Mortality due to Multidrug-Resistant Gram-Negative Bacteremia in an Endemic Region: No Better than a Toss of a Coin.

The incidence of multidrug-resistant (MDR) bloodstream infections (BSIs) is associated with high morbidity and mortality. Little evidence exists regarding the epidemiology of BSIs and the use of appropriate empirical antimicrobial therapy in endemic regions. Novel diagnostic tests (RDTs) may facilitate and improve patient management. Data were assessed from patients with MDR Gram-negative bacteremia at a university tertiary hospital over a 12-month period. In total, 157 episodes of MDR Gram-negative BSI were included in the study. The overall mortality rate was 50.3%. Rapid molecular diagnostic tests were used in 94% of BSI episodes. In univariate analysis, age (OR 1.05 (95% CI 1.03, 1.08) p < 0.001), Charlson Comorbidity Index (OR 1.51 (95% CI 1.25, 1.83) p < 0.001), procalcitonin ≥ 1(OR 3.67 (CI 95% 1.73, 7.79) p < 0.001), and monotherapy with tigecycline (OR 3.64 (95% CI 1.13, 11.73) p = 0.030) were the only factors associated with increased overall mortality. Surprisingly, time to appropriate antimicrobial treatment had no impact on mortality. MDR pathogen isolation, other than Klebsiella pneumoniae and Acinetobacter baumanii, was associated with decreased mortality (OR 0.35 (95% CI 0.16, 0.79) p = 0.011). In multivariate analysis, the only significant factor for mortality was procalcitonin ≥ 1 (OR 2.84 (95% CI 1.13, 7.11) p = 0.025). In conclusion, in an endemic area, mortality rates in MDR BSI remain notable. High procalcitonin was the only variable that predicted death. The use of rapid diagnostics did not improve mortality rate.

Circulating microRNAs Related to Bone Metabolism in HIV-Associated Bone Loss.

The pathophysiology of human immunodeficiency virus (HIV)-associated bone loss is complex and to date largely unknown. In this study, we investigated serum expression of microRNAS (miRNAs) linked to bone metabolism in HIV-associated bone loss. This was a case-control study. Thirty male individuals with HIV infection (HIV+) and osteoporosis/osteopenia (HIV+/OP+) (cases) and 30 age-matched male HIV+ individuals with normal bone mass (HIV+/OP-) (controls) were included in the analysis. Thirty male individuals matched for age without HIV infection (HIV-), were also included as second controls. The selected panel of miRNAs was as follows: hsa-miRNA-21-5p; hsa-miRNA-23a-3p; hsa-miRNA-24-2-5p; hsa-miRNA-26a-5p; hsa-miRNA-29a-3p; hsa-miRNA-124-3p; hsa-miRNA-33a-5p; and hsa-miRNA-133a-3p. Within the cohort of HIV+ individuals, relative serum expression of miRNA-21-5p and miRNA-23a-3p was significantly lower (p < 0.001) while the expression of miRNA-24-2-5p was significantly higher (p = 0.030) in HIV+/OP+ compared to HIV+/OP-. Expression of miRNA-21-5p demonstrated a sensitivity of 84.6% and a specificity of 66.7 in distinguishing HIV+/OP+ individuals. Expression of circulating miRNAs related to bone metabolism; miRNA-23a-3p, miRNA-24-2-5p, and miRNA-21-5p is significantly altered in HIV+OP+ individuals, in line with data on other causes of osteoporosis, suggesting a common pattern of circulating miRNAs independent of the underlying cause.

Wave reflections and systemic vascular resistance are stronger determinants of pulse pressure amplification than aortic stiffness in drug-naïve hypertensives.

Background: Aortic-to-brachial pulse pressure (PP) amplification is a novel biomarker that prognosticates the cardiovascular risk above and beyond central aortic and brachial blood pressure. This phenomenon is modulated by left ventricular contractility and chronotrophy, large-artery stiffness and reflecting properties of microcirculation. However, the relative importance of these parameters as hemodynamic determinant of PP amplification remains elusive.Methods: A total of 88 consecutive drug-naïve hypertensives underwent a non-invasive assessment of central and peripheral hemodynamics via impedance cardiography and pulse wave analysis. Participants were classified into tertiles according to the magnitude of PP amplification. Hemodynamic determinants of low PP amplification were explored in univariate and multivariate regression analysis.Results: Compared with the high tertile, patients within the low PP amplification tertile were older and more commonly female and had lower height, weight and heart rate. Augmentation index (AIx) and systemic vascular resistance index (SVRI) were higher among patients within the low PP amplification tertile, whereas aortic pulse wave velocity (PWV) did not differ among groups. In multivariate analysis, higher AIx (OR: 1.27; 95% CI: 1.09-1.48) and higher SVRI were independently associated with higher odds for low PP amplification, whereas higher heart rate was the only parameter related to lower odds for low PP amplification (OR: 0.84; 95% CI: 0.71-0.99).Conclusion: This study shows that among newly-diagnosed drug-naïve hypertensives, elevated wave reflections and systemic vascular resistance are stronger determinants of PP amplification than aortic stiffness.

Predictors of humoral response to recommended vaccines in HIV-infected adults.

Humoral response to vaccination has been found to be inadequate in individuals infected with the human immunodeficiency virus (HIV). We retrospectively assessed antibody responses to three routinely recommended vaccines, against hepatitis B, hepatitis A and S. pneumoniae, in HIV-infected individuals. Data regarding age at HIV diagnosis, years of infection, sex, nationality, HIV mode of transmission, CD4 cell count, nadir CD4 count, plasma viral load, HIV stage, insurance status, educational level and treatment with Highly Active Antiretroviral Therapy (HAART) were collected. Univariate and multivariate analysis was performed in order to detect factors associated with response to vaccination. 437 patients were assessed for hepatitis B, 627 patients for hepatitis A and 66 patients for S. pneumoniae serologic vaccine responsiveness. Regarding hepatitis B and hepatitis A, education level and insurance status were the only predictors of response. As for S. pneumoniae vaccination HAART and control of viremia were correlated with better response to vaccination.

Pyoderma gangrenosum in a patient with chronic granulomatous disease: A case report.

RATIONALE: The simultaneous occurrence of pyoderma gangrenosum (PG) and chronic granulomatous disease (CGD) is uncommon and few cases have been reported worldwide. PATIENT CONCERNS: PG is a rare, chronic, ulcerative, neutrophilic skin disease of unknown etiology that requires immunosuppressive treatment. CGD belongs to Primary Immune Deficiencies in which the main defect lies in an inability of the phagocytic cells to generate superoxide making patients susceptible to serious, potentially life-threatening bacterial and fungal infections. DIAGNOSES: In this manuscript, we present a case of ulcerative pyoderma gangrenosum in a 28-year-old man with recent diagnosis of chronic granulomatous disease during hospitalization for resistant pulmonary tuberculosis complicated with Aspergillus infection. INTERVENTIONS: Second-line therapy with dapsone and intravenous immunoglobulin was initially administered but eventually corticosteroids were added to treatment because of disease progression and further ulceration. OUTCOMES: Patient's ulcers were gradually healed with no side effects. LESSONS: Corticosteroids could be used under close monitoring for the treatment of PG in a patient with CGD, despite the increased risk for infections.

Prolonged and high dosage of tigecycline - successful treatment of spondylodiscitis caused by multidrug-resistant Acinetobacter baumannii: a case report.

BACKGROUND: The incidence of infectious spondylodiscitis has been increasing over the last few years. This reflects the expanding elderly and immunocompromised populations and the rising implementation of invasive spinal procedures. Infection may be inoculated into the disc space directly during invasive spinal procedures. Osteomyelitis caused by Acinetobacter species is rare and mainly caused by multidrug-resistant strains. CASE PRESENTATION: We present the case of a 72-year-old Greek woman with postoperative spondylodiscitis caused by a multidrug-resistant Acinetobacter baumannii strain that was successfully treated, after she declined surgical treatment, with prolonged and high dosage of tigecycline. She received intravenously administered tigecycline 200 mg per day for 60 days and then 100 mg per day for a total of 102 days and was infection-free. CONCLUSIONS: We reviewed the literature on the role of Acinetobacter baumannii as a cause of osteomyelitis, emphasizing the difficulty of treatment and the potential role of tigecycline in conservative treatment of the infection. We believe that 102 days in total is the longest time that any patient has received tigecycline in the literature, thus our patient is a unique case of successful treatment of spondylodiscitis.

The Role of MicroRNAs in Arterial Stiffness and Arterial Calcification. An Update and Review of the Literature.

Arterial stiffness is an independent risk factor for fatal and non-fatal cardiovascular events, such as systolic hypertension, coronary artery disease, stroke, and heart failure. Moreover it reflects arterial aging which in many cases does not coincide with chronological aging, a fact that is in large attributed to genetic factors. In addition to genetic factors, microRNAs (miRNAs) seem to largely affect arterial aging either by advancing or by regressing arterial stiffness. MiRNAs are small RNA molecules, ~22 nucleotides long that can negatively control their target gene expression posttranscriptionally. Pathways that affect main components of stiffness such as fibrosis and calcification seem to be influenced by up or downregulation of specific miRNAs. Identification of this aberrant production of miRNAs can help identify epigenetic changes that can be therapeutic targets for prevention and treatment of vascular diseases. The present review summarizes the specific role of the so far discovered miRNAs that are involved in pathways of arterial stiffness.