Site-Specific Mutagenesis Screening in KRASG12D Mutant Library to Uncover Resistance Mechanisms to KRASG12D Inhibitors.

KRAS plays a crucial role in regulating cell survival and proliferation and is one of the most commonly mutated oncogenes in human cancers. The novel KRASG12D inhibitor, MRTX1133, demonstrates promising antitumor efficacy in vitro and in vivo. However, the development of acquired resistance in treated patients presents a considerable challenge to sustained therapeutic effectiveness. In response to this challenge, we conducted site-specific mutagenesis screening to identify potential secondary mutations that could induce resistance to MRTX1133. We screened a range of KRASG12D variants harboring potential secondary mutations, and 44 representative variants were selected for in-depth validation of the pooled screening outcomes. We identified eight variants (G12D with V9E, V9W, V9Q, G13P, T58Y, R68G, Y96W, and Q99L) that exhibited substantial resistance, with V9W showing notable resistance, and downstream signaling analyses and structural modeling were conducted. We observed that secondary mutations in KRASG12D can lead to acquired resistance to MRTX1133 and BI-2865, a novel pan-KRAS inhibitor, in human cancer cell lines. This evidence is critical for devising new strategies to counteract resistance mechanisms and, ultimately, enhance treatment outcomes in patients with KRASG12D-mutant cancers.

Skin biomarkers predict the development of food allergy in early life.

BACKGROUND: Food allergy (FA) often occurs in early childhood with and without atopic dermatitis (AD). FA can be severe and even fatal. For primary prevention, it is important to find early biomarkers to predict the future onset of FA before any clinical manifestations. OBJECTIVE: Our aim was to find early predictors of future onset of FA in the stratum corneum (SC). METHODS: Skin tape strips were collected from the forearm of newborns (n = 129) at age 2 months, before any signs of clinical FA or AD. Children were clinically monitored until they reached age 2 years to confirm the presence or absence of FA and AD. Skin tape strips were subjected to lipidomic analyses by liquid chromatography-tandem mass spectrometry and cytokine determination by Meso Scale Discovery U-Plex assay. RESULTS: Overall, 9 of 129 infants (7.0%) developed FA alone and 9 of 129 infants (7.0%) developed FA concomitantly with AD. In the stratum corneum of children with future FA and concomitant AD and FA, absolute amounts of unsaturated (N24:1)(C18-sphingosine)ceramide and (N26:1)(C18-sphingosine)ceramide and their relative percentages within the molecular group were increased compared with the amounts and percentages in healthy children, with P values ranging from less than .01 to less than .05 according to ANOVA. The children with future AD had normal levels of these molecules. IL-33 level was upregulated in those infants with future FA but not in those with future AD, whereas thymic stromal lymphopoietin was upregulated in those with future AD but not in those with future FA. Logistic regression analysis revealed strong FA predicting power for the combination of dysregulated lipids and cytokines, with an odds ratio reaching 101.4 (95% CI = 5.4-1910.6). CONCLUSION: Noninvasive skin tape strip analysis at age 2 months can identify infants at risk of FA in the future.

Postpartum Maternal Anxiety Affects the Development of Food Allergy Through Dietary and Gut Microbial Diversity During Early Infancy.

PURPOSE: We aimed to investigate the mediating factors between maternal anxiety and the development of food allergy (FA) in children until 2 years from birth. METHODS: In this longitudinal cohort of 122 mother-child dyads from pregnancy to 24 months of age, we regularly surveyed maternal psychological states, infant feeding data, and allergic symptoms and collected stool samples at 6 months of age for microbiome analysis. Considering the temporal order of data collection, we investigated serial mediating effects and indirect effects among maternal anxiety, dietary diversity (DD), gut microbial diversity, and FA using structural equation modeling. RESULTS: Among the 122 infants, 15 (12.3%) were diagnosed with FA. Increased maternal anxiety between 3 and 6 months after delivery was associated with a lower DD score. Infants with low DD at 4 months showed low gut microbial richness, which was associated with FA development. When the infants were grouped into 4 subtypes, using consensus clustering of 13 gut bacteria significantly associated with maternal anxiety and DD, Prevotella, Eubacterium, Clostridiales and Lachnospiraceae were more abundant in the group with lower FA occurrence. CONCLUSIONS: Postpartum maternal anxiety, mediated by reduced DD and gut microbial diversity, may be a risk factor for the development of FA in infants during the first 2 years of life.

AI-assisted Analysis to Facilitate Detection of Humeral Lesions on Chest Radiographs.

Purpose To develop an artificial intelligence (AI) system for humeral tumor detection on chest radiographs (CRs) and evaluate the impact on reader performance. Materials and Methods In this retrospective study, 14 709 CRs (January 2000 to December 2021) were collected from 13 468 patients, including CT-proven normal (n = 13 116) and humeral tumor (n = 1593) cases. The data were divided into training and test groups. A novel training method called false-positive activation area reduction (FPAR) was introduced to enhance the diagnostic performance by focusing on the humeral region. The AI program and 10 radiologists were assessed using holdout test set 1, wherein the radiologists were tested twice (with and without AI test results). The performance of the AI system was evaluated using holdout test set 2, comprising 10 497 normal images. Receiver operating characteristic analyses were conducted for evaluating model performance. Results FPAR application in the AI program improved its performance compared with a conventional model based on the area under the receiver operating characteristic curve (0.87 vs 0.82, P = .04). The proposed AI system also demonstrated improved tumor localization accuracy (80% vs 57%, P < .001). In holdout test set 2, the proposed AI system exhibited a false-positive rate of 2%. AI assistance improved the radiologists' sensitivity, specificity, and accuracy by 8.9%, 1.2%, and 3.5%, respectively (P < .05 for all). Conclusion The proposed AI tool incorporating FPAR improved humeral tumor detection on CRs and reduced false-positive results in tumor visualization. It may serve as a supportive diagnostic tool to alert radiologists about humeral abnormalities. Keywords: Artificial Intelligence, Conventional Radiography, Humerus, Machine Learning, Shoulder, Tumor Supplemental material is available for this article. © RSNA, 2024.

The associations of herpes simplex virus and varicella zoster virus infection with dementia: a nationwide retrospective cohort study.

BACKGROUND: In this study, the risk of dementia in patients with a history of herpes simplex virus (HSV) or varicella zoster virus (VZV) infection was evaluated. METHODS: This nationwide cohort study used data from the Korean National Health Insurance Service collected between 2006 and 2017. A total of 752,205 subjects ≥ 45 years of age not diagnosed with dementia until 2006 were included. A multivariate Cox regression model, adjusted for age, sex, and other comorbidities, was used to assess the hazard ratio (HR) for dementia based on VZV or HSV infection. The interaction effects of both viral infections were analysed. Viral infections are classified into four categories: eye, central nervous system (CNS), simple, and complicated. The hazard ratio (HR) of viral infection was analysed based on the type of dementia. RESULTS: In multivariable analysis, both HSV and VZV infection were associated with an increased risk of dementia (HR = 1.38, 95% confidence interval, CI:1.33-1.43) and (HR = 1.41, 95% CI:1.37-1.46), respectively. Patients who experienced both HSV and VZV infections were also at an increased risk of dementia (HR = 1.57, 95% CI:1.50-1.63). The co-infection group showed the shortest time from viral infection to dementia diagnosis (4.09 ± 3.02 years). In the subgroup analysis, all types of HSV and VZV infections were associated with an increased risk of dementia compared to the non-infection group. The eye, CNS, and complicated VZV infections were associated with a significantly higher risk than simple VZV infections. There were no significant differences between the subtypes of HSV infection. Furthermore, HSV, VSV, and co-infection were associated with an increased risk of all dementia types, including Alzheimer's disease (AD) and vascular dementia (VD). CONCLUSIONS: Individual HSV and VZV infections were associated with an increased risk of all types of dementia, including AD and VD. Patients co-infected with HSV and VZV, VZV infection in the eye, CNS, or complicated type were more vulnerable to the development of dementia.

Rebamipide Prevents the Hemoglobin Drop Related to Mucosal-Damaging Agents at a Level Comparable to Proton Pump Inhibitors.

Background/Aims: : The effect of proton pump inhibitors (PPIs) on the lower gastrointestinal (GI) tract is uncertain, with potential to worsen damage. This study aimed to find the best method for protecting the entire GI tract from mucosal damage. Methods: : A retrospective cohort study at Samsung Medical Center (2002-2019) included 195,817 patients prescribed GI mucosa-damaging agents. The primary goal was to assess the effectiveness of GI protective agents in preventing significant hemoglobin drops (>2 g/dL), indicating overall GI mucosal damage. Self-controlled case series and landmark analysis were used to address biases in real-world data. Results: : The incidence rate ratios for rebamipide, PPI, and histamine-2 receptor antagonist (H2RA) were 0.34, 0.33, and 0.52, respectively. Rebamipide showed a significantly lower incidence rate than H2RA and was comparable to PPIs. Landmark analysis revealed significant reductions in hemoglobin drop risk with rebamipide and H2RA, but not with PPI. Conclusions: : Rebamipide, like PPIs, was highly effective in preventing blood hemoglobin level decreases, as shown in real-world data. Rebamipide could be a comprehensive strategy for protecting the entire GI tract, especially when considering PPIs' potential side effects on the lower GI tract.

A meta-analysis comparing efficacy and safety between proton beam therapy versus carbon ion radiotherapy.

BACKGROUND: This study aimed to compare the outcomes of proton beam therapy (PBT) and carbon ion radiotherapy (CIRT) by a systematic review and meta-analysis of the existing clinical evidence. METHODS: A systematic literature search was performed to identify studies comparing the clinical outcomes of PBT and CIRT. The included studies were required to report oncological outcomes (local control [LC], progression-free survival [PFS], or overall survival [OS]) or adverse events. RESULTS: Eighteen articles comprising 1857 patients (947 treated with PBT and 910 treated with CIRT) were included in the analysis. The pooled analysis conducted for the overall population yielded average hazard ratios of 0.690 (95% confidence interval (CI), 0.493-0.967, p = 0.031) for LC, 0.952 (95% CI, 0.604-1.500, p = 0.590) for PFS, and 1.183 (0.872-1.607, p = 0.281) for OS with reference to CIRT. The subgroup analyses included patients treated in the head and neck, areas other than the head and neck, and patients with chordomas and chondrosarcomas. These analyses revealed no significant differences in most outcomes, except for LC in the subgroup of patients treated in areas other than the head and neck. Adverse event rates were comparable in both groups, with an odds ratio (OR) of 1.097 (95% CI, 0.744-1.616, p = 0.641). Meta-regression analysis for possible heterogeneity did not demonstrate a significant association between treatment outcomes and the ratio of biologically effective doses between modalities. CONCLUSION: This study highlighted the comparability of PBT and CIRT in terms of oncological outcomes and adverse events.

Impact and optimal timing of local therapy addition in borderline resectable or locally advanced pancreatic cancer after FOLFIRINOX chemotherapy.

Background: To evaluate the efficacy and optimal timing of local treatment in patients with borderline resectable (BR) or locally advanced pancreatic cancer (LAPC) treated with upfront FOLFIRINOX. Method: Between 2015 and 2020, 258 patients with pancreatic ductal adenocarcinoma (PDAC) were analysed. Treatment outcomes were compared between systemic treatment group (ST) and multimodality treatment groups (MT) using Kaplan-Meier curves and log-rank test. The MT were stratified as follows: FOLFIRINOX + radiation therapy (RT) (MT1), FOLFIRINOX + surgical resection (MT2), and FOLFIRINOX + RT + surgical resection (MT3). Results: With median follow-up period of 18 months, the 2-year overall survival (OS) for the ST was 22.0%, and it was significantly worse than MT (MT1, 46.3%; MT2, 65.7% and MT3; 90.2%; P < .001). The 2-year locoregional progression free survival (LRPFS) and overall PFS in ST were 10.7% and 7.0%, which were also significantly lower than those of MT (2-year LRPFS: MT1, 31.8%; MT2, 45.3%; MT3, 81.0%; 2-year overall PFS: MT1, 23.3%; MT2, 35.0%; MT3, 66.3%; P < .001). In time-varying multivariate Cox proportional hazard model, local treatment contributed to better treatment outcomes, with adjusted hazard ratios of 0.568 (95% confidence interval [CI], 0.398-0.811), 0.490 (95% CI, 0.331-0.726), and 0.656 (95% CI, 0.458-0.940) for OS, LRPFS, and overall PFS, respectively. The time window of 11-17 months after FOLFIRINOX appeared to demonstrate the maximal efficacy of local treatments in OS. Conclusions: Adding local treatment in BR/LAPC patients treated with upfront FOLFIRINOX seemed to contribute in improved treatment outcomes, and it showed maximal efficacy in OS when applied 11-17 months after the initiation of FOLFIRINOX. We suggest that administration of sufficient period of upfront FOLFIRINOX may intensify the efficacy of local treatments, and well controlled prospective trials are expected.

Correlation of body composition metrics with bone mineral density and computed tomography-based trabecular attenuation.

PURPOSE: To investigate the relationship of body composition metrics with bone mineral density (BMD) and trabecular attenuation in a cohort of healthy individuals. METHODS: We retrospectively analyzed data of consecutively evaluated individuals who underwent dual-energy X-ray absorptiometry (DXA) and abdominopelvic computed tomography (CT) on the same day during routine medical check-ups between January 2021 and December 2021. Trabecular attenuation was measured at L1 level, while body composition metrics, including skeletal muscle index (SMI), skeletal muscle attenuation (SMA), visceral fat index (VFI), and subcutaneous fat index (SFI), were measured at L3 level. The association of body composition metrics with BMD and trabecular attenuation was analyzed using partial correlation analysis. RESULTS: A total of 634 patients (median age, 56 years; range 50-62 years; 392 men) were included. In men, the SMI and SMA were positively correlated with BMD and trabecular attenuation, both before (r, 0.157-0.344; p < 0.05) and after (r, 0.103-0.246; p < 0.05) adjusting for age and body mass index. The VFI showed negative correlations with trabecular attenuation in both men (r, -0.170; p = 0.001) and women (r, -0.394; p < 0.001), which remained significant after adjusting for age and body mass index (r, -0.181 to -0.122; p < 0.05). CONCLUSION: Low skeletal muscle mass and attenuation were significantly correlated with low BMD and trabecular attenuation in men. Visceral adiposity was associated with reduced BMD and trabecular attenuation in both men and women, demonstrating a stronger correlation with trabecular attenuation.

Preoperative prediction of early recurrence in resectable pancreatic cancer integrating clinical, radiologic, and CT radiomics features.

OBJECTIVES: To use clinical, radiographic, and CT radiomics features to develop and validate a preoperative prediction model for the early recurrence of pancreatic cancer. METHODS: We retrospectively analyzed 190 patients (150 and 40 in the development and test cohort from different centers) with pancreatic cancer who underwent pancreatectomy between January 2018 and June 2021. Radiomics, clinical-radiologic (CR), and clinical-radiologic-radiomics (CRR) models were developed for the prediction of recurrence within 12 months after surgery. Performance was evaluated using the area under the curve (AUC), Brier score, sensitivity, and specificity. RESULTS: Early recurrence occurred in 36.7% and 42.5% of the development and test cohorts, respectively (P = 0.62). The features for the CR model included carbohydrate antigen 19-9 > 500 U/mL (odds ratio [OR], 3.60; P = 0.01), abutment to the portal and/or superior mesenteric vein (OR, 2.54; P = 0.054), and adjacent organ invasion (OR, 2.91; P = 0.03). The CRR model demonstrated significantly higher AUCs than the radiomics model in the internal (0.77 vs. 0.73; P = 0.048) and external (0.83 vs. 0.69; P = 0.038) validations. Although we found no significant difference between AUCs of the CR and CRR models (0.83 vs. 0.76; P = 0.17), CRR models showed more balanced sensitivity and specificity (0.65 and 0.87) than CR model (0.41 and 0.91) in the test cohort. CONCLUSIONS: The CRR model outperformed the radiomics and CR models in predicting the early recurrence of pancreatic cancer, providing valuable information for risk stratification and treatment guidance.

Deep learning-based optic disc classification is affected by optic-disc tilt.

We aimed to determine the effect of optic disc tilt on deep learning-based optic disc classification. A total of 2507 fundus photographs were acquired from 2236 eyes of 1809 subjects (mean age of 46 years; 53% men). Among all photographs, 1010 (40.3%) had tilted optic discs. Image annotation was performed to label pathologic changes of the optic disc (normal, glaucomatous optic disc changes, disc swelling, and disc pallor). Deep learning-based classification modeling was implemented to develop optic-disc appearance classification models with the photographs of all subjects and those with and without tilted optic discs. Regardless of deep learning algorithms, the classification models showed better overall performance when developed based on data from subjects with non-tilted discs (AUC, 0.988 ± 0.002, 0.991 ± 0.003, and 0.986 ± 0.003 for VGG16, VGG19, and DenseNet121, respectively) than when developed based on data with tilted discs (AUC, 0.924 ± 0.046, 0.928 ± 0.017, and 0.935 ± 0.008). In classification of each pathologic change, non-tilted disc models had better sensitivity and specificity than the tilted disc models. The optic disc appearance classification models developed based all-subject data demonstrated lower accuracy in patients with the appearance of tilted discs than in those with non-tilted discs. Our findings suggested the need to identify and adjust for the effect of optic disc tilt on the optic disc classification algorithm in future development.

Different glaucoma progression rates by age groups in young myopic glaucoma patients.

We aimed to investigate the age-related glaucoma progression rates in myopic normal tension glaucoma (NTG). In this long-term retrospective cohort (7.2 ± 3.5 years), we grouped patients based on their age at initial presentation: group A (age < 30 years, 60 eyes), group B (30 ≤ age < 40, 66 eyes), and group C (40 ≤ age < 50 years, 63 eyes). We used a linear mixed-effects model to estimate retinal nerve fiber layer (RNFL) defect width enlargement rates. Group A showed a significantly faster rate of RNFL defect progression (3.01 ± 1.74°/year) than those of groups B and C (2.05 ± 1.55°/year and 2.06 ± 1.29°/year, P = 0.004 and 0.002). The difference was more marked when calculated for the first 10 years of follow-up in group A, B, and C (3.95 ± 2.70°/year, 2.39 ± 1.64°/year, and 1.98 ± 1.31°/year), and between the periods of age < 30 years, 30 ≤ age < 40 years, and 40 ≤ age < 50 years within group A. This is the first evidence of rapid glaucoma progression in the young adulthood and stabilization in older age in myopic NTG. Clinicians should consider the potentially aggressive course of glaucoma, especially in younger patients with myopic NTG, in contrast to the general slow progression in adulthood.

Development and Validation of a Robust and Interpretable Early Triaging Support System for Patients Hospitalized With COVID-19: Predictive Algorithm Modeling and Interpretation Study.

BACKGROUND: Robust and accurate prediction of severity for patients with COVID-19 is crucial for patient triaging decisions. Many proposed models were prone to either high bias risk or low-to-moderate discrimination. Some also suffered from a lack of clinical interpretability and were developed based on early pandemic period data. Hence, there has been a compelling need for advancements in prediction models for better clinical applicability. OBJECTIVE: The primary objective of this study was to develop and validate a machine learning-based Robust and Interpretable Early Triaging Support (RIETS) system that predicts severity progression (involving any of the following events: intensive care unit admission, in-hospital death, mechanical ventilation required, or extracorporeal membrane oxygenation required) within 15 days upon hospitalization based on routinely available clinical and laboratory biomarkers. METHODS: We included data from 5945 hospitalized patients with COVID-19 from 19 hospitals in South Korea collected between January 2020 and August 2022. For model development and external validation, the whole data set was partitioned into 2 independent cohorts by stratified random cluster sampling according to hospital type (general and tertiary care) and geographical location (metropolitan and nonmetropolitan). Machine learning models were trained and internally validated through a cross-validation technique on the development cohort. They were externally validated using a bootstrapped sampling technique on the external validation cohort. The best-performing model was selected primarily based on the area under the receiver operating characteristic curve (AUROC), and its robustness was evaluated using bias risk assessment. For model interpretability, we used Shapley and patient clustering methods. RESULTS: Our final model, RIETS, was developed based on a deep neural network of 11 clinical and laboratory biomarkers that are readily available within the first day of hospitalization. The features predictive of severity included lactate dehydrogenase, age, absolute lymphocyte count, dyspnea, respiratory rate, diabetes mellitus, c-reactive protein, absolute neutrophil count, platelet count, white blood cell count, and saturation of peripheral oxygen. RIETS demonstrated excellent discrimination (AUROC=0.937; 95% CI 0.935-0.938) with high calibration (integrated calibration index=0.041), satisfied all the criteria of low bias risk in a risk assessment tool, and provided detailed interpretations of model parameters and patient clusters. In addition, RIETS showed potential for transportability across variant periods with its sustainable prediction on Omicron cases (AUROC=0.903, 95% CI 0.897-0.910). CONCLUSIONS: RIETS was developed and validated to assist early triaging by promptly predicting the severity of hospitalized patients with COVID-19. Its high performance with low bias risk ensures considerably reliable prediction. The use of a nationwide multicenter cohort in the model development and validation implicates generalizability. The use of routinely collected features may enable wide adaptability. Interpretations of model parameters and patients can promote clinical applicability. Together, we anticipate that RIETS will facilitate the patient triaging workflow and efficient resource allocation when incorporated into a routine clinical practice.

Association of Glycemic Variability With Imaging Markers of Vascular Burden, ß-Amyloid, Brain Atrophy, and Cognitive Impairment.

BACKGROUND AND OBJECTIVE: We aimed to investigate the association between glycemic variability (GV) and neuroimaging markers of white matter hyperintensities (WMH), beta-amyloid (Aß), brain atrophy, and cognitive impairment. METHODS: This was a retrospective cohort study that included participants without dementia from a memory clinic. They all had Aß PET, brain MRI, and standardized neuropsychological tests and had fasting glucose (FG) levels tested more than twice during the study period. We defined GV as the intraindividual visit-to-visit variability in FG levels. Multivariable linear regression and logistic regression were used to identify whether GV was associated with the presence of severe WMH and Aß uptake with DM, mean FG levels, age, sex, hypertension, and presence of APOE4 allele as covariates. Mediation analyses were used to investigate the mediating effect of WMH and Aß uptake on the relationship between GV and brain atrophy and cognition. RESULTS: Among the 688 participants, the mean age was 72.2 years, and the proportion of female participants was 51.9%. Increase in GV was predictive of the presence of severe WMH (coefficient [95% CI] 1.032 [1.012-1.054]; p = 0.002) and increased Aß uptake (1.005 [1.001-1.008]; p = 0.007). Both WMH and increased Aß uptake partially mediated the relationship between GV and frontal-executive dysfunction (GV → WMH → frontal-executive; direct effect, -0.319 [-0.557 to -0.080]; indirect effect, -0.050 [-0.091 to -0.008]) and memory dysfunction (GV → Aß â†’ memory; direct effect, -0.182 [-0.338 to -0.026]; indirect effect, -0.067 [-0.119 to -0.015]), respectively. In addition, increased Aß uptake completely mediated the relationship between GV and hippocampal volume (indirect effect, -1.091 [-2.078 to -0.103]) and partially mediated the relationship between GV and parietal thickness (direct effect, -0.00101 [-0.00185 to -0.00016]; indirect effect, -0.00016 [-0.00032 to -0.000002]). DISCUSSION: Our findings suggest that increased GV is related to vascular and Alzheimer risk factors and neurodegenerative markers, which in turn leads to subsequent cognitive impairment. Furthermore, GV can be considered a potentially modifiable risk factor for dementia prevention.

Trends in colorectal cancer incidence according to an increase in the number of colonoscopy cases in Korea.

BACKGROUND: The incidence of colorectal cancer (CRC) and preinvasive CRC (e.g., early colon cancer and advanced adenoma) is gradually increasing in several countries. AIM: To evaluate the trend in incidence of CRC and preinvasive CRC according to the increase in the number of colonoscopies performed in Korea. METHODS: This retrospective cohort study enrolled Korean patients from 2002 to 2020 to evaluate the incidence of CRC and preinvasive CRC, and assess the numbers of diagnostic colonoscopies and colonoscopic polypectomies. Colonoscopy-related complications by age group were also determined. RESULTS: The incidence of CRC showed a rapid increase, then decreased after 2012 in the 50-75 year-age group. During the study period, the rate of incidence of preinvasive CRC increased at a similar level in patients under 50 and 50-75 years of age. Since 2009, the increase has been rapid, showing a pattern similar to the increase in colonoscopies. The rate of colonoscopic polypectomy in patients aged under 50 was similar to the rate in patients over 75 years of age after 2007. The rate of complications after colonoscopy and related deaths within 3 mo was high for those over 75 years of age. CONCLUSION: The diagnosis of preinvasive CRC increased with the increase in the number of colonoscopies performed. As the risk of colonoscopy-related hospitalization and death is high in the elderly, if early lesions at risk of developing CRC are diagnosed and treated under or at the age of 75, colonoscopy-related complications can be reduced for those aged 76 years or over.

Recurrence-free Survival After Liver Transplantation Versus Surgical Resection for Hepatocellular Carcinoma: Role of High-risk MRI Features.

BACKGROUND: This study aimed to evaluate recurrence-free survival (RFS) and overall survival (OS) after liver transplantation (LT) or liver resection (LR) for hepatocellular carcinoma (HCC) and perform subgroup analysis for HCC with high-risk imaging findings for recurrence on preoperative liver magnetic resonance imaging (MRI; high-risk MRI features). METHODS: We included patients with HCC eligible for both LT and LR and received either of the treatments between June 2008 and February 2021 from 2 tertiary referral medical centers after propensity score-matching. RFS and OS were compared between LT and LR using Kaplan-Meier curves with the log-rank test. RESULTS: Propensity score-matching yielded 79 patients in the LT group and 142 patients in the LR group. High-risk MRI features were noted in 39 patients (49.4%) in the LT group and 98 (69.0%) in the LR group. The Kaplan-Meier curves for RFS and OS were not significantly different between the 2 treatments among the high-risk group (RFS, P = 0.079; OS, P = 0.755). Multivariable analysis showed that treatment type was not a prognostic factor for RFS and OS ( P = 0.074 and 0.937, respectively). CONCLUSIONS: The advantage of LT over LR for RFS may be less evident among patients with high-risk MRI features.

Refining MRI-based criteria for portal vein invasion in hepatocellular carcinoma: improving sensitivity beyond portal vein tumor thrombosis.

PURPOSE: To investigate the imaging features indicating portal vein invasion (PVI) of hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced MRI and to create more accurate diagnostic criteria than the presence of portal vein tumor thrombosis (PVTT) on MRI. METHODS: This retrospective study included patients with surgically resected HCC larger than 5 cm, and the presence of PVI was investigated. On MRI, we evaluated the image findings of portal vein occlusion, the parenchymal signal change caused by hemodynamic alterations of the portal vein, and their combination showing the highest odds ratio (OR) to define the diagnostic criteria for radiological PVI detection (rPVI criteria). The diagnostic performance and recurrence-free survival were compared between the rPVI criteria and the presence of PVTT using McNemar's test and Kaplan-Meier method, respectively. Interobserver agreement was evaluated using Cohen's weighted ĸ statistics. RESULTS: Of 189 enrolled patients, 25 (13.2%) had PVI on histology. To diagnose PVI on MRI, either peripheral wedge-shaped arterial peritumoral hyperemia with an abrupt cut-off of a portal vein or the presence of PVTT had the highest OR (41.67, p < 0.001). The sensitivity of PVI was significantly increased under this diagnostic criterion (64.0% to 88.0%; p = 0.031) with comparable accuracy (95.2% vs. 94.7%; p > 0.999). In terms of recurrence-free survival, the patient group with rPVI was significantly worse (p = 0.017) compared with the patients without rPVI. Interobserver agreement of radiologic findings was substantial (ĸ = 0.64). CONCLUSION: Diagnostic criteria for radiologically PVI detection increase the sensitivity more than the only presence of PVTT.

LI-RADS category is associated with treatment outcomes of small single HCC: surgical resection vs. radiofrequency ablation.

OBJECTIVES: To assess whether the Liver Imaging Reporting and Data System (LI-RADS) category is associated with the treatment outcomes of small single hepatocellular carcinoma (HCC) after surgical resection (SR) and radiofrequency ablation (RFA). METHODS: This retrospective study included 357 patients who underwent SR (n = 209) or RFA (n = 148) for a single HCC of ≤ 3 cm between 2014 and 2016. LI-RADS categories were assigned. Overall survival (OS), recurrence-free survival (RFS), and local tumor progression (LTP) rates after treatment were compared according to the LI-RADS category (LR-4/5 vs. LR-M) before and after propensity score matching (PSM). Prognostic factors for treatment outcomes were assessed. RESULTS: In total, 357 patients (mean age, 59 years; men, 272) with 357 HCCs (294 LR-4/5 and 63 LR-M) were included. After PSM (n = 78 in each treatment group), there were 10 and 11 LR-M HCCs in the SR and RFA group, respectively. There were no significant differences in OS or RFS. However, SR provided a lower 5-year LTP rate than RFA (1.4% vs. 14.9%, p = 0.001). SR provided a lower 5-year LTP rate than RFA for LR-M HCCs (0% vs. 34.4%, p = 0.062) and LR-4/5 HCCs (1.5% vs. 12.0%, p = 0.008). The LI-RADS category was the sole risk factor associated with poor OS (hazard ratio [HR] 3.79, p = 0.004), RFS (HR 2.12; p = 0.001), and LTP (HR 2.89; p = 0.032). CONCLUSION: LI-RADS classification is associated with the treatment outcome of HCC, supporting favorable outcomes of SR over RFA for LTP, especially for HCCs categorized as LR-M. CLINICAL RELEVANCE STATEMENT: Liver Imaging Reporting and Data System category has a potential prognostic role, supporting favorable outcomes of surgical resection over radiofrequency ablation for local tumor progression, especially for hepatocellular carcinoma categorized as LR-M. KEY POINTS: • SR provided a lower 5-year LTP rate than RFA for HCCs categorized as LR-M (0% vs. 34.4%, p = 0.062) and HCCs categorized as LR-4/5 (1.5% vs. 12.0%, p = 0.008). • There is a steeply increased risk of LTP within 1 year after RFA for LR-M HCCs, compared to SR. • The LI-RADS category was the sole risk factor associated with poor OS (HR 3.79, p = 0.004), RFS (HR 2.12; p = 0.001), and LTP (HR 2.89; p = 0.032) in patients with HCC of ≤ 3 cm treated with SR or RFA.

Internal structural analysis of the nasomaxillary complex in patients with skeletal class III asymmetry: A study on asymmetry patterns.

OBJECTIVES: To investigate the internal structure of the nasomaxillary complex, including the maxillary sinus, nasal cavity and nasal septum according to the facial asymmetry pattern and to evaluate its correlation with external maxillomandibular asymmetry in Class III patients based on cone-beam computerized tomography (CBCT) images. MATERIALS AND METHODS: Facial asymmetry was analysed in a total of 100 Class III patients aged 16 years or older using CBCT scans. Patients were categorized into subgroups based on asymmetry pattern. Measurements of the nasomaxillary complex were obtained from the CBCT scans, including the volume and width of the maxillary sinuses and nasal cavities on deviated and non-deviated sides, as well as the displacement of the nasal septum. Statistical analysis was performed to compare the internal nasomaxillary variables within and between groups, and regression analysis was conducted to evaluate the correlation between facial asymmetry and the internal nasomaxillary variables. RESULTS: Group comparisons showed that there were no significant differences in the volume of the maxillary sinus and nasal cavity. However, the direction and extent of nasal septum deviation, as well as the width of the nasal cavity, varied depending on the maxillary asymmetry pattern. Regression analysis indicated a correlation between nasal septum deviation and the difference in maxillary height, while the difference in nasal cavity width was correlated with the difference in maxillary width. CONCLUSION: A comprehensive evaluation of the internal nasal anatomy is vital for understanding the intricate relationship between nasal structure and maxillary growth.

Short-term effects of ambient temperature on acute exacerbation of inflammatory bowel disease: A nationwide case-crossover study with external validation.

Inflammatory bowel disease (IBD) is an idiopathic inflammatory disorder characterized by chronic and relapsing manifestations. Several environmental factors are known as triggers for exacerbation of IBD. However, an association between exacerbation of IBD and ambient temperature is uncertain. This study aimed to estimate the risk of acute exacerbation of IBD due to ambient temperature. We performed a bidirectional case-crossover study using a nationwide claim data from South Korea. The external validation was conducted with a large prospective cohort in the United Kingdom. We confirmed significant associations between acute exacerbation of IBD and the short-term ambient temperature changes toward severe temperatures, in the cold weather (-19.4°C-4.3°C) (odd ratio [OR] = 1.13, 95% confidence interval [CI]: 1.13-1.14) and in the hot weather (21.3°C-33.5°C) (OR = 1.16, 95% CI: 1.15-1.17). However, the association was not significant in the moderate weather (4.3°C-21.3°C). The external validation suggested consistent results with additional elevation of acute exacerbation risk in the colder weather (-13.4°C to 2.6°C) (OR = 1.90, 95% CI: 1.62-2.22) and in the hotter weather (15.7°C-28.4°C) (OR = 1.41, 95% CI: 1.32-1.51). We observed and validated that the short-term ambient temperature changes were associated with acute exacerbation of IBD in the cold and hot weathers. Our findings provide evidence that temperature changes are associated with the acute exacerbation of IBD.