Jien-Wei Liu

Correlation of pandemic (H1N1) 2009 viral load with disease severity and prolonged viral shedding in children.

Younger children may require a longer isolation period and more aggressive treatment.

Fatal Dengue Hemorrhagic Fever in Adults: Emphasizing the Evolutionary Pre-fatal Clinical and Laboratory Manifestations

Background A better description of the clinical and laboratory manifestations of fatal patients with dengue hemorrhagic fever (DHF) is important in alerting clinicians of severe dengue and improving management. Methods and Findings Of 309 adults with DHF, 10 fatal patients and 299 survivors (controls) were retrospectively analyzed. Regarding causes of fatality, massive gastrointestinal (GI) bleeding was found in 4 patients, dengue shock syndrome (DSS) alone in 2; DSS/subarachnoid hemorrhage, Klebsiella pneumoniae meningitis/bacteremia, ventilator associated pneumonia, and massive GI bleeding/Enterococcus faecalis bacteremia each in one. Fatal patients were found to have significantly higher frequencies of early altered consciousness (≤24 h after hospitalization), hypothermia, GI bleeding/massive GI bleeding, DSS, concurrent bacteremia with/without shock, pulmonary edema, renal/hepatic failure, and subarachnoid hemorrhage. Among those experienced early altered consciousness, massive GI bleeding alone/with uremia/with E. faecalis bacteremia, and K. pneumoniae meningitis/bacteremia were each found in one patient. Significantly higher proportion of bandemia from initial (arrival) laboratory data in fatal patients as compared to controls, and higher proportion of pre-fatal leukocytosis and lower pre-fatal platelet count as compared to initial laboratory data of fatal patients were found. Massive GI bleeding (33.3%) and bacteremia (25%) were the major causes of pre-fatal leukocytosis in the deceased patients; 33.3% of the patients with pre-fatal profound thrombocytopenia (<20000/µL), and 50% of the patients with pre-fatal prothrombin time (PT) prolongation experienced massive GI bleeding. Conclusions Our report highlights causes of fatality other than DSS in patients with severe dengue, and suggested hypothermia, leukocytosis and bandemia may be warning signs of severe dengue. Clinicians should be alert to the potential development of massive GI bleeding, particularly in patients with early altered consciousness, profound thrombocytopenia, prolonged PT and/or leukocytosis. Antibiotic(s) should be empirically used for patients at risk for bacteremia until it is proven otherwise, especially in those with early altered consciousness and leukocytosis.

Tuberculous parotitis: case report and literature review.

Objectives: Our aim was to better understand the rarely encountered tuberculous (TB) parotitis. Methods: A case of TB parotitis is reported, and the literature is reviewed. Results: Forty-nine patients (27 men, 22 women; mean age, 38.3 ± 16.4 years) were enrolled. The median duration of symptoms before these patients sought medical help was 6 months. Except for 1 patient with bilateral TB parotitis, all had unilateral involvement; complications included draining sinuses in 4 patients (8%) and facial palsy in 2 patients (4%). Twenty-one of 36 patients (58%) had a painless parotid mass, 12 of 19 (63%) had cervical lymphadenitis, 8 of 11 (73%) had fever, and 11 of 44 (25%) had pulmonary tuberculosis (4 active and 7 inactive cases). Neoplasm was the most common presumptive diagnosis. The diagnosis of TB parotitis in most cases was made on the basis of cytologic analysis of the fine-needle aspirate or histopathologic analysis of the excised tissue. Forty-six patients with TB parotitis who had a traceable outcome survived after 6 to 10 months of antituberculosis chemotherapy. Conclusions: Physicians should have a high index of suspicion for TB parotitis in patients with a chronic parotid lump, even if the chest radiographs appear normal. Fine-needle aspiration should be performed first for diagnosis, and TB parotitis should be medically treated.

Altered p38 Mitogen-Activated Protein Kinase Expression in Different Leukocytes with Increment of Immunosuppressive Mediators in Patients with Severe Acute Respiratory Syndrome

Severe acute respiratory syndrome (SARS) has spread to a global pandemic, especially in Asia. The transmission route of SARS has been clarified, but the immunopathogenesis of SARS is unclear. In an age-matched case-control design, we studied immune parameters in 15 SARS patients who were previously healthy. Plasma was harvested for detection of virus load, cytokines, and nitrite/nitrate levels, and blood leukocytes were subjected to flow cytometric analysis of intracellular mitogen-activated protein kinases (MAPKs) in different leukocytes. Patients with SARS had significantly higher IL-8 levels (p = 0.016) in early stage, and higher IL-2 levels (p = 0.039) in late stage than normal controls. Blood TNF-α, IL-6, and IL-10, and nitrite/nitrate levels were not significantly elevated. In contrast, TGF-β and PGE2 levels were significantly elevated in SARS patients. Five of the 15 SARS patients had detectable coronaviruses in blood, but patients with detectable and undetectable viremia had no different profiles of immune mediators. Flow cytometric analysis of MAPKs activation by phospho-p38 and phospho-p44/42 (extracellular signal-regulated kinase) expression showed that augmented p38 activation (p = 0.044) of CD14 monocytes associated with suppressed p38 activation (p = 0.033) of CD8 lymphocytes was found in SARS patients. These results suggest that regulation of TGF-β and PGE2 production and MAPKs activation in different leukocytes may be considered while developing therapeutics for the SARS treatment.

Clinical Features of and Risk Factors for Rhabdomyolysis Among Adult Patients with Dengue Virus Infection

Among 1,076 dengue patients, 9 patients with rhabdomyolysis and 1,067 patients without rhabdomyolysis (controls) were retrospectively analyzed. Of nine patients with rhabdomyolysis, the most commonly reported symptom other than fever was myalgia; dengue hemorrhagic fever (DHF) was found in seven cases, and acute kidney injury was found in six cases. Furthermore, one (11.1%) patient died. The median duration from hospital admission to rhabdomyolysis diagnosis was 3 days. Patients with rhabdomyolysis had higher age, proportion of men, prevalence of hypertension, frequency of myalgia, and incidences of DHF, pleural effusion, and acute kidney injury than controls. Multivariate analysis showed that hypertension (odds ratio [OR] = 14.270), myalgia (OR = 20.377), and acute kidney injury (OR = 65.547) were independent risk factors for rhabdomyolysis. Comparison of cytokine/chemokine concentrations in 101 DHF patients, including those with (N = 4) and without (N = 97) rhabdomyolysis, showed that interleukin-6 and tumor necrosis factor-α levels were significantly increased in the former.

Combination of CTLA-4 and TGFβ1 gene polymorphisms associated with dengue hemorrhagic fever and virus load in a dengue-2 outbreak

The pathogenesis of dengue hemorrhagic fever (DHF) has been considered to be massive immune activation of T cells. Abnormal expression of the immune regulatory molecules, CTLA-4 and TGFbeta1, leads to disturbances of regulatory T cell immune response. We investigate the contribution of CTLA-4 and TGFbeta1 in DHF by analyzing them for association with virus load in blood and polymorphisms of CTLA-4 +49A/G, and TGFbeta1 -509C/T in a DEN-2 outbreak. The increased frequency of the TGFbeta1 -509 CC genotype in patients with DHF was compared to those with dengue fever (OR=1.9, p=0.034). Moreover, the presence of the CTLA-4 +49 G allele and TGFbeta1 -509 CC genotype increased the susceptibility to risk of DHF (OR=2.1, p=0.028) and significantly higher virus load (p=0.013). This finding suggests that a combination of CTLA-4 and TGFbeta1 polymorphisms is associated with the susceptibility of DHF and higher virus load.

Antibiotic Consumption and Healthcare-Associated Infections Caused by Multidrug-Resistant Gram-Negative Bacilli at a Large Medical Center in Taiwan from 2002 to 2009: Implicating the Importance of Antibiotic Stewardship

Background Better depicting the relationship between antibiotic consumption and evolutionary healthcare-associated infections (HAIs) caused by multidrug-resistant Gram-negative bacilli (MDR-GNB) may help highlight the importance of antibiotic stewardship. Methodology/Principal Findings The correlations between antibiotic consumption and MDR-GNB HAIs at a 2,700-bed primary care and tertiary referral center in Taiwan between 2002 and 2009 were assessed. MDR-GNB HAI referred to a HAI caused by MDR-Enterobacteriaceae, MDR-Pseudomonas aeruginosa or MDR-Acinetobacter spp. Consumptions of individual antibiotics and MDR-GNB HAI series were first evaluated for trend over time. When a trend was significant, the presence or absence of associations between the selected clinically meaningful antibiotic resistance and antibiotic consumption was further explored using cross-correlation analyses. Significant major findings included (i) increased consumptions of extended-spectrum cephalosporins, carbapenems, aminopenicillins/β-lactamase inhibitors, piperacillin/tazobactam, and fluoroquinolones, (ii) decreased consumptions of non-extended-spectrum cephalosporins, natural penicillins, aminopenicillins, ureidopenicillin and aminoglycosides, and (iii) decreasing trend in the incidence of the overall HAIs, stable trends in GNB HAIs and MDR-GNB HAIs throughout the study period, and increasing trend in HAIs caused by carbapenem-resistant (CR) Acinetobacter spp. since 2006. HAIs due to CR-Acinetobacter spp. was found to positively correlate with the consumptions of carbapenems, extended-spectrum cephalosporins, aminopenicillins/β-lactamase inhibitors, piperacillin/tazobactam and fluoroquinolones, and negatively correlate with the consumptions of non-extended-spectrum cephalosporins, penicillins and aminoglycosides. No significant association was found between the increased use of piperacilllin/tazobactam and increasing HAIs due to CR-Acinetobacter spp. Conclusions The trend in overall HAIs decreased and trends in GNB HAIs and MDR-GNB HAIs remained stable over time suggesting that the infection control practice was effective during the study period, and the escalating HAIs due to CR- Acinetobacter spp. were driven by consumptions of broad-spectrum antibiotics other than piperacillin/tazobactam. Our data underscore the importance of antibiotic stewardship in the improvement of the trend of HAIs caused by Acinetobacter spp.

Molecular signature of clinical severity in recovering patients with severe acute respiratory syndrome coronavirus (SARS-CoV)

BackgroundSevere acute respiratory syndrome (SARS), a recent epidemic human disease, is caused by a novel coronavirus (SARS-CoV). First reported in Asia, SARS quickly spread worldwide through international travelling. As of July 2003, the World Health Organization reported a total of 8,437 people afflicted with SARS with a 9.6% mortality rate. Although immunopathological damages may account for the severity of respiratory distress, little is known about how the genome-wide gene expression of the host changes under the attack of SARS-CoV.ResultsBased on changes in gene expression of peripheral blood, we identified 52 signature genes that accurately discriminated acute SARS patients from non-SARS controls. While a general suppression of gene expression predominated in SARS-infected blood, several genes including those involved in innate immunity, such as defensins and eosinophil-derived neurotoxin, were upregulated. Instead of employing clustering methods, we ranked the severity of recovering SARS patients by generalized associate plots (GAP) according to the expression profiles of 52 signature genes. Through this method, we discovered a smooth transition pattern of severity from normal controls to acute SARS patients. The rank of SARS severity was significantly correlated with the recovery period (in days) and with the clinical pulmonary infection score.ConclusionThe use of the GAP approach has proved useful in analyzing the complexity and continuity of biological systems. The severity rank derived from the global expression profile of significantly regulated genes in patients may be useful for further elucidating the pathophysiology of their disease.

Increasing trend of fluconazole-non-susceptible Cryptococcus neoformans in patients with invasive cryptococcosis: a 12-year longitudinal study

BackgroundThis study aimed to investigate the rate of fluconazole-non-susceptible Cryptococcus neoformans in Southern Taiwan for the period 2001–2012 and analyze the risk factors for acquiring it among patients with invasive cryptococcosis.MethodsAll enrolled strains were isolated from blood or cerebrospinal fluid samples of the included patients. If a patient had multiple positive results for C. neoformans, only the first instance was enrolled. Susceptibility testing was performed using the Clinical and Laboratory Standards Institutes M27-A3 broth micro-dilution method. The MIC interpretative criteria for susceptibility to fluconazole were ≤8xa0μg/ml. A total of 89 patients were included. Patients (nu2009=u200959) infected by fluconazole-susceptible strains were compared with those (nu2009=u200930) infected by non-susceptible strains. The patients’ demographic and clinical characteristics were analyzed.ResultsThe rate of fluconazole-non-susceptible C. neoformans in the study period significantly increased over time (pu2009<u20090.001). The C. neoformans isolated in 2011–2012 (odds ratio: 10.68; 95xa0% confidence interval: 2.87-39.74; pu2009<u20090.001) was an independent predictive factor for the acquisition of fluconazole-non-susceptible C. neoformans.ConclusionsThe rate of fluconazole-non-susceptible C. neoformans has significantly increased recently. Continuous and large-scale anti-fungal susceptibility tests for C. neoformans are warranted to confirm this trend.

Impacts of Pretransplant Infections on Clinical Outcomes of Patients with Acute-On-Chronic Liver Failure Who Received Living-Donor Liver Transplantation

Background Liver transplantation is the only therapeutic modality for patients with acute-on chronic liver failure (ACLF). These patients are at high risk for bacterial infections while awaiting transplantation. The aim of this study was to elucidate whether an adequately treated bacterial infection influences the outcomes after transplantation in this patient population. Methodology/Principal Findings 54 recipients (median age, 49.5 years [range, 22–60]) of adult-to-adult living donor liver transplant (LDLT) for ACLF were categorized as those with pretransplant infection (Group 1, nu200a=u200a34) or without pretransplant infection (Group 2, nu200a=u200a20) for retrospective analyses. With the exception of a higher male-female ratio (Pu200a=u200a0.046) and longer length of pretransplant hospital stay (Pu200a=u200a0.026) in Group 1, similar demographic, laboratory and clinical features were found in both groups. Patients in Group 1 (totally 42 pretransplant infection episodes) were adequately treated with effective antibiotic(s) before receiving LDLT. All included patients were followed up until one year after transplantation or death. Sixty-one posttransplant infection episodes were found in an overall of 44 ACLF patients (27 in Group 1 vs. 15 in Group 2; Pu200a=u200a0.352). Frequently encountered posttransplant infections were intraabdominal infection, pneumonia, bloodstream infection and urinary tract infection. Two patients died in each group (Pu200a=u200a0.622). No significant difference was found in the length of posttransplant ICU stay, and in one-year survival, graft rejection, and posttransplant infection rate between both groups. The longer overall hospital stay (mean day, 89.0 vs. 65.5, Pu200a=u200a0.024) found in Group 1 resulted from a longer pretransplant hospital stay receiving treatment for pretransplant infection(s) and/or awaiting transplantation. Conclusions These data suggested that an adequately treated pretransplant infection do not pose a significant risk for clinical outcomes including posttransplant fatality in recipients in adult-to-adult LDLT for ACLF.