The Prevalence of Depression and Its Potential Link to Liver Fibrosis in Patients Diagnosed With Chronic Hepatitis C Virus Infection Prior to the Initiation of Direct-Acting Antiviral Treatment.

Introduction Chronic hepatitis C virus (HCV) infection is associated with various extrahepatic manifestations, including depression. This study aimed to determine the prevalence of depression in treatment-naive HCV patients and explore its potential association with liver fibrosis severity. Methodology A consecutive cohort of 50 treatment-naive HCV patients without coinfections was enrolled over six months. Depression was assessed using the Hamilton Depression Rating Scale (HAM-D), and the liver fibrosis stage was evaluated using Fibroscan elastography. Results The cohort comprised 62% females (n=31) and 38% males (n=19), with ages ranging from 27 to 76 years. HAM-D scores indicated mild depression in 78% (n=39) and moderate depression in 16% (n=8) of patients. Notably, patients with mild depression displayed varying degrees of liver fibrosis (F0, F1, and F2), while all patients with moderate depression had advanced fibrosis (F3). Based on the multiple regression model, fibrosis was a statistically significant independent predictor with an unstandardized regression coefficient (B) of 3.115 (p=0.007). Conclusions Our findings point to a high prevalence of depression in treatment-naive HCV patients. Interestingly, there might be a link between depression severity and the stage of liver fibrosis, with advanced fibrosis potentially associated with more severe depression.

Carbapenem-Resistant NDM and OXA-48-like Producing K. pneumoniae: From Menacing Superbug to a Mundane Bacteria; A Retrospective Study in a Romanian Tertiary Hospital.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (Cr-Kpn) is becoming a growing public health problem through the failure of adequate treatment. This study's objectives are to describe the sources of Cr-Kpn in our hospital over 22 months, associating factors with the outcome of Cr-Kpn-positive patients, especially those with NDM+OXA-48-like (New Delhi Metallo-ß-Lactamase and oxacillinase-48), and the effectiveness of the treatments used. METHODS: A retrospective observational cohort study including all hospitalized patients with Cr-Kpn isolates. We reported data as percentages and identified independent predictors for mortality over hospital time through multivariate analysis. RESULTS: The main type of carbapenemases identified were NDM+OXA-48-like (49.4%). The statistical analysis identified that diabetes and co-infections with the Gram-negative, non-urinary sites of infection were factors of unfavorable evolution. The Cox regression model identified factors associated with a poor outcome: ICU admission (HR of 2.38), previous medical wards transition (HR of 4.69), and carbapenemase type NDM (HR of 5.98). We did not find the superiority of an antibiotic regimen, especially in the case of NDM+OXA-48-like. CONCLUSIONS: The increase in the incidence of Cr-Kpn infections, especially with NDM+OXA-48-like pathogens, requires a paradigm shift in both the treatment of infected patients and the control of the spread of these pathogens, which calls for a change in public health policy regarding the use of antibiotics and the pursuit of a One Health approach.

Results of Response-Guided Therapy with Pegylated Interferon Alpha 2a in Chronic Hepatitis B and D.

Pegylated interferon alpha 2a continues to be used for the treatment of chronic hepatitis D. The reported on-treatment virologic response varies between 17 and 47%, with relapses in more than 50% of these patients. No stopping rules have been defined, and the duration of the treatment is not clearly established, but it should be between 48 and 96 weeks. In total, 76 patients with compensated liver disease treated with peg-interferon according to the Romanian National protocol for the treatment of hepatitis D were retrospectively included. The duration of treatment was up to 96 weeks, with the following stopping rules: less than a 2 log HDV RNA decrease by week 24 and less than a 1 log decrease every 6 months afterwards. Six months after stopping the treatment, it can be restarted for unlimited cycles. The inclusion criteria were aged above 18, HBs Ag-positive, HDV RNA detectable, ALT above ULN and/or liver fibrosis at least F1 at liver biopsy, or Fibrotest and/or Fibroscan higher than 7 KPa and/or inflammation at least A1 at liver biopsy or Fibrotest. We monitored our patients for a total period of 4 years (including those that repeated the cycle). After the first 6 months of treatment, 27 patients (35.5%) had a greater than 2 log HDV RNA decrease, 19 of them achieving undetectable HDV RNA. Seventeen patients (22.3%) had undetectable HDV RNA 24 weeks after stopping 96 weeks of treatment, and none relapsed in the following 2 years. Of these 17 patients, 6 were cirrhotic, and 4 had F3. Undetectable HDV RNA at 24 weeks was the only parameter that predicted a long-term suppression of HDV RNA. In 49 patients, the treatment was stopped after 6 months according to protocol, but it was restarted 6 months later. Five of these patients finished a 48-week course of treatment; none achieved undetectable HDV RNA. During the first course of therapy, 45 patients had at least one moderate adverse reaction to treatment. In one patient, the treatment was stopped due to a serious adverse event (osteomyelitis). Treatment doses had to be reduced in 29 patients. The virologic response at week 24 can select the patients who will benefit from continuing the treatment from those who should be changed to another type of medication when available.

Attributable mortality of infections caused by carbapenem-resistant Enterobacterales: results from a prospective, multinational case-control-control matched cohorts study (EURECA).

OBJECTIVES: To assess the mortality attributable to infections caused by carbapenem-resistant Enterobacterales (CRE) and to investigate the effect of clinical management on differences in observed outcomes in a multinational matched cohort study. METHODS: A prospective matched-cohorts study (NCT02709408) was performed in 50 European hospitals from March 2016 to November 2018. The main outcome was 30-day mortality with an active post-discharge follow-up when applied. The CRE cohort included patients with complicated urinary tract infections, complicated intra-abdominal infections, pneumonia, or bacteraemia from other sources because of CRE. Two control cohorts were selected: patients with infection caused by carbapenem-susceptible Enterobacterales (CSE) and patients without infection. Matching criteria included type of infection for the CSE group, hospital ward of CRE detection, and duration of hospital admission up to CRE detection. Multivariable and stratified Cox regression was applied. RESULTS: The cohorts included 235 patients with CRE infection, 235 patients with CSE infection, and 705 non-infected patients. The 30-day mortality (95% CI) was 23.8% (18.8-29.6), 10.6% (7.2-15.2), and 8.4% (6.5-10.6), respectively. The difference in 30-day mortality rates between patients with CRE infection when compared with patients with CSE infection was 13.2% (95% CI, 6.3-20.0), (HR, 2.57; 95% CI, 1.55-4.26; p < 0.001), and 15.4% (95% CI, 10.5-20.2) when compared with non-infected patients (HR, 3.85; 95% CI, 2.57-5.77; p < 0.001). The population attributable fraction for 30-day mortality for CRE vs. CSE was 19.28%, and for CRE vs. non-infected patients was 9.61%. After adjustment for baseline variables, the HRs for mortality were 1.87 (95% CI, 0.99-3.50; p 0.06) and 3.65 (95% CI, 2.29-5.82; p < 0.001), respectively. However, when treatment-related time-dependent variables were added, the HR of CRE vs. CSE reduced to 1.44 (95% CI, 0.78-2.67; p 0.24). DISCUSSION: CRE infections are associated with significant attributable mortality and increased adjusted hazard of mortality when compared with CSE infections or patients without infection. Underlying patient characteristics and a delay in appropriate treatment play an important role in the CRE mortality.

Mpox-Related Ophthalmic Disease: A Rare Case Report.

Monkeypox virus (mpox), a double-stranded DNA virus belonging to the Orthopox genus, can affect vulnerable anatomic sites, including the eyes, causing a monkeypox-related ophthalmic disease. The mpox virus may enter the eye via autoinoculation and cause multiple problems from mild lesions including conjunctivitis, blepharitis, keratitis, to severe ones such as corneal ulcers, corneal scarring, and rarely loss of vision. The aim of this article is to aggregate from an ophthalmologic point of view what is presently known about mpox-related ophthalmic disease (mpoxROD) and to present a particular case of a 41-year-old, white, bisexual, HIV positive male, with severe ocular complications. This article presents the first reported case in Romania, of severe mpoxROD, with clinically relevant information for infectious disease doctors and especially for ophthalmologists.

Cerebrospinal fluid cytokines and chemokines exhibit distinct profiles in bacterial meningitis and viral meningitis.

Differential diagnosis of bacterial meningitis (BM) and viral meningitis (VM) is a critical clinical challenge, as the early and accurate identification of the causative agent determines the appropriate treatment regimen and markedly improves patient outcomes. Clinical and experimental studies have demonstrated that the pathogen and the host immune response contribute to mortality and neurological sequelae. As BM is associated with the activation of an inflammatory cascade, the patterns of pro- and anti-inflammatory cytokines/chemokines (CTs/CKs) present in the cerebrospinal fluid (CSF) in response to the immune assault may be useful as sensitive markers for differentiating BM from VM. In the present study, the ability of CTs/CKs in the CSF to differentiate between BM and VM was investigated. For this, biochemical markers and CT/CK profiles were analysed in 145 CSF samples, divided into three groups: BM (n=61), VM (n=58) and the control group (C; n=26) comprising patients with meningism. The CSF concentrations of monocyte chemoattractant protein-1, interleukin (IL)-8, IL-1ß, IL-6, macrophage inflammatory protein-1α (MIP-1α), epithelial-neutrophil activating peptide, IL-10, tumour necrosis factor-α (TNF-α), proteins and white blood cells were significantly higher and the CSF glucose level was significantly lower in the BM group compared with the VM and C groups (P<0.01). Correlation analysis identified 28 significant correlations between various CTs/CKs in the BM group (P<0.01), with the strongest positive correlations being for TNF-α/IL-6 (r=0.75), TNF-α/MIP-1α (r=0.69), TNF-α/IL-1ß (r=0.64) and IL-1ß/MIP-1α (r=0.64). To identify the optimum CT/CK patterns for predicting and classifying BM and VM, a dataset of 119 BM and VM samples was divided into training (n=90) and testing (n=29) subsets for use as input for a Random Forest (RF) machine learning algorithm. For the 29 test samples (15 BM and 14 VM), the RF algorithm correctly classified 28 samples, with 92% sensitivity and 93% specificity. The results show that the patterns of CT/CK levels in the CSF can be used to aid discrimination of BM and VM.

Can Biomarkers of Oxidative Stress in Serum Predict Disease Severity in West Nile Virus Infection? A Pilot Study.

West Nile virus (WNV) can cause asymptomatic infection in humans, result in self-limiting febrile illness, or lead to severe West Nile Neuroinvasive disease (WNND). We conducted a pilot study to compare selected biomarkers of oxidative stress in sera of viremic West Nile virus patients and asymptomatic infected blood donors to investigate their potential as predictors of disease severity. We found that total oxidant status was elevated in WNND and in uncomplicated WNV infections (median 9.05 (IQR 8.37 to 9.74) and 7.14 (7.03 to 7.25) µmol H2O2 equiv./L, respectively) compared to asymptomatic infections (0.11 (0.07 to 0.19) µmol H2O2 equiv./L) (p = 0.048). MDA levels showed a similar trend to TOS, but differences were not significant at α = 0.05. Total antioxidant status did not differ significantly between different disease severity groups. Oxidative stress appears to be associated with more severe disease in WNV-infected patients. Our preliminary findings warrant prospective studies to investigate the correlation of oxidative stress with clinical outcomes and severity of WNV infection.

A Randomized Clinical Trial of Regdanvimab in High-Risk Patients With Mild-to-Moderate Coronavirus Disease 2019.

Background: We evaluated clinical effectiveness of regdanvimab (CT-P59), a severe acute respiratory syndrome coronavirus 2 neutralizing monoclonal antibody, in reducing disease progression and clinical recovery time in patients with mild-to-moderate coronavirus disease 2019 (COVID-19), primarily Alpha variant. Methods: This was phase 3 of a phase 2/3 parallel-group, double-blind, randomized clinical trial. Outpatients with mild-to-moderate COVID-19 were randomized to single-dose regdanvimab 40 mg/kg (n = 656) or placebo (n = 659), alongside standard of care. The primary endpoint was COVID-19 disease progression up to day 28 among "high-risk" patients. Key secondary endpoints were disease progression (all randomized patients) and time to recovery (high-risk and all randomized patients). Results: Of 1315 randomized patients, 880 were high risk; the majority were infected with Alpha variant. The proportion with disease progression was lower (14/446, 3.1% [95% confidence interval {CI}, 1.9%-5.2%] vs 48/434, 11.1% [95% CI, 8.4%-14.4%]; P < .001) and time to recovery was shorter (median, 9.27 days [95% CI, 8.27-11.05 days] vs not reached [95% CI, 12.35-not calculable]; P < .001) with regdanvimab than placebo. Consistent improvements were seen in all randomized and non-high-risk patients who received regdanvimab. Viral load reductions were more rapid with regdanvimab. Infusion-related reactions occurred in 11 patients (4/652 [0.6%] regdanvimab, 7/650 [1.1%] placebo). Treatment-emergent serious adverse events were reported in 5 of (4/652 [0.6%] regdanvimab and 1/650 [0.2%] placebo). Conclusions: Regdanvimab was an effective treatment for patients with mild-to-moderate COVID-19, significantly reducing disease progression and clinical recovery time without notable safety concerns prior to the emergence of the Omicron variant. Clinical Trials Registration: NCT04602000; 2020-003369-20 (EudraCT).

Assessment of the Humoral Immune Response Following COVID-19 Vaccination in Healthcare Workers: A One Year Longitudinal Study.

The continuous variability of SARS-CoV-2 and the rapid waning of specific antibodies threatens the efficacy of COVID-19 vaccines. We aimed to evaluate antibody kinetics one year after SARS-CoV-2 vaccination with an mRNA vaccine in healthcare workers (HCW), with or without a booster. A marked decline in anti-Spike(S)/Receptor Binding Domain (RBD) antibody levels was registered during the first eight months post-vaccination, followed by a transitory increase after the booster. At three months post-booster an increased antibody level was maintained only in HCW vaccinated after a prior infection, who also developed a higher and long-lasting level of anti-S IgA antibodies. Still, IgG anti-nucleocapsid (NCP) fades five months post-SARS-CoV-2 infection. Despite the decline in antibodies one-year post-vaccination, 68.2% of HCW preserved the neutralization capacity against the ancestral variant, with a decrease of only 17.08% in the neutralizing capacity against the Omicron variant. Nevertheless, breakthrough infections were present in 6.65% of all participants, without any correlation with the previous level of anti-S/RBD IgG. Protection against the ancestral and Omicron variants is maintained at least three months after a booster in HCW, possibly reflecting a continuous antigenic stimulation in the professional setting.

Histopathologically Confirmed Pulmonary Mucormycosis as a Complication of COVID-19: a Case Report from Romania and Insight into Pathology.

COVID-19 has proven to be an independent risk factor for secondary infectious complications. Amongst them, mucormycosis has recently been noticed more frequently than in the past. Caused by molds belonging to the Mucorales order, this is a rare, but potentially fatal infection unless adequately treated. Ear, nose and throat involvement is prevalent with often expansion to the orbit, sinuses or brain. Pulmonary, cutaneous and gastrointestinal infections are also recognized. Classical risk factors for progression to angioinvasive disease include poorly controlled diabetes mellitus, defects in phagocytic function (prolonged neutropenia, glucocorticoid treatment), immunosuppressive therapy associated with transplantation, malignancy, elevated levels of free iron as well as iron chelators (deferoxamine). In addition, immune dysregulation rendered by COVID-19 itself may contribute or solely lead to invasive mold disease. The largest experience comes from India, which has dealt with a challenging epidemic of COVID-19-associated mucormycosis (CAM). To our knowledge, no previous studies have reported CAM in Romania. We therefore present a case of severe COVID-19 pneumonia initially complicated by bacterial superinfection and secondary sepsis at admission in an unvaccinated 61-year-old male who presented in our clinic with respiratory failure and digestive symptoms. Although improvement occurred rapidly following antiviral, empiric large spectrum Intraantibiotics and pathogenic medication, unfavorable clinical course ensued later on. Biological and imaging investigations were consistent with pulmonary superinfection in the form of multiple different-sized upper right field opacities, which eventually evolved to form cavities. Differential diagnosis was thoroughly performed. Since unable to sterilize the lung by means of medication alone, the patient underwent major thoracic surgery with removal of the entire right lung. Microscopic study of the damaged tissue was able to determine the presence of broad, aseptate hyphae which morphologically belong to Mucorales. A diagnosis of pulmonary mucormycosis was established and proper antifungal treatment was initiated, with full recovery of the patient.

Anthrax meningoencephalitis complicated with brain abscess - A case report.

Bacillus anthracis is a sporulating gram-positive rod whose main route of entry into the human body is cutaneous. Anthrax meningitis is usually fulminant and fatal. We present here a successfully treated case of anthrax meningoencephalitis complicated with brain abscess. The patient was a shepherd, with disease onset 7 days prior to hospital admission with fever, chills, occipital headache, and vertigo, followed by right hemiplegia, motor aphasia, agitation and coma. He had cutaneous lesions with black eschar on the limbs, which was a clue (along with his occupation), for diagnosis suspicion. The polymerase chain reaction for B. anthracis DNA was positive in both cerebrospinal fluid and cutaneous lesions. The cerebrospinal fluid was compatible with bacterial meningitis without being haemorrhagic. Magnetic resonance imaging showed meningeal enhancement and multiple intraparenchymal heterogeneous lesions with an important haemorrhagic component in the left parietal lobe, surrounded by vasogenic oedema with maintenance, 22 days later, of the left parietal lobe lesion, having a ring contrast enhancement and a central diffusion restriction, compatible with an abscess. From admission, he was intensively treated with combined large-spectrum antibiotics; this could be the most valuable factor in the successful outcome.

Emergence of Toscana Virus, Romania, 2017-2018.

We describe a series of severe neuroinvasive infections caused by Toscana virus, identified by real-time reverse transcription PCR testing, in 8 hospitalized patients in Bucharest, Romania, during the summer seasons of 2017 and 2018. Of 8 patients, 5 died. Sequencing showed that the circulating virus belonged to lineage A.

Travel-related infections presenting in Europe: A 20-year analysis of EuroTravNet surveillance data.

BACKGROUND: Disease epidemiology of (re-)emerging infectious diseases is changing rapidly, rendering surveillance of travel-associated illness important. METHODS: We evaluated travel-related illness encountered at EuroTravNet clinics, the European surveillance sub-network of GeoSentinel, between March 1, 1998 and March 31, 2018. FINDINGS: 103,739 ill travellers were evaluated, including 11,239 (10.8%) migrants, 89,620 (86.4%) patients seen post-travel, and 2,880 (2.8%) during and after travel. Despite increasing numbers of patient encounters over 20 years, the regions of exposure by year of clinic visits have remained stable. In 5-year increments, greater proportions of patients were migrants or visiting friends and relatives (VFR); business travel-associated illness remained stable; tourism-related illness decreased. Falciparum malaria was amongst the most-frequently diagnosed illnesses with 5,254 cases (5.1% of all patients) and the most-frequent cause of death (risk ratio versus all other illnesses 2.5:1). Animal exposures requiring rabies post-exposure prophylaxis increased from 0.7% (1998-2002) to 3.6% (2013-2018). The proportion of patients with seasonal influenza increased from zero in 1998-2002 to 0.9% in 2013-2018. There were 44 cases of viral haemorrhagic fever, most during the past five years. Arboviral infection numbers increased significantly as did the range of presenting arboviral diseases, dengue and chikungunya diagnoses increased by 2.6% and 1%, respectively. INTERPRETATION: Travel medicine must adapt to serve the changing profile of travellers, with an increase in migrants and persons visiting relatives and friends and the strong emergence of vector-borne diseases, with potential for further local transmission in Europe. FUNDING: This project was supported by a cooperative agreement (U50CK00189) between the Centers for Disease Control and Prevention to the International Society of Travel Medicine (ISTM) and funding from the ISTM and the Public Health Agency of Canada.