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Effectiveness and safety of injectable human papilloma virus vaccine administered as eyedrops
No full textMucosal vaccines have the advantages of ease of administration and the induction of strong mucosal immunity and a systemic immune response. Recently, the eye mucosa has been shown to be an effective and safe alternative vaccination route against influenza, Toxoplasma gondii infection, and hemolytic uremic syndrome in mice. In this study, we showed that the commercially available human papilloma virus (HPV) vaccine, Cervarix, induced significant immune reactions in terms of anti-HPV antigen (Ag)-specific immunoglobulin G (IgG) and IgA antibody production following eyedrop (ED) vaccination in mice. The HPV ED vaccines (EDV) provoked no signs of inflammation within 24 h, as indicated by the inflammatory cytokine mRNA levels and infiltration of mononuclear cells in inoculation sites. Moreover, the morphology of the cornea and retina and intraocular pressure of mice did not change after the HPV EDV. The functions of photoreceptor cells, including rod and cone cells, were normal following the HPV EDV inoculation in mice. These results suggest that Cervarix EDV could be a potent, safe, and effective mucosal vaccine against HPV-associated cancers.restrictio
Concentration-Dependent Efficacy of Recombinant Human Bone Morphogenetic Protein-2 Using a HA/β-TCP Hydrogel Carrier in a Mini-Pig Vertebral Oblique Lateral Interbody Fusion Model
Get PDFBone morphogenetic protein-2 (BMP-2) is used in the treatment of degenerative spinal disease and vertebral fractures, spine fusion, dental surgery, and facial surgery. However, high doses are associated with side effects such as inflammation and osteophytes. In this study, we performed spinal fusion surgery on mini-pigs using BMP-2 and a HA/β-TCP hydrogel carrier, and evaluated the degree of fusion and osteophyte growth according to time and dosage. Increasing the dose of BMP-2 led to a significantly higher fusion rate than was observed in the control group, and there was no significant difference between the 8-week and 16-week samples. We also found that the HA + β-TCP hydrogel combination helped maintain the rate of BMP-2 release. In conclusion, the BMP-2-loaded HA/β-TCP hydrogel carrier used in this study overcame the drawback of potentially causing side effects when used at high concentrations by enabling the sustained release of BMP-2. This method is also highly efficient, since it provides mineral matter to accelerate the fusion rate of the spine and improve bone quality.ope
Endovascular treatment of ruptured basilar artery trunk aneurysm in the acute period: risk factors for periprocedural complications
No full textObjectives: Endovascular treatment (EVT) has become a popular option for the treatment of basilar artery (BA) trunk aneurysms because microsurgery of these lesions is difficult due to narrow surgical fields and perforating arteries or cranial nerves in the brainstem. The purpose of this study is to report our experiences using EVT for ruptured BA trunk aneurysms in the acute period and to evaluate the risk factors for periprocedural complications.
Methods: From October 2004 to December 2020, a total of 27 consecutive patients with ruptured BA trunk aneurysms were treated with EVT. All patients met the following criteria: presence of ruptured BA trunk aneurysms and treatment with EVT for those aneurysms within 72 hours of rupture. The incidence of and risk factors for periprocedural complications were evaluated retrospectively.
Results: Among the 27 patients, periprocedural complications occurred in 4 patients (14.8%); mass effect inducing cranial neuropathy due to brainstem compression in 1 (3.7%) and brainstem infarction in 3 (11.1%). Hemorrhagic complications did not occur within 30 days. Subacute or delayed thromboembolic complications were not observed during the follow-up period. Large/giant aneurysm (odds ratio [OR], 6.417; 95% confidence interval [CI], 1.732-18.031; P = 0.045) and stent-assisted coiling (OR, 4.145; 95% CI, 1.018-14.212; P = 0.031) remained independent risk factors for periprocedural complications based on multiple logistic regression analysis.
Conclusions: When performing stent-assisted coiling for ruptured large/giant BA trunk aneurysms, awareness of and caution regarding periprocedural complications, such as brainstem infarction caused by thromboembolism or brainstem compression due to mass effect, are necessary.restrictio
Automatic diagnosis of retention pseudocyst in the maxillary sinus on panoramic radiographs using a convolutional neural network algorithm
Get PDFThe evaluation of the maxillary sinus is very important in dental practice such as tooth extraction and implantation because of its proximity to the teeth, but it is not easy to evaluate because of the overlapping structures such as the maxilla and the zygoma on panoramic radiographs. When doom-shaped retention pseudocysts are observed in sinus on panoramic radiographs, they are often misdiagnosed as cysts or tumors, and additional computed tomography is performed, resulting in unnecessary radiation exposure and cost. The purpose of this study was to develop a deep learning model that automatically classifies retention pseudocysts in the maxillary sinuses on panoramic radiographs. A total of 426 maxillary sinuses from panoramic radiographs of 213 patients were included in this study. These maxillary sinuses included 86 sinuses with retention pseudocysts, 261 healthy sinuses, and 79 sinuses with cysts or tumors. An EfficientDet model first introduced by Tan for detecting and classifying the maxillary sinuses was developed. The developed model was trained for 200 times on the training and validation datasets (342 sinuses), and the model performance was evaluated in terms of accuracy, sensitivity, and specificity on the test dataset (21 retention pseudocysts, 43 healthy sinuses, and 20 cysts or tumors). The accuracy of the model for classifying retention pseudocysts was 81%, and the model also showed higher accuracy for classifying healthy sinuses and cysts or tumors (98% and 90%, respectively). One of the 21 retention pseudocysts in the test dataset was misdiagnosed as a cyst or tumor. The proposed model for automatically classifying retention pseudocysts in the maxillary sinuses on panoramic radiographs showed excellent diagnostic performance. This model could help clinicians automatically diagnose the maxillary sinuses on panoramic radiographs.ope
Proposal of a revised International Association for the Study of Lung Cancer grading system in pulmonary non-mucinous adenocarcinoma: The importance of the lepidic proportion
No full textObjectives: We aimed to measure the validity of the International Association for the Study of Lung Cancer (IASLC) grading system in Korean patients and propose a modification for an increase of its predictability, especially in grade 2 patients.
Materials and methods: From 2012 to 2017, histopathologic characteristics of 1358 patients with invasive pulmonary adenocarcinoma (stage I-III) from two institutions were retrospectively reviewed and re-classified according to the IASLC grading system. Considering the amount of the lepidic proportion, the validity of the revised model (Lepidic-10), derived from the training cohort (hospital A), was measured using the validation cohort (hospital B). Its predictability was compared to that of the IASLC system.
Results: Of the 1358 patients, 259 had a recurrence, and 189 died during follow-up. The Harrell's concordance index and area under the curve of the IASLC system were 0.685 and 0.699 for recurrence-free survival (RFS) and 0.669 and 0.679 for death, respectively. From the training cohort, the IASLC grade 2 patients were divided into grades 2a and 2b (Lepidic-10 model) with a 10 % lepidic pattern. This new model further distinguished patients in both institutions that had better performance than the IASLC grading (Hospital A, p < 0.001 for RFS and death; Hospital B, p = 0.0215 for RFS, p = 0.0429 for death).
Conclusion: The IASLC grading system was easily applicable; its clinical use in predicting the prognosis of Korean patients with pulmonary adenocarcinoma was validated. Furthermore, the introduction of the lepidic proportion as an additional criterion to differentiate grade 2 patients improved its predictability.restrictio
Factors Influencing the Initial Constraint Level of the Knee Joint and Its Effect on Clinical Outcomes After ACL Reconstruction With Hamstring Graft
Get PDFBackground: A force-based tension protocol that uses a certain amount of tension at graft fixation could still give rise to variations in initial constraint levels of the knee joint in terms of side-to-side difference (SSD) in anterior translation.
Purpose: To investigate the factors influencing the initial constraint level in anterior cruciate ligament (ACL)-reconstructed knees and compare outcomes according to the level of constraint in terms of anterior translation SSD.
Study design: Cohort study; Level of evidence, 3.
Methods: Included were 113 patients who underwent ipsilateral ACL reconstruction using an autologous hamstring graft and had minimum 2-year follow-up outcomes. All grafts were tensioned and fixed at 80 N using a tensioner at the time of graft fixation. The patients were classified into the following 2 groups according to the initial anterior translation SSD, measured using the KT-2000 arthrometer: a physiologic constraint group with restored anterior laxity ≤2 mm (group P; n = 66) and a high-constraint group with restored anterior laxity >2 mm (group H; n = 47). Clinical outcomes were compared between the groups, and preoperative and intraoperative variables were evaluated to identify factors affecting the initial constraint level.
Results: Between group P and group H, generalized joint laxity (P = .005), posterior tibial slope (P = .022), and anterior translation measured in the contralateral knee (P < .001) were found to differ significantly. Measured anterior translation in the contralateral knee was the only significant predictor of high initial graft tension (P = .001). No significant differences were found between the groups regarding clinical outcomes and subsequent surgery.
Conclusion: Greater anterior translation measured in the contralateral knee was an independent predictor of a more constrained knee after ACL reconstruction. The short-term clinical outcomes after ACL reconstruction were comparable, regardless of the initial constraint level in terms of anterior translation SSD.ope
PD-L1 Upregulation by the mTOR Pathway in VEGFR-TKI-Resistant Metastatic Clear Cell Renal Cell Carcinoma
Get PDFPurpose: Tyrosine kinase inhibitors (TKI) targeting vascular endothelial growth factor receptor (VEGFR) signaling pathways have been used for metastatic clear cell renal cell carcinoma (mCCRCC), but resistance to the drug develops in most patients. We aimed to explore the underlying mechanism of the TKI resistance with regard to programmed death-ligand 1 (PD-L1) and to investigate signaling pathway associated with the resistant mechanism.
Materials and methods: To determine the mechanism of resistance, 10 mCCRCC patients from whom tumor tissues were harvested at both the pretreatment and the TKI-resistant post-treatment period were included as the discovery cohort, and their global gene expression profiles were compared. A TKI-resistant renal cancer cell line was established by long-term treatment with sunitinib.
Results: Among differentially expressed genes in the discovery cohort, increased PD-L1 expression in post-treatment tissues was noted in four patients. Pathway analysis showed that PD-L1 expression was positively correlated with the mammalian target of rapamycin (mTOR) signaling pathway. The TKI-resistant renal cancer cells showed increased expression of PD-L1 and mTOR signaling proteins and demonstrated aggressive tumoral behaviour. Treatment with mTOR inhibitors down-regulated PD-L1 expression and suppressed aggressive tumoral behaviour, which was reversed with stimulation of the mTOR pathway.
Conclusion: These results showed that PD-L1 expression may be increased in a subset of VEGFR-TKI-resistant mCCRCC patients via the mTOR pathway.ope
Healthcare use and medical cost before and after diagnosis of nontuberculous mycobacterial infection in Korea: the National Health Insurance Service-National Sample Cohort Study
Get PDFBackground and objective: The global prevalence and incidence of nontuberculous mycobacterial (NTM) infections are increasing; however, population-level data on healthcare use and medical costs for people with NTM infections are limited. Thus, we investigated the rates of healthcare use and medical costs of people with NTM infections in South Korea using the National Health Insurance Service-National Sample Cohort from 2002 to 2015.
Methods: In this cohort study, people with and without NTM infection aged 20-89 years were matched 1 to 4 by sex, age, Charlson comorbidity index, and year of diagnosis. The overall and annual average healthcare use and medical costs were calculated. In addition, trends in healthcare use and medical costs for each of the 3 years before and after NTM diagnosis were investigated for people diagnosed with NTM infection.
Results: A total of 798 individuals (336 men and 462 women) diagnosed with NTM infection and 3192 controls were included in the study. NTM-infected patients had significantly higher rates of healthcare use and medical costs than those in the control group (p < 0.05). NTM-infected patients showed 1.5 times the medical cost and 4.5 times the respiratory disease cost of the control group. People diagnosed with NTM infection incurred the highest medical costs in the 6 months before diagnosis.
Conclusion: NTM infection increases the economic burden on Korean adults. Appropriate diagnostic tests and treatment plans for NTM infections are needed to reduce the burden of the disease caused by such infection.ope
Machine Learning-Based Mortality Prediction Model for Critically Ill Cancer Patients Admitted to the Intensive Care Unit (CanICU)
Get PDFBackground: Although cancer patients are increasingly admitted to the intensive care unit (ICU) for cancer- or treatment-related complications, improved mortality prediction remains a big challenge. This study describes a new ML-based mortality prediction model for critically ill cancer patients admitted to ICU.
Patients and methods: We developed CanICU, a machine learning-based 28-day mortality prediction model for adult cancer patients admitted to ICU from Medical Information Mart for Intensive Care (MIMIC) database in the USA (n = 766), Yonsei Cancer Center (YCC, n = 3571), and Samsung Medical Center in Korea (SMC, n = 2563) from 2 January 2008 to 31 December 2017. The accuracy of CanICU was measured using sensitivity, specificity, and area under the receiver operating curve (AUROC).
Results: A total of 6900 patients were included, with a 28-day mortality of 10.2%/12.7%/36.6% and a 1-year mortality of 30.0%/36.6%/58.5% in the YCC, SMC, and MIMIC-III cohort. Nine clinical and laboratory factors were used to construct the classifier using a random forest machine-learning algorithm. CanICU had 96% sensitivity/73% specificity with the area under the receiver operating characteristic (AUROC) of 0.94 for 28-day, showing better performance than current prognostic models, including the Acute Physiology and Chronic Health Evaluation (APACHE) or Sequential Organ Failure Assessment (SOFA) score. Application of CanICU in two external data sets across the countries yielded 79-89% sensitivity, 58-59% specificity, and 0.75-0.78 AUROC for 28-day mortality. The CanICU score was also correlated with one-year mortality with 88-93% specificity.
Conclusion: CanICU offers improved performance for predicting mortality in critically ill cancer patients admitted to ICU. A user-friendly online implementation is available and should be valuable for better mortality risk stratification to allocate ICU care for cancer patients.ope
Association between weekend catch-up sleep and dyslipidemia among Korean workers
Get PDFWithin competitive sociocultural environments, most Korean workers are likely to shorten their sleep duration during the weekday. Short sleep duration is associated with dyslipidemia; however, studies on the correlation between various sleep patterns and dyslipidemia are still lacking. In hence this study aimed to investigate the association between weekend catch-up sleep (CUS) and dyslipidemia among South Korean workers. Our study used data from the 8th Korea National Health and Nutrition Examination Survey (KNHANES). The analysis covered 4,085 participants, excluding those who were diagnosed with dyslipidemia and not currently participating in economic activities. Weekend CUS was calculated as the absolute difference between self-reported weekday and weekend sleep duration. Dyslipidemia was diagnosed based on the levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides in blood samples collected after 9-12 h of fasting. After adjusting for sociodemographic, economic, health-related, and sleep-related factors, a negative association of weekend CUS with dyslipidemia was observed in male workers (odds ratio: 0.76, 95% confidence interval: 0.61-0.95). Further, workers with total sleep duration of 7-8 h, night workers, and white-collar workers with CUS were at relatively low risk of dyslipidemia compared to the non-CUS group. Less than 2 h of weekend CUS was negatively related to dyslipidemia in Korean workers, especially males. This suggests that sleeping more on weekends for workers who had a lack of sleep during the week can help prevent dyslipidemia.ope