Multicentre, randomised, double-blind, placebo-controlled, proof of concept study of LSALT peptide as prevention of acute respiratory distress syndrome and acute kidney injury in patients infected with SARS-CoV-2 (COVID-19).

OBJECTIVE: Dipeptidase-1 (DPEP-1) is a recently discovered leucocyte adhesion receptor for neutrophils and monocytes in the lungs and kidneys and serves as a potential therapeutic target to attenuate inflammation in moderate-to-severe COVID-19. We aimed to evaluate the safety and efficacy of the DPEP-1 inhibitor, LSALT peptide, to prevent specific organ dysfunction in patients hospitalised with COVID-19. DESIGN: Phase 2a randomised, placebo-controlled, double-blinded, trial. SETTING: Hospitals in Canada, Turkey and the USA. PARTICIPANTS: A total of 61 subjects with moderate-to-severe COVID-19. INTERVENTIONS: Randomisation to LSALT peptide 5 mg intravenously daily or placebo for up to 14 days. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was the proportion of subjects alive and free of respiratory failure and/or the need for renal replacement therapy (RRT). Numerous secondary and exploratory endpoints were assessed including ventilation-free days, and changes in kidney function or serum biomarkers. RESULTS: At 28 days, 27 (90.3%) and 28 (93.3%) of subjects in the placebo and LSALT groups were free of respiratory failure and the need for RRT (p=0.86). On days 14 and 28, the number of patients still requiring more intensive respiratory support (O2 ≥6 L/minute, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation) was 6 (19.4%) and 3 (9.7%) in the placebo group versus 2 (6.7%) and 2 (6.7%) in the LSALT group, respectively (p=0.14; p=0.67). Unadjusted analysis of ventilation-free days demonstrated 22.8 days for the LSALT group compared with 20.9 in the placebo group (p=0.4). LSALT-treated subjects had a significant reduction in the fold expression from baseline to end of treatment of serum CXCL10 compared with placebo (p=0.02). Treatment-emergent adverse events were similar between groups. CONCLUSION: In a Phase 2 study, LSALT peptide was demonstrated to be safe and tolerated in patients hospitalised with moderate-to-severe COVID-19. TRIAL REGISTRATION NUMBER: NCT04402957.

Bone Metabolism in Men who Live with HIV Aged 50 years and Over: Impact of Infection Duration.

BACKGROUND: Early diagnosis and effective antiretroviral therapy (ART) lead to similar life expectancy in people living with HIV (PLWH) compared to the general population. This population faces problems such as decreased bone mineral density (BMD) and increased fracture risk. The aim of this study was to determine the prevalence of osteoporosis in men aged 50 years and over who were PLWH and to determine risk factors and changes in bone metabolism with bone turnover markers. METHODS: 79 male PLWH aged 50 years and over were followed up in our outpatient clinic between May 2021 and October 2021. The patients' demographic, clinical, laboratory, and DEXA data were analyzed. Serum levels of bone turnover markers were measured. RESULTS: The prevalence of osteopenia, osteoporosis, and normal BMD was found to be 55.7%, 13.9%, and 30.4%, respectively. A correlation was found between low BMD and low body mass index, elapsed time since diagnosis of HIV infection, high rate of use of ART, and long usage time of tenofovir disoproxil fumarate + protease inhibitor. A one-year increase in HIV infection duration was associated with an increased risk of low BMD by 1.246. CONCLUSION: Compared to studies conducted on the general population, the prevalence of osteoporosis in male PLWH aged 50 years and older was two times higher. The limited effect of the duration of ART use on low BMD may be due to the patients' histories of replacement therapy. Therefore, to eliminate the negative effects of ART on BMD, it may be beneficial to start replacement therapy when necessary.

Increased prevalence of mild myopathic changes in the post-COVID-19 duration.

OBJECTIVE: There are reports of peripheral nerve and muscle involvement during or after coronavirus disease 2019 (COVID-19), even following a mild infection. Here, we aimed to analyze the objective findings regarding peripheral nerve, neuromuscular junction, and muscle function using electrophysiology in patients with a previous COVID-19 infection. METHODS: All consecutive patients with a history of COVID-19 were questioned for post-COVID-19 duration-related neurological complaints via Composite Autonomic Symptom Score-31 (COMPASS-31), modified Toronto Neuropathy score (mTORONTO), and Fatigue Severity Scale (FSS). Patients were dichotomized into two groups based on their scores in the questionnaire. Group 1 (patients with high scores in any area of the questionnaire) and Group 2 (patients with normal scores in all sections of the questionnaire). In the second step, Group 1 was invited to a preplanned hospital visit for electrophysiological analysis, including nerve conduction studies, repetitive nerve stimulation, needle electromyography (EMG), quantitative motor unit potential analysis (qMUP), and single fiber EMG. We included 106 patients in the study. According to the questionnaire, 38 patients constituted Group 1, and 68 formed Group 2. RESULTS: Of the 38 patients, 14 accepted and underwent preplanned electrophysiological examinations. Needle EMG revealed small, short, polyphasic MUPs with early recruitment, and qMUP analysis demonstrated an increased percentage of polyphasic potentials in three patients. The examinations in other patients were unremarkable. CONCLUSIONS: The high prevalence of complaints and objective myopathic findings in our cohort implicated the role of muscle involvement in the post-COVID-19 duration. Considering the socioeconomic and psychological burden of the post-COVID-19 duration among individuals and societies, a better understanding of the symptoms and myopathy is warranted.

Effectiveness of the BNT162b2 and the CoronaVac vaccines and boosters in healthcare workers.

The evidence on the waning protection of COVID-19 vaccines has been reviewed by the World Health Organization and has led to consideration of the need for booster doses. This study aimed to evaluate vaccine effectiveness against COVID-19, and the COVID-19 infections among healthcare workers who received various types (inactive or m-RNA) and doses (2 to 4 doses) of the COVID-19 vaccine. The study was conducted with a total of 3,009 healthcare workers between August 1 and November 30, 2021 at a university hospital. Six different vaccination statuses were evaluated in the study. The effectiveness for COVID-19 infection, after adjusting for age, sex, and position, was highest in those who received two doses of CoronaVac and two doses of BNT162b2 (89.3%, 95% CI 72.2-95.9%) and was lowest in those who received two doses of CoronaVac (29%, 95% CI - 8-53%). The adjusted effectiveness of two doses of CoronaVac for COVID-19 infection was not significant (21.0%, 95% CI - 20.7-48.3%) but increased significantly with a booster dose of CoronaVac or BNT162b2. One or two doses of the BNT162b2 booster demonstrated higher effectiveness in comparison to a single dose of the CoronaVac booster. These results indicate the need for a booster dose, and heterologous boosting with BNT162b2 may be a better option for higher effectiveness for those who received two doses of CoronaVac. Future studies should evaluate the need for further booster doses and their long-term effects.

Talaromyces marneffei infection in an HIV infected patient with hematological malignancy - first report from Turkey.

T.marneffei, encountered mostly in Southeast Asia, leads to a systemic infection, especially in immunocompromised individuals such as HIV-infected patients with low CD4 level. A 32-year-old male patient, residing in Hong Kong for the last two years, admitted with fever, cough, weakness, and weight loss. Physical examination revealed bilateral cervical and axillary multiple lymph nodes and hepatosplenomegaly. Screening of the pancytopenic patient revealed HIV infection. Histopathological examination of the cervical lymph node revealed plasmoblastic lymphoma. Blood and urine cultures remained sterile. Antiretroviral therapy was started. Fungal hyphae were detected in Gram staining of hemocultures taken in the third week due to ongoing fever, and antifungal therapy was started empirically. Red pigment around colonies on Sabouraud dextrose agar and microscopic appearance arose suspicion of Talaromyces spp. T.marneffei was identified by ITS 1-4 sequence analysis. Chemotherapy was started when fungemia was controlled. On the fifth day of chemotherapy, the patient's general condition deteriorated, broad-spectrum antibiotics were started and the patient was transferred to ICU. The cultures remained sterile and he expired five days later. In conclusion, although talaromycosis is not endemic in Turkey, it should be considered in patients with travel history to endemic regions and/or an underlying immunosuppressive disease such as HIV infection.

Discontinuation of Nucleos(t)ide Analog treatment in HBeAg-Negative Non-Cirrhotic Chronic Hepatitis B Patients: Real-Life Data of 20 Years.

BACKGROUND/AIMS: Discontinuation of nucleos(t)ide analog is controversial in HBeAg-negative chronic hepatitis B patients not achieved HBsAg loss. We aimed to evaluate re-treatment rates and risk factors in non-cirrhotic HbeAg-negative chronic hepatitis B patients for whom nucleosi(t)ides analogs were discontinued. MATERIALS AND METHODS: Demographic, clinical, and laboratory data before and at the end after discontinuation of nucleos(t)ide analogs were collected retrospectively. RESULTS: Seventy-two patients followed up between January 2000 and December 2019 were included; 43 were male, with a mean age of 46.3 (±10.8). Baseline median alanine aminotransferase (ALT) and hepatitis B virus DNA levels were 55.5 IU/L and 465 925 IU/mL, respectively. The median histologic activity index was 5.5 and the fibrosis score was 2. The median duration of treatment and consolidation therapy were 59 and 56 months, respectively. The median follow-up time after discontinuation of treatment was 55 months. Among 56 patients eligible for evaluation according to proposed re-treatment criteria, 29 (51.7%) patients were re-treated. The median time for relapse was 11 months. Re-treatment was significantly common in males (P = .034) and patients treated with tenofovir/entecavir (P = .04). Baseline hepatitis B virus DNA and levels of ALT, aspartate aminotransferase (AST) at the third and sixth months of treatment and at the end of treatment were statistically significantly higher in re-treated patients. A cutoff value of ≥405 000 IU/L for hepatitis B virus DNA discriminated patients for re-treatment. HBsAg was lost permanently in 2 non-re-treated patients. CONCLUSION: In resource-limited areas where follow-up of HBsAg or other markers is not possible, nucleos(t)ide analog discontinuation can be considered in patients in the early stage, with low baseline hepatitis B virus DNA and ALT levels, after a long consolidation therapy.

Homologous or heterologous COVID-19 vaccine schemes: comparison of immune responses and side effects.

Real-life data are needed regarding the appropriate time and selection of vaccination strategies, homologous or heterologous. We aimed to compare neutralizing antibody levels and side effects in different vaccination schemes. The study included 310 Health Care Workers (HCWs) vaccinated with 5 different schemes. Antispike/RBD IgG levels were measured between 28 and 60 days after the last dose. Side effects in participants were recorded, and pharmacovigilance records were reviewed from the outpatient vaccine clinic. Mean age of the participants was 38 ± 11 years of whom 226 (72.9%) were female, and 84 (27.1%) were male. After booster doses, increasing antibody levels were detected in all groups. Mean antibody levels were detected to be statistically lower in 3 doses of inactivated vaccines group. The side effects were no significant difference between groups. Booster dose administration with mRNA vaccines stands out as the most accurate strategy for those at risk of contracting severe COVID-19 and HCWs caring for this population.

Prospective analysis of febrile neutropenia patients with bacteraemia: the results of an international ID-IRI study.

OBJECTIVES: Bacteraemia during the course of neutropenia is often fatal. We aimed to identify factors predicting mortality to have an insight into better clinical management. METHODS: The study has a prospective, observational design using pooled data from febrile neutropenia patients with bacteraemia in 41 centres in 16 countries. Polymicrobial bacteraemias were excluded. It was performed through the Infectious Diseases-International Research Initiative platform between 17 March 2021 and June 2021. Univariate analysis followed by a multivariate binary logistic regression model was used to determine independent predictors of 30-d in-hospital mortality (sensitivity, 81.2%; specificity, 65%). RESULTS: A total of 431 patients were enrolled, and 85 (19.7%) died. Haematological malignancies were detected in 361 (83.7%) patients. Escherichia coli (n = 117, 27.1%), Klebsiellae (n = 95, 22% %), Pseudomonadaceae (n = 63, 14.6%), Coagulase-negative Staphylococci (n = 57, 13.2%), Staphylococcus aureus (n = 30, 7%), and Enterococci (n = 21, 4.9%) were the common pathogens. Meropenem and piperacillin-tazobactam susceptibility, among the isolated pathogens, were only 66.1% and 53.6%, respectively. Pulse rate (odds ratio [OR], 1.018; 95% confidence interval [CI], 1.002-1.034), quick SOFA score (OR, 2.857; 95% CI, 2.120-3.851), inappropriate antimicrobial treatment (OR, 1.774; 95% CI, 1.011-3.851), Gram-negative bacteraemia (OR, 2.894; 95% CI, 1.437-5.825), bacteraemia of non-urinary origin (OR, 11.262; 95% CI, 1.368-92.720), and advancing age (OR, 1.017; 95% CI, 1.001-1.034) were independent predictors of mortality. Bacteraemia in our neutropenic patient population had distinctive characteristics. The severity of infection and the way to control it with appropriate antimicrobials, and local epidemiological data, came forward. CONCLUSIONS: Local antibiotic susceptibility profiles should be integrated into therapeutic recommendations, and infection control and prevention measures should be prioritised in this era of rapidly increasing antibiotic resistance.

Epidemiology and risk factors of 28-day mortality of hospital-acquired bloodstream infection in Turkish intensive care units: a prospective observational cohort study.

OBJECTIVES: To uncover clinical epidemiology, microbiological characteristics and outcome determinants of hospital-acquired bloodstream infections (HA-BSIs) in Turkish ICU patients. METHODS: The EUROBACT II was a prospective observational multicontinental cohort study. We performed a subanalysis of patients from 24 Turkish ICUs included in this study. Risk factors for mortality were identified using multivariable Cox frailty models. RESULTS: Of 547 patients, 58.7% were male with a median [IQR] age of 68 [55-78]. Most frequent sources of HA-BSIs were intravascular catheter [182, (33.3%)] and lower respiratory tract [175, (32.0%)]. Among isolated pathogens (n = 599), 67.1% were Gram-negative, 21.5% Gram-positive and 11.2% due to fungi. Carbapenem resistance was present in 90.4% of Acinetobacter spp., 53.1% of Klebsiella spp. and 48.8% of Pseudomonas spp. In monobacterial Gram-negative HA-BSIs (n = 329), SOFA score (aHR 1.20, 95% CI 1.14-1.27), carbapenem resistance (aHR 2.46, 95% CI 1.58-3.84), previous myocardial infarction (aHR 1.86, 95% CI 1.12-3.08), COVID-19 admission diagnosis (aHR 2.95, 95% CI 1.25-6.95) and not achieving source control (aHR 2.02, 95% CI 1.15-3.54) were associated with mortality. However, availability of clinical pharmacists (aHR 0.23, 95% CI 0.06-0.90) and source control (aHR 0.46, 95% CI 0.28-0.77) were associated with survival. In monobacterial Gram-positive HA-BSIs (n = 93), SOFA score (aHR 1.29, 95% CI 1.17-1.43) and age (aHR 1.05, 95% CI 1.03-1.08) were associated with mortality, whereas source control (aHR 0.41, 95% CI 0.20-0.87) was associated with survival. CONCLUSIONS: Considering high antimicrobial resistance rate, importance of source control and availability of clinical pharmacists, a multifaceted management programme should be adopted in Turkish ICUs.

Comparison of Hospitalized COVID-19 Patients in Terms of Disease Course According to the Presence of Gastrointestinal Symptoms Before and After Admission.

BACKGROUND: This study aimed to find the prevalence of gastrointestinal symptoms in hospitalized COVID-19 patients and to investigate the effects of gastrointestinal symptoms on the course of the disease during hospitalization. METHODS: Patients who were hospitalized due to COVID-19 were included in this retrospective study. The diagnostic method of COVID-19 was either a positive reverse transcription polymerase chain reaction test or a typical finding in chest computed tomography. This study was conducted by contacting patients by phone 1 month after they were discharged from hospital to investigate gastrointestinal symptoms. Patients' laboratory findings at the time of admission, medications they used, and clinical findings were obtained from hospital records retrospectively. Patients with gastrointestinal symptoms were divided into 2 groups according to the start of treatment: pre-treatment and post-treatment groups. RESULTS: At least 1 gastrointestinal symptom (anorexia, weight loss, diarrhea, nausea, vomiting, and abdominal pain) was present in 67.5% of 435 patients (55.6% male, mean age 52.8). If anorexia and weight loss are excluded, the rate of the presence of at least 1 gastrointestinal symptom is 54%. Gastrointestinal symptoms were present in 48.9% before the initiation of COVID-19 treatment. The most prevalent 3 symptoms were anorexia, weight loss, and diarrhea (56%, 52%, and 35.6%, respectively). Presence of pre-treatment gastrointestinal symptoms was associated with elevated C-reactive protein levels. Pre-treatment gastrointestinal symptoms were more common in those who received oxygen supply and who were intubated. Resolution of gastrointestinal symptoms takes longer time in those who were admitted to intensive care unit. Weight loss and diarrhea were more common in COVID-19 patients with gastrointestinal symptoms who were intubated than who were not intubated. Abdominal pain was not found to be a significant predictor of disease severity. CONCLUSION: The prevalence of at least 1 gastrointestinal symptom in hospitalized COVID-19 patients was 67%. The most prevalent symptoms were anorexia, weight loss, and diarrhea. Presence of pre-treatment gastrointestinal symptoms was associated with elevated C-reactive protein levels, use of oxygen supply, and intubation. Gastrointestinal symptoms persist longer in those admitted to intensive care unit.

Waning immunity to inactive SARS-CoV-2 vaccine in healthcare workers: booster required.

AIMS: Despite high vaccination rates, increasing case numbers continue to be reported with the identification of new variants of concern, and the issue of durability of the vaccine-induced immune response remains hot topic. Real-life data regarding time-dependent immunogenicity of inactivated COVID-19 vaccines are scarce. We aimed to investigate the changes in the antibody at the different times after the second dose of the CoronaVac vaccine. METHODS: The study included 175 HCWs vaccinated with inactive CoronaVac (Sinovac Life Sciences, China) SARS-CoV-2 vaccine in two doses. Anti-spike/RBD IgG levels were measured first, third, and sixth months after the second dose. Chemiluminescent microparticle immunoassay (IgG II Quant test, Abbott, USA), which is 100% compatible with plaque reduction neutralization test, was used. RESULTS: Mean age of the participants was 38 ± 11.23 years (range between 22 and 66) of whom 119 (63.9%) were female, and 56 (32%) were male. Dramatic reductions were demonstrated in median antibody levels particularly in the infection-naïve group, comprising 138 HCWs compared to those with prior history of COVID-19 infection (n = 37) (p < 0.001). There was no difference between the two groups in terms of age, gender, blood groups, BMI, and comorbid diseases. CONCLUSIONS: While antibody positivity remained above 90% in the 6th month after two doses of inactivated vaccine in HCWs, the median titers of neutralizing antibodies decreased rapidly. The decrease was more rapid and significant in those with no history of prior COVID-19 infection. In this critical phase of the pandemic, where we are facing the dominance of the Omicron variant after Delta, booster doses have become vital.

Long-term follow-up of treatment-naïve HBeAg-negative patients with chronic hepatitis B.

BACKGROUND/AIMS: We aimed to explore long-term results of oral antiviral agents in treatment-naïve "HBeAg negative chronic hepatitis B (CHB)" and determine the factors affecting the complete virological response. METHOD: Patients with HBeAg-negative CHB who used oral antiviral agents for at least 3 years were evaluated retrospectively. RESULTS: A total of 173 patients were recorded. The mean duration of treatment was 62.2 ± 28.9 months. Complete virological responses (CVR) were 82.8% (n = 53/64) in tenofovir disoproxil fumarate (TDF), 84.4% (n = 49/58) in lamivudine (LAM), 83.9% (n = 26/31) in entecavir (ETV), 95% in telbivudine (LdT) (n = 19/20) (p = 0.290). Multivariate analysis revealed age ≤ 40 (p = 0.012, 95%CI = 1.38-13.76, OR = 4.36) and baseline HBV DNA value (p = 0.003, 95%CI = 1.23-2.63, OR = 1.78) as independent factors for CVR. Virological breakthrough was detected in 29 (50%) patients on LAM therapy, two (6.4%) patients on ETV therapy, and two (10%) patients on LdT therapy. Treatment was switched to another antiviral agent due to osteoporosis in four patients in the TDF group, muscle pain in nine patients in the LDT group, and headache in one patient in the ETV group. Hepatocelluler cancer was detected in five patients. HBsAg seroclearance developed in two patients. Anti-HBs seroconversion was not detected. CONCLUSION: CVR was achieved at similar rates with all four antiviral agents, while younger age (≤ 40) and low baseline viral load were the main factors for virological response. However, drug resistance and virological breakthrough in the LAM group and side effects in the LdT group were detected during the long-term follow-up. Moreover, HBsAg seroclearance was achieved at very low rates with oral antiviral agents.

Performance of noninvasive fibrosis indices in chronic hepatitis B during pretreatment and post-treatment periods.

Background: Pretreatment and post-treatment performances of noninvasive fibrosis indices were determined in patients with chronic hepatitis B. Method: This was a retrospective, single-center study. Results: The best area under the receiver operating characteristic curve values were detected for aspartate aminotransferase-to-alanine aminotransferase ratio (0.685) for ≥F2, Fibrosis Index (FI; 0.703) for ≥F3; FI (0.872) for ≥F4 and FI (0.864) for cirrhosis. After antiviral treatment, the best area under the receiver operating characteristic curve values were detected in aspartate aminotransferase-to-alanine aminotransferase ratio (0.615) for ≥F2; in FI based on four factors (FIB-4; 0.634) for ≥F3; in FIB-4 (0.678) for ≥F4 and in FIB-4 (0.814) for cirrhosis. Conclusion: FIB-4 and FI showed better performance in defining advanced fibrosis (≥F4) and cirrhosis.

Remdesivir treatment for patients with moderate to severe COVID-19.

BACKGROUND: Remdesivir, which was first developed for the treatment of Ebola disease but failed to meet expectations, has become hope in the fight against the COVID-19 pandemic. This study aimed to evaluate risk factors for mortality and prognosis of adult moderate/severe COVID-19 patients treated with remdesivir, and safety and tolerability of 5 days of remdesivir treatment. METHODS: This multicenter prospective observational study was conducted in 14 centers in Turkey. Pregnancy or breastfeeding, multiorgan failure, or usage of vasopressors for septic shock, ALT > 5 × the upper limit of the normal range, or eGRF <30 mL/min or dialysis and receiving favipiravir were the exclusion criteria of the study. RESULTS: Among 500 patients, 494 patients were included in the study. On admission, 392 (79.3%) patients had moderate and 102 (20.6%) patients had severe COVID-19. The 28-day mortality was 10.1%. The median of the scores of the seven-category ordinal scale assessed on days 0, 3, 5, 7 were 4 and 3 on day 14. When the survival status of the patients was evaluated according to the time between the remdesivir start date and the end date of the symptoms, no statistically significant difference was found between the medians of the groups (p = 0.404). In multivariable analysis, age (OR, 1.05; 95%CI, 1.02-1.08; p = 0.003), SpO2 level on admission (OR, 3.03; 95%CI, 1.35-6.81; p = 0.007), heart rate (OR, 2.48; 95%CI, 1.01-6.07; p = 0.047), follow-up site at the hospital (clinic/ICU) (OR, 26.4; 95%CI, 11.6-60.17; p < 0.001) were independently associated with increased mortality. Grade 3 adverse event (AE) was observed in 4 (0.8%) patients. None of the patients experienced grade 4 or 5 AEs. DISCUSSION: Remdesivir is a safe and well-tolerated drug and older age, low SpO2 level on admission, tachycardia, and ICU admission are independently associated with increased mortality among patients with moderate/severe COVID-19 receiving remdesivir treatment.

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.

Changing Bacterial Etiology and Antimicrobial Resistance Profiles as Prognostic Determinants of Diabetic Foot Infections: A Ten-Year Retrospective Cohort Study.

Background: In this single-center study, we analyzed a retrospective cohort of patients with diabetic foot infections (DFIs) between 2011 and 2020. Patients and Methods: The first and second five-year periods were compared. A poor prognosis was defined as a primary composite end point including re-infection, major amputation, or mortality at six months. Results: A total of 484 patients were enrolled. Overall, 269 patients had the primary composite end point. A substantial decrease was detected in the second five-year period in terms of re-infection (n = 132, 66.0% vs. n = 68, 23.9%; p < 0.001) and mortality (n = 22, 11.0% vs. n = 7, 2.5%; p < 0.001). A total of 798 micro-organisms were isolated from 484 patients. A substantial increase was detected in polymicrobial infections (48.5% vs. 65.1%; p = 0.001) as well as Streptococcus spp. (2.5% vs. 9.2%; p = 0.003), Corynebacterium spp. (9.5% vs. 22.9%; p < 0.001), and extended-spectrum ß-lactamase (ESBL) producing Escherichia coli (3.0% vs. 12.7%; p < 0.001) in the second five-year period, whereas the prevalence of multi-drug-resistanct (MDR) Pseudomonas aeruginosa (17.0% vs. 10.2%; p = 0.029) and carbapenem-resistant Acinetobacter baumannii (7.5% vs. 2.8%; p = 0.017) decreased. Multivariable regression analysis revealed that MDR Pseudomonas aeruginosa (odds ratio [OR], 1.917; 95% confidence interval [CI], 1.074-3.420; p = 0.028) and carbapenem-resistant Acinetobacter baumannii (OR, 3.069; 95% CI, 1.114-8.453; p = 0.030) were independent predictors for poor prognosis. Conclusions: This 10-year cohort study provides reassuring information about the changing epidemiology of DFIs and the prognostic determinants in patients with DFIs.

Association of SARS-CoV-2 IgG Antibody Levels with Clinical/Laboratory Characteristics in COVID-19 Patients: Data from a Turkish Study.

BACKGROUND: COVID-19 causes clinical manifestations ranging from asymptomatic infection to multi-organ failure. It is reported that those with severe disease have higher anti-SARS-CoV-2 antibody titers compared to asymptomatic or mild cases. We evaluated the correlation of antibody responses with laboratory and clinical indicators in COVID-19 patients. METHODS: Seventy-nine male and 66 female patients (mean age: 39) with at least one positive SARS-CoV-2 RT-PCR test and SARS-CoV-2 IgG antibody result after acute infection were included. RESULTS: Seventy-six (52%), 45 (31%), and 24 (17%) patients had mild, moderate, and severe clinical findings, respectively. Patients with high body mass index and advanced age had significantly more severe disease (p < 0.001). A significant correlation was found between the increase in lymphopenia, C-reactive protein, ferritin, D-dimer, and lactate dehydrogenase and the severity of clinical findings (p = 0.0001). SARS-CoV-2 IgG antibody test was positive in 128 (88.3%) patients. A significant correlation was found between disease severity and antibody levels in the comparison of all groups (p < 0.001). CONCLUSIONS: Long-term monitoring of immune responses will be required to determine the appropriate time for the administration of new vaccines.

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.

Self-reported antibiotic stewardship and infection control measures from 57 intensive care units: An international ID-IRI survey.

We explored the self-reported antibiotic stewardship (AS), and infection prevention and control (IPC) activities in intensive care units (ICUs) of different income settings. A cross-sectional study was conducted using an online questionnaire to collect data about IPC and AS measures in participating ICUs. The study participants were Infectious Diseases-International Research Initiative (IDI-IR) members, committed as per their institutional agreement form. We analyzed responses from 57 ICUs in 24 countries (Lower-middle income (LMI), n = 13; Upper-middle income (UMI), n = 33; High-income (HI), n = 11). This represented (~5%) of centers represented in the ID-IRI. Surveillance programs were implemented in (76.9%-90.9%) of ICUs with fewer contact precaution measures in LMI ones (p = 0.02); (LMI:69.2%, UMI:97%, HI:100%). Participation in regional antimicrobial resistance programs was more significantly applied in HI (p = 0.02) (LMI:38.4%,UMI:81.8%,HI:72.2%). AS programs are implemented in 77.2% of institutions with AS champions in 66.7%. Infectious diseases physicians and microbiologists are members of many AS teams (59%&50%) respectively. Unqualified healthcare professionals(42.1%), and deficient incentives(28.1%) are the main barriers to implementing AS. We underscore the existing differences in IPC and AS programs' implementation, team composition, and faced barriers. Continuous collaboration and sharing best practices on APM is needed. The role of regional and international organizations should be encouraged. Global support for capacity building of healthcare practitioners is warranted.