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    Mixed neuroendocrine-non-neuroendocrine carcinoma (MiNEN) in gallbladder with liver metastasis of neuroendocrine carcinoma component: a case report

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    Mixed neuroendocrine-non-neuroendocrine neoplasms of the gallbladder are rare with a lack of established standardized therapeutic strategies. We report a case of gallbladder mixed neuroendocrine-non-neuroendocrine neoplasm with liver metastasis of neuroendocrine carcinoma. A patient who underwent radical cholecystectomy for gallbladder adenocarcinoma was detected with increasing liver mass, and hepatectomy was performed. Pathological report revealed neuroendocrine carcinoma. To find primary origin, pathological review of the old specimen from previous cholecystectomy with a slightly different perspective was conducted, where the neuroendocrine component was positively dyed. In conclusion, though it might be impossible to review every pathological result in cases with ambiguous findings, reviewing the previous specimen can be a useful option in diagnosis. Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2023.ope

    Evaluating motion of pancreatic tumors and anatomical surrogates using cine MRI in 0.35T MRgRT under free breathing conditions

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    Treatment tolerability is a significant limitation to pancreatic cancer treatment with radiotherapy due to proximity to highly radiosensitive organs and respiratory motion necessitating expanded target margins. Further, pancreatic tumors are difficult to visualize on conventional radiotherapy systems. Surrogates are often used to locate the tumor but are often inconsistent and do not provide strong positional relations throughout the respiratory cycle. This work utilizes a retrospective dataset of 45 pancreatic cancer patients treated on an MR-Linac system with cine MRI acquired for real-time target tracking. We investigated intra-fraction motion of tumors and two abdominal surrogates, leading to prediction models between the tumor and surrogate. Patient specific motion evaluation and prediction models were generated from 225 cine MRI series acquired during treatment. Tumor contours were used to evaluate the pancreatic tumor motion. Linear regression and principal component analysis (PCA) based models were used to predict tumor position from the anterior-posterior (AP) motion of the abdominal surface, the superior-inferior (SI) motion of the diaphragm, or a combination. Models were evaluated using mean squared error (MSE) and mean absolute error (MAE). Contour analysis showed the average pancreatic tumor motion range was 7.4 ± 2.7 mm and 14.9 ± 5.8 mm in the AP and SI directions, respectively. The PCA model had MSE of 1.4 mm2 and 0.6 mm2 , for the SI and AP directions, respectively, with both surrogates as inputs for the models. When only the abdomen surrogate was used, MSE was 1.3 mm2 and 0.4 mm2 in the SI and AP directions, while it was 0.4 mm2 and 1.3 mm2 when only the diaphragm surrogate was used. We evaluated intra-fraction pancreatic tumor motion and demonstrated prediction models between the tumor and surrogate. The models calculated the pancreatic tumor position from diaphragm, abdominal, or both contours within standard pancreatic cancer target margin, and the process could be applied to other disease sites in the abdominothoracic cavity.ope

    Effect of dementia on all-cause mortality in hip fracture surgery: a retrospective study on a nationwide Korean cohort

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    Objectives: We aimed to evaluate the effect of dementia on the 1-year all-cause mortality in elderly patients who underwent hip fracture surgery, using a nationwide cohort in Korea. Design, setting, and participants: This was a nationwide, retrospective study. Elderly patients (≥60 years) with and without dementia who underwent hip fracture surgery between January 2005 and December 2012 were distinguished using the data from the Korean National Health Insurance Service-Senior cohort. Interventions: None. Primary and secondary outcome measures: The mortality rates with 95% CIs and the impact of dementia on all-cause mortality were calculated using a generalised linear model with Poisson distribution and a multivariable-adjusted Cox proportional hazards model, respectively. Results: Among the 10 833 patients who underwent hip fracture surgery, 13.4% were diagnosed with dementia. During the 1-year follow-up period, 1586 patients with hip fracture without dementia died in 8356.5 person-years (incidence rate (IR)=189.2 per 1000 person-years, 95% CI 179.91 to 198.99), while 340 deaths were confirmed in patients with hip fracture with dementia in 1240.8 person-years (IR, 273.1 per 1000 person-years, 95% CI 244.94 to 304.58). Patients with hip fracture and dementia were 1.23 times more likely to die than those in the control group in the same period (HR=1.23, 95% CI 1.09 to 1.39). Conclusion: Dementia is a risk factor for 1-year all-cause mortality after hip fracture surgery. To improve the postoperative outcomes of patients with dementia who have undergone hip fracture surgery, effective treatment models such as multidisciplinary diagnosis and strategic rehabilitation should be established.ope

    Feasibility and Efficacy of Morning Light Therapy for Adults with Insomnia: A Pilot, Randomized, Open-Label, Two-Arm Study

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    Background and Objectives: Light therapy (LT) is used as an adjunctive treatment for sleep problems. This study evaluates the impact of LT on sleep quality and sleep-related parameters in patients with sleep disorders. Materials and Methods: We performed a pilot, randomized, open-label clinical trial. Fourteen patients aged 20-60 years with insomnia were randomized into the control and LT groups (1:1 ratio). The LT group was instructed to use a device that provides bright LT (6000 K, 380 lux, wavelength 480 nm) for at least 25 min before 09:00 a.m. for two weeks. A self-reported questionnaire was used to evaluate circadian preference, mood, and sleep-related parameters. We analyzed serum cortisol levels and clock genes' expression. Results: The Epworth Sleepiness Scale (ESS), insomnia severity index(ISI), and Pittsburgh Sleep Quality index(PSQI) were significantly improved within the LT group only after the two-week period. When comparing the two groups, only the change in ESS was significant (mean difference, control: -0.14 vs. LT: -1.43, p = 0.021) after adjusting for the baseline characteristics. There were no significant differences in serum cortisol or clock genes' expression. Conclusions: LT can improve daytime sleepiness in patients with sleep disorders; however, further well-designed studies are warranted to confirm its efficacy.ope

    Development and Validation of a Joint Attention-Based Deep Learning System for Detection and Symptom Severity Assessment of Autism Spectrum Disorder

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    Importance: Joint attention, composed of complex behaviors, is an early-emerging social function that is deficient in children with autism spectrum disorder (ASD). Currently, no methods are available for objectively quantifying joint attention. Objective: To train deep learning (DL) models to distinguish ASD from typical development (TD) and to differentiate ASD symptom severities using video data of joint attention behaviors. Design, setting, and participants: In this diagnostic study, joint attention tasks were administered to children with and without ASD, and video data were collected from multiple institutions from August 5, 2021, to July 18, 2022. Of 110 children, 95 (86.4%) completed study measures. Enrollment criteria were 24 to 72 months of age and ability to sit with no history of visual or auditory deficits. Exposures: Children were screened using the Childhood Autism Rating Scale. Forty-five children were diagnosed with ASD. Three types of joint attention were assessed using a specific protocol. Main outcomes and measures: Correctly distinguishing ASD from TD and different levels of ASD symptom severity using the DL model area under the receiver operating characteristic curve (AUROC), accuracy, precision, and recall. Results: The analytical population consisted of 45 children with ASD (mean [SD] age, 48.0 [13.4] months; 24 [53.3%] boys) vs 50 with TD (mean [SD] age, 47.9 [12.5] months; 27 [54.0%] boys). The DL ASD vs TD models showed good predictive performance for initiation of joint attention (IJA) (AUROC, 99.6% [95% CI, 99.4%-99.7%]; accuracy, 97.6% [95% CI, 97.1%-98.1%]; precision, 95.5% [95% CI, 94.4%-96.5%]; and recall, 99.2% [95% CI, 98.7%-99.6%]), low-level response to joint attention (RJA) (AUROC, 99.8% [95% CI, 99.6%-99.9%]; accuracy, 98.8% [95% CI, 98.4%-99.2%]; precision, 98.9% [95% CI, 98.3%-99.4%]; and recall, 99.1% [95% CI, 98.6%-99.5%]), and high-level RJA (AUROC, 99.5% [95% CI, 99.2%-99.8%]; accuracy, 98.4% [95% CI, 97.9%-98.9%]; precision, 98.8% [95% CI, 98.2%-99.4%]; and recall, 98.6% [95% CI, 97.9%-99.2%]). The DL-based ASD symptom severity models showed reasonable predictive performance for IJA (AUROC, 90.3% [95% CI, 88.8%-91.8%]; accuracy, 84.8% [95% CI, 82.3%-87.2%]; precision, 76.2% [95% CI, 72.9%-79.6%]; and recall, 84.8% [95% CI, 82.3%-87.2%]), low-level RJA (AUROC, 84.4% [95% CI, 82.0%-86.7%]; accuracy, 78.4% [95% CI, 75.0%-81.7%]; precision, 74.7% [95% CI, 70.4%-78.8%]; and recall, 78.4% [95% CI, 75.0%-81.7%]), and high-level RJA (AUROC, 84.2% [95% CI, 81.8%-86.6%]; accuracy, 81.0% [95% CI, 77.3%-84.4%]; precision, 68.6% [95% CI, 63.8%-73.6%]; and recall, 81.0% [95% CI, 77.3%-84.4%]). Conclusions and relevance: In this diagnostic study, DL models for identifying ASD and differentiating levels of ASD symptom severity were developed and the premises for DL-based predictions were visualized. The findings suggest that this method may allow digital measurement of joint attention; however, follow-up studies are necessary for further validation.ope

    Late recurrence of atrial fibrillation 5 years after catheter ablation: predictors and outcome

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    Aims: Atrial fibrillation (AF) is a chronic progressive disease that continuously recurs even after successful AF catheter ablation (AFCA). We explored the mechanism of long-term recurrence by comparing patient characteristics and redo-ablation findings. Methods and results: Among the 4248 patients who underwent a de novo AFCA and protocol-based rhythm follow-up at a single centre, we enrolled 1417 patients [71.7% male, aged 60.0 (52.0-67.0) years, 57.9% paroxysmal AF] who experienced clinical recurrences (CRs), and divided them according to the period of recurrence: within one year (n = 645), 1-2 years (n = 339), 2-5 years (n = 308), and after 5 years (CR>5 yr, n = 125). We also compared the redo-mapping and ablation outcomes of 198 patients. In patients with CR>5 yr, the proportion of paroxysmal AF was higher (P = 0.031); however, the left atrial (LA) volume (quantified by computed tomography, P = 0.003), LA voltage (P = 0.003), frequency of early recurrence (P 5 yr was independently associated with a low LA volume [odds ratio (OR) 0.99 (0.98-1.00), P = 0.035], low LA voltage [OR 0.61 (0.38-0.94), P = 0.032], and lower early recurrence [OR 0.40 (0.23-0.67), P 5 yr, despite no difference in the de novo protocol (P for trend 0.003). The rhythm outcomes of repeat ablation procedures did not differ according to the timing of the CR (log-rank P = 0.330). Conclusions: Patients with a later CR exhibited a smaller LA volume, lower LA voltage, and higher extra-pulmonary vein triggers during the repeat procedure, suggesting AF progression.ope

    Changing the strategic paradigm for the treatment of adult acute myeloid leukemia

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    Background: Acute myeloid leukemia (AML) is a representative blood cancer, accounting for most adult leukemia cases in Korea. Until recently, intensive chemotherapy and hematopoietic stem cell transplantation were the only curative treatment options for AML. However, the recent introduction of new drugs is bringing about changes in the strategic paradigm for the treatment of AML. Current Concepts: Along with the clinical eligibility for receiving intensive treatment and hematopoietic stem cell transplantation, the most critical determinants in treating AML are precise classification and risk stratification based on cytogenetic and molecular information. The recently revised World Health Organization classification, newly proposed International Consensus Classification, and the latest version of the European LeukemiaNet risk stratification reflect the importance of cytogenetic and molecular information. Although there have been no significant changes for a long time in the landscape of AML, especially in the field of treatment, the treatment paradigm has started to evolve with the introduction of new drugs. This evolution is led by FLT3 inhibitors, Bcl-2 inhibitors, isocitrate dehydrogenase inhibitors, target agents against CD33 antigens, and liposomal formulations of chemotherapeutics. Discussion and Conclusion: Successful initial treatment to induce complete remission followed by post-remission treatment to remove residual disease can lead to the achievement of long-term survival and cure goals in AML. We hope that new drugs will markedly improve the treatment outcomes for patients with AML. © Korean Medical Association.ope

    Prognostic value of central blood pressure on the outcomes of embolic stroke of undetermined source

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    We investigated the prognostic impact of central blood pressure (BP) on outcomes in patients with embolic stroke of undetermined source (ESUS). The prognostic value of central BP according to ESUS subtype was also evaluated. We recruited patients with ESUS and data on their central BP parameters (central systolic BP [SBP], central diastolic BP [DBP], central pulse pressure [PP], augmentation pressure [AP], and augmentation index [AIx]) during admission. ESUS subtype classification was arteriogenic embolism, minor cardioembolism, two or more causes, and no cause. Major adverse cardiovascular event (MACE) was defined as recurrent stroke, acute coronary syndrome, hospitalization for heart failure, or death. Over a median of 45.8 months, 746 patients with ESUS were enrolled and followed up. Patients had a mean age of 62.8 years, and 62.2% were male. Multivariable Cox regression analysis showed that central SBP and PP were associated with MACE. All-cause mortality was independently associated with AIx. In patients with no cause ESUS, central SBP and PP, AP, and AIx were independently associated with MACE. AP and AIx were independently associated with all-cause mortality (all p < 0.05). We demonstrated that central BP can predict poor long-term prognosis in patients with ESUS, especially those with the no cause ESUS subtype.ope

    Phosphodiesterase-5 Inhibitor Use in Robot Assisted Radical Prostatectomy Patients Is Associated with Reduced Risk of Death: A Propensity Score Matched Analysis of 1,058 Patients

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    Purpose: We investigated whether the use of a phosphodiesterase-5 inhibitor (PDE5i) after robot assited radical prostatectomy has a survival benefit over non-use patients because there are controversial results on the association between PDE5i use and survival outcomes for prostate cancer patients in literature. Materials and methods: We designed a retrospective, matched, large-sample cohort study of 5,545 patients who underwent robot assisted radical prostatectomy (RARP) during 2013-2021 in a single institute. The exclusion criteria was patients who were aged >70 years at surgery, American Society of Anesthesiologists (ASA) physical status classification grade 4 or 5, history of other malignancies, patients who started PDE5i 6 months after survery and patients with follow up period less than 24 months after surgery. Among the 1,843 included patients, 1,298 were PDE5i users, and 545 were PDE5i non-users. We performed propensity score matching (PSM) of PDE5i users (n=529) with non-users (n=529) by adjusting for the variables of age, Gleason grade group, pathological T stage, preoperative ASA physical status grade, and International Index of Erectile Function score. Results: There were no significant difference in patient characteristics according to PSM. Kaplan-Meier curve revealed the difference of overall survival for PDE5i users and non-users (clustered log-rank test p<0.05). In a stratified Cox regression analysis, PDE5i use after RARP was associated with improved overall survival and reduced risk of death (hazard ratio 0.43; confidence interval 0.24-0.79; p=0.007). The limitation of this study was that the indication for the prescription of PDE5i was not given. Conclusions: PDE5i administration after RARP were associated with overall survival of patients with prostate cancer. A further randomized control trial may reveal whether routine use of PDE5i after prostatectomy can improve survival of prostate cancer patient.ope

    Corticosteroid-Antibiotic Interactions in Bacteria that Cause Corneal Infection

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    Purpose: Although a comprehensive knowledge of antibiotic/corticosteroid combinations is essential for the appropriate treatment of eye infections, the impact of their co-administration has not been well studied to date. A systematic pharmacodynamic/pharmacokinetic study to determine the effects of cotreatment with various antibiotics and corticosteroids was conducted. Methods: Four bacterial strains, seven antibiotics, and four corticosteroids were used in the analyses. Drug interactions were evaluated by considering antibacterial effects with a checkerboard assay and intracellular concentrations in human corneal epithelial cells. Results: The drug combinations that showed the most stable effects against Pseudomonas aeruginosa was levofloxacin-prednisolone. Stable combinations against the three types of Gram-positive bacteria were neomycin-prednisolone, ofloxacin-dexamethasone, ofloxacin-prednisolone, and polymyxin-dexamethasone. The cellular concentrations were changed for the gatifloxacin-fluorometholone, moxifloxacin-fluorometholone, tobramycin-dexamethasone, and tobramycin-prednisolone combinations. Conclusions: Loteprednol and fluorometholone reduced the antibacterial effects of all of the tested antibiotics in this study. Dexamethasone and prednisolone showed various effects in this regard, depending on the co-administered antibiotic. Prior knowledge of specific antibiotic/corticosteroid interactions provides valuable information to clinical practitioners by combining data on the antibacterial and intracellular uptake effects of their co-administration. Translational relevance: When using antibiotics and corticosteroids, drug combinations can be selected by referring to the results of this study.ope

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