Lazertinib is an oral, third-generation, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for the treatment of non-small cell lung cancer (NSCLC). This case report presents a rare instance of small cell carcinoma transformation in pancreatic metastasis in a patient with EGFR-mutated NSCLC undergoing treatment with lazertinib. Small cell carcinoma transformation indicates a mechanism of treatment resistance, and tissue biopsy is essential to confirm this. When isolated progression of a lesion is suspected during TKI therapy in EGFR-mutated NSCLC, histological evaluation is necessary to confirm the transformation for the treatment strategy.

Objective: Previous studies have reported an association between cancer-related symptoms and perceived social support (PSS). The objective of this study was to analyze whether Chemotherapy-Induced Peripheral Neuropathy (CIPN), a prevalent side effect of chemotherapy, varies according to PSS level using a validated tool for CIPN at prospective follow-up. Methods: A total of 39 breast cancer patients were evaluated for PSS using the Multidimensional Scale of Perceived Social Support (MSPSS) prior to chemotherapy and were subsequently grouped into one of two categories for each subscale: low-to-moderate PSS and high PSS. CIPN was prospectively evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN20) at five time points. A linear mixed-effects model with square root transformation was employed to investigate whether the CIPN20 scales varied by PSS level and time point. Results: Statistical analysis of the MSPSS total scale and subscales revealed a significant effect of the friends subscale group and time point on the CIPN20 sensory scale. The sensory scale score of CIPN20 was found to be lower in participants with high PSS from friends in comparison to those with low-to-moderate PSS at 1 month post-chemotherapy (p=0.010). Conclusion This is the first study to prospectively follow the long-term effect of pre-treatment PSS from friends on CIPN. Further studies based on larger samples are required to analyze the effects of PSS on the pathophysiology of CIPN.

Objective: Non-pharmacological interventions (NPIs) are effective in treating gaming disorder (GD). However, studies have not comprehensively evaluated the most effective NPIs. This systematic review and meta-analysis aimed to evaluate the effects of NPIs on the prevention and reduction of GD in the general population with GD. Methods: We searched five databases (MEDLINE, Embase, Cochrane CENTRAL, PsycINFO, and CINAHL) for English-language randomized controlled trials (RCTs) published till May 12, 2024, using Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Two independent reviewers selected studies, extracted data, and assessed quality using the Cochrane Risk of Bias Tool (RoB2). Meta-analyses were conducted using a random-effect model, with effect sizes calculated using Hedges’s g and heterogeneity assessed using I2 statistics. Results: A total of 18 RCTs involving 1,950 participants were included. The NPIs included psychotherapy, behavioral interventions, and other strategies. The pooled analysis showed a significant reduction in GD severity (Hedges’s g=-0.82; 95% confidence interval, -1.23 to -0.52; I2=90.36%). Psychotherapy, particularly cognitive-behavioral therapy, showed the most substantial effect (10 studies, 1,036 participants; Hedges’s g=-1.34). Behavioral interventions (4 studies, 456 participants) and prevention-focused interventions (6 studies, 1,164 participants) had smaller but positive effects. Subgroup analyses revealed greater effectiveness of treatment interventions in adults than in adolescents. Sensitivity analyses confirmed the robustness of these results despite high heterogeneity (I2=90.36%). Conclusion NPIs, particularly psychotherapy, are effective in reducing GD severity. However, more high-quality RCTs are needed robust, evidence-based treatment guidelines.

Purpose: The associated factors for hypertensive retinopathy (HTR) are rarely investigated. This study aimed to identify the associated factors for HTR using a systematic review. Methods: The review included cross-sectional, case-controlled, and cohort studies on HTR risk factors published in Korean and English with full texts available from PubMed, Embase, CINAHL, Web of Science, and Korean databases. Methodological quality was assessed using the Joanna Briggs Institute (JBI) checklist. Results: Eleven studies were finally selected, and three studies including patients with hypertension without diabetes mellitus, older age, male sex, alcohol consumption, the duration of hypertension, hyperglycemia, dyslipidemia, microalbuminuria, high creatinine levels, chronic kidney disease, and cardiovascular changes were identified as factors associated with HTR. Conversely, in the remaining eight studies, younger age, non-smoking status, and renal function indicators (albuminuria, high creatinine levels, chronic kidney disease, and uric acid) were identified as associated factors. Conclusions Regardless of the inclusion of patients with diabetes mellitus, impaired kidney functions were determined as significant factors associated with retinopathy in patients with HTR. However, considering a limited number of evidence and lack of evidence to confirm causality, we recommend further research on renal function and HTR.

The brain’s substantial metabolic requirements, consuming a substantial fraction of the body’s total energy despite its relatively small mass, necessitate sophisticated metabolic mechanisms for efficient energy distribution and utilization.The astrocyte-neuron lactate shuttle (ANLS) hypothesis has emerged as a fundamental framework explaining the metabolic cooperation between astrocytes and neurons, whereby astrocyte-derived lactate serves as a crucial energy substrate for neurons. This review synthesizes current understanding of brain energy metabolism, focusing on the dual roles of lactate as both an energy substrate and a signaling molecule. We examine the molecular underpinnings of metabolic compartmentalization, particularly the differential expression of lactate dehydrogenase (LDH) isozymes between astrocytes and neurons, which facilitates directional lactate flux. Recent evidence has challenged aspects of the classical ANLS model, revealing greater metabolic flexibility in neurons than previously recognized, including substantial LDHA expression and direct glucose utilization capabilities. Our recent studies on LDHB-deficient neurons provide new insights into the compensatory mechanisms and limitations of neuronal lactate metabolism, suggesting a more nuanced understanding of the ANLS hypothesis. Furthermore, we discuss lactate’s emerging role as a signaling molecule in synaptic plasticity, memory formation, and neuroprotection, particularly in ischemic conditions where elevated lactate levels correlate with enhanced neuronal survival through prostaglandin E 2 -mediated vasodilation. This comprehensive review integrates classical perspectives with recent advances, providing an updated framework for understanding brain lactate metabolism and its therapeutic implications in neurological disorders.

Purpose: Rare diseases occur in <50 per 100000 people and require lifelong management. However, essential epidemiological data on such diseases are lacking, and a consecutive monitoring system across time and regions remains to be established. Standardized digital phenotypes are required to leverage an international data network for research on rare endocrine diseases. We developed digital phenotypes for rare endocrine diseases using the observational medical outcome partnership common data model. Materials and Methods: Digital phenotypes of three rare endocrine diseases (medullary thyroid cancer, hypoparathyroidism, pheochromocytoma/paraganglioma) were validated across three databases that use different vocabularies: Severance Hospital’s electronic health record from South Korea; IQVIA’s United Kingdom (UK) database for general practitioners; and IQVIA’s United States (US) hospital database for general hospitals. We estimated the performance of different digital phenotyping methods based on International Classification of Diseases (ICD)-10 in the UK and the US or systematized nomenclature of medicine clinical terms (SNOMED CT) in Korea. Results: The positive predictive value of digital phenotyping was higher using SNOMED CT-based phenotyping than ICD-10-based phenotyping for all three diseases in Korea (e.g., pheochromocytoma/paraganglioma: ICD-10, 58%–62%; SNOMED CT, 89%). Estimated incidence rates by digital phenotyping were as follows: medullary thyroid cancer, 0.34–2.07 (Korea), 0.13–0.30 (US); hypoparathyroidism, 0.40–1.20 (Korea), 0.59–1.01 (US), 0.00–1.78 (UK); and pheochromocytoma/paraganglioma, 0.95–1.67 (Korea), 0.35–0.77 (US), 0.00–0.49 (UK). Conclusion Our findings demonstrate the feasibility of developing digital phenotyping of rare endocrine diseases and highlight the importance of implementing SNOMED CT in routine clinical practice to provide granularity for research.

Background: Complete revascularization has demonstrated better outcomes in patients with acute myocardial infarction (AMI) and multivessel disease. However, in the case of left main (LM) culprit lesion AMI with multivessel disease, there is limited evidence to suggest that complete revascularization is better. Methods: We reviewed 16,831 patients in the Korea Acute Myocardial Infarction Registry who were treated from July 2016 to June 2020, and 399 patients were enrolled with LM culprit lesion AMI treated with percutaneous coronary intervention. We categorized the patients as those treated with complete revascularization (n=295) or incomplete revascularization (n=104). The study endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction, ischemia-driven revascularization, stent thrombosis, and stroke. We performed propensity score matching (PSM) and analyzed the incidence of MACCE at 1 year. Results: After PSM, the two groups were well balanced. There was no significant difference between the two groups in MACCE at 1 year (12.1% vs. 15.2%; hazard ratio, 1.28; 95% confidence interval, 0.60–2.74; p=0.524) after PSM. The components of MACCE and major bleeding were also not significantly different. Conclusion There was no significant difference in clinical outcomes between the groups treated with complete or incomplete revascularization for LM culprit lesion AMI with multivessel disease.

Objective: Previous studies have reported an association between cancer-related symptoms and perceived social support (PSS). The objective of this study was to analyze whether Chemotherapy-Induced Peripheral Neuropathy (CIPN), a prevalent side effect of chemotherapy, varies according to PSS level using a validated tool for CIPN at prospective follow-up. Methods: A total of 39 breast cancer patients were evaluated for PSS using the Multidimensional Scale of Perceived Social Support (MSPSS) prior to chemotherapy and were subsequently grouped into one of two categories for each subscale: low-to-moderate PSS and high PSS. CIPN was prospectively evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN20) at five time points. A linear mixed-effects model with square root transformation was employed to investigate whether the CIPN20 scales varied by PSS level and time point. Results: Statistical analysis of the MSPSS total scale and subscales revealed a significant effect of the friends subscale group and time point on the CIPN20 sensory scale. The sensory scale score of CIPN20 was found to be lower in participants with high PSS from friends in comparison to those with low-to-moderate PSS at 1 month post-chemotherapy (p=0.010). Conclusion This is the first study to prospectively follow the long-term effect of pre-treatment PSS from friends on CIPN. Further studies based on larger samples are required to analyze the effects of PSS on the pathophysiology of CIPN.

Objective: Non-pharmacological interventions (NPIs) are effective in treating gaming disorder (GD). However, studies have not comprehensively evaluated the most effective NPIs. This systematic review and meta-analysis aimed to evaluate the effects of NPIs on the prevention and reduction of GD in the general population with GD. Methods: We searched five databases (MEDLINE, Embase, Cochrane CENTRAL, PsycINFO, and CINAHL) for English-language randomized controlled trials (RCTs) published till May 12, 2024, using Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Two independent reviewers selected studies, extracted data, and assessed quality using the Cochrane Risk of Bias Tool (RoB2). Meta-analyses were conducted using a random-effect model, with effect sizes calculated using Hedges’s g and heterogeneity assessed using I2 statistics. Results: A total of 18 RCTs involving 1,950 participants were included. The NPIs included psychotherapy, behavioral interventions, and other strategies. The pooled analysis showed a significant reduction in GD severity (Hedges’s g=-0.82; 95% confidence interval, -1.23 to -0.52; I2=90.36%). Psychotherapy, particularly cognitive-behavioral therapy, showed the most substantial effect (10 studies, 1,036 participants; Hedges’s g=-1.34). Behavioral interventions (4 studies, 456 participants) and prevention-focused interventions (6 studies, 1,164 participants) had smaller but positive effects. Subgroup analyses revealed greater effectiveness of treatment interventions in adults than in adolescents. Sensitivity analyses confirmed the robustness of these results despite high heterogeneity (I2=90.36%). Conclusion NPIs, particularly psychotherapy, are effective in reducing GD severity. However, more high-quality RCTs are needed robust, evidence-based treatment guidelines.