Results of Nucleos(t)ide Analog Treatment Discontinuation in Hepatitis B e-Antigen-Negative Chronic Hepatitis B: NUCSTOP Study.

BACKGROUND/AIMS: This study aims to investigate the effects of nucleos(t)ide analogs (NAs) discontinuation in eligible patients in accordance with the Asian Pacific Association for the Study of the Liver hepatitis B guideline and the factors affecting clinical and virological relapses. MATERIALS AND METHODS: In this prospectively designed study, hepatitis B e antigen (HBeAg)-negative chronic hepatitis B patients who were followed up between 2012 and 2019 were evaluated and 57 patients were included. All participants enrolled the study were HBeAgnegative status at NA initiation. RESULTS: The median age of the patients was 49 (29-72) years and 24 (42%) were females. The median treatment duration was 96 (36- 276) months and patients were followed for a median duration of 27 months. Sixteen patients had a previous history of NA switch, and thirteen of these patients had a history of lamivudine resistance. Thirty-eight of 57 patients (66%) developed an elevated hepatitis B virus deoxyribonucleic acid level of >2000 IU/mL at least once, defined as virological relapse and 23 (60%) of them, experienced clinical relapse. Thirty-one of 57 patients were re-treated during the follow-up, and hepatitis B surface antigen (HBsAg) loss occurred among 4 (7%) patients. All patients who experienced HBsAg loss had a history of lamivudine resistance (P = .002). CONCLUSION: Despite receiving NAs suppression therapy for a long time, HBsAg loss occurs rarely. Although it was not life-threatening, most patients experienced relapses and treatment should be restarted. In our study, whether it is a coincidence that all patients with HBsAg loss are patients in whom NAs are used sequentially due to lamivudine resistance is an issue that needs to be further investigated.

Factors Influencing HIV Infection in Children Born to HIV-Infected Mothers in Turkey

Background: Human immunodeficiency virus (HIV) is still a challenge for children. About 15 to 45% of the HIV positive pregnant women can transmit the virus to their children during pregnancy, delivery and/or breastfeeding. The risk of transmission can be decreased my several measures. Aims: To identify factors associated with HIV infection in children born to HIV-infected mothers. Study Design: A multi-center retrospective cohort study. Methods: A ten-year retrospective cohort study in five dedicated HIV centers was conducted. The 325 women in our cohort were between the ages of 18 and 45. During the study period, 44 (13.5%) of these women gave birth and 51 babies were born. Of the 51 infants, 7 (13.7%) were HIV/AIDS positive. Results: Among the factors studied, breastfeeding, having a HIV-positive sibling and being on antiretroviral treatment during pregnancy and detectable HIV-RNA during delivery were found statistically significant. A multivariable logistic regression analysis showed that being on antiretroviral treatment during pregnancy is the most important predictor of mother-to-child transmission. Conclusion: Mother-to-child transmission appears to be an important route of HIV transmission in Turkey. Lack of antiretroviral treatment during pregnancy appears to be a key factor in transmission.

Vector-borne and zoonotic infections and their relationships with regional and socioeconomic statuses: An ID-IRI survey in 24 countries of Europe, Africa and Asia.

BACKGROUND: In this cross-sectional, international study, we aimed to analyze vector-borne and zoonotic infections (VBZI), which are significant global threats. METHOD: VBZIs' data between May 20-28, 2018 was collected. The 24 Participatingcountries were classified as lower-middle, upper-middle, and high-income. RESULTS: 382 patients were included. 175(45.8%) were hospitalized, most commonly in Croatia, Egypt, and Romania(P = 0.001). There was a significant difference between distributions of VBZIs according to geographical regions(P < 0.001). Amebiasis, Ancylostomiasis, Blastocystosis, Cryptosporidiosis, Giardiasis, Toxoplasmosis were significantly more common in the Middle-East while Bartonellosis, Borreliosis, Cat Scratch Disease, Hantavirus syndrome, Rickettsiosis, Campylobacteriosis, Salmonellosis in Central/East/South-East Europe; Brucellosis and Echinococcosis in Central/West Asia; Campylobacteriosis, Chikungunya, Tick-borne encephalitis, Visceral Leishmaniasis, Salmonellosis, Toxoplasmosis in the North-Mediterranean; CCHF, Cutaneous Leishmaniasis, Dengue, Malaria, Taeniasis, Salmonellosis in Indian Subcontinent; Lassa Fever in West Africa. There were significant regional differences for viral hemorrhagic fevers(P < 0.001) and tick-borne infections(P < 0.001), and according to economic status for VBZIs(P < 0.001). The prevalences of VBZIs were significantly higher in lower-middle income countries(P = 0.001). The most similar regions were the Indian Subcontinent and the Middle-East, the Indian Subcontinent and the North-Mediterranean, and the Middle-East and North-Mediterranean regions. CONCLUSIONS: Regional and socioeconomic heterogeneity still exists for VBZIs. Control and eradication of VBZIs require evidence-based surveillance data, and multidisciplinary efforts.

Managing adult patients with infectious diseases in emergency departments: international ID-IRI study.

We aimed to explore factors for optimizing antimicrobial treatment in emergency departments. A single-day point prevalence survey was conducted on January 18, 2020, in 53 referral/tertiary hospitals in 22 countries. 1957 (17%) of 11557 patients presenting to EDs had infections. The mean qSOFA score was 0.37 ± 0.74. Sepsis (qSOFA ≥ 2) was recorded in 218 (11.1%) patients. The mean qSOFA score was significantly higher in low-middle (1.48 ± 0.963) compared to upper-middle (0.17 ± 0.482) and high-income (0.36 ± 0.714) countries (P < 0.001). Eight (3.7%) patients with sepsis were treated as outpatients. The most common diagnoses were upper-respiratory (n = 877, 43.3%), lower-respiratory (n = 316, 16.1%), and lower-urinary (n = 201, 10.3%) infections. 1085 (55.4%) patients received antibiotics. The most-commonly used antibiotics were beta-lactam (BL) and BL inhibitors (n = 307, 15.7%), third-generation cephalosporins (n = 251, 12.8%), and quinolones (n = 204, 10.5%). Irrational antibiotic use and inappropriate hospitalization decisions seemed possible. Patients were more septic in countries with limited resources. Hence, a better organizational scheme is required.

Efficacy and safety of co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in HIV-positive patients: real-world data.

OBJECTIVES: Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) is a recommended and widely used regimen for HIV infection. In this study, we aimed to determine the efficacy and safety of E/C/F/TAF in people living with HIV (PLWH), who are either treatment-naïve or switched from any tenofovir disoproxil fumarate-containing regimen. For switched patients, we aimed to determine the impact of switching from tenofovir disoproxil fumarate (TDF) to TAF on lipid profile and kidney functions. METHODS: ACTHIV-IST Study Group produced a database, and five dedicated HIV centres in Istanbul entered data of PLWH who switched from any TDF-containing regimen to E/C/F/TAF and treatment-naïve patients who were initiated with the E/C/F/TAF regimen between January 2017 and December 2019. Clinical findings, viral parameters, lipid studies, renal function tests, adverse events and adherence to the treatment were recorded in this prospective observational study. RESULTS: The study included a total of 614 switched and treatment-naïve patients. Of 430 treatment-experienced patients, 89% (382) were men, and the mean age was 42 ± 12 years. Among them, 47% (181/382) self-identified as men who have sex with men (MSM). The median duration of HIV diagnosis was 54 ± 29 months. The median duration of E/C/F/TAF use was 20 ± 36 months and that of previous treatment was 23 ± 18 months. HIV-RNA was undetectable at baseline and month 12 in 84.1% (360/428) and 86.1% (328/381) of patients, respectively (p > 0.05). Mean CD4 counts were 708 ± 287 cells/µL and 802 ± 305 cells/µL at baseline and month 12, respectively (p < 0.001). Serum creatinine levels remained stable during the treatment period. Mean total cholesterol levels at baseline and month 12 were 172 and 211 mg/dL (p < 0.01), LDL-cholesterol 104 and 138 mg/dL (p < 0.01), HDL-cholesterol 39 and 49 mg/dL (p < 0.01) and triglycerides 134 and 174 mg/dL (p < 0.01), respectively. The treatment was generally well tolerated. Eight patients discontinued the therapy (drug interaction: 3; lost to follow-up: 1; pregnancy: 1; pulmonary tuberculosis: 1; side effect: 1; patient's decision: 1). Of 184 treatment-naïve patients, 88% (162) were men, and the mean age was 36.5± 12 years. Among them, 50% (81/162) self-identified as MSM. The mean duration of HIV infection was 21.6 ± 17.1 months. The mean duration of E/C/F/TAF use was 16 ± 4 months. HIV-RNA was undetectable at baseline and month 12 in 1% and 89.1% of patients, respectively. Mean CD4 counts at baseline and month 12 were 469 ± 223 cells/µL and 740 ± 298 cells/µL, respectively. During the treatment period, creatinine levels remained stable. Total cholesterol, LDL-cholesterol, triglyceride and also HDL-cholesterol levels increased. Mean total cholesterol levels at baseline and month 12 were 167 and 211 mg/dL (p < 0.01), LDL-cholesterol 108 and 143 mg/dL (p < 0.01), HDL-cholesterol 41 and 47 mg/dL (p < 0.01) and triglycerides 136 and 172 mg/dL, respectively (p < 0.01). The treatment was generally well tolerated. Three patients discontinued the therapy (drug interaction: 1; non-responder: 1; patient's decision: 1). CONCLUSION: Starting with or switching to E/C/F/TAF in PLWH effectively suppresses HIV infection, is associated with an increase in CD4 cell count and is well tolerated in a real-life setting. Renal functions remained stable during the treatment. E/C/F/TAF use was associated with an increase in LDL-cholesterol and triglyceride levels along with an increase in HDL-cholesterol levels.

COVID-19 infection in a membranous nephropathy patient treated with rituximab.

While COVID-19 pandemic continues to affect our country and most countries in the world, we have to make some changes both in our social life and our approach to healthcare. We have to struggle with the pandemic on one hand and also try to follow up and treat our patients with chronic diseases in the most appropriate way. In this period, one of our group of patients who are challenging us for follow-up and treatment are those who should start or continue to use immunosuppressive therapy. In order to contribute to the accumulation of knowledge in this area, we wanted to report a patient who was followed up with the diagnosis of COVID-19 and had been administered rituximab very recently due to a nephrotic syndrome caused by membranous nephropathy.

Evaluation of hepatitis B vaccine efficacy and factors affecting vaccine nonresponse in patients receiving anti-tumor necrosis factor agents.

OBJECTIVES: The response rate of patients to hepatitis B virus (HBV) vaccination receiving anti-tumor necrosis factor (TNF) agents is quite low. We aimed to assess the efficiency of HBV vaccination in patients with chronic inflammatory diseases (CIDs) receiving anti-TNF agents as well as in healthy controls. We also evaluated the impact of different factors on the efficacy of HBV vaccination. METHODS: Patients with CIDs receiving anti-TNF agents and healthy controls vaccinated for HBV were included in the study during 2018-2019. An adequate immune response and an effective immune response to HBV were defined as >10 IU/L and > 100 IU/L, respectively. RESULTS: Among 274 participants, 187 were patients with CID and 87 were healthy controls. The mean age of the patients with CID (43.9 ± 11.7 years) was significantly higher than that of the healthy controls (31.4 ± 7 years) (P = 0.000). Adequate immune response was 60.8 and 94.3% in patients with CID and healthy controls (P = 0.000), respectively, whereas effective immune response was 37.9 and 75.9% (P = 0.000), respectively. In logistic regression analysis, male sex [odds ratio (OR), 0.408; 95% confidence interval (CI), 0.201-0.830; P = 0.013), use of infliximab (OR, 2.694; 95% CI, 1.203-6.035; P = 0.016) and sertoluzimab (OR, 3.307; 95% CI, 1.287-8.498; P = 0.013), vaccination after anti-TNF treatment (OR, 0.224; 95% CI, 0.083-0.602; P = 0.003) were identified as risk factors of nonresponse to HBV vaccine. CONCLUSIONS: Infliximab and sertoluzimab usage, male sex, and vaccination after anti-TNF treatment were risk factors of nonresponse. HBV vaccination should be given to patients with CID before initiation of anti-TNF treatment and awareness should be spread on this subject.

Consensus Report on Diagnosis, Treatment and Prevention of Infective Endocarditis by Turkish Society of Cardiovascular Surgery (TSCVS), Turkish Society of Clinical Microbiology and Infectious Diseases (KLIMIK), Turkish Society of Cardiology (TSC), Turkish Society of Nuclear Medicine (TSNM), Turkish Society of Radiology (TSR), Turkish Dental Association (TDA) and Federation of Turkish Pathology Societies (TURKPATH) Cardiovascular System Study Group.

Infective endocarditis (IE) is rare, but associated with significant morbidity and mortality rates. Estimates of the incidence of IE in Turkey are compromised by the absence of population-based prospective studies. Due to the frequent presence of predisposing cardiac conditions and higher rates of nosocomial bacteremia in highrisk groups, the incidence of IE is expected to be higher in Turkey. Additionally, while IE generally affects older people in developed countries, it still affects young people in Turkey. In order to reduce the mortality and morbidity, it is critical to diagnose the IE to determine the causative agent and to start treatment rapidly. However, most of the patients cannot be diagnosed in their first visits, about half of them can be diagnosed after three months, and the disease often goes unnoticed. In patients diagnosed with IE, the rate of identification of causative organisms is significantly lower in Turkey than in developed countries. Furthermore, most of the centers do not perform some essential microbiological diagnostic tests as a routine practice. Some antimicrobials that are recommended as the first-line of treatment for IE, particularly antistaphylococcal penicillins, are not available in Turkey. These problems necessitate reviewing the epidemiological, laboratory, and clinical characteristics of IE in our country, as well as the current information about its diagnosis, treatment, and prevention together with local data. Physicians can follow patients with IE in many specialties. Diagnosis and treatment processes of IE should be standardized at every stage so that management of IE, a setting in which many physicians are involved, can always be in line with current recommendations. Study Group for Infective Endocarditis and Other Cardiovascular Infections of the Turkish Society of Clinical Microbiology and Infectious Diseases has called for collaboration of the relevant specialist organizations to establish a consensus report on the diagnosis, treatment, and prevention of IE in the light of current information and local data in Turkey.

Treatment of ventilator-associated pneumonia (VAP) caused by Acinetobacter: results of prospective and multicenter ID-IRI study.

Ventilator-associated pneumonia (VAP) due to Acinetobacter spp. is one of the most common infections in the intensive care unit. Hence, we performed this prospective-observational multicenter study, and described the course and outcome of the disease. This study was performed in 24 centers between January 06, 2014, and December 02, 2016. The patients were evaluated at time of pneumonia diagnosis, when culture results were available, and at 72 h, at the 7th day, and finally at the 28th day of follow-up. Patients with coexistent infections were excluded and only those with a first VAP episode were enrolled. Logistic regression analysis was performed. A total of 177 patients were included; empiric antimicrobial therapy was appropriate (when the patient received at least one antibiotic that the infecting strain was ultimately shown to be susceptible) in only 69 (39%) patients. During the 28-day period, antibiotics were modified for side effects in 27 (15.2%) patients and renal dose adjustment was made in 38 (21.5%). Ultimately, 89 (50.3%) patients died. Predictors of mortality were creatinine level (OR, 1.84 (95% CI 1.279-2.657); p = 0.001), fever (OR, 0.663 (95% CI 0.454-0.967); p = 0.033), malignancy (OR, 7.095 (95% CI 2.142-23.500); p = 0.001), congestive heart failure (OR, 2.341 (95% CI 1.046-5.239); p = 0.038), appropriate empiric antimicrobial treatment (OR, 0.445 (95% CI 0.216-0.914); p = 0.027), and surgery in the last month (OR, 0.137 (95% CI 0.037-0.499); p = 0.003). Appropriate empiric antimicrobial treatment in VAP due to Acinetobacter spp. was associated with survival while renal injury and comorbid conditions increased mortality. Hence, early diagnosis and appropriate antibiotic therapy remain crucial to improve outcomes.

Foot self-care in diabetes mellitus: Evaluation of patient awareness.

AIMS: To assess diabetic patients' knowledge and practices regarding foot care. METHODS: This study was conducted as a cross-sectional study in 1030 patients between November 2017 and February 2018.The descriptive survey instrument was developed by the investigators. Survey content and format were based on prior surveys and guidelines. The survey sought socio-demographic characteristics of the patients and the level of knowledge about diabetic foot care practice. RESULTS: 29.5% of patients had bad foot care, 49.6% of patients had moderate foot care and 20.8% of patients had good foot care. There were no significant differences between patient groups in regard to age, gender, foot infection history and having undergone amputation surgery. We found that patients who good at foot care had higher education status (p<0.001), were more likely live in a city (p<0.001), had higher income (p<0.001), had been trained about foot care (p<0.001) and were more likely to have type I DM (p=0.015). Disease duration was longer in those who had good foot care compared to the other groups (p=0.010). CONCLUSIONS: The mean knowledge and practice scores of our patients were moderate, indicating that much is to be done for the education of patients on this matter. We also found that knowledge about the importance of this practice, education status and disease duration had significant influence on the practice of foot-care in patients with DM.

Portraying infective endocarditis: results of multinational ID-IRI study.

Infective endocarditis is a growing problem with many shifts due to ever-increasing comorbid illnesses, invasive procedures, and increase in the elderly. We performed this multinational study to depict definite infective endocarditis. Adult patients with definite endocarditis hospitalized between January 1, 2015, and October 1, 2018, were included from 41 hospitals in 13 countries. We included microbiological features, types and severity of the disease, complications, but excluded therapeutic parameters. A total of 867 patients were included. A total of 631 (72.8%) patients had native valve endocarditis (NVE), 214 (24.7%) patients had prosthetic valve endocarditis (PVE), 21 (2.4%) patients had pacemaker lead endocarditis, and 1 patient had catheter port endocarditis. Eighteen percent of NVE patients were hospital-acquired. PVE patients were classified as early-onset in 24.9%. A total of 385 (44.4%) patients had major embolic events, most frequently to the brain (n = 227, 26.3%). Blood cultures yielded pathogens in 766 (88.4%). In 101 (11.6%) patients, blood cultures were negative. Molecular testing of vegetations disclosed pathogens in 65 cases. Overall, 795 (91.7%) endocarditis patients had any identified pathogen. Leading pathogens (Staphylococcus aureus (n = 267, 33.6%), Streptococcus viridans (n = 149, 18.7%), enterococci (n = 128, 16.1%), coagulase-negative staphylococci (n = 92, 11.6%)) displayed substantial resistance profiles. A total of 132 (15.2%) patients had cardiac abscesses; 693 (79.9%) patients had left-sided endocarditis. Aortic (n = 394, 45.4%) and mitral valves (n = 369, 42.5%) were most frequently involved. Mortality was more common in PVE than NVE (NVE (n = 101, 16%), PVE (n = 49, 22.9%), p = 0.042).

Risk Factors Affecting Patterns of Antibiotic Resistance and Treatment Efficacy in Extreme Drug Resistance in Intensive Care Unit-Acquired Klebsiella Pneumoniae Infections: A 5-Year Analysis.

BACKGROUND We investigated the factors affecting antibiotic resistance in the intensive care unit (ICU)-related hospital-acquired infections caused by Klebsiella pneumoniae (KP-HAI) and the effects of antibiotics used for high-level antibiotic resistance on patient survival. MATERIAL AND METHODS This retrospective study was performed at the adult ICU of Bezmialem Vakif University Hospital. Patients who were followed up between 01 January 2012 and 31 May 2017 were evaluated. Each KP strain was categorized according to resistance patterns and analyzed. The efficiency of antibiotic therapy for highly-resistant KP-HAI was determined by patients' lifespans. RESULTS We evaluated 208 patients. With the prior use of carbapenem, antibiotics against resistant Gram-positives, and tigecycline, it was observed that the resistance rate of the infectious agents had a significant increase. As the resistance category increases, a significant decrease was seen in the survival time. We observed that if the treatment combination included trimethoprim-sulfamethoxazole, the survival time became significantly longer, and tigecycline-carbapenem-colistin and tigecycline-carbapenem combination patients showed significantly shorter survival times. CONCLUSIONS When the resistance increases, delays will occur in starting suitable and effective antibiotic treatment, with increased sepsis frequency and higher mortality rates. Trimethoprim-sulfamethoxazole can be an efficient alternative to extend survival time in trimethoprim-sulfamethoxazole-susceptible KP infections that have extensive drug resistance.

Comparison of brucellar and tuberculous spondylodiscitis patients: results of the multicenter "Backbone-1 Study".

BACKGROUND CONTEXT: No direct comparison between brucellar spondylodiscitis (BSD) and tuberculous spondylodiscitis (TSD) exists in the literature. PURPOSE: This study aimed to compare directly the clinical features, laboratory and radiological aspects, treatment, and outcome data of patients diagnosed as BSD and TSD. STUDY DESIGN: A retrospective, multinational, and multicenter study was used. PATIENT SAMPLE: A total of 641 (TSD, 314 and BSD, 327) spondylodiscitis patients from 35 different centers in four countries (Turkey, Egypt, Albania, and Greece) were included. OUTCOME MEASURES: The pre- and peri- or post-treatment spinal deformity and neurologic deficit parameters, and mortality were carried out. METHODS: Brucellar spondylodiscitis and TSD groups were compared for demographics, clinical, laboratory, radiological, surgical interventions, treatment, and outcome data. The Student t test and Mann-Whitney U test were used for group comparisons. Significance was analyzed as two sided and inferred at 0.05 levels. RESULTS: The median baseline laboratory parameters including white blood cell count, C-reactive protein, and erythrocyte sedimentation rate were higher in TSD than BSD (p<.0001). Prevertebral, paravertebral, epidural, and psoas abscess formations along with loss of vertebral corpus height and calcification were significantly more frequent in TSD compared with BSD (p<.01). Surgical interventions and percutaneous sampling or abscess drainage were applied more frequently in TSD (p<.0001). Spinal complications including gibbus deformity, kyphosis, and scoliosis, and the number of spinal neurologic deficits, including loss of sensation, motor weakness, and paralysis were significantly higher in the TSD group (p<.05). Mortality rate was 2.22% (7 patients) in TSD, and it was 0.61% (2 patients) in the BSD group (p=.1). CONCLUSIONS: The results of this study show that TSD is a more suppurative disease with abscess formation requiring surgical intervention and characterized with spinal complications. We propose that using a constellation of constitutional symptoms (fever, back pain, and weight loss), pulmonary involvement, high inflammatory markers, and radiological findings will help to differentiate between TSD and BSD at an early stage before microbiological results are available.

[A case of Crimean-Congo hemorrhagic fever with long incubation period in Kocaeli, Turkey]. / Kocaeli'de Uzun Inkübasyon Süreli Sporadik Kirim-Kongo Kanamali Atesi Olgusu.

Crimean-Congo hemorrhagic fever (CCHF) is a viral hemorrhagic disease with high mortality rate. CCHF is endemic in Central Anatolia and East and Central Black Sea parts of Turkey, however sporadic cases have been detected in the other regions. The incubation period of the disease is between 1-3 days (maximum 12 days). In this report, a very rare CCHF case with a long incubation period of 30 days, was reported. A 40-year-old female patient living in a village of Kocaeli, Turkey was admitted to a health center in June 2010 with the complaints of headache, myalgia, nausea, vomiting, fatigue and fever. Since laboratory results revealed severe thrombocytopenia (18.300/mm3), the patient was referred to the university hospital in Kocaeli. It was learned from her history that she had been working in the garden and removed a tick from the skin of gluteal area a month ago without seeking any medical help. Physical examination of the patient revealed that her general condition was well, oriented and cooperative, body temperature was 36.6°C, pulse 82/minute, trombocyte count 69.400/mm3 and liver enzymes were elevated (ALT: 194 U/L, AST: 499 U/L, GGT: 384 U/L, LDH: 1290 U/L). Petecchial lesions were seen on hard palate and extremities and a hyperemic lesion was detected at the gluteal area where the tick had attached. In-house real-time polymerase chain reaction test for CCHF, performed at Refik Saydam National Public Health Agency, Virology Reference and Research Laboratory, revealed positive result. This case was presented to withdraw attention to a long incubation period CCHF and also of its epidemiological importance since it was the first case in Kocaeli province, Turkey.