Purpose: Pulmonary sarcomatoid carcinoma (PSC) is a rare aggressive subtype of non–small cell lung cancer (NSCLC) with limited therapeutic strategies. We attempted to elucidate the evolutionary trajectories of PSC using multiregional and longitudinal tumor samples. Materials and Methods: A total of 31 patients were enrolled in this study and 11 longitudinal samples were available from them. Using whole exome sequencing data, we analyzed the mutational signatures in both carcinomatous and sarcomatous areas in primary tumors of the 31 patients and longitudinal samples obtained from 11 patients. Furthermore, digital droplet polymerase chain reaction (ddPCR), and programmed death-ligand 1 (PD-L1) immunohistochemistry using the Ventana SP263 assay were performed. Results: TP53 was identified as the most frequently altered gene in the primary (74%) and metastatic (73%) samples. MET exon 14 skipping mutations, confirmed by ddPCR, and TP53 mutations were mutually exclusive; whereas, MET exon 14 skipping mutations frequently co-occurred with MDM2 amplification. Metastatic tumors showed dissimilar genetic profiles from either primary component. During metastasis, the signatures of APOBEC decreased in metastatic lesions compared with that in primary lesions. PSC showed higher MET and KEAP1 mutations and stronger PD-L1 protein expression compared with that recorded in other NSCLCs. Conclusion Decreased APOBEC signatures and subclonal diversity were detected during malignant progression in PSC. Frequent MET mutations and strong PD-L1 expression distinguished PSC from other NSCLCs. The aggressiveness and therapeutic difficulties of PSC were possibly attributable to profound intratumoral and intertumoral genetic diversity. Next-generation sequencing could suggest the appropriate treatment strategy for PSC.

Purpose: To report a case of recurrent optic neuritis with uveitis in a patient with myelin oligodendrocyte glycoprotein (MOG)- associated disease.Case summary: A 16-year-old female presented with left eye hyperemia, glare, and headache. The best corrected visual acuity was 1.2 in both eyes with a left relative afferent pupillary defect. Cells in the anterior chamber, optic disc edema, and subretinal fluid were present, and the distal optic nerve was enhanced on orbital magnetic resonance imaging. Although it improved with steroid treatment, it recurred 3 times in 9 months. At the second recurrence, her visual acuity was reduced to light perception, but she responded well to steroids. During the third recurrence, she visited our hospital for the first time and improved with steroid treatment. However, 18 months after treatment, optic neuritis, uveitis, and macular edema occurred, so oral steroids and eye drops were maintained. Serum anti-MOG antibody came out positive, and at the last visit, visual acuity of 1.2 in the left eye and visual function were maintained well. Conclusions MOG antibody disease (MOGAD) frequently recurs and invades various structures of the eye and various clinical manifestations have been reported. Therefore, if optic neuritis is accompanied by inflammation of the anterior chamber and retinal vessels, the possibility of MOGAD should be considered.

Background: Large-scale studies about epidemiologic characteristics of renal infarction (RI) are few. In this study, we aimed to analyze the incidence and prevalence of RI with comorbidities in the South Korean population. Methods: We investigated the medical history of the entire South Korean adult population between 2013 and 2019 using the National Health Insurance Service database (n = 51,849,591 in 2019). Diagnosis of RI comorbidities were confirmed with International Classification of Disease, Tenth Revision, Clinical Modification codes. Epidemiologic characteristics, distribution of comorbidities according to etiologic mechanisms, and trend of antithrombotic agents were estimated. Results: During the 7-years, 10,496 patients were newly diagnosed with RI. The incidence rate increased from 2.68 to 3.06 per 100,000 person-years during the study period.The incidence rate of RI increased with age peaking in the 70s with 1.41 times male predominance. The most common comorbidity was hypertension, followed by dyslipidemia and diabetes mellitus. Regarding etiologic risk factor distribution, high embolic risk group, renovascular disease group, and hypercoagulable state group accounted for 16.6%, 29.1%, and 13.7% on average, respectively. For the antithrombotic treatment of RI, the prescription of antiplatelet agent gradually decreased from 17.0% to 13.0% while that of anticoagulation agent was maintained around 35%. The proportion of non-vitamin K antagonist oral anticoagulants remarkably increased from only 1.4% to 17.6%. Conclusion Considering the progressively increasing incidence of RI and high prevalence of coexisting risk factors, constant efforts to raise awareness of the disease are necessary. The current epidemiologic investigation of RI would be the stepping-stone to establishing future studies about clinical outcomes and optimal treatment strategies.

Objective: Dysphagia is a common clinical condition characterized by difficulty in swallowing. It is sub-classified into oropharyngeal dysphagia, which refers to problems in the mouth and pharynx, and esophageal dysphagia, which refers to problems in the esophageal body and esophagogastric junction. Dysphagia can have a significant negative impact one’s physical health and quality of life as its severity increases. Therefore, proper assessment and management of dysphagia are critical for improving swallowing function and preventing complications. Thus a guideline was developed to provide evidence-based recommendations for assessment and management in patients with dysphagia. Methods: Nineteen key questions on dysphagia were developed. These questions dealt with various aspects of problems related to dysphagia, including assessment, management, and complications. A literature search for relevant articles was conducted using Pubmed, Embase, the Cochrane Library, and one domestic database of KoreaMed, until April 2021. The level of evidence and recommendation grade were established according to the Grading of Recommendation Assessment, Development and Evaluation methodology. Results: Early screening and assessment of videofluoroscopic swallowing were recommended for assessing the presence of dysphagia. Therapeutic methods, such as tongue and pharyngeal muscle strengthening exercises and neuromuscular electrical stimulation with swallowing therapy, were effective in improving swallowing function and quality of life in patients with dysphagia. Nutritional intervention and an oral care program were also recommended. Conclusion This guideline presents recommendations for the assessment and management of patients with oropharyngeal dysphagia, including rehabilitative strategies.

Background/Aims: Transarterial radioembolization (TARE) has shown promising results in treating advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). However, whether TARE can provide superior or comparable outcomes to tyrosine kinase inhibitor (TKI) in patients with HCC and PVTT remains unclear. We compared the outcomes of TARE and TKI therapy in treatment-naïve patients with locally advanced HCC and segmental or lobar PVTT. Methods: This multicenter study included 216 patients initially treated with TARE (n=124) or TKI (sorafenib or lenvatinib; n=92) between 2011 and 2021. Baseline characteristics were balanced using propensity score matching (PSM) or inverse probability of treatment weighting (IPTW). The primary outcome was overall survival (OS). The secondary outcomes included progression-free survival (PFS) and objective response rate (ORR). Results: In the unmatched cohort, the median OS of the TARE and TKI groups were 28.2 and 7.2 months, respectively (p<0.001), and the TARE group experienced significantly and independently longer OS compared to the TKI group (adjusted hazard ratio=0.41, 95% confidence interval=0.28–0.60, p<0.001). Similar results were observed in the study cohorts balanced with IPTW (p=0.003) or PSM (p=0.004). Although PFS was comparable between the two groups, the TARE group showed a trend of prolonged PFS in a subpopulation of patients with Vp1 or Vp2 PVTT (p=0.052). In the matched cohorts, the ORR of the TARE group was 53.0–56.7%, whereas that of the TKI group was 12.3–15.0%. Conclusions For patients with advanced HCC with segmental or lobar PVTT and well-preserved liver function, TARE may provide superior OS compared to sorafenib or lenvatinib.

Background and Objectives: The colonic epithelial layer is a complex structure consisting of multiple cell types that regulate various aspects of colonic physiology, yet the mechanisms underlying epithelial cell differentiation during development remain unclear. Organoids have emerged as a promising model for investigating organogenesis, but achieving organ-like cell configurations within colonic organoids is challenging. Here, we investigated the biological significance of peripheral neurons in the formation of colonic organoids. Methods: and Results: Colonic organoids were co-cultured with human embryonic stem cell (hESC)-derived peripheralneurons, resulting in the morphological maturation of columnar epithelial cells, as well as the presence of enterochromaffin cells. Substance P released from immature peripheral neurons played a critical role in the development of colonic epithelial cells. These findings highlight the vital role of inter-organ interactions in organoid development and provide insights into colonic epithelial cell differentiation mechanisms. Conclusions Our results suggest that the peripheral nervous system may have a significant role in the development ofcolonic epithelial cells, which could have important implications for future studies of organogenesis and disease modeling.

Background/Aims: We aimed to analyze the efficacy of angiotensin receptor-neprilysin inhibitor (ARNI) by the disease course of heart failure (HF). Methods: We evaluated 227 patients with HF in a multi-center retrospective cohort that included those with left ventricular ejection fraction (LVEF) ≤ 40% undergoing ARNI treatment. The patients were divided into patients with newly diagnosed HF with ARNI treatment initiated within 6 months of diagnosis (de novo HF group) and those who were diagnosed or admitted for HF exacerbation for more than 6 months prior to initiation of ARNI treatment (prior HF group). The primary outcome was a composite of cardiovascular death and worsening HF, including hospitalization or an emergency visit for HF aggravation within 12 months. Results: No significant differences in baseline characteristics were reported between the de novo and prior HF groups. The prior HF group was significantly associated with a higher primary outcome (23.9 vs. 9.4%) than the de novo HF group (adjusted hazard ratio 2.52, 95% confidence interval 1.06–5.96, p = 0.036), although on a higher initial dose. The de novo HF group showed better LVEF improvement after 1 year (12.0% vs 7.4%, p = 0.010). Further, the discontinuation rate of diuretics after 1 year was numerically higher in the de novo group than the prior HF group (34.4 vs 18.5%, p = 0.064). Conclusions The de novo HF group had a lower risk of the primary composite outcome than the prior HF group in patients with reduced ejection fraction who were treated with ARNI.

Background: To report the clinical manifestations of non-arteritic anterior ischemic optic neuropathy (NAION) cases after coronavirus disease 2019 (COVID-19) vaccination in Korea. Methods: This multicenter retrospective study included patients diagnosed with NAION within 42 days of COVID-19 vaccination. We collected data on vaccinations, demographic features, presence of vascular risk factors, ocular findings, and visual outcomes of patients with NAION. Results: The study included 16 eyes of 14 patients (6 men, 8 women) with a mean age of 63.5 ± 9.1 (range, 43–77) years. The most common underlying disease was hypertension, accounting for 28.6% of patients with NAION. Seven patients (50.0%) had no vascular risk factors for NAION. The mean time from vaccination to onset was 13.8 ± 14.2 (range, 1–41) days. All 16 eyes had disc swelling at initial presentation, and 3 of them (18.8%) had peripapillary intraretinal and/or subretinal fluid with severe disc swelling. Peripapillary hemorrhage was found in 50% of the patients, and one (6.3%) patient had peripapillary cotton-wool spots. In eight fellow eyes for which we were able to review the fundus photographs, the horizontal cup/ disc ratio was less than 0.25 in four eyes (50.0%). The mean visual acuity was logMAR 0.6 ± 0.7 at the initial presentation and logMAR 0.7 ± 0.8 at the final visit. Conclusion Only 64% of patients with NAION after COVID-19 vaccination have known vascular and ocular risk factors relevant to ischemic optic neuropathy. This suggests that COVID-19 vaccination may increase the risk of NAION. However, overall clinical features and visual outcomes of the NAION patients after COVID-19 vaccination were similar to those of typical NAION.

Objective: To examine the prognostic value of electroneuronography (ENoG) in predicting functional recovery in severe cases of acute facial palsy. Methods: Patients with severe degrees of facial palsy (initial House–Brackmann [HB] grades IV to VI) with available electrodiagnostic studies conducted 2–4 weeks after symptom onset were reviewed retrospectively. The patients were categorized into “good recovery” and “poor recovery” groups, with the former showing mild to no dysfunction (HB I to III) and the latter exhibiting moderate to severe dysfunction (HB IV to VI) on follow-up evaluation, 2 months after onset. ENoG amplitudes in four facial muscles (frontalis, nasalis, orbicularis oculi, and orbicularis oris), as well as age, sex, affected side, disease etiology, comorbidities, and laboratory findings, were compared between the two groups. Results: Thirty-seven patients were included. Twenty-nine of the patients showed “good recovery,” and eight showed “poor recovery” at 2 months after symptom onset. Univariate analysis yielded no significant difference in age, sex, affected side, disease etiology, comorbidities, and laboratory findings between the two groups. Preserved ENoG amplitudes (individual, average, and trimmed means) were significantly higher in the good recovery group than in the poor recovery group (p<0.005). Sex (p=0.038) and the ENoG of the nasalis muscle, acquired 2–4 weeks from symptom onset (p=0.004), showed significant differences in multivariate regression analysis. Conclusion This study suggests that the female sex and lower ENoG of the nasalis muscle, acquired 2–4 weeks from symptom onset, have negative prognostic value for the 2-month functional outcome of severe facial palsy cases.

This study aims to investigate the relationship between ipsilesional upper extremity (UE) motor function and the integrity of the subregions of the corpus callosum in hemiparetic stroke patients with motor deficits of the dominant or non-dominant ipsilesional side.Twenty participants with unilateral UE deficits after stroke were included. Each of the 10 participants had lesions on the left and right sides. The ipsilesional UE function was assessed with the Jebsen-Taylor hand function test (JHFT), the 9-hole peg test (9HPT), and grip and pinch strength tests. Fractional anisotropy (FA) was calculated for the integrity of the 5 subregions of the corpus callosum. Pearson’s correlation analysis was conducted to investigate the relationship between UE function and the integrity of the callosal subregions.The results of JHFT and 9HPT showed a significant correlation with the FA value of the corpus callosum I projecting to the frontal lobe in the left lesion group (p < 0.05). There was no correlation between the ipsilesional UE motor function and the FA value of the ulnar subregion in the right lesion group (p > 0.05). These results showed that the motor deficits of the ipsilesional UE correlated with the integrity of callosal fiber projection to the prefrontal area when the ipsilesional side was non-dominant.