Background: Psittacosis ranges from a mild illness to fulminant severe pneumonia with multi-organ failure.It's crucial to understand the clinical characteristics and identify risk factors for a better outcome. Methods:We conducted a retrospective analysis designed to identify risk factors for severe Chlamydia psittaci pneumonia (C. psittaci pneumonia) by comparing the clinical characteristics of patients with severe and less severe forms of the disease. Epidemiological, clinical, laboratory, computed tomography (CT) imaging, and outcome data were collected.Results: We enrolled 27 patients with C. psittaci pneumonia, with a median age of 63 (range, 47-82) years, and 23 of whom (85.2%) had a history of avian exposure. Dyspnea was seen in 15 patients with severe C. psittaci pneumonia (100%), and four in 12 non-severe patients (33.3%) (P<0.01). Compared to nonsevere patients, those with severe C. psittaci pneumonia had significantly higher levels of procalcitonin, urea nitrogen, lactate dehydrogenase, creatine kinase (CK), B natriuretic peptide (BNP), myoglobin, IL-6, and IL-10, as well as lower lymphocyte and CD8+ T cell counts, and P a O 2 /F i O 2 ratio. Among patients with severe infection, CT showed that 46.7% had multi-lobar (more than two lobes) pneumonia, whereas its incidence was 0% in non-severe patients (P=0.01). Multivariate analysis revealed that the independent risk factors associated with severe C.

BackgroundClinicians may fail to make an early diagnosis of pulmonary cryptococcosis (PC) without HIV infection. Serum cryptococcal capsular polysaccharide antigen (CrAg) test, histopathology and culture of lung tissue play different roles in diagnosis of PC.ObjectiveTo investigate the performance of serum CrAg test, histopathology and culture of the lung tissue in diagnosis of PC without HIV infection.Patients/methodsFrom January 2011 to September 2017, patients with proven PC were recruited from a teaching hospital in southern China. Those patients with HIV infection, PC confirmed by surgery or PC with probable or possible diagnosis were excluded from the study. Latex agglutination test and CrAg lateral flow assay were used for detection of serum CrAg. Lung biopsy and needle aspiration were performed under computed tomography guidance.ResultsEighty-nine patients with proven PC including 41 male (46.1%) and 48 female (53.9%) were enrolled. Fifty-one (57.3%) patients had underlying disease. Positive CrAg test was found in 83 (93.3%) cases. Among six cases with negative CrAg test, PC was confirmed by histology in two cases and positive culture in four cases. The histopathological results of 77 (86.5%) cases revealed cryptococcal granuloma and 12 cases showed chronic inflammation, which was confirmed by positive culture. Among 65 cases, the diseased tissue of 46 (70.8%) cases presented Cryptococcus neoformans in the culture and one case was diagnosed with lung cancer coexisting with PC.ConclusionOur findings showed that serum CrAg test is rapid and sensitive in diagnosing PC, histology is important for confirming PC and culture plays a complementary role. Biopsied lung tissue should be submitted for cultures whenever feasible.

Background To evaluate the diagnostic value of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) in immunocompromised patients for the diagnosis of suspected pneumonia in comparison with that of conventional microbiological tests (CMTs). Methods Sixty-nine immunocompromised patients with suspected pneumonia received both CMTs and mNGS of BALF were analyzed retrospectively. The diagnostic value was compared between CMTs and mNGS, using the clinical composite diagnosis as the reference standard. Results Sixty patients were diagnosed of pneumonia including fifty-two patients with identified pathogens and eight patients with probable pathogens. Taking the composite reference standard as a gold standard, 42 pathogens were identified by CMTs including nine bacteria, 17 fungi, 8 virus, 6 Mycobacterium Tuberculosis, and two Legionella and 19(45%) of which were detected by BALF culture. As for mNGS, it identified 76 pathogens including 20 bacteria, 31 fungi, 14 virus, 5 Mycobacterium Tuberculosis, four Legionella and two Chlamydia psittaci. The overall detection rate of mNGS for pathogens were higher than that of CMTs. However, a comparable diagnostic accuracy of mNGS and CMTs were found for bacterial and viral infections. mNGS exhibited a higher diagnostic accuracy for fungal detection than CMTs (78% vs. 57%, P < 0.05), which mainly because of the high sensitivity of mNGS in patients with Pneumocystis jirovecii pneumonia (PJP) (100% vs. 28%, P < 0.05). Nineteen patients were identified as pulmonary co-infection, mNGS test showed a higher detection rate and broader spectrum for pathogen detection than that of CMTs in co-infection. Moreover, Pneumocystis jirovecii was the most common pathogen in co-infection and mNGS have identified much more co-pathogens of PJP than CMTs. Conclusions mNGS of BALF improved the microbial detection rate of pathogens and exhibited remarkable advantages in detecting PJP and identifying co-infection in immunocompromised patients.

BackgroundPatients with high-titer anti-IFN-γ autoantibodies present disseminated non-tuberculous mycobacterial (NTM) and other opportunistic infections. Due to its rare occurrence and non-specific symptoms, this syndrome is difficult to diagnose during early disease stages. Here, we report a case with high-concentrations of serum anti-IFN-γ autoantibodies who presented with disseminated Talaromyces marneffei and NTM disease accompanied Sweet’s syndrome.Case presentationA 62-year-old Chinese woman with no previous history was admitted to our hospital in August 2016 due to intermittent fever for 2 years, left chest wall redness, and swelling for 3 months. During hospitalization, the patient was confirmed with disseminated T. marneffei and successfully treated with antifungal therapy. In July 2017, upon second admission, Mycobacterium avium intracellular (MAC) pulmonary infection was established after positive cultures from the right lung tissue. The patient failed treatment after 1 month of anti-NTM therapy due to side effects. In May 2018, she was confirmed as having disseminated MAC disease accompanied by hand rashes, which was considered as Sweet’s syndrome. High-level anti-IFN-γ antibodies in the patient serum were detected upon comparison with normal controls (2.85-fold increase). Following anti-NTM therapy, both symptoms and pulmonary infiltration gradually improved, and joint destruction and lymphadenitis remained.ConclusionsPatients with anti-interferon-γ autoantibodies should be considered for severe, recurrent infections in adults in the absence of other known risk factors. Sweet’s syndrome is a common skin manifestation of the syndrome.

Purpose This study aims to evaluate the diagnostic application and performance of the metagenomic next-generation sequencing (mNGS) in patients suspected of local pulmonary infection by comparing it to the traditional pathogen detection methods in lung tissue specimens obtained by a computerized tomography-guided biopsy (CT-guided biopsy). Methods We retrospectively reviewed patients, admitted to the First Affiliated Hospital of Wenzhou Medical University, China from May 2018 to December 2020, who were suspected of local pulmonary infection. All cases received a CT-guided lung biopsy, tissue samples were sent both for conventional examinations (CE) and mNGS tests. The sensitivity and specificity of the two diagnostic approaches were compared. Results 106 patients enrolled, 76 patients were diagnosed with a pulmonary infection. Among 49 patients with identified pathogens, CE confirmed pathogenic infections in 32 cases. Mycobacterium spp. and fungi accounted for 37.5% (12/32) and 28.1% (9/32), respectively, with bacteria 34.4% (11/32). The mNGS examination detected extra pathogenic microorganisms in 22 patients that were consistent with the patients' clinical and radiographic pictures. The sensitivity of mNGS was 53.9% vs. 42.1% for the CE, while the specificity was 56.7% versus 96.7%. For detection rate, mNGS was significantly superior to CE in bacterial (96.3% vs. 40.7%, p < 0.05), and mixed infections (100% vs. 50%, p < 0.05), but inferior to CE in fungal (60% vs. 90%, p > 0.05) and Mycobacterium spp. infections (66.7% vs. 100%, p > 0.05) with no significant difference. Among 31 cases diagnosed with lung abscess, the diagnostic performance of the detection rate was 67.7% (21/31) in favour of mNGS compared to 29.0% (9/31) for CE (p < 0.05). Most polymicrobial infections were induced by anaerobic species that coexisted with Streptococcus constellatus. And Klebsiella pneumoniae was the most common isolated monomicrobial infection. Conclusions The most commonly detected causative pathogens for local pulmonary infections were bacteria, Mycobacterium spp. and fungi. Compared with the CE, the advantages of mNGS in the pathogens detection lie in the discovery of bacterial and mixed infections, as well as in the detection of lung abscess. Conversely, mNGS is not good enough to be recommendable for the detection of Mycobacterium spp. and fungi.

Background: CACNA1D gene, which encodes the a1 subunit of the Cav1.3 L-type calcium channel effectively regulates intracellular Ca 2þ stability. In recent years, clinical studies have shown that the CACNA1D polymorphisms were associated with hypertension.Objective: The purpose of this study was to evaluate the effects of CACNA1D exon mutation on blood pressure (BP) in Sprague-Dawley rats. Methods:The rats with CACNA1D p.D307G, CACNA1D p.V936I or CACNA1D p.R1516Q were constructed using CRISPR-Cas9 technology. SBP measurements of rats were taken for 32 weeks. Tissue morphology of rats and vasoactive substances in serum was tested. Furthermore, the effects of L-type calcium channel blocker isradipine and endothelin-1 (ET-1) inhibitor BQ-123 on BP of double mutation rats (CACNA1D p.D307G/p.R1516Q) were tested. Then we examined the effects of CACNA1D gene mutation on gene expression in human umbilical vein endothelial cells (HUVECs) and vascular smooth muscle cells (VSMCs).Results: Elevated SBP and increased circulating ET-1 was observed in CACNA1D p.D307G mutant rats. Morphological assessments showed that the vascular, cardiac and renal remodeling could also be observed in rats with p.D307G mutant. Cav1.3 protein expression and calcineurin phosphatase activity in VSMCs of rats with CACNA1D p.D307G were increased in vitro, and the vascular ring tension test of mesenteric grade 3 arteries in CACNA1D p.D307G rats were increased in vivo. Furthermore, ET-1 expression were increased in isolated primary aortic endothelial cells in p.D307G mutant rats and transfected p.D307G mutant HUVECs. Finally, double heterozygosity rats with CACNA1D p.D307G/p.R1516Q or CACNA1D p.D307G/p.V936I further accelerated the rise of SBP compared with p.D307G mutation rats, and isradipine and BQ-123 reduced BP to the same extent in CACNA1D p.D307G/p.R1516Q rats. Conclusion:CACNA1D gene is key players in the regulation of blood pressure. CACNA1D mutation rat may be a new hypertension animal model.

Background: To evaluate the diagnostic value of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) in immunocompromised patients for the diagnosis of suspected pneumonia in comparation to that of conventional microbiological tests (CMTs).Methods: Sixty-nine immunocompromised patients with suspected pneumonia received both CMTs and mNGS of BALF were analyzed retrospectively. The diagnostic value was compared between CMTs and mNGS, using the clinical composite diagnosis as the reference standard. Results: Sixty patients were diagnosed of pneumonia including fifty-two patients with identified pathogens and eight patients with probable pathogens. The overall detection rate of mNGS for pathogens were higher than that of CMTs. However, a comparable diagnostic accuracy of mNGS and CMTs were found for bacterial and viral infections. mNGS exhibited a higher diagnostic accuracy for fungal detection than CMTs (78% vs. 54%, P＜0.05), which mainly because of the high sensitivity of mNGS in patients with Pneumocystis jirovecii pneumonia (PJP) (100% vs. 28%, P＜0.05). Among fifty-two patients with definite pathogens, nineteen patients (37%) were identified as pulmonary mixed infection, mNGS test showed a higher detection rate and broader spectrum for pathogen detection than that of CMTs in mixed infection. Moreover, Pneumocystis jirovecii was the most common pathogen in mix infection and mNGS have identified much more co-pathogens of PJP than CMTs.Conclusions: mNGS of BALF improved the microbial detection rate of pathogens and exhibited remarkable advantages in detecting PJP and identifying mixed infections in immunocompromised patients.

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