Morbidity and Mortality After Laparoscopy-Assisted Distal Gastrectomy and Totally Laparoscopic Distal Gastrectomy to Treat Gastric Cancer: An Interim Report: A Phase III Multicenter, Prospective, Randomized Trial (The KLASS-07 Trial).

PURPOSE: We conducted a randomized prospective trial (KLASS-07 trial) to compare laparoscopy-assisted distal gastrectomy (LADG) and totally laparoscopic distal gastrectomy (TLDG) for gastric cancer. In this interim report, we describe short-term results in terms of morbidity and mortality. METHODS AND METHODS: The sample size was 442 participants. At the time of the interim analysis, 314 patients were enrolled and randomized. After excluding patients who did not undergo planned surgeries, we performed a modified per-protocol analysis of 151 and 145 patients in the LADG and TLDG groups, respectively. RESULTS: The baseline characteristics, including comorbidity status, did not differ between the LADG and TLDG groups. Blood loss was somewhat higher in the LADG group, but statistical significance was not attained (76.76±72.63 vs. 62.91±65.68 mL; P=0.087). Neither the required transfusion level nor the operation or reconstruction time differed between the 2 groups. The mini-laparotomy incision in the LADG group was significantly longer than the extended umbilical incision required for specimen removal in the TLDG group (4.79±0.82 vs. 3.89±0.83 cm; P<0.001). There were no between-group differences in the time to solid food intake, hospital stay, pain score, or complications within 30 days postoperatively. No mortality was observed in either group. CONCLUSIONS: Short-term morbidity and mortality rates did not differ between the LADG and TLDG groups. The KLASS-07 trial is currently underway. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03393182.

Establishment of canine mammary gland tumor cell lines harboring PI3K/Akt activation as a therapeutic target.

Canine mammary gland tumors (MGT) have a poor prognosis in intact female canines, posing a clinical challenge. This study aimed to establish novel canine mammary cancer cell lines from primary tumors and characterize their cellular and molecular features to find potential therapeutic drugs. The MGT cell lines demonstrated rapid cell proliferation and colony formation in an anchorage-independent manner. Vimentin and α-SMA levels were significantly elevated in MGT cell lines compared to normal canine kidney (MDCK) cells, while CDH1 expression was either significantly lower or not detected at all, based on quantitative real-time PCR (qRT-PCR) analysis. Functional annotation and enrichment analysis revealed that epithelial-mesenchymal transition (EMT) phenotypes and tumor-associated pathways, particularly the PI3K/Akt signaling pathway, were upregulated in MGT cells. BYL719 (Alpelisib), a PI3K inhibitor, was also examined for cytotoxicity on the MGT cell lines. The results show that BYL719 can significantly inhibit the proliferation of MGT cell lines in vitro. Overall, our findings suggest that the MGT cell lines may be valuable for future studies on the development, progression, metastasis, and management of tumors.

Totally laparoscopic versus laparoscopy-assisted distal gastrectomy: the KLASS-07, a randomized controlled trial.

BACKGROUNDS: Strong evidence is lacking as no confirmatory randomized controlled trials (RCTs) have compared the efficacy of totally laparoscopic distal gastrectomy (TLDG) with laparoscopy-assisted distal gastrectomy (LADG). We performed an RCT to confirm if TLDG is different from LADG. METHODS: The KLASS-07 trial is a multicentre, open-label, parallel-group, phase III, RCT of 442 patients with clinical stage I gastric cancer. Patients were enrolled from 21 cancer care centers in South Korea between January 2018 and September 2020 and randomized to undergo TLDG or LADG using blocked randomization with a 1:1 allocation ratio, stratified by the participating investigators. Patients were treated through R0 resections by TLDG or LADG as the full analysis set of the KLASS-07 trial. The primary endpoint was morbidity within postoperative day 30, and the secondary endpoint was QoL for 1 year. This trial is registered at ClinicalTrials.gov (NCT NCT03393182). RESULTS: 442 patients were randomized (222 to TLDG, 220 to LADG), and 422 patients were included in the pure analysis (213 and 209, respectively). The overall complication rate did not differ between the two groups (TLDG vs. LADG: 12.2% vs. 17.2%). However, TLDG provided less postoperative ileus and pulmonary complications than LADG (0.9% vs. 5.7%, P= 0.006; and 0.5% vs. 4.3%, P= 0.035, respectively). The QoL was better after TLDG than after LADG regarding emotional functioning at 6 months, pain at 3 months, anxiety at 3 and 6 months, and body image at 3 and 6 months (all P< 0.05). However, these QoL differences were resolved at 1 year. CONCLUSIONS: The KLASS-07 trial confirmed that TLDG is not different from LADG in terms of postoperative complication but has advantages to reduce ileus and pulmonary complications. TLDG can be a good option to offer better QoL in terms of pain, body image, emotion, and anxiety at 3-6 months.

Acer tegmentosum extract-mediated silver nanoparticles loaded chitosan/alginic acid scaffolds enhance healing of E. coli-infected wounds.

This work developed Acer tegmentosum extract-mediated silver nanoparticles (AgNPs) loaded chitosan (CS)/alginic acid (AL) scaffolds (CS/AL-AgNPs) to enhance the healing of E. coli-infected wounds. The SEM-EDS and XRD results revealed the successful formation of the CS/AL-AgNPs. FTIR analysis evidenced that the anionic group of AL (-COO-) and cationic amine groups of CS (-NH3+) were ionically crosslinked to form scaffold (CS/AL). The CS/AL-AgNPs exhibited significant antimicrobial activity against both Gram-positive (G+) and Gram-negative (G-) bacterial pathogens, while being non-toxic to red blood cells (RBCs), the hen's egg chorioallantoic membrane (HET-CAM), and a non-cancerous cell line (NIH3T3). Treatment with CS/AL-AgNPs significantly accelerated the healing of E. coli-infected wounds by regulating the collagen deposition and blood parameters as evidenced by in vivo experiments. Overall, these findings suggest that CS/AL-AgNPs are promising for the treatment of infected wounds.

Clinical implication of megestrol acetate in metastatic gastric cancer: a big data analysis from Health Insurance Review and Assessment (HIRA) database.

OBJECTIVE: Megestrol acetate (MA) is used to manage anorexia and cachexia in patients with advanced cancer. This study investigated the prescription patterns of MA in patients with metastatic gastric cancer, as well as evaluated its impact on survival outcomes and the incidence of venous thromboembolism (VTE). METHODS: A Health Insurance Review and Assessment (HIRA) service database was used to investigate differences in baseline characteristics, survival, and the incidence of VTE according to MA prescription patterns (i.e., prescription vs. no prescription) in patients diagnosed with metastatic gastric cancer from July 2014 to December 2015. RESULTS: A total of 1938 patients were included in this study. In total, 65% of the patients were prescribed MA. Older age, treatment in tertiary hospitals, and palliative chemotherapy were statistically significant predictive factors for MA prescription. Continuous prescription of MA was observed in 37% of patients. There was no statistically significant difference in survival between the MA and non-MA prescription groups on multivariate analysis. Among the 1427 patients included in the analysis for VTE incidence, 4.3% and 2.9% were diagnosed with VTE during the follow-up period in the MA and non-MA prescription groups, respectively. However, there was no statistically significant difference in VTE diagnosis between the groups on multivariate analysis. CONCLUSION: MA is commonly prescribed for metastatic gastric cancer, especially in elderly patients and those undergoing palliative chemotherapy, without significantly affecting survival or VTE risk.

Therapeutic potential of AAV-FL-Klotho in obesity: Impact on weight loss and lipid metabolism in mice.

Klotho, an anti-aging protein, has gained attention for its protective effects against various diseases, including metabolic disorders, through recombinant Klotho administration. However, the potential of Klotho as a target for gene therapy requires further exploration, as it remains relatively understudied in the context of metabolic disorders. In this study, we demonstrate that AAV-full length(FL)-Klotho administration induces weight loss in mice and provides protection against high-fat diet (HFD)-induced obesity and hepatic steatosis, concurrently reducing the weights of white adipose tissue and liver. AAV-FL-Klotho administration also enhanced thermogenic gene expression in brown adipose tissue (BAT) and improved the morphology of interscapular BAT. The weight loss effect of AAV-FL-Klotho was found to be, at least in part, mediated by UCP1-dependent thermogenesis in brown adipocytes, potentially influenced by hepatokines secreted from AAV-FL-Klotho-transduced hepatocytes. These findings suggest that AAV-FL-Klotho is an attractive candidate for gene therapy to combat obesity. Nevertheless, unbiased experiments have also revealed disturbances in lipid metabolism due to AAV-FL-Klotho, as evidenced by the emergence of lipomas and increased expression of hepatic lipogenic proteins.

NG ,NG -Dimethylarginine Dimethylaminohydrolase 1 Expression Is Dispensable for Cold- or Diet-Induced Thermogenesis.

The strategy to activate thermogenic adipocytes has therapeutic potential to overcome obesity as they dissipate surplus energy as heat through various mechanisms. NG,NG-dimethylarginine dimethylaminohydrolases (DDAHs) are enzymes involved in the nitric oxide-protein kinase G signaling axis which increases thermogenic gene expression. However, the role of DDAHs in thermogenic adipocytes has not been elucidated. The adipocyte-specific Ddah1 knockout mice are generated by crossing Ddah1fl/fl mice with adiponectin Cre recombinase mice. Adipocyte-specific DDAH1 overexpressing mice are generated using adeno-associated virus-double-floxed inverse open reading frame (AAV-DIO) system. These mice are analyzed under basal, cold exposure, or high-fat diet (HFD) conditions. Primary inguinal white adipose tissue cells from adipocyte-specific Ddah1 knockout mice expressed comparable amounts of Ucp1 mRNA. Adipocyte-specific DDAH1 overexpressing mice do not exhibit enhanced activation of thermogenic adipocytes. In addition, when these mice are exposed to cold environment or fed an HFD, their body temperature/weight and thermogenesis-related gene and protein expressions are unchanged. These findings indicate that DDAH1 does not play a role in either cold- or diet-induced thermogenesis. Therefore, adipocyte targeting DDAH1 gene therapy for the treatment of obesity is unlikely to be effective.

Reappraisal of optimal reconstruction after distal gastrectomy - a study based on the KLASS-07 database.

BACKGROUNDS: This study aimed to compare the incidence of bile reflux, quality of life (QoL), and nutritional status among Billroth II (BII), Billroth II with Braun anastomosis (BII-B), and Roux-en-Y (RY) reconstruction after laparoscopic distal gastrectomy (LDG). MATERIALS AND METHODS: We reviewed the prospective data of 397 patients from a multicentre database who underwent LDG for gastric cancer between 2018 and 2020 at 20 tertiary teaching hospitals in Korea. Postoperative endoscopic findings, QoL surveys using the European Organization for Research and Treatment of Cancer questionnaire (C30 and STO22), and nutritional and surgical outcomes were compared among groups. RESULTS: In endoscopic findings, bile reflux was the lowest in the RY group ( n =67), followed by the BII-B ( n =183) and BII groups ( n =147) at 1 year (3.0 vs. 67.8 vs. 84.4%, all P <0.05). The anti-reflux capability of BII-B was statistically better than that of BII, but not as perfect as that of RY. From the perspective of QoL, BII-B was not inferior to RY, but better than BII reconstruction in causing fewer STO22 reflux symptoms at 6 and 12 months. However, only RY caused fewer C30 nausea symptoms than BII at 6 and 12 months, but not BII-B. Nutritional status and morbidities were similar among the three groups, and the operative time did not differ between the BII-B and RY groups. CONCLUSIONS: BII-B cannot substitute for RY in preventing bile reflux, shortening the operative time, or reducing morbidities. Regarding short-term QoL, BII-B was sufficient to reduce STO22 reflux symptoms but failed to reduce C30 nausea symptoms postoperatively.

Clinical relevance of serum ionized magnesium concentration in dogs with myxomatous mitral valve disease.

BACKGROUND: Hypomagnesemia is associated with a poor prognosis in humans with congestive heart failure (CHF), but studies in veterinary medicine are limited. HYPOTHESIS: Serum ionized magnesium concentration [iMg2+ ] would decrease as CHF progresses compared with the initial diagnostic levels and that lower [iMg2+ ] would be negatively associated with prognosis in dogs with CHF. ANIMALS: A total of 181 client-owned dogs with myxomatous mitral valve disease (MMVD) were included. They were classified into the preclinical stage (NO-CHF, n = 108), stage C (n = 42), and stage D (n = 31) based on the American College of Veterinary Internal Medicine MMVD classification. METHODS: This is a retrospective study from 2 referral centers. The [iMg2+ ] was compared among the NO-CHF, stage C, and stage D groups. Kaplan-Meier curves and the log-rank test were used to compare the incidence of death between groups. Multivariable Cox regression analysis was used to estimate the association of hypomagnesemia with the death. RESULTS: In the stage D group, the [iMg2+ ] was lower than that in the NO-CHF (P < .0001) and stage C groups (P < .003). In the Kaplan-Meier survival analysis, the 1-year cumulative survival rate in hypomagnesemic dogs was 53% compared with 91.5% in normomagnesemic dogs (log-rank test, P < .0001). In the multivariable Cox analysis, lower concentration of [K+ ] and [iMg2+ ], along with higher Evel , were associated with negative prognoses. Specifically, hypomagnesemia was associated with an approximately 4-fold increased risk of death (hazard ratio = 4.015; 95% confidence interval, 1.537-10.488; P = .005). CONCLUSIONS AND CLINICAL IMPORTANCE: Assessing the [iMg2+ ] might serve as a potential marker for estimating the severity and prognosis indirectly in dogs with MMVD. Combining [iMg2+ ] measurement with other diagnostic methods, such as echocardiography, could improve the prognostic evaluation of MMVD in dogs.

Trans-Umbilical Lymphadenectomy Using an Articulating Bipolar Vessel-Sealing Device (TULAB) during Robotic Surgery for Gastric Cancer: Enhancing the Surgeon's Eye for Reduced-Port Robotic Gastrectomy.

BACKGROUND: Docking the scope and instruments through a multi-channel trocar has enabled reduced-port robotic distal gastrectomy (RRDG) for gastric cancer. To facilitate lymphadenectomy over the anatomical hindrances during RRDG, we recently introduced the Vessel Sealer Extend® (VSE) (Intuitive Surgical, Sunnyvale, CA, USA), a bipolar vessel-sealing device (BVSD) with an articulating jaw. METHODS: From May 2020 to August 2023, we performed RRDG to treat T1 gastric cancer. One endoscope arm and three instrument arms of the da Vinci® Xi Surgical System (Intuitive Surgical) were used. During the lymphadenectomy, the endoscope and VSE (Intuitive Surgical) were docked through a multi-channel trocar established on a trans-umbilical incision. Two Cardiere forceps were docked through cannulas established on each flank. A trans-umbilical lymphadenectomy using an articulating BVSD (TULAB) was then performed. RESULTS: A total of 42 patients underwent planned RRDG with the TULAB technique. The number of retrieved lymph nodes did not differ between the patients who underwent RRDG and those who underwent conventional laparoscopic distal gastrectomies (CLDG) (p = 0.362). There was no statistically significant difference in postoperative complications between the RRDG and CLDG group (p = 0.189). The mean time to first semi-fluid diet was shorter in the patients who underwent RRDG than CLDG (p = 0.030), and the incidence of postoperative ileus was lower in the RRDG group than the CLDG group (0% and 9.9%, respectively, p = 0.034). CONCLUSIONS: Despite use of fewer ports, RRDG with TULAB had similar outcomes to CLDG in terms of the incidence of postoperative morbidity and the number of harvested lymph nodes. Furthermore, by reducing the number of incisions, the incidence of the intra-abdominal adhesions can potentially be lowered when RRDG is used.

The Usefulness of Present-on-Admission Data as an Indicator of Healthcare Quality Evaluation Using the Korean National Hospital Discharge in-Depth Injury Survey Data from 2006 to 2019.

Purpose: Comorbidities of a principal diagnosis have varying impacts on disease and require different management depending on the onset timing. This study investigated the usefulness of present-on-admission (POA), specifically focusing on decubitus ulcers, delirium, and hypokalemia, as an indicator of healthcare quality. Patients and Methods: We analyzed patient discharge data for 14 years from 2006 to 2019 using Korean National Hospital Discharge In-Depth Injury Survey (KNHDIS). Results: Out of 3,231,731 discharged patients, 19,871 had secondary diagnosis codes for decubitus ulcers (n=10,390, 52.3%), delirium (n=6103, 30.7%), or hypokalemia (n=3378, 17.0%). Analysis of patients with secondary diagnoses of decubitus ulcers, delirium, or hypokalemia revealed notable differences in demographics, including gender distribution, mean age, admission route, insurance type, surgical intervention rates, mortality rates, and length of stay (LOS). Among patients with one of the top 20 principal diagnoses, those with secondary diagnoses of decubitus ulcers, delirium, or hypokalemia exhibited higher odds of surgery, increased mortality risks, and longer LOS compared to those without these secondary diagnoses. Conclusion: All three of these diseases commonly occur postoperatively or during treatment and thus should be designated as potentially preventable complications that require special attention, and should also be considered as quality-of-care indicators.

Genome-wide association study of mammary gland tumors in Maltese dogs.

Background: A genome-wide association study (GWAS) is a valuable tool for investigating genetic and phenotypic variation in many diseases. Objective: The objective of this study was to identify variations in the genomes of Maltese dogs that are associated with the mammary gland tumor (MGT) phenotype and to assess the association between each biological condition and MGT phenotype in Maltese dogs. Methods: DNA was extracted from 22 tumor samples and 11 whole blood samples from dogs with MGTs. Genome-wide single-nucleotide polymorphism (SNP) genotyping was performed, and the top 20 SNPs associated with various conditions and genetic variations were mapped to their corresponding gene locations. Results: The genotyping process successfully identified 173,662 loci, with an overall genotype completion rate of 99.92%. Through the quality control analysis, 46,912 of these SNPs were excluded. Allelic tests were conducted to generate Manhattan plots, which showed several significant SNPs associated with MGT phenotype in intergenic region. The most prominent SNP, located within a region associated with transcription and linked to the malignancy grade of MGT, was identified on chromosome 5 (p = 0.00001) though there may be lack of statistical significance. Other SNPs were also found in several genes associated with oncogenesis, including TNFSF18, WDR3, ASIC5, STAR, and IL1RAP. Conclusion: To our knowledge, this is the first GWAS to analyze the genetic predisposition to MGT in Maltese dogs. Despite the limited number of cases, these analyzed data could provide the basis for further research on the genetic predisposition to MGTs in Maltese dogs.

AAV-mediated skeletal muscle specific irisin expression does not contribute to weight loss in mice.

Obesity, a chronic disease, significantly increases the risk of various diseases, including diabetes, cardiovascular diseases, and cancers. Exercise is crucial for weight management not only through energy expenditure by muscle activity but also through stimulating the secretion of myokines, which affect various tissues. Irisin, derived from the proteolytic processing of fibronectin type III domain-containing protein 5 (Fndc5), is a well-studied myokine with beneficial effects on metabolism. This study explored the feasibility of adeno-associated virus (AAV)-mediated Fndc5 gene therapy to treat obesity in a mouse model using the AAV-DIO system to express Fndc5 specifically in skeletal muscle, and investigated its anti-obesity effect. Although Fndc5 was specifically expressed in the muscle, no significant impact on body weight under normal chow or high-fat diets was observed, and no change in thermogenic gene expression in inguinal white adipose tissue was detected. Notably, Fndc5 transduction did affect bone metabolism, consistent with previous reports. These findings suggest that AAV-mediated Fndc5 gene therapy may not be an efficient strategy for obesity, contrary to our expectations. Further research is needed to elucidate the complex mechanisms involved in irisin's role in obesity and related disorders.

1-Methoxyerythrabyssin II Induces Autophagy in Leukemia Cells via PI3K/Akt/mTOR Pathways.

Leukemia, despite currently being one of the most lethal cancers worldwide, still lacks a focused treatment. The purpose of the present investigation was to evaluate the pharmacological effect of 1-methoxyerythrabyssin II, a pterocarpan identified in the roots of Lespedeza bicolor, on leukemic cells and to explore its underlying mechanism using a network pharmacology strategy. 1-Methoxyerythrabyssin II showed an antiproliferative effect in a concentration-dependent manner and exhibited a higher potency in human acute leukemia T cells (Jurkat). The G1 phase arrest induced by 1-methoxyerythrabyssin II was confirmed using a cell cycle assay, and the downregulation of CDK2 and cyclin D1 was observed using an immunoblot assay. Moreover, 1-methoxyerythrabyssin II-treated cells exhibited higher expression levels of LC3B, Atg-7, and Beclin 1 in addition to an enhanced fluorescence intensity in monodansylcadaverine staining, indicating autophagy induction by 1-methoxyerythrabyssin II. Furthermore, network pharmacology and molecular docking analyses revealed that the PI3K/Akt/mTOR pathway is a potential target of 1-methoxyerythrabyssin II in leukemic cells. In vitro assays further demonstrated that 1-methoxyerythrabyssin II promoted autophagy and suppressed cell proliferation by inhibiting the PI3K/Akt/mTOR pathway in leukemic cells. This discovery will contribute to the development of novel therapeutics and prophylactics against leukemia.

Case report: Successful medical management of adrenocortical carcinoma with metastasis in a Maltese dog.

Introduction: Adrenocortical carcinoma (ACC) with metastasis has a grave prognosis, and adrenalectomy is associated with a high perioperative mortality rate in dogs. A favorable outcome following trilostane treatment in patients with metastatic ACC confirmed by a decreased size of the adrenal tumor and metastatic lesions has not been reported in dogs. Case description: A 12-year-old neutered male Maltese dog was diagnosed with a right adrenal tumor and a hepatic mass. Adrenal-dependent hyperadrenocorticism (ADH) was diagnosed based on clinical signs and an adrenocorticotropic hormone stimulation test (ACTHST). In addition, tests for plasma metanephrine and normetanephrine ruled out a pheochromocytoma. Based on cytology and computed tomography, unresectable metastatic ACC was confirmed. The dog was managed with trilostane due to the presence of distant metastasis. Medical management improved the clinical signs and post-ACTHST cortisol concentrations. One year after the first presentation, the clinical signs and ACTHST test showed a favorable outcome. In addition, computed tomography revealed a decreased size of the right adrenal tumor and resolution of the hepatic mass. Conclusions: Trilostane could be considered as a treatment option for unresectable metastatic ACC. A decrease in tumor size following treatment with trilostane has not been reported in dogs. This case report is the first to demonstrate a favorable outcome of metastatic ACC following trilostane mono therapy for >1 year.

Short-term outcomes and cost-effectiveness of laparoscopic gastrectomy with articulating instruments for gastric cancer compared with the robotic approach.

To overcome the limitations of laparoscopic surgery, robotic systems have been commonly used in the era of minimally invasive surgery despite their high cost. However, the articulation of instruments can be achieved without a robotic system at lower cost using articulating laparoscopic instruments (ALIs). Between May 2021 and May 2022, perioperative outcomes following laparoscopic gastrectomy using ALIs versus robotic gastrectomy were compared. A total of 88 patients underwent laparoscopic gastrectomy using ALIs, while 96 underwent robotic gastrectomy. Baseline characteristics were similar between the groups except for a higher proportion of patients with a medical history in the ALI group (p = 0.013). Clinicopathologic and perioperative outcomes were not significantly different between the groups. However, the operation time was significantly shorter in the ALI group (p = 0.026). No deaths occurred in either group. In conclusion, laparoscopic gastrectomy using ALIs was associated with comparable perioperative surgical outcomes and a shorter operation time compared to robotic gastrectomy in this prospective cohort study.

Derrone Targeting the TGF Type 1 Receptor Kinase Improves Bleomycin-Mediated Pulmonary Fibrosis through Inhibition of Smad Signaling Pathway.

Transforming growth factor-ß (TGF-ß) has a strong impact on the pathogenesis of pulmonary fibrosis. Therefore, in this study, we investigated whether derrone promotes anti-fibrotic effects on TGF-ß1-stimulated MRC-5 lung fibroblast cells and bleomycin-induced lung fibrosis. Long-term treatment with high concentrations of derrone increased the cytotoxicity of MRC-5 cells; however, substantial cell death was not observed at low concentrations of derrone (below 0.05 µg/mL) during a three-day treatment. In addition, derrone significantly decreased the expressions of TGF-ß1, fibronectin, elastin, and collagen1α1, and these decreases were accompanied by downregulation of α-SMA expression in TGF-ß1-stimulated MRC-5 cells. Severe fibrotic histopathological changes in infiltration, alveolar congestion, and alveolar wall thickness were observed in bleomycin-treated mice; however, derrone supplementation significantly reduced these histological deformations. In addition, intratracheal administration of bleomycin resulted in lung collagen accumulation and high expression of α-SMA and fibrotic genes-including TGF-ß1, fibronectin, elastin, and collagen1α1-in the lungs. However, fibrotic severity in intranasal derrone-administrated mice was significantly less than that of bleomycin-administered mice. Molecular docking predicted that derrone potently fits into the ATP-binding pocket of the TGF-ß receptor type 1 kinase domain with stronger binding scores than ATP. Additionally, derrone inhibited TGF-ß1-induced phosphorylation and nuclear translocations of Smad2/3. Overall, derrone significantly attenuated TGF-ß1-stimulated lung inflammation in vitro and bleomycin-induced lung fibrosis in a murine model, indicating that derrone may be a promising candidate for preventing pulmonary fibrosis.

Exploring objective factors to predict successful outcomes after laparoscopic Nissen fundoplication.

BACKGROUND: Currently, the reported parameters that predict the resolution of symptoms after surgery are largely subjective and unreliable. Considering that fundoplication rebuilds the structural integrity of the lower esophageal sphincter (LES), the authors focused on searching for objective and quantitative predictors for the resolution of symptoms based on the anatomical issues and whether an antireflux barrier can be well established or not. MATERIALS AND METHODS: The authors reviewed the prospectively collected data of 266 patients with gastroesophageal reflux disease (GERD) who had undergone laparoscopic Nissen fundoplication (LNF). All patients were diagnosed with GERD using preoperative esophagogastroduodenoscopy, 24-h ambulatory esophageal pH monitoring, and high-resolution esophageal manometry. The patients received GERD symptom surveys using the validated Korean Antireflux Surgery Group questionnaire twice: preoperatively and 3 months after the surgery. RESULTS: After excluding patients with insufficient follow-up data, 152 patients were included in the analysis. Multivariate logistic regression analyses revealed that a longer length of the LES and lower BMI determined better resolution of typical symptoms after LNF (all P <0.05). Regarding atypical symptoms, higher resting pressure of LES and DeMeester score greater than or equal to 14.7 were associated with better resolution after the surgery (all P <0.05). After LNF, typical symptoms improved in 34 out of 37 patients (91.9%) with a length of LES >greater than .05 cm, BMI less than 23.67 kg/m 2 , and atypical symptoms were resolved in 16 out of 19 patients (84.2%) with resting pressure of LES greater than or equal to 19.65 mm Hg, DeMeester score greater than or equal to 14.7. CONCLUSION: These results show that the preoperative length and resting pressure of LES is important in the objective prediction of symptom improvement after LNF.

Laparoscopic fluorescence imaging technique for visualizing biliary structures using sodium fluorescein: the result of a preclinical study in a porcine model.

Purpose: Near-infrared fluorescence imaging has been recently applied in the field of hepatobiliary surgery. Our objective was to apply blue-light fluorescence cholangiography during laparoscopic surgery. Therefore, we designed a preclinical study to evaluate the feasibility of using blue-light fluorescence for cholangiography in a porcine model. Methods: Five millimeters of sodium fluorescein (SF) solution was administered into the gallbladder of 20 male 3-way crossbred (Landrace × Yorkshire × Duroc) pigs in laparoscopic approach. The biliary tree was observed under blue light (a peak wavelength of 450 nm) emitted from a commercialized light-emitting diode (LED) light source (XLS1 extreme, Chammed). Results: In 18 of 20 porcine models, immediately after SF solution was administered into the gallbladder, it was possible to visualize the biliary tree under blue light emitted from the LED light source. Conclusion: This study provided a preclinical basis for using blue-light fluorescence cholangiography using SF in laparoscopic surgery. The clinical feasibility of blue-light fluorescence imaging techniques for laparoscopic cholecystectomy remained to be demonstrated.

The effect of biological agent on body composition in patients with Crohn's disease.

BACKGROUND: Crohn's disease (CD) is associated with altered body composition, affecting clinical outcomes. We evaluated the impact of biologics on body composition in CD patients. METHODS: This multicenter longitudinal study across four Korean university hospitals conducted from January 2009 to August 2021 retrospectively reviewed data of CD patients with abdominal computed tomography (CT) before and after the biologic treatment. Skeletal muscle area (SMA), visceral fat area (VFA), and subcutaneous fat area (SFA) of the third lumbar vertebra (L3) on CT were measured. Myopenia was defined as L3 skeletal muscle index (SMI) of < 49 and < 31 cm2/m2 for men and women, respectively. RESULTS: Among 112 participants, 79 (70.5%) had myopenia. In the myopenia group, all body composition parameters were significantly increased after the biologic treatment: SMI (37.68 vs. 39.40 cm2/m2; P < 0.001), VFA (26.12 vs. 54.61 cm2; P < 0.001), SFA (44.29 vs. 82.42 cm2; P < 0.001), while no significant differences were observed in the non-myopenia group. In multivariate analysis, penetrating CD (hazard ratio, 5.40; P = 0.020) was the independent prognostic factor for surgery. Operation-free survival rate tended to decrease in the myopenia group (Log-rank test, P = 0.090). CONCLUSIONS: Biological agents can increase all body composition parameters in CD patients with myopenia. These patients are more likely to experience surgery.