Clinical outcomes of conjunctivochalasis treatment with a new ophthalmic radiofrequency device.

PURPOSE: To investigate the safety and efficacy of a new micro-controlled radiofrequency device for treatment of conjunctivochalasis (Cch). METHODS: Data of 127 patients (230 eyes) who underwent ophthalmic radiofrequency treatment for Cch from January 2020 to June 2023 were analyzed retrospectively. Cch coagulation was performed with a radiofrequency electrode tip (OcuRF®, Ilooda, Korea) and a high-frequency radio-wave electric unit (0.6 ~ 0.8 watts, 2 MHz, Acutron™, Ilooda, Korea). Pre- and postoperative Cch grading, slit-lamp photography, tear film break-up time (TBUT), and bulbar conjunctival hyperemia using Keratograph 5 M (Oculus, Wetzlar, Germany) were evaluated. Cch grade 0 or 1 after surgery was regarded as 'success'. Complications, recurrence, and additional treatment rates were analyzed. RESULTS: In 227 (98.7%) eyes, the radiofrequency treatment led to marked improvement of Cch, with 224 (97.4%) eyes achieving grade 0 or 1 at 2 months postoperatively. Eight eyes (3.5%) received additional treatment. TBUT improved from 3.17 ± 0.82 s to 5.28 ± 1.10 s after surgery (P < 0.001). The total bulbar conjunctival hyperemia value showed an improvement from 1.7 ± 0.6 to 1.4 ± 0.6 postoperatively (P < 0.05). No serious complications were observed. CONCLUSION: The novel ophthalmic radiofrequency device led to a marked improvement of Cch with no serious adverse events during the entire follow-up period. Our results suggest that the radiofrequency device presents a safe and efficacious treatment option for Cch.

Re-Esterified Triglyceride ω-3 Fatty Acids in Dry Eye Disease With Meibomian Gland Dysfunction: A Randomized Clinical Trial.

Importance: Taking ω-3 supplements has been associated with a reduction in symptoms of dry eye disease (DED) associated with meibomian gland dysfunction (MGD). However, a recent relatively large clinical trial concluded that treating DED with ω-3 consumption was ineffective, potentially warranting additional investigations. Objectives: To investigate the effect of re-esterified triglyceride (rTG) ω-3 fatty acid supplementation on DED associated with MGD. Design, Setting, and Participants: This double-masked, parallel-group, randomized clinical trial was conducted at 7 institutions from September 2020 to January 2023. Patients with DED associated with MGD were included and randomly assigned to the ω-3 group (received 1680 mg of eicosapentaenoic acid and 560 mg of docosahexaenoic acid), whereas those in the grape-seed group received 3000 mg of grape-seed oil daily. Interventions: rTG ω-3 Fatty acid supplementation vs grape-seed oil. Main Outcome Measures: The primary end point was the Ocular Surface Disease Index (OSDI) from baseline to 6 and 12 weeks. The safety parameters were visual acuity and intraocular pressure change. Results: A total of 132 patients (mean [SD] age, 50.6 [13.8] years; 103 female [78.0%]) were included in this study. The mean (SD) baseline OSDI scores of the ω-3 and grape-seed groups were 43.5 (16.5) and 44.1 (16.6), respectively. A total of 58 patients (87.9%) and 57 patients (86.4%) in the ω-3 and grape-seed groups, respectively, completed 12 weeks of follow-up. There were no differences in compliance with the dietary supplement intake between groups (ω-3, 95.8% and grape-seed, 95.4%). The OSDI (SD) change from baseline to 6 and 12 weeks was -20.5 (16.0) and -22.7 (15.7), respectively, in the ω-3 group and -15.1 (20.2) and -18.8 (21.7), respectively, in the grape-seed control group (difference at 6 weeks = -5.4; 95% CI, -12.15 to 1.33; P = .12 and at 12 weeks = -3.9; 95% CI, -10.90 to 3.13; P = .28). There were no changes in safety parameters or adverse events related to taking the dietary supplement in either group. Conclusions and Relevance: This randomized clinical trial did not show a benefit of the rTG form of ω-3 for ameliorating symptoms of DED associated with MGD, although fewer than 60 participants were evaluated in each group. Any secondary outcomes from this study should be considered for hypothesis generation of future evaluations of the effect of the rTG form of ω-3 on DED associated with MGD. Trial Registration: CRIS Identifier: KCT0004927.

Long Term Psychiatric and Endocrine Complications Following Hematopoietic Stem Cell Transplantation in Hematologic Disease in Korea: A Nation-wide Cohort Study.

Purpose: Numerous patients experience long-term complications after HSCT. This study aimed to identify the frequency and risk factors for psychiatric and endocrine complications following HSCT through big data analyses. Materials and Methods: We established a cohort of patients with hematologic disease who underwent HSCT in Korea between 2010 and 2012 using the Health Insurance Review & Assessment Service data. A total of 3,636 patients were identified, and insurance claims were tracked using psychiatric and endocrine diagnostic International Classification of Diseases-10th Revision codes for the ensuing decade. We identified the incidence rates of long-term complications based on the baseline disease and HSCT type. Prognostic factors for each complication were scrutinized using logistic regression analysis. Results: A total of 1,879 patients underwent allogeneic HSCT and 1,757 patients received autologous HSCT. Post-HSCT, 506 patients were diagnosed with depression, 465 with anxiety disorders, and 659 with diabetes. The highest incidence of long-term complications occurred within the first year post-HSCT (12.2%), subsequently decreasing over time. Risk factors for depressive disorders after allogeneic HSCT included female sex, a total body irradiation based conditioning regimen, and cyclosporine. Identified risk factors for diabetes mellitus comprised old age, TBI-based conditioning regimen, and non-Antithymocyte globulin protocol. Regarding autologous HSCT, only female sex was identified as a risk factor for depressive disorders, whereas elderly patients and those with multiple myeloma were identified as poor prognostic factors for diabetes mellitus. Conclusion: The incidence of long-term psychiatric and endocrine complications post-HSCT remains high, and patients with risk factors for these complications require vigilant follow-up.

Clinical Outcomes of a New Hydrophobic Trifocal Intraocular Lens with Hydroxyethyl Methacrylate in Cataract Surgery: A Prospective Multicenter Study.

PURPOSE: To investigate the clinical outcomes of new hydrophobic trifocal intraocular lens with hydroxyethyl methacrylate in the Korean population. METHODS: This prospective, multicenter, and observational study evaluated the clinical outcomes of 80 eyes of 40 patients with age-related cataract underwent cataract surgery using CNWT (Clareon PanOptix). Assessment included monocular and binocular uncorrected distance visual acuity, corrected distance visual acuity, uncorrected intermediate visual acuity (at 60cm), near visual acuity (at 40 and 33 cm), uncorrected defocus curves, questionnaires evaluating photic phenomena, spectacle independence, and spectacle free satisfaction. RESULTS: At postoperative 3 months, mean uncorrected binocular visual acuities were 0.04, 0.04, 0.03 logarithm of the minimum angle of resolution (logMAR) at far, intermediate, and near distances, respectively. All patients achieved uncorrected binocular visual acuity of 0.2 logMAR or better. Monocular and binocular defocus curve indicated a mean visual acuity of 0.2 logMAR or better at the defocus range of +1.0 to - 3.0 diopters (100 to 33 cm) and +1.0 to - 3.5 diopters (100 to 28 cm). High spectacle independence was observed at all distances, with 37.5% patients reporting photic phenomena. CONCLUSIONS: The Clareon PanOptix intraocular lens has shown positive clinical outcomes, providing a viable option for cataract surgery. These lenses effectively address patients' visual needs, especially in intermediate and near distance tasks, reducing dependence on glasses.

Mitochondrial dysfunction precedes hippocampal IL-1ß transcription and cognitive impairments after low-dose lipopolysaccharide injection in aged mice.

Acute cognitive impairments termed delirium often occur after inflammatory insults in elderly patients. While previous preclinical studies suggest mitochondria as a target for reducing neuroinflammation and cognitive impairments after LPS injection, fewer studies have evaluated the effects of a low-grade systemic inflammation in the aged brain. Thus, to identify the significance of mitochondrial dysfunction after a clinically relevant systemic inflammatory stimulus, we injected old-aged mice (18-20 months) with low-dose lipopolysaccharide (LPS, 0.04 mg/kg). LPS injection reduced mitochondrial respiration in the hippocampus 24 h after injection (respiratory control ratio [RCR], state3u/state4o; control = 2.82 ± 0.19, LPS = 2.57 ± 0.08). However, gene expression of the pro-inflammatory cytokine IL-1ß was increased (RT-PCR, control = 1.00 ± 0.30; LPS = 2.01 ± 0.67) at a more delayed time point, 48 h after LPS injection. Such changes were associated with cognitive impairments in the Barnes maze and fear chamber tests. Notably, young mice were unaffected by low-dose LPS, suggesting that mitochondrial dysfunction precedes neuroinflammation and cognitive decline in elderly patients following a low-grade systemic insult. Our findings highlight mitochondria as a potential therapeutic target for reducing delirium in elderly patients.

Development and Validation of a High-Performance Liquid Chromatography Method to Quantify Marker Compounds in Lysimachia vulgaris var. davurica and Its Effects in Diarrhea-Predominant Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS), a common gastrointestinal disorder worldwide, is characterized by chronic abdominal pain, bloating, and disordered defecation. IBS is associated with several factors, including visceral hypersensitivity, gut motility, and gut-brain interaction disorders. Because currently available pharmacological treatments cannot adequately improve symptoms and may cause adverse effects, the use of herbal therapies for managing IBS is increasing. Lysimachia vulgaris var. davurica (LV) is a medicinal plant used in traditional medicine to treat diarrhea. However, information on whether LV can effectively improve diarrhea-predominant IBS (IBS-D) remains limited. In this study, using an experimental mouse model of IBS-D, we elucidated the effects of the LV extract. The methanol extract of LV decreased fecal pellet output in the restraint stress- or 5-hydroxytryptamine (5-HT)-induced IBS mouse model and inhibited 5-HT-mediated [Ca2+]i increase in a dose-dependent manner. Furthermore, we developed and validated a high-performance liquid chromatography method using two marker compounds, namely, chlorogenic acid and rutin, for quality control analysis. Our study results suggest the feasibility of the methanol extract of LV for developing therapeutic agents to treat IBS-D by acting as a 5-HT3 receptor antagonist.

Effect of Corneal and Lens Eccentricity Difference on Rigid Corneal Lens Treatment in Patients With Keratoconus.

OBJECTIVE: To evaluate the effects of rigid corneal lenses (RCL) in patients with keratoconus, based on eccentricity. METHODS: Eighty-four eyes from 84 patients were included in this retrospective comparative study. Based on the median value of eccentricity difference between the cornea and back surface of the RCL, the patients were divided into groups 1 (<0.08) and 2 (≥0.08). Visual acuity, refractive index, and corneal topography indices were compared before and three months after lens use. RESULTS: Visual acuity, astigmatism, refractive error, corneal curvature, and corneal thickness improved significantly in both groups. Apical power and anterior elevation improved significantly in group 1, with small differences in eccentricity, but not in group 2. Changes in apical power before and after lens use were significantly different between the two groups. CONCLUSION: The RCL was effective for the cornea of keratoconus, especially when the prescription was made with a small difference in eccentricity.

Identification and characterization of Acinetobacter nosocomialis BfmRS, two-component regulatory system, essential for biofilm development.

BACKGROUND: Biofilm development by bacteria is considered to be an essential stage in the bacterial infection. Acinetobacter nosocomialis is an important nosocomial pathogen causing a variety of human infections. However, characteristics and specific determinants of biofilm development have been poorly characterized in A. nosocomialis. OBJECTIVE: The aim of this study was to investigate the factors involved in the biofilm development by A. nosocomialis. METHODS: Library of random transposon mutants was constructed using the Tn5 mutagenesis. The mutant strains, in which the ability of biofilm formation was significantly impaired, were screened by gentian violet staining. The roles of BfmR and BfmS were determined by constructing a bfmR and bfmS deletion mutant and analyzing the effects of bfmR and bfmS mutation on the biofilm development and motility of A. nosocomialis. RESULTS: We identified a biofilm-defective mutant in which a transposon insertion inactivated an open reading frame encoding the BfmR in a two-component regulatory system consisting of BfmR and BfmS. The bfmR mutant revealed a significant reduction in biofilm formation and motility compared to wild-type strain. Deficiency in the biofilm formation and motility of the bfmR mutant was restored by single copy bfmR complementation. In contrast, the bfmS mutant had no effect on biofilm formation. CONCLUSION: A. nosocomialis has a two-component regulatory system, BfmRS. BfmR is a response regulator required for the initial attachment and maturation of biofilm during the biofilm development as well as the bacterial growth. BfmR could be a potential drug target for A. nosocomialis infection.

Assessment of Bone Marrow Involvement in B-Cell non-Hodgkin Lymphoma Using Immunoglobulin Gene Rearrangement Analysis with Next-Generation Sequencing.

BACKGROUND: Assessment of bone marrow involvement (BMI) in non-Hodgkin lymphoma (NHL) is crucial for determining patient prognosis and treatment strategy. We assessed the prognostic value of next-generation sequencing (NGS)-based immunoglobulin (Ig) gene clonality analysis as an ancillary test for BMI evaluation in NHL. METHODS: A retrospective cohort of 124 patients newly diagnosed with B-cell NHL between 2019 and 2022 was included. NGS-based Ig clonality analysis was conducted using LymphoTrak IGH FR1 Assay and IGK Assay (Invivoscribe Technologies, San Diego, CA, USA) on BM aspirate samples, and the results were compared with those of histopathological BMI (hBMI). RESULTS: Among the 124 patients, hBMI was detected in 16.9% (n = 21). The overall agreement of BMI between Ig clonality analyses and histopathological analysis for IGH, IGK, and either IGH or IGK was 86.3%, 92.7%, and 90.3%. The highest positive percent agreement was observed with clonal rearrangements of either IGH or IGK gene (90.5%), while the highest negative percent agreement was observed with clonal rearrangement of IGK gene (96.1%). For the prediction of hBMI, positive prediction value ranged between 59.1% and 80.0% and the negative prediction value ranged between 91.3% and 97.9%. CONCLUSION: NGS-based clonality analysis is an analytic platform with a substantial overall agreement with histopathological analysis. Assessment of both IGH and IGK genes for the clonal rearrangement analysis could be considered for the optimal diagnostic performance of BMI detection in B-cell NHL.

Risk stratification for early mortality in newly diagnosed acute promyelocytic leukemia: a multicenter, non-selected, retrospective cohort study.

Introduction: Despite the current effective treatments for acute promyelocytic leukemia (APL), early mortality (EM), defined as death within 30 days of presentation, is a major hurdle to long-term survival. Methods: We performed a multicenter retrospective study to evaluate the incidence and clinical characteristics of EM in patients with newly diagnosed APL and to develop a risk stratification model to predict EM. Results: We identified 313 eligible patients diagnosed between 2000 and 2021 from five academic hospitals. The median age was 50 years (range 19-94), and 250 (79.9%) patients were <65 years. Most patients (n=274, 87.5%) received their first dose of all-trans retinoic acid (ATRA) within 24 hours of presentation. EM occurred in 41 patients, with a cumulative incidence of 13.1%. The most common cause of EM was intracranial hemorrhage (n=22, 53.6%), and most EMs (31/41, 75.6%) occurred within the first seven days of APL presentation. In a multivariable analysis, we identified three independent factors predicting EM: age ≥65 years (HR, 2.56), white blood cell count ≥8.0 x 109/L (HR, 3.30), and ATRA administration >24 hours of presentation (HR, 2.95). Based on these factors, patients were stratified into three categories with a significantly increasing risk of EM: 4.1% for low risk (54.3%; no risk factors; HR 1), 18.5% for intermediate risk (34.5%; 1 factor; HR 4.81), and 40.5% for high risk (11.2%; 2-3 factors; HR 13.16). Discussion: The risk of EM is still not negligible in this era of ATRA-based therapies. Our risk model serves as a clinically useful tool to identify high-risk patients for EM who may be candidates for novel treatments and aggressive supportive strategies.

Clinical Outcomes and Indications of In-Office Sutureless Dried Gamma Ray-Sterilized Human Amniotic Membrane Transplantation With Bandage Contact Lenses in Various Ocular Surface Disorders.

PURPOSE: The purpose of this study was to investigate the efficacy and indications of using dried gamma ray-sterilized amniotic membrane (AM) transplantation with bandage contact lenses for the in-office sutureless treatment of various ocular surface diseases. METHODS: This study retrospectively included 56 eyes of 52 patients with various ocular surface diseases treated with sutureless dehydrated AM-assisted therapeutic contact lenses. The patients were followed up and assessed 1, 2, and 4 weeks after the treatment, and the therapeutic contact lenses were removed after 1 or 2 weeks. The size of the corneal lesion and the degree of pain experienced by each patient before and after the procedure were measured. Corneal re-epithelization rate and clinical aspects related to re-epithelialization were evaluated. RESULTS: Complete corneal re-epithelialization of the epithelial defect was observed in 40 eyes. The complete re-epithelialization rates of persistent epithelial defect caused by infectious ulcers, neurotrophic ulcers, ulcers due to burn, toxic keratopathy, previous penetrating keratoplasty or other corneal surgeries, and severe dry eye disease were 69.2%, 80.0%, 77.8%, 100%, 75.0%, and 100%, respectively. Five patients with uncontrolled infectious ulcers, neurotrophic ulcer, bullous keratopathy, and ulcers associated with rheumatic disease did not show significant improvement. Patient pain scores significantly decreased after the procedure. CONCLUSIONS: Dehydrated AM transplantation with a bandage contact lens is minimally invasive and easily applicable through in-office procedures. This approach is expected to be more actively applied in various ocular surface disorders, not only in severe corneal diseases but also in relatively mild corneal surface diseases.

Differences in Clinical Outcomes Between Hydroxyurea-Resistant and -Intolerant Polycythemia Vera Patients.

BACKGROUND: Previous studies have suggested that patients with polycythemia vera (PV) who exhibit hydroxyurea-resistance (HU-R) and -intolerance (HU-I) may have distinct characteristics and clinical outcomes. However, to date, no studies have reported a comparison between these two groups or assessed prognostic factors in these patients. METHODS: The objective of this study was to evaluate clinical outcomes and identify prognostic factors among PV patients with HU-R or HU-I. We conducted a review of PV patients who received frontline treatment with HU from nine centers and identified 90 patients with HU-R or HU-I. RESULTS: The cumulative incidence of thrombosis after 7 years of HU-R/I was 21.4%, and the incidence of disease progression was 22.5%. Comparing the HU-R and HU-I groups, the HU-R group had a significantly higher rate of disease progression (36.7% vs. 0.56%, P = 0.009), while there was no significant difference in thrombosis incidence (19.0% vs. 22.9%, P = 0.463). Multivariate analysis revealed that HU-R was an independent prognostic factor for progression-free survival (hazard ratio, 6.27, 95% confidence interval, 1.83-21.47, P = 0.003). Additionally, higher lactate dehydrogenase levels, multiple cardiovascular risk factors, and prior thrombosis were identified as unfavorable predictors of overall survival. CONCLUSION: These findings suggest that patients with HU-R face a higher risk of hematological transformation, but have a comparable risk of thrombosis to patients with HU intolerance. These distinctions should guide decisions on second-line treatment options and clinical trials involving these patients.

Clinical Evaluation of a Hydrophobic Intraocular Lens Using a Preloaded Automated Injector in a Korean Population.

Purpose: This study assessed post-market clinical outcomes of the Clareon monofocal intraocular lens (IOL) preloaded in the AutonoMe Delivery System in a real-world setting of Korean patients. Methods: This prospective, multicenter, single-arm study in Korea was conducted from July 2020 to December 2021. Patients were ≥20 years old with unilateral or bilateral cataracts who received Clareon IOLs (CNA0T0) preloaded in an automated injector system. Best corrected distance visual acuity (BCDVA) and uncorrected distance visual acuity (UCDVA) were evaluated under photopic conditions. Surgeon delivery system preference was assessed using a survey questionnaire. Glistenings, surface haze, adverse events, posterior capsule opacification (PCO), and Nd:YAG capsulotomy rates were also assessed during the 12-month postoperative follow-up. Results: Mean ± SD monocular BCDVA was 0.02 ± 0.11 and 0.00 ± 0.10 logMAR at 1 month and 12 months, respectively. BCDVA of 0.2 logMAR or better was achieved by 94.4% and 99.1% of eyes at 1 month and 12 months after implantation, respectively. Mean monocular UCDVA was 0.11 ± 0.14 and 0.07 ± 0.13 logMAR at 1 month and 12 months, respectively. UCDVA of 0.3 logMAR or better was achieved by 97.4% of eyes at 12 months after implantation. Preparation of the automated injector system was rated as "very easy" or "easy" and CNA0T0 IOL delivery was rated as "very controllable" or "controllable" by all surgeons. Only grade 0 glistenings and no surface haze were observed during the 12-month follow-up. No clinically significant PCO or Nd:YAG capsulotomy were reported throughout the study; clinically nonsignificant PCO was reported in 23% of eyes. Conclusion: This 12-month real-world study of the CNA0T0 IOL and the automated injector system demonstrated excellent visual outcomes and high surgeon satisfaction.

Long-Term Efficacy and Safety of Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria and High Disease Burden: Real-World Data From Korea.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder characterized by uncontrolled terminal complement activation. Eculizumab, a monoclonal antibody C5 inhibitor was introduced in Korea in 2009 and has been the standard treatment option for PNH. METHODS: This study assessed the long-term efficacy/safety of eculizumab in PNH using real-world data from the Korean Health Insurance Review and Assessment Service. Eighty patients who initiated eculizumab from 2009-2020 were enrolled. RESULTS: At eculizumab initiation, the median age was 51.5 years, lactate dehydrogenase (LDH) 6.8 × upper limit of normal, and granulocyte clone size 93.0%. All patients had at least one PNH-related complication before eculizumab initiation, including renal failure (n = 36), smooth muscle spasm (n = 24), thromboembolism (n = 20), and pulmonary hypertension (n = 15). The median (range) duration of eculizumab treatment was 52.7 (1.0, 127.3) months (338.6 total treated patient-years). Despite high disease activity in the study population before treatment initiation, overall survival was 96.2% and LDH levels were stabilized in most patients during treatment. PNH-related complications at treatment initiation were resolved in 44.4% of patients with renal failure, 95.8% with smooth muscle spasm, 70.0% with thromboembolism, and 26.7% with pulmonary hypertension. Extravascular hemolysis occurred in 28.8% of patients (n = 23; 0.09 per patient-year) and breakthrough hemolysis in 18.8% (n = 15; 0.06 per patient-year). No treatment discontinuation cases related to eculizumab were observed. CONCLUSION: These data provided evidence for the long-term efficacy and safety of eculizumab in Korean PNH patients with high disease burdens.

Cytomegalovirus reactivation under pre-emptive therapy following allogeneic hematopoietic stem cell transplant: Pattern, survival, and risk factors in the Republic of Korea.

INTRODUCTION: Pre-emptive therapy for cytomegalovirus (CMV) reactivation has been used in allogeneic hematopoietic stem cell transplantation (allo-HSCT). It is unclear if this strategy has poorer clinical outcomes in CMV-endemic areas and if more aggressive prophylaxis is required. METHODS: We retrospectively analyzed the patterns and survival after CMV reactivation in patients undergoing pre-emptive therapy following allo-HSCT and assessed high-risk patients who could benefit from aggressive CMV prophylaxis in endemic areas. RESULTS: Of the 292 patients who underwent allo-HSCT, 70.5% (donor+ or recipient+) were CMV seropositive. CMV reactivation occurred in 139 patients (47.6%), with a median of 31.5 days from day 0 of allo-HSCT. The overall survival of patients with CMV reactivation who received pre-emptive therapy did not differ from those without reactivation. Of the 139 patients with CMV reactivation, 78 (56.1%) underwent ≥2 rounds of pre-emptive therapy. In multivariate analysis, the risk of CMV reactivation was higher in patients with multiple myeloma, with CMV seropositivity of the recipient and donor, administered with a higher dose of anti-thymocyte globulin (ATG), and with acute graft-versus-host disease (aGVHD) ≥ grade 2. CONCLUSION: Although half of the patients with allo-HSCT were administered with pre-emptive therapy for CMV, CMV reactivation did not affect their survival, indicating the advantages of pre-emptive therapy, even in CMV-endemic areas. The cost-effectiveness of more aggressive CMV prophylaxis should be re-evaluated in patients at a high risk for CMV reactivation.

Management of classical Philadelphia chromosome-negative myeloproliferative neoplasms in Asia: consensus of the Asian Myeloid Working Group.

Myeloproliferative neoplasms (MPN) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized clinically by the proliferation of one or more hematopoietic lineage(s). The classical Philadelphia-chromosome (Ph)-negative MPNs include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The Asian Myeloid Working Group (AMWG) comprises representatives from fifteen Asian centers experienced in the management of MPN. This consensus from the AMWG aims to review the current evidence in the risk stratification and treatment of Ph-negative MPN, to identify management gaps for future improvement, and to offer pragmatic approaches for treatment commensurate with different levels of resources, drug availabilities and reimbursement policies in its constituent regions. The management of MPN should be patient-specific and based on accurate diagnostic and prognostic tools. In patients with PV, ET and early/prefibrotic PMF, symptoms and risk stratification will guide the need for early cytoreduction. In younger patients requiring cytoreduction and in those experiencing resistance or intolerance to hydroxyurea, recombinant interferon-α preparations (pegylated interferon-α 2A or ropeginterferon-α 2b) should be considered. In myelofibrosis, continuous risk assessment and symptom burden assessment are essential in guiding treatment selection. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in MF should always be based on accurate risk stratification for disease-risk and post-HSCT outcome. Management of classical Ph-negative MPN entails accurate diagnosis, cytogenetic and molecular evaluation, risk stratification, and treatment strategies that are outcome-oriented (curative, disease modification, improvement of quality-of-life).

Efficacy and safety of 1% and 2% rebamipide clear solution in dry eye disease: a multicenter randomized trial.

BACKGROUND: To evaluate the efficacy of 1% and 2% rebamipide clear solution in the treatment of dry eye disease (DED). METHODS: Two hundred twenty patients with DED were randomly assigned to one of three groups: the 1% rebamipide, 2% rebamipide, or placebo (eye drops containing the same ingredients, except for the active components). Each eye drop was instilled four times daily for 12 weeks. Changes in tear film break-up time (TBUT), corneal and conjunctival staining score, Schirmer 1 test, and the Ocular Surface Disease Index (OSDI) from baseline to 12-week visit between the study groups were compared for efficacy assessment. RESULTS: The mean age of study patients was 43.8±14.2 years. The 1% and 2% rebamipide groups showed greater improvement in TBUT (1.99±1.87 and 2.02±2.21 s) at 12 weeks from baseline than the placebo group (1.25±2.93 s). The 2% rebamipide group showed greater improvement in the corneal staining score (- 3.15±2.00) at 12 weeks from baseline than the placebo group (- 2.85±1.80). The 1% and 2% rebamipide groups showed improvement in Schirmer 1 test (1.27±3.86 and 1.50±4.14 mm) at 12 weeks of treatment, but not the placebo group (0.55±2.99 mm). Both the rebamipide groups and the placebo group showed significantly improved OSDI after treatment for 12 weeks; however, there was no significant difference among the three groups. CONCLUSIONS: 1% and 2% rebamipide clear solutions are an effective therapeutic option for improving TBUT and tear volume, and stabilizing the corneal staining score in DED.

Identification and overcoming rituximab resistance in diffuse large B-cell lymphoma using next-generation sequencing.

BACKGROUND/AIMS: Although rituximab, an antiCD20 monoclonal antibody, has dramatically improved the clinical outcomes of diffuse large B-cell lymphoma, rituximab resistance remains a challenge. METHODS: We developed a rituximab-resistant cell line (RRCL) by sequential exposure to gradually increasing concentrations of rituximab in a rituximab-sensitive cell line (RSCL). When the same dose of rituximab was administered, RRCL showed a smaller decrease in cell viability and apoptosis than RSCL. To determine the differences in gene expression between RSCL and RRCL, we performed next-generation sequencing. RESULTS: In total, 1,879 differentially expressed genes were identified, and in the over-representation analysis of Consensus-PathDB, mitogen-activated protein kinase (MAPK) signaling pathway showed statistical significance. MAPK13, which encodes the p38δ protein, was expressed more than four-fold in RRCL. Western blot analysis revealed that phosphop38 expression mainwas increased in RRCL, and when p38 inhibitor was administered, phosphop38 expression was significantly decreased. Therefore, we hypothesized that p38 MAPK activation was associated with rituximab resistance. Previous studies have suggested that p38 is associated with NF-κB activation. Deferasirox has been reported to inhibit NF-κB activity and suppress phosphorylation of the MAPK pathway. Furthermore, it also has cytotoxic effects on various cancers and synergistic effects in overcoming drug resistance. In this study, we confirmed that deferasirox induced dose-dependent cytotoxicity in both RSCL and RRCL, and the combination of deferasirox and rituximab showed a synergistic effect in RRCL at all combination concentrations. CONCLUSION: We suggest that p38 MAPK, especially p38δ, activation is associated with rituximab resistance, and deferasirox may be a candidate to overcome rituximab resistance.

Sesamin ameliorates lipotoxicity and lipid accumulation through the activation of the estrogen receptor alpha signaling pathway.

Nonalcoholic fatty liver disease (NAFLD) has been linked to fat accumulation in the liver and lipid metabolism imbalance. Sesamin, a lignan commonly found in sesame seed oil, possesses antioxidant, anti-inflammatory, and anticancer properties. However, the precise mechanisms by which sesamin prevents hepatic steatosis are not well understood. This study aimed to explore the molecular mechanisms by which sesamin may improve lipid metabolism dysregulation. A in vitro hepatic steatosis model was established by exposing HepG2 cells to palmitate sodium. The results showed that sesamin effectively mitigated lipotoxicity and reduced reactive oxygen species production. Additionally, sesamin suppressed lipid accumulation by regulating key factors involved in lipogenesis and lipolysis, such as fatty acid synthase (FASN), sterol regulatory element-binding protein 1c (SREBP-1c), forkhead box protein O-1, and adipose triglyceride lipase. Molecular docking results indicated that sesamin could bind to estrogen receptor α (ERα) and reduce FASN and SREBP-1c expression via the Ca2+/calmodulin-dependent protein kinase kinase ß (CaMKKß)/AMP-activated protein kinase (AMPK) signaling pathway. Sesamin attenuated palmitate-induced lipotoxicity and regulated hepatic lipid metabolism in HepG2 cells by activating the ERα/CaMKKß/AMPK signaling pathway. These findings suggest that sesamin can improve lipid metabolism disorders and is a promising candidate for treating hepatic steatosis.

Imaging Function and Relative Light Transmission of Explanted Opacified Hydrophilic Acrylic Intraocular Lenses.

We evaluated the influence of intraocular lens (IOL) opacification on the optical performance of explanted hydrophilic acrylic IOLs. We performed a laboratory analysis of 32 Lentis LS-502-1 (Oculentis GmbH, Berlin, Germany) IOLs, explanted due to opacification, in comparison with six clear unused samples of the same IOL model. Using an optical bench setup, we obtained modulation transfer function (MTF), Strehl ratio, two-dimensional MTF, and United States Air Force (USAF) chart images. In addition, we assessed light transmission through the IOLs. The MTF values of opacified IOLs at 3-mm aperture were similar to those of clear lenses, with the median (interquartile range) values of 0.74 (0.01) vs. 0.76 (0.03) at the spatial frequency of 50 line pairs per millimeter in clear and opacified IOLs, respectively. The Strehl ratio of opacified lenses was not lower than that of clear lenses. The USAF-chart analysis showed a considerable reduction in brightness in opacified IOLs. The median (interquartile range) relative light transmission of opacified IOLs in comparison to clear lenses was 55.6% (20.8%) at the aperture size of 3 mm. In conclusion, the explanted opacified IOLs had comparable MTF values to those of clear lenses but significantly reduced light transmission.