Isolated gastric varices associated with antiphospholipid syndrome and protein S deficiency: a case report and review of the literature.

The mortality rate of gastric varices bleeding can reach 20% within 6 weeks. Isolated gastric varices (IGVs) refer to gastric varices without esophageal varices and typically arise as a common complication of left portal hypertension. Although IGVs commonly form in the setting of splenic vein occlusion, the combination of antiphospholipid syndrome and protein S deficiency leading to splenic vein occlusion is rare. We herein present a case of a 28-year-old woman with intermittent epigastric pain and melena. She was diagnosed with antiphospholipid syndrome based on the triad of pregnancy morbidity, unexplained venous occlusion, and positive lupus anticoagulant. Laparoscopic splenectomy and pericardial devascularization were performed for the treatment of IGVs. During the 6-month postoperative follow-up, repeated endoscopy and contrast-enhanced computed tomography revealed disappearance of the IGVs. This is the first description of splenic vein occlusion associated with both antiphospholipid syndrome and protein S deficiency. We also provide a review of the etiology, clinical manifestations, diagnosis, and treatment methods of IGVs.

Association between the ratio of serum eicosapentaenoic acid to arachidonic acid and risk of coronary artery disease in young Chinese patients.

Objective: Long-chain (LC) omega-3 PUFAs, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may play an anti-inflammatory effect and decrease the risk of coronary artery disease (CAD). In contrast, omega-6 PUFA, mainly arachidonic acid (AA), has pro-inflammatory and pro-aggregatory effects, which may increase the risk of CAD. This study evaluated the associations between EPA, DHA, AA, and their ratios (EPA/AA and DHA/AA) with the risk of CAD in young Chinese patients. Methods: A total of 182 young patients with CAD and 143 age-matched controls were included. Traditional cardiovascular risk factors were recorded. Serum EPA, DHA and AA were measured by ultra-performance liquid chromatography-mass spectrometry. Results: The level of AA was significantly higher, while the level of EPA was lower in the CAD group than that in the control group. There was no significant difference in DHA level in the two groups. Both the ratios of EPA/AA and DHA/AA were lower in the CAD group than that in the control. Multivariate logistic regression analysis showed that higher serum AA level was associated with the increased risk of CAD, while EPA was a protective factor for CAD. There was no significant association between DHA level and the risk of CAD. Although both higher ratios of EPA/AA [per tertile increment, adjusted odds ratios (ORs) (OR) 0.356, 95% confidence intervals (CI) 0.247-0.513] and DHA/AA (adjusted OR = 0.465, 95%CI = 0.332-0.653) were associated with a lower risk of CAD in young patients. Receiver operating characteristic (ROC) curve analysis showed that compared with AA, the diagnostic value was increased in EPA/AA, but not in DHA/AA. Conclusion: EPA, but not DHA may play a protective role in CAD, while AA may be associated with the increased risk of CAD in young Chinese patients. The ratio of EPA/AA can increase the predictive value for diagnosing CAD than EPA or AA alone.

Reprogrammed fecal and mucosa-associated intestinal microbiota and weakened mucus layer in intestinal goblet cell- specific Piezo1-deficient mice.

Dysfunction of the mucus layer allows commensal and pathogenic microorganisms to reach the intestinal epithelium, thereby leading to infection and inflammation. This barrier is synthesized and secreted by host goblet cells. Many factors that influence the function of goblet cells (GCs) have been studied. However, how the microenvironment surrounding GCs influences the mucus layer and microbiota of the colon is unclear. To explore the effect of GC Piezo1 on the mucus layer and microbiota in the colon, we generated an intestinal epithelial Piezo1 conditional knockout mouse model. The fecal-associated microbiota (FAM) and mucosa-associated microbiota (MAM) of the two groups were characterized based on amplicon sequencing of the 16S rRNA gene. Our results showed that GC Piezo1-/- mice developed decreased GC numbers, thinner mucus layer, and increased inflammatory cytokines (e.g., CXCL1, CXCL2, IL-6) on the 7th day. In addition, decreased Spdef and increased DOCK4 were discovered in KO mice. Meanwhile, the diversity and richness were increased in MAM and decreased in FAM in the GC Piezo1-/- group compared with the GC Piezo1+/+ group. We also observed increased abundances of Firmicutes and decreased abundances of Verrucomicrobiota and Actinobacteriota in the MAM of the GC Piezo1-/- group. Additionally, BugBase predicts that potentially pathogenic bacteria may have increased in the inner mucus layer, which is consistent with the higher abundance of Helicobacter hepaticus, Lactobacillus johnsonii, Escherichia-Shigella and Oscillospiraceae in MAM. These results further support the hypothesis that the role of Piezo1 in GCs is important for maintaining the function of the mucus layer and intestinal microbiota balance in the mouse colon.

The association between heart failure and risk of fractures: Pool analysis comprising 260,410 participants.

Background: HF and osteoporosis shared many common etiological risk factors. However, studies exploring whether patients with HF were associated with a higher risk of osteoporotic fracture resulted in inconsistent findings. This meta-analysis aimed to summarize the association between HF and the risk of incident fracture. Methods: Following the Meta-analysis of Observational Studies in Epidemiology group recommendations, we searched multiple electronic databases (PubMed, Cochran Library, and EMBASE) for related studies from inception to April 30, 2021. Studies evaluating the risk of incident fracture in patients with HF compared with those without HF were included for analysis. The random-effects models were used to combine the estimated hazard ratios (HRs) of incident fracture associated with HF. Results: We included 8 observational studies for meta-analysis. The sample size ranged from 5,613 to 87,748 participants, with a total of 260,410 participants included. The median follow-up duration was 5.0 years. Random-effects model analyses showed that compared with control groups, patients with HF were associated with a higher risk of all incident fractures (HR = 1.67, 95% CI = 1.30-2.16, P < 0.001) and hip fracture (HR = 2.20, 95% CI = 1.28-3.77, P < 0.001). The risk of all incident fractures was increased in all subgroup analyses according to age, sample size, sex, and follow-up duration. Conclusions: Patients with HF were associated with a higher risk of incident fracture, as well as hip fracture.

Massive gastrointestinal bleeding after endoscopic rubber band ligation of internal hemorrhoids: A case report.

BACKGROUND: Rubber band ligation (RBL) using rigid anoscope is a commonly recommended therapy for grade I-III symptomatic internal hemorrhoids. Severe complications of RBL include pain, hemorrhage and sepsis. Flexible endoscopic RBL (ERBL) is now more commonly used in RBL therapy but few severe complications have been reported. Here we report on a case of massive bleeding after ERBL. CASE SUMMARY: A 31-year-old female was admitted to the department of gastroenterology with a chief complaint of discontinuous hematochezia for 2 years. No previous history, accompanying diseases or drug use was reported. Physical examination and colonoscopy showed grade II internal hemorrhoids. The patient received ERBL therapy. Five days after ligation, the patient presented with mild hematochezia. On days 7 and 9 after ligation, she presented with a large amount of rectal bleeding, dizziness and weakness. Emergency colonoscopy revealed active bleeding and an ulcer in the anal wound. The patient received two sessions of hemoclipping on days 7 and 9 to treat the bleeding. No further bleeding was reported up to day 15 and she was discharged home. Although the hemorrhoid prolapse disappeared after ERBL, she was dissatisfied with the subsequent complications. CONCLUSION: ERBL therapy is an effective treatment for symptomatic internal hemorrhoids with satisfactory short and long-term recovery. Pain and anal bleeding are the most frequently reported postoperative complications. Coagulation disorders complicate the increased risk of bleeding. Although rarely reported, our case reminds us that those patients without coagulation disorders are also at risk of massive life-threatening bleeding and need strict follow-up after ligation.

Association Between Prognostic Nutritional Index and Prognosis in Patients With Heart Failure: A Meta-Analysis.

Background: The prognostic nutritional index (PNI) has been proposed as a marker of malnutrition and associated with the prognosis of cardiovascular disease. However, whether PNI can serve as a potential biomarker for the prognosis of heart failure (HF) upon those established risk factors were still controversial. This meta-analysis aimed to generate comprehensive evidence on the prognostic value of PNI in patients with HF. Methods: Multiple databases (PubMed, Embase, the Cochrane Library, and Google Scholar) were searched for related studies up to January 31, 2022. Observational studies accessed associations between PNI levels and the prognosis in patients with HF were included for meta-analysis. The hazard ratios (HRs) and 95% confidence intervals (CI) were calculated. Results: Fourteen studies, comprising 19,605 patients with HF were included for meta-analysis. The median follow-up duration was 18.5 months. Compared with those with higher PNI (normal nutritional status), patients with HF with lower PNI (malnourished) were associated with a higher risk of all-cause mortality (HR 1.53, 95% CI 1.27-1.85) and composite major adverse cardiac outcomes (MACEs; HR 2.26, 95% CI 1.54-3.31) in the multivariable-adjusted model. Furthermore, when PNI was defined as per 1 increment as a continuous metric, higher PNI was associated with a decrease in all-cause mortality (per 1 increment of PNI: HR 0.94, 95% CI 0.88-0.96) and MACEs (per 1 increment of PNI: HR 0.97, 95% CI 0.95-0.98). Conclusions: The PNI can serve as an easily calculated bedside "malnutrition-inflammation" biomarker in HF. Lower PNI was associated with a worse prognosis in patients with HF.

Long-chain omega-3 polyunsaturated fatty acids and the risk of heart failure.

Aims: Adequate intake of long-chain (LC) omega-3 polyunsaturated fatty acids (n-3 PUFAs) is considered important for cardiovascular health. However, the effects of LC n-3 PUFAs on the risk of heart failure (HF) remain unclear. This systematic review and meta-analysis aimed to determine the role of LC n-3 PUFAs in the incidence of HF. Materials and Methods: Electronic databases were searched for studies up to 31 July 2021. Studies were included for the meta-analysis if they reported the adjusted associations between different dietary intakes or circulating concentrations of LC n-3 PUFAs and the risk of HF. A random-effect model was used to calculate the pooled estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for higher LC n-3 PUFA concentrations. Results: Thirteen studies were included in the meta-analysis. Eight studies comprising 316,698 individuals (11,244 incident HF cases), with a median follow-up of 10.7 years, showed that a higher dietary intake of LC n-3 PUFAs was associated with a lower risk of HF (highest versus lowest quintile: HR = 0.84, 95% CI = 0.75-0.94). Six studies, comprising 17,163 participants (2520 HF cases) with a median follow-up of 9.7 years, showed that higher circulating LC n-3 PUFA concentrations were associated with a lower risk of HF (highest versus lowest quintile: HR = 0.59, 95% CI = 0.39-0.91). Higher circulating docosahexaenoic acid concentrations were associated with a decreased risk of HF (top versus bottom quintile: HR = 0.44, 95% CI = 0.26-0.77). The associations between eicosapentaenoic acid (HR = 0.58, 95% CI = 0.26-1.25), docosahexaenoic acid (HR = 0.66, 95% CI = 0.24-1.82), and the risk of HF were not significant. Conclusion: High LC n-3 PUFA concentrations measured by dietary intake or circulating biomarkers are associated with a lower risk of developing HF.

Plexiform angiomyxoid myofibroblastic tumor treated by endoscopic submucosal dissection: A case report and review of the literature.

BACKGROUND: Plexiform angiomyxoid myofibroblastic tumor (PAMT) is a rare mesenchymal tumor characterized by multiple nodular plexiform growth patterns and an immunophenotype with myofibroblasts. The pathological characteristics, immunohistochemistry, diagnostic criteria, differential diagnosis, and gene-level changes of PAMT have been reported in many studies. At present, the main treatment for PAMT in the reported cases is surgery; only eight cases were treated via endoscopy (excluding 1 thoracoscopic resection), and the lesions were all smaller than 5 cm. There are no reports on the prognosis and follow-up of young patients with lesion sizes reaching 5 cm who undergo endoscopic submucosal dissection (ESD). Herein, we present the first case of a young patient with a lesion size reaching 5 cm who was diagnosed with PAMT via endoscopic submucosal dissection. CASE SUMMARY: A 15-year-old young man with upper abdominal pain for 2 years presented to the Gastroenterology Department of our hospital. Painless gastroscopy showed a semicircular bulge approximately 5 cm in size in the lesser curvature near the cardia of the fundus; the surface was eroded, and shallow ulcers had formed. The pathological manifestations of the biopsy were spindle cell proliferative lesions with interstitial mucinous changes, and the surface mucosa showed chronic inflammatory changes with active lesions; immunohistochemistry showed smooth muscle actin (SMA) (+), CD117 (-), CD34 (-), DOG-1 (-), S-100 (-), and Ki67 (LI: < 1%). We performed ESD on the patient. The lesion that we removed was 5 cm × 4 cm × 2 cm in size. Pathologically, the resected tissue displayed typical manifestations, such as fat spindle-shaped fibroblasts and myofibroblast-like cells showing irregular nodular hyperplasia. Immunohistochemistry staining of the tumor cells revealed the following: CD34 (partially +), SMA (weakly +), CD117 (-), DOG-1 (-), S-100 (-), SDHB (+), PCK (-), and Ki67 (labelling index: 2%). There was no recurrence or metastasis during the 3-mo follow-up after the operation, and the treatment effect was good. We also performed a review of the literature on the clinical manifestations, pathological features, immunohistochemistry, and differential diagnosis of PAMT. CONCLUSION: At present, the diagnostic criteria for PAMT are relatively clear, but the pathogenesis and genetic changes require further study. PAMT is benign in nature, and these patients are less likely to experience local or metastatic recurrence. The main treatment is still surgery if the lesion is in the stomach. Partial gastrectomy and distal gastrectomy are the most frequently performed surgical treatments for PAMT, followed by local resection, subtotal gastrectomy, and wedge resection. But for comprehensive evaluation of the disease, ESD can be considered a suitable method to avoid excessive treatment.

Association Between Hemoglobin Glycation Index and Risk of Cardiovascular Disease and All Cause Mortality in Type 2 Diabetic Patients: A Meta-Analysis.

Background: The hemoglobin glycation index (HGI) has been proposed as a marker to quantify inter-individual variation in hemoglobin glycosylation. However, whether HGI is associated with an increased risk of diabetic complications independent of glycated hemoglobin (HbA1c) remains unclear. This meta-analysis aimed to determine the association between HGI and the risk of all cause mortality and composite cardiovascular disease (CVD). Methods: PubMed, and EMBASE databases were searched for related studies up to March 31, 2021. Observational studies reported associations between HGI levels and composite CVD and all cause mortality were included for meta-analysis. A random effect model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CI) for higher HGI. Results: A total of five studies, comprising 22,035 patients with type two diabetes mellitus were included for analysis. The median follow-up duration was 5.0 years. After adjusted for multiple conventional cardiovascular risk factors, an increased level of HGI was associated with a higher risk of composite CVD (per 1 SD increment: HR = 1.14, 95% CI = 1.04-1.26) and all cause mortality (per 1 SD increment: HR = 1.18, 95% CI = 1.05-1.32). However, when further adjusted for HbA1c, the association between HGI and risk of composite CVD (per 1 SD increment of HGI: HR = 1.01, 95% CI = 0.93-1.10) and all cause mortality (per 1 SD increment of HGI: HR = 1.03, 95% CI = 0.96-1.10) became insignificant. Conclusions: High HGI was associated with an increased risk of composite CVD and all cause mortality after adjustment for multiple conventional cardiovascular risk factors. However, the association was mainly mediating by the level of HbA1c.

Prediabetes and risk of heart failure: the link grows stronger.

In a recently published paper in Cardiovascular Diabetology, Sinha et al. (Association of fasting glucose with lifetime risk of incident heart failure: the Lifetime Risk Pooling Project. Cardiovasc Diabetol. 2021;20(1):66) reported that prediabetes (defined as a fasting plasma glucose concentration of 100-125 mg/dL) was associated with a higher lifetime risk of heart failure in middle-aged White adults and Black women, with the association attenuating in older Black women. This study provides important evidence that the risk of heart failure is increased in people with a fasting plasma glucose concentration as low as 100 mg/dL, supporting the definition of prediabetes according to the American Diabetes Association guideline. The study also strongly supports the notion that prediabetes should be regarded not only as a high-risk state for the development of diabetes but also as a risk factor for cardiovascular morbidity.

α-Linolenic Acid and Risk of Heart Failure: A Meta-Analysis.

Background: The α-linolenic acid is a plant origin n-3 fatty acid that may reduce the risk of cardiovascular disease. However, the effect of α-linolenic acid (ALA) on the risk of heart failure (HF) remains unclear. In this meta-analysis, we aimed to determine the role of ALA in the risk of incident HF. Methods: Electronic databases were searched for studies up to August 10, 2021. Studies were included for meta-analysis if the adjusted risk of HF in different dietary intake or circulating levels of ALA was reported. We used the random-effects model to calculate the estimated hazard ratios (HRs) and 95% CI for higher ALA. Results: A total of 6 studies (7 cohorts) comprising 135,270 participants were included for meta-analysis. After a median follow-up duration of 10 years, 5,905 cases of HF were recorded. No significant heterogeneity was observed among all the included studies. Random-effects model analyses showed that there was no significant association between ALA and the risk of incident HF, either assessed as quintiles (highest quintile vs. lowest quintile: HR = 0.95, 95% CI = 0.86-1.06) or per 1 SD increment (HR = 0.99, 95% CI = 0.95-1.01). Furthermore, we did not observe any association between ALA and the risk of HF in subgroup analyses performed according to age, sex, follow-up duration, and measuring method of ALA. Conclusions: We found no association between ALA and the risk of incident HF, suggesting that ALA might not be effective in the prevention of HF.

Modulation of miRNAs by vitamin C in H2O2­exposed human umbilical vein endothelial cells.

Vitamin C plays a protective role in oxidative damage by blocking the effects of free radicals. The present study investigated the mechanisms through which vitamin C partly mediates anti­apoptotic and antioxidant functions via the regulation of microRNAs (miRNAs or miRs). For this purpose, a global miRNA expression analysis on human umbilical vein endothelial cells (HUVECs) treated with vitamin C was conducted using microarrays containing human precursor and mature miRNA probes. The results revealed that there were 42 identical miRNAs among the differentially expressed miRNAs in the HUVEC group and H2O2 + vitamin C­treated HUVEC group compared to the H2O2­exposed HUVEC group, including 41 upregulated miRNAs and 1 down­regulated miRNA. Using bioinformatics analysis, differentially expressed miRNAs were investigated to identify novel target mRNAs and signaling pathways. Pathway enrichment analyses revealed that apoptosis, the mitogen­activated protein kinase (MAPK) signaling pathway, phosphoinositide 3­kinase (PI3K)/Akt signaling pathway and oxidative phosphorylation were significantly enriched. The results from western blot analysis demonstrated that the interleukin (IL)10, matrix metalloproteinase (MMP)2, cAMP­response element binding protein (CREB) and p­CREB protein expression levels in HUVECs transfected with hsa­miR­3928­5p and induced by H2O2 were significantly downregulated; the MAPK9, caspase­3 (CASP3) and p­CASP3 protein expression levels in HUVECs transfected with hsa­miR­323a­5p and induced by H2O2 were significantly downregulated. The present study therefore demonstrates that vitamin C partly exerts protective effects on HUVECs through the regulation of miRNA/mRNA axis expression.

Resveratrol Improves Bnip3-Related Mitophagy and Attenuates High-Fat-Induced Endothelial Dysfunction.

Statin treatment reduces cardiovascular risk. However, individuals with well-controlled low-density lipoprotein (LDL) levels may remain at increased risk owing to persistent high triglycerides and low high-density lipoprotein cholesterol. Because resveratrol promotes glucose metabolism and mitigates cardiovascular disorders, we explored its mechanism of protective action on high-fat-induced endothelial dysfunction. Human umbilical venous endothelial cells were treated with oxidized LDL (ox-LDL) in vitro. Endothelial function, cell survival, proliferation, migration, and oxidative stress were analyzed through western blots, quantitative polymerase chain reaction, ELISA, and immunofluorescence. ox-LDL induced endothelial cell apoptosis, proliferation arrest, and mobilization inhibition, all of which resveratrol reduced. ox-LDL suppressed the activities of mitochondrial respiration complex I and III and reduced levels of intracellular antioxidative enzymes, resulting in reactive oxygen species overproduction and mitochondrial dysfunction. Resveratrol treatment upregulated Bnip3-related mitophagy and prevented ox-LDL-mediated mitochondrial respiration complexes inactivation, sustaining mitochondrial membrane potential and favoring endothelial cell survival. We found that resveratrol enhanced Bnip3 transcription through hypoxia-inducible factor 1 (HIF1) and 5' AMP-activated protein kinase (AMPK). Inhibition of AMPK and HIF1 abolished resveratrol-mediated protection of mitochondrial redox balance and endothelial viability. Together, these data demonstrate resveratrol reduces hyperlipemia-related endothelial damage by preserving mitochondrial homeostasis.

Prognostic Value of Secreted Frizzled-Related Protein 5 in Heart Failure Patients With and Without Type 2 Diabetes Mellitus.

BACKGROUND: Patients with heart failure (HF) with diabetes mellitus have distinct biomarker profiles compared with those without diabetes mellitus. SFRP5 (secreted frizzled-related protein 5) is an anti-inflammatory adipokine with an important suppressing role on the development of type 2 diabetes mellitus (T2DM). This study aimed to evaluate the prognostic value of SFRP5 in patients with HF with and without T2DM. METHODS: The study included 833 consecutive patients with HF, 312 (37.5%) of whom had T2DM. Blood samples were collected at presentation, and SFRP5 levels were measured. The primary outcome was the composite end points of first occurrence of HF rehospitalization or all-cause mortality during follow-up. RESULTS: During median follow-up of 2.1 years, 335 (40.2%) patients in the cohort experienced the composite primary outcome. After adjustment for multiple risk factors, each doubling of SFRP5 level was associated with a 21% decreased risk of primary outcomes in the overall study population (P<0.001). Subgroup analyses showed that the association between level of SFPR5 and primary outcomes may be stronger in patients with T2DM (hazard ratio, 0.69 [95% CI, 0.61-0.79]) than in patients without T2DM (hazard ratio, 0.89 [95% CI, 0.79-1.01]; interaction P=0.006). Similar associations were observed when taking SFRP5 as a categorical variable. Addition of SFRP5 significantly improved discrimination and reclassification of the incident primary outcomes beyond clinical risk factors and N-terminal pro-B-type natriuretic peptide in all patients with HF and those with T2DM (all P<0.01). CONCLUSIONS: SFRP5 is an independent novel biomarker for risk stratification in HF, especially in HF with T2DM.

A subset of circulating microRNAs is expressed differently in patients with myocardial infarction.

The objective of the present study was to analyze the differences in the plasma microRNA (miRNA) expression profiles between patients with myocardial infarction (MI) (with or without heart failure) and individuals in a normal control group using an miRNA array. Specific miRNAs were selected to explore novel circulating markers for MI and heart failure. A total of 15 patients with heart failure and 10 patients without heart failure following acute MI (AMI) were recruited as the AMI with heart failure (AMHF) and with no heart failure (AMNHF) groups, respectively. In addition, 10 patients with an older (≥ 1 year) MI with heart failure were selected as the old MI and heart failure (OMHF) group. Finally, 10 patients with normal coronary angiograms were recruited as the control (N) group. The plasma of peripheral venous blood was collected for miRNA array detection. In the AMHF group, the expression of 17 miRNAs was upregulated and the expression of 21 miRNAs was downregulated by >1.5-fold compared with that in the AMNHF group. Compared with the N group, the expression of miRNAs in the AMNHF group was upregulated in 38 and downregulated in 48 cases by >1.5-fold. Compared with the OMHF group, 13 miRNAs were upregulated and 43 were downregulated by >1.5-fold in the AMHF group. Significant differences in the miRNA expression profiles were observed between patients with different stages of heart failure following MI and individuals in the normal control group. These differences were determined using miRNA array analysis methods based on the peripheral blood plasma. Thus, the specific miRNAs identified in this study may be novel circulating markers for MI and heart failure.