Resident-Championed Quality Improvement Provides Value: Confronting Prolonged Mechanical Ventilation.

BACKGROUND: The Quality In-Training Initiative (QITI) provides hands-on quality improvement education for residents. As our institution has ranked in the bottom quartile for prolonged mechanical ventilation (PMV) according to the National Surgical Quality Improvement Program (NSQIP), we sought to illustrate how our resident-led QITI could be used to determine perioperative contributors to PMV. MATERIALS AND METHODS: The Model for Improvement framework (developed by Associates in Process Improvement) was used to target postoperative ventilator management. However, baseline findings from our 2016 NSQIP data suggested that preoperative patient factors were more likely contributing to PMV. Subsequently, a retrospective one-to-one case-control study was developed, comparing preoperative NSQIP risk calculator profiles for PMV patients to case-matched patients for age, sex, procedure, and emergent case status. Chart review determined ventilator time, 30-d outcomes, and all-cause mortality. RESULTS: Forty-five patients with PMV (69% elective) had a median ventilator time of 134 h (interquartile range 87-254). The NSQIP calculator demonstrated increased preoperative risk percentages in PMV patients when compared to case-matched patients for any complication (includes PMV), predicted length of stay, and death (all P < 0.05). Thirty-day outcomes were worse for the PMV group in categories for sepsis, pneumonia, unplanned reoperation, 30-d mortality, rehab facility discharge, and length of stay (all P < 0.05). All-cause mortality was also significantly higher for PMV patients (P < 0.05). CONCLUSIONS: Resident-led QITI projects enhance resident education while exposing opportunities for improving care. Preoperative patient factors play a larger-than-anticipated role in PMV at our institution. Ongoing efforts are aimed toward preoperative identification and optimization of high-risk patients.

Identification of benzimidazole-based inhibitors of the mitogen activated kinase-5 signaling pathway.

The MEK-signaling pathways are complex but critical signaling cascades that correlate an extracellular signaling event with internal cell processes. To date at least seven MEK isozymes have been identified. MEK5, in particular, is upregulated in multiple forms of tumors. Analysis of the EGF-induced MEK5 signaling cascade in cultured HEK cells has identified compounds that can inhibit MEK5 phosphorylation of ERK5; observed biological activity is dependent on chemical variation.

Resveratrol and pinostilbene confer neuroprotection against aging-related deficits through an ERK1/2-dependent mechanism.

Age-related declines in motor function may be due, in part, to an increase in oxidative stress in the aging brain leading to dopamine (DA) neuronal cell death. In this study, we examined the neuroprotective effects of natural antioxidants resveratrol and pinostilbene against age-related DAergic cell death and motor dysfunction using SH-SY5Y neuroblastoma cells and young, middle-aged, and old male C57BL/6 mice. Resveratrol and pinostilbene protected SH-SY5Y cells from a DA-induced decrease in cell viability. Dietary supplementation with resveratrol and pinostilbene inhibited the decline of motor function observed with age. While DA and its metabolites (DOPAC and HVA), dopamine transporter, and tyrosine hydroxylase levels remain unchanged during aging or treatment, resveratrol and pinostilbene increased ERK1/2 activation in vitro and in vivo in an age-dependent manner. Inhibition of ERK1/2 in SH-SY5Y cells decreased the protective effects of both compounds. These data suggest that resveratrol and pinostilbene alleviate age-related motor decline via the promotion of DA neuronal survival and activation of the ERK1/2 pathways.

A unique presentation of ectopic thyroid, a case report.

INTRODUCTION: This case presents a painful ectopic thyroid, an unusual presentation, in an atypical location. The patient's history of an ingested fish bone, her acute presentation, and inconclusive imaging, made this case a diagnostic dilemma. PRESENTATION OF CASE: 61-year-old female presented with acutely worsening history of left throat pain and dysphagia after swallowing a fish bone. CT scan showed a foreign body in the anterior wall of the cervical esophagus. EGD studies were inconclusive. Surgical exploration identified and excised a multinodular cystic lesion without connection to esophageal lumen. Pathology described multinodular thyroid parenchyma with chronic inflammation and no evidence of malignancy. No foreign body was located. DISCUSSION: Based on the patient's history, imaging, and acute presentation, an esophageal perforation with abscess formation was the most likely diagnosis. Surgical exploration was the necessary intervention for this patient's acute symptoms as both a diagnostic and therapeutic tool. The diagnosis of ectopic thyroid tissue from pathology of the excised cystic lesion was unexpected, as the location of tissue and the painful presentation are not typical characteristics of ectopic thyroid tissue. Management of the this case illustrates the dilemma faced in determining the appropriate work up for a patient, without compromising the patient's safety. CONCLUSION: Though painful presentation and this case's location are rare, ectopic thyroid tissue should be included in the differential diagnosis of point tenderness with an associated lesion on imaging.

Sensory systems: their impact on C. elegans survival.

An animal's survival strongly depends on a nervous system that can rapidly process and integrate the changing quality of its environment and promote the most appropriate physiological responses. This is amply demonstrated in the nematode worm Caenorhabditis elegans, where its sensory system has been shown to impact multiple physiological traits that range from behavior and developmental plasticity to longevity. Because of the accessibility of its nervous system and the number of tools available to study and manipulate its neural circuitry, C. elegans has thus become an important model organism in dissecting the mechanisms through which the nervous system promotes survival. Here we review our current understanding of how the C. elegans sensory system affects diverse physiological traits, whose coordination would be essential for survival under fluctuating environments. The knowledge we derive from the C. elegans studies should provide testable hypotheses in discovering similar mechanisms in higher animals.

Loss of motor coordination in an aging mouse model.

With age, there is an increase in motor deficits that leads to an increased incidence of slips and falls. As the elderly population continues to grow, there is a need for aging models and research that focus on behavioral deficits that occur with normal, non-diseased aging. The present study was designed to examine the appropriateness of C57Bl/6 male mice as aging animal models using the challenging beam and cylinder tests to measure motor coordination and spontaneous activity, respectively. Using young (2-4 mo), middle-aged (10-12 mo), and aged (22-24 mo) mice, we observed that aged C57Bl/6 male mice make more errors on the challenging beam task and take fewer hind limb steps as compared to young and middle-aged mice. Body weight and food intake were also measured to determine if these parameters were confounding factors in the interpretation of the behavioral data. Increases in body weight and food consumption were not observed in the oldest group that made the most errors. Together these data indicate that aged C57BL/6 mice display age-related motor deficits similar to those seen in humans and are an appropriate model of motor deficits that occur with age.

L-DOPA reverses motor deficits associated with normal aging in mice.

We wished to determine whether L-DOPA, a common treatment for the motor deficits in Parkinson's disease, could also reverse the motor deficits that occur during aging. We assessed motor performance in young (2-3 months) and old (20-21 months) male C57BL/6 mice using the challenge beam and cylinder tests. Prior to testing, mice were treated with L-DOPA or vehicle. Following testing, striatal tissue was analyzed for phenotypic markers of dopamine neurons: dopamine, dopamine transporter, and tyrosine hydroxylase. Although the dopaminergic markers were unchanged with age or L-DOPA treatment, L-DOPA reversed the motor deficits in the old animals such that their motor coordination was that of a young mice. These findings suggest that some of the locomotor deficits that accompany normal aging are responsive to L-DOPA treatment and may be due to subtle alterations in dopaminergic signaling.