The role of pancreatic stone protein as a prognostic factor for COVID-19 patients.

OBJECTIVE: The outbreak of Severe Acute Respiratory Syndrome-CoronaVirus 2 (SARS-CoV-2) has rapidly spread throughout the world straining health care systems. Several biomarkers indicate the presence of hyper-inflammation and evaluate the severity of the disease. Our aim was to investigate the prognostic value of pancreatic stone protein plasma concentration in patients with SARS-CoV-2 pneumonia. PATIENTS AND METHODS: We prospectively studied 55 patients with acute SARS-CoV-2 pneumonia admitted to our tertiary hospital. Sepsis biomarkers, including pancreatic stone protein (PSP), were measured on admission. The role of these biomarkers in the prediction of in-hospital mortality (28 day) and length of hospital stay was investigated. RESULTS: Although Pancreatic stone protein did not have significant prognostic value for in-hospital mortality, there was a moderate accuracy for prolonged length of stay. The optimal cut-off value for prolonged hospital stay was 51 ng/dL (Sensitivity: 0.65, Specificity: 0.913). CONCLUSIONS: Pancreatic Stone Protein on admission could accurately identify patients requiring prolonged hospitalization. The results of this study can serve as a strong early basis for future validation studies of such an innovative approach.

Toxoplasma gondii meningoencephalitis without cerebral MRI findings in a patient with ulcerative colitis under immunosuppressive treatment.

Toxoplasmosis is the most common opportunistic infection of the central nervous system in immunosupressed patients. It is usually presented as a space-occupying lesion detected by cerebral computerized tomography or magnetic resonance imaging. The diffuse form of the disease (diffuse toxoplasmic meningoencephalitis) lacks the characteristic cerebral radiologic findings rendering pre-mortem diagnosis much more difficult. Herein, we describe a case of toxoplasmic menincoencephalitis, without evidence of cerebral space-occupying lesions, in a patient with ulcerative colitis under combined therapy with systemic glucocorticoids and azathioprine. Diagnosis was based on microscopic examination of cerebrospinal fluid (CSF) for the parasite, whereas, RT-PCR for Toxoplasma gondii was negative. Taking into consideration the limitations of molecular methods, investigation of the etiology of meningeal involvement in patients under immunosuppressive therapy presenting positive serology of previous T. gondii infection, should include microscopic examination of CSF for parasite presence.

The role of obesity in the immune response during sepsis.

BACKGROUND/OBJECTIVES: Sepsis is one of the most important causes of mortality in the developed world, where almost two-thirds of the population suffer from obesity. Therefore, the coexistence of both conditions has become frequent in clinical practice and a growing number of clinical studies attempts to examine the potential effect of obesity on sepsis with controversial results up to now. The present study investigates how obesity influences the immune response of septic patients, by assessing the number and activation state of adipose tissue macrophages, serum and adipose tissue tumor necrosis factor-alpha (TNFα) levels and plasma oxidative stress markers. SUBJECTS/METHODS: The study included 106 patients, divided into four groups (control n=26, obesity n=27, sepsis n=27 and sepsis and obesity n=26). The number of macrophages in subcutaneous and visceral adipose tissue (SAT and VAT) and their subtypes (M1 and M2) were defined with immunohistochemical staining techniques under light microscopy. TNFα mRNA levels were determined in SAT and VAT using real-time reverse transcription-PCR. Serum levels of TNFα were determined with sandwich enzyme-linked immunosorbent assay. Plasma oxidative stress was evaluated using selective biomarkers (thiobarbituric acid-reactive substances (TBARS), protein carbonyls and total antioxidant capacity (TAC)). RESULTS: Sepsis increased the total number of macrophages and their M2 subtype in (VAT), whereas obesity did not seem to affect the concentration of macrophages in fat. Obesity increased TNFα mRNA levels (P<0.05) in VAT as well as the plasma TBARS (P<0.001) and protein carbonyls (P<0.001) in septic patients. The plasma TAC levels were decreased and the serum TNFα levels were increased in sepsis although they were not influenced by obesity. CONCLUSIONS: Obesity is associated with elevated TNFα adipose tissue production and increased oxidative stress biomarkers, promoting the proinflammatory response in septic patients.

Intestinal barrier dysfunction in HIV infection: pathophysiology, clinical implications and potential therapies.

INTRODUCTION: Current pathogenetic aspects on HIV infection highlight the importance of a chronic immune activation ultimately leading to T lymphocyte homeostasis disruption and immune deregulation associated with disease manifestations and progression. It is widely accepted that this continuous immune activation in HIV infection is principally driven by the phenomenon of pathological microbial translocation (MT). METHODS: Review of the literature on the role of intestinal barrier dysfunction in HIV infection, with emphasis on the implicated pathophysiological mechanisms, clinical implications and potentially effective therapeutic interventions. FINDINGS: MT in HIV infection is promoted by a multifactorial disruption of all major levels comprising the intestinal barrier defense. Specifically, HIV infection disrupts the integrity of the intestinal biological (quantitative and qualitative alterations of gut microecology, overgrowth of pathogenic bacteria), immune (depletion of CD4(+) T cells, especially Th17 cells, increased CD4+ FoxP3+ Tregs, decreased mucosal macrophages phagocytic capacity, development of intestinal proinflammatory milieu) and mechanical barrier (enterocytes' apoptosis, disruption of tight junctions). Intestinal barrier dysfunction allows the passage of microbes and immunostimulatory bioproducts from the gut lumen first in the lamina propria and thereafter in the systemic circulation, thus continuously promoting a local and systemic inflammatory response. This chronic immune activation is associated with HIV disease progression, suboptimal response to HAART and development of non-AIDS comorbidities. CONCLUSIONS: We have reached a point where the effective control of HIV viremia by HAART should be combined with emerging pharmacological approaches aiming at the restoration of the intestinal barrier, targeting its diverse levels of structure and function. Elimination of the MT phenomenon would mitigate its effect on immune homeostasis, which might improve the prognosis of the HIV-infected patient in terms of morbidity and mortality.

Serum adiponectin levels in different types of non alcoholic liver disease. Correlation with steatosis, necroinflammation and fibrosis.

BACKGROUND AND STUDY AIMS: In recent studies adiponectin has been implicated in the pathogenesis of non alcoholic liver disease (NAFLD), a common chronic liver disease with a broad spectrum of histopathologic findings. The aim of this study was to investigate the correlation between serum adiponectin levels and steatosis, necroinflammation and fibrosis in different types of NAFLD patients. PATIENTS AND METHODS: Forty three patients with elevated liver enzymes and biopsy proven non alcoholic fatty liver disease and 38 patients with clinically diagnosed NAFLD and permanently normal liver enzymes were prospectively enrolled in the study. Patients with biopsy proven NAFLD were divided into two groups: non alcoholic steatohepatitis (NASH): 25 patients and simple steatosis: 18 patients. Serum adiponectin levels were measured with an ELISA immunoassay, and BMI, fasting serum glucose, total and HDL cholesterol, fasting triglyceride levels and insulin resistance were determined. RESULTS: Groups did not differ in age, sex, BMI, waist circumference and HOMA - IR. Only patients with confirmed NASH had lower serum adiponectin levels in comparison to NAFLD patients with both abnormal (6.6 +/- 4.7 microg/mL vs 10.8 +/- 5.6 microg/mL, p = 0.01) as well as normal liver enzymes (6.6 +/- 4.7 microg/mL vs 9.2 +/- 4.8 microg/mL, p = 0.01). For the whole NAFLD group with elevated liver enzymes no correlation was found between serum adiponectin levels and the degree of liver steatosis or fibrosis stage. Also no correlation was found between adiponectin levels and BMI, ALT, AST, gamma GT or HOMA-IR. CONCLUSIONS: Patients with established NASH have lower serum adiponectin levels than NAFLD patients with normal or abnormal liver enzymes. Adiponectin was not associated with the severity of hepatic fibrosis.

Endoscopic retrogade cholangiopancreatography is safe and effective method for diagnosis and treatment of biliary and pancreatic disorders in octogenarians.

BACKGROUND AND AIM: Diagnosis and treatment of pancreatic and biliary diseases represents a special problem in old patients who often suffer from one or more concomitant diseases. The aim of this study was to evaluate the safety and efficacy of ERCP in very old patients (octogenarians). PATIENTS AND METHODS: Patients 80 years or older who underwent ERCP from October 2001 to December 2005 were studied retrospectively. RESULTS: A total of 209 patients (121 women, 88 men), with a mean age 86 +/- 4.4 years old (80-102) underwent 251 ERCPs. All but three patients tolerated the procedure well. Three procedures were not completed due to patients' discomfort (1.4%). Two of these patients underwent percutaneous transhepatic cholangiography and the other one was treated conservatively. A cholangiogram was obtained in 193 cases (92.3%), although in 7 patients an additional attempt was required. The main endoscopic findings were common bile duct stones in 51.8% (100/193) and cancer in 28% (54/193) of patients. Based on the diagnostic findings, a therapeutic intervention was indicated in 189 patients (90.4%) and was achieved in 181 of them (95.8%). Complications were observed in 9.6% of ERCPs (24/251). Post - ERCP mild pancreatitis was the more frequent complication in 11 procedures (4.4%). No severe pancreatitis was observed. Six procedures were complicated by cholangitis (2.4%) and two by cholecystitis (0.8%). Early surgical intervention was required in 2 cases because of oesophageal perforation and retroperitoneal perforation respectively. Two patients died (0.8%); one patient with pancreatic cancer died due to septic shock after inadequate biliary drainage and the other one died after operation for retroperitoneal perforation. CONCLUSIONS: In conclusion, ERCP is safe and effective method for diagnosis and treatment of biliary and pancreatic disorders in octogenarians despite the high comorbidity in this group of patients.

Evidence for intestinal oxidative stress in patients with obstructive jaundice.

BACKGROUND: Obstructive jaundice results in failure of the intestinal barrier with consequent systemic endotoxemia associated with septic complications. We have recently shown that gut barrier failure in experimental obstructive jaundice is associated with high intestinal oxidative stress. This study was undertaken to investigate whether oxidative alterations occur in the intestinal mucosa of patients with obstructive jaundice. PATIENTS AND METHODS: Fifteen patients with malignant biliary obstruction and no signs of cholangitis and 15 control patients were subjected to duodenal biopsy to assess intestinal oxidative stress, estimated by lipid peroxidation (malondialdehyde - MDA) and glutathione redox state [reduced glutathione (GSH), glutathione disulphide (GSSG) and GSH/GSSG ratio]. In addition, mucosal biopsies were examined histologically and intestinal mucosal protein content was determined biochemically as an index of intestinal trophic state. RESULTS: Patients with obstructive jaundice presented high levels of intestinal oxidative stress, with significantly increased lipid peroxidation (P < 0.001). Glutathione redox state was also suggestive of high intestinal oxidative stress in jaundiced patients, indicated by significantly decreased GSH (P = 0.001) and GSH/GSSG ratio (P = 0.006) and increased GSSG (P = 0.026). Histological examination showed a mild infiltration of the lamina propria by chronic inflammatory cells in obstructive jaundice, whereas duodenal architecture remained intact and epithelial continuity was retained. Duodenal mucosa was atrophic in jaundiced patients as indicated by a significant reduction of mucosal protein content compared with controls (P = 0.001). Among oxidative stress parameters, intestinal GSH exhibited a significant positive correlation with mucosal protein content (r = 0.588, P = 0.021). CONCLUSIONS: Obstructive jaundice in humans induces intestinal oxidative stress, which may be a key factor contributing to intestinal barrier failure and the development of septic complications in this patient population.

Evidence for intestinal oxidative stress in obstructive jaundice-induced gut barrier dysfunction in rats.

AIM: An important factor that promotes bacterial and endotoxin translocation in obstructive jaundice is intestinal injury that causes increased permeability. However, little is known of the submicroscopic biochemical events leading to defects of the intestinal barrier. This study was undertaken to investigate the effect of experimental obstructive jaundice on intestinal lipid peroxidation, protein oxidation and thiol redox state. METHODS: Rats were randomly divided into controls, sham operated and bile duct ligated (BDL). After 10 days, intestinal barrier function was assessed by measuring endotoxin in portal and aortic blood. Tissue samples from the terminal ileum were examined histologically and morphometrically, while other samples were homogenized for the determination of lipid peroxidation, protein oxidation and thiol redox state [reduced glutathione (GSH), oxidized glutathione (GSSG), total non-protein mixed disulphides (NPSSR), protein thiols (PSH) and protein disulphides (PSSP)]. RESULTS: Obstructive jaundice compromised intestinal barrier function leading to significant portal and systemic endotoxaemia. The intestinal mucosa in jaundiced rats was atrophic with significantly decreased villous density and total mucosal thickness. Determination of biochemical parameters of oxidative stress in the intestine showed increased lipid peroxidation and protein oxidation in BDL-rats. Thiol redox state revealed the presence of intestinal oxidative stress in jaundiced rats, indicated by a decrease in GSH and increased GSSG, NPSSR and PSSP. CONCLUSIONS: This study shows that experimental obstructive jaundice induces intestinal oxidative stress, which may be a key factor contributing to intestinal injury and leading to endotoxin translocation.