Lipoprotein(a) as a risk factor for atherosclerotic cardiovascular disease in patients in non-metropolitan areas of Brandenburg, Germany.

Background and aims: In the non-metropolitan region of Brandenburg (Germany), which is characterized by high rates of cardiovascular diseases and underserved medical care, there is a lack of awareness regarding lipoprotein(a) [Lp(a)] as a risk factor. In addition, data from patients with atherosclerotic cardiovascular disease (ASCVD) in diverse regional backgrounds, including the understudied Brandenburg cohort, and various healthcare statuses remain insufficient. Methods: In this WalkByLab study, Lp(a) levels were monitored in a non-metropolitan cohort (n = 850) in Brandenburg, Germany, comprising 533 patients at high cardiovascular risk and 317 healthy controls. Patients underwent a comprehensive angiological screening, which included blood serum analysis, assessment of medical and family history, cardiovascular risk, and disease status, and evaluation of lifestyle and quality of life. All parameters were evaluated with regard to two groups based on Lp(a) levels: low (<50 mg/dl) and high (≥50 mg/dl). Results: Brandenburg patients with cardiovascular diseases showed higher Lp(a) levels than healthy controls (24.2% vs. 14.8%, p = 0.001). Logistic regression analysis with different characteristics revealed that Lp(a) was an independent risk factor significantly associated with ASCVD (OR 2.26, 95% CI 1.32-3.95, p = 0.003). The high-Lp(a) group showed a higher proportion of patients with coronary artery disease, peripheral artery disease, or cerebrovascular disease compared to the low-Lp(a) group (50% vs. 36.8%; 57.7% vs. 45.8%; 17.6% vs. 9.2%; p = 0.004); also, a higher percentage of patients in the high-Lp(a) group had heart failure (72.8% vs. 53.2%, p = 0.014) and myocardial infarction (24.7% vs. 13.9%, p = 0.001). The high-Lp(a) group exhibited higher rates of statins (63.1% vs. 50.4%, p = 0.003), ezetimibe (14.8% vs. 5.5.%, p = 0.001), and beta-blockers (55.7% vs. 40.7%, p = 0.001) use. Lp(a) levels were found to be independent of physical activity or smoking behavior and did not change over time (12 months). Conclusions: Our study highlights the significance of elevated Lp(a) levels in Brandenburg cardiovascular patients and identifies them as an independent risk factor for ASCVD, which has implications for addressing cardiovascular health of non-metropolitan populations.

Percutaneous Magnetic Resonance Imaging-Guided Coaxial Cutting Needle Biopsy of Pancreatic Lesions: Diagnostic Accuracy and Safety.

PURPOSE: To appraise the diagnostic performance of magnetic resonance imaging-guided percutaneous coaxial cutting needle biopsy of pancreatic lesions using a 0.4-T open magnetic resonance imaging scanner with optical tracking navigation. MATERIALS AND METHODS: This retrospective study included 158 patients who underwent magnetic resonance imaging-guided pancreatic lesion biopsy procedures from May 2019 to December 2020. Two to four specimens were collected from each patient. Pathological diagnosis and clinical follow-ups were conducted to establish the final diagnosis. The procedures were evaluated for sensitivity, specificity, positive and negative predictive values, diagnostic accuracy, and complications. The Cardiovascular and Interventional Radiological Society of Europe guidelines were used to classify complications. RESULTS: Biopsy pathology revealed 139 pancreatic tumor malignancies and 19 benign pancreatic lesions. Finally, 151 patients were diagnosed with pancreatic malignancy and 7 with benign disease confirmed by surgery, re-biopsy, and clinical follow-up. The sensitivity, specificity, positive and negative predictive value, and accuracy for diagnosis of pancreatic diseases were 92.1%, 100%, 100%, 36.8%, and 92.4%, respectively. The biopsy accuracy was significantly related to the size (≤ 2 cm, 76.2%; 2-4 cm, 94.0%; > 4 cm, 96.2%, P = .02) and not the lesion's location (head of pancreas, 90.7%; neck of pancreas, 88.9%; body of pancreas, 94.3%; tail of pancreas, 96.7%, P = .73). Minor complications included two patients experiencing mild abdominal pain and two with a minor occurrence of hemorrhage. CONCLUSIONS: Percutaneous magnetic resonance imaging-guided pancreatic lesion biopsy combined with optical navigation has high diagnostic accuracy and is safe for clinical practice. Level of Evidence Level 4, Case-series.

Autophagy-related genes analysis reveals potential biomarkers for prediction of the impaired walking capacity of peripheral arterial disease.

BACKGROUND: The role of autophagy and autophagy-related genes in peripheral arterial disease (PAD) remains unknown and may be of diagnostic and prognostic value. The aim of this study is to investigate the relationship between autophagy and PAD, and identify potential diagnostic or prognostic biomarkers for medical practice. METHODS: Differentially expressed autophagy-related genes in PAD were explored from GSE57691 and validated in our WalkByLab registry participants by quantitative real-time polymerase chain reaction (qRT-PCR). The level of autophagy in peripheral blood mononuclear cells (PBMCs) of WalkByLab participants was assessed by analyzing autophagic marker proteins (beclin-1, P62, LC3B). Single sample gene set enrichment analysis (ssGSEA) was used to evaluate the immune microenvironment within the artery wall of PAD patients and healthy persons. Chemokine antibody array and enzyme-linked immunosorbent assay were used to assess the chemokines in participants' plasma. Treadmill testing with Gardner protocol was used to evaluate participants' walking capacity. Pain-free walking distance, maximum walking distance, and walking time were recorded. Finally, a nomogram model based on logistic regression was built to predict impaired walking performance. RESULTS: A total of 20 relevant autophagy-related genes were identified, and these genes were confirmed to be expressed at low levels in our PAD participants. Western blotting demonstrated that the expression of autophagic marker proteins beclin-1 and LC3BII were significantly reduced in PAD patients' PBMCs. ssGSEA revealed that most of the autophagy-related genes were strongly correlated with immune function, with the largest number of associated genes showing interaction between cytokine-and-cytokine receptors (CCR). In this context, the chemokines growth-related oncogene (GRO) and neutrophil activating protein2 (NAP2) are highly expressed in the plasma of WalkByLab PAD patients and were significantly negatively correlated with the walking distance assessed by Gardner treadmill testing. Finally, the plasma NAP2 level (AUC: 0.743) and derived nomogram model (AUC: 0.860) has a strong predictive potential to identify a poor walking capacity. CONCLUSIONS: Overall, these data highlight both the important role of autophagy and autophagy-related genes in PAD and link them to vascular inflammation (expression of chemokines). In particular, chemokine NAP2 emerged as a novel biomarker that can be used to predict the impaired walking capacity in PAD patients.

Generation of hepatic spheroids using human hepatocyte-derived liver progenitor-like cells for hepatotoxicity screening.

Rationale: The idiosyncratic drug-induced liver injury (iDILI) is a major cause of acute liver injury and a key challenge in late-stage drug development. Individual heterogeneity is considered to be an essential factor of iDILI. However, few in vitro model can predict heterogeneity in iDILI. We have previously shown that mouse and human hepatocytes can be converted to expandable liver progenitor-like cells in vitro (HepLPCs). However, the limited proliferation potential of human HepLPCs confines its industrial application. Here, we reported the generation of a novel hepatocyte model not only to provide unlimited cell sources for human hepatocytes but also to establish a tool for studying iDILI in vitro. Methods: Human primary hepatocytes were isolated by modified two-step perfusion technique. The chemical reprogramming culture condition together with gene-transfer were then used to generate the immortalized HepLPC cell lines (iHepLPCs). Growth curve, doubling time, and karyotype were analyzed to evaluate the proliferation characteristics of iHepLPCs. Modified Hepatocyte Maturation Medium and 3D spheroid culture were applied to re-differentiate iHepLPCs. Results: iHepLPCs exhibited efficient expansion for at least 40 population doublings, with a stable proliferative ability. They could easily differentiate back into metabolically functional hepatocytes in vitro within 10 days. Furthermore, under three-dimensional culture conditions, the formed hepatic spheroids showed multiple liver functions and toxicity profiles close to those of primary human hepatocytes. Importantly, we established a hepatocyte bank by generating a specific number of such cell lines. Screening for population heterogeneity allowed us to analyze the in vitro heterogeneous responses to hepatotoxicity induced by molecular targeted drugs. Conclusions: In light of the proliferative capacity and the heterogeneity they represented, these iHepLPCs cell lines may offer assistance in studying xenobiotic metabolism as well as liver diseases in vitro.

Hyperoside Attenuates Hepatic Ischemia-Reperfusion Injury by Suppressing Oxidative Stress and Inhibiting Apoptosis in Rats.

PURPOSE: Hepatic ischemia-reperfusion (IR) injury is a serious complication of many clinical conditions, which may lead to liver or multiple organ failure. Hyperoside, a flavonoid compound, has been reported to protect against myocardial and cerebral injury induced by IR. This study aimed to investigate the protective effects of hyperoside on hepatic IR injury in rats. METHODS: Using the 70% hepatic IR injury model, we divided 32 male Wistar rats into 4 groups (n = 8): sham-operated, IR+saline (saline/p.o.), IR+vehicle (carboxy methyl cellulose/p.o.), and IR+hyperoside (50 mg/kg/d/p.o.). At 24 hours after reperfusion, blood and liver tissue were collected. The effects of hyperoside on hepatic IR injury were assessed through tests of serum transaminase, hepatic histopathology, and measurement of markers of oxidative stress and apoptosis. RESULTS: Pretreatment with hyperoside protected the liver from IR injury by a reduction in serum aspartate aminotransferase/alanine aminotransferase levels and a decrease in the severity of histologic changes. Hyperoside treatment also decreased the activity of malondialdehyde, increased the activities of superoxide dismutase and glutathione peroxidase, up-regulated the expression of heme oxygenase 1 and NAD(P)H:quinone oxidoreductase 1, and reduced the apoptotic index after IR injury. A decrease in the expression of caspase-3 and an increase in the ratio of B cell lymphoma 2 to B cell lymphoma 2-associated X also were observed. CONCLUSION: Hyperoside has a protective effect on hepatic IR injury in rats, which may be due to its antioxidant and antiapoptotic properties.

Navigated magnetic resonance imaging-guided celiac plexus neurolysis using an open magnetic resonance system for pancreatic cancer patients with upper abdominal pain.

AIMS: The study aimed to evaluate the safety and efficacy of navigated magnetic resonance imaging (MRI)-guided celiac plexus neurolysis (CPN) using a 0.4 T open magnetic resonance system. MATERIALS AND METHODS: A retrospective analysis was performed on 23 patients with unresectable pancreatic cancer who underwent MRI-guided CPN between January 2013 and October 2017. Clinical outcomes were evaluated by recording the complications, the opioid intake, and questionnaire before the intervention and at the time point of 1 day, 1 month, and 3 months postprocedure using a numerical visual analog scale (VAS). RESULTS: Navigated MRI guidance allowed the precise placement of needle in the targeted area and the visualization of the injected neurolysis agents for all cases. The VAS scores decreased from 8.8 ± 1.0 to 2.9 ± 0.9, 4.2 ± 1.7, and 4.7 ± 1.8 at 1 day, 1 month, and 3 months postprocedure (P < 0.05). This intervention reduced the dosage of opioid consumption 1 month after the procedure (52.3 ± 10.4 mg before the treatment vs. 28.2 ± 4.9 mg after the treatment; P < 0.001). Treatment-related side effects included hematoma in one patient, short episodes of diarrhea in three patients, and hypotension in four patients. CONCLUSIONS: With the assistance of the navigation system, MRI-guided CPN is a safe and effective treatment approach for managing the upper abdominal pain in patients with unresectable pancreatic cancer.

Pre-cesarean prophylactic balloon placement in the internal iliac artery to prevent postpartum hemorrhage among women with pernicious placenta previa.

OBJECTIVE: To evaluate pre-cesarean prophylactic balloon placement (PBP) in the internal iliac artery among women with pernicious placenta previa. METHODS: The present retrospective study included women with pernicious placenta previa who underwent cesarean delivery at Shanghai Renji Hospital, Shanghai, China, between March 1, 2011, and June 30, 2017. Data were compared between patients who did and did not undergo PBP. RESULTS: Among 42 patients included, 20 underwent PBP and 22 did not. Mean ± SD estimated blood loss was 2900.00 ± 2352.21 mL in the PBP group, and 4549.77 ± 2366.67 mL in the non-PBP group (P=0.025). The amount of transfused red blood cells was 8.40 ± 7.14 U and 13.00 ± 7.93 U (P=0.018), respectively. No patients in the PBP group developed postoperative disseminated intravascular coagulopathy, compared with 3 (14%) in the non-PBP group (P=0.087). In the PBP and non-PBP groups, the hospital stay duration was 7.40 ± 3.07 and 8.68 ± 2.58 days (P=0.029), and there were 1 and 7 patients who had obstetric hysterectomies (P=0.027), respectively. Two patients experienced PBP-related adverse events, including thrombosis and re-bleeding. There were no deaths. CONCLUSION: Pre-cesarean PBP in the internal iliac artery was a safe and effective treatment that could reduce the incidence of both postpartum hemorrhage and hysterectomy among women with pernicious placenta previa.