Purpose: Total neoadjuvant therapy (TNT) is becoming the standard of care for locally advanced rectal cancer. However, surgery is deferred for months after completion, which may lead to fibrosis and increased surgical difficulty. The aim of this study was to assess whether TNT (TNT-RAPIDO) is associated with increased difficulty of total mesorectal excision (TME) compared with long-course chemoradiotherapy (LCRT) and upfront surgery. Methods: Twelve laparoscopic videos of low anterior resection with TME for rectal cancer were prospectively collected from January 2020 to October 2021, with 4 videos in each arm. Seven colorectal surgeons assessed the videos independently, graded the difficulty of TME using a visual analog scale and attempted to identify which category the videos belonged to. Results: The median age was 67 years, and 10 patients were male. The median interval to surgery from radiotherapy was 13 weeks in the LCRT group and 24 weeks in the TNT-RAPIDO group. There was no significant difference in the visual analog scale for difficulty in TME between the 3 groups (LCRT, 3.2; TNT-RAPIDO, 4.6; upfront, 4.1; P=0.12). A subgroup analysis showed similar difficulty between groups (LCRT 3.2 vs. TNT-RAPIDO 4.6, P=0.05; TNT-RAPIDO 4.6 vs. upfront 4.1, P=0.54). During video assessments, surgeons correctly identified the prior treatment modality in 42% of the cases. TNT-RAPIDO videos had the highest recognition rate (71%), significantly outperforming both LCRT (29%) and upfront surgery (25%, P=0.01). Conclusion TNT does not appear to increase the surgical difficulty of TME.

Differentiated thyroid cancer demonstrates a wide range of clinical presentations, from very indolent cases to those with an aggressive prognosis. Therefore, diagnosing and treating each cancer appropriately based on its risk status is important. The Korean Thyroid Association (KTA) has provided and amended the clinical guidelines for thyroid cancer management since 2007. The main changes in this revised 2024 guideline include 1) individualization of surgical extent according to pathological tests and clinical findings, 2) application of active surveillance in low-risk papillary thyroid microcarcinoma, 3) indications for minimally invasive surgery, 4) adoption of World Health Organization pathological diagnostic criteria and definition of terminology in Korean, 5) update on literature evidence of recurrence risk for initial risk stratification, 6) addition of the role of molecular testing, 7) addition of definition of initial risk stratification and targeting thyroid stimulating hormone (TSH) concentrations according to ongoing risk stratification (ORS), 8) addition of treatment of perioperative hypoparathyroidism, 9) update on systemic chemotherapy, and 10) addition of treatment for pediatric patients with thyroid cancer.

Noncirrhotic hyperammonemia as a cause of acute confusion remains diagnostic challenge. Deficiency of ornithine transcarbamylase (OTC) is the urea cycle disorder, inborn errors caused by a defect of the enzymes in the urea cycle, leading to an accumulation of ammonia mainly in newborn. There were very few cases, in which OTC deficiency result in hyperammonemia in adulthood. Herein, we report a young adult woman of hyperammonemic encephalopathy with OTC deficiency, diagnosed by high blood ammonia, glutamine and low plasma levels of citrulline. Next generation sequencing showed the c.386+5G>A mutation of the OTC gene.

Despite efforts to treat critically ill patients who require continuous renal replacement therapy (CRRT) due to acute kidney injury (AKI), their mortality risk remains high. This condition may be attributable to complications of CRRT, such as arrhythmias. Here, we addressed the occurrence of ventricular tachycardia (VT) during CRRT and its relationship with patient outcomes. Methods: This study retrospectively enrolled 2,397 patients who started CRRT due to AKI from 2010 to 2020 at Seoul National University Hospital in Korea. The occurrence of VT was evaluated from the initiation of CRRT until weaning from CRRT. The odds ratios (ORs) of mortality outcomes were measured using logistic regression models after adjustment for multiple variables. Results: VT occurred in 150 patients (6.3%) after starting CRRT. Among them, 95 cases were defined as sustained VT (i.e., lasting ≥30 seconds), and the other 55 cases were defined as non-sustained VT (i.e., lasting <30 seconds). The occurrence of sustained VT was associated with a higher mortality rate than a nonoccurrence (OR, 2.04 and 95% confidence interval [CI], 1.23–3.39 for the 30- day mortality; OR, 4.06 and 95% CI, 2.04–8.08 for the 90-day mortality). The mortality risk did not differ between patients with non-sustained VT and nonoccurrence. A history of myocardial infarction, vasopressor use, and certain trends of blood laboratory findings (such as acidosis and hyperkalemia) were associated with the subsequent risk of sustained VT. Conclusion: Sustained VT occurrence after starting CRRT is associated with increased patient mortality. The monitoring of electrolytes and acid-base status during CRRT is essential because of its relationship with the risk of VT.

Purpose: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) are frequently employed to counteract the detrimental effects of proteinuria on glomerular diseases. However, the effects of ARBs remain poorly examined in pediatric patients with immunoglobulin A (IgA) nephropathy. Herein, we evaluated the efficacy and safety of losartan, an ARB, in pediatric IgA nephropathy with proteinuria. Methods: This prospective, single-arm, multicenter study included children with IgA nephropathy exhibiting proteinuria. Changes in proteinuria, blood pressure, and kidney function were prospectively evaluated before and 4 and 24 weeks after losartan administration. The primary endpoint was the difference in proteinuria between baseline and 24 weeks. Results: In total, 29 patients were enrolled and received losartan treatment. The full analysis set included 28 patients who received losartan at least once and had pre- and post-urinary protein to creatinine ratio measurements (n=28). The per-protocol analysis group included 22 patients who completed all scheduled visits without any serious violations during the study period. In both groups, the mean log (urine protein to creatinine ratio) value decreased significantly at 6 months. After 24 weeks, the urinary protein to creatinine ratio decreased by more than 50% in approximately 40% of the patients. The glomerular filtration rate was not significantly altered during the observation period. Conclusions Losartan decreased proteinuria without decreasing kidney function in patients with IgA nephropathy over 24 weeks. Losartan could be safely employed to reduce proteinuria in this patient population. ClinicalTrials.gov trial registration (NCT0223277)

Background: This study aimed to investigate the recent prevalence, management, and comorbidities of diabetes among Korean adults aged ≥30 years by analyzing nationally representative data. Methods: This study used data from the Korea National Health and Nutrition Examination Survey from 2016 to 2018, and the percentage and total number of people ≥30 years of age with diabetes and impaired fasting glucose (IFG) were estimated. Results: In 2018, 13.8% of Korean adults aged ≥30 years had diabetes, and adults aged ≥65 years showed a prevalence rate of 28%. The prevalence of IFG was 26.9% in adults aged ≥30 years. From 2016 to 2018, 35% of the subjects with diabetes were not aware of their condition. Regarding comorbidities, 53.2% and 61.3% were obese and hypertensive, respectively, and 72% had hypercholesterolemia as defined by low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dL in people with diabetes. Of the subjects with diabetes, 43.7% had both hypertension and hypercholesterolemia. With regard to glycemic control, only 28.3% reached the target level of <6.5%. Moreover, only 11.5% of subjects with diabetes met all three targets of glycosylated hemoglobin, blood pressure, and LDL-C. The percentage of energy intake from carbohydrates was higher in diabetes patients than in those without diabetes, while that from protein and fat was lower in subjects with diabetes. Conclusion The high prevalence and low control rate of diabetes and its comorbidities in Korean adults were confirmed. More stringent efforts are needed to improve the comprehensive management of diabetes to reduce diabetes-related morbidity and mortality.

Purpose: We report two cases of tacrolimus-related transplant-associated thrombotic microangiopathy (TA-TMA) retinopathy in leukemia patients who had undergone allogenic peripheral blood stem cell transplantation (PBSCT).Case summary: (Case 1) A 58-year-old woman with a history of PBSCT due to acute myelocytic leukemia and taking tacrolimus was referred to the ophthalmology clinic with visual disturbance. Her visual acuity (VA) was 0.4 in the right eye and 0.5 in the left eye. Multiple cotton wool spots and retinal hemorrhages were found in both eyes on fundus examination. Multiple capillary non-perfusions were seen on fluorescein angiography (FA). Tacrolimus-related TA-TMA retinopathy was suspected. Tacrolimus was discontinued and plasmapheresis was performed. After 3 months, neovascular glaucoma developed and her VA became “counting fingers” at 20 cm in both eyes. (Case 2) A 20-year-old man with a history of PBSCT due to acute lymphocytic leukemia and taking tacrolimus was referred to our clinic because of decreased VA in both eyes. His VA was 0.05 in the right eye and 0.025 in the left eye. Fundus and FA findings were the same as in Case 1, and the patient was suspected to have tacrolimus-related TA-TMA retinopathy. Tacrolimus was discontinued and plasmapheresis was performed. His VA was 0.2 in the right eye and 0.4 in the left eye at 1 month after treatment. Conclusions It is necessary to consider TA-TMA retinopathy in leukemia patients taking calcineurin inhibitors, such as tacrolimus, who have decreased VA. Early diagnosis and treatment are important.

This paper describes a community effort to improve earlier versions of the full-text corpus of Genomics & Informatics by semi-automatically detecting and correcting PDF-to-text conversion errors and optical character recognition errors during the first hackathon of Genomics & Informatics Annotation Hackathon (GIAH) event. Extracting text from multi-column biomedical documents such as Genomics & Informatics is known to be notoriously difficult. The hackathon was piloted as part of a coding competition of the ELTEC College of Engineering at Ewha Womans University in order to enable researchers and students to create or annotate their own versions of the Genomics & Informatics corpus, to gain and create knowledge about corpus linguistics, and simultaneously to acquire tangible and transferable skills. The proposed projects during the hackathon harness an internal database containing different versions of the corpus and annotations.

Objective: The aim of this study was to prospectively evaluate whether liver stiffness (LS) assessments, obtained by twodimensional (2D)-shear wave elastography (SWE) with a propagation map, can evaluate liver fibrosis stage using histopathology as the reference standard. Materials and Methods: We prospectively enrolled 123 patients who had undergone percutaneous liver biopsy from two tertiary referral hospitals. All patients underwent 2D-SWE examination prior to biopsy, and LS values (kilopascal [kPa]) were obtained. On histopathologic examination, fibrosis stage (F0–F4) and necroinflammatory activity grade (A0–A4) were assessed. Multivariate linear regression analysis was performed to determine the significant factors affecting the LS value.The diagnostic performance of the LS value for staging fibrosis was assessed using receiver operating characteristic (ROC) analysis, and the optimal cut-off value was determined by the Youden index. Results: Reliable measurements of LS values were obtained in 114 patients (92.7%, 114/123). LS values obtained from 2D-SWE with the propagation map positively correlated with the progression of liver fibrosis reported from histopathology (p < 0.001). According to the multivariate linear regression analysis, fibrosis stage was the only factor significantly associated with LS (p < 0.001). The area under the ROC curve of LS from 2D-SWE with the propagation map was 0.773, 0.865, 0.946, and 0.950 for detecting F ≥ 1, F ≥ 2, F ≥ 3, and F = 4, respectively. The optimal cut-off LS values were 5.4, 7.8, 9.4, and 12.2 kPa for F ≥ 1, F ≥ 2, F ≥ 3, and F = 4, respectively. The corresponding sensitivity and specificity of the LS value for detecting cirrhosis were 90.9% and 88.4%, respectively. Conclusion The LS value obtained from 2D-SWE with a propagation map provides excellent diagnostic performance in evaluating liver fibrosis stage, determined by histopathology.

Pancreatic ductal adenocarcinoma is a lethal cancer type that is associated with multiple gene mutations in somatic cells. Genetically engineered mouse is hardly applicable for developing a pancreatic cancer model, and the xenograft model poses a limitation in the reflection of early stage pancreatic cancer. Thus, in vivo somatic cell gene engineering with clustered regularly interspaced short palindromic repeats is drawing increasing attention for generating an animal model of pancreatic cancer. In this study, we selectedKras, Trp53, Ink4a, Smad4, and Brca2 as target genes, and applied Campylobacter jejuni Cas9 (CjCas9) andStreptococcus pyogens Cas9 (SpCas9) for developing pancreatic cancer using adeno associated virus (AAV) transduction. After confirming multifocal and diffuse transduction of AAV2, we generated SpCas9 overexpression mice, which exhibited high double-strand DNA breakage (DSB) in target genes and pancreatic intraepithelial neoplasia (PanIN) lesions with two AAV transductions; however, wild-type (WT) mice with three AAV transductions did not develop PanIN. Furthermore, small-sized Cjcas9 was applied to WT mice with two AAV system, which, in addition, developed high extensive DSB and PanIN lesions. Histological changes and expression of cancer markers such as Ki67, cytokeratin, Mucin5a, alpha smooth muscle actin in duct and islet cells were observed. In addition, the study revealed several findings such as 1) multiple DSB potential of AAV-CjCas9, 2) peri-ductal lymphocyte infiltration, 3) multi-focal cancer marker expression, and 4) requirement of > 12 months for initiation of PanIN in AAV mediated targeting. In this study, we present a useful tool for in vivo cancer modeling that would be applicable for other disease models as well.