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Kwang Je Lee,1 Jae-Kean Ryu,2 Yun-Hyeong Cho,3 Won Yong Shin,4 Jeong Su Kim,5 Young Won Yoon,6 Ji Yong Jang,7 Won Ho Kim,8 Jong Wook Beom,9 Seok-Min Kang10 On behalf of LG-VROS001 STUDY INVESTIGATOR GROUP1Department of Internal Medicine, Chung-Ang University Hospital, Seoul, Korea; 2Department of Internal Medicine, Daegu Catholic University Medical Center, Daegu, Korea; 3Cardiovascular Center, Myongji Hospital, Goyang, Korea; 4Department of Cardiology, Soon Chun Hyang University Hospital Cheonan, Cheonan, Korea; 5Cardiovascular Center, Pusan National University Yangsan Hospital, Yangsan, Korea; 6Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; 7Department of Cardiology, National Health Insurance Service Ilsan Hospital, Ilsan, Korea; 8Eulji University School of Medicine, Daejeon, Korea; 9Department of Cardiology, Jeju National University Hospital, Jeju, Korea; 10Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, KoreaCorrespondence: Seok-Min Kang, Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea, Tel +82 2-2647-3225, Email SMKANG@yuhs.acPurpose: This study aimed to assess the effectiveness and safety of a fixed-dose combination of rosuvastatin and valsartan (Rovatitan®) in Korean patients with concomitant hypertension and hyperlipidemia.Patients and Methods: A total of 1008 eligible patients with concomitant hypertension and hyperlipidemia were enrolled and treated for 12 weeks. Both upward and downward drug dose titrations were allowed based on the investigator’s discretion. This study evaluated the effectiveness of the study drug, defined by the percentage of patients achieving the blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) treatment targets. Additionally, regression analyses were conducted to evaluate the factors associated with the effectiveness and safety of the study drug. Of the 1008 patients enrolled in the study, 911 were analyzed for clinical effectiveness.Results: At 12 weeks, 84.6% and 75.9% of patients treated with the study drug achieved their BP and LDL-C targets, respectively, and 64.8% of patients achieved both targets simultaneously. Furthermore, the percentage of patients who achieved their BP and LDL-C treatment targets demonstrated a trend across the respective risk groups; the higher the risk group, the lower the success of attaining the respective target. This trend was also observed regardless of the prior antihypertensive and/or lipid-lowering treatments. According to regression analysis, poor metabolic profiles, including a higher body mass index (BMI) and higher BP and LDL-C levels at baseline, were significantly associated with treatment failure for BP. Among the 1005 patients included in the safety analysis, 17 patients (1.7%) experienced serious adverse events; however, none were considered related to the study drug.Conclusion: The study drug used for the treatment of concomitant hypertension and hyperlipidemia in a real-world setting was effective and was well tolerated. Therefore, the study drug is suggested as a good alternative to increase patient convenience and compliance, particularly in those taking multiple medications.Keywords: hypertension, hyperlipidemia, rosuvastatin, valsartan, effectiveness, safety

The current study examined the effect of the Integrated Model of Advice-giving (Emotional Support—Problem Inquiry and Analysis—Advice) on recipients’ responses to advice, exploring the mediating roles of perceived regard for face and normativeness. Participants read and responded to a conversation in which they received advice from a friend regarding a problematic situation. Results indicated that perceived regard for positive face mediated the relationship between the sequential placement of emotional support and recipients’ responses to advice. Neither perceived regard for face nor normativeness mediated the relationship between the sequential placement of problem inquiry and analysis and recipients’ responses to advice. Findings of this study suggest that the provision of emotional support has a primary role in IMA and is effective in addressing the positive face needs of advice recipient.

Chungam Choi,1 Byung Won Yoo,2 Choon Ok Kim,2 Taegon Hong,2 Byung Hak Jin,2 Kwang-Seok Seo,3 Ja Yun Jang,4 Min Soo Park2 1Department of Nuclear Medicine, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea; 2Department of Clinical Pharmacology, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea; 3Biopharmaceutical Research Laboratories, Dong-A Socio R&D Center, Yongin-si, Republic of Korea; 4Product Development Division, Dong-A ST Co., Ltd, Seoul, Republic of Korea Purpose: Filgrastim, a granulocyte-colony stimulating factor, is used to treat patients with neutropenia, including neutropenic fever. Leucostim® is a recombinant filgrastim product tested for biosimilarity with its reference product, Neupogen®. We conducted a comparative clinical trial of the 2 products. Patients and methods: A randomized, open-label, 2-way crossover, single-dose Phase I study was conducted for 56 healthy subjects. After a 5 and 10 μg/kg single subcutaneous administration of test and reference product, pharmacokinetic and pharmacodynamic parameters (absolute neutrophil count and CD34+ cell count) were compared. During the study, safety tests and adverse event monitoring were performed. Results: The test and the reference products had a comparable pharmacokinetic, pharmacodynamic, and safety profile. In both 5 and 10 μg/kg dosing, the 90% CIs of the test to reference ratio for primary parameters (peak plasma concentration and area under the plasma concentration vs time curve from time 0 extrapolated to the infinite time for plasma filgrastim concentration; maximal effect and area under the time-effect curve from time 0 to time of the last quantifiable effect for absolute neutrophil count) were within the 0.8–1.25 range. In addition, safety profiles between the 2 products were similar without any serious adverse events. Conclusion: This study has provided firm clinical evidence that the test filgrastim product is similar to its reference filgrastim product. Keywords: bioequivalence, biosimilar, G-CSF, biologics

Mi Jin Lee,1 Seung Jun Lee,1,2,* Su Jin Yun,1,2,* Ji-Young Jang,3 Hangoo Kang,3 Kyongmin Kim,1,2 In-Hong Choi,3,4 Sun Park1,2 1Department of Microbiology, Ajou University School of Medicine, 2Department of Biomedical Sciences, The Graduate School, Ajou University, Suwon, 3Department of Microbiology, The Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Korea; 4Brain Korea 21 Plus Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Korea *These authors contributed equally to this work Abstract: The silver nanoparticle (AgNP) is a candidate for anticancer therapy because of its effects on cell survival and signaling. Although numerous reports are available regarding their effect on cell death, the effect of AgNPs on metabolism is not well understood. In this study, we investigated the effect of AgNPs on glucose metabolism in hepatoma cell lines. Lactate release from both HepG2 and Huh7 cells was reduced with 5 nm AgNPs as early as 1 hour after treatment, when cell death did not occur. Treatment with 5 nm AgNPs decreased glucose consumption in HepG2 cells but not in Huh7 cells. Treatment with 5 nm AgNPs reduced nuclear factor erythroid 2-like 2 expression in both cell types without affecting its activation at the early time points after AgNPs’ treatment. Increased reactive oxygen species (ROS) production was detected 1 hour after 5 nm AgNPs’ treatment, and lactate release was restored in the presence of an ROS scavenger. Our results suggest that 5 nm AgNPs affect glucose metabolism by producing ROS. Keywords: metal nanoparticles, carbohydrate metabolism, lactic acid, cytotoxicity

A new nondestructive method to estimate the remaining fatigue life of a fatigue specimen with unknown knowledge of the loading history is presented. It requires only one short-time excitation test. The method utilizes the concept of damage parameter and the temperature rise to reliably predict the remaining number of cycles before fracture. A generalized procedure and numerous experimentally verified examples are presented. It is shown that the method can be applied to both constant and variable stress levels. Extensive laboratory tests reveal that the results of the remaining fatigue life predictions are in very good agreement with measurements. [ABSTRACT FROM AUTHOR]

Resting-state or intrinsic connectivity network functional magnetic resonance imaging provides a new tool for mapping large-scale neural network function and dysfunction. Recently, we showed that behavioural variant frontotemporal dementia and Alzheimer's disease cause atrophy within two major networks, an anterior 'Salience Network' (atrophied in behavioural variant frontotemporal dementia) and a posterior 'Default Mode Network' (atrophied in Alzheimer's disease). These networks exhibit an anti-correlated relationship with each other in the healthy brain. The two diseases also feature divergent symptom-deficit profiles, with behavioural variant frontotemporal dementia undermining social-emotional function and preserving or enhancing visuospatial skills, and Alzheimer's disease showing the inverse pattern. We hypothesized that these disorders would exert opposing connectivity effects within the Salience Network (disrupted in behavioural variant frontotemporal dementia but enhanced in Alzheimer's disease) and the Default Mode Network (disrupted in Alzheimer's disease but enhanced in behavioural variant frontotemporal dementia). With task-free functional magnetic resonance imaging, we tested these ideas in behavioural variant frontotemporal dementia, Alzheimer's disease and healthy age-matched controls (n = 12 per group), using independent component analyses to generate group-level network contrasts. As predicted, behavioural variant frontotemporal dementia attenuated Salience Network connectivity, most notably in frontoinsular, cingulate, striatal, thalamic and brainstem nodes, but enhanced connectivity within the Default Mode Network. Alzheimer's disease, in contrast, reduced Default Mode Network connectivity to posterior hippocampus, medial cingulo-parieto-occipital regions and the dorsal raphe nucleus, but intensified Salience Network connectivity. Specific regions of connectivity disruption within each targeted network predicted intrinsic connectivity enhancement within the reciprocal network. In behavioural variant frontotemporal dementia, clinical severity correlated with loss of right frontoinsular Salience Network connectivity and with biparietal Default Mode Network connectivity enhancement. Based on these results, we explored whether a combined index of Salience Network and Default Mode Network connectivity might discriminate between the three groups. Linear discriminant analysis achieved 92% clinical classification accuracy, including 100% separation of behavioural variant frontotemporal dementia and Alzheimer's disease. Patients whose clinical diagnoses were supported by molecular imaging, genetics, or pathology showed 100% separation using this method, including four diagnostically equivocal 'test' patients not used to train the algorithm. Overall, the findings suggest that behavioural variant frontotemporal dementia and Alzheimer's disease lead to divergent network connectivity patterns, consistent with known reciprocal network interactions and the strength and deficit profiles of the two disorders. Further developed, intrinsic connectivity network signatures may provide simple, inexpensive, and non-invasive biomarkers for dementia differential diagnosis and disease monitoring. [ABSTRACT FROM AUTHOR]

BACKGROUND: Very few clinical trials have reported on the success rate of frequency-doubled double-pulse yttrium aluminum garnet (YAG) laser (FREDDY) technology for removal of difficult bile duct stones. OBJECTIVE: Our purpose was to evaluate the role of FREDDY technology for removing difficult bile duct stones. DESIGN: Nonrandomized, retrospective study. SETTING: Academic medical center. PATIENTS: Fifty-two patients with difficult bile duct stones were treated via the transpapillary route by using a FREDDY system. The inclusion criteria were impacted or large common bile duct stones (>15 mm, mean 23.5 mm, range 15-35 mm, mean number of stones 1.7, range 1-4). Laser lithotripsy was performed with cholangioscopy guidance in 7 patients and fluoroscopic guidance alone in 45 patients. MAIN OUTCOME MEASUREMENTS: The success rate of complete stone removal and the complication rate related to the procedure. RESULTS: Of the 52 patients treated via the transpapillary route, complete stone removal was achieved in 48 patients (92.3%). The complete removal of stones required a mean of 1.4 (range 1-2) endoscopic sessions. The rate of complications related to laser lithotripsy was 23.0% (acute pancreatitis, 3 cases; transient hemobilia, 8 cases; acute cholangitis, 1 case). LIMITATIONS: Nonrandomized, retrospective design. CONCLUSION: Laser lithotripsy by using the FREDDY system seems safe and effective and allows 'blind' fragmentation of bile duct stones under fluoroscopic guidance only. [ABSTRACT FROM AUTHOR]

Background: Adenine nucleotide translocase (ANT) is located in the inner mitochondrial membrane and catalyzes the exchange of mitochondrial ATP for cytosolic ADP. ANT has been known to be a major component of the permeability transition pore complex of mitochondria and contributes to mitochondria-mediated apoptosis. Human ANT has four isoforms (ANT1, ANT2, ANT3, and ANT4), and the expression of the ANT isoforms is variable depending on the tissue and cell type, developmental stage, and proliferation status. Among the isoforms, ANT1 is highly expressed in terminally-differentiated tissues, but expressed in low levels in proliferating cells, such as cancer cells. In particular, over-expression of ANT1 induces apoptosis in cultured tumor cells.Methods: We applied an ANT1 gene transfer approach to induce apoptosis and to evaluate the anti-tumor effect of ANT1 in a nude mouse model.Results: We demonstrated that ANT1 transfection induced apoptosis of MDA-MB-231 cells, inactivated NF-kappaB activity, and increased Bax expression. ANT1-inducing apoptosis was accompanied by the disruption of mitochondrial membrane potential, cytochrome c release and the activation of caspases-9 and -3. Moreover, ANT1 transfection significantly suppressed tumor growth in vivo.Conclusion: Our results suggest that ANT1 transfection may be a useful therapeutic modality for the treatment of cancer. [ABSTRACT FROM AUTHOR]

Background: Pancreatoduodenectomy (PD) is a complex abdominal surgery, and the adoption of robotic PD has been on the rise because of its numerous benefits. This study aimed to investigate the current PD trends, focusing on advancements in robotic surgery., Methods: Between 2015 and 2023, 1231 patients underwent open PD, whereas 630 underwent robot-assisted PD (RAPD). Demographics and surgical outcomes were analyzed according to the time period. Moreover, a propensity score-matched (PSM) analysis was performed to evaluate the clinical outcomes., Results: The proportion of RAPD cases gradually increased from 6.3% in 2015 to 50.9% in 2020, reaching a plateau of >50% thereafter. The proportion of patients receiving neoadjuvant chemotherapy increased during the late period (11.4% vs. 17.6%), with many of these patients undergoing open PD. Additionally, RAPD was performed in patients with a high probability of postoperative pancreatic fistula. However, the two groups demonstrated no significant difference in the occurrence of clinically relevant postoperative pancreatic fistula (10.6% vs. 9.5%, p = .532). Among periampullary cancer cases, RAPD demonstrated comparable survival outcomes to open PD after PSM (5-year survival rate: 61.8% vs. 49.8%, p = .189)., Conclusions: RAPD has become a stable approach, accounting for over 50% of all PD cases in high-volume centers, and it can be safely performed. However, open PD remains important owing to the development of neoadjuvant therapy and the aging population. Therefore, establishing appropriate indications to maximize the benefits of both RAPD and open PD is necessary., (© 2024 Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

Background/aims: : The relationship between genetic polymorphisms and gastric inflammation remains unclear. This study aimed to evaluate the impact of genetic polymorphisms on Helicobacter pylori (HP)-associated gastritis according to sex., Methods: : Two hundred thirty-two male and 404 female subjects with current HP infection were prospectively enrolled. The genotyping of IL-1B-511 C/T, IL-1RN variable number of tandem repeats, IL-6-572 G/C, IL-8-251 A/T, IL-8-781 C/T, IL-10-1082 G/A, IL-10-592 C/A, TNF-A-308 G/A, and transforming growth factor ( TGF )- B-509 C/T, was determined by polymerase chain reaction-restriction fragment length polymorphism. The degree of monocyte or neutrophil infiltration, atrophic gastritis, and intestinal metaplasia was evaluated using the updated Sydney system., Results: : Among the male subjects, moderate/severe atrophic gastritis of the corpus was higher in IL-1B-511 CC carriers than in CT and TT carriers independent of age, alcohol consumption, and HP virulence factors (26.9% vs 10.4%; adjusted hazard ratio [HR], 4.377; 95% confidence interval, 1.387 to 13.814). In females, IL-8-251 AA carriers were independently and significantly associated with moderate/severe atrophic gastritis of the corpus compared with that in AT and TT carriers (21.4% vs 6.0%, adjusted HR=3.799). In males, the IL-8-251 TT genotype was associated with moderate/severe intestinal metaplasia of the corpus compared with the AT and AA genotypes (13.4% vs 5.6%, adjusted HR=3.128), while the IL-10-592 CA and CC genotypes were associated with moderate/severe monocyte infiltration of the antrum compared with AA genotype (83.6% vs 71.8%, adjusted HR=2.227)., Conclusions: : Genetic polymorphisms in cytokines play different roles in HP-associated gastritis according to sex.

Background/aims: Non-alcoholic fatty liver disease (NAFLD), now the most common chronic liver worldwide, has become a significant public health concern. This study aims to analyze the evolving epidemiology of NAFLD in South Korea., Methods: We utilized claim data from the Korean National Health Insurance Service from 2010 to 2022 to analyze NAFLD's incidence, prevalence, and progression., Results: From 2010 to 2022, the incidence and prevalence rates of NAFLD each increased from 1.87% to 4.47% and from 10.49% to 17.13%, respectively. The differences in prevalence rates between urban and rural areas were minimal in 2012 and 2022, yet both areas showed significant increases in the prevalence of NAFLD over the decade. The NAFLD group had a higher prevalence of comorbidities compared to the control group, and the most common comorbid condition was hypertension. Moreover, the ten-year incidence rates of malignancy, heart disease, and stroke in the NAFLD group were 13.42%, 15.72%, and 8.36%, respectively, which were significantly higher than those in the control group. The incidence rates of cirrhosis and hepatocellular carcinoma in NAFLD over 10 years were 2.22% and 0.77%, respectively. The total medical costs of NAFLD patients more than doubled over ten years and were all significantly higher than those of the control group., Conclusion: A significant increase in NAFLD prevalence and its impact on healthcare utilization was observed in South Korea. With NAFLD leading to serious liver diseases and increased healthcare costs, integrated care strategies that include both medical treatment and lifestyle modifications are essential.

Tetraspanin superfamily proteins not only facilitate the trafficking of specific proteins to distinct plasma membrane domains but also influence cell-to-cell and cell-extracellular matrix interactions. Among these proteins, Epithelial Membrane Protein 2 (EMP2), a member of the growth arrest-specific gene 3/peripheral myelin protein 22 (GAS3/PMP22) family, is known to affect key cellular processes. Recent studies have revealed that EMP2 modulates critical signaling pathways and interacts with adhesion molecules and growth factor receptors, underscoring its potential as a biomarker for cancer diagnosis and prognosis. These findings suggest that EMP2 expression patterns could provide valuable insights into tumorigenesis and metastasis. Moreover, EMP2 has emerged as a promising therapeutic target, with approaches aimed at inhibiting or modulating its activity showing potential to disrupt tumor growth and metastasis. This review provides a comprehensive overview of recent advances in understanding the multifaceted roles of EMP2 in cancer, with a focus on its underlying mechanisms and clinical significance.

Background: Coexistent sarcopenia and frailty is more strongly associated with adverse health outcomes than each condition alone. As the importance of coexistent sarcopenia and frailty increases, exploring their underlying mechanisms is warranted. Recently, noncoding ribonucleic acids (RNAs) have been suggested as potential biomarkers of sarcopenia and frailty. This systematic review aimed to summarize noncoding RNAs commonly expressed in sarcopenia and frailty, and to search the predicted target genes and biological pathways of them., Methods: We systematically searched the literatures on PubMed, Embase, Cochrane Library, Web of Science, and Scopus for literature published till November 15, 2023. A total of 7,202 literatures were initially retrieved. After de-duplication, 34 studies (26 sarcopenia-related and 8 frailty-related) were full-text reviewed, and 15 studies (11 sarcopenia-related and 4 frailty-related) were finally included., Results: miR-29a-3p, miR-29b-3p, and miR-328 were identified as commonly expressed in same direction in sarcopenia and frailty. These microRNAs (miRNAs), identified in the literature search using PubMed, modulate transforming growth factor-β signaling via extracellular matrix components and calcineurin/nuclear factor of activated T cells 3 signaling via sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase 2a, which are involved in regulating skeletal muscle fibrosis and the growth of slow-twitch muscle fibers, respectively. miR-155-5p, miR-486, and miR-23a-3p were also commonly expressed in two conditions, although in different or conflicting directions., Conclusion: In this systematic review, we highlight the potential of shared miRNAs that exhibit consistent expression patterns as biomarkers for the early diagnosis and progression assessment of both sarcopenia and frailty., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Host N-glycans play an essential role in the attachment, invasion, and infection processes of viruses, including zoonotic infectious diseases. The similarity of N-glycans in the trachea and lungs of humans and pigs facilitates the cross-species transmission of influenza viruses through respiratory tracts. In this study, the structure and quantity of N-glycans in the plasma of humans, pigs, and chickens were analyzed using liquid chromatography-quadrupole-Orbitrap-tandem mass spectrometry. N-glycans in humans (35), pigs (28), and chickens (53) were identified, including the most abundant, species-common, and species-specific N-glycans. Among the N-glycans (relative quantity >0.5%), the sialic acid derivative of N-acetylneuraminic acid was identified in humans (the sum of the relative quantities of each; 64.3%), pigs (45.5%), and chickens (64.4%), whereas N-glycolylneuraminic acid was only identified in pigs (18.1%). Sialylated N-glycan linkage isomers are the influenza virus receptors (α2-6 in humans, α2-3 and α2-6 in pigs, and α2-3 in chickens). Only α2-6 linkages (human, 58.2%; pig, 44.8%; and chicken, 60.6%) were more abundant than α2-3/α2-6 linkages (human, 4.6%; pig, 0.6%; and chicken, 3.4%) and only α2-3 linkages (human, 1.5%; pig, 0.1%; and chicken, 0.4%). Fucosylation, which can promote viral infection through immune modulation, was more abundant in pigs (76.1%) than in humans (36.4%) and chickens (16.7%). Bisecting N-acetylglucosamine, which can suppress viral infection by inhibiting sialylation, was identified in humans (10.3%) and chickens (16.9%), but not in pigs. These results indicate that plasma N-glycans are similar in humans and chickens. This is the first study to compare plasma N-glycans in humans, pigs, and chickens., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To investigate the long-term efficacy and safety of intravitreal brolucizumab (BRZ) injections in patients with typical neovascular age-related macular degeneration (typical nAMD) and polypoidal choroidal vasculopathy (PCV)., Methods: This multicentre retrospective study included 401 eyes of 398 patients with nAMD who received BRZ injection(s), with a follow-up duration of ≥12 months. Changes in best-corrected visual acuity (BCVA), retinal fluid evaluation and central subfield thickness (CST) on optical coherence tomography were assessed. The efficacy of BRZ was compared between typical nAMD and PCV groups., Results: Analyses were conducted with 280 eyes of 278 patients with typical nAMD and 121 eyes of 120 patients with PCV (mean age, 71.1 ± 8.6 years). 29 eyes (7.2%) were treatment naïve. The mean follow-up period was 15.3 ± 2.8 months; the mean number of BRZ injections within 1 year was 4.5 ± 1.7. BCVA was maintained during the follow-up period, and CST significantly improved from the first injection month and was maintained for 12 months in both the typical nAMD and PCV groups. The dry macula proportion increased from 2.7% at baseline to 56.1% at 1 month and 42.9% at 12 months. Among the 18 eyes that underwent indocyanine green angiography both before and after treatment, 10 (55.6%) showed polyp regression. Overall, the incidence of intraocular inflammation (IOI), retinal vasculitis and occlusive retinal vasculitis was 9.4% (38 eyes), 1.2% (5 eyes) and 0.5% (2 eyes), respectively. IOI occurred from the first to the sixth injections, with an average IOI onset of 28.5 ± 1.4 days. All eyes achieved IOI resolution, although the two eyes with occlusive retinal vasculitis showed a severe visual decline after IOI resolution., Conclusion: Brolucizumab was effective in maintaining BCVA and managing fluid in eyes with nAMD for up to 1 year, exhibiting a high polyp regression rate. However, the not uncommon incidence of IOI and the severe visual decline caused by the rare occlusive retinal vasculitis following BRZ treatment underscore the importance of careful monitoring and timely management., (© 2024 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: Laryngopharyngeal reflux disease (LPRD) is mainly treated with proton pump inhibitors (PPI) such as esomeprazole, which have shortcomings like delayed absorption and increased osteoporosis. Fexuprazan is a novel potent potassium-competitive acid blocker that inhibits gastric acid secretion with rapid onset and long duration of action. To assess the efficacy and safety of fexuprazan compared to esomeprazole in patients with LPRD., Methods: This prospective, randomized, double-blinded, multicenter, active-controlled trial was conducted in nine otolaryngologic clinics. Patients with reflux symptom index (RSI) ≥ 13 and reflux finding score (RFS) ≥ 7 were randomly assigned to the fexuprazan or esomeprazole groups, and received fexuprazan 40-mg or esomeprazole 40-mg once daily for 8 weeks. The outcomes were (1) mean change, change rate, and valid rate in RSI, RFS, and LPR-related questionnaires; and (2) adverse events., Results: A total of 136 patients (fexuprazan n = 68, esomeprazole n = 68) were followed up for ≥ 1 month. Each parameter significantly improved after 4 and 8 weeks in each group, with no significant differences between the two groups. For those with severe symptoms (RSI ≥ 18), the fexuprazan group (n = 32) showed more improvement in the mean change and change rate in the RSI than esomeprazole group (n = 31) after 4 weeks (p = .036 and .045, respectively). This phenomenon was especially observed in hoarseness and troublesome cough., Conclusion: Fexuprazan improved symptoms and signs without no serious adverse events in patients with LPRD. In patients with severe symptoms, fexuprazan resulted in a faster symptom improvement than PPI., Trial Registration: KCT0007251, https://cris.nih.go.kr/cris/search/detailSearch.do?seq=22100 ., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To determine the interobserver variability for complications of pancreatoduodenectomy as defined by the International Study Group for Pancreatic Surgery (ISGPS) and others., Background: Good interobserver variability for the definitions of surgical complications is of major importance in comparing surgical outcomes between and within centers. However, data on interobserver variability for pancreatoduodenectomy-specific complications are lacking., Methods: International cross-sectional multicenter study including 52 raters from 13 high-volume pancreatic centers in 8 countries on 3 continents. Per center, 4 experienced raters scored 30 randomly selected patients after pancreatoduodenectomy. In addition, all raters scored 6 standardized case vignettes. This variability and the "within centers" variability were calculated for 2-fold scoring (no complication/grade A vs grade B/C) and 3-fold scoring (no complication/grade A vs grade B vs grade C) of postoperative pancreatic fistula, postpancreatoduodenectomy hemorrhage, chyle leak, bile leak, and delayed gastric emptying. Interobserver variability is presented with Gwet AC-1 measure for agreement., Results: Overall, 390 patients after pancreatoduodenectomy were included. The overall agreement rate for the standardized cases vignettes for 2-fold scoring was 68% (95% CI: 55%-81%, AC1 score: moderate agreement), and for 3-fold scoring 55% (49%-62%, AC1 score: fair agreement). The mean "within centers" agreement for 2-fold scoring was 84% (80%-87%, AC1 score; substantial agreement)., Conclusions: The interobserver variability for the ISGPS-defined complications of pancreatoduodenectomy was too high even though the "within centers" agreement was acceptable. Since these findings will decrease the quality and validity of clinical studies, ISGPS has started efforts aimed at reducing the interobserver variability., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

A building block containing eight zincs and eight iodo groups (8 Zn) is obtained by the Zn complexation of a salen ligand bearing two additional hydroxy groups. Through the Sonogashira-Hagihara coupling of 8 Zn with 1,3,5,7-tetra(4-ethynylphenyl) adamantane, microporous organic polymers bearing octanuclear zinc clusters (MOP-8 Zn) are prepared, exhibiting a high surface area of 562 m 2  g -1 , microporosity, and a particulate morphology with an average diameter of 249 nm. The MOP-8 Zn exhibits significantly enhanced catalytic performance, compared to molecular counterparts, in the reductive carbon dioxide fixation to formamides, possibly due to the cooperative adsorption and confinement effect of networks on substrates., (© 2024 Wiley‐VCH GmbH.)

Background: The Delphi consensus study was carried out under the auspices of the International and Asia-Pacific Hepato-Pancreato-Biliary Associations (IHPBA-APHPBA) to develop practice guidelines for management of gallbladder cancer (GBC) globally., Method: GBC experts from 17 countries, spanning 6 continents, participated in a hybrid four-round Delphi consensus development process. The methodology involved email, online consultations, and in-person discussions. Sixty eight clinical questions (CQs) covering various domains related to GBC, were administered to the experts. A consensus recommendation was accepted only when endorsed by more than 75% of the participating experts., Results: Out of the sixty experts invited initially to participate in the consensus process 45 (75%) responded to the invitation. The consensus was achieved in 92.6% (63/68) of the CQs. Consensus covers epidemiological aspects of GBC, early, incidental and advanced GBC management, definitions for radical GBC resections, the extent of liver resection, lymph node dissection, and definitions of borderline resectable and locally advanced GBC., Conclusions: This is the first international Delphi consensus on GBC. These recommendations provide uniform terminology and practical clinical guidelines on the current management of GBC. Unresolved contentious issues like borderline resectable/locally advanced GBC need to be addressed by future clinical studies., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The Hugo™ Robotic-Assisted Surgery (RAS) System is an emergent device in the robotic surgery field. This study aims to describe the first general surgery-focused clinical study in Korea using the novel Hugo™ RAS System., Methods: This study was a prospective, single-center, single-arm, confirmatory clinical study conducted at Seoul National University Hospital where 20 cholecystectomies were performed. To evaluate the safety and performance of the Hugo™ RAS System the incidence of conversion to laparoscopy or open surgery, major complication (Clavien-Dindo Grade ≥ III) rate, overall complication rate, readmission rate, and reoperation rate were evaluated. All parameters were assessed within 30 days post-procedure. Any device deficiencies encountered during our initial experience and device data such as setup, console, and operative times were also reported., Results: We confirmed that our trial achieved the primary objective with a success rate of at least 95%. This was accomplished with no conversions to other types of surgery due to serious system malfunction and with only one major complication within 24 h post-procedure. The 20 consecutively enrolled patients had a median age and BMI of 58 years old and 23.9 kg/m 2 , respectively. The major complication rate was 10% (2/20 patients), the overall complication rate was 15% (3/20 patients), the readmission rate was 15% (3/20 patients), and the reoperation rate was 0% (0/20 patients). None of the complications were definitively device related. The median setup, console, and operative times were 16, 17, and 55 min, respectively. The device deficiency rate was 15% (3/20 patients), but all device deficiencies were minor, occurred before the first incision, and did not present a risk to the patient., Conclusion: Based on our initial experience with the Hugo™ RAS System, cholecystectomy is feasible and safe. This trial is registered with ClinicalTrials.gov (NCT05715827)., (© 2024. The Author(s).)

Background: Pancreatoduodenectomy in elderly patients may be associated with increased postoperative mortality, but studies in minimally invasive pancreatoduodenectomy (MIPD) are scarce., Methods: International multicenter retrospective study including patients aged >60 years undergoing MIPD (robot-assisted and laparoscopic) and open pancreatoduodenectomy (OPD), were categorized by age: 60-69, 70-79, and 80+ years. In each category, propensity score matching (PSM) was performed (1:1 ratio) between MIPD and OPD. Primary outcome was 30-day/in-hospital mortality., Results: Among 3820 patients, we matched 1468 patients aged 60-69, 1154 patients aged 70-79, and 196 patients aged 80+ years. In patients aged 60-69 and 70-79 years, MIPD was associated with longer operative time, less blood loss and a longer length of stay. Major morbidity was higher after MIPD with similar 30-day/in-hospital mortality. The R0 resection rate was higher after MIPD. In patients aged 80+ years, besides a longer operative time in MIPD, outcomes were comparable between both groups., Conclusion: This study found no evidence that increasing age worsens mortality of MIPD. MIPD was associated with longer operative time, higher rate of major morbidity, prolonged length of stay versus less blood loss and a higher R0 resection in patients aged 60-69 and 70-79 years. These differences continue in patients aged 80+ years, but became less evident., Competing Interests: Conflict of interest LRJ and MGB received funding from the Intuitive Surgical® for the investigator-initiated LEARNBOT study on safe implementation and training of robot pancreatoduodenectomy in Europe. MGB and MAH received funding from Intuitive Surgical® (LEARNBOT 24445; DIPLOMA-2 24904) and Ethicon EndoSurgery (994492729) to support the ongoing quality registry for minimally invasive pancreatic surgery in Europe and from Intuitive Surgical® for the investigator-initiated DIPLOMA-2 randomized trial comparing minimally invasive and open pancreaticoduodenectomy. The other authors have nothing to disclose relevant to this study or manuscript., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This study investigated the role of Ninjurin1 (Ninj1), encoding a small transmembrane protein, in colitis-associated colon tumorigenesis in relation to sex hormones. Male and female wild-type (WT) and Ninj1 knockout (KO) mice were treated with azoxymethane (AOM) and dextran sulfate sodium (DSS), with or without testosterone propionate (TP). At week 2 (acute colitis stage), Ninj1 KO exhibited an alleviation in the colitis symptoms in both male and female mice. The M2 macrophage population increased and CD8 + T cell population decreased only in the female Ninj1 KO than in the female WT AOM/DSS group. In the female AOM/DSS group, TP treatment exacerbated colon shortening in the Ninj1 KO than in the WT. At week 13 (tumorigenesis stage), male Ninj1 KO mice had fewer tumors, but females showed similar tumors. In the WT AOM/DSS group, females had more M2 macrophages and fewer M1 macrophages than males, but this difference was absent in Ninj1 KO mice. In the Ninj1 KO versus WT group, the expression of pro-inflammatory mediators and Ho-1 and CD8 + T cell populations decreased in both female and male Ninj1 KO mice. In the WT group, M2 macrophage populations were increased by AOM/DSS treatment and decreased by TP treatment. However, neither treatment changed the cell populations in the Ninj1 KO group. These results suggest that Ninj1 is involved in colorectal cancer development in a testosterone-dependent manner, which was different in male and female. This highlights the importance of considering sex disparities in understanding Ninj1's role in cancer pathogenesis., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Purpose: Our study aims to examine perceptions of sarcopenia among doctors and patients for improved management strategies in the future., Methods: We analyzed nine matched items from separate surveys involving 80 community-based primary care doctors, recruited online (55%) and offline (45%), and 80 community-dwelling older patients who visited 6 of the 80 primary care clinics in South Korea., Results: Doctors had a mean age of 58.3 ± 9.1 years, with 17.5% women; patients had a mean age of 74.1 ± 6.1 years, with 61.3% women. Twenty-eight patients (35.4%) had heard of sarcopenia, while only 19 doctors (23.8%) knew the diagnostic criteria of sarcopenia. Patients were more likely to believe they had sarcopenia than doctors assumed their patients had sarcopenia (patients, 35%; doctors, 16.9%; P = 0.0039). Patients desired more exercise and nutritional education than doctors reported they could provide (all P < 0.01). More patients preferred regular text messages for exercise or nutritional education (for exercise: patients 16.5%, doctors 5.8%, P = 0.0428; for nutrition: patients 17.1%, doctors 4.4%, P = 0.0154). Many patients were unaware of available community services for sarcopenia management (patients 48.8%, doctors 10.0%, P < 0.001)., Conclusion: Both patients and doctors in community-based primary care clinics lacked awareness of sarcopenia. Significant discrepancies existed between the exercise and nutritional education patients desired and what doctors could provide. These findings can inform the development of sarcopenia management programs in primary care clinics., (© 2024. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

Introduction: Erlotinib is an epidermal growth factor receptor (EGFR) inhibitor that is approved by the FDA to treat non-small cell lung cancer (NSCLC). Several membrane receptors, including EGFR, interact with amyloid β (Aβ), raising the possibility that erlotinib could have therapeutic effects on Alzheimer's disease (AD). However, the effects of erlotinib on Aβ/tau-related pathology and cognitive function in mouse models of AD and its mechanisms of action have not been examined in detail., Methods: To investigate the effects of erlotinib on cognitive function and AD pathology, 3 to 6-month-old PS19 mice and 3 to 3.5-month-old 5xFAD mice and WT mice were injected with vehicle (5% DMSO + 10% PEG + 20% Tween80 + 65% D.W.) or erlotinib (20 mg/kg, i.p.) daily for 14 or 21 days. Then, behavioral tests, Golgi staining, immunofluorescence staining, western blotting ELISA, and real-time PCR were conducted., Results and Discussion: We found that erlotinib significantly enhanced short-term spatial memory and dendritic spine formation in 6-month-old P301S tau transgenic (PS19) mice. Importantly, erlotinib administration reduced tau phosphorylation at Ser202/Thr205 (AT8) and Thr231 (AT180) and further aggregation of tau into paired helical fragments (PHFs) and neurofibrillary tangles (NFTs) in 3-month-old and/or 6-month-old PS19 mice by suppressing the expression of the tau kinase DYRK1A. Moreover, erlotinib treatment decreased astrogliosis in 6-month-old PS19 mice and reduced proinflammatory responses in primary astrocytes (PACs) from PS19 mice. In 3- to 3.5-month-old 5xFAD mice, erlotinib treatment improved short-term spatial memory and hippocampal dendritic spine number and diminished Aβ plaque deposition and tau hyperphosphorylation. Furthermore, erlotinib-treated 5xFAD mice exhibited significant downregulation of astrocyte activation, and treating PACs from 5xFAD mice with erlotinib markedly reduced cxcl10 (reactive astrocyte marker) and gbp2 (A1 astrocyte marker) mRNA levels and proinflammatory cytokine mRNA and protein levels. Taken together, our results suggest that erlotinib regulates tau/Aβ-induced AD pathology, cognitive function, and Aβ/tau-evoked astrogliosis and therefore could be a potent therapeutic drug for ameliorating AD symptoms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Lee, Hwang, Kim, Jo, Park, Jeong, Jang, Kim, Song and Hoe.)

Purpose: Accurate clinical staging of potentially resectable pancreatic ductal adenocarcinoma (PDAC) is critical for establishing optimal treatment strategies. While the efficacy of fluorine-18-fluorodeoxyglucose ([ 18 F]FDG) positron emission tomography/computed tomography (PET/CT) in clinical staging is unclear, PET/CT detecting fibroblast-activation protein (FAP) expression has recently received considerable attention for detecting various tumors, including PDAC, with high sensitivity. We explored the efficacy of [ 18 F]FDG and [ 18 F]AIF-FAPI-74 PET/CT in the initial evaluation of potentially resectable PDAC., Procedures: Between 2021 and 2022, twenty participants with newly diagnosed potentially resectable PDAC were enrolled. After the initial evaluation with pancreatic CT, [ 18 F]FDG PET/CT, and [ 18 F]AIF-FAPI-74 PET/CT, treatment strategies were determined considering the participant's general status, clinical staging, and resectability. Pathological information from the surgical specimens was only available in 17 participants who underwent curative-intent surgery. Head-to-head comparisons of quantitative radiotracer uptake and diagnostic performance were performed among imaging modalities., Results: [ 18 F]AIF-FAPI-74 PET/CT showed a significantly higher maximum standardized uptake value than [ 18 F]FDG PET/CT did in evaluating primary pancreatic lesions (median [interquartile range]; 12.6 [10.7-13.7] vs. 6.3 [4.8-9.2]; P < 0.001). In contrast, [ 18 F]AIF-FAPI-74 PET/CT showed a significantly lower mean standardized uptake value than [ 18 F]FDG PET/CT did in evaluating background organ (median [interquartile range]) 0.8 [0.7-0.9] vs. 2.6 [2.3-2.7]; P < 0.001). In addition, the sensitivity of [ 18 F]AIF-FAPI-74 PET/CT in detecting metastatic lymph nodes was higher than that of [ 18 F]FDG PET/CT (50.0% vs. 0.0%; P = 0.026)., Conclusion: This study demonstrated that [ 18 F]AIF-FAPI-74 PET/CT could improve the clinical staging of potentially resectable PDAC., (© 2024. The Author(s).)