Precision medicine within health professions education: Defining a research agenda for emergency medicine using a foresight and strategy technique (FaST) review.

Background: Precision medicine, sometimes referred to as personalized medicine, is rapidly changing the possibilities for how people will engage health care in the near future. As technology to support precision medicine exponentially develops, there is an urgent need to proactively improve our understanding of precision medicine and pose important research questions (RQs) related to its inclusion in the education and training of future emergency physicians. Methods: A seven-step process was employed to develop a research agenda exploring the intersection of precision and emergency medicine education/training. A literature search of articles about precision medicine was conducted first, which informed the creation of future four scenarios in which trainees and practicing physicians regularly discuss and incorporate precision medicine tools into their discussions and work. Based on these futurist narratives, potential education RQs were generated by an expert panel. A total of 59 initial questions were subsequently categorized and refined to a priority list through a nominal group voting method. The top/priority questions were presented at the 2023 SAEM Consensus Conference on Precision Medicine, Austin, Texas, for further input. Results: Eight high-value education RQs were developed, reflecting a holistic view of the challenges and opportunities for precision medicine education in the knowledge, skills, and attitudes relevant to emergency medicine. These questions contend with topics such as most effective pedagogical methods; intended resulting outcomes and behaviors; the generational differences between practicing emergency physicians, educators, and future trainees; and the desires and expectations of patients. Conclusions: Emergency medicine and emergency physicians must be prepared to understand precision medicine and incorporate this information into their "toolbox" of thinking, problem solving, and communication with patients and colleagues. This research agenda on how best to educate future emergency physicians in the use of personalized data to provide optimal health care is the focus of this article.

The Janus of a disease: Diabetes and metabolic dysfunction-associated fatty liver disease.

Metabolic Dysfunction-Associated Fatty Liver Disease and Diabetes Mellitus are two prevalent metabolic disorders that often coexist and synergistically contribute to the progression of each other. Several pathophysiological pathways are involved in the association, including insulin resistance, inflammation, and lipotoxicity, providing a foundation for understanding the complex interrelationships between these conditions. The presence of MASLD has a significant impact on diabetes risk and the development of microvascular and macrovascular complications, and diabetes significantly contributes to an increased risk of liver fibrosis progression in MASLD and the development of hepatocellular carcinoma. Moreover, both pathologies have a synergistic effect on cardiovascular events and mortality. Therapeutic interventions targeting MASLD and diabetes are discussed, considering lifestyle modifications, pharmacological agents, and emerging treatment modalities. The review also addresses the challenges in managing these comorbidities, such as the need for personalized approaches and the potential impact on cardiovascular health. The insights gleaned from this analysis can inform clinicians, researchers, and policymakers in developing integrated strategies for preventing, diagnosing, and managing these metabolic disorders.

Role of the ubiquitin-proteasome system in the sarcopenic-like phenotype induced by CCL5/RANTES.

Sarcopenia is characterized by reduced muscle strength and mass and a decline in muscle fiber diameter and amount of sarcomeric proteins. Sarcopenia involves the activation of the ubiquitin-proteasome system (UPS). MuRF-1 and atrogin-1 are E3 ubiquitin ligases belonging to UPS, leading to proteolysis mediated by the PSMB 5, 6, and 7 subunits of 20S proteasome. CCL5/RANTES induces a sarcopenic-like effect in muscle cells. The present work explored the impact of CCL5 on UPS components and the influence of UPS on its sarcopenic-like effect. We demonstrated that CCL5 increased MuRF-1 and atrogin-1 protein levels and mRNA levels of subunits PSMB 5, 6, and 7. We used the MG132 inhibitor to elucidate the role of the 20S proteasome in the CCL5-induced sarcopenic-like effect. This inhibitor prevented the decrease in troponin and MHC protein levels and partially prevented the reduction in the diameter of single-isolated FDB muscle fibers induced by CCL5. These findings indicate that CCL5 actively modulates the UPS. Moreover, our results show the direct participation of UPS in the sarcopenic-like phenotype induced by CCL5.

Second Hematologic Malignancies Associated With Primary Mediastinal Germ Cell Tumors: A Population-based Study.

BACKGROUND: Studies addressing second hematologic malignancies (SHMs) in patients with primary mediastinal germ cell tumors (PMGCTs) are scarce. To better describe this phenomenon, we analyzed a large case series from a population-based registry. METHODS: The Surveillance, Epidemiology, and End Results database was used to report the clinical characteristics and incidence of SHMs in patients with PMGCT. RESULTS: Among 1297 PMGCTs, 27 cases (2.08%) of SHM were found, with a median latency period of 12 months (95% CI: 5-41). All SHM occurred in males, 20 of whom (74.1%) had a previous nonseminomatous tumor. Acute myeloid leukemia was the most frequent SHM, accounting for 13 cases, 4 of which were acute megakaryoblastic leukemia that occurred within 5 months of diagnosis. The median survival after the diagnosis of SHM was 6 months (95% CI: 2-41). The risk of SHM was significantly higher than expected for the reference population, with a standardized incidence ratio of 6.21 (95% CI: 3.31-10.62) and an absolute excess risk of 19.19 per 10,000 person-years. CONCLUSIONS: Patients with PMGCT are at a higher risk of developing SHMs than the general population, particularly acute myeloid leukemia. This risk ranges from synchronous diagnosis of acute megakaryoblastic leukemia to the later onset of other hematological disorders that might be related to PMGCT therapies. Our findings may help create follow-up schedules for patients with PMGCT and raise the level of suspicion surrounding this association.

Angiotensin-(1-7) improves skeletal muscle regeneration.

Skeletal muscle possesses regenerative potential via satellite cells, compromised in muscular dystrophies leading to fibrosis and fat infiltration. Angiotensin II (Ang-II) is commonly associated with pathological states. In contrast, Angiotensin (1-7) [Ang-(1-7)] counters Ang-II, acting via the Mas receptor. While Ang-II affects skeletal muscle regeneration, the influence of Ang-(1-7) remains to be elucidated. Therefore, this study aims to investigate the role of Ang-(1-7) in skeletal muscle regeneration. C2C12 cells were differentiated in the absence or presence of 10 nM of Ang-(1-7). The diameter of myotubes and protein levels of myogenin and myosin heavy chain (MHC) were determined. C57BL/6 WT male mice 16-18 weeks old) were randomly assigned to injury-vehicle, injury-Ang-(1-7), and control groups. Ang-(1-7) was administered via osmotic pumps, and muscle injury was induced by injecting barium chloride to assess muscle regeneration through histological analyses. Moreover, embryonic myosin (eMHC) and myogenin protein levels were evaluated. C2C12 myotubes incubated with Ang-(1-7) showed larger diameters than the untreated group and increased myogenin and MHC protein levels during differentiation. Ang-(1-7) administration enhances regeneration by promoting a larger diameter of new muscle fibers. Furthermore, higher numbers of eMHC (+) fibers were observed in the injured-Ang-(1-7), which also had a larger diameter. Moreover, eMHC and myogenin protein levels were elevated, supporting enhanced regeneration due to Ang-(1-7) administration. Ang-(1-7) effectively promotes differentiation in vitroand improves muscle regeneration in the context of injuries, with potential implications for treating muscle-related disorders.

Continuing Medical Education in the Post COVID-19 Pandemic Era.

Continuing medical education (CME) is a requirement for medical professionals to stay current in their ever-changing fields. The recent significant changes that have occurred due to the COVID-19 pandemic have significantly impacted the process of providing and obtaining CME. In this paper, an updated approach to successfully creating and administering CME is offered. Recommendations regarding various aspects of CME development are covered, including competitive assessment, marketing, budgeting, property sourcing, program development, and speaker and topic selection. Strategies for traditional and hybrid CME formats are also explored. Readers and institutions interested in developing CME, especially in the setting of the ongoing pandemic, will be able to use these strategies as a solid framework for producing CME. The recommendations and strategies presented within this paper are based on the authors' opinions, expert opinions, and experiences over 13 years of creating CME events and challenges brought about due to the COVID-19 pandemic.

Real world utilization of Andexanet alfa in the management of oral factor Xa inhibitor-associated gastrointestinal bleeding.

BACKGROUND: Andexanet alfa (AA) is approved for reversal of factor Xa inhibitor (FXaI) bleeds; however, there are limited reports of its use for gastrointestinal bleeding (GIB) in real-world populations. The objective of this study was to report real-world utilization and evaluation of the effectiveness of AA for FXaI-associated GIB. METHODS: This retrospective cohort study including consecutive patients receiving AA for FXaI-associated GIB (7/2018-2/2021). Demographics, blood product administration, hemostatic efficacy, rebleeding, thrombosis, and mortality rates were collected. Hemostatic efficacy (HE), based on corrected hemoglobin at 12 h compared to baseline, was categorized as excellent (<10% decrease), good (≤ 20% decrease), or poor (>20% decrease, > 2 units of additional coagulation intervention or death prior to repeat hemoglobin). Comparative transfusion requirements between efficacy groups was assessed by Wilcoxon-Rank test. RESULTS: Twenty-two patients were included (64% male, median (IQR) age 76 years (67, 80). Most patients (59%, n = 13) were on apixaban, and the primary anticoagulation indication was atrial fibrillation (64%, n = 14). Median initial hemoglobin was 7.5 g/dL (IQR 6.4, 8.8) and 50% (n = 11) were upper GIB. Hemostatic efficacy was excellent in 46% (n = 10), good in 23% (n = 5), and poor in 32% (n = 7). There was no statistically significant difference in red blood cells (RBCs) received between those with excellent/good hemostasis (median 2, IQR 1 to 2) and those with poor hemostasis (median 4, IQR 1.5 to 4.5). Two patients (9%) had arterial thrombotic events within 30 days of reversal. CONCLUSION: In this multicenter, single arm, real-world observational analysis of patients with factor Xa inhibitor associated GIB most patients achieved good hemostasis following administration of AA. There was a 9% 30-day thrombotic event rate. The lack of a control group limits the strength of the conclusions that can be drawn from this study.

Teaching Palliative Care to Emergency Medicine Residents Using Gamified Deliberate Practice-Based Simulation: Palliative Gaming Simulation Study.

BACKGROUND: Emergency departments (EDs) care for many patients nearing the end of life with advanced serious illnesses. Simulation training offers an opportunity to teach physicians the interpersonal skills required to manage end-of-life care. OBJECTIVE: We hypothesized a gaming simulation of an imminently dying patient using the LIVE. DIE. REPEAT (LDR) format, would be perceived as an effective method to teach end-of-life communication and palliative care management skills. METHODS: This was a gaming simulation replicating the experience of caring for a dying patient with advanced serious illness in the ED. The scenario involved a patient with pancreatic cancer presenting with sepsis and respiratory distress, with a previously established goal of comfort care. The gaming simulation game was divided into 4 stages, and at each level, learners were tasked with completing 1 critical action. The gaming simulation was designed using the LDR serious game scheme in which learners are allowed infinite opportunities to progress through defined stages depicting a single patient scenario. If learners successfully complete the predetermined critical actions of each stage, the game is paused, and there is a debriefing to reinforce knowledge or skills before progressing to the next stage of the gaming simulation. Conversely, if learners do not achieve the critical actions, the game is over, and learners undergo debriefing before repeating the failed stage with an immediate transition into the next. We used the Simulation Effectiveness Tool-Modified survey to evaluate perceived effectiveness in teaching end-of-life management. RESULTS: Eighty percent (16/20) of residents completed the Simulation Effectiveness Tool-Modified survey, and nearly 100% (20/20) either strongly or somewhat agreed that the gaming simulation improved their skills and confidence at the end of life in the following dimensions: (1) better prepared to respond to changes in condition, (2) more confident in assessment skills, (3) teaching patients, (4) reporting to the health care team, (5) empowered to make clinical decisions, and (6) able to prioritize care and interventions. All residents felt the debriefing contributed to learning and provided opportunities to self-reflect. All strongly or somewhat agree that they felt better prepared to respond to changes in the patient's condition, had a better understanding of pathophysiology, were more confident on their assessment skills, and had a better understanding of the medications and therapies after the gaming simulation. A total of 88% (14/16) of them feel more empowered to make clinical decisions. After completing the gaming simulation, 88% (14/16) of residents strongly agreed that they would feel more confident communicating with a patient and prioritizing care interventions in this context. CONCLUSIONS: This palliative gaming simulation using the LDR format was perceived by resident physicians to improve confidence in end-of-life communication and palliative care management.

Neurolupus como manifestación de primer brote psicótico Reporte de caso / Neurolupus as a manifestation of the first psychotic episode: case report

Resumen Antecedentes: El lupus eritematoso sistémico (LES) es una enfermedad auto inmunitaria crónica multisistémica con diversas manifestaciones clínicas. Siendo las mujeres la pobla ción vulnerable y con mayor afectación a nivel neurológico, al presentar mayor riesgo de convulsiones. Las manifestaciones neuropsiquiátricas ocurren en etapas tempranas de la enfermedad y del diagnóstico, ya que pueden presentarse junto con manifestaciones sistémicas o no. La frecuencia de manifestaciones neuropsiquiátricas en el lupus eritematoso sistémico se ha descrito del 14 al 75%, siendo las alteraciones cognitivas uno de los grandes síntomas a destacar1. La cual puede ir acompañada de trastornos afectivos de tipo depresión y ansiedad. Ya que la psicosis secundaria a LES se remarca por su baja prevalencia (10%)2, los estudios de laboratorio nos suelen orientar hacia el diagnóstico definitivo, siendo los anticuerpos ribosomales P los que se han relacionado más específicamente con la psicosis lúpica. La resonancia magnética es la prueba de elección y las lesiones cerebrales están dominadas por hiperintensidades de materia blanca en forma de punción3. En el siguiente reporte de caso, presentamos a una paciente de 20 años, la cual contaba con antecedentes de esteatosis hepática diagnosticado, diabetes tipo MODY y resección de ovario derecho por teratoma maduro de 9 años de evolución, pero sin antecedentes psiquiátricos de importancia para el momento de su valoración. Sin embargo, de forma aguda presentó un brote psicótico caracterizado por ideas delirantes de grandiosidad y referencia, así como alteraciones conductuales, cognitivas y afectivas. Por las que tuvieron que acudir a hospital de 3er nivel durante el periodo de contingencia sanitaria en el 2020. Tras el antecedente de presentar infección por SARS-CoV-2 tres meses antes de su patología neuropsiquiátricas. Se sospechó en síntomas neurológicos secundarios a infección por COVID-19, así como patología psiquiátrica aislada. Por lo que se realizó abordaje de estudio de primer brote psicótico, diagnosticándose lupus eritematoso sistémico con manifestaciones neuropsiquiátricas. El tratamiento se basó en un bolo de metilprednisolona y antipsicóticos, luego modificada por terapia con corticoesteroides orales y antipsicótico de depósito. Conclusión: El lupus eritematoso sistémico con manifestaciones neuropsiquiátricas es una presentación poco frecuente del padecimiento, por la amplia variación en la aparición de este, los pacientes con síntomas psiquiátricos en contexto de hospital general deben de ser tomados en cuenta para abordajes extensos4. De la misma forma, el tener este conocimiento del caso podrá ampliar nuestro conocimiento sobre las complicaciones de esta patología reumatológica. Y una de sus complicaciones más graves como la psicosis lúpica para poder realizar un mejor abordaje del primer brote psicótico en hospitales generales, donde la valoración de un especialista puede ser más complicada para mejorar las condiciones médicas de estos pacientes.

Abstract Background: Systemic lupus erythematosus is a chronic multisystemic autoimmune disease with diverse clinical manifestations. Women are the most vulnerable population and have the greatest neurological involvement with a higher risk of seizures. Neuropsychiatric manifestations occur in early stages of the disease and diagnosis since they can occur together with systemic manifestations or not. The frequency of neuropsychiatric manifestations in systemic lupus erythematosus has been described from 14 to 75%; being cognitive alterations one of the major symptoms to highlight. Which, in the same way can be accompanied by affective disorders such as depression and anxiety. Since psychosis, secondary to SLE, stands out for its low prevalence (10%), laboratory studies usually guide us towards a definitive diagnosis, being ribosomal P antibodies the ones that have been more specifically related to lupus psychosis. MRI is the test of choice and brain lesions are dominated by punctate white matter hyperintensities. In the following case report, we present a 20-year-old patient who had a history of diagnosed hepatic steatosis, MODY type diabetes and resection of the right ovary for mature teratoma of 9 years of evolution; but with no psychiatric history of importance at the time of her evaluation. However, she acutely presented a psychotic outbreak characterized by delusions of grandiosity and reference; as well as behavioral, cognitive, and affective alterations. For which she had to go to a 3rd level hospital during the period of health contingency in 2020. After a history of SARS-CoV-2 infection three months before her neuropsychiatric pathology, neurological symptoms secondary to COVID-19 infection were suspected, as well as isolated psychiatric pathology. Therefore, a study approach of the first psychotic outbreak was performed, diagnosing systemic lupus erythematosus with neuropsychiatric manifestations. Treatment was based on a bolus of methylprednisolone and antipsychotics; later modified by therapy with oral corticosteroids and depot antipsychotic. Conclusion: Systemic lupus erythematosus with neuropsychiatric manifestations is an infrequent presentation of the disease, because of the wide variation in its appearance, patients with psychiatric symptoms in a general hospital setting should be considered for extensive approaches. In the same way, having this knowledge of this case may broaden our knowledge about the complications of this rheumatologic pathology. And one of its most serious complications such as lupus psychosis to be able to make a better approach to the first psychotic outbreak in general hospitals, where the assessment of a specialist can be more complicated.

Knockout of AMD-associated gene POLDIP2 reduces mitochondrial superoxide in human retinal pigment epithelial cells.

Genetic and epidemiologic studies have significantly advanced our understanding of the genetic factors contributing to age-related macular degeneration (AMD). In particular, recent expression quantitative trait loci (eQTL) studies have highlighted POLDIP2 as a significant gene that confers risk of developing AMD. However, the role of POLDIP2 in retinal cells such as retinal pigment epithelium (RPE) and how it contributes to AMD pathology are unknown. Here we report the generation of a stable human RPE cell line ARPE-19 with POLDIP2 knockout using CRISPR/Cas, providing an in vitro model to investigate the functions of POLDIP2. We conducted functional studies on the POLDIP2 knockout cell line and showed that it retained normal levels of cell proliferation, cell viability, phagocytosis and autophagy. Also, we performed RNA sequencing to profile the transcriptome of POLDIP2 knockout cells. Our results highlighted significant changes in genes involved in immune response, complement activation, oxidative damage and vascular development. We showed that loss of POLDIP2 caused a reduction in mitochondrial superoxide levels, which is consistent with the upregulation of the mitochondrial superoxide dismutase SOD2. In conclusion, this study demonstrates a novel link between POLDIP2 and SOD2 in ARPE-19, which supports a potential role of POLDIP2 in regulating oxidative stress in AMD pathology.

Development of a CRISPRi Human Retinal Pigmented Epithelium Model for Functional Study of Age-Related Macular Degeneration Genes.

Age-related macular degeneration (AMD) is a blinding disease characterised by dysfunction of the retinal pigmented epithelium (RPE) which culminates in disruption or loss of the neurosensory retina. Genome-wide association studies have identified >60 genetic risk factors for AMD; however, the expression profile and functional role of many of these genes remain elusive in human RPE. To facilitate functional studies of AMD-associated genes, we developed a human RPE model with integrated CRISPR interference (CRISPRi) for gene repression by generating a stable ARPE19 cell line expressing dCas9-KRAB. We performed transcriptomic analysis of the human retina to prioritise AMD-associated genes and selected TMEM97 as a candidate gene for knockdown study. Using specific sgRNAs, we showed that knockdown of TMEM97 in ARPE19 reduced reactive oxygen species (ROS) levels and exerted a protective effect against oxidative stress-induced cell death. This work provides the first functional study of TMEM97 in RPE and supports a potential role of TMEM97 in AMD pathobiology. Our study highlights the potential for using CRISPRi to study AMD genetics, and the CRISPRi RPE platform generated here provided a useful in vitro tool for functional studies of AMD-associated genes.

The incidence of cardiovascular instability in patients receiving various vasopressor strategies for peri-intubation hypotension.

INTRODUCTION: Patients frequently experience hypotension in the peri-intubation period. This can be due to the underlying disease process, physiologic response to the intervention, or adverse effect from medications. With the heterogeneity in cause for hypotension, the duration can also be short or prolonged. Initiation of vasopressors for peri-intubation hypotension includes various strategies using continuous infusion norepinephrine (NE) or push-dose phenylephrine (PDPE) to obtain goal mean arterial pressure. There is a paucity of data describing cardiovascular stability outcomes in patients receiving vasopressors for peri-intubation hypotension. METHODS: This is a retrospective cohort study including emergency department patients across three academic medical centers and smaller health system sites who received vasopressors for hypotension within 30 min of intubation. Patients were matched based on factors likely to influence vasopressor selection and were divided into groups if they received PDPE alone, continuous infusion NE alone, or PDPE followed by continuous infusion NE. The primary outcome was a composite of the incidence of hypotension (systolic blood pressure < 90 mmHg), bradycardia (HR < 60 beats per minute), and cardiac arrest within 2 h following initiation of vasopressors. RESULTS: Screening occurred for 2518 patients, with 105 patients undergoing matching. Mean time to vasopressor initiation was 10 min following intubation. The composite primary outcome was not statistically different between groups and occurred 88.6%, 80.0%, and 88.6% in the NE, PDPE, and PDPE+NE groups, respectively. A subgroup analysis of patients with an ED diagnosis of sepsis or septic shock were more likely to receive PDPE before starting continuous infusion NE (41.3% vs. 27.1%, p = 0.075) and more frequently experienced the primary composite outcome (p = 0.045) but was not correlated with vasopressor strategy (p = 0.55). DISCUSSION: Cardiovascular instability following vasopressor initiation for peri-intubation hypotension was no different depending on the selected vasopressor strategy. This held true in patients with a sepsis or septic shock diagnosis. Selection of vasopressors should continue to include patient specific factors and product availability.

Comparison of clinical note quality between an automated digital intake tool and the standard note in the emergency department.

BACKGROUND: Medical encounters require an efficient and focused history of present illness (HPI) to create differential diagnoses and guide diagnostic testing and treatment. Our aim was to compare the HPI of notes created by an automated digital intake tool versus standard medical notes created by clinicians. METHODS: Prospective trial in a quaternary academic Emergency Department (ED). Notes were compared using the 5-point Physician Documentation Quality Instrument (PDQI-9) scale and the Centers for Medicare & Medicaid Services (CMS) level of complexity index. Reviewers were board certified emergency medicine physicians blinded to note origin. Reviewers received training and calibration prior to note assessments. A difference of 1 point was considered clinically significant. Analysis included McNemar's (binary), Wilcoxon-rank (Likert), and agreement with Cohen's Kappa. RESULTS: A total of 148 ED medical encounters were charted by both digital note and standard clinical note. The ability to capture patient information was assessed through comparison of note content across paired charts (digital-standard note on the same patient), as well as scores given by the reviewers. Reviewer agreement was kappa 0.56 (CI 0.49-0.64), indicating moderate level of agreement between reviewers scoring the same patient chart. Considering all 18 questions across PDQI-9 and CMS scales, the average agreement between standard clinical note and digital note was 54.3% (IQR 44.4-66.7%). There was a moderate level of agreement between content of standard and digital notes (kappa 0.54, 95%CI 0.49-0.60). The quality of the digital note was within the 1 point clinically significant difference for all of the attributes, except for conciseness. Digital notes had a higher frequency of CMS severity elements identified. CONCLUSION: Digitally generated clinical notes had moderate agreement compared to standard clinical notes and within the one point clinically significant difference except for the conciseness attribute. Digital notes more reliably documented billing components of severity. The use of automated notes should be further explored to evaluate its utility in facilitating documentation of patient encounters.

Immunotherapy for Cancer: Common Gastrointestinal, Liver, and Pancreatic Side Effects and Their Management.

Cancer cells can block the activation of T lymphocytes by deploying inhibitory signals to cell surface receptors that downregulate the immune response. Immune checkpoint inhibitors (ICI) are monoclonal antibodies that regulate the immune response by acting on these receptors. The use of ICI has been successful for cancer types that do not respond well to conventional chemotherapy, showing clinical benefit in various advanced and metastatic cancers and supporting the promise of cancer immunotherapy. However, in some cases, these treatments are associated with immune-related adverse events, many of which affect the digestive system. The treatment of immune-related adverse events depends on the affected organ and the severity of symptoms. Here, we review the commonly used US FDA-approved ICI and briefly outline their mechanism of action. We also describe the resulting collateral effects on the gastrointestinal tract, liver, and pancreas and discuss their management and prognosis.

Virtual residency recruitment: future directions in the new era.

INTRODUCTION: The COVID-19 pandemic led to many changes in healthcare including graduate medical education (GME). Residency and fellowship programs halted in-person recruitment and pivoted to virtual models. Residency selection and recruitment were practices ripe for redesign, as they relied on in-person interviewing as the major point of contact prior to match list creation. In this commentary, we review the state of virtual interviewing and propose a future state where virtual interactions are commonplace and integrated into a comprehensive recruitment process. DISCUSSION: Virtual recruitment has led to a reduction of expenses, improved time efficiency for all parties and a reduced carbon footprint. Residency match outcomes have not changed substantially with the advent of virtual interviewing. Hybrid approaches, including virtual and in-person options have significant drawbacks and pitfalls which may limit adoption. Given the upheaval in GME recruitment caused by the pandemic, and the limitations of current methods for candidate assessment and interactions with programs, further innovation is needed to achieve an optimal state for all stakeholders. Multiple technology innovations are on the horizon which may improve the ability to interact virtually. Adoption of new technology along with expanding the timeline for residency recruitment may further optimize the process for both applicants and programs. CONCLUSIONS: The GME community was able to adopt technology for the recruitment interview rapidly due to the pandemic. As more opportunities for technology-based interactions grow, the opportunity exists to reimagine recruitment beyond the interview. While resources are constrained, some of the efficiencies gained by adopting virtual interviewing can be leveraged to expand the interactions between programs and applicants. Incorporation of in-person interaction may still be needed. Models will need to be developed to build upon the best characteristics of the virtual and in-person environments to optimize GME recruitment.KEY MESSAGES:Virtual communication methods have substantially changed residency recruitment during the COVID -19 pandemic.COVID -19 related changes in residency recruitment, including wide adoption of virtual methods, should be maintained and strengthened.Efforts should be made to advance the gains in residency recruitment strategy during the pandemic by use of technologies that expand virtual interactions beyond the interview.

Extragonadal Germ Cell Tumors of the Mediastinum and Retroperitoneum: A Surveillance, Epidemiology, and End Results-based Study.

OBJECTIVES: Extragonadal germ cell tumors (EGCT) are a rare entity, most of them being located in the mediastinum and retroperitoneum. Information on these tumors is scarce, requiring carrying out large population-based studies to better understand these diseases. We aimed to determine the clinical features and prognosis of patients with EGCT of the mediastinum and retroperitoneum. MATERIALS AND METHODS: Demographic and clinicopathological features of patients diagnosed with EGCT of the mediastinum and retroperitoneum from 1975 to 2016 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: A total of 1674 patients were included, 1297 (77.5%) of mediastinal origin and 377 (22.5%) of retroperitoneum. Nonseminomatous tumors (56.3%) were slightly more frequent than seminomas (43.7%) with similar distribution between mediastinum and retroperitoneum. After a median follow-up of 137 months, the median overall survival was 263 months (95% CI, 220-296) whereas the median cause-specific survival (CSS) has still not been reached. The 10-year overall survival and CSS were 57.4% (95% CI, 55-59.7) and 63% (95% CI, 60.6-65.2) respectively. Multivariate analysis showed that older age, mediastinal location, nonseminomatous histology, and distant disease at diagnosis were independent prognostic factors correlated with a worse prognosis. Patients with mediastinal choriocarcinoma and embryonal carcinoma have the worst prognosis, both with a median CSS of only 12 months. CONCLUSIONS: Despite a decreasing incidence observed in recent decades, EGCT continues to represent a challenge for oncologists. The prognosis of choriocarcinoma and embryonal carcinoma of the mediastinum remains poor and treatment strategies need to be improved urgently.

Comparable diagnostic accuracy of SARS-CoV-2 Spike RBD and N-specific IgG tests to determine pre-vaccination nation-wide baseline seroprevalence in Mexico.

A major challenge for developing countries during the COVID-19 pandemic is affordable and adequate monitoring of disease progression and population exposure as the primary source relevant epidemiological indicators. Serology testing enables assessing population exposure and to guide vaccination strategies but requires rigorous accuracy validation before population-wide implementation. We adapted a two-step ELISA protocol as a single-step protocol for detection of IgG against the Receptor Binding Domain (RBD) of SARS-CoV-2 spike protein and compared its diagnostic accuracy with a commercial immunoassay anti-nucleoprotein IgG. Both methods yielded adequate and comparable diagnostic accuracy after 3 weeks post-symptom onset and were implemented in a nation-wide population based serological survey during August-November 2020. Anti-RBD National seroprevalence was 23.6%, 1.3% lower, but not significantly, than for anti-N. Double positive seroprevalence was 19.7%. Anti-N single-positive seroprevalence was 3.72% and anti-RBD single-positive seroprevalence was 1.98%. Discrepancies in the positivity to either single marker may be due to different kinetics of each antibody marker as well as the heterogeneity of the sampling time in regards to local epidemic waves. Baseline single positivity prevalence will be useful to assess the serological impact of vaccination and natural infection in further serosurveillance efforts.

Bile Acids Induce Alterations in Mitochondrial Function in Skeletal Muscle Fibers.

Cholestatic chronic liver disease is characterized by developing sarcopenia and elevated serum levels of bile acids. Sarcopenia is a skeletal muscle disorder with the hallmarks of muscle weakness, muscle mass loss, and muscle strength decline. Our previous report demonstrated that deoxycholic acid (DCA) and cholic acid (CA), through the membrane receptor TGR5, induce a sarcopenia-like phenotype in myotubes and muscle fibers. The present study aimed to evaluate the impact of DCA and CA on mitochondrial mass and function in muscle fibers and the role of the TGR5 receptor. To this end, muscle fibers obtained from wild-type and TGR5-/- mice were incubated with DCA and CA. Our results indicated that DCA and CA decreased mitochondrial mass, DNA, and potential in a TGR5-dependent fashion. Furthermore, with TGR5 participation, DCA and CA also reduced the oxygen consumption rate and complexes I and II from the mitochondrial electron transport chain. In addition, DCA and CA generated more mitochondrial reactive oxygen species than the control, which were abolished in TGR5-/- mice muscle fibers. Our results indicate that DCA and CA induce mitochondrial dysfunction in muscle fibers through a TGR5-dependent mechanism.

Effective Low-Cost Ophthalmological Screening With a Novel iPhone Fundus Camera at Community Centers.

Ophthalmologic care is inaccessible to many people due to a variety of factors, including the availability of providers, cost of equipment for ophthalmologic care, and transportation to clinics and appointments. Because many causes of blindness are both highly prevalent and preventable once identified, it is essential to address gaps in care for underserved populations. We developed a novel 3D-printed mobile retinal camera. In this study, we organized recurring student-run screening events around New York City that took place in community centers and churches, at which we utilized our device to take retinal images. Our screening events reached a diverse population of New Yorkers, disproportionately those with lower household income, many of whom had not had recent eye exams. To validate the device for use in telehealth ophthalmologic visits, we transmitted the images to a remote ophthalmologist for evaluation and compared the result with an on-site attending physician's dilated eye exam. The subjective assessment indicated that 97% of images captured with the mobile retinal camera were acceptable for telehealth analysis. Remote image assessment by achieved 92% sensitivity and 83% specificity in detecting optic disc cupping, compared to the gold-standard on-site dilated eye exam. In addition, the device was portable, affordable, and able to be used by those with relatively little ophthalmologic training. We have demonstrated the utility of this affordable mobile retinal camera for telehealth ophthalmologic evaluation during community screening events that reached an underserved population to detect disease and connect with long-term care.

Combinatorial Approach of Binary Colloidal Crystals and CRISPR Activation to Improve Induced Pluripotent Stem Cell Differentiation into Neurons.

Conventional methods of neuronal differentiation in human induced pluripotent stem cells (iPSCs) are tedious and complicated, involving multistage protocols with complex cocktails of growth factors and small molecules. Artificial extracellular matrices with a defined surface topography and chemistry represent a promising venue to improve neuronal differentiation in vitro. In the present study, we test the impact of a type of colloidal self-assembled patterns (cSAPs) called binary colloidal crystals (BCCs) on neuronal differentiation. We developed a CRISPR activation (CRISPRa) iPSC platform that constitutively expresses the dCas9-VPR system, which allows robust activation of the proneural transcription factor NEUROD1 to rapidly induce neuronal differentiation within 7 days. We show that the combinatorial use of BCCs can further improve this neuronal differentiation system. In particular, our results indicate that fine tuning of silica (Si) and polystyrene (PS) particle size is critical to generate specific topographies to improve neuronal differentiation and branching. BCCs with 5 µm silica and 100 nm carboxylated PS (PSC) have the most prominent effect on increasing neurite outgrowth and more complex ramification, while BCCs with 2 µm Si and 65 nm PSC particles are better at promoting neuronal enrichment. These results indicate that biophysical cues can support rapid differentiation and improve neuronal maturation. In summary, our combinatorial approach of CRISPRa and BCCs provides a robust and rapid pipeline for the in vitro production of human neurons. Specific BCCs can be adapted to the late stages of neuronal differentiation protocols to improve neuronal maturation, which has important implications in tissue engineering, in vitro biological studies, and disease modeling.