Perylene-Mediated Cytoskeletal Dysfunction Remodels Cancer-Associated Fibroblasts to Augment Antitumor Immunotherapy.

Targeted reprogramming of cancer-associated fibroblasts (CAFs) is one of the most essential cancer therapies. However, how to reprogram active CAFs toward deactivated state still remains immense challenge. To tackle this challenge, herein, one perylene N, N'-bis(2-((dimethylammonium)ethylene)-2-(methoxylethyl))-1, 6, 7, 12-tetrachloroperylene-3, 4, 9, 10-tetracarboxylic diimide (PDIC-OC) is prepared, which can trigger endogenous reactive oxygen species (ROS) burst to result in cytoskeletal dysfunction and cell apoptosis so that suppress transforming growth factor ß (TGF-ß) production. As a result, PDIC-OC can reprogram the activated CAFs and relieve immunosuppressive tumor microenvironment by efficient polarization of M2-typed macrophages into M1-typed ones, downregulation of alpha-smooth muscle actin (α-SMA), alleviation of hypoxic state to promote infiltration of cytotoxic T lymphocytes, and ultimately realizes outstanding antitumor performance on B16F10 tumor-xenografted and lung-metastatic mouse model even at low concentration of 1 mg kg-1 body weight. This work thus presents a novel strategy that cytoskeleton dysfunction and cell apoptosis cooperatively suppress the secretion of TGF-ß to reprogram CAFs and meanwhile clarifies intrinsic mechanism for perylene-triggered chemo-immunotherapy against hypoxic tumors.

Impact of Fellowship Training on Practice Patterns of Glaucoma Surgeons Treating Medicare fee-for-service Beneficiaries.

PURPOSE: Analyze practice patterns of glaucoma surgeons with and without fellowship training. MATERIALS AND METHODS: Physician-specific 2017 Medicare data were obtained from the Centers for Medicare & Medicaid Services website. Current Procedural Terminology codes identified procedures including iStent, tube shunts, trabeculectomy, complicated trabeculectomy, endoscopic cyclophotocoagulation, internal Xen Implant, external Xen or Express shunt, Gonioscopy-Assisted Transluminal Trabeculotomy, and Kahook Dual Blade Goniotomy. Physicians with fellowship training were identified via the American Glaucoma Society website. RESULTS: A total of 1547 glaucoma surgeons were identified, of which 319 had completed fellowship training. Overall, fellowship-trained glaucoma surgeons performed more services (50.4 ± 47.0 vs 40.5 ± 35.3, P < .001) with a larger variety of procedures (1.8 ± 1.0 vs 1.3 ± 0.6, P < .001) than those without fellowship training. Surgeons without fellowship training were more likely to perform iStent and endoscopic cyclophotocoagulation and less likely to perform the remaining procedures than their fellowship-trained counterparts. Medicare payments did not differ between groups and the number of Medicare beneficiaries only differed for internal Xen implant (P = .03). Patient comorbidity burden was similar between groups with about one-third of patients being diagnosed with ischemic heart disease. CONCLUSIONS: Surgeons without fellowship training can treat a similar volume of glaucoma patients as those with fellowship training. However, based on surgical procedures employed, their practices are skewed towards mild and moderate glaucoma and they are more limited in their breadth of procedures. In addition, ischemic heart disease was prevalent in the glaucoma patient population.

Factors Associated with 5-year Glaucomatous Progression in Glaucoma Suspect Eyes: A Retrospective Longitudinal Study.

Purpose: Using demographic, clinical, visual field, and optical coherence tomography (OCT) variables to study the association of 5-year glaucomatous progression in glaucoma suspect eyes. Patients and methods: This is a retrospective longitudinal clinical study. Inclusion criteria consisted of glaucoma suspect eyes (i.e., concerning cup-to-disk ratio and/or intraocular pressure (IOP) >21 mm Hg), age ≥ 30 years old, follow-up time of 5 years, best-corrected visual acuity (BCVA) of 20/100 or better, spherical equivalent (SE) higher than 8 diopters and an astigmatism less than 3 diopters. Eyes with glaucoma-determined by two consecutive, reliable visual field tests-were excluded, as well as any eyes with any clinically significant retinal or neurological disease. The percentage of glaucoma suspect eyes, which progressed to glaucoma within a 5-year period, was calculated. Study subjects were divided into the following groups: eyes that progressed to glaucoma and those that did not. Results: In the 288 patients which we looked at, 365 total eyes, 323 eyes had concerning cup-to-disk ratio and 42 had ocular hypertension. Bivariate analysis showed that the eyes which progressed to glaucoma had significantly worse mean deviation, increased pattern standard deviation (PSD), and less visual field index (VFI). Our bivariate analysis also showed a thinner average, superior and inferior retinal nerve fiber layer thickness (RNFL), and more severe average, superior, and inferior RNFL damages (i.e., color grading scale) at baseline. Logistic regression analysis showed that only PSD and severe inferior RNFL damage (i.e., red color) to be significantly associated with 5-year glaucomatous progression. Conclusion: Segmental RNFL damage and pattern standard deviation are associated with 5-year glaucomatous progression in glaucoma suspect eyes. How to cite this article: Nassiri N, Das S, Patel V, et al. Factors Associated with 5-year Glaucomatous Progression in Glaucoma Suspect Eyes: A Retrospective Longitudinal Study. J Curr Glaucoma Pract 2022;16(1):11-16.

Anterior segment ultrasound biomicroscopy image analysis using ImageJ software: Intra-observer repeatability and inter-observer agreement.

PURPOSE: In this novel study, we demonstrate a standardized imaging and measurement protocol of anterior segment (AS) structures with reliability analysis using ultrasound biomicroscopy (UBM) and ImageJ software. METHODS: Ten pediatric and young adult patients undergoing examination under anesthesia for AS pathology were imaged using UBM. Four trained observers analyzed 20 images using ImageJ. Forty-five structural parameters were measured. Those that relied on the trabecular-iris angle (TIA) as a reference landmark were labeled TIA-dependent (TD) and all others were labeled non-TIA dependent (NTD). Intra-observer repeatability (IOR) and inter-observer agreement (IOA) of measurements were determined using coefficient of variation (CV) and intra-class correlation (ICC) followed by assessment of Bland-Altman plots (BAP) for each pair of observers, respectively. RESULTS: For NTD parameters, non-ciliary body (CB) related measurements showed CV range 0.60-16.22% and ICC range 0.84-0.89, whereas CB-related parameters showed CV range 2.86-23.40% and ICC range 0.29-0.92. For TD parameters, parameters < 2 degrees removed from reference showed CV range 0.02-5.40% and ICC range 0.89-1.00, whereas parameters > 1 degree removed showed CV range 0.63-27.44% and ICC range 0.22-1.00. No systematic proportional bias was detected by BAPs. CONCLUSIONS: Preplaced landmarks yielded good IOR and IOA in quantitative assessment of AS structures that were NTD and non-CB-related or less removed from the reference. CB-related NTD measurements varied greatly in IOR and IOA, indicating protocol modifications or CB qualitative assessments needed to improve accuracy. Variability in TD measurements increased the further removed from the reference, which supports implementation of a reliable reference landmark to minimize variation.

Can MDCT Unmask Instability in Binder-Stabilized Pelvic Ring Disruptions?

OBJECTIVE: Pelvic binders may hinder radiologic assessment of pelvic instability after trauma, and avulsive injuries can potentially unmask instability in this setting. We compare the performance of MDCT for the detection of pelvic disruptions in patients with binders to a matched cohort without binders, and we assess the utility of avulsive injuries as signs of pelvic instability. MATERIALS AND METHODS: MDCT examinations of 56 patients with binders were compared with MDCT examinations of 54 patients without binders. Tile grading by an experienced orthopedic surgeon was used as the reference standard (A, stable; B, rotationally unstable; C, rotationally and vertically unstable). Two radiologists performed blinded reviews of CT studies in two reading sessions (sessions 1 and 2). In session 1, Tile grade was predicted on the basis of established signs of instability, including pubic symphysis and sacroiliac (SI) joint widening. In session 2, readers could change the Tile grade when avulsive injuries were seen. Diagnostic performance for predicting rotational instability and vertical instability was assessed. RESULTS: In the binder group, AUCs under the ROC curves for rotational instability increased from fair (0.73-0.77) to good (0.82-0.89) when avulsive signs were considered. In the control group, AUCs were good in both sessions. AUCs for vertical instability were fair with binders in both sessions. Agreement with the reference standard increased from fair (0.30-0.32) to moderate (0.46-0.54) when avulsive signs were considered in the binder group but were in the moderate range for both sessions in the control group. Combined evaluation for inferolateral sacral fractures, ischial spine fractures, and rectus abdominis avulsions resulted in optimal discrimination of rotational instability. CONCLUSION: Evaluation for avulsive signs improves MDCT sensitivity for the detection of rotational instability but not vertical instability in patients with binders.

Investigation of Multiple Frequency Ranges Using Discrete Wavelet Decomposition of Resting-State Functional Connectivity in Mild Traumatic Brain Injury Patients.

The aim of this study was to investigate if discrete wavelet decomposition provides additional insight into resting-state processes through the analysis of functional connectivity within specific frequency ranges within the default mode network (DMN) that may be affected by mild traumatic brain injury (mTBI). Participants included 32 mTBI patients (15 with postconcussive syndrome [PCS+] and 17 without [PCS-]). mTBI patients received resting-state functional magnetic resonance imaging (rs-fMRI) at acute (within 10 days of injury) and chronic (6 months postinjury) time points and were compared with 31 controls (healthy control [HC]). The wavelet decomposition divides the time series into multiple frequency ranges based on four scaling factors (SF1: 0.125-0.250 Hz, SF2: 0.060-0.125 Hz, SF3: 0.030-0.060 Hz, SF4: 0.015-0.030 Hz). Within each SF, wavelet connectivity matrices for nodes of the DMN were created for each group (HC, PCS+, PCS-), and bivariate measures of strength and diversity were calculated. The results demonstrate reduced strength of connectivity in PCS+ patients compared with PCS- patients within SF1 during both the acute and chronic stages of injury, as well as recovery of connectivity within SF1 across the two time points. Furthermore, the PCS- group demonstrated greater network strength compared with controls at both time points, suggesting a potential compensatory or protective mechanism in these patients. These findings stress the importance of investigating resting-state connectivity within multiple frequency ranges; however, many of our findings are within SF1, which may overlap with frequencies associated with cardiac and respiratory activities.