Objective: To quantitatively analyze and compare the forces and moments generated by thermoformed polyethylene terephthalate glycol (PETG) and direct-printed TC-85 clear aligners (CAs), with various margin designs, during premolar rotation. Methods: In total, 132 CAs were fabricated and divided into four groups (n = 33 per group). Group C consisted of thermoformed PETG aligners with a 2 mm gingival margin. Group E comprised direct-printed TC-85 aligners with equi-gingival margin, whereas Group G utilized direct-printed TC-85 aligners with 2 mm gingival margins.Finally, Group T featured direct-printed TC-85 aligners with an additional 1 mm thickness at the mesial embrasure. The forces and moments were measured using a 6-axis force/moment transducer at 2°, 3°, and 4° of rotation. All measurements were conducted at 37°C to simulate intraoral conditions. Forces were measured in the buccolingual, anteroposterior, and vertical directions, while moments were measured in the mesiodistal, buccolingual, and rotational planes. Results: The PETG aligners (Group C) showed significantly increased buccal and posterior force across the rotation angles (P < 0.05), whereas the intrusive force remained consistent. In contrast, the TC-85 aligners maintained consistent forces across all rotation angles.Direct-printed aligners demonstrated significantly lower intrusive forces than PETG aligners (P < 0.001). Group T exhibited reduced unwanted forces while maintaining effective rotational moments. Furthermore, all direct-printed aligners showed more predictable force delivery patterns than thermoformed aligners. Conclusions Direct-printed TC-85 aligners demonstrated superior force consistency and reduced unwanted side effects compared with traditional PETG aligners. Although marginal design modifications did not significantly improve rotational efficiency, they effectively reduced unwanted intrusive forces.

Background: Chronic pain significantly affects daily activities, mental health, and the interpersonal relationships of patients. Consequently, physicians use various treatments to manage pain. This study investigated the perceptions of treatment, accompanying symptoms, and other problems in patients with chronic pain. Methods: The authors enrolled patients with chronic pain from 19 university hospitals in South Korea. Data was collected on age, gender, diagnosis, disease duration, severity of pain, perception of pain treatment, and accompanying symptoms or problems using an anonymous survey comprising 19 questions. Results: In total, 833 patients with chronic pain completed the survey, and 257 (31.0%) and 537 (64.5%) patientsexpressed concerns about the potential adverse effects of medication and opioid addiction, respectively. Personalitychanges such as irritability or anger were the most frequent accompanying symptoms in 507 (63.8%) patients, followed by depression and sleep disturbance in 462 (58.1%) and 450 (54.5%) patients, respectively. Depression (P = 0.001) and anxiety (P = 0.029) were more common among women, whereas divorce (P = 0.016), family conflict (P < 0.001), unemployment (P < 0.001), suicide attempts (P < 0.001), and restrictions on economic activity (P < 0.001) were more common among men. The frequency of accompanying symptoms, except for suicidal ideation,was higher in the younger patients aged ≤ 40 years than in the older patients aged > 40 years. Conclusions Many patients with chronic pain had concerns about adverse effects or medication tolerance and experienced anxiety, depression, or sleep disturbances. The prevalence of accompanying problems varies according to age and gender.

Idiopathic nonspecific interstitial pneumonia (iNSIP) is recognized as a distinct entity among various types of idiopathic interstitial pneumonias. It is identified histologically by the nonspecific interstitial pneumonia pattern. A diagnosis of iNSIP is feasible once secondary causes or underlying diseases are ruled out. Usually presenting with respiratory symptoms such as shortness of breath and cough, iNSIP has a subacute or chronic course. It predominantly affects females aged 50 to 60 years who are non-smokers. Key imaging findings on chest high-resolution computed tomography include bilateral reticular opacities in lower lungs, traction bronchiectasis, reduced lung volumes and, ground-glass opacities. Abnormalities are typically diffuse across both lungs with subpleural distributions. Treatment often involves systemic steroids, either alone or in combination with other immunosuppressants, although evidence supporting effectiveness of these treatments is limited. Prognosis is generally more favorable for iNSIP than for idiopathic pulmonary fibrosis, with many studies reporting a 5-year survival rate above 70%. Antifibrotic agents should be considered in a condition, termed progressive pulmonary fibrosis, where pulmonary fibrosis progressively worsens.

Background: Small cell lung cancer (SCLC) is called ‘smoker’s disease’ because it is strongly associated with smoking and most cases occur in smokers. However, it can also occur in never smokers. We investigated the clinical features of never smokers with SCLC and compared their treatment outcomes with those of smokers with SCLC. Methods: We retrospectively reviewed the clinical data of patients who had proven SCLC and had received chemotherapy at a single cancer center between July 2002 and April 2021. Results: Of 1,643 patients, 1,416 (86.2%) were enrolled in this study. A total of 162 (11.4%) and 1,254 (88.6%) patients were never smokers and smokers, respectively. There were more female never smokers than smokers (n=130; 80.2% vs. 79, 6.3%, p=0.000), and the incidence of ischemic heart disease was lower among never smokers than among smokers (4/1,416, [2.5%] vs. 83/1,416 [6.6%], p=0.036). Never smokers showed less symptoms at diagnosis than smokers (80.9% vs. 87.2%, p=0.037); however, they showed more toxicity after first-line treatment (61.7% vs. 47.8%, p=0.001). The objective response rate (ORR) was significantly higher in never smokers (74.1% vs. 59.6%, p=0.000). In the multivariate analysis, never smoking and second-line treatment were associated with a better ORR. However, progression-free survival and overall survival were not significantly different between never smokers and smokers. Conclusion In conclusion, never smokers accounted for 11.4% of patients with SCLC. They had distinguishing clinical characteristics and showed better chemotherapeutic responses than smokers.

Purpose: In pancreatic cancer, therapeutic investigations targeting liver metastases could improve survival. However, the use of local treatment for oligometastasis in pancreatic cancer remains controversial. This study aimed to investigate the oncological role of local therapy in patients who underwent curative pancreatectomy and subsequently developed liver metastases. Materials and Methods: Data concerning patients who underwent curative pancreatectomy for pancreatic cancer at Severance Hospital in Seoul, South Korea between 2006 and 2018 were retrospectively reviewed. We included patients with one or two liver metastases, as confirmed on imaging. We excluded those with metastases in other organs. The patients were divided into two groups: the NT group, receiving conventional therapy without local treatment; and the LT group, receiving local treatments for liver metastases alongside standard therapy. Results: Of the 43 included patients (NT group, n=33; LT group, n=10), no significant differences were observed in overall survival (OS) [hazard ratio (HR) 0.846; 95% confidence interval (CI) 0.397–1.804; p=0.665] or post-recurrence survival (HR 0.932; 95% CI 0.437–1.985, p=0.855) between the two groups. In multivariate analysis, early recurrence within 6 months (p<0.001) and the use of 5-fluorouracil (FU)-based adjuvant chemotherapy (CTx) (p=0.011), as well as 5-FU-based CTx after liver metastasis (p=0.008) when compared with gemcitabine-based regimens, were significant predictors of poor OS. Conclusion The oncologic role of local treatment for hepatic metastasis remains controversial in patients with hepatic metastasis after radical pancreatectomy. In the era of potent chemotherapeutic regimens, further research is needed to clarify the efficacy of such regimens.

Purpose: This study aimed to identify independent risk factors for middle ear barotrauma (MEB) symptoms in patients undergoing monoplace hyperbaric oxygen therapy (HBOT). Materials and Methods: We analyzed data from a single-center study involving 296 patients who received monoplace HBOT.Through multivariable logistic regression analysis, we examined the relationship between various factors and the occurrence of MEB to identify significant independent risk factors. Results: The multivariable logistic regression analysis indicated that an altered mental state was associated with increased odds of MEB occurrence [odds ratio (OR) 2.50; 95% confidence interval (CI): 1.13–5.51]. Furthermore, patients in the emergency treatment group for HBOT, as defined by the national health insurance in Korea, were found to be 6.75 times more likely to experience MEB (95% CI: 1.33–34.20). Conclusion This study identified altered mental status and classification in the emergency treatment group for monoplace HBOT as independent risk factors for MEB. These findings can aid in developing safer protocols for monoplace HBOT chamber operations.

Irritable bowel syndrome (IBS) is a chronic, disabling, and functional bowel disorder that significantly affects social functioning and reduces quality of life and increases social costs. The Korean Society of Neurogastroenterology and Motility published clinical practice guidelines on the management of IBS based on a systematic review of the literature in 2017, and planned to revise these guidelines in light of new evidence on the pathophysiology, diagnosis, and management of IBS. The current revised version of the guidelines is consistent with the previous version and targets adults diagnosed with or suspected of having IBS. These guidelines were developed using a combination of de novo and adaptation methods, with analyses of existing guidelines and discussions within the committee, leading to the identification of key clinical questions. Finally, the guidelines consisted of 22 recommendations, including 3 concerning the definition and risk factors of IBS, 4 regarding diagnostic modalities and strategies, 2 regarding general management, and 13 regarding medical treatment. For each statement, the advantages, disadvantages, and precautions were thoroughly detailed. The modified Delphi method was used to achieve expert consensus to adopt the core recommendations of the guidelines. These guidelines serve as a reference for clinicians (including primary care physicians, general healthcare providers, medical students, residents, and other healthcare professionals) and patients, helping them to make informed decisions regarding IBS management.

Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

Melanin is a bio-pigment molecule synthesized by melanocytes. Its role is to shield the skin from ultraviolet radiation. Nonetheless, aberrant melanin production, whether excessive or deficient, can lead to conditions such as vitiligo, freckles, melanocytic nevi, and even melanoma. The biosynthetic pathway of melanin is known as melanogenesis, which is regulated by various transcription factors and enzymatic processes. Piperine (PPN), an alkaloid compound extracted from Piper retrofractum Vahl., was investigated for its potential anti-fungal and anti-inflammatory effects. Our hypothesis centered on the inhibition of melanin biosynthesis in response to PPN treatment. Subsequently, it was observed that PPN treatment resulted in a dose-dependent reduction in melanin production, accompanied by a decrease in tyrosinase activity. Furthermore, PPN was found to downregulate the protein levels of key melanogenesis-related genes. Additionally, PPN was observed to elevate the phosphorylation levels of ERK. To assess the role of ERK signaling in PPN-induced melanogenesis regulation, PD98059, an ERK inhibitor, was used. When Melan-A cells were treated with PD98059, the reduced expression level of MITF and melanin content induced by piperine were restored. Additionally, phosphorylation of ERK increased the phosphorylation of MITF at Ser73. This phosphorylated MITF leads to ubiquitination, and ultimately, the protein level of MITF decreases through proteasomal degradation. Likewise, when Melan-A cells were treated with MG132, a proteasomal inhibitor, the reduced expression level of MITF and melanin content induced by piperine were restored.Consequently, PPN can be a potential candidate for application as a skin whitening agent or in formulations to mitigate hyperpigmentation.

Purpose: Inotuzumab ozogamicin (INO) has demonstrated a safe bridging role to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). How‑ ever, hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is frequently observed. This study aimed to identify significant features of INO-associated VOD/SOS. Methods: We reviewed seven cases of hepatic VOD/SOS that developed either during INO salvage or after alloge‑ neic HSCT following INO-induced complete remission (CR). Diagnosis and severity grading of VOD/SOS were based on the revised criteria from the European Society for Blood and Marrow Transplantation. Defibrotide was used to treat severe to very severe cases. Results: Four patients developed VOD/SOS during INO salvage therapy (at 21 and 36 days post-INO1, 77 days postINO3, and 21 days post-INO5), while three were diagnosed at 2, 5, and 10 days post-HSCT following INO-induced CR.Doppler ultrasonography revealed preserved portal vein flow (range 10.2–26.0 cm/sec) and normal hepatic artery resistive index (RI, range 0.56–0.74) in all but one patient (RI 0.83). Despite this, all patients presented with massive ascites and progressively elevated total bilirubin levels. All cases were classified as severe to very severe; six were treated with defibrotide and one underwent liver transplantation. Most patients ultimately died owing to VOD/SOS progression. Conclusion Post-INO VOD/SOS manifested as two different clinical settings and was characterized by preserved portal vein flow, which complicated diagnosis. Despite timely defibrotide administration, clinical outcomes were poor.These findings emphasize the need for vigilance and potential consideration of prophylactic strategies for prevention of INO-associated VOD/SOS.