Racial Disparities and Other Socioeconomic Predictors of Mortality in Acute Pulmonary Embolism Treatment from the National Inpatient Sample.

PURPOSE: To explore the significance of socioeconomic factors such as race and ethnicity as predictors of mortality in sub-massive and massive acute pulmonary embolism (PE). MATERIALS AND METHODS: Hospitalizations aged > 18 years with acute, non-septic PE from 2016 to 2019 were identified in the National Inpatient Sample and divided into IR (CDT and thrombectomy) and non-IR (tPA) treatments. Statistical analyses calculated significant odds ratios via 95% confidence intervals. The primary outcome of interest was mortality rate. Comorbidities affecting mortality were examined secondarily. RESULTS: Non-Hispanic (NH) Black, Hispanic, and Asian/Pacific Islander patients were significantly less likely to undergo an IR procedure for acute, non-septic PE compared to White patients (NH Black 0.83 [0.76 - 0.90], p<0.05; Hispanic 0.78 [0.68 - 0.89], p=0.06; Asian/Pacific Islander 0.71 [0.51 - 0.98], p=0.72; OR [95% CI]); however, these differences were eliminated when propensity score matching for age, biological sex, and primary insurance-type or primary insurance-type alone. NH Black patients were significantly more likely than White patients to die regardless of undergoing non-IR or an IR treatment. Overall risk of death was 41% higher for NH Black patients compared to White patients (RR [95% CI] 1.41 [1.24 - 1.60], p<0.001). CONCLUSION: NH Black patients have a higher risk of mortality from acute, non-septic PE than White patients. Independent of race, undergoing IR management for acute, non-septic pulmonary embolisms was associated with a lower mortality rate. Matching for primary insurance-type eliminates difference in mortality between races suggest socioeconomic status (SES) may determine outcomes in acute PE.

Novel combination approaches to locoregional and systemic therapy in the management of primary and metastatic liver tumors.

Several pathways and mutations must develop or be in place for the onset of cancer. Therefore, therapies should ideally target as many of these pathways as possible to improve outcomes. Combining several agents has proven to be more effective than the use of monotherapy in the treatment of renal cell carcinoma, hepatocellular carcinoma, and other cancers. Combination therapy can also include locoregional therapies such as ablation and embolization with systemic agents for synergistic effects. This review article discusses the current literature and clinical trials covering these multifactorial combination therapies in primary and metastatic liver tumors.

Medical student exam performance and perceptions of a COVID-19 pandemic-appropriate pre-clerkship medical physiology and pathophysiology curriculum.

BACKGROUND: Medical schools were compelled to abruptly transition pre-clerkship curricula to remote learning formats due to the emergence of the Coronavirus Disease 2019 (COVID-19) pandemic. We evaluated student perceptions of remote learning, exam performance, and utilization of third-party learning resources to assess the implementation of a newly developed pandemic-appropriate physiology curriculum. METHODS: This was an observational study based on a survey conducted in the Spring of 2021 at the University of California, Irvine, School of Medicine (UCISOM). This study aimed to assess first (MS1) and second year (MS2) medical students' perceptions of satisfaction, support, academic performance, and connectedness before and during the COVID-19 pandemic. The MS1 class began medical school during the first year of the COVID-19 pandemic, whereas the MS2 class did so prior to the start of the pandemic. A survey instrument was developed and validated to identify the impact remote learning had on student self-perceptions of the Medical Physiology and Pathophysiology course. Surveys were distributed to all students and responses were collected on a voluntary basis. Exam scores on a customized National Board of Medical Examiners (NBME) physiology shelf exam were also compared to objectively identify how the remote curriculum during the pandemic impacted academic performance. RESULTS: Of 204 students enrolled, 74 responses were analyzed, with 42 MS1 (40% of MS1s) and 32 MS2 (31% of MS2s) responses. Overall, MS1s and MS2s were satisfied with the curriculum they received (95 and 97% respectively) and the school's support of their concerns (86 and 100% respectively). Notably, only 50% of MS1s felt connected to their peers, compared to 94% of MS2s. Lecture attendance and self-perception of their academic performance were similar between both classes. Interestingly, the intra-pandemic class's NBME exam average in 2020 (60.2% ± 8.9, n = 104) was significantly higher than the pre-pandemic class average in 2019 (56.8% ± 11.3, n = 100). Both classes primarily used course materials over third-party learning resources. An additional set of survey questions distributed only to the MS1 class found that the majority of MS1s reported minimal barriers with regards to accessibility, including internet connectivity, study-conducive environments, and balancing family commitments. Overall, pre-clerkship medical students had positive perceptions of the newly developed pandemic-appropriate physiology curriculum. CONCLUSIONS: Changes to the pre-clerkship physiology curriculum during the COVID-19 pandemic were met with overall satisfaction from the students and an increase in NBME scores. More attention to student connectedness is needed to improve how remote learning can be best optimized into future curricula development.

The transcription factors SIX3 and VAX1 are required for suprachiasmatic nucleus circadian output and fertility in female mice.

The homeodomain transcription factors sine oculis homeobox 3 (Six3) and ventral anterior homeobox 1 (Vax1) are required for brain development. Their expression in specific brain areas is maintained in adulthood, where their functions are poorly understood. To identify the roles of Six3 and Vax1 in neurons, we conditionally deleted each gene using Synapsincre , a promoter targeting maturing neurons, and generated Six3syn and Vax1syn mice. Six3syn and Vax1syn females, but not males, had reduced fertility, due to impairment of the luteinizing hormone (LH) surge driving ovulation. In nocturnal rodents, the LH surge requires a precise timing signal from the brain's circadian pacemaker, the suprachiasmatic nucleus (SCN), near the time of activity onset. Indeed, both Six3syn and Vax1syn females had impaired rhythmic SCN output, which was associated with weakened Period 2 molecular clock function in both Six3syn and Vax1syn mice. These impairments were associated with a reduction of the SCN neuropeptide vasoactive intestinal peptide in Vax1syn mice and a modest weakening of SCN timekeeping function in both Six3syn and Vax1syn mice. Changes in SCN function were associated with mistimed peak PER2::LUC expression in the SCN and pituitary in both Six3syn and Vax1syn females. Interestingly, Six3syn ovaries presented reduced sensitivity to LH, causing reduced ovulation during superovulation. In conclusion, we have identified novel roles of the homeodomain transcription factors SIX3 and VAX1 in neurons, where they are required for proper molecular circadian clock function, SCN rhythmic output, and female fertility.

The transcription factor VAX1 in VIP neurons of the suprachiasmatic nucleus impacts circadian rhythm generation, depressive-like behavior, and the reproductive axis in a sex-specific manner in mice.

Background: The suprachiasmatic nucleus (SCN) within the hypothalamus is a key brain structure required to relay light information to the body and synchronize cell and tissue level rhythms and hormone release. Specific subpopulations of SCN neurons, defined by their peptide expression, regulate defined SCN output. Here we focus on the vasoactive intestinal peptide (VIP) expressing neurons of the SCN. SCN VIP neurons are known to regulate circadian rhythms and reproductive function. Methods: To specifically study SCN VIP neurons, we generated a novel knock out mouse line by conditionally deleting the SCN enriched transcription factor, Ventral Anterior Homeobox 1 (Vax1), in VIP neurons (Vax1Vip; Vax1fl/fl:VipCre). Results: We found that Vax1Vip females presented with lengthened estrous cycles, reduced circulating estrogen, and increased depressive-like behavior. Further, Vax1Vip males and females presented with a shortened circadian period in locomotor activity and ex vivo SCN circadian period. On a molecular level, the shortening of the SCN period was driven, at least partially, by a direct regulatory role of VAX1 on the circadian clock genes Bmal1 and Per2. Interestingly, Vax1Vip females presented with increased expression of arginine vasopressin (Avp) in the paraventricular nucleus, which resulted in increased circulating corticosterone. SCN VIP and AVP neurons regulate the reproductive gonadotropin-releasing hormone (GnRH) and kisspeptin neurons. To determine how the reproductive neuroendocrine network was impacted in Vax1Vip mice, we assessed GnRH sensitivity to a kisspeptin challenge in vivo. We found that GnRH neurons in Vax1Vip females, but not males, had an increased sensitivity to kisspeptin, leading to increased luteinizing hormone release. Interestingly, Vax1Vip males showed a small, but significant increase in total sperm and a modest delay in pubertal onset. Both male and female Vax1Vip mice were fertile and generated litters comparable in size and frequency to controls. Conclusion: Together, these data identify VAX1 in SCN VIP neurons as a neurological overlap between circadian timekeeping, female reproduction, and depressive-like symptoms in mice, and provide novel insight into the role of SCN VIP neurons.

A Preference for Peers over Faculty in the Pandemic Era: Development and Evaluation of a Medical Student-led Virtual Physiology Exam Review.

In the middle of the COVID-19 pandemic, students at the University of California, Irvine, reimagined their peer-led, small-group, tutorial sessions into an online format. The virtual sessions improved student-reported understanding of physiological principles and reduced exam anxiety. Peer-led review remains a valuable resource in the era of virtual medical education.

Interventional oncology: new techniques and new devices.

Interventional oncology is a rapidly emerging field in the treatment of cancer. Minimally invasive techniques such as transarterial embolization with chemotherapeutic and radioactive agents are established therapies and are found in multiple guidelines for the management of primary and metastatic liver lesions. Percutaneous ablation is also an alternative to surgery for small liver, renal, and pancreatic tumors. Recent research in the niche of interventional oncology has focused on improving outcomes of established techniques in addition to the development of novel therapies. In this review, we address the recent and current advancements in devices, technologies, and techniques of chemoembolization and ablation: thermal ablation, histotripsy, high-intensity focused ultrasound, embolization strategies, liquid embolic agents, and local immunotherapy/antiviral therapies.

Deletion of Six3 in post-proliferative neurons produces weakened SCN circadian output, improved metabolic function, and dwarfism in male mice.

OBJECTIVE: The increasing prevalence of obesity makes it important to increase the understanding of the maturation and function of the neuronal integrators and regulators of metabolic function. METHODS: Behavioral, molecular, and physiological analyses of transgenic mice with Sine oculis 3 (Six3) deleted in mature neurons using the Synapsincreallele. RESULTS: Conditional deletion of the homeodomain transcription factor Six3 in mature neurons causes dwarfism and weakens circadian wheel-running activity rhythms but increases general activity at night, and improves metabolic function, without impacting pubertal onset or fertility in males. The reduced growth in 6-week-old Six3fl/fl:Synapsincre (Six3syn) males correlates with increased somatostatin (SS) expression in the hypothalamus and reduced growth hormone (GH) in the pituitary. In contrast, 12-week-old Six3syn males have increased GH release, despite an increased number of the inhibitory SS neurons in the periventricular nucleus. GH is important in glucose metabolism, muscle function, and bone health. Interestingly, Six3syn males have improved glucose tolerance at 7, 12, and 18 weeks of age, which, in adulthood, is associated with increased % lean mass and increased metabolic rates. Further, 12-week-old Six3syn males have reduced bone mineralization and a lower bone mineral density, indicating that reduced GH levels during early life cause a long-term reduction in bone mineralization. CONCLUSION: Our study points to the novel role of Six3 in post-proliferative neurons to regulate metabolic function through SS neuron control of GH release.

Transforming University of California, Irvine medical physiology instruction into the pandemic era.

At the University of California, Irvine, School of Medicine (UCISOM), the COVID-19 pandemic is accelerating the transition of face-to-face didactic lectures to online platforms. Institutions nationwide have opted to transition their lectures into remote instruction for the upcoming Fall 2020 academic year. UCISOM's pre-clerkship Medical Immunology course in the Spring 2020 serves as a template for other medical courses to successfully transform lecture content into virtual presentations. To help facilitate successful large-scale transition to online courses, UCI developed institutional support and implemented a Division of Teaching Excellence and Innovation (DTEI) Fellowship and iMedEd programs to support medical educators throughout Summer. Previously developed E-learning modules for renal and acid-base physiology serve as the foundation for novel pulmonary E-learning modules at UCISOM. In preparation for the new academic year, in a collaboration between faculty, UCISOM's top performing second-year medical students (MS2s) and DTEI fellows worked together during the summer to transition UCISOM's Medical Physiology and Pathophysiology course online. With over 100 first-year medical students attending the Medical Physiology course over live synchronous Zoom instruction, formative and summative assessments were incorporated into Canvas modules along with peer-led review sessions and new E-learning modules to educate and monitor student progress. The course will maintain existing in-person active learning activities for students to get hands-on experience using the latest medical devices while maintaining social distancing. Successful transition to online medical education at UCISOM will depend on increasing use of formative assessments, increased utilization of peer-led review sessions, and efficient communication to help foster self-directed learning.

The Homeodomain Transcription Factors Vax1 and Six6 Are Required for SCN Development and Function.

The brain's primary circadian pacemaker, the suprachiasmatic nucleus (SCN), is required to translate day-length and circadian rhythms into neuronal, hormonal, and behavioral rhythms. Here, we identify the homeodomain transcription factor ventral anterior homeobox 1 (Vax1) as required for SCN development, vasoactive intestinal peptide expression, and SCN output. Previous work has shown that VAX1 is required for gonadotropin-releasing hormone (GnRH/LHRH) neuron development, a neuronal population controlling reproductive status. Surprisingly, the ectopic expression of a Gnrh-Cre allele (Gnrhcre) in the SCN confirmed the requirement of both VAX1 (Vax1flox/flox:Gnrhcre, Vax1Gnrh-cre) and sine oculis homeobox protein 6 (Six6flox/flox:Gnrhcre, Six6Gnrh-cre) in SCN function in adulthood. To dissociate the role of Vax1 and Six6 in GnRH neuron and SCN function, we used another Gnrh-cre allele that targets GnRH neurons, but not the SCN (Lhrhcre). Both Six6Lhrh-cre and Vax1Lhrh-cre were infertile, and in contrast to Vax1Gnrh-cre and Six6Gnrh-cre mice, Six6Lhrh-cre and Vax1Lhrh-cre had normal circadian behavior. Unexpectedly, ~ 1/4 of the Six6Gnrh-cre mice were unable to entrain to light, showing that ectopic expression of Gnrhcre impaired function of the retino-hypothalamic tract that relays light information to the brain. This study identifies VAX1, and confirms SIX6, as transcription factors required for SCN development and function and demonstrates the importance of understanding how ectopic CRE expression can impact the results.