VAULT: vault accuracy using deep learning technology: new image-based artificial intelligence model for predicting implantable collamer lens postoperative vault.

PURPOSE: To develop an accurate deep learning model to predict postoperative vault of phakic implantable collamer lenses (ICLs). SETTING: Parkhurst NuVision LASIK Eye Surgery, San Antonio, Texas. DESIGN: Retrospective machine learning study. METHODS: 437 eyes of 221 consecutive patients who underwent ICL implantation were included. A neural network was trained on preoperative very high-frequency digital ultrasound images, patient demographics, and postoperative vault. RESULTS: 3059 images from 437 eyes of 221 patients were used to train the algorithm on individual ICL sizes. The 13.7 mm size was excluded because of insufficient data. A mean absolute error of 66.3 µm, 103 µm, and 91.8 µm were achieved with 100%, 99.0%, and 96.6% of predictions within 500 µm for the 12.1 mm, 12.6 mm, and 13.2 mm sizes, respectively. CONCLUSIONS: This deep learning model achieved a high level of accuracy of predicting postoperative ICL vault with the overwhelming majority of predictions successfully within a clinically acceptable margin of vault.

Utility of CT in the workup of adults with sore throat in the emergency department.

OBJECTIVE: The goal of this study was to determine if computed tomography (CT) added any clinical information that was incorporated into the decision regarding treatment for patients who presented to the Emergency Department (ED) with sore throat. METHODS: A retrospective chart review of adult patients who presented to the ED with a chief complaint of sore throat who subsequently underwent CT during that ED visit between 1/1/18 and 12/31/18 at our tertiary academic health center was performed. The association between palatal bulge on Otolaryngology physical exam with successful drainage procedure was examined. The mean Hounsfield units (HU) and maximum dimension of measurable fluid collection on CT were compared between patients who underwent a successful drainage procedure and those who did not undergo a drainage procedure or attempted drainage was unsuccessful. RESULTS: Ninety-four patients met inclusion criteria, with 53% (50/94) men. Of the 22 patients with a palatal bulge on physical examination by Otolaryngology, 86% (19/22) underwent a successful drainage procedure (p < 0.001) when compared to those not undergoing successful drainage. Notably, 56% (53/94) of CT scans were interpreted as normal or tonsillitis. The mean HU was 42.0 in those patients who underwent a successful drainage procedure and 74.1 in those who did not undergo a drainage procedure (p < 0.001). Overall, 21/35 fluid collections had a palatal bulge (p < 0.001). CONCLUSION: Palatal bulge is a reliable finding in identifying patients with a drainable peritonsillar abscess, and CT scans could largely be avoided in patients without physical exam findings suggestive of more extensive deep neck space abscesses. If a CT scan is obtained, HU should be measured and incorporated into the shared decision-making process with the patient.

Effect of Excisional Goniotomy with the Kahook Dual Blade (KDB) on Surgically Induced Astigmatism.

PURPOSE: To determine the effect of Kahook Dual Blade goniotomy with phacoemulsification (Phaco-KDB) compared to phacoemulsification alone (Phaco) on surgically induced astigmatism (SIA). DESIGN: Prospective study. PARTICIPANTS: Forty eyes of 28 patients treated with Phaco-KDB and 20 eyes of 13 patients treated with Phaco between 12/27/16 and 7/23/19 with a minimum 1 month follow-up were prospectively enrolled. METHODS: Corneal astigmatism was assessed pre- and post-operatively using the simulated K (simK) values from the Pentacam Holladay report. MAIN OUTCOME MEASURES: SIA was compared between Phaco-KDB and Phaco groups using mean magnitude SIA, rate of ≥0.50 D SIA, and SIA centroids. RESULTS: The difference in mean magnitude SIA was not statistically significant between Phaco-KDB and Phaco (mean = 0.28 D and 0.25 D, respectively, P = 0.621). The difference in the rate of ≥0.50 D SIA was not statistically significant between Phaco-KDB and Phaco (11.6% and 10.0%, respectively, P = 1.00). The SIA centroid for Phaco-KDB was 0.05 D @ 51° ± 0.40 D and 0.07 D @ 3° ± 0.32 D for Phaco. CONCLUSION: Neither the mean magnitude SIA nor the rate of astigmatic change ≥0.50 D was significantly different between Phaco-KDB and Phaco groups. SIA centroids between groups showed comparable and negligible effect on corneal astigmatism. KDB combined with phacoemulsification may not significantly affect SIA compared to phacoemulsification alone based on postoperative topography and is likely an astigmatically neutral procedure.

Chemerin Reactivates PTEN and Suppresses PD-L1 in Tumor Cells via Modulation of a Novel CMKLR1-mediated Signaling Cascade.

PURPOSE: Chemerin (retinoic acid receptor responder 2, RARRES2) is an endogenous leukocyte chemoattractant that recruits innate immune cells through its receptor, ChemR23. RARRES2 is widely expressed in nonhematopoietic tissues and often downregulated across multiple tumor types compared with normal tissue. Recent studies show that augmenting chemerin in the tumor microenvironment significantly suppresses tumor growth, in part, by immune effector cells recruitment. However, as tumor cells express functional chemokine/chemoattractant receptors that impact their phenotype, we hypothesized that chemerin may have additional, tumor-intrinsic effects. EXPERIMENTAL DESIGN: We investigated the effect of exogenous chemerin on human prostate and sarcoma tumor lines. Key signaling pathway components were elucidated using qPCR, Western blotting, siRNA knockdown, and specific inhibitors. Functional consequences of chemerin treatment were evaluated using in vitro and in vivo studies. RESULTS: We show for the first time that human tumors exposed to exogenous chemerin significantly upregulate PTEN expression/activity, and concomitantly suppress programmed death ligand-1 (PD-L1) expression. CMKLR1 knockdown abrogated chemerin-induced PTEN and PD-L1 modulation, exposing a novel CMKLR1/PTEN/PD-L1 signaling cascade. Targeted inhibitors suggested signaling was occurring through the PI3K/AKT/mTOR pathway. Chemerin treatment significantly reduced tumor migration, while significantly increasing T-cell-mediated cytotoxicity. Chemerin treatment was as effective as both PD-L1 knockdown and the anti-PD-L1 antibody, atezolizumab, in augmenting T-cell-mediated tumor lysis. Forced expression of chemerin in human DU145 tumors significantly suppressed in vivo tumor growth, and significantly increased PTEN and decreased PD-L1 expression. CONCLUSIONS: Collectively, our data show a novel link between chemerin, PTEN, and PD-L1 in human tumor lines, which may have a role in improving T-cell-mediated immunotherapies.

Chemerin Suppresses Breast Cancer Growth by Recruiting Immune Effector Cells Into the Tumor Microenvironment.

Infiltration of immune cells into the tumor microenvironment (TME) can regulate growth and survival of neoplastic cells, impacting tumorigenesis and tumor progression. Correlations between the number of effector immune cells present in a tumor and clinical outcomes in many human tumors, including breast, have been widely described. Current immunotherapies utilizing checkpoint inhibitors or co-stimulatory molecule agonists aim to activate effector immune cells. However, tumors often lack adequate effector cell numbers within the TME, resulting in suboptimal responses to these agents. Chemerin (RARRES2) is a leukocyte chemoattractant widely expressed in many tissues and is known to recruit innate leukocytes. CMKLR1 is a chemotactic cellular receptor for chemerin and is expressed on subsets of dendritic cells, NK cells, and macrophages. We have previously shown that chemerin acts as a tumor suppressive cytokine in mouse melanoma models by recruiting innate immune defenses into the TME. Chemerin/RARRES2 is down-regulated in many tumors, including breast, compared to normal tissue counterparts. Here, using a syngeneic orthotopic EMT6 breast carcinoma model, we show that forced overexpression of chemerin by tumor cells results in significant recruitment of NK cells and T cells within the TME. While chemerin secretion by EMT6 cells did not alter their phenotypic behavior in vitro, it did significantly suppress tumor growth in vivo. To define the cellular effectors required for this anti-tumor phenotype, we depleted NK cells or CD8+ T cells and found that either cell type is required for chemerin-dependent suppression of EMT6 tumor growth. Finally, we show significantly reduced levels of RARRES2 mRNA in human breast cancer samples compared to matched normal tissues. Thus, for the first time we have shown that increasing chemerin expression within the breast carcinoma TME can suppress growth by recruitment of NK and T cells, thereby supporting this approach as a promising immunotherapeutic strategy.

Trends in Adult Alcohol Use and Binge Drinking in the Early 21st-Century United States: A Meta-Analysis of 6 National Survey Series.

BACKGROUND: Recent trends in alcoholic liver disease, alcohol-related emergency room admissions, and alcohol use disorder prevalence as measured by general-population surveys have raised concerns about rising alcohol-related morbidity and mortality in the United States. In contrast, upward trends in per capita alcohol consumption have been comparatively modest. METHODS: To resolve these discordant observations, we sought to examine trends in the prevalence of alcohol use and binge drinking from 6 regularly or periodically administered national surveys using a meta-analytic approach. Annual or periodic prevalence estimates for past-12-month or past-30-day alcohol use and binge drinking were estimated for available time points between the years 2000 and 2016. Estimates were combined in a random-effects regression model in which prevalence was modeled as a log-linear function of time to obtain meta-analytic trend estimates for the full population and by sex, race, age, and educational attainment. RESULTS: Meta-analysis-derived estimates of average annual percentage increase in the prevalence of alcohol use and binge drinking were 0.30% per year (95% CI: 0.22%, 0.38%) and 0.72% per year (95% CI: 0.46%, 0.98%), respectively. There was substantial between-survey heterogeneity among trend estimates, although there was notable consistency in the degree to which trends have impacted various demographic groups. For example, most surveys found that the changes in prevalence for alcohol use and binge drinking were large and positive for ages 50 to 64 and 65 and up, and smaller, negative, or nonsignificant for ages 18 to 29. CONCLUSIONS: Significant increases in the prevalence of alcohol use and of binge drinking over the past 10 to 15 years were observed, but not for all demographic groups. However, the increase in binge drinking among middle-aged and older adults is substantial and may be driving increasing rates of alcohol-related morbidity and mortality.

Endonasal Access to the Upper Cervical Spine: Part 2-Cadaveric Analysis.

Objectives The study aims to determine factors that augment endonasal exposure of the cervical spine. Setting We used fluoroscopy and endoscopy to study endonasal visualization of the upper cervical spine. Participants Ten cadavers with normal anatomy were studied. Main Outcome Measures Endoscopic visualization was simulated with projected lines from an endoscope to the cervical spine in multiple positions. Results Neck position alone did not affect the extent of endonasal exposure of the upper cervical spine, although there was a trend correlating the extended neck position with more caudal exposure. The greatest impact was with concurrent use of a 30-degree endoscope and neck extension, and more caudal access was achieved by tilting the endoscope against the piriform aperture, using the posterior tip of the hard palate as the fulcrum. Conclusions Concurrent use of a 30-degree endoscope and neck extension increased the degree of exposure down the cervical spine. Maximum endonasal exposure of the upper cervical spine was obtained by maneuvering instruments at the fulcrum of the posterior hard palate and the nares, rather than changing the position of the neck alone. These results complement radiographic morphometric data in Part 1 of this study for preoperative assessment and surgical planning.