Sheng-Yuan Ruan

Invasive Trichosporonosis Caused by Trichosporon asahii and Other Unusual Trichosporon Species at a Medical Center in Taiwan

BACKGROUND During the past 2 decades, invasive trichosporonosis has emerged as an opportunistic infectious disease in immunocompromised patients. However, no case series have been reported recently. METHODS All patients with a culture that was positive for Trichosporon species from May 2000 through May 2008 at a medical center were evaluated. The identity of all Trichosporon species was confirmed by analysis of the intergenic spacer 1 region of the fungal ribosomal RNA gene. In vitro susceptibility testing was performed using the reference broth microdilution method. RESULTS Forty-three patients were found to have a culture that was positive for Trichosporon species. T. asahii was the most frequently isolated species (32 isolates; 74%), followed by T. dermatis (5; 12%), T. montevideense (2; 5%), and T. asteroides (1; 2%), T. cutaneum (1; 2%), T. faecale (1; 2%), and T. ovoides (1; 2%). Nineteen patients had invasive infections; 16 (84%) were caused by T. asahii, and 1 (5%) each was caused by T. dermatis, T. montevideense, and T. asteroides. Of the 19 episodes of invasive trichosporonosis, 14 (74%) were fungemia, 3 (16%) were pulmonary infection, and 1 (5%) each was soft-tissue infection and meningitis. Most invasive infections were associated with prior antibiotic therapy (95%), use of a central catheter (90%), malignancy (58%), and intensive care unit admission (47%). Azoles had good in vitro activity, whereas amphotericin B and echinocandins were not active against Trichosporon isolates. The 30-day all-cause mortality rate was 42% and was higher among patients with a malignancy (55%) than among those without an underlying malignancy (25%). CONCLUSIONS Invasive trichosporonosis tended to develop in patients with an underlying malignancy and to be associated with higher mortality. T. asahii and other unusual Trichosporon species may cause invasive trichosporonosis.

Revisiting tuberculous pleurisy: pleural fluid characteristics and diagnostic yield of mycobacterial culture in an endemic area

Background Tuberculous pleurisy is traditionally indicated by extreme lymphocytosis in pleural fluid and low yield of effusion culture. However, there is considerable inconsistency among previous study results. In addition, these data should be updated due to early effusion studies and advances in culture methods. Methods From January 2004 to June 2009, patients with tuberculous pleurisy were retrospectively identified from the mycobacteriology laboratories and the pathology and tuberculosis registration databases of two hospitals in Taiwan where tuberculosis is endemic. Pleural fluid characteristics and yields of mycobacterial cultures using liquid media were evaluated. Results A total of 382 patients with tuberculous pleurisy were identified. The median lymphocyte percentage of total cells in pleural fluids was 84% (IQR 64–95%) and 17% of cases had a lymphocyte percentage of <50%. The lymphocyte percentage was negatively associated with the probability of a positive effusion culture (OR 0.97; 95% CI 0.96 to 0.99). The diagnostic yields were 63% for effusion culture, 48% for sputum culture, 79% for the combination of effusion and sputum cultures, and 74% for histological examination of pleural biopsy specimens. Conclusion The degree of lymphocyte predominance in tuberculous pleurisy was lower than was previously thought. The lymphocyte percentage in pleural fluid was negatively associated with the probability of a positive effusion culture. With the implementation of a liquid culture method, the sensitivity of effusion culture was much higher than has been previously reported, and the combination of effusion and sputum cultures provided a good diagnostic yield.

Exploring the heterogeneity of effects of corticosteroids on acute respiratory distress syndrome: a systematic review and meta-analysis

IntroductionThe effectiveness of corticosteroid therapy on the mortality of acute respiratory distress syndrome (ARDS) remains under debate. We aimed to explore the grounds for the inconsistent results in previous studies and update the evidence.MethodsWe searched MEDLINE, Cochrane Central Register of Controlled Trials and Web of Science up to December 2013. Eligible studies included randomized clinical trials (RCTs) and cohort studies that reported mortality and that had corticosteroid nonusers for comparison. The effect of corticosteroids on ARDS mortality was assessed by relative risk (RR) and risk difference (RD) for ICU, hospital, and 60-day mortality using a random-effects model.ResultsEight RCTs and 10 cohort studies were included for analysis. In RCTs, corticosteroids had a possible but statistically insignificant effect on ICU mortality (RD, −0.28; 95% confidence interval (CI), −0.53 to −0.03 and RR, 0.55; 95% CI, 0.24 to 1.25) but no effect on 60-day mortality (RD, −0.01; 95% CI, −0.12 to 0.10 and RR, 0.97; 95% CI, 0.75 to 1.26). In cohort studies, corticosteroids had no effect on ICU mortality (RR, 1.05; 95% CI, 0.74 to 1.49) but non-significantly increased 60-day mortality (RR, 1.30; 95% CI, 0.96 to 1.78). In the subgroup analysis by ARDS etiology, corticosteroids significantly increased mortality in influenza-related ARDS (three cohort studies, RR, 2.45, 95% CI, 1.40 to 4.27).ConclusionsThe effects of corticosteroids on the mortality of ARDS differed by duration of outcome measures and etiologies. Corticosteroids did not improve longer-term outcomes and may cause harm in certain subgroups. Current data do not support routine use of corticosteroids in ARDS. More clinical trials are needed to specify the favorable and unfavorable subgroups for corticosteroid therapy.

Skin and soft-tissue infection caused by non-tuberculous mycobacteria in Taiwan, 1997-2008.

The aim of this study was to investigate the clinical, microbiological, and pathological characteristics and the outcomes of skin and soft-tissue infection (SSTI) caused by non-tuberculous mycobacteria (NTM). Medical records of 50 patients with SSTI caused by NTM identified from 2005 to 2008 and 63 patients previously reported in a medical centre from 1997 to 2004 were reviewed. The annual incidence (per 100,000 outpatients and in-patients) ranged from 0·57 in 2005, 0·38 in 2007, to 1·1 in 2008, with an average of 0·62/100,000. From 1997 to 2008, the average incidence was 1·39/100,000 patients. The average annual incidence of SSTI caused by NTM was 0·62/100,000 outpatients and in-patients during 2005 and 2008. Of the total of 113 patients identified during the 12-year period, patients infected with Mycobacterium fortuitum and M. marinum were younger than those infected with M. avium-intracellulare complex (MAC) (36 and 44 years vs. 55 years, P=0·004 and P=0·056, respectively), and were more likely to have previous invasive procedures than those infected with MAC and M. abscessus (81·8% and 72·0% vs. 27·8% and 54·8%, P=0·007), and less likely to have associated immunosuppression (9·1% and 24% vs. 66·7% and 45·2%, P=0·006). Granuloma was more often observed in immunocompetent patients (60·1% vs. 40%, P=0·019), and in M. marinum-infected specimens (78·3%). There were significant differences in the demographic and clinical features of patients with NTM SSTI, including immunosuppression, trauma experience, and depth of tissue infections.

In Vitro Susceptibilities of Invasive Isolates of Candida Species: Rapid Increase in Rates of Fluconazole Susceptible-Dose Dependent Candida glabrata Isolates

ABSTRACT Voriconazole, posaconazole, caspofungin, micafungin, and anidulafungin demonstrated potent in vitro activities against 286 invasive Candida isolates. Analysis of the fluconazole susceptibilities of 204 bloodstream Candida glabrata isolates revealed a rapid shift from susceptible (64% in 1999 to 2001 to 19% in 2007) to susceptible-dose dependent (27% in 1999 to 2001 and 75% in 2007).

Multi-gene analyses from waste brushing specimens for patients with peripheral lung cancer receiving EBUS-assisted bronchoscopy.

OBJECTIVES Although flexible bronchoscopy with the assistance of miniature radial-probe endobronchial ultrasound (EBUS) is increasingly employed to diagnose peripheral lung cancer, transbronchial biopsies typically offer an insufficient amount of tissue to conduct additional molecular analysis. We evaluated the feasibility of multi-gene analyses from waste brushing samples obtained by EBUS-assisted bronchoscopy. MATERIALS AND METHODS For lung cancer patients with positive brushing cytology, analysis of EGFR, K-ras and EML4-ALK fusions were carried out, utilizing reverse transcription-polymerase chain reaction and Sanger sequencing on the cell-derived RNA retrieved from waste brushing samples. RESULTS EBUS-guided brushings were judged positive for tumor cells in 84 (68.9%) of the 122 patients with peripheral lung cancer receiving flexible bronchoscopy. Genotyping of EGFR and K-ras was successfully implemented in 80 (95.2%) of the 84 cytology-proven brushing samples, along with satisfactory yields to detect EGFR (55.0%) and K-ras (2.5%) mutations. The results of EGFR genotyping from the brushing specimens were highly concordant with those provided from other corresponding samples (concordance rate: 94%, kappa: 0.92). Of the 19 patients with adenocarcinoma or non-small cell lung cancer not otherwise specified harboring wild-type EGFR and K-ras, two cases (10.5%) were identified to harbor EML4-ALK fusions. CONCLUSION Our results suggest that multi-gene analyses from waste brushing specimens using RNA-based Sanger sequencing is highly feasible. This approach offers an opportunity to overcome the dilemma of flexible bronchoscopy in molecular diagnostics for lung cancer, and could potentially recruit more patients for targeted therapy according to the molecular characteristics of the tumor cells.

Infections due to Candida haemulonii: species identification, antifungal susceptibility and outcomes

Here we report the clinical features and treatment outcomes of three patients with Candida haemulonii infection. Candida haemulonii was confirmed by sequence analysis of the internal transcribed spacer (ITS) regions of the rRNA genes and the 18S rRNA genes. Two of the three isolates were associated with fungaemia and reduced susceptibility to fluconazole [minimum inhibitory concentrations (MICs) of 16 mg/L] and amphotericin B (MICs of 2 mg/L). However, one of these two patients responded to fluconazole therapy. Echinocandins, voriconazole and posaconazole demonstrated excellent in vitro potency against the isolates.

In-hospital and one-year mortality and their predictors in patients hospitalized for first-ever chronic obstructive pulmonary disease exacerbations: a nationwide population-based study.

Introduction Natural history of chronic obstructive pulmonary disease (COPD) is punctuated by exacerbations; however, little is known about prognosis of the first-ever COPD exacerbation and variables predicting its outcomes. Materials and Methods A population-based cohort study among COPD patients with their first-ever exacerbations requiring hospitalizations was conducted. Main outcomes were in-hospital mortality and one-year mortality after discharge. Demographics, comorbidities, medications and in-hospital events were obtained to explore outcome predictors. Results The cohort comprised 4204 hospitalized COPD patients, of whom 175 (4%) died during the hospitalization. In-hospital mortality was related to higher age (odds ratio [OR]: 1.05 per year; 95% confidence interval [CI]: 1.03–1.06) and Charlson comorbidity index score (OR: 1.08 per point; 95% CI: 1.01–1.15); angiotensin II receptor blockers (OR: 0.61; 95% CI: 0.38–0.98) and β blockers (OR: 0.63; 95% CI: 0.41–0.95) conferred a survival benefit. At one year after discharge, 22% (871/4029) of hospital survivors were dead. On multivariate Cox regression analysis, age and Charlson comorbidity index remained independent predictors of one-year mortality. Longer hospital stay (hazard ratio [HR] 1.01 per day; 95% CI: 1.01–1.01) and ICU admission (HR: 1.33; 95% CI: 1.03–1.73) during the hospitalization were associated with higher mortality risks. Prescription of β blockers (HR: 0.79; 95% CI: 0.67–0.93) and statins (HR: 0.66; 95% CI: 0.47–0.91) on hospital discharge were protective against one-year mortality. Conclusions Even the first-ever severe COPD exacerbation signifies poor prognosis in COPD patients. Comorbidities play a crucial role in determining outcomes and should be carefully assessed. Angiotensin II receptor blockers, β blockers and statins may, in theory, have dual cardiopulmonary protective properties and probably alter prognosis of COPD patients. Nevertheless, the limitations inherent to a claims database study, such as the diagnostic accuracy of COPD and its exacerbation, should be born in mind.

Coexistence of EGFR T790M mutation and common activating mutations in pretreatment non-small cell lung cancer: A systematic review and meta-analysis

OBJECTIVE Previous studies have indicated that EGFR exon 19 deletions in non-small cell lung cancer (NSCLC) are associated with better outcomes to tyrosine kinase inhibitors (TKIs) than the L858R mutation. This study aimed to evaluate whether T790M, a resistant mutation, is more likely to coexist with L858R mutation than with exon 19 deletions in pretreatment NSCLC patients. MATERIALS AND METHOD We searched MEDLINE and EMBASE up to Nov 30th, 2015 to identify randomized controlled trials (RCTs) and observational studies that reported pretreatment T790M and EGFR-activating mutation. A meta-analysis was performed using a random-effects model. The primary outcome was odds ratio (OR) of pretreatment T790M mutation in NSCLC co-existing with L858R mutation and exon 19 deletions. Stratified analysis was performed based on sensitivity of mutation detection methods for T790M. RESULTS We identified 15 observational studies and 3 RCTs for analysis. Pretreatment T790M was more frequent in L858R than in exon 19 mutated patients. The association of T790M and L858R was statistically significant in observational studies (OR, 1.65, 95% CI, 1.17-2.32), with less precision in RCTs (OR, 1.84, 95% CI, 0.96-3.52). In the stratified analysis based on the sensitivity of the mutation detection methods, the association was observed in the studies using intermediately (detection limit <5% and ≥ 0.1%; OR, 2.23, 95% CI, 1.19-4.17) and highly sensitive methods (detection limit <0.1%; OR, 1.74, 95% CI, 1.10-2.73), but not in those using low sensitivity methods (detection limit >5%; OR, 1.28, 95% CI, 0.74-2.23). CONCLUSIONS Pretreatment EGFR T790M mutation is more likely to coexist with L858R mutation than with exon 19 deletions in NSCLC. This association was observed only in studies using sensitive mutation detection methods (<5%).

Inhaled nitric oxide therapy and risk of renal dysfunction: a systematic review and meta-analysis of randomized trials

IntroductionInhaled nitric oxide (iNO) is an important therapy for acute respiratory distress syndrome (ARDS), pulmonary hypertension and pediatric hypoxemic respiratory failure. Safety concerns regarding iNO and renal dysfunction have been reported; however, there are currently no systematic reviews on this issue. Our objective was to evaluate published randomized controlled trials (RCTs) to ascertain the risk of renal dysfunction associated with iNO therapy in patients with and without ARDS.MethodsA systematic review of databases was performed to identify RCTs which compared iNO with controls up to September 2014. Effect estimates for risk ratio (RR) of acute kidney injury (AKI) were pooled using a random-effects model.ResultsTen RCTs involving 1363 participants were included. Inhaled nitric oxide significantly increased the risk of AKI compared with controls (RR, 1.4, 95%CI, 1.06 to 1.83, p = 0.02). In the stratified analysis, a high cumulative-dose of iNO significantly increased the risk of AKI (RR, 1.52, 95%CI, 1.14 to 2.02, p = 0.004), whereas medium and low cumulative-doses did not (RR, 0.64, 95%CI, 0.23 to 1.81 and RR, 0.56, 95%CI, 0.11 to 2.86 respectively). In subgroup analysis by study population, an increased risk of AKI was observed in patients with ARDS (RR, 1.55, 95%CI, 1.15 to 2.09, p = 0.005) but not in those without (RR, 0.90, 95%CI, 0.49 to 1.67, p = 0.75).ConclusionsThe available data show that iNO therapy may increase the risk of renal dysfunction, especially with prolonged use and in patients with ARDS. The risk in pediatric population is unknown owing to limited data. We suggest monitoring renal function during iNO therapy, and that future trials of iNO should evaluate renal safety.