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OBJECTIVE: Timely intervention for clinically deteriorating ward patients requires that care teams accurately diagnose and treat their underlying medical conditions. However, the most common diagnoses leading to deterioration and the relevant therapies provided are poorly characterized. Therefore, we aimed to determine the diagnoses responsible for clinical deterioration, the relevant diagnostic tests ordered, and the treatments administered among high-risk ward patients using manual chart review. DESIGN: Multicenter retrospective observational study. SETTING: Inpatient medical-surgical wards at four health systems from 2006-2020 PATIENTS: Randomly selected patients (1,000 from each health system) with clinical deterioration, defined by reaching the 95th percentile of a validated early warning score, electronic Cardiac Arrest Risk Triage (eCART), were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical deterioration was confirmed by a trained reviewer or marked as a false alarm if no deterioration occurred for each patient. For true deterioration events, the condition causing deterioration, relevant diagnostic tests ordered, and treatments provided were collected. Of the 4,000 included patients, 2,484 (62%) had clinical deterioration confirmed by chart review. Sepsis was the most common cause of deterioration (41%; n=1,021), followed by arrhythmia (19%; n=473), while liver failure had the highest in-hospital mortality (41%). The most common diagnostic tests ordered were complete blood counts (47% of events), followed by chest x-rays (42%), and cultures (40%), while the most common medication orders were antimicrobials (46%), followed by fluid boluses (34%), and antiarrhythmics (19%). CONCLUSIONS: We found that sepsis was the most common cause of deterioration, while liver failure had the highest mortality. Complete blood counts and chest x-rays were the most common diagnostic tests ordered, and antimicrobials and fluid boluses were the most common medication interventions. These results provide important insights for clinical decision-making at the bedside, training of rapid response teams, and the development of institutional treatment pathways for clinical deterioration. KEY POINTS: Question: What are the most common diagnoses, diagnostic test orders, and treatments for ward patients experiencing clinical deterioration? Findings: In manual chart review of 2,484 encounters with deterioration across four health systems, we found that sepsis was the most common cause of clinical deterioration, followed by arrythmias, while liver failure had the highest mortality. Complete blood counts and chest x-rays were the most common diagnostic test orders, while antimicrobials and fluid boluses were the most common treatments. Meaning: Our results provide new insights into clinical deterioration events, which can inform institutional treatment pathways, rapid response team training, and patient care.
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In vitiligo, gradual cutaneous depigmentation and cytotoxic T-cell activity against melanocytes are accompanied by a paucity of regulatory T cells (Tregs) in vitiligo patient skin, indicating that autoimmune responses are not adequately held in check. Thus, we sought a means to repopulate patient skin with Tregs. We hypothesized that enhanced expression of CCL22 can promote Treg skin homing to suppress depigmentation. The mouse Ccl22 gene was cloned into an expression vector and resulting DNA was used for gene gun treatment. Two spontaneous depigmentation models with different kinetics of melanocyte loss were utilized, expressing tyrosinase-reactive and gp100-reactive TCR transgenes. Mice were subjected to five gene gun treatments 6 days apart, scanned for depigmentation weekly thereafter, and monitored for activation and proliferation of relevant T cells and for Treg infiltration to the skin. Significantly reduced depigmentation 2 weeks after treatment was accompanied by a markedly increased abundance of Tregs in the skin at the expense of melanocyte-reactive, TCR transgenic T cells, as well as by reduced proliferation and reduced IFN-γ production in response to cognate peptide. Continued treatment may be necessary for sustained, local immunosuppression. These findings suggest that topical CCL22 may be used for the treatment of vitiligo.