Fibrosis scores that can be used in follow-up of after direct-acting antiviral treatment: APRI, FIB-4, King score and GUCI.

INTRODUCTION: Sustained virologic response in the treatment of chronic hepatitis C can be achieved with direct-acting antivirals (DAA) in recent years. Monitoring virologic and histologic response to treatment is essential and noninvasive methods are preferred. In our study, we aimed to determine the regression of fibrosis following DAA treatment with serum fibrosis indices constituting a noninvasive method. METHOD: Patients with chronic hepatitis C to whom DAA treatment is started between January 2016 and January 2018 in our clinic are evaluated retrospectively. The fibrosis scores [fibrosis 4 index (FIB-4), aminotransferase platelet ratio (APRI), Fibro QKing score, age platelet index, Goteburg University Cirrhosis Index (GUCI), aspartate transaminase/alanine transaminase ratio (AAR)] are calculated with routine biochemical and hematologic tests of DAA-treated patients before treatment, at the end of treatment, and in the 12th and 24th weeks of treatment. In total, the course of seven scores calculated at four separate times including baseline was recorded and compared. RESULTS: In total 91 patients are included in the study. The average age was 51.16 ± 13.78 and 59.3% (n = 54) of patients were women. According to the baseline FIB-4 values, the patients were grouped as cirrhotic or noncirrhotic, and 11 of them were cirrhotic (12.1%). Statistically significant regression in APRI, FIB-4, GUCI and King scores is seen in all groups regardless of their cirrhotic status, treatment experience or genotype (P < 0.001). Specified scores had a positive, significant correlation with pretreatment biopsy results [area under curve (AUC): 0.800, 0.782, 0.749 and 0.746]. CONCLUSION: APRI, FIB-4, GUCI and King scores that have a positive correlation with biopsy can also be used for fibrosis recovery follow-up after treatment with DAAs.

Adherence to Treatment with Oral Nucleoside/Nucleotide Analogs in Patients with Chronic Hepatitis B.

Objectives: Adherence to antiviral treatment is important for treatment success and prevention of resistance. It was aimed to determine treatment adherence to nucleoside/nucleotide analogs and factors influencing on adherence. Methods: The study included 168 patients who received oral nucleoside/nucleotide analog with diagnosis of chronic hepatitis for at least 1 year. Data regarding demographic characteristics and missed drug were collected using a survey, while list of medication within prior year were extracted from pharmacy registry and Medication Possession Rate (MPR) was calculated. Results: There were 60 women (35.7%) and 108 men (64.3%) in the study. Mean age was calculated as 43.61±10.35 years. It was found that 29.2% of patients were non-adherent based on MPR (MPR<0.90). It was observed that adherence was improved on middle age. Treatment adherence was found to be higher in patients receiving medication due to disorders other than hepatitis B. It was found that there was no significant difference in adherence according to age, gender, occupation status, marital status, smoking or alcohol consumption habits, type of antiviral treatment, time and mode of drug intake, and biopsy finding at time of drug prescription. The most common cause was identified as forgetfulness for missed drug. Other common causes were inoccupation and alteration in daily routine. Conclusion: In our study, the treatment adherence determined by MPR was 70.8%. This rate was lower than those reported for chronic hepatitis B in the literature. It is important to monitor and encourage treatment adherence in patients with chronic hepatitis B by clinicians.

Cognitive Assessment of Young Adults Before and After Initiation of Combination Antiretroviral Therapy.

Objective: In the determination and monitoring of neurocognitive disorders in human immunodeficiency virus (HIV)-positive individuals, there is a need for significantly more practical methods which provide results in a shorter time than the tests that require challenging and specialized expertise. This study aimed to evaluate cognitive functions and the factors affecting them in naïve HIV-positive patients using by Montreal Cognitive Assessment (MoCA) test before and after the initiation of combination antiretroviral therapy. Materials and Methods: HIV-positive, treatment-naïve patients monitored between January-June 2017 were included in the study. The MoCA test was performed at the beginning and the sixth month of the treatment. Results: Forty male patients were included in the study. The mean age was calculated as 29.1±4.0. When the factors affecting the MoCA score were examined, there was a significant relationship between the education level and the MoCA score. Smoking, using alcohol, and substance did not have a significant impact on baseline MoCA values. A significant correlation was found between cluster differentiation 4 (CD4) count and HIV RNA level and attention function. There was a significant increase in the total MoCA score and the MoCA subgroup scores at the end of the sixth month of the treatment. Conclusion: MoCA test is one of the most practical tests that can be applied in a short time period, and it was found useful in evaluating the changes in the cognitive functions of HIV-positive patients during antiretroviral treatment.

Evaluation of Relationship between fQRS and CD4/CD8 Ratio in Patients with HIV.

OBJECTIVES: Myocardial dysfunction is an important cause of morbidity in human immunodeficiency virus (HIV)-infected patients. Decline in CD4 T-cell level and reversal of CD4/CD8 ratio was associated with cardiovascular events. Fragmented QRS (fQRS) can show myocardial dysfunction and cardiovascular events. The aim of this study is to investigate the presence of fQRS in HIV-infected patients and the factors affecting it. METHODS: This case-control study included 153 outpatient HIV patients (97% male) and 141 healthy subjects (96% male). Patients with cardiac disease history, arrhythmia, diabetes, cancer disease, and thyroid dysfunction were excluded from the study. Electrocardiogram, echocardiography, and biochemistry tests were performed to all participants. CD4 and CD8 T cell count, and HIV RNA level were measured in HIV-infected patients. RESULTS: Both groups had similar basal characteristics. Mean CD4 T-cell level was 356 cell/cm3, HIV was under control in 48%, and the rate of antiretroviral treatment use was 64%. HIV-infected patients had lower left ventricular ejection fraction (LVEF), higher Tei index, and more fQRS. HIV-infected patients with fQRS had lower nadir CD4 T-cell levels, lower CD4/CD8 ratio, and higher Tie index. In multivariate analysis, CD4/CD8 ratio and LVEF were found to be independent predictors of fQRS in HIV-infected patients. CONCLUSION: Myocardial dysfunction can be seen in HIV-infected patients. Caution should be exercised in terms of myocardial dysfunction in HIV-infected patients with low CD4/CD8 ratio.

Demographic, clinical and laboratory characteristics for differential diagnosis of peripheral lymphadenopathy (LAP) and the etiologic distribution of LAP in adults; a multicenter, nested case-control study including 1401 patients from Turkey.

Peripheral lymphadenopathy (LAP) is an important and common abnormal finding of the physical exam in general medical practice. We aimed to reveal the LAP etiology and demographic, clinical and laboratory variables that may be useful in the differential evaluation of LAP. This multicenter, nested case-control study including 1401 patients between 2014 and 2019 was conducted in 19 tertiary teaching and research hospitals from different regions in Turkey. The ratio of infectious, malign and autoimmune/inflammatory diseases was 31.3%, 5% and 0.3%, respectively. In 870 (62%) of patients had nonspecific etiology. Extrapulmonary tuberculosis (n: 235, 16.8%) was the most frequent cause of LAP. The ratio of infective etiology of LAP was significantly lower in patients older than 65 years-old compared to younger patients with the rate of 66.67% and 83.84%, respectively (p 0.016, OR 0.386, 95% Cl 0.186-0.803). The probability of malign etiology was higher both in patients who are older than 45 years-old (p < 0.001, OR 3.23, 95% Cl 1.99-5.26) and older than 65 years-old (p 0.002, OR 3.36, 95% Cl 1.69-6.68). Age, localization and duration of LAP, leukocytosis, anemia, thrombocytopenia, CRP and sedimentation rate were important parameters to differentiate infections. Size of lymph node and splenomegaly in addition to the parameters above were useful parameters for differentiating malign from benign etiology. Despite the improvements in diagnostic tools, reaching a definite differential diagnosis of lymphadenopathy is still challenging. Our results may help clinicians to decide in which cases they need an aggressive workup and set strategies on optimizing the diagnostic approach of adulthood lymphadenopathy.

Fever of unknown origin (FUO) on a land on cross-roads between Asia and Europa; a multicentre study from Turkey.

AIMS: The differential diagnosis of Fever of Unknown Origin (FUO) is still a major clinical challenge despite the advances in diagnostic procedures. In this multicentre study, we aimed to reveal FUO aetiology and factors influencing the final diagnosis of FUO in Turkey. METHODS: A total of 214 patients with FUO between the years 2015 and 2019 from 13 tertiary training and research hospitals were retrospectively evaluated. RESULTS: The etiologic distribution of FUO was infections (44.9%), malignancies (15.42%), autoimmune/inflammatory (11.68%) diseases, miscellaneous diseases (8.41%) and undiagnosed cases (19.62%). Brucellosis (10.25%), extrapulmonary tuberculosis (6.54%) and infective endocarditis (6.54%) were the most frequent three infective causes. Solid malignancies (7.1%) and lymphoma (5.6%), adult-onset still's disease (6.07%) and thyroiditis (5.14%) were other frequent diseases. The aetiological spectrum did not differ in elderly people (P < .05). Infections were less frequent in Western (34.62%) compared with Eastern regions of Turkey (60.71%) (P < .001, OR: 0.31, 95% Cl: 0.19 to 0.60). The ratio of undiagnosed aetiology was significantly higher in elderly people (p: 0.046, OR: 2.34, 95% Cl: 1.00 to 5.48) and significantly lower in Western Turkey (P: .004, OR: 3.07, 95% Cl: 1.39 to 6.71). CONCLUSIONS: Brucellosis, extrapulmonary tuberculosis and infective endocarditis remain to be the most frequent infective causes of FUO in Turkey. Solid tumours and lymphomas, AOSD and thyroiditis are the other common diseases. The aetiological spectrum did not differ in elderly people, on the other hand, infections were more common in Eastern Turkey. A considerable amount of aetiology remained undiagnosed despite the state-of-the-art technology in healthcare services.

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.

Symptomatology of COVID-19 from the otorhinolaryngology perspective: a survey of 223 SARS-CoV-2 RNA-positive patients.

PURPOSE: To determine prevalence, severity, duration, and time from onset to diagnosis of general and Otorhinolaryngologic symptoms related to COVID-19 in whole disease spectrum: from mild to critical patients. METHODS: All adult patients with positive SARS-CoV-2 RNA found in nasopharyngeal and oropharyngeal swabs between March 10 and April 21, 2020 were surveyed by the authors for new onset symptoms during disease course. Demographic features, general symptoms, and Otorhinolaryngological symptoms were evaluated and compared by disease severity. RESULTS: Of 223 included patients, 18.4% had mild, 61.4%; moderate, 14.3%; severe, and 5.8%; critical disease. Median age was 51 (range 20-93), 113 (50.7%) were male and 110 (49.3%) were female. The most common general symptoms were fatigue, cough, and fever with respective frequencies of 71.3%, 54.3%, and 50.7%. The most common Otorhinolaryngologic symptoms were taste loss, smell loss, and sore throat with respective frequencies of 34.5%, 31.8%, and 26%. Fatigue, fever, and dyspnea were more common in severe-critical patients compared to mild-moderate patients (p = 0.029, p = 0.016, and p < 0.001, respectively). Only smell loss was more common in mild-moderate group (p = 0.003). Prevalence of other symptoms did not differ between groups. Symptom durations and onset time to diagnosis varied. CONCLUSION: When compared to the previous studies, while general symptoms were less common, Otorhinolaryngologic symptoms were more common in our study population. Considering high infection risks, Otorhinolaryngologists should be aware of COVID-19 patients presenting with Otorhinolaryngologic complaints.

Prevalence and mortality of cancer among people living with HIV and AIDS patients: a large cohort study in Turkey.

BACKGROUND: Cancer is responsible for elevated human immunodeficiency virus (HIV)-related mortality but there are insufficient data about cancer in HIV-positive patients in Turkey. AIMS: We aimed to investigate the prevalence and mortality of cancer among people living with HIVand AIDS patients in Istanbul, Turkey. METHODS: Between January 1998 and December 2016, people living with HIVand AIDS patients were enrolled in this study by the ACTHIV-IST Study Group, which consists of 5 centres to follow-up HIV-positive patients in Istanbul. The cancer diagnoses included AIDS-defining cancers (ADCs) and non AIDS-defining cancers (NADCs). RESULTS: Among 1872 patients, 37 (1.9%) were diagnosed with concurrent cancer. Eleven patients were diagnosed during follow-up; the prevalence of cancer among people living with HIVand AIDS patients was 2.6%. Among 48 cancer patients, 35 patients had ADCs, and 32 of them were diagnosed at their first hospital admission. There were 1007 late presenters and 39 of them had cancer (29 were ADCs). The most prevalent NADCs were gastrointestinal, genitourinary, and pulmonary cancers. NADCs were mostly diagnosed during follow-up of patients. The mortality of this group was significantly higher than that of patients with ADCs (53.9% vs 22.9%). CONCLUSIONS: These results indicate the importance of cancer screening at diagnosis and during follow-up of HIV infection. A detailed physical examination contributes to diagnosis of the most prevalent ADCs (Kaposi's sarcoma and non-Hodgkin's lymphoma), especially in late presenters. For NADCs, individual risk factors should be considered.

Diagnostic accuracy of different noninvasive scores for detecting advanced fibrosis in chronic hepatitis B.

OBJECTIVES: The liver biopsy is the gold standard for determining the level of fibrosis in chronic hepatitis B infection (CHBI). Nonetheless, it is possible to predict liver fibrosis through some noninvasive methods such as noninvasive scoring (NIS) of some serum biomarkers obtained from routine blood tests. We aimed to evaluate the diagnostic accuracy of nine NIS for detecting advanced fibrosis in CHBI. PATIENTS AND METHODS: We reviewed the hospital records of CHBI cases with liver biopsy between January 2011 and December 2016 retrospectively. Using Ishak scoring method, we classified fibrosis stage 1-2 as mild and 3-6 as advanced fibrosis. We calculated the NIS by considering the age, platelet count, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, platelet, and international normalized ratio values at the time of the biopsy. RESULTS: The mean age of 202 patients was 37.69± 11.33 years. In cases with advanced fibrosis, the age, gammaglutamyltransferase, and international normalized ratio values were higher and platelet count was lower (P < 0.05). Mean platelet volume was not different between the two groups (P = 0.499). The median values of γ-glutamyl peptidase-platelet ratio (GPR), FibroQ, Goteborg University Cirrhosis Index, fibrosis-4 (FIB-4), aspartate aminotransferase-platelet ratio index, age-platelet index, and King scoring were significantly higher in the advanced fibrosis group. The highest area under the curve value was in GPR [AUC = 0.731 (0.639-0.788); P = 0.000] in the receiver operating characteristic curve analysis. Cirrhosis Discriminant Score and Aspartate aminotransferase-to-alanine aminotransferase ratio tests were not valuable in detecting advanced fibrosis. FIB-4 had the highest (0.678) diagnostic accuracy rate. CONCLUSION: We found that the calculation of NIS before liver biopsy, especially GPR and FIB-4, may be useful for predicting advanced fibrosis in cases with CHBI.

Miliary tuberculosis: Epidemiologicaland clinical analysis of large-case series from moderate to low tuberculosis endemic Country.

The aim of this study was to determine the clinical features, and outcome of the patients with miliary tuberculosis (TB).We retrospectively evaluated 263 patients (142 male, 121 female, mean age: 44 years, range: 16-89 years) with miliary TB. Criteria for the diagnosis of miliary TB were at least one of the followings in the presence of clinical presentation suggestive of miliary TB such as prolonged fever, night sweats, anorexia, weight loss: radiologic criterion and pathological criterion and/or microbiological criterion; pathological criterion and/or microbiological criterion.The miliary pattern was seen in 88% of the patients. Predisposing factors were found in 41% of the patients. Most frequent clinical features and laboratory findings were fever (100%), fatigue (91%), anorexia (85%), weight loss (66%), hepatomegaly (20%), splenomegaly (19%), choroid tubercules (8%), anemia (86%), pancytopenia (12%), and accelerated erythrocyte sedimentation rate (89%). Tuberculin skin test was positive in 29% of cases. Fifty percent of the patients met the criteria for fever of unknown origin. Acid-fast bacilli were demonstrated in 41% of patients (81/195), and cultures for Mycobacterium tuberculosis were positive in 51% (148/292) of tested specimens (predominantly sputum, CSF, and bronchial lavage). Blood cultures were positive in 20% (19/97). Granulomas in tissue samples of liver, lung, and bone marrow were present in 100% (21/21), 95% (18/19), and 82% (23/28), respectively. A total of 223 patients (85%) were given a quadruple anti-TB treatment. Forty-four (17%) patients died within 1 year after diagnosis established. Age, serum albumin, presence of military pattern, presence of mental changes, and hemoglobin concentration were found as independent predictors of mortality. Fever resolved within first 21 days in the majority (90%) of the cases.Miliary infiltrates on chest X-ray should raise the possibility of miliary TB especially in countries where TB is endemic. Although biopsy of the lungs and liver may have higher yield rate of organ involvement histopathologicaly, less invasive procedures including a bone marrow biopsy and blood cultures should be preferred owing to low complication rates.

Serum soluble urokinase-type plasminogen activator receptor and interferon-γ-induced protein 10 levels correlate with significant fibrosis in chronic hepatitis B.

BACKGROUND: Hepatitis B virus (HBV) presents an important public health problem. Liver biopsy is currently the gold standard for assessing the degree of intrahepatic inflammation and for staging liver fibrosis. However, the value of liver biopsies is limited by sampling errors, understaging and interobserver variability in interpretation. There is, therefore, a need to identify novel, non-invasive serologic biomarkers for the development of new predictive models of fibrosis. METHODS: We enrolled patients with chronic hepatitis B infection (CHB) and examined the relationships between serum soluble urokinase plasminogen activator receptor (suPAR) and interferon-induced protein-10 (IP-10), and the results of liver biopsies. Healthy volunteers with normal aminotransferase levels and negative serological results for HBV, hepatitis C virus and human immunodeficiency virus were recruited as controls. RESULTS: Mean platelet volume, serum suPAR and IP-10 were significantly elevated in patients with CHB compared with controls. Median serum suPAR and IP-10 levels were significantly higher in patients with liver fibrosis compared with patients with mild fibrosis. There was no significant difference in mean platelet volume or aspartate aminotransferase-to-platelet ratio index scores between patients with mild and significant fibrosis. CONCLUSION: suPAR and IP-10 were able to distinguish between significant and mild fibrosis with good sensitivity and specificity, and may thus represent useful biomarkers for identifying patients with significant fibrosis.

Sequential determination of serum viral titers, virus-specific IgG antibodies, and TNF-α, IL-6, IL-10, and IFN-γ levels in patients with Crimean-Congo hemorrhagic fever.

BACKGROUND: Although there have been a number of studies on the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF) recently, knowledge on this topic is still insufficient. This study aims to reveal the kinetics of serum CCHF virus (CCHFV) titers, serum levels of anti-CCHFV immunoglobulin (Ig)G, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and interferon (IFN)-γ in CCHF patients. METHODS: In total, 31 CCHF cases (11 fatal) were studied. Serum samples were obtained daily from all patients from the time of admission and continued for a 7-day hospitalization period for serologic (ELISA), virologic (real-time PCR), and cytokine (ELISA) analysis. RESULTS: The mean serum CCHFV titer at admission was 5.5E + 09 copies/mL in fatal cases and 5.7E + 08 copies/mL in survivors (p < 0.001). Compared to survivors, both the mean serum levels of IL-6 and TNF-α at admission were found to be significantly increased in fatal cases. The serum levels of IL-6, TNF-α and serum CCHFV titer at admission were significantly and positively correlated with disseminated intravascular coagulation (DIC) scores (r = 0.626, p = 0.0002; r = 0.461, p = 0.009; and r = 0.625, p = 0.003, respectively). When the data obtained from the sequential determination of CCHFV titer and levels of anti-CCHFV IgG, IL-6, TNF-α, IL-10 and IFN-γ were grouped according to the days of illness, the initial serum CCHFV titer of a fatal patient was 5.5E + 09 (copies/mL) and it was 6.1E + 09 (copies/mL) in a survivor on the 2 day of illness. While significant alterations were observed in all cytokines during the monitoring period, IL-6 levels remained consistently higher in fatal cases and TNF-α levels increased in both in fatal and non-fatal CCHF cases. CONCLUSIONS: The increased CCHFV load and higher concentrations of IL-6 and TNF-α, the presence of DIC, and the absence of CCHFV specific immunity are strongly associated with death in CCHF.

Evaluation of respiratory findings in Crimean-Congo hemorrhagic fever.

Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease with a high mortality rate causing viral hemorrhagic fever. We studies the respiratory system findings, demographics, clinical and laboratory findings of patients with CCHF admitted to our hospital. In this retrospective study we evaluated 108 patients with CCHF confirmed by laboratory findings. The charts of all hospitalized patients were reviewed, and the age, sex, occupation, city of residence, history of tick bite or of removing a tick, smoking history, chest X-ray results, outcome and clinical and laboratory findings were recorded for each patient. Sixty of the chest radiographs were read as normal, 33 were read as showing unilateral pathology and 15 showed bilateral pathology. Seven of the 108 patients died due to severe pulmonary infection and hemorrhage. The frequency of pathological chest radiographs was higher among the CCHF patients who died than among the survivors, but the difference was not significant. Pulmonary parenchyma hemorrhage can occur in CCHF patients with hemoptysis, dyspnea, chest pain and infiltration on chest radiographs and may lead to morality.