesentérica/cirurgia , Isquemia Mesentérica/mortalidade , Idoso , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Estudos Retrospectivos , Pessoa de Meia-Idade , Doença Crônica , Fatores de Risco , Fatores de Tempo , Medição de Risco , Reoperação , Oclusão Vascular Mesentérica/cirurgia , Oclusão Vascular Mesentérica/mortalidade , Oclusão Vascular Mesentérica/diagnóstico por imagem , Oclusão Vascular Mesentérica/fisiopatologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Recidiva , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Implante de Prótese Vascular/instrumentação , Florida , Resultado do Tratamento
4.
Ann Vasc Surg ; 98: 342-349, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37423327

RESUMO

BACKGROUND: Postoperative acute kidney injury (AKI) is common after major surgery and is associated with increased morbidity, mortality, and cost. Additionally, there are recent studies demonstrating that time to renal recovery may have a substantial impact on clinical outcomes. We hypothesized that patients with delayed renal recovery after major vascular surgery will have increased complications, mortality, and hospital cost. METHODS: A single-center retrospective cohort of patients undergoing nonemergent major vascular surgery between 6/1/2014 and 10/1/2020 was analyzed. Development of postoperative AKI (defined using Kidney Disease Improving Global Outcomes (KDIGO) criteria: >50% or > 0.3 mg/dl absolute increase in serum creatinine relative to reference after surgery and before discharge) was evaluated. Patients were divided into 3 groups: no AKI, rapidly reversed AKI (<48 hours), and persistent AKI (≥48 hours). Multivariable generalized linear models were used to evaluate the association between AKI groups and postoperative complications, 90-day mortality, and hospital cost. RESULTS: A total of 1,881 patients undergoing 1,980 vascular procedures were included. Thirty five percent of patients developed postoperative AKI. Patients with persistent AKI had longer intensive care unit and hospital stays, as well as more mechanical ventilation days. In multivariable logistic regression analysis, persistent AKI was a major predictor of 90-day mortality (odds ratio 4.1, 95% confidence interval 2.4-7.1). Adjusted average cost was higher for patients with any type of AKI. The incremental cost of having any AKI ranged from $3,700 to $9,100, even after adjustment for comorbidities and other postoperative complications. The adjusted average cost for patients stratified by type of AKI was higher among patients with persistent AKI compared to those with no or rapidly reversed AKI. CONCLUSIONS: Persistent AKI after vascular surgery is associated with increased complications, mortality, and cost. Strategies to prevent and aggressively treat AKI, specifically persistent AKI, in the perioperative setting are imperative to optimize care for this population.


Assuntos
Injúria Renal Aguda , Custos Hospitalares , Humanos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Complicações Pós-Operatórias , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Mortalidade Hospitalar
5.
Ann Vasc Surg ; 106: 99-107, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38574807

RESUMO

BACKGROUND: Recently the Society for Vascular Surgery (SVS) and Society for Thoracic Surgeons (STS) published contemporary guidelines clearly defining complicated versus uncomplicated acute type B aortic dissections (TBADs) with an additional high-risk grouping. Few studies have evaluated outcomes associated with "high-risk" TBADs. The objective of this study was to assess differences in demographics, clinical presentation, symptom onset, and outcomes in high-risk patients that underwent either thoracic endovascular aortic repair (TEVAR) or best medical management for acute TBAD compared to those with complicated and uncomplicated acute TBAD. METHODS: Patients admitted with acute TBADs from a single academic medical center from October 2011 to March 2020 were analyzed. Per the STS/SVS 2020 guidelines, high risk was defined as refractory pain/hypertension, bloody pleural effusion, aortic diameter >4 cm, false lumen diameter >22 mm, radiographic malperfusion, and early readmission, and complicated was defined as ruptured/malperfusion presentation. Uncomplicated patients were those without malperfusion/rupture and without high-risk features. The primary end-point was inpatient mortality. Secondary end-points included complications, reintervention, and survival. RESULTS: Of the 159 patients identified with acute TBAD, 63 (40%) met the high-risk criteria. In the high-risk cohort, 38 (60%) underwent TEVAR (HR-TEVAR), with refractory pain as the most common indication, while 25 (40%) were managed medically (HR-medical). Malperfusion or rupture was present in 63 (40%) patients (complicated TBAD (C-TBAD)), all of whom underwent TEVAR. An additional 33 patients had no high-risk features and were all managed medically (uncomplicated TBAD). There were no differences in age, body mass index, and race between groups. Among the 4 groups, there were variable distributions in sex, insurance status, and incidence of several baseline comorbidities including congestive heart failure, chronic obstructive pulmonary disease, and renal dysfunction (P < 0.05 for all). C-TBAD had increased length of stay (12, interquartile range [IQR] 9-22) compared to HR-TEVAR (11.5, IQR 7-15), HR-medical (6, IQR 5-8), and uncomplicated TBAD (7, IQR 5-10) (P < 0.01). C-TBAD had decreased days from admission to repair (0, IQR 0-2) compared to HR-TEVAR (3.5, IQR 1-8) (P < 0.01). C-TBAD patients had worse 3-year survival compared to other groups (log-rank P < 0.01), although when in-hospital mortality was excluded, survival was similar among groups (P = 0.37). Of patients initially managed medically, outpatient TEVAR was performed in 6 (24%) HR-medical and 4 (12%) uncomplicated patients, with no difference between rate of intervention between groups (P = 0.22). CONCLUSIONS: High-risk features, as defined in updated SVS/STS guidelines, are common in patients presenting with acute TBAD. High-risk patients had acceptable outcomes when managed either surgically or medically. High-risk patients that underwent TEVAR had improved perioperative outcomes and mortality compared to those undergoing TEVAR for C-TBAD, a finding which may help guide preoperative risk stratification and patient counseling.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Procedimentos Endovasculares , Mortalidade Hospitalar , Humanos , Dissecção Aórtica/cirurgia , Dissecção Aórtica/mortalidade , Dissecção Aórtica/diagnóstico por imagem , Masculino , Feminino , Fatores de Risco , Procedimentos Endovasculares/mortalidade , Procedimentos Endovasculares/efeitos adversos , Resultado do Tratamento , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Tempo , Implante de Prótese Vascular/mortalidade , Implante de Prótese Vascular/efeitos adversos , Doença Aguda , Aneurisma da Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/mortalidade , Aneurisma da Aorta Torácica/diagnóstico por imagem , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/etiologia , Bases de Dados Factuais
6.
J Am Coll Surg ; 238(4): 404-413, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38224109

RESUMO

BACKGROUND: Variability in operating room supply cost is a modifiable cause of suboptimal resource use and low value of care (outcomes vs cost). This study describes implementation of a quality improvement intervention to decrease operating room supply costs. STUDY DESIGN: An automated electronic health record data pipeline harmonized operating room supply cost data with patient and case characteristics and outcomes. For inpatient procedures, predicted mortality and length of stay were used to calculate observed-to-expected ratios and value of care using validated equations. For commonly performed (1 or more per week) procedures, the pipeline generated figures illustrating individual surgeon performance vs peers, costs for each surgeon performing each case type, and control charts identifying out-of-control cases and surgeons with more than 90th percentile costs, which were shared with surgeons and division chiefs alongside guidance for modifying case-specific supply instructions to operating room nurses and technicians. RESULTS: Preintervention control (1,064 cases for 7 months) and postintervention (307 cases for 2 months) cohorts had similar baseline characteristics across all 16 commonly performed procedures. Median costs per case were lower in the intervention cohort ($811 [$525 to $1,367] vs controls: $1,080 [$603 to $1,574], p < 0.001), as was the incidence of out-of-control cases (19 (6.2%) vs 110 (10.3%), p = 0.03). Duration of surgery, length of stay, discharge disposition, and 30-day mortality and readmission rates were similar between cohorts. Value of care was higher in the intervention cohort (1.1 [0.1 to 1.5] vs 1.0 [0.2 to 1.4], p = 0.04). Pipeline runtime was 16:07. CONCLUSIONS: An automated, sustainable quality improvement intervention was associated with decreased operating room supply costs and increased value of care.


Assuntos
Salas Cirúrgicas , Cirurgiões , Humanos , Equipamentos e Provisões Hospitalares , Melhoria de Qualidade , Redução de Custos , Tempo de Internação
7.
J Am Coll Surg ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38895939

RESUMO

BACKGROUND: Previous research has highlighted concerns among trainees and attendings that general surgery training and fellowship are inadequately preparing trainees for practice. Providing trainees with supervision that matches their proficiency may help bridge this gap. We sought to benchmark operative performance and supervision levels among senior surgery residents (post-graduate year 4 or 5) and fellows performing general surgical oncology procedures. STUDY DESIGN: Observational data were obtained from the Society for Improving Medical Procedural Learning (SIMPL) OR application for core general surgical oncology procedures performed at 103 unique residency and fellowship programs. Procedures were divided into breast and soft tissue, endocrine, and hepatopancreatobiliary (HPB). Case evaluations completed by trainees and attendings were analyzed to benchmark trainee operative performance and level of supervision. RESULTS: There were 4,907 resident cases and 425 fellow cases. Practice-ready performance, as assessed by trainees and faculty, was achieved by relatively low proportions of residents and fellows for breast and soft tissue cases (residents: 38%, fellows: 48%), endocrine cases (residents: 22%, fellows: 41%), and HPB cases (residents: 10%, fellows: 40%). Among cases in which trainees did achieve practice-ready performance, supervision only was provided for low proportions of cases as rated by trainees (residents: 17%, fellows: 18%) and attendings (residents: 21%, fellows 25%). CONCLUSION: In a sample of 103 residency and fellowship programs, attending surgeons rarely provided senior residents and fellows with levels of supervision commensurate to performance for surgical oncology procedures, even for high performing trainees. These findings suggest a critical need for surgical training programs to prioritize providing greater levels of independence to trainees that have demonstrated excellent performance.

8.
Surgery ; 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39112327

RESUMO

BACKGROUND: Effective communication in the operating room is crucial for patient safety and optimal outcomes. Structured debriefing communication tools can improve team coordination and address recurring safety concerns. During the unique circumstances of the COVID-19 pandemic, this study evaluated an approach to documentation and loop closure that functioned under constrained hospital resources, a loss of capacity for face-to-face provider training and loop closure, and periods of performing only urgent and emergent surgery for which some debriefing elements, like patient disposition and equipment needs, are more dynamic. METHODS: Employing a longitudinal repeated-measures design, this quality improvement study used a newly integrated module within the electronic health record system to document debriefings, which were linked to surveys assessing perceptions of the debriefing process. Data were collected from 56 operating rooms in 3 separate hospital towers during a 3-year period ending December 2023, encompassing 4 reiterative Plan-Do-Study-Act cycles. RESULTS: The study recorded 49,426 surgical debriefings. The overall incidence of debriefing increased 111% during the study period, reaching 88% during the third and final year of the project. Compared with 193 preintervention surveys, 129 postintervention surveys demonstrated increased incidence of perceiving debriefings as very or extremely effective (52% vs 38%, P = .02), greater frequency of discussing whether equipment issues occurred (87% vs 75%, P = .008), and greater frequency of loop closure (46% vs 34%, P = .03) and leadership (Chair or Program Director of Quality) involvement in loop closure activities (14% vs 3%, P = .008) addressing issues identified during debriefs. CONCLUSION: Despite challenges associated with implementation during a viral pandemic, the intervention was associated with increased incidence and perceived effectiveness of documented surgical debriefings, greater frequency of downstream loop closure, and positive impacts on team communication.

9.
bioRxiv ; 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38464077

RESUMO

Abdominal aortic aneurysm (AAA) formation is a chronic vascular pathology characterized by inflammation, leukocyte infiltration and vascular remodeling. The aim of this study was to delineate the protective role of Resolvin D2 (RvD2), a bioactive isoform of specialized proresolving lipid mediators, via G-protein coupled receptor 18 (GPR18) receptor signaling in attenuating AAAs. Importantly, RvD2 and GPR18 levels were significantly decreased in aortic tissue of AAA patients compared with controls. Furthermore, using an established murine model of AAA in C57BL/6 (WT) mice, we observed that treatment with RvD2 significantly attenuated aortic diameter, pro-inflammatory cytokine production, immune cell infiltration (neutrophils and macrophages), elastic fiber disruption and increased smooth muscle cell α-actin expression as well as increased TGF-ß2 and IL-10 expressions compared to untreated mice. Moreover, the RvD2-mediated protection from vascular remodeling and AAA formation was blocked when mice were previously treated with siRNA for GPR18 signifying the importance of RvD2/GPR18 signaling in vascular inflammation. Mechanistically, RvD2-mediated protection significantly enhanced infiltration and activation of monocytic myeloid-derived suppressor cells (M-MDSCs) by increasing TGF-ß2 and IL-10 secretions that mitigated smooth muscle cell activation in a GPR18-dependent manner to attenuate aortic inflammation and vascular remodeling via this intercellular crosstalk. Collectively, this study demonstrates RvD2 treatment induces an expansion of myeloid-lineage committed progenitors, such as M-MDSCs, and activates GPR18-dependent signaling to enhance TGF-ß2 and IL-10 secretion that contributes to resolution of aortic inflammation and remodeling during AAA formation.

10.
bioRxiv ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38712069

RESUMO

BACKGROUND: Post-lung transplantation (LTx) injury can involve sterile inflammation due to ischemia-reperfusion injury (IRI). We investigated the cell-specific role of ferroptosis (excessive iron-mediated cell death) in mediating lung IRI and determined if specialized pro-resolving mediators such as Lipoxin A4 (LxA 4 ) can protect against ferroptosis in lung IRI. METHODS: Single-cell RNA sequencing of lung tissue from post-LTx patients was analyzed. Lung IRI was evaluated in C57BL/6 (WT), formyl peptide receptor 2 knockout ( Fpr2 -/- ) and nuclear factor erythroid 2-related factor 2 knockout ( Nrf2 -/- ) mice using a hilar-ligation model with or without LxA 4 administration. Furthermore, the protective efficacy of LxA 4 was evaluated employing a murine orthotopic LTx model and in vitro studies using alveolar type II epithelial (ATII) cells. RESULTS: Differential expression of ferroptosis-related genes was observed in post-LTx patient samples compared to healthy controls. A significant increase in the levels of oxidized lipids and reduction in the levels of intact lipids were observed in mice subjected to IRI compared to shams. Furthermore, pharmacological inhibition of ferroptosis with liproxstatin-1 mitigated lung IRI and lung dysfunction. Importantly, LxA 4 treatment attenuated pulmonary dysfunction, ferroptosis and inflammation in WT mice subjected to lung IRI, but not in Fpr2 -/- or Nrf2 -/- mice, after IRI. In the murine LTx model, LxA 4 treatment increased PaO 2 levels and attenuated lung IRI. Mechanistically, LxA 4 -mediated protection involves increase in NRF2 activation and glutathione concentration as well as decrease in MDA levels in ATII cells. CONCLUSIONS: LxA 4 /FPR2 signaling on ATII cells mitigates ferroptosis via NRF2 activation and protects against lung IRI.

11.
JCI Insight ; 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39172530

RESUMO

Lung transplantation (LTx) outcomes are impeded by ischemia-reperfusion injury (IRI) and subsequent chronic lung allograft dysfunction (CLAD). We examined the undefined role of MerTK (receptor Mer tyrosine kinase) on monocytic myeloid-derived suppressor cells (M-MDSCs) in efferocytosis to facilitate resolution of lung IRI. Single-cell RNA sequencing of lung tissue and bronchoalveolar lavage (BAL) from post-LTx patients were analyzed. Murine lung hilar ligation and allogeneic orthotopic LTx models of IRI were used with Balb/c (WT), Cebpb-/- (MDSC-deficient), Mertk-/- or MerTK-CR (cleavage resistant) mice. A significant downregulation in MerTK-related efferocytosis genes in M-MDSC populations of CLAD patients was observed compared to healthy subjects. In the murine IRI model, significant increase in M-MDSCs, MerTK expression, efferocytosis and attenuation of lung dysfunction was observed in WT mice during injury resolution that was absent in Cebpb-/- and Mertk-/- mice. Adoptive transfer of M-MDSCs in Cebpb-/- mice significantly attenuated lung dysfunction and inflammation. Additionally, in a murine orthotopic LTx model, increases in M-MDSCs were associated with resolution of lung IRI in the transplant recipients. In vitro studies demonstrated the ability of M-MDSCs to efferocytose apoptotic neutrophils in a MerTK-dependent manner. Our results suggest that MerTK-dependent efferocytosis by M-MDSCs can substantially contribute to the resolution of post-LTx IRI.

12.
bioRxiv ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-39149340

RESUMO

The pathogenesis of abdominal aortic aneurysm (AAA) formation involves vascular inflammation, thrombosis formation and programmed cell death leading to aortic remodeling. Recent studies have suggested that ferroptosis, an excessive iron-mediated cell death, can regulate cardiovascular diseases, including AAAs. However, the role of ferroptosis in immune cells, like macrophages, and ferroptosis-related genes in AAA formation remains to be deciphered. Single cell-RNA sequencing of human aortic tissue from AAA patients demonstrates significant differences in ferroptosis-related genes compared to control aortic tissue. Using two established murine models of AAA and aortic rupture in C57BL/6 (WT) mice, we observed that treatment with liproxstatin-1, a specific ferroptosis inhibitor, significantly attenuated aortic diameter, pro-inflammatory cytokine production, immune cell infiltration (neutrophils and macrophages), increased smooth muscle cell α-actin expression and elastic fiber disruption compared to mice treated with inactivated elastase in both pre-treatment and treatment after a small AAA had already formed. Lipidomic analysis using mass spectrometry shows a significant increase in ceramides and a decrease in intact lipid species levels in murine tissue compared to controls in the chronic AAA model on day 28. Mechanistically, in vitro studies demonstrate that liproxstatin-1 treatment of macrophages mitigated the crosstalk with aortic smooth muscle cells (SMCs) by downregulating MMP2 secretion. Taken together, this study demonstrates that pharmacological inhibition by liproxstatin-1 mitigates macrophage-dependent ferroptosis contributing to inhibition of aortic inflammation and remodeling during AAA formation.

13.
bioRxiv ; 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38328174

RESUMO

Rationale: Patients with end stage lung diseases require lung transplantation (LTx) that can be impeded by ischemia-reperfusion injury (IRI) leading to subsequent chronic lung allograft dysfunction (CLAD) and inadequate outcomes. Objectives: We examined the undefined role of MerTK (receptor Mer tyrosine kinase) on monocytic myeloid-derived suppressor cells (M-MDSCs) in efferocytosis (phagocytosis of apoptotic cells) to facilitate resolution of lung IRI. Methods: Single-cell RNA sequencing of lung tissue and BAL from post-LTx patients was analyzed. Murine lung hilar ligation and allogeneic orthotopic LTx models of IRI were used with Balb/c (WT), cebpb -/- (MDSC-deficient), Mertk -/- or MerTK-CR (cleavage resistant) mice. Lung function, IRI (inflammatory cytokine and myeloperoxidase expression, immunohistology for neutrophil infiltration), and flow cytometry of lung tissue for efferocytosis of apoptotic neutrophils were assessed in mice. Measurements and Main Results: A significant downregulation in MerTK-related efferocytosis genes in M-MDSC populations of CLAD patients compared to healthy subjects was observed. In the murine IRI model, significant increase in M-MDSCs, MerTK expression and efferocytosis was observed in WT mice during resolution phase that was absent in cebpb -/- Land Mertk -/- mice. Adoptive transfer of M-MDSCs in cebpb -/- mice significantly attenuated lung dysfunction, and inflammation leading to resolution of IRI. Additionally, in a preclinical murine orthotopic LTx model, increases in M-MDSCs were associated with resolution of lung IRI in the transplant recipients. In vitro studies demonstrated the ability of M-MDSCs to efferocytose apoptotic neutrophils in a MerTK-dependent manner. Conclusions: Our results suggest that MerTK-dependent efferocytosis by M-MDSCs can significantly contribute to the resolution of post-LTx IRI.

14.
Surgery ; 175(6): 1600-1605, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38461121

RESUMO

BACKGROUND: Health literacy is a crucial aspect of informed decision-making, and limited health literacy has been associated with worse health care outcomes. To date, health literacy has not been examined in vascular surgery patients. Therefore, we conducted a prospective observational study to determine the prevalence and factors associated with poor health literacy in vascular surgery patients. METHODS: The Newest Vital Sign (Pfizer, New York, NY), a validated instrument, was used to appraise the health literacy of 150 patients who visited the outpatient vascular clinic at UF Health Shands Hospital between April 2022 and August 2022. Patients who scored a 4 (out of 6) or higher were classified as having adequate health literacy. Each study participant also completed a sociodemographic questionnaire. RESULTS: In total, 82 out of the 150 (54%) patients we screened had limited health literacy. The prevalence of limited health literacy varied and was independently associated with increased age (odds ratio 1.06; 95% [1.02 to 1.10], P = .004), having not attended college (high school diploma versus college+ odds ratio 3.5; 95% [1.26 to 10.1], P = .018), and African American race (odds ratio 5.3; 95% [1.59 to 22.3], P = .012). A total of 83% of African American patients had limited health literacy, compared to 49% of Asian and White patients. CONCLUSION: Most vascular surgery patients have limited health literacy. Increased age, fewer years of education, and African American race were associated with limited health literacy. Physicians caring for patients with lower health literacy should investigate and use communication strategies tailored to patients with limited health literacy.


Assuntos
Letramento em Saúde , Procedimentos Cirúrgicos Vasculares , Humanos , Letramento em Saúde/estatística & dados numéricos , Masculino , Feminino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Vasculares/estatística & dados numéricos , Estudos Prospectivos , Idoso , Adulto , Inquéritos e Questionários/estatística & dados numéricos
15.
Crit Care Explor ; 6(8): e1131, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39132980

RESUMO

BACKGROUND: Surrogates, proxies, and clinicians making shared treatment decisions for patients who have lost decision-making capacity often fail to honor patients' wishes, due to stress, time pressures, misunderstanding patient values, and projecting personal biases. Advance directives intend to align care with patient values but are limited by low completion rates and application to only a subset of medical decisions. Here, we investigate the potential of large language models (LLMs) to incorporate patient values in supporting critical care clinical decision-making for incapacitated patients in a proof-of-concept study. METHODS: We simulated text-based scenarios for 50 decisionally incapacitated patients for whom a medical condition required imminent clinical decisions regarding specific interventions. For each patient, we also simulated five unique value profiles captured using alternative formats: numeric ranking questionnaires, text-based questionnaires, and free-text narratives. We used pre-trained generative LLMs for two tasks: 1) text extraction of the treatments under consideration and 2) prompt-based question-answering to generate a recommendation in response to the scenario information, extracted treatment, and patient value profiles. Model outputs were compared with adjudications by three domain experts who independently evaluated each scenario and decision. RESULTS AND CONCLUSIONS: Automated extractions of the treatment in question were accurate for 88% (n = 44/50) of scenarios. LLM treatment recommendations received an average Likert score by the adjudicators of 3.92 of 5.00 (five being best) across all patients for being medically plausible and reasonable treatment recommendations, and 3.58 of 5.00 for reflecting the documented values of the patient. Scores were highest when patient values were captured as short, unstructured, and free-text narratives based on simulated patient profiles. This proof-of-concept study demonstrates the potential for LLMs to function as support tools for surrogates, proxies, and clinicians aiming to honor the wishes and values of decisionally incapacitated patients.


Assuntos
Procurador , Humanos , Diretivas Antecipadas , Tomada de Decisões , Tomada de Decisão Clínica/métodos , Estudo de Prova de Conceito , Inquéritos e Questionários , Idioma , Cuidados Críticos/métodos
16.
Ann Surg Open ; 5(2): e429, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38911666

RESUMO

Objective: To determine whether certain patients are vulnerable to errant triage decisions immediately after major surgery and whether there are unique sociodemographic phenotypes within overtriaged and undertriaged cohorts. Background: In a fair system, overtriage of low-acuity patients to intensive care units (ICUs) and undertriage of high-acuity patients to general wards would affect all sociodemographic subgroups equally. Methods: This multicenter, longitudinal cohort study of hospital admissions immediately after major surgery compared hospital mortality and value of care (risk-adjusted mortality/total costs) across 4 cohorts: overtriage (N = 660), risk-matched overtriage controls admitted to general wards (N = 3077), undertriage (N = 2335), and risk-matched undertriage controls admitted to ICUs (N = 4774). K-means clustering identified sociodemographic phenotypes within overtriage and undertriage cohorts. Results: Compared with controls, overtriaged admissions had a predominance of male patients (56.2% vs 43.1%, P < 0.001) and commercial insurance (6.4% vs 2.5%, P < 0.001); undertriaged admissions had a predominance of Black patients (28.4% vs 24.4%, P < 0.001) and greater socioeconomic deprivation. Overtriage was associated with increased total direct costs [$16.2K ($11.4K-$23.5K) vs $14.1K ($9.1K-$20.7K), P < 0.001] and low value of care; undertriage was associated with increased hospital mortality (1.5% vs 0.7%, P = 0.002) and hospice care (2.2% vs 0.6%, P < 0.001) and low value of care. Unique sociodemographic phenotypes within both overtriage and undertriage cohorts had similar outcomes and value of care, suggesting that triage decisions, rather than patient characteristics, drive outcomes and value of care. Conclusions: Postoperative triage decisions should ensure equality across sociodemographic groups by anchoring triage decisions to objective patient acuity assessments, circumventing cognitive shortcuts and mitigating bias.

17.
Shock ; 62(2): 208-216, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38713581

RESUMO

ABSTRACT: Postsepsis early mortality is being replaced by survivors who experience either a rapid recovery and favorable hospital discharge or the development of chronic critical illness with suboptimal outcomes. The underlying immunological response that determines these clinical trajectories remains poorly defined at the transcriptomic level. As classical and nonclassical monocytes are key leukocytes in both the innate and adaptive immune systems, we sought to delineate the transcriptomic response of these cell types. Using single-cell RNA sequencing and pathway analyses, we identified gene expression patterns between these two groups that are consistent with differences in TNF-α production based on clinical outcome. This may provide therapeutic targets for those at risk for chronic critical illness in order to improve their phenotype/endotype, morbidity, and long-term mortality.


Assuntos
Monócitos , Sepse , Transcriptoma , Humanos , Monócitos/metabolismo , Monócitos/imunologia , Sepse/imunologia , Sepse/genética , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Fator de Necrose Tumoral alfa/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA