Determination of 16 ultraviolet-absorbing compounds in marine invertebrates by using LC-USI-MS/MS coupled with QuEChERS.

In this study, we examined multiple endocrine-disrupting ultraviolet-absorbing compounds (UVACs) in marine invertebrates used in personal care products and packaging. Modified QuEChERS and liquid chromatography UniSpray ionization tandem mass spectrometry were used to identify 16 UVACs in marine invertebrates. Matrix-matched calibration curves revealed high linearity (r ≥ 0.9929), with limits of detection and quantification of 0.006-1.000 and 0.020-3.000 ng/g w.w., respectively. In oysters, intraday and interday analyses revealed acceptable accuracy (93%-120%) and precision (≤18%), except for benzophenone (BP) and ethylhexyl 4-(dimethylamino) benzoate. Analysis of 100 marine invertebrate samples revealed detection frequencies of 100%, 98%, 89%, 64%, and 100% for BP, 4-hydroxybenzophenone, 4-methylbenzophenone, 4-methylbenzylidene camphor, and benzophenone-3 (BP-3), respectively. BP and BP-3 were detected at concentrations of 4.40-27.39 and < 0.020-0.560 ng/g w.w., respectively, indicating their widespread presence. Overall, our proposed method successfully detected UVACs in marine invertebrates, raising concerns regarding their potential environmental and health effects.

Leveraging a Longitudinally Linked Dataset to Assess Recurrence of Severe Maternal Morbidity.

OBJECTIVES: Among those with a severe maternal morbidity (SMM) event and a subsequent birth, we examined how the risk of a second SMM event varied by patient characteristics and intrapartum hospital utilization. METHODS: We used a Massachusetts population-based dataset that longitudinally linked in-state births, hospital discharge records, prior and subsequent births, and non-birth-related hospital utilizations for birthing individuals and their children from January 1, 1999, to December 31, 2018, representing 1,460,514 births by 907,530 birthing people. We restricted our study sample to 2,814 people who had their first SMM event associated with a singleton birth and gave birth a second time within the study period. Our outcome measure was recurrence of SMM in the second birth. We calculated the prevalence of SMM at second birth, compared SMM conditions between births, and estimated the adjusted risk ratios and 95% confidence intervals for having an SMM event at second birth among those who had an SMM at the first birth. We also examined overall hospital utilization including inpatient admissions, emergency room visits, and observational stays, and hospital utilization by interpregnancy intervals (IPIs) between the first and second birth. RESULTS: There were 2,814 birthing people with at least one birth after the first SMM singleton birth. Among those, 198 (7.0%) had a subsequent SMM. The percentage of people with a second SMM event varied by age, race/ethnicity, insurance, IPI, and history of hypertension at first case of SMM (all p < .05). Between births, people with a second SMM event had significantly higher proportions of inpatient admissions (60.1% vs. 33.2.0%; p < .001), emergency room visits (71.7% vs. 57.7%; p < .001), and observational stays (35.4% vs. 19.5%; p < .001) compared with those who did not experience a second SMM event. CONCLUSION: Hospital utilization after a birth with SMM might indicate an elevated risk of a second SMM event. Providers should counsel their patients about prevention and warning signs.

The Clinical Characteristics and Manifestation of Anxious Depression Among Patients With Major Depressive Disorders-Results From a Taiwan Multicenter Study.

OBJECTIVE: Anxious depression is a prevalent characteristic observed in Asian psychiatric patients diagnosed with major depressive disorder (MDD). This study aims to investigate the prevalence and clinical presentation of anxious depression in Taiwanese individuals diagnosed with MDD. METHODS: We recruited psychiatric outpatients aged over 18 who had been diagnosed with MDD through clinical interviews. This recruitment took place at five hospitals located in northern Taiwan. We gathered baseline clinical and demographic information from the participants. Anxious depression was identified using a threshold of an anxiety/somatization factor score ≥7 on the 21-item Hamilton Rating Scale for Depression (HAM-D). RESULTS: In our study of 399 patients (84.21% female), 64.16% met the criteria for anxious depression. They tended to be older, married, less educated, with more children, and an older age of onset. Anxious depression patients had higher HAM-D and Clinical Global Impression-Severity scale score, more panic disorder (without agoraphobia), and exhibited symptoms like agitation, irritability, concentration difficulties, psychological and somatic anxiety, somatic complaints, hypochondriasis, weight loss, and increased insight. Surprisingly, their suicide rates did not significantly differ from non-anxious depression patients. This highlights the importance of recognizing and addressing these unique characteristics. CONCLUSION: Our study findings unveiled that the prevalence of anxious depression among Taiwanese outpatients diagnosed with MDD was lower compared to inpatients but substantially higher than the reported rates in European countries and the United States. Furthermore, patients with anxious depression exhibited a greater occurrence of somatic symptoms.

Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference.

INTRODUCTION: The apolipoprotein E gene (APOE) is an established central player in the pathogenesis of Alzheimer's disease (AD), with distinct apoE isoforms exerting diverse effects. apoE influences not only amyloid-beta and tau pathologies but also lipid and energy metabolism, neuroinflammation, cerebral vascular health, and sex-dependent disease manifestations. Furthermore, ancestral background may significantly impact the link between APOE and AD, underscoring the need for more inclusive research. METHODS: In 2023, the Alzheimer's Association convened multidisciplinary researchers at the "AAIC Advancements: APOE" conference to discuss various topics, including apoE isoforms and their roles in AD pathogenesis, progress in apoE-targeted therapeutic strategies, updates on disease models and interventions that modulate apoE expression and function. RESULTS: This manuscript presents highlights from the conference and provides an overview of opportunities for further research in the field. DISCUSSION: Understanding apoE's multifaceted roles in AD pathogenesis will help develop targeted interventions for AD and advance the field of AD precision medicine. HIGHLIGHTS: APOE is a central player in the pathogenesis of Alzheimer's disease. APOE exerts a numerous effects throughout the brain on amyloid-beta, tau, and other pathways. The AAIC Advancements: APOE conference encouraged discussions and collaborations on understanding the role of APOE.

GDF-15 Attenuates the Epithelium-Mesenchymal Transition and Alleviates TGFß2-Induced Lens Opacity.

Purpose: We sought to evaluate the efficacy of growth differentiation factor (GDF)-15 treatment for suppressing epithelial-mesenchymal transition (EMT) and alleviating transforming growth factor ß2 (TGFß2)-induced lens opacity. Methods: To test whether GDF-15 is a molecule that prevents EMT, we pretreated the culture with GDF-15 in neural progenitor cells, retinal pigment epithelial cells, and lens epithelial cells and then treated with factors that promote EMT, GDF-11, and TGFß2, respectively. To further investigate the efficacy of GDF-15 on alleviating lens opacity, we used mouse lens explant culture to mimic secondary cataracts. We pretreated the lens culture with GDF-15 and then added TGFß2 to develop lens opacity (n = 3 for each group). Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to measure EMT protein and gene expression, respectively. Results: In cell culture, GDF-15 pretreatment significantly attenuated EMT marker expression in cultured cells induced by treatment with GDF-11 or TGFß2. In the lens explant culture, GDF-15 pretreatment also reduced mouse lens opacity induced by exposure to TGFß2. Conclusions: Our results indicate that GDF-15 could alleviate TGFß2-induced EMT and is a potential therapeutic agent to slow or prevent posterior capsular opacification (PCO) progression after cataract surgery. Translational Relevance: Cataracts are the leading cause of blindness worldwide, with the only current treatment involving surgical removal of the lens and replacement with an artificial lens. However, PCO, also known as secondary cataract, is a common complication after cataract surgery. The development of an adjuvant that slows the progression of PCO will be beneficial to the field of anterior complications.

Recommendations and guidance for herpes zoster vaccination for adults in Taiwan.

Herpes zoster (HZ) is a painful, vesicular, cutaneous eruption from reactivation of varicella zoster virus (VZV), which can lead to potentially debilitating complications. The lifetime risk of HZ is estimated to be 20%-30% in the general population, with an increased risk in the elderly and immunocompromised populations. The most effective strategy to prevent HZ and its complications is by vaccination. Two types of HZ vaccines, zoster vaccine live and recombinant zoster vaccine, have been approved for use. This guidance offers recommendations and suggestions for HZ vaccination in adults, aiming to reduce the disease burden of HZ and its complications. It is intended as a guide to first-line healthcare providers, but does not supersede clinical judgement when assessing risk and providing recommendations to individuals. The Working Group on Adult Immunization Practice was appointed by the Infectious Diseases Society of Taiwan (IDST) and recommendations were drafted after a full literature review, using the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. The recommendations were reviewed and revised by expert review panels during a series of consensus meetings and endorsed by the IDST, Taiwan Association of Family Medicine, the Taiwanese Dermatological Association, the Taiwan Oncology Society, the Taiwan Society of Blood and Marrow Transplantation, the Transplantation Society of Taiwan, the Taiwan AIDS Society, and the Taiwan College of Rheumatology. This guidance describes the epidemiology of HZ and provides recommendations for HZ vaccination in adults with varying levels of risk, differing history of previous VZV infection and past varicella or zoster vaccinations.

Associations of Cardiorespiratory Fitness and Muscular Endurance Fitness With Pulmonary Function in Physically Active Young Adults.

RATIONALE: While the beneficial effects of physical fitness on general health are well-documented, the specific relationship between different types of physical fitness, particularly cardiorespiratory fitness (CRF) and muscular endurance fitness (MEF), and lung function in physically active young adults remains less explored. OBJECTIVE: This study investigated the relationship between CRF and MEF, and their correlation with lung function in physically active young adults. METHODS: This cross-sectional study involved a cohort of 1227 physically active young adults without lung diseases. Lung function was assessed using FEV1, FVC, and FEV1/FVC measurements. The 3000-m run was used to assess CRF, and the 2-min push-up and sit-up tests were used to assess MEF. Multivariable linear regression analysis was used to evaluate the relationships between these fitness measures and lung function, adjusting for potential covariates. RESULTS: Enhanced CRF was associated with superior FEV1 and FVC after adjusting for covariates (ß=-.078, p=.015 for FEV1; ß=-.086, p=.009 for FVC). Push-ups were positively associated with FEV1 (ß=.102, p=.014), but not with FVC. In contrast, sit-ups showed no significant correlation with lung function in the fully adjusted model. CONCLUSION: The study demonstrated a clear association between improved physical fitness and better lung function in physically active young adults, with various exercises showing distinct associations with lung metrics. Notably, push-ups were particularly associated with higher FEV1. A future prospective study is necessary to determine whether routine exercises, such as push-ups, might lead to greater lung function.

Using large language model (LLM) to identify high-burden informal caregivers in long-term care.

BACKGROUND: The rising global elderly population increases the demand for caregiving, yet traditional methods may not fully assess the challenges faced by vital informal caregivers. OBJECTIVE: To investigate the efficacy of Large Language Model (LLM) in detecting overburdened informal caregivers, benchmarking against rule-based and machine learning methods. METHODS: 1,791 eligible informal caregivers from Southern Taiwan and utilized their textual case summary reports for the LLM. We also employed structured questionnaire results for machine learning models. Furthermore, we leveraged the visualization of the LLM's attention mechanisms to enhance our understanding of the model's interpretative capabilities. RESULTS: The LLM achieved an Area Under the Receiver Operating Characteristic (AUROC) curve of 0.84 and an Area Under the Precision-Recall Curve (AUPRC) of 0.70, marking an 8% and 14% improvement over traditional methods. The visualization of the attention mechanism accurately reflected the evaluations of human experts, concentrating on descriptions of high-burden descriptions and the relationships between caregivers and recipients. CONCLUSION: This research demonstrates the notable capability of LLM to accurately identify high-burden caregivers in Long-term Care (LTC) settings. Compared to traditional approaches, LLM offers an opportunity for the future of LTC research and policymaking.

Gastric adenocarcinoma predictive long intergenic noncoding RNA (GAPLINC) promotes oral cancer stemness by acting as a molecular sponge of miR331-3p.

Background/purpose: Accumulating evidence has suggested that treatment failure of cancer therapy can be attributed to cancer stem cells (CSCs). Among numerous regulators of cancer stemness, non-coding RNAs (ncRNAs) have gained significant attention recently. In this study, we examined the role of gastric adenocarcinoma predictive long intergenic noncoding RNA (GAPLINC) in oral CSCs (OCSCs). Materials and methods: RNA Sequencing and quantitative real-time polymerase chain reaction (qRT-PCR) were used to determine the expression of GAPLINC. Flow cytometry and sphere-forming assay were exploited to isolate OCSCs. Measurement of aldehyde dehydrogenase 1 (ALDH1) activity, CD44 expressing cells, and various phenotypic assays, such as self-renewal, migration, invasion, and colony-forming abilities, were conducted in CSCs of two types of oral cancer cells (SAS and GNM) following the knockdown of GAPLINC. A luciferase reporter was also carried out to validate the direct interaction between GAPLINC and microRNA (miR)-331-3p. Results: Our results showed that GAPLINC was overexpressed in OCSCs from patient-derived and oral cancer cell lines. We demonstrated that silencing of GAPLINC in OCSCs downregulated various CSC hallmarks, such as ALDH1 activity, percentage of CD44-expressing cells, self-renewal capacity, and colony-forming ability. Moreover, our results revealed that the effect of GAPLINC on cancer stemness was mediated by direct repression of miR-331-3p. Conclusion: These data have potential clinical implications in that we unraveled the aberrant upregulation of GAPLINC and demonstrated that suppression of GAPLINC may reduce cancer stemness via sequestering miR-331-3p.

Impact of Early Bleeding on Long-Term Mortality Following Left Atrial Appendage Occlusion.

BACKGROUND: Short-term antithrombotic therapy is recommended after left atrial appendage occlusion(LAAO) to reduce the risk of device-related thrombosis(DRT). However, patients referred for LAAO have excess bleeding risk. Yet, short-term bleeding events post-LAAO are not well characterized. OBJECTIVE: We aimed to evaluate the incidence of early bleeding post-LAAO and its association with long-term mortality risk. We also sought to identify predictors of early bleeding. METHODS: Patients who underwent LAAO at Mayo Clinic between 2018 and 2023 were included. Early bleeding was defined as bleeding that occurred within three months of discharge. A multivariable Cox proportional hazards model was used to assess the association between early bleeding and death and to estimate the hazard ratio(HR). Multivariable regression analysis was used to identify predictors of early bleeding. RESULTS: Among the 592 patients included, 389(66%) were male, and mean age was 75.6 years. Eighty-three patients(14.0%) experienced early bleeding, with the majority having minimal(63.4%) or minor(17.3%) bleeding. At a median follow-up of 14.4 months(IQR 4.2-27.9), early bleeding after LAAO was associated with an increased risk of all-cause mortality (adjustedHR, 2.07; 95%CI, 1.15-3.75; P=0.02). A history of intracranial bleeding, non-paroxysmal atrial fibrillation, CHA2DS2VASc score, and early DRT were independent predictors of early bleeding. Anti-thrombotic therapy on discharge was not associated with early non-procedural bleeding. CONCLUSIONS: One in seven patients experience a non-procedural bleeding event within 90 days after LAAO. Early bleeding after LAAO is associated with a higher all-cause mortality during mid-term follow-up. Further studies are needed to optimize the management of patients undergoing LAAO.

MPT0E028, a novel pan-HDAC inhibitor, prevents pulmonary fibrosis through inhibition of TGF-ß-induced CTGF expression in human lung fibroblasts: Involvement of MKP-1 activation.

Histone deacetylase (HDAC) inhibitors are potential candidates for treating pulmonary fibrosis. MPT0E028, a novel pan-HDAC inhibitor, has been reported to exhibit antitumor activity in several cancer cell lines. In this study, we investigated the mechanism underlying the inhibitory effects of MPT0E028 on the expression of fibrogenic proteins in human lung fibroblasts (WI-38). Our results revealed that MPT0E028 inhibited transforming growth factor-ß (TGF-ß)-, thrombin-, and endothelin 1-induced connective tissue growth factor (CTGF) expression in a concentration-dependent manner. In addition, MPT0E028 suppressed TGF-ß-stimulated expression of fibronectin, collagen I, and α-smooth muscle actin (α-SMA). Furthermore, MPT0E028 inhibited the TGF-ß-induced phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK). MPT0E028 reduced the increase in SMAD3 and c-Jun phosphorylation, and SMAD3-and activator protein-1 (AP-1)-luciferase activities under TGF-ß stimulation. Transfection with mitogen-activated protein kinase phosphatase-1 (MKP-1) siRNA reversed the suppressive effects of MPT0E028 on TGF-ß-induced increases in CTGF expression; JNK, p38, and ERK phosphorylation; and SMAD3 and AP-1 activation. Moreover, MPT0E028 increased MKP-1 acetylation and activity in WI-38 cells. Pretreatment with MPT0E028 reduced the fibrosis score and fibronectin, collagen, and α-SMA expression in bleomycin-induced pulmonary fibrosis mice. In conclusion, MPT0E028 induced MKP-1 acetylation and activation, which in turn inhibited TGF-ß-stimulated JNK, p38, and ERK phosphorylation; SMAD3 and AP-1 activation; and subsequent CTGF expression in human lung fibroblasts. Thus, MPT0E028 may be a potential drug for treating pulmonary fibrosis.

Update on Imaging-based Noninvasive Methods for Assessing Hepatic Steatosis in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD), among the most common chronic liver diseases worldwide, affects approximately 25% of the global population. Its incidence is increasing owing to various risk factors, including genetic variation, metabolic health, dietary habits, and microbiota. Hepatic steatosis is a critical histological characteristic of NAFLD. Evaluating liver fat content is vital for identifying and following up with patients at risk of developing NAFLD. NAFLD includes simple liver steatosis and more severe forms such as inflammation, nonalcoholic steatohepatitis, fibrosis, and cirrhosis. The early assessment of fatty liver is important for reversing liver disease progression. Metabolic (dysfunction)-associated fatty liver disease recently replaced NAFLD as the most common hepatic disease worldwide. This article reviews the current state of noninvasive imaging, especially ultrasound, for liver fat quantification.

Lymphovenous Anastomosis for the External and Internal Types of Head and Neck Lymphedema: A Case Series and Preliminary Clinical Results.

Background: Head and neck lymphedema (HNL), including external and internal types, could be a possible consequence for patients who have received neck dissection and radiotherapy for head and neck cancer. Initially, the common presentations are heaviness or tightness, followed by swelling in appearance, or difficulty speaking and swallowing in internal edema cases. Lymphovenous anastomosis (LVA) is an established approach to treat extremity lymphedema. We hereby present our preliminary experience in using LVA to treat HNL. Methods: Between March 2021 and January 2024, six patients with HNL were treated with LVA via a preauricular or submandibular incision of the obstructed side. Lymphedema Symptom Intensity and Distress Surveys-Head and Neck (LSIDS-H&N) were used for evaluation. In addition, for the external type, MD Anderson Cancer Center Head and Neck Lymphedema (MDACC HNL) rating scale was used for evaluation. For the internal type, Swallowing Quality of Life was used for evaluation. Results: With an average follow-up period of 15.4 ±â€…15.9 months, LSIDS-H&N improved from 1.11 ±â€…0.54 to 0.44 ±â€…0.66 (P = 0.02). For patients with the external type, within an average follow-up period of 15 ±â€…16.1 months, the MDACC HNL rating scale improved from level 2 to 0 or 1a (P = 0.008). For patients with the internal type, within an average follow-up period of 21 ±â€…17.3 months, Swallowing Quality of Life improved from 130.5 ±â€…9.2 to 151 ±â€…19.8 (P = 0.5). Conclusions: Based on our preliminary results, LVA could be a potential solution to both external and internal HNL.

Climate Change and Cardiovascular Health: A Systematic Review.

Importance: Climate change may increase the risk of adverse cardiovascular outcomes by causing direct physiologic changes, psychological distress, and disruption of health-related infrastructure. Yet, the association between numerous climate change-related environmental stressors and the incidence of adverse cardiovascular events has not been systematically reviewed. Objective: To review the current evidence on the association between climate change-related environmental stressors and adverse cardiovascular outcomes. Evidence Review: PubMed, Embase, Web of Science, and Cochrane Library were searched to identify peer-reviewed publications from January 1, 1970, through November 15, 2023, that evaluated associations between environmental exposures and cardiovascular mortality, acute cardiovascular events, and related health care utilization. Studies that examined only nonwildfire-sourced particulate air pollution were excluded. Two investigators independently screened 20 798 articles and selected 2564 for full-text review. Study quality was assessed using the Navigation Guide framework. Findings were qualitatively synthesized as substantial differences in study design precluded quantitative meta-analysis. Findings: Of 492 observational studies that met inclusion criteria, 182 examined extreme temperature, 210 ground-level ozone, 45 wildfire smoke, and 63 extreme weather events, such as hurricanes, dust storms, and droughts. These studies presented findings from 30 high-income countries, 17 middle-income countries, and 1 low-income country. The strength of evidence was rated as sufficient for extreme temperature; ground-level ozone; tropical storms, hurricanes, and cyclones; and dust storms. Evidence was limited for wildfire smoke and inadequate for drought and mudslides. Exposure to extreme temperature was associated with increased cardiovascular mortality and morbidity, but the magnitude varied with temperature and duration of exposure. Ground-level ozone amplified the risk associated with higher temperatures and vice versa. Extreme weather events, such as hurricanes, were associated with increased cardiovascular risk that persisted for many months after the initial event. Some studies noted a small increase in cardiovascular mortality, out-of-hospital cardiac arrests, and hospitalizations for ischemic heart disease after exposure to wildfire smoke, while others found no association. Older adults, racial and ethnic minoritized populations, and lower-wealth communities were disproportionately affected. Conclusions and Relevance: Several environmental stressors that are predicted to increase in frequency and intensity with climate change are associated with increased cardiovascular risk, but data on outcomes in low-income countries are lacking. Urgent action is needed to mitigate climate change-associated cardiovascular risk, particularly in vulnerable populations.

The UFMylation pathway is impaired in Alzheimer's disease.

Background: Alzheimer's disease (AD) is characterized by the presence of neurofibrillary tangles made of hyperphosphorylated tau and senile plaques composed of beta-amyloid. These pathognomonic deposits have been implicated in the pathogenesis, although the molecular mechanisms and consequences remain undetermined. UFM1 is an important, but understudied ubiquitin-like protein that is covalently attached to substrates. This UFMylation has recently been identified as major modifier of tau aggregation upon seeding in experimental models. However, potential alterations of the UFM1 pathway in human AD brain have not been investigated yet. Methods: Here we used frontal and temporal cortex samples from individuals with or without AD to measure the protein levels of the UFMylation pathway in human brain. We used multivariable regression analyses followed by Bonferroni correction for multiple testing to analyze associations of the UFMylation pathway with neuropathological characteristics, primary biochemical measurements of tau and additional biochemical markers from the same cases. We further studied associations of the UFMylation cascade with cellular stress pathways using Spearman correlations with bulk RNAseq expression data and functionally validated these interactions using gene-edited neurons that were generated by CRISPR-Cas9. Results: Compared to controls, human AD brain had increased protein levels of UFM1. Our data further indicates that this increase mainly reflects conjugated UFM1 indicating hyperUFMylation in AD. UFMylation was strongly correlated with pathological tau in both AD-affected brain regions. In addition, we found that the levels of conjugated UFM1 were negatively correlated with soluble levels of the deUFMylation enzyme UFSP2. Functional analysis of UFM1 and/or UFSP2 knockout neurons revealed that the DNA damage response as well as the unfolded protein response are perturbed by changes in neuronal UFM1 signaling. Conclusions: There are marked changes in the UFMylation pathway in human AD brain. These changes are significantly associated with pathological tau, supporting the idea that the UFMylation cascade might indeed act as a modifier of tau pathology in human brain. Our study further nominates UFSP2 as an attractive target to reduce the hyperUFMylation observed in AD brain but also underscores the critical need to identify risks and benefits of manipulating the UFMylation pathway as potential therapeutic avenue for AD.

Combined Dacomitinib and Selpercatinib Treatment for a Patient with EGFR-Mutant Non-Small Cell Lung Cancer and Acquired CCDC6-RET Fusion.

RET rearrangements are recognized drivers in lung cancer, representing a small subset (1-2%) of non-small cell lung cancer (NSCLC). Additionally, RET fusions also serve as a rare acquired resistance mechanism in EGFR-mutant NSCLC. Only a few NSCLC cases have been reported with co-occurrence of EGFR mutations and RET fusions as an acquired resistance mechanism induced by EGFR-tyrosine kinase inhibitors (TKIs). A 68-year-old man diagnosed with lung adenocarcinoma harboring EGFR L858R mutation initially responded well to dacomitinib, a second-generation EGFR-tyrosine kinase inhibitor (TKI). Afterward, he developed acquired resistance accompanied by a RET rearrangement. Next-generation sequencing (NGS) analysis revealed that the tumor possessed both the new CCDC6-RET fusion and the EGFR L858R mutation. Subsequently, he was treated with a combination of cisplatin, pemetrexed, and bevacizumab resulting in a partial response. Nevertheless, his condition deteriorated as the disease progressed, manifesting as hydrocephalus, accompanied by altered consciousness and lower limb weakness. The subsequent combined treatment with dacomitinib and selpercatinib resulted in a significant improvement in neurological symptoms. Here, we first identified acquired CCDC6-RET fusion with a coexisting EGFR L858R mutation following dacomitinib treatment. Our findings highlight the importance of NGS for identifying RET fusions and suggest the potential combination of dacomitinib and selpercatinib to overcome this resistance. For NSCLC patients with RET rearrangements and no access to RET inhibitors, pemetrexed-based chemotherapy provides a feasible alternative.