A pilot clinical study to evaluate feasibility of using single patient classifier as a prognostic test in stage II-III gastric cancer patients.

Objective: Precision medicine approaches emphasize the importance of reliable prognostic tools for guiding individualized therapy decisions. In this study, we evaluated the clinical feasibility of the single patient classifier (SPC) test, a new clinical-grade prognostic assay, in stage II-III gastric cancer patients. Methods: A prospective multicenter study was conducted, involving 237 patients who underwent gastrectomy between September 2019 and August 2020 across nine hospitals. The SPC test was employed to stratify patients into risk groups, and its feasibility and performance were evaluated. The primary endpoint was the proportion of the cases in which the test results were timely delivered before selecting postoperative treatment. Furthermore, 3-year disease-free survivals of risk groups were analyzed. Results: The SPC test met the primary endpoint criteria. The 99.5% of SPC tests were timely delivered to hospitals before the postoperative treatment started. In a clinical setting, the median time from the specimen transfer to laboratory to the result delivery to hospital was 4 d. Furthermore, 3-year disease-free survivals were significantly different between risk groups classified with SPC tests. Conclusions: This study highlights the SPC test's feasibility in offering crucial information timely delivered for making informed decisions regarding postoperative treatment strategies. It also provides evidence to support the implementation of a future prospective clinical trial aimed at evaluating the clinical utility of the SPC test in guiding personalized treatment decisions for gastric cancer patients.

Laparoscopic Pylorus Preserving Gastrectomy vs Distal Gastrectomy for Early Gastric Cancer; A Multicenter Randomized Controlled Trial (KLASS-04).

OBJECTIVE: To evaluate the long-term outcomes of laparoscopic pylorus preserving gastrectomy (LPPG) with laparoscopic distal gastrectomy (LDG) for early gastric cancer (EGC). SUMMARY BACKGROUND DATA: PPG is considered as a function preserving surgery for EGC. However, there has been no multicenter randomized controlled trial comparing PPG with DG until now. METHODS: A multicenter randomized controlled trial (KLASS-04) with 256 patients with cT1N0M0 gastric cancer located in the mid portion of the stomach was conducted. The primary endpoint was the incidence of dumping syndrome at postoperative 1 year. Secondary endpoints included survival and recurrence, gallstone formation, nutritional parameters, gastroscopic findings, and quality of life (QOL) for 3 years. RESULTS: In the intention-to-treat analyses, there was no difference in the incidence of dumping syndrome at one year postoperatively (13.2% in LPPG vs. 15.8% in LDG, P=0.622). Gallstone formation after surgery was significantly lower in LPPG than in LDG (2.33% vs. 8.66%, P=0.026). Hemoglobin (+0.01 vs. -0.76 gm/dL, P<0.001) and serum protein (-0.15 vs. -0.35 gm/dL, P=0.002) were significantly preserved after LPPG. However, reflux esophagitis (17.8% vs. 6.3%, P=0.005) and grade IV delayed gastric emptying (16.3% vs. 3.9%, P=0.001) were more common in LPPG. Changes in body weight and postoperative QOL were not significantly different between groups. Three-year overall survival and disease-free survival were not different (1 case of recurrence of in each group, P=0.98). CONCLUSIONS: LPPG can be used as an alternative surgical option for cT1N0M0 gastric cancer in the mid portion of the stomach.

Gait pattern modification based on ground contact adaptation using the robot-assisted training platform (RATP).

Robot-assisted rehabilitation and training systems are utilized to improve the functional recovery of individuals with mobility limitations. These systems offer structured rehabilitation through precise human-robot interaction, outperforming traditional physical therapy by delivering advantages such as targeted muscle recovery, optimization of walking patterns, and automated training routines tailored to the user's objectives and musculoskeletal attributes. In our research, we propose the development of a walking simulator that considers user-specific musculoskeletal information to replicate natural walking dynamics, accounting for factors like joint angles, muscular forces, internal user-specific constraints, and external environmental factors. The integration of these factors into robot-assisted training can provide a more realistic rehabilitation environment and serve as a foundation for achieving natural bipedal locomotion. Our research team has developed a robot-assisted training platform (RATP) that generates gait training sets based on user-specific internal and external constraints by incorporating a genetic algorithm (GA). We utilize the Lagrangian multipliers to accommodate requirements from the rehabilitation field to instantly reshape the gait patterns while maintaining their overall characteristics, without an additional gait pattern search process. Depending on the patient's rehabilitation progress, there are times when it is necessary to reorganize the training session by changing training conditions such as terrain conditions, walking speed, and joint range of motion. The proposed method allows gait rehabilitation to be performed while stably satisfying ground contact constraints, even after modifying the training parameters.

Amine-bearing hydrocarbon cross-links: Tailoring helix stability, hydrophilicity, and synthetic adaptability in peptides.

This study comprehensively explored the helix-stabilizing effects of amine-bearing hydrocarbon cross-links (ABXs), revealing their context-dependent nature influenced by various structural parameters. Notably, we identified a 9-atom ABX as a robust helix stabilizer, showcasing versatile synthetic adaptability while preserving peptide water solubility. Future investigations are imperative to fully exploit this system's potential and enrich our chemical toolkit for designing innovative peptide-based biomolecules.

Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1 for Resectable Advanced Gastric Cancer: Updated Overall Survival Outcomes From Phase III PRODIGY.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The phase III PRODIGY study demonstrated that neoadjuvant chemotherapy with docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 chemotherapy (CSC) improved progression-free survival (PFS) compared with surgery followed by adjuvant S-1 (SC) for patients with resectable locally advanced gastric cancer (LAGC) with clinical T2-3N+ or T4Nany disease. The primary end point was PFS. Overall survival (OS) was the secondary end point. We herein report the long-term follow-up outcomes, including OS, from this trial. A total of 238 and 246 patients were randomly assigned to the CSC and SC arms, respectively, and were treated (full analysis set). As of the data cutoff (September 2022), the median follow-up duration of the surviving patients was 99.5 months. Compared with SC, CSC significantly increased the OS (adjusted hazard ratio [HR], 0.72; stratified log-rank P = .027) with an 8-year OS rate of 63.0% and 55.1% for the CSC and SC arms, respectively. CSC also significantly improved the PFS (HR, 0.70; stratified log-rank P = .016). In conclusion, neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, prolonged the OS of Asian patients with LAGC relative to patients treated with surgery and adjuvant S-1. It should be considered one of the standard treatment options for patients with LAGC in Asia.

Feasibility of Regional Lymphadenectomy for Stomach-Preserving Surgery in Early Gastric Cancer Omitting Sentinel Node Navigation: A Post Hoc Analysis of the SENORITA Trial.

BACKGROUND: Sentinel node navigation (SNN) has been known as the effective treatment for stomach-preserving surgery in early gastric cancer; however, SNN presents several technical difficulties in real practice. OBJECTIVE: This study aimed to evaluate the feasibility of regional lymphadenectomy omitting SNN, using the post hoc analysis of a randomized controlled trial. METHODS: Using data from the SENORITA trial that compared laparoscopic standard gastrectomy with lymphadenectomy and laparoscopic SNN, 237 patients who underwent SNN were included in this study. Tumor location was divided into longitudinal and circumferential directions. According to the location of the tumor, the presence or absence of lymph node (LN) metastases between sentinel and non-sentinel basins were analyzed. Proposed regional LN stations were defined as the closest area to the primary tumor. Sensitivities, specificities, positive predictive values, and negative predictive values (NPV) of SNN and regional lymphadenectomy were compared. RESULTS: Metastasis to non-sentinel basins with tumor-free in sentinel basins was observed in one patient (0.4%). The rate of LN metastasis to non-regional LN stations without regional LN metastasis was 2.5% (6/237). The sensitivity and NPV of SNN were found to be significantly higher than those of regional lymphadenectomy (96.8% vs. 80.6% [p = 0.016] and 99.5% vs. 97.2% [p = 0.021], respectively). CONCLUSIONS: This study showed that regional lymphadenectomy for stomach-preserving surgery, omitting SNN, was insufficient; therefore, SNN is required in stomach-preserving surgery.

Adjuvant nivolumab plus chemotherapy versus placebo plus chemotherapy for stage III gastric or gastro-oesophageal junction cancer after gastrectomy with D2 or more extensive lymph-node dissection (ATTRACTION-5): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: In Asia, adjuvant chemotherapy after gastrectomy with D2 or more extensive lymph-node dissection is standard treatment for people with pathological stage III gastric or gastro-oesophageal junction (GEJ) cancer. We aimed to assess the efficacy and safety of adjuvant nivolumab plus chemotherapy versus placebo plus chemotherapy administered in this setting. METHODS: ATTRACTION-5 was a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial conducted at 96 hospitals in Japan, South Korea, Taiwan, and China. Eligible patients were aged between 20 years and 80 years with histologically confirmed pathological stage IIIA-C gastric or GEJ adenocarcinoma after gastrectomy with D2 or more extensive lymph-node dissection, with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 and available tumour tissue for PD-L1 expression analysis. Patients were randomly assigned (1:1) to receive either nivolumab plus chemotherapy or placebo plus chemotherapy via an interactive web-response system with block sizes of four. Investigational treatment, either nivolumab 360 mg or placebo, was administered intravenously for 30 min once every 3 weeks. Adjuvant chemotherapy was administered as either tegafur-gimeracil-oteracil (S-1) at an initial dose of 40 mg/m2 per dose orally twice per day for 28 consecutive days, followed by 14 days off per cycle, or capecitabine plus oxaliplatin consisting of an initial dose of intravenous oxaliplatin 130 mg/m2 for 2 h every 21 days and capecitabine 1000 mg/m2 per dose orally twice per day for 14 consecutive days, followed by 7 days off treatment. The primary endpoint was relapse-free survival by central assessment. The intention-to-treat population, consisting of all randomly assigned patients, was used for analysis of efficacy endpoints. The safety population, defined as patients who received at least one dose of trial drug, was used for analysis of safety endpoints. This trial is registered with ClinicalTrials.gov (NCT03006705) and is closed. FINDINGS: Between Feb 1, 2017, and Aug 15, 2019, 755 patients were randomly assigned to receive either adjuvant nivolumab plus chemotherapy (n=377) or adjuvant placebo plus chemotherapy (n=378). 267 (71%) of 377 patients in the nivolumab group and 263 (70%) of 378 patients in the placebo group were male; 110 (29%) of 377 patients in the nivolumab group and 115 (31%) of 378 patients in the placebo group were female. 745 patients received assigned treatment (371 in the nivolumab plus chemotherapy group; 374 in the placebo plus chemotherapy group), which was the safety population. Median time from first dose to data cutoff was 49·1 months (IQR 43·1-56·7). 3-year relapse-free survival was 68·4% (95% CI 63·0-73·2) in the nivolumab plus chemotherapy group and 65·3% (59·9-70·2) in the placebo plus chemotherapy group; the hazard ratio for relapse-free survival was 0·90 (95·72% CI 0·69-1·18; p=0·44). Treatment-related adverse events occurred in 366 (99%) of 371 patients in the nivolumab plus chemotherapy group and 364 (98%) of 374 patients in the placebo plus chemotherapy group. Discontinuation due to adverse events was more frequent in the nivolumab plus chemotherapy group (34 [9%] of 371 patients) than the placebo plus chemotherapy group (13 [4%] of 374 patients). The most common treatment-related adverse events were decreased appetite, nausea, diarrhoea, neutrophil count decreased, and peripheral sensory neuropathy. INTERPRETATION: The results of this trial do not support the addition of nivolumab to postoperative adjuvant therapy for patients with untreated, locally advanced, resectable gastric or GEJ cancer. FUNDING: Ono Pharmaceutical and Bristol Myers Squibb.

Association between Near Work, Physical Activities and Myopia in Korean Adults During COVID-19 Outbreak.

PURPOSE: This study investigated the relationship between near work hours and myopia in Korean adults. METHODS: We used data from the 2021 Korean National Health and Nutrition Examination Survey. Associations between near work time, physical activity, and myopia were assessed using chi-square tests and multiple logistic regression analyses. RESULTS: The overall prevalence of myopia was 60.2% in adults aged 19-59 years. The prevalence of myopia was 46.2% for individuals who used smart devices for less than one hour per day, while it was 68.0% for those who used smart devices for more than four hours. In the multiple logistic regression analysis, the odds ratio (OR) for myopia was significantly higher among individuals using smart devices for 3 hours (OR = 1.55, 95% CI = 1.08-2.23) or more than 4 hours (OR = 1.75, 95% CI = 1.27-2.42), compared to users with less than 1 hour of usage. Regarding sitting time, the OR for myopia was significantly higher in individuals who sat for more than 12 hours (OR = 1.66, 95% CI = 1.05-2.61) compared to those who sat less than 4 hours. CONCLUSION: This study found that near work and sitting times were positively associated with myopia. Given the high prevalence of myopia and its implications for serious eye diseases, it is essential to implement measures to manage myopia. Considering the increased near work hours resulting from the COVID-19 pandemic, it is necessary to adopt supplementary measures, such as ensuring sufficient rest time for the eyes and adjusting the brightness of lights, to improve eye health.

Deep Learning-Based Automated Imaging Classification of ADPKD.

Introduction: The Mayo imaging classification model (MICM) requires a prestep qualitative assessment to determine whether a patient is in class 1 (typical) or class 2 (atypical), where patients assigned to class 2 are excluded from the MICM application. Methods: We developed a deep learning-based method to automatically classify class 1 and 2 from magnetic resonance (MR) images and provide classification confidence utilizing abdominal T 2 -weighted MR images from 486 subjects, where transfer learning was applied. In addition, the explainable artificial intelligence (XAI) method was illustrated to enhance the explainability of the automated classification results. For performance evaluations, confusion matrices were generated, and receiver operating characteristic curves were drawn to measure the area under the curve. Results: The proposed method showed excellent performance for the classification of class 1 (97.7%) and 2 (100%), where the combined test accuracy was 98.01%. The precision and recall for predicting class 1 were 1.00 and 0.98, respectively, with F 1 -score of 0.99; whereas those for predicting class 2 were 0.87 and 1.00, respectively, with F 1 -score of 0.93. The weighted averages of precision and recall were 0.98 and 0.98, respectively, showing the classification confidence scores whereas the XAI method well-highlighted contributing regions for the classification. Conclusion: The proposed automated method can classify class 1 and 2 cases as accurately as the level of a human expert. This method may be a useful tool to facilitate clinical trials investigating different types of kidney morphology and for clinical management of patients with autosomal dominant polycystic kidney disease (ADPKD).

Quality of Life and Nutritional Outcomes of Stomach-Preserving Surgery for Early Gastric Cancer: A Secondary Analysis of the SENORITA Randomized Clinical Trial.

Importance: The Sentinel Node Oriented Tailored Approach (SENORITA) randomized clinical trial evaluated quality of life (QoL) and nutritional outcomes between the laparoscopic sentinel node navigation surgery (LSNNS) and laparoscopic standard gastrectomy (LSG). However, there has been no report on the QoL and nutritional outcomes of patients who underwent stomach-preserving surgery among the LSNNS group. Objective: To compare long-term QoL and nutritional outcomes between patients who underwent stomach-preserving surgery and those who underwent standard gastrectomy and to identify factors associated with poor QoL outcomes in patients who underwent stomach-preserving surgery. Design, Setting, and Participants: This study is a secondary analysis of the SENORITA trial, a randomized clinical trial comparing LSNNS with LSG. Patients from 7 tertiary or general hospitals across the Republic of Korea were enrolled from March 2013 to December 2016, with follow-up through 5 years. Data were analyzed between August and September 2022. Among trial participants, patients who underwent actual laparoscopic standard gastrectomy in the LSG group and those who underwent stomach-preserving surgery in the LSNNS group were included. Patients who did not complete the baseline or any follow-up questionnaire were excluded. Intervention: Stomach-preserving surgery vs standard gastrectomy. Main Outcomes and Measures: Overall European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 (EORTC QLQ-C30) and stomach module (STO22) scores, body mass index, hemoglobin, protein, and albumin levels. Results: A total of 194 and 257 patients who underwent stomach-preserving surgery and standard gastrectomy, respectively, were included in this study (mean [SD] age, 55.6 [10.6] years; 249 [55.2%] male). The stomach-preserving group had better QoL scores at 3 months postoperatively in terms of physical function (87.2 vs 83.9), dyspnea (5.9 vs 11.2), appetite loss (13.1 vs 19.4), dysphagia (8.0 vs 12.7), eating restriction (10.9 vs 18.2), anxiety (29.0 vs 35.2), taste change (7.4 vs 13.0), and body image (19.5 vs 27.2). At 1 year postoperatively, the stomach-preserving group had significantly higher body mass index (23.9 vs 22.1, calculated as weight in kilograms divided by height in meters squared) and hemoglobin (14.3 vs 13.3 g/dL), albumin (4.3 vs 4.25 g/dL), and protein (7.3 vs 7.1 g/dL) levels compared to the standard group. Multivariable analyses showed that tumor location (greater curvature, lower third) was favorably associated with global health status (ß, 10.5; 95% CI, 3.2 to 17.8), reflux (ß, -8.4; 95% CI, -14.7 to -2.1), and eating restriction (ß, -5.7; 95% CI, -10.3 to -1.0) at 3 months postoperatively in the stomach-preserving group. Segmental resection was associated with risk of diarrhea (ß, 40.6; 95% CI, 3.1 to 78.1) and eating restriction (ß, 15.1; 95% CI, 1.1 to 29.1) at 3 years postoperatively. Conclusions and Relevance: Stomach-preserving surgery after sentinel node evaluation was associated with better long-term QoL and nutritional outcomes than standard gastrectomy. These findings may help facilitate decision-making regarding treatment for patients with early-stage gastric cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT01804998.

Laparoscopy-assisted trans gastric wedge resection: A safe treatment for gastric pyloric liposarcoma: A case report and literature review.

Background: Gastric liposarcoma (GL) is extremely rare and radical surgery has been the conventional treatment, even in small tumors. Laparoscopic wedge resection has been reported worldwide for subepithelial tumors of the stomach. Case presentation: The patient was an asymptomatic 63-year-old man presenting with a subepithelial gastric tumor. The esophagogastroduodenoscopy showed a 3 cm ulcerated soft tumor located in the posterior wall of the antrum just above the pylorus. Two preoperative biopsies were performed with a negative result for malignant neoplasm. Dynamic computerized tomography revealed 35 × 35 mm well-defined pyloric mass with fat density. Despite the difficult location of the tumor, function-preserving surgery was performed. Surgery was initiated by a laparoscopic approach with four trocars. After the dissection of the greater omentum, the greater curvature and the posterior wall of the stomach were exposed. A gastrostomy was performed in the anterior wall of the antrum. Due to the difficulty in identifying the tumor location, a mini-laparotomy was conducted. After assessing the pylorus and section parameters, the tumor was extracted by gastrostomy and resected with a linear stapler. The patient was discharged after five days with no complications. The histological diagnosis was a well-differentiated liposarcoma. Resection margins were clear. The tumor cells tested negative for MDM2. No adjuvant therapy was indicated. The patient is alive without recurrence. Conclusions: Despite its rarity, gastric liposarcoma should be respected for differential diagnosis in submucosal tumors. The main diagnostic method is histological, and surgery is the conventional treatment without yet having a consensus. Minimally invasive wedge resection might be a suitable treatment even if the location is close to the pylorus. Multicenter studies are required to obtain better results in the management of this pathology.

Ziziphus jujuba Miller Ethanol Extract Restores Disrupted Intestinal Barrier Function via Tight Junction Recovery and Reduces Inflammation.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition caused by the disruption of the intestinal barrier. The intestinal barrier is maintained by tight junctions (TJs), which sustain intestinal homeostasis and prevent pathogens from entering the microbiome and mucosal tissues. Ziziphus jujuba Miller (Z. jujuba) is a natural substance that has been used in traditional medicine as a therapy for a variety of diseases. However, in IBD, the efficacy of Z. jujuba is unknown. Therefore, we evaluated ZJB in Caco2 cells and a dextran sodium sulfate (DSS)-induced mouse model to demonstrate its efficacy in IBD. Z. jujuba extracts were prepared using 70% ethanol and were named ZJB. ZJB was found to be non-cytotoxic and to have excellent antioxidant effects. We confirmed its anti-inflammatory properties via the down-regulation of inflammatory factors, including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). To evaluate the effects of ZJB on intestinal barrier function and TJ improvement, the trans-epithelial electrical resistance (TEER) and fluorescein isothiocyanate-dextran 4 kDa (FITC-Dextran 4) permeability were assessed. The TEER value increased by 61.389% and permeability decreased by 27.348% in the 200 µg/mL ZJB group compared with the 50 ng/mL IL-6 group after 24 h. Additionally, ZJB alleviated body weight loss, reduced the disease activity index (DAI) score, and induced colon shortening in 5% DSS-induced mice; inflammatory cytokines, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were down-regulated in the serum. TJ proteins, such as Zonula occludens (ZO)-1 and occludin, were up-regulated by ZJB in an impaired Caco2 mouse model. Additionally, according to the liquid chromatography results, in tandem with mass spectrometry (LC-MS/MS) analysis, seven active ingredients were detected in ZJB. In conclusion, ZJB down-regulated inflammatory factors, protected intestinal barrier function, and increased TJ proteins. It is thus a safe, natural substance with the potential to be used as a therapeutic agent in IBD treatment.

Lysine-homologue substitution: Impact on antimicrobial activity and proteolytic stability of cationic stapled heptapeptides.

Numerous natural antimicrobial peptides (AMPs) exhibit a cationic amphipathic helical conformation, wherein cationic amino acids, such as lysine and arginine, play pivotal roles in antimicrobial activity by aiding initial attraction to negatively charged bacterial membranes. Expanding on our previous work, which introduced a de novo design of amphipathic helices within cationic heptapeptides using an 'all-hydrocarbon peptide stapling' approach, we investigated the impact of lysine-homologue substitution on helix formation, antimicrobial activity, hemolytic activity, and proteolytic stability of these novel AMPs. Our results demonstrate that substituting lysine with ornithine enhances both the antimicrobial activity and proteolytic stability of the stapled heptapeptide AMP series, while maintaining low hemolytic activity. This finding underscores lysine-homologue substitution as a valuable strategy for optimizing the therapeutic potential of diverse cationic AMPs.

The Impact of Pelvic Incidence on Spinopelvic and Hip Alignment and Mobility in Asymptomatic Subjects.

BACKGROUND: The influence of pelvic incidence (PI) on spinopelvic and hip alignment and mobility has not been well investigated. The aim of this study was to evaluate the influence of PI on spinopelvic and hip alignment and mobility, including the pelvic-femoral angle (PFA) and motion (ΔPFA), in functional positions in a cohort of asymptomatic volunteers. METHODS: This was a single-center, prospective, cross-sectional study. We included 136 healthy volunteers (69% female; mean age, 38 ± 11 years; mean body mass index, 22 ± 3 kg/m2) divided into 3 subgroups on the basis of their PI: PI < 45° (low PI), 45° ≤ PI ≤ 60° (medium PI), and PI > 60° (high PI). We made full-body lateral radiographs in free-standing, standing with extension, relaxed-seated, and flexed-seated positions. We measured the sacral slope (SS), lumbar lordosis (LL), and PFA. We calculated lumbar (∆LL), pelvic (∆SS), and hip (∆PFA) mobilities as the change between the standing (i.e., standing with or without extension) and sitting (i.e., relaxed-seated or flexed-seated) positions. RESULTS: There were significant differences between some of the 3 subgroups with respect to the LL, SS, and PFA in each of the 4 positions. There were no significant differences in ΔLL, ΔSS, or ΔPFA between the 3 groups when moving from a standing to a sitting position. PI had an inverse linear correlation with PFAextension (R = -0.48; p < 0.0001), PFAstanding (R = -0.53; p < 0.0001), PFArelaxed-seated (R = -0.37; p < 0.0001), and PFAflexed-seated (R = -0.47; p < 0.0001). However, PI was not correlated with ΔPFAstanding/relaxed-seated (R = -0.062; p = 0.48) or ΔPFAextension/flexed-seated (R = -0.12; p = 0.18). Similarly, PI was not significantly correlated with ΔLL or ΔSS in either pair of positions. CONCLUSIONS: This study confirmed that spinopelvic and hip parameters in functional positions were affected by PI, whereas lumbar, pelvic, and hip mobilities did not depend on PI. These findings suggest that hip surgeons should consider the PI of the patient to determine the patient's specific functional safe zones before and after total hip arthroplasty. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Comparative Short-Term Outcomes of Femoral Neck System (FNS) and Cannulated Screw Fixation in Patients with Femoral Neck Fractures: A Multicenter Study.

Background: Femoral neck fractures need to be treated in their early stages with accurate reduction and stable fixation to reduce complications. The authors compared the early radiologic outcomes of femoral neck fractures treated with the recently introduced Femoral Neck System (FNS, Depuy-Synthes) with conventional cannulated screws (CS) in a multicenter design. Furthermore, the factors associated with early failure after FNS were analyzed. Methods: The FNS group included 40 patients treated between June 2019 and January 2020, and the CS group included 65 patients treated between January 2015 and May 2019. The operation was performed in 3 university hospitals. Patient demographics, fracture classification, postoperative reduction quality, sliding distance of FNS or CS, union and time to union, and complication rates were examined. Logistic regression analysis was performed on candidate factors for early failure of the FNS group. Results: The FNS group had a 90% union rate and a mean time to union of 4.4 months, while the CS group had similar results with an 83.1% union rate and a mean time to union of 5.1 months. In the subgroup analysis of Pauwels type III fractures, the union rates were 75.0% and 58.8% in the FNS and CS groups, respectively, and the time to union was significantly shorter in the FNS group with 4.8 months compared to 6.8 months in the CS group. Early failure rate within 6 months of FNS fixation was observed to be 10%, which included 3 reduction failures and 1 excessive sliding with a broken implant. Risk factors for early failure after FNS were identified as displaced fractures (Garden classification type III or IV), poor reduction quality, longer tip-apex distance, greater sliding distance, and 1-hole implants, of which sliding distance was the only significant risk factor in multivariate analysis. Conclusions: In femoral neck fractures, FNS and CS did not show significant differences for short-term radiologic results. FNS resulted in shorter operative time than cannulated screw fixation and favorable outcomes in Pauwels type III femoral neck fractures. The FNS could be considered a reliable and safe alternative to CS when treating femoral neck fractures.

Real-world Nationwide Outcomes of Minimally Invasive Surgery for Advanced Gastric Cancer Based on Korean Gastric Cancer Association-Led Survey.

PURPOSE: The study aimed to investigate real-world surgical outcomes of minimally invasive surgery (MIS) for advanced gastric cancer using Korean Gastric Cancer Association (KGCA)-led nationwide data. MATERIALS AND METHODS: A nationwide survey of patients who underwent surgical treatment for gastric cancer in 2019 was conducted by the KGCA. A total of 14,076 patients from 68 institutions underwent surgery, and 4,953 patients diagnosed with pathological stages IB-III gastric cancer were included. Among them, 1,689 patients who underwent MIS (MIS group) and 1,689 who underwent the open approach (open group) were matched using propensity score in a 1:1 ratio. Surgical outcomes were compared, and multivariate analysis was performed to identify the independent factors for overall morbidity. RESULTS: The MIS group had a lower proportion of D2 lymphadenectomy, total omentectomy, and combined resection. However, the number of harvested lymph nodes was higher in the MIS group. Better surgical outcomes, including less blood loss and shorter hospital stay, were observed in the MIS group, and the overall morbidity rate was significantly lower in the MIS group (17.5% vs. 21.9%, P=0.001). The mortality rates did not differ significantly between the 2 groups. In the multivariate analysis, the minimally invasive approach was a significant protective factor against overall morbidity (odds ratio, 0.799; P=0.006). CONCLUSIONS: Based on the Korean nationwide data, MIS for stage IB-III gastric cancer had better short-term outcomes than the open approach, including lower rates of wound complications, intra-abdominal abscesses, and cardiac problems.

Streptomyces tagetis sp. nov., a chromomycin producing bacteria isolated from the roots of Tagetes patula.

A novel halotolerant actinobacterium, designated as RG38T, capable of producing black extracellular melanin pigment on SP2 agar, was isolated from the roots of Tagetes patula. Comparative analysis of the 16S rRNA gene sequence revealed the highest similarity to Streptomyces collinus NBRC 12759T (99.3%). Phylogenetic analysis showed that strain RG38T clustered within the genus Streptomyces forming a monophyletic cluster with its close relatives. The average nucleotide identity (ANI), digital DNA-DNA hybridization (dDDH), and amino-acid identity (AAI) values between strain RG38T and related species within the genus Streptomyces were below the standard threshold for prokaryotic species delineation. The DNA G + C content of the strain RG38T was determined to be 73.3%. The genome size measured 7,150,598 bp comprising 17 contigs and encompassed 6,053 protein coding genes. AntiSMASH analysis of the whole genome revealed 35 putative biosynthetic gene clusters (BGCs) responsible for various secondary metabolites. Among these clusters, two gene clusters exhibited 100% similarity to the chromomycin A3, albaflavenone, and anthracimycin, respectively. These compounds were reported to possess significant anticancer and antibacterial activities. LC-MS-based analysis, coupled with further isolation studies, confirmed the production of chromomycins A2 (1), A3 (2), and their derivatives, along with their antibiotic activities. These findings underscore the potential of this novel strain as a novel resource for the discovery of diverse antimicrobial compounds. This study is the first to report an antimicrobial compound producing Streptomyces species isolated from medicinal plant T. patula. Based on a polyphasic study, the strain RG38T isolated from an unexplored habitat with a high potential for new natural products represents a novel species within the genus Streptomyces. Accordingly, we propose the name Streptomyces tagetis sp. nov. for this novel species, with the type strain is RG38T (=KCTC 49624T = TBRC 15113T).

Assessment of Pharmacokinetic Effects of Herbal Medicines on Escitalopram.

Purpose: Herbal medicines are occasionally used in combination with conventional antidepressants to mitigate various depression-associated symptoms. However, there is limited information on herb-antidepressant interactions. In this study, we investigated the pharmacokinetic (PK) effects of four herbal medicines (Gami-soyosan, Banhasasim-tang, Ojeok-san, and Bojungikgi-tang) on escitalopram, a commonly used antidepressant. Patients and Methods: In this open-label, fixed-sequence, three-period, crossover study, 18 participants were enrolled and divided into two groups. Each group received a 10 mg oral dose of escitalopram in period 1. Participants took escitalopram once daily and their assigned herbal medicines thrice a day for 7 d in periods 2 (group 1: Gami-soyosan, group 2: Ojeok-san) and 3 (group 1: Banhasasim-tang; group 2: Bojungikgi-tang). The primary endpoints were Cmax,ss and AUCtau,ss of escitalopram. Cmax,ss and AUCtau,ss in period 1 were obtained using nonparametric superposition from single-dose data. The PK endpoints were classified according to the CYP2C19 phenotype. Results: Of 18 participants, 16 completed the study. Systemic exposure to escitalopram resulted in a minor increase in the presence of each herbal medicine. The geometric mean ratios (GMRs, combination with herbal medicines/escitalopram monotherapy) and their 90% confidence intervals (CIs) for Cmax,ss and AUCtau,ss were as follows: Gamisoyosan- 1.1454 (0.9201, 1.4258) and 1.0749 (0.8084, 1.4291), Banhasasim-tang-1.0470 (0.7779, 1.4092) and 1.0465 (0.7035, 1.5568), Ojeok-san-1.1204 (0.8744, 1.4357) and 1.1267 (0.8466, 1.4996), and Bojungikgi-tang-1.1264 (0.8594, 1.4762) and 1.1400 (0.8515, 1.5261), respectively. Furthermore, no significant differences in the GMRs of Cmax,ss and AUCtau,ss were observed across different CYP2C19 phenotypes in any of the groups. Conclusion: The co-administration of escitalopram with Gami-soyosan, Banhasasim-tang, Ojeok-san, or Bojungikgi-tang did not exert significant PK effects on escitalopram. These findings provide valuable insights into the safe use of herbal medicines along with escitalopram.

Comparative study of retrograde intramedullary nailing versus locking extramedullary plating in complete articular fractures with metaphyseal comminution of the distal femur.

INTRODUCTION: Fractures of the distal femur with metaphyseal comminution and complete intra-articular involvement (AO/OTA classifications 33C2 and 33C3) present challenges for reduction and fixation. However, an optimal fixation method remains unknown. This study aimed to compare the clinical and radiographic outcomes of locking extramedullary plating (LEP) and retrograde intramedullary nailing (RIN) for complete distal femoral intra-articular fractures with metaphyseal comminution. MATERIALS AND METHODS: Between January 2016 and May 2022, 80 patients (45 men and 35 women; average age, 56.7 years) diagnosed with AO/OTA 33C2 and 33C3 were treated with either LEP or RIN and followed up for at least one year. Post-operative evaluations included radiographic assessments of bone union rate, timing, and alignment. Clinically, the knee joint range of motion (ROM), lower extremity functional scale (LEFS), and Kellgren and Lawrence (KL) grade were analyzed. The complications were also compared. RESULTS: 36 underwent LEP and 44 underwent RIN. Bone union was observed in 69.4% and 63.6% of the patients in the LEP and RIN groups, respectively (p = 0.64). The average union time was 6.9 months for the LEP group and 6.6 months for the RIN group (p = 0.51). A tendency toward varus deformity was observed in the RIN group, although the difference was not statistically significant. No significant differences were observed in knee ROM, LEFS, or KL grade. Complications included non-union (33.8%; RIN, 11; LEP, 16), varus deformity (5%; RIN, 4; LEP, 0), infection (1.3%; RIN, 0; LEP, 1), heterotrophic ossification (1.3%; RIN, 0; LEP, 1), and wound dehiscence (2.5%; RIN, 2; LEP, 0). CONCLUSIONS: The surgical fixation methods, RIN and LEP, for complete distal femoral intra-articular fractures with metaphyseal comminution showed similar clinical and radiological outcomes. However, regardless of the type of fixation device used, there was a reduced rate of bone union owing to high energy and a less favorable prognosis.

Protective Effects of Red Ginseng Against Tacrine-Induced Hepatotoxicity: An Integrated Approach with Network Pharmacology and Experimental Validation.

Introduction: Tacrine, an FDA-approved acetylcholinesterase inhibitor, has shown efficacy in treating Alzheimer's disease, but its clinical use is limited by hepatotoxicity. This study investigates the protective effects of red ginseng against tacrine-induced hepatotoxicity, focusing on oxidative stress. Methods: A network depicting the interaction between compounds and targets was constructed for RG. Effect of RG was determined by MTT and FACS analysis with cells stained by rhodamine 123. Proteins were extracted and subjected to immunoblotting for apoptosis-related proteins. Results: The outcomes of the network analysis revealed a significant association, with 20 out of 82 identified primary RG targets aligning with those involved in oxidative liver damage including notable interactions within the AMPK pathway. in vitro experiments showed that RG, particularly at 1000µg/mL, mitigated tacrine-induced apoptosis and mitochondrial damage, while activating the LKB1-mediated AMPK pathway and Hippo-Yap signaling. In mice, RG also protected the liver injury induced by tacrine, as similar protective effects to silymarin, a well-known drug for liver toxicity protection. Discussion: Our study reveals the potential of RG in mitigating tacrine-induced hepatotoxicity, suggesting the administration of natural products like RG to reduce toxicity in Alzheimer's disease treatment.