Charalambos Gogos

Pro- versus Anti-inflammatory Cytokine Profile in Patients with Severe Sepsis: A Marker for Prognosis and Future Therapeutic Options

Serum concentrations of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6, and the anti-inflammatory cytokine Il-10, and IL-1 receptor antagonists (IL-1ra) and soluble TNF receptors (sTNFRs) were measured in 65 patients with severe sepsis. All patients were evaluated clinically and microbiologically and were followed up for clinical outcome. Levels of both pro- and anti-inflammatory cytokines were significantly elevated in patients with sepsis. Elevated serum IL-10 and TNF-alpha levels and a high IL-10 to TNF-alpha ratio were associated with death, whereas higher levels of TNF-alpha, IL-6, IL-1ra, and sTNFR were detected in patients with an early hemodynamic deterioration. Interleukin-10 and IL-10:TNF-alpha ratio remained higher in nonsurvivors, whereas IL-10 paralleled the sepsis score. Although both the inflammatory and anti-inflammatory response is profoundly augmented in patients with severe sepsis, the sustained overproduction of the anti-inflammatory cytokine IL-10 is the main predictor of severity and fatal outcome.

Dietary omega-3 polyunsaturated fatty acids plus vitamin E restore immunodeficiency and prolong survival for severely ill patients with generalized malignancy

The aim of the current prospective, randomized control study was to investigate the effect of dietary omega‐3 polyunsaturated fatty acids plus vitamin E on the immune status and survival of well‐nourished and malnourished patients with generalized malignancy.

Virological suppression does not prevent the development of hepatocellular carcinoma in HBeAg-negative chronic hepatitis B patients with cirrhosis receiving oral antiviral(s) starting with lamivudine monotherapy: results of the nationwide HEPNET. Greece cohort study

Objective To evaluate the risk and predictors of hepatocellular carcinoma (HCC) in HBeAg-negative chronic hepatitis B patients of the large HEPNET.Greece cohort study who received long-term oral antivirals starting with lamivudine monotherapy. Design Retrospective analysis of HCC incidence in HBeAg-negative chronic hepatitis B patients from a retrospective–prospective cohort who were treated with nucleos(t)ide analogue(s) starting with lamivudine monotherapy for ≥12 months. Setting A nationwide network of liver centres. Patients 818 patients were included: 517 with chronic hepatitis B only; 160 with compensated cirrhosis; 56 with decompensated cirrhosis; 85 with unclassified disease severity. Interventions All patients were treated with nucleos(t)ide analogue(s) starting with lamivudine monotherapy. Main outcome measures Development of HCC. Results During a median follow-up of 4.7 years, HCC developed in 49 (6.0%) patients. The 5-year cumulative incidence of HCC was higher in patients with cirrhosis than in those with chronic hepatitis B only (11.5% vs 3.2%, respectively; p<0.001). HCC developed in 0.7%, 6.7% and 11.7% of patients <50, 50–60 and >60 years old, respectively (p<0.001). Virological on-therapy remission did not significantly affect the incidence of HCC in all patients or those with cirrhosis, but it showed a trend for lower HCC incidence in patients with chronic hepatitis B only (p=0.076). In multivariate analysis, age, gender and cirrhosis were independently associated with HCC risk regardless of virological remission. Conclusions Long-term therapy with nucleos(t)ide analogue(s) starting with lamivudine monotherapy does not eliminate HCC risk in HBeAg-negative chronic hepatitis B. The risk of HCC is particularly high in patients with cirrhosis, who should remain under HCC surveillance even during effective therapy. Older age and male gender remain independent risk factors for HCC, while virological on-therapy remission does not seem to significantly reduce the overall incidence of HCC.

Prevalence of liver steatosis in patients with chronic hepatitis B: a study of associated factors and of relationship with fibrosis.

Objectives The clinical significance of hepatic steatosis in chronic hepatitis B virus patients is poorly understood. The purpose of this study was to determine risk factors for liver steatosis in chronic hepatitis B patients and its relationship with fibrosis. Methods We retrospectively evaluated liver biopsies from patients with chronic hepatitis B treated in our department. Patients co-infected with other viruses (hepatitis C virus, HIV) or suffering from liver disease of any other cause were excluded from the study, as well as patients consuming alcohol above 30 g/day for males or 20 g/day for females. Liver steatosis, necroinflammation and fibrosis were assessed. Results A total of 233 patients with chronic hepatitis B were included in the study. The mean age was 44.7±16.2 years. There were 164 men (70.4%) and 69 women (29.6%). The majority of patients were HbeAg-negative, 196/233 (84.1%). Thirty-seven patients had cirrhosis (15.9%). Steatosis was present in 42 patients (18%). Steatosis was independently associated with fasting glucose level (P=0.019) and being overweight (body mass index ≥25; P=0.021). No correlation was found with stage of fibrosis, grade of inflammation, alcohol use or other parameters. Ninety-four out of 233 patients (40.3%) had advanced fibrosis. Patients with advanced fibrosis were older than those with minimal or no fibrosis (47.6±17 versus 42.3±15.2 years, P=0.024) and more frequently had a higher grade of necroinflammation activity (57/94 (60.6%) versus 26/139 (18.7%), P<0.0001). There was no significant association between advanced fibrosis and the presence of steatosis or mild alcohol consumption. Conclusion Hepatic steatosis is present in 18% of our patients with biopsy-proven chronic hepatitis B. Steatosis is independently associated only with body mass index and fasting glucose level, risk factors for metabolic steatohepatitis, and was not correlated with the degree of fibrosis.

Early alterations of the innate and adaptive immune statuses in sepsis according to the type of underlying infection

IntroductionAlthough major changes of the immune system have been described in sepsis, it has never been studied whether these may differ in relation to the type of underlying infection or not. This was studied for the first time.MethodsThe statuses of the innate and adaptive immune systems were prospectively compared in 505 patients. Whole blood was sampled within less than 24 hours of advent of sepsis; white blood cells were stained with monoclonal antibodies and analyzed though a flow cytometer.ResultsExpression of HLA-DR was significantly decreased among patients with severe sepsis/shock due to acute pyelonephritis and intraabdominal infections compared with sepsis. The rate of apoptosis of natural killer (NK) cells differed significantly among patients with severe sepsis/shock due to ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP) compared with sepsis. The rate of apoptosis of NKT cells differed significantly among patients with severe sepsis/shock due to acute pyelonephritis, primary bacteremia and VAP/HAP compared with sepsis. Regarding adaptive immunity, absolute counts of CD4-lymphocytes were significantly decreased among patients with severe sepsis/shock due to community-acquired pneumonia (CAP) and intraabdominal infections compared with sepsis. Absolute counts of B-lymphocytes were significantly decreased among patients with severe sepsis/shock due to CAP compared with sepsis.ConclusionsMajor differences of the early statuses of the innate and adaptive immune systems exist between sepsis and severe sepsis/shock in relation to the underlying type of infection. These results may have a major impact on therapeutics.

Risk assessment in sepsis: a new prognostication rule by APACHE II score and serum soluble urokinase plasminogen activator receptor.

IntroductionEarly risk assessment is the mainstay of management of patients with sepsis. APACHE II is the gold standard prognostic stratification system. A prediction rule that aimed to improve prognostication by APACHE II with the application of serum suPAR (soluble urokinase plasminogen activator receptor) is developed.MethodsA prospective study cohort enrolled 1914 patients with sepsis including 62.2% with sepsis and 37.8% with severe sepsis/septic shock. Serum suPAR was measured in samples drawn after diagnosis by an enzyme-immunoabsorbent assay; in 367 patients sequential measurements were performed. After ROC analysis and multivariate logistic regression analysis a prediction rule for risk was developed. The rule was validated in a double-blind fashion by an independent confirmation cohort of 196 sepsis patients, predominantly severe sepsis/septic shock patients, from Sweden.ResultsSerum suPAR remained stable within survivors and non-survivors for 10 days. Regression analysis showed that APACHE II ≥17 and suPAR ≥12 ng/ml were independently associated with unfavorable outcome. Four strata of risk were identified: i) APACHE II <17 and suPAR <12 ng/ml with mortality 5.5%; ii) APACHE II < 17 and suPAR ≥12 ng/ml with mortality 17.4%; iii) APACHE II ≥ 17 and suPAR <12 ng/ml with mortality 37.4%; and iv) APACHE II ≥17 and suPAR ≥12 ng/ml with mortality 51.7%. This prediction rule was confirmed by the Swedish cohort.ConclusionsA novel prediction rule with four levels of risk in sepsis based on APACHE II score and serum suPAR is proposed. Prognostication by this rule is confirmed by an independent cohort.

Clinical prognostic markers in patients with severe sepsis: a prospective analysis of 139 consecutive cases

OBJECTIVES To analyze the clinical characteristics and determine predictive factors of mortality in previously healthy individuals suffering from severe sepsis. METHODS The study included 139 patients with severe sepsis, admitted to the Department of Medicine over a two years period. Data recorded on admission included demographic information, blood pressure, core temperature, white blood count, hepatic and renal function tests, coagulation factors, blood gases, serum lactic acid levels, simplified acute physiology score (SAPS-II) and Glasgow Coma Scale (GCS). RESULTS On admission, 62 patients were hypotensive, 52 had signs of diffuse intravascular coagulation (DIC), 72 had renal and 27 hepatic dysfunction. The overall mortality rate was 27.3%. Twenty-nine patients had septic shock on admission with a mortality rate of 62.07%. Hypoxemia, metabolic acidosis and the presence of DIC were more frequent in non-survivors, who also had significantly higher SAPS-II on admission and days 3 and 7. Independent factors associated with mortality were older age, septic shock, DIC and acute renal failure on admission, as well as SAPS-II at all time points and lactic acid levels on day 7. CONCLUSIONS Septic patients with advanced age, septic shock, renal failure, DIC and metabolic acidosis on admission are at increased risk of mortality. The sustained presence of high SAPS-II and lactacidemia one week after admission are also important risk factors of poor outcome.

Varicella Pneumonia in Adults, A Review of Pulmonary Manifestations, Risk Factors and Treatment

Pneumonia is a rare but serious and occasionally fatal complication of varicella. Two cases of varicella pneumonia were successfully treated with acyclovir in our department. We reviewed the pulmonary manifestations of varicella, the risk factors and the effect of acyclovir on varicella pneumonia on immunocompetent adults. Early, aggressive therapy with acyclovir seems to abort the catastrophic consequences of varicella pneumonia, while oral acyclovir chemoprophylaxis is probably beneficial in high-risk populations with chickenpox.

Serum lipid profile, cytokine production, and clinical outcome in patients with severe sepsis.

PURPOSE The purpose of the study is to evaluate the prevalence and clinical significance of hypolipidemia and the relationship to cytokine concentrations and outcomes in septic patients. MATERIALS AND METHODS A prospective study was undertaken including 50 patients with severe sepsis due to community-acquired infections. Serum concentrations of total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein as well as tumor necrosis factor α (TNF-α), interleukin (IL) 6, IL-8, IL-10, and transforming growth factor (TGF) β1 were determined on admission and days 3 and 10 during hospitalization. RESULTS Of the 50 patients enrolled, 28 survived, whereas 22 died during their hospital stay. Sepsis survivors had significantly higher HDL-C concentrations than nonsurvivors, whereas all patients with HDL-C values greater than 25 mg/dL survived. Baseline levels of TGF-β1 were significantly higher in survivors. High-density lipoprotein levels correlated inversely with TNF-α, IL-6, and IL-10 concentrations and positively with baseline TGF-β1 levels. Independent risk factors of mortality were IL-10 levels on day 3, whereas HDL-C concentration on admission was related to survival. CONCLUSIONS Low cholesterol and lipoprotein concentrations are detected in septic patients, especially in individuals with poor outcome. High-density lipoprotein cholesterol concentration seems to be an early independent predictive marker of survival in severe sepsis.

Procalcitonin as an early indicator of outcome in sepsis: a prospective observational study

This study explores the role of procalcitonin (PCT) in predicting the outcome of sepsis. In a prospective multicentre observational investigation, blood was sampled within 24 h of onset of sepsis in 1156 hospitalised patients; 234 were in the intensive care unit (ICU) at the point of presentation of sepsis while 922 were not. PCT was estimated in serum by the ultrasensitive Kryptor assay in a double-blinded fashion. Among patients outside the ICU, mortality was 8% in those with PCT ≤0.12 ng/mL but 19.9% in those with PCT >0.12 ng/mL [P<0.0001, odds ratio (OR) for death: 2.606; 95% confidence interval (CI): 1.553-4.371]. Among patients whose sepsis presented in ICU, mortality was 25.6% in those with PCT ≤0.85 ng/mL but 45.3% in those with PCT >0.85 ng/mL (P=0.002; OR for death: 2.404; 95% CI: 1.385-4.171). It is concluded that PCT cut-off concentrations can contribute to predicting the outcome of sepsis and might be of particular value in identifying patients who would benefit from ICU admission.