The Rounds Efficiency Index: A Novel Physics-Based Construct for Patient- and Family-Centered Rounds.

BACKGROUND AND OBJECTIVES: Efficiently conducting patient- and family-centered rounds (PFCR) is challenging, particularly without a measure of efficiency. In physics, efficiency is the ratio of work output to work input. We sought to evaluate PFCR efficiency via a novel construct rooted in physics. Our objectives were to (1) Establish baseline work output for clinical work (CW), educational effectiveness (EE), and family experience (FE); (2) establish baseline work input for rounds length (RL); and (3) begin preliminary construction of a rounds efficiency index (REI) as a measure of PFCR efficiency. METHODS: Four components of rounds efficiency were collected on 5 inpatient acute care teams during a baseline period. CW consisted of the percentage of daily orders placed on rounds. EE was assessed via survey for trainees and FE by families. RL was recorded in minutes per patient. During an 8-week intensive period, the REI (reported as %) was calculated as a ratio of work output/work input using aggregate mean/median ratings for CW, EE, FE, and RL. RESULTS: Baseline data included 809 orders, 28 EE ratings, 21 FE ratings, and RL mean of 11.4 minutes per patient. During the intensive period, the median team-specific weekly REI for the end versus beginning of the academic year was 58% and 52.5% (P = .17), respectively. The median REI during the start and end of the block was 49% and 57% (P = .15), respectively. CONCLUSIONS: The study assessed 4 components of efficiency (CW, EE, FE, RL) and calculated REI allowing for a preliminary tool to measure rounding efficiency. With this, targeted interventions can improve PFCR efficiency.

Primary Malignant Melanoma of the Gastroesophageal Junction Treated With Immunotherapy: A Case Report.

INTRODUCTION: Primary malignant melanoma of the esophagus constitutes 0.1% to 0.5% of all primary malignant esophageal neoplasms. Melanocytes are present within the squamous epithelium of the esophagus in the stratum basale layer with melanocytosis rare within the esophagus. Primary esophageal melanoma is aggressive and has a poor survival rate; 80% of patients have metastatic disease at diagnosis. Resection surgery is usually first-line treatment for localized primary malignant esophageal melanoma, but recurrence rates remain high. Tumor-specific immunotherapy has shown promising results. We report a case of primary malignant esophageal melanoma with metastasis to the liver treated with immunotherapy. CASE PRESENTATION: A 66-year-old woman presented with 2 months of progressive dysphagia and 3 episodes of hematemesis the previous night. Endoscopic examination showed a hypervascular distal esophageal mass. Biopsy was positive for S-100, SOX-10, and HMB-45 and showed rare mitotic figures with scattered pigment, consistent with melanoma. She was scheduled for esophagectomy initially, but instead pursued immunotherapy after liver metastasis was diagnosed during preop magnetic resonance imaging. Immunotherapy consisted of 8 cycles of pembrolizumab, followed by 4 months nivolumab and ipilimumab. The patient remains in remission 3 years after completing immunotherapy. DISCUSSION/CONCLUSIONS: Our patient was diagnosed with primary malignant esophageal melanoma of the distal esophagus with metastasis to the liver, a presentation that typically has a poor prognosis. Despite this, remission was achieved with immunotherapy without surgical intervention. Only a small number of cases of primary esophageal melanoma treated with immunotherapy have been reported-one showcasing tumor stabilization following several cycles of therapy with eventual metastasis, while our patient had a stable response to treatment. Further exploration of medical management with immunotherapy should be conducted, as it represents an alternative treatment for patients who do not have the option of surgical management.

Retinoic acid receptor alpha activation is necessary and sufficient for plasticity induced by recurrent central apnea.

Reductions in respiratory-related synaptic inputs to inspiratory motor neurons initiate a form of plasticity that proportionally enhances inspiratory motor output, even in the absence of changing blood gases. This form of plasticity is known as inactivity-induced inspiratory motor facilitation (iMF). iMF triggered by brief, recurrent reductions in respiratory neural activity requires local retinoic acid (RA) synthesis, but receptor subtypes activated by RA are unknown. To test the hypothesis that retinoic acid receptor alpha (RARα) is necessary for iMF, RAR subtype-specific inhibitors were delivered intrathecally above the phrenic motor pool in urethane-anesthetized, ventilated rats before 5, ∼1 min central apneas (without hypoxia; separated by 5 min) while monitoring phrenic inspiratory output. Pretreatment with a spinal RARα inhibitor impaired the capacity for recurrent central apnea to trigger long-lasting increases in phrenic inspiratory output, but plasticity was expressed in rats pretreated with an RARß/γ inhibitor. Intrathecal RA application in the absence of reduced respiratory neural activity elicited an increase in phrenic inspiratory output, which was prevented by pretreatment with an RARα inhibitor. These data indicate that spinal RARα activation is necessary for iMF triggered by recurrent reductions in respiratory neural activity, and that RARα activation in/near the phrenic motor pool in the absence of respiratory neural activity deprivation is sufficient to elicit phrenic inspiratory motor facilitation. Understanding cellular cascades underlying plasticity induced by reductions in respiratory neural activity may define avenues for pharmacological intervention in disorders in which endogenous compensatory mechanisms that defend ongoing inspiratory motor output are impaired.NEW & NOTEWORTHY Local mechanisms near phrenic motor neurons respond to reductions in respiratory-related synaptic inputs by triggering a chemoreflex-independent, proportional enhancement in inspiratory output, a form of plasticity called inactivity-induced inspiratory motor facilitation (iMF). Here, we show that activation of spinal retinoic acid receptor alpha (RARα) is necessary to trigger phrenic iMF, and that spinal RARα activation in the absence of respiratory neural activity deprivation is sufficient to elicit phrenic inspiratory facilitation.

Prior Hypoxia Exposure Enhances Murine Microglial Inflammatory Gene Expression in vitro Without Concomitant H3K4me3 Enrichment.

Hypoxia (Hx) is a component of multiple disorders, including stroke and sleep-disordered breathing, which often precede or are comorbid with neurodegenerative diseases. However, little is known about how hypoxia affects the ability of microglia, resident CNS macrophages, to respond to subsequent inflammatory challenges that are often present during neurodegenerative processes. We, therefore, tested the hypothesis that hypoxia would enhance or "prime" microglial pro-inflammatory gene expression in response to a later inflammatory challenge without programmatically increasing basal levels of pro-inflammatory cytokine expression. To test this, we pre-exposed immortalized N9 and primary microglia to hypoxia (1% O2) for 16 h and then challenged them with pro-inflammatory lipopolysaccharide (LPS) either immediately or 3-6 days following hypoxic exposure. We used RNA sequencing coupled with chromatin immunoprecipitation sequencing to analyze primed microglial inflammatory gene expression and modifications to histone H3 lysine 4 trimethylation (H3K4me3) at the promoters of primed genes. We found that microglia exhibited enhanced responses to LPS 3 days and 6 days post-hypoxia. Surprisingly, however, the majority of primed genes were not enriched for H3K4me3 acutely following hypoxia exposure. Using the bioinformatics tool MAGICTRICKS and reversible pharmacological inhibition, we found that primed genes required the transcriptional activities of NF-κB. These findings provide evidence that hypoxia pre-exposure could lead to persistent and aberrant inflammatory responses in the context of CNS disorders.