Abstract 494: Mitral to Meninges: Aspergillus Endocarditis With Septic Emboli

Introduction: Fungal endocarditis comprises less than 2% of infective endocarditis, with Aspergillus causing less than 28% of fungal endocarditis. Fungal endocarditis should be suspected in immunocompromised patients with persistent fevers, negative blood cultures, and vegetation on echocardiography. Invasive Aspergillus can affect any organ, but typically begins in the respiratory tract. Mortality rates climb to 90% with signs of hematogenous spread, such as cerebral abscesses. Case Presentation: Patient is a 53-year-old female with a past medical history of Sweet syndrome and chronic pancreatitis. Patient was admitted for persistent fevers and confusion. Patient was tachycardic but normotensive with a temperature of 102.5 F. Labs included significantly elevated serum LDH and Beta-D-Glucan. Blood cultures remained negative. Lumbar puncture cultures were negative; CSF cytology revealed pleocytosis with positive Aspergillus galactomannan serum antigen. Head MRI revealed multiple peripherally enhancing supratentorial lesions and intracranial abscesses (largest 8.4 mm) with ventriculitis of lateral ventricles, right greater than left. Transesophageal Echocardiogram (TEE) revealed mitral valve vegetation at A2 segment, no surrounding perivalvular abscess, minimal mitral regurgitation (MR). Management: Antibiotics were discontinued and patient was counseled on avoiding glucocorticoids. Patient was transferred to large tertiary center for Neurosurgery evaluation but was not candidate for biopsy/aspiration of the ring-enhancing lesions per Neurosurgery. Cardiothoracic Surgery was also consulted and patient was not a candidate for mitral valve replacement due to small size of vegetation without abscess and only mild MR. Voriconazole was continued and patient ultimately demonstrated a slow improvement in her strength and mental status over the next 6 months. Discussion: Mitral endocarditis from Aspergillus is rare but has a very high mortality rate. This case illustrates the importance of early recognition of systemic fungal infections in the setting of immunosuppression. Glucocorticoids and broad-spectrum antibiotics placed this patient at elevated risk for invasive Aspergillosis, which led to mitral endocarditis and subsequent cerebral abscesses from septic emboli.

Proteomic analyses of ECM during pancreatic ductal adenocarcinoma progression reveal different contributions by tumor and stromal cells

Pancreatic ductal adenocarcinoma (PDAC) has prominent extracellular matrix (ECM) that compromises treatments yet cannot be nonselectively disrupted without adverse consequences. ECM of PDAC, despite the recognition of its importance, has not been comprehensively studied in patients. In this study, we used quantitative mass spectrometry (MS)-based proteomics to characterize ECM proteins in normal pancreas and pancreatic intraepithelial neoplasia (PanIN)- and PDAC-bearing pancreas from both human patients and mouse genetic models, as well as chronic pancreatitis patient samples. We describe detailed changes in both abundance and complexity of matrisome proteins in the course of PDAC progression. We reveal an early up-regulated group of matrisome proteins in PanIN, which are further up-regulated in PDAC, and we uncover notable similarities in matrix changes between pancreatitis and PDAC. We further assigned cellular origins to matrisome proteins by performing MS on multiple lines of human-to-mouse xenograft tumors. We found that, although stromal cells produce over 90% of the ECM mass, elevated levels of ECM proteins derived from the tumor cells, but not those produced exclusively by stromal cells, tend to correlate with poor patient survival. Furthermore, distinct pathways were implicated in regulating expression of matrisome proteins in cancer cells and stromal cells. We suggest that, rather than global suppression of ECM production, more precise ECM manipulations, such as targeting tumor-promoting ECM proteins and their regulators in cancer cells, could be more effective therapeutically.

Evaluation clinical and biochemical characteristics of patients with chronic pancreatitis

Objective: Chronic pancreatitis is a chronic, progressive, irreversible benign inflammatory process, resulting in structural changes with disorders of functional exocrine and endocrine parenchyma by a fibrotic and inflammatory tissue. Based on clinical characteristics and morphology to diagnose chronic pancreatitis. This study was assessing the clinical, biochemical characteristics of chronic pancreatitis patients; and evaluating the relationship between grade chronic pancreatitis and clinical, biochemical characteristics. Subjects and methods: A cross-sectional study was conducted on 51 patients with chronic pancreatitis diagnosed based on Rosemont Criteria in endoscopic ultrasound and Japanese clinical diagnostic criteria for chronic pancreatitis. Results: The prevalence of male was higher than female (70.5%/29.5%) and most common in the age group of 41 - 60 about 55%. The prevalence of patients with a history of alcohol abuse was highest with 31.3%, smoking cigarette more than 20 pack-years about 4.1%. The clinical characteristics of patients with chronic pancreatitis are highest in abdominal pain about 66.6% and lowest in jaundice about 5.8%. About biochemical characteristics, an increase of amylase, lipase were found in 29.5% and 31.5%, respectively. The diabetes mellitus were found in 25.6%. A statistically significative difference of abdominal pain was found between the chronic pancreatitis and early chronic pancreatitis patients (p=0.0003). Mean level of lipase in chronic pancreatitis patient is 33.7 U/L(3.3-195) and early chronic pancreatitis patient is 53.1 U/L (20.5-109), with significiant difference (p=0.04). Conclusions: Alcohol consumption, heavy smoking and diabetes mellitus were the most important risk factors of chronic pancreatitis. Abdominal pain was constant while hyperamylasemia and hyperlipasemia was found only in 29.5% and 31.5% patients. Rate of abdominal pain and mean level of serum lipase were different between chronic pancreatitis and early chronic pancreatitis patients. Key words: chronic pancreatitis, endoscopic ultrasound

Hydrogen Treatment Protects Mice Against Chronic Pancreatitis by Restoring Regulatory T Cells Loss

Background/Aims: Chronic pancreatitis is an inflammatory disease of the pancreas characterized by progressive tissue destruction and fibrogenesis. The development of chronic pancreatitis is associated with immune cell dysregulation. Currently, the specific and effective treatment of chronic pancreatitis remains absent. Methods: By using an L-arginine induced chronic pancreatitis mouse model, we tested the therapeutic potential of hydrogen, a strong hydroxyl radicals scavenger, in the chronic pancreatitis model. Tissue inflammation, damage and fibrosis were analyzed on HE, TUNEL, MPO, and sirius staining. Pancreas levels of MDA content, SOD activity, TNF-α , IL-10 cytokine expression and serum amylase and lipase activity were determined by ELISA and absorbance assay. Apoptosis, T cells subtype proportion and intracellular level of reactive oxygen species (ROS) were analyzed by flow cytometry. Tregs adoptive transfer and CD25 neutralization were used to validate the role of Tregs in chronic pancreatitis. Results: We found that hydrogen treatment significantly improved multiple symptoms of chronic pancreatitis. The number of Tregs was reduced in chronic pancreatitis mice, while hydrogen treatment restored the Treg loss by L-arginine administrations. Depletion of Tregs abolished the protective effect of hydrogen treatment in chronic pancreatitis. In vitro study showed that hydrogen blocked ROS generation in Tregs and promoted Tregs survival. Conclusion: Hydrogen treatment showed reliable benefits in controlling the severity of chronic pancreatitis. Our study supported that hydrogen could be used as a novel treatment in chronic pancreatitis patient in the future.

Combined Medical Treatment Of Chronic Pancreatitis

The aim of the study was to determine the most effective medical treatment of patients with chronic pancreatitis, by using either pancreatin alone or in combination with proton pump inhibitor (PPI) or PPI and non-steroidal anti-inflammatory drug (NSAID). Patients with chronic pancreatitis, who did not require a surgical treatment, received medical treatment for a one–month period: 20 patients received pancreatin monotherapy; 48 patients were given a combination of pancreatin and PPI; 38 patients were treated with a combination of pancreatin, PPI and NSAID (PNP therapy group). In comparison with other groups, patients in the PNP therapy group showed improvement in body mass index, abdominal pain, bowel movements, chronic pancreatitis severity, as well as their quality of life assessment (p< 0.05). The combination of pancreatin, PPI and NSAID was the most effective among those applied in chronic pancreatitis patient treatment. A one–month long course of this therapy was safe and did not cause any significant adverse effects. The combination of pancreatin, PPI and NSAID for treatment of chronic pancreatitis can be recommended, as it is based on pathogenesis of the disease, effective, safe and economically advantageous.