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.

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.

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.

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.

Airway and Airway Obstruction Site Segmentation Study Using U-Net with Drug-Induced Sleep Endoscopy Images.

Obstructive sleep apnea is characterized by a decrease or cessation of breathing due to repetitive closure of the upper airway during sleep, leading to a decrease in blood oxygen saturation. In this study, employing a U-Net model, we utilized drug-induced sleep endoscopy images to segment the major causes of airway obstruction, including the epiglottis, oropharynx lateral walls, and tongue base. The evaluation metrics included sensitivity, specificity, accuracy, and Dice score, with airway sensitivity at 0.93 (± 0.06), specificity at 0.96 (± 0.01), accuracy at 0.95 (± 0.01), and Dice score at 0.84 (± 0.03), indicating overall high performance. The results indicate the potential for artificial intelligence (AI)-driven automatic interpretation of sleep disorder diagnosis, with implications for standardizing medical procedures and improving healthcare services. The study suggests that advancements in AI technology hold promise for enhancing diagnostic accuracy and treatment efficacy in sleep and respiratory disorders, fostering competitiveness in the medical AI market.

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.

Deep-Transfer-Learning-Based Natural Language Processing of Serial Free-Text Computed Tomography Reports for Predicting Survival of Patients With Pancreatic Cancer.

PURPOSE: To explore the predictive potential of serial computed tomography (CT) radiology reports for pancreatic cancer survival using natural language processing (NLP). METHODS: Deep-transfer-learning-based NLP models were retrospectively trained and tested with serial, free-text CT reports, and survival information of consecutive patients diagnosed with pancreatic cancer in a Korean tertiary hospital was extracted. Randomly selected patients with pancreatic cancer and their serial CT reports from an independent tertiary hospital in the United States were included in the external testing data set. The concordance index (c-index) of predicted survival and actual survival, and area under the receiver operating characteristic curve (AUROC) for predicting 1-year survival were calculated. RESULTS: Between January 2004 and June 2021, 2,677 patients with 12,255 CT reports and 670 patients with 3,058 CT reports were allocated to training and internal testing data sets, respectively. ClinicalBERT (Bidirectional Encoder Representations from Transformers) model trained on the single, first CT reports showed a c-index of 0.653 and AUROC of 0.722 in predicting the overall survival of patients with pancreatic cancer. ClinicalBERT trained on up to 15 consecutive reports from the initial report showed an improved c-index of 0.811 and AUROC of 0.911. On the external testing set with 273 patients with 1,947 CT reports, the AUROC was 0.888, indicating the generalizability of our model. Further analyses showed our model's contextual interpretation beyond specific phrases. CONCLUSION: Deep-transfer-learning-based NLP model of serial CT reports can predict the survival of patients with pancreatic cancer. Clinical decisions can be supported by the developed model, with survival information extracted solely from serial radiology reports.

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.

Flavonoid gossypetin protects alveolar bone and limits inflammation in ligature-induced periodontitis in mice.

BACKGROUND: Bacterial-induced inflammation instigates the destruction of hard and soft tissues surrounding teeth in periodontitis. In severe cases, the increased number and activity of osteoclasts induces the resorption of alveolar bones, ultimately leading to tooth loss. Because of their diverse chemical structures and bioactivities, natural compounds are often suggested to treat a wide variety of diseases, including inflammatory disorders. METHODS: In the present study, we demonstrated an inhibitory effect of gossypetin, a hexahydroxy flavone, on osteoclast differentiation and bone resorption using in vitro culture of osteoclasts from mouse bone marrow macrophage (BMM) precursors and in vivo model of ligature-induced periodontitis in mice. RESULTS: Gossypetin significantly reduced the differentiation of osteoclasts from mouse BMM precursors in the presence of the receptor activator of nuclear factor κB ligand (RANKL). In vitro, gossypetin inhibited critical signaling events downstream of RANKL including the auto-amplification of nuclear factor of activated T-cells, cytoplasmic 1, Ca2+ oscillations, and the generation of reactive oxygen species. In a mouse ligature-induced periodontitis model, the administration of gossypetin significantly reduced osteoclastogenesis and alveolar bone resorption. Furthermore, gossypetin prevented the ligature-induced increase in macrophages and T cells and reduced the production of tumor necrosis factor-α and interleukin-6. CONCLUSION: Taken together, these results show anti-osteoclastogenic and anti-inflammatory effects of gossypetin, suggesting the potential use of this natural compound in periodontitis.