Purpose: Neoadjuvant treatment (NAT) is now the standard for borderline resectable pancreatic cancer (RPC) and is being considered for RPC. Early recurrence after curative surgery in RPC is often seen as a treatment failure, prompting considerations for NAT. Our goal was to develop an artificial intelligence (AI)-based predictive model utilizing preoperatively available factors to forecast early recurrences of resected RPC. Methods: This study included 469 patients who underwent surgery for RPC between 2011 and 2019. Clinicopathologic and oncologic data were retrospectively reviewed. Preoperative variables, including laboratory data and imaging findings, were collected. Early recurrence was defined as recurrence occurring within a year after surgery. Deep neural networks were then used to select variables by assessing their importance. A new model predicting early recurrence of RPC was subsequently developed. Results: Of the patients evaluated, 199 (42.4%) experienced early recurrence. The predictive model included 14 preoperative variables: CA 19-9, preoperative pancreatitis, serum albumin, platelet count, lymphocyte count, the American Society of Anesthesiologists physical status classification, tumor size, monocyte count, age, body mass index, CRP, hemoglobin, WBC count, and CEA. The area under the curve for the model was 0.786 in the training set and 0.734 in the test set. Conclusion We developed an AI-based model to predict the early recurrence of RPC using preoperative parameters. By identifying patients at risk of early recurrence, optimal individualized treatments such as NAT can be considered. Future prospective studies are crucial to establish clear indications for NAT in RPC.

Purpose: Limited treatment options exist for patients with metastatic castration-resistant prostate cancer (mCRPC) after the failure of taxane-based chemotherapy and novel hormonal therapy. Here, we report the safety and efficacy of ifosfamide and mesna in patients with mCRPC after the failure of taxane-based chemotherapy and novel hormonal therapy (NCT06236789). Materials and Methods: Patients with histologically confirmed prostate cancer who had failed taxane-based chemotherapy and novel hormonal therapy received ifosfamide 2,500 mg/m2 and mesna 1,500 mg/m2 on days 1–3, repeated every 21 days. Safety, objective response rate, disease control rate, reduction in serum prostate-specific antigen (PSA) concentration by >50% (PSA50) or >90% (PSA90), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed. Results: A total of 47 patients with mCRPC were included in the study. The median number of lines of treatment was 5 (range, 3 to 7). All patients were previously administered docetaxel and novel hormonal therapies including abiraterone (51.1%) and/or enzalutamide (61.7%). Thirty-eight patients (80.9%) were administered cabazitaxel. The objective response and disease control rates were 21.3% and 80.9%, respectively. PSA50 and PSA90 were achieved in 31.9% and 10.6%, respectively. During a median follow-up duration of 54.3 months, rPFS and OS were 5.0 and 9.0 months, respectively. All the patients experienced treatment-related adverse events of any grades; however, no new safety signs were detected. Genomic biomarker analysis revealed that alterations in the TP53 pathway were associated with inferior rPFS and OS. Conclusion Ifosfamide and mesna showed appreciable efficacy and manageable safety profiles in heavily treated patients with mCRPC.

Spinal melanocytoma (SMC) is a rare, slow-growing tumor arising from melanocytes in the spinal cord. We report a patient with a cervical intra- and extradural spinal tumor causing progressive weakness and numbness. On magnetic resonance imaging (MRI), the lesion showed intense homogeneous enhancement, similar to that seen in common neurogenic spinal tumors. After complete resection, pathological examination confirmed melanocytoma. A review of previously reported cases identified 26 reports of this tumor in the cervical spine, most of which were treated with complete surgical resection. Gross total resection is the preferred treatment, although radiation therapy may be considered when residual tumor remains. We report a 25-year-old male patient who presented with progressive weakness and numbness in both the upper and lower extremities for 3 months. MRI showed homogeneous enhancement. The mass compressed the spinal cord at C6–7 and extended through the neural foramen. Based on the MRI findings, spinal schwannoma was suspected preoperatively. Surgical resection was performed with laminectomy, durotomy, and right facetectomy. A dark-colored mass with well-demarcated margins was exposed and removed. Postoperative MRI confirmed complete removal of the mass. The patient recovered well, and his preoperative myelopathic symptoms gradually improved. SMC is a rare benign tumor that may be mistaken for schwannoma. The treatment of choice is gross total resection.

Purpose: This study evaluated the clinical outcomes and prognostic factors in patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) treated with upfront FOLFIRINOX followed by local-regional therapy (LRT), surgical resection (SR), and radiotherapy (RT). We aimed to identify specific patient subgroups for which RT may serve as a reasonable alternative to SR for local tumor control. Methods: We retrospectively analyzed 116 patients (SR group, n= 70; RT group, n= 46) at a single center between 2015 and 2020. Survival outcomes were compared based on LRT modalities, focusing on identifying subgroups in which RT provided an efficacy comparable to that of SR. Results: Among 116 patients, the SR group achieved a significantly higher 5-year overall survival (OS) than the RT group (27.1% vs. 8.7%, P< 0.0001), despite similar progression-free survival (P= 0.23). Significant prognostic factors for OS included carbohydrate antigen 19-9 (CA19-9) response in BRPC (P= 0.02) and radiologic partial response in LAPC (P= 0.05). Subgroup analysis revealed that, while SR provided a survival advantage in CA19-9 responders, no significant difference in OS was observed between SR and RT in CA19-9 non-responders (P= 0.37). Conclusion Although surgery remains the gold standard, RT may be considered a justifiable local alternative for CA19-9 non-responders and surgically ineligible patients with LAPC, yielding comparable outcomes in these specific, biologically unfavorable subgroups.

This study investigated the molecular mechanism of phenotypic switching of vascular smooth muscle cells (VSMCs), which play a crucial role in vascular remodeling using 9H-Carbazol-3-yl 4-aminobenzoate (CAB). CAB significantly attenuated platelet-derived growth factor (PDGF)-induced VSMC proliferation and migration. CAB suppressed PDGF-induced STAT3 activation by directly binding to the SH2 domain of STAT3. Downregulation of STAT3 phosphorylation by CAB attenuated CIAPIN1/JAK2/STAT3 axis through a decrease in CIAPIN1 transcription. Furthermore, abrogated CIAPIN1 decreased KLF4-mediated VSMC dedifferentiation and increased CDKN1B-induced cell cycle arrest and MMP9 suppression. CAB inhibited intimal hyperplasia in injury-induced neointima animal models by inhibition of the CIAPIN1/JAK2/STAT3 axis. However, CIAPIN1 overexpression attenuated CAB-mediated suppression of VSMC proliferation, migration, phenotypic switching, and intimal hyperplasia. Our study clarified the molecular mechanism underlying STAT3 inhibition of VSMC phenotypic switching and vascular remodeling and identified novel active CAB. These findings demonstrated that STAT3 can be a major regulator to control CIAPIN1/JAK2/STAT3 axis that may be a therapeutic target for treating vascular proliferative diseases.

Background: Patients with septic shock frequently require tracheal intubation in the emergency department (ED). However, the criteria for tracheal intubation are subjective, based on physician experience, or require serial evaluations over relatively long intervals to make accurate predictions, which might not be feasible in the ED. We used supervised learning approaches and features routinely available during the initial stages of evaluation and resuscitation to stratify the risks of tracheal intubation within a 24-hour time window. Methods: We retrospectively analyzed the data of patients diagnosed with septic shock based on the SEPSIS-3 criteria across 21 university hospital EDs in the Republic of Korea. A principal component analysis revealed a complex, non-linear decision boundary with respect to the application of tracheal intubation within a 24-hour time window. Stratified five-fold cross validation and a grid search were used with extreme gradient boost. Shapley values were calculated to explain feature importance and preferences. Results: In total, data for 4,762 patients were analyzed; within that population, 1,486 (31%) were intubated within a 24-hour window, and 3,276 (69%) were not. The area under the receiver operating characteristic curve and F1 scores for intubation within a 24-hour window were 0.829 (95% CI, 0.801–0.878) and 0.654 (95% CI, 0.627–0.681), respectively. The Shapley values identified lactate level after initial fluids, suspected lung infection, initial pH, Sequential Organ Failure Assessment score at enrollment, and respiratory rate at enrollment as important features for prediction. Conclusions An extreme gradient boosting machine can moderately discriminate whether intubation is warranted within 24 hours of the recognition of septic shock in the ED.

RESULTS: Resveratrol significantly reduced cardiac hypertrophy and remodeling in aging hearts. In addition, resveratrol significantly ameliorated aging-induced mitochondrial dysfunction (e.g., decreased oxygen respiration and increased hydrogen peroxide emission) and mitochondria-dependent apoptotic signaling (the Bax/Bcl-2 ratio, mitochondrial permeability transition pore opening sensitivity, and cleaved caspase-3 protein levels).Resveratrol also significantly attenuated aging-induced apoptosis (determined via cleaved caspase-3 staining and TUNEL-positive myonuclei) in cardiac muscles. CONCLUSION This study demonstrates that resveratrol treatment has a beneficial effect on aging-induced cardiac remodeling by ameliorating mitochondrial dysfunction and inhibiting mitochondria-mediated apoptosis in the heart.

Background: Aerobic exercise training and drug therapy are well-established interventions for the prevention and treatment of hypertension and dyslipidemia. We investigated the synergistic effects of aerobic exercise and olmesartan/rosuvastatin on epicardial fat thickness (EFT) and endothelial function in patients with hypertension and dyslipidemia. Methods: A sample of 75 participants with hypertension and dyslipidemia was evaluated for multifactorial cardiovascular risk at baseline and at 6 months of intervention according to anthropometric and hemodynamic components, lipid profile, glycemia, brachial artery flow-mediated dilation (FMD), and EFT. After 3 months of drug therapy only, participants were allocated to one of three conditions: treadmill (n=22), exergame (n=29), or control (n=24). Results: After 12 weeks of drug therapy only, systolic and diastolic blood pressure (3% and 2%, both p<0.05), total cholesterol (6.3%, p<0.01), low-density lipoprotein cholesterol (4.9%, p<0.05), triglycerides (11.1%, p<0.05), fasting blood glucose (10.2%, p<0.01), and glycosylated hemoglobin (3%, p<0.01) were significantly reduced. After 12 weeks of combined aerobic exercise and drug therapy, both the treadmill and exergame groups showed a significant improvement in FMD (both p<0.001) and reduction in EFT (both p<0.001). Systolic and diastolic blood pressures decreased in the treadmill group only (1.9% and 2.7%, respectively, p<0.05). Conclusions Incorporating aerobic exercise into drug therapy regimens can yield synergistic effects, particularly in improving endothelial function and reducing EFT, providing a comprehensive approach to managing cardiovascular risk in patients with hypertension and dyslipidemia.

RESULTS: Resveratrol significantly reduced cardiac hypertrophy and remodeling in aging hearts. In addition, resveratrol significantly ameliorated aging-induced mitochondrial dysfunction (e.g., decreased oxygen respiration and increased hydrogen peroxide emission) and mitochondria-dependent apoptotic signaling (the Bax/Bcl-2 ratio, mitochondrial permeability transition pore opening sensitivity, and cleaved caspase-3 protein levels).Resveratrol also significantly attenuated aging-induced apoptosis (determined via cleaved caspase-3 staining and TUNEL-positive myonuclei) in cardiac muscles. CONCLUSION This study demonstrates that resveratrol treatment has a beneficial effect on aging-induced cardiac remodeling by ameliorating mitochondrial dysfunction and inhibiting mitochondria-mediated apoptosis in the heart.