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1.
J Surg Res ; 301: 371-377, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39029259

RESUMEN

INTRODUCTION: Resident physicians play an important role in teaching the next generation of health-care providers, yet limited research has explored factors influencing effective teaching, such as preresidency experiences or barriers within residency. This study examines residents' prior teaching experience, its correlation with teaching attitudes, and identifies potential barriers to sustained teaching engagement. METHODS: This cross-sectional study surveyed residents across multiple specialties at a single academic center. The survey assessed preresidency teaching experience, perceived barriers, and attitudes toward teaching. Univariate and multivariate analyses identified differences in teaching attitudes based on prior teaching experience and gender. RESULTS: Ninety-two residents across 11 specialties participated (52.2% female). Internal Medicine (28.3%) and General Surgery (26.1%) had the highest representation. Two-thirds of respondents (69.6%) had formal teaching experience before residency. After adjustment, prior teaching experience and male gender were associated with feeling prepared to teach medical students (P = 0.014 and P = 0.001). Male gender was also linked to confidence in teaching material on the wards (P = 0.015). Barriers identified included time constraints (73.9%), lack of content clarity (28.3%), and uncertainty about teaching methods (33.7%). CONCLUSIONS: Residents with prior teaching experience exhibit higher levels of preparedness, content clarity, and confidence in their teaching abilities, underscoring the importance of teaching experience before residency. This study also identified significant barriers to effective teaching, including time constraints, lack of content clarity, uncertainty about teaching methods, and perceived disinterest from medical students. Addressing these barriers is essential for optimizing medical student education.


Asunto(s)
Actitud del Personal de Salud , Internado y Residencia , Enseñanza , Humanos , Estudios Transversales , Internado y Residencia/estadística & datos numéricos , Masculino , Femenino , Adulto , Enseñanza/estadística & datos numéricos , Encuestas y Cuestionarios/estadística & datos numéricos
2.
HLA ; 104(1): e15599, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39041289

RESUMEN

Xenotransplantation is a potential option for individuals for whom an acceptable human allograft is unavailable. Individuals with broadly reactive HLA antibodies due to prior exposure to foreign HLA are potential candidates for a clinical xenotransplant trial. It remains controversial if allosensitisation results in the development of cross-reactive antibodies against SLA. This may require increased histocompatibility scrutiny for highly sensitised individuals prior to enrollment in a clinical trial. Serum samples were obtained from non-human primates sensitised via serial skin transplantation from maximally MHC-mismatched donor, as reported. Sera from pre- and post-allosensitisation timepoints were assessed in a flow crossmatch (FXM) for IgM and IgG binding to pig splenocytes with or without red blood cell adsorption. Xenoreactive antibodies were eluted from pig splenocytes and screened on a single antigen HLA bead assay. A MHC Matchmaker algorithm was developed to predict potential conserved amino acid motifs among the pig, NHP, and human. Our sensitised NHP model was used to demonstrate that allosensitisation does not result in an appreciable difference in xenoreactive antibody binding in a cell-based FXM. However, antibody elution and screening on single antigen HLA beads suggest the existence of potential cross-reactive antibodies against SLA. The cross-reactive IgG after allosensitisation were predicted by comparing the recipient Mamu alleles against its previous allograft donor Mamu alleles and the donor pig SLA alleles. Our study suggests that allosensitisation could elevate cross-reactive antibodies, but a more sensitive assay than a cell-based FXM is required to detect them. The MHC Matchmaker algorithm was developed as a potential tool to help determine amino acid motif conservation and reactivity pattern.


Asunto(s)
Reacciones Cruzadas , Citometría de Flujo , Antígenos de Histocompatibilidad Clase I , Prueba de Histocompatibilidad , Animales , Humanos , Reacciones Cruzadas/inmunología , Prueba de Histocompatibilidad/métodos , Citometría de Flujo/métodos , Porcinos , Antígenos de Histocompatibilidad Clase I/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina G/sangre , Isoanticuerpos/inmunología , Isoanticuerpos/sangre , Trasplante Heterólogo , Antígenos de Histocompatibilidad Clase II/inmunología , Trasplante de Piel , Inmunoglobulina M/inmunología , Inmunoglobulina M/sangre , Antígenos HLA/inmunología , Linfocitos/inmunología , Algoritmos
3.
Cells ; 13(10)2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38786047

RESUMEN

Autophagy is a highly conserved cellular recycling process which enables eukaryotes to maintain both cellular and overall homeostasis through the catabolic breakdown of intracellular components or the selective degradation of damaged organelles. In recent years, the importance of autophagy in vascular endothelial cells (ECs) has been increasingly recognized, and numerous studies have linked the dysregulation of autophagy to the development of endothelial dysfunction and vascular disease. Here, we provide an overview of the molecular mechanisms underlying autophagy in ECs and our current understanding of the roles of autophagy in vascular biology and review the implications of dysregulated autophagy for vascular disease. Finally, we summarize the current state of the research on compounds to modulate autophagy in ECs and identify challenges for their translation into clinical use.


Asunto(s)
Autofagia , Células Endoteliales , Humanos , Autofagia/fisiología , Células Endoteliales/metabolismo , Animales , Enfermedades Vasculares/patología , Enfermedades Vasculares/metabolismo
4.
J Surg Res ; 299: 155-162, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38759331

RESUMEN

INTRODUCTION: Responses to COVID-19 within medical education prompted significant changes to the surgical clerkship. We analyzed the changes in medical student end of course feedback before and after the COVID-19 outbreak. METHODS: Postclerkship surveys from 2017 to 2022 were analyzed including both Likert scale data and free text, excluding the COVID outbreak year 2019-2020. Likert scale questions were compared between pre-COVID (2017-2019) and COVID-era cohorts (2020-2022) with the Mann-Whitney U-test. Free-text comments were analyzed using both thematic analysis and natural language processing including sentiment, word and phrase frequency, and topic modeling. RESULTS: Of the 483 medical students surveyed from 2017 to 2022, 297 responded (61% response rate) to the included end of clerkship surveys. Most medical students rated the clerkship above average or excellent with no significant difference between the pre-COVID and COVID-era cohorts (70.4% Versus 64.8%, P = 0.35). Perception of grading expectations did significantly differ, 51% of pre-COVID students reported clerkship grading standards were almost always clear compared to 27.5% of COVID-era students (P = 0.01). Pre-COVID cohorts more frequently mentioned learning and feedback while COVID-era cohorts more frequently mentioned case, attending, and expectation. Natural language processing topic modeling and formal thematic analysis identified similar themes: team, time, autonomy, and expectations. CONCLUSIONS: COVID-19 presented many challenges to undergraduate medical education. Despite many changes, there was no significant difference in clerkship satisfaction ratings. Unexpectedly, the greater freedom and autonomy of asynchronous lectures and choice of cases became a highlight of the new curriculum. Future research should investigate if there are similar associations nationally with a multi-institutional study.


Asunto(s)
COVID-19 , Prácticas Clínicas , Procesamiento de Lenguaje Natural , Estudiantes de Medicina , Humanos , COVID-19/epidemiología , Estudiantes de Medicina/psicología , Estudiantes de Medicina/estadística & datos numéricos , Cirugía General/educación , Encuestas y Cuestionarios , Evaluación Educacional , Femenino , Masculino
5.
Xenotransplantation ; 31(3): e12862, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38761019

RESUMEN

Prolonged survival in preclinical renal xenotransplantation demonstrates that early antibody mediated rejection (AMR) can be overcome. It is now critical to evaluate and understand the pathobiology of late graft failure and devise new means to improve post xenograft outcomes. In renal allotransplantation the most common cause of late renal graft failure is transplant glomerulopathy-largely due to anti-donor MHC antibodies, particularly anti-HLA DQ antibodies. We evaluated the pig renal xenograft pathology of four long-surviving (>300 days) rhesus monkeys. We also evaluated the terminal serum for the presence of anti-SLA class I and specifically anti-SLA DQ antibodies. All four recipients had transplant glomerulopathy and expressed anti-SLA DQ antibodies. In one recipient tested for anti-SLA I antibodies, the recipient had antibodies specifically reacting with two of three SLA I alleles tested. These results suggest that similar to allotransplantation, anti-MHC antibodies, particularly anti-SLA DQ, may be a barrier to improved long-term xenograft outcomes.


Asunto(s)
Rechazo de Injerto , Xenoinjertos , Antígenos de Histocompatibilidad Clase I , Trasplante de Riñón , Macaca mulatta , Trasplante Heterólogo , Animales , Trasplante Heterólogo/métodos , Rechazo de Injerto/inmunología , Trasplante de Riñón/métodos , Antígenos de Histocompatibilidad Clase I/inmunología , Porcinos , Xenoinjertos/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Supervivencia de Injerto/inmunología , Isoanticuerpos/inmunología , Humanos
6.
Transplant Direct ; 10(6): e1633, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38807861

RESUMEN

Background: Ex vivo kidney perfusion is an evolving platform that demonstrates promise in preserving and rehabilitating the kidney grafts. Despite this, there is little consensus on the optimal perfusion conditions. Hypothermic perfusion offers limited functional assessment, whereas normothermic perfusion requires a more complex mechanical system and perfusate. Subnormothermic machine perfusion (SNMP) has the potential to combine the advantages of both approaches but has undergone limited investigation. Therefore, the present study sought to determine the suitability of SNMP for extended kidney preservation. Methods: SNMP at 22-25 °C was performed on a portable device for 24 h with porcine kidneys. Graft assessment included measurement of mechanical parameters and biochemical analysis of the perfusate using point-of-care tests. To investigate the viability of kidneys preserved by SNMP, porcine kidney autotransplants were performed in a donation after circulatory death (DCD) model. SNMP was also compared with static cold storage (SCS). Finally, follow-up experiments were conducted in a subset of human kidneys to test the translational significance of findings in porcine kidneys. Results: In the perfusion-only cohort, porcine kidneys all displayed successful perfusion for 24 h by SNMP, evidenced by stable mechanical parameters and biological markers of graft function. Furthermore, in the transplant cohort, DCD grafts with 30 min of warm ischemic injury demonstrated superior posttransplant graft function when preserved by SNMP in comparison with SCS. Finally, human kidneys that underwent 24-h perfusion exhibited stable functional and biological parameters consistent with observations in porcine organs. Conclusions: These observations demonstrate the suitability and cross-species generalizability of subnormothermic machine perfusion to maintain stable kidney perfusion and provide foundational evidence for improved posttransplant graft function of DCD kidneys after SNMP compared with SCS.

7.
J Gastrointest Surg ; 28(5): 738-745, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38704208

RESUMEN

BACKGROUND: Liver transplantation (LT) has been shown to be superior to resection in highly selected patients with perihilar cholangiocarcinoma (CCA), yet has traditionally been contraindicated for intrahepatic CCA (iCCA). Herein, we aimed to examine contemporary trends and outcomes for surgical resection and LT for iCCA. METHODS: The National Cancer Database was queried for patients presenting with stage I-III iCCA between 2010 and 2018 who underwent resection or LT. Overall survival (OS) was compared with Kaplan-Meier and multivariable Cox proportional hazards methods stratified by management. Secondary analysis of patients undergoing transplant for CCA was performed with the United Network for Organ Sharing database. RESULTS: Of 2565 patients, 2412 (94.0%) underwent resection and 153 (5.96%) LT of whom 84 (54.9%) received neoadjuvant therapy. Utilization of LT remained between 3.9% and 7.8% annually. Unadjusted 5-year OS was higher for LT than resection (59.8% vs 39.9%, P = .0067), yet adjusted analysis revealed no significant difference in mortality (hazard ratio, 0.91; 95% CI, 0.66-1.27; P = .58). On secondary analysis including 437 patients with all subtypes of CCA, unadjusted 5-year OS was higher for non-CCA indications (79% vs 52%-54%, P < .001). CONCLUSION: Utilization of LT for iCCA remains low and many cases are likely incidental. Although partial hepatectomy remains the standard of care for patients with resectable disease, our findings suggest that highly selected patients with unresectable iCCA may achieve favorable outcomes after LT. Granular, prospective data are needed to identify patients most likely to benefit from transplant and allocate scarce liver grafts.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Hepatectomía , Trasplante de Hígado , Humanos , Trasplante de Hígado/estadística & datos numéricos , Masculino , Femenino , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/patología , Persona de Mediana Edad , Anciano , Colangiocarcinoma/cirugía , Colangiocarcinoma/mortalidad , Colangiocarcinoma/patología , Resultado del Tratamiento , Terapia Neoadyuvante/estadística & datos numéricos , Tasa de Supervivencia , Bases de Datos Factuales , Modelos de Riesgos Proporcionales , Estimación de Kaplan-Meier , Estudios Retrospectivos , Estadificación de Neoplasias
8.
Gastroenterol Clin North Am ; 53(2): 221-231, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38719374

RESUMEN

Intestinal allotransplantation was first described in the 1960s and successfully performed in the 1980s. Since that time, less progress has been made in the preservation of the allograft before transplantation and static cold storage remains the current standard. Normothermic machine perfusion represents an opportunity to simultaneously preserve, assess, and recondition the organ for transplantation and improve the procurement radius for allografts. The substantial progress made in the field during the last 60 years, coupled with the success of the preclinical animal model of machine perfusion-preserved intestinal transplantation, suggest we are approaching the point of clinical application.


Asunto(s)
Aloinjertos , Intestinos , Preservación de Órganos , Preservación de Órganos/métodos , Humanos , Intestinos/trasplante , Animales , Perfusión/métodos , Trasplante Homólogo , Soluciones Preservantes de Órganos
9.
Kidney Int ; 105(5): 921-922, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38642988

RESUMEN

Because of the global shortage of donor kidneys, xenotransplantation emerges as a potential solution for individuals with kidney failure who face challenges in securing a suitable donor kidney. A study featured in this month's issue of Kidney International assesses the kidney physiology of a porcine kidney transplanted into a brain-dead human with kidney failure, demonstrating life-sustaining physiological function for 7 days. Together with preclinical nonhuman primate studies, decedent models provide complementary data for development of clinical kidney xenotransplantation.


Asunto(s)
Trasplante de Riñón , Insuficiencia Renal , Humanos , Animales , Porcinos , Trasplante de Riñón/efectos adversos , Riñón/fisiología , Trasplante Heterólogo , Donantes de Tejidos , Rechazo de Injerto , Animales Modificados Genéticamente
10.
J Surg Res ; 294: 37-44, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37857141

RESUMEN

INTRODUCTION: The surgical clerkship is a formative experience in the medical school curriculum and can leave a lasting impression on students' perception of surgery. Given the historical negative stereotypes of surgeons, the clerkship represents an opportunity to impact students in a meaningful way. METHODS: Our institution developed a program in which research residents can serve as junior clerkship coordinators and educators; working closely with medical students on their surgery clerkship. At the end of their clerkship, students were administered a survey with Likert-scale and free text responses regarding satisfaction with the rotation, lectures, feedback, and value of the clerkship. Student survey results were compared before (2015-2016) and after (2017-2019) the implementation of the scholar program with nonparametric statistical analysis and qualitative text analysis. RESULTS: A total of 413 students responded to the survey with no significant difference in response rate by term (P = 0.88). We found no statistical difference with respect to overall course perception (92.3% versus 91.2%, P = 0.84), but a statistically significant difference was noted for the clarity of the provided written clerkship materials (80.3% versus 91.3%, P = 0.02) and usefulness of the feedback (57.5% versus 78.7%, P = 0.01). Qualitative analysis demonstrated an overall positive shift in perception of the clerkship, improvement in the course materials, and organization. CONCLUSIONS: The scholar program was overall well received by the students with improvements in certain aspects of the clerkship: organization, feedback, and course materials. This program represents a potential strategy to improve certain portions of the medical school clerkship experience.


Asunto(s)
Prácticas Clínicas , Educación de Pregrado en Medicina , Cirugía General , Internado y Residencia , Estudiantes de Medicina , Cirujanos , Humanos , Actitud , Curriculum , Prácticas Clínicas/métodos , Percepción , Cirugía General/educación , Educación de Pregrado en Medicina/métodos
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