Search

Background: Sasanlimab (PF-06801591), a humanized immunoglobulin G4 monoclonal antibody, binds to programmed cell death protein-1 (PD-1), preventing ligand (PD-L1) interaction. Objectives: To evaluate pharmacokinetics (PK), safety, tolerability, and efficacy of two subcutaneous sasanlimab dosing regimens. Design: An open-label study consisting of phases Ib and II. Phase Ib: non-randomized, dose escalation, and expansion study in Asian participants with advanced malignancies. Phase II: conducted globally in participants with non-small-cell lung cancer with PD-L1 positive or PD-L1 status unknown tumors; participants were randomized 1:2 to receive subcutaneous sasanlimab 300 mg once every 4 weeks (300 mg-Q4W) or 600 mg once every 6 weeks (600 mg-Q6W). Methods: Primary endpoint in phase Ib: dose-limiting toxicity (DLT) occurring in first treatment cycle; in phase II: C trough and AUC. Results: A total of 155 participants (phase Ib, n = 34; phase II, n = 121) received sasanlimab. Phase Ib: no DLT reported. Phase II: ratio of adjusted geometric mean for AUC tau was 231.2 (90% CI, 190.1–281.2) and C trough was 111.5 (90% CI, 86.3–144.0) following 600 mg-Q6W (test) versus 300 mg-Q4W (reference). Phase Ib: grade 3 treatment-related adverse events (TRAEs) occurred in 1/4 (25%) and 3/12 (25%) participants treated in 300 mg-Q4W dose escalation and expansion cohorts, respectively. Phase II: grade 3 TRAEs occurred in 3/41 (7.3%) and 3/80 (3.8%) participants treated with 300 mg-Q4W and 600 mg-Q6W, respectively; no grade 4/5 TRAEs. Phase II: confirmed objective response was observed in 11/41 (26.8% (95% CI, 14.2–42.9)) and 12/80 (15.0% (95% CI, 8.0–24.7)) participants treated with 300 mg-Q4W and 600 mg-Q6W, respectively. Conclusions: Phase Ib regimens were considered safe with no DLTs reported. In phase II, 600 mg-Q6W regimen criteria were met for AUC tau and C trough metrics to support PK-based extrapolation of efficacy of alternative regimen. Regimens were well tolerated, showing anti-tumor activity in participants with advanced solid tumors. Administration of sasanlimab at a dose of 600 mg-Q6W subcutaneously may serve as a convenient alternative to 300 mg-Q4W administration. Trial registration: NCT04181788 (ClinicalTrials.gov); 2019-003818-14 (EudraCT).

Background Inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR), serve as valuable prognostic indicators in various cancers. This multicenter, retrospective cohort study assessed the treatment outcomes of lenvatinib in 71 patients with radioactive iodine (RAI)-refractory thyroid cancer, considering the baseline inflammatory biomarkers. Methods This study retrospectively included patients from five tertiary hospitals in Korea whose complete blood counts were available before lenvatinib treatment. Progression-free survival (PFS) and overall survival (OS) were evaluated based on the median value of inflammatory biomarkers. Results No significant differences in baseline characteristics were observed among patients grouped according to the inflammatory biomarkers, except for older patients with a higher-than-median NLR (≥2) compared to their counterparts with a lower NLR (P= 0.01). Patients with a higher-than-median NLR had significantly shorter PFS (P=0.02) and OS (P=0.017) than those with a lower NLR. In multivariate analysis, a higher-than-median NLR was significantly associated with poor OS (hazard ratio, 3.0; 95% confidence interval, 1.24 to 7.29; P=0.015). However, neither the LMR nor the PLR was associated with PFS. A higher-than-median LMR (≥3.9) was significantly associated with prolonged OS compared to a lower LMR (P=0.036). In contrast, a higher-than-median PLR (≥142.1) was associated with shorter OS compared to a lower PLR (P=0.039). Conclusion Baseline inflammatory biomarkers can serve as predictive indicators of PFS and OS in patients with RAI-refractory thyroid cancer treated with lenvatinib.

Background/Aims: Peroral cholangioscopy (POC) has been used to assess intrahepatic duct (IHD) lesions but with a limited role. A new multibending (MB) ultraslim endoscope has been designed to improve POC performance. We evaluated the usefulness of POC using the MB ultraslim endoscope for the management of IHD lesions. Methods : Between March 2017 and March 2020, 22 patients underwent direct POC using the MB ultraslim endoscope for IHD lesions documented by previous imaging or cholangiopancreatography. The primary outcome was technical success of POC, and secondary outcomes were technical success of POC-guided interventions, median procedure time, and POC-related adverse events. Results : The technical success rate for POC using the MB ultraslim endoscope for IHD lesions was 95.5% (21/22). Free-hand insertion was successful in 95.2% (20/21). The overall technical success rate for POC-guided intervention was 100% (21/21), including nine diagnostic and 12 therapeutic procedures (eight direct stone removal and four intraductal lithotripsies). The median procedure time was 29 minutes (range, 9 to 79 minutes). There were no procedure-related adverse events. Conclusion : s: Direct POC using the MB ultraslim endoscope allows direct visualization of IHD lesions and may be useful for diagnosis and therapeutic management in selected patients.

Background : Recent lifestyle changes have increased the prevalence of dyslipidemia in Korea. Young men are known to have a low awareness of dyslipidemia and a lack of motivation to maintain their weight. However, the association between weight change and dyslipidemia in young adults has not been thoroughly examined. Methods : Data from the Armed Forces Medical Command Defense Medical Information System database were used. In this study, 15,068 soldiers who underwent private and corporal health examinations between May 2020 and April 2022 were included. The difference in weights between the two different health examinations was used to quantify weight change. Four components of the lipid profile were used to assess dyslipidemia during the corporal health examination. Results : After adjusting for relevant covariates, weight gain was associated with increased risk of dyslipidemia (adjusted odds ratio [OR], 1.38 [95% confidence interval, CI, 1.15 to 1.64] for the 5% to 10% weight gain group; and OR, 2.02 [95% CI, 1.59 to 2.55] for the ≥10% weight gain group), whereas weight loss was associated with decreased risk (adjusted OR, 0.82 [95% CI, 0.68 to 0.98] for the 5% to 10% weight loss group; and OR, 0.38 [95% CI, 0.27 to 0.53] for the ≥10% weight loss group). In subgroup analysis based on the participants’ baseline body mass index, smoking status, regular exercise habits, and hypertension status, there were no significant differences between the subgroups. Conclusion : Weight change was associated with dyslipidemia in Korean male soldiers. The findings suggest that limiting weight gain in young adults by encouraging a healthy lifestyle may help prevent dyslipidemia.

Abstract In order to explore the spectrum of mitochondrial DNA (mtDNA) mutations in Korean patients with Leber's hereditary optic neuropathy (LHON), we investigated the spectrum of mtDNA mutations in 145 Korean probands confirmed with the diagnosis of LHON. Total genomic DNA was isolated from the peripheral blood leukocytes of the patients with suspected LHON, and mtDNA mutations were identified by direct sequencing. Analysis of mtDNA mutations revealed seven primary LHON mutations including the nucleotide positions (nps) 11778A (101 probands, 69.2%), 14484C (31 probands, 21.2%), 3460A (5 probands, 3.4%), and G3635A, G3733A, C4171A, and G13051A mutations in one proband each. In addition, two provisional mtDNA mutations at nps T3472C, and G13259A were each found in one proband, respectively. Another provisional mtDNA mutation at np T3394C was found in two probands. In conclusion, the spectrum of mtDNA mutations in Korean patients with LHON may differ from other ethnicities, which is characterized by high prevalence of 11778A and 14484C mutations, and a low prevalence of the 3460A mutation.

Abstract Background Plant viruses cause economic losses by reducing the quantity and quality of major crops. This issue is a growing concern due to the expansion of global trade and climate change. In addition, the emergence of new pathogen strains increases the difficulty of controlling viral diseases. Effective management strategies are therefore needed. The control strategy for viral diseases relies primarily on non-chemical and cultural practices, as no commercial viricides are currently available. Some compounds have been identified as effective against certain viruses, but their use in the field is limited due to issues such as concentration, toxicity, and efficacy. Therefore, it is imperative to discover novel antiviral agents that address the existing challenges associated with the identified antiviral candidate compounds. Results In this study, we evaluated iodine-conjugated organic compounds mixed with sialic acid, whey, and blood meal for virus disease management against seven viruses that cause significant yield losses and economic damage to plants. The candidate compounds reduced virus accumulation and symptom development. Treatment with candidate compounds, A4 and A5, reduced viral RNA accumulation to about half that of those in the control group and showed reduced symptoms along with healthier growth. In addition, we performed transcriptome analysis of treatment with two viruses, which suggested that the mechanism of viral RNA replication inhibition might relate to plant defense systems based on phytohormone pathways. Conclusions This study demonstrated that treatments with naturally derived materials, such as iodine, nitrogen, and sialic acid-conjugated organic substances, may directly or indirectly impact the host plant's resistance to various virus infections. Moreover, our findings suggest that these natural candidate materials could be utilized for managing virus diseases in the field. Graphical Abstract

Abstract Achieving optimal camouflage in an aquatic environment necessitates the ability to modulate transmittance in response to the surrounding obscurity and potential threats. This adaptation involves a dynamic transition from transparency to a deep-blue color, especially in low-light or dark situations. Such a strategy promotes a seamless assimilation with the surroundings, enabling the absorption of searchlights and, subsequently, diminishing the risk of detection by predators. Therefore, the presence of sophisticated mechanisms that facilitates stable and efficient control of transmittance is imperative, enabling smooth transition between transparent and deep-blue hues within the aquatic environment. This study presents nature-inspired programmable camouflage system that integrates an electrochromic display as the primary transmittance change element and a wireless base module for power and data transmission. Such technology offers a robust and flexible construction, ensuring stable operation as demonstrated through mechanical-fatigue experiments and quantitative simulation. A custom circuit and a power-control software package enable active control of multiple electrochromic displays while submerged in water.

We present a rare case of histiocytic sarcoma (HS) occurring in the foot of a 12-year-old male, initially misdiagnosed as localized tenosynovial giant cell tumor (TSGCT). HS is an exceptionally uncommon hematologic malignant neoplasm, with its occurrence in children and extranodal sites being even rarer. To our knowledge, this is the first reported case of extranodal HS in the foot, emphasizing comprehensive MRI findings. Initially, the patient was diagnosed with TSGCT based on histological results following surgical resection. However, after recurrence and subsequent surgical resection, histological and immunochemical analyses led to a revised diagnosis of HS. This report focuses on the MRI findings of HS, highlighting the distinctions from localized TSGCT. While both conditions share histopathological similarities, immunohistochemical tests are crucial for accurate diagnosis. The report underscores the importance of differentiating HS for appropriate treatment.

Abstract Over the past decade, numerous studies have highlighted the importance of acid sphingomyelinase (ASM) in disease treatment in humans. This enzyme functions primarily to generate ceramide, maintain the cellular membrane, and regulate cellular function. However, in the blood and brain of patients with neurological disorders, including major depression, ischemic stroke, amyotrophic lateral sclerosis, multiple sclerosis, and Alzheimer’s disease (AD), elevated ASM levels significantly suggest disease onset or progression. In these diseases, increased ASM is profoundly involved in neuronal death, abnormal autophagy, neuroinflammation, blood–brain barrier disruption, hippocampal neurogenesis loss, and immune cell dysfunction. Moreover, genetic and pharmacological inhibition of ASM can prevent or ameliorate various diseases. The therapeutic effects of ASM inhibition have prompted the urgent need to develop ASM inhibitors, and several ASM inhibitors have been identified. In this review, we summarize the current knowledge on the critical roles and mechanisms of ASM in brain cells and blood that are associated with different neuropathological features, especially those observed in AD. Furthermore, we elucidate the potential possibility and limitations of existing ASM-targeting drugs according to experimental studies in neurological disorder mouse models.

Abstract We conducted a prospective study to evaluate the efficacy of simulation-based education using a three-dimensional (3D)-printed schematic eye model in improving the retinoscopy refraction skills of medical students. A schematic eye model was printed using a fused deposition modeling-based 3D printer. Twenty medical students randomized into 3D (n = 10) and control (n = 10) groups received a 1-h lecture on the principles and methods of manifest refraction and were shown how to use the retinoscope and sciascope bars. The 3D group additionally attended a tutorial on the schematic eye. Both groups performed refractive examinations on four eyes of volunteer patients, and the results were recorded as a baseline. Instructor feedback and refraction practice was provided with the 3D group or with control group. To account for subject fatigue, patients spent no more than 8 min on the examination. After a 1-h break to allow for fatigue and familiarity, refraction tests were repeated on four randomly selected eyes of patients. Students’ refraction readings were compared with the autorefractor values using a spherical equivalent value and blur strength. All participants measured the time required to complete the refraction test and reported their subjective confidence in the results of each refraction test. Refractive errors before and after training did not differ between the control and 3D groups, with a significant improvement in errors observed in both groups (p = 0.005 and 0.008, respectively). The time to complete refraction before and after training did not differ between the two groups, both of which showed a significant reduction in time (p = 0.005 and 0.028, respectively). Pre- and post-training confidence scores for the accuracy of each refraction on a 10-point Likert scale were not significantly different. However, when comparing score changes between pre- and post-training, only the control group showed a significant increase in confidence (p = 0.005). Tests for the non-inferiority of refractive errors after training indicated that the 3D group was non-inferior to the control group. In conclusion, training in retinoscopy refraction skills using a 3D-printed eye model resulted in significant improvement in accuracy and speed compared to practice with real patients. Except for better confidence in the control group, schematic eye model training was not inferior to practice with real patients.

Abstract Rehabilitation improves symptoms, quality of life, and survival in patients with chronic respiratory or cardiovascular disease. We evaluated smartphone application-based rehabilitation programs for patients with chronic respiratory or cardiovascular diseases. This was a single-center prospective single arm study. Participants underwent smartphone application-based pulmonary or cardiac rehabilitation for 12 weeks. A total of 93 participants were recruited, and 75 visited after rehabilitation. Their median age was 67.0 (interquartile range, 60.0–70.8) years, and 60 (80.0%) were men. For patients with chronic respiratory disease (n = 41), VO2peak (median 13.7 to 15.4 ml/kg/min, P = 0.049), chronic obstructive pulmonary disease assessment test (median 14 to 6, P

Background Active surveillance (AS) has been introduced as a management strategy for low-risk papillary thyroid carcinoma (PTC) due to its typically indolent nature. Despite this, the widespread adoption of AS has encountered several challenges. The aim of this systematic review was to evaluate the safety of AS related to disease progression and its benefits compared with immediate surgery (IS). Methods Studies related to AS in patients with low-risk PTC were searched through the Ovid MEDLINE, Embase, Cochrane Library, and KoreaMed databases. Studies on disease progression, surgical complication, quality of life (QoL), and cost-effectiveness were separately analyzed and narratively synthesized. Results In the evaluation of disease progression, the proportions of cases with tumor growth ≥3 mm and a volume increase >50% were 2.2%–10.8% and 16.0%–25.5%, respectively. Newly detected lymph node metastasis was identified in 0.0%–1.4% of patients. No significant difference was found between IS and delayed surgery in surgical complications, including vocal cord paralysis and postoperative hypoparathyroidism. AS was associated with better QoL than IS. Studies on the cost-effectiveness of AS reported inconsistent data, but AS was more cost-effective when quality-adjusted life years were considered. Conclusion AS is an acceptable management option for patients with low-risk PTC based on the low rate of disease progression and the absence of an increased mortality risk. AS has additional benefits, including improved QoL and greater QoL-based cost-effectiveness.

Background: Esophagogastric and pancreaticobiliary cancers are associated with chronic blood loss, poor nutrition, and surgical interventions that interfere with iron absorption. Patients with these cancers often have a higher incidence of chemotherapy-induced anemia (CIA) than patients with other malignancies. Objectives: To investigate the efficacy of intravenous iron or erythropoietin-stimulating agents (ESA) for CIA treatment in patients with esophagogastric or pancreaticobiliary cancer. Design: Retrospective, comparative chart review of patients with esophagogastric or pancreaticobiliary cancer who received ferric carboxymaltose (FCM), or darbepoetin alfa (DA), and myelosuppressive chemotherapy at Chungbuk National University Hospital between June 2018 and December 2022. Methods: To assess the efficacy of FCM or DA over time, data on hemoglobin (Hb) levels were collected from the time of administration of FCM or DA (baseline) until 6 months post-baseline, when available. Results: In total, 214 patients (124 in the FCM and 90 in the DA group) were included in the analysis. The FCM group had a higher maximum Hb level and Hb changes for 3 months (mean ± standard deviation) following FCM or DA administration from baseline than the DA group (11.3 ± 1.5 versus 10.9 ± 1.2 g/dL, p = 0.02 and 2.0 ± 1.4 versus 1.5 ± 1.1 g/dL, p = 0.004, respectively). The FCM group had a higher proportion of Hb responders than the DA group (83.9% versus 68.9%, p = 0.013). Based on multivariable analysis, only the CIA treatment group was a significant factor for Hb response (odds ratio = 2.06, 95% confidence interval = 1.05–4.06, p = 0.036). Conclusion: Both FCM and DA are effective, and FCM showed a higher Hb response than DA for CIA treatment in patients with esophagogastric or pancreaticobiliary cancer. Therefore, further randomized controlled trials should determine the optimal treatment for CIA in patients with these cancers undergoing myelosuppressive chemotherapy.

PurposePancreatic ductal adenocarcinoma (PDAC) is an aggressive tumor with a poor prognosis that poses challenges for diagnosis using traditional tissue-based techniques. DNA methylation alterations have emerged as potential and promising biomarkers for PDAC. In this study, we aimed to assess the diagnostic potential of a novel DNA methylation assay based on epigenetic-specific peptide nucleic acid (Epi-sPNA) in both tissue and plasma samples for detecting PDAC.Materials and methodsThe study involved 46 patients with PDAC who underwent surgical resection. Epi-TOP pancreatic assay was used to detect PDAC-specific epigenetic biomarkers. The Epi-sPNA allowed accurate and rapid methylation analysis without bisulfite sample processing. Genomic DNA extracted from paired normal pancreatic and PDAC tissues was used to assess the diagnostic efficacy of epigenetic biomarkers for PDAC. Subsequent validation was conducted on cell-free DNA (cfDNA) extracted from plasma samples, with 10 individuals represented in each group: PDAC, benign pancreatic cystic neoplasm, and healthy control.ResultsThe combination of seven epigenetic biomarkers (HOXA9, TWIST, WT1, RPRM, BMP3, NPTX2, and BNC1) achieved 93.5% sensitivity and 96.7% specificity in discerning normal pancreatic from PDAC tissues. Plasma cfDNA, analyzed using these markers and KRAS mutations, exhibited a substantial 90.0% sensitivity, 95.0% specificity, and an overall 93.3% accuracy for discriminating PDAC. Notably, cancer antigen 19-9 and carcinoembryonic antigen both had an accuracy of 90.0%.ConclusionOur study suggests that analyzing seven differentially methylated genes with KRAS mutations in cfDNA using the novel Epi-TOP pancreatic assay is a potential blood-based biomarker for the diagnosis of PDAC.

BackgroundPapillary thyroid microcarcinoma (PTMC) is characterized by its favorable prognosis and potential for active surveillance (AS) as a management option. However, the presence of cervical lymph node (LN) metastasis, especially lateral LN metastasis, significantly impacts management and prognosis. Previous studies have focused on post-surgery risk factors for cervical LN metastasis. This study aims to identify predictors of lateral LN metastasis by analyzing pre-operative ultrasonographic findings alongside clinicopathological factors.MethodsA retrospective review of medical records was conducted for patients with PTMC who underwent surgery at Chonnam National University Hwasun Hospital between 2004 and 2013. This is a case–control study that compares patients with lateral LN metastasis (N1b) to age- and sex-matched patients without LN metastasis (N0). Subgroup analysis was performed to evaluate risk factors of skip metastasis.ResultsThe study included 90 patients with PTMC with lateral LN metastasis (N1b) and 268 age- and sex-matched patients without LN metastasis (N0). The mean age was 49.3 years, and female patients were dominant in both groups. Structural recurrences of 4.4% (4/90) were observed only in the N1b group. The N1b group exhibited a higher frequency of upper lobe tumor location compared to the N0 group (38.9% vs. 16.0%, p < 0.001). There was no significant difference in the locations with the presence of invasion to adjacent organs. A higher proportion of non-parallel shape was observed in the N1b group than the N0 group (80.0% vs. 66.0%, p = 0.013). There were no differences in echogenicity, sonographic feature, margin, and AP diameter of the thyroid gland between the two groups. In multivariate analysis, independent risk factors for lateral LN metastasis included extrathyroidal extension, multiplicity, upper lobe tumor location, and non-parallel shape. Skip metastasis in patients with PTMC was associated with upper lobe tumor location.ConclusionDetailed ultrasound examinations, evaluating tumor location, number, orientation, and the presence of ETE, are crucial in accurately predicting lateral LN metastasis especially when primary tumor was in the upper lobe to avoid missing skip metastasis. These evaluations can help guide the decision between AS and immediate surgery in patients with PTMC.