Mitogen-activated protein kinases (MAPKs), including Jun N-terminal kinase (JNK), promote inflammatory and proliferative responses to infection and other environmental stimuli including stress. Relevant to negative regulation of inflammatory pathways by glucocorticoids and the development of glucocorticoid resistance (observed in inflammatory disorders as well as certain neuropsychiatric disorders such as major depression), activation of JNK has been reported to inhibit glucocorticoid receptor (GR) function. In this study, the role of JNK pathways in modulating GR function was further investigated. Treatment of mouse hippocampal (HT22) cells with the selective JNK inhibitor, SP-600125 (0.1-10 mM), resulted in dose-dependent induction of GR-mediated MMTV-luciferase activity. SP-600125 also significantly enhanced dexamethasone-induced MMTV-luciferase activity, while increasing GR binding to the glucocorticoid responsive element, both in the presence and absence of Dex. Similar effects were observed in mouse fibroblast cells (LMCAT), and in HT22 cells treated with a JNK specific antisense oligonucleotide. The induction of GR-mediated function by SP-600125 was not due to altered cytosolic GR binding or GR protein expression or enhancement of GR nuclear translocation as determined by Western blot. Taken together, the data indicate that constitutive expression of JNK plays a tonic inhibitory role in GR function, which is consistent with findings that activation of JNK pathways inhibits GR. The data also identify potential pathways involved in the pathogenesis of the glucocorticoid resistance found in certain chronic immune/inflammatory diseases and subgroups of patients with major depression. Moreover, JNK pathways may represent a therapeutic target for normalization of GR function in these disorders.

BackgroundLacerations account for a large number of ED visits. Is there a “golden period” beyond which lacerations should not be repaired primarily? What type of relationship exists between time of repair and wound infection rates? Is it linear or exponential? Currently, the influence of laceration age on the risk of infection in simple lacerations repaired is not clearly defined. We conducted this study to determine the influence of time of primary wound closure on the infection rate.MethodsThis is a prospective observational study of patients who presented to the Emergency Department (ED) with a laceration requiring closure from April 2009 to November 2010. The wound closure time was defined as the time interval from when the patient reported laceration occurred until the time of the start of the wound repair procedure. Univariate analysis was performed to determine the factors predictive of infection. A non-parametric Wilcoxon rank-sum test was performed to compare the median differences of time of laceration repair. Chi-square (Fisher's exact) tests were performed to test for infection differences with regard to gender, race, location of laceration, mechanism of injury, co-morbidities, type of anesthesia and type of suture material used.ResultsOver the study period, 297 participants met the inclusion criteria and were followed. Of the included participants, 224 (75.4%) were male and 73 (24.6%) were female. Ten patients (3.4%) developed a wound infection. Of these infections, five occurred on hands, four on extremities (not hands) and one on the face. One of these patients was African American, seven were Hispanic and two were Caucasian (p = 0.0005). Median wound closure time in the infection group was 867 min and in the non-infection group 330 min (p = 0.03).ConclusionsWithout controlling various confounding factors, the median wound closure time for the lacerations in the wound infection group was statistically significantly longer than in the non-infection group.

Background: The coronavirus disease (COVID)-19 pandemic quickly challenged New York City health care systems. Telemedicine has been suggested to manage acute complaints and divert patients from inperson care. Objectives: The objective of this study was to describe and assess the impact of a rapidly scaled virtual urgent care platform during the COVID-19 pandemic. Methods: This was a retrospective cohort study of all patients who presented to a virtual urgent care platform over 1 month during the COVID-19 pandemic surge. We described scaling our telemedicine urgent care capacity, described patient clinical characteristics, assessed for emergency department (ED) referrals, and analyzed postvisit surveys. Results: During the study period, a total of 17,730 patients were seen via virtual urgent care; 454 (2.56%) were referred to an ED. The most frequent diagnoses were COVID-19 related or upper respiratory symptoms. Geospatial analysis indicated a wide catchment area. There were 251 providers onboarded to the platform; at peak, 62 providers supplied 364 h of coverage in 1 day. The average patient satisfaction score was 4.4/5. There were 2668 patients (15.05%) who responded to the postvisit survey; 1236 (49.35%) would have sought care in an ED (11.86%) or inperson urgent care (37.49%). Conclusions: A virtual urgent care platform was scaled to manage a volume of more than 800 patients a day across a large catchment area during the pandemic surge. About half of the patients would otherwise have presented to an ED or urgent care in person. Virtual urgent care is an option for appropriate patients while minimizing in-person visits during the COVID-19 pandemic.

Introduction Telemedicine use rapidly increased during the coronavirus disease 2019 pandemic. We assessed quality aspects of rapid expansion of a virtual urgent care (VUC) telehealth system and the effects of a secondary telephonic screening initiative during the pandemic. Methods We performed a retrospective cohort analysis in a single hospital network of VUC patients from March 1, 2020 through April 20, 2020. We abstracted demographic data, comorbidities, VUC return visits, emergency department (ED) referrals, and ED visits, dispositions, intubations, and deaths. We also reviewed incomplete visits. For comparison, we evaluated outcomes of non-admission dispositions from the ED: return visits with and without admission and deaths. We separately analyzed the effects of enhanced callback system targeting higher risk patients with COVID-like illness during the last two weeks of the study period. Results A total of 18,278 unique adult patients completed 22,413 VUC visits. Separately, 718 patient-scheduled visits were incomplete; the majority were no-shows. 50.9% of all patients and 74.0% of patients aged 60 years or older had comorbidities. Of VUC visits, 6.8% had a subsequent VUC encounter within 72 hours; 1.8% had a subsequent ED visit. Of patients with enhanced follow-up, 4.3% were referred for ED evaluation. Mortality was 0.20% overall; 0.21% initially and 0.16% with enhanced follow-up ( p = 0.59). Males and black patients were significantly overrepresented in decedents. Conclusion Appropriately deployed VUC services can provide a pragmatic strategy to care for large numbers of patients. Ongoing surveillance of operational, technical, and clinical factors is critical for patient quality and safety with this modality.