Apophysomyces variabilis as an emerging pathogen in Mainland China.

BACKGROUND: Mucormycosis is a rare form of invasive, rapidly progressive and lethal opportunistic fungal infection caused by Mucorales. Although Rhizopus arrhizus (R. arrhizus) is the most commonly isolated Mucorales worldwide, infections caused by Apophysomyces variabilis (A. variabilis) are increasing. OBJECTIVES AND METHODS: We present a case of necrotizing fasciitis caused by A. variabilis in an immunocompetent woman. In order to further understand the characteristics of the strain isolated from the patient, we identified the strain through ITS sequencing, assessed the ability to tolerate salt concentrations and temperature conditions, in addition to performing in vitro drug susceptibility testing against common antifungal agents. RESULTS: The strain showed 98.76% identity with A. variabilis in the NCBI database, and it was found to tolerate higher temperatures and salt concentrations than previously reported strains. The strain was sensitive to amphotericin B and posaconazole, but not to voriconazole, itraconazole, 5-fluorocytosine and echinocandins. CONCLUSIONS: This case indicates that Mucorales caused by A. variabilis should be recognised as an emerging pathogen that can cause a high mortality rate in the absence of prompt diagnosis and proper treatment in China, aggressive surgical debridement combined with prompt and appropriate antifungal treatment may improve outcomes.

A Special Tinea Nigra Caused by Curvularia lunata: Case Report and Literature Review.

Tinea nigra is a superficial fungal infection usually caused by Hortaea werneckii (H. werneckii). We report a special case of tinea nigra in an immunocompetent child who developed a unilateral, rapidly growing pigmented lesion on her palm. Interestingly, Curvularia lunata (C. lunata) was isolated from the lesion scrapes and was identified by both morphological features and molecular biology methods. The lesion was completely cleared by topical naftifine hydrochloride and ketoconazole cream. We present-to the best of our knowledge-the first case of tinea nigra where the causative pathogen was identified as C. lunata. We therefore provide a brief literature review of previously reported cases of tinea nigra to broaden the knowledge of the potential causative pathogens. The etiology, demography, clinical features, diagnostic methods, and treatment of the reviewed cases are summarized and analyzed.

In Vitro Susceptibility of Berberine Combined with Antifungal Agents Against the Yeast Form of Talaromyces marneffei.

Talaromyces (Penicillium) marneffei can cause fatal disseminated infection in immunocompromised hosts. However, therapeutic strategies for the mycosis are limited. Reports of the other fungi suggest that berberine, a component of traditional herb, inhibitors interact with antifungal agents to improve the treatment outcomes. In the study, we evaluated the in vitro efficacy of berberine in combination with conventional antifungal agents against the pathogenic yeast form of T. marneffei. We demonstrate the synergistic effect of combination of berberine with fluconazole (52.38%), itraconazole (66.67%), voriconazole (71.43%), amphotericin B (71.43%) or caspofungin (52.38%) of T. marneffei strains, respectively. Time-kill curves confirmed the synergistic interaction, and no antagonistic was observed in all of the combinations. In conclusion, berberine could enhance the efficacy of conventional antifungal agents against the yeast form of T. marneffei in vitro. The results indicated berberine might have a potential role in combination therapy for talaromycosis.

Hydroxysafflor yellow A attenuates lymphostatic encephalopathy-induced brain injury in rats.

Hydroxysafflor yellow A (HSYA) is a main chemical component of the flower of Carthamus tinctorius. The present study investigated whether HSYA could attenuate brain injury induced by lymphostatic encephalopathy (LE). This was induced in adult male Wistar rats by cervical lymphatic blockade (CLB). Heart rate variability (HRV) was used as an indirect measurement of the regulatory function of the autonomic nervous system by recording the ECG signals from rats. It was shown that treatment with HSYA (5 mg/kg, i.p.) significantly alleviated the neurological deficits observed in rats with LE. Histological staining revealed that HSYA treatment attenuated LE-induced cell apoptosis in the rostral ventrolateral medullus (RVLM). Animals in the LE groups exhibited impaired regulatory roles of the autonomic nervous system in cardiovascular function, which was suppressed by pretreatment with HSYA. Additionally, HSYA administration significantly prevented the decrease of endothelial nitric oxide synthase (eNOS) mRNA and protein expression in the RVLM of rats with LE. These findings suggest that HSYA might provide neuroprotection against LE-induced brain injury and the associated functional alterations, which is likely regulated by the nitric oxide pathway.

Experimental Phaeohyphomycosis of Curvularia lunata.

Originally considered to be a plant pathogen, reports of phaeohyphomycosis due to Curvularia lunata (C. lunata) in animals and humans are increasing. However, studies on the pathogenesis, virulence, and epidemiology of C. lunata have rarely been discussed. In the present study, BALB/c mice were experimentally inoculated with C. lunata suspension by different routes and the course of infection was evaluated. In addition, the in vitro antifungal susceptibility of C. lunata against six commonly used antifungals was evaluated using the microdilution method. Inoculation resulted in skin lesions in animals inoculated intraperitonially and subcutaneously. Infection was confirmed by both mycological and histopathologic examination. C. lunata spores and hyphae were detected in the histopathologic sections stained with hexamine silver staining. In addition, voriconazole (VRC) demonstrated greater activity against C. lunata when compared to the other antifungals, whereas fluconazole (FLC) was the least active antifungal with a minimum inhibitory concentration (MIC) range of 8-16 µg/mL. Further studies are necessary to understand the pathogenicity of C. lunata and uncover the mystery of this fungus.

In vitro Antifungal Susceptibility Profiles of Cryptococcus neoformans var. grubii and Cryptococcus gattii Clinical Isolates in Guangxi, Southern China.

This study analyzed the in vitro drug sensitivity of Cryptococcus spp. from Guangxi, Southern China. One hundred three strains of Cryptococcus were recovered from 86 patients; 14 were HIV positive and 72 were HIV negative. Ninety-two strains were identified as Cryptococcus neoformans var. grubii, while 11 strains were identified as Cryptococcus gattii (5 C. gattii sensu stricto and 6 Cryptococcus deuterogattii). The recovered strains were tested against commonly used antifungal drugs (fluconazole, amphotericin B, 5-fluorocytosine, itraconazole, and voriconazole) and to novel antifungal drugs (posaconazole and isavuconazole) using CLSI M27-A4 method. The results showed that all isolates were susceptible to most antifungal drugs, of which the minimum inhibitory concentration (MIC) ranges were as follows: 0.05-4 µg/ml for fluconazole, 0.25-1 µg/ml for amphotericin B; 0.0625-2 µg/ml for 5-fluorocytosine, 0.0625-0.25 µg/ml for itraconazole, 0.0078-0.25 µg/ml for voriconazole, 0.0313-0.5 µg/ml for posaconazole, 0.0020-0.125 µg/ml for isavuconazole for C. neoformans var. grubii isolates, and 1-16 µg/ml for fluconazole, 0.125-1 µg/ml for 5-fluorocytosine, 0.25-1 µg/ml for amphotericin B, 0.0625-0.25 µg/ml for itraconazole, 0.0156-0.125 µg/ml for voriconazole, 0.0156-0.25 µg/ml for posaconazole, and 0.0078-0.125 µg/ml for isavuconazole for C. gattii isolates. Furthermore, some C. neoformans var. grubii isolates were found to be susceptible-dose dependent to 5-fluorocytosine and itraconazole. In addition, a reduction in the potency of fluconazole against C. gattii is possible. We observed no statistical differences in susceptibility of C. neoformans var. grubii and C. gattii in the tested strains. Continuous observation of antifungal susceptibility of Cryptococcus isolates is recommended to monitor the emergence of resistant strains.

Impaired Left Atrial Performance Resulting From Age-Related Arial Fibrillation Is Associated With Increased Fibrosis Burden: Insights From a Clinical Study Combining With an in vivo Experiment.

Background: Atrial fibrillation (AF) is increasingly considered an age-related degenerative disease, whose process is associated with the development of impaired left atrial (LA) performance. However, the subtle dynamic changes of LA performance in AF during aging have yet to be fully elucidated. Atrial fibrosis is a key substrate for the development of AF, but the progression of fibrosis during aging and its relationship with LA dysfunction need to be further explored. Methods: A total of 132 control individuals and 117 persistent AF patients were prospectively studied. Subjects were further stratified into three age groups (age group 1: younger than 65 years, age group 2: between 65 and 79 years old, and age group 3: older than 80 years). The two-dimensional speckle tracking imaging was carried out for analyzing the alterations in LA function underlying LA remodeling, whereas electroanatomic mapping was performed to investigate LA fibrosis burden. In animal study, aged mice and young mice served as research subjects. Echocardiography and histological staining were used to assess LA performance and fibrosis burden, respectively. Results: Echocardiography showed progressive increases in LA dimension and LA stiffness index, and progressive decreases in LA global longitudinal strain and LA strain rates with advancing age in both AF and control cohorts, which was more prominent in AF cohort. Electroanatomic mapping showed progressive decrease in mean LA voltage and progressive increases in LA surface area, low-voltage area %, and LA volume with advancing age, whereas more significant alterations were observed in AF patients. Moreover, left atrial global longitudinal strain was positively correlated with mean LA voltage, whereas LA stiffness index was negatively related to mean LA voltage. In animal experiment, increased LA size and pulmonary artery dimension as well as longer P-wave duration and more prominent LA fibrosis were found in aged mice. Conclusions: This study provides new evidence of subtle changes in structure and performance of left atrium and their association with atrial fibrosis in both AF and non-AF subjects during physiological aging. In addition, our study also provides normal values for LA structure and performance in both AF and non-AF conditions during aging. These measurements may provide an early marker for onset of AF and LA adverse remodeling.

The value of left atrial strain and strain rate in predicting left atrial appendage stasis in patients with nonvalvular atrial fibrillation.

BACKGROUND: This study aimed to investigate the value of left atrial (LA) strain and strain rate (S/SR) by transthoracic echocardiography (TTE) in predicting left atrial appendage (LAA) stasis, in order to find a way for LAA stasis screening which is easily performed in patients with nonvalvular atrial fibrillation (NVAF). METHODS: One hundred and thirty NVAF patients prepared for AF ablation were enrolled. TTE and transesophageal echocardiography (TEE) were performed in all patients. LA S/SR in each phase was analyzed off-line. LAA blood flow state and LAA function were assessed by using TEE. RESULTS: LA S/SRs during atrial reservoir phase (LA Sres/SRres) were significantly negatively cor-related with LAA spontaneous echo contrast (SEC) grade (r = -0.567 and -0.520, respectively; all p < 0.01), and positively correlated with LAA emptying fraction (r = 0.602 and 0.619, respectively; all p < 0.01) and with LAA peak emptying flow velocity (r = 0.623 and 0.642, respectively; all p < 0.01). The multivariate logistic regression analysis showed LA Sres to be the strongest independent predictor of LAA stasis, followed by LA volume index. LA Sres < 13% was recommended to predict LAA stasis with sensitivity of 90% and specificity of 74%. CONCLUSIONS: LA Sres by TTE can noninvasively predict LAA stasis and may be used as a screening tool to assist in the detection of LAA stasis in patients with NVAF. (Cardiol J 2018; 25, 1: 87-96).

The usefulness of global left atrial strain for predicting atrial fibrillation recurrence after catheter ablation in patients with persistent and paroxysmal atrial fibrillation.

BACKGROUND: Given the potential complications of atrial fibrillation (AF) recurrence after ablation, better predictors of the effectiveness of the procedure are necessary to guide patient selection. AIM: This prospective study was conducted to evaluate the clinical relevance of global left atrial longitudinal strain (GLAS) and AF recurrence after catheter ablation. METHODS: In 115 consecutive patients with AF (persistent, n=62; paroxysmal, n=53), transthoracic echocardiography was performed before catheter ablation to assess baseline left atrial mechanical function using speckle tracking echocardiography (STE). RESULTS: After 12 months of follow-up, 22 (35.5%) patients in the persistent AF group and 15 (28.3%) in the paroxysmal AF group exhibited AF recurrence. In both the paroxysmal and persistent AF populations, patients with recurrence presented with significantly impaired GLAS compared with patients without recurrence. Patients with recurrence also had a significantly higher pro-B-type natriuretic peptide concentration. A receiver operator curve analysis yielded area under the curve values of 0.94 and 0.86 for paroxysmal and persistent AF, respectively. In a multivariable Cox proportional-hazards analysis, GLAS was an independent predictor of AF recurrence after catheter ablation in both the paroxysmal AF group (hazard ratio: 0.79, 95% confidence interval: 0.67-0.96; P=0.01) and the persistent AF group (hazard ratio: 0.81, 95% confidence interval: 0.71-0.93; P=0.004). CONCLUSIONS: In both paroxysmal and persistent AF, decreased baseline left atrial deformation capabilities assessed by two-dimensional STE can help to identify patients at high risk of AF recurrence after catheter ablation. This variable may help to guide candidate selection and improve therapeutic strategies.

Association between left atrial appendage emptying velocity, N-terminal plasma brain natriuretic peptide levels, and recurrence of atrial fibrillation after catheter ablation.

PURPOSE: Multiple studies have shown the efficacy and potentially curative effect of catheter ablation (CA). However, CA is always accompanied by a considerable recurrence rate for atrial fibrillation (AF). We hypothesized that pre-procedure assessments of baseline left atrial appendage emptying flow velocity (LAAFV) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels would help identify abnormal atrial substrate and offer preliminary evidence regarding susceptibility to AF recurrence in patients with paroxysmal or persistent AF, respectively. METHODS: In 120 patients with AF (paroxysmal, 55; persistent, 65), transesophageal echocardiography was performed with assessment of LAAFV and NT-proBNP was measured before the first AF ablation. RESULTS: After 12 months of follow-up, 16 patients (29.1%) in the paroxysmal AF and 23 patients (35.4%) in the persistent AF experienced recurrence of AF. In ROC analysis, a NT-proBNP value of ≥291 pg/ml in the paroxysmal AF and ≥368 pg/ml in the persistent AF discriminated AFR and non-AFR with the greatest sensitivity and specificity. In multivariate regression analysis, LAAFV (OR 0.88, 95% CI 0.79-0.98, p = 0.023) was identified as an independent predictor of AFR in the paroxysmal AF population post-CA after adjustment for other risk factors; however, in the persistent AF population, LAAFV (OR 0.81, 95% CI 0.68-0.94, p = 0.007) and a NT-proBNP value ≥368 pg/ml (OR 18.29, 95% CI 1.32-252.84, p = 0.030) were identified as independent predictors for rhythm outcome compared to other parameters. CONCLUSIONS: In patients with persistent AF, elevated plasma NT-proBNP concentrations combined with low LAAFV were associated with rhythm outcome after AF ablation; however, LAAFV was the only independent predictor of CA efficacy in patients with paroxysmal AF.

Predictive value of quantitative contrast-enhanced ultrasound in hepatocellular carcinoma recurrence after ablation.

AIM: To investigate the relationship between contrast-enhanced ultrasound (CEUS), basic fibroblast growth factor (bFGF), endothelin-1 (ET-1), and hepatocellular carcinoma (HCC) recurrence after ablation. METHODS: A total of 51 HCC patients (38 males and 13 females) who received radiofrequency ablation in our hospital from June 2012 to July 2014 were enrolled in this study. The patients were divided into two groups: recurrence group and non-recurrence group. Routine abdominal examination was first performed in the horizontal position. Then the patients underwent CEUS and immunohistochemical staining before receiving radiofrequency ablation. All patients were followed-up every three months for one year. The results of CEUS and serum tumor marker levels were evaluated and combined together to estimate HCC recurrence and metastasis. Patients were divided into two groups: recurrence group and non-recurrence group. Quantitative parameters of CEUS and tumor expression levels of bFGF and ET-1 were compared between the two groups, respectively. Binary logistic regression analysis was used to analyze the relationship between CEUS quantitative parameters, expression levels of ET-1 and bFGF, and HCC recurrence after ablation. RESULTS: Based on the quantitative parameters of CEUS before patients received radiofrequency ablation, the levels of tumor rise time (tRT), tumor time to peak (tTTP), tumor peak intensity (tPI) and tumor-parenchymal peak intensity (t-pPI) in the recurrence group were significantly lower than those in the non-recurrence group (16.6 ± 6.1 vs 23.2 ± 7.0, P = 0.000; 41.2 ± 10.2 vs 59.6 ± 14.2, P = 0.000; 23.8 ± 6.7 vs 31.4 ± 6.4, P = 0.000; 7.1 ± 3.4 vs 14.6 ± 7.4, P = 0.000; respectively). The expression levels of bFGF in the recurrence group were significantly higher than those in the non-recurrence group (P < 0.05). Levels of tTTP showed a significant inverse correlation with the level of bFGF in tumors (r = -0.312, P = 0.037). The Binary logistic regression analysis results revealed that the levels of tRT, tTTP, tPI and the level of bFGF were associated with HCC recurrence after radiofrequency ablation (P < 0.05). CONCLUSION: CEUS is a noninvasive and effective method for evaluating the angiogenesis of HCC, and predicting its recurrence and prognosis.