Colon cancer: the 2023 Korean clinical practice guidelines for diagnosis and treatment.

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients' values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

Mdivi-1: Effective but complex mitochondrial fission inhibitor.

Mdivi-1, Mitochondrial DIVIsion inhibitor 1, has been widely employed in research under the assumption that it exclusively influences mitochondrial fusion, but effects other than mitochondrial dynamics have been underinvestigated. This paper provides transcriptome and DNA methylome-wide analysis for Mdivi-1 treated SH-SY5Y human neuroblastoma cells using RNA sequencing (RNA-seq) and methyl capture sequencing (MC-seq) methods. Gene ontology analysis of RNA sequences revealed that p53 transcriptional gene network and DNA replication initiation-related genes were significantly up and down-regulated, respectively, showing the correlation with the arrest cell cycle in the G1 phase. MC-seq, a powerful sequencing method for capturing DNA methylation status in CpG sites, revealed that although Mdivi-1 does not induce dramatic DNA methylation change, the subtle alterations were concentrated within the CpG island. Integrative analysis of both sequencing data disclosed that the p53 transcriptional network was activated while the Parkinson's disease pathway was halted. Next, we investigated several changes in mitochondria in response to Mdivi-1. Copy number and transcription of mitochondrial DNA were suppressed. ROS levels increased, and elevated ROS triggered mitochondrial retrograde signaling rather than inducing direct DNA damage. In this study, we could better understand the molecular network of Mdivi-1 by analyzing DNA methylation and mRNA transcription in the nucleus and further investigating various changes in mitochondria, providing inspiration for studying nuclear-mitochondrial communications.

Modulation of TRPV4-mediated TNF-α expression in Müller glia and subsequent RGC apoptosis by statins.

In addition to regulating cholesterol synthesis, statins have neuroprotective effects. Apoptosis of retinal ganglion cells (RGCs) causes a gradual loss of visual function in glaucoma. This study aimed to investigate the neuroprotective effect of statins on the RGC apoptosis induced by activated Müller glia. Primary Müller cells and RGCs were cultured from the retina of C57BL6 mice. Müller cells were activated with GSK101, a transient receptor potential vanilloid 4 (TRPV4) agonist, and tumor necrosis factor-alpha (TNF-α) released to the medium was measured using an enzyme-linked immunosorbent assay. Cells were pretreated with simvastatin or lovastatin before GSK101. RGCs were treated with conditioned media from Müller glia cultures, and apoptosis was determined using flow cytometry. TRPV4 activation through GSK101 treatment induced gliosis of Müller cells, and the conditioned media from activated Müller cells was potent to induce RGC apoptosis. Statins suppress both gliosis in Müller cells and subsequent RGC apoptosis. TNF-α release to the media was increased in GSK101-treated Müller cells, and TNF-α in the conditioned media was the critical factor causing RGC apoptosis. The increase in TRPV4-mediated TNF-α expression occurred through the nuclear factor kappa-light chain enhancer of activated B cell pathway activation, which was inhibited by statins. Herein, we showed that statins can modulate gliosis and TNF-α expression in Müller cells, protecting RGCs. These data further support the neuroprotective effect of statins, promoting them as a potential treatment for glaucoma.

Synergistic Improvement of Flame Retardancy and Mechanical Properties of Epoxy/Benzoxazine/Aluminum Trihydrate Adhesive Composites.

Epoxy resin was mixed with benzoxazine resin and an aluminum trihydrate (ATH) additive to provide flame retardancy and good mechanical properties. The ATH was modified using three different silane coupling agents and then incorporated into a 60/40 epoxy/benzoxazine mixture. The effect of blending compositions and surface modification on the flame-retardant and mechanical properties of the composites was investigated by performing UL94, tensile, and single-lap shear tests. Additional measurements were conducted including thermal stability, storage modulus, and coefficient of thermal expansion (CTE) assessments. The mixtures containing more than 40 wt% benzoxazine revealed a UL94 V-1 rating with high thermal stability and low CTE. Mechanical properties including storage modulus, and tensile and shear strength, also increased in proportion to the benzoxazine content. Upon the addition of ATH to the 60/40 epoxy/benzoxazine mixture, a V-0 rating was achieved at 20 wt% ATH. The pure epoxy passed a V-0 rating by the addition of 50 wt% ATH. The lower mechanical properties at high ATH loading could have been improved by introducing a silane coupling agent to the ATH surface. The composites containing surface-modified ATH with epoxy silane revealed about three times higher tensile strength and one and a half times higher shear strength compared to the untreated ATH. The enhanced compatibility between the surface-modified ATH and the resin was confirmed by observing the fracture surface of the composites.

Optical Coherence Tomography Angiography of the Retinal Circulation Following Trabeculectomy for Glaucoma.

PRCIS: Despite successful trabeculectomy, eyes with similar levels of peripapillary and macular vessel densities but with worse preoperative visual field mean deviations may experience functional and vascular decline after surgery. PURPOSE: To evaluate the retinal microcirculation change after trabeculectomy according to glaucoma severity using optical coherence tomography angiography (OCTA). METHODS: We enrolled 59 eyes of primary open angle glaucoma patients who underwent trabeculectomy. The eyes were categorized into 3 groups by preoperative visual field (VF) mean deviation (MD), group 1: MD>-12.0 dB, group 2: MD -12.0 to -20.0 dB, and group 3: MD <-20.0 dB. OCTA was performed preoperatively and 1 year after trabeculectomy. The differences in the radial peripapillary capillary vessel density (pVD) and macular VD between preoperative and postoperative assessment were analyzed and compared in each group. Factors associated with the VD change after trabeculecomy were determined using linear regression analysis. RESULTS: Mean postoperative IOP and IOP reduction did not differ among the 3 groups after trabeculectomy. Preoperative pVD (37.2 vs. 36.6%, P =1.00) and macular VD (39.0 vs. 38.4%, P =1.00) did not differ between groups 1 and 2. Group 1 and 3 showed no changes in VD parameters after trabeculectomy (all, P >0.05). However, group 2 showed statistically significant decreases in pVD (36.6 vs. 32.9%, P <0.001) and macular VD (38.4 vs. 36.0%, P =0.010) after trabeculectomy. The reduction of pVD was associated with a decrease of IOP (Coefficient (ß); 0.14, P =0.032) and VF MD (ß; 0.15, P =0.0116) in group 2, respectively. CONCLUSION: Following successful trabeculectomy surgery for uncontrolled glaucoma with similar IOP reduction, glaucoma eyes with advanced visual field loss showed reduced pVD and macular VD measured by OCT-A. These findings may be relevant to disease progression.

Association between 20% Albumin Use and Acute Kidney Injury in Major Abdominal Surgery with Transfusion.

Red blood cell (RBC) transfusion and albumin administration can affect kidney function. We aimed to evaluate the association between intraoperative 20% albumin administration and acute kidney injury (AKI), along with the duration of hospitalization and 30-day mortality in patients undergoing major abdominal surgery with RBC transfusion. This retrospective study included 2408 patients who received transfusions during major abdominal surgery. Patients were categorized into albumin (n = 842) or no-albumin (n = 1566) groups. We applied inverse probability of treatment weighting (IPTW), propensity score (PS) matching (PSM), and PS covariate adjustment to assess the effect of albumin administration on the outcomes. In the unadjusted cohort, albumin administration was significantly associated with increased risk of AKI, prolonged hospitalization, and higher 30-day mortality. However, there was no significant association between albumin administration and AKI after adjustment (OR 1.26, 95% CI 0.90-1.76 for the IPTW; OR 1.03, 95% CI 0.72-1.48 for the PSM; and OR 1.04, 95% CI 0.76-1.43 for the PS covariate adjustment methods). While albumin exposure remained associated with prolonged hospitalization after adjustment, it did not affect 30-day mortality. Our findings suggest that hyper-oncotic albumin can be safely administered to patients who are at risk of developing AKI due to RBC transfusion.

Cessation of Immunomodulatory Medication Use in Dermatomyositis: A Single-Center Cohort Study.

OBJECTIVE: To determine the frequency with which adults with dermatomyositis (DM) are able to discontinue systemic immunomodulatory therapy and factors associated with medication cessation. METHODS: We studied a cohort of adult DM patients seen in a rheumatology/dermatology clinic between 2013 and 2020. All patients had exposure to at least 1 systemic immunomodulatory medication for a minimum of 3 months and were followed until medications were discontinued for at least 12 months. Survival analysis was performed using Kaplan-Meier curves with log-rank analyses, and multivariate analysis was done using Cox proportional hazards models. RESULTS: A total of 246 DM patients were followed up for a median time of ∼7 years (47-134 months). Forty-seven patients (19%) discontinued all immunomodulatory medications with a median follow-up of ∼3 years (interquartile range 22-108 months) following DM onset. Log-rank analysis demonstrated that those with anti-MDA5 autoantibodies discontinued medications faster compared with those without autoantibodies (P = 0.03). Multivariate modeling showed that clinically amyopathic patients were 2.7-fold (95% confidence interval [95% CI] 1.34-5.59) more likely to discontinue medications than those with muscle disease. Those with anti-MDA5, anti-NXP2, and anti-SAE1 antibodies had increased likelihood of medication cessation with hazard ratios of 9.83 (95% CI 2.00-48.2), 8.92 (95% CI 1.69-47.0), and 10.8 (95% CI 2.06-56.6), respectively, when compared with the autoantibody-negative group. CONCLUSION: Approximately 20% of adult DM patients discontinued immunomodulatory medications over a median 7-year follow-up. Those with clinically amyopathic disease, anti-MDA5, anti-NXP2, and anti-SAE1 antibodies have a higher likelihood of medication cessation.

Non-adherence of surgical treatment in patients with non-melanoma skin cancer: a retrospective cohort pilot study.

There is limited data on non-adherence for surgical treatment in non-melanoma skin cancer (NMSC) patients. The objective of this single-center, retrospective cohort study is to compare rates of non-adherence of surgical treatment options, determine factors associated with non-adherence, and identify barriers for non-adherence. All adult patients with NMSC (> 18 years) seen between 2015 and 2017 recommended surgical treatment (surgical excision and electrodessication and curettage (ED&C) or Mohs surgery) were eligible. Non-adherence was defined as not completing recommended treatment and reasons for non-adherence were collected. Out of 427 patients that met inclusion criteria, patients recommended surgical excision and ED&C had a lower non-adherence rate of 3.4% compared to those recommended Mohs (11.4%) (p = 0.006). Factors associated with non-adherence included self-pay patients (19.07% adherent vs. 43.24% non-adherent, p = 0.004). Multivariate logistic regression analysis confirmed that Mohs patients were more likely to be non-adherent (odds ratio (OR) = 3.839, 95% confidence interval (CI) (1.435-10.270), p = 0.007) compared to surgical excision and ED&C patients. Males were more likely to be non-adherent (OR = 2.474, 95% CI (1.105-5.542), p = 0.028) to females, and self-pay patients were more likely to be non-adherent than those with other payers (OR = 3.050, 95% CI (1.437-6.475), p = 0.004). Of the 37 patients who were non-adherent, the most common reasons were loss to follow-up (46%), social reasons (41%), medical reasons (38%), and financial reasons (22%). There was a significant difference in non-adherence rates between surgical treatments for NMSCs in our cohort. Our study suggests the need for future interventional studies that implement strategies and patient education to decrease non-adherence rates.

Assessment of Iridotrabecular Contact and Its Association With Intraocular Pressure After Phacoemulsification in Primary Angle Closure.

PURPOSE: To investigate the association between the quantitative assessment of iridotrabecular contact (ITC), measured by swept-source anterior segment optical coherence tomography (SS AS-OCT), and intraocular pressure (IOP) control after phacoemulsification in patients with primary angle closure disease (PACD). DESIGN: Retrospective, clinical cohort study. METHODS: Preoperative and postoperative anterior chamber angle parameters were measured using SS AS-OCT. IOP was measured preoperatively and until 6 months postoperatively. Percent IOP reduction and fluctuation after surgery were calculated, and their relationships with SS AS-OCT parameters were assessed by correlation analyses and locally weighted scatterplot smoothing (LOWESS) regression with change-point analysis. RESULTS: A total of 51 eyes of 51 PACD patients were included. Preoperative ITC index and area (r = 0.626, r = 0.551), as well as changes in ITC index and area (r = 0.632, r = 0.543) after surgery, were significantly correlated with postoperative IOP reduction, after adjusting for age and gender (all P <.001). Higher postoperative ITC index (r = 0.405, P = .005) and ITC area (r = 0.460, P = 0.001) were associated with greater postoperative IOP fluctuations. Change points on LOWESS curves were observed for preoperative ITC index (33.0%) and change in ITC index (27.0%) and percent IOP reductions were significantly correlated with them above (ß = 0.386, ß = 0.664, all P < .001) but not below the change points. CONCLUSIONS: Quantitative assessment of circumferential ITC can predict postoperative IOP control after phacoemulsification, and thus it may be used as a reference for determining lens extraction in PACD eyes.

Modeling immunity in microphysiological systems.

There is a need for better predictive models of the human immune system to evaluate safety and efficacy of immunomodulatory drugs and biologics for successful product development and regulatory approvals. Current in vitro models, which are often tested in two-dimensional (2D) tissue culture polystyrene, and preclinical animal models fail to fully recapitulate the function and physiology of the human immune system. Microphysiological systems (MPSs) that can model key microenvironment cues of the human immune system, as well as of specific organs and tissues, may be able to recapitulate specific features of the in vivo inflammatory response. This minireview provides an overview of MPS for modeling lymphatic tissues, immunity at tissue interfaces, inflammatory diseases, and the inflammatory tumor microenvironment in vitro and ex vivo. Broadly, these systems have utility in modeling how certain immunotherapies function in vivo, how dysfunctional immune responses can propagate diseases, and how our immune system can combat pathogens.

A microphysiological system-based potency bioassay for the functional quality assessment of mesenchymal stromal cells targeting vasculogenesis.

Mesenchymal stromal cells (MSCs) continue to be proposed for use in clinical trials to treat various diseases due to their therapeutic potential to pleiotropically influence endogenous regenerative processes, such as vasculogenesis. However, the functional heterogeneity of MSCs has hampered their clinical success and poses a significant manufacturing challenge with respect to MSC quality control. Here, we evaluated and qualified a quantitative bioassay based on an enhanced-throughput, microphysiological system to measure the specific paracrine bioactivity of MSCs to stimulate vasculogenesis as a measure of MSC potency. Using this novel bioassay, MSCs derived from multiple donors at different passages were co-cultured with human umbilical vein endothelial cells (HUVECs) and exhibited significant heterogeneity in vasculogenic potency between donors and cell passage. Using our microphysiological system (MPS)-based platform, we demonstrated that variations in MSC vasculogenic bioactivity were maintained when assayed across laboratories and operators. The differences in MSC vasculogenic bioactivity were also correlated with the baseline expression of several genes involved in vasculogenesis (hepatocyte growth factor (HGF), angiopoietin-1 (ANGPT)) or the production of matricellular proteins (fibronectin (FN), insulin-like growth factor-binding protein 7 (IGFBP7)). These findings emphasize the significant functional heterogeneity of MSCs in vasculogenic bioactivity and suggest that changes in baseline gene expression of vasculogenic or matricellular protein genes during manufacturing may affect this bioactivity. The development of a reliable and functionally relevant potency assay for measuring the specific vasculogenic bioactivity of manufactured MSCs will help to reliably assure their quality when used in appropriate clinical trials.

The SUMO protease SENP1 promotes aggressive behaviors of high HIF2α expressing renal cell carcinoma cells.

While an important role for the SUMO protease SENP1 is recognized in multiple solid cancers, its role in renal cell carcinoma (RCC) pathogenesis, particularly the most dominant subtype, clear cell RCC (ccRCC), is poorly understood. Here we show that a combination of high HIF2α and SENP1 expression in ccRCC samples predicts poor patient survival. Using ccRCC cell models that express high HIF2α but low SENP1, we show that overexpression of SENP1 reduces sumoylation and ubiquitination of HIF2α, increases HIF2α transcriptional activity, and enhances expression of genes associated with cancer cell invasion, stemness and epithelial-mesenchymal transition. Accordingly, ccRCC cells with high HIF2α and SENP1 showed increased invasion and sphere formation in vitro, and local invasion and metastasis in vivo. Finally, SENP1 overexpression caused high HIF2α ccRCC cells to acquire resistance to a clinical mTOR inhibitor, everolimus. These results reveal a combination of high SENP1 and HIF2α expression gives particularly poor prognosis for ccRCC patients and suggest that SENP1 may be an attractive new target for treating metastatic RCC (mRCC).

Impact of Wildfire Smoke Exposure on Health in Korea.

PURPOSE: The characteristic topography and climate often affect the occurrence of large-scale wildfires in the Eastern Gangwon-do region of Korea. However, there are no studies on the health effects of these wildfires in Korea. This study aimed to analyze the differences in medical use between a wildfire-affected area and an adjacent non-affected area before and after a wildfire in 2019 in Gangwon-do, Korea. MATERIALS AND METHODS: We used medical usage data from the Korean National Health Insurance Corporation. Rates of medical use were determined for citizens of a wildfire-affected area in the Eastern Yeongdong region and a non-affected area in the Western Yeongseo region. Logistic regression analysis was performed considering an increase in medical use per individual as a dependent variable; age, sex, income, smoking, drinking, and exercise were included as confounding variables. RESULTS: The odds ratio for medical use in Yeongdong region increased significantly after 3 days, 3 months, and 1 year after a fire occurred, compared with Yeongseo region. CONCLUSION: The results of this study confirmed that the use of medical care increased for residents of a wildfire-affected area, compared with those of an adjacent non-affected area. This is the first study on the relationship between wildfires and inpatient medical use in Korea.

Read-out Segmented Echo Planar Imaging with Two-Dimensional Navigator Correction (RESOLVE): An Alternative Sequence to Improve Image Quality on Diffusion-Weighted Imaging of Prostate.

OBJECTIVE: We aimed to investigate if the use of read-out segmented echoplanar imaging with additional two-dimensional navigator correction (Readout Segmentation of Long Variable Echo, RESOLVE) for acquiring prostate diffusion-weighted imaging (DWI) improves image quality, compared to single-shot echoplanar imaging (ss-EPI). METHODS: This single-center prospective study cohort included 162 males with suspected prostate cancer, who underwent 3 Tesla multiparametric MRI (3T-mpMRI). Two abdominal radiologists, blinded to the clinical information, separately reviewed each 3T-mpMRI study to rank geometrical distortion, degree of rectal distention, lesion conspicuity, and anatomic details delineation first on ss-EPI-DWI and later on RESOLVE-DWI using 5-point scales (1 = excellent, 5 = poor). The average of the ranking scores given by two readers was generated and used as the final score. RESULTS: There was good-to-excellent interreader agreement for scoring image quality parameters on both ss-EPI and RESOLVE. Geometrical distortion scores > 3 was seen in 12.3% (20/162) of ss-EPI images, with all having geometrical distortion score <3 on RESOLVE (p < .001). The mean image distortion score was significantly less on RESOLVE than ss-EPI (1.16 vs 1.61, p < .01 regardless of rectal gas, p< .05 when stratified by the degree of rectal distention ). RESOLVE was superior to ss-EPI for lesion conspicuity (mean 1.35 vs 1.53, p< .002) and anatomic delineation (2.60 vs 2.68, p< .001) of prostate on DWI. CONCLUSION: Compared to conventional ss-EPI, the use of RESOLVE for acquisition of prostate DWI resulted in significantly enhanced image quality and reduced geometrical distortion. ADVANCES IN KNOWLEDGE: RESOLVE could be an alternative or replacement of ss-EPI for acquiring prostate DWI with significantly less geometrical distortion and significantly improved lesion conspicuity and anatomic delineation.

Statins Inhibit the Gliosis of MIO-M1, a Müller Glial Cell Line Induced by TRPV4 Activation.

We characterized Müller cell gliosis induced by the activation of transient receptor potential vanilloid-type 4 (TRPV4) and assessed whether statins could modulate the gliosis. The human Müller cell line, MIO-M1, was used to analyze the gliosis caused by glaucomatous stimulation. To induce Müller gliosis in MIO-M1 cells, GSK101 was used to activate TRPV4, and Müller gliosis was evaluated by analyzing vimentin, nestin, and glial fibrillary acidic protein (GFAP) expression. The expression level of TNF-α was determined by ELISA. To evaluate the GSK101 activation of the NF-κB pathway, p65 phosphorylation was measured by Western blotting, and the nuclear translocation of p65 and IκBα phosphorylation were assessed by immunostaining. To assess the effect of statins on MIO-M1 gliosis, cells were pretreated for 24 h with statins before GSK101 treatment. Vimentin, nestin, and GFAP expression were upregulated by GSK101, while statins effectively inhibited them. The expression of TNF-α was increased by GSK101. The phosphorylation and nuclear translocation of p65 and IκBα phosphorylation, which occurs prior to p65 activation, were induced. Statins suppressed the GSK101-mediated phosphorylation of IκBα and p65 translocation. Statins can mitigate gliosis in the human Müller cell line. Because TRPV4 activation in Müller cells reflects glaucoma pathophysiology, statins may have the potential to prevent RGC death.

Relationship Between Poor Sleep Quality and Injury Experience in Korea.

To develop preventive policies to reduce injuries, the responsible factors should be identified. In this study, causative factors were identified by analyzing data from the Korean Community Health Survey. Logistic regression was used to analyze the data of 192 480 individuals in the survey. Correlations were found between the injury experience and the following socioeconomic factors: age, sex, monthly income, smoking status, education, marital status, and neuropsychiatric factors: depressive symptoms, cognitive decline, and stress. The study subjects were divided into two groups based on sleep quality, as determined by Pittsburgh Sleep Quality Indices of ≤5 or >5. Logistic regression analysis adjusted for potential confounders revealed a correlation between sleep quality and injury experience. The odds ratio (OR) of poor sleep quality was associated with higher odds of injury (OR: 1.26), and it was also associated with higher odds of severe injury (OR: 1.23), even in the adjustment of socioeconomic factors only as well as in the adjustment of socioeconomic and neuropsychiatric factors. Poor sleep quality was associated with higher odds of several injury mechanisms of severe injury, such as slipping, poisoning, and falling into water.

Glaucoma Progression After Lens Extraction in Primary Angle-closure Glaucoma According to Angle-closure Mechanism.

PRCIS: Long-term prognosis of primary angle-closure was assessed after lens extraction (LE) according to different mechanisms of angle closure (AC). Patients with pupillary block (PB) had a higher probability of glaucomatous progression than patients with plateau iris configuration (PIC). PURPOSE: The aim was to investigate and compare the clinical characteristics and long-term prognosis of primary angle-closure disease (PACD) after LE according to different mechanisms of AC. METHODS: In this retrospective observational cohort study, 118 eyes with PACD that underwent LE (mean follow-up; 6.0±3.5 y after surgery) were included. PACD eyes were categorized into three subgroups according to their dominant AC mechanisms, determined by anterior segment optic coherent tomography obtained before LE; PB, PIC, and exaggerated lens vault (ELV). Postoperative glaucomatous progression was determined according to functional (visual field) or structural (optic disc photographs or optic coherent tomography measured retinal nerve fiber layer thickness) criteria. Univariate and multivariate logistic regression analysis was performed to determine the risk factors associated with glaucomatous progression. RESULTS: Fifty-two, 51, and 15 eyes with PB, PIC, and ELV, respectively, were included. All eyes showed significant intraocular pressure reduction, with a greater reduction in the ELV group than in the PB group after LE (27.0% vs. 12.5%, P=0.018). Lower baseline retinal nerve fiber layer thickness [odds ratio (OR): 0.966, P=0.004] and thinner central corneal thickness (OR: 0.985, P=0.021), and the PB group (OR: 2.891, P=0.022, reference to PIC group) were significantly associated with glaucomatous progression after LE. CONCLUSIONS: In eyes with PACD, glaucoma progression was observed following LE despite reduced intraocular pressure. The probability of progression was highest in eyes with pupil block as a mechanism of AC. Close monitoring of glaucoma in these patients is suggested.

Prostaglandin-associated periorbitopathy syndrome (PAPS): Addressing an unmet clinical need.

BACKGROUND: Topical prostaglandin analogs (PGAs) are widely approved and preferred first-line options for glaucoma and elevated intraocular pressure (IOP). However, prostaglandin-associated periorbitopathy syndrome (PAPS) is now a well-recognized clinical and cosmetic concern for patients receiving PGAs, especially during long-term and unilateral therapy. PGA-associated periocular changes occur in a substantial proportion of patients, with older patients (>60 years) at greater risk of clinical presentation. PAPS may hinder long-term management of glaucoma, including treatment adherence, ophthalmic surgery outcomes, and reliable IOP measurements. RECOMMENDATION: New therapeutic approaches may address this unmet clinical need. Omidenepag isopropyl (OMDI) is a novel, non-prostaglandin, selective EP2 receptor agonist in ongoing development, which provides a unique pharmacological mechanism of action. OMDI appears to provide IOP reductions comparable to PGAs, but without PAPS-related undesirable effects. OMDI may offer a suitable long-term option for patients who demonstrate decreased efficacy, or failure, of PGAs, plus patients with significant PAPS, while fulfilling international guidelines.

Functional heterogeneity of IFN-γ-licensed mesenchymal stromal cell immunosuppressive capacity on biomaterials.

Mesenchymal stromal cells (MSCs) are increasingly combined with biomaterials to enhance their therapeutic properties, including their immunosuppressive function. However, clinical trials utilizing MSCs with or without biomaterials have shown limited success, potentially due to their functional heterogeneity across different donors and among different subpopulations of cells. Here, we evaluated the immunosuppressive capacity, as measured by the ability to reduce T-cell proliferation and activation, of interferon-gamma (IFN-γ)-licensed MSCs from multiple donors on fibrin and collagen hydrogels, the two most commonly utilized biomaterials in combination with MSCs in clinical trials worldwide according to ClinicalTrials.gov Variations in the immunosuppressive capacity between IFN-γ-licensed MSC donors on the biomaterials correlated with the magnitude of indoleamine-2,3-dioxygenase activity. Immunosuppressive capacity of the IFN-γ-licensed MSCs depended on the αV/α5 integrins when cultured on fibrin and on the α2/ß1 integrins when cultured on collagen. While all tested MSCs were nearly 100% positive for these integrins, sorted MSCs that expressed higher levels of αV/α5 integrins demonstrated greater immunosuppressive capacity with IFN-γ licensing than MSCs that expressed lower levels of these integrins on fibrin. These findings were equivalent for MSCs sorted based on the α2/ß1 integrins on collagen. These results demonstrate the importance of integrin engagement to IFN-γ licensed MSC immunosuppressive capacity and that IFN-γ-licensed MSC subpopulations of varying immunosuppressive capacity can be identified by the magnitude of integrin expression specific to each biomaterial.

Unusual presentation of granulomatosis with polyangiitis causing periaortitis and consequent subclavian steal syndrome: A case report.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is a rare autoimmune disease that involves small-to-medium-sized vessels and forms necrotizing vasculitis with granulomatous inflammation. The formation of a large vessel lesion in GPA patients has been scarcely reported, and it can cause confusion in the diagnosis. CASE SUMMARY: A 27-year-old man presented with mild left-sided pleuritic chest pain that started one year prior. An imaging study revealed up to 2.5 cm-sized two irregular nodular consolidation nodule in the left lower lobe. Both nodules showed central necrosis. Also, there was a periaortic mass occluding the branching porting of the subclavian artery. He had positive anti-neutrophil cytoplasmic antibodies (ANCAs), but myeloperoxidase-ANCAs and proteinase 3-ANCAs were negative. The patient also developed symptoms of subclavian vein syndrome during the follow-up. Wedge resection of the lung revealed necrotizing vasculitis, destructive parenchymal abscess and surrounding granuloma, and therefore diagnosed of GPA. The patient started on methotrexate and steroid therapy with a relief of symptomatic. CONCLUSION: Here, we present an unusual manifestation of GPA with periaortitis and consequent subclavian steal syndrome, which has never been previously described. This case alerts us that we should include GPA in the differential diagnosis of large vessel vasculitis as well as subclavian steal syndrome.