Celiac disease in toddler with atypical onset. Case report.

Celiac disease is a chronic immune-mediated disorder induced in genetically susceptible individuals after ingestion of gluten proteins. An early diagnosis is of highest importance. Ultrasound might show small-bowel intussusception. We present a toddler with one month history of diarrhea and abdominal ultrasound showing ileo-ileal intussusception. Specific serological markers for celiac disease were positive. The duodenal endoscopy showed normal architecture but pathology indicated fully developed celiac disease (Marsh 3c). In conclusion, toddlers, who have even a short history of diarrhea with ultrasound showing ileo-ileal intussusception, can be suspected of celiac disease by positive serologic markers and can be confirmed by duodenal biopsy and pathology.

Assesment of the Duke criteria for the diagnosis of infective endocarditis after twenty-years. An analysis of 241 cases.

BACKGROUND AND AIMS: In the absence of classical features (fever, cardiac murmur, and peripheral vascular stigmata) the diagnosis of infective endocarditis (IE) may be difficult. Current clinical guidelines for the diagnosis and management of IE recommend the use of modified Duke criteria. Correct and prompt diagnosis of IE is crucial for the treatment and outcome of the patients. The aim of this study was to evaluate the presence and the individual value of each criterion of the modified Duke criteria in our patients with infective endocarditis. METHODS: We performed a prospective observational study between January 2008 - June 2014, in which we enrolled consecutive adult patients admitted for suspicion of IE to the Hospital of Infectious Diseases and at the Heart Institute . We used and extensive database in order to collect demographic data, laboratory and echocardiography results, evolution and outcome of the patients. Using the modified Duke criteria we identified 3 categories of IE: definite, possible and rejected. In order to evaluate the importance of each criterion in the diagnosis of IE we tested two hypotheses. First, we excluded each criterion from the final diagnosis and we counted how many cases felt into a lower category. Second, after adding each major and minor criterion, we tested how many cases would have been classifiable as definite IE. RESULTS: The study included 241 adult patients with a mean age 58.16 years and sex ratio male/female 1.94. According to the modified Duke criteria 137 patients had definite IE, 79 patients had possible IE and 25 cases had rejected IE We had blood cultures positive IE in 109 cases and blood culture negative IE (BCNE) in 132 (71.21%) cases. Antibiotic treatment prior to blood culture was recorded in 152 (63.07%) patients. In the absence of the echocardiography major criterion, 43% of cases would become possible. After extraction of major microbiological criterion, only one third of definite cases would become possible. Minor criteria such as fever and predisposition contributed to the diagnosis only in 10% of cases. In the presence of vascular or immunological phenomena, or in the presence of minor microbiological criterion, half of the possible IE cases could become possible. CONCLUSION: Twenty-years after their launch, the Duke criteria for the diagnosis of IE continue to be important tools. Low index of suspicion of IE and inappropriate use of antibiotics may have a great negative impact on the diagnosis of IE. Nowadays, the scarcity of classical Osler manifestations - bacteremia, fever and peripheral stigmata - makes the diagnosis of IE a challenge.

The discriminative capacity of soluble Toll-like receptor (sTLR)2 and sTLR4 in inflammatory diseases.

BACKGROUND: The extracellular domains of cytokine receptors are released during inflammation, but little is known about the shedding of Toll-like receptors (TLR) and whether they can be used as diagnostic biomarkers. METHODS: The release of sTLR2 and sTLR4 was studied in in-vitro stimulations, as well as in-vivo during experimental human endotoxemia (n = 11, 2 ng/kg LPS), and in plasma of 394 patients with infections (infectious mononucleosis, measles, respiratory tract infections, bacterial sepsis and candidemia) or non-infectious inflammation (Crohn's disease, gout, rheumatoid arthritis, autoinflammatory syndromes and pancreatitis). Using C-statistics, the value of sTLR2 and sTLR4 levels for discrimination between infections and non-infectious inflammatory diseases, as well as between viral and bacterial infections was analyzed. RESULTS: In-vitro, peripheral blood mononuclear cells released sTLR2 and sTLR4 by exposure to microbial ligands. During experimental human endotoxemia, plasma concentrations peaked after 2 hours (sTLR4) and 4 hours (sTLR2). sTLR4 did not correlate with cytokines, but sTLR2 correlated positively with TNFα (rs = 0.80, P < 0.05), IL-6 (rs = 0.65, P < 0.05), and IL-1Ra (rs = 0.57, P = 0.06), and negatively with IL-10 (rs = -0.58, P = 0.06), respectively. sTLR4 had a similar area under the ROC curve [AUC] for differentiating infectious and non-infectious inflammation compared to CRP: 0.72 (95% CI 0.66-0.79) versus 0.74 (95% CI 0.69-0.80) [P = 0.80], while sTLR2 had a lower AUC: 0.60 (95% CI 0.54-0.66) [P = 0.0004]. CRP differentiated bacterial infections better from viral infections than sTLR2 and sTLR4: AUC 0.94 (95% CI 0.90-0.96) versus 0.58 (95% CI 0.51-0.64) and 0.75 (95% CI 0.70-0.80), respectively [P < 0.0001 for both]. CONCLUSIONS: sTLRs are released into the circulation, and suggest the possibility to use sTLRs as diagnostic tool in inflammatory conditions.

Characterization of the Acute Inflammatory Response in Measles Infection.

Among 167 hospitalized children with measles, circulating concentrations of interleukin (IL)-6, IL-1ß, IL-1Ra, IL-4, interferon (IFN)-α, IFN-ß, and T helper-17 cytokines were low, whereas leukopenia, increased lactate dehydrogenase, IL-18, and IFN-γ concentrations characterized the inflammatory response. In addition to understanding measles-induced immunologic responses, this profile may assist in differential diagnosis.

Charlson's weighted index of comorbidities is useful in assessing the risk of death in septic patients.

PURPOSE: We investigated the efficiency of the Charlson's weighted index of comorbidities (WIC) in predicting the risk of death in septic patients. MATERIALS AND METHODS: A single-center, 3-year analysis of all septic patients was conducted; WIC and organ failure assessed using the Sepsis-related Organ Failure Assessment (SOFA) score were calculated retrospectively. RESULTS: Of 250 septic patients, 60 patients (34%) had WIC above 2. Fifty-five patients (22%) died during the hospitalization. Increasing WIC was associated with increased mortality. Mean WIC differed significantly between survivors and nonsurvivors (P < .0001), and the univariate logistic regression revealed that risk of death depends significantly of WIC with odds ratio of 1.59 (95% confidence interval, 1.31-1.93; P < .001). The accuracy of prediction for the risk of death was 79.2%. Receiver operating characteristics curve indicated a WIC of 2 as a cutoff value, the association between WIC greater than 2, and the risk of death being described by an odds ratio of 1.87 (95% confidence interval, 1.017-3.457; P = .042); the area under the receiver operating characteristics curve in predicting mortality was 0.81 for the SOFA score and 0.68 for WIC; WIC correlated positively with SOFA (r = 0.27; P < .0001). CONCLUSION: In septic patients, WIC is predictive for hospital mortality, and the risk of death significantly depends on WIC.

Multiplex cytokine profiling in patients with sepsis.

A major goal for the clinical research in sepsis is mapping the various mediators driving the systemic manifestations of infection. Identifying relevant mediators responsible for the physiological alterations during sepsis may offer diagnostic and therapeutic opportunities. We aimed to explore the novel approach of simultaneously measuring several biomolecules using the multiplex technique and to study its relevance in diagnosing and monitoring septic patients. In 30 patients fulfilling American College of Chest Physicians and the Society of Critical Care Medicine sepsis criteria, we simultaneously measured 17 cytokines during the first 7 days after admission. We analysed the results with respect to the presence of septic shock and survival. Five patients died during the study. We found a significant positive correlation between the monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1ß and interleukin (IL)-8 levels in the first 3 days and Sepsis-related Organ Failure Assessment score on day 1. Most cytokines showed no significant difference between patients with mild or severe sepsis. The initial levels of MIP-1ß and granulocyte macrophage colony-stimulating factor were lower in patients with septic shock than in patients without shock. IL-8 and MCP-1 early after admission were higher in the non-survivors (p < 0.05). In the multivariate logistical regression, the initial levels of IL-8 were the most predictive for fatal outcome. Moreover, IL-1ß, IL-6, IL-8, IL-12, interferon-γ, granulocyte colony-stimulating factor and tumour necrosis factor-α exhibited persistent increases in non-survivors. The simultaneous evaluation of multiple cytokines in sepsis may identify complex cytokine patterns that reflect the systemic response associated with shock and mortality.

Clinical aspects and cytokine response in severe H1N1 influenza A virus infection.

INTRODUCTION: The immune responses in patients with novel A(H1N1) virus infection (nvA(H1N1)) are incompletely characterized. We investigated the profile of Th1 and Th17 mediators and interferon-inducible protein-10 (IP-10) in groups with severe and mild nvA(H1N1) disease and correlated them with clinical aspects. METHODS: Thirty-two patients hospitalized with confirmed nvA(H1N1) infection were enrolled in the study: 21 patients with nvA(H1N1)-acute respiratory distress syndrome (ARDS) and 11 patients with mild disease. One group of 20 patients with bacterial sepsis-ARDS and another group of 15 healthy volunteers were added to compare their cytokine levels with pandemic influenza groups. In the nvA(H1N1)-ARDS group, the serum cytokine samples were obtained on admission and 3 days later. The clinical aspects were recorded prospectively. RESULTS: In the nvA(H1N1)-ARDS group, obesity and lymphocytopenia were more common and IP-10, interleukin (IL)-12, IL-15, tumor necrosis factor (TNF)α, IL-6, IL-8 and IL-9 were significantly increased versus control. When comparing mild with severe nvA(H1N1) groups, IL-6, IL-8, IL-15 and TNFα were significantly higher in the severe group. In nonsurvivors versus survivors, IL-6 and IL-15 were increased on admission and remained higher 3 days later. A positive correlation of IL-6, IL-8 and IL-15 levels with C-reactive protein and with > 5-day interval between symptom onset and admission, and a negative correlation with the PaO(2):FiO(2) ratio, were found in nvA(H1N1) groups. In obese patients with influenza disease, a significant increased level of IL-8 was found. When comparing viral ARDS with bacterial ARDS, the level of IL-8, IL-17 and TNFα was significantly higher in bacterial ARDS and IL-12 was increased only in viral ARDS. CONCLUSIONS: In our critically ill patients with novel influenza A(H1N1) virus infection, the hallmarks of the severity of disease were IL-6, IL-15, IL-8 and TNFα. These cytokines, except TNFα, had a positive correlation with the admission delay and C-reactive protein, and a negative correlation with the PaO(2):FiO(2) ratio. Obese patients with nvA(H1N1) disease have a significant level of IL-8. There are significant differences in the level of cytokines when comparing viral ARDS with bacterial ARDS.

Central venous catheter colonization and catheter-related bloodstream infections in critically ill patients: a comparison between standard and silver-integrated catheters.

BACKGROUND AND OBJECTIVE: Catheter-related bloodstream infections are one of the main complications affecting patients in intensive care units. This prospective, randomized, unblinded, controlled study investigated colonization and infection rates of standard central venous catheters in comparison with the rates for silver-integrated catheters in the intensive care unit. METHODS: Complete data were evaluated for 272 catheters inserted into 230 patients (141 standard and 131 silver-integrated central venous catheters). Patient and catheter characteristics were documented for all patients. Positive catheters were detected by semi-quantitative and quantitative microbiologic techniques. Peripheral blood cultures were obtained at the time of catheter removal. RESULTS: There was no significant difference in the colonization rates and the colonization per 1000 catheter days between the standard and silver-integrated catheters. Using the Kaplan-Meier curves (long-rank test), there was a significant difference in the incidence of colonization and infections over time between standard and silver-integrated catheters (P<0.01 and P<0.05, respectively). Whereas standard catheters were first colonized 3 days after the insertion, silver-integrated catheters were first colonized 5 days after insertion. CONCLUSION: Silver-integrated central venous catheters did not prevent catheter colonization and infections in critically ill patients, but there might be a significant difference in the incidence of colonization and infections over time between standard polyurethane and silver-integrated catheters.