Advancements in diagnostic technology have led to the improved detection of pancreatic neuroendocrine tumors (PNETs) and thus to an increase in the number of reported cases. Endoscopic ultrasound (EUS) technology, including in combination with contrast-enhanced harmonic imaging, aids in distinguishing PNETs from other tumors, while EUS-guided fine-needle aspiration or biopsy has improved the histological diagnosis and grading of tumors. The recent introduction of EUS-guided ablation using ethanol injection or radiofrequency ablation has offered an alternative to surgery in the management of PNETs. Comparisons with surgery have shown similar outcomes but fewer adverse effects. Although standardized protocols and prospective studies with long-term follow-up are still needed, EUS-based methods are promising approaches that can contribute to a better quality of life for PNET patients.

Purpose: This study elucidates the mechanism of the physiological effect of cannabidiol (CBD) by assessing its impact on lipopolysaccharide (LPS)-induced inflammation in RWPE-1 cells and prostatitis-induced by 17β-estradiol and dihydrotestosterone in a rat model, focusing on its therapeutic potential for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Materials and Methods: RWPE-1 cells were stratified in vitro into three groups: (1) controls, (2) cells with LPS-induced inflammation, and (3) cells with LPS-induced inflammation and treated with CBD. Enzyme-linked immunosorbent assays and western blots were performed on cellular components and supernatants after administration of CBD. Five groups of six Sprague–Dawley male rats were assigned: (1) control, (2) CP/CPPS, (3) CP/CPPS and treated with 50 mg/kg CBD, (4) CP/CPPS and treated with 100 mg/kg CBD, and (5) CP/CPPS and treated with 150 mg/kg CBD. Prostatitis was induced through administration of 17β-estradiol and dihydrotestosterone. After four weeks of CBD treatment, a pain index was evaluated, and prostate tissue was collected for subsequent histologic examination and western blot analysis. Results: CBD demonstrated efficacy in vivo for CP/CPPS and in vitro for inflammation. It inhibited the toll-like receptor 4 (TLR4)uclear factor-kappa B (NF-κB) pathway by activating the CB2 receptor, reducing expression of interleukin-6, tumor necrosis factor-alpha, and cyclooxygenase-2 (COX2) (p<0.01). CBD exhibited analgesic effects by activating and desensitizing the TRPV1 receptor. Conclusions CBD inhibits the TLR4/NF-κB pathway by activating the CB2 receptor, desensitizes the TRPV1 receptor, and decreases the release of COX2. This results in relief of inflammation and pain in patients with CP/CPPS, indicating CBD as a potential treatment for CP/CPPS.

Background: Differentiating between asymptomatic bacteriuria (ASB) and urinary tract infection (UTI) is difficult in patients who have difficulty communicating their symptoms.This study aimed to evaluate the diagnostic accuracy of urine leukocytes in distinguishing between UTI and ASB, and the clinical outcomes of patients with UTI according to the degree of pyuria. Methods: This retrospective cohort study included patients with positive urine cultures between July 2022 and June 2023 at two hospitals. UTI and ASB were diagnosed through a comprehensive review of medical records. We evaluated the differences in urine leukocyte counts between patients with UTI and ASB. The diagnostic performance of urine leukocytes to differentiate between UTI and ASB was evaluated. To investigate the clinical outcomes based on the degree of pyuria, we classified patients with upper UTI according to their urine leukocyte counts. Results: Of the 1,793 eligible patients with bacteriuria included, 1,464 had UTI and 329 had ASB. Patients with UTI had higher urinary leukocytes than patients with ASB did (490.4 vs.123.5 cells/µL; P < 0.001). The area under the receiver operating characteristic curve was 0.702 for discriminating between ASB and UTI. The optimal urine leukocyte cutoff was 195.35 cells/µL, with a sensitivity and specificity of 0.70 and 0.60, respectively. A sequential rise in secondary bacteremia rate was observed according to an increase in urine leukocytes in patients with upper UTI, whereas in-hospital mortality showed no corresponding trend. Conclusion Urine leukocyte counts could be used to predict UTI occurrence and bacteremia secondary to UTI. Higher degrees of pyuria were associated with bacteremia but not with mortality. Urine leukocyte counts can provide additive information for patients with bacteriuria with vague symptoms.

Purpose: This study elucidates the mechanism of the physiological effect of cannabidiol (CBD) by assessing its impact on lipopolysaccharide (LPS)-induced inflammation in RWPE-1 cells and prostatitis-induced by 17β-estradiol and dihydrotestosterone in a rat model, focusing on its therapeutic potential for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Materials and Methods: RWPE-1 cells were stratified in vitro into three groups: (1) controls, (2) cells with LPS-induced inflammation, and (3) cells with LPS-induced inflammation and treated with CBD. Enzyme-linked immunosorbent assays and western blots were performed on cellular components and supernatants after administration of CBD. Five groups of six Sprague–Dawley male rats were assigned: (1) control, (2) CP/CPPS, (3) CP/CPPS and treated with 50 mg/kg CBD, (4) CP/CPPS and treated with 100 mg/kg CBD, and (5) CP/CPPS and treated with 150 mg/kg CBD. Prostatitis was induced through administration of 17β-estradiol and dihydrotestosterone. After four weeks of CBD treatment, a pain index was evaluated, and prostate tissue was collected for subsequent histologic examination and western blot analysis. Results: CBD demonstrated efficacy in vivo for CP/CPPS and in vitro for inflammation. It inhibited the toll-like receptor 4 (TLR4)uclear factor-kappa B (NF-κB) pathway by activating the CB2 receptor, reducing expression of interleukin-6, tumor necrosis factor-alpha, and cyclooxygenase-2 (COX2) (p<0.01). CBD exhibited analgesic effects by activating and desensitizing the TRPV1 receptor. Conclusions CBD inhibits the TLR4/NF-κB pathway by activating the CB2 receptor, desensitizes the TRPV1 receptor, and decreases the release of COX2. This results in relief of inflammation and pain in patients with CP/CPPS, indicating CBD as a potential treatment for CP/CPPS.

Background: Differentiating between asymptomatic bacteriuria (ASB) and urinary tract infection (UTI) is difficult in patients who have difficulty communicating their symptoms.This study aimed to evaluate the diagnostic accuracy of urine leukocytes in distinguishing between UTI and ASB, and the clinical outcomes of patients with UTI according to the degree of pyuria. Methods: This retrospective cohort study included patients with positive urine cultures between July 2022 and June 2023 at two hospitals. UTI and ASB were diagnosed through a comprehensive review of medical records. We evaluated the differences in urine leukocyte counts between patients with UTI and ASB. The diagnostic performance of urine leukocytes to differentiate between UTI and ASB was evaluated. To investigate the clinical outcomes based on the degree of pyuria, we classified patients with upper UTI according to their urine leukocyte counts. Results: Of the 1,793 eligible patients with bacteriuria included, 1,464 had UTI and 329 had ASB. Patients with UTI had higher urinary leukocytes than patients with ASB did (490.4 vs.123.5 cells/µL; P < 0.001). The area under the receiver operating characteristic curve was 0.702 for discriminating between ASB and UTI. The optimal urine leukocyte cutoff was 195.35 cells/µL, with a sensitivity and specificity of 0.70 and 0.60, respectively. A sequential rise in secondary bacteremia rate was observed according to an increase in urine leukocytes in patients with upper UTI, whereas in-hospital mortality showed no corresponding trend. Conclusion Urine leukocyte counts could be used to predict UTI occurrence and bacteremia secondary to UTI. Higher degrees of pyuria were associated with bacteremia but not with mortality. Urine leukocyte counts can provide additive information for patients with bacteriuria with vague symptoms.

Background: Differentiating between asymptomatic bacteriuria (ASB) and urinary tract infection (UTI) is difficult in patients who have difficulty communicating their symptoms.This study aimed to evaluate the diagnostic accuracy of urine leukocytes in distinguishing between UTI and ASB, and the clinical outcomes of patients with UTI according to the degree of pyuria. Methods: This retrospective cohort study included patients with positive urine cultures between July 2022 and June 2023 at two hospitals. UTI and ASB were diagnosed through a comprehensive review of medical records. We evaluated the differences in urine leukocyte counts between patients with UTI and ASB. The diagnostic performance of urine leukocytes to differentiate between UTI and ASB was evaluated. To investigate the clinical outcomes based on the degree of pyuria, we classified patients with upper UTI according to their urine leukocyte counts. Results: Of the 1,793 eligible patients with bacteriuria included, 1,464 had UTI and 329 had ASB. Patients with UTI had higher urinary leukocytes than patients with ASB did (490.4 vs.123.5 cells/µL; P < 0.001). The area under the receiver operating characteristic curve was 0.702 for discriminating between ASB and UTI. The optimal urine leukocyte cutoff was 195.35 cells/µL, with a sensitivity and specificity of 0.70 and 0.60, respectively. A sequential rise in secondary bacteremia rate was observed according to an increase in urine leukocytes in patients with upper UTI, whereas in-hospital mortality showed no corresponding trend. Conclusion Urine leukocyte counts could be used to predict UTI occurrence and bacteremia secondary to UTI. Higher degrees of pyuria were associated with bacteremia but not with mortality. Urine leukocyte counts can provide additive information for patients with bacteriuria with vague symptoms.

Primary cilia function as critical sensory organelles that mediate multiple signaling pathways, including the Hedgehog (Hh) pathway, which is essential for organ patterning and morphogenesis. Disruptions in Hh signaling have been implicated in supernumerary tooth formation and molar fusion in mutant mice. Cilk1, a highly conserved serine/threonine-protein kinase localized within primary cilia, plays a critical role in ciliary transport. Loss of Cilk1 results in severe ciliopathy phenotypes, including polydactyly, edema, and cleft palate. However, the role of Cilk1 in tooth development remains unexplored. In this study, we investigated the role of Cilk1 in tooth development. Cilk1 was found to be expressed in both the epithelial and mesenchymal compartments of developing molars. Cilk1 deficiency resulted in altered ciliary dynamics, characterized by reduced frequency and increased length, accompanied by downregulation of Hh target genes, such as Ptch1 and Sostdc1, leading to the formation of diastemal supernumerary teeth. Furthermore, in Cilk1^-/-;PCS1-MRCS1^△/△ mice, which exhibit a compounded suppression of Hh signaling, we uncovered a novel phenomenon: diastemal supernumerary teeth can be larger than first molars. Based on these findings, we propose a progressive model linking Hh signaling levels to sequential changes in tooth patterning: initially inducing diastemal supernumerary teeth, then enlarging them, and ultimately leading to molar fusion. This study reveals a previously unrecognized role of Cilk1 in controlling tooth morphology via Hh signaling and highlights how Hh signaling levels shape tooth patterning in a gradient-dependent manner.
Animals ; Hedgehog Proteins/physiology* ; Mice ; Signal Transduction/physiology* ; Tooth, Supernumerary ; Molar ; Cilia/physiology* ; Odontogenesis/physiology* ; Patched-1 Receptor ; Protein Serine-Threonine Kinases/physiology* ; Mice, Knockout ; Adaptor Proteins, Signal Transducing

Background: Sepsis is a leading cause of intensive care unit (ICU) admission. However, few studies have evaluated how the ICU model affects the outcomes of patients with sepsis. Methods: This post hoc analysis of data from the Management of Severe Sepsis in Asia’s Intensive Care Units II study included 537 patients with sepsis admitted to 27 ICUs in Korea. The outcome measures of interest were compared between the closed ICU group, patients admitted under the full responsibility of an intensivist as the primary attending physician, and the open ICU group. The association between a closed ICU and ICU mortality was evaluated using a logistic regression analysis. Results: Altogether, 363 and 174 enrolled patients were treated in open and closed ICUs, respectively. Compliance with the sepsis bundles did not differ between the two groups; however, the closed ICU group had a higher rate of renal replacement therapy and shorter duration of ventilator support. The closed ICU group also had a lower ICU mortality rate than the open ICU group (24.7% vs. 33.1%). In a logistic regression analysis, management in the closed ICU was significantly associated with a decreased ICU mortality rate even after adjusting for potential confounding factors (adjusted odds ratio, 0.576; 95% CI, 0.342–0.970), and that association was observed for up to 90 days. Conclusions Sepsis management in closed ICUs was significantly associated with improved ICU survival and decreased length of ICU stay, even though the compliance rates for the sepsis bundles did not differ between open and closed ICUs.