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Background Klebsiella pneumoniae is a primary pathogen of pyogenic liver abscess (PLA). However, little data are available on combination with sepsis. In this study, we aimed to evaluate the clinical characteristics and prognostic differences of PLA patients with sepsis. Methods This retrospective cohort study was conducted to investigate 135 patients with confirmed Klebsiella pneumoniae-caused liver abscesses (KPLA) from a tertiary teaching hospital, from 2013 to 2019. The patients were divided into two groups, KPLA with sepsis and KPLA without sepsis. The demographic characteristics, clinical features as well as laboratory and microbiologic findings were analyzed. Results A total of 135 patients with KPLA were analyzed. The mean age of patients was 60.9 ± 12.7 years, and the percentage of men was 59.3%. Among them, 37/135 (27.4%) of patients had sepsis and the mortality rate was 1.5%. The most common symptom was fever (91.1%). KPLA patients with sepsis had a significantly higher proportion of frailty, diarrhea, fatty liver, chronic renal insufficiency, and hepatic dysfunction compared to KPLA patients without sepsis (p < 0.05). Antibiotic therapy and percutaneous drainage were most frequently therapeutic strategy. Furthermore, the incidences of sepsis shock and acute respiratory distress syndrome were higher in the sepsis group compared to the non-sepsis group. As for metastatic infections, the lung was the most common site. In addition, KPLA patients with sepsis showed respiratory symptoms in 11 patients, endophthalmitis in 4 patients, and meningitis in 1 patient. Conclusion Our findings emphasize that KPLA patients combined with or without sepsis have different clinical features, but KPLA patients with sepsis have higher rates of complications and metastatic infections. Taken together, further surveillance and control of septic spread is essential for KPLA patients.

Objective Reactive oxygen species are believed to be involved in the onset of RA, and the association between nuclear-encoded mitochondrial respiratory chain-related variants and RA has recently been revealed. However, little is known about the landscape of mitochondrial DNA (mtDNA) variants in RA. Methods Next-generation sequencing was conducted to profile mtDNA germline and somatic variants in 124 RA patients and 123 age- and sex-matched healthy controls in the Taizhou area, China. Fisher’s exact test, SKAT and SKAT-O were used for gene-burden tests to investigate RA-related variants of mitochondrial genes. Predictive tools were applied to evaluate the pathogenicity of mtDNA variants, and mtDNA haplogroups were assigned according to mtDNA mutations recorded in PhyloTree database. The frequency distribution of mtDNA haplogroups between the groups was compared using χ2 analysis. Results We identified 467 RA-unique and 341 healthy control-unique mtDNA variants, with 443 common variants. Only MT-ATP6 with a significant burden of variants was identified by Fisher’s exact test, SKAT and SKAT-O, even after Bonferroni adjustment, and the enrichment variants in MT-ATP6 was mainly driven by m.8830C&gt;A, m.8833G&gt;C and m.8843T&gt;A variants. Besides, four frequently low-heteroplasmic variants including the three variants above and m.14135T&gt;G of MT-ND5 were detected in RA only; except for m.8830C&gt;A, they are considered potential pathogenicity based on functional predictions. χ2 analysis before Bonferroni adjustment revealed haplogroup F1/F1a to be negatively associated with RA (P &lt; 0.05). Conclusion These results profiled the landscape of germline and somatic mtDNA variants in RA and supported the effects of mitochondrial genes on RA.

Purpose We analyzed the clinical concordance of mNGS test results from blood samples and improved the clinical efficiency of mNGS in the diagnosis of suspected sepsis pathogens. Patients and Methods In this study, 99 samples of suspected blood flow infection were included for plasma mNGS, and the correlation between mNGS results and blood culture results, serum inflammatory indices, clinical symptoms and antibiotic treatment was analyzed, as well as the comparison with the detection rate of BALF pathogens, as well as the classification of different pathogens in the mNGS results were analyzed. Results The mNGS pathogen detection rate was higher than that of traditional blood culture (83.02% vs 35.82%). The rate of the mNGS results being consistent with the clinical diagnosis was also higher than that of traditional blood culture (58.49% vs 20.75%). This study shows that bacteria and fungi are the main pathogens in sepsis, and viral sepsis is very rare. In this study, 32% of sepsis patients were secondary to pneumonia. Compared with the pathogen detection rate using alveolar lavage fluid, the detection rate from plasma mNGS was 62.5%. Samples were also easy to sample, noninvasive, and more convenient for clinical application. Conclusion This study shows that compared with blood culture, the detection rate of mNGS pathogen that meets the diagnosis of sepsis is higher. We need a combination of multiple indicators to monitor the early diagnosis and treatment of sepsis.

Purpose: Cerebral aspergillosis (CA) is a rare but often fatal, difficult-to-diagnose, opportunistic infection. The utility of metagenomic next-generation sequencing (mNGS) for diagnosis of CA is unclear. We evaluated the usefulness of mNGS of the cerebrospinal fluid (CSF) for the diagnosis of CA.Methods: This prospective study involved seven consecutive patients with confirmed CA in whom CSF mNGS was performed. Serum (1→3)-β-D-glucan and galactomannan levels were determined, and histopathological examination and mNGS of the CSF were conducted. CSF specimens from three non-infected patients were used as positive controls.Results: mNGS of the CSF was positive in six of the seven confirmed CA cases (85.71% sensitivity). In the cryptococcal meningitis group (control), mNGS of the CSF was positive for Aspergillus in two patients (84.62% specificity). The positive likelihood ratio, negative likelihood ratio, and Youden’s index of mNGS for CA in the CSF were 5.565, 0.169, and 0.7, respectively. Among the six mNGS-positive cases, more than two Aspergillus species were found in four (4/6, 66.67%). In the positive controls, the addition of one A. fumigatus spore yielded a standardised species-specific read number (SDSSRN) of 25.45 by mNGS; the detection rate would be 0.98 if SDSSRN was 2.Conclusion: mNGS facilitates the diagnosis of CA and may reduce the need for cerebral biopsy in patients with suspected CA.Trial Registration Number: Chinese Clinical Trial Registry, ChiCTR1800020442.

Objective The purpose of the current study was to evaluate the association between C-reactive protein-to-platelet ratio (CPR), neutrophil-to-lymphocyte*platelet ratio (NLPR) and fibrinogen-to-platelet ratio (FPR) and the prognoses of pyogenic liver abscess (PLA) patients. Methods A cohort of 372 patients with confirmed PLA were enrolled in this retrospective study between 2015 and 2021. Laboratory data were collected on admission within 24 h. The demographic characteristics and clinical features were recorded. Risk factors for outcomes of PLA patients were determined via multivariate logistic regression analyses, and optimal cut-off values were estimated by using the receiver operating characteristic (ROC) curve analysis. Results Out of 372 patients, 57.8% were men, 80 (21.5%) developed sepsis, and 33 (8.9%) developed septic shock. The levels of CPR, NLPR and FPR were significantly increased in the development of sepsis, and prolonged hospital stays in PLA patients. The multivariate logistic regression analysis indicated that the CPR (OR: 2.262, 95% CI: 1.586–3.226, p < 0.001), NLPR (OR: 1.118, 95% CI: 1.070–1.167, p < 0.001) and FPR (OR: 1.197, 95% CI: 1.079–1.329, p = 0.001) were independent risks of PLA patients with sepsis, and NLPR (OR: 1.019, 95% CI: 1.004–1.046, p = 0.019) was shown to be an independent predictor of prolonged hospital stays. The ROC curve results showed that the three biomarkers had different predictive values, and CPR proved to work best, with a ROC value of 0.851 (95% CI: 0.807–0.896, p < 0.001) for sepsis. Conclusion Higher levels of CPR, NLPR and FPR were associated with a higher risk of poor outcomes. Moreover, a high CPR level performed best when predicting the clinical outcome in PLA patients.

Progranulin (PGRN) is a secreted protein that can regulate cell cycle progression, cell motility, and tumorigenesis. The PGRN expression in hematological malignancies is limited to multiple myeloma, but its expression and survival prognostic role in acute myeloid leukemia (AML) is still controversial. To evaluate the PGRN expression and estimate its survival prognostic role in AML patients. In this study, all patients were divided into three groups, which included 38 newly diagnosed adult AML patients, 33 complete remissions (CR-AML) patients, and 60 healthy control (HC) patients. The endpoints were relapse-free survival (RFS) and overall survival (OS). We investigated plasma PGRN levels by using enzyme-linked immunosorbent assay. Plasma PGRN levels in AML patients were higher than that in CR-AML and HC groups. After two chemo cycles, 16 patients had complete remission (CR). The level of plasma PGRN in non-CR patients compared to CR patients was obviously different (median 44.19 vs 21.10 ng/mL) (P = .025). In non-M3 (French–American–British classification) patients, 70% (21/30) patients relapsed in 1 year and 80% (24/80) patients died in the observed time. Using the value (median 19.95) as a “cut-off” value, we have divided non-M3 patients into low- and high-PGRN expression groups. High-PGRN expression patients had a poorer RFS with a median of 5.4 months (95% CI 3.7–7.1) and low-PGRN expression patients had a good RFS with a median of 8.9 months (95% CI 6.3–11.5; P = .027). In the survival analyses, high-PGRN expression of AML patients had shorter OS than low-PGRN expression of AML patients (6.2 vs 20.5 months, P = .008). PGRN is overexpressed in AML, which is a convenient and independent prognostic marker that is measured easily in AML patients.

ObjectiveMetagenomic next-generation sequencing (mNGS) technology has the potential to detect a wide range of pathogenic microorganisms. However, reports on the diagnostic value and clinical significance of different platforms of mNGS for patients with lower respiratory tract infections (LRTIs) remain scarce.MethodsA total of 306 patients with suspected LRTIs were enrolled from January 2019 to December 2021. The diagnostic performance of conventional methods and mNGS on bronchoalveolar lavage fluid (BALF) were compared. BALF mNGS was performed using a commercial and an in-house laboratory. The diagnostic value and the clinical implications of mNGS for LRTIs were analyzed for the different platforms.ResultsThe positive rate of mNGS in the in-house group was higher than that in the commercial group (85.26% vs. 70.67%, p &lt; 0.001). mNGS significantly increased the pathogen detection rate compared with conventional methods [from 70.67% vs. 22.67% (p &lt; 0.001) to 85.26% vs. 30.77% (p &lt; 0.001)]. The pathogens detected using mNGS included bacteria, fungi, viruses, and atypical pathogens. The in-house platform performed well on a wider spectrum of microbial distribution. Furthermore, it showed an advantage in detecting mixed pathogens in immunocompromised patients. Among the mNGS positive cases, 34 (32.0%) cases had their antibiotics adjusted in the commercial group, while 51 (38.3%) cases had a change of treatment in the in-house group. Moreover, the turnaround time of mNGS and the time from mNGS to discharge in the in-house group were significantly shorter than those in the commercial group.ConclusionIn-house mNGS had a higher detection rate and can show a wider spectrum of pathogens, with potential benefits for the clinic by shortening the turnaround time and hospitalization, and it may be more suitable for clinical microbiology laboratories.