Examining the impact of a 9-component bundle and the INICC multidimensional approach on catheter-associated urinary tract infection rates in 32 countries across Asia, Eastern Europe, Latin America, and the Middle East.

BACKGROUND: Catheter-Associated Urinary Tract Infections (CAUTIs) frequently occur in the intensive care unit (ICU) and are correlated with a significant burden. METHODS: We implemented a strategy involving a 9-element bundle, education, surveillance of CAUTI rates and clinical outcomes, monitoring compliance with bundle components, feedback of CAUTI rates and performance feedback. This was executed in 299 ICUs across 32 low- and middle-income countries. The dependent variable was CAUTI per 1,000 UC days, assessed at baseline and throughout the intervention, in the second month, third month, 4 to 15 months, 16 to 27 months, and 28 to 39 months. Comparisons were made using a 2-sample t test, and the exposure-outcome relationship was explored using a generalized linear mixed model with a Poisson distribution. RESULTS: Over the course of 978,364 patient days, 150,258 patients utilized 652,053 UC-days. The rates of CAUTI per 1,000 UC days were measured. The rates decreased from 14.89 during the baseline period to 5.51 in the second month (risk ratio [RR] = 0.37; 95% confidence interval [CI] = 0.34-0.39; P < .001), 3.79 in the third month (RR = 0.25; 95% CI = 0.23-0.28; P < .001), 2.98 in the 4 to 15 months (RR = 0.21; 95% CI = 0.18-0.22; P < .001), 1.86 in the 16 to 27 months (RR = 0.12; 95% CI = 0.11-0.14; P < .001), and 1.71 in the 28 to 39 months (RR = 0.11; 95% CI = 0.09-0.13; P < .001). CONCLUSIONS: Our intervention, without substantial costs or additional staffing, achieved an 89% reduction in CAUTI incidence in ICUs across 32 countries, demonstrating feasibility in ICUs of low- and middle-income countries.

Prospective Cohort Study of Incidence and Risk Factors for Catheter-associated Urinary Tract Infections in 212 Intensive Care Units of Nine Middle Eastern Countries.

Objectives: To identify urinary catheter (UC)-associated urinary tract infections (CAUTI) incidence and risk factors (RF) in nine Middle Eastern countries. Methods: We conducted a prospective cohort study between 1 January 2014 and 2 December 2022 in 212 intensive care units (ICUs) of 67 hospitals in 38 cities in nine Middle Eastern countries (Bahrain, Egypt, Jordan, Kuwait, Lebanon, Morocco, Saudi Arabia, Turkey, and the UAE). To estimate CAUTI incidence, we used the number of UC days as denominator and the number of CAUTIs as numerator. To estimate CAUTI RFs, we analyzed the following 10 variables using multiple logistic regression: patient sex, age, length of stay (LOS) before CAUTI acquisition, UC-days before CAUTI acquisition, UC-device utilization (DU) ratio, hospitalization type, ICU type, facility-ownership, country income level classified by World Bank, and time period. Results: Among 50 637 patients hospitalized for 434 523 patient days, there were 580 cases of acquired CAUTIs. The pooled CAUTI rate per 1000 UC days was 1.84. The following variables were independently associated with CAUTI: age, rising risk 1.0% yearly (adjusted odds ratio [aOR] = 1.01, 95% CI: 1.01-1.02; p < 0.0001); female sex (aOR = 1.31, 95% CI: 1.09-1.56; p < 0.0001); LOS before CAUTI acquisition, rising risk 6.0% daily (aOR = 1.06, 95% CI: 1.05-1.06; p < 0.0001); and UC/DU ratio (aOR = 1.11, 95% CI: 1.06-1.14; p < 0.0001). Patients from lower-middle-income countries (aOR = 4.11, 95% CI: 2.49-6.76; p < 0.0001) had a similar CAUTI risk to the upper-middle countries (aOR = 3.75, 95% CI: 1.83-7.68; p < 0.0001). The type of ICU with the highest risk for CAUTI was neurologic ICU (aOR = 27.35, 95% CI: 23.03-33.12; p < 0.0001), followed by medical ICU (aOR = 6.18, 95% CI: 2.07-18.53; p < 0.0001) when compared to cardiothoracic ICU. The periods 2014-2016 (aOR = 7.36, 95% CI: 5.48-23.96; p < 0.001) and 2017-2019 (aOR = 1.15, 95% CI: 3.46-15.61; p < 0.001) had a similar risk to each other, but a higher risk compared to 2020-2022. Conclusions: The following CAUTI RFs are unlikely to change: age, sex, ICU type, and country income level. Based on these findings, it is suggested to focus on reducing LOS, UC/DU ratio, and implementing evidence-based CAUTI prevention recommendations.

Safety, efficacy, and pharmacokinetics of gremubamab (MEDI3902), an anti-Pseudomonas aeruginosa bispecific human monoclonal antibody, in P. aeruginosa-colonised, mechanically ventilated intensive care unit patients: a randomised controlled trial.

BACKGROUND: Ventilator-associated pneumonia caused by Pseudomonas aeruginosa (PA) in hospitalised patients is associated with high mortality. The effectiveness of the bivalent, bispecific mAb MEDI3902 (gremubamab) in preventing PA nosocomial pneumonia was assessed in PA-colonised mechanically ventilated subjects. METHODS: EVADE (NCT02696902) was a phase 2, randomised, parallel-group, double-blind, placebo-controlled study in Europe, Turkey, Israel, and the USA. Subjects ≥ 18 years old, mechanically ventilated, tracheally colonised with PA, and without new-onset pneumonia, were randomised (1:1:1) to MEDI3902 500, 1500 mg (single intravenous dose), or placebo. The primary efficacy endpoint was the incidence of nosocomial PA pneumonia through 21 days post-dose in MEDI3902 1500 mg versus placebo, determined by an independent adjudication committee. RESULTS: Even if the initial sample size was not reached because of low recruitment, 188 subjects were randomised (MEDI3902 500/1500 mg: n = 16/87; placebo: n = 85) between 13 April 2016 and 17 October 2019. Out of these, 184 were dosed (MEDI3902 500/1500 mg: n = 16/85; placebo: n = 83), comprising the modified intent-to-treat set. Enrolment in the 500 mg arm was discontinued due to pharmacokinetic data demonstrating low MEDI3902 serum concentrations. Subsequently, enrolled subjects were randomised (1:1) to MEDI3902 1500 mg or placebo. PA pneumonia was confirmed in 22.4% (n = 19/85) of MEDI3902 1500 mg recipients and in 18.1% (n = 15/83) of placebo recipients (relative risk reduction [RRR]: - 23.7%; 80% confidence interval [CI] - 83.8%, 16.8%; p = 0.49). At 21 days post-1500 mg dose, the mean (standard deviation) serum MEDI3902 concentration was 9.46 (7.91) µg/mL, with 80.6% (n = 58/72) subjects achieving concentrations > 1.7 µg/mL, a level associated with improved outcome in animal models. Treatment-emergent adverse event incidence was similar between groups. CONCLUSIONS: The bivalent, bispecific monoclonal antibody MEDI3902 (gremubamab) did not reduce PA nosocomial pneumonia incidence in PA-colonised mechanically ventilated subjects. Trial registration Registered on Clinicaltrials.gov ( NCT02696902 ) on 11th February 2016 and on EudraCT ( 2015-001706-34 ) on 7th March 2016.

Structural characterization of protective non-neutralizing antibodies targeting Crimean-Congo hemorrhagic fever virus.

Crimean-Congo Hemorrhagic Fever Virus (CCHFV) causes a life-threatening disease with up to a 40% mortality rate. With no approved medical countermeasures, CCHFV is considered a public health priority agent. The non-neutralizing mouse monoclonal antibody (mAb) 13G8 targets CCHFV glycoprotein GP38 and protects mice from lethal CCHFV challenge when administered prophylactically or therapeutically. Here, we reveal the structures of GP38 bound with a human chimeric 13G8 mAb and a newly isolated CC5-17 mAb from a human survivor. These mAbs bind overlapping epitopes with a shifted angle. The broad-spectrum potential of c13G8 and CC5-17 and the practicality of using them against Aigai virus, a closely related nairovirus were examined. Binding studies demonstrate that the presence of non-conserved amino acids in Aigai virus corresponding region prevent CCHFV mAbs from binding Aigai virus GP38. This information, coupled with in vivo efficacy, paves the way for future mAb therapeutics effective against a wide swath of CCHFV strains.

In a Real-Life Setting, Direct-Acting Antivirals to People Who Inject Drugs with Chronic Hepatitis C in Turkey.

BACKGROUND: People who inject drugs (PWID) should be treated in order to eliminate hepatitis C virus in the world. The aim of this study was to compare direct-acting antivirals treatment of hepatitis C virus for PWID and non-PWID in a real-life setting. METHODS: We performed a prospective, non-randomized, observational multicenter cohort study in 37 centers. All patients treated with direct-acting antivirals between April 1, 2017, and February 28, 2019, were included. In total, 2713 patients were included in the study among which 250 were PWID and 2463 were non-PWID. Besides patient characteristics, treatment response, follow-up, and side effects of treatment were also analyzed. RESULTS: Genotype 1a and 3 were more prevalent in PWID-infected patients (20.4% vs 9.9% and 46.8% vs 5.3%). The number of naïve patients was higher in PWID (90.7% vs 60.0%), while the number of patients with cirrhosis was higher in non-PWID (14.1% vs 3.7%). The loss of follow-up was higher in PWID (29.6% vs 13.6%). There was no difference in the sustained virologic response at 12 weeks after treatment (98.3% vs 98.4%), but the end of treatment response was lower in PWID (96.2% vs 99.0%). In addition, the rate of treatment completion was lower in PWID (74% vs 94.4%). CONCLUSION: Direct-acting antivirals were safe and effective in PWID. Primary measures should be taken to prevent the loss of follow-up and poor adherence in PWID patients in order to achieve World Health Organization's objective of eliminating viral hepatitis.

Efficacy and Safety of Direct-Acting Antivirals in Elderly Patients with Chronic Hepatitis C: A Nationwide Real-Life, Observational, Multicenter Study from Turkey.

BACKGROUND: The number and proportion of elderly patients living with chronic hepatitis C are expected to increase in the coming years. We aimed to compare the real-world efficacy and safety of direct-acting antiviral treatment in elderly and younger Turkish adults infected with chronic hepatitis C. METHODS: In this multicenter prospective study, 2629 eligible chronic hepatitis C patients treated with direct-acting antivirals between April 2017 and December 2019 from 37 Turkish referral centers were divided into 2 age groups: elderly (≥65 years) and younger adults (<65 years) and their safety was compared between 2 groups in evaluable population. Then, by matching the 2 age groups for demographics and pretreatment risk factors for a non-sustained virological response, a total of 1516 patients (758 in each group) and 1244 patients (622 in each group) from the modified evaluable population and per-protocol population were included in the efficacy analysis and the efficacy was compared between age groups. RESULTS: The sustained virological response in the chronic hepatitis C patients was not affected by the age and the presence of cirrhosis both in the modified evaluable population and per-protocol population (P = .879, P = .508 for modified evaluable population and P = .058, P = .788 for per-protocol population, respectively). The results of the per-protocol analysis revealed that male gender, patients who had a prior history of hepatocellular carcinoma, patients infected with non-genotype 1 hepatitis C virus, and patients treated with sofosbuvir+ribavirin had a significantly lower sustained virological response 12 rates (P < .001, P = .047, P = .013, and P = .025, respectively). CONCLUSION: Direct-acting antivirals can be safely used to treat Turkish elderly chronic hepatitis C patients with similar favorable efficacy and safety as that in younger adults.

In-vitro activity of fosfomycin against Escherichia coli and Klebsiella pneumoniae bloodstream isolates and frequency of OXA-48, NDM, KPC, VIM, IMP types of carbapenemases in the carbapenem-resistant groups.

The aim of this study was to determine the in-vitro activity of fosfomycin against Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) isolates and the frequency of OXA-48, NDM, KPC, VIM, IMP types of carbapenemases in the carbapenem-resistant (CR) groups. A total of 346 isolates (126 E. coli and 220 K. pneumoniae) from nosocomial bloodstream infections were included. Carbapenem and fosfomycin susceptibility were tested by Etest (bioMerieux, France) and agar dilution methods, respectively and evaluated in accordance with EUCAST criteria. The presence of OXA-48, NDM, KPC, VIM, IMP types of carbapenemases were conducted by using PCR method. Of the total 346 isolates, 185 (41 E. coli, 144 K. pneumoniae) were CR. Fosfomycin susceptibility of E. coli was higher than 95% and was not statistically significant between the CR and carbapenem-susceptible (CS) groups. Fosfomycin susceptibility of CS and CR K. pneumoniae was 90.7% and 69.4%, respectively, and statistically significantly lower in CR group. Of the total 185 CR isolates, 163 (32 E. coli, 131 K. pneumoniae) were producing carbapenemases. OXA-48 was the prominent carbapenemase type produced by E. coli (96.8%) and K. pneumoniae (70.9%). The frequency of NDM and KPC types produced by K. pneumoniae was 20.6% and 15.2%, respectively. Fosfomycin has substantial in-vitro activity against nosocomial CS and CR E. coli and CS K. pneumoniae bloodstream isolates. However, due to the risk of emerging resistance with fosfomycin monotherapy, combination therapy should be considered to obtain the possible additive or synergistic activity. Emerging fosfomycin resistance of CR K. pneumoniae isolates is alarming and OXA-48 is still the prominent carbapenemase type in Turkey.

Sunitinib induced colitis manifesting as invasive diarrhea in a patient with renal cell carcinoma.

INTRODUCTION: Sunitinib is a tyrosine kinase inhibitor that binds to vascular endothelial factor receptor currently used for the treatment of renal cell carcinoma, as well as for several other conditions such as gastrointestinal stromal tumors and pancreatic neuroendocrine tumors. We present a patient with invasive diarrhea who was treated with sunitinib for metastatic renal cell carcinoma. CASE REPORT: Drug induced colitis was confirmed with colonoscopy from histopathological specimens. Clinical recovery of diarrhea was achieved with oral budesonide. Remarkably, the pathologic findings were observed in both the macroscopically normal mucosa and the mucosa with aphthous ulcers in the colon. MANAGEMENT & OUTCOME: The patient was treated for sunitinib associated diarrhea, after exclusion of the other reasons. Metronidazole and piperacillin/tazobactam treatment were prescribed. DISCUSSION: Diarrhea is a frequent symptom in patients treated with tyrosine kinase inhibitors, however the described pathologic findings have rarely been reported. Our aim is to emphasize the importance of close follow-up in patients treated with tyrosine kinase inhibitors, and to raise awareness on the management of sunitinib induced colitis.

Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey.

BACKGROUND: CoronaVac, an inactivated whole-virion SARS-CoV-2 vaccine, has been shown to be well tolerated with a good safety profile in individuals aged 18 years and older in phase 1/2 trials, and provided a good humoral response against SARS-CoV-2. We present the interim efficacy and safety results of a phase 3 clinical trial of CoronaVac in Turkey. METHODS: This was a double-blind, randomised, placebo-controlled phase 3 trial. Volunteers aged 18-59 years with no history of COVID-19 and with negative PCR and antibody test results for SARS-CoV-2 were enrolled at 24 centres in Turkey. Exclusion criteria included (but were not limited to) immunosuppressive therapy (including steroids) within the past 6 months, bleeding disorders, asplenia, and receipt of any blood products or immunoglobulins within the past 3 months. The K1 cohort consisted of health-care workers (randomised in a 1:1 ratio), and individuals other than health-care workers were also recruited into the K2 cohort (randomised in a 2:1 ratio) using an interactive web response system. The study vaccine was 3 µg inactivated SARS-CoV-2 virion adsorbed to aluminium hydroxide in a 0·5 mL aqueous suspension. Participants received either vaccine or placebo (consisting of all vaccine components except inactivated virus) intramuscularly on days 0 and 14. The primary efficacy outcome was the prevention of PCR-confirmed symptomatic COVID-19 at least 14 days after the second dose in the per protocol population. Safety analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT04582344) and is active but no longer recruiting. FINDINGS: Among 11 303 volunteers screened between Sept 14, 2020, and Jan 5, 2021, 10 218 were randomly allocated. After exclusion of four participants from the vaccine group because of protocol deviations, the intention-to-treat group consisted of 10 214 participants (6646 [65·1%] in the vaccine group and 3568 [34·9%] in the placebo group) and the per protocol group consisted of 10 029 participants (6559 [65·4%] and 3470 [34·6%]) who received two doses of vaccine or placebo. During a median follow-up period of 43 days (IQR 36-48), nine cases of PCR-confirmed symptomatic COVID-19 were reported in the vaccine group (31·7 cases [14·6-59·3] per 1000 person-years) and 32 cases were reported in the placebo group (192·3 cases [135·7-261·1] per 1000 person-years) 14 days or more after the second dose, yielding a vaccine efficacy of 83·5% (95% CI 65·4-92·1; p<0·0001). The frequencies of any adverse events were 1259 (18·9%) in the vaccine group and 603 (16·9%) in the placebo group (p=0·0108) with no fatalities or grade 4 adverse events. The most common systemic adverse event was fatigue (546 [8·2%] participants in the vaccine group and 248 [7·0%] the placebo group, p=0·0228). Injection-site pain was the most frequent local adverse event (157 [2·4%] in the vaccine group and 40 [1·1%] in the placebo group, p<0·0001). INTERPRETATION: CoronaVac has high efficacy against PCR-confirmed symptomatic COVID-19 with a good safety and tolerability profile. FUNDING: Turkish Health Institutes Association.

The Role of Pneumococcal Pneumonia among Community-Acquired Pneumonia in Adult Turkish Population: TurkCAP Study.

OBJECTIVE: To evaluate the rate of pneumococcal pneumonia (PP) among patients with community-acquired pneumonia (CAP) in Turkey and to investigate and compare features of PP and non-PP CAP patients. MATERIAL AND METHODS: This multicenter, non-interventional, prospective, observational study included adult CAP patients (age ≥ 18 years). Diagnosis of PP was based on the presence of at least 1 positive laboratory test result for Streptococcus pneumoniae (blood culture or sputum culture or urinary antigen test [UAT]) in patients with radiographic findings of pneumonia. RESULTS: Four hundred sixty-five patients were diagnosed with CAP, of whom 59 (12.7%) had PP. The most common comorbidity was chronic obstructive pulmonary disease (30.1%). The mean age, smoking history, presence of chronic neurological disease, and CURB-65 score were significantly higher in PP patients, when compared to non-PP patients. In PP patients, 84.8% were diagnosed based ony on the UAT. The overall rate of PP patients among CAP was calculated as 22.8% considering the UAT sensitivity ratio of 63% (95% confidence interval: 45-81). The rate of intensive care treatment was higher in PP patients (P = .007). While no PP patients were vaccinated for pneumococcus, 3.8% of the non-PP patients were vaccinated (P = .235). Antibiotic use in the preceding 48 hours was higher in the non-PP group than in the PP group (31.8% vs. 11.1%, P = .002). The CURB-65 score and the rate of patients requiring inpatient treatment according to this score were higher in the PP group. CONCLUSION: The facts that PP patients were older and required intensive care treatment more frequently as compared to non-PP patients underline the burden of PP.

Determination of levofloxacin, ciprofloxacin, moxifloxacin and gemifloxacin in urine and plasma by HPLC-FLD-DAD using pentafluorophenyl core-shell column: Application to drug monitoring.

Concentrations of fluoroquinolones, which are used in the treatment of many bacterial infections, should be monitored in biological fluids as they exhibit concentration-dependent bactericidal activity. In this study, a liquid chromatography method for the determination of levofloxacin, ciprofloxacin, moxifloxacin and gemifloxacin in human urine and plasma was developed for the first time. The efficiency of five different columns for the separation of these fluoroquinolones was compared. Experimental parameters that affect the separation, such as percentage of organic solvent, pH, temperature, gradient shape and detector wavelength, were optimized by a step-by-step approach. Using a pentafluorophenyl core-shell column (100 × 4.6 mm, 2.7 µm), the separation of four analytes was accomplished in <7.5 min. The developed method was validated for the determination of analytes in both urine and plasma with respect to sensitivity, specificity, linearity (r ≥ 0.9989), recovery (79.46-102.69%), accuracy, precision and stability (85.79-111.07%). The intra- and inter-day accuracies were within 89.55-111.94% with relative standard deviations of 0.35-8.05%. The feasibility of method was demonstrated by analyzing urine and plasma samples of patients orally receiving levofloxacin, ciprofloxacin or moxifloxacin. The developed method is suitable for therapeutic drug monitoring of these fluoroquinolones and can be applied to pharmacokinetic and toxicological studies.

Treatment of HCV infection with direct-acting antiviral agents. Real life experiences from the Euro-Asian region.

BACKGROUND/AIMS: Hepatitis C virus (HCV) infection is a common disease that causes liver cirrhosis, hepatocellular carcinoma, and extra hepatic manifestations with high mortality and morbidity rates. This study aimed to present real-life experiences and results of treatment of HCV infection with direct-acting antiviral agents (DAAs) from the Euro-Asian region, including Turkey and Azerbaijan. MATERIALS AND METHODS: A total of 1224 patients with chronic HCV infection were treated with DAAs in accordance with the international guidelines for the management of HCV infection. The mean age was 58.74±14.75 years, with 713 (58.25%) females. The genotypes of the patients were as follows: genotype 1b, 83.36% (n=1024); genotype 1a, 8.08% (n=99); genotype 2, 2.85% (n=35); genotype 3, 3.34% (n=41); genotype 4, 1.71% (n=21); and combined genotypes, 0.32% (n=4). Approximately 808 patients were treated with sofosbuvir-based DAAs with or without Ribavirin for 12 or 24 weeks, whereas 416 patients were treated with the Paritaprevir, Ombitasvir, Ritonavir.Dasabuvir (PROD) regimen with or without Ribavirin for 12 weeks or 24 weeks. RESULTS: At the end of follow-up examinations, 1183 patients (97.93%) had sustained virological response (SVR), 17 (1.40%) died of reasons unrelated to the treatment regimen, 12 had recurrence after treatment, and 129 (10.67%) had adverse events like anemia, itching, and weakness. CONCLUSION: In this large cohort of HCV-infected patients, treatment with DAAs yielded a high overall SVR rate of 97.93%. DAAs were safe and well-tolerated. Thus, the elimination of HCV infection is no longer a dream worldwide.

RESTORE-IMI 1: A Multicenter, Randomized, Double-blind Trial Comparing Efficacy and Safety of Imipenem/Relebactam vs Colistin Plus Imipenem in Patients With Imipenem-nonsusceptible Bacterial Infections.

BACKGROUND: The ß-lactamase inhibitor relebactam can restore imipenem activity against imipenem-nonsusceptible gram-negative pathogens. We evaluated imipenem/relebactam for treating imipenem-nonsusceptible infections. METHODS: Randomized, controlled, double-blind, phase 3 trial. Hospitalized patients with hospital-acquired/ventilator-associated pneumonia, complicated intraabdominal infection, or complicated urinary tract infection caused by imipenem-nonsusceptible (but colistin- and imipenem/relebactam-susceptible) pathogens were randomized 2:1 to 5-21 days imipenem/relebactam or colistin+imipenem. Primary endpoint: favorable overall response (defined by relevant endpoints for each infection type) in the modified microbiologic intent-to-treat (mMITT) population (qualifying baseline pathogen and ≥1 dose study treatment). Secondary endpoints: clinical response, all-cause mortality, and treatment-emergent nephrotoxicity. Safety analyses included patients with ≥1 dose study treatment. RESULTS: Thirty-one patients received imipenem/relebactam and 16 colistin+imipenem. Among mITT patients (n = 21 imipenem/relebactam, n = 10 colistin+imipenem), 29% had Acute Physiology and Chronic Health Evaluation II scores >15, 23% had creatinine clearance <60 mL/min, and 35% were aged ≥65 years. Qualifying baseline pathogens: Pseudomonas aeruginosa (77%), Klebsiella spp. (16%), other Enterobacteriaceae (6%). Favorable overall response was observed in 71% imipenem/relebactam and 70% colistin+imipenem patients (90% confidence interval [CI] for difference, -27.5, 21.4), day 28 favorable clinical response in 71% and 40% (90% CI, 1.3, 51.5), and 28-day mortality in 10% and 30% (90% CI, -46.4, 6.7), respectively. Serious adverse events (AEs) occurred in 10% of imipenem/relebactam and 31% of colistin+imipenem patients, drug-related AEs in 16% and 31% (no drug-related deaths), and treatment-emergent nephrotoxicity in 10% and 56% (P = .002), respectively. CONCLUSIONS: Imipenem/relebactam is an efficacious and well-tolerated treatment option for carbapenem-nonsusceptible infections. CLINICAL TRIALS REGISTRATION: NCT02452047.

The "MICE" scoring system in differentiating the identical twins leptospirosis and hantavirus infection.

PURPOSE: To develop a practical scoring system to assist clinicians in differentiating leptospirosis and hantavirus infections, whose epidemiological, clinical, and laboratory characteristics are literally like identical twins. METHODS: The study population consisted of 162 patients admitted to hospital with a confirmed diagnosis of leptospirosis (LG group, n = 92) and hantavirus infections (HG, group = 70) between January 2000 and January 2019. The two groups were compared in terms of demographic, clinical and laboratory features. Sensitivity, specificity, and positive and negative predictive values were determined from ROC analysis for findings of significance in the diagnosis of leptospirosis, and a scoring system for diagnosis was developed ("MICE" score). During the development of this scoring system, we were careful to employ parameters that would not affect one another statistically, to reflect the involvement of very different systems (such as the hematological, hepatic, renal, and musculoskeletal systems) due to the multisystemic effect of the disease in the organism, and to ensure that the system should be simple to apply and understand. Accordingly, five parameters, serum WBC, creatinine, creatine kinase, total bilirubin, and C-reactive protein, were employed in the "MICE" scoring system. RESULTS: Three cut-off values were determined using ROC analysis for the five parameters included in the MICE system. Accordingly, scores of 0, 1, or 2 were given based on the values WBC (/µL): ≤ 7500, 7500-15,000, and > 15,000; total bilirubin (mg/dL): ≤ 3, 3-10, and > 10; CRP (mg/dL): ≤ 5, 5-15, and > 15; creatinine (mg/dL): ≤ 1.5, 1.5-3, and > 3; CK (U/L): ≤ 500, 500-1000, > 1000. AUC was calculated as 0.964 at ROC analysis, while the most noteworthy cut-off point was obtained when MICE score was ≥ 3, exhibiting 93.5% sensitivity, 92.9% specificity, PPV 94.5% and NPV 91.5%. A test score ≥ 3 was regarded as positive. In addition, our patients were evaluated using other current scoring systems in addition to "MICE," and our scoring system exhibited a greater diagnostic power in our subjects. CONCLUSIONS: Leptospirosis and hantavirus infections can be accurately predicted by the MICE scoring system. Early diagnosis and rational treatment will also help to lower the mortality rates in these diseases.

Low recurrence rate of hepatocellular carcinoma following ledipasvir and sofosbuvir treatment in a real-world chronic hepatitis C patients cohort.

The aims of the present study were to evaluate the efficacy and tolerability of ledipasvir/sofosbuvir (LDV/SOF) with or without ribavirin in the treatment of chronic hepatitis C (CHC) in patients with advanced liver disease and to analyse whether the use of LDV/SOF treatment is associated with a new occurrence of hepatocellular carcinoma (HCC) during and after LDV/SOF treatment. The Turkish Early Access Program provided LDV/SOF treatment to a total of 200 eligible CHC patients with advanced liver disease. The median follow-up period was 22 months. All patients were Caucasian, 84% were infected with genotype 1b, and 24% had a liver transplantation before treatment. The sustained virological response (SVR12) was 86.0% with ITT analysis. SVR12 was similar among patients with Child-Pugh classes A, B and C disease and transplant recipients. From baseline to SVR12, serum ALT level and MELD score were significantly improved (P < 0.001). LDV/SOF treatment was generally well tolerated. Only one patient developed a new diagnosed HCC. Seventeen of the 35 patients, who had a history of previous HCC, developed HCC recurrence during the LDV/SOF treatment or by a median follow-up of 6 months after treatment. HCC recurrence was less commonly observed in patients who received curative treatment for HCC compared with those patients who received noncurative treatment (P = 0.007). In conclusion, LDV/SOF with or without ribavirin is an effective and tolerable treatment in CHC patients with advanced liver disease. Eradication is associated with improvements in liver function and a reduced risk of developing a new occurrence of HCC.

Diagnostic value of combined serum biomarkers for the evaluation of liver fibrosis in chronic hepatitis C infection: A multicenter, noninterventional, observational study.

BACKGROUND/AIMS: The hepatitis C virus (HCV) infection is important cause of chronic hepatitis. Liver biopsy is considered the gold standard for assessment of fibrosis but this procedure is an invasive procedure. We aimed to evaluate the diagnostic efficiency of non-invasive serum biomarkers, separately and in combinations, on liver fibrosis in treatment-naive chronic hepatitis C (CHC) patients. MATERIALS AND METHODS: Two hundred and sixteen treatment-naive CHC patients were enrolled from 32 locations across Turkey in this open-labelled, non-interventional prospective observational study. FibroTest®, aspartate aminotransferase-to-platelet ratio index(APRI), aspartate aminotransferase and alanine aminotransferase ratio (AAR), fibrosis index based on four factors (FIB-4), Age-platelet(AP) index and Forns index were measured and compared with Metavir scores got from liver biopsies. RESULTS: Data from 182 patients with baseline liver biopsy were suitable for analysis. One hundred and twenty patients (65.9%) had F0-F1 fibrosis and 62 patients (34.1%) had F2-F4 fibrosis. APRI 0.732 area under the curve(AUC) indicated advanced fibrosis with 69% sensitivity and 77% specificity. FIB-4 0.732 AUC and FibroTest 0.715 AUC indicated advanced fibrosis with 69% and 78.4% sensitivity, and 75% and 71.4% specificity, respectively. The combined use of tests also led to an increase in AUC and specificity. Combinations of FibroTest with APRI and/or FIB-4, and FIB-4 with APRI were optimal for the evaluation of liver fibrosis. CONCLUSION: Fibrotest, FIB-4, APRI, AP index and Forns index exhibit good diagnostic performance for determining liver fibrosis in CHC patients, and the use of at least two tests together will increase their diagnostic value still further.

Immunosuppressive therapy and the risk of hepatitis B reactivation: Consensus report.

This consensus report includes expert opinions and recommendations regarding the screening, and if necessary, the follow-up, prophylaxis, and treatment of hepatitis B before the treatment in patients who will undergo immunosuppressive therapy due to an emergency risk of hepatitis B reactivation. To increase awareness regarding the risk of hepatitis B reactivation in immunosuppressive patients, academicians from several university health research and training centers across Turkey came together and discussed the importance of the subject, current status, and issues in accordance with the current literature data and presented solutions.

Carbonic anhydrase I-II autoantibodies and oxidative status in long-term follow-up of patients with Crimean-Congo haemorrhagic fever.

CONTEXT: Crimean-Congo haemorrhagic fever (CCHF) is a life-threatening acute febrile haemorrhagic disease. OBJECTIVE: This study was to measure levels of the oxidative stress biomarkers malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) and of CA I-II autoantibodies as biomarkers for autoimmunity and course of disease in patients with CCHF. METHODS: Seventy CCHF patients and 39 healthy control volunteers were included in the study. RESULTS: Serum MDA and TAS levels were significantly higher (p < .0001) and serum TOS and OSI levels were significantly lower (p < .0001) in both the acute period and at 6th-month follow-up in the CCHF patients compared to the healthy volunteers. CA II levels were significantly higher in the acute period compared to the healthy volunteers (p < .005) and were significantly lower at 6th-month follow-up (p < .05). CONCLUSION: Serum MDA and CA II autoantibodies appear to reflect oxidative stress status and disease progression in CCHF and may be used as biomarkers for oxidative stress and disease progression.

The importance of risk factors for the prediction of patients with invasive pulmonary aspergillosis

Summary Objective: Invasive pulmonary aspergillosis (IPA) is a major challenge in the management of immunocompromised patients. Despite all the advances in diagnosis, it remains a problem. The purpose of our study was to investigate the risk factors associated with IPA seen in patients with hematological malignancies. Method: A total of 152 febrile neutropenia (FEN) patients with hematological malignancies aged over 18 years and receiving high-dose chemotherapy or stem cell transplant between January 1, 2010, and December 31, 2012 were included in the study. Sixty-five (65) cases with IPA according to the European Organization for the Research and Treatment of Cancer and Infectious Diseases Mycoses Study Group criteria were enrolled as the case group, while 87 patients without IPA development during concomitant monitoring were enrolled as the control group. Incidence of IPA was 21.4% (3/14) in patients receiving bone marrow transplant (allogeneic 2, autologous 1) and those cases were also added into the case group. The two groups were compared in terms of demographic, clinical and laboratory findings and risk factors associated with IPA investigated retrospectively. Results: Presence of relapse of primary disease, neutropenia for more than 3 weeks, presence of bacterial infection, and non-administration of antifungal prophylaxis were identified as risk factors associated with IPA. Conclusion: It may be possible to reduce the incidence of the disease by eliminating preventable risk factors. Predicting those risks would, per se, enable early diagnosis and treatment and, thus, the mortality rate of these patients would unquestionably decline.