Patients With Autoimmune Hepatitis and Nonalcoholic Fatty Liver Disease: Characteristics, Treatment, and Outcomes.

GOAL: The objective of this study was to characterize an autoimmune hepatitis (AIH)/nonalcoholic fatty liver disease (NAFLD) overlap cohort, determine if they received standard of care treatment, and delineate their outcomes in comparison with patients with AIH or NAFLD alone. BACKGROUND: AIH is a relatively rare and heterogeneously presenting liver disease of unknown etiology. NAFLD is a leading cause of liver disease worldwide. AIH treatment includes steroids, which have adverse metabolic effects that can worsen NAFLD. No treatment guidelines are available to mitigate this side on AIH/NAFLD overlap patients. Few studies to date have examined these patients' characteristics, management practices, and outcomes. MATERIALS AND METHODS: A single-center, retrospective chart review study examining biopsy-proven AIH/NAFLD, AIH, and NAFLD patients. Characteristics, treatment, and 1- and 3-year outcomes (all-cause mortality, need for liver transplantation, or decompensated cirrhosis) were evaluated. RESULTS: A total of 72 patients (36.1% AIH/NAFLD, 34.7% AIH, and 29.2% NAFLD) were included. AIH/NAFLD patients were found to be more often Hispanic/Latino, female, and with lower liver aminotransaminases, immunoglobulin G, and anti-smooth muscle antibody positivity. AIH/NAFLD patients were less likely to receive standard of care treatment. No significant differences in outcomes were seen between AIH/NAFLD and either AIH or NAFLD. CONCLUSIONS: Our study demonstrated that AIH/NAFLD patients have unique characteristics and are less likely to receive standard of care treatment compared with patients with AIH alone. Despite this, no difference in outcomes (all-cause mortality, need for liver transplantation, or decompensated cirrhosis) was seen. Given NAFLD's rising prevalence, AIH/NAFLD cases will likely increase, and may benefit from alternative treatment guidelines to prevent worsening of NAFLD.

A nationwide analysis of salvage surgery for laryngeal cancer in the elderly.

BACKGROUND: We aim to describe outcomes of elderly patients undergoing salvage surgery for laryngeal cancer and to characterize the interplay of age with various other factors in this growing population. METHODS: Using the National Cancer Database, we identified cases of salvage laryngectomy in patients who failed chemoradiation. An age cutoff of 70 years was used to separate subjects into two groups. Various factors were compared. RESULTS: Of the 825 patients included, 166 (20.1%) were elderly. Elderly patients had worse overall survival (p = 0.001), higher 30-day and 90-day mortality (p = 0.006, p < 0.001), and a longer length of stay (LOS) (p = 0.015). LOS over 1 week was associated with worse survival (p = 0.032). CONCLUSION: Elderly patients had worse overall perioperative survival than their younger counterparts. LOS and 30-day readmissions were associated with higher risk of mortality in this group. We provide a contemporary set of relevant information for head and neck cancer providers to consider in this growing population.

Written Communication, Visitation Policies, and Awareness of Medical Issues Among Intensive Care Unit Families.

BACKGROUND: Open intensive care unit (ICU) visitation policies facilitate communication between clinicians and patients' families. Restrictive visitation policies (eg, during a pandemic) may reduce families' comprehension of information. OBJECTIVES: To determine whether written communication increased awareness of medical issues among ICU families and whether the effect size depended on the visitation policies in place when participants were enrolled. METHODS: Families of ICU patients were randomly assigned to receive usual care with or without daily written patient care updates from June 2019 to January 2021. Participants were asked whether patients had experienced 6 ICU problems at up to 2 time points during the ICU stay. Responses were compared with the study investigators' consensus. RESULTS: Of 219 participants, 131 (60%) were restricted from visiting. Participants in the written communication group were more likely than participants in the control group to correctly identify shock, renal failure, and weakness and were just as likely as participants in the control group to correctly identify respiratory failure, encephalopathy, and liver failure. Participants in the written communication group were more likely than participants in the control group to correctly identify the patient's ICU problems when all 6 were grouped as a composite outcome, with the adjusted odds ratio of correct identification tending to be higher among participants enrolled during restricted versus open visitation periods: 2.9 (95% CI, 1.9-4.2; P < .001) vs 1.8 (95% CI, 1.1-3.1; P = .02), P = .17 for difference. CONCLUSIONS: Written communication helps families correctly identify ICU issues. The benefit may be enhanced when families cannot visit the hospital. ClinicalTrials.gov Identifier: NCT03969810.

Disparities in Utilization of Same-Day Discharge Following Appendectomy in Children.

INTRODUCTION: Disparities in the delivery of pediatric surgical care exist for racial and ethnic minority groups. Utilization of same-day discharge (SDD) following appendectomy for acute, uncomplicated appendicitis is increasing; however, rates among diverse populations have not been explored to evaluate equitable care delivery and healthcare utilization. Our objective was to determine whether race and ethnicity are associated with rates of SDD and postdischarge healthcare utilization. We hypothesized that racial and ethnic minority groups would have lower rates of SDD. METHODS: This retrospective cohort study used data from the 2015-2019 American College of Surgeons National Surgical Quality Improvement Program-Pediatric clinical registry and included children who underwent appendectomy. Patients with complicated appendicitis were excluded. Primary exposure was racial or ethnic group. The primary outcome was SDD, and secondary outcomes included postdischarge emergency department visits and hospital readmissions. RESULTS: Of 37,579 simple appendicitis patients, SDD after appendectomy occurred in 10,012 (26.6%). On multivariable analysis, Black or African American race was associated with lower likelihood of SDD (adjusted odds ratio [aOR]: 0.85; 95% confidence interval [95% CI]:0.79-0.92; P < 0.0001). Hispanic ethnicity was associated with higher likelihood of SDD (aOR: 1.19; 95% CI: 1.12-1.25; P < 0.0001). Likelihood of postoperative emergency department visits was higher in Black or African American patients (aOR: 1.36; 95% CI: 1.14-1.62; P < 0.001) and Hispanic patients (aOR: 1.37; 95% CI: 1.12-1.58; P < 0.0001). Hospital readmission rates were similar across groups. CONCLUSIONS: Rates of SDD following appendectomy vary among racial and ethnic groups. Interventions to achieve equitable healthcare delivery including SDD after appendectomy are needed.

Understanding Opioid Prescribing Practices of Resident Physicians.

BACKGROUND: To compare opioid prescribing practices of resident physicians across a variety of surgical and nonsurgical specialties; to identify factors which influence prescribing practices; and to examine resident utilization of best practice supplemental resources. METHODS: An anonymous survey which assessed prescribing practices was completed by residents from one of several different subspecialties, including internal medicine, obstetrics and gynecology, general surgery, neurosurgery, orthopedic surgery, and urology. Fisher's exact test assessed differences in prescribing practices between specialties. RESULTS: Only 35% of residents reported receiving formal training in safe opioid prescribing. Overall, the most frequently reported influences on prescribing practices were the use of standardized order sets for specific procedures, attending preference, and patient's history of prescribed opioids. Resident physicians significantly underutilize best practice supplemental resources, such as counseling patients on pain expectations prior to prescribing opioid medication; contacting established pain specialists; screening patients for opioid abuse; referring to the Prescription Monitoring Program; and counseling patients on safe disposal of unused pills (P < .001). DISCUSSION: The incorporation of comprehensive prescribing education into resident training and the utilization of standardized order sets can promote safe opioid prescribing.

Daily Written Care Summaries for Families of Critically Ill Patients: A Randomized Controlled Trial.

OBJECTIVES: To determine the effect of daily written updates on the satisfaction and psychologic symptoms of families of ICU patients. DESIGN: Randomized controlled trial. SETTING: Single, urban academic medical center. SUBJECTS: Surrogates of nondecisional, critically ill adults with high risk of mortality ( n = 252) enrolled from June 2019 to January 2021. INTERVENTIONS: Usual communication with the medical team with or without written communication detailing the suspected cause and management approach of each ICU problem, updated each day. MEASUREMENTS AND MAIN RESULTS: Participants completed surveys at three time points during the ICU stay: enrollment ( n = 252), 1 week ( n = 229), and 2 weeks ( n = 109) after enrollment. Satisfaction with care was measured using the Critical Care Family Needs Inventory (CCFNI). The presence of anxiety, depression, and acute stress were assessed using the Hospital Anxiety and Depression Scale (HADS) and Impact of Events Scale Revised (IES-R). CCFNI, HADS, and IES-R scores were similar among participants assigned to the intervention group and control group upon enrollment and during the first week after enrollment ( p > 0.05). From enrollment to the second week after enrollment, there was an improvement in CCFNI and HADS scores among participants assigned to the intervention group versus the control group. At week 2, CCFNI scores were significantly lower among participants in the intervention group versus the control group, indicating greater satisfaction with care: 15.1 (95% CI, 14.2-16.0) versus 16.4, (95% CI, 15.5-17.3); p = 0.04. In addition, 2 weeks after enrollment, the odds of symptoms of anxiety, depression, and acute stress among participants assigned to the intervention versus control group were 0.16 (95% CI, 0.03-0.82; p = 0.03); 0.15 (95% CI, 0.01-1.87; p = 0.14); and 0.27 (95% CI, 0.06-1.27; p = 0.10), respectively. CONCLUSIONS: Written communication improved satisfaction and the emotional well-being of families of critically ill patients, supporting its use as a supplement to traditional communication approaches.

Healthy lifestyle and life expectancy with and without Alzheimer's dementia: population based cohort study.

OBJECTIVE: To determine the impact of lifestyle factors on life expectancy lived with and without Alzheimer's dementia. DESIGN: Prospective cohort study. SETTING: The Chicago Health and Aging Project, a population based cohort study in the United States. PARTICIPANTS: 2449 men and women aged 65 years and older. MAIN EXPOSURE: A healthy lifestyle score was developed based on five modifiable lifestyle factors: a diet for brain health (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay-MIND diet score in upper 40% of cohort distribution), late life cognitive activities (composite score in upper 40%), moderate or vigorous physical activity (≥150 min/week), no smoking, and light to moderate alcohol consumption (women 1-15 g/day; men 1-30 g/day). MAIN OUTCOME: Life expectancy with and without Alzheimer's dementia in women and men. RESULTS: Women aged 65 with four or five healthy factors had a life expectancy of 24.2 years (95% confidence interval 22.8 to 25.5) and lived 3.1 years longer than women aged 65 with zero or one healthy factor (life expectancy 21.1 years, 19.5 to 22.4). Of the total life expectancy at age 65, women with four or five healthy factors spent 10.8% (2.6 years, 2.0 to 3.3) of their remaining years with Alzheimer's dementia, whereas women with zero or one healthy factor spent 19.3% (4.1 years, 3.2 to 5.1) with the disease. Life expectancy for women aged 65 without Alzheimer's dementia and four or five healthy factors was 21.5 years (20.0 to 22.7), and for those with zero or one healthy factor it was 17.0 years (15.5 to 18.3). Men aged 65 with four or five healthy factors had a total life expectancy of 23.1 years (21.4 to 25.6), which is 5.7 years longer than men aged 65 with zero or one healthy factor (life expectancy 17.4 years, 15.8 to 20.1). Of the total life expectancy at age 65, men with four or five healthy factors spent 6.1% (1.4 years, 0.3 to 2.0) of their remaining years with Alzheimer's dementia, and those with zero or one healthy factor spent 12.0% (2.1 years, 0.2 to 3.0) with the disease. Life expectancy for men aged 65 without Alzheimer's dementia and four or five healthy factors was 21.7 years (19.7 to 24.9), and for those with zero or one healthy factor life expectancy was 15.3 years (13.4 to 19.1). CONCLUSION: A healthy lifestyle was associated with a longer life expectancy among men and women, and they lived a larger proportion of their remaining years without Alzheimer's dementia. The life expectancy estimates might help health professionals, policy makers, and stakeholders to plan future healthcare services, costs, and needs.

Imposter Syndrome in Surgical Trainees: Clance Imposter Phenomenon Scale Assessment in General Surgery Residents.

BACKGROUND: Imposter syndrome occurs when high-achieving individuals have a pervasive sense of self-doubt combined with fear of being exposed as a fraud, despite objective measures of success. This threatens mental health and well-being. The prevalence and severity of imposter syndrome has not been studied among general surgery residents on a large scale. The primary outcomes of this study were the prevalence and severity of imposter syndrome. STUDY DESIGN: The Clance Impostor Phenomenon Scale was administered to residents at 6 academic general surgery residency programs. Multivariable analysis was performed to identify significant differences among groups and predictive characteristics of imposter syndrome. RESULTS: One hundred and forty-four residents completed the assessment (response rate 46.6%; 47.2% were male). Only 22.9% had "none to mild" or "moderate" imposter syndrome. A majority (76%) had "significant" or "severe" imposter syndrome. There were no significant differences in mean scores among male and female residents (p = 0.69). White residents had a mean score of 71.3 and non-White residents had a mean score of 68.3 (p = 0.24). There was no significant difference between PGY1 to PGY5 or research residents (p = 0.72). There were no significant differences based on US Medical Licensing Examination or American Board of Surgery In-Service Training Examination scores (p = 0.18 and p = 0.37, respectively). CONCLUSIONS: Imposter syndrome is prevalent among general surgery residents, with 76% of residents reporting either significant or severe imposter syndrome. There were no predictive characteristics based on demographics or academic achievement, suggesting that there is something either inherent to those choosing general surgery training or the general surgery training culture that leads to such substantive levels of imposter syndrome.

A Dual-Platform Point-of-Care Test for Neurosyphilis Diagnosis.

BACKGROUND: The diagnosis of neurosyphilis relies on cerebrospinal fluid (CSF) abnormalities (pleocytosis, elevated protein) and CSF-Venereal Disease Research Laboratory (VDRL) test. In resource-limited settings, the CSF-VDRL test may not be widely available. METHODS: We optimized a commercial immunochromatographic strip test, the DPP Chembio syphilis assay, for performance with CSF and tested centrifuged CSF samples of 71 patients with syphilis (35 with neurosyphilis and 36 without neurosyphilis). A CSF dilution of 1:4 was chosen based on agreement with CSF pools with documented results from the CSF-VDRL test and fluorescent treponemal antibody absorption test on CSF. Using an electronic reader, we obtained unit values of treponemal and nontreponemal antibodies for all study samples and generated a receiver operating characteristic curve; using the Youden index, we established diagnostic cutoffs with optimal sensitivity and specificity. RESULTS: Diagnostic sensitivity of the nontreponemal test was 80% (95% confidence interval, 63%-92%) and specificity was 97% (95% confidence interval, 85%-100%) for neurosyphilis diagnosis using a reactive CSF-VDRL that improved after neurosyphilis therapy as a criterion standard. CONCLUSIONS: In this small study, the DPP Chembio test showed promising results for neurosyphilis diagnosis. Further studies are needed to assess its performance in resource-limited settings.

Voice-related quality of life: Relation to objective spirometry measures in subglottic stenosis.

OBJECTIVES: The current study seeks to identify the correlation between in-office spirometry data and voice-related quality of life in patients with subglottic stenosis (SGS). METHODS: Patients with SGS of any etiology were included when in-office spirometric data was available in addition to voice-related patient-reported outcomes (PROM) data in the form of the Voice Handicap Index-10 (VHI-10) and/or the Voice-Related Quality of Life (V-RQOL) survey. Overall survey scores and individual question responses were assessed for degree of correlation to spirometric data. RESULTS: Twenty-nine patients were included in the final analysis. Overall mean total VHI-10 scores totaled 7.15 (SD 9.11), while mean overall V-RQOL scores totaled 78.41 (SD 16.45). Both PEF and PIF rates correlated to total scores on the VHI and V-RQOL surveys. This correlation was stronger with PIF than with PEF, and with the V-RQOL than with the VHI. Questions related to breathlessness most closely correlated with spirometric data. CONCLUSION: Voice-related QOL is impacted in patients with SGS in a predictable way. Breathlessness while speaking may be more impactful than inability to produce speech in this population.

Neutrophil-to-Lymphocyte Ratio Is a Predictive Biomarker in Patients with Epidermal Growth Factor Receptor (EGFR) Mutated Advanced Non-Small Cell Lung Cancer (NSCLC) Treated with Tyrosine Kinase Inhibitor (TKI) Therapy.

BACKGROUND: First-line treatment for patients with non-small cell lung cancer (NSCLC) with a sensitizing epidermal growth factor receptor (EGFR) mutation is a tyrosine kinase inhibitor (TKI). Despite higher response rates and prolonged progression free survival (PFS) compared with platinum doublet chemotherapy, a subset of these patients do not receive prolonged benefit from these agents. We investigate if the neutrophil-to-lymphocyte ratio (NLR) and other markers of cachexia and chronic inflammation correlate with worse outcomes in these patients. METHODS: This study is a retrospective review of 137 patients with advanced EGFR-mutated NSCLC treated with TKIs at Rush University Medical Center and University of Chicago Medicine from August 2011 to July 2019, with outcomes followed through July 2020. The predictive value of NLR and body mass index (BMI) was assessed at the start of therapy, and after 6 and 12 weeks of treatment by univariable and multivariable analyses. RESULTS: On univariable analysis, NLR ≥ 5 or higher NLR on a continuous scale were both associated with significantly worse PFS and overall survival (OS) at treatment initiation, and after 6 or 12 weeks of treatment. On multivariable analysis, NLR ≥ 5 was associated with increased risk of death at 12 weeks of therapy (HR 3.002, 95% CI 1.282-7.029, p = 0.011), as was higher NLR on a continuous scale (HR 1.231, 95% CI 1.063-1.425, p = 0.0054). There was no difference in PFS and OS and amongst BMI categories though number of disease sites and Eastern Cooperative Oncology Group (ECOG) performance status was associated with worse PFS and OS. CONCLUSIONS: Patients with NLR ≥ 5 have a worse median PFS and median OS than patients with NLR < 5. NLR may have value as a predictive biomarker and may be useful for selecting patients for therapy intensification in the front-line setting either at diagnosis or after 12 weeks on therapy. NLR needs to be validated prospectively.

Surgical Residents' Perspective on Informed Consent-How Does It Compare With Attending Surgeons?

BACKGROUND: The informed consent discussion (ICD) is a compulsory element of clinical practice. Surgical residents are often tasked with obtaining informed consent, but formal instruction is not included in standard curricula. This study aims to examine attitudes of surgeons and residents concerning ICD. MATERIALS AND METHODS: A survey regarding ICD was administered to residents and attending surgeons at an academic medical center with an Accreditation Council for Graduate Medical Education-accredited general surgery residency. RESULTS: In total, 44 of 64 (68.75%) residents and 37 of 50 (72%) attending surgeons participated. Most residents felt comfortable consenting for elective (93%) and emergent (82%) cases, but attending surgeons were less comfortable with resident-led ICD (51% elective, 73% emergent). Resident comfort increased with postgraduate year (PGY) (PGY1 = 39%, PGY5 = 85%). A majority of participants (80% attending surgeons, 73% residents) believed resident ICD skills should be formally evaluated, and most residents in PGY1 (61%) requested formal instruction. High percentages of residents (86%) and attendings (100%) believed that ICD skills were best learned from direct observation of attending surgeons. CONCLUSIONS: Resident comfort with ICD increases as residents advance through training. Residents acknowledge the importance of their participation in this process, and in particular, junior residents believe formal instruction is important. Attending surgeons are not universally comfortable with resident-led ICDs, particularly for elective surgeries. Efforts for improving ICD education including direct observation between attending surgeons and residents and formal evaluation may benefit the residency curriculum.

CD32 is enriched on CD4dimCD8bright T cells.

CD4dimCD8bright T cells, a genuine population of CD8+ T cells, are highly activated and cytolytic. Recently, the low affinity IgG Fc fragment receptor CD32a was described as marker of HIV latency while others reported that CD32a is associated with T cell activation. Given that we have previously established that CD4dimCD8bright T cells are highly activated, mediate anti-HIV responses, and are infected by HIV, we assessed here CD32 expression on CD4dimCD8bright T cells in context of HIV. CD32 frequency on peripheral CD4dimCD8bright and CD4+ T cells was determined by flow cytometry among HIV negative and HIV positive patients. We report that among HIV- individuals, mean CD32 percent expression was 60% on CD4dimCD8bright T cells and 17% on CD4+ T cells (p<0.01). Among HIV+ patients, mean CD32 percent expression was 54% on CD4dimCD8bright T cells and 12% on CD4+ T cells (p<0.001). CD32 expression on CD4dimCD8bright T cells did not correlate with CD4 count and viral load and was not different by HIV serostatus. CD32 was also higher on other double positive T cell populations in both HIV negative and HIV positive donors in comparison to their single positive T cell counterpart. Together, these studies indicate that CD32 is enriched on double positive T cells regardless of HIV serostatus. The functional role of CD32 on these double positive T cells remains to be elucidated.

Negative regulation of IL-8 in human astrocytes depends on ß-catenin while positive regulation is mediated by TCFs/LEF/ATF2 interaction.

Expression of cytokines/chemokines is tightly regulated at the transcription level. This is crucial in the central nervous system to maintain neuroimmune homeostasis. IL-8 a chemoattractant, which recruits neutrophils, T cells, and basophils into the brain in response to inflammation and/or injury is secreted predominantly by neurons, microglia, and astrocytes. Here, we investigated the mechanism by which astrocytes regulate IL-8 expression. We demonstrate that while ß-catenin negatively regulated IL-8 transcription, its canonical transcriptional partners, members of the TCF/LEF transcription factors (TCF1, TCF3, TCF4 and LEF1) and Activating transcription factor 2 (ATF2) positively regulated IL-8 transcription. We further identified a putative TCF/LEF binding site at -175nt close to the minimal transcription region on the IL-8 promoter, mutation of which caused a significant reduction in IL-8 promoter activity. Chromatin immunoprecipitation demonstrated binding of TCF1, TCF4, LEF1 and ATF2 on the IL-8 promoter suggesting that TCFs/LEF partner with ATF2 to induce IL-8 transcription. These findings demonstrate a novel role for ß-catenin in suppression of IL-8 expression and for TCFs/LEF/ATF2 in inducing IL-8. These findings reveal a unique mechanism by which astrocytes tightly regulate IL-8 expression.

Patient Race and Insurance Status Do Not Impact the Treatment of Simple Mandibular Fractures.

INTRODUCTION: Health-care disparities have been reported throughout medical literature for decades. While blatant explicit bias is not prevalent, a substantial body of research has been published suggesting that systemic biases related to sex, race, income, and insurance status likely exist. To our knowledge, no study has assessed the impact of patient race and insurance status on clinical decision-making in facial fracture repair in the United States. Thus, the objective of this project was to assess if race and insurance status impacted whether patients obtained open or closed treatment of simple mandibular fractures. METHODS: Patients who had either open or closed treatment of mandibular fractures were extracted from the 2012 and 2013 National Inpatient Sample and analyzed. Patients who had a length of stay longer than 3 days or died during their inpatient stay were excluded. These exclusion criteria were used to control for patients with polytrauma as well as complicated fractures. Univariate analysis was undertaken to elucidate different variable associations with the type of reduction performed. All covariates were then entered into a multivariable logistic regression model to test the variables simultaneously. RESULTS: Patients with simple condylar, alveolar border, and closed mandibular fractures were more likely to undergo closed reduction (CR) on univariate analysis, as were patients with female gender and a fall mechanism (P value < .05). African Americans, Hispanics, and patients without insurance were more likely to undergo open reduction on univariate analysis (P value < .05). Multivariate analysis demonstrated that patients with simple condylar, subcondylar, alveolar border, or closed mandibular fractures were more likely to undergo a CR, as were patients with female gender and a firearm or fall mechanism (P < .05). However, neither race nor insurance status demonstrated a statistically significant association with closed or open reduction. CONCLUSION: Anatomic location and mechanism of injury were the variables found to be significantly associated with patients undergoing open reduction versus CR of simple mandibular fractures-not race or insurance status.

Prior smoking and nasoseptal flap usage adversely impact quality of life and healing after endoscopic pituitary surgery.

OBJECTIVE: Endoscopic pituitary surgery (EPS) via the endonasal transsphenoidal approach is well established as an effective treatment modality for sellar masses. The objective of this study was to determine the relationship between key patient and operative variables and rhinological outcomes as determined by the 22-item Sino-Nasal Outcome Test (SNOT-22) and endoscopic scores following EPS. METHODS: Prospectively collected SNOT-22 scores and objective endoscopic data were analyzed from a cohort of 109 patients who underwent EPS and had at least 90 days of postoperative follow-up. Trends in postoperative SNOT-22 scores were analyzed using linear mixed-effects models. Time to return to baseline endoscopic score was analyzed using Cox regression. RESULTS: After adjusting for age and sex, the authors found that prior smokers had higher total and rhinological subdomain SNOT-22 scores (p < 0.01, 95% CI 5.82-16.39; p = 0.01, 95% CI 1.38-5.09, respectively) following EPS. Nasoseptal flap use also showed higher total and rhinological subdomain SNOT-22 scores (p = 0.01, 95% CI 1.62-12.60; p = 0.02, 95% CI 0.42-4.30, respectively). Prior sinonasal surgery and concurrent septoplasty did not affect the change in SNOT-22 total scores over time (p = 0.08, 95% CI -0.40 to 0.02; p = 0.33, 95% CI -0.09 to 0.29). CONCLUSIONS: The findings suggest that the evolution of healing and patient-reported quality of life (QOL) measures are multifaceted with contributions from two key variables. Nasoseptal flap usage and prior smoking status may adversely impact postoperative QOL. No variables were found to be associated with objective postoperative endoscopic findings.

ß-Catenin and TCFs/LEF signaling discordantly regulate IL-6 expression in astrocytes.

BACKGROUND: The Wnt/ß-catenin signaling pathway is a prolific regulator of cell-to-cell communication and gene expression. Canonical Wnt/ß-catenin signaling involves partnering of ß-catenin with members of the TCF/LEF family of transcription factors (TCF1, TCF3, TCF4, LEF1) to regulate gene expression. IL-6 is a key cytokine involved in inflammation and is particularly a hallmark of inflammation in the brain. Astrocytes, specialized glial cells in the brain, secrete IL-6. How astrocytes regulate IL-6 expression is not entirely clear, although in other cells NFκB and C/EBP pathways play a role. We evaluated here the interface between ß-catenin, TCFs/LEF and C/EBP and NF-κB in relation to IL-6 gene regulation in astrocytes. METHODS: We performed molecular loss and/or gain of function studies of ß-catenin, TCF/LEF, NFκB, and C/EBP to assess IL-6 regulation in human astrocytes. Specifically, siRNA mediated target gene knockdown, cDNA over expression of target gene, and pharmacological agents for regulation of target proteins were used. IL-6 levels was evaluated by real time quantitative PCR and ELISA. We also cloned the IL-6 promoter under a firefly luciferase reporter and used bioinformatics, site directed mutagenesis, and chromatin immunoprecipitation to probe the interaction between ß-catenin/TCFs/LEFs and IL-6 promoter activity. RESULTS: ß-catenin binds to TCF/LEF to inhibits IL-6 while TCFs/LEF induce IL-6 transcription through interaction with ATF-2/SMADs. ß-catenin independent of TCFs/LEF positively regulates C/EBP and NF-κB, which in turn activate IL-6 expression. The IL-6 promoter has two putative regions for TCFs/LEF binding, a proximal site located at -91 nt and a distal site at -948 nt from the transcription start site, both required for TCF/LEF induction of IL-6 independent of ß-catenin. CONCLUSION: IL-6 regulation in human astrocytes engages a discordant interaction between ß-catenin and TCF/LEF. These findings are intriguing given that no role for ß-catenin nor TCFs/LEF to date is associated with IL-6 regulation and suggest that ß-catenin expression in astrocytes is a critical regulator of anti-inflammatory responses and its disruption can potentially mediate persistent neuroinflammation. Video Abstract.

Level of Evidence in Facial Plastic Surgery Research: A Procedure-Level Analysis.

BACKGROUND: As evidence-based medicine has taken hold across medical specialties, the level of evidence within the facial plastic surgery literature has risen, but remains weak in comparison. There has not yet been a systematic, critical appraisal of the relative strength of evidence among subsets of the practice of facial plastic surgery. METHODS: The current study is a systematic review, designed to evaluate the level of evidence observed in the facial plastic surgery literature. Five journals were queried using facial plastic surgery terms for four selected years over a 10-year period. Following screening, articles were assigned to a category regarding subject matter, assessed for the presence of various methodological traits, and evaluated for overall level of evidence. Comparisons were made in regard to level of evidence across the breadth of facial plastic surgery subject matter. RESULTS: A total of 826 articles were included for final review. Studies on operative facial rejuvenation and rhinoplasty had significantly fewer authors on average than studies on cancer reconstruction or craniofacial topics. Craniofacial studies demonstrated higher levels of evidence relative to all other categories, with the exception of facial paralysis and facial trauma studies, from which there was no significant difference. In general, reconstructive studies had significantly more authors and higher levels of evidence than did articles with an aesthetic focus. CONCLUSION: Level of evidence in facial plastic surgery remains relatively weak overall. Reconstructive and particularly craniofacial studies demonstrate higher mean level of evidence, relative to other subsets of facial plastic surgery. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.