A Multisite Survey of Pediatric Hospitalists' Practices in Soliciting Feedback From Trainees.

OBJECTIVE: There is evidence that pediatric attending physicians value receiving feedback from trainees. With this study, we sought to determine the extent to which pediatric hospitalists value, solicit, and receive feedback from residents and medical students on specific areas of the attending's performance and identify perceived barriers to trainees' providing feedback. METHODS: A web-based survey was sent to pediatric hospitalists at 9 institutions in 2022. Survey questions were developed from existing literature, trainee input, faculty expertise, and a framework on the qualities of exemplary pediatric educators. Respondents answered yes-no and multiitem Likert scale questions and selected answers from predetermined lists related to feedback solicitation from trainees. χ-Square and Wilcoxon rank test statistics were used to analyze questions. RESULTS: Responses were gathered from 91 of 189 surveyed individuals (response rate: 48.1%). Respondents almost unanimously "agreed" or "strongly agreed" that feedback from medical students (88, 96.7%) and residents (89, 97.8%) can be valuable, but feedback was considered more valuable from residents (P <.05). Attending physicians asked for and received feedback more from residents than from medical students (P <.05). Attending physicians most commonly asked for feedback on "teaching skills." The largest perceived barriers to receiving feedback from trainees were trainee lacking comfort with giving feedback, trainee lacking awareness that providing feedback is within their role, and fear of retaliation. CONCLUSIONS: Although pediatric hospitalist respondents nearly unanimously valued feedback from trainees, attending physicians were inconsistent in their feedback solicitation practices. Attending physicians were more likely to ask for and receive feedback from residents than from medical students.

H2A Ubiquitination Alters H3-tail Dynamics on Linker-DNA to Enhance H3K27 Methylation.

Polycomb repressive complex 1 (PRC1) and PRC2 are responsible for epigenetic gene regulation. PRC1 ubiquitinates histone H2A (H2Aub), which subsequently promotes PRC2 to introduce the H3 lysine 27 tri-methyl (H3K27me3) repressive chromatin mark. Although this mechanism provides a link between the two key transcriptional repressors, PRC1 and PRC2, it is unknown how histone-tail dynamics contribute to this process. Here, we have examined the effect of H2A ubiquitination and linker-DNA on H3-tail dynamics and H3K27 methylation by PRC2. In naïve nucleosomes, the H3-tail dynamically contacts linker DNA in addition to core DNA, and the linker-DNA is as important for H3K27 methylation as H2A ubiquitination. H2A ubiquitination alters contacts between the H3-tail and DNA to improve the methyltransferase activity of the PRC2-AEBP2-JARID2 complex. Collectively, our data support a model in which H2A ubiquitination by PRC1 synergizes with linker-DNA to hold H3 histone tails poised for their methylation by PRC2-AEBP2-JARID2.

Preoperative ß-Blocker Therapy and Stroke or Major Adverse Cardiac Events in Major Abdominal Surgery: A Retrospective Cohort Study.

BACKGROUND: Perioperative ß-blocker therapy has been associated with increased risk of stroke. However, the association between ß-blocker initiation before the day of surgery and the risk of stroke is unknown. The authors hypothesized there would be no association between preoperative ß-blocker initiation within 60 days of surgery or chronic ß-blockade (more than 60 days) and the risk of stroke in patients undergoing major abdominal surgery. METHODS: Data on elective major abdominal surgery were obtained from the IBM (USA) Truven Health MarketScan 2005 to 2015 Commercial and Medicare Supplemental Databases. Patients were stratified by ß-blocker dispensing exposure: (1) ß-blocker-naïve, (2) preoperative ß-blocker initiation within 60 days of surgery, and (3) chronic ß-blocker dispensing (more than 60 days). The authors compared in-hospital stroke and major adverse cardiac events between the different ß-blocker therapy exposures. RESULTS: There were 204,981 patients who underwent major abdominal surgery. ß-Blocker exposure was as follows: perioperative initiation within 60 days of surgery for 4,026 (2.0%) patients, chronic ß-blocker therapy for 45,424 (22.2%) patients, and ß-blocker-naïve for 155,531 (75.9%) patients. The unadjusted frequency of stroke for patients with ß-blocker initiation (0.4%, 17 of 4,026) and chronic ß-blocker therapy (0.4%, 171 of 45,424) was greater than in ß-blocker-naïve patients (0.2%, 235 of 155,531; P < 0.001). After propensity score weighting, patients initiated on a ß-blocker within 60 days of surgery (odds ratio, 0.90; 95% CI, 0.31 to 2.04; P = 0.757) or on chronic ß-blocker therapy (odds ratio, 0.86; 95% CI, 0.65 to 1.15; P = 0.901) demonstrated similar stroke risk compared to ß-blocker-naïve patients. Patients on chronic ß-blocker therapy demonstrated lower adjusted risk of major adverse cardiac events compared to ß-blocker-naïve patients (odds ratio, 0.81; 95% CI, 0.72 to 0.91; P = 0.007), despite higher unadjusted absolute event rate (2.6% [1,173 of 45,424] vs. 0.6% [872 of 155,531]). CONCLUSIONS: Among patients undergoing elective major abdominal surgery, the authors observed no association between preoperative ß-blocker initiation within 60 days of surgery or chronic ß-blocker therapy and stroke.

Vascular Surgery Curriculum for Medical Students: A National Targeted Needs Assessment.

BACKGROUND: At present, neither the American College of Surgeons (ACS) nor the Society for Vascular Surgery (SVS) provides curriculum recommendations for medical students rotating on a vascular surgery service. We sent a targeted needs assessment to vascular surgeons across the country in order to investigate the need for a structured curriculum for medical students participating in a vascular surgery rotation during their clinical clerkships. METHODS: The survey was developed with input from medical students, vascular surgeons, and medical educators. Respondents were identified from the Fellowship and Residency Electronic Interactive Database (FREIDA). The needs assessment was sent to program directors of vascular residencies and fellowships and to other vascular surgery educators. The survey collected data regarding the existing vascular surgery curriculum at the respondent's institution, the need for a standardized curriculum, desired experiences for medical students, and important vascular topics for medical students to cover while on rotation. RESULTS: Responses were obtained from 50 of the 146 surveyed individuals (response rate = 34.2%). 48 respondents (96%) worked in an academic hospital or academic affiliated hospital. With regard to the existing vascular surgery curriculum, only 28 respondents (61%) indicated that they had a curriculum approved by the surgery clerkship director. 37 respondents (77.1%) said there were at least goals and objectives for students on the vascular surgery service, and 29 respondents (60.4%) indicated that there was dedicated time for didactic sessions. Only 17 respondents (35.4%) indicated students gave a case presentation on the service. 29 respondents (63%) agreed or strongly agreed that there should be a standardized vascular curriculum for medical students. When asked to rank 9 topics from most important to least important for students to learn, respondents ranked peripheral arterial disease, aortic disease, and carotid disease highest. Simulation experience was most frequently indicated as a desired addition to the curriculum, and only 16 respondents (33.3%) reported opportunities for vascular surgery specific simulation experiences. CONCLUSIONS: This study identified the lack of an existing structured curriculum for medical students, the desire for a standardized curriculum, and key topics and experiences that are felt to be important for students to cover.  With this information in hand, vascular educators have the potential to enhance the learning experience of medical students rotating through the service by developing a standardized curriculum.

A Circle RNA Regulatory Axis Promotes Lung Squamous Metastasis via CDR1-Mediated Regulation of Golgi Trafficking.

Lung squamous carcinoma (LUSC) is a highly metastatic disease with a poor prognosis. Using an integrated screening approach, we found that miR-671-5p reduces LUSC metastasis by inhibiting a circular RNA (circRNA), CDR1as. Although the putative function of circRNA is through miRNA sponging, we found that miR-671-5p more potently silenced an axis of CDR1as and its antisense transcript, cerebellar degeneration related protein 1 (CDR1). Silencing of CDR1as or CDR1 significantly inhibited LUSC metastases and CDR1 was sufficient to promote migration and metastases. CDR1, which directly interacted with adaptor protein 1 (AP1) complex subunits and coatomer protein I (COPI) proteins, no longer promoted migration upon blockade of Golgi trafficking. Therapeutic inhibition of the CDR1as/CDR1 axis with miR-671-5p mimics reduced metastasis in vivo. This report demonstrates a novel role for CDR1 in promoting metastasis and Golgi trafficking. These findings reveal an miRNA/circRNA axis that regulates LUSC metastases through a previously unstudied protein, CDR1. SIGNIFICANCE: This study shows that circRNA, CDR1as, promotes lung squamous migration, metastasis, and Golgi trafficking through its complimentary transcript, CDR1.

Postlaparotomy pain management: Comparison of patient-controlled analgesia pump alone, with subcutaneous bupivacaine infusion, or with injection of liposomal bupivacaine suspension.

OBJECTIVE: Efforts to achieve balance between effective pain management and opioid-related adverse events (ORAEs) have led to multimodal analgesia regimens. This study compared opioids delivered via patient-controlled analgesia (PCA) plus liposomal bupivacaine, a long-acting local anesthetic with potential to be an effective component of such regimens, to opioids delivered through PCA alone or PCA plus subcutaneous bupivacaine infusion (ONQ), following laparotomy. DESIGN: Prospective, randomized controlled trial. SETTING: Single, tertiary-care institution. PATIENTS: One hundred patients undergoing nonemergent laparotomy. INTERVENTIONS: Patients were randomly assigned to one of three study treatments: PCA only (PCAO), PCA with ONQ, or PCA with injectable liposomal bupivacaine suspension (EXP). MAIN OUTCOME MEASURES: Cumulative opioid use, daily mean patient-reported pain scores, and ORAEs through 72 hours postoperatively. RESULTS: On average, the EXP (n = 31) group exhibited less than 50 percent of the total opioid consumption of the PCAO (n = 36) group, and less than 60 percent of that for the ONQ (n = 33) group. Postoperative days 1 and 3 pain scores were significantly lower for the EXP group as compared to the ONQ and PCAO groups (p ≤ 0.005). Fewer patients in the EXP group (19.4 percent) experienced ORAEs compared to the PCAO (41.1 percent) and ONQ (45.5 percent) groups (p = 0.002). CONCLUSIONS: Laparotomy patients treated with liposomal bupivacaine as part of a multimodal regimen consumed less opioids, had lower pain scores, and had fewer ORAEs. The role of liposomal bupivacaine in the postoperative care of laparotomy patients merits further study.

RNA exploits an exposed regulatory site to inhibit the enzymatic activity of PRC2.

Polycomb repressive complex 2 (PRC2) is a histone methyltransferase that maintains cell identity during development in multicellular organisms by marking repressed genes and chromatin domains. In addition to four core subunits, PRC2 comprises multiple accessory subunits that vary in their composition during cellular differentiation and define two major holo-PRC2 complexes: PRC2.1 and PRC2.2. PRC2 binds to RNA, which inhibits its enzymatic activity, but the mechanism of RNA-mediated inhibition of holo-PRC2 is poorly understood. Here we present in vivo and in vitro protein-RNA interaction maps and identify an RNA-binding patch within the allosteric regulatory site of human and mouse PRC2, adjacent to the methyltransferase center. RNA-mediated inhibition of holo-PRC2 is relieved by allosteric activation of PRC2 by H3K27me3 and JARID2-K116me3 peptides. Both holo-PRC2.1 and holo-PRC2.2 bind RNA, providing a unified model to explain how RNA and allosteric stimuli antagonistically regulate the enzymatic activity of PRC2.