Influence of Metabolic Risk Factors on the Risk of Bacterial Infections in Hepatitis B-Related Cirrhosis: A 10-Year Cohort Study.

Aim: The effect of metabolic factors on the risk of bacterial infections (BIs) in patients with hepatitis B virus (HBV)-related cirrhosis has not been demonstrated. This study aimed to explore specific metabolic factors associated with the BIs in these patients. Methods: A population-based cohort of 471 patients with HBV-related cirrhosis was retrospectively enrolled between 2009 and 2019. The primary end point was the incidence of BIs during hospitalization, which were compared according to the metabolism-related indicators, namely, presence of diabetes, level of high-density lipoprotein cholesterol (HDLC) and triglyceride, and body mass index (BMI). The propensity score matching (PSM) was adopted to eliminate baseline discrepancies. Results: Compared with the non-diabetic group, the incidences of BIs were higher in the diabetic group before and after PSM (p = 0.029 and p = 0.027). Similar results were found in the low HDLC group as compared with the normal HDLC group before and after PSM (p < 0.001 and p = 0.025). Further analysis showed that the incidences of BIs in patients with low HDLC alone were lower than patients with both low HDLC and diabetes before and after PSM (p = 0.003 and p = 0.022). Similarly, the incidence of BIs in patients with diabetes alone was lower than those in patients with both low HDLC and diabetes both before and after PSM (p = 0.002 and p = 0.018). However, neither triglyceride nor BMI level was related to BIs in our cohort. Conclusion: In patients with HBV-related cirrhosis, the presence of diabetes and low level of HDLC were risk factors of BIs, showing a synergistic effect.

Immune-related cholangitis induced by immune checkpoint inhibitors: a systematic review of clinical features and management.

BACKGROUND AIMS: Immune checkpoint inhibitors (ICIs) improve the survival of patients with advanced tumors. However, immune-related adverse events limit the use of ICIs. Although liver toxicity has been concerned gradually, little is known about bile duct injury associated with ICIs. Hence, this review aims to describe clinicopathological features, imaging, and management of immune-mediated cholangitis (IMC) induced by ICIs. METHODS: We retrieved the literature from the PubMed database for case reports and series of IMC induced by ICIs. IMC was then classified as small-ducts type, large-ducts type and mixed type. Biochemical parameters, pathological characteristics, imaging features, treatment and response were evaluated and compared among three patterns. RESULTS: Fifty-three cases of IMC were enrolled. The median values of alkaline phosphatase and alanine transaminase of IMC were 1328 and 156 IU/L. The ALP level of the large-ducts type was higher than that of the small-ducts type (P = 0.021). The main pathological characteristics of small-ducts cholangitis were portal inflammation, bile duct injury and ductular reaction. The imaging features of large-duct cholangitis were bile duct dilatation, stenosis and bile duct wall thickening and irregularity. Forty-eight (90%) cases received immunosuppression therapy. Biliary enzymes reduced in 79% of cases receiving immunosuppression therapy, but only 8.5% of cases returned to normal. It took a long time for biliary enzymes to recover. CONCLUSIONS: The clinicians should be aware of the possibility of IMC if the biliary enzymes increase significantly after the use of ICIs. The liver function can be improved partially by immunosuppressive therapy in the majority of IMC.

Delayed diagnosis of hyperimmunoglobulin E syndrome with STAT3 mutation in mainland China: a case report and literature review.

Hyperimmunoglobulin E syndrome (HIES) is a rare immunologic disorder. Typical clinical features of HIES include recurrent bacterial pneumonia, lung cysts, characteristic facial features, and newborn dermatitis. The varied clinical presentation can lead to a delayed diagnosis. We herein present a sporadic case of HIES in a man who initially presented with a longstanding history of intractable skin abscesses.

Dual Role of gnaA in Antibiotic Resistance and Virulence in Acinetobacter baumannii.

Acinetobacter baumannii is an important Gram-negative pathogen in hospital-related infections. However, treatment options for A. baumannii infections have become limited due to multidrug resistance. Bacterial virulence is often associated with capsule genes found in the K locus, many of which are essential for biosynthesis of the bacterial envelope. However, the roles of other genes in the K locus remain largely unknown. From an in vitro evolution experiment, we obtained an isolate of the virulent and multidrug-resistant A. baumannii strain MDR-ZJ06, called MDR-ZJ06M, which has an insertion by the ISAba16 transposon in gnaA (encoding UDP-N-acetylglucosamine C-6 dehydrogenase), a gene found in the K locus. The isolate showed an increased resistance toward tigecycline, whereas the MIC decreased in the case of carbapenems, cephalosporins, colistin, and minocycline. By using knockout and complementation experiments, we demonstrated that gnaA is important for the synthesis of lipooligosaccharide and capsular polysaccharide and that disruption of the gene affects the morphology, drug susceptibility, and virulence of the pathogen.

Diffusion-weighted imaging and variable flip angle T1 mapping: a supplement for image-guided biopsy in follow-up analysis of liver fibrosis.

Purpose To evaluate the performance of diffusion-weighted imaging (DWI) and variable flip angle (VFA) T1 mapping as a supplement to image-guided biopsy in follow-up analysis of liver fibrosis. Materials and Methods This prospective study was approved by the institution's committee on human research, and written informed consent was provided from the enrolled patients. We investigated five MRI parameters of DWI and VFA T1 mapping, collected from 11 patients who underwent serial ultrasound image-guided biopsy with follow-up MRI within 1.5 years after treatment for liver fibrosis/cirrhosis. For each patient, four consecutive MRI examinations were conducted, including baseline MRI before treatment and three follow-up MRI examinations after treatment at each 0.5-year interval. ADC values at four b values and T1 relaxation times were correlated to pathology-confirmed liver fibrosis stages, which were subsequently divided into two groups, stages F2-3 and F4. The receiver operating characteristic (ROC) analysis and repeated measurement analysis of variance were used for statistical analysis. Results Among these ADC parameters, ADC value (b = 500 s/mm2) was the most consistent in differentiating between stage F2-3 and F4 liver fibrosis. Repeated measurement analysis showed that the intra-group and inter-group differences were 0.447 and 0.024, respectively. T1 relaxation time could not consistently differentiate between the F2-3 and F4 groups; however, it was repeatable, and the intra-group and inter-group differences were 0.410 and 0.042, respectively. Conclusion MRI-ADC value at a b value of 500 s/mm2 can be a promising biomarker for differentiating stages F2-3 and F4 liver fibrosis. A combination of this biomarker with repeatable T1 relaxation time may function as a non-invasive tool for follow-up liver fibrosis in patients who reject repeated image-guided biopsy.

Genomic and transcriptome analysis of triclosan response of a multidrug-resistant Acinetobacter baumannii strain, MDR-ZJ06.

During the last decade, an increasing amount of attention has focused on the potential threat of triclosan to both the human body and environmental ecology. However, the role of triclosan in the development of drug resistance and cross resistance is still in dispute ascribed to largely unknown of triclosan resistance mechanism. In this work, Acinetobacter baumannii MDR-ZJ06, a multidrug-resistant strain, was induced by triclosan, and the genomic variation and transcriptional levels were investigated, respectively. The comparative transcriptomic analysis found that several general protective mechanisms were enhanced under the triclosan condition, including responses to reactive oxygen species and cell membrane damage. Meanwhile, all of the detected fifteen single nucleotide polymorphisms were not directly associated triclosan tolerance. In summary, this work revealed the crucial role of the general stress response in A. baumannii under a triclosan stress condition, which informs a more comprehensive understanding of the role of triclosan in the spread of drug-resistant bacteria.

A genomics based discovery of secondary metabolite biosynthetic gene clusters in Aspergillus ustus.

Secondary metabolites (SMs) produced by Aspergillus have been extensively studied for their crucial roles in human health, medicine and industrial production. However, the resulting information is almost exclusively derived from a few model organisms, including A. nidulans and A. fumigatus, but little is known about rare pathogens. In this study, we performed a genomics based discovery of SM biosynthetic gene clusters in Aspergillus ustus, a rare human pathogen. A total of 52 gene clusters were identified in the draft genome of A. ustus 3.3904, such as the sterigmatocystin biosynthesis pathway that was commonly found in Aspergillus species. In addition, several SM biosynthetic gene clusters were firstly identified in Aspergillus that were possibly acquired by horizontal gene transfer, including the vrt cluster that is responsible for viridicatumtoxin production. Comparative genomics revealed that A. ustus shared the largest number of SM biosynthetic gene clusters with A. nidulans, but much fewer with other Aspergilli like A. niger and A. oryzae. These findings would help to understand the diversity and evolution of SM biosynthesis pathways in genus Aspergillus, and we hope they will also promote the development of fungal identification methodology in clinic.

Diversity and evolution of oligopeptide permease systems in staphylococcal species.

Several oligopeptide permease (Opp) systems have been found in staphylococcal species, including Opp1-4, Opp3' and the arginine catabolic mobile element (ACME)-encoded Opp system (ACME-Opp). They confer upon bacteria the increasing fitness, but their evolutionary histories remain unclear. In this work, we performed a genome-wide identification of Opp systems in staphylococcal species. Novel Opp systems were identified, including the duplicate of Opp4 in Staphylococcus pseudintermedius and the ACME-Opp-like systems in coagulase-negative staphylococci (CoNS). Phylogenetic analysis revealed that all of the identified Opp systems were derived from Opp3 system by operon duplication during species divergence, while lateral gene transfer might also confer to the dissemination of Opp in staphylococci. In addition, we proposed an improved theory on evolution of ACME: the Opp and arginine-deiminase systems were firstly transferred from Staphylococcus haemolyticus to Staphylococcus epidermidis independently; in S. epidermidis they were assembled together and then transferred to Staphylococcus aureus.

Characterization of the staphylococcal cassette chromosome composite island of Staphylococcus haemolyticus SH32, a methicillin-resistant clinical isolate from China.

Staphylococcal cassette chromosome (SCC) elements contribute considerably to virulence and resistance to antibiotic agents in staphylococci. SCC elements in coagulase-negative staphylococci (CoNS) are highly diverse and there is evidence suggesting that they serve as a reservoir for antibiotic resistance genes in methicillin-resistant Staphylococcus aureus (MRSA). However, only a small number of SCC elements have been characterized in CoNS and their exact roles in the emergence and evolution of MRSA remain to be demonstrated. Here, we determined the structure of an SCC composite island (CISH32) found in the clinical Staphylococcus haemolyticus isolate SH32 by whole-genome DNA sequencing. CISH32 was 48 kb in length and mainly composed of two imperfect SCC elements, namely (i) a ΨSCCmec(SH32) part containing a class C1 mec gene complex but lacking ccr genes and (ii) a SCCSH32 part with a ccrA5B3 gene complex but lacking mec genes. In addition, CISH32 contained a type III restriction-modification system and several resistance loci, for example genes conferring resistance to cadmium and arsenic. ΨSCCmec(SH32) is almost entirely identical to a pseudo SCCmec element found in S. haemolyticus WCH1 and shares pronounced sequence similarity to a ΨSCCmec element of S. haemolyticus JCSC1435. However, staphylococci other than S. haemolyticus, including S. aureus and S. epidermidis, contain homologs of SCCSH32 that are more similar to SCCSH32 than those elements found in S. haemolyticus, suggesting that CISH32 of S. haemolyticus SH32 was assembled in recent evolutionary events. Moreover, the composite structure of CISH32 indicates that the detection of class C1 mec and ccrA5B3 gene complexes in S. haemolyticus does not always indicate the existence of a UT9-type SCCmec element, which has remained questionable.

Genomic analysis of the multidrug-resistant Acinetobacter baumannii strain MDR-ZJ06 widely spread in China.

We previously reported that the multidrug-resistant (MDR) Acinetobacter baumannii strain MDR-ZJ06, belonging to European clone II, was widely spread in China. In this study, we report the whole-genome sequence of this clinically important strain. A 38.6-kb AbaR-type genomic resistance island (AbaR22) was identified in MDR-ZJ06. AbaR22 has a structure similar to those of the resistance islands found in A. baumannii strains AYE and AB0057, but it contained only a few antibiotic resistance genes. The region of resistant gene accumulation as previously described was not found in AbaR22. In the chromosome of the strain MDR-ZJ06, we identified the gene bla(oxa-23) in a composite transposon (Tn2009). Tn2009 shared the backbone with other A. baumannii transponsons that harbor bla(oxa-23), but it was bracketed by two ISAba1 elements which were transcribed in the same orientation. MDR-ZJ06 also expressed the armA gene on its plasmid pZJ06, and this gene has the same genetic environment as the armA gene of the Enterobacteriaceae. These results suggest variability of resistance acquisition even in closely related A. baumannii strains.

Triclosan resistance in clinical isolates of Acinetobacter baumannii.

The susceptibility to triclosan of 732 clinical Acinetobacter baumannii isolates obtained from 25 hospitals in 16 cities in China from December 2004 to December 2005 was screened by using an agar dilution method. Triclosan MICs ranged between 0.015 and 16 mg l(-1), and the MIC(90) was 0.5 mg l(-1), lower than the actual in-use concentration of triclosan. Twenty triclosan-resistant isolates (MICs >or=1 mg l(-1)) were characterized by antibiotic susceptibility, clonal relatedness, fabI mutation, fabI expression, and efflux pump phenotype and expression to elucidate the resistance mechanism of A. baumannii to triclosan. The resistance rates of triclosan-resistant isolates to imipenem, levofloxacin, amikacin and tetracycline were higher than those of triclosan-sensitive isolates. Triclosan resistance was artificially classified as low level (MICs 1-2 mg l(-1)) or high level (MICs >or=4 mg l(-1)). High-level triclosan resistance could be explained by a Gly95Ser mutation of FabI, whilst wild-type fabI was observed to be overexpressed in low-level resistant isolates. Active efflux did not appear to be a major reason for acquired triclosan resistance, but acquisition of resistance appeared to be dependent on a background of intrinsic triclosan efflux.

Distribution of the ACME-arcA gene among meticillin-resistant Staphylococcus haemolyticus and identification of a novel ccr allotype in ACME-arcA-positive isolates.

The aim of this study was to investigate the prevalence and characteristics of ACME (arginine catabolic mobile element)-arcA-positive isolates among meticillin-resistant Staphylococcus haemolyticus (MRSH). ACME-arcA, native arcA and SCCmec elements were detected by PCR. Susceptibilities to 10 antimicrobial agents were compared between ACME-arcA-positive and -negative isolates by chi-square test. PFGE was used to investigate the clonal relatedness of ACME-arcA-positive isolates. The phylogenetic relationships of ACME-arcA and native arcA were analysed using the neighbour-joining methods of mega software. A total of 42 (47.7 %) of 88 isolates distributed in 13 PFGE types were positive for the ACME-arcA gene. There were no significant differences in antimicrobial susceptibility between ACME-arcA-positive and -negative isolates. A novel ccr allotype (ccrAB(SHP)) was identified in ACME-arcA-positive isolates. Among 42 ACME-arcA-positive isolates: 8 isolates harboured SCCmec V, 8 isolates harboured class C1 mec complex and ccrAB(SHP); 22 isolates harbouring class C1 mec complex and 4 isolates harbouring class C2 mec complex were negative for all known ccr allotypes. The ACME-arcA-positive isolates were first found in MRSH with high prevalence and clonal diversity, which suggests a mobility of ACME within MRSH. The results from this study revealed that MRSH is likely to be one of the potential reservoirs of ACME for Staphylococcus aureus.

Dissemination of imipenem-resistant Acinetobacter baumannii strains carrying the ISAba1 blaOXA-23 genes in a Chinese hospital.

An outbreak of 95 clinical infections with imipenem-resistant Acinetobacter baumannii in a Chinese hospital was investigated and the carbapenemase-encoding genes and their relationship with ISAba1 of these and a further 16 isolates recovered from the intensive care unit (ICU) environment were analysed. Almost all isolates were resistant to a wide range of antimicrobials; the lowest resistance rates were found for polymyxin E (17.1 %), cefoperazone/sulbactam (30.6 %) and ampicillin/sulbactam (67.6 %). Six pattern types defined by DNA macrorestriction patterns were distinguished among the clinical isolates with dissemination of pattern A (50 isolates) to patients in seven hospital units and pattern B (35 isolates) to eight units; the environmental isolates from ICUs were also of pattern A. All isolates were positive for the bla(OXA-66) and bla(OXA-23) genes. The OXA-23-encoding gene was located 34 bp downstream of ISAba1. No plasmids were detected and conjugal transfer of resistance was not demonstrated. The bla(OXA-23) probe hybridized with 200 and 220 kb ApaI chromosomal fragments for type patterns A and B, respectively.