Influence of Appropriate Empirical Antibiotic Treatment on the Prognosis of ICU Patients with HAP Caused by Carbapenem-Resistant Gram-Negative Bacteria.

Purpose: In patients with carbapenem-resistant Gram-negative bacteria (CRGNB) infection, the impact of appropriate empirical antibiotic treatment (AEAT) initialized before culture results were available remains controversial. We aimed to investigate the effect of AEAT on the prognosis of critically ill patients with hospital-acquired pneumonia (HAP) caused by CRGNB. Patients and Methods: Patients with CRGNB-infected HAP and received empirical antibiotic treatment (EAT) for at least 3 days in the intensive care unit (ICU) of a tertiary teaching hospital in China from February 2017 to September 2021 were included in the retrospective cohort study. Patients were categorized into AEAT and inappropriate empirical antibiotic treatment (IEAT) groups based on whether they received EAT covering CRGNB. The associations of AEAT with ICU and 28-day mortality were assessed using multivariable logistic regression model. Results: A total of 94 patients were enrolled, including 29 patients in AEAT group and 65 patients in IEAT group. Patients in AEAT group had a higher Sequential Organ Failure Assessment (SOFA) score (P = 0.003), levels of procalcitonin (PCT) (P = 0.001), and lactic acid (LAC) (P = 0.026); while patients in the IEAT group had a higher platelet count (PLT) (P = 0.001). There was no significant difference in the length of ICU stay between the two groups (P = 0.051). Compared with IEAT, AEAT was associated with an increased risk of 28-day mortality in the univariable logistic regression model (OR: 2.618, 95% CI: 1.063-6.448). However, after adjusted for SOFA score, PLT, PCT, and LAC level, the association between AEAT and 28-day mortality diminished (OR: 1.028, 95% CI: 0.353-2.996). AEAT showed no significant association with ICU mortality in neither univariable (OR: 1.167, 95% CI: 0.433-3.142) nor multivariable (OR: 0.357, 95% CI: 0.097-1.320) models. Conclusion: AEAT showed no significant influence on ICU or 28-day mortality in critically ill patients with HAP caused by CRGNB infection.

A Novel Human Acute Encephalitis Caused by Pseudorabies Virus Variant Strain.

BACKGROUND: Pseudorabies virus (PRV) is a common pathogen in multiple animal species, particularly in pigs. However, PRV infection in humans is rare and, to the best of our knowledge, PRV has never been isolated from human cases before. METHODS: Four acute encephalitis cases in humans were confirmed as PRV infection based on clinical symptoms, laboratory diagnosis, and metagenomic next-generation sequencing (mNGS). Cerebrospinal fluid (CSF) samples were collected and applied for virus isolation. Etiological and genetic characteristics of this PRV human isolate were further determined. RESULTS: The patients manifested respiratory dysfunction and acute neurological symptoms. The mNGS revealed PRV-specific nucleotide sequences in patients' CSF samples (7-6198 reads and 0.2446%-80.58% coverage). The PRV envelope glycoprotein B antibody, glycoprotein E antibody, and neutralizing antibody were positively detected. For the first time, a PRV strain, designated hSD-1/2019, was isolated and identified from a CSF sample, and transmission electron microscopy revealed that hSD-1/2019 had typical morphology similar to that of swine PRV. Phylogenetic analysis illustrated that hSD-1/2019 was genetically closest to those PRV variant strains currently circulating in pigs in China, and this strain showed similar etiological characteristics to Chinese PRV variant strains, while different from Chinese classical strain. Moreover, hSD-1/2019 showed high pathogenicity and induced acute neurological symptoms in pigs. CONCLUSIONS: A PRV strain was isolated from an acute human encephalitis case. This isolate showed close phylogenetic relationships and similar etiological characteristics to Chinese PRV variant strains, implying the great risk of PRV transmission from pigs to humans.

A multi-facet comparative analysis of neuromyelitis optica spectrum disorders in patients with seropositive and seronegative AQP4-IgG.

INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD), a rare, serious, demyelinating disease of the central nervous system (CNS), is associated with immunoglobulin G (IgG) antibodies targeting aquaporin-4 (AQP4-IgG). This study retrospectively analyzed the clinical features of 67 patients. 49 and 18 of 67 cases (male/female: 11/56) were AQP4-IgG (+) and AQP4-IgG (-), respectively. The initial symptoms were optic neuritis [n = 34, AQP4-IgG (+)/(-): 31/3], myelitis [n = 18, AQP4-IgG(+)/(-): 13/5], co-occurrence of ON and myelitis [n = 15, AQP4-IgG (+)/(-): 5/10]. CONCLUSIONS: There was no statistically significant difference between the 2 groups in terms of ages, and magnetic resonance imaging findings, but the patients had a significant difference (P <.05) in sex, the course of disease and Expanded Disability Status Scale (EDSS) scores after drug treatment. Patients with AQP4-IgG (-) are likely to have a better prognosis and a favorable monophasic course.

Missense mutations in COL4A5 or COL4A6 genes may cause cerebrovascular fibromuscular dysplasia: Case report and literature review.

INTRODUCTION: Fibromuscular dysplasia (FMD) is a rare and controversial disease that is seldom associated with genes. Here, we report the discovery of 2 missense mutations in COL4A5 and COL4A6 that may be risk factors for causing cerebrovascular FMD. We performed high-throughput sequencing on a patient with FMD and her probable healthy daughter, then annotated the frequency of a variant in a control or general population and assessed its deleterious effects according to published guidelines. CONCLUSIONS: We identified missense mutations in COL4A5 (exon43:c.C3940 > T:p.P1314S) and COL4A6 (exon36:c.C3538 > T:p.P1180S) from the proband and her daughter. Sanger sequencing revealed that these probable causal variants were passed to her from her mother. The two missense mutations may have complex functional effects on the integrity of the cerebral vessel walls, including modulating collagens and promoting angiogenesis expression, may be responsible for cerebrovascular FMD.