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.

The diagnostic utility of the "Thwaites' system" and "lancet consensus scoring system" in tuberculous vs. non-tuberculous subacute and chronic meningitis: multicenter analysis of 395 adult patients.

BACKGROUND: Tuberculous meningitis (TBM) represents a diagnostic and management challenge to clinicians. The "Thwaites' system" and "Lancet consensus scoring system" are utilized to differentiate TBM from bacterial meningitis but their utility in subacute and chronic meningitis where TBM is an important consideration is unknown. METHODS: A multicenter retrospective study of adults with subacute and chronic meningitis, defined by symptoms greater than 5 days and less than 30 days for subacute meningitis (SAM) and greater than 30 days for chronic meningitis (CM). The "Thwaites' system" and "Lancet consensus scoring system" scores and the diagnostic accuracy by sensitivity, specificity, and area under the curve of receiver operating curve (AUC-ROC) were calculated. The "Thwaites' system" and "Lancet consensus scoring system" suggest a high probability of TBM with scores ≤4, and with scores of ≥12, respectively. RESULTS: A total of 395 patients were identified; 313 (79.2%) had subacute and 82 (20.8%) with chronic meningitis. Patients with chronic meningitis were more likely caused by tuberculosis and had higher rates of HIV infection (P < 0.001). A total of 162 patients with TBM and 233 patients with non-TBM had unknown (140, 60.1%), fungal (41, 17.6%), viral (29, 12.4%), miscellaneous (16, 6.7%), and bacterial (7, 3.0%) etiologies. TMB patients were older and presented with lower Glasgow coma scores, lower CSF glucose and higher CSF protein (P < 0.001). Both criteria were able to distinguish TBM from bacterial meningitis; only the Lancet score was able to differentiate TBM from fungal, viral, and unknown etiologies even though significant overlap occurred between the etiologies (P < .001). Both criteria showed poor diagnostic accuracy to distinguish TBM from non-TBM etiologies (AUC-ROC was <. 5), but Lancet consensus scoring system was fair in diagnosing TBM (AUC-ROC was .738), sensitivity of 50%, and specificity of 89.3%. CONCLUSION: Both criteria can be helpful in distinguishing TBM from bacterial meningitis, but only the Lancet consensus scoring system can help differentiate TBM from meningitis caused by fungal, viral and unknown etiologies even though significant overlap occurs and the overall diagnostic accuracy of both criteria were either poor or fair.

Cranial imaging findings in neurobrucellosis: results of Istanbul-3 study.

OBJECTIVE: Neuroimaging abnormalities in central nervous system (CNS) brucellosis are not well documented. The purpose of this study was to evaluate the prevalence of imaging abnormalities in neurobrucellosis and to identify factors associated with leptomeningeal and basal enhancement, which frequently results in unfavorable outcomes. METHODS: Istanbul-3 study evaluated 263 adult patients with CNS brucellosis from 26 referral centers and reviewed their 242 magnetic resonance imaging (MRI) and 226 computerized tomography (CT) scans of the brain. RESULTS: A normal CT or MRI scan was seen in 143 of 263 patients (54.3 %). Abnormal imaging findings were grouped into the following four categories: (a) inflammatory findings: leptomeningeal involvements (44), basal meningeal enhancements (30), cranial nerve involvements (14), spinal nerve roots enhancement (8), brain abscesses (7), granulomas (6), and arachnoiditis (4). (b) White-matter involvement: white-matter involvement (32) with or without demyelinating lesions (7). (c) Vascular involvement: vascular involvement (42) mostly with chronic cerebral ischemic changes (37). (d) Hydrocephalus/cerebral edema: hydrocephalus (20) and brain edema (40). On multivariate logistic regression analysis duration of symptoms since the onset (OR 1.007; 95 % CI 1-28, p = 0.01), polyneuropathy and radiculopathy (OR 5.4; 95 % CI 1.002-1.013, p = 0.044), cerebrospinal fluid (CSF)/serum glucose rate (OR 0.001; 95 % CI 000-0.067, p = 0.001), and CSF protein (OR 2.5; 95 % CI 2.3-2.7, p = 0.0001) were associated with diffuse inflammation. CONCLUSIONS: In this study, 45 % of neurobrucellosis patients had abnormal neuroimaging findings. The duration of symptoms, polyneuropathy and radiculopathy, high CSF protein level, and low CSF/serum glucose rate were associated with inflammatory findings on imaging analyses.

A case of mucosal leishmaniasis: Mimicking intranasal tumor with perforation of septum.

A 79-year-old male suffering from nasal congestion was referred to our hospital. Endoscopic examination revealed a hyperemic mass obstructing the left nasal passage. The lesion's surface was smooth. The findings of imaging studies were consistent with a benign tumor despite the erosion and perforation of the septum. The lesion originated from the middle concha and was attached to it with a thin stalk. It was removed easily by endoscopic resection. Histopathology revealed significant infiltration of mononuclear inflammatory cells, mostly lymphocytes and histiocytes, into the edematous subepithelial connective tissue. High-power magnification showed numerous Leishmania amastigotes in the cytoplasm of the histiocytes. A polymerase chain reaction experiment for Leishmania also confirmed the morphological diagnosis. No relapse was observed in the 12 months after surgery and the patient was doing well.

[Progressive multifocal leukoencephalopathy in an elderly patient with no obvious immunosuppression]. / Belirlenebilen bir immünyetmezligi olmayan yasli bir hastada gelisen progresif multifokal lökoensefalopati.

Progressive multifocal leukoencephalopathy (PML) which is a severe demyelinating disease of the central nervous system (CNS), is caused by a human polyomavirus known as JC virus (JCV). PML is seen primarily in immunosuppressed (AIDS, organ transplant or malignancy) patients. In this report, a case of PML that developed in a 75-years-old female patient with no known immunosuppression was presented. The patient was admitted to the emergency department with complaints of headache and burning sensation in head. Cerebrospinal fluid (CSF) examination revealed increase in lymphocytic cells. Since lesions compatible with tuberculoma were detected in brain tissue by magnetic resonance imaging, antituberculous therapy initiated empirically. The disease exhibited a progressive course and all the serological, molecular, microbiological and biochemical tests performed in blood and CSF failed to identify the causative agent. Pathological and immunohistochemical examination of the brain biopsy specimens demonstrated demyelinating disease. Brain biopsy, CSF, serum and urine specimens were investigated by real-time polymerase chain reaction specific for JCV and JCV-DNA was detected in the urine samples. Follow-up visits of the patient indicated a progressive course. In conclusion, after ruling out the other primary causes, JCV should be investigated in patients with demyelinating CNS disease even in the absence of significant immunosuppressive condition. Elderly patients should be considered in the risk group for demyelinating disease of CNS due to JCV.

Stress-related Epstein-Barr virus reactivation.

Epstein-Barr virus (EBV) remains latent in 90% of the patients following primary infection. The infection might be reactivated due to various stress factors. We, therefore, examined the levels of stress hormones (epinephrine, norepinephrine and cortisol), viral capsid antigen (VCA) immunoglobulin Ig G, VCA IgM, EBV early antigen IgG, Epstein-Barr nuclear antigen (EBNA) IgG, EBNA IgM antibody screening tests and performed EBV polymerized chain reaction (PCR) test and EBV DNA PCR in 100 draftees on their first day of recruitment and at the end of 1 month. Examination of the initial samples revealed that 94 (94%) subjects previously had EBV infection and 6 (6%) were seronegative. Second samples obtained at the end of first month showed that 7 (7.4%) reactivations occurred in 94 subjects who previously had EBV infection (P < 0.001). Two out of six (33.3%) who were initially seronegative had acute infection (P = 0.289). There was no significant difference between the median values of the levels of stress hormones in the initial and second serum and plasma samples. There was a significant difference between the rates of acute infection and reactivation among subjects with elevated cortisol and epinephrine levels in the second samples compared to subjects with normal levels (P < 0.001). No significant difference was determined between the first and second sample hormone levels of all nine subjects whose EBV-DNA turned positive. Routine examinations might not reveal any specific findings since EBV infection often has an asymptomatic course. EBV reactivations should always be kept in mind in patients subject to such stressful conditions.

The spectrum of diseases causing fever of unknown origin in Turkey: a multicenter study.

OBJECTIVE: The purpose of this trial was to determine the spectrum of diseases with fever of unknown origin (FUO) in Turkey. METHODS: A prospective multicenter study of 154 patients with FUO in twelve Turkish tertiary-care hospitals was conducted. RESULTS: The mean age of the patients was 42+/-17 years (range 17-75). Fifty-three (34.4%) had infectious diseases (ID), 47 (30.5%) had non-infectious inflammatory diseases (NIID), 22 (14.3%) had malignant diseases (MD), and eight (5.2%) had miscellaneous diseases (Mi). In 24 (15.6%) of the cases, the reason for high fever could not be determined despite intensive efforts. The most common ID etiologies were tuberculosis (13.6%) and cytomegalovirus (CMV) infection (3.2%). Adult Still's disease was the most common NIID (13.6%) and hematological malignancy was the most common MD (7.8%). In patients with NIID, the mean duration of reaching a definite diagnosis (37+/-23 days) was significantly longer compared to the patients with ID (25+/-12 days) (p=0.007). In patients with MD, the mean duration of fever (51+/-35 days) was longer compared to patients with ID (37+/-38 days) (p=0.052). CONCLUSIONS: Although infection remains the most common cause of FUO, with the highest percentage for tuberculosis, non-infectious etiologies seem to have increased when compared with previous studies.