Time-dependent Pax3-mediated chromatin remodeling and cooperation with Six4 and Tead2 specify the skeletal myogenic lineage in developing mesoderm.

The transcriptional mechanisms driving lineage specification during development are still largely unknown, as the interplay of multiple transcription factors makes it difficult to dissect these molecular events. Using a cell-based differentiation platform to probe transcription function, we investigated the role of the key paraxial mesoderm and skeletal myogenic commitment factors-mesogenin 1 (Msgn1), T-box 6 (Tbx6), forkhead box C1 (Foxc1), paired box 3 (Pax3), Paraxis, mesenchyme homeobox 1 (Meox1), sine oculis-related homeobox 1 (Six1), and myogenic factor 5 (Myf5)-in paraxial mesoderm and skeletal myogenesis. From this study, we define a genetic hierarchy, with Pax3 emerging as the gatekeeper between the presomitic mesoderm and the myogenic lineage. By assaying chromatin accessibility, genomic binding and transcription profiling in mesodermal cells from mouse and human Pax3-induced embryonic stem cells and Pax3-null embryonic day (E)9.5 mouse embryos, we identified conserved Pax3 functions in the activation of the skeletal myogenic lineage through modulation of Hedgehog, Notch, and bone morphogenetic protein (BMP) signaling pathways. In addition, we demonstrate that Pax3 molecular function involves chromatin remodeling of its bound elements through an increase in chromatin accessibility and cooperation with sine oculis-related homeobox 4 (Six4) and TEA domain family member 2 (Tead2) factors. To our knowledge, these data provide the first integrated analysis of Pax3 function, demonstrating its ability to remodel chromatin in mesodermal cells from developing embryos and proving a mechanistic footing for the transcriptional hierarchy driving myogenesis.

Developing Leaders in Surgical Residency: A Curriculum for Success.

OBJECTIVE: As surgical residents continue in their training, they are expected to not only take part in more complicated procedures, but to also serve as leaders in their respective care teams. While surgical skills are intensively taught in surgical residency programs, leadership is often learned informally, to the detriment of residents. Our curriculum was developed and implemented to provide foundational knowledge for surgical residents as they take on senior roles so that they may successfully act as leaders. This educational workshop was effective and efficient and can be applied at other residency programs that seek to improve the leadership skills of their residents. DESIGN: Implementation of a 3-day program focused on leadership, surgical skills, and career development to provide rising PGY-4 surgical residents with the abilities necessary for successful training. SETTING: This program was implemented at the University of Minnesota General Surgery residency program. PARTICIPANTS: Rising PGY-4 general surgery residents. RESULTS: The program consisted of a 3-day workshop which all rising PGY-4 residents participating in before transitioning into their respective roles. The program was led by the general surgery faculty. CONCLUSIONS: Curricula focused on developing leadership skills in residents can be effectively applied in a time-efficient manner that can benefit the residents as they move into official leadership roles on the care team.

A Single-Center Retrospective Evaluation of Unplanned Pediatric Critical Care Upgrades.

Background Inappropriate triage of critically ill pediatric patients can lead to poor outcomes and suboptimal resource utilization. This study aimed to determine and describe the demographic characteristics, diagnostic categories, and timing of unplanned upgrades to the pediatric intensive care unit (PICU) that required short (< 24 hours of care) and extended (≥ 24 hours of care) stays. In this article, we hypothesized that we will identify demographic characteristics, diagnostic categories, and frequent upgrade timing periods in both of these groups that may justify more optimal triage strategies. Methods This was a single-institution retrospective study of unplanned PICU upgrades between 2012 and 2018. The cohort was divided into two groups (short and extended PICU stay). We reviewed the electronic health record and evaluated for: demographics, mortality scores, upgrade timing (7a-3p, 3p-11p, 11p-7a), lead-in time (time spent on clinical service before upgrade), patient origin, and diagnostic category. Results Four hundred and ninety-eight patients' unplanned PICU upgrades were included. One hundred and nine patients (21.9%) required a short and 389 (78.1%) required an extended PICU stay. Lead-in time (mean, standard deviation) was significantly lower in the short group (0.65 ± 0.66 vs. 0.91 ± 0.82) ( p = 0.0006). A higher proportion of short group patients (59, 46.1%) were upgraded during the 3p-11p shift ( p = 0.0077). Conclusion We found that approximately one-fifth of PICU upgrades required less than 24 hours of critical care services, were more likely to be transferred between 3p-11p, and had lower lead-in times. In institutions where ill pediatric patients can be admitted to either a PICU or a monitored step-down unit, this study highlights quality improvement opportunities, particularly in recognizing which pediatric patients truly need critical care.

Use of Venovenous Extracorporeal Membrane Oxygenation in Patients With Acute Respiratory Distress Syndrome Caused by Fungal Pneumonia.

Background: Patients with fungal pneumonias sometimes progress to acute respiratory distress syndrome (ARDS). Mortality has been reported as high as 60% to 90% in this group. Venovenous extracorporeal membrane oxygenation (VV-ECMO) can be used to support such patients, however, outcomes are not well understood. Patients and Methods: This was a retrospective study across the four adult ECMO centers in Minnesota for one decade (2012-2022). The outcomes of interest were duration of ECMO, survival rate, and complications. Data were extracted from the electronic medical record and analyzed using descriptive statistics. Results: Fungal pneumonia was the etiology of ARDS in 22 of 422 (5%) adults supported with VV-ECMO during the 10-year study period. Median patient age was 43 years (interquartile range [IQR], 35-56) and 68% were male. By type of fungal infection, 16 (72%) had blastomycosis, five (22%) had pneumocystis, and one (5%) had cryptococcus. Of the 16 patients with blastomycosis two were immunosuppressed whereas all five of the pneumocystis patients were immunosuppressed. The overall survival rate was 73%; most patients with blastomycosis (67%) and pneumocystis (80%) survived to hospital discharge. The duration of ECMO support was greater for the pneumocystis group (median, 30 days; IQR, 21-43) compared with blastomycosis (median, 10 days; IQR, 8-18). Conclusions: Our findings support the use of VV-ECMO for ARDS caused by fungal pneumonias in select immunocompetent and immunocompromised patients. Although survival was high, patients with pneumocystis required longer ECMO runs.

Extracorporeal Membrane Oxygenation Patient Outcomes Following Restrictive Blood Transfusion Protocol.

OBJECTIVES: To investigate the effect of a restrictive blood product utilization protocol on blood product utilization and clinical outcomes. DESIGN: We retrospectively reviewed all adult extracorporeal membrane oxygenation (ECMO) patients from January 2019 to December 2021. The restrictive protocol, implemented in March 2020, was defined as transfusion of blood products for a hemoglobin level less than 7, platelet levels less than 50, and/or fibrinogen levels less than 100. Subgroup analysis was performed based on the mode of ECMO received: venoarterial ECMO, venovenous ECMO, and ECMO support following extracorporeal cardiopulmonary resuscitation (ECPR). SETTING: M Health Fairview University of Minnesota Medical Center. PATIENTS: The study included 507 patients. INTERVENTIONS: One hundred fifty-one patients (29.9%) were placed on venoarterial ECMO, 70 (13.8%) on venovenous ECMO, and 286 (56.4%) on ECPR. MEASUREMENTS AND MAIN RESULTS: For patients on venoarterial ECMO (48 [71.6%] vs. 52 [63.4%]; p = 0.374), venovenous ECMO (23 [63.9%] vs. 15 [45.5%]; p = 0.195), and ECPR (54 [50.0%] vs. 69 [39.2%]; p = 0.097), there were no significant differences in survival on ECMO. The last recorded mean hemoglobin value was also significantly decreased for venoarterial ECMO (8.10 [7.80-8.50] vs. 7.50 [7.15-8.25]; p = 0.001) and ECPR (8.20 [7.90-8.60] vs. 7.55 [7.10-8.88]; p < 0.001) following implementation of the restrictive transfusion protocol. CONCLUSIONS: These data suggest that a restrictive transfusion protocol is noninferior to ECMO patient survival. Additional, prospective randomized trials are required for further investigation of the safety of a restrictive transfusion protocol.