Pharmacokinetic comparison of subcutaneously administered CT-P13 (biosimilar of infliximab) via autoinjector and pre-filled syringe in healthy participants.

CT-P13, a biosimilar of infliximab, is used to treat inflammatory diseases that arise from immune system complications, resulting in excessive and persistent inflammation. The subcutaneous (SC) formulation of CT-P13 overcomes the drawback of prolonged administration associated with the intravenous (IV) infliximab biosimilar, necessitating autoinjector (AI) administration. This randomized, open-label, two-arm, parallel-group, single-dose clinical pharmacology study aimed to evaluate the pharmacokinetics (PK) and safety of CT-P13 SC administration via AI compared with the existing pre-filled syringe (PFS) method. A total of 147 healthy participants were randomized into two groups, of which 139 completed the study. Blood samples were collected from before CT-P13 SC administration to 2016 h after the start of the administration. Serum concentrations were analyzed using the Meso Scale Discovery electrochemiluminescence method. Geometric mean ratios (90% confidence interval) of the AUCinf (areas under the concentration-time curve from zero to infinity) and Cmax (The maximum serum concentration) for CT-P13 SC AI versus CT-P13 SC PFS groups, were 94.15% (85.02%-104.26%), 92.48% (84.66%-101.01%), respectively. CT-P13 SC AI and CT-P13 SC PFS achieved comparable PK because the 90% CI was within the predefined equivalence margin. At the end of the study, immunogenicity results revealed that 70 (97.22%) and 73 (98.65%) participants tested positive for anti-drug antibody (ADA) in the CT-P13 SC AI and CT-P13 SC PFS groups, respectively. They were tested positive for neutralizing antibodies. No other significant safety differences were observed between the treatment groups. In conclusion, both administrations demonstrated PK equivalence and were both safe and well-tolerated.

Sarcomatoid change in combined hepatocellular carcinoma and cholangiocarcinoma as a poor prognostic factor.

Background: Sarcomatoid change is rarely seen in epithelial malignancy that can be observed in diverse organs. Although a sarcomatoid change in combined hepatocellular-cholangiocarcinoma (cHCC-CC) is assumed to be a poor prognostic factor, this issue has not been studied due to its rare incidence. In this study, we aimed to identify the oncological impact of sarcomatoid change in patients with cHCC-CC and verify that sarcomatoid change is a poor prognostic factor for resected cHCC-CC. Methods: Between January 2006 and December 2020, 102 patients who underwent surgical resection for cHCC-CC were retrospectively reviewed. The hazard ratio (HR) according to sarcomatoid change was calculated using other known prognostic factors for cHCC-CC. In addition, the patients were divided into two groups according to the sarcomatoid change, and their survival was compared. Results: The multivariate analysis demonstrated that sarcomatoid change in cHCC-CC is a poor prognostic factor {disease-free survival (DFS), HR =3.84 [95% confidence interval (CI): 1.63-9.10], P=0.002; overall survival (OS), HR =3.94 (95% CI: 1.67-9.31), P=0.002}. In the survival analysis, the sarcomatoid change group displayed a worse prognosis compared to the non-sarcomatoid change group {DFS: 4.0 [interquartile range (IQR): 1.2-6.8] vs. 23.0 (IQR: 9.3-36.7) months, P=0.001; OS: 19.0 (IQR: 7.2-30.8) vs. 85.0 (IQR: 31.8-138.2) months, P=0.004}. Conclusions: Sarcomatoid change is a poor prognostic factor for resected cHCC-CC.

Minimally invasive pancreatoduodenectomy with combined venous vascular resection: A comparative analysis with open approach.

Backgrounds/Aims: This study aimed to compare the minimally invasive pancreatoduodenectomy with venous vascular resection (MI-PDVR) and open pancreatoduodenectomy with venous vascular resection (O-PDVR) for periampullary cancer. Methods: Data of 124 patients who underwent PDVR (45 MI-PDVR, 79 O-PDVR) between January 1, 2016, and December 31, 2023, was retrospectively reviewed. Results: MI-PDVR is significantly better than O-PDVR in terms of perioperative outcomes (median operation time [452.69 minutes vs. 543.91 minutes; p = 0.004], estimated blood loss [410.44 mL vs. 747.59 mL; p < 0.01], intraoperative transfusion rate [2 cases vs. 18 cases; p = 0.01], and hospital stay [18.16 days vs. 23.91 days; p = 0.008]). The complications until the discharge day showed no significant difference between the two groups (Clavien-Dindo < 3, 84.4% vs. 82.3%; Clavien-Dindo ≥ 3, 15.6% vs. 17.7%; p = 0.809). In terms of long-term oncological outcomes, there was no statistical difference in overall survival (OS, 51.55 months [95% CI: 35.95-67.14] vs. median 49.92 months [95% CI: 40.97-58.87]; p = 0.340) and disease-free survival (DFS, median 35.06 months [95% CI: 21.47-48.65] vs. median 38.77 months [95% CI: 29.80-47.75]; p = 0.585), between the two groups. Long-term oncological outcomes for subgroup analysis focusing on pancreatic ductal adenocarcinoma also showed no statistical differences in OS (40.86 months [95% CI: 34.45-47.27] vs. 48.48 months [95% CI: 38.16-58.59]; p = 0.270) and DFS (24.42 months [95% CI: 17.03-31.85] vs. 34.35 months, [95% CI: 25.44-43.27]; p = 0.740). Conclusions: MI-PDVR can provide better perioperative outcomes than O-PDVR, and has similar oncological impact.

Gender-specific alteration of steroid metabolism and its impact on viral replication in a mouse model of hepatitis B virus infection.

Hepatitis B virus (HBV) is a sex-specific pathogen that is more severe in males than in females. Sex disparities in HBV infection have been attributed to hormonal differences between males and females. However, whether HBV infection affects the metabolic signatures of steroid hormones and how these influences viral replication remains unclear. In this study, we investigated whether HBV infection alters steroid metabolism and its effects on HBV replication. Serum samples from male and female mice obtained after the hydrodynamic injection of replication-competent HBV plasmids were subjected to quantitative steroid profiling. Serum steroid levels in mice were analyzed using an in vitro metabolism assay with the mouse liver S9 fraction. The alteration of steroids by HBV infection was observed only in male mice, particularly with significant changes in androgens, whereas no significant hormonal changes were observed in female mice. Among the altered steroids, dehydroepiandrosterone (DHEA) levels increased the most in male mice after HBV infection. An in vitro metabolism assay revealed that androgen levels were significantly reduced in HBV-infected male mice. Furthermore, the genes involved in DHEA biosynthesis were significantly upregulated in HBV-infected male mice. Interestingly, reduced dihydrotestosterone in male mice significantly inhibits viral replication by suppressing HBV promoter activity, suggesting a viral strategy to overcome the antiviral effects of steroid hormones in males. Our data demonstrated that HBV infection can cause sex-specific changes in steroid metabolism.

Robotic single-port plus one-port splenic vessel-conserving spleen-preserving distal pancreatectomy: a case report.

Minimally invasive distal pancreatectomy is a safe and effective surgical approach for the treatment of distal pancreatic tumors. Recently, the da Vinci single-port (SP) system (Intuitive Surgical, Inc.) was introduced to overcome the previously known limitations of this approach. Here, we report our experience with robotic SP plus one-port splenic vessel-conserving spleen-preserving distal pancreatectomy (RSP + 1 SVc-SpDP). A 38-year-old male patient was incidentally found to have a pancreatic neuroendocrine tumor. On May 12, 2023, RSP + 1 SVc-SpDP was performed. The robotic SP was placed at the transumbilical site, and an additional 12-mm port was placed on the left side of the patient's abdomen. The surgical procedure was based on splenic vessel-conserving, spleen-preserving distal pancreatectomy. The operative time was 350 minutes, and the patient was discharged on postoperative day 8 without any complications. The initial experience of RSP + 1 SVc-SpDP using the da Vinci SP system showed the possibility of an alternative operation for distal pancreatectomy.

Artisential®-assisted pancreatoduodenectomy: a comparative analysis with Robot(Da Vinci®)-assisted pancreatoduodenectomy.

BACKGROUND: Robot-assisted pancreaticoduodenectomy (R-PD) helps further improve the safety and efficacy of minimally invasive pancreaticoduodenectomy. However, it faces challenges such as high costs and limitations in availability at different centers, making it difficult for patients to access. In this study, we evaluate the initial experience of Artisential®-assisted PD (A-PD) and compare its perioperative outcomes with R-PD, discussing the clinical applicability of A-PD. METHODS: This study reviewed cases of R-PD and A-PD conducted between 2022 and 2023. A total of 34 patients underwent R-PD, while 26 patients underwent A-PD. Statistical analysis was conducted based on factors related to the patient's surgical procedure and postoperative prognostic indicators. RESULTS: There were no significant differences observed between the two groups in terms of surgical factors. There were also no differences in the occurrence of postoperative complications. However, there was a significant difference in the length of hospital stay, with the Artisential® group having an average of 11.50 ± 5.54 days and the Robot group having 15.06 ± 5.34 days (p = 0.001). CONCLUSIONS: R-PD and A-PD showed no differences in procedures or outcomes. Using a multi-articulated device is beneficial where robot use is challenging.

Respiratory Responses to a Single Oral Dose of Caffeine in Male Sprague-Dawley Rats.

Caffeine is a key component of beverages such as coffee and tea and has effects on the cardiovascular and respiratory systems, prompting a variety of physiological changes. In our previous study, intravenously administered caffeine at high concentrations significantly influenced respiratory rates. However, comparative research on the potential adverse effects of caffeine consumption on the respiratory system is limited. To address this issue, in this study, we focused on evaluating the effects of orally administered caffeine (0, 2, 6, and 20 mg/kg) on the respiratory system of 6-week-old male Sprague-Dawley rats. We measured the respiratory rate, tidal volume, and minute volume following the guidelines set forth by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use, specifically adhering to Harmonized Tripartite Guideline S7A for Safety Pharmacology Studies for Human Pharmaceuticals. Caffeine administration led to a notable increase in both the respiratory rate and the tidal volume. Conversely, a marked reduction in minute volume was recorded between 0.5 and 2 h following caffeine administration in doses exceeding 6 mg/kg.

Nontuberculous mycobacterial pulmonary disease presenting as bronchiolitis pattern on CT without cavity or bronchiectasis.

BACKGROUND: This study aimed to investigate the radiological changes in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) having bronchiolitis patterns on computed tomography (CT). METHODS: We retrospectively reviewed the final diagnosis and radiologic changes of patients suspected of having NTM-PD without cavity or bronchiectasis on CT image, between January 1, 2005 and March 31, 2021. NTM-PD was diagnosed based on the American Thoracic Society and Infectious Diseases Society of America criteria. The initial and final CT findings (bronchiectasis, cellular bronchiolitis, cavity formation, nodules, and consolidation) were compared between patients diagnosed with and without NTM-PD. RESULTS: This study included 96 patients and 515 CT images. The median CT follow-up duration was 1510.5 (interquartile range: 862.2-3005) days. NTM-PD was recognized in 43 patients. The clinical variables were not significantly different between patients with and without NTM-PD, except for underlying chronic airway disease (P < 0.001). Nodule and consolidation were more frequently observed on the initial CT scans of patients with NTM-PD compared with those without (P < 0.05). On the final follow-up CT scan, bronchiectasis (P < 0.001), cavity (P < 0.05), nodule (P < 0.05), and consolidation (P < 0.05) were more frequently observed in patients with NTM-PD. Among the 43 patients with NTM-PD, 30 showed a radiological progression on CT, with bronchiectasis (n = 22) being the most common finding. The incidence of bronchiectasis increased over time. CONCLUSION: The bronchiolitis pattern on CT images of patients with NTM-PD showed frequent radiological progression during the follow-up period.

Prognostic Role of Pre-Treatment Body Composition Parameters in Patients Undergoing First-Line Immunotherapy for Metastatic Renal Cell Carcinoma.

Purpose: We investigated the relationship between body mass index (BMI), radiological body composition, and survival outcomes in patients with metastatic renal cell carcinoma (mRCC) underwent first-line immune checkpoint inhibitor (ICI)-based therapy. Methods: Analyzing data from 102 patients treated between November 2019 and March 2023, pre-treatment computed tomography (CT) scans assessed fat and muscle areas. BMI and body composition indices were examined, including skeletal muscle index, subcutaneous fat index (SFI), visceral fat index, and total fat index. Kaplan-Meier curves and Log rank tests compared progression-free survival (PFS) and overall survival (OS), while multivariable Cox proportional regression analysis was performed to identify the variables significantly associated with survival outcomes. Results: 54 patients (52.9%) experienced disease progression, and 26 (25.5%) died during a median follow-up of 17.4 months. High SFI was significantly associated with improved OS (p = 0.018) but not PFS (p = 0.090). Multivariable analysis confirmed the positive impact of high SFI on OS (adjusted HR: 0.37, p = 0.029) and suggested a trend towards improved PFS (adjusted HR: 0.61, p = 0.088). Notably, in the ipilimumab + nivolumab subgroup, high SFI significantly correlated with both PFS and OS (p = 0.047 and p = 0.012, respectively). Conclusion: High SFI predicts favorable OS in patients with mRCC receiving first-line ICI-based therapy, especially patients treated with ipilimumab + nivolumab displayed a significant association between high SFI and favorable PFS and OS.

Suprasellar teratoma to germinoma recurrence: implications for diagnosis and follow-up.

Mature teratoma is a subtype of intracranial germ cell tumors (GCTs), distinguished from malignant GCTs by its benign nature and excellent prognosis. Typically, no adjuvant therapy is recommended following gross total resection (GTR). We report a case of a prepubertal girl with a suprasellar mature teratoma that recurred as a germinoma 6 months post-GTR. A 7-year-old girl presented with headache and polydipsia. Imaging revealed a suprasellar mass. The patient underwent GTR, and pathological diagnosis confirmed a mature teratoma without other GCT components. Six months later, MRI identified a newly developed suprasellar mass adjacent to the optic chiasm. A second surgery confirmed the mass as a germinoma. The patient subsequently underwent adjuvant chemotherapy combined with proton therapy, resulting in complete remission. The diagnosis of mature teratoma must be approached with caution, and thorough follow-up is imperative, particularly in cases involving female patients, prepubertal age, or non-pineal locations.

Impact of pretreatment body mass index on clinical outcomes in patients with metastatic renal cell carcinoma receiving first-line immune checkpoint inhibitor-based therapy: A systematic review and meta-analysis.

This study aimed to assess the prognostic role of body mass index (BMI) in patients with metastatic renal cell carcinoma (mRCC) treated with first-line immune checkpoint inhibitor (ICI)-based therapy. We searched for relevant studies in the MEDLINE, Embase, and Cochrane Library databases. The initial search yielded 599 records, of which seven articles (2,517 patients) were selected for analysis. Patients with a high BMI had a favorable overall survival (OS) based on hazard ratio (HR) (crude HR 0.69, 95% confidence interval [CI] 0.57-0.83, p<0.0001; adjusted (a)HR 0.75, 95% CI 0.59-0.95, p=0.02), but not relative risk (RR 0.88, 95% CI 0.67-1.16, p=0.37). In the subgroup analysis, patients with a high BMI had better OS in the ICI with tyrosine kinase inhibitor (TKI) subgroup (aHR 0.71, 95% CI 0.55-0.92, p=0.01), while no significant difference was found in the ICI-only subgroup (aHR 1.02, 95% CI 0.56-1.87, p=0.95). Adjusted statistics for progression-free survival (PFS) were assessable in predominantly ICI-only studies and demonstrated a favorable outcome for patients with a low BMI (aHR 1.67, 95% CI 1.14-2.45, p=0.01). In conclusion, the impact of high BMI varies depending on the treatment type, exhibiting a favorable correlation with OS within ICI with TKI subgroup, but indicating an adverse association with PFS in the ICI-only subgroup. Further research is needed to clarify the influence of BMI by stratifying patients into ICI-only and ICI with TKI treatment to provide more insights.

Impact of the Korea Early Childhood Home-visiting Intervention (KECHI) on child health and development and maternal health: a randomised controlled trial protocol.

INTRODUCTION: Randomised controlled trials (RCTs) of early childhood home-visiting interventions led by nurses have been conducted mainly in Western countries, whereas such trials have been limited in non-Western cultures, including Asia. In South Korea, a national nurse home visit programme (Korea Early Childhood Home-visiting Intervention (KECHI)) was developed in 2020 and launched throughout the country. We designed a pragmatic RCT to evaluate the effectiveness of KECHI on child health and development and maternal health. METHODS AND ANALYSIS: Eligible participants will be pregnant women at <37 weeks of gestation with risk factor scores of 2 or over, who are sufficiently fluent in Korean to read and answer the questionnaire written in Korean and live in districts where the KECHI services are available. Eight hundred participants will be recruited from the general community and through the District Public Health Centres. The participants will be randomised 1:1 to KECHI plus usual care or usual care. KECHI encompasses 25-29 home visits, group activities and community service linkage. Participants will complete assessments at baseline (<37 weeks gestation), 6 weeks, 6 months, 12 months, 18 months and 24 months post partum. The six primary outcomes will be (1) home environment (assessed by Infant/Toddler Home Observation for Measurement of the Environment), (2) emergency department visits due to injuries, (3) child development (assessed using Korean Bayley Scales of Infant and Toddler Development-III), (4) breastfeeding duration, (5) maternal self-rated health and (6) community service linkage. ETHICS AND DISSEMINATION: This trial has received full ethical approval from the Institutional Review Board of the Seoul National University Hospital. Written consent will be obtained from the participants. The results will be reported at conferences, disseminated through peer-reviewed publications and used by the Korean government to expand the KECHI services. TRIAL REGISTRATION NUMBER: NCT04749888.

Artificial intelligence algorithm for neoplastic cell percentage estimation and its application to copy number variation in urinary tract cancer.

BACKGROUND: Bladder cancer is characterized by frequent mutations, which provide potential therapeutic targets for most patients. The effectiveness of emerging personalized therapies depends on an accurate molecular diagnosis, for which the accurate estimation of the neoplastic cell percentage (NCP) is a crucial initial step. However, the established method for determining the NCP, manual counting by a pathologist, is time-consuming and not easily executable. METHODS: To address this, artificial intelligence (AI) models were developed to estimate the NCP using nine convolutional neural networks and the scanned images of 39 cases of urinary tract cancer. The performance of the AI models was compared to that of six pathologists for 119 cases in the validation cohort. The ground truth value was obtained through multiplexed immunofluorescence. The AI model was then applied to 41 cases in the application cohort that underwent next-generation sequencing testing, and its impact on the copy number variation (CNV) was analyzed. RESULTS: Each AI model demonstrated high reliability, with intraclass correlation coefficients (ICCs) ranging from 0.82 to 0.88. These values were comparable or better to those of pathologists, whose ICCs ranged from 0.78 to 0.91 in urothelial carcinoma cases, both with and without divergent differentiation/ subtypes. After applying AI-driven NCP, 190 CNV (24.2%) were reclassified with 66 (8.4%) and 78 (9.9%) moved to amplification and loss, respectively, from neutral/minor CNV. The neutral/minor CNV proportion decreased by 6%. CONCLUSIONS: These results suggest that AI models could assist human pathologists in repetitive and cumbersome NCP calculations.

Neuro-protective effects of increased O-GlcNAcylation by glucosamine in an optic tectum traumatic brain injury model of adult zebrafish.

This study investigated the behavioral and molecular changes in the telencephalon following needle stab-induced injury in the optic tectum of adult zebrafish. At 3 days post-injury (dpi), there was noticeable structural damage to brain tissue and reduced neuronal proliferation in the telencephalon that persisted until 30 dpi. Neurobehavioral deficits observed at 3 dpi included decreased exploratory and social activities and impaired learning and memory (L/M) functions; all of these resolved by 7 dpi. The injury led to a reduction in telencephalic phosphorylated cAMP response element-binding protein and O-GlcNAcylation, both of which were restored by 30 dpi. There was an increase in GFAP expression and nuclear translocation of NF-κB p65 at 3 dpi, which were not restored by 30 dpi. The injury caused decreased O-GlcNAc transferase and increased O-GlcNAcase levels at 3 dpi, normalizing by 30 dpi. Glucosamine (GlcN) treatment at 3 dpi significantly restored O-GlcNAcylation levels and L/M function, also reducing GFAP activation. Glucose treatment recovered L/M function by 7 dpi, but inhibition of the hexosamine biosynthetic pathway by 6-diazo-5-oxo-L-norleucine blocked this recovery. These findings suggest that the O-GlcNAc pathway is a potential therapeutic target for addressing L/M impairment following traumatic brain injury in zebrafish.

FR-MIL: Distribution Re-calibration based Multiple Instance Learning with Transformer for Whole Slide Image Classification.

In digital pathology, whole slide images (WSI) are crucial for cancer prognostication and treatment planning. WSI classification is generally addressed using multiple instance learning (MIL), alleviating the challenge of processing billions of pixels and curating rich annotations. Though recent MIL approaches leverage variants of the attention mechanism to learn better representations, they scarcely study the properties of the data distribution itself i.e., different staining and acquisition protocols resulting in intra-patch and inter-slide variations. In this work, we first introduce a distribution re-calibration strategy to shift the feature distribution of a WSI bag (instances) using the statistics of the max-instance (critical) feature. Second, we enforce class (bag) separation via a metric loss assuming that positive bags exhibit larger magnitudes than negatives. We also introduce a generative process leveraging Vector Quantization (VQ) for improved instance discrimination i.e., VQ helps model bag latent factors for improved classification. To model spatial and context information, a position encoding module (PEM) is employed with transformer-based pooling by multi-head self-attention (PMSA). Evaluation of popular WSI benchmark datasets reveals our approach improves over state-of-the-art MIL methods. Further, we validate the general applicability of our method on classic MIL benchmark tasks and for point cloud classification with limited points https://github.com/PhilipChicco/FRMIL.

Single-molecule structural and kinetic studies across sequence space.

At the core of molecular biology lies the intricate interplay between sequence, structure, and function. Single-molecule techniques provide in-depth dynamic insights into structure and function, but laborious assays impede functional screening of large sequence libraries. We introduce high-throughput Single-molecule Parallel Analysis for Rapid eXploration of Sequence space (SPARXS), integrating single-molecule fluorescence with next-generation sequencing. We applied SPARXS to study the sequence-dependent kinetics of the Holliday junction, a critical intermediate in homologous recombination. By examining the dynamics of millions of Holliday junctions, covering thousands of distinct sequences, we demonstrated the ability of SPARXS to uncover sequence patterns, evaluate sequence motifs, and construct thermodynamic models. SPARXS emerges as a versatile tool for untangling the mechanisms that underlie sequence-specific processes at the molecular scale.

Clinical application of whole-genome sequencing of solid tumors for precision oncology.

Genomic alterations in tumors play a pivotal role in determining their clinical trajectory and responsiveness to treatment. Targeted panel sequencing (TPS) has served as a key clinical tool over the past decade, but advancements in sequencing costs and bioinformatics have now made whole-genome sequencing (WGS) a feasible single-assay approach for almost all cancer genomes in clinical settings. This paper reports on the findings of a prospective, single-center study exploring the real-world clinical utility of WGS (tumor and matched normal tissues) and has two primary objectives: (1) assessing actionability for therapeutic options and (2) providing clarity for clinical questions. Of the 120 patients with various solid cancers who were enrolled, 95 (79%) successfully received genomic reports within a median of 11 working days from sampling to reporting. Analysis of these 95 WGS reports revealed that 72% (68/95) yielded clinically relevant insights, with 69% (55/79) pertaining to therapeutic actionability and 81% (13/16) pertaining to clinical clarity. These benefits include the selection of informed therapeutics and/or active clinical trials based on the identification of driver mutations, tumor mutational burden (TMB) and mutational signatures, pathogenic germline variants that warrant genetic counseling, and information helpful for inferring cancer origin. Our findings highlight the potential of WGS as a comprehensive tool in precision oncology and suggests that it should be integrated into routine clinical practice to provide a complete image of the genomic landscape to enable tailored cancer management.

Silibinin Mitigates Vanadium-induced Lung Injury via the TLR4/MAPK/NF-κB Pathway in Mice.

BACKGROUND/AIM: Silibinin, has been investigated for its potential benefits and mechanisms in addressing vanadium pentoxide (V2O5)-induced pulmonary inflammation. This study explored the anti-inflammatory activity of silibinin and elucidate the mechanisms by which it operates in a mouse model of vanadium-induced lung injury. MATERIALS AND METHODS: Eight-week-old male BALB/c mice were exposed to V2O5 to induce lung injury. Mice were pretreated with silibinin at doses of 50 mg/kg and 100 mg/kg. Histological analyses were performed to assess cell viability and infiltration of inflammatory cells. The expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) and activation of the MAPK and NF-[Formula: see text]B signaling pathways, as well as the NLRP3 inflammasome, were evaluated using real-time PCR, western blot analysis, and immunohistochemistry. Whole blood analysis was conducted to measure white blood cell counts. RESULTS: Silibinin treatment significantly improved cell viability, reduced inflammatory cell infiltration, and decreased the expression of pro-inflammatory cytokines in V2O5-induced lung injury. It also notably suppressed the activation of the MAPK and NF-[Formula: see text]B signaling pathways, along with a marked reduction in NLRP3 inflammasome expression levels in lung tissues. Additionally, silibinin-treated groups exhibited a significant decrease in white blood cell counts, including neutrophils, lymphocytes, and eosinophils. CONCLUSION: These findings underscore the potent anti-inflammatory effects of silibinin in mice with V2O5-induced lung inflammation, highlighting its therapeutic potential. The study not only confirms the efficacy of silibinin in mitigating inflammatory responses but also provides a foundational understanding of its role in modulating key inflammatory pathways, paving the way for future therapeutic strategies against pulmonary inflammation induced by environmental pollutants.

Comparative study on the impact of remimazolam and sevoflurane on quality of recovery after transurethral resection of bladder tumor: A randomized controlled noninferiority study.

BACKGROUND: Remimazolam is manifested by rapid action, hemodynamic stability, and fast recovery. Our study aimed to investigate whether the quality of recovery (QoR) after remimazolam anesthesia in patients undergoing transurethral resection of bladder tumor, which is predominantly performed in the elderly population, is not inferior to that after conventional anesthesia using sevoflurane. METHODS: Thirty-four patients were randomly allocated into either of group S (n = 17, receiving sevoflurane anesthesia), or group R (n = 17, receiving remimazolam anesthesia). The QoR was assessed by Korean version of QoR-15 questionnaire, on the day before and after the surgery. Scores acquired for each individual item, QoR-15 scores categorized into 5 dimensions (physical comfort, physical independence, psychological support, emotional state, and pain), and overall global score were subjected to comparative analysis. The primary outcome was postoperative global QoR-15, and a noninferiority delta value of 8.0 was employed. RESULTS: The postoperative global QoR-15 in the group S was 141 (134-146), and in the groups R was 133 (128-142) (P = .152). The mean difference of global QoR-15 (group S-group R) was 1.471 (95% confidence interval of -10.204 to 13.146), and the lower 95% confidence interval margin was lower than the noninferiority margin of -8.0. When comparing the QoR-15 sorted by 5 dimensions, pain scored higher in the group S (20 [18-20]) compared to the group R (15 [15-20], P = .032). CONCLUSION: The postoperative QoR following transurethral resection of bladder tumor was found to be lower in patients anesthetized with remimazolam in comparison to those anesthetized with sevoflurane.

The Destiny of the Subscapularis Tendon after Arthroscopic Supraspinatus Repair.

Background: The purpose of this study was to identify the changes in untreated subscapularis in patients who underwent supraspinatus repair and to evaluate the factors related to the changes in the subscapularis. Methods: A cohort of patients who underwent isolated supraspinatus repair with preservation of the subscapularis was reviewed. Changes in the subscapularis, including any newly formed lesion and aggravation of an existing lesion, were evaluated 12 months postoperatively on magnetic resonance imaging along with an examination to identify causative factors after supraspinatus repair. Clinical scores were compared between patients with and without subscapularis changes. Results: A total of 528 patients were reviewed. Changes in the subscapularis, including newly formed lesions and aggravation of an existing lesion, were shown in 90 patients (17.0%). Upon regression analysis, changes in the subscapularis were associated with the initial existence of a subscapularis lesion (grade I: p = 0.042, grade II: p = 0.025), an accompanying biceps lesion (p = 0.038), and a retear of the repaired supraspinatus (p = 0.024). No significant differences were shown in clinical scores between patients with and without subscapularis changes after supraspinatus repair. Conclusions: Untreated asymptomatic subscapularis may undergo morphological changes even after repair of the torn supraspinatus. Preoperative subscapularis lesions, biceps long head pathology, and retears of the repaired supraspinatus were associated with subscapularis pathology in patients who underwent supraspinatus repair.