Ribotype 027 Clostridium difficile infections with measurable stool toxin have increased lactoferrin and are associated with a higher mortality

We evaluated clinical and diagnostic indicators of severe C. difficile infection (CDI) and their association with poor clinical outcome. A total of 210 patients positive according to PCR (toxin B: tcdB) were included, with patients having a median age of 62 years and a Charlson co-morbidity index (CI) score of 5. Ninety-one percent (n?=?191) were positive by toxigenic culture and 61 % (n?=?129) had stool toxin. Toxin-positive patients had significantly higher fecal lactoferrin (mean 316 μg/g versus 106 μg/g stool; p?<?0.0001). Forty percent of patients (n?=?85) were infected with ribotype 027 and significantly more of these patients had measurable stool toxin (79 % vs. 50 %; p?<?0.0001). The mean fecal lactoferrin was significantly higher for toxin-positive 027 CDI compared with the 027 toxin-negative group (317 vs 60 μg/g; p?=?0.0014). Ribotype 027 CDI with stool toxin showed a higher all-cause, 100-day mortality compared with non-027 with stool toxin (36 % vs 18 %; p?=?0.017). Logistic regression univariate analysis for odds ratio (OR) and p values revealed that age (OR?=?1.1), intensive care unit treatment (OR?=?2.7), CI (OR?=?1.2), 027 CDI (OR?=?2.1), white blood cell count (OR?=?1.0), albumin level (OR?=?0.1), and stool toxin-positive 027 CDI (OR?=?2.5) were significantly associated with 100-day mortality (p?<?0.05). In conclusion, CDI PCR-positive patients with 027 infection and stool toxin have increased lactoferrin and are at an increased risk of death.     

Which patients should be tested for viruses on bronchoalveolar lavage fluid?

Bronchoalveolar lavage (BAL) is a major diagnostic tool in lung diseases, including viral respiratory infections. We aimed to better define the situations where viral tests should be performed on BAL fluid (BALF). We retrospectively studied all cases where viral tests [immunofluorescence, immunocytochemistry, viral culture, and/or polymerase chain reaction (PCR)] were performed on BALF during a period of 1 year (2008) in our institution. We compared the characteristics of patients with virus-positive versus virus-negative BALF. Of the 636 BALF samples sent to the microbiology laboratory, 232 underwent viral tests. Of these, 70 (30 %) were positive and identified 85 viruses: herpes simplex virus (HSV)-1 (n?=?27), cytomegalovirus (CMV, n?=?23), Epstein–Barr virus (EBV, n?=?18), human herpesvirus (HHV)-6 (n?=?12), respiratory syncytial virus (RSV, n?=?3), rhinovirus (n?=?1), and adenovirus (n?=?1). The variables associated with positive viral tests on univariate analysis were immunosuppression [human immunodeficiency virus (HIV), corticosteroids >10 mg/day for ≥3 weeks, or other immunosuppressive therapy], ground-glass attenuations on computed tomography (CT) scanning, late-onset ventilator-associated pneumonia (VAP), and durations of (i) hospital stay, (ii) intensive care unit (ICU) stay, and (iii) mechanical ventilation before BAL (p?<?0.01 for each comparison). On multivariate analysis, only immunosuppression [odds ratio (OR) 6.4, 95 % confidence interval (CI) [2.8–14.3], p?<?0.0001] and ground-glass attenuations (OR 3.7, 95 % CI [1.8–7.7], p?=?0.0004) remained associated with virus-positive BAL. None of the viral tests performed on BALF for the initial assessment of diffuse infiltrative lung disease (n?=?15) was positive. PCR improved the diagnostic yield of viral tests on BALF by 50 %. Testing for viruses on BALF should be mostly restricted to immunocompromised patients with acute respiratory diseases and/or patients with unexplained ground-glass attenuations on CT scanning.     

Comparison of colistin–carbapenem,colistin–sulbactam,and colistin plus other antibacterial agents for the treatment of extremely drug-resistant Acinetobacter baumannii bloodstream infections

The purpose of this investigation was to compare the efficacy of colistin-based therapies in extremely drug-resistant Acinetobacter spp. bloodstream infections (XDR-ABSI). A retrospective study was conducted in 27 tertiary-care centers from January 2009 to August 2012. The primary end-point was 14-day survival, and the secondary end-points were clinical and microbiological outcomes. Thirty-six and 214 patients [102 (47.7 %): colistin–carbapenem (CC), 69 (32.2 %): colistin–sulbactam (CS), and 43 (20.1 %: tigecycline): colistin with other agent (CO)] received colistin monotherapy and colistin-based combinations, respectively. Rates of complete response/cure and 14-day survival were relatively higher, and microbiological eradication was significantly higher in the combination group. Also, the in-hospital mortality rate was significantly lower in the combination group. No significant difference was found in the clinical (p?=?0.97) and microbiological (p?=?0.92) outcomes and 14-day survival rates (p?=?0.79) between the three combination groups. Neither the timing of initial effective treatment nor the presence of any concomitant infection was significant between the three groups (p?>?0.05) and also for 14-day survival (p?>?0.05). Higher Pitt bacteremia score (PBS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Charlson comorbidity index (CCI), and prolonged hospital and intensive care unit (ICU) stay before XDR-ABSI were significant risk factors for 14-day mortality (p?=?0.02, p?=?0.0001, p?=?0.0001, p?=?0.02, and p?=?0.01, respectively). In the multivariable analysis, PBS, age, and duration of ICU stay were independent risk factors for 14-day mortality (p?<?0.0001, p?<?0.0001, and p?=?0.001, respectively). Colistin-based combination therapy resulted in significantly higher microbiological eradication rates, relatively higher cure and 14-day survival rates, and lower in-hospital mortality compared to colistin monotherapy. CC, CS, and CO combinations for XDR-ABSI did not reveal significant differences with respect to 14-day survival and clinical or microbiological outcome before and after propensity score matching (PSM). PBS, age, and length of ICU stay were independent risk factors for 14-day mortality.     

Bilirubin in the early course of venovenous extracorporeal membrane oxygenation support for refractory ARDS

Bilirubin is known as a marker of hepatic dysfunction and is incorporated in scoring algorithms to assess prognosis in critically ill patients. No data are so far available on the prognostic role of hepatic dysfunction in patients with severe ARDS on venovenous extracorporeal membrane oxygenation (VV-ECMO) support. In 112 consecutive patients with severe ARDS treated with VV-ECMO, we aimed at assessing whether increased bilirubin during the first 72 h could affect early death. Increased serum bilirubin (≥1.2 mg/dl) was detectable in 29 patients (25.9%) who were older (p = 0.031), exhibited a higher SOFA score (p = 0.006), were more frequently given pre-ECMO muscular blockers (p = 0.001) and supported with ECMO for a longer period (p = 0.024), when compared to patients with normal bilirubin. No difference in in-ICU mortality rate was observed between the two subgroups. In survivors, bilirubin showed a progressive and significant decrease (p = 0.032) during the first 72 h of ECMO support, while it increased in dead patients (p = 0.007).The mortality rate was higher in patients with increased bilirubin at 24, 48 and 72 h after ECMO start in respect to that of patients with normal values. Pre-ECMO increased bilirubin values (≥1.2 mg/dl), being detectable in about one-fourth of the entire population, is not associated with increased in-ICU mortality, while the persistence of increased bilirubin values after 24 h of ECMO start and within the first 3 days identified a subgroup of patients at higher risk of death.     

Efficacy evaluation of iclaprim in a neutropenic rat lung infection model with methicillin-resistant <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> entrapped in alginate microspheres

The objective of this study was to demonstrate the efficacy of iclaprim in a neutropenic rat lung infection model with methicillin-resistant Staphylococcus aureus (MRSA) entrapped in alginate beads. An inoculum of 5.25?×?10⁵ colony-forming units (CFU)/mL of S. aureus strain AH1252 was administered intratracheally to rats with prepared alginate bacteria suspensions. Beginning 2 h post-infection, rats received: (1) iclaprim 80 mg/kg (n?=?16); (2) iclaprim 60 mg/kg (n?=?16), or (3) vancomycin 50 mg/kg (n?=?24), for 3 days via subcutaneous (SC) injection every 12 h. Twelve hours after the last treatment, rats were euthanized and lungs collected for CFU determination. Iclaprim administered at 80 mg/kg or 60 mg/kg or vancomycin 50 mg/kg SC twice a day for 3 days resulted in a 6.05 log₁₀ CFU reduction (iclaprim 80 mg/kg compared with control, p?<?0.0001), 5.11 log₁₀ CFU reduction (iclaprim 60 mg/kg compared with control, p?<?0.0001), and 3.42 log₁₀ CFU reduction, respectively, from the controls (p?<?0.0001). Iclaprim 80 mg/kg and 60 mg/kg resulted in 2.59 and 1.69 log₁₀ CFU reductions, respectively, from vancomycin-treated animals (80 mg/kg iclaprim vs. vancomycin, p?=?0.0005; 60 mg/kg iclaprim vs. vancomycin, p?=?0.07). Animals receiving iclaprim, vancomycin, and controls demonstrated 100%, 91.7%, and 48.3% survival, respectively. In this neutropenic rat S. aureus lung infection model, rats receiving iclaprim demonstrated a greater CFU reduction than the controls or those receiving vancomycin.     

Liver involvement in patients with brucellosis: results of the Marmara study

Brucellosis is a zoonotic disease that primarily affects the reticuloendothelial system. But, the extent of liver damage in due course of the disease is unclear. This study included 325 brucellosis patients with significant hepatobiliary involvement identified with microbiological analyses from 30 centers between 2000 and 2013. The patients with ≥5 times of the upper limit of normal for aminotransferases, total bilirubin level ≥2 mg/dl or local liver lesions were enrolled. Clinical hepatitis was detected in 284 patients (87.3 %) and cholestasis was detected in 215 (66.1 %) patients. Fatigue (91 %), fever (86 %), sweating (83 %), arthralgia (79 %), and lack of appetite (79 %) were the major symptoms. Laboratory tests showed anemia in 169 (52 %), thrombocytopenia in 117 (36 %), leukopenia in 81 (25 %), pancytopenia in 42 (13 %), and leukocytosis in 20 (6 %) patients. The most commonly used antibiotic combinations were doxycycline plus an aminoglycoside (n?=?73), doxycycline plus rifampicin (n?=?71), doxycycline plus rifampicin and an aminoglycoside (n?=?27). The duration of ALT normalization differed significantly in three treatment groups (p?<?0.001). The use of doxycycline and an aminoglycoside in clinical hepatitis showed better results compared to doxycycline and rifampicin or rifampicin, aminoglycoside, doxycycline regimens (p?<?0.05). However, the length of hospital stay did not differ significantly between these three combinations (p?>?0.05). During the follow-up, treatment failure occurred in four patients (1 %) and relapse was seen in three patients (0.9 %). Mortality was not observed. Hepatobiliary involvement in brucellosis has a benign course with suitable antibiotics and the use of doxycycline and an aminoglycoside regimen seems a better strategy in select patients.     

Serum Growth Arrest-Specific Protein 6 Levels are a Reliable Biomarker of Disease Activity in Systemic Lupus Erythematosus

Purpose

Growth arrest-specific protein 6 (Gas6) has been suggested to be a biomarker of disease activity in patients with systemic lupus erthematosus (SLE). We investigated the clinical significance of this protein in Korean SLE.

Methods

Blood samples were collected from 150 SLE patients and 50 normal controls (NC). In addition, follow-up samples were collected from 50 SLE patients.

Results

Serum Gas6 levels of SLE patients (43.01?±?28.02 ng/mL) were higher than those of NC (20.15?±?9.23 ng/mL, p?<?0.001). When evaluated sensitivity and specificity of the Gas6 for diagnosing SLE using ROC curves, the sensitivity and specificity were 72.7 % and 84 % with a cut-off value of 25.3 ng/mL. In the ROC analysis of Gas6, anti-dsDNA antibody, ESR, complement 3 and complement 4 to identify patients with active lupus, area under the curve (AUC) of Gas6 was highest with 0.763. Serum Gas6 levels were significantly higher in the patients with serositis (70.04?±?30.85 ng/mL) and renal disorder (65.66 ±32.28 ng/mL) compared to those without (41.88?±?27.44 ng/mL, p?=?0.033, 40.3?±?26.33 ng/mL, p?=?0.001, respectively). Gas6 levels were correlated positively with anti-dsDNA antibody (r?=?0.199, p?=?0.015), ESR (r?=?0.204, p?=?0.013) and SLEDAI (r?=?0.512, p?<?0.001). In addition, serum Gas6 levels were correlated negatively with hemoglobin (r?=??0.165, p?=?0.043), lymphocyte count (r?=??0.165, p?=?0.043), complement 3 (r?=??0.343, p?<?0.001) and complement 4 (r?=??0.316, p?<?0.001). Furthermore, change in serum Gas6 levels was correlated with change in SLEDAI levels in the SLE patients that were followed up (r?=?0.524, p?<?0.001).

Conclusion

These results suggest that serum Gas6 can be a reliable clinical marker for monitoring disease activity and treatment response in SLE.     

Hyperferritinemia is Associated with Serologic Antiphospholipid Syndrome in SLE Patients

Ferritin may play a direct role on the immune system. We sought to determine if elevated levels of ferritin in lupus patients correlate with disease activity and organ involvement in a large cohort. Ferritin levels (gender and age adjusted) were assessed in 274 lupus serum samples utilizing the LIASON Ferritin automated immunoassay method. Significant disease activity was determined if European Consensus Lupus Activity Index (ECLAM)?>?2 or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)?>?4. Utilizing an EXCEL database, we compared elevated ferritin levels to manifestations grouped by organ involvement, serology, and previous therapy. The patients were predominantly female (89%), median age was 37 years old, and disease duration was 10.6?±?7.7 years. Hyperferritinemia was found in 18.6% of SLE patients. Compared to subjects with normal ferritin levels, a significantly greater proportion of patients with hyperferritinemia had thrombocytopenia (15.4% vs. 33.3%, p?=?0.003) and lupus anticoagulant (11.3% vs. 29.0%, p?=?0.01). Additionally, compared to normoferritinemic subjects, hyperferritinemic subjects had significantly higher total aCL (99.7?±?369 vs. 30.9?±?17.3 GPI, p?=?0.02) and aCL IgM antibody levels (75.3?±?357.4 vs. 9.3?±?10.3 GPI, p?=?0.02), and marginally lower aCL IgG antibody levels (9.2?±?4.9 vs. 9.7?±?3.9 GPI, p?=?0.096). While the ECLAM score significantly correlated with hyperferritinemia (p?=?0.04), the SLEDAI score was marginally associated with hyperferritinemia (p?=?0.1). Serositis was marginally associated with hyperferritinemia, but not with other manifestations. An association with serologic APS was encountered. Hyperferritinemia was associated with thrombocytopenia, lupus anticoagulant, and anti-cardiolipin antibodies suggest that it may be an early marker for secondary antiphospholipid syndrome in SLE patients.     

Asthma and Hypogammaglobulinemia: an Asthma Phenotype with Low Type 2 Inflammation

Purpose

Little is known about hypogammaglobulinemia (HGG) in asthma patients. No data are available on the characteristics of adult patients with asthma and HGG.

Methods

We conducted a retrospective monocentric study between January 2006 and December 2012. Asthma patients with a serum immunoglobulin (Ig) quantitative analysis were included and classified into two groups depending on their serum IgG concentration: presence or absence of HGG. Clinical, biological, functional, and radiologic characteristics were compared in univariate and multivariate analysis, using a logistic regression model.

Results

In univariate analysis, asthma patients with HGG (n?=?25) were older (58 years old?±?18 vs 49?±?18, p?=?0.04) and more frequently active or former smokers as compared to patients with normoglobulinemia (n?=?80) (56.0 vs 35.0 %, p?=?0.01). Total IgE?<?30 kUI/L was more frequently observed in patients with HGG (53.0 vs 18.3 %, p?=?0.01). HGG asthma patients had lower fraction of exhaled nitric oxide (p?=?0.02), blood eosinophilia (p?=?0.0009), and presented with more severe composite score for bronchiectasis (p?=?0.01). In multivariate analysis, asthma patients with HGG had increased risk of being smokers [OR?=?6.11 (IC 95 %?=?1.16–32.04)], having total IgE concentration?<?30 kUI/L [OR?=?12.87 (IC 95 %?=?2.30–72.15)], and a more severe composite score of bronchiectasis [OR?=?20.65 (IC 95 %?=?2.13–199.74)].

Conclusion

Asthma patients with HGG are older and more often tobacco smoker than asthma patients without HGG. These patients have low type-2 inflammation markers.

     

Risk prediction in infective endocarditis by modified MELD-XI score

The suitability of the model for end-stage liver disease excluding international normalized ratio (MELD-XI) score to predict adverse outcomes in infective endocarditis (IE) patients remains uncertain. This study was performed to explore the prognostic value of the MELD-XI score and modified MELD-XI score for patients with IE. A total of 858 patients with IE were consecutively enrolled and classified into two groups: MELD-XI ≤?10 (n?=?588) and MELD-XI >?10 (n?=?270). Multivariate analysis was performed to determine risk factors independent of MELD-XI score. Higher MELD-XI score was associated with higher in-hospital mortality (15.6 vs. 4.8%, p?<?0.001) and major adverse clinical events (33.3 vs. 18.4%, p?<?0.001). MELD-XI score was an independent predictor of in-hospital death (odds ratio [OR]?=?1.06, 95% CI, 1.02–1.10, p?=?0.005). Based on a multivariate analysis, NYHA class III or IV (3 points), C-reactive protein >?9.5 mg/L (4 points), and non-surgical treatment (6 points) were added to MELD-XI score. Modified MELD-XI score produced higher predictive power than previous (AUC 0.823 vs. 0.701, p?<?0.001). The cumulative incidence of long-term mortality (median 29 months) was significantly higher in patients with modified MELD-XI score >?13 than those without (log-rank?=?25.30, p?<?0.001). Modified MELD-XI score was independently associated with long-term mortality (hazard ratio?=?1.08, 95% CI, 1.04–1.12, p?<?0.001). MELD-XI score could be used as a risk assessment tool in IE. Furthermore, modified MELD-XI score remained simple and more effective in predicting poor prognosis.     

Thirteen years of antibiotic susceptibility surveillance of Pseudomonas aeruginosa from intensive care units and urology services in the Netherlands

The purpose of this study was the evaluation of trends in the antimicrobial resistance of Pseudomonas aeruginosa from intensive care unit (ICU) patients and urology patients in the Netherlands. From 1998 to 2010, 1,927 consecutive P. aeruginosa isolates from ICU (n?=?1,393) and urology service patients (n?=?534) of 14 university and referral hospitals all over the Netherlands were collected and their susceptibility to relevant antibiotics was determined according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. Over time, a significant upward trend in the resistance of P. aeruginosa strains collected from ICUs to piperacillin (1.2 % to 10.6 %, p?=?0.0175), piperacillin–tazobactam (1.2 % to 12.1 %, p?=?0.0008), ceftazidime (1.2 % to 7.8 %, p?=?0.0064), cefepime (4.8 % to 6.4 %, p?=?0.0166), imipenem (6 % to 19.1 %, p?<?0.0001), meropenem (8.3 % to 17 %, p?=?0.0022) and ciprofloxacin (13.1 % to 31.2 %, p?=?0.0024) was observed, as was the prevalence of multi-resistance (1.2 % to 8.5 %, p?=?0.0002). For P. aeruginosa isolates from the urology services, the resistance to imipenem increased (4.1 % to 7.8 %, p?=?0.0006) and to ciprofloxacin it decreased (22.4 % to 18.8 %, p?=?0.025). Like in other countries, in the Netherlands, an increase in multi-resistant Gram-negatives is observed, suggesting the presence and dissemination of several mechanisms of resistance. Our findings emphasise the importance of local surveillance for the setting up of local antibiotic guidelines and to support optimal empiric therapy. With the observed increase in multi-resistance, the direct testing of alternative antibiotics like polymyxins and fosfomycin is essential. Our data also illustrate the importance of adequate outbreak control measures.     

Clinical outcomes and treatment approach for community-associated methicillin-resistant <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> (CA-MRSA) infections in Israel

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are increasingly documented worldwide. We recently identified two major CA-MRSA clones in Israel: USA300 and t991. Here, we assessed clinical outcomes by CA-MRSA clones and the physicians’ treatment approach to CA-MRSA infections. All community-onset, clinical MRSA isolates detected during 2011–2013 by Maccabi Healthcare Services were collected and characterized phenotypically and genotypically; data were collected retrospectively from electronic medical records. Of 309 patients with MRSA infections, 64 were identified as CA-MRSA (21 %). Of the CA-MRSA infections, 72 % had skin and soft tissue infections (SSTIs), 38 % were Panton–Valentine leukocidin (PVL)+, the major clone being USA300 (n?=?13, 54 %). Of PVL? isolates (n?=?40, 62 %), t991 was the major clone. Age was the only predictor for PVL+ CA-MRSA infection (p?<?0.001). Patients with PVL+ CA-MRSA had higher incidence of SSTI recurrences (1.061 vs. 0.647 events per patient/per year, p?<?0.0001) and were more likely to have the SSTI drained (64 % vs. 21 %, p?=?0.003) when compared to PVL? CA-MRSA. USA300 was more common among adults, while t991 was more common among children (p?=?0.002). The physician’s referral to culture results and susceptibility were the only predictors of appropriate antibiotic therapy (p?<?0.001). However, only a minority of physicians referred to culture results, regardless of subspecialties. PVL+ CA-MRSA isolates caused significantly more recurrences of SSTIs and increased the need for drainage compared with PVL? isolates. Physicians’ awareness of CA-MRSA as a cause of SSTIs in the community was suboptimal. Culturing of pus-producing SSTIs is crucial for providing adequate antimicrobials and elucidating MRSA epidemiology.     

White Blood Cell Subtypes after STEMI: Temporal Evolution, Association with Cardiovascular Magnetic Resonance��Derived Infarct Size and Impact on Outcome

The evolution of white blood cells after ST elevation myocardial infarction (STEMI) and their association with infarct size and major adverse cardiac events (MACE) remains unclear. Two hundred eleven patients underwent CMR after STEMI. Infarct mass (grams) was determined. Neutrophil, lymphocyte, and monocyte counts (×1,000 cells/ml) were measured upon arrival and at 12, 24, 48, 72, and 96 h. Patients with large infarctions (3rd tertile????28.5 g vs. 1st and 2nd tertiles?<?28.5 g) showed a larger neutrophil count at 12 h (14.8?±?4.8 vs. 11.4?±?3.3, p?<?0.0001) and an increased monocyte count (maximum at 24 h (0.65[0.50?C0.91] vs. 0.55[0.42?C0.71], p?=?0.004)) but no difference in lymphocyte count. Neutrophil count at 12 h independently predicted large infarctions (OR 1.14, 95%CI [1.04?C1.26], p?=?0.008). During follow-up (median 504 days), 25 MACE occurred. Neutrophil count at 96 h independently predicted MACE (HR 1.2, 95%CI [1.1?C1.4], p?=?0.003). Large infarctions show a marked neutrophil peak and an increasing monocyte count. Neutrophil count independently predicts large infarctions and MACE.     

Clinical Utility of KAP-1 Expression in Thyroid Lesions

Although there are evidences of the involvement of KAP-1 in other tumors, data on differentiated thyroid carcinomas (DTC) are still lacking. We aimed to evaluate KAP-1 clinical utility in the diagnosis and prognosis of DTC. We used both visual immunohistochemistry and a semiquantitative analysis to evaluate KAP-1 expression in 230 thyroid carcinomas and 131 noncancerous thyroid nodules. There were 43 follicular carcinomas (FC) and 187 papillary thyroid carcinomas (PTC), including 130 classic (CPTC), 4 tall cells (TCPTC), and 53 follicular variants (FVPTC). Patients were followed up for 53.8?±?41 months. They were classified as free-of-disease (142 cases) or poor outcome (25 cases—10 deaths), according to their serum Tg levels and image evidences. KAP-1 was identified in 78 % PTC, 75 % TCPTC, 74 % FC, 72 % FVPTC, 55 % FA, 44 % hyperplasia, and 11 % normal thyroid tissues. A ROC analysis identified malignant nodules with 69 % sensitivity and 75 % specificity, using a cutoff of 73.19. In addition to distinguishing benign from malignant thyroid tissues (p?<?0.0001), KAP-1 expression differentiated CPTC from nodular hyperplasia (p?<?0.0001), CPTC from FA (p?=?0.0028), FVPTC from hyperplasia (p?=?0.0039), and FC from hyperplasia (p?=?0.0025). Furthermore, KAP-1 was more expressed in larger tumors (>4 cm; p?=?0.0038) and in individuals who presented recurrences/metastases (p?=?0.0130). We suggest that KAP-1 may help diagnose thyroid nodules, characterize follicular-patterned thyroid lesions, and identify individuals with poor prognosis.     

Optimization of Computed Tomography Protocols: Limitations of a Methodology Employing a Phantom with Location-Known Opacities

This study aimed to determine if phantom-based methodologies for optimization of hepatic lesion detection with computed tomography (CT) require randomization of lesion placement and inclusion of normal images. A phantom containing fixed opacities of varying size (diameters, 2.4, 4.8, and 9.5 mm) was scanned at various exposure and slice thickness settings. Two image sets were compared: All images in the first image set contained opacities with known location; the second image set contained images with opacities in random locations. Following Institutional Review Board approval, nine experienced observers scored opacity visualization using a 4-point confidence scale. Comparisons between image sets were performed using Spearman, Kappa, and Wilcoxon techniques. Observer scores demonstrated strong correlation between both approaches when all opacity sizes were combined (r?=?0.92, p?<?0.0001), for the 9.5 mm opacity (r?=?0.96, p?<?0.0001) and for the 2.4 mm opacity (r?=?0.64, p?<?0.05). There was no significant correlation for the 4.8 mm opacity. A significantly higher sensitivity score for the known compared with the unknown location was found for the 9.5 mm opacity and 4.8 mm opacity for a single slice thickness and exposure condition (p?<?0.05). Phantom-based optimization of CT hepatic examinations requires randomized lesion location when investigating challenging conditions; however, a standard phantom with fixed lesion location is suitable for the optimization of routine liver protocols. The development of more sophisticated phantoms or methods than those currently available is indicated for the optimization of CT protocols for diagnostic tasks involving the detection of subtle change.     

Correlation of methicillin-resistant Staphylococcus aureus vancomycin minimal inhibitory concentration results by Etest and broth microdilution methods with population analysis profile: lack of Etest overestimation of the MIC

Methicillin-resistant Staphylococcus aureus (MRSA) vancomycin minimum inhibitory concentrations (V-MICs) are sometimes reported to be higher according to Etest versus broth microdilution (BMD). These observations are often interpreted as an Etest overestimation of the actual MIC. We measured V-MIC of 484 MRSA blood isolates using Etest, BMD, and a modified BMD (M-BMD) with incremental dilutions parallel to the Etest scale, correlated the results with population analysis profile–area under the curve (PAP-AUC). All MIC tests were done in parallel. The mean V-MIC was comparable (1.83?±?0.44 [Etest], 1.88?±?0.67 [BMD] and 1.75?±?0.57 mg/L [M-BMD]; p?=?0.9 [ANOVA]). The V-MICs/PAP-AUC correlation coefficient was 0.555 (Etest), 0.513 (BMD), and 0.586 (M-BMD). Etest MICs were equal (44.2 %), one dilution higher (21.9 %), two dilutions higher (2.5 %), one dilution lower (29.8 %), and two dilutions lower (1.6 %) than BMD MICs and were equal (61.5 %), one dilution higher (28.3 %), two dilutions higher (0.4 %), one dilution lower (9.5 %), and two dilutions lower (0.2 %) than M-BMD MICs. The mean PAP-AUC for Etest vs M-BMD among isolates with similar Etest/M-BMD MIC values was 0.25?±?0.15 vs 0.35?±?0.13 (p?=?0.8), 0.46?±?0.16 vs 0.50?±?0.17 (p?=?0.8), 0.64?±?0.19 vs 0.67?±?0.21 (p?=?0.9), and 0.90?±?0.31 vs 0.88?±?0.25 (p?=?1.0) for isolates with V-MIC of ≤1, 1.5, 2, and ≥3 mg/L respectively. These results suggest that Etest might not overestimate V-MIC in comparison to M-BMD or BMD; Etest and M-BMD tests depict comparable PAP-AUC and have a higher correlation with PAP-AUC than the conventional BMD, probably because of the more detailed results. Etest may be more suitable than conventional BMD for MIC outcome assessment because of the more detailed MICs.     

Peri-Infarct Zone Characterized by Cardiac Magnetic Resonance Imaging is Directly Associated with the Inflammatory Activity During Acute Phase Myocardial Infarction

Enhanced systemic inflammatory activity (SIA) during myocardial infarction (MI) and the extent of the peri-infarct zone characterized by cardiac magnetic resonance imaging (CMRi) are both associated with increased risk of life-threatening arrhythmias and sudden cardiac death. The present study investigated the existence of association between these two phenomena in 98 patients (55?±?10 years) with ST segment elevation MI. Plasma levels of C-reactive protein (CRP), interleukin-2 (IL-2), and tumor necrosis factor (TNF) were measured on admission (D1) and on the fifth day post-MI (D5). CMRi was performed 2 weeks after MI to quantify peri-infarct zone (PIZ). Between D1 and D5, the increase in CRP (6.0 vs. 5.6 times; p?=?0.02), IL-2 (3.6 vs. 3.4 times; p?=?0.04) and tumor necrosis factor type α (TNF-α; 4.6 vs. 3.9 times; p?=?0.001) were higher in patients with PIZ above the median than in the counterparts. PIZ was correlated with CRP-D5 (r?=?0.69), delta-CRP (r?=?0.7), IL-2-D5 (r?=?0.5), delta-IL-2 (r?=?0.6), TNF-α (r?=?0.5), delta-TNF-α (r?=?0.4; p?=?0.0001). Enhanced activation of SIA during the acute phase of MI is directly related with generation of PIZ.     

Biliary tract infections caused by Aeromonas species

This study investigated the clinical and microbiological characteristics of patients with Aeromonas infections of the biliary tract. Patients with bile cultures positive for Aeromonas species during the period July 2004 to December 2011 were identified from a computerized database of a hospital in Taiwan. Patients with Aeromonas infections of the biliary tract were further identified. During the study period, a total of 1,142 isolates of Aeromonas species were obtained from 750 patients. Of those patients, 91 (12.1 %) had Aeromonas infections of the biliary tract. The annual incidence (episodes per 10,000 patient-days) of biliary tract infections caused by all Aeromonas species was 0.31 in 2007, 0.12 in 2010, and 0.27 in 2011. A. hydrophila was the most common species isolated (n?=?41, 45.1 %), followed by A. caviae (n?=?30, 33.0 %), A. veronii biovar sobria (n?=?15, 16.5 %), and A. veronii biovar veronii (n?=?5, 5.5 %). The majority of patients (n?=?77, 84.6 %) had polymicrobial infections. Hepatobiliary stones (n?=?50, 54.9 %) and hepatobiliary cancer (n?=?38, 41.8 %) were the most common underlying diseases, followed by diabetes mellitus (n?=?29, 31.9 %) and liver cirrhosis (n?=?7, 7.7 %). The in-hospital mortality rate was 8.8 %. Infection-related mortality was associated with underlying immunocompromised condition (p?=?0.044) and use of mechanical ventilation (p?=?0.004), but was not associated with inappropriate antibiotic usage or concomitant bacteremia (n?=?8, 8.8 %). In conclusion, biliary tract infections caused by Aeromonas species are not uncommon and can develop in both immunocompromised and immunocompetent patients; however, patients with underlying hepatobiliary diseases are particularly susceptible to these infections.     

Infective endocarditis in patients with hepatic diseases

Few data have been published regarding the epidemiology and outcome of infective endocarditis (IE) in patients with chronic hepatic disease (CHD). A retrospective analysis of the Studio Endocarditi Italiano (SEI) database was performed to evaluate the epidemiology and outcome of CHD+ patients compared with CHD? patients. The diagnosis of IE was defined in accordance with the modified Duke criteria. Echocardiography, diagnosis, and treatment procedures were in accordance with current clinical practice. Among the 1722 observed episodes of IE, 300 (17.4 %) occurred in CHD+ patients. The cause of CHD mainly consisted of chronic viral infection. Staphylococcus aureus was the most common bacterial species in CHD+ patients; the frequency of other bacterial species (S. epidermidis, streptococci, and enterococci) were comparable among the two groups. The percentage of patients undergoing surgery for IE was 38.9 in CHD+ patients versus 43.7 in CHD? patients (p?=?0.06). Complications were more common among CHD+ patients (77 % versus 65.3 %, p?<?0.001); embolization (43.3 % versus 26.1 %, p?<?0.001) and congestive heart failure (42 % versus 34.1 %, p?=?0.01) were more frequent among CHD+ patients. Mortality was comparable (12.5 % in CHD? and 15 % in CHD+ patients). At multivariable analysis, factors associated with hospital-associated mortality were having an infection sustained by S. aureus, a prosthetic valve, diabetes and a neoplasia, and CHD. Being an intravenous drug user (IVDU) was a protective factor and was associated with a reduced death risk. CHD is a factor worsening the prognosis in patients with IE, in particular in patients for whom cardiac surgery was required.     

Circulating Levels of the Shed Scavenger Receptor sCD163 and Association with Outcome of Critically Ill Patients

Purpose

CD163, a scavenger receptor for haptoglobin-hemoglobin complexes, is almost exclusively expressed by monocytes and macrophages and is shedded (as sCD163) by inflammatory stimuli. Thus, high serum levels of sCD163 predicted mortality in certain inflammatory diseases. We investigated baseline levels, time course of sCD163 levels and CD163 gene expression in relation to mortality and clinical complications in a large heterogeneous cohort of critically ill patients.

Methods

In this pre-planned secondary analysis of two randomized clinical studies, critically ill patients (n?=?1657) were randomized to “conventional” (insulin administered only for blood glucose levels above 215 mg/dL) or “intensive” insulin therapy (glycemia maintained at 80–110 mg/dL) and compared with healthy controls (n?=?112).

Results

Upon admission, critically ill patients had 1.6-fold higher sCD163 levels than controls (P?<?0.0001). Long-stay patients (ICU stay >5 days), non-survivors and patients who developed liver dysfunction or kidney injury had higher baseline sCD163 levels. In multivariable analyses, elevated baseline sCD163 levels were independently associated with ICU mortality, liver dysfunction, and time to discharge from ICU and hospital. sCD163 further increased during ICU stay in patients who developed organ dysfunction and in non-survivors. Avoiding hyperglycemia with insulin slightly reduced circulating sCD163 levels. Hepatic CD163 gene expression in patients was higher than in controls (P?=?0.002) and correlated positively with sCD163 levels (P?=?0.345, P?<?0.0001).

Conclusions

This study hallmarks the association of elevated sCD163 with organ dysfunction and adverse outcome of critical illness and may point to the liver as a potential source.