Investigation and long-term monitoring of the presence of neutralizing antibody in patients with COVID-19 disease of different clinical severity.

Understanding the immune responses elicited by severe acute respiratory syndrome virus (SARS-CoV-2) infection is critical to public health policy and vaccine development and prevention of reinfections for COVID-19. It is important to know the neutralizing capacity of antibodies and to monitor their persistence. Patients with COVID-19 were divided into four groups (severe-critical, moderate, mild, and asymptomatic) according to their clinical severity. Antibodies against SARS-CoV-2 spike viral surface protein were investigated by ELISA method 3 and 9 months after the onset of the disease. Neutralizing antibody (NAb) response was evaluated by microneutralization test. Patients who received at least two doses of COVID-19 vaccine after illness were enrolled. SARS-CoV-2 immunoglobulin G (IgG) and NAb titers were shown to be strongly correlated with disease severity. Anti-SARS-CoV-2 IgG and NAb levels were found to be compatible with each other. After 9 months of follow-up, both IgG and NAb levels continued unabated in individuals who had the disease. In individuals who received at least two doses of the vaccine, these levels increased, except for severe-critical patients. High levels of anti-SARS-CoV-2 IgG are indicative, as it is difficult to investigate NAb in routine laboratories. At the same time, it can be predicted that this period may be much longer if it continues for at least 9 months and is reinforced with vaccination.

Tocilizumab treatment in severe COVID-19: a multicenter retrospective study with matched controls.

Coronavirus disease-2019 (COVID-19) associated pneumonia may progress into acute respiratory distress syndrome (ARDS). Some patients develop features of macrophage activation syndrome (MAS). Elevated levels of IL-6 were reported to be associated with severe disease, and anti-IL-6R tocilizumab has been shown to be effective in some patients. This retrospective multicenter case-control study aimed to evaluate the efficacy of tocilizumab in hospitalized COVID-19 patients, who received standard of care with or without tocilizumab. Primary outcome was the progression to intubation or death. PSMATCH (SAS) procedure was used to achieve exact propensity score (PS) matching. Data from 1289 patients were collected, and study population was reduced to 1073 based on inclusion-exclusion criteria. The composite outcome was observed more frequently in tocilizumab-users, but there was a significant imbalance between arms in all critical parameters. Primary analyses were carried out in 348 patients (174 in each arm) after exact PS matching according to gender, ferritin, and procalcitonin. Logistic regression models revealed that tocilizumab significantly reduced the intubation or death (OR 0.40, p = 0.0017). When intubation is considered alone, tocilizumab-users had > 60% reduction in odds of intubation. Multiple imputation approach, which increased the size of the matched patients up to 506, provided no significant difference between arms despite a similar trend for intubation alone group. Analysis of this retrospective cohort showed more frequent intubation or death in tocilizumab-users, but PS-matched analyses revealed significant results for supporting tocilizumab use overall in a subset of patients matched according to gender, ferritin and procalcitonin levels.

A case of Mediterranean spotted fever mimicking severe sepsis.

Mediterranean spotted fever (MSF) is a tick-borne acute endemic infectious disease caused by Rickettsia conorii. While MSF may progress asymptomatically, it may lead to clinical pictures like severe hemorrhagic fever. In this article, we are presenting an MSF case with signs of high fever, headache, nausea, weakness and generalized maculopapular rash. The diagnosis of the female patient who had a history of contact with a tick-infested dog was confirmed with her clinical and laboratory data. The clinical and laboratory findings of the patient who was given doxycycline by 200 mg/day for 7 days were improved in a short time. Rickettsia conorii serology by indirect immunofluorescence assay method confirmed the diagnosis of MSF. In cases of severe sepsis accompanied by high fever and generalized maculopapular rash where the source of the infection cannot be determined in the short term, carefully questioning exposure to ticks by considering the existing geographical, seasonal and endemic environmental factors may be life-saving in terms of early diagnosis and treatment of MSF, which may become fatal even in the absence of eschars (tache noire). The symptomatology of hemorrhagic fever associated with Rickettsia conorii may be confused with that of sepsis in clinical practice.

Hepatitis B virus-induced hepatocarcinogenesis: A virological and oncological perspective.

Hepatitis B virus (HBV) is a partially double-stranded DNA virus associated with hepatocellular carcinoma (HCC). The viral integration into the hepatocyte genome, the viral protein-induced oncogenesis, the increased hepatocyte turnover and the chronic inflammatory response towards HBV are all hypothesized mechanisms for the development of HCC. The fact that HBV infection and HCC prevalence show different correlations in various regions of the world indicates that there may be virus-independent phenomena for cancer development in these regions. From this point of view, it is important to review our knowledge and to examine the relationship between HBV and HCC in the light of current data. In this article, we investigate the relationship between HBV and HCC by presenting epidemiological and microbiological data, accompanied by the principles of viral oncogenesis.

Rifampin-accompanied antibiotic regimens in the treatment of prosthetic joint infections: a frequentist and Bayesian meta-analysis of current evidence.

Prosthetic joint infections cause serious morbidity and mortality among joint arthroplasty patients. Rifampin-accompanied antibiotic regimens are recommended for gram-positive infections. This study aimed to combine current evidence supporting the rifampin supplement to an effective antibiotic in the treatment of prosthetic joint infections. We conducted a random-effects meta-analysis with frequentist and Bayesian approaches. A total of 13 studies, all observational, were included in the final analysis. The predominant bacteria in eight, two, and three studies were Staphylococcus spp., Propionibacterium spp., and Streptococcus spp., respectively. We pooled data from 568 patients in the staphylococcus subset (OR, 1.18; 95% CIs, [0.76; 1.82]; I2 = 23%) and data from 80 patients in the propionibacterium subset (REM OR, 1.61; 95% CIs [0.58; 4.47]; I2 = 0%). Both were insignificant with little heterogeneity. We pooled data from 483 patients in the streptococcus subset; the pooled estimate in this subset favored the use of rifampin supplemented regimens (1.84; [0.90; 3.76]) with moderate to high unaccounted heterogeneity (I2 = 57%). Bayesian random-effects models produced a posterior probability density indicating that future studies will not favor rifampin supplementation in Staphylococcus infections (µ, 0.074; τ, 0.570; 89% HPD, [- 0.48; 0.54]). Bayesian posterior distribution in the Streptococcus subset displayed a tendency toward rifampin supplementation. Studies had a substantial selection bias. Available evidence did not encourage rifampin-accompanied regimens for staphylococcal infections.

A novel approach to managing COVID-19 patients; results of lopinavir plus doxycycline cohort.

This manuscript aims to present a treatment algorithm we applied to manage COVID-19 patients admitted to our hospital. During the study period, 2043 patients with suspected COVID-19 were admitted to the emergency department. Molecular tests indicated that 475 of these patients tested positive for COVID-19. We administered hydroxychloroquine plus doxycycline to mild cases (isolated at home) for 3 days and lopinavir plus doxycycline to moderate and severe cases (hospitalized) for 5 days. The overall case fatality rate was 4.2% (20/475).

Risk factors for noncatheter-related Candida bloodstream infections in intensive care units: A multicenter case-control study.

Candida bloodstream infections are associated with high mortality among critically ill patients in intensive care units (ICUs). Studies that explore the risk factors for candidemia may support better patient care in intensive care units. We conducted a retrospective, multicenter case-control study to investigate the risk factors for noncatheter-related Candida bloodstream infections (CBSI) in adult ICUs. Participants selected controls randomly on a 1:1 basis among all noncase patients stayed during the same period in ICUs. Data on 139 cases and 140 controls were deemed eligible. Among the controls, 69 patients died. The stratified Fine-Gray model was used to estimate the subdistribution Hazard ratios. The subdistribution hazards and 95% confidence intervals for final covariates were as follows: prior exposure to antimycotic agents, 2.21 (1.56-3.14); prior exposure to N-acetylcysteine, 0.11 (0.03-0.34) and prior surgical intervention, 1.26 (0.76-2.11). Of the patients, those exposed to antimycotic drugs, 87.1% (54/62) had breakthrough candidemia. Serious renal, hepatic, or hematologic side effects were comparable between patients those exposed and not-exposed to systemic antimycotic drugs. Untargeted administration of antimycotic drugs did not improve survival among candidemic patients (not-exposed, 63.6% [49/77]; exposed % 66.1 [41/62]; P = .899). This study documented that exposure to an antifungal agent is associated with increased the risk of subsequent development of CBSIs among nonneutropenic adult patients admitted to the ICU. Only two centers regularly prescribed N-acetylcysteine. Due to the limited number of subjects, we interpreted the positive effect of N-acetylcysteine on the absolute risk of CBSIs with caution.

Efficacy of antiviral treatment in cytomegalovirus detected ulcerative colitis: meta-analysis of available data.

Aim: This meta-analysis aimed to pool available data regarding the efficacy of ganciclovir treatment among cytomegalovirus-detected ulcerative colitis patients.Methods: We screened PubMed, Ovid, Web of Science and Cochrane databases for relevant studies, and four investigators independently evaluated the studies for eligibility. The primary outcome was surgical resection or death from ulcerative colitis. The data were then pooled via DerSimonian-Laird estimator and Mantel-Haenszel (MH) method, two points added for continuity correction and random-effects model fitted in the Bayesian framework. We first constructed a Bugs model with Student t-distribution as prior for between-study heterogeneity. The model was fitted by Gibbs sampler (JAGS) to produce a marginal posterior distribution.Results: Our screening identified 15 eligible studies for final data synthesis and combined data from 191 ganciclovir-treated and 166 non-treated patients. Effect estimates from the fixed-effects meta-analysis model did not encourage ganciclovir treatment (OR, 1.43; 95% CIs [0-95, 2.16]), with a negligible unaccounted heterogeneity (I2 = 0%). The Bayesian random-effects model generated high-density credible intervals, suggesting a high probability, that future studies will also not encourage ganciclovir treatment (mu, 1.028; 95% credible intervals [0.054, 2.238]; 80% credible intervals [0.401, 1.703]) which indicates that future studies will favor non-treatment of ulcerative colitis with ganciclovir.Conclusions: Data produced in this study do not encourage ganciclovir treatment for UC patients. However, studies included in this analysis were observational, and thus, inherited severe selection bias. We suggest randomized controlled studies be conducted to make firm recommendations in this context.

Comparison of universal prophylaxis and preemptive approach for cytomegalovirus associated outcome measures in renal transplant patients: A meta-analysis of available data.

Cytomegalovirus (CMV) is a ubiquitous latent human virus that often causes complications in renal transplantation recipients. Universal prophylaxis and preemptive therapy are alternative strategies to prevent CMV associated complications. This meta-analysis aimed to assess available data comparing the effectiveness of prophylaxis and preemptive therapy for preventing adverse outcomes. We searched the PubMed, Ovid, Web of Science, Cochrane Library, and Open Grey databases using a combination of keywords. Random effects models along with the Paule-Mandel estimator were used to synthesize pooled effect estimates. Eleven studies were eligible for the final analysis. Universal prophylaxis was better at preventing CMV disease than the preemptive approach (risk difference = -0.0459; confidence intervals = -0.0791, -0.0127; P-value = 0.0067; number needed to treat [NNT] = 22 [1/0.0459]; high, 79 [1/0.0127] patients; low, 13 [1/0.0791] patients). Subgroup analysis revealed a more consistent effect among studies published after 2010, with negligible between-study heterogeneity. The NNT for universal prophylaxis to prevent one excess CMV disease concerning preemptive therapy was 16 (1/0.0630) patients (high, 25 [1/0.0394]; low, 12 [1/0.0867] patients) in the subgroup of studies performed after 2010. We detected no significant difference between the two strategies regarding acute rejection and graft loss, with negligible variability due to heterogeneity between studies. Although universal prophylaxis performed better than the preemptive strategy for the prevention of CMV disease, the high NNT value may discourage the use of CMV prophylaxis. Since there were no differences between the strategies concerning acute rejection and graft loss, this study supports the use of the preemptive approach as an alternative to universal prophylaxis.

Mortality predictors of Staphylococcus aureus bacteremia: a prospective multicenter study.

BACKGROUND: Staphylococcus aureus is one of the causes of both community and healthcare-associated bacteremia. The attributable mortality of S. aureus bacteremia (SAB) is still higher and predictors for mortality and clinical outcomes of this condition are need to be clarified. In this prospective observational study, we aimed to examine the predictive factors for mortality in patients with SAB in eight Turkish tertiary care hospitals. METHODS: Adult patients with signs and symptoms of bacteremia with positive blood cultures for S. aureus were included. All data for episodes of SAB including demographics, clinical and laboratory findings, antibiotics, and outcome were recorded for a 3-year (2010-2012) period. Cox proportional hazard model with forward selection was used to assess the independent effect of risk factors on mortality. A 28-day mortality was the dependent variable in the Cox regression analysis. RESULTS: A total of 255 episodes of SAB were enrolled. The median age of the patients was 59 years. Fifty-five percent of the episodes were considered as primary SAB and vascular catheter was the source of 42.1 %. Healthcare associated SAB was defined in 55.7 %. Blood cultures yielded methicillin-resistant S. aureus (MRSA) as a cause of SAB in 39.2 %. Initial empirical therapy was inappropriate in 28.2 %. Although overall mortality was observed in 52 (20.4 %), 28-day mortality rate was 15.3 %. Both the numbers of initial inappropriate empirical antibiotic treatment and the median hours to start an appropriate antibiotic between the cases of fatal outcome and survivors after fever onset were found to be similar (12/39 vs 60/216 and 6 vs 12 h, respectively; p > 0.05). High Charlson comorbidity index (CCI) score (p = 0.002), MRSA (p = 0.017), intensive care unit (ICU) admission (p < 0.001) and prior exposure to antibiotics (p = 0.002) all were significantly associated with mortality. The Cox analysis defined age [Hazard Ratio (HR) 1.03; p = 0.023], ICU admission (HR 6.9; p = 0.002), and high CCI score (HR 1.32; p = 0.002) as the independent predictive factors mortality. CONCLUSIONS: The results of this prospective study showed that age, ICU stay and high CCI score of a patient were the independent predictors of mortality and MRSA was also significantly associated with mortality in SAB.

Luteolin ameliorates colistin-induced nephrotoxicity in the rat models.

INTRODUCTION AND AIM: To study the protective, preventive effect of luteolin from colistin-induced nephrotoxicity. MATERIAL AND METHOD: Four different treatment options were tested on rats: colistin, luteolin, and a combination of colistin and luteolin, intraperitoneally as two doses a day, for seven days. Another group of rats were used as the control and treated with sterile saline. Serum creatinine levels were measured before and after treatment. Histological changes and colistin-induced apoptosis (Insitu BrdU-red DNA Fragmentation Assay Kit) of the renal tissues were examined after the scarification procedure. RESULTS: In the Colistin Group, post-treatment creatinine levels were statistically higher than the pretreatment levels (p = .001). In the remaining groups, no significant changes were observed. Cells that undergo apoptosis were counted and it was shown that all groups except the colistin-treated group had a similar number of apoptotic cells, whereas the colistin-treated group had statistically higher number of apoptotic cells compared to other groups (p = .0001). Renal histological damage was also measured and the score of the colistin treated group was higher as compared to other groups. CONCLUSION: The results obtained from this study demonstrated us that luteolin was capable of preventing colistin-induced nephrotoxicity and that this effect was significant at histopathological level.

Urinary tuberculosis: a cohort of 79 adult cases.

We aimed to investigate the demographic, clinical, diagnostic, treatment and outcome features of patients with urinary tuberculosis (UTB). Patients with UTB admitted to seven separate centers across Turkey between 1995 and 2013 were retrospectively evaluated. The diagnosis of UTB was made by the presence of any clinical finding plus positivity of one of the following: (1) acid-fast bacilli (AFB) in urine, (2) isolation of Mycobacterium tuberculosis, (3) polymerase chain reaction (PCR) for M. tuberculosis, (4) histopathological evidence for TB. Seventy-nine patients (49.36% male, mean age 50.1 ± 17.4 years) were included. Mean time between onset of symptoms and clinical diagnosis was 9.7 ± 8.9 months. The most common signs and symptoms were hematuria (79.7%), sterile pyuria (67.1%), dysuria (51.9%), weakness (51.9%), fever (43%) and costovertebral tenderness (38%). Cystoscopy was performed in 59 (74.6%), bladder biopsy in 18 (22.8%), kidney biopsy in 1 (1.26%) and nephrectomy in 12 (15.2%) patients. Histopathological verification of UTB was achieved in 12 (63.1%) patients who undergone biopsy and in 100% of those undergone nephrectomy. Mycobacterium tuberculosis was isolated in the urine of 50 (63.3%) cases. Four-drug standard anti-TB treatment was the preferred regimen for 87.3% of the patients. Mean treatment duration was 10.5 ± 2.7 months. Deterioration of renal function occurred in 15 (18.9%) patients two of whom progressed to end-stage renal disease and received hemodialysis. Only one patient died after 74-day medical treatment period. Cases with UTB may present with non-specific clinical features. All diagnostic studies including radiology, cyctoscopy and histopathology are of great importance to exclude UTB and prevent renal failure.

Spread of NDM-1-producing Enterobacteriaceae in a neonatal intensive care unit in Istanbul, Turkey.

Twenty-two consecutive carbapenem-resistant enterobacterial isolates were recovered from patients hospitalized between January and April 2013 in different units at a university hospital in Istanbul, Turkey. These were Klebsiella pneumoniae isolates producing the carbapenemases OXA-48, NDM-1, and KPC-2, Enterobacter cloacae isolates producing NDM-1, and Escherichia coli isolates producing OXA-48. Most of the OXA-48-producing K. pneumoniae and all the NDM-1-producing E. cloacae were clonally related. The NDM-1-producing E. cloacae isolates recovered from a single neonatal intensive care unit corresponded to a single cluster, highlighting the spread of that clone in that setting.

Comparison of cellular immunity in patients with chronic hepatitis B, inactive hepatitis B surface antigen carriers and spontaneously recovered individuals.

Different clinical outcomes of acute HBV infection have been partially explained by individual differences in immune response. In this study we investigated interferon gamma (IFN-γ) secretion of peripheral blood mononuclear cells (PBMC) in vitro against specific (Hepatitis B core antigen; recombinant HB-cAg) and non-specific (CMV, EBV, Influenza peptide pool; CTL CEF peptide pool "plus") antigens using enzyme linked immunospot (ELISPOT) assay in 7 patients with chronic hepatitis B (CHB group), 8 inactive carriers Of HBV (carrier group) and 8 subjects who spontaneously recovered from acute HBV infection as detected by anti-HBs positivity (immune group). Phytohemaglutinin served as the positive test control. Response against recombinant HBcAg was 88±135, 50±110, 105±150 spot forming cell (SFC)/10(5) PBMC, in CHB, carrier and immune groups, respectively. HBcAg-specific T-cell response was slightly higher in the immune group; however, statistically there was no significant difference between the groups. Assessment of cellular immunity by IFN-γ ELISPOT was not sufficient to explain the various outcomes of HBV infection such as resolution, chronicity and carriership.