Optical manipulation of the charge-density-wave state in RbV3Sb5.

Broken time-reversal symmetry in the absence of spin order indicates the presence of unusual phases such as orbital magnetism and loop currents1-4. The recently discovered kagome superconductors AV3Sb5 (where A is K, Rb or Cs)5,6 display an exotic charge-density-wave (CDW) state and have emerged as a strong candidate for materials hosting a loop current phase. The idea that the CDW breaks time-reversal symmetry7-14 is, however, being intensely debated due to conflicting experimental data15-17. Here we use laser-coupled scanning tunnelling microscopy to study RbV3Sb5. By applying linearly polarized light along high-symmetry directions, we show that the relative intensities of the CDW peaks can be reversibly switched, implying a substantial electro-striction response, indicative of strong nonlinear electron-phonon coupling. A similar CDW intensity switching is observed with perpendicular magnetic fields, which implies an unusual piezo-magnetic response that, in turn, requires time-reversal symmetry breaking. We show that the simplest CDW that satisfies these constraints is an out-of-phase combination of bond charge order and loop currents that we dub a congruent CDW flux phase. Our laser scanning tunnelling microscopy data open the door to the possibility of dynamic optical control of complex quantum phenomenon in correlated materials.

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.

Platelet-Rich Plasma, Bone Marrow Aspirate Concentrate, and Hyaluronic Acid Injections Outperform Corticosteroids in Pain and Function Scores at a Minimum of 6 Months as Intra-Articular Injections for Knee Osteoarthritis: A Systematic Review and Network Meta-analysis.

PURPOSE: To compare the efficacy of common intra-articular injections used in the treatment of knee osteoarthritis, including corticosteroid (CS), hyaluronic acid (HA), platelet-rich plasma (PRP), and bone marrow aspirate concentrate (BMAC), with a minimum follow-up of 6-months. METHODS: A literature search was conducted using the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in August 2022 in the following databases: PubMed/MEDLINE, Scopus, Cochrane Database of Controlled Trials, and the Cochrane Database of Systematic Reviews. Level I to II randomized clinical trials with a minimum follow-up of 6 months that investigated the treatments of interest were included. Patient-reported outcome scores for pain and function at baseline and at latest follow-up were extracted, and the change in scores was converted to uniform 0 to 100 scales. Arm-based Bayesian network meta-analysis using a random-effects model was created to compare the treatment arms in pain and function. RESULTS: Forty-eight studies comprising a total of 9,338 knees were included. The most studied intra-articular injection was HA (40.9%), followed by placebo (26.2%), PRP (21.5%), CS (8.8%), and then BMAC (2.5%). HA and PRP both led to a significant improvement in pain compared with placebo. HA, PRP, and BMAC all led to a significant improvement in function scores when compared with placebo. Surface under the cumulative ranking curves (SUCRAs) of the interventions revealed that PRP, BMAC, and HA were the treatments with the highest likelihood of improvement in both pain and function, with overall SUCRA scores of 91.54, 76.46, and 53.12, respectively. The overall SUCRA scores for CS and placebo were 15.18 and 13.70, respectively. CONCLUSIONS: At a minimum 6-month follow-up, PRP demonstrated significantly improved pain and function for patients with knee osteoarthritis compared with placebo. Additionally, PRP exhibited the highest SUCRA values for these outcomes when compared with BMAC, HA, and CS. LEVEL OF EVIDENCE: Level II, meta-analysis of Level I to II studies.

A DIEP Dive into Patient Risk Factors for Hernia and Bulge Development: A Meta-regression.

BACKGROUND: This meta-regression aims to investigate risk factors for abdominal hernia and bulge in patients undergoing deep inferior epigastric perforator (DIEP) flaps and the effect of prophylactic mesh placement on postoperative complications. METHODS: A systematic search was conducted in July of 2022 in alignment with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Seventy-four studies published between 2000 and 2022 met the inclusion criteria. Sixty-four studies were included in the analysis for bulge and 71 studies were included in the analysis for hernia. Meta-regressions were run on the proportion of patients experiencing hernia or bulge to assess for patient risk factors and the role of prophylactic mesh placement. Proportions were transformed using the Freeman-Tukey double arcsine method. RESULTS: The average rates of hernia and bulge after DIEP flaps were found to be 0.18% and 1.26%, respectively. Increased age (ß = 0.0059, p = 0.0117), prior abdominal surgery (ß = 0.0008, p = 0.046), and pregnancy history (ß = -0.0015, p = 0.0001) were significantly associated with hernia. Active smoking (ß = 0.0032, p = 0.0262) and pregnancy history (ß = 0.0019, p < 0.0001) were significantly associated with bulge. Neither the perforator vessel laterality nor the number of perforator vessels harvested had any association with hernia or bulge. Prophylactic mesh placement was not associated with hernia or bulge. CONCLUSION: Understanding the comorbidities associated with hernia or bulge following DIEP flap breast reconstruction, such as advanced age, prior abdominal surgery, pregnancy history, and active smoking status, allows surgeons to proactively identify and educate high-risk patients. Future studies may further explore whether prophylactic mesh placement offers patients any benefit.

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.

Defining diverticular fistula through inpatient admissions: a population study.

BACKGROUND: Diverticular fistula, a pathologic connection from the colon to the skin or another organ, is an uncommon sequela of diverticular disease. It is generally considered an indication for surgery. The current literature is limited in terms of defining the epidemiology of this disease process. This analysis defines the demographics of fistulous diverticular disease on a national level. METHODS: A retrospective review of the 2018 National Inpatient Sample (NIS) was conducted, using ICD-10 codes for diverticular disease, diverticular-associated fistulas, and associated surgeries. Demographic factors were compared between groups, and several sub-group analyses were performed. RESULTS: A total of 7,105,498 discharges were recorded: 119,115 (1.68%) with non-fistulizing diverticular disease and 3,843 (0.05%) with diverticular fistula. Patients with diverticular fistula were more likely to be younger (64.7 v 68.2 years, p < .0001) and female (57.3% v 55.4%, p = 0.028) than patients with non-fistulizing disease. They were also more likely to undergo surgery (64.9% v 25.7%, p < .0001), to be admitted electively (44.7% v 12.0%, p < .0001), and to have a longer length of stay (LOS) (mean 8.07 v 5.20 days, p < .0001). Diverticular fistula patients that underwent surgery were more likely to be male (44.8% v 39.0%, p = 0.003), to be admitted electively (65.3% v 6.7%, p < .0001), and to have longer LOS (mean 8.74 v 6.81 days, p < .0001) than those who received medical treatment alone. CONCLUSION: Diverticular fistula is a rare diagnosis, accounting for 0.05% of total admissions and 3.12% of admissions for diverticular disease. However, this is more common than the previously reported rate of < 0.1% of diverticular disease admissions. While surgery is generally indicated for diverticular fistula, only 64.9% of patients underwent surgical treatment. Although this study is limited by its retrospective nature and use of administrative data, our findings elucidate the prevalence and patterns of inpatient admissions for diverticular fistula in the United States.

A new index, Respiratory Insufficiency index and Modified Early Warning Scores predict extubation failure.

Background: Extubation failure occurs in 5%-20% of patients and is associated with poor clinical outcomes. The primary aim of this project was to determine the predictive ability of the Respiratory Insufficiency (RI) index, Respiratory Oxygenation (ROX) index and Modified Early Warning Score (MEWS) in identifying extubation failure. Methods: This was a secondary analysis of a prior cross-sectional retrospective study conducted from February 2018 through December 2018 among adult subjects who received mechanical ventilation for more than 24 h. Extubation failure was defined as the need for reintubation or rescue non-invasive ventilation (NIV) within 48 h after planned extubation. Univariate analysis and logistic regression were used to identify the predictors and final model was validated using 10-fold cross validation. Nomogram was constructed based on the final model. Results: Of 216 enrolled subjects, 46 (21.3%) experienced extubation failure. The median RI index 1-h post extubation was 20 [interquartile range [IQR] 16.33-24.24] for success group and 27.02 [IQR 22.42-33.83] for the failure group (P<0.001). The median ROX index 1-h post extubation was 16.66 [IQR 12.57-19.84] for success group and 11.11 [IQR 8.09-14.67] for failure group (P<0.001). The median MEWS 1-h post extubation was 2 [IQR 1-3] for the success group and 4 [IQR 3-5] for the failure group (P<0.001). In multivariable analysis, age >60 years [OR 3.89 (95% CI 1.56-9.73); P=0.004], MEWS >4 [OR 4.01 (95% CI (1.59-10.14); P=0.003] and, RI index >20 [OR 4.50 (95% CI 1.43-14.21); P=0.010] were independently associated with extubation failure. Conclusion: In the present study, RI index and MEWS were independently associated with predicting extubation failure within 1 h of extubation. A prospective validation study is warranted to establish the role of these indices in predicting extubation outcome.

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.

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.

Interobserver reliability of methods to determine complete resection of adenomas in colonoscopy.

BACKGROUND: Forceps margin biopsy and polypectomy specimen margins have both been used to assess for polypectomy resection adequacy. The interobserver reliability of the two methods has not been well described. METHODS: The interpretability of polypectomy specimens for presence of residual neoplasia at the margin was assessed by two blinded pathologists. Next, the concordance of forceps margin biopsy interpretations between three blinded pathologists was evaluated by calculation of interobserver κ. RESULTS: Rates of polypectomy specimen margin interpretability were low: 24/92 (26 %) for pathologist A, 28/92 (30.4 %) for pathologist B. Concordance of forceps margin biopsy interpretations (n = 129) between pathologists was high. Two internal pathologists showed substantial agreement in margin biopsy interpretations (κ 0.779; 95 %CL 0.543, 0.912). The concordance remained strong after biopsies were reviewed by a third, external pathologist (κ 0.829; 95 %CL 0.658, 0.924). There was complete agreement on 123/129 (95.3 %) between all three pathologists for presence of neoplasia. CONCLUSION: The majority of polypectomy specimen margins were uninterpretable by pathologists for presence of residual neoplasia. Forceps margin biopsy shows strong interobserver reliability in adenomatous lesions.

Impact of Inequities on Delay in Breast Cancer Management in Women Undergoing Second Opinions.

BACKGROUND: Inequities in breast cancer treatment lead to delay in therapy, decreased survival and lower quality of life. This study aimed to examine demographics and clinical factors impacting time to treatment for second-opinion breast cancer patients. MATERIALS AND METHODS: We performed a retrospective chart review to analyze patients presenting to one academic institution for second opinion of breast imaging, diagnosis, or breast-related treatment. Data from women with stage I-III breast cancer who received treatment at this institution were evaluated to determine the impact of patient demographics and clinical characteristics on time to first treatment. RESULTS: Of the 1006 charts reviewed, 307 met inclusion criteria. Low-income patients averaged 58 days from diagnosis to surgery compared to 35 days for high-income patients (incidence rate ratio [IRR] 0.64, P<0.01). Black patients averaged 56 days from diagnosis to surgery compared to 42 days for White patients (IRR 1.37, P<0.01). Latina patients averaged 38 days from initial encounter to neoadjuvant chemotherapy compared to 20 days for White patients (IRR 1.69, P<0.05). CONCLUSION: Patients with low-income, of Black race and Latina ethnicity experienced increased time to treatment. Additionally, time to mastectomy with and without reconstruction was longer than time to partial mastectomy. Further exploration is needed to determine why certain factors lead to treatment delay and how inequities can be eliminated.

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.

Outcomes of Laparoscopic Versus Open Resection of Meckel's Diverticulum.

BACKGROUND: Meckel's Diverticulum (MD) is a common congenital anomaly accounting for half of pediatric gastrointestinal bleeds. No large-scale studies exist comparing open and laparoscopic surgery and conversion rates remain high. We sought to compare postoperative outcomes associated with each approach and to determine risk factors for conversion. MATERIALS AND METHODS: NSQIP-Pediatric was used to identify patients who underwent a MD resection from 2012 to 2018. Outcomes between patients treated with a laparoscopic versus open versus laparoscopic converted to open (LCO) surgery were compared. Chi-square tests and adjusted logistic regression analysis were used to determine significance and factors associated with conversion. RESULTS: Six hundred eighty-one patients were identified, 295 (43.3%) underwent open, 267 (39.2%) laparoscopic, and 119 (17.5%) LCO resection. Patients undergoing laparoscopic compared to open procedures had shorter length of stay (LOS; 3 versus 4, P= 0.009), and similar morbidities (10.5% versus 16.6%, P= 0.164) and operative times (71.6 versus 76.6 mins, P= 0.449) on adjusted analysis. Patients with LCO compared to open procedures had similar LOS (4 versus 4, P= 0.334) and morbidities (14.3% versus 16.6%, P= 0.358), but longer operative times (90.1 versus 76.6 mins, P= 0.002) on adjusted analysis. Patients with laparoscopic and LCO procedures had fewer unplanned intubations compared to open procedures (0.0% versus 0.0% versus 2.4%, P= 0.011) and lower mortality (0.0% versus 0.0% versus 1.7%, P= 0.046) on univariate analysis. CONCLUSIONS: Laparoscopic MD resection has shorter LOS and similar complications and operative time compared to an open approach while LCO resection increases operative time but not LOS or morbidities.

Efficacy of Arthroscopic Surgery in the Management of Adhesive Capsulitis: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.

PURPOSE: To determine which interventions optimize clinical outcomes in adhesive capsulitis by performing a network meta-analysis of randomized controlled trials. METHODS: A systematic review was conducted of all clinical trials on adhesive capsulitis published since 2008. Patient cohorts were grouped into treatment categories; data collected included range of motion (ROM) and patient-reported outcome measures (PROMs). Interventions were compared across groups by means of arm-based Bayesian network meta-analysis in a random-effects model. RESULTS: Sixty-six studies comprising 4042 shoulders (57.6% female patients, age 54.8 ± 3.2 years [mean ± standard deviation]) were included. The most commonly studied interventions were physical therapy (PT) or shoulder injections. Network meta-analysis demonstrated that arthroscopic surgical capsular release was the most effective treatment in increasing ROM. This effect was apparent in forward flexion (effect difference [ED] versus placebo, 44°, 95% confidence interval [CI] 31° to 58°), abduction (ED 58°, 45° to 71°), internal rotation (ED 34°, 24° to 44°), and external rotation (ED 59°, 37° to 80°). Interventions most effective for pain relief included PT supplemented with either medical therapy (ED -4.50, -9.80 to 2.80) or ultrasound therapy (ED -5.10, -5.10 to -1.40). Interventions most effective for improvement of functional status included PT, manipulation under anesthesia (MUA), intra-articular or subacromial steroid injection, surgical capsular release, and supplementation of PT with alternative therapy. CONCLUSIONS: No one treatment emerged superior in regard to ROM, pain symptoms, and functional status. Surgery (after failure of conservative treatment) ranked highest across all ROM domains. Treatments that ranked highest for treatment of pain included PT supplemented with either medical therapy or ultrasound. Finally, treatments that ranked highest for improvements in functional status included MUA, PT with medical therapy, surgical intervention, PT with ultrasound, PT with injection, and injection alone. LEVEL OF EVIDENCE: II, systematic review and network meta-analysis of level I and II studies.

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.

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.

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.

Early feeding in colorectal surgery patients: safe and cost effective.

PURPOSE: Enhanced recovery after surgery (ERAS) pathways has demonstrated improved outcomes in colorectal surgery. An important component of ERAS is early oral intake. The aim of this study is to determine the impact of early oral intake in patients following colorectal surgery. METHODS: A retrospective analysis of patients who underwent colectomy and proctectomy at an academic institution from January 2015 to November 2018 was performed. Postoperative outcomes were compared between patients who had postoperative day 0 (POD 0) oral intake and those who did not. RESULTS: A total of 436 ERAS patients had oral intake timing documented. The majority of patients were women (241, 55.3%) and white (313, 71.8%). The mean age was 57 ± 15.09. Patients who had early intake were found to have lower 30-day overall morbidity and length of stay (p < 0.05), and no difference in serious adverse events. Additionally, hospital costs were lower in the POD 0 feeding group for all patients (p < 0.05). CONCLUSION: We have demonstrated that early oral feeding in an established ERAS pathway is associated with improved clinical outcomes as well as decreased total hospital costs. Early postoperative feeding is safe in colorectal patients and should be prioritized to decrease complications and healthcare costs.

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.

The anesthesia airway evaluation: Correlation with sleep endoscopy findings.

PURPOSE: Drug-induced sleep endoscopy (DISE) is a cost-effective, safe, and reliable tool to evaluate obstructive sleep apnea (OSA) patients by revealing upper airway sites, patterns, and severity of obstruction. DISE provides valuable data because reliable evaluation of the OSA airway while awake has remained elusive. Few studies (with mixed results) have analyzed the correlation between pre-operation, awake airway assessments routinely performed by anesthesia and DISE results. METHODS: Preoperative anesthesia evaluation records and subsequent DISE reports were obtained for 99 adult patients undergoing DISE between 2016 and 2018. All patients carried the diagnosis of OSA, based on polysomnography. Anesthesia-collected variables were compared with DISE findings in an effort to determine if commonly-utilized physical exam findings correlated to patterns of upper airway collapse observed on sleep endoscopy. RESULTS: Most anesthesia preoperative evaluation variables were not found to be predictive of any identifiable patterns of collapse on DISE, including Mallampati score, ability to prognath, and overall airway assessment score. Obesity did not correlate with circumferential collapse at the velopharynx, or to multi-level collapse. Thyromental distance <6.5 cm was found to be statistically correlated to total epiglottic collapse (E = 2+). Friedman tongue position scores were found to be correlated to velopharyngeal collapse (p < 0.05). CONCLUSIONS: Anesthesia airway assessment algorithms and physical exam findings do not correlate well with findings on sleep endoscopy. DISE remains the gold standard for evaluating levels of collapse and operative planning in the OSA population.