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INTRODUCTION: Training for mass casualty incident (MCI) response is critical to ensure that resource allocation and treatment priorities limit preventable mortality. Previous research has investigated the use of immersive virtual environments as an alternative to high fidelity MCI training, which is expensive and logistically challenging to implement. While these have demonstrated positive early results, they still require complex technology deployment, dedicated training facilities, and significant time from instructors and facilitators. This study explores the feasibility of a smartphone-based application for trauma care training and MCI triage to fill the gap between classroom learning and high-fidelity simulation. The goals of this investigation were to evaluate clinician perceptions of a virtual MCI training simulator's usability, acceptability, fidelity, functionality, and pacing. MATERIALS AND METHODS: This study used a smartphone-based training simulation called Extensible Field and Evacuation Care Training in a Virtual Environment (EFECTIVE), which presents virtual patient scenarios in a gamified, but visually high-fidelity environment. A total of 21 participants were recruited as a convenience sample of medical students, paramedics, nurses, and emergency medicine resident and attending physicians at University of Massachusetts Memorial Medical Center, an urban tertiary care medical center. Participants completed a brief tutorial and then performed a series of virtual patient scenarios and 1 MCI scenario on the simulator, each of which was 5 minutes in duration. Then, each participant completed a survey assessing the perceived usability, acceptability, fidelity, functionality, and pacing of the virtual training simulator. The research protocol was approved by the University of Massachusetts Chan Medical School Institutional Review Board. RESULTS: 48% of participants disagreed that a virtual simulator could completely replace live MCI training, though 71% agreed that app-based simulations could effectively supplement live MCI training and 67% felt that they could be used to learn how to order medical interventions in care under fire scenarios. 80% of participants agreed that the simulation could be used to practice MCI triage and to gain experience with coordinating movement of casualties to casualty collection points. 67% of participants believed that use of virtual simulators would increase their MCI preparedness. 76% agreed that the clinical cases depicted were medically realistic and that the clinical cases presented accurately represented the scenarios described. In addition, despite being presented on a smartphone as opposed to virtual reality, 62% of participants rated the experience immersive. CONCLUSIONS: This study provides encouraging evidence that easy to deploy smartphone-based simulations may be an effective way to supplement MCI and care under fire training. Although the study is limited by a small sample size, there was strong agreement among participants from a wide variety of emergency medicine roles that such a simulation could train core topics associated with MCI triage. Because app-based simulations are easily deployable and can be executed quickly and frequently, they could be used as a more flexible training model compared to large scale live or virtual reality-based simulations. The results of this investigation also indicate that a sufficient level of medical realism can be achieved without live simulation.
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Incidentes con Víctimas en Masa , Teléfono Inteligente , Humanos , Masculino , Adulto , Femenino , Entrenamiento Simulado/métodos , Entrenamiento Simulado/normas , Entrenamiento Simulado/estadística & datos numéricos , Massachusetts , Encuestas y Cuestionarios , Realidad Virtual , Triaje/métodos , Triaje/normasRESUMEN
Background: Simulations are used to improve professional practice across multiple health professions; however, the application of simulations in pharmacy curricula has been limited by a lack of evidence. Objectives: To delineate the competencies of pharmacy residents needed to assess their progress while participating in a high-fidelity simulation training program and to create a reliable assessment tool based on these competencies. Methods: A literature review was conducted, followed by application of a modified Delphi method. An assessment tool based on the results of these activities was drafted (in French). A second modified Delphi process was carried out to assess the reliability of the tool, and the tool was modified accordingly. Results: The literature search yielded a total of 2670 articles, of which 289 were included for analysis. The first modified Delphi process involved 19 experts in the first round and 10 experts in the second round. The Cronbach α was 0.866 (95% confidence interval [CI] 0.713-0.960), indicating good reliability. A total of 7 competencies were retained for inclusion in the SIMPHARM assessment tool: professionalism, leadership, teamwork, communication, critical thinking, preparation and packaging of medications, and pharmaceutical calculations. The second modified Delphi process involved 9 experts in the first round and 11 experts in the second round. The final Cronbach α was 0.877 (95% CI 0.741-0.960). Conclusions: To the authors' knowledge, this was one of the largest studies exploring pharmacy competencies in the context of simulations. This work yielded a reliable framework for the assessment of pharmacy residents' competencies. This assessment tool may help evaluators in assessing the competencies of pharmacy trainees after simulation training.
Contexte: Les simulations sont utilisées dans le but d'améliorer la pratique professionnelle de plusieurs professions de la santé; cependant, le manque de données probantes limite leur application dans les programmes d'enseignement en pharmacie. Objectifs: Décrire les compétences nécessaires pour évaluer le progrès des résidents en pharmacie qui participent à une formation basée sur un programme de simulation haute-fidélité; et mettre au point un outil d'évaluation fiable qui se base sur ces compétences. Méthodologie: Une revue de littérature a été effectuée, avant d'appliquer une méthode Delphi modifiée et de faire l'ébauche d'un outil d'évaluation (en français) basé sur les résultats de ces activités. Une deuxième méthode Delphi modifiée a été appliquée pour évaluer la fiabilité de l'outil et celui-ci a fait l'objet de modifications en conséquence. Résultats: La revue de littérature a donné un total de 2670 articles, parmi lesquels 289 ont été inclus à des fins d'analyse. La première méthode Delphi modifiée a impliqué 19 experts pour la première phase, et 10 pour la seconde. Le coefficient alpha de Cronbach était de 0,866 (intervalle de confiance [IC] à 95 % 0,7130,960), indiquant une bonne fiabilité. Au total, 7 compétences à inclure dans l'outil d'évaluation ont été retenues: professionnalisme, leadership, travail d'équipe, communication, pensée critique, préparation et conditionnement des médicaments, et calculs pharmaceutiques. La deuxième méthode Delphi modifiée impliquait quant à elle 9 experts pour la première phase et 11 pour la seconde. Le coefficient alpha de Cronbach final était de 0,877 (IC à 95 % 0,7410,960). Conclusions: À la connaissance des auteurs, cette étude était l'une des plus importantes se penchant sur les compétences en pharmacie dans le contexte des simulations. Ce travail a donné lieu à un cadre de référence fiable pour évaluer les compétences des résidents en pharmacie. Cet outil d'évaluation pourrait aider les évaluateurs à évaluer les compétences des stagiaires à la suite d'une formation par simulation.
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The monitoring of body temperature is a recent addition to the plethora of parameters provided by wellness and fitness wearable devices. Current wearable temperature measurements are made at the skin surface, a measurement that is impacted by the ambient environment of the individual. The use of near-infrared spectroscopy provides the potential for a measurement below the epidermal layer of skin, thereby having the potential advantage of being more reflective of physiological conditions. The feasibility of noninvasive temperature measurements is demonstrated by using an in vitro model designed to mimic the near-infrared spectra of skin. A miniaturizable solid-state laser-diode-based near-infrared spectrometer was used to collect diffuse reflectance spectra for a set of seven tissue phantoms composed of different amounts of water, gelatin, and Intralipid. Temperatures were varied between 20-24 °C while collecting these spectra. Two types of partial least squares (PLS) calibration models were developed to evaluate the analytical utility of this approach. In both cases, the collected spectra were used without pre-processing and the number of latent variables was the only optimized parameter. The first approach involved splitting the whole dataset into separate calibration and prediction subsets for which a single optimized PLS model was developed. For this first case, the coefficient of determination (R2) is 0.95 and the standard error of prediction (SEP) is 0.22 °C for temperature predictions. The second strategy used a leave-one-phantom-out methodology that resulted in seven PLS models, each predicting the temperatures for all spectra in the held-out phantom. For this set of phantom-specific predicted temperatures, R2 and SEP values range from 0.67-0.99 and 0.19-0.65 °C, respectively. The stability and reproducibility of the sample-to-spectrometer interface are identified as major sources of spectral variance within and between phantoms. Overall, results from this in vitro study justify the development of future in vivo measurement technologies for applications as wearables for continuous, real-time monitoring of body temperature for both healthy and ill individuals.
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Fantasmas de Imagen , Espectroscopía Infrarroja Corta , Espectroscopía Infrarroja Corta/métodos , Espectroscopía Infrarroja Corta/instrumentación , Humanos , Análisis de los Mínimos Cuadrados , Calibración , Piel/química , Gelatina/química , Temperatura , Agua/química , Dispositivos Electrónicos Vestibles , Emulsiones/química , Aceite de Soja/química , FosfolípidosRESUMEN
Hippo was first identified in a genetic screen as a protein that suppressed proliferation and cell growth. Subsequently, it was shown that hippo acted in a so-called canonical cascade to suppress Yorkie, the Drosophila equivalent of Yes-activated protein (YAP), a mechanosensitive transcriptional cofactor that enhances the activity of the TEAD family of transcription factors. YAP promotes fibrosis, activation of cancer-associated fibroblasts, angiogenesis and cancer cell invasion. YAP activates the expression of the matricellular proteins CCN1 (cyr61) and CCN2 (ctgf), themselves mediators of fibrogenesis and oncogenesis, and coordination of matrix deposition and angiogenesis. This review discusses how therapeutically targeting YAP through YAP inhibitors verteporfin and celastrol and its downstream mediators CCN1 and CCN2 might be useful in treating melanoma.
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PURPOSE: To determine the effect of aromatherapy on postoperative anxiety and pain in patients undergoing oculoplastic surgery. METHODS: A randomized controlled study of 60 patients who underwent monitored anesthesia care sedation for oculoplastic procedures from August 2018 to November 2020. Patients were randomized to an aromatherapy (n = 32) or placebo (n = 28) condition. Anxiety was measured with State-Trait Anxiety Inventory and visual analog scale for anxiety. Pain was measured with a visual analog scale for pain. RESULTS: Compared with control patients, aromatherapy patients had significantly lower postoperative State-Trait Anxiety Inventory state anxiety (24.1 vs. 29.1; p = 0.05) and visual analog scale pain scores (1.9 vs. 3.2; p = 0.05). Aromatherapy patients also had shorter stays in the postanesthesia care unit than control patients (57.7 vs. 79.4 minutes; p = 0.03). CONCLUSIONS: Patients who received aromatherapy reported lower postoperative anxiety and pain. Aromatherapy may be a useful adjuvant analgesic and/or anxiolytic for patients undergoing oculoplastic procedures with monitored anesthesia care sedation.
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PURPOSE: To describe the outcomes of acellular fish skin grafts for repair of periocular anterior lamella skin defects after Mohs surgery for skin cancers. METHODS: Following the institutional review board approval, we conducted a retrospective chart review of patients treated with acellular fish skin grafts between January 2022 and December 2023. Indication was to repair defects after Mohs excision of basal cell carcinoma and squamous cell carcinoma. Demographics, smoking and diabetes status, diagnosis, defect location, graft size, and complications were evaluated. Outcomes were analyzed using the scar cosmesis assessment and rating scale. RESULTS: Six patients (3 females and 3 males) with a mean age of 60.8 (range 44-80) had Mohs surgery for basal cell carcinoma (4) and squamous cell carcinoma (2). Location of defects included eyebrow (3 cases), lateral nasal wall (1 case), lower eyelid (1 case), and medial lower eyelid/nasal wall (1 case). Defect size ranged from 8 × 10 mm to 30 × 40 mm. Two patients had more than 1 application of xenograft. One patient developed a mild cicatricial ectropion. No other postoperative complications were seen, and all had good wound healing and cosmetically acceptable results. CONCLUSIONS: In this pilot study, acellular fish skin xenografts are shown to be promising skin graft substitutes in patients with Mohs defects and decrease the need for autologous skin harvesting or allogenic skin donation.
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Identifying optimal reaction coordinates for complex conformational changes and protein folding remains an outstanding challenge. This study combines collective variable (CV) discovery based on chemical intuition and machine learning with enhanced sampling to converge the folding free energy landscape of lasso peptides, a unique class of natural products with knot-like tertiary structures. This knotted scaffold imparts remarkable stability, making lasso peptides resistant to proteolytic degradation, thermal denaturation, and extreme pH conditions. Although their direct synthesis would enable therapeutic design, it has not yet been possible due to the improbable occurrence of spontaneous lasso folding. Thus, simulations characterizing the folding propensity are needed to identify strategies for increasing access to the lasso architecture by stabilizing the pre-lasso ensemble before isopeptide bond formation. Herein, harmonic linear discriminant analysis (HLDA) is combined with metadynamics-enhanced sampling to discover CVs capable of distinguishing the pre-lasso fold and converging the folding propensity. Intuitive CVs are compared to iterative rounds of HLDA to identify CVs that not only accomplish these goals for one lasso peptide but also seem to be transferable to others, establishing a protocol for the identification of folding reaction coordinates for lasso peptides.
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Aprendizaje Automático , Péptidos , Pliegue de Proteína , Péptidos/química , Simulación de Dinámica Molecular , Termodinámica , Análisis DiscriminanteRESUMEN
BACKGROUND: An accurate, rapid estimate of glomerular filtration rate (GFR) in kidney transplant patients affords early detection of transplant deterioration and timely intervention. This study compared the performance of serum creatinine (Cr) and cystatin C (CysC)-based GFR equations to measured GFR (mGFR) using iohexol among pediatric kidney transplant recipients. METHODS: CysC, Cr, and mGFR were obtained from 45 kidney transplant patients, 1-18 years old. Cr- and CysC-estimated GFR (eGFR) was compared against mGFR using the Cr-based (Bedside Schwartz, U25-Cr), CysC-based (Gentian CysC, CAPA, U25-CysC), and Cr-CysC combination (CKiD Cr-CysC, U25 Cr-CysC) equations in terms of bias, precision, and accuracy. Bland-Altman plots assessed the agreement between eGFR and mGFR. Secondary analyses evaluated the formulas in patients with biopsy-proven histological changes, and K/DOQI CKD staging. RESULTS: Bias was small with Gentian CysC (0.1 ml/min/1.73 m2); 88.9% and 37.8% of U25-CysC estimations were within 30% and 10% of mGFR, respectively. In subjects with histological changes on biopsy, Gentian CysC had a small bias and U25-CysC were more accurate-both with 83.3% of and 41.7% of estimates within 30% and 10% mGFR, respectively. Precision was better with U25-CysC, CKiD Cr-CysC, and U25 Cr-CysC. Bland-Altman plots showed the Bedside Schwartz, Gentian CysC, CAPA, and U25-CysC tend to overestimate GFR when > 100 ml/min/1.72 m2. CAPA misclassified CKD stage the least (whole cohort 24.4%, histological changes on biopsy 33.3%). CONCLUSIONS: In this small cohort, CysC-based equations with or without Cr may have better bias, precision, and accuracy in predicting GFR.
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Creatinina , Cistatina C , Tasa de Filtración Glomerular , Trasplante de Riñón , Humanos , Cistatina C/sangre , Niño , Masculino , Femenino , Trasplante de Riñón/efectos adversos , Creatinina/sangre , Adolescente , Preescolar , Lactante , Yohexol/administración & dosificación , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Riñón/fisiopatología , Riñón/patología , Biomarcadores/sangre , Receptores de Trasplantes/estadística & datos numéricosRESUMEN
Solitary fibrous tumor (SFT) is a rare, non-hereditary soft tissue sarcoma thought to originate from fibroblastic mesenchymal stem cells. The etiology of SFT is thought to be due to an environmental intrachromosomal gene fusion between NGFI-A-binding protein 2 (NAB2) and signal transducer and activator protein 6 (STAT6) genes on chromosome 12, wherein the activation domain of STAT6 is fused with the DNA-binding domain of NAB2 resulting in the oncogenesis of SFT. All NAB2-STAT6 fusion variations discovered in SFTs contain the C-terminal of STAT6 transcript, and thus can serve as target site for antisense oligonucleotides (ASOs)-based therapies. Indeed, our in vitro studies show the STAT6 3' untranslated region (UTR)-targeting ASO (ASO 993523) was able to reduce expression of NAB2-STAT6 fusion transcripts in multiple SFT cell models with high efficiency (half-maximal inhibitory concentration: 116-300 nM). Encouragingly, in vivo treatment of SFT patient-derived xenograft mouse models with ASO 993523 resulted in acceptable tolerability profiles, reduced expression of NAB2-STAT6 fusion transcripts in xenograft tissues (21.9%), and, importantly, reduced tumor growth (32.4% decrease in tumor volume compared with the untreated control). Taken together, our study established ASO 993523 as a potential agent for the treatment of SFTs.
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OBJECTIVE: To determine whether celastrol, an inhibitor of the mechanosensitive transcriptional cofactor yes-associated protein-1 (YAP1), impairs the ability of TGFß1 to stimulate fibrogenic activity in human gingival fibroblast cell line. DESIGN: Human gingival fibroblasts were pre-treated with celastrol or DMSO followed by stimulation with or without TGFß1 (4 ng/ml). We then utilized bulk RNA sequencing (RNAseq), real-time polymerase chain reaction (RT-PCR), Western blot, immunofluorescence, cell proliferation assays to determine if celastrol impaired TGFß1-induced responses in a human gingival fibroblast cell line. RESULTS: Celastrol impaired the ability of TGFß1 to induce expression of the profibrotic marker and mediator CCN2. Bulk RNAseq analysis of gingival fibroblasts treated with TGFß1, in the presence or absence of celastrol, revealed that celastrol impaired the ability of TGFß1 to induce mRNA expression of genes within extracellular matrix, wound healing, focal adhesion and cytokine/Wnt signaling clusters. RT-PCR analysis of extracted RNAs confirmed that celastrol antagonized the ability of TGFß1 to induce expression of genes anticipated to contribute to fibrotic responses. Celastrol also reduced gingival fibroblast proliferation, and YAP1 nuclear localization in response to TGFß1. CONCLUSION: YAP1 inhibitors such as celastrol could be used to impair pro-fibrotic responses to TGFß1 in human gingival fibroblasts.
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Factor de Crecimiento del Tejido Conjuntivo , Triterpenos Pentacíclicos , Factor de Crecimiento Transformador beta , Humanos , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Proteínas Señalizadoras YAP , Factor de Crecimiento Transformador beta1/farmacología , Factor de Crecimiento Transformador beta1/metabolismo , Factores de Transcripción/metabolismo , Fibroblastos/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Células CultivadasRESUMEN
Melanoma is the leading cause of skin cancer-related death. As prognosis of patients with melanoma remains problematic, identification of new therapeutic targets remains essential. Matricellular proteins are nonstructural extracellular matrix proteins. They are secreted into the tumor microenvironment to coordinate behavior among different cell types, yet their contribution to melanoma is underinvestigated. Examples of matricellular proteins include those comprising the CCN family. The CCN family member, CCN1, is highly proangiogenic. Herein, we show that, in human patients with melanoma, although found in several tumor cell types, CCN1 is highly expressed by a subset of cancer-associated fibroblasts (CAF) in patients with melanoma and this expression correlates positively with expression of proangiogenic genes and progressive disease/resistance to anti-PD1 checkpoint inhibitors. Consistent with these observations, in a syngeneic C57BL6 mouse model of melanoma, loss of CCN1 expression from Col1A2-Cre-, herein identified as "universal," fibroblasts, impaired metastasis of subcutaneously injected B16F10 tumor cells to lung, concomitant with disrupted neovascularization and collagen organization. Disruption of the extracellular matrix in the loss of CCN1 was validated using a novel artificial intelligence-based image analysis platform that revealed significantly decreased phenotypic fibrosis and composite morphometric collagen scores. As drug resistance is linked to matrix deposition and neoangiogenesis, these data suggest that CCN1, due to its multifaceted role, may represent a novel therapeutic target for drug-resistant melanoma. Our data further emphasize the essential role that cancer-associated, (universal) Col1A2-Cre-fibroblasts and extracellular matrix remodeling play in coordinating behavior among different cell types within the tumor microenvironment. SIGNIFICANCE: In human patients, the expression of proangiogenic matricellular protein CCN1 in CAFs correlates positively with expression of stroma and angiogenic markers and progressive disease/resistance to checkpoint inhibitor therapy. In an animal model, loss of CCN1 from CAFs impaired metastasis of melanoma cells, neovascularization, and collagen deposition, emphasizing that CAFs coordinate cellular behavior in a tumor microenvironment and that CCN1 may be a novel target.
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Fibroblastos Asociados al Cáncer , Melanoma , Animales , Humanos , Ratones , Inteligencia Artificial , Fibroblastos Asociados al Cáncer/metabolismo , Colágeno , Proteína 61 Rica en Cisteína/genética , Melanoma/genética , Neovascularización Patológica/genética , Microambiente Tumoral/genéticaRESUMEN
Poly (ADP-ribose) polymerase inhibitors (PARPi) are used for patients with BRCA1/2 mutations, but patients with other mutations may benefit from PARPi treatment. Another mutation that is present in more cancers than BRCA1/2 is mutation to the TP53 gene. In 2D breast cancer cell lines, mutant p53 (mtp53) proteins tightly associate with replicating DNA and Poly (ADP-ribose) polymerase (PARP) protein. Combination drug treatment with the alkylating agent temozolomide and the PARPi talazoparib kills mtp53 expressing 2D grown breast cancer cell lines. We evaluated the sensitivity to the combination of temozolomide plus PARPi talazoparib treatment to breast and lung cancer patient-derived tumor organoids (PDTOs). The combination of the two drugs was synergistic for a cytotoxic response in PDTOs with mtp53 but not for PDTOs with wtp53. The combination of talazoparib and temozolomide induced more DNA double-strand breaks in mtp53 expressing organoids than in wild-type p53 expressing organoids as shown by increased γ-H2AX protein expression. Moreover, breast cancer tissue microarrays (TMAs) showed a positive correlation between stable p53 and high PARP1 expression in sub-groups of breast cancers, which may indicate sub-classes of breast cancers sensitive to PARPi therapy. These results suggest that mtp53 could be a biomarker to predict response to the combination of PARPi talazoparib-temozolomide treatment.
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Antineoplásicos , Neoplasias de la Mama , Neoplasias Pulmonares , Femenino , Humanos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Proteína BRCA2/genética , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , ADN , Genes p53 , Neoplasias Pulmonares/genética , Mutación , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Poli(ADP-Ribosa) Polimerasas/metabolismo , Temozolomida/farmacología , Temozolomida/uso terapéutico , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
INTRODUCTION: There is limited information regarding the utility of preoperative urine culture (Ucx) screening to decrease postoperative UTI rates following midurethral sling (MUS). HYPOTHESIS: The primary objective of this study was to determine if the rate of postoperative UTI within the first 6 weeks after surgery is lower in women undergoing MUS when preoperative Ucx is obtained compared to when it is not. Secondary objectives were to determine clinical factors associated with postoperative UTI risk. METHODS: This is a retrospective cohort study of women who did not have symptoms of or a diagnosis of cystitis at the time of their preoperative evaluation and are undergoing MUS. Patients were grouped into those who had preoperative Ucx screening within 6 weeks preceding surgery and those who did not. UTI rates 6 weeks following surgery were compared between groups. Additionally, factors impacting the risk of developing a UTI within 6 weeks of surgery were assessed. RESULTS: Among 661 patients, 13.2% had a UTI within the first 6 weeks. There was no significant difference in UTI rates between those who did and did not have preoperative Ucx, respectively (14.9% vs 10.2%, p = 0.09). On multivariable analysis, current smoker status (OR 3.02, 95% CI 1.10-8.26), history of recurrent UTI (OR 3.00, 95% CI 1.14-7.86), and requiring postoperative SIC (OR 8.75, 95% CI 1.83-41.74) were independently associated with a UTI within 6 weeks of MUS. CONCLUSION: Obtaining preoperative Ucx in asymptomatic women prior to MUS does not appear to be associated with lower postoperative UTIs rates within 6 weeks of surgery.
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Cistitis , Cabestrillo Suburetral , Infecciones Urinarias , Humanos , Femenino , Estudios Retrospectivos , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/epidemiología , Infecciones Urinarias/etiología , Periodo PosoperatorioRESUMEN
BACKGROUND: Potential organ donors often exhibit abnormalities on electrocardiograms (ECGs) after brain death, but the physiological and prognostic significance of such abnormalities is unknown. OBJECTIVES: This study sought to characterize the prevalence of ECG abnormalities in a nationwide cohort of potential cardiac donors and their associations with cardiac dysfunction, use for heart transplantation (HT), and recipient outcomes. METHODS: The Donor Heart Study enrolled 4,333 potential cardiac organ donors at 8 organ procurement organizations across the United States from 2015 to 2020. A blinded expert reviewer interpreted all ECGs, which were obtained once hemodynamic stability was achieved after brain death and were repeated 24 ± 6 hours later. ECG findings were summarized, and their associations with other cardiac diagnostic findings, use for HT, and graft survival were assessed using univariable and multivariable regression. RESULTS: Initial ECGs were interpretable for 4,136 potential donors. Overall, 64% of ECGs were deemed clinically abnormal, most commonly as a result of a nonspecific St-T-wave abnormality (39%), T-wave inversion (19%), and/or QTc interval >500 ms (17%). Conduction abnormalities, ectopy, pathologic Q waves, and ST-segment elevations were less common (each present in ≤5% of donors) and resolved on repeat ECGs in most cases. Only pathological Q waves were significant predictors of donor heart nonuse (adjusted OR: 0.39; 95% CI: 0.29-0.53), and none were associated with graft survival at 1 year post-HT. CONCLUSIONS: ECG abnormalities are common in potential heart donors but often resolve on serial testing. Pathologic Q waves are associated with a lower likelihood of use for HT, but they do not portend worse graft survival.
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Cardiopatías , Insuficiencia Cardíaca , Trasplante de Corazón , Obtención de Tejidos y Órganos , Humanos , Donantes de Tejidos , Muerte Encefálica , Electrocardiografía , Arritmias CardíacasRESUMEN
The application of frontal polymerization to additive manufacturing has advantages in energy consumption and speed of printing. Additionally, with frontal polymerization, it is possible to print free-standing structures that require no supports. A resin was developed using a mixture of epoxies and vinyl ether with an iodonium salt and peroxide initiating system that frontally polymerizes through radical-induced cationic frontal polymerization. The formulation, which was optimized for reactivity, physical properties, and rheology, allowed the printing of free-standing structures. Increasing ratios of vinyl ether and reactive cycloaliphatic epoxide were found to increase the front velocity. Addition of carbon nanofibers increased the front velocity more than the addition of milled carbon fibers. The resin filled with carbon nanofibers and fumed silica exhibited shear-thinning behavior and was suitable for extrusion-based printing at a weight fraction of 4 wt %. A desktop 3D printer was modified to control resin extrusion and deposition with a digital syringe dispenser. Flexural properties of molded and 3D-printed specimens showed that specimens printed in the transverse direction exhibited the lowest strength, likely due to the presence of voids, adhesion issues between filaments, and preferential carbon nanofiber alignment along the filaments. Finally, free-standing printing of single, angled filaments and helical geometries was successfully demonstrated by coordinating ultraviolet-based reaction initiation, low air pressure for resin extrusion, and printing speed to match front velocity.
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PURPOSE: To analyze the kinematics of the upper eyelid and the globe on downward excursion for potential use in monitoring thyroid eye disease (TED) progression in an objective manner. METHODS: Ten normal volunteers and 10 patients with TED were studied. A high-speed (240 fps) digital camera with a coaxial light source set at a constant distance from the subjects' eyes was used to record the excursion of the upper eyelid and the globe from extreme upgaze to extreme downgaze. Clinical data, including age, gender, race, thyroid function tests, Vision, Inflammation/Congestion, Strabismus/motility restriction, Appearance/exposure score (primary surgeons' preference of TED grading system), exophthalmometry, and eyelid measurements were collected for all patients with TED. Frame-by-frame analyses of the videos were performed using Python software (version 3.6) and the Open Source Computer Vision Library. Temporal resolution was obtained by measuring the number of frames from initiation of eyelid and globe movement from extreme upgaze (t 0 ) to extreme downgaze (t f ). Spatial resolution was obtained by measuring the number of pixels the eyelid margin and the globe traversed from t 0 to t f . The data were then plotted on a graph to calculate the velocity of the upper eyelid and the globe during downward excursion. RESULTS: Velocimetric calculations using high-speed photography suggests that downward excursion of the upper eyelid, and the globe occurs in 2 phases: the acceleration phase and the deceleration phase. Comparative analysis of slow-motion videography demonstrates that patients with TED were found to have attenuation in the early acceleration phase of upper eyelid excursion compared with normal subjects. In patients with TED, the difference in velocity between the eyelid and the globe occurs in the early deceleration phase. CONCLUSIONS: The upper eyelid normally synchronizes intimately with the globe during downward eye movement. Data from this study reveal that attenuation mostly in the early deceleration phase of eyelid movement relative to the globe accounts for the dynamic eyelid lag seen on clinical examination. Further analysis is needed to show if a quantified von Graefe sign can be used as an objective means of monitoring progression in TED.
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Oftalmopatía de Graves , Humanos , Oftalmopatía de Graves/diagnóstico , Fenómenos Biomecánicos , Párpados , Inflamación , Movimientos OcularesRESUMEN
PURPOSE: This study aims to compare the readability of patient education materials (PEM) of the American Society of Ophthalmic Plastic and Reconstructive Surgery to that of PEMs generated by the AI-chat bots ChatGPT and Google Bard. METHODS: PEMs on 16 common American Society of Ophthalmic Plastic and Reconstructive Surgery topics were generated by 2 AI models, ChatGPT 4.0 and Google Bard, with and without a 6th-grade reading level prompt modifier. The PEMs were analyzed using 7 readability metrics: Flesch Reading Ease Score, Gunning Fog Index, Flesch-Kincaid Grade Level, Coleman-Liau Index, Simple Measure of Gobbledygook Index Score, Automated Readability Index, and Linsear Write Readability Score. Each AI-generated PEM was compared with the equivalent American Society of Ophthalmic Plastic and Reconstructive Surgery PEM. RESULTS: Across all readability indices, PEM generated by ChatGPT 4.0 consistently had the highest readability scores, indicating that the material generated by this AI chatbot may be most difficult to read in its unprompted form (Flesch Reading Ease Score: 36.5; Simple Measure of Gobbledygook: 14.7). Google's Bard was able to generate content that was easier to read than both the American Society of Ophthalmic Plastic and Reconstructive Surgery and ChatGPT 4.0 (Flesch Reading Ease Score: 52.3; Simple Measure of Gobbledygook: 12.7). When prompted to produce PEM at a 6th-grade reading level, both ChatGPT 4.0 and Bard were able to significantly improve in their readability scores, with prompted ChatGPT 4.0 being able to consistently generate content that was easier to read (Flesch Reading Ease Score: 67.9, Simple Measure of Gobbledygook: 10.2). CONCLUSION: This study suggests that AI tools, when guided by appropriate prompts, can generate accessible and comprehensible PEMs in the field of ophthalmic plastic and reconstructive surgeries, balancing readability with the complexity of the necessary information.
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Oftalmología , Cirugía Plástica , Humanos , Comprensión , Folletos , Educación del Paciente como AsuntoRESUMEN
Poly (ADP-ribose) polymerase inhibitors (PARPi) are used for patients with BRCA1/2 mutations, but patients with other mutations may benefit from PARPi treatment. Another mutation that is present in more cancers than BRCA1/2 is mutation to the TP53 gene. In 2D breast cancer cell lines, mutant p53 (mtp53) proteins tightly associate with replicating DNA and Poly (ADP-ribose) polymerase (PARP) protein. Combination drug treatment with the alkylating agent temozolomide and the PARPi talazoparib kills mtp53 expressing 2D grown breast cancer cell lines. We evaluated the sensitivity to the combination of temozolomide plus PARPi talazoparib treatment to breast and lung cancer patient-derived tumor organoids (PDTOs). The combination of the two drugs was synergistic for a cytotoxic response in PDTOs with mtp53 but not for PDTOs with wtp53. The combination of talazoparib and temozolomide induced more DNA double-strand breaks in mtp53 expressing organoids than in wild-type p53 expressing organoids as shown by increased γ-H2AX protein expression. Moreover, breast cancer tissue microarrays (TMAs) showed a positive correlation between stable p53 and high PARP1 expression in sub-groups of breast cancers, which may indicate sub-classes of breast cancers sensitive to PARPi therapy. These results suggest that mtp53 could be a biomarker to predict response to the combination of PARPi talazoparib-temozolomide treatment.
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Background Surgical ward round documentation, essential for high-quality patient care, is often completed poorly. The advent of electronic medical records offers an opportunity to introduce proformas, aiding junior staff in completing notes both timely and accurately. We aimed to assess whether the introduction of a proforma would improve the quality and speed of ward round documentation. Methods We completed a prospective cohort analysis of ward round documentation at a single institution. Analysis was conducted on the documentation of a single surgical team over a 10-week period, comprising five weeks of baseline data collection followed by five weeks with implementation of a proforma. This proforma was based on the "David & Wendy" acronym, encompassing diet, activity, vital signs, investigations/IV therapy, drains/lines, wound assessment, examination findings, nursing concerns, drugs/deep vein thrombosis (DVT) prophylaxis, and barriers to discharge. Results A total of 711 ward round notes were analyzed, 349 with proforma and 362 without. Statistically significant improvements were observed in the documentation of diet, activity, investigations/IV therapy, drains/lines, wound assessment, nursing concerns, drugs/DVT prophylaxis, and barriers to discharge (p < 0.05) with proforma use. No significant difference was noted in the documentation of vital signs or examination findings. The time taken to finalize ward round notes was significantly reduced with the proforma (M = 31.28 vs. 60.05 minutes, p < 0.001). Conclusion The introduction of the David & Wendy proforma significantly improved the speed and quality of documentation for key surgical ward round information during our study.
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Chimeric antigen receptor (CAR)-T cell therapies have been approved by FDA to treat relapsed or refractory hematological malignancies. However, the adverse effects of CAR-T cell therapies are complex and can be challenging to diagnose and treat. In this review, we summarize the major adverse events, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and CAR T-cell associated HLH (carHLH), and discuss their pathophysiology, symptoms, grading, and diagnosis systems, as well as management. In a future outlook, we also provide an overview of measures and modifications to CAR-T cells that are currently being explored to limit toxicity.