Tigecycline-associated hypofibrinogenemia: A single center, retrospective, controlled study.

BACKGROUND: Tigecycline-associated hypofibrinogenemia has been reported as an important adverse effect in recent years, but controlled studies minimizing confounding factors are needed. The objective of our study was to assess changes in fibrinogen levels in patients for hospitalization, comparing two antibiotic episodes (tigecycline and other) within the same patients. METHODS: The retrospective, self-controlled case series study was conducted at our University Hospitals. The study compared the change in fibrinogen levels during the patient's hospitalization for tigecycline (TigePer) and another antibiotic period (OtherPer). In addition, bleeding events, bleeding risk (determined by the IMPROVE bleeding risk score), as well as 15- and 30-day mortality rates between TigePer and OtherPer were compared. RESULTS: The study enrolled 50 patients with 100 episodes of antibiotic treatment. The median age (interquartile range) of the patients was 68.5 (21.5) years, and 38 % were female. As compared to OtherPer, TigePer had a statistically significant reduction in fibrinogen levels (p < 0.001), with a hypofibrinogenemia rate of 40 % in TigePer as compared to 2 % in OtherPer (p < 0.001). TigePer demonstrated a significantly higher 15-day mortality rate (p = 0.006). No significant differences were observed between the two periods in terms of bleeding risk, rate of bleeding events, and 30-day mortality rate (p > 0.05). CONCLUSION: Hypofibrinogenemia and other coagulopathies, without associated bleeding events, are more frequently observed in patients receiving tigecycline. Therefore, it is crucial for clinicians to monitor fibrinogen levels during tigecycline use.

Compliance with guideline recommendations in the management of patients with hospitalized community-acquired pneumonia.

Compliance with guidelines in the empirical treatment for community-acquired pneumonia (CAP) is very important to increase treatment success and reduce mortality. This study aimed to determine compliance with guideline recommendations for CAP and define the role of the clinical pharmacist (CP). Patients diagnosed with CAP were evaluated retrospectively between January 2018 and January 2020 and prospectively between February 2020 and February 2021. Compliance with guidelines was evaluated according to the local, national (Turkish Thoracic Society), and international (American Thoracic Society and Infectious Disease Society of America, European Society of Clinical Microbiology and Infectious Diseases) guidelines. A total of 751 patients (423 in the retrospective and 328 in the prospective period) were included. It was determined that the 30-day mortality and length of stay were higher in patients who were not treated according to the guidelines. The compliance for empirical treatments was 16.3%-59.1% and 7.8%-30.1% in retrospective and prospective periods, respectively. During the prospective period, a total of 603 recommendations were made by CP, and 578 (95.9%) were accepted and implemented. In the prospective period, treatment duration was shortened, inappropriate fluoroquinolone use was decreased, the switch to oral treatment was increased, and the number of potential drug-drug interactions was decreased (p < 0.001). Compliance with guidelines is essential to be improved to reduce mortality, shorten the length of stay, determine the appropriate antimicrobial duration, and reduce the use of fluoroquinolones and broad-spectrum antibiotics unless necessary. CP intervention contributes to the rational selection of antimicrobials, limiting drug-drug interactions, avoiding toxicities, and compliance with guidelines.

Comparison of clinician preference and HIV-ASSIST recommendations in antiretroviral therapy decision-making: A single center experience from Turkiye.

Background: HIV-ASSIST is a free, continuously updated, clinically validated online algorithm tool that synthesizes participant- and virus-specific characteristics and provides ART decision support based on the goals of maximizing viral suppression and tolerability. The aim of this study was to analyze the concordance of clinicians' ART preferences with HIV-ASSIST recommendations and the influencing factors. Methods: We conducted a cross-sectional retrospective cohort study using electronic medical records of people with HIV (PWH) followed in the Infectious Diseases and Clinical Microbiology Department of Health Sciences University Izmir Tepecik Training and Research Hospital. The concordance between prescribed ART and HIV-ASSIST recommendations was evaluated. Results: The study included 101 participants (92 male, 91.1%), median age was 35 (20-67), and 24.8% of participants were treatment-experienced. The concordance between prescribed ART and HIV-ASSIST recommendations was 90.1% (absolute concordance 60.4%). The concordance rate was 89.5% (absolute concordance rate was 64.5%) in treatment-naive participants; 92% (absolute concordance rate was 48%) in treatment-experienced participants. Factors that were associated with discordance in the multivariate analysis were co-trimoxazole prophylaxis and hyperlipidemia. Conclusion: The recommendations of the HIV-ASSIST algorithm were found to be highly concordant with the ART prescriptions of our clinicians.

Prevention strategies for sexually transmitted infections, HIV, and viral hepatitis in Europe.

The current prevention efforts for STIs, HIV and viral hepatitis in the WHO European Region, especially in the Central and Eastern subregions, are hindered by healthcare disparities, data gaps, and limited resources. In this comprehensive narrative review, we aim to highlight both achievements and persisting challenges while also exploring new developments that could significantly impact the prevention of these infections in the near future. While pre-exposure prophylaxis (PrEP) for HIV has been broadly approved and implemented in 38 out of 53 countries in the region, challenges remain, including cost, limited licensing, and incomplete adherence. We explore innovative approaches like on-demand PrEP, long-acting injectable cabotegravir, and intravaginal rings that have shown promising results, alongside the use of six-monthly lenacapavir, the outcomes of which are pending. Additionally, the potential of doxycycline post-exposure prophylaxis has been discussed, revealing efficacy in reducing chlamydia and syphilis risk, but effectiveness against gonorrhoea being contingent on tetracycline resistance rates, and the need of further data to determine potential resistance development in other bacteria and its impact on the gut microbiome. We examine successful vaccination campaigns against HBV and HPV, the ongoing development of vaccines for chlamydia, syphilis, herpesvirus, and gonorrhoea, and challenges in HIV vaccine research, including lines of research with significant potential like sequential immunization, T-cell responses, and mRNA technology. This review underscores the research endeavors that pave the way for a more resilient and robust approach to combating STIs, HIV, and viral hepatitis in the region.

[Investigation of the Frequency of Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis and Mycoplasma genitalium in Men Living with HIV in Terms of Sociodemographic Characteristics and Behavioral Risk Factors]. / HIV ile Yasayan Erkeklerde Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis ve Mycoplasma genitalium Sikliginin Sosyodemografik Özellikler ve Davranissal Risk Faktörleri ile Birlikte Arastirilmasi.

The aim of this study was to investigate the frequency of Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis and Mycoplasma genitalium in men living with HIV in terms of sociodemographic characteristics and behavioral risk factors. In this cross-sectional, single center study, all HIV-infected male patients, aged ≥ 18 years, including those being followed-up (n= 142) and the new admissions (n= 16) at Hacettepe University, Department of Infectious Diseases between March 1st, 2017 and May 1st, 2018 were included. After obtaining the informed consent form; age, follow-up days in STI-clinic, marital status, education, employment status; STI-related sign and symptoms, prior STI diagnosis, multiple sexual partners during the last year, exchanging sex for money, sexual orientation, drug use, condom use with regular and casual partner and also risk factors regarding partners were inquired as behavioural risk factors. A sample of first-voided urine of each participant was tested for the presence of Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis and Mycoplasma genitalium by using nucleic acid amplification test (NAAT) (BD-MAX system, BD Diagnostics, USA) and BD MAX Mycoplasma-Ureaplasma-OSR for BioGX, (BD Diagnostics, The Netherlands). All participants living with HIV, men who have sex with men (MSM) and heterosexual men were grouped as STI-positive and STI-negative and compared. For all statistical analysis, SPSS 24 software was used. During the period of 14 months; the data was determined as follows: median follow-up time was 1138 (IQR= 159.5- 1494.5) days, median age was 35 (IQR= 28-42) years, 73.3% were single, 68.3% were at least college graduates or had higher educational attainment, 78.1% were currently employed. Of the participants, 26.9% reported STI-related sign and symptoms, 50.0% at least one STI episode in the past. Nine (5.6%) M.genitalium, five (3.1%) N.gonorrhoeae, and four (2.5%) C.trachomatis were detected in the urine samples of 17 (10.7%) individuals. N.gonorrhoeae and C.trachomatis were detected simultaneously in only one patient's urine sample. STI-positive patients (n= 17) were determined to be younger compared to STI-negative group [(p= 0.02; 27 years (IQR= 24-37) vs 35 years (IQR= 28-42)], had prominent STI-related signs and symptoms (p< 0.001) and had more multiple sexual partners (p= 0.03). The median CD4+ T lymphocyte count were relatively lower (p= 0.03) in STI-positive patients and plasma HIV RNA level was higher compared to the STI-negative participants (p= 0.05). STI-positive MSM group were younger [p= 0.01; 26 years (IQR= 23.5-29) vs 33 years, (IQR= 28-40)], STI-related signs and symptoms were more prominent (p= 0.02), the frequency of exchanging sex for money/drugs among their partners (p= 0.03) was higher compared to their STI-negative counterparts. Among STI-positive heterosexual patients, the presence of STI-related signs and symptoms (p= 0.04), drug use among their partners (p= 0.04) and plasma HIV RNA level (p<0.01) were significantly higher. STI was identified as an important health problem in this series of men living with HIV, 63.0% of whom had MSM and had a relatively high education level and socioeconomic status. Young age, having multiple partners, drug use, exchanging sex for money/drugs were prominent among the participants and their partners. Public health studies should focus on preventing STIs in young people living with HIV who have behavioral risk factors.

Detection of Non-Alcoholic Fatty Liver Disease with Non-invasive Tools in Turkish People Living with HIV and with Apparently Normal Liver Function.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become a significant cause of mortality and morbidity in people living with HIV. OBJECTIVE: We aimed to investigate NAFLD presence by magnetic resonance imaging (MRI) methods, including MRI-derived proton density fat fraction (MRI-PDFF) and MRE, and ultrasound elastography among Turkish people living with HIV (PLWH), and identify factors correlated with fatty liver. METHODS: We included 57 PLWH attending outpatient clinics on antiretroviral therapy (ART) for more than six months, without HBV/HCV co-infection, significant alcohol consumption, active opportunistic infection, previously diagnosed hepatobiliary disease, T2DM, and hyperlipidemia. We performed MRI, MRE, and US elastography on all participants. RESULTS: The mean age of the participants (M/F, 47/10) was 41.7± 12 years. The median duration of HIV infection was 3 (0.5-19 years) years. The mean MRI-PDFF was 4.4 ± 3.8 %, and 11 had fatty liver. The mean MRE value was 2.27 ± 0.6 kPa, inflammation was present in 16, and 4 participants had values consistent with fibrosis. The mean US elastography of the study population was 4.1±2.4 kPa. The mean right and left CCA intima-media of the study population was 0.65± 0.23 mm and 0.66± 0.25 mm; 16 had increased intima-media thickness. In patients with fatty liver, a significant positive correlation was present between MRE and CCA intima-media thickness (rs=0.82, p:0.006 for MRE-left CCA; r=0.68, p=0.042 for MRE-right CCA). CONCLUSION: We demonstrated that even a significant proportion of PLWH individuals with normal transaminase levels have fatty liver. Future prospective trials are warranted to understand and mitigate the risk factors, course of NAFLD, and accurate non-invasive tests, predicting fibrosis in people living with HIV.

Human memory T cell dynamics after aluminum-adjuvanted inactivated whole-virion SARS-CoV-2 vaccination.

This study evaluates the functional capacity of CD4+ and CD8+ terminally-differentiated effector (TEMRA), central memory (TCM), and effector memory (TEM) cells obtained from the volunteers vaccinated with an aluminum-adjuvanted inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac). The volunteers were followed for T cell immune responses following the termination of a randomized phase III clinical trial. Seven days and four months after the second dose of the vaccine, the memory T cell subsets were collected and stimulated by autologous monocyte-derived dendritic cells (mDCs) loaded with SARS-CoV-2 spike glycoprotein S1. Compared to the placebo group, memory T cells from the vaccinated individuals significantly proliferated in response to S1-loaded mDCs. CD4+ and CD8+ memory T cell proliferation was detected in 86% and 78% of the vaccinated individuals, respectively. More than 73% (after a short-term) and 62% (after an intermediate-term) of the vaccinated individuals harbored TCM and/or TEM cells that responded to S1-loaded mDCs by secreting IFN-γ. The expression of CD25, CD38, 4-1BB, PD-1, and CD107a indicated a modulation in the memory T cell subsets. Especially on day 120, PD-1 was upregulated on CD4+ TEMRA and TCM, and on CD8+ TEM and TCM cells; accordingly, proliferation and IFN-γ secretion capacities tended to decline after 4 months. In conclusion, the combination of inactivated whole-virion particles with aluminum adjuvants possesses capacities to induce functional T cell responses.

Prevalence of Common Human Coronaviruses (NL63, 229E, and OC43) in Adults before the COVID-19 Pandemic: a Single-Center Study from Turkey, 2015-2020.

Common Human Coronaviruses (HCoVs), such as NL63, HKU1, 229E, and OC43, induce respiratory tract infections worldwide. Epidemiological studies of HCoVs are of paramount importance because the disease burden and trajectory (in years) have not been well addressed in adults. Here, we aimed to describe the burden of HCoVs in a hospital setting over five years before the coronavirus disease 2019 pandemic. This was a retrospective study of patients (>18 years) between January 1, 2015, and January 1, 2020, whose respiratory specimens were tested by multiplex real-time polymerase chain reaction. In total, 7,861 respiratory samples (4,540 patients) were included, 38% of which tested positive for any respiratory virus. Of these, 212 (12.2%) samples were positive for HCoVs, and their co-infection with other respiratory viruses was 30.6%. Rhinovirus (27.6%) was the most common co-infection among all three HCoVs. The overall prevalence of HCoVs tended to be the highest in the winter (40.9%). Patients aged ≥60 years had the highest prevalence of overall HCoVs (39.7%). Given the duration and large sample size, this study from Turkey is one of the largest to date among adults in the literature. These epidemiological data and molecular surveillance of HCoVs have important implications for the control and prevention of respiratory infections.

Effectiveness of Mesenchymal Stem Cell Therapy for COVID-19 Patients in the Intensive Care Unit: A Case-Control Study

Objective: Many methods are used in the treatment of coronavirus disease 2019 (COVID-19), which causes acute respiratory distress syndrome (ARDS), and there are conflicting reports in the literature regarding the results of mesenchymal stem cell (MSC) therapy, which is one of those methods. The aim of our study is to evaluate the effect of MSC treatment applied together with standard treatments on survival. Materials and Methods: This retrospective case-control study evaluates the survival effect of MSC treatment administered to patients treated in intensive care after the development of ARDS due to COVID-19 between March 2020 and March 2021. The age, gender, comorbid disease status, APACHE II score, and overall and comorbidity-based survival rates were compared between patients who received standard medical treatment (SMT) and patients who received MSC treatment together with SMT. Results: There were 62 patients in the group receiving only SMT and 81 patients in the group receiving SMT and MSC. No difference was observed between the groups in terms of age, gender, presence of comorbid diseases, or APACHE II scores. There were also no differences according to Kaplan-Maier analysis for the survival statuses of the groups. There was no serious adverse effect due to MSC treatment among these patients. Conclusion: Our study presents the largest case series in the literature, and it was observed that MSC treatment may not significantly affect overall survival or comorbid disease-based survival, in contrast to many other studies in the literature.

Behçet's Disease-related Budd-Chiari Syndrome Successfully Managed with anti-TNF Antibody: A Case Report and Review of the Literature.

Behçet's disease (BD) is multisystemic vasculitis with heterogeneous clinical manifestations. We describe the case of a 26-year-old man who presented with Budd-Chiari syndrome (BCS) related to BD. The patient received infliximab (IFX) due to the severity of vascular involvement. Subsequently, after IFX therapy, hospital-acquired pneumonia, trapped lung, and fungal infection of the lung and central nervous system developed as complications. The patient benefited from a second course of IFX and clinical remission was achieved following early identification and treatment of complications. Data on the presentation and prognosis of BCS related to BD are extremely limited. Our case report supports the growing evidence that anti-TNF antibody is a promising treatment for BD-related BCS. LEARNING POINTS: Behçet's disease-related Budd-Chiari syndrome is a rare form of vascular involvement that severely affects mortality.Behçet's disease-related Budd-Chiari syndrome is frequently confused with idiopathic thrombosis and may be underdiagnosed.Infliximab could be a therapeutic option for refractory Behçet's disease with major vascular involvement, but the increased risk of opportunistic infections should be kept in mind.

Integrase inhibitor-based regimens are related to favorable systemic inflammatory index and platecrit scores in people living with HIV (PLWH) up to 2 years.

OBJECTIVES: Despite the advances in antiretroviral treatment (ART), persistent inflammation remained a challenge. We analyzed the inflammatory-score changes through 2-years in people living with HIV (PLWH) treated with different antiretroviral regimes. METHODS: This study was conducted in Hacettepe University HIV/AIDS Treatment and Research Center. PLWH diagnosed between 2014 and 2020 were included. Inflammatory and metabolic markers (CD4/CD8 ratio, C-reactive protein (CRP), Systemic Inflammatory Index (SII), Neutrophil-Lymphocyte Ratio (NLR), Mean Platelet Volume (MPV), Platecrite (PCT), and Low-Density Lipoprotein/High-Density Lipoprotein (LDL/HDL), Platelet-to-Lymphocyte Ratio (PLR) and ARTs were captured from database through 2-years from the diagnosis. The 2-year change (Δ) in markers was calculated and compared by ART type (backbone and 3rd agent). Mann-Whitney-U test and T-test were used for statistical analysis. RESULTS: This study included 205 PLWH; 175 (85.4%) were male, and the mean age was 38.98 (±10.88) years. The number of PLWH with suppressed viremia (<40 HIV-RNA copies/ml) was 164 (80%) at the end of the second year. MPV increased significantly higher among PLWH receiving ABC/3TC compared to PLWH receiving TDF/FTC (p < 0.05). The CD4:CD8 ratio increased, and SII, NLR, LDL/HDL ratios decreased significantly among PLWH treated with integrase strand transfer inhibitors (INSTI) compared with protease inhibitors (PI) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) (p < 0.05). CONCLUSIONS: Integrase inhibitor treatment is related to favorable inflammatory marker profile among PLWH in the 2-year follow-up. A favorable inflammatory profile may, in turn, contribute to the prevention of non-communicable diseases (NCD) among PLWH. This study showed that simple, easy-to-calculate markers could be implemented to define ongoing inflammation among PLWH under suppressive ART.

Frailty and sarcopenia among Turkish people aged 40 and above living with HIV.

BACKGROUND: People living with HIV face a variety of challenges, including accelerated ageing and geriatric syndromes. In this study, we aimed to examine the prevalence of frailty and sarcopenia among Turkish people living with HIV. METHODS: In total, 100 people living with HIV were recruited in this study. Frailty was determined using Fried's frailty phenotype, and we calculated the Charlson Comorbidity Index, Veterans Aging Cohort Study (VACS) index, fracture risk assessment tool scores, and Mini-Mental State Exam scores. We determined muscle mass using bioelectric impedance analysis, gastrocnemius muscle thickness using ultrasonography, and muscle strength using handgrip strength. RESULTS: The mean ± standard deviation age was 50.0 ± 8.3 years. In total, 11% of the patients were frail. The risk of comorbidity and mortality, VACS index, and 5-year mortality risk was significantly higher in the frail group, as was sarcopenia. Fat-free muscle mass and handgrip strength were correlated with gastrocnemius muscle thickness. Gastrocnemius muscle thickness suggestive of sarcopenia was defined as 13.05 mm. The cognitive impairment rate was 5% and was associated with physical frailty. CONCLUSION: Frailty is common and associated with higher morbidity and mortality rates among Turkish people living with HIV.

Evaluation of the peripheral blood T and B cell subsets and IRF-7 variants in adult patients with severe influenza virus infection.

BACKGROUND AND AIMS: Influenza virus is one of the leading infections causing death among human being. Despite known risks, primary immune deficiency due to Interferon Regulatory Factor-7 (IRF7) gene defect was reported as a possible cause of the risk factors for complicated influenza. We aimed to investigate the changes in peripheral T and B cell subsets in adult patients with severe seasonal influenza virus infection and the investigation of variants of IRF7 gene. METHODS: In this study, 32 patients, hospitalized due to influenza infection-related acute respiratory failure were included. RESULTS: The median age of the patients was 76 years (26-96), and 13/32 (40.6%) were in the intensive care unit. Central memory Th, effector memory Th, TEMRA Th, cytotoxic T lymphocytes (CTL), central memory CTL of the patients were found to be increased, naive CTL were decreased. There was a significant increase in the percentage of effector memory Th, and a decrease in the percentage of naive CTL in patients ≥65 years-old compared to patients <65 years old (P = .039, and P = .017, respectively). IRF7 gene analysis revealed two different nucleotide changes in three patients; c.535 A > G; p.Lys179Glu (K179E) and c584A > T; p.His195Leu (H195L), located in the fourth exon of the IRF7 gene. DISCUSSION: The increases in central and effector memory Th, central memory CTL and decrease of naive CTLs may be secondary to the virus infection. K179E (rs1061502) and H195L (rs139709725) variants were not reported to be related with susceptibility to an infection yet. It is conceivable to investigate for novel variants in other genes related to antiviral immunity.

Seroprevalence of SARS-CoV-2 Antibodies and Associated Factors in Healthcare Workers before the Era of Vaccination at a Tertiary Care Hospital in Turkey.

Healthcare workers (HCWs), as frontliners, are assumed to be among the highest risk groups for COVID-19 infection, especially HCWs directly involved in patient care. However, the data on the COVID-19 infection and seroprevalence rates are limited in HCWs. Therefore, we aimed to evaluate the seroprevalence rates in HCWs according to risk groups for COVID-19 contraction in a large cross-sectional study from a tertiary care hospital in Turkey. We enrolled 1974 HCWs before the vaccination programs. In two separate semi-quantitative ELISAs, either IgA or IgG antibodies against SARS-CoV-2 spike protein subunit 1 (S1) were measured. The proportion of positive test results for IgG, IgA, or both against SARS-CoV-2 of study subjects was 19% (375/1974). Frontline HCWs who had contact with patients (21.7%, RR 2.1 [1.51-2.92]) and HCWs in working in the COVID-19 units, intensive care units, or emergency department (19.7%, RR 1.61 [1.12-2.32]) had a notably higher Anti-SARS-CoV-2 IgG compared to the rest of HCWs who has no daily patient contacts ([11.1%]; p < 0.0001). HCWs who care for regular patients in the medium-risk group have also experienced a sustained higher risk of exposure to SARS-CoV-2. We should enhance the precaution against COVID-19 to protect HCW's safety through challenging times.

An Unusual Case of Early Dental Implant Failure in an Otherwise-Healthy Patient due to Actinomycosis.

Actinomyces species are members of normal oral flora that may give rise to a rare disease-oral actinomycosis. Presented herein is a case of early implant failure associated with actinomycosis in an otherwise healthy 43-year-old female and the treatment adopted after explantation. Clinically, 1 month after the implant placement, the peri-implant soft tissues were hyperplastic and associated with an excessive tissue reaction, bleeding, suppuration, deep probing depth, and implant mobility of #19 and #20 implants. Both implants were removed and all granulomatous tissues were thoroughly debrided. Histopathological examination revealed signs of acute ulcerative inflammatory reaction and Actinomyces colonies. The patient was prescribed short-term oral penicillins. Six months after explantation, the deficient bone was augmented using a combination of absorbable collagen membrane, autogenous block bone, and xenograft. The patient was followed for 1 year; and subsequently, 2 implants were re-inserted at the same positions. The patient was followed and no recurrences were observed. Implant failure due to actinomycosis is an extremely rare condition, and a definitive diagnosis is therefore essential for successful treatment.