Risk of non-typhoidal Salmonella vascular infections is increased with degree of atherosclerosis and inflammation: A multicenter study in southern Taiwan.

BACKGROUND: Atherosclerosis and vascular inflammatory response have been considered as risk factors for non-typhoidal Salmonella (NTS) vascular infection. The study aims to assess the risk of vascular infection by measuring atherosclerosis severity, NTS vascular infection (NTSVI) score, and serum levels of inflammatory markers in people with NTS bacteremia. METHODS: A prospective observational study was conducted in two medical centers and two regional hospitals. Adults aged ≥50 years with NTS bacteremia who underwent computed tomography (CT) scan for revealing vascular infections were enrolled. The degree of atherosclerosis was scaled by a calcium score determined by a CT scan. Serum concentrations of inflammatory biomarkers were determined in the patients enrolled in a medical center. RESULTS: Fourteen (20.3%) of 69 patients with NTS bacteremia had vascular infections. Calcium scores over the thoracic (12,540 vs. 3,261, P = 0.0005) and abdominal (9755 vs. 3,461, P = 0.0006) aorta of those with vascular infections were higher than those without vascular infection. All vascular infections were present in the high-risk group (NTSVI score ≥1), yielding a sensitivity of 100% and specificity of 30.9%. Among 17 low-risk patients (NTSVI score <1), none had vascular infections, resulting in a negative predictive value of 100%. Higher plasma concentrations of IL-1ß were detected in the cases of vascular infection than those in the control group (23.6 vs. 1.06 pg/mL, P = 0.001). CONCLUSION: Atherosclerosis of the aorta which is associated with a positive NTSVI score can predict the occurrence of vascular infections and serum IL-1ß could be a biomarker for vascular infection in patients with NTS bacteremia.

Differential risk group of developing stroke among older women with gouty arthritis: A latent transition analysis.

OBJECTIVE: Gout-related comorbidities are intricate and its clinical features may demonstrate sex difference; however, few studies have evaluated the links between comorbidities and gout in a female population. The objectives of this study were to compare the aggregation and transitive trajectories of comorbidities of gout, and their consequences in female and male gout populations. METHODS: A prospective cohort study was conducted using data from the Taiwan National Health Insurance Research Database. A female and male gout population were followed up from 2000 to 2009 to identify the comorbidities of cardiovascular disease, hyperlipidemia, hypertension, diabetes mellitus (DM) and chronic kidney disease. The cumulative incidence of stroke from 2000 to 2010 was examined. A latent trajectory analysis was used to determine the transitive trajectories of the comorbidities of gout. RESULTS: Both female and male patients with gout had five risk cluster transition (CT) phenotypes of comorbidities within 10-year follow-up: CT1 and CT2, with various persistent comorbidities; CT3, with few persistent comorbidities; and CT4 and CT5, with transfer to cluster 1 from other clusters. The female participants in CT2 predominantly experienced DM and were associated with significantly increased risk of developing stroke. CONCLUSION: Diabetes is a notable risk factor for the development of stroke in female patients with gout. Early assessment and management for the comorbidities of gout, particularly in DM, would effectively reduce future stroke risk in female gout population.

Longitudinal transition trajectory of gouty arthritis and its comorbidities: a population-based study.

The aim of the study was to investigate the longitudinal transition trajectory of gout and its comorbidities in male patients with gout in different age groups. A total of 3973 male patients who received a new diagnosis of gouty arthritis were identified from the Taiwan Longitudinal Health Insurance Database and divided into two age cohorts (<50 and ≥50 years). Each patient was individually followed from 2000 to 2009 to identify associated comorbidities, namely hypertension, hypercholesterolemia, diabetes mellitus, cardiovascular diseases, and chronic kidney disease. Two outcome measurements of stroke and all-cause cancer were further identified until 2010. The transition trajectory was divided into the following five phenotype groups: persistent hypertension combined with a high prevalence of various gout-related comorbidities, persistent hypercholesterolemia combined with a moderate prevalence of various gout-related comorbidities, persistent low prevalence of various gout-related comorbidities, moderate to high prevalence of various gout-related comorbidities, and low to high prevalence of various gout-related comorbidities. Although the younger and older patients had a similar longitudinal transition trajectory of gout-related comorbidities, the older patients had a higher 10-year likelihood of transition from a low or moderate to a high prevalence of various gout-related comorbidities. In addition, the incidences of stroke and all-cause cancer were higher in the groups with high and moderate to high prevalences of various gout-related comorbidities than in the other groups. The occurrence of gouty arthritis in different life stages can cause cluster effects involving varying degrees of comorbidities over time. The findings of the current study can provide additional knowledge and increase clinical awareness regarding the early assessment and management of gout-related comorbidities in clinical practice.

Interlukin-18 Is a Pivot Regulatory Factor on Matrix Metalloproteinase-13 Expression and Brain Astrocytic Migration.

The expression of matrix metalloproteinase-13 (MMP-13) has been shown to be elevated in some pathophysiological conditions and is involved in the degradation of extracellular matrix in astrocytes. In current study, the function of MMP-13 was further investigated. The conditioned medium (CM) collected from activated microglia increased interleukin (IL)-18 production and enhanced MMP-13 expression in astrocytes. Furthermore, treatment with recombinant IL-18 increased MMP-13 protein and mRNA levels in astrocytes. Recombinant IL-18 stimulation also increased the enzymatic activity of MMP-13 and the migratory activity of astrocytes, while administration of MMP-13 or pan-MMP inhibitors antagonized IL-18-induced migratory activity of astrocytes. In addition, administration of recombinant IL-18 to astrocytes led to the phosphorylation of JNK, Akt, or PKCδ, and treatment of astrocytes with JNK, PI3 kinase/Akt, or PKCδ inhibitors significantly decreased the IL-18-induced migratory activity. Taken together, the results suggest that IL-18-induced MMP-13 expression in astrocytes is regulated by JNK, PI3 kinase/Akt, and PKCδ signaling pathways. These findings also indicate that IL-18 is an important regulator leading to MMP-13 expression and cell migration in astrocytes.

Cytomegalovirus disease in nonimmunocompromised, human immunodeficiency virus-negative adults with chronic kidney disease.

BACKGROUND/PURPOSE(S): To identify the clinical characteristics of cytomegalovirus (CMV) disease in chronic kidney disease (CKD) patients. METHODS: Patients from two sources were reviewed: (1) a retrospective study of hospitalized patients admitted between January 1990 and February 2009 was performed at a tertiary hospital in Taiwan; (2) the English literature from 1990 to 2009 was reviewed for additional cases, and adults with CKD and histopathologically documented cytomegalovirus disease were included. RESULTS: Seven CKD patients from our hospital and seven from the literature were included. Nine (64.3%) patients were males, and the mean age was 66 years. Histopathologically proven CMV disease was present in the gastrointestinal (GI) tract of 13 (92.9%) and in the skin of one (7.1%) patient. GI symptoms included bleeding (78.6%), abdominal pain (35.7%), and diarrhea (28.6%).The most common comorbidities were diabetes mellitus (7, 50%) and hypertension (8, 57.1%). Thirteen patients had CMV GI disease. The endoscopic gross features of the GI tract lesions included single or multiple ulcers and a large polypoid or uneven surface mass. Of the seven cases with available data, a low body mass index (22.3 ± 1.3 kg/m(2)) and hypoalbuminemia (25 ± 7.0 g/L) were noted. Twelve patients had received ganciclovir or valganciclovir therapy. Five (35.7%) patients died, and the death of two patients was directly related to bowel perforation caused by CMV colitis. CONCLUSION: CMV disease may occur in CKD patients without the presence of overt immunodeficiency. The gastrointestinal tract is the most common site of involvement. Clinicians should be aware of this possibility in CKD patients who have GI symptoms.

Nontyphoidal Salmonella bacteremia in patients with connective tissue diseases.

BACKGROUND/PURPOSE: Nontyphoidal Salmonella (NTS) is a crucial pathogen in immunocompromised patients, especially those with connective tissue disease (CTD) and corticosteroid or immunosuppressant therapy. The aim of this study is to identify the clinical characteristics and outcomes of patients with CTD and NTS bacteremia, and the clinical variations between systemic lupus erythematosus (SLE) and other CTDs. METHODS: During a 15-year study period, from 1994 to 2009, NTS bacteremia patients were reviewed from the database of clinical microbiology laboratory. Medical records were reviewed for clinical information and only patients with underlying CTD were included. RESULTS: From 1994 to 2009, there were 299 patients with NTS bacteremia. Forty-six (15.4%) patients had certain connective tissue diseases, and SLE was the major CTD, accounting for 73.9% (34) of 46 patients. In comparison with patients without CTD, the patients with CTD were younger (p<0.0001), had a predominance of female gender (p<0.0001), fewer extra-intestinal focal infections (p=0.011), and a lower mortality rate (p=0.008). Overall, there were four fatal cases, accounting for a mortality rate of 8.7% of those afflicted with CTD. The factors of old age (p<0.006), shock at presentation (p=0.033), acute renal failure (p=0.001), and presence of any extra-intestinal focal infection (p<0.0001) were associated with mortality in the univariate analysis. CONCLUSION: Nontyphoidal Salmonella bacteremia causes substantial morbidity and mortality in patients with connective tissue disease, especially in the elderly population. The aggressive detection of extra-intestinal infections may be beneficial.

Cultures of Holder-pasteurized donor human milk after use in a neonatal intensive care unit.

OBJECTIVE: Current guidelines state that human milk, once thawed, should be kept in a refrigerator for only 24 hours. We cultured Holder-pasteurized donor human milk (DHM) after thawing and refrigeration under clinical conditions. STUDY DESIGN: Bottles of pasteurized DHM were thawed and used in a regional level 3 neonatal intensive care unit (NICU) in standard clinical fashion and kept refrigerated when not in use. Once no longer needed clinically, aliquots were cultured for bacteria. RESULTS: In total, 30 bottles were returned for culture; six were excluded from analysis because human milk fortifier had been added, and two had been left out of the refrigerator. The remaining 22 bottles were culture-negative after having been thawed for 7-122 hours. CONCLUSIONS: DHM without additives was culture-negative for 24 hours or longer after thawing and routine NICU handling. These data indicate that unfortified Holder-pasteurized DHM handled appropriately and refrigerated remains sterile for 24 hours after thawing and perhaps longer. Further study is needed to confirm this.

Clinical manifestations and prognostic factors in cancer patients with bacteremia due to extended-spectrum ß-lactamase-producing Escherichia coli or Klebsiella pneumoniae.

BACKGROUND: Clinical information about bacteremia due to extended-spectrum ß-lactamase (ESBL)-producing pathogens in cancer patients was limited. The study was aimed to identify the clinical manifestations and risk factors for mortality in ESBL-producer bacteremia in cancer patients. METHODS: A retrospective study of bacteremia caused by ESBL-producing Escherichia coli or Klebsiella pneumoniae in adults with cancer in National Cheng Kung University Hospital and National Taiwan University Hospital from July 2002 to August 2007 was conducted. Clinical characteristics, initial manifestations, and antimicrobial therapy were analyzed for their association with crude mortality at 14 days after bacteremia onset. RESULTS: A total 113 episodes of bacteremia caused by E coli (59.3%), K pneumoniae (39.8%) or both (0.9%) were included. Patients with hematological malignancy were younger (55 ± 22 vs. 69 ± 14 years, p < 0.003) and had less co-morbidity, but were more likely to have neutropenia (73.1% vs. 4.6%, p < 0.001) than those with solid tumor. By the univariate analysis in 113 episodes of ESBL-producer bacteremia, several risk factors, including pneumonia or soft-tissue infection as the bacteremia source, initial manifestations with high Pitt bacteremia scores, shock, respiratory failure or severe sepsis, and inappropriate definitive therapy were associated with 14-day crude mortality. By multivariate analysis, only pneumonia [adjusted odds ratio (AOR), 5.2; 95% confident interval (CI), 1.3-21.0; p = 0.021], severe sepsis (AOR, 24.3; 95% CI, 5.6-105.0; p < 0.001), and inappropriate definitive therapy (AOR, 11.3; 95% CI, 1.7-72.8; p = 0.011) were independently associated with a fatal outcome. CONCLUSION: The presence of neutropenia or underlying hematological malignancy in cancer patients with ESBL-producer bacteremia was not associated with an increase in the mortality rate. Appropriate definitive antimicrobial therapy will be beneficial in improving clinical outcome.

Voltage-gated K+ channels play a role in cAMP-stimulated neuritogenesis in mouse neuroblastoma N2A cells.

Neuritogenesis is essential in establishing the neuronal circuitry. An important intracellular signal causing neuritogenesis is cAMP. In this report, we showed that an increase in intracellular cAMP stimulated neuritogenesis in neuroblastoma N2A cells via a PKA-dependent pathway. Two voltage-gated K(+) (Kv) channel blockers, 4-aminopyridine (4-AP) and tetraethylammonium (TEA), inhibited cAMP-stimulated neuritogenesis in N2A cells in a concentration-dependent manner that remarkably matched their ability to inhibit Kv currents in these cells. Consistently, siRNA knock down of Kv1.1, Kv1.4, and Kv2.1 expression reduced Kv currents and inhibited cAMP-stimulated neuritogenesis. Kv1.1, Kv1.4, and Kv2.1 channels were expressed in the cell bodies and neurites as shown by immunohistochemistry. Microfluorimetric imaging of intracellular [K(+)] demonstrated that [K(+)] in neurites was lower than that in the cell body. We also showed that cAMP-stimulated neuritogenesis may not involve voltage-gated Ca(2+) or Na(+) channels. Taken together, the results suggest a role of Kv channels and enhanced K(+) efflux in cAMP/PKA-stimulated neuritogenesis in N2A cells.

Efficacy of Monascus purpureus Went rice on lowering lipid ratios in hypercholesterolemic patients.

BACKGROUND: Several lipid ratios may be predictors of coronary artery disease risk. We assessed the efficacy of Monascus purpureus Went rice (red yeast rice) on lowering lipid ratios. METHOD AND RESULTS: We evaluated 79 hypercholesterolemic patients (aged 23-65 years) who received a twice-daily dose of either red yeast rice or a placebo at 600 mg for 8 weeks. The 8-week treatment with red yeast rice showed significantly greater reduction than the placebo treatment in low-density lipoprotein cholesterol levels, total cholesterol/high-density lipoprotein cholesterol, low-density lipoprotein cholesterol/high-density lipoprotein cholesterol and apolipoprotein B/apolipoprotein A-I ratios. CONCLUSIONS: Red yeast rice can reduce lipid ratios in hypercholesterolemic patients.