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A type of ultrathin films has been developed for suppressing capsule formation induced by medical silicone implants and hence reducing the inflammation response to such formation and the differentiation to myofibroblasts. The films were each fabricated from hyaluronic acid (HA) and modified β-cyclodextrin (Mod-β-CyD) polymer which was synthesized with a cyclodextrin with partially substituted quaternary amine. Ultrathin films comprising HA and Mod-β-CyD or poly(allylamine hydrochloride) (PAH) were fabricated by using a layer-by-layer dipping method. The electrostatic interactions produced from the functional groups of Mod-β-CyD and HA influenced the surface morphology, wettability, and bio-functional activity of the film. Notably, medical silicone implants coated with PAH/HA and Mod-β-CyD multilayers under a low pH condition exhibited excellent biocompatibility and antibiofilm and anti-inflammation properties. Implantation of these nanoscale film-coated silicones showed a reduced capsular thickness as well as reduced TGFβ-SMAD signaling, myofibroblast differentiation, biofilm formation, and inflammatory response levels. We expect our novel coating system to be considered a strong candidate for use in various medical implant applications in order to decrease implant-induced capsule formation.

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) have been reported to exhibit immature embryonic or fetal cardiomyocyte-like phenotypes. To enhance the maturation of hESC-CMs, we identified a natural steroidal alkaloid, tomatidine, as a new substance that stimulates the maturation of hESC-CMs. Treatment of human embryonic stem cells with tomatidine during cardiomyocyte differentiation stimulated the expression of several cardiomyocyte-specific markers and increased the density of T-tubules. Furthermore, tomatidine treatment augmented the number and size of mitochondria and enhanced the formation of mitochondrial lamellar cristae. Tomatidine treatment stimulated mitochondrial functions, including mitochondrial membrane potential, oxidative phosphorylation, and ATP production, in hESC-CMs. Tomatidine-treated hESC-CMs were more sensitive to doxorubicin-induced cardiotoxicity than the control cells. In conclusion, the present study suggests that tomatidine promotes the differentiation of stem cells to adult cardiomyocytes by accelerating mitochondrial biogenesis and maturation and that tomatidine-treated mature hESC-CMs can be used for cardiotoxicity screening and cardiac disease modeling.

Treatment with filler injections using a microneedle fractional radiofrequency (MFRF) device is a promising modality with proven efficacy for acne scar treatment.To investigate the efficacy and histologic differences of intradermal injection of a filler (poly-d, l-lactic acid, PDLA) using an MFRF device for the treatment of acne scars.Patients with acne scars on both cheeks were included. Poly-d, l-lactic acid was injected via the MFRF device every 4 weeks for a total of 4 sessions. Patients were evaluated using the grading system for acne scars before each session, as well as personal satisfaction. For histologic evaluation, 2 patients (who consented) underwent a skin biopsy from the upper arm before and after the same single session.After the final session, the acne scar grading (échelle d'évaluation clinique des cicatrices d'acné) scale and visual analog scale for evaluation of satisfaction showed improvement compared with initial assessment (36.99% and 79.65% respectively [p.001, respectively]). For histologic evaluation, biodegradation of PDLA materials and increase in collagen and elastic fibers were observed after 5 months of treatment.Intradermal injection of PDLA using the MFRF device could be used as an effective treatment with fewer side effects in acne scar patients with Fitzpatrick skin type III-IV.

Although the density of tumor-infiltrating lymphocytes (TILs) is known to be linked to prognosis in various cancers, the prognostic impact and immunologic significance of the spatial heterogeneity of TILs have been rarely investigated. In this study, CD3+ and CD8+ TILs were quantified in independent cohorts (discovery, n = 73; and external validation, n = 93) of colorectal carcinomas (CRCs) with microsatellite instability-high (MSI-H) utilizing whole-slide image analysis of CD3/CD8 immunohistochemistry. The Shannon and Simpson indices, which measure intratumoral patch-to-patch evenness of TIL densities, were used to quantitatively assess the spatial heterogeneity of TILs in each case. To uncover immune-related gene expression signatures of spatial heterogeneity-based TIL subgroups of MSI-H CRCs, representative cases were subjected to GeoMx digital spatial profiler (DSP) analysis. As expected, a low density of TILs was significantly associated with poor disease-free survival (DFS) in MSI-H CRCs. The TIL-low tumors were further classified into two subgroups based on the spatial heterogeneity of TILs: TIL-low/heterogeneity-high and TIL-low/heterogeneity-low subgroups. In both discovery and validation cohorts, the TIL-low/heterogeneity-high, TIL-low/heterogeneity-low, and TIL-high subgroups were significantly associated with poor, intermediate, and good DFS, respectively. In the DSP analysis, the TIL-low/heterogeneity-high subgroup showed higher spatial diversity in the expression of immune-related genes than that of the TIL-low/heterogeneity-low subgroup and exhibited upregulation of genes related to immune checkpoints, chemokine/cytokine receptors, and myeloid cells. TIL-low/heterogeneity-high tumors were also enriched with gene sets related to good response to immune checkpoint inhibitor therapy. In conclusion, TIL-low MSI-H CRCs are prognostically heterogeneous and can be divided into prognostically and immunologically distinct subgroups by considering the spatial heterogeneity of TILs. Our data suggest that intratumoral spatial heterogeneity of TILs can be used as a key element for clinically relevant immunologic subtyping of tumors.

Infective endocarditis is a life-threatening condition and is associated with embolic events. We aimed to evaluate the association of vegetation size, multiplicity, and position with cerebral embolism and late mortality in patients with infective endocarditis.We retrospectively reviewed patients with infective endocarditis who were admitted to a single institution between November 2005 and August 2017. A total of 419 patients with infective endocarditis were included in the study, 273 of whom had undergone surgery. The primary endpoint was all-cause mortality, and the secondary endpoint was cerebral embolism. Multivariate Cox regression and logistic regression analyses were performed to identify independent risk factors for 30-day mortality, late mortality, and cerebral embolism.Age (hazard ratio [HR] 1.02; 95% confidence interval [CI], 1.00 to 1.04), renal failure (HR 4.21; 95% CI, 2.67 to 6.65), surgery (HR 0.31; 95% CI, 0.21 to 0.46), and Acute Physiology and Chronic Health Evaluation II score (HR 1.08; 95% CI, 1.01 to 1.15) were associated with late mortality. Vegetation size, multiplicity, and position were not significantly associated with late mortality, but a mitral vegetation size of greater than 10 mm (odds ratio 2.25; 95% CI, 1.32 to 3.84) was an independent risk factor for cerebral embolism.A vegetation size of greater than 10 mm and the mitral position were found to be significant risk factors for cerebral embolism, and for this group, early surgery might be considered to prevent cerebral embolism.

Distinct, irregular, and hard, nodular labial protuberances (LPs) that were due to differential alveolar bone modeling can be noted on the labial gingival surface of the incisors after orthodontic treatment. Clinically, LPs cause patient discomfort and esthetic issues, but information on this phenomenon is limited. This study aimed to evaluate the incidence of LPs and demonstrate the etiology and clinical risk factors associated with this phenomenon.Differential alveolar bone modeling was defined as present (+) when ≥1 distinct LPs (diameter 1 mm) developed after orthodontic treatment by comparing pretreatment and posttreatment intraoral photographs and casts of an orthodontic patient cohort treated with fixed appliances (n = 872). The incidence rate, affected sites, and their association with age, sex, and orthodontic treatment modalities were evaluated.The incidence rate of differential alveolar bone modeling among orthodontic patients was 3.2% (28 out of 872). The maxillary lateral incisor region was the most frequently affected site. Males (vs females) (odds ratio, 2.56 [95% confidence interval, 1.155-5.604]), adults (aged ≥ 20 years) (vs teens) (12.84 [3.003-54.866]), and those who had orthodontic extraction (vs nonextraction) (11.60 [3.434-39.156]) demonstrated significantly higher odds of developing LPs after orthodontic treatment (P 0.05).The incidence rate of the development of notable LPs after orthodontic treatment was 3.2%. Adult males and those who undergo orthodontic extraction have a higher risk of developing LPs. Clinicians should be aware that distinct LPs may develop when large amounts of incisal retraction are planned in adults.

This meta-analysis assessed the impact of off-hour hospitalization (weekends, and evenings or nighttime on weekdays) on mortality and morbidity in patients with nontraumatic subarachnoid hemorrhage (SAH).Electronic databases were systematically searched for studies comparing outcomes between patients with nontraumatic SAH hospitalized during off-hour and on-hour periods (daytime on weekdays). The primary outcome was mortality (in-hospital and at different follow-up periods after hospitalization). Secondary outcomes included delays in treatment, and complications. Sensitivity analysis including only studies in which adjusted multivariate analyses were performed for any of the outcomes, and meta-regression controlling for clinically important patient factors, were also performed.Sixteen studies were included. There was no significant difference in in-hospital mortality (adjusted odds ratio, 1.03; 95% confidence interval [CI], 0.97-1.09; P = 0.30) and at all follow-up periods (7/14 days and 1/3/6 months) after hospitalization between SAH patients who were admitted during off-hour compared with on-hour periods, despite adjusted multivariate meta-analysis being performed. However, patients who were admitted during off-hour periods experienced greater delays from their initial scan to treatment (mean difference, 42.7, 25.2-60.1 hours; P0.0001) and had higher rates of pneumonia (odds ratio, 1.65, 1.12-2.44; P = 0.011).This meta-analysis has not shown an increased risk of mortality in the short-term and long-term among patients with nontraumatic SAH who were hospitalized during off-hour compared with on-hour periods, despite adjusting for potentially confounding patient factors. The delays to treatment and higher observed rates of pneumonia highlight areas in which hospital services and resources should be targeted during these off-hour periods in patients presenting with nontraumatic SAH.

The prospective Crohn's Disease Clinical Network and Cohort Study is a nationwide multicenter cohort study of patients with Crohn's disease (CD) in Korea, aiming to prospectively investigate the clinical features and long-term prognosis associated with CD.Patients diagnosed with CD between January 2009 and September 2019 were prospectively enrolled. They were divided into two cohorts according to the year of diagnosis: cohort 1 (diagnosed between 2009 and 2011) versus cohort 2 (between 2012 and 2019).A total of 1,175 patients were included, and the median follow-up duration was 68 months (interquartile range, 39.0 to 91.0 months). The treatment-free durations for thiopurines (p0.001) and anti-tumor necrosis factor agents (p=0.018) of cohort 2 were shorter than those of cohort 1. Among 887 patients with B1 behavior at diagnosis, 149 patients (16.8%) progressed to either B2 or B3 behavior during follow-up. Early use of thiopurine was associated with a reduced risk of behavioral progression (adjusted hazard ratio [aHR], 0.69; 95% confidence interval [CI], 0.50 to 0.90), and family history of inflammatory bowel disease was associated with an increased risk of behavioral progression (aHR, 2.29; 95% CI, 1.16 to 4.50). One hundred forty-one patients (12.0%) underwent intestinal resection, and the intestinal resection-free survival time was significantly longer in cohort 2 than in cohort 1 (p=0.003). The early use of thiopurines (aHR, 0.35; 95% CI, 0.23 to 0.51) was independently associated with a reduced risk of intestinal resection.The prognosis of CD in Korea appears to have improved over time, as evidenced by the decreasing intestinal resection rate. Early use of thiopurines was associated with an improved prognosis represented by a reduced risk of intestinal resection.

Previous genomewide association studies (GWASs), single nucleotide polymorphisms (SNPs) on cyclin-dependent kinase inhibitor 2 A (CDKN2A), cyclin-dependent kinase inhibitor 2B (CDKN2B), and cyclin-dependent kinase inhibitor 2B antisense RNA1 (CDKN2B-AS1) were reported as risk loci for glioma, a subgroup of the brain tumor. To further characterize this association with the risk of brain tumors in a Korean population, we performed a fine-mapping association study of CDKN2A, CDKN2B, and CDKN2B-AS1.A total of 17 SNPs were selected and genotyped in 1,439 subjects which were comprised of 959 patients (pituitary adenoma 335; glioma 324; meningioma 300) and 480 population controls (PCs). We discovered that a 3'untranslated region (3'UTR) variant, rs181031884 of CDKN2B (Asian-specific variant), had significant association with the risk of pituitary adenoma (PA) (Odds ratio = 0.58, P = 0.00003). Also, rs181031884 appeared as an independent causal variant among the significant variants in CDKN2A and CDKN2B, and showed dose-dependent effects on PA.Although further studies are needed to verify the impact of this variant on PA susceptibility, our results may help to understand CDKN2B polymorphism and the risk of PA.

This study investigated survival outcomes for platinum-sensitive relapsed ovarian clear cell carcinoma (OCCC) by treatment method.OCCC patients with platinum-sensitive recurrence that received secondary treatment at five institutions between July 2007 and June 2021 were included. Patient characteristics and survival outcomes were compared according to the use of bevacizumab (BEV) during second-line chemotherapy and secondary cytoreductive surgery (CRS).138 patients were included. The BEV (n = 36) and non-BEV (n = 102) groups had similar initial FIGO stages and proportions of secondary CRS. The BEV group showed improved progression-free survival (PFS; median, 15.4 vs. 7.5 months; P = 0.042) and overall survival (OS; P = 0.043) compared to the non-BEV group. In multivariate analyses, BEV was identified as an independent prognostic factor for PFS (adjusted hazard ratio [aHR], 0.571; 95% confidence interval [CI], 0.354-0.921; P = 0.022) and OS (aHR, 0.435; 95%CI, 0.195-0.970; P = 0.042). The secondary CRS group (n = 42) had early-stage disease at diagnosis more frequently (P = 0.009) and multi-site metastasis (P0.001) at recurrence less frequently than the no surgery group (n = 96). The secondary CRS group showed significantly better PFS (median, 33.7 vs. 7.2 months; P0.001) and OS (P0.001). Secondary CRS was associated with a significantly improved PFS (aHR, 0.297; 95% CI, 0.183-0.481; P0.001) and OS (aHR, 0.276; 95% CI, 0.133-0.576; P = 0.001). The BEV and non-BEV groups showed similar PFS and OS among the patients who underwent secondary CRS. In contrast, the BEV group showed improved PFS and OS among patients who did not undergo surgery.The use of BEV during second-line chemotherapy and secondary CRS may improve PFS and OS in patients with platinum-sensitive relapsed OCCC. Further prospective studies are warranted.

Background Both predictions and predictors of difficult laryngoscopy are controversial. Machine learning is an excellent alternative method for predicting difficult laryngoscopy. This study aimed to develop and validate practical predictive models for difficult laryngoscopy through machine learning. Methods Variables for the prediction of difficult laryngoscopy included age, Mallampati grade, body mass index, sternomental distance, and neck circumference. Difficult laryngoscopy was defined as grade 3 and 4 by the Cormack-Lehane classification. Pre-anesthesia and anesthesia data of 616 patients who had undergone anesthesia at a single center were included. The dataset was divided into a base training set (n = 492) and a base test set (n = 124), with equal distribution of difficult laryngoscopy. Training data sets were trained with six algorithms (multilayer perceptron, logistic regression, supportive vector machine, random forest, extreme gradient boosting, and light gradient boosting machine), and cross-validated. The model with the highest area under the receiver operating characteristic curve (AUROC) was chosen as the final model, which was validated with the test set. Results The results of cross-validation were best using the light gradient boosting machine algorithm with Mallampati score x age and sternomental distance as predictive model parameters. The predicted AUROC for the difficult laryngoscopy class was 0.71 (95% confidence interval, 0.59–0.83; p = 0.014), and the recall (sensitivity) was 0.85. Conclusion Predicting difficult laryngoscopy is possible with three parameters. Severe damage resulting from failure to predict difficult laryngoscopy with high recall is small with the reported model. The model’s performance can be further enhanced by additional data training.

In this retrospective study, the effectiveness of short-term teriparatide with denosumab in reducing fragility fracture risk was determined in comparison with denosumab monotherapy. Administration of sequential teriparatide with denosumab showed excellent outcomes in suppressing the risk for fragility fractures compared with denosumab monotherapy.To determine the effectiveness of short-term teriparatide with denosumab in reducing the risk of fragility fractures in comparison to denosumab monotherapy.The data of postmenopausal patients treated with denosumab for 2 years between August 2015 and October 2020 were retrospectively analyzed. One hundred sixty four postmenopausal women of a total 615 were excluded, since they did not undergo 2 bone mineral density (BMD) tests, were lost to follow-up, or received long-term teriparatide therapy. Total 320 patients received denosumab monotherapy and 131 patients received teriparatide for ≥ 3 months followed by denosumab. The number of osteoporotic fractures, presence of back pain before and after treatment, and annual BMD during treatment were comparatively assessed using t-test, Chi-square test, and linear mixed model analysis.Before treatment, the denosumab monotherapy group had fewer osteoporotic fractures (mean ± standard deviation; 0.459 ± 0.689) than the sequential therapy group had (1.037 ± 0.871; p 0.001). After treatment, the sequential therapy group had fewer osteoporotic fractures than the denosumab monotherapy group had (0.119 ± 0.348 versus 0.144 ± 0.385; p 0.001). At 1 and 2 years after treatment, the increase in lumbar spine BMD was greater in the sequential therapy group than in the denosumab monotherapy group (p = 0.08, group × time). The difference between post and pre-treatment back pain visual analog scale score was significantly lower in the sequential therapy group than in the monotherapy group (3.246 ± 3.426 versus 1.734 ± 3.049; p 0.001).Short-term teriparatide use before denosumab showed excellent outcomes in suppressing the risk of fragility fractures compared with denosumab monotherapy.

In this post hoc analysis of the PRODIGY study, we aimed to investigate factors associated with survival outcomes and provide evidence for designing optimal perioperative treatment strategies for gastric cancer patients receiving neoadjuvant chemotherapy.A total of 212 patients in the neoadjuvant chemotherapy group of the PRODIGY study were included as the study population. The prognostic impact of clinicopathologic factors, including the initial radiological clinical stage (cStage) and post-neoadjuvant chemotherapy pathological stage (ypStage), was analyzed.The median age was 58 years. The majority of patients (77.4%) had cStage III disease, and about 10% and 25% had ypStage 0 and I disease, respectively. According to the initial cStage, progression-free survival (PFS) and overall survival (OS) were significantly different (P 0.01). PFS and OS were also different according to the ypStage (P 0.01). In multivariate analyses, cStage IIIC disease (vs. cStage II) and ypStage II and III disease (vs. ypStage 0/I) were independent factors for poor survival outcomes. Based on the patterns of PFS and OS according to both cStage and ypStage, three patient groups were defined. These groups showed distinct PFS and OS (P 0.01) with 5-year PFS rates of 95.7%, 77.9%, and 31.3% and 5-year OS rates of 95.7%, 82.4%, and 42.5%, respectively.Both initial cStage and ypStage were independent factors for survival outcomes of gastric cancer patients treated with neoadjuvant chemotherapy. Efforts should be made to develop optimal peri-operative treatment strategies for patients at different risks according to cStage and ypStage.

Pulmonary vein stump thrombosis (PVST) is uncommonly encountered postoperative in-situ thrombosis in the stump of pulmonary veins after lung resection. Data regarding the incidence and clinical behaviour of PVST are scarce. Thus, this study aims to investigate the incidence, clinical characteristics and outcome of PVST after lung resection in patients with lung cancer. Follow-up enhanced chest computed tomography (CT) scans acquired after the surgery were retrospectively reviewed to determine PVST presence for patients with lung cancer who underwent lung resection in two tertiary referral centres. Out of the 1885 patients with lung cancer who underwent lobectomy or more extensive lung resection, PVST was observed in 37 patients (2.0%) on their follow-up chest CT. Most stump thrombi were observed in the left superior pulmonary vein [35 (94.6%)] and in patients who underwent left upper lobectomy [34 (91.9%)]. At the last CT follow-up of each patient, 33 (89.2%) exhibited complete resolution, three partial resolution and one stabilization. Eleven (29.7%) patients received anticoagulant therapy after the diagnosis. The rate of complete PVST resolution did not differ significantly between the anticoagulation and nonanticoagulation groups. None of the PVST patients experienced systemic embolic events, regardless of anticoagulation. The PVST incidence diagnosed at routine chest CT follow-up following lung cancer surgery was 2%. PVST was characterized by a benign clinical course without progression and systemic embolization, regardless of anticoagulation. However, further studies are required to determine individualized therapeutic strategies, including anticoagulation.

PurposeMelanoma incidence is rising worldwide along with the associated personal and socioeconomic health expenditures. We investigated the incidence and survival-rate patterns of melanoma in South Korea using nationwide data. Materials and MethodsThis retrospective cohort study included patients with melanoma between 2004 and 2017, based on National Health Insurance (NHI) claims data in South Korea. The incidence, prevalence, and survival rate were analyzed along with baseline demographic characteristics. We collected solar irradiation dose (SID) and healthcare ranking score (HRS) according to the administrative district from the Korea Meteorological Administration and Korea Health Promotion Institute. The incidence and survival rates were assessed using Pearson's correlation, the Kaplan-Meier estimation, multiple linear regression, and multiple logistic regression methods.ResultsTwenty-five thousand, five hundred ninety-one patients with melanoma were diagnosed during the study period. The age-standardized incidence of melanoma steadily increased from 2004 to 2017 from 2.6 to 3.0/100,000/yr. The incidence of melanoma increased with significantly higher income (p < 0.05). The prevalence followed a similar pattern as the incidence. According to multivariate analysis, HRS significantly influenced the incidence of melanoma in high sun-exposed sites (p < 0.001). There was no significant change in annual mortality. Women had a higher 5-year survival rate than men (78.4% vs. 72.8%). Mortality by the administrative district was highly correlated with HRS.ConclusionThe incidence of melanoma is increasing in South Korea. A low HRS is associated with both higher incidence and mortality. The findings of this study could be utilized as a guideline for treating melanoma patients.

Metformin is a widely used drug for type 2 diabetes mellitus and has recently attracted broad attention for its therapeutic effects on many cancers. This study aimed to investigate the molecular mechanism of metformin's anticancer activity.Cell viability was measured by MTT assay. Gene and protein expression levels were determined by reverse transcription-polymerase chain reaction and western blot analyses, respectively.Metformin and phenformin markedly induced NUPR1 expression in a dose- and time-dependent manner in H1299 non-small-cell lung cancer (NSCLC) cells. The silencing of NUPR1 in H1299 NSCLC cells enhanced cell sensitivity to metformin or ionizing radiation. Our previous report showed that metformin induces AKT serine/threonine kinase (AKT) activation in an activating transcription factor 4 (ATF4)-dependent manner and that the inhibition of AKT promotes cell sensitivity to metformin in H1299 NSCLC cells. Interestingly, ATF4-induced AKT activation in H1299 NSCLC cells treated with metformin was suppressed by the knockdown of NUPR1.Targeting NUPR1 could enhance the sensitivity of H1299 NSCLC cells to metformin by AKT inhibition.

It remains unclear whether immunotherapy, which is not generally considered for microsatellite stable (MSS) colorectal cancer (CRC), can be used to effectively treat select CRC patients. We investigated the feasibility of obesity-associated MSS CRC patients for immunotherapy based on genomic alterations.We evaluated differences in genomic alteration types and immune signatures between obese and non-obese patients with MSS CRC. We performed genomic analyses using 434 CRC patients from The Cancer Genome Atlas (TCGA). Patients with MSS CRC were stratified into subgroups based on their BMI and numbers of nonsynonymous single nucleotide variants (nsSNVs) and frameshift insertions and deletions (fs INDELs) using machine learning.The obese subgroup showed higher incidences of single nucleotide variants (SNV) and insertions and deletions (INDELs) in comparison with healthy weight patients with MSS CRC. The subgroup, who had higher numbers of nsSNVs and fs INDLEs, exhibited increased immune signatures, increased number of SNV-derived neoantigens, and had up-regulated two immune checkpoint genes in comparison with healthy weight patients with MSS CRC, reflecting interactions between the cancer genome and immune system.This study suggests that immunotherapy may be suitable for some obesity-associated CRC patients.

BACKGROUND Violence in emergency departments poses a threaten to both medical personnel and patients. We investigated the risk factors for high burnout status and the association between the impact of violence and burnout status of paramedics in emergency departments. METHODS We included paramedics of emergency departments in Korea. We conducted a survey on the emotional, physical, and social responses to violence using an assault response questionnaire. Additionally, we evaluated burnout status using the Maslach Burnout Inventory. RESULTS This study included 141 participants (57 females), with a mean age of 25.9 years. The burnout status was positively correlated with physical, emotional, and social responses, and the overall impact of violence (r = 0.576, 0.559, 0.446, and 0.590, respectively). Female sex, specialized centers, and emergency departments with

Vertical bony step (VBS) occurs between proximal and distal segments of the mandible during mandibular setback surgery with bilateral sagittal split ramus osteotomy. The purpose of this study was to investigate whether VBS is correlated with the relapse of mandibular setback using 3-dimensional models constructed from cone-beam computed tomography.The subjects consisted of 30 patients who underwent bilateral sagittal split ramus osteotomy for a mandibular setback. Double jaw surgery was performed in 18 patients, and isolated mandibular setback surgery was performed in 12 patients. Cone-beam computed tomography scans were taken at pretreatment (T0), postsurgery (T1), and posttreatment (T2). Treatment changes and the correlations between measurements were evaluated.The mean mandibular setback was -11.9 mm, and the mean VBS was -5.6 mm. Correlations with the relapse of mandibular setback were found in the amount of mandibular setback (T1 - T0), development of VBS (T1 - T0), posterior movement of the proximal segment (T1 - T0), counterclockwise rotation of symphysis (T2 - T1), and the resolution of VBS (T2 - T1).The development and resolution of VBS were correlated with the relapse of mandibular setback. Minimizing VBS is recommended to reduce the relapse of mandibular setback.

To evaluate the surgical effects of robotic paravaginal repair and sacrocolpopexy in patients diagnosed with lateral cystocele due to paravaginal defect.Robotic paravaginal repair and sacrocolpopexy were performed contemporaneously in 43 patients with high-grade pelvic organ prolapse combined with a lateral or mixed cystocele. To objectively evaluate prolapse correction, the Pelvic Organ Prolapse Quantification (POP-Q) test was performed at the 12-month visit and the results compared to those of the preoperative period. Subjective satisfaction was scored using the Patient Global Impression of Improvement (PGI-I) questionnaire.POP-Q measurement results before and after surgery, an objective indicator of surgery, the Ba and C scores improved significantly from 2.1 ± 1.2 preoperatively to -2.0 ± 1.1 postoperatively (P.01), and from 0.3 ± 1.3 preoperatively to -4.3 ± 1.1 postoperatively (P.01), respectively. In PGI-I questionnaire, the numbers of patients who awarded scores of 1 and 2 (evidencing high-level symptom improvement) were 33 at 1 month (76.7%), 30 at 3 months (69.8%), and 28 (65.1%) at 12 months. When respondents awarding 3 points (a little improvement) were included, the numbers rose to 38 (88.4%) at 1 and 3 months and 35 (81.4%) at 12 months, indicating satisfaction with symptom improvement. There were no critical complications during and after surgery, but complications such as de novo stress urinary incontinence that lower patient satisfaction occurred in some cases.Robot-assisted paravaginal repair and sacrocolpopexy can be safely performed in patients with cystocele-predominant pelvic organ prolapse and good surgical results can be expected with excellent effects.

A multicenter prospective study to evaluate the feasibility of Physician Orders for Life-Sustaining Treatment (POLST) in oncology practice was conducted between June and December 2017. Factors associated with POLST completion and follow-up outcomes were analyzed.Patients with terminal cancer, aged ≥ 20 years and capable of communicating, were enrolled from seven hospitals. Demographic data were collected and updated in February 2021. Descriptive statistics and logistic regression analyses were conducted.Among 336 patients, 105 (31.3%) completed POLST, which was more common in male (p = 0.029), patients with better performance (p 0.001), longer duration of follow-up (p = 0.037), and those living with children (p = 0.023). Male (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.17-3.51; p = 0.012), having good performance status (OR, 2.38; 95% CI, (1.35-4.19); p = 0.003), transferred from other departments (OR, 0.50; 95% CI, (0.26-0.98); p = 0.045), and living with children (OR, 1.94; 95% CI, (1.11-3.47); p = 0.020) were significant predictors of POLST completion. Patients who completed POLST were more likely to enroll in hospice care (p = 0.012) or experience out-of-hospital death (p = 0.016) at end-of-life (EOL). POLST completion showed a strong association with hospice enrollment at EOL (OR, 2.61; 95% CI, (1.08-6.32); p = 0.033).Gender, patient performance, timing of POLST discussion, and type of household were associated with POLST completion. Earlier discussions on POLST could reinforce hospice enrollment or non-aggressive EOL care.

We have developed a wireless, wearable Doppler ultrasound system that continuously measures the common carotid artery Doppler pulse. A novel measure from this device, the Doppler shock index, accurately detected moderate-to-severe central blood volume loss in a human hemorrhage model generated by lower body negative pressure. In this analysis, we tested whether the wearable Doppler could identify only mild-to-moderate central blood volume loss.Eleven healthy volunteers were recruited and studied in a physiology laboratory at the Mayo Clinic. Each participant underwent a lower body negative protocol in duplicate. Carotid Doppler measures including Doppler shock indices were compared with blood pressure and the shock index for their ability to detect both 10% and 20% reductions in stroke volume.All carotid Doppler measures were better able to detect diminishing stroke volume than either systolic or mean arterial pressure. Falling carotid artery corrected flow time and rising heart rate/corrected flow time (DSI FTc ) were the most sensitive measures for detecting 10% and 20% stroke volume reductions, respectively. The area under the receiver operator curves (AUROCs) for all shock indices was at least 0.86; however, the denominators of the two Doppler shock indices (i.e., the corrected flow time and velocity time integral) had AUROCs ranging between 0.81 and 0.9, while the denominator of the traditional shock index (i.e., systolic blood pressure) had AUROCs between 0.54 and 0.7.The wearable Doppler ultrasound was able to continuously measure the common carotid artery Doppler pulse. Carotid Doppler measures were highly sensitive at detecting both 10% and 20% stroke volume reduction. All shock indices performed well in their diagnostic ability to measure mild-to-moderate central volume loss, although the denominators of both Doppler shock indices individually outperformed the denominator of the traditional shock index.Diagnostic test or criteria; Level III.

Although successful short-term results of the intra-articular injection of mesenchymal stem cells (MSCs) for the conservative treatment of knee osteoarthritis (OA) have been reported, the mid-term results of the injection of adipose-derived (AD) MSCs remains unknown. We assessed the mid-term safety and efficacy of the intra-articular injection of ADMSCs in patients with knee OA. Eleven patients with knee OA were prospectively enrolled and underwent serial evaluations during a 5-year follow-up of a single intra-articular injection of autologous high-dose (1.0 × 108) ADMSCs. The safety profiles were assessed using the World Health Organization Common Toxicity Criteria. The clinical evaluations included visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores for pain and function, respectively. The radiologic evaluations included chondral defect area and whole-organ magnetic resonance imaging scores (WORMS) by serial magnetic resonance imaging (MRI). Hip-knee-ankle axis (HKAA) and Kellgren-Lawrence (K-L) grades were assessed on simple radiographs. No treatment-related adverse events occurred during the 5-year follow-up. Both VAS and total WOMAC scores improved significantly at 6 months after the injection and until the latest follow-up. Total WORMS was significantly improved until 3 years after the injection. However, the chondral defect size on MRI or other radiologic evaluations did not change significantly. A single intra-articular injection of autologous, high-dose ADMSCs provided safe and clinical improvement without radiologic aggravation for 5 years. Furthermore, structural changes in the osteoarthritic knee showed significant improvement up to 3 years, suggesting a possible option for disease-modifying outpatient treatment for patients with knee OA.

The genetic test solely based on the clinical features of hereditary colorectal cancer has limitations in clinical practice.This study aimed to analyze the results of comprehensive multigene panel tests based on clinical findings.This was a cross-sectional study based on a prospectively compiled database.The study was conducted at a tertiary hospital.A total of 381 patients with high risk for hereditary colorectal cancer syndromes were enrolled between March 2014 and December 2019.The primary outcome was to describe the mutational spectrum based on genotype-phenotype concordance and discordance.Germline mutations were identified in 89 patients for polyposis hereditary colorectal cancer genes (76 in APC; 4 in PTEN; 4 in STK11; 3 in BMPR1A; 1 in POLE; 1 in POLD1), 89 patients for nonpolyposis hereditary colorectal cancer genes (41 in MLH1; 40 in MSH2; 6 in MSH6; and 2 in PMS2), and 12 patients for other cancer predisposition genes (1 in ATM; 2 in BRCA1; 1 in BRCA2; 1 in BRIP1; 1 in MLH3; 1 in NBN; 1 in PMS1; 1 in PTCH1; 1 in TP53; and 2 in monoallelic MUTYH). If we had used direct sequencing tests of 1 or 2 major genes based on phenotype, 48 (25.3%) of 190 mutations would not have been detected due to technical differences (12.1%), less frequent genotype (4.2%), unclear phenotype (3.7%), and genotype-phenotype discordance (4.7%). The genotype-phenotype discordance is probably linked to compound heterozygote, less distinctive phenotype, and insufficient information for colorectal cancer risk.This study included a small number of patients with insufficient follow-up duration.A comprehensive multigene panel is expected to identify more genetic mutations than phenotype-based direct sequencing, with special utility for unclear phenotype or genotype-phenotype discordance. See Video Abstract at http://links.lww.com/DCR/B844.ANTECEDENTES:La prueba genética basada únicamente en la característica clínica del cáncer colorrectal hereditario tiene limitaciones en la práctica clínica.OBJETIVO:Este estudio tuvo como objetivo analizar el resultado de pruebas integrales de panel multigénico basadas en hallazgos clínicos.DISEÑO:Este fue un estudio transversal basado en una base de datos recopilada prospectivamente.AJUSTE:El estudio se realizó en un hospital terciario.PACIENTES:Se inscribió un total de 381 pacientes con alto riesgo de síndromes de cáncer colorrectal hereditario entre marzo del 2014 y diciembre del 2019.PRINCIPALES MEDIDAS DE RESULTADO:El resultado principal fue describir el espectro mutacional basado en la concordancia y discordancia genotipo-fenotipo.RESULTADOS:Se identificaron mutaciones de la línea germinal en 89 pacientes para genes de cáncer colorrectal hereditario con poliposis (76 en APC; 4 en PTEN; 4 en STK11; 3 en BMPR1A; 1 en POLE; 1 en POLD1), 89 pacientes para genes de CCR hereditario sin poliposis (41 en MLH1; 40 en MSH2; 6 en MSH6; y 2 ​​en PMS2) y 12 pacientes por otro gen de predisposición al cáncer (1 en ATM; 2 en BRCA1; 1 en BRCA2; 1 en BRIP1; 1 en MLH3; 1 en NBN; 1 en PMS1; 1 en PTCH1; 1 en TP53; y 2 ​​en MUTYH monoalélico). Si hubiéramos utilizado pruebas de secuenciación directa de uno o dos genes principales basados ​​en el fenotipo, 48 (25,3%) de 190 mutaciones no se habrían detectado debido a diferencias técnicas (12,1%), genotipo menos frecuente (4,2%), fenotipo poco claro (3,7%) y discordancia genotipo-fenotipo (4,7%). La discordancia genotipo-fenotipo probablemente esté relacionada con el heterocigoto compuesto, el fenotipo menos distintivo y la información insuficiente para el riesgo de cáncer colorrectal.LIMITACIONES:Este estudio incluyó una pequeña cantidad de pacientes con una duración de seguimiento insuficiente.CONCLUSIONES:Se espera que un panel multigénico completo identifique más mutaciones genéticas que la secuenciación directa basada en el fenotipo, con especial utilidad para la discordancia de fenotipo o genotipo-fenotipo poco clara. Consulte Video Resumen en http://links.lww.com/DCR/B844. Traducción- Dr. Francisco M. Abarca-Rendon).

This study aimed to establish a new classification using locked-plate fixation for periprosthetic distal femoral fracture (PDFF) following total knee arthroplasty (TKA) and to determine when dual locked-plate fixation is necessary through defining this classification.One-hundred fifteen consecutive PDFFs that underwent operative treatment were reviewed from 2011 to 2019 with minimum 1-year follow-up. Most PDFFs were fixed with single or dual locked-plate fixations using the minimally invasive plate osteosynthesis technique. Based on preoperative radiographs, PDFFs were classified according to the level of main fracture line relative to the anterior flange of femoral component: type I and II, main fracture line located proximal and distal to the anterior flange; and type III, component instability regardless of fracture line requiring revisional TKA. Furthermore, type II fractures were subclassified based on the direction of fracture beak as follows: type IIIncidences of type I, IIThe new classification provides practical and obvious strategies for the treatment of PDFF following TKA using locked-plate fixation. For type II

This study aimed to quantify the buccal alveolar bone thickness (BABT) in the maxillary molar region to provide a practical guideline for vertical temporary skeletal anchorage device (TSAD) placement using cone-beam computed tomography (CBCT). It also aimed to develop a linear regression model for use in digital models to predict available BABT.The sample for this retrospective study consisted of 31 sites (24 patients; mean age, 28.75 years; range, 18-44 years) in which vertical TSADs were placed successfully in the maxillary posterior interradicular area during the total arch distalization procedure. BABT was measured at 3 points of the interradicular space using CBCT, and the buccal alveolar region thickness (BART), which included buccal-attached gingival thickness and the buccal alveolar bone, was measured using the digital model. In CBCT, BABT was measured at the most convex point of the lamina dura of the root adjacent to the vertical TSAD mesially, at the most convex point of the lamina dura of the root adjacent to the vertical TSAD distally, and the central point between the mesial and distal points. Three linear measurements were obtained at 2, 4, and 6 mm apical to the alveolar crest: the mesial thickness, the central thickness (centralBoth BABT and BART at the central position (centralThe mean BABT and BART at the central position, in which we suggest placing vertical TSADs, were 3.44 ± 0.69 mm in CBCT and 6.28 ± 1.11 mm in the digital model, respectively. The minimum BABT and BART at the central position in which vertical TSAD was placed successfully were 2.38 mm in CBCT and 4.25 mm in the digital model. There was a strong correlation between central

Background: Remifentanil reduces cough during extubation. Ramosetron, a 5-HT3 receptor antagonist, is a potent antiemetic. Regarding the antitussive property of 5-HT receptor agonists, ramosetron can mediate the cough reflex by increasing the remifentanil requirement. This study evaluated the effect of ramosetron on the optimal effect-site concentration (Ce) of remifentanil for preventing emergence cough from sevoflurane anesthesia in female patients. Methods: Forty-seven randomly selected female patients undergoing laparoscopic cholecystectomy received either ramosetron 0.3 mg (n = 23) or the same volume of normal saline (n = 24) intravenously at the end of surgery. The remifentanil Ce using target-controlled infusion in 50% of patients (EC50) and 95% of patients (EC95) were assessed using Dixon’s up-and-down or isotonic regression method with a bootstrapping approach. Results: Using Dixon’s up-and-down method, the EC50 of remifentanil in the control group (1.33 ± 0.38 ng/mL) was comparable to that of ramosetron group (1.50 ± 0.69 ng/mL) (P = 0.615). Using isotonic regression analysis, the EC50 (83% confidence interval) did not differ between the two groups (1.17 [0.86-1.43] ng/mL and 1.13 [0.68-1.56] ng/mL in control and ramosetron groups). However, the EC95 (95% confidence interval) was significantly lower in the control group than in the ramosetron group (1.90 [1.45-1.96] ng/mL and 2.92 [2.35-2.97] ng/mL). Conclusion: Remifentanil Ce for preventing emergence cough was higher in the ramosetron group than in the control group. It may indicate the lowering effect of ramosetron on the antitussive activity of remifentanil. Clinical Trial Registration No: (KCT0005441).

Background/Aims: The study investigated the incidence of thromboembolic events (TEE) in head and neck (H&N) cancer patients who received concurrent chemoradiotherapy (CCRT) with cisplatin, and analyzed the factors affecting TEE occurrenceMethods: Two hundred and fifty-seven patients who started CCRT with cisplatin for H&N cancer from January 2005 to December 2019 were analyzed.Results: TEE occurred in five patients, an incidence rate of 1.9%. The 2-, 4-, and 6-month cumulative incidences of TEE were 0.8%, 1.6%, and 1.9%, respectively. Khorana score was the only factor associated with TEE occurrence (p = 0.010).Conclusions: The incidence of TEE in H&N cancer patients who underwent CCRT with cisplatin was relatively low when compared to other types of cancer. However, patients with a high Khorana score require more careful surveillance for possible TEE occurrence.

Previous studies have reported the protective effects of tauroursodeoxycholic acid (TUDCA) on gastric epithelial cells in some animal models, but the precise mechanisms are unclear. This study examined the effects of TUDCA on NF-κB signaling in gastric epithelial cells. Moreover, the protective effects of TUDCA in experimental gastritis models induced by ethanol and NSAID were evaluated and compared with ursodeoxycholic acid (UDCA).After a pretreatment with TUDCA or UDCA, human gastric epithelial MKN-45 cells were stimulated with tumor necrosis factor (TNF)-α to activate NF-κB signaling. A real-time PCR (RT-PCR) for human interleukin (IL)-1 mRNA was performed. An electrophoretic mobility shift assay (EMSA) and immunoblot analyses were carried out. In murine models, after a pretreatment with TUDCA or UDCA, ethanol and indomethacin were administered via oral gavage. Macroscopic and microscopic assessments were performed to evaluate the preventive effects of TUDCA and UDCA on murine gastritis.A pretreatment with TUDCA downregulated the IL-1α mRNA levels in MKN-45 cells stimulated with TNF-α, as assessed by RT-PCR. As determined using EMSA, a pretreatment with TUDCA reduced the TNF-α-induced NF-κB DNA binding activity. A pretreatment with TUDCA inhibited IκBα phosphorylation induced by TNF-α, as assessed by immunoblot analysis. TUDCA attenuated the ethanol-induced and NSAID-induced gastritis in murine models, as determined macroscopically and microscopically.TUDCA inhibited NF-κB signaling in gastric epithelial cells and ameliorated ethanol- and NSAID-induced gastritis in murine models. These results support the potential of TUDCA for the prevention of gastritis in humans.

Heart disease is one of the largest burdens to human health worldwide and has very limited therapeutic options. Engineered three-dimensional (3D) vascularized cardiac tissues have shown promise in rescuing cardiac function in diseased hearts and may serve as a whole organ replacement in the future. One of the major obstacles in reconstructing these thick myocardial tissues to a clinically applicable scale is the integration of functional vascular networks capable of providing oxygen and nutrients throughout whole engineered constructs. Without perfusion of oxygen and nutrient flow throughout the entire engineered tissue not only is tissue viability compromised, but also overall tissue functionality is lost. There are many supporting technologies and approaches that have been developed to create vascular networks such as 3D bioprinting, co-culturing hydrogels, and incorporation of soluble angiogenic factors. In this state-of-the-art review, we discuss some of the most current engineered vascular cardiac tissues reported in the literature and future directions in the field. IMPACT STATEMENT: The field of cardiac tissue engineering is rapidly evolving and is now closer than ever to having engineered tissue models capable of predicting preclinical responses to therapeutics, modeling diseases, and being used as a means of rescuing cardiac function following injuries to the native myocardium. However, a major obstacle of engineering thick cardiac tissue remains to be the integration of functional vasculature. In this review, we highlight seminal and recently published works that have influenced and pushed the field of cardiac tissue engineering toward achieving vascularized functional tissues.

Colorectal cancer is reported to have the highest mortality rate among human malignancies. Although many research results for the treatment of colorectal cancer have been reported, there is no suitable treatment when resistance has developed. Therefore, it is necessary to develop new therapeutic agents. Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling plays an essential role in cell differentiation, proliferation, and survival. Abnormal activation of the JAK/STAT signaling pathway, by gene mutation or amplification, may induce cancer development, and sustained JAK/STAT activation is involved in chemoresistance. While many therapeutic agents have been developed to treat colon cancer, there remains no drug to overcome resistance to chemotherapies. The purpose of this study was to determine the potential of CJ14939 as a novel JAK inhibitor for the treatment of colorectal cancer.In this study, cell culture, cell death assay, 3- (4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, colony formation assay, immunoblot analysis and tumor xenograft were applied.CJ14939 induced cell death, and inhibited phosphorylation of JAK1 and STAT3 in colorectal cancer cells. Furthermore, CJ14939 also promoted oxaliplatin-induced cell death, up-regulated expression of cleaved caspase-3, and down-regulated expression of phospho-JAK1 and phospho-STAT3. In vivo, co-treatment with CJ14939 and oxaliplatin notably reduced tumor growth when compared with CJ14939 or oxaliplatin treatment alone.This study identifies the important potential of CJ14939 in colorectal cancer treatment and suggests that combining CJ14939 with oxaliplatin might be a novel therapeutic strategy for patients with colorectal cancer.

Some young individuals present with shoulder pain without a definite history or complaint of instability. However, careful history taking, physical examination, and high-quality magnetic resonance imaging may reveal evidence of instability of which the patient is unaware. Therefore, a clearer definition of these ambiguous patients is needed. This study aimed to report the characteristics and surgical outcomes of patients with microinstability compared to those of patients with classic recurrent anterior shoulder instability.From 2005 to 2018, 35 patients with microinstability (group M) underwent arthroscopic anterior labral repair (AALR) and were compared to 35 sex- and age-matched patients with classic recurrent anterior shoulder instability (group C) who also underwent AALR. Baseline characteristics, preoperative apprehension test findings, preoperative imaging for the presence of anterior labral and Hill-Sachs lesions, preoperative and postoperative (over 2 years) range of motion (ROM) and functional scores, final complications, and patient satisfaction were analysed.The most common chief complaints in groups M and C were pain (29/35) and both pain and instability (27/35), respectively. Only pain during the apprehension test was predominant in group M (M vs. C, 27 vs. 1, p 0.001). High incidence of chronic repetitive injuries (26/35) and acute trauma (28/35) were observed in groups M and C, respectively. Over half of the patients in group M showed anterior labral lesions on magnetic resonance arthrography (MRA, 18/35), and 21 patients had Hill-Sachs lesions on MRA/three-dimensional computed tomography. Finally, 29 patients showed either anterior labral or Hill-Sachs lesions on preoperative imaging. The lesion severity was higher in group C than that in group M. All patients underwent AALR with/without the remplissage procedure, with no significant differences in final clinical outcomes, complications, and patient satisfaction between the groups.Microinstability is diagnostically challenging and can be diagnosed in young patients with ambiguous shoulder pain during motion, without instability. Pain on anterior apprehension test and subtle labral and/or Hill-Sachs lesion on imaging study could be diagnostic clues. This condition can be managed with arthroscopic anterior labral repair with or without the remplissage procedure. The possibility of microinstability in young patients with shoulder pain should always be considered, and small anterior labral or Hill-Sachs lesions should be closely monitored.III.

Peritoneal metastasis (PM) remains a major obstacle in the treatment of stage IV gastric cancer. This is a dose-escalation study of intraperitoneal (IP) paclitaxel combined with intravenous (IV) fluorouracil, leucovorin, and oxaliplatin (FOLFOX) to determine the recommended phase II dose in gastric cancer patients.Patients with gastric adenocarcinoma and PM were enrolled. The recommended phase II dose of IP paclitaxel was determined using the standard "3 + 3" dose escalation with planned doses ranging from 40 to 100 mg/mAmong the 13 patients, there was no DLT at 40 and 60 mg/mThe biweekly regimen of IP paclitaxel and FOLFOX is safe and the recommended dose of IP paclitaxel for a phase II trial is 60 mg/m

The primary aim of this laboratory-based human subject study was to evaluate the biomechanical loading associated with mining vehicles' multi-axial whole body vibration (WBV) by comparing joint torque and muscle activity in the neck and low back during three vibration conditions: mining vehicles' multi-axial, on-road vehicles' vertical-dominant, and no vibration. Moreover, the secondary aim was to determine the efficacy of a vertical passive air suspension and a prototype multi-axial active suspension seat in reducing WBV exposures and associated biomechanical loading measures. The peak joint torque and muscle activity in the neck and low back were higher when exposed to multi-axial vibration compared to the vertical-dominant or no vibration condition. When comparing the two suspension seats, there were limited differences in WBV, joint torque, and muscle activity. These results indicate that there is a need to develop more effective engineering controls to lower exposures to multi-axial WBV and related biomechanical loading.

Few studies have been conducted on sex differences in the incidence, pathophysiology, and prognosis of gastric cancer (GC).To analyze the differences in GC characteristics according to sex in patients who underwent surgical treatment for GC.A total of 2983 patients diagnosed with gastric adenocarcinoma who received surgical treatment at the Seoul National University Bundang Hospital between 2003 and 2017 were included. Baseline clinicopathological characteristics, histologic type of GC, overall and GC-specific survival rates, and associated risk factors were analyzed.Among the 2983 patients, 2005 (67.2%) and 978 (32.8%) were males and females, respectively. The average age of the female group (59.36 years) was significantly younger than that of the male group (61.66 years;Sex-based differences in GC were observed in clinicopathological features, including age at diagnosis, tumor location, histologic type, survival rate, and comorbidities.

To evaluate the efficacy and safety of reducing target volume in definitive radiotherapy for HPV-associated tonsil cancer.A single-institution cohort of 90 patients with human papillomavirus (HPV)-associated tonsil cancer who received definitive radiotherapy with a 5-mm expansion from the gross tumor volume to clinical target volume between 2008 and 2019 were included. The overlapping volume of initial planning target volume and the recurrent tumor was calculated and categorized as one of three failure types: in-field: ≥95%; marginal-field: 50%-94%; and out-field:50%.With a median follow-up of 59.4 months, the 3-year and 5-year local control rates were 94.4% and 92.8%, respectively. A total of seven local failures were identified, of which 4 (4.4%) were in-field, 2 (2.2%) were marginal-field, and 1 (1.1%) was out-field. Grade 3 acute and late toxicities developed in 30 (33.3%) and 5 (5.6%) patients, respectively.Reducing target volume could be an alternative option for selected patients with HPV-associated tonsil cancer.

Amidst the Coronavirus Disease 2019 (COVID-19) pandemic, vaccination against severe acute respiratory syndrome 2 (SARS-CoV-2) is recommended for everyone over 18 years in South Korea, with the exception of pregnant women. Unexpected adverse cutaneous reactions after the COVID-19 vaccination have been recently reported. Cutaneous small-vessel vasculitis (CSVV) predominantly affects small blood vessels, defined as small intraparenchymal arteries, arterioles, capillaries, and venules, without any detectable involvement of non-cutaneous organs. We report five cases of CSVV after the ChAdOx1 COVID-19 vaccination in 44- to 68-year-old women. The symptoms commonly appeared within 2 days after vaccination. The lesion was localized to the lower limbs in four patients and spread to the upper limbs in one patient. All patients demonstrated a favorable response to oral methylprednisolone, antihistamines, and topical steroids. Considering the importance of the COVID-19 vaccination, clinicians should be aware of CSVV as a potential adverse event. Further studies are required to elucidate the causative link and pathogenesis.

Bromodomain and extraterminal domain (BET) proteins are epigenetic readers that regulate gene expression. We investigated whether variants in BET genes are associated with survival outcomes for lung cancer. To do this, the associations between 77 variants in BET family genes and survival outcomes were analyzed in 773 non‐small‐cell lung cancer (NSCLC) patients who underwent surgery (349 and 424 patients in the discovery and validation cohorts, respectively). We found that six variants were significantly associated with overall survival (OS) in the discovery cohort, and one variant (rs2506711C>T) was replicated in the validation cohort. BRD3 rs2506711C>T is located in the repressed area and has a strong linkage disequilibrium with rs2427964C>T in the promoter region. BRD3 rs2427964C>T was significantly associated with worse OS in the discovery cohort, validation cohort, and combined analysis. In a luciferase assay, promoter activity in the BRD3 rs2427964 T allele was significantly higher than that in the BRD3 rs2427964 C allele, which selectively bound with the transcriptional repressor SIN3A. Knockdown of BRD3 with BRD3‐specific siRNA decreased the proliferation and migration of lung cancer cells while also increasing the rate of apoptosis. These results suggest that BRD3 rs2427964C>T increases BRD3 expression through increased promoter activity, which is associated with poor prognosis for lung cancer., In this study, we investigated the association of BET gene variants with survival of patients with non‐small‐cell lung cancer (NSCLC). We observed that the rs2427964C>T SNP in the BRD3 promoter region was associated with poorer survival outcome. BRD3 promoter activity was higher in rs2427964_T than in rs2427964_C, which selectively bound with the transcriptional repressor SIN3A. Additionally, BRD3 silencing decreased the proliferation and migration of NSCLC cells. Our data suggest that elevated BRD3 expression regulated by rs2427964C>T leads to reduced overall survival in patients with NSCLC.

Purpose Despite the increasing use of stereotactic body radiation therapy for non–spine bone metastases (NSBM), there is no established standard for target delineation. The objective of this study was to provide consensus recommendations on clinical target volume (CTV) delineation based on international expert contours. Methods and Materials Eleven cases of NSBM were contoured by 9 international radiation oncologists. For each case, the gross tumor volume was provided on the simulation computed tomography scans with accompanying magnetic resonance imaging. Participants contoured the CTV and completed a clinical survey. Agreement between CTV contours were analyzed with simultaneous truth and performance level estimation using the kappa coefficient and the Dice similarity coefficient (DSC) and summarized to establish contouring recommendations. A direction-dependent analysis was applied to the consensus contours to quantify margins. Results All CTV contours were completed. Six participants used a single-dose level, whereas 3 used a 2-dose level simultaneous integrated boost (SIB) technique. For the SIB cases, the largest volume receiving a stereotactic body radiation therapy (SBRT) dose was used for contour analysis. There was substantial agreement between contours across cases with a mean kappa of 0.72 (mean sensitivity 0.85, mean specificity 0.97). The mean DSC value was 0.77 (range, 0.67-0.87). Consensus CTV contouring recommendations were (1) an intraosseous CTV margin of 5 to 10 mm should be strongly considered within contiguous bone; (2) an extraosseous margin of 5 to 10 mm should be strongly considered where there is soft tissue disease or cortical bone disruption; (3) CTVs should be manually cropped to respect anatomic barriers to spread (eg, peritoneal cavity, pleura, uninvolved joint space and cortical bone). Conclusions CTV contouring recommendations for NSBM-SBRT were established based on analysis of international expert consensus contours with a high level of agreement. These principles may provide guidance to treating physicians and inform future study until prospective clinical data can provide further refinement.

Background Although surgical treatment is considered reliable for lateral elbow tendinosis, local injection therapy may be preferable, as it avoids surgery. Among a number of local injections, platelet-rich plasma has been used successfully to treat lateral elbow tendinosis. The purpose of this study was to compare the outcomes in patients treated with either platelet-rich plasma injections or surgery for lateral elbow tendinosis using a systematic literature review and meta-analysis. Methods MEDLINE, Embase, and Cochrane Library databases were systematically searched for studies published before March 1, 2021, that compared platelet-rich plasma with operative treatment for lateral elbow tendinosis. The pooled analysis was designed to compare the visual analog scale scores and the Patient-Related Tennis Elbow Evaluation scores between the platelet-rich plasma and surgical treatment groups at serial time points. Results We included five studies involving 340 patients with lateral elbow tendinosis, comprising of 154 patients treated with platelet-rich plasma and 186 patients who underwent surgical treatment. The pooled analysis showed no statistically significant differences in the visual analog scale scores at any of the follow-up time points, namely post-intervention 2 months (mean difference = 1.11, 95% confidence interval: −2.51 to 4.74, P = 0.55, I2 = 94%), 6 months (mean difference = 0.80, 95% confidence interval: −2.83 to 4.42, P = 0.67, I2 = 92%), and 12 months (mean difference = −0.92, 95% confidence interval: −4.63 to 2.80, P = 0.63, I2 = 93%) and in the Patient-Related Tennis Elbow Evaluation scores at post-intervention 12 weeks (mean difference = −1.86, 95% confidence interval: −22.30 to 18.58, P = 0.86, I2 = 81%), 24 weeks (mean difference = −3.33, 95% confidence interval: −21.82 to 15.17, P = 0.72, I2 = 74%), and 52 weeks (mean difference = −3.64, 95% confidence interval: −19.65 to 12.37, P = 0.66, I2 = 69%). Conclusions Local platelet-rich plasma injections and surgical treatment produced equivalent pain scores and functional outcomes in patients with lateral elbow tendinosis. Thus, platelet-rich plasma injections may represent a reasonable alternative treatment for patients who are apprehensive to proceed with surgery or for poor surgical candidates.

Mycobacterium tuberoculosis (Mtb) is a contagious pathogen that causes human tuberculosis (TB). TB is a major global health threat that causes 9.6 million illnesses and 1.5 million deaths per year. Recent studies have suggested Mtb-secreted proteins as new candidates for therapeutic drugs and vaccines. LprG is a Mtb-secreted surface glycolipoprotein encoded by lprG (Rv1411c), which forms an operon with Rv1410c, where Rv1410c encodes P55, an efflux pump membrane protein. Various in vitro and in vivo studies have reported on the target-binding activity, cell envelope biosynthesis, and mycobacterial virulence of LprG. However, the anti-inflammatory effect of LprG in macrophages has not yet been investigated. In this study, we demonstrated that LprG can suppress lipopolysaccharide (LPS)-induced inflammation in a macrophage model. LprG inhibited LPS-stimulated nitric oxide (NO) production. LprG also suppressed expression of inducible cyclooxygenase-2 (COX-2) and nitric oxide synthase (iNOS) at the transcriptional and protein levels. In addition, LprG decreased mRNA expression of the pro-inflammatory cytokines interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Furthermore, LprG attenuated nuclear factor kappa-B (NF-κB) translocation and IκB phosphorylation. Moreover, LprG specifically inhibited phosphorylated kinases such as c-Jun N-terminal kinase (p-JNK) and extracellular signal-regulated kinase 1/2 (p-ERK1/2), but not p-p38. Taken together, these results suggest that LprG inhibits LPS-stimulated inflammation via downregulation of NO, COX-2, iNOS, and pro-inflammatory cytokines through the NF-κB, AP-1, and MAPK signaling pathways. The present study will aid in the development of anti-inflammatory medications using Mtb. The organism, which has long been regarded as a human pathogenic or human health-threating agent, can be utilized as a future medical resource.

Purpose This study aimed to develop a model for predicting pathologic extracapsular extension (ECE) and seminal vesicle invasion (SVI) while integrating magnetic resonance imaging-based T-staging (cTMRI, cT1c-cT3b).Materials and Methods A total of 1,915 who underwent radical prostatectomy between 2006-2016 met the inclusion/exclusion criteria. We performed a multivariate logistic regression analysis as well as Bayesian network (BN) modeling based on possible confounding factors. The BN model was internally validated using 5-fold validation.Results According to the multivariate logistic regression analysis, initial prostate-specific antigen (iPSA) (β=0.050, p < 0.001), percentage of positive biopsy cores (PPC) (β=0.033, p < 0.001), both lobe involvement on biopsy (β=0.359, p=0.009), Gleason score (β=0.358, p < 0.001), and cTMRI (β=0.259, p < 0.001) were significant factors for ECE. For SVI, iPSA (β=0.037, p < 0.001), PPC (β=0.024, p < 0.001), Gleason score (β=0.753, p < 0.001), and cTMRI (β=0.507, p < 0.001) showed statistical significance. BN models to predict ECE and SVI were also successfully established. The overall area under the receiver operating characteristic curve (AUC)/accuracy of the BN models were 0.76/73.0% and 0.88/89.6% for ECE and SVI, respectively. According to internal comparison between the BN model and Roach formula, BN model had improved AUC values for predicting ECE (0.76 vs. 0.74, p=0.060) and SVI (0.88 vs. 0.84, p < 0.001).Conclusion Two models to predict pathologic ECE and SVI integrating cTMRI were established and installed on a separate website for public access to guide radiation oncologists.

Caudal-type homeobox 2 (CDX2), special AT-rich sequence-binding protein 2 (SATB2), and keratin 20 (KRT20) are frequently used as intestinal epithelium-specific markers in immunohistochemical studies. However, subsets of colorectal carcinomas (CRCs) show loss of these markers. We analyzed The Cancer Genome Atlas data to explore molecular correlates of CDX2, SATB2, and KRT20 genes in 390 CRCs. The decreased mRNA expression of each of the three genes commonly correlated with microsatellite instability-high (MSI-H), CpG island methylator phenotype-high (CIMP-H), BRAF/RNF43 mutations, consensus molecular subtype 1, and high tumor mutational burden. The downregulation of CDX2 or SATB2 was dependent on both MSI-H and CIMP-H, whereas that of KRT20 was more dependent on MSI-H than on CIMP-H. Next, we evaluated the immunohistochemical expression of CDX2, SATB2, and KRT20 in 436 primary CRCs. In contrast to RNA-level expression, decreased expression of CDX2 and SATB2 was more dependent on CIMP-H than on MSI-H. However, consistent with RNA-level expression, decreased expression of KRT20 was more dependent on MSI-H than on CIMP-H. CIMP-H and lymphatic invasion were consistently associated with both CDX2 loss and SATB2 loss in CRCs, regardless of MSI status. In microsatellite stable CRCs, CDX2 loss correlated with BRAF mutation, whereas SATB2 loss was associated with KRAS mutations and decreased T-cell infiltration. Cases with concurrent loss of all three markers were found exclusively in MLH1-methylated MSI-H/CIMP-H CRCs. In conclusion, MSI-H and/or CIMP-H are major common correlates of decreased CDX2/SATB2/KRT20 expression in CRCs, but the specific features associated with the loss of each marker are different in CRCs.

The necessity of managing stress levels is becoming increasingly apparent as the world suffers from different kinds of stresses including the extent of pandemic, the corona virus disease 2019 (COVID-19). Cortisol, a clinically confirmed stress hormone related to depression and anxiety, affects individuals mentally and physically. However, current cortisol monitoring methods require expert personnel, large and complex machines, and long time for data analysis. Here, we present a flexible and wearable cortisol aptasensor for simple and rapid cortisol real-time monitoring. The sensing channel was produced by electrospinning conducting polyacrylonitrile (PAN) nanofibers (NFs) and subsequent vapor deposition of carboxylated poly(3,4-ethylenedioxythiophene) (PEDOT). The conjugation of the cortisol aptamer on the PEDOT-PAN NFs provided the critical sensing mechanism for the target molecule. The sensing test was performed with a liquid-ion gated field-effect transistor (FET) on a polyester (polyethylene terepthalate). The sensor performance showed a detection limit of 10 pM (5 s) and high selectivity in the presence of interference materials at 100 times higher concentrations. The practical usage and real-time monitoring of the cortisol aptasensor with a liquid-ion gated FET system was demonstrated by successful transfer to the swab and the skin. In addition, the real-time monitoring of actual sweat by applying the cortisol aptasensor was also successful since the aptasensor was able to detect cortisol approximately 1 nM from actual sweat in a few minutes. This wearable biosensor platform supports the possibility of further application and on-site monitoring for changes of other numerous biomarkers.

Single-incision laparoscopic surgery is gaining more attention due to advancements in surgical devices and techniques. Ten years have passed since the first report of single-incision distal gastrectomy. This study aims to analyze the long-term oncological safety of single-incision distal gastrectomy by comparing it with multiport distal gastrectomy.Patients diagnosed with gastric cancer who underwent laparoscopic distal gastrectomy from January 2010 to December 2017 were enrolled. Palliative surgery, history of other malignancy, preoperative chemotherapy, and distant metastasis were excluded. The 5-year overall survival and 5-year disease-free survival were set as coprimary endpoints. Operative time, blood loss, postoperative outcome, and risk factors for survival were secondary endpoints. Propensity score matching of 1:1 ratio was performed to adjust for age, sex, body mass index, comorbidities, tumor size, operation history, and clinical stage.A total of 3,097 patients were enrolled. After propensity score matching, 378 patients were allocated to each group. There was no difference in patient demographics after matching. Operation time was faster (170.8 ± 65.3 minutes vs 147.2 ± 44.1 minutes, p0.001), with less blood loss in the single-port group (84.1 ± 87.6 mL vs 34.9 ± 49.9 mL, p0.001). Administration of additional intravenous analgesics was less frequent in the single-port group (p = 0.043). There was no difference in long-term survival (5-year overall survival: multiport 94.2%, single-port 95.8%, p = 0.43; 5-year disease-free survival: multiport 94.1%, single-port 95.8%, p = 0.32).Single-incision distal gastrectomy is safe and feasible with good long-term outcomes and less use of additional analgesics for patients diagnosed with early gastric cancer.

Background Multidrug-resistant organisms (MDROs) such as vancomycin-resistant enterococci (VRE) and carbapenemase-producing Enterobacteriaceae (CPE) are associated with prolonged hospitalisation, increased medical costs, and severe infections. Faecal microbiota transplantation (FMT) has emerged as an important strategy for decolonisation. This study aimed to evaluate the genetic response of MDROs to FMT. Methods A single-centre prospective study was conducted on patients infected with VRE, CPE, or VRE/CPE who underwent FMT between May 2018 and April 2019. Genetic response was assessed as the change in the expression of the resistance genes VanA, blaKPC, blaNDM, and blaOXA on days 1, 7, 14, and 28 by real-time reverse-transcription polymerase chain reaction. Results Twenty-nine patients received FMT, of which 26 (59.3%) were infected with VRE, 5 (11.1%) with CPE, and 8 (29.6%) with VRE/CPE. The mean duration of MDRO carriage before FMT was 71 days. Seventeen patients (63.0%) used antibiotics within a week of FMT. In a culture-dependent method, the expression of VanA and overall genes significantly decreased (p = 0.011 and p = 0.003 respectively). In a culture-independent method, VanA, blaNDM, and overall gene expression significantly decreased over time after FMT (p = 0.047, p = 0.048, p = 0.002, respectively). Similar results were confirmed following comparison between each time point in both the culture-dependent and -independent methods. Regression analysis did not reveal important factors underlying the genetic response after FMT. No adverse events were observed. Conclusion FMT in patients infected with MDROs downregulates the expression of resistance genes, especially VanA, and facilitates MDRO decolonisation.

Background & Aims Tumor necrosis factor alpha (TNFα) is considered a major tissue damage-promoting effector in Crohn’s disease (CD) pathogenesis. Patient-derived intestinal organoid (enteroid) recapitulates the disease-specific characteristics of the intestinal epithelium. This study aimed to evaluate the intestinal epithelial responses to TNFα in enteroids derived from healthy controls and compare them with those of CD patient-derived enteroids. Methods Human enteroids derived from patients with CD and controls were treated with TNFα (30 ng/mL), and cell viability and gene expression patterns were evaluated. Results TNFα induced MLKL-mediated necroptotic cell death, which was more pronounced in CD patient-derived enteroids than in control enteroids. Immunohistochemistry and RNA sequencing revealed that treatment with TNFα caused expansion of the intestinal stem cell (ISC) populations. However, expanded ISC subpopulations differed in control and CD patient-derived enteroids, with LGR5+ active ISCs in control enteroids and reserve ISCs, such as BMI1+ cells, in CD patient-derived enteroids. In single-cell RNA sequencing, LGR5+ ISC-enriched cell cluster showed strong expression of TNFRSF1B (TNFR2) and cyclooxygenase-prostaglandin E2 (PGE2) activation. In TNFα-treated CD patient-derived enteroids, exogenous PGE2 (10 nmol/L) induced the expansion of the LGR5+ ISC population and improved organoid-forming efficiency, viability, and wound healing. Conclusions TNFα increases necroptosis of differentiated cells and induces the expansion of LGR5+ ISCs. In CD patient-derived enteroids, TNFα causes LGR5+ stem cell dysfunction (expansion failure), and exogenous PGE2 treatment restored the functions of LGR5+ stem cells. Therefore, PGE2 can be used to promote mucosal healing in patients with CD., Graphical abstract

Objective Doppler ultrasonography of the common carotid artery is used to infer stroke volume change and a wearable Doppler ultrasound has been designed to improve this workflow. Previously, in a human model of hemorrhage and resuscitation comprising approximately 50,000 cardiac cycles, we found a strong, linear correlation between changing stroke volume, and measures from the carotid Doppler signal, however, optimal Doppler thresholds for detecting a 10% stroke volume change were not reported. In this Research Note, we present these thresholds, their sensitivities, specificities and areas under their receiver operator curves (AUROC). Results Augmentation of carotid artery maximum velocity time integral and corrected flowtime by 18% and 4%, respectively, accurately captured 10% stroke volume rise. The sensitivity and specificity for these thresholds were identical at 89% and 100%. These data are similar to previous investigations in healthy volunteers monitored by the wearable ultrasound.