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BACKGROUND: Patient satisfaction is critical for referrals and reimbursement of surgical faculty but remains poorly characterized for residents. We investigated whether patient evaluations of surgical trainees vary by resident gender. METHODS: Surgical inpatients evaluated surgical resident care postoperatively after positively identifying trainees. Evaluations (Consumer Assessment of Healthcare Providers and Systems Surgical Care Surveys (S-CAHPS)) were scored by the "top-box" method, stratified by training level, and compared between women and men residents. RESULTS: Ninety-one percent of patients participated (n â= â324/357). Patients recognized women interns less than men (75.0 â% vs 87.2 â%, p â= â0.01). S-CAHPS scores for women vs men interns were equivalent except for spending sufficient time with patients (75.6 â% vs 88.0 â%, p â= â0.02). For senior residents, there was no difference in patient recognition of women vs men (83.9 â% vs 85.2 â%, p â= â0.91) or in any S-CAHPS scores (p â> â0.05). CONCLUSIONS: Gendered differences in patient evaluations of surgical trainees exist for interns but resolve by senior years. Future work should explore how patient evaluations can support trainee development while ensuring patients recognize the role of surgical residents regardless of gender.
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Cirugía General , Internado y Residencia , Satisfacción del Paciente , Humanos , Femenino , Masculino , Satisfacción del Paciente/estadística & datos numéricos , Cirugía General/educación , Adulto , Persona de Mediana Edad , Factores Sexuales , Médicos Mujeres/estadística & datos numéricos , AncianoRESUMEN
OBJECTIVES: This trial examines the impact of the Provider Awareness and Cultural dexterity Toolkit for Surgeons (PACTS) curriculum on surgical residents' knowledge, cross-cultural care, skills, and beliefs. SUMMARY BACKGROUND DATA: Cross-cultural training of providers may reduce healthcare outcome disparities, but its effectiveness in surgical trainees is unknown. METHODS: PACTS focuses on developing skills needed for building trust, working with patients with limited English proficiency, optimizing informed consent, and managing pain. The PACTS trial was a randomized crossover trial of 8 academic general surgery programs in the United States: The Early group ("Early") received PACTS between Periods 1 and 2, while the Delayed group ("Delayed") received PACTS between Periods 2 and 3. Residents were assessed pre- and post-intervention on Knowledge, Cross-Cultural Care, Self-Assessed Skills, and Beliefs. Chi-square and Fisher's exact tests were conducted to evaluate within- and between-intervention group differences. RESULTS: Of 406 residents enrolled, 315 were exposed to the complete PACTS curriculum. Early residents' Cross-Cultural Care (79.6% to 88.2%, P<0.0001), Self-Assessed Skills (74.5% to 85.0%, P<0.0001), and Beliefs (89.6% to 92.4%, P=0.0028) improved after PACTS; Knowledge scores (71.3% to 74.3%, P=0.0661) were unchanged. Delayed resident scores pre- to post-PACTS showed minimal improvements in all domains. When comparing the two groups at Period 2, Early residents had modest improvement in all 4 assessment areas, with statistically significant increase in Beliefs (92.4% vs 89.9%, P=0.0199). CONCLUSION: The PACTS curriculum is a comprehensive tool that improved surgical residents' knowledge, preparedness, skills, and beliefs, which will help with caring for diverse patient populations.
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BACKGROUND: ChatGPT-4 is a large language model with possible applications to surgery education The aim of this study was to investigate the accuracy of ChatGPT-4's surgical decision-making compared with general surgery residents and attending surgeons. METHODS: Five clinical scenarios were created from actual patient data based on common general surgery diagnoses. Scripts were developed to sequentially provide clinical information and ask decision-making questions. Responses to the prompts were scored based on a standardized rubric for a total of 50 points. Each clinical scenario was run through Chat GPT-4 and sent electronically to all general surgery residents and attendings at a single institution. Scores were compared using Wilcoxon rank sum tests. RESULTS: On average, ChatGPT-4 scored 39.6 points (79.2%, standard deviation ± 0.89 points). A total of five junior residents, 12 senior residents, and five attendings completed the clinical scenarios (resident response rate = 15.9%; attending response rate = 13.8%). On average, the junior residents scored a total of 33.4 (66.8%, standard deviation ± 3.29), senior residents 38.0 (76.0%, standard deviation ± 4.75), and attendings 38.8 (77.6%, standard deviation ± 5.45). ChatGPT-4 scored significantly better than junior residents (P = .009) but was not significantly different from senior residents or attendings. ChatGPT-4 was significantly better than junior residents at identifying the correct operation to perform (P = .0182) and recommending additional workup for postoperative complications (P = .012). CONCLUSION: ChatGPT-4 performed superior to junior residents and equivalent to senior residents and attendings when faced with surgical patient scenarios. Large language models, such as ChatGPT, may have the potential to be an educational resource for junior residents to develop surgical decision-making skills.
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Competencia Clínica , Toma de Decisiones Clínicas , Cirugía General , Internado y Residencia , Humanos , Cirugía General/educaciónRESUMEN
OBJECTIVE: Surgery for primary tumors of the mobile spine and sacrum often requires complex reconstruction techniques to cover soft-tissue defects and to treat wound and CSF-related complications. The anatomical, vascular, and immunoregulatory characteristics of the omentum make it an excellent local substrate for the management of radiation soft-tissue injury, infection, and extensive wound defects. This study describes the authors' experience in complex wound reconstruction using pedicled omental flaps to cover defects in surgery for mobile spine and sacral primary tumors. METHODS: A retrospective cohort analysis was conducted on 34 patients who underwent pedicled omental flap reconstruction after en bloc resection of primary sacral and mobile spine tumors between 2010 and 2020. The study focused on assessing the indications for omental flap usage, including soft-tissue coverage, protection against postoperative radiation therapy, infection management, vascular supply for bone grafts, and dural defect and CSF leak repair. Patient demographic characteristics, tumor characteristics, surgical outcomes, and follow-up data were analyzed to determine the procedure's efficacy and complication rates. RESULTS: From 2010 to 2020, 34 patients underwent pedicled omental flap reconstruction after en bloc resection of sacral (24 of 34 [71%]) and mobile spine (10 of 34 [29%]) primary tumors, mostly chordomas. The patient cohort included 21 men and 13 women with a median (range) age of 60 (32-89) years. The most common indication for omental flap was soft-tissue coverage (20 of 34 [59%]). Other indications included protecting abdominopelvic organs for postoperative radiation therapy (6 of 34 [18%]), treating infections (5 of 34 [15%]), providing vascular supply for free fibular bone graft (1 of 34 [3%]), and repairing large dural defects and CSF leak (2 of 34 [6%]). The median (range) follow-up was 24 (0-132) months, during which 71% (24 of 34) of patients did not require additional surgery for wound-related complications. At last follow-up, 59% (20 of 34) had stable disease and 32% (11 of 34) had recurrence, had progression of disease, or had been discharged to hospice after treatment. CONCLUSIONS: The pedicled omentum is an effective local tissue graft that can be used for complex wound reconstruction and management of high-risk closures in primary spine tumors. This technique may have a lower rate of complications than other approaches and may influence surgical planning and flap selection in challenging cases.
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Epiplón , Procedimientos de Cirugía Plástica , Sacro , Neoplasias de la Columna Vertebral , Colgajos Quirúrgicos , Humanos , Masculino , Femenino , Neoplasias de la Columna Vertebral/cirugía , Persona de Mediana Edad , Epiplón/trasplante , Epiplón/cirugía , Sacro/cirugía , Procedimientos de Cirugía Plástica/métodos , Adulto , Estudios Retrospectivos , AncianoRESUMEN
Diagnosis of desmoid-type fibromatosis (DF) may be challenging on biopsy due to morphologic overlap with reactive fibrosis (scar) and other uniform spindle cell neoplasms. Evaluation of nuclear ß-catenin, a surrogate of Wnt pathway activation, is often difficult in DF due to weak nuclear expression and high background membranous/cytoplasmic staining. Lymphoid enhancer-factor 1 (LEF1) is a recently characterized effector partner of ß-catenin which activates the transcription of target genes. We investigated the performance of LEF1 and ß-catenin immunohistochemistry in a retrospective series of 156 soft tissue tumors, including 35 DF, 3 superficial fibromatosis, and 121 histologic mimics (19 soft tissue perineurioma, 8 colorectal perineurioma, 4 intraneural perineurioma, 26 scars, 23 nodular fasciitis, 6 low-grade fibromyxoid sarcomas, 6 angioleiomyomas, 5 neurofibromas, 5 dermatofibrosarcoma protuberans, 3 low-grade myofibroblastic sarcomas, 3 synovial sarcomas, 3 inflammatory myofibroblastic tumors, 2 schwannomas, and 1 each of Gardner-associated fibroma, radiation-associated spindle cell sarcoma, sclerotic fibroma, dermatofibroma, and glomus tumor). LEF1 expression was not only seen in 33/35 (94%) of DF but also observed in 19/23 (82%) nodular fasciitis, 7/19 (37%) soft tissue perineurioma, 2/3 (66%) synovial sarcoma, and 6/26 (23%) scar, as well as in 1 radiation-associated spindle cell sarcoma. The sensitivity and specificity of LEF1 IHC for diagnosis of DF were 94% and 70%, respectively. By comparison, ß-catenin offered similar sensitivity, 94%, but 88% specificity. Positivity for LEF1 and ß-catenin in combination showed sensitivity of 89%, lower than the sensitivity of ß-catenin alone (94%); however, the combination of both LEF1 and ß-catenin improved specificity (96%) compared to the specificity of ß-catenin alone (88%). Although LEF1 has imperfect specificity in isolation, this stain has diagnostic utility when used in combination with ß-catenin.
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Biomarcadores de Tumor , Fibromatosis Agresiva , Inmunohistoquímica , Factor de Unión 1 al Potenciador Linfoide , Neoplasias de los Tejidos Blandos , beta Catenina , Femenino , Humanos , Masculino , beta Catenina/análisis , beta Catenina/metabolismo , Biomarcadores de Tumor/análisis , Diagnóstico Diferencial , Fibromatosis Agresiva/diagnóstico , Fibromatosis Agresiva/patología , Factor de Unión 1 al Potenciador Linfoide/análisis , Estudios Retrospectivos , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/patologíaRESUMEN
BACKGROUND: The multimodality management of patients with gastroesophageal cancers is rapidly evolving, with the introduction of new therapies against potential molecular targets paving the way to personalized medicine for patients with both resectable and metastatic disease. Over the past 2 years, several important studies evaluating these new targeted therapies, as well as minimally invasive surgical approaches to gastric cancer, have been published. METHODS: This review article summarizes the top studies published in gastric cancer over the past 2 years that are fundamentally changing our practice approach to gastric cancer patients. RESULTS: First, the long-term safety and efficacy of laparoscopic distal gastrectomy as compared with open gastrectomy for locally advanced gastric cancer was confirmed with the publication of the 5-year outcomes of the CLASS-01 and KLASS-02 randomized clinical trials. In addition, several important studies of perioperative immunotherapy for patients with resectable gastric or gastroesophageal junction cancers are ongoing, and in 2022, an interim analysis of the DANTE trial and the final results of the GERCOR NEONIPIGA study were reported. Lastly, the KEYNOTE-859 and SPOTLIGHT trials address an unmet need for additional targeted therapies for patients with previously untreated, human epidermal growth factor receptor-2 (HER2)-negative, unresectable or metastatic gastroesophageal cancers, incorporating immune checkpoint inhibitors and targeting Claudin-18 isoform 2 (CLDN18.2) with the monoclonal antibody zolbetuximab, respectively. CONCLUSIONS: This article summarizes the findings and implications of several important studies published over the past 2 years that are fundamentally changing the way we treat patients with gastroesophageal cancer.
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Gastrectomía , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/terapia , Neoplasias Gástricas/tratamiento farmacológico , Terapia Combinada , Laparoscopía/métodos , Inmunoterapia/métodos , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/terapia , PronósticoRESUMEN
The Provider Awareness and Cultural dexterity Toolkit for Surgeons (PACTS) curriculum was developed to improve surgical resident cultural dexterity, with the goal of promoting health equity by developing cognitive skills to adapt to individual patients' needs to ensure personal, patient-centered surgical care through structured educational interventions for surgical residents. Funded by the National Institute of Health (NIH)'s National Institute on Minority Health and Health Disparities, PACTS addresses surgical disparities in patient care by incorporating varied educational interventions, with investigation of both traditional and nontraditional educational outcomes such as patient-reported and clinical outcomes, across multiple hospitals and regions. The unique attributes of this multicenter, multiphased research trial will not only impact future surgical education research, but hopefully improve how surgeons learn nontechnical skills that modernize surgical culture and surgical care. The present perspective piece serves as an introduction to this multifaceted surgical education trial, highlighting the rationale for the study and critical curricular components such as key stakeholders from multiple institutions, multimodal learning and feedback, and diverse educational outcomes.
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Internado y Residencia , Cirujanos , Humanos , Competencia Clínica , Curriculum , Educación de Postgrado en Medicina , Estudios Multicéntricos como Asunto , Ensayos Clínicos como AsuntoRESUMEN
BACKGROUND: As the US healthcare sector contributes to 5-10% of national CO2 emissions, with a substantial contribution from surgical services, a collective effort is important to minimize the climate footprint of surgery. Solid plastic waste generated from single-use items in operating rooms is a major contributor to greenhouse gas emissions. To address this problem, we implemented a pilot study to replace single-use scrub caps with reusable caps. METHODS: Ninety-two surgical trainees at the Massachusetts General Hospital, Boston, were provided reusable personalized scrub caps. Over 6 months, their use of the reusable cap was compared with corresponding use of disposable single-use caps. We then used the cost of raw materials, fabric and cap manufacturing, transportation, and end-of-life/waste treatment to perform an economic and environmental burden analysis. RESULTS: After 6 months of reusable scrub cap use, 33 participants (51.6%) reported that due to their use of a reusable scrub cap, their utilization of disposable bouffant or caps had decreased by 76-100%. This was associated with a significant reduction in the use of single-use caps after adjusting for surgical case volume. The carbon footprint of single-use scrub caps was significantly higher than reusable caps during the study period. Reusable scrub cap usage also strongly correlated with substantial reductions in energy consumption and freshwater toxicity. CONCLUSIONS: Reusable personalized cloth scrub caps are cost-effective and can help reduce surgery's carbon footprint by reducing waste generated from disposable scrub cap use. More programs should consider replacing single-use polypropylene caps with reusable scrub caps for their operating room staff.
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Quirófanos , Polipropilenos , Humanos , Análisis Costo-Beneficio , Proyectos PilotoRESUMEN
This survey study investigates whether personalized scrub caps for surgical trainees can help decrease role and name misidentification, microaggressions, and miscommunication-related delays in patient care.
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Amplification of MDM2 on supernumerary chromosomes is a common mechanism of P53 inactivation across tumors. Here, we investigated the impact of MDM2 overexpression on chromatin, gene expression, and cellular phenotypes in liposarcoma. Three independent regulatory circuits predominate in aggressive, dedifferentiated tumors. RUNX and AP-1 family transcription factors bind mesenchymal gene enhancers. P53 and MDM2 co-occupy enhancers and promoters associated with P53 signaling. When highly expressed, MDM2 also binds thousands of P53-independent growth and stress response genes, whose promoters engage in multi-way topological interactions. Overexpressed MDM2 concentrates within nuclear foci that co-localize with PML and YY1 and could also contribute to P53-independent phenotypes associated with supraphysiologic MDM2. Importantly, we observe striking cell-to-cell variability in MDM2 copy number and expression in tumors and models. Whereas liposarcoma cells are generally sensitive to MDM2 inhibitors and their combination with pro-apoptotic drugs, MDM2-high cells tolerate them and may underlie the poor clinical efficacy of these agents.
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OBJECTIVE: Recent studies have demonstrated burnout in surgeons, with trainees affected at alarming levels. However, few studies have focused on specific wellbeing initiatives in surgical residency. We implemented facilitated process groups at our residency program and aimed to understand the feasibility and perception of this program. DESIGN: We recruited a psychologist to conduct weekly process groups. Each postgraduate year (PGY) class was scheduled for a rotating 1-hour session every 6 weeks during protected didactic time. A presurvey was conducted shortly following program commencement for PGY1-5 residents (11/2020-1/2021) and a postsurvey conducted after 9 to 10 months of implementation for PGY2-5 residents. Surveys included demographics, a 2-item Maslach Burnout Inventory, and questions about stress, lifestyle, and perception of the process groups, including qualitative feedback. SETTING: The study took place at within the General Surgery Residency at Massachusetts General Hospital, a tertiary-care institution in Boston, Massachusetts. PARTICIPANTS: Participants in process groups were all General Surgery residents during the timeframe of the study. Participation in the presurvey and postsurvey was voluntary for residents. RESULTS: A total of 32 and 35 residents completed the presurveys and postsurveys, respectively. Groups were similar with regards to gender and race. A total of 97% and 57% of postsurvey respondents attended ≥1 and ≥3 process groups, respectively, with 95% citing clinical/other obligations as the cause of missing sessions. Perception of process groups was highly positive and persisted across both surveys. There were no significant differences in perception or burnout questions, except for a slight decrease in "I think process groups might help me process personal challenges" on postsurvey. Of 15 qualitative postsurvey responses, 73% were positive and the remainder were neutral. CONCLUSIONS: Based on current measures, it is feasible to implement facilitated process groups for surgical residents. Resident perception of these groups was persistently positive.
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Agotamiento Profesional , Cirugía General , Internado y Residencia , Cirujanos , Humanos , Estudios de Factibilidad , Encuestas y Cuestionarios , Agotamiento Profesional/prevención & control , Percepción , Cirugía General/educaciónRESUMEN
OBJECTIVES: Epicardial adipose tissue (EAT) thickness, a novel marker of cardiovascular disease (CVD), is increased in children with a healthy weight and type 1 diabetes (T1D). The prevalence of obesity has increased in children with T1D and may confer additional CVD risk. The purpose of this study was to examine EAT thickness in youth with and without T1D in the setting of overweight/obesity. METHODS: Youth with overweight/obesity and T1D (n=38) or without T1D (n=34) between the ages of 6-18 years were included in this study. Echocardiogram using spectral and color flow Doppler was used to measure EAT and cardiac function. Waist circumference, blood pressure, and HbA1c, were used to calculate estimated glucose disposal rate (eGDR) to estimate insulin resistance in children with T1D. RESULTS: EAT thickness was not significantly different in youth with T1D compared to controls (2.10 ± 0.67 mm vs. 1.90 ± 0.59 mm, p=0.19). When groups were combined, EAT significantly correlated with age (r=0.449, p≤0.001), BMI (r=0.538, p≤0.001), waist circumference (r=0.552, p≤0.001), systolic BP (r=0.247, p=0.036), myocardial performance index (r=-0.287, p=0.015), ejection fraction (r=-0.442, p≤0.001), and cardiac output index (r=-0.306, p=0.009). In the group with T1D, diastolic BP (r=0.39, p=0.02) and eGDR (r=-0.48, p=0.002) correlated with EAT. CONCLUSIONS: EAT was associated with measures of adiposity and insulin resistance but does not differ by diabetes status among youth with overweight/obesity. These findings suggest that adiposity rather than glycemia is the main driver of EAT thickness among youth with T1D.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 1 , Resistencia a la Insulina , Adolescente , Humanos , Niño , Diabetes Mellitus Tipo 1/complicaciones , Sobrepeso/complicaciones , Resistencia a la Insulina/fisiología , Factores de Riesgo , Obesidad/complicaciones , Glucosa , Tejido Adiposo/diagnóstico por imagen , Pericardio/diagnóstico por imagenRESUMEN
The glandular stomach is composed of two regenerative compartments termed corpus and antrum, and our understanding of the transcriptional networks that maintain these tissues is incomplete. Here we show that cell types with equivalent functional roles in the corpus and antrum share similar transcriptional states including the poorly characterized stem cells of the isthmus region. To further study the isthmus, we developed a monolayer two-dimensional (2D) culture system that is continually maintained by Wnt-responsive isthmus-like cells capable of differentiating into several gastric cell types. Importantly, 2D cultures can be converted into conventional three-dimensional organoids, modelling the plasticity of gastric epithelial cells in vivo. Finally, we utilized the 2D culture system to show that Sox2 is both necessary and sufficient to generate enterochromaffin cells. Together, our data provide important insights into gastric homeostasis, establish a tractable culture system to capture isthmus cells and uncover a role for Sox2 in enterochromaffin cells.
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Mucosa Gástrica , Estómago , Mucosa Gástrica/metabolismo , Diferenciación Celular , Células Madre/metabolismo , HomeostasisRESUMEN
OBJECTIVE: To investigate inpatient satisfaction with surgical resident care. BACKGROUND: Surgical trainees are often the primary providers of care to surgical inpatients, yet patient satisfaction with surgical resident care is not well characterized or routinely assessed. METHODS: English-speaking, general surgery inpatients recovering from elective gastrointestinal and oncologic surgery were invited to complete a survey addressing their satisfaction with surgical resident care. Patients positively identified photos of surgical senior residents and interns before completing a modified version of the Consumer Assessment of Healthcare Providers and Systems Surgical Care Survey (S-CAHPS). Adapted S-CAHPS items were scored using the "top-box" method. RESULTS: Ninety percent of recruited patients agreed to participate (324/359, mean age=62.2, 50.3% male). Patients were able to correctly identify their seniors and interns 85% and 83% of the time, respectively ( P =0.14). On a 10-point scale, seniors had a mean rating of 9.23±1.27 and interns had a mean rating of 9.01±1.49 ( P =0.14). Ninety-nine percent of patients agreed it was important to help in the education of future surgeons. CONCLUSIONS: Surgical inpatients were able to recognize their resident physicians with high frequency and rated resident care highly overall, suggesting that they may serve as a willing source of feedback regarding residents' development of core competencies such as interpersonal skills, communication, professionalism, and patient care. Future work should investigate how to best incorporate patient evaluation of surgical resident care routinely into trainee assessment to support resident development.
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Cirugía General , Internado y Residencia , Humanos , Masculino , Femenino , Pacientes Internos , Encuestas y Cuestionarios , Satisfacción del Paciente , Personal de Salud/educación , Cirugía General/educación , Competencia ClínicaRESUMEN
OBJECTIVE: The effects of stroke and delirium on postdischarge cognition and patient-centered health outcomes after surgical aortic valve replacement (SAVR) are not well characterized. Here, we assess the impact of postoperative stroke and delirium on these health outcomes in SAVR patients at 90 days. METHODS: Patients (N = 383) undergoing SAVR (41% received concomitant coronary artery bypass graft) enrolled in a randomized trial of embolic protection devices underwent serial neurologic and delirium evaluations at postoperative days 1, 3, and 7 and magnetic resonance imaging at day 7. Outcomes included 90-day functional status, neurocognitive decline from presurgical baseline, and quality of life. RESULTS: By postoperative day 7, 25 (6.6%) patients experienced clinical stroke and 103 (28.5%) manifested delirium. During index hospitalization, time to discharge was longer in patients experiencing stroke (hazard ratio, 0.62; 95% confidence interval [CI], 0.42-0.94; P = .02) and patients experiencing delirium (hazard ratio, 0.68; 95% CI, 0.54-0.86; P = .001). At day 90, patients experiencing stroke were more likely to have a modified Rankin score >2 (odds ratio [OR], 5.9; 95% CI, 1.7-20.1; P = .01), depression (OR, 5.3; 95% CI, 1.6-17.3; P = .006), a lower 12-Item Short Form Survey physical health score (adjusted mean difference -3.3 ± 1.9; P = .08), and neurocognitive decline (OR, 7.8; 95% CI, 2.3-26.4; P = .001). Delirium was associated with depression (OR, 2.2; 95% CI, 0.9-5.3; P = .08), lower 12-Item Short Form Survey physical health (adjusted mean difference -2.3 ± 1.1; P = .03), and neurocognitive decline (OR, 2.2; 95% CI, 1.2-4.0; P = .01). CONCLUSIONS: Stroke and delirium occur more frequently after SAVR than is commonly recognized, and these events are associated with disability, depression, cognitive decline, and poorer quality of life at 90 days postoperatively. These findings support the need for new interventions to reduce these events and improve patient-centered outcomes.
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Left ventricular assist device (LVAD) use in patients with dilated cardiomyopathy (DCM) can lead to a differential response in the LV and right ventricle (RV), and RV failure remains the most common complication post-LVAD insertion. We assessed transcriptomic signatures in end-stage DCM, and evaluated changes in gene expression (mRNA) and regulation (microRNA/miRNA) following LVAD. LV and RV free-wall tissues were collected from end-stage DCM hearts with (n = 8) and without LVAD (n = 8). Non-failing control tissues were collected from donated hearts (n = 6). Gene expression (for mRNAs/miRNAs) was determined using microarrays. Our results demonstrate that immune response, oxygen homeostasis, and cellular physiological processes were the most enriched pathways among differentially expressed genes in both ventricles of end-stage DCM hearts. LV genes involved in circadian rhythm, muscle contraction, cellular hypertrophy, and extracellular matrix (ECM) remodelling were differentially expressed. In the RV, genes related to the apelin signalling pathway were affected. Following LVAD use, immune response genes improved in both ventricles; oxygen homeostasis and ECM remodelling genes improved in the LV and, four miRNAs normalized. We conclude that LVAD reduced the expression and induced additional transcriptomic changes of various mRNAs and miRNAs as an integral component of the reverse ventricular remodelling in a chamber-specific manner.
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Cardiomiopatía Dilatada/metabolismo , Corazón Auxiliar/efectos adversos , Transcriptoma , Adulto , Cardiomiopatía Dilatada/patología , Cardiomiopatía Dilatada/terapia , Femenino , Ventrículos Cardíacos/metabolismo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: The optimal timing of chemoradiotherapy (CRT) for patients with localized gastric cancer remains unclear. This study aimed to compare the survival outcomes between neoadjuvant and postoperative CRT for patients with gastric and gastroesophageal junction (GEJ) cancer. METHODS: This retrospective study analyzed 152 patients with gastric (42%) or GEJ (58%) adenocarcinoma who underwent definitive surgical resection and received either neoadjuvant or postoperative CRT between 2005 and 2017 at the authors' institution. The primary end point of the study was overall survival (OS). RESULTS: The median follow-up period was 37.5 months. Neoadjuvant CRT was performed for 102 patients (67%) and postoperative CRT for 50 patients (33%). The patients who received neoadjuvant CRT were more likely to be male and to have a GEJ tumor, positive lymph nodes, and a higher clinical stage. The median radiotherapy (RT) dose was 50.4 Gy for neoadjuvant RT and 45.0 Gy for postoperative RT (p < 0.001). The neoadjuvant CRT group had a pathologic complete response (pCR) rate of 26% and a greater rate of R0 resection than the postoperative CRT group (95% vs. 76%; p = 0.002). Neoadjuvant versus postoperative CRT was associated with a lower rate of any grade 3+ toxicity (10% vs. 54%; p < 0.001). The multivariable analysis of OS showed lower hazards of death to be independently associated neoadjuvant versus postoperative CRT (hazard ratio [HR] 0.57; 95% confidence interval [CI] 0.36-0.91; p = 0.020) and R0 resection (HR 0.50; 95% CI 0.27-0.90; p = 0.021). CONCLUSIONS: Neoadjuvant CRT was associated with a longer OS, a higher rate of R0 resection, and a lower treatment-related toxicity than postoperative CRT. The findings suggest that neoadjuvant CRT is superior to postoperative CRT in the treatment of gastric and GEJ cancer.