There are multiple lines of evidence for the existence of communication between the central nervous system (CNS), gut, and intestinal microbiome. Despite extensive analysis conducted on various ...neurological disorders, the gut microbiome was not yet analyzed in neuroinfections. In the current study, we analyzed the gut microbiome in 47 consecutive patients hospitalized with neuroinfection (26 patients had viral encephalitis/meningitis; 8 patients had bacterial meningitis) and in 20 matched for age and gender health controls. Using the QIIME pipeline, 16S rRNA sequencing and classification into operational taxonomic units (OTUs) were performed on the earliest stool sample available. Bacterial taxa such as Clostridium, Anaerostipes, Lachnobacterium, Lachnospira, and Roseburia were decreased in patients with neuroinfection when compared to controls. Alpha diversity metrics showed lower within-sample diversity in patients with neuroinfections, though there were no differences in beta diversity. Furthermore, there was no significant change by short-term (1–3 days) antibiotic treatment on the gut microbiota, although alpha diversity metrics, such as Chao1 and Shannon’s index, were close to being statistically significant. The cause of differences between patients with neuroinfections and controls is unclear and could be due to inflammation accompanying the disease; however, the effect of diet modification and/or hospitalization cannot be excluded.
Clostridioides difficile (C.difficile) is a Gram-positive, spore-forming, toxin-producing anaerobic bacillus, which is one of the most common causes of health-care-associated infection developed ...mainly by elderly patients. The objective of this study was to assess mortality among the patients of the Hospital for Infectious Diseases in Warsaw related to C.difficile infection. Analysis was conducted of 1638 records reporting the medical histories of patients hospitalized for the first time due to Clostridioides difficile infection (CDI) in the Hospital for Infectious Diseases in Warsaw from 2010 to 2017. The inclusion criteria were any (principal or secondary) discharge diagnosis code for CDI according to ICD-10 and being an adult (≥ 18 years). 108 out of 1638 (7%) of the patients died. The median age in this group was 83 years. The largest number of deaths (90%) occurred in the group of patients aged 65 years or older and 81-90 years old (53% of all the deaths). In the multivariate logistic regression model relevant only to the age groups, not to sepsis-age over 80 and over 90 were independent predictors of death, increasing the risk of death by 3.4 and 1.8 times, respectively. The result of the receiver operating curve (ROC) analysis determined the age of 77 years as the threshold value, indicating the increased risk of death (AUC 0.727, standard error 0.025, 95% CI 0.678-0.776, p < 0.0001). In addition, other quantitative variables, namely CRP, creatinine and leucocytes were studied and turned out to be independent death predictors as well. The diagnosis of sepsis increased the risk of death fourfold (OR = 4.042; 95% Cl 2.4-6.7; p < 0.001). Increased inflammatory parameters, namely CRP and white blood cell count, advanced age, particularly over the age of 80, as well as a diagnosis of sepsis are independent risk factors for death and could be used as predictive markers of poor outcome in CDI.
•Patients with Lyme neuroborreliosis are rarely examined for the presence of neurovirulent viruses.•Enteroviruses were identified in 13 % of patients with Lyme neuroborreliosis.•The possible ...co-occurrence of enterovirus and Lyme neuroborreliosis infections may warrant further research.•Metagenomic next-generation sequencing is prone to false signals.
Patients with Lyme neuroborreliosis (LNB) are rarely tested for the presence of neurovirulent viruses other than tick-borne encephalitis virus (TBEV); however, such coinfections could be of clinical importance. The aim of the study was to search for the presence of neurotropic viruses in a LNB patients.
Fourteen patients admitted with signs and symptoms of neuroinfection who were eventually diagnosed to have LNB (according to the guidelines of the European Federation of Neurological Societies) were subjects of the study. Sera and cerebrospinal fluid (CSF) collected at the time of initial presentation were tested for viral pathogens most common in our geographical area: human enteroviruses (EV), herpes simplex virus type 1 and 2, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, human herpesvirus type 6, human adenoviruses, and TBEV using PCR/RT-PCR and serological assays. RNA and DNA-based metagenomic next-generation sequencing (mNGS) was used to detect other viral pathogens.
EV was detected in CSF from two (14 %) LNB patients and viral loads were similar (220 and 270 copies/ml). The mMGS analysis were performed on CSFs from 10 patients and generated a total 213,750,885 NGS reads, 0.05 % of which were viral. However, none of potential pathogens fulfilled the criteria for positive viral detection by mNGS.
Using a number of PCR/RT-PCR assays and mNGS we identified EV infection in two out of 14 LNB patients. The possible co-occurrence of enterovirus and Lyme neuroborreliosis infections may warrant further research.
Background: The first case of coronavirus disease 2019 (COVID-19) in Poland was reported on 4 March 2020. We aim to compare the clinical course and outcomes of patients hospitalized in the Hospital ...for Infectious Diseases in Warsaw due to COVID-19 during three pandemic waves. Materials and methods: The medical data were collected for all patients diagnosed with COVID-19 hospitalized in our hospital from 6 March 2020 till 30 November 2021. COVID-19 diagnosis was confirmed by nasopharyngeal swabs using real-time polymerase chain reaction assay (RT-PCR) or SARS-CoV-2 antigen test. COVID-19 waves were defined based on the number and dynamics of cases. Results: Altogether, 2138 patient medical records were analyzed. The majority of the cohort was male (1235/2138, 57.8%), and the median age was 65 years IQR: 50−74 years. Patients hospitalized during the third wave had lower oxygen saturation on admission (p < 0.001) and were more likely to receive oxygen supplementation (p < 0.001). Serious complications, including pneumothorax (p < 0.001) and thromboembolic complications (p < 0.001), intensive care unit admission (p = 0.034), and death (p = 0.003), occurred more often in patients of the third wave. Conclusions: During the third wave, patients in our cohort experienced a more severe course of the disease and poorer outcomes.
Lipoprotein X (LpX) is an abnormal lipoprotein fraction, which can be detected in patients with severe hypercholesterolaemia and cholestatic liver disease. LpX is composed largely of phospholipid and ...free cholesterol, with small amounts of triglyceride, cholesteryl ester and protein. There are no widely available methods for direct measurement of LpX in routine laboratory practice. We present the heterogeneity of clinical and laboratory manifestations of the presence of LpX, a phenomenon which hinders LpX detection.
The study was conducted on a 26-year-old female after liver transplantation (LTx) with severely elevated total cholesterol (TC) of 38 mmol/L and increased cholestatic liver enzymes. TC, free cholesterol (FC), cholesteryl esters (CE), triglycerides, phospholipids, HDL-C, LDL-C, and apolipoproteins AI and B were measured. TC/apoB and FC:CE ratios were calculated. Lipoprotein electrophoresis was performed using a commercially available kit and laboratory-prepared agarose gel.
Commercially available electrophoresis failed to demonstrate the presence of LpX. Laboratory-prepared gel clearly revealed the presence of lipoproteins with γ mobility, characteristic of LpX. The TC/apoB ratio was elevated and the CE level was reduced, confirming the presence of LpX. Regular lipoprotein apheresis was applied as the method of choice in LpX disease and a bridge to reLTx due to chronic liver insufficiency.
The detection of LpX is crucial as it may influence the method of treatment. As routinely available biochemical laboratory tests do not always indicate the presence of LpX, in severe hypercholesterolaemia with cholestasis, any discrepancy between electrophoresis and biochemical tests should raise suspicions of LpX disease.
The aim of the study was to determine the effect of chronic alcohol abuse on the course and outcome of bacterial meningitis (BM). We analyzed records of patients with BM who were hospitalized between ...January 2010 and December 2017 in the largest neuroinfection center in Poland. Out of 340 analyzed patients, 45 (13.2%) were alcoholics. Compared with non-alcoholics, alcoholics were more likely to present with seizures (
p
< 0.001), scored higher on the Sequential Organ Failure Assessment (SOFA) (
p
= 0.002) and lower on the Glasgow Coma Scale (GCS) (
p
< 0.001), and had worse outcome as measured by the Glasgow Outcome Score (GOS) (
p
< 0.001). Furthermore, alcoholics were less likely to complain of headache (
p
< 0.001) and nausea/vomiting (
p
= 0.005) and had lower concentration of glucose in cerebrospinal fluid (CSF) (
p
= 0.025). In the multiple logistic regression analysis, alcoholism was associated with lower GCS (
p
= 0.036), presence of seizures (
p
= 0.041), male gender (
p
= 0.042), and absence of nausea/vomiting (
p
= 0.040). Furthermore, alcoholism (
p
= 0.031), lower GCS score (
p
= 0.001), and higher blood urea concentration (
p
= 0.018) were independently associated with worse outcome measured by GOS. Compared with non-alcoholics, chronic alcohol abusers are more likely to present with seizures, altered mental status, and higher SOFA score and have an increased risk of unfavorable outcome. In multivariate analysis, seizures and low GCS were independently associated with alcoholism, while alcoholism was independently associated with worse outcome.
Abstract
Background
It has been reported that virus-mediated brain tissue damage can lead to autoimmune encephalitis (AE) characterized by the presence of antibodies against neuronal surface ...antigens. In the study, we investigate the presence of viruses in cerebrospinal fluid (CSF) from patients with AE using reverse transcription polymerase chain reaction (RT-PCR)/PCR and shotgun metagenomics.
Methods
CSF samples collected from 200 patients with encephalitis were tested for the presence of antibodies against antiglutamate receptor (NMDAR), contactin-associated protein 2 (CASPR2), glutamate receptors (type AMPA1/2), leucine-rich glioma-inactivated protein 1 (LGI1), dipeptidyl aminopeptidase-like protein 6 (DPPX), and GABA B receptor, and those found positive were further analyzed with real-time RT-PCR/PCR for common viral neuroinfections and shotgun DNA- and RNA-based metagenomics.
Results
Autoantibodies against neuronal cells were detected in CSF from 8 individuals (4% of all encephalitis patients): 7 (3.5%) had anti-NMDAR and 1 (0.5%) had anti-GABA B. RT-PCR/PCR identified human herpes virus type 1 (HSV-1; 300 copies/mL) and the representative of Enterovirus genus (550 copies/mL) in 1 patient each. Torque teno virus (TTV) was found in another patient using metagenomic analysis, and its presence was confirmed by specific PCR.
Conclusions
We detected the presence of HSV, TTV, and Enterovirus genus in CSF samples from 3 out of 8 AE patients. These findings support the concept of viral involvement in the pathogenesis of this disease.
Little is known about concomitant central nervous system (CNS) infections by more than one virus. Current diagnostics are based on molecular tests for particular pathogens making it difficult to ...identify multi-viral infections. In the present study, we applied DNA- and RNA-based next-generation sequencing metagenomics (mNGS) to detect viruses in cerebrospinal fluids from 20 patients with herpes simplex encephalitis. Coinfection was detected in one patient: sequences in cerebrospinal fluids matched enterovirus A (2.660 reads; 4% of recovered genome) and enterovirus B (1.571 reads; 13% of recovered genome). Subsequent PCR combined with serotyping allowed to identify human echovirus 6, a representative of enterovirus B. Several other mNGS hits (human pegivirus, Merkel cell polyomavirus, human papillomavirus type 5) were not considered to represent a genuine signal as they could not be confirmed by specific RT-PCR/PCR. HSV DNA, while being detectable by PCR in every patient, was detected by mNGS in only one. In conclusion, contaminations and false signals may complicate mNGS interpretation; however, the method can be useful in diagnostics of viral coinfections in CNS, particularly in the case of rare pathogens.
The aim of the study was to determine the course and outcome of bacterial meningitis (BM) in patients with cancer. We retrospectively reviewed files of patients with community-acquired BM, ...hospitalized in a single neuroinfection center between January 2010 and December 2017. There were 209 patients included in the analysis: 28 had cancer (9 women, 19 men; median age 76, IQR 67-80 years) and 181 were cancer-free (76 women, 105 men; median age 52, IQR 33-65 years) and constituted the control group. Cancer patients, compared with controls, were more likely to present with seizures (25% vs. 8%, p = 0.019), scored higher on the Sequential Organ Failure Assessment, and had a higher mortality rate (32% vs. 13%, p = 0.025). Further, cancer patients were less likely (64% vs. 83%, p = 0.033) to present with two or more out of four clinical manifestations of BM (pyrexia, neck stiffness, altered mental status, and headache) and had a lower white blood cell (WBC) count than non-cancer controls. In multiple regression analysis, the presence of bacterial meningitis in cancer patients was independently associated only with older age (p = 0.001) and lower WBC count (p = 0.007), while mortality was associated with lower Glasgow Coma Score (p = 0.003). In conclusion, bacterial meningitis in cancer patients is characterized by atypical symptoms and high mortality, which requires physicians' vigilance and a prompt investigation of cerebrospinal fluid in suspected cases. However, multiple regression analysis suggests that differences in clinical presentation and outcomes of bacterial meningitis between cancer and cancer-free patients may also be attributable to other factors, such as age differences.
The primary symptom of Clostridioides difficile infection (CDI) is diarrhea of varying severity. Both malnutrition and clinical nutrition increase the risk for contracting Clostridioides difficile ...(C. difficile) infection and the likelihood of relapses. Moreover, the risk for recurrence is higher if there is infection with a hypervirulent strain (NAP1/BI/027). Hypoalbuminemia predisposes to a severe course of the disease and morbidity.
Analysis was carried out of the data regarding patients hospitalized at the Regional Hospital for Infectious Diseases in Warsaw from 01 January 2020 to 31 December 2021 who were diagnosed with C. difficile infection. A severe course of infection was diagnosed when a blood test showed a leukocyte count greater than or equal to 15,000/μl and/or a creatinine concentration >1.5 mg/dl (>132.6 mmol/l).
Clostridioides difficile infection was the reason for 185 hospitalizations (involving 108 women and 77 men), of 167 patients aged from 22 to 93 years old. There were 68 (37%) cases of recurrent infection. Seventy-five (41%) infections met the study's criteria for severe CDI, and 12 (7%) patients died. Out of the total number of hospitalizations, 41 (22%) were due SARS-CoV-2 co-infection. PCR tests detecting binary toxin revealed 34 (18%) positive results. Infection with a hypervirulent strain was an independent risk factor for the recurrence of diarrhea which had C. difficile etiology. Overall, during an episode of diarrhea, one antibacterial drug was used in 139 cases (75%), two in 27 (15%), three in 14 (8%) situations, and four - twice (1%). Among these, drugs not recommended for the treatment of CDI were used in 21 (11%) cases. The number of antibacterial drugs administered during an episode of diarrhea was an independent risk factor for the death of the infected person. Clinical nutrition was applied during 19 hospitalizations (10%), out of which 12 (63%) cases showed a severe course of C. difficile infection, while four patients (21%) died. Using clinical nutrition methods was an independent risk factor for a severe course of the disease and patient death.
Clinical nutrition and the number of antibiotics used during an episode of diarrhea are independent risk factors for the death of a patient with CDI. Infection with a hypervirulent strain increases the risk for relapse.
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