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.

Background: Psoriasis is a persistent systemic inflammatory condition mediated by the interleukin (IL)-23/IL-17 signaling pathway. Existing murine models, including imiquimod (IMQ)-applied wild-type (WT) mice, may not reflect chronicity and systemic comorbidities of psoriasis, particularly gut-related manifestations linked to the gut–skin axis. Objective: To establish a murine model that more accurately reflects chronic psoriasis, its systemic comorbidities, and associated gut environment alterations. Methods: C57BL/6 IL-10-deficient (IL-10 knockout [KO]) and WT mice received topical IMQ or vehicle for 6 weeks. Subsequently, tissue samples from skin, colon, joints, kidneys, liver, abdominal aortas, lymph nodes, and spleens, as well as fecal and blood samples, were collected for histopathologic, immunologic, gut environment analysis. Results: IMQ-treated IL-10 KO mice developed prolonged psoriatic inflammatory responses with increased epidermal thickness and higher infiltration of CD45+, myeloperoxidase+, and IL-17+ cells. They also exhibited early-onset, severe colitis with marked weight loss, shortened colon length, and elevated colitis severity scores. While IMQ induced systemic inflammation in multiple organs, IL-10 KO mice did not show more severe joint, liver, or kidney involvement than WT mice. Elevated serum tumor necrosis factor alpha and plasminogen activator inhibitor-1 levels, increased heart/body weight ratio, enhanced gut permeability, and distinct gut microbiota profiles were observed in IL-10 KO mice. Conclusion The 6-week IMQ-applied IL-10 KO model may better reflect chronic and severe psoriasis with gut-related comorbidities, offering a valuable platform to investigate the gut–skin axis.

Symmetrical peripheral gangrene is a severe condition marked by symmetric acral necrosis without obstruction of the major blood vessels. This case report examines the critical decisions involved in choosing between early and delayed amputation, as well as determining the extent of the necessary amputation. We present three cases: one involving antiphospholipid syndrome, another with disseminated intravascular coagulation, and a third associated with diabetes mellitus. All three cases ultimately required amputation due to symmetrical peripheral gangrene. In the first two cases, amputation was delayed, which is typically advantageous as it allows for the clear demarcation of necrotic tissue. However, in the third case, where infection was evident, immediate amputation was necessary despite the patient's overall poor health.

Symmetrical peripheral gangrene is a severe condition marked by symmetric acral necrosis without obstruction of the major blood vessels. This case report examines the critical decisions involved in choosing between early and delayed amputation, as well as determining the extent of the necessary amputation. We present three cases: one involving antiphospholipid syndrome, another with disseminated intravascular coagulation, and a third associated with diabetes mellitus. All three cases ultimately required amputation due to symmetrical peripheral gangrene. In the first two cases, amputation was delayed, which is typically advantageous as it allows for the clear demarcation of necrotic tissue. However, in the third case, where infection was evident, immediate amputation was necessary despite the patient's overall poor health.

Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and lacks clinical biomarkers. Exosomes are extracellular vesicles that facilitate cell–cell communication by distributing macromolecules, such as small RNAs (smRNAs). We assessed the potential of exosome-derived small RNAs (Ex-smRNAs) as PDAC biomarkers. Methods: Peripheral blood was collected from 51 patients with PDAC and 15 control individuals. Exosomes were isolated using an aqueous two-phase system. Ex-smRNAs were analyzed using smRNA sequencing. smRNA-mediated target gene regulation was verified via The Cancer Genome Atlas analysis and in vitro transfection and wound-healing assays using PDAC organoids. Results: The total Ex-smRNA count was substantially reduced in patients with PDAC compared with that in control individuals. The levels of microRNAs (miRNAs) miR-125a-5p, miR-30e-5p, miR-16-2-3p, miR-98-5p, and the let-7 family were significantly suppressed, whereas that of miR-6731-5p was significantly elevated. Let-7c-5p and miR-98-5p were found to interact with the long non-coding RNA OLMALINC to regulate their common target genes, BACH1 and CCND1, thus controlling PDAC proliferation and migration. The expressions of CARS1-AS1 and miR-142-5p were upregulated in treatment-responsive patients.Multivariable Cox regression analyses, adjusting for potential prognostic factors such as sex, Eastern Cooperative Oncology Group performance status, and tumor size and stage, revealed that CARS1-AS1 (adjusted hazard ratio [HR] 0.33; 95% confidence interval [CI], 0.15–0.73; P = 0.0061) and miR-142-5p (adjusted HR 0.79; 95% CI, 0.61–1.01; P = 0.0581) were associated with improved overall survival. Conclusions We identified potential Ex-smRNA biomarkers involved in PDAC progression and prognosis that reflect key molecular alterations in PDAC and may serve as clinically relevant biomarkers for disease monitoring.

Background and Objectives: Outcomes of deferring percutaneous coronary intervention (PCI) without invasive physiologic assessment for intermediate coronary lesions is uncertain.We sought to compare long-term outcomes between medical treatment and PCI of intermediate lesions without invasive physiologic assessment. Methods: A total of 899 patients with intermediate coronary lesions between 50% and 70% diameter-stenosis were randomized to the conservative group (n=449) or the aggressive group (n=450). For intermediate lesions, PCI was performed in the aggressive group, but was deferred in the conservative group. The primary endpoint was major adverse cardiac events (MACE, a composite of all-cause death, myocardial infarction [MI], or ischemia-driven any revascularization) at 3 years. Results: The number of treated lesions per patient was 0.8±0.9 in the conservative group and 1.7±0.9 in the aggressive group (p=0.001). At 3 years, the conservative group had a significantly higher incidence of MACE than the aggressive group (13.8% vs. 9.3%; hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.00–2.21; p=0.049), mainly driven by revascularization of target intermediate lesion (6.5% vs. 1.1%; HR, 5.69; 95% CI, 2.20–14.73;p<0.001). Between 1 and 3 years after the index procedure, compared to the aggressive group, the conservative group had significantly higher incidence of cardiac death or MI (3.2% vs.0.7%; HR, 4.34; 95% CI, 1.24–15.22; p=0.022) and ischemia-driven any revascularization. Conclusions For intermediate lesions, medical therapy alone, guided only by angiography, was associated with a higher risk of MACE at 3 years compared with performing PCI, mainly due to increased revascularization.

Background and Objectives: Outcomes of deferring percutaneous coronary intervention (PCI) without invasive physiologic assessment for intermediate coronary lesions is uncertain.We sought to compare long-term outcomes between medical treatment and PCI of intermediate lesions without invasive physiologic assessment. Methods: A total of 899 patients with intermediate coronary lesions between 50% and 70% diameter-stenosis were randomized to the conservative group (n=449) or the aggressive group (n=450). For intermediate lesions, PCI was performed in the aggressive group, but was deferred in the conservative group. The primary endpoint was major adverse cardiac events (MACE, a composite of all-cause death, myocardial infarction [MI], or ischemia-driven any revascularization) at 3 years. Results: The number of treated lesions per patient was 0.8±0.9 in the conservative group and 1.7±0.9 in the aggressive group (p=0.001). At 3 years, the conservative group had a significantly higher incidence of MACE than the aggressive group (13.8% vs. 9.3%; hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.00–2.21; p=0.049), mainly driven by revascularization of target intermediate lesion (6.5% vs. 1.1%; HR, 5.69; 95% CI, 2.20–14.73;p<0.001). Between 1 and 3 years after the index procedure, compared to the aggressive group, the conservative group had significantly higher incidence of cardiac death or MI (3.2% vs.0.7%; HR, 4.34; 95% CI, 1.24–15.22; p=0.022) and ischemia-driven any revascularization. Conclusions For intermediate lesions, medical therapy alone, guided only by angiography, was associated with a higher risk of MACE at 3 years compared with performing PCI, mainly due to increased revascularization.

Symmetrical peripheral gangrene is a severe condition marked by symmetric acral necrosis without obstruction of the major blood vessels. This case report examines the critical decisions involved in choosing between early and delayed amputation, as well as determining the extent of the necessary amputation. We present three cases: one involving antiphospholipid syndrome, another with disseminated intravascular coagulation, and a third associated with diabetes mellitus. All three cases ultimately required amputation due to symmetrical peripheral gangrene. In the first two cases, amputation was delayed, which is typically advantageous as it allows for the clear demarcation of necrotic tissue. However, in the third case, where infection was evident, immediate amputation was necessary despite the patient's overall poor health.

Background and Objectives: Outcomes of deferring percutaneous coronary intervention (PCI) without invasive physiologic assessment for intermediate coronary lesions is uncertain.We sought to compare long-term outcomes between medical treatment and PCI of intermediate lesions without invasive physiologic assessment. Methods: A total of 899 patients with intermediate coronary lesions between 50% and 70% diameter-stenosis were randomized to the conservative group (n=449) or the aggressive group (n=450). For intermediate lesions, PCI was performed in the aggressive group, but was deferred in the conservative group. The primary endpoint was major adverse cardiac events (MACE, a composite of all-cause death, myocardial infarction [MI], or ischemia-driven any revascularization) at 3 years. Results: The number of treated lesions per patient was 0.8±0.9 in the conservative group and 1.7±0.9 in the aggressive group (p=0.001). At 3 years, the conservative group had a significantly higher incidence of MACE than the aggressive group (13.8% vs. 9.3%; hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.00–2.21; p=0.049), mainly driven by revascularization of target intermediate lesion (6.5% vs. 1.1%; HR, 5.69; 95% CI, 2.20–14.73;p<0.001). Between 1 and 3 years after the index procedure, compared to the aggressive group, the conservative group had significantly higher incidence of cardiac death or MI (3.2% vs.0.7%; HR, 4.34; 95% CI, 1.24–15.22; p=0.022) and ischemia-driven any revascularization. Conclusions For intermediate lesions, medical therapy alone, guided only by angiography, was associated with a higher risk of MACE at 3 years compared with performing PCI, mainly due to increased revascularization.

Symmetrical peripheral gangrene is a severe condition marked by symmetric acral necrosis without obstruction of the major blood vessels. This case report examines the critical decisions involved in choosing between early and delayed amputation, as well as determining the extent of the necessary amputation. We present three cases: one involving antiphospholipid syndrome, another with disseminated intravascular coagulation, and a third associated with diabetes mellitus. All three cases ultimately required amputation due to symmetrical peripheral gangrene. In the first two cases, amputation was delayed, which is typically advantageous as it allows for the clear demarcation of necrotic tissue. However, in the third case, where infection was evident, immediate amputation was necessary despite the patient's overall poor health.