Metagenomic next-generation sequencing indicates more precise pathogens in patients with pulmonary infection: A retrospective study.

Background: Timely identification of causative pathogens is important for the diagnosis and treatment of pulmonary infections. Metagenomic next-generation sequencing (mNGS), a novel approach to pathogen detection, can directly sequence nucleic acids of specimens, providing a wide range of microbial profile. The purpose of this study was to evaluate the diagnostic performance of mNGS in the bronchoalveolar lavage fluid (BALF) of patients with suspected pulmonary infection. Methods: From April 2019 to September 2021, 502 patients with suspected pneumonia, who underwent both mNGS of BALF and conventional microbiological tests (CMTs), were classified into different groups based on comorbidities. The diagnostic performances of mNGS and CMTs were compared. Comprehensive clinical analysis was used as the reference standard. Results: The diagnostic accuracy and sensitivity of mNGS were 74.9% (95% confidence interval [CI], 71.7-78.7%) and 72.5% (95% CI, 68.2-76.8%) respectively, outperformed those of CMTs (36.9% diagnostic accuracy, 25.4% sensitivity). For most pathogens, the detection rate of mNGS was higher than that of CMTs. Polymicrobial infections most often occurred in immunocompromised patients (22.1%). Only 2.3% patients without underlying diseases developed polymicrobial infections. Additionally, the spectrums of pathogens also varied among the different groups. We found the positive predictive values (PPV) to be dependent upon both the pathogen of interest as well as the immunologic status of the patient (e.g., the PPV of Mycobacterium tuberculosis was 94.9% while the PPV of Pneumocystis jirovecii in immunocompetent individuals was 12.8%). This information can help physicians interpret mNGS results. Conclusion: mNGS of BALF can greatly enhance the accuracy and detection rate of pathogens in patients with pulmonary infections. Moreover, the comorbidities and types of pathogens should be taken consideration when interpreting the results of mNGS.

A meta-analysis of the association between CTLA-4 genetic polymorphism and susceptibility of asthma.

BACKGROUND: Numerous studies have reported an association between cytotoxic T-lymphocyte associated antigen 4 gene (CTLA4) polymorphism and susceptibility to asthma, in different populations, but the results have been inconsistent. We performed a meta-analysis of 19 published case-control studies to obtain a reasonably accurate estimation of the relationship between CTLA4 polymorphism and asthma. METHODS: We searched the Pubmed, EMBASE, Chinese National Knowledge Infrastructure, and Wanfang databases and extracted data from 19 independent, eligible studies. Odds ratios (ORs) with 95% confidence intervals (CIs) and Egger test were separately used to assess the strength of associations and publication bias. RESULTS: A total of 19 case-control studies involving 4831 cases and 4534 controls were identified. The combined results revealed that there was significant association between the +49A/G polymorphism and asthma (for GG + GA vs. AA: OR = 0.82, 95% CI = 0.70-0.97, P = .02). Stratification by race or age indicated a significant association between the CTLA-4 +49 GA+GG genotype and asthma in Asians (OR = 0.80, 95% CI = 0.68-0.95, P = .01) and children (OR = 0.75, 95% CI = 0.62-0.90, P = .002), but there was no association in whites (OR = 0.94, 95% CI = 0.80-1.10, P = .44) and adults (OR = 0.85, 95% CI = 0.68-1.06, P = .15). Additionally, there was a significant association with atopic asthma under the random-effects model (OR = 0.81, 95% CI = 0.67-0.98, P = .03). In addition, there was no significant association between the -318 C/T polymorphism and asthma risk. CONCLUSIONS: Our meta-analysis results suggested that the +49A/G polymorphism in CTLA-4 was an important risk factor for asthma susceptibility, especially in Asian individuals, children, and atopic patients.

A systematic review of malignancy-associated hemophagocytic lymphohistiocytosis that needs more attentions.

As an infrequent but potentially life-threatening hyperinflammatory syndrome, hemophagocytic lymphohistiocytosis (HLH) is clinically characterized with prolonged fever, hepatosplenomegaly, cytopenia, hypertriglyceridemia, hyperferritinemia and hemophagocytosis in bone marrow, liver, spleen or lymph nodes. Malignancy-associated HLH (M-HLH), one type of acquired HLH, usually presents variable overlaps of symptoms with other types of HLH, thus resulting in higher incidence of misdiagnosis and mortality. In recent years, with the increasing awareness to this disease, the diagnosis and management of HLH have gained more and more attention, and improvements have been made accordingly. As a result, the survival of patients is greatly prolonged. However, there is still no consensus on the diagnostic criteria and treatment strategies due to lack of large samples or prospective clinical trials. In order to improve recognition and diagnosis, and provide guidance regarding the treatment of M-HLH, the Study Group in HLH Subtypes of the Histiocyte Society has developed consensus recommendations for the diagnosis and management of M-HLH in 2015. In the present article, we summarized and discussed some updated understandings in M-HLH.

In vitro interaction between coxsackievirus B3 VP1 protein and human pleckstrin homology domain retinal protein (PHR1).

Coxsackievirus B3 (CVB3) infection causes central nervous system diseases including aseptic meningitis and encephalitis. To understand the mechanism of this virus, a yeast two-hybrid system was used to screen cellular proteins from a human heart cDNA library. The results revealed that the human Pleckstrin Homology Domain Retinal protein (PHR1), a PH domain-containing protein with low expression in the heart and high expression in the brain, interacts with CVB3 VP1, a major structural protein of CVB3. Yeast mating assays and in vitro coimmunoprecipitation verified the interaction between CVB3 VP1 and PHR1. An α-galactosidase assay indicated that of α-galactosidase activity was higher in positive clones than in controls suggesting a strong interaction. Furthermore, assay of deletion mutants defined the minimal region of PHR1 required for its interaction with VP1 as amino acids 95-172 and two regions of VP1 required for its interaction with PHR1 as amino acids 729-767 and 811-859. The results revealed multiple binding sites between PHR1 and CVB3 VP1 and suggested that the strong interaction between these two proteins might play an important role in central nervous system disease in the human brain.