Pyloric dysfunction is defined as hypertonia or spasm of the pyloric sphincter. The pylorus plays a key role in gastric emptying, but its function remains incompletely understood. Most studies have focused on gastroparesis regardless of the underlying pathophysiology. Few studies have reported pyloric dysfunction in patients with gastroparesis, and the diagnostic and treatment modalities for pyloric dysfunction are not well established. Recently developed diagnostic modalities assessing pyloric function, such as high-resolution antroduodenal manometry and endoluminal functional lumen imaging, are currently being evaluated. A variety of therapeutic interventions targeting the pylorus, including pharmacologic agents, intrapyloric botulinum injection, endoscopic balloon dilation, stent insertion, surgical pyloroplasty, and gastric peroral endoscopic pyloromyotomy, have been proposed. Among these, gastric peroral endoscopic pyloromyotomy has emerged as a novel, minimally invasive therapy with demonstrated efficacy and safety for refractory gastroparesis. This article reviews the pathophysiology of pyloric dysfunction and the potential diagnostic and therapeutic modalities based on the latest literature.

Pyloric dysfunction is defined as hypertonia or spasm of the pyloric sphincter. The pylorus plays a key role in gastric emptying, but its function remains incompletely understood. Most studies have focused on gastroparesis regardless of the underlying pathophysiology. Few studies have reported pyloric dysfunction in patients with gastroparesis, and the diagnostic and treatment modalities for pyloric dysfunction are not well established. Recently developed diagnostic modalities assessing pyloric function, such as high-resolution antroduodenal manometry and endoluminal functional lumen imaging, are currently being evaluated. A variety of therapeutic interventions targeting the pylorus, including pharmacologic agents, intrapyloric botulinum injection, endoscopic balloon dilation, stent insertion, surgical pyloroplasty, and gastric peroral endoscopic pyloromyotomy, have been proposed. Among these, gastric peroral endoscopic pyloromyotomy has emerged as a novel, minimally invasive therapy with demonstrated efficacy and safety for refractory gastroparesis. This article reviews the pathophysiology of pyloric dysfunction and the potential diagnostic and therapeutic modalities based on the latest literature.

Pyloric dysfunction is defined as hypertonia or spasm of the pyloric sphincter. The pylorus plays a key role in gastric emptying, but its function remains incompletely understood. Most studies have focused on gastroparesis regardless of the underlying pathophysiology. Few studies have reported pyloric dysfunction in patients with gastroparesis, and the diagnostic and treatment modalities for pyloric dysfunction are not well established. Recently developed diagnostic modalities assessing pyloric function, such as high-resolution antroduodenal manometry and endoluminal functional lumen imaging, are currently being evaluated. A variety of therapeutic interventions targeting the pylorus, including pharmacologic agents, intrapyloric botulinum injection, endoscopic balloon dilation, stent insertion, surgical pyloroplasty, and gastric peroral endoscopic pyloromyotomy, have been proposed. Among these, gastric peroral endoscopic pyloromyotomy has emerged as a novel, minimally invasive therapy with demonstrated efficacy and safety for refractory gastroparesis. This article reviews the pathophysiology of pyloric dysfunction and the potential diagnostic and therapeutic modalities based on the latest literature.

Pyloric dysfunction is defined as hypertonia or spasm of the pyloric sphincter. The pylorus plays a key role in gastric emptying, but its function remains incompletely understood. Most studies have focused on gastroparesis regardless of the underlying pathophysiology. Few studies have reported pyloric dysfunction in patients with gastroparesis, and the diagnostic and treatment modalities for pyloric dysfunction are not well established. Recently developed diagnostic modalities assessing pyloric function, such as high-resolution antroduodenal manometry and endoluminal functional lumen imaging, are currently being evaluated. A variety of therapeutic interventions targeting the pylorus, including pharmacologic agents, intrapyloric botulinum injection, endoscopic balloon dilation, stent insertion, surgical pyloroplasty, and gastric peroral endoscopic pyloromyotomy, have been proposed. Among these, gastric peroral endoscopic pyloromyotomy has emerged as a novel, minimally invasive therapy with demonstrated efficacy and safety for refractory gastroparesis. This article reviews the pathophysiology of pyloric dysfunction and the potential diagnostic and therapeutic modalities based on the latest literature.

Objective: Familial hypercholesterolaemia (FH) variant positive subjects have over double the cardiovascular risk of low-density-lipoprotein-cholesterol (LDL-C) matched controls. It is desirable to optimise FH variant detection. Methods: We identified 213 subjects with FH gene panel reports (LDLR, APOB, PCSK9, and APOE) based on total cholesterol >310 mg/dL; excluding triglycerides >400 mg/dL, cascade screening, and patients without pre-treatment LDL-C recorded. Demographic, clinical and lipid parameters were recorded. Results: A 31/213 (14.6%) patients had pathogenic or likely pathogenic FH variants. 10/213 (4.7%) had variants of uncertain significance. Compared with patients without FH variants, patients with FH variants were younger (median age, 39 years vs. 48 years), had more tendon xanthomata (25.0% vs. 11.4%), greater proportion of first degree relatives with total cholesterol >95th percentile (40.6% vs. 16.5%), higher LDL-C (median, 271 mg/dL vs. 236 mg/dL), and lower triglycerides (median, 115 mg/dL vs. 159 mg/dL). The Besseling et al. model (c-statistic 0.798) improved FH variant discrimination over Friedewald LDL-C (c-statistic 0.724), however, Dutch Lipid Clinic Network Score (DLCNS) did not (c-statistic 0.665). Sampson LDL-C (c-statistic 0.734) had similar discrimination to Friedewald. Conclusion Although tendon xanthomata and first degree relatives with high total cholesterol >95th percentile were associated with FH variants, DLCNS or Simon Broome criteria did not improve FH detection over LDL-C. Sampson LDL-C did not significantly improve discrimination over Friedewald. Although lower triglycerides and younger age of presentation are positively associated with presence of FH variants, this information is not commonly used in FH detection algorithms apart from Besseling et al.

BACKGROUND: Previous investigations have shown that local application of nanoparticles presenting the carbohydrate moiety galactose-a-1,3-galactose (α-gal epitopes) enhance wound healing by activating the complement system and recruiting pro-healing macrophages to the injury site. Our companion in vitro paper suggest α-gal epitopes can similarly recruit and polarize human microglia toward a pro-healing phenotype. In this continuation study, we investigate the in vivo implications of α-gal nanoparticle administration directly to the injured spinal cord. METHODS: α-Gal knock-out (KO) mice subjected to spinal cord crush were injected either with saline (control) or with α-gal nanoparticles immediately following injury. Animals were assessed longitudinally with neurobehavioral and histological endpoints. RESULTS: Mice injected with α-gal nanoparticles showed increased recruitment of anti-inflammatory macrophages to the injection site in conjunction with increased production of anti-inflammatory markers and a reduction in apoptosis. Further, the treated group showed increased axonal infiltration into the lesion, a reduction in reactive astrocyte populations and increased angiogenesis. These results translated into improved sensorimotor metrics versus the control group. CONCLUSIONS Application of α-gal nanoparticles after spinal cord injury (SCI) induces a pro-healing inflammatory response resulting in neuroprotection, improved axonal ingrowth into the lesion and enhanced sensorimotor recovery. The data shows α-gal nanoparticles may be a promising avenue for further study in CNS trauma.GRAPHICAL ABSTRACT Putative mechanism of therapeutic action by α-gal nanoparticles. A. Nanoparticles injected into the injured cord bind to anti-Gal antibodies leaked from ruptured capillaries. The binding of anti-Gal to α-gal epitopes on the α-gal nanoparticles activates the complement system to release complement cleavage chemotactic peptides such as C5a, C3a that recruit macrophages and microglia. These recruited cells bind to the anti-Gal coated α-gal nanoparticles and are further polarized into the M2 state. B. Recruited M2 macrophages and microglia secrete neuroprotective and prohealing factors to promote tissue repair, neovascularization and axonal regeneration (C.).

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Objective: To clarify the values of autotaxin (ATX) in patients with primary biliary cholangitis (PBC) and PBC-related hepatocellular carcinoma (HCC). Methods: 179 patients with PBC were selected from prospective cohorts of autoimmune liver diseases at the time of first diagnosis of PBC in Department of Hepatology, the Fifth Medical Center of PLA General Hospital, from January 2016 to January 2018, all patients with PBC received UDCA therapy, primary endpoint was event of HCC, the follow-up period was censored at the date of HCC. The relationship between level of ATX and clinical features in patients with PBC and its potential value in predicting disease progression and PBC-related HCC were analyzed. Results: The ATX level in the peripheral blood of patients with PBC was significantly higher than that of alcoholic liver cirrhosis(ALC) (t = 3.278, P = 0.001) and healthy controls(HC) (t = 6.594, P < 0.001), however, when comparing PBC to non-PBC related HCC, no significant difference was found between the groups(t=-0.240, P = 0.811). Consistent with peripheral blood levels, histochemical staining indicated that ATX in the liver of patients with PBC was significantly higher than that of HC (Z=-3.633, P < 0.001) and ALC (Z=-3.283, P < 0.001), and the expression of ATX in PBC with advanced histological stage was significantly higher than PBC with early stage (Z=-2.018, P = 0.034). The baseline ATX level in PBC patients without developing to HCC during follow-up had significant difference to patients with developing to HCC (228.451 ± 124.093 ng/ml vs 301.583 ± 100.512 ng/ml, t = 2.339, P = 0.021). The result in multivariate logistic regression analysis showed that ATX were independent predictors of PBC related HCC(OR 1.245, 95%CI 1.097-1.413). The optimal critical value of peripheral blood ATX level at baseline for predicting HCC was 235.254 ng/ml, with the cut-off value of 0.714 in AUC of the ROC (95% CI was 0.597~ 0.857), sensitivity and specificity were 84.6% and 59.0%, respectively. Conclusion: ATX level was significantly higher in PBC patients over controls, and it's concentration was correlated with UDCA efficacy and fibrosis stage. ATX has potential values in predicting disease progression and PBC-related HCC.

Purinergic P2Y Receptor Antagonists ; Consensus ; Cardiovascular System ; Cardiology ; Asia