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1.
Article in English | MEDLINE | ID: mdl-39090817

ABSTRACT

The prevalence of obesity in Korea has steadily increased over the past decade, reaching 38.4% in 2021. Notably, the rate of class II- III obesity, defined as a body mass index (BMI) of 30 kg/m2 or higher, exceeded 7% in the same year. Since January 2019, the National Health Insurance Service (NHIS) has provided coverage for bariatric surgery (BS) for eligible patients. Coverage is available for individuals with a BMI of 35 kg/m2 or higher, or those with a BMI of 30 kg/m2 or higher who also have obesity-related comorbidities. Additionally, partial reimbursement is offered for BS in patients with type 2 diabetes mellitus who have BMI values between 27.5 and 30 kg/m2. From 2019 to 2022, the NHIS recorded 9,080 BS procedures, with sleeve gastrectomy being the most commonly performed. The average percentage of weight loss 198±99.7 days post-surgery was 17.9%, with 80.0% of patients losing more than 10% of their body weight. This article presents the trends in obesity and BS in Korea.

2.
Sci Rep ; 14(1): 16934, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39043675

ABSTRACT

Dupilumab is a biologic medication that is used for the treatment of moderate-to-severe atopic dermatitis (AD). Long-term data on dupilumab drug survival in Asia patients with AD are limited. A single-center, retrospective study was performed to assess drug survival between March 2019 and March 2023. Drug survival and associated characteristics were analyzed using Kaplan-Meier survival curves and multivariate Cox regression analysis, respectively. A total of 124 patients with AD (Mean age [standard deviation], 26.0 [8.6] years) with a 4 years-overall dupilumab drug survival rate of 87.9%, were included in this study. Characteristics associated with shorter drug survival were the low eczema area and severity index (EASI) scores at baseline (hazard ratio [HR] 0.84; 95% confidence interval [CI] 0.75-0.94, p-value = 0.003) and non-insurance coverage of dupilumab (HR 11.87; 95% CI 3.28-42.99, p-value = 0.001). This retrospective study demonstrated good overall 4-year dupilumab survival (87.6%) in South Korea. Patients with low baseline EASI scores and those who did not have insurance for dupilumab treatment discontinued the therapy frequently. To the best of our knowledge, this is the first long-term dupilumab drug survival study conducted in Asia with predictors.


Subject(s)
Antibodies, Monoclonal, Humanized , Dermatitis, Atopic , Humans , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/mortality , Antibodies, Monoclonal, Humanized/therapeutic use , Female , Male , Retrospective Studies , Adult , Republic of Korea , Young Adult , Severity of Illness Index , Adolescent , Kaplan-Meier Estimate , Treatment Outcome , Middle Aged
3.
Korean J Orthod ; 54(4): 257-263, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39048921

ABSTRACT

Objective: Lingual fixed retainers, made from 0.0175-inch 3-strand twisted stainless steel wire (TW) and 0.016 × 0.022-inch straight rectangular wire (RW), are generally used in clinical practice. This study aimed to calculate their accuracy by comparing the discrepancy between computer-aided customized retainers made from these two types of wires. Methods: Eleven orthodontic patients were selected, resulting in 22 maxillary and mandibular three-dimensional printing dental models. Two types of lingual fixed retainers were bonded from canine to canine. To determine the accuracy, five points were chosen for each model, resulting in 110 selected points. The absolute values of the distances on the x-, y-, and z-axes were measured to compare the accuracy of the two types of computer-aided retainers. Results: The accuracy of the two types of retainers did not differ significantly in the x- and z-axes, but only in the y-axis (P < 0.01), where RW-fixed retainers exhibited a slightly but significantly increased distance compared to the TW. Conclusions: Both types of retainers showed high accuracy; however, RW had a slight but statistically significant difference along the y-axis compared with TW. This type of computer-aided design/computer-aided manufacturing bending machine is limited to two dimensions, and the dental arch is curved. Therefore, RW may require slight manual adjustment by the practitioner after manufacturing.

4.
ESC Heart Fail ; 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39054783

ABSTRACT

AIMS: An association between obesity, metabolic abnormalities and clinical hypertrophic cardiomyopathy (HCM) expression has been reported. We investigated whether managing dyslipidaemia with fibrates could affect the clinical expression of HCM. METHODS: We screened patients who used fibrates between 2010 and 2017 from a nationwide database. After excluding patients with a history of HCM, we identified fibrate-user group (n = 412 823). We then constructed a 1:1 matched cohort of fibrate-naïve participants (n = 412 823). After a 1 year lag period, we identified the incident HCM cases for the following 5 years. RESULTS: During a median follow-up period of 3.96 years, we identified 454 incident clinical HCM cases. After adjusting for covariates, fibrate use was associated with a lower risk of clinical HCM expression [hazard ratio (HR) 95% confidence interval (CI): 0.763 (0.630-0.924)]. In subgroup analyses, fibrate use was associated with a reduced risk of clinical HCM expression in patients with a body mass index ≥25 kg/m2 and those with abdominal obesity [HR (95% CI): 0.719 (0.553-0.934) and 0.655 (0.492-0.872)], but not in those without obesity. Fibrate use was also associated with lower risks of incident clinical HCM in patients with triglyceride levels ≥150 mg/dL and those with metabolic syndrome [HR (95% CI): 0.741 (0.591-0.929) and 0.750 (0.609-0.923)], but not in their counterparts. Regarding lifestyle behaviours, fibrate use appeared to provide more prognostic benefits in patients who currently smoked, consumed alcohol or did not engage in regular physical activities. CONCLUSION: The use of fibrates is associated with a lower incidence of clinical HCM expression. This association was also more prominent in those with obesity, unhealthy metabolic profiles and poor lifestyle behaviours.

6.
Cancers (Basel) ; 16(13)2024 Jul 03.
Article in English | MEDLINE | ID: mdl-39001507

ABSTRACT

BACKGROUND: The aim of this study was to establish a deep learning prediction model for neoadjuvant FLOT chemotherapy response. The neural network utilized clinical data and visual information from whole-slide images (WSIs) of therapy-naïve gastroesophageal cancer biopsies. METHODS: This study included 78 patients from the University Hospital of Cologne and 59 patients from the University Hospital of Heidelberg used as external validation. RESULTS: After surgical resection, 33 patients from Cologne (42.3%) were ypN0 and 45 patients (57.7%) were ypN+, while 23 patients from Heidelberg (39.0%) were ypN0 and 36 patients (61.0%) were ypN+ (p = 0.695). The neural network had an accuracy of 92.1% to predict lymph node metastasis and the area under the curve (AUC) was 0.726. A total of 43 patients from Cologne (55.1%) had less than 50% residual vital tumor (RVT) compared to 34 patients from Heidelberg (57.6%, p = 0.955). The model was able to predict tumor regression with an error of ±14.1% and an AUC of 0.648. CONCLUSIONS: This study demonstrates that visual features extracted by deep learning from therapy-naïve biopsies of gastroesophageal adenocarcinomas correlate with positive lymph nodes and tumor regression. The results will be confirmed in prospective studies to achieve early allocation of patients to the most promising treatment.

7.
Neurology ; 103(3): e209657, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39008797

ABSTRACT

BACKGROUND AND OBJECTIVES: While emerging theories suggest that vascular dysfunction may occur concurrently with the amyloid cascade in Alzheimer disease (AD) pathogenesis, the role of vascular components as primary neurodegeneration triggers remains uncertain. The aim of this retrospective, population-based cohort study conducted in Korea was to explore the link between nonarteritic anterior ischemic optic neuropathy (NAION) and dementia risk. METHODS: In this nationwide, population-based, retrospective cohort study, we identified newly diagnosed NAION from 2010 to 2017 in the Korean National Health Insurance Service database. The primary outcome was new dementia diagnoses confirmed by new ICD-10 claims coupled with antidementia medication prescriptions. We assessed dementia risk using hazard ratios (HRs) with 95% CIs over an average 2.69-year follow-up after a 1-year lag period. RESULTS: The cohort consisted of 42,943 patients with NAION and 214,715 age-matched and sex-matched controls without NAION (mean age 61.37 years ± 10.75 SD, 55.48% female). The study found a higher risk of all-cause dementia (ACD; HR 1.28, 95% CI 1.20-1.36), AD (HR 1.27, 95% CI 1.18-1.36), vascular dementia (VaD; HR 1.31, 95% CI 1.09-1.58), and other dementia (HR 1.39, 95% CI 1.11-1.73) among patients with NAION, regardless of other potential confounding factors such as age, sex, lifestyle behaviors, economic status, and preexisting health conditions. In subgroup analysis, the associations between NAION and ACD were stronger in the younger age group (HR 1.83 for those younger than 65 years vs 1.23 for those 65 years or older; p for interaction <0.001). Moreover, the association of NAION with both ACD and VaD was particularly strong among current smokers. DISCUSSION: We found a significant association between NAION and increased risk for ACD, AD, VaD, and other dementia even after adjusting for potential confounders such as lifestyle, health conditions, and demographic factors within a nationwide cohort. This study highlights the potential role of vascular pathology in dementia progression and suggests that NAION may serve as a robust predictor for dementia, highlighting the need for comprehensive neurologic assessment in patients with NAION. Further research is needed to clarify the association between NAION and dementia risk.


Subject(s)
Dementia , Optic Neuropathy, Ischemic , Humans , Male , Female , Aged , Dementia/epidemiology , Dementia/etiology , Middle Aged , Retrospective Studies , Optic Neuropathy, Ischemic/epidemiology , Republic of Korea/epidemiology , Cohort Studies , Risk Factors
8.
Int J Numer Method Biomed Eng ; : e3845, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38979678

ABSTRACT

Virtual compression tests based on finite element analysis are representative noninvasive methods to evaluate bone strength. However, owing to the characteristic porous structure of bones, the material obtained from micro-computed tomography images in the finite-element model is not uniformly distributed. These characteristics cause differences in the apparent elastic moduli depending on the boundary conditions and affect the accuracy of bone-strength evaluation. Therefore, this study aimed to evaluate and compare the apparent elastic moduli under various, virtual-compression and shear-test boundary conditions. Four, nonuniform models were constructed with increasing model complexity. For representative boundary conditions, two, different, testing directions, and constrained surfaces were applied. As a result, the apparent elastic moduli of the nonuniform model varied up to 55.2% based on where the constrained surface was located in the single-end-cemented condition. Additionally, when connectivity in the test direction was lost, the accuracy of the apparent elastic moduli was low. A graphical comparison showed that the equivalent-stress distribution was more advantageous for analyzing load transferability and physical behavior than the strain-energy distribution. These results clearly show that the prediction accuracy of the apparent elastic moduli can be guaranteed if the boundary condition on the constraint and loading surfaces of the nonuniform model are applied symmetrically and the connectivity of the elements in the testing direction is well maintained. This study will aid in precision improvement of bone-strength-indicator determination for osteoporosis prevention.

9.
Food Chem ; 458: 140169, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38968713

ABSTRACT

This study was aimed to investigate the effectiveness of activated carbon on reduction in biogenic amines (BAs) via two-stage adsorption process at industrial scale, and the consequent effect was evaluated by the taste and aroma of anchovy fish sauce. Through reaction surface methodology, the optimal working paratmeters were determined to adsorbent composition of 2% activated carbon and 0.9% diatomite under temperature of 27 °C for 97 min. Upon optimized settings at industrial scale, there were effective reductions in tryptamine (by 100%), cadaverine (by 10%), histamine (by 61%), and tyramine (by 96%), while the changes in taste-related amino nitrogen, total nitrogen, free amino acids, and color were minimum. In addition, off-flavor-causing compounds, such as alcohols and acids, were removed by the developed method. From the obtained results, the activated carbon-based two-stage adsorption approach can provide the framework for control of BAs contents in fish-based sauces or stocks at commercial and industrial scales.

10.
Comput Biol Med ; 180: 108929, 2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39068904

ABSTRACT

The bone microstructure of the human proximal femur is clinically crucial for diagnosing skeletal pathologies, such as osteoporosis and bone metastases. The topology optimization-based bone microstructure method obtains these bone microstructures by converting low-resolution (LR) images into high-resolution images. However, this method is inherently computationally inefficient as it requires numerous finite elements, iterative analyses, and parallel computations. Therefore, this study proposes a novel topology optimization-based localised bone microstructure reconstruction method using the dominant load, which highly affects the selected region of interest (ROI), for efficient resolution enhancement. The load dependency of selected ROIs is quantified with a load dependency score. Then, the localised finite element model is constructed based on the local load estimation. Finally, the selected dominant load is applied as an input for the topology optimization-based bone microstructure reconstruction method. The reconstructed bone microstructure was similar to that of the conventional method. The localised finite element model applied by the dominant load effectively and accurately reconstructed the bone morphology and exhibited high computational efficiency. In conclusion, the dominant load-based approach can be used to construct a reasonable trabecular bone structure for ROI with high computational efficiency. The predictive performance of the proposed method was validated and showed promise for accurate trabecular bone structure prediction without additional radiation exposure.

11.
Eur Neurol ; 2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39068915

ABSTRACT

INTRODUCTION: Accurately discerning periods of heightened risk of stroke or transient ischemic attack (TIA) recurrence and managing modifiable risk factors are essential for minimizing overall recurrence risk. This study identified differences in the timing of stroke or TIA recurrence based on risk factors and patient characteristics to develop strategies for reducing recurrence in clinical practice. METHODS: We retrospectively selected patients with ischemic stroke or TIA at the Korea University Ansan Hospital Stroke Center between March 2014 and December 2021 using the prospective institutional database of the Korea University Stroke Registry. We collected demographic, clinical data and categorized participants by recurrence timing (early within or late after 3 months). Using multinomial logistic regression analysis, we examined variables associated with early and late recurrent stroke or TIAs. RESULTS: Among 3,646 patients, 255 experienced a recurrent stroke or TIA and 3,391 experienced their first stroke or TIA. Multinomial logistic regression analysis revealed significant associations between early recurrent stroke or TIA and diabetes mellitus (odds ratio [OR] 1.98, 95% confidence interval [CI] 1.25-3.15), other determined etiologies in the Trial of Org 10172 in the Acute Stroke Treatment classification (OR 3.00, 95% CI 1.37-6.61), and white matter changes (OR 1.97, 95% CI 1.17-3.33). Late recurrence showed a significant correlation with TIA (OR 2.95, 95% CI 1.52-5.71) and cerebral microbleeds (OR 2.22, 95% CI 1.32-3.75). CONCLUSION: Substantial differences in factors contribute to stroke or TIA recurrence based on timing. Managing the risk of recurrence in clinical practice necessitates accurate identification of heightened risk periods and rigorous control of modifiable risk factors.

13.
PLoS One ; 19(6): e0303841, 2024.
Article in English | MEDLINE | ID: mdl-38865352

ABSTRACT

A significant crop pest, Mythimna loreyi, migrates annually to Korea and has been frequently observed in rice and corn fields. However, the phenology of this pest, particularly in relation to its ecological interactions and host crop seasons in Korea, remains poorly understood. This study aims to clarify the timing of the second generation of M. loreyi in Korea to enhance pest management strategies. To achieve this, we developed temperature-dependent models for developmental and ovipositional rates, studying these processes across five constant temperatures (15, 20, 25, 30, and 35°C). Our models, which showed a high correlation with observed data (r2 ≥ 0.93), include a theoretical approach that combines the developmental variation of immatures with the necessary degree-days for 50% egg laying and complete egg development. These predictions allow for the forecasting of the second generation's occurrence, with relatively small deviations (one to three days) observed at two different field sites. The insights from this study are critical for both understanding the ecology of M. loreyi and for informing practical management decisions, such as optimal placement of barriers to prevent immigration and strategies for controlling local populations.


Subject(s)
Oviposition , Temperature , Animals , Oviposition/physiology , Female , Republic of Korea , Moths/physiology , Moths/growth & development , Models, Biological , Seasons
14.
BMC Med ; 22(1): 251, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38886720

ABSTRACT

BACKGROUND: We investigated the association between exercise habits before or after thyroidectomy and incident type 2 diabetes mellitus (T2DM) in patients with thyroid cancer. METHODS: An observational cohort study of 69,526 thyroid cancer patients who underwent thyroidectomy for the treatment of thyroid cancer between 2010 and 2016 was performed using the Korean National Health Information Database. Regular exercise was defined as mid-term or vigorous exercise at least 1 day in a week based on a self-reported questionnaire. Patients were divided into four groups according to exercise habits before and after thyroidectomy: persistent non-exercisers, new exercisers, exercise dropouts, and exercise maintainers. RESULTS: During a median follow-up of 4.5 years, 2,720 (3.91%) patients developed T2DM. The incidence of T2DM per 1,000 person years was lower in patients who performed regular exercise before or after thyroidectomy than in persistent non-exercisers (10.77 in persistent non-exerciser group, 8.28 in new exerciser group, 8.59 in exercise dropout group, and 7.61 in exercise maintainer group). Compared with the persistent non-exerciser group, the new exerciser group (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.78-0.97), the exercise dropout group (HR 0.81, 95% CI 0.72-0.91), and the exercise maintainer group (HR 0.84, 95% CI 0.76-0.93) had lower risks of incident T2DM. Exercising < 1,500 MET-minutes/week in the exercise maintainer group was associated with a lower risk of incident T2DM compared with persistent non-exercisers (< 500: HR 0.80, 95% CI 0.67-0.96, P = 0.002; 500 to < 1,000: HR 0.81, 95% CI 0.71-0.93, P < 0.001; 1,000 to < 1,500: HR 0.81, 95% CI 0.69-0.94, P < 0.001). CONCLUSIONS: Regular exercise before or after thyroidectomy was associated with a lower risk of incident T2DM in patients with thyroid cancer.


Subject(s)
Diabetes Mellitus, Type 2 , Exercise , Thyroid Neoplasms , Thyroidectomy , Humans , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/complications , Male , Female , Middle Aged , Exercise/physiology , Thyroid Neoplasms/epidemiology , Thyroid Neoplasms/surgery , Incidence , Adult , Republic of Korea/epidemiology , Thyroidectomy/adverse effects , Aged , Cohort Studies
15.
Nat Commun ; 15(1): 4909, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38851766

ABSTRACT

Tobacco smoking (TS) is implicated in lung cancer (LC) progression through the development of metabolic syndrome. However, direct evidence linking metabolic syndrome to TS-mediated LC progression remains to be established. Our findings demonstrate that 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and benzo[a]pyrene (NNK and BaP; NB), components of tobacco smoke, induce metabolic syndrome characteristics, particularly hyperglycemia, promoting lung cancer progression in male C57BL/6 J mice. NB enhances glucose uptake in tumor-associated macrophages by increasing the expression and surface localization of glucose transporter (GLUT) 1 and 3, thereby leading to transcriptional upregulation of insulin-like growth factor 2 (IGF2), which subsequently activates insulin receptor (IR) in LC cells in a paracrine manner, promoting its nuclear import. Nuclear IR binds to nucleophosmin (NPM1), resulting in IR/NPM1-mediated activation of the CD274 promoter and expression of programmed death ligand-1 (PD-L1). Restricting glycolysis, depleting macrophages, or blocking PD-L1 inhibits NB-mediated LC progression. Analysis of patient tissues and public databases reveals elevated levels of IGF2 and GLUT1 in tumor-associated macrophages, as well as tumoral PD-L1 and phosphorylated insulin-like growth factor 1 receptor/insulin receptor (pIGF-1R/IR) expression, suggesting potential poor prognostic biomarkers for LC patients. Our data indicate that paracrine IGF2/IR/NPM1/PD-L1 signaling, facilitated by NB-induced dysregulation of glucose levels and metabolic reprogramming of macrophages, contributes to TS-mediated LC progression.


Subject(s)
B7-H1 Antigen , Benzo(a)pyrene , Disease Progression , Hyperglycemia , Insulin-Like Growth Factor II , Lung Neoplasms , Mice, Inbred C57BL , Nuclear Proteins , Nucleophosmin , Receptor, Insulin , Animals , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Male , Humans , Receptor, Insulin/metabolism , Receptor, Insulin/genetics , Mice , B7-H1 Antigen/metabolism , B7-H1 Antigen/genetics , Hyperglycemia/metabolism , Benzo(a)pyrene/toxicity , Insulin-Like Growth Factor II/metabolism , Insulin-Like Growth Factor II/genetics , Nuclear Proteins/metabolism , Nuclear Proteins/genetics , Nitrosamines/toxicity , Tumor-Associated Macrophages/metabolism , Cell Line, Tumor , Paracrine Communication , Gene Expression Regulation, Neoplastic , Smoking/adverse effects , Macrophages/metabolism
16.
J Am Heart Assoc ; 13(12): e033437, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38879451

ABSTRACT

BACKGROUND: This cohort study aims to examine the relationship between the occurrence of cranial nerve palsy (CNP) affecting the third, fourth, or sixth cranial nerve and the subsequent risk of stroke, with a particular focus on the modulating effect of age on this association. METHODS AND RESULTS: We established a cohort of individuals diagnosed with third, fourth, or sixth CNP who underwent national health screening within 2 years of diagnosis from 2010 to 2017. A control group was matched by sex and age at a ratio of 1:5. Participants were followed until December 31, 2019. We use multivariable Cox proportional hazards regression analyses to assess the association between ocular motor CNP and subsequent stroke stratified by age. Covariates including lifestyle, health behavior, underlying comorbidities, and Charlson comorbidity index score were also adjusted. Compared with the control group, the ocular motor CNP group had a higher risk of stroke after adjusting for potential confounders (hazard ratio [HR], 1.23 [95% CI,, 1.08-1.39]). The risk of stroke increased by 8.91 times in individuals with ocular motor CNP who were in their 30s (HR, 8.91 [95% CI, 1.63-48.66]). The risk increased by 2.49 times in those who were in their 40s, 1.78 times in those who were in their 50s, and 1.32 times in those who were in their 60s (HRs, 2.49, 1.78, and 1.32 [95% CI, 1.39-4.45, 1.31-2.42, and 1.08-1.62], respectively). However, for those who were in their 20s, 70s, or 80s, the incidence of stroke did not significantly increase. CONCLUSIONS: Our study establishes an association between ocular motor CNP and an increased risk of stroke, particularly in young adults.


Subject(s)
Oculomotor Nerve Diseases , Stroke , Humans , Male , Female , Middle Aged , Stroke/epidemiology , Adult , Risk Factors , Aged , Age Factors , Incidence , Oculomotor Nerve Diseases/epidemiology , Oculomotor Nerve Diseases/diagnosis , Risk Assessment , Republic of Korea/epidemiology , Young Adult
17.
Neuroepidemiology ; : 1-9, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38880093

ABSTRACT

INTRODUCTION: Although the relationship between migraine and multiple sclerosis (MS) has been reported, the risk of migraine in MS and neuromyelitis optica spectrum disorder (NMOSD) is unclear. Therefore, this study investigated the risk of migraine in the Korean MS and NMOSD populations. METHODS: This study analyzed claims data from 1,492 patients with MS and 1,551 patients with NMOSD based on diagnostic codes in the Korean National Health Insurance Service. Migraine risk was compared with a control group (matched 1:5 for age, sex, and comorbidities) using Cox proportional hazards analysis. Patients aged <20 years and with previous migraine were excluded. RESULTS: Migraine risk was higher in patients with MS (adjusted hazard ratio [aHR] 1.37; 95% confidence interval [CI]: 1.15-1.62) but did not differ significantly in patients with NMOSD (aHR 1.05; 95% CI: 0.87-1.27) compared to controls. No significant sex-based differences in migraine risk were observed. Patients with NMOSD showed decreasing risk with age (p for interaction = 0.040). Comorbidities like hypertension, diabetes, or dyslipidemia did not significantly alter migraine risk in either group. CONCLUSION: The study results revealed an increased risk of migraines in patients with MS but not in patients with NMSOD compared with matched controls.

19.
Cell Death Differ ; 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38926528

ABSTRACT

Cellular senescence, a hallmark of aging, is pathogenically linked to the development of aging-related diseases. This study demonstrates that FRMD6, an upstream component of the Hippo/YAP signaling cascade, is a key regulator of senescence. Proteomic analysis revealed that FRMD6 is upregulated in senescent IMR90 fibroblasts under various senescence-inducing conditions. Silencing FRMD6 mitigated the senescence of IMR90 cells, suggesting its requirement in senescence. Conversely, the overexpression of FRMD6 alone induced senescence in cells and in lung tissue, establishing a causal link. The elevated FRMD6 levels correlated well with increased levels of the inhibitory phosphorylated YAP/TAZ. We identified cellular communication network factor 3 (CCN3), a key component of the senescence-associated secretory phenotype regulated by YAP, whose administration attenuated FRMD6-induced senescence in a dose-dependent manner. Mechanistically, FRMD6 interacted with and activated MST kinase, which led to YAP/TAZ inactivation. The expression of FRMD6 was regulated by the p53 and SMAD transcription factors in senescent cells. Accordingly, the expression of FRMD6 was upregulated by TGF-ß treatment that activates those transcription factors. In TGF-ß-treated IMR90 cells, FRMD6 mainly segregated with p21, a senescence marker, but rarely segregated with α-SMA, a myofibroblast marker, which suggests that FRMD6 has a role in directing cells towards senescence. Similarly, in TGF-ß-enriched environments, such as fibroblastic foci (FF) from patients with idiopathic pulmonary fibrosis, FRMD6 co-localized with p16 in FF lining cells, while it was rarely detected in α-SMA-positive myofibroblasts that are abundant in FF. In sum, this study identifies FRMD6 as a novel regulator of senescence and elucidates the contribution of the FRMD6-Hippo/YAP-CCN3 axis to senescence.

20.
Surgery ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38944588

ABSTRACT

BACKGROUND: Multimodal therapy regimens became the standard of care for patients with esophageal cancer, whereas surgical resection remains at the center of curative treatment modalities. Current guidelines provide no recommendations on the extent of the oral resection margin, especially in the era of neoadjuvant therapy. Therefore, this study aimed to evaluate the relationship between the oral tumor-free resection margin and overall survival. METHODS: Retrospective study with 382 1:1 propensity-matched patients out of 660 patients, operated between 2013 and 2019, with an Ivor-Lewis-esophagectomy for adenocarcinoma and squamous cell carcinoma of the esophagus or esophagogastric junction after neoadjuvant therapy. Independent pathologists measured the oral resection margin after formalin fixation. RESULTS: The mean oral tumor-free resection margin was 37.2 ± 0.6 mm. The ideal cut-off for survival differences was determined for 33 mm. Patients with an oral resection margin of more than 33 mm had a better median overall survival (≤33 mm: 45.0 months, 95% confidence interval: 22.4-67.6 months, >33 mm: not reached, P = .005). An oral resection margin of more than 33 mm proved to be an independent favorable prognostic factor for patients' overall survival in multivariate Cox regression analyses (P = .049). CONCLUSION: This study analyzed a patient cohort retrospectively after curative intended Ivor-Lewis-esophagectomy after neoadjuvant therapy. An oral resection margin of more than 33 mm is a factor for improved overall survival. Therefore, a minimum resection margin of 34 mm after fixation could be suggested.

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