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Real-world clinical practice and outcomes in treating stage III non-small cell lung cancer: KINDLE-Asia subset
Get PDFIntroduction: Stage III non-small cell lung cancer (NSCLC) is a heterogeneous disease requiring multimodal treatment approaches. KINDLE-Asia, as part of a real world global study, evaluated treatment patterns and associated survival outcomes in stage III NSCLC in Asia.
Methods: Retrospective data from 57 centers in patients with stage III NSCLC diagnosed between January 2013 and December 2017 were analyzed. Median progression free survival (mPFS) and median overall survival (mOS) estimates with two sided 95% confidence interval (CI) were determined by applying the Kaplan-Meier survival analysis.
Results: Of the total 1874 patients (median age: 63.0 years [24 to 92]) enrolled in the Asia subset, 74.8% were men, 54.7% had stage IIIA disease, 55.7% had adenocarcinoma, 34.3% had epidermal growth factor receptor mutations (EGFRm) and 50.3% had programmed death-ligand 1 (PD-L1) expression (i.e. PD-L1 ≥1%). Of the 31 treatment approaches as initial therapy, concurrent chemoradiotherapy (CRT) was the most frequent (29.3%), followed by chemotherapy (14.8%), sequential CRT (9.5%), and radiotherapy (8.5%). Targeted therapy alone was used in 81 patients of the overall population. For the Asia cohort, the mPFS and mOS were 12.8 months (95% CI, 12.2-13.7) and 42.3 months (95% CI, 38.1-46.8), respectively. Stage IIIA disease, Eastern Cooperative Oncology Group ≤1, age ≤65 years, adenocarcinoma histology and surgery/concurrent CRT as initial therapy correlated with better mOS (p < 0.05).
Conclusions: The results demonstrate diverse treatment patterns and survival outcomes in the Asian region. The high prevalence of EGFRm and PD-L1 expression in stage III NSCLC in Asia suggests the need for expanding access to molecular testing for guiding treatment strategies with tyrosine kinase inhibitors and immunotherapies in this region.ope
Increased expression of sodium-glucose cotransporter 2 and O-GlcNAcylation in hepatocytes drives non-alcoholic steatohepatitis
No full textAims: Steatosis reducing effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in non-alcoholic steatohepatitis (NASH) has been consistently reported in humans, but their mechanism remains uncertain. In this study, we examined the expression of SGLT2 in human livers and investigated the crosstalk between SGLT2 inhibition and hepatic glucose uptake, intracellular O-GlcNAcylation, and autophagic regulation in NASH.
Materials and methods: Human liver samples obtained from subjects with/without NASH were analyzed. For in vitro studies, human normal hepatocytes and hepatoma cells were treated with SGLT2 inhibitor under high-glucose and high-lipid conditions. NASH in vivo was induced by a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day).
Results: Liver samples from subjects with NASH were associated with increased SGLT2 and O-GlcNAcylation expression compared with controls. Under NASH condition (in vitro condition with high glucose and lipid), intracellular O-GlcNAcylation and inflammatory markers were increased in hepatocytes and SGLT2 expression was upregulated; SGLT2 inhibitor treatment blocked these changes by directly reducing hepatocellular glucose uptake. In addition, decreased intracellular O-GlcNAcylation by SGLT2 inhibitor promoted autophagic flux through AMPK-TFEB activation. In the AMLN diet-induced NASH mice model, SGLT2 inhibitor alleviated lipid accumulation, inflammation, and fibrosis through autophagy activation related to decreased SGLT2 expression and O-GlcNAcylation in the liver.
Conclusions: This study firstly demonstrates increased SGLT2 expression in NASH and secondly reveals the novel effect of SGLT2 inhibition on NASH through autophagy activation mediated by inhibition of hepatocellular glucose uptake and consequently decreased intracellular O-GlcNAcylation.restrictio
Major clinical research advances in gynecologic cancer in 2022: highlight on late-line PARP inhibitor withdrawal in ovarian cancer, the impact of ARIEL-4, and SOLO-3
Get PDFIn the 2022 series, we summarized the major clinical research advances in gynecologiconcology based on communications at the conference of Asian Society of GynecologicOncology Review Course. The review consisted of 1) Ovarian cancer: long-term follow-updata, new poly (ADP-ribose) polymerase (PARP) inhibitors, overall sur vival (OS) issues withPARP inhibitor monotherapy, hyperthermic intraperitoneal chemotherapy, immunotherapy,and antibody-drug conjugate; 2) Cer vical cancer: surger y in early stage disease, therapyfor locally advanced stage and advanced, metastatic, or recurrent setting; and 3) Corpuscancer: follow-up regimen, immune checkpoint inhibitor, WEE1 inhibitor, selective inhibitorof nuclear export. A special note was made on the withdrawal of PARP inhibitor from themarket for heavily pretreated ovarian cancer patients based on the final OS results of ARIEL-4and SOLO-3 due to concerns of increased risk of death.ope
Nodular mass in the nasal columella of a 15-year-old girl
No full text[No abstract available]restrictio
Korean Society of Endourology and Robotics (KSER) recommendation on the diagnosis, treatment, and prevention of urolithiasis
Get PDFThis article provides evidence-based recommendations and expert opinions to aid urologists in making optimal decisions regarding managing urolithiasis in various clinical scenarios. The most frequently asked questions by urologists in their clinical practice have been collected and answered in the form of FAQs; based on the latest evidence and expert opinions. The natural history of urolithiasis is divided into active treatment and silent phases, with the active treatment stage divided into typical and special situations and peri-treatment management. The authors address 28 key questions, offering practical guidance for the proper diagnosis, treatment, and prevention of urolithiasis in clinical practice. This article is expected to be served as a valuable resource for urologists.ope
Oxidative balance score is inversely associated with the incidence of non-alcoholic fatty liver disease
No full textBackground & aims: The contribution of the balance between overall oxidative stress and antioxidant status in non-alcoholic fatty liver disease (NAFLD) is unclear. The oxidative balance score (OBS) comprises dietary and lifestyle pro- and antioxidant components that indicate the overall oxidative stress burden. We investigated the association between OBS and the incidence of NAFLD in middle-aged and older Korean adults.
Methods: Among the 10,030 participants of the Korean Genome and Epidemiology Study_Ansan and Ansung cohort, 5065 without NAFLD at baseline were selected for secondary analysis. OBS was categorized into quartiles. Multiple Cox proportional hazard regression analyses were performed to estimate the hazard ratio (HR) and 95% confidence interval (CI) for NAFLD incidence by sex-specific OBS quartile groups after adjusting for confounders.
Results: During the follow-up period (median 13.4 years), 913 (43.2%) men and 1288 (43.9%) women were newly diagnosed with NAFLD. Compared with that of the lowest quartile (Q1) group, the adjusted HR (95% CI) for NAFLD incidence in Q2, Q3, and Q4 groups was 0.85 (0.71-1.00), 0.65 (0.54-0.78), and 0.50 (0.40-0.62) in men, and 0.85 (0.73-0.99), 0.66 (0.56-0.77), and 0.48 (0.40-0.59) in women, respectively, and for NAFLD incidence, per incremental change in OBS, was 0.90 (0.87-0.92) in men and 0.88 (0.86-0.90) in women.
Conclusions: A higher OBS was significantly associated with a lower risk for NAFLD incidence. Maintaining a healthy lifestyle and an antioxidant-rich diet is a potentially viable strategy for preventing NAFLD.restrictio
Asia-Pacific Consensus Recommendations on X-Linked Hypophosphatemia: Diagnosis, Multidisciplinary Management, and Transition From Pediatric to Adult Care
Get PDFX-linked hypophosphatemia (XLH) is a rare, inherited, multisystem disorder characterized by hypophosphatemia that occurs secondary to renal phosphate wasting. Mutations in PHEX gene (located at Xp22.1) in XLH alter bone mineral metabolism, resulting in diverse skeletal, dental, and other extraskeletal abnormalities that become evident in early childhood and persist into adolescence and adult life. XLH impacts physical function, mobility, and quality of life, and is associated with substantial socioeconomic burden and health care resource utilization. As the burden of illness varies with age, an appropriate transition of care from childhood and adolescence to adulthood is necessary to meet growth-related changes and minimize long-term sequelae of the condition. Previous XLH guidelines that encompassed transition of care have focused on Western experience. Regional differences in resource availability warrant tailoring of recommendations to the Asia-Pacific (APAC) context. Hence, a core expert panel of 15 pediatric and adult endocrinologists from nine countries/regions across APAC convened to formulate evidence-based recommendations for optimizing XLH care. A comprehensive literature search on PubMed using MeSH and free-text terms relevant to predetermined clinical questions on diagnosis, multidisciplinary management, and transition of care of XLH revealed 2171 abstracts. The abstracts were reviewed independently by two authors to shortlist a final of 164 articles. A total of 92 full-text articles were finally selected for data extraction and drafting the consensus statements. Sixteen guiding statements were developed based on review of evidence and real-world clinical experience. The GRADE criteria were used to appraise the quality of evidence supporting the statements. Subsequently, a Delphi technique was utilized to rate the agreement on statements; 38 XLH experts (15 core, 20 additional, 3 international) from 15 countries/regions (12 APAC, 3 EU) participated in the Delphi voting to further refine the statements. Statements 1-3 cover the screening and diagnosis of pediatric and adult XLH; we have defined the clinical, imaging, biochemical, and genetic criteria and raised red flags for the presumptive and confirmatory diagnosis of XLH. Statements 4-12 tackle elements of multidisciplinary management in XLH such as therapeutic goals and options, composition of the multidisciplinary team, follow-up assessments, required monitoring schedules, and the role of telemedicine. Treatment with active vitamin D, oral phosphate, and burosumab is discussed in terms of applicability to APAC settings. We also expound on multidisciplinary care for different age groups (children, adolescents, adults) and pregnant or lactating women. Statements 13-15 address facets of the transition from pediatric to adult care: targets and timelines, roles and responsibilities of stakeholders, and process flow. We explain the use of validated questionnaires, desirable characteristics of a transition care clinic, and important components of a transfer letter. Lastly, strategies to improve XLH education to the medical community are also elaborated in statement 16. Overall, optimized care for XLH patients requires prompt diagnosis, timely multidisciplinary care, and a seamless transfer of care through the coordinated effort of pediatric and adult health care providers, nurse practitioners, parents or caregivers, and patients. To achieve this end, we provide specific guidance for clinical practice in APAC settings. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.ope
Development of Competencies for New Nurses and Verification of Content Validity through a Delphi Survey
Get PDFThe purpose of this study was to develop and validate a competency tool for new nurses and to pilot-test it with new nurses. A Delphi survey was conducted to develop a competency tool, and a self-evaluation was conducted among new nurses who pilot-tested the finally derived competencies. The Delphi survey panel consisted of 18 people, including adjunct professors at the College of Nursing, nursing managers, and nurses with master’s degrees. The Delphi survey asked about the validity of the competencies constructed in two rounds. After analyzing the Delphi results with mean, standard deviation, content validity ratio, degrees of convergence, and degrees of consensus, 12 core competencies and 36 enabling competencies were finally derived. The competencies consisted of clinical judgment and management (nine items), task competence (four items), patient orientation (five items), moral value orientation (three items), cooperation (two items), supply management (two items), professional development (three items), confidence (one item), self-control (two items), flexibility (two items), influence (one item), and nurturing others (two items). The finally derived competencies were pilot-tested with 229 new nurses who had worked for 2–12 months. The self-evaluation scores of new nurses were distributed differently according to their working period. In this study, the competencies required for new nurses were identified and the corresponding enabling competencies were identified. In the future, it is expected that a competency-based education program will be prepared based on these findings, and furthermore, it will be possible to provide high-quality medical and nursing services that meet patients’ needs by improving the competency of new nurses and lowering the turnover rate.ope
Clinical utility of a plasma-based comprehensive genomic profiling test in patients with non-small cell lung cancer in Korea
Get PDFObjectives: Plasma-based comprehensive circulating cell-free DNA (cfDNA) next generation sequencing (NGS) has shown utility in advanced non-small cell lung cancer (aNSCLC). The aim of this study was to determine the feasibility of cfDNA-based NGS to identify actionable gene alterations in patients with aNSCLC. Patients and methods: This single-center non-interventional retrospective study evaluated Korean patients with biopsy-confirmed stage III/IV non-squamous aNSCLC. Tissue biopsy samples were collected at baseline, and/or at progression and analysed with Standard of Care (SOC) testing; cfDNA was analyzed by NGS in some patients concurrently. Results: aNSCLC patients with cfDNA test results (n = 405) were categorized into three groups: treatment naïve (n = 182), progressive aNSCLC after chemotherapy and/or immunotherapy (n = 157), and progressive aNSCLC after tyrosine kinase inhibitors (TKIs) (n = 66). Clinically informative driver mutations were identified for 63.5% of patients which were classified as OncoKB Tiers 1 (44.2%), 2 (3.4%), tier 3 (18.9%), and 4 (33.5%). Concordance between cfDNA NGS and tissue SOC methods for concurrently collected tissue samples (n = 221) with common EGFR mutations or ALK/ROS1 fusions was 96.9%. cfDNA analysis identified tumor genomic alterations in 13 patients that were unidentified with tissue testing, enabling initiation of targeted treatment. Conclusions: In clinical practice, results of cfDNA NGS are highly concordant with those of tissue SOC testing in aNSCLC patients. Plasma analysis identified actionable alterations that were missed or not evaluated by tissue testing, enabling the initiation of targeted therapy. Results from this study add to the body of evidence in the support routine use of cfDNA NGS for patients with aNSCLC. © 2023 The Author(s)ope
The Impact of Persistent Noise Exposure under Inflammatory Conditions
Get PDFThe aim of this study was to investigate the impact of noise exposure in an intensive care unit (ICU) environment on the development of postoperative delirium in a mouse model that mimics the ICU environment. Additionally, we aimed to identify the underlying mechanisms contributing to delirium and provide evidence for reducing the risk of delirium. In this study, to mimic an ICU environment, lipopolysaccharide (LPS)-injected sepsis mouse models were exposed to a 75 dB noise condition. Furthermore, we assessed neurobehavioral function and observed the level of neuroinflammatory response and blood-brain barrier (BBB) integrity in the hippocampal region. The LPS-injected sepsis mouse model exposed to noise exhibited increased anxiety-like behavior and cognitive impairment. Moreover, severe neuroinflammation and BBB disruption were detected in the hippocampal region. This study provides insights suggesting that persistent noise exposure under systemic inflammatory conditions may cause cognitive dysfunction and anxiety- like behavior via the mediation of BBB disruption and neuroinflammation. As a result, we suggest that the detailed regulation of noise exposure may be required to prevent the development of postoperative delirium.ope