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.

Survival in rhino-orbito-cerebral mucormycosis: An international, multicenter ID-IRI study.

BACKGROUND: Mucormycosis is an emerging aggressive mold infection. This study aimed to assess the outcome of hospitalized adults with rhino-orbito-cerebral mucormycosis (ROCM). The secondary objective was to identify prognostic factors in this setting. METHODS: This study was an international, retrospective, multicenter study. Patients' data were collected from 29 referral centers in 6 countries. All qualified as "proven cases" according to the EORTC/MSGERC criteria. RESULTS: We included 74 consecutive adult patients hospitalized with ROCM. Rhino-orbito-cerebral type infection was the most common presentation (n = 43; 58.1%) followed by rhino-orbital type (n = 31; 41.9%). Twenty (27%) had acquired nosocomial bacterial infections. A total of 59 (79.7%) patients (16 in combination) received appropriate antifungal treatment with high-doses of liposomal amphotericin B. Fifty-six patients (75.7%) underwent curative surgery. Thirty-five (47.3%) required intensive care unit admission (27; 36.5% under mechanical ventilation). Hospital survival was 56.8%, being reduced to 7.4% in patients with invasive mechanical ventilation. A multivariate binary backward logistic regression model identified confusion at admission (OR 11.48), overlapping hospital-acquired infection (OR 10.27), use of antifungal treatment before diagnosis (OR 10.20), no surgical debridement (OR 5.92), and the absence of prior sinusitis (OR 6.32) were independently associated with increased risk for death. CONCLUSION: Today, ROCM still has high mortality rate. Improving source control, rational therpy, and preventing nosocomial infections may improve survival in this severe infection.

[Comparison of Candida Polymerase Chain Reaction Method and Blood Culture in Patients with High Risk of Candidemia in Intensive Care Unit]. / Yogun Bakim Ünitesinde Takip Edilen Kandidemi Riski Yüksek Hastalarda Candida Polimeraz Zincir Reaksiyonu Yöntemi ve Kan Kültürünün Karsilastirilmasi.

Candida species are responsible for 70-90% of invasive fungal infections in the intensive care unit. Early diagnosis and treatment is important in candidemia. Improper diagnosis and treatment increases mortality and morbidity significantly. Because of the late results of blood cultures and low sensitivity of the serological tests when used alone, molecular methods should be investigated in this field. In this study, the results of the Candida real-time polymerase chain reaction (Rt-PCR) test, which was studied from blood culture and whole blood, were compared in patients with high candidemia risk who were followed in the General Surgery Intensive Care and Anesthesiology and Reanimation Unit of Cukurova University Faculty of Medicine. It was aimed to investigate the practical utility of Candida RT-PCR test, which is a rapid diagnosis method in patients with suspected candidemia. In our study, 90 patients with high risk of candidemia according to the criteria determined according to the guidelines were evaluated prospectively. Urine, perineum, axilla, tracheal aspirate culture and two sets of blood cultures were obtained from the patients. Blood sample was also drawn into an ethylenediaminetetraacetic acid (EDTA) tube and stored at -40°C for later Candida Rt-PCR study. In Candida Rt- PCR, species-specific primers were used to distinguish species. Candida score (CS) of the patients was calculated. Forty one (45.5%) of the patients were female and 49 (55.5%) were male. The median age of the patients was 61.5 years. Candida was positive in blood culture in three (3.3%) of the patients included in the study, while Candida Rt-PCR was positive in 17 (18.9%). Candida species detected in the blood culture and Rt-PCR test were compatible with each other. Rt-PCR was significantly more positive (p= 0.006). Candida Rt-PCR positivity was significantly higher in patients receiving total parenteral nutrition (p= 0.028), malignancy (p= 0.021), and history of surgery in the last three months (p=0.003). The difference in CS between patients with PCR positive and PCR negative was statistically significant (p= 0.015). Our study was conducted in a high-risk population for candidemia and the results of Candida Rt-PCR was found to be more positive than blood culture. Rt-PCR positivity and blood culture positivity were associated with high CS. In the light of these data, it was thought that it would be appropriate to use molecular methods in the diagnosis and support them with CS, especially in patients with high risk of candidemia. Considering that blood culture, which is the gold standard for the diagnosis of candidemia, gives late results and is 50% positive, using faster diagnostic methods for candidemia is important to reduce mortality and morbidity. The fast and good results of Candida PCR method have shown that it can be used in diagnosis. However, lack of standardization of primers used in PCR tests may cause false positives. Additional studies are needed in this respect.

COVID-19 patients' sera induce epithelial mesenchymal transition in cancer cells.

Covid-19 Pneumonia of SARS-CoV-2 pandemic infection, persists to have high disease burden especially in cancer patients. Increased inflammation and thromboembolic processes are blamed to influence cancer patients more than the others but due to lack of knowledge regarding the pathophysiology of the both the virus itself and the response of the host, more basic and translational disease modeling research is needed to understand Cancer-Covid-19 interaction. In this study, serum samples from the patients, who were hospitalized due to Covid-19 pneumonia, applied to different cancer cells and cytotoxicity, motility, proliferation and gene expression analysis were performed. Serum samples derived from healthy volunteers and the fetal bovine serum that is used regularly in cell culture experiments used as controls. Hospitalized Covid-19 patients who had also cancer, were retrospectively screened, and their clinical course were recorded. Overall 12 Patient (PS) and 4 healthy serums (CS) were included in the experiments. PS applied cells showed increased motility in A549 cells as well as lost cell to cell connection in MCF7 and HCT116 cells, and induced expression of VIM, ZEB1 and SNAIL2 mRNA levels. Eight cancer diagnosed patients who were hospitalized due to Covid-19 between April and September 2020 were also reviewed retrospectively, which 5 of them were dead during SARS-CoV-2 infection. Thorax CT images of the 2 patients showed increased metastatic nodules in the lungs as of January 2021. The results of the study indicate that metastasis may be one of the prolonged consequences of COVID-19 pandemic in cancer sufferers.

The Causes of Postoperative Meningitis: The Comparison of Gram-Negative and Gram-Positive Pathogens.

AIM: To determine the microbiological etiology in critically ill neurosurgical patients with nosocomial meningitis (NM) and to show the impact of Gram-negative rods and the differences between patient characteristics and the clinical and prognostic measures in Gram-negative and Gram-positive meningitis. MATERIAL AND METHODS: In this prospective, single-center study, we reviewed all adult patients hospitalized during a 12-year period and identified pathogens isolated from post-neurosurgical cases of NM. Demographic, clinical, and treatment characteristics were noted from the medical records. RESULTS: Of the 134 bacterial NM patients, 78 were male and 56 were female, with a mean age of 46±15.9 and a median age of 50 (18-80) years. One hundred and forty-one strains were isolated; 82 (58.2%) were Gram-negative, 59 (41.8%) were Grampositive. The most commonly isolated microorganism was Acinetobacter baumannii (34.8%). Comparison of mortality data shows that the patients who have meningitis with Gram-negative pathogens have higher mortality than with Gram-positives (p=0.034). The duration between surgery and meningitis was shorter in Gram-negative meningitis cases compared to others (p=0.045) but the duration between the diagnosis and death was shorter in Gram-positive meningitis cases compared to Gram-negatives (p=0.017). Cerebrospinal fluid protein and lactate levels were higher and glucose level was lower in cases of NM with Gram-negatives (p values were respectively, 0.022, 0.039 and 0.049). CONCLUSION: In NM, Gram-negative pathogens were seen more frequently; A. baumanni was the predominant pathogen; and NM caused by Gram-negatives had worse clinical and laboratory characteristic and prognostic outcome than Gram-positives.

Furuncular Myiasis Caused by Dermatobia hominis in a Traveler Returning from the Amazon Jungle.

A 39-year-old man who was returning from the Amazon Jungle and had no medical history presented with a furuncular lesion on his right parietal scalp. Despite receiving appropriate antimicrobial treatment, his lesion did not heal. After surgical intervention, a Dermatobia hominis larva was extracted. The human botfly D. hominis is the most common causative agent of furuncular myiasis among travelers returning from Central and South America. Surgery is the main treatment option, and secondary bacterial infection should be kept in mind.

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.

Mucormycosis: a 10-year experience at a tertiary care center in Turkey.

BACKGROUND/AIM: Mucormycosis is a rare invasive fungal infection most commonly encountered in the immunocompromised host. We analyzed 51 adult patients treated for mucormycosis between 2003 and 2013 and recorded at a tertiary university hospital in Turkey. MATERIALS AND METHODS: We examined the following data for all patients: age, sex, predisposing disease, symptoms, treatment, surgical procedure, concomitant infections, intensive care requirement, and outcomes. RESULTS: During the study period 51 cases of mucormycosis were documented; 54.9% of the patients were female. The mean age was 44.2 ± 18.2 years. Rhinocerebral presentation was reported in 94.1% of patients. Almost all patients (88.2%) had at least one risk factor. The common predisposing factors were hematologic malignancies (52.9%), diabetes mellitus (25.5%), and solid malignancies (5.8%). The most common initial symptoms were fever, cellulitis, and facial pain. The primary medication used was liposomal amphotericin B or conventional amphotericin B. Surgery was performed in 94.1% of patients. Mortality was 52.9%. CONCLUSION: Our study revealed that mucormycosis continues to be a mortal disease in about half of the cases. Our findings indicate that treatment with L-AMB is associated with a favorable response. Also, in the case of facial pain, the low mortality rate may indicate the importance of early diagnosis.