Background: The retinoblastoma (RB) protein which is encoded by RB gene selectively provides a cell type-specific function in malignancies. In colorectal carcinoma, RB has been highly expressed and related cyclin/cyclin-dependent kinase 4/6 inhibitors have shown improved therapeutic effects in some patients. However, little is known about RB in small intestinal adenocarcinoma (SIAC). Methods: Here, we conducted a multi-institutional study of RB expression in 229 surgically resected SIACs to explore the clinicopathologic and prognostic implications and the relationship with microsatellite instability (MSI) status and KRAS mutations. Results: High RB expression (RBHigh ) was more commonly observed in SIACs (76/229, 33%) than in normal small intestinal mucosa (27/188, 14%; P < 0.001). RBHigh was associated with nodular growth patterns (P = 0.028), the absence of lymphovascular (P = 0.001) and perineural invasion (P = 0.048), and a lower T category (P = 0.042) and indicated better overall survival (P = 0.003). In multivariate analysis, RBHigh (P = 0.049) was an independent prognostic predictor of better prognosis, along with younger patient age (P = 0.049), the absence of retroperitoneal seeding (P = 0.004), lower tumor stage (P < 0.001), and MSI (P = 0.005). The prognostic impact of RB expression was consistently observed regardless of MSI status and specifically persistent in SIACs with lower stages (stages I and II). Conclusion RBHigh was related to favorable clinicopathologic SIAC characteristics and indicated better patient prognosis. The prognostic predictability of RB was found in SIACs with lower stages, independent of MSI status. RB expression is a reliable and potent prognostic indicator for SIAC and may aid in selecting chemotherapy for patients.

Background: The retinoblastoma (RB) protein which is encoded by RB gene selectively provides a cell type-specific function in malignancies. In colorectal carcinoma, RB has been highly expressed and related cyclin/cyclin-dependent kinase 4/6 inhibitors have shown improved therapeutic effects in some patients. However, little is known about RB in small intestinal adenocarcinoma (SIAC). Methods: Here, we conducted a multi-institutional study of RB expression in 229 surgically resected SIACs to explore the clinicopathologic and prognostic implications and the relationship with microsatellite instability (MSI) status and KRAS mutations. Results: High RB expression (RBHigh ) was more commonly observed in SIACs (76/229, 33%) than in normal small intestinal mucosa (27/188, 14%; P < 0.001). RBHigh was associated with nodular growth patterns (P = 0.028), the absence of lymphovascular (P = 0.001) and perineural invasion (P = 0.048), and a lower T category (P = 0.042) and indicated better overall survival (P = 0.003). In multivariate analysis, RBHigh (P = 0.049) was an independent prognostic predictor of better prognosis, along with younger patient age (P = 0.049), the absence of retroperitoneal seeding (P = 0.004), lower tumor stage (P < 0.001), and MSI (P = 0.005). The prognostic impact of RB expression was consistently observed regardless of MSI status and specifically persistent in SIACs with lower stages (stages I and II). Conclusion RBHigh was related to favorable clinicopathologic SIAC characteristics and indicated better patient prognosis. The prognostic predictability of RB was found in SIACs with lower stages, independent of MSI status. RB expression is a reliable and potent prognostic indicator for SIAC and may aid in selecting chemotherapy for patients.

Background: The retinoblastoma (RB) protein which is encoded by RB gene selectively provides a cell type-specific function in malignancies. In colorectal carcinoma, RB has been highly expressed and related cyclin/cyclin-dependent kinase 4/6 inhibitors have shown improved therapeutic effects in some patients. However, little is known about RB in small intestinal adenocarcinoma (SIAC). Methods: Here, we conducted a multi-institutional study of RB expression in 229 surgically resected SIACs to explore the clinicopathologic and prognostic implications and the relationship with microsatellite instability (MSI) status and KRAS mutations. Results: High RB expression (RBHigh ) was more commonly observed in SIACs (76/229, 33%) than in normal small intestinal mucosa (27/188, 14%; P < 0.001). RBHigh was associated with nodular growth patterns (P = 0.028), the absence of lymphovascular (P = 0.001) and perineural invasion (P = 0.048), and a lower T category (P = 0.042) and indicated better overall survival (P = 0.003). In multivariate analysis, RBHigh (P = 0.049) was an independent prognostic predictor of better prognosis, along with younger patient age (P = 0.049), the absence of retroperitoneal seeding (P = 0.004), lower tumor stage (P < 0.001), and MSI (P = 0.005). The prognostic impact of RB expression was consistently observed regardless of MSI status and specifically persistent in SIACs with lower stages (stages I and II). Conclusion RBHigh was related to favorable clinicopathologic SIAC characteristics and indicated better patient prognosis. The prognostic predictability of RB was found in SIACs with lower stages, independent of MSI status. RB expression is a reliable and potent prognostic indicator for SIAC and may aid in selecting chemotherapy for patients.

Background: The retinoblastoma (RB) protein which is encoded by RB gene selectively provides a cell type-specific function in malignancies. In colorectal carcinoma, RB has been highly expressed and related cyclin/cyclin-dependent kinase 4/6 inhibitors have shown improved therapeutic effects in some patients. However, little is known about RB in small intestinal adenocarcinoma (SIAC). Methods: Here, we conducted a multi-institutional study of RB expression in 229 surgically resected SIACs to explore the clinicopathologic and prognostic implications and the relationship with microsatellite instability (MSI) status and KRAS mutations. Results: High RB expression (RBHigh ) was more commonly observed in SIACs (76/229, 33%) than in normal small intestinal mucosa (27/188, 14%; P < 0.001). RBHigh was associated with nodular growth patterns (P = 0.028), the absence of lymphovascular (P = 0.001) and perineural invasion (P = 0.048), and a lower T category (P = 0.042) and indicated better overall survival (P = 0.003). In multivariate analysis, RBHigh (P = 0.049) was an independent prognostic predictor of better prognosis, along with younger patient age (P = 0.049), the absence of retroperitoneal seeding (P = 0.004), lower tumor stage (P < 0.001), and MSI (P = 0.005). The prognostic impact of RB expression was consistently observed regardless of MSI status and specifically persistent in SIACs with lower stages (stages I and II). Conclusion RBHigh was related to favorable clinicopathologic SIAC characteristics and indicated better patient prognosis. The prognostic predictability of RB was found in SIACs with lower stages, independent of MSI status. RB expression is a reliable and potent prognostic indicator for SIAC and may aid in selecting chemotherapy for patients.

Background: s/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

Background: Although many studies have been conducted on the association between the intercondylar notch size and the risk of anterior cruciate ligament (ACL) injury, few studies have examined its relationship with the condition after surgical treatment.Therefore, this study aimed to investigate the surgical outcomes of anatomical single-bundle ACL reconstruction according to intercondylar notch volumes. Methods: Medical records of patients who underwent anatomical single-bundle ACL reconstruction using a tibialis anterior allograft between 2015 and 2019 were retrospectively reviewed. For each sex, eligible patients were classified into two groups based on their percentile of intercondylar notch volumes, which were measured using postoperative three-dimensional computed tomography images (group S, ≤ 50th percentile of included patients; group L, > 50th percentile of included patients). Additional grouping was performed based on the group’s percentiles of normalized values of intercondylar notch volumes to body heights.Between-group comparative analyses were performed on the perioperative data and surgical outcomes in both objective and subjective aspects. Results: One hundred patients were included in the study. For male patients, there were no differences in the overall surgical outcomes between groups, whereas group L showed a significantly greater knee anteroposterior (AP) laxity than group S at the final follow-up (p = 0.042 for the side-to-side differences [SSD] at the maximum manual force). Similarly, there were no differences in the female patients in the overall surgical results between the groups, whereas group L showed a significantly greater knee AP laxity at the final follow-up (p = 0.020 for the SSD at 134 N; p = 0.011 for the SSD at the maximum manual force). Additional analyses based on the normalized values of the intercondylar notch volume showed consistent results for male patients, and additional grouping for female patients was identical to the existing grouping. Conclusions The surgical outcomes of anatomical single-bundle ACL reconstruction in patients with relatively small intercondylar notch volumes were comparable to those with large notch volumes, but rather showed favorable outcomes in postoperative knee AP laxity.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Objective: : Collateral circulation is associated with the differential treatment effect of endovascular thrombectomy (EVT) in acute ischemic stroke. We aimed to verify the ability of the collateral map to predict futile EVT in patients with acute anterior circulation ischemic stroke. Methods: : This secondary analysis of a prospective observational study included data from participants underwent EVT for acute ischemic stroke due to occlusion of the internal carotid artery and/or the middle cerebral artery within 8 hours of symptom onset. Multiple logistic regression analyses were conducted to identify independent predictors of futile recanalization (modified Rankin scale score at 90 days of 4–6 despite of successful reperfusion). Results: : In a total of 214 participants, older age (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.56 to 3.67; p<0.001), higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (OR, 1.12; 95% CI, 1.04 to 1.21; p=0.004), very poor collateral perfusion grade (OR, 35.09; 95% CI, 3.50 to 351.33; p=0.002), longer door-to-puncture time (OR, 1.08; 95% CI, 1.02 to 1.14; p=0.009), and failed reperfusion (OR, 3.73; 95% CI, 1.30 to 10.76; p=0.015) were associated with unfavorable functional outcomes. In 184 participants who achieved successful reperfusion, older age (OR, 2.30; 95% CI, 1.44 to 3.67; p<0.001), higher baseline NIHSS scores (OR, 1.12; 95% CI, 1.03 to 1.22; p=0.006), very poor collateral perfusion grade (OR, 4.96; 95% CI, 1.42 to 17.37; p=0.012), and longer door-to-reperfusion time (OR, 1.09; 95% CI, 1.03 to 1.15; p=0.003) were associated with unfavorable functional outcomes. Conclusion : The assessment of collateral perfusion status using the collateral map can predict futile EVT, which may help select ineligible patients for EVT, thereby potentially reducing the rate of futile EVT.

Background: This study aimed to investigate real-world data of C-terminal telopeptide (CTX), propeptide of type I collagen (P1NP), and osteocalcin through present multicenter clinical study, and retrospectively analyze the usefulness of bone turnover markers (BTMs) in Koreans. Methods: The study focused on pre- and post-menopausal patients diagnosed with osteoporosis and excluded patients without certain test results or with test intervals of over 1 year. The demographic data and 3 BTMs (CTX, P1NP, and osteocalcin) were collected. The patients were classified by demographic characteristics and the BTM concentrations were analyzed by the group. Results: Among women with no history of fractures, the levels of P1NP (N=2,100) were 43.544±36.902, CTX (N=1,855) were 0.373 ±0.927, and osteocalcin (N=219) were 10.81 ±20.631. Among men with no history of fractures, the levels of P1NP (N=221) were 48.498±52.892, CTX (N=201) were 0.370±0.351, and osteocalcin (N=15) were 7.868 ±10.674. Treatment with teriparatide increased the P1NP levels after 3 months in both men and women, with a 50% increase observed in women. Similarly, treatment with denosumab decreased the CTX levels after 3 months in both men and women, with a reduction of 50% observed in women. Conclusions The results of this study can contribute to the accurate assessment of bone replacement status in Koreans. We also provide the P1NP level in the Korean population for future comparative studies with other populations.

Background: The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection. Results: K18-hACE2 mice were intranasally infected with 1 × 105 PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection. Conclusion Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.