ABSTRACT
Computational models of homologous protein groups are essential in sequence bioinformatics. Due to the diversity and rapid evolution of viruses, the grouping of protein sequences from virus genomes is particularly challenging. The low sequence similarities of homologous genes in viruses require specific approaches for sequence- and structure-based clustering. Furthermore, the annotation of virus genomes in public databases is not as consistent and up to date as for many cellular genomes. To tackle these problems, we have developed VOGDB, which is a database of virus orthologous groups. VOGDB is a multi-layer database that progressively groups viral genes into groups connected by increasingly remote similarity. The first layer is based on pair-wise sequence similarities, the second layer is based on the sequence profile alignments, and the third layer uses predicted protein structures to find the most remote similarity. VOGDB groups allow for more sensitive homology searches of novel genes and increase the chance of predicting annotations or inferring phylogeny. VOGD B uses all virus genomes from RefSeq and partially reannotates them. VOGDB is updated with every RefSeq release. The unique feature of VOGDB is the inclusion of both prokaryotic and eukaryotic viruses in the same clustering process, which makes it possible to explore old evolutionary relationships of the two groups. VOGDB is freely available at vogdb.org under the CC BY 4.0 license.
Subject(s)
Computational Biology , Genome, Viral , Phylogeny , Viruses , Viruses/genetics , Viruses/classification , Computational Biology/methods , Databases, Genetic , Viral Proteins/genetics , Viral Proteins/chemistryABSTRACT
PURPOSE: For men with intermediate-risk prostate cancer treated with definitive therapy, the addition of androgen deprivation therapy (ADT) reduces the risk of distant metastasis and cancer-related mortality. However, the absolute benefit of ADT varies by baseline cancer risk. Estimates of prognosis have improved over time, and little is known about ADT decision making in the modern era. We sought to characterize variability and identify factors associated with intended ADT use within the Michigan Radiation Oncology Quality Consoritum (MROQC). MATERIALS AND METHODS: Patients with localized prostate cancer undergoing definitive radiation therapy were enrolled from June 9, 2020, to June 26, 2023 (n = 815). Prospective data were collected using standardized patient, physician, and physicist forms. Intended ADT use was prospectively defined and was the primary outcome. Associations with patient, tumor, and practice-related factors were tested with multivariable analyses. Random intercept modeling was used to estimate facility-level variability. RESULTS: Five hundred seventy patients across 26 facilities were enrolled with intermediate-risk disease. ADT was intended for 46% of men (n = 262/570), which differed by National Comprehensive Cancer Network favorable intermediate-risk (23.5%, n = 38/172) versus unfavorable intermediate-risk disease (56.3%, n = 224/398; P < .001). After adjusting for the statewide case mix, the predicted probability of intended ADT use varied significantly across facilities, ranging from 15.4% (95% CI, 5.4%-37.0%) to 71.7% (95% CI, 57.0%-82.9%), with P < .01. Multivariable analyses showed that grade group 3 (OR, 4.60 [3.20-6.67]), ≥50% positive cores (OR, 2.15 [1.43-3.25]), and prostate-specific antigen 10 to 20 (OR, 1.87 [1.24-2.84]) were associated with ADT use. Area under the curve was improved when incorporating MRI adverse features (0.76) or radiation treatment variables (0.76), but there remained significant facility-level heterogeneity in all models evaluated (P < .05). CONCLUSIONS: Within a state-wide consortium, there is substantial facility-level heterogeneity in intended ADT use for men with intermediate-risk prostate cancer. Future efforts are necessary to identify patients who will benefit most from ADT and to develop strategies to standardize appropriate use.
ABSTRACT
Lower-intensity interventions delivered in primary and community care contacts could provide more equitable and scalable weight management support for postnatal women. This mixed-methods systematic review aimed to explore the effectiveness, implementation, and experiences of lower-intensity weight management support delivered by the non-specialist workforce. We included quantitative and qualitative studies of any design that evaluated a lower-intensity weight management intervention delivered by non-specialist workforce in women up to 5 years post-natal, and where intervention effectiveness (weight-related and/or behavioural outcomes), implementation and/or acceptability were reported. PRISMA guidelines were followed, and the review was prospectively registered on PROSPERO (CRD42022371828). Nine electronic databases were searched to identify literature published between database inception to January 2023. This was supplemented with grey literature searches and citation chaining for all included studies and related reviews (completed June 2023). Screening, data extraction and risk of bias assessments were performed in duplicate. Risk of bias was assessed using the Joanna Briggs Institute appraisal tools. Narrative methods were used to synthesise outcomes. Seven unique studies described in 11 reports were included from the Netherlands (n = 2), and the United Kingdom, Germany, Taiwan, Finland, and the United States (n = 1 each). All studies reported weight-related outcomes; four reported diet; four reported physical activity; four reported intervention implementation and process outcomes; and two reported intervention acceptability and experiences. The longest follow-up was 13-months postnatal. Interventions had mixed effects on weight-related outcomes: three studies reported greater weight reduction and/or lower postnatal weight retention in the intervention group, whereas four found no difference or mixed effects. Most studies reporting physical activity or diet outcomes showed no intervention effect, or mixed effects. Interventions were generally perceived as acceptable by women and care providers, although providers had concerns about translation into routine practice. The main limitations of the review were the limited volume of evidence available, and significant heterogeneity in interventions and outcome reporting which limited meaningful comparisons across studies. There is a need for more intervention studies, including process evaluations, with longer follow-up in the postnatal period to understand the role of primary and community care in supporting women's weight management. Public Health Wales was the primary funder of this review.
Subject(s)
Diet , Exercise , Weight Loss , Female , Humans , Bias , Workforce , Postnatal CareABSTRACT
The germinal center (GC) dark zone (DZ) and light zone (LZ) regions spatially separate expansion and diversification from selection of antigen-specific B-cells to ensure antibody affinity maturation and B cell memory. The DZ and LZ differ significantly in their immune composition despite the lack of a physical barrier, yet the determinants of this polarization are poorly understood. This study provides novel insights into signals controlling asymmetric T-cell distribution between DZ and LZ regions. We identify spatially-resolved DNA damage response and chromatin compaction molecular features that underlie DZ T-cell exclusion. The DZ spatial transcriptional signature linked to T-cell immune evasion clustered aggressive Diffuse Large B-cell Lymphomas (DLBCL) for differential T cell infiltration. We reveal the dependence of the DZ transcriptional core signature on the ATR kinase and dissect its role in restraining inflammatory responses contributing to establishing an immune-repulsive imprint in DLBCL. These insights may guide ATR-focused treatment strategies bolstering immunotherapy in tumors marked by DZ transcriptional and chromatin-associated features.
ABSTRACT
Deregulation of the DNA damage response (DDR) plays a critical role in the pathogenesis and progression of many cancers. The dependency of certain cancers on DDR pathways has enabled exploitation of such through synthetically lethal relationships e.g., Poly ADP-Ribose Polymerase (PARP) inhibitors for BRCA deficient ovarian cancers. Though lagging behind that of solid cancers, DDR inhibitors (DDRi) are being clinically developed for haematological cancers. Furthermore, a high proliferative index characterize many such cancers, suggesting a rationale for combinatorial strategies targeting DDR and replicative stress. In this review, we summarize pre-clinical and clinical data on DDR inhibition in haematological malignancies and highlight distinct haematological cancer subtypes with activity of DDR agents as single agents or in combination with chemotherapeutics and targeted agents. We aim to provide a framework to guide the design of future clinical trials involving haematological cancers for this important class of drugs.
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BACKGROUND: Recent work has suggested that outcomes among heart transplant patients listed at the lower-urgency (United Network for Organ Sharing Status 4 or 6) status may not be significantly impacted by donor comorbidities. The purpose of this study was to investigate outcomes of extended criteria donors (ECD) in lower versus higher urgency patients undergoing heart transplantation. METHODS: The United Network for Organ Sharing (UNOS) database was queried for all adult patients undergoing heart transplantation from October 18, 2018 through December 31, 2021. Patients were stratified by degree of urgency (higher urgency: UNOS 1 or 2 vs lower urgency: UNOS 4 or 6) and receipt of ECD hearts, as defined by donor hearts failing to meet established acceptable use criteria. Outcomes were compared using propensity score matched cohorts. RESULTS: Among 9,160 patients included, 2,320 (25.4%) were low urgency. ECD hearts were used in 35.5% of higher urgency (HU) patients and 39.2% of lower urgency (LU) patients. While ECD hearts had an impact on survival among high-urgency patients (p < 0.01), there was no difference in 1- and 2-year survival (p > 0.05) found among low urgency patients receiving ECD versus standard hearts. Neither ECDs nor individual ECD criteria were independently associated with mortality in low urgency patients (p > 0.05). CONCLUSIONS: Post-transplant outcomes among low urgency patients are not adversely affected by receipt of ECD vs. standard hearts. Expanding the available donor pool by optimizing use of ECDs in this population may increase transplant frequency, decrease waitlist morbidity, and improve postoperative outcomes for the transplant community at large.
Subject(s)
Heart Transplantation , Tissue Donors , Adult , Humans , Heart Transplantation/adverse effects , Time Factors , Waiting Lists , Databases, Factual , Retrospective StudiesABSTRACT
OBJECTIVES: This study aimed to evaluate employing the German Registry of Acute Aortic Dissection Type A (GERAADA) score to predict 30-day mortality in an aortic centre in the USA. METHODS: Between January 2010 and June 2021, 689 consecutive patients underwent surgery for acute type A dissection at a single institution. Excluded were patients with missing clinical data (N = 4). The GERAADA risk score was retrospectively calculated via a web-based application. Model discrimination power was calculated with c-statistics from logistic regression and reported as the area under the receiver operating characteristic curve with 95% confidence intervals. The calibration was measured by calculating the observed versus estimated mortality ratio. The Brier score was used for the overall model evaluation. RESULTS: Included were 685 patients [mean age 60.6 years (SD: 13.5), 64.8% male] who underwent surgery for acute type A aortic dissection. The 30-day mortality rate was 12.0%. The GERAADA score demonstrated very good discrimination power with an area under the receiver operating characteristic curve of 0.762 (95% confidence interval 0.703-0.821). The entire cohort's observed versus estimated mortality ratio was 0.543 (0.439-0.648), indicating an overestimation of the model-calculated risk. The Brier score was 0.010, thus revealing the model's acceptable overall performance. CONCLUSIONS: The GERAADA score is a practical and easily accessible tool for reliably estimating the 30-day mortality risk of patients undergoing surgery for acute type A aortic dissection. This model may naturally overestimate risk in patients undergoing surgery in experienced aortic centres.
Subject(s)
Aortic Dissection , Humans , Male , Middle Aged , Female , Retrospective Studies , Aortic Dissection/surgery , Registries , Risk FactorsABSTRACT
Background: Debate still persists on whether valve-sparing root reimplantation (VSRR) of a very asymmetric bicuspid aortic valve (BAV) should be completed such that the asymmetry of the native commissural orientation is retained, or if it should be made symmetric (180°-180°). Herein, we present our approach, in which the native asymmetry is preserved, and the valve is reimplanted in a 210°-150° orientation. Methods: A retrospective review was performed of 130 patients with BAV who underwent VSRR between January 1, 2004 and March 1, 2023 at a single institution. Of this total, 37 were reimplanted asymmetrically (210°-150°). The primary outcome was > moderate aortic insufficiency (AI). Secondary outcomes included severe aortic stenosis (AS), reintervention, and survival. Results: The included 37 patients were mostly male [94.6% (35/37)] with mean age of 46.3 years, and with low rates of comorbidities. At least moderate AI was present in 40.5% (15/37) prior to surgery. All BAV in this series were Sievers Type 1 with a mean commissural angle of 128.2°. Leaflet repair was required in 81.1% (30/37), most commonly involving central plication of the conjoined cusp [96.7% (29/30)] and raphe release [73.3% (22/30)]. There was no 30-day mortality or stroke. At 10 years, the cumulative incidences of > moderate AI, severe AS, and reintervention were 7.6% (0-17.2%), 7.1% (0-19.7%), and 5.3% (0.3-22%), respectively. There was no mortality for the entire duration of the study period. Conclusions: This series demonstrates excellent 10-year outcomes of maintaining commissural orientation in asymmetric BAV reimplantation procedures. However, further study with additional patients, longer follow-up, and direct comparison to symmetric reimplantation for similar BAV morphology is required.
ABSTRACT
BACKGROUND: In 2018, the United Network for Organ Sharing (UNOS) modified their heart allocation policy to reduce waitlist mortality. The rates of simultaneous heart-kidney transplant (SHKT) have dramatically increased in recent years, despite increased rates of posttransplant renal failure in the new policy era. This study sought to investigate the impact of the new allocation system on waitlist and posttransplant outcomes of simultaneous heart-kidney transplantation. METHODS: Adult patients listed for SHKT between 2012 and 2021 were included. Patients were cross-validated across both Thoracic and Kidney UNOS databases to confirm accurate listing and transplant data. Patients were stratified according to listing era. The Fine and Gray model was used to assess waitlist outcomes and posttransplant renal graft function. Kaplan-Meier analysis and Cox regression were used to compare posttransplant survival. RESULTS: A total of 2,588 patients were included, of whom 1,406 (54.1%) were listed between 2012 and 2018 (era 1) and 1,182 (45.9%) between 2019 and 2021 (era 2). Era 2 was associated with increased likelihood of transplant (adjusted Sub-hazard ratios (aSHR): 1.52; p < 0.01) and decreased waitlist mortality (aSHR: 0.63; p < 0.01). Posttransplant survival at 2 years was decreased in era 2 (78.8% vs 86.9%; p < 0.01). Undersized hearts (hazard ratio [HR]: 2.02; p < 0.01), use of extracorporeal membrane oxygenation (HR: 2.67; p < 0.1), and transplants performed following the policy change (HR: 1.45; p = 0.03) were associated with increased mortality. Actuarial survival (combined waitlist and posttransplant) was significantly lower in the modern era (71.6% vs 62.2%; p = 0.02). CONCLUSIONS: The allocation policy change has improved waitlist outcomes in patients listed for SHKT but potentially at the cost of worsened posttransplant outcomes.
Subject(s)
Heart Transplantation , Kidney Transplantation , Adult , Humans , Heart Transplantation/adverse effects , Proportional Hazards Models , Survival Rate , Waiting Lists , Kidney , Retrospective StudiesABSTRACT
SUMMARY: The existence of "transitional muscular structures" between subendocardial branches (Purkinje fibers) and ventricular working muscle fibers (WF) was first described by the German anatomist, Kurt Goerttler, in 1964. He designated them as "subendocardial nucleus organs." He supposed such fibers functioned as mechanoreceptors, controlling of the intensity of contraction of the ventricular musculature. Brazilian anatomist Ferraz de Carvalho described similar structures in 1993. A thorough literature search failed to identify any other research articles confirming or denying their existence. The objective of this work was to find such structures in subendocardial ventricular walls in human hearts. We collected fifteen formalin-preserved hearts from the Anatomy Department of São Paulo University and sectioned the apical portions on the right and left ventricles according to method used by Goerttler. We utilized conventional histology (light microscopy- LM), scanning electron microscopy (SEM), and a new preservation method called micro- plastination (MP). At the anterior wall of the right ventricle in the subendocardial region between the interventricular septum and moderator band, we found several bundles of fusiform and helicoidal fibers of similar histology to the WF. The bundles measured between 400 and 1150 µm in length and were separated from adjacent muscular fibers by thin collagen fiber, thus acting as a "pseudo capsule." Some structures seemed to be linked to PF and were appeared to be lymphatic and blood vessels and nerves. We called those structures "cardiac corpuscles" (CC). The observation of the previously "unknown" CC in this initial study confirmed the previous descriptions and its discovery may contribute to new perspectives in the study of cardiac muscle structure and function.
La existencia de "estructuras musculares de transición" entre los ramos subendocárdicos (fibras de Purkinje) y las fibras musculares ventriculares activas(FMV) fue descrita por primera vez por el anatomista alemán Kurt Goerttler en 1964, quien las denominó "órganos del núcleo subendocárdico". Supuso que tales fibras funcionaban como mecanoreceptores, controlando la intensidad de la contracción de la musculatura ventricular. El anatomista brasileño Ferraz de Carvalho describió estructuras similares en 1993. Una búsqueda bibliográfica exhaustiva no logró identificar ningún otro artículo de investigación que confirmara o negara su existencia. El objetivo de este trabajo fue encontrar dichas estructuras en las paredes ventriculares subendocárdicas de corazones humanos. Recolectamos 15 corazones conservados en formalina del Departamento de Anatomía de la Universidad de São Paulo y seccionamos las porciones apicales de los ventrículos derecho e izquierdo según el método utilizado por Goerttler. Utilizamos histología convencional (microscopía de luz-LM), microscopía electrónica de barrido (SEM) y un nuevo método de conservación llamado microplastinación (MP). En la pared anterior del ventrículo derecho en la región subendocárdica entre el tabique interventricular y la banda moderadora, encontramos varios haces de fibras fusiformes y helicoidales de histología similar a la FMV. Los haces medían entre 400 y 1150 µm de longitud y estaban separados de las fibras musculares adyacentes por una fina fibra de colágeno, actuando así como una "pseudocápsula". Algunas estructuras parecían estar vinculadas a la fibras de purkinje y parecían ser vasos linfáticos, sanguíneos y nerviosos. Llamamos a esas estructuras "corpúsculos cardíacos" (CC). La observación del CC previamente "desconocido" en este estudio inicial confirmó las descripciones anteriores y su descubrimiento puede contribuir a nuevas perspectivas en el estudio de la estructura y función del músculo cardíaco.
Subject(s)
Humans , Purkinje Fibers/anatomy & histology , Heart/anatomy & histology , Heart Ventricles/anatomy & histology , Microscopy, Electron, ScanningABSTRACT
BACKGROUND: This study evaluated midterm outcomes of a 3-pronged algorithm for bicuspid aortic valve (BAV) repair. Valve-sparing root reimplantation (VSRR) was performed for patients with aortic root dilatation. In those without a root aneurysm, external subannular ring (ESAR) was performed for annuli ≥28 mm and subcommissural annuloplasty (SCA) for annuli <28 mm. METHODS: This was a retrospective review of prospectively collected data of 242 patients undergoing primary BAV repair from April 29, 2004, to March 1, 2023, at a single institution. Primary end points were mortality, structural valve degeneration (SVD), which was defined as a composite of more than moderate aortic insufficiency or severe aortic stenosis, and reintervention. RESULTS: The algorithm was used to treat 201 patients; of these, 130 underwent VSRR, 35 had ESAR, and 36 underwent SCA. Most were men with mean age of 43.8 years (SD, 12.0 years), which was similar between groups. Preoperative aortic insufficiency more than moderate was more common for ESAR compared with VSRR and SCA (74.3% vs 37.7% vs 44.4%, P < .001). At 30 days, mortality was 0.8% (n = 1) for VSRR and 0% for ESAR and SCA. At 6 years, overall Kaplan-Meier survival was 98.9% (95% CI, 97.3%-100%), with no differences between groups (P = .5). The cumulative incidence of SVD was 4.7% (95% CI, 0.1%-9.2%) for VSRR, 6.4% (95% CI, 0%-14.6%) for ESAR, and 0% for SCA (P = .4). Similarly, the cumulative incidence of reintervention with all-cause mortality as a competing risk was 2.2% (95% CI, 0.4%-6.9%), 6.1% (95% CI, 1%-17.9%), and 0% for VSRR, ESAR, and SCA, respectively (P = .506). CONCLUSIONS: A 3-pronged algorithmic approach to BAV repair results in excellent survival and freedom from reoperation at 6 years.
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BACKGROUND: Extended criteria donors (ECD) hearts have demonstrated acceptable outcomes in select populations. However, their use in patients undergoing simultaneous heart-kidney transplantation (SHKT) has not been explored. This study is assessed the effect of ECD hearts in patients undergoing SHKT vs isolated heart transplants (IHT). METHODS: The United Network for Organ Sharing (UNOS) database was queried for all adult patients undergoing IHT and SHKT. Patients were stratified by receipt of ECD heart, defined as donor hearts failing to meet established acceptable use criteria. Interaction effects between ECDs and simultaneous kidney transplants were generated. Postoperative outcomes, risk factors, and patient/graft survival were compared across cohorts using Fine-Gray, Kaplan Meier, and Cox Proportional Hazards analyses. RESULTS: Among 26,207 patients included, 1,766 (7%) underwent SHKT. ECD hearts were used in 25% of both IHT and SHKT cohorts. Five-year survival among SHKT/ECD patients (67.3%) was reduced (p < 0.01) compared to SHKT/SDC (80.3%), IHT/ECD (78.1%) and IHT/SCD (80.0%) groups. Among SHKT patients, use of ECD hearts was associated with increased risk (SHR: 1.48; p < 0.01) of renal graft failure compared to SCD hearts. Among SHKT patients, receipt of an ECD heart, and individual ECD criteria (coronary disease and size mismatch >20%), predicted mortality. The interaction effect of receiving both ECD and SHKT predicted mortality and graft failure (HR 1.43; p < 0.01). CONCLUSIONS: Patients undergoing SHKT with an ECD heart face greater risks of mortality and graft failure in comparison to those undergoing IHT with ECD hearts. Careful selection of donor organs should be applied to this high-risk cohort.
Subject(s)
Heart Transplantation , Kidney Transplantation , Adult , Humans , Tissue Donors , Treatment Outcome , Retrospective Studies , Graft Survival , KidneyABSTRACT
The global volume of surgery is increasing. Adverse outcomes after surgery have resource implications and long-term impact on quality of life and consequently represent a significant and underappreciated public health issue. Standardization of outcome reporting is essential for evidence synthesis, risk stratification, perioperative care planning, and to inform shared decision-making. The association between short- and long-term outcomes, which persists when corrected for base-line risk, has significant implications for patients and providers and warrants further investigation. Candidate mechanisms include sustained inflammation and reduced physician activity, which may, in the future, be mitigated by targeted interventions.
Subject(s)
Decision Making, Shared , Quality of Life , HumansABSTRACT
SUMMARY: The study on cadavers, although considered fundamental in the teaching of human anatomy, is limited in several universities, mainly due to the acquisition and manipulation of cadaveric material. Throughout history, several artificial anatomical models have been used to complement the real anatomical pieces. The present study offers a new alternative: the making of three-dimensional models from Computed Tomography (3D-CT) patient image acquisition. CT images from the USP University Hospital database were used. Patients underwent examinations for reasons other than the present study and were anonymized to maintain confidentiality. The CT slices obtained in thin cross-sections (approximately 1.0 mm thick) were converted into three-dimensional images by a technique named Volume Rendering for visualization of soft tissue and bone. The reconstructions were then converted to an STL (Standard Triangle Language) model and printed through two printers (LONGER LK4 Pro® and Sethi S3®), using PLA and ABS filaments. The 3D impressions of the thigh and leg muscles obtained better visual quality, being able to readily identify the local musculature. The images of the face, heart, and head bones, although easily identifiable, although seemed to present lower quality aesthetic results. This pilot study may be one of the first to perform 3D impressions of images from CT to visualize the musculature in Brazil and may become an additional tool for teaching.
El estudio en cadáveres, a pesar de considerarse un aspecto fundamental en la enseñanza de la anatomía humana, se encuentra limitado en varias universidades, principalmente por la adquisición y manipulación de material cadavérico. A lo largo de la historia se han utilizado varios modelos anatómicos artificiales para complementar las piezas anatómicas reales. El presente estudio ofrece una nueva alternativa: la elaboración de modelos tridimensionales a partir de la adquisición de imágenes de pacientes por Tomografía Computarizada (3D-CT). Se utilizaron imágenes de TC de la base de datos del Hospital Universitario de la USP. Los pacientes se sometieron a exámenes por razones distintas al presente estudio y fueron anonimizados para mantener la confidencialidad. Los cortes de TC obtenidos en secciones transversales delgadas (aproximadamente 1,0 mm de grosor) se convirtieron en imágenes tridimensionales mediante una técnica denominada Volume Rendering para la visualización de tejido blando y hueso. Luego, las reconstrucciones se convirtieron a un modelo STL (Standard Triangle Language) y se imprimieron a través de dos impresoras (LONGER LK4 Pro® y Sethi S3®), utilizando filamentos PLA y ABS. Se obtuvo una mejor calidad visual de las impresiones 3D de los músculos del muslo y la pierna, pudiendo identificar fácilmente la musculatura local. Las imágenes de la cara, el corazón y los huesos de la cabeza, aunque fácilmente identificables, parecían presentar resultados estéticos de menor calidad. Este estudio piloto puede ser uno de los primeros en realizar impresiones 3D de imágenes de TC para visualizar la musculatura y podría ser en una herramienta adicional para la enseñanza.
Subject(s)
Humans , Tomography, X-Ray Computed , Printing, Three-Dimensional , Anatomy/education , Models, AnatomicABSTRACT
BACKGROUND: Socioeconomic status has increasingly recognized influence on outcomes after cardiac surgery. However, singular metrics fail to fully capture the socioeconomic context within which patients live, which vary greatly between neighborhoods. We sought to explore the impact of neighborhood-level socioeconomic status on patients undergoing mitral valve surgery in the United States. METHODS: Adults undergoing first-time, isolated mitral valve surgery were queried from The Society of Thoracic Surgeons Adult Cardiac Surgery Database between 2012 and 2018. Socioeconomic status was quantified using the Area Deprivation Index, a weighted composite including average housing prices, household incomes, education, and employment levels. The associations between regional deprivation, access to mitral surgery, valve repair rates, and outcomes were evaluated using logistic regression. RESULTS: Among 137,100 patients included, patients with socioeconomic deprivation had fewer elective presentations, more comorbidity burden, and more urgent/emergent surgery. Patients from less disadvantaged areas received operations from higher volume surgeons and had higher repair rates (highest vs lowest quintile: 72% vs 51%, P < .001, more minimally-invasive approach (33% vs 20%, P < .001), lower composite complication rate (42% vs 50%, P < .001), and lower 30-day mortality (1.8% vs 3.9%, P < .001). After hierarchical multivariable adjustment, the Area Deprivation Index significantly predicted 30-day mortality and repair rate (P < .001). CONCLUSIONS: In a risk-adjusted national analysis of mitral surgery, patients from more deprived areas were less likely to undergo mitral repair and more likely to have complications. Further work at targeting neighborhood-level disparity is important to improving mitral surgical outcomes in the United States.
Subject(s)
Cardiac Surgical Procedures , Heart Valve Prosthesis Implantation , Mitral Valve Insufficiency , Adult , Humans , United States/epidemiology , Mitral Valve/surgery , Treatment Outcome , Mitral Valve Insufficiency/surgery , Social ClassABSTRACT
Subacute groin complications associated with extracorporeal membrane oxygenation (ECMO) cannulation are well recognized, yet their effects on clinical outcomes remain unknown. This single-center, retrospective study reviewed all patients receiving venoarterial ECMO from 01/2017 to 02/2020. Cohorts analyzed included transplanted patients (TPs) and non-transplanted patients (N-TPs) who did or did not develop ECMO-related subacute groin complications. Standard descriptive statistics were used for comparisons. Logistic regressions identified associated risk factors. Overall, 82/367 (22.3%) ECMO patients developed subacute groin complications, including 25/82 (30.5%) seromas/lymphoceles, 32/82 (39.0%) hematomas, 18/82 (22.0%) infections, and 7/82 (8.5%) non-specified collections. Of these, 20/82 (24.4%) underwent surgical interventions, most of which were muscle flaps (14/20, 70.0%). TPs had a higher incidence of subacute groin complications than N-TPs (14/28, 50.0% vs. 68/339, 20.1%, P = 0.001). Seromas/lymphoceles more often developed in TPs than N-TPs (10/14, 71.4% vs. 15/68, 22.1%, P = 0.001). Most patients with subacute groin complications survived to discharge (60/68, 88.2%). N-TPs who developed subacute groin complications had longer post-ECMO lengths of stay than those who did not (34 days, IQR 16-53 days vs. 17 days, IQR 8-34 days, P < 0.001). Post-ECMO length of stay was also longer among patients who underwent related surgical interventions compared to those who did not (50 days, IQR 35-67 days vs. 29 days, IQR 16-49 days, P = 0.007). Transplantation was the strongest risk factor for developing subacute groin complications (OR 3.91, CI95% 1.52-10.04, P = 0.005). Subacute groin complications and related surgical interventions are common after ECMO cannulation and are associated with longer hospital stays. When surgical management is warranted, muscle flaps may reduce lengths of stay compared to other surgical interventions.
Subject(s)
Extracorporeal Membrane Oxygenation , Lymphocele , Humans , Extracorporeal Membrane Oxygenation/adverse effects , Groin , Retrospective Studies , Lymphocele/etiology , Seroma/etiology , Length of Stay , CatheterizationABSTRACT
BACKGROUND: In 2018, a United Network for Organ Sharing (UNOS) policy change increased prioritization of patients bridged with temporary mechanical circulatory support devices, such as venoarterial ECMO, for cardiac transplantation. Considering increased waitlist acuity, we sought to characterize whether this was associated with an increased risk for development of postoperative acute renal failure requiring dialysis (AKI-D) and risk of death after transplantation. METHODS: Dialysis-naive adults receiving single-organ heart transplant between November 2009 and February 2020 were stratified by receipt of AKI-D. Era 1 and era 2 were defined by the periods of UNOS allocation before and after policy change, respectively. Multivariable logistic regression was performed to determine risk factors for AKI-D. Rates of AKI-D were compared by propensity score-matched cohorts. Survival was compared by Kaplan-Meier analysis. RESULTS: A total of 20 698 patients were included. Venoarterial ECMO use significantly increased in era 2 (5.6% vs 0.58%; P < .01). Overall prevalence of AKI-D was greater in era 2 (13.5% vs 10.2%; P < .01). Use of preoperative ECMO, intra-aortic balloon pump, and ventilators and longer ischemia times were identified as independent risk factors for development of AKI-D. Five- and 10-year survival rates were significantly decreased for patients with AKI-D. There was no short-term survival difference of patients with AKI-D between era 2 and the more contemporary era 1. CONCLUSIONS: Patients in whom AKI-D develops after transplantation have significantly worse short- and long-term outcomes. Preoperative use of ECMO, preoperative ventilator support, and longer ischemia times are risk factors for development of AKI-D, and their prevalence has increased since the allocation policy change.
Subject(s)
Acute Kidney Injury , Heart Failure , Heart Transplantation , Adult , Humans , Renal Dialysis , Retrospective Studies , Heart Transplantation/adverse effects , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Ischemia/etiology , Heart Failure/surgeryABSTRACT
OBJECTIVE: This study aims to investigate overall career satisfaction rate amongst US-based oral and maxillofacial surgeons (OMSs) and to evaluate possible predictors of professional stress and quality of life. STUDY DESIGN: Members of the American Association of Oral and Maxillofacial Surgeons were invited to complete an online survey-based assessment. Descriptive statistics were computed; univariate analysis was performed to identify predictors for satisfaction. RESULTS: The overall response rate was 29%. Most of respondents were male (88.6%), aged >45 years (71.7%), married (91.7%), and working at private and/or group-based practices (55.9%) for >15 years (66.6%). Most surgeons 91.3% reported being satisfied with their career with 84.9% willing to choose a career in OMS again. No significant difference was noted in satisfaction rates between academic and non-academic surgeons. On univariate analysis, no demographic characteristic was predictive of satisfaction. CONCLUSIONS: Reportedly, 91.3% of US-based OMSs have a significant degree of career satisfaction, and a majority would choose the specialty as their profession again.
Subject(s)
Oral and Maxillofacial Surgeons , Quality of Life , Humans , Male , United States , Female , Job Satisfaction , Surveys and Questionnaires , Life Style , Personal SatisfactionABSTRACT
BACKGROUND: The University of Pennsylvania classification system (Penn class) of acute type A aortic dissection (aTAAD) is used to evaluate the impact of malperfusion on surgical outcomes. The purpose of this analysis was to determine the validity of Penn class in a larger and more contemporary cohort and to compare its performance with other classification systems. METHODS: This was a retrospective study of patients who underwent aTAAD repair at our institution from 1993 to 2020. Patients were assigned to Penn class on the basis of burden of preoperative malperfusion syndrome. The association of Penn class and 30-day mortality was evaluated by multivariable regression. The discriminatory ability of Penn class for mortality was determined by a bootstrapped C statistic. RESULTS: There were 1192 patients, of whom 50% were assigned to Penn class A (no ischemia), 21% (253/1192) to class B (local ischemia), 14% (171/1192) to class C (generalized ischemia), and 14% (167/1192) to class B-C (combined ischemia). The incidence of mortality rose significantly with increasing Penn class from 5% (31/601) in class A to 35% (59/167) in class B-C (P < .001). After adjustment, 30-day mortality increased significantly with class B (odds ratio [OR], 2.43; 95% CI, 1.38-4.27), class C (OR, 3.39; 95% CI, 1.90-6.03), and class B-C (OR, 13.08; 95% CI, 7.90-22.15) compared with class A. The C statistic was 0.77 (95% CI, 0.72-0.80) and was significantly higher than for models featuring alternative classification systems (P < .05). CONCLUSIONS: Penn class provides excellent discrimination for 30-day mortality after repair of aTAAD.
Subject(s)
Aortic Dissection , Vascular Surgical Procedures , Humans , Treatment Outcome , Retrospective Studies , Vascular Surgical Procedures/adverse effects , Aortic Dissection/complications , Aortic Dissection/surgery , Ischemia/etiology , Ischemia/surgery , Acute DiseaseABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic continues to pose a significant threat to patients receiving advanced heart failure therapies. The current study was undertaken to better understand the relationship between obesity and outcomes of SARS-CoV-2 infection in patients with a left ventricular assist device (LVAD) or heart transplant. We performed a retrospective review of patients with a heart transplant or LVAD who presented to one of the participating 11 institutions between April 1 and November 30, 2020. Patients were grouped by body mass index (BMI) into obese (BMI ≥ 30 k/m2) and nonobese cohorts (BMI < 30 kg/m2). Multivariable logistic regression models were used to estimate effects of obesity on outcomes of interest. Across all centers, 162 heart transplant and 81 LVAD patients were identified; 54 (33%) and 38 (47%) were obese, respectively. Obese patients tended to have more symptoms at presentation. No differences in rates of hospitalization or ICU admission were noted. Obese patients with LVADs were more likely to require mechanical ventilation (39% vs. 8%, p < 0.05). No differences in renal failure or secondary infection were noted. Mortality was similar among heart transplant patients (11% [obese] vs. 16% [nonobese], p = 0.628) and LVAD patients (12% vs. 15%, p = 1.0). BMI was not associated with increased adjusted odds of mortality, ICU admission, or mechanical ventilation (all p > 0.10). In summary, acute presentations of SARS-CoV-2 among heart transplant and LVAD recipients carry a significantly higher mortality than the general population, although BMI does not appear to impact this. Further studies on the longer-term effects of COVID-19 on this population are warranted.