The changing epidemiology of delta hepatitis in Türkiye over three decades: A systematic review.

Hepatitis D virus (HDV) infection represents the most serious form of chronic hepatitis. Turkey is among the countries with high HDV and intermediate hepatitis B virus prevalence. In Turkey, hepatitis B virus (HBV) vaccine series was included in the routine vaccination program in 1998. There have been regional differences in prevalence of HBV and HDV. Although a decline in HDV prevalence is estimated, there are uncertainties about the epidemic patterns of it. HDV prevalence was studied in varying groups and geographic regions. In this study, we aimed to analyse hepatitis D epidemiology in all groups and geographic regions in recent 35 years. During the study period of 35 years, 111 publications were noted. The analysis was done on the basis of three periods: 1999 and before (Period 1), 2000-2009 (Period 2), and 2010 and after (Period 3). The groups studied included inactive carrier state, chronic hepatitis B, all HBsAg-positive individuals and special groups. Among inactive HBV carriers, HDV prevalence did not change significantly over three decades. Among patients with chronic hepatitis, studies reported decreasing (from Period 1 to Period 2) and then increasing (from Period 2 to period 3) HDV prevalence. The studies including all HBsAg-positive patients reported decreasing (from Period 1 to Period 2) and then increasing (from Period 2 to period 3) HDV prevalence. Cumulative data of these 3 groups were taken to reveal HDV prevalence in HBV-infected patients, and it showed decreasing (from Period 1 to Period 2) and then increasing (from Period 2 to period 3) HDV prevalence. Cumulative data of these 3 groups analysed according to the geographic regions of the country showed that Eastern and Southeastern Anatolia regions still have a high burden of HDV. The study showed that although HDV prevalence decreased from 8.3% in Period 1 to 4.8% in Period 2, it tended to increase 5.5% in Period 3. HDV infection is still a healthcare problem in Turkey.

Talaromyces marneffei infection in an HIV infected patient with hematological malignancy - first report from Turkey.

T.marneffei, encountered mostly in Southeast Asia, leads to a systemic infection, especially in immunocompromised individuals such as HIV-infected patients with low CD4 level. A 32-year-old male patient, residing in Hong Kong for the last two years, admitted with fever, cough, weakness, and weight loss. Physical examination revealed bilateral cervical and axillary multiple lymph nodes and hepatosplenomegaly. Screening of the pancytopenic patient revealed HIV infection. Histopathological examination of the cervical lymph node revealed plasmoblastic lymphoma. Blood and urine cultures remained sterile. Antiretroviral therapy was started. Fungal hyphae were detected in Gram staining of hemocultures taken in the third week due to ongoing fever, and antifungal therapy was started empirically. Red pigment around colonies on Sabouraud dextrose agar and microscopic appearance arose suspicion of Talaromyces spp. T.marneffei was identified by ITS 1-4 sequence analysis. Chemotherapy was started when fungemia was controlled. On the fifth day of chemotherapy, the patient's general condition deteriorated, broad-spectrum antibiotics were started and the patient was transferred to ICU. The cultures remained sterile and he expired five days later. In conclusion, although talaromycosis is not endemic in Turkey, it should be considered in patients with travel history to endemic regions and/or an underlying immunosuppressive disease such as HIV infection.

Incidence, Risk Factors, and Prognosis of Bloodstream Infections in COVID-19 Patients in Intensive Care: A Single-Center Observational Study.

BACKGROUND: Critically ill COVID-19 patients are prone to bloodstream infections (BSIs). AIM: To evaluate the incidence, risk factors, and prognosis of BSIs developing in COVID-19 patients in the intensive care unit (ICU). METHODS: Patients staying at least 48 h in ICU from 22 March 2020 to 25 May 2021 were included. Demographic, clinical, and laboratory data were analyzed. RESULTS: The median age of the sample (n = 470) was 66 years (IQR 56.0-76.0), and 64% were male. The three most common comorbidities were hypertension (49.8%), diabetes mellitus (32.8%), and coronary artery disease (25.7%). Further, 252 BSI episodes developed in 179 patients, and the BSI incidence rate was 50.2 (95% CI 44.3-56.7) per 1000 patient-days. The source of BSI is central venous catheter in 42.5% and lower respiratory tract in 38.9% of the episodes. Acinetobacter baumannii (40%) and carbapenem-resistant Klebsiella pneumoniae (21%) were the most common pathogens. CRP levels were lower in patients receiving tocilizumab. Multivariable analysis revealed that continuous renal replacement therapy, extracorporeal membrane oxygenation, and treatment with a combination of methylprednisolone and tocilizumab were independent risk factors for BSI. The estimated cumulative risk of developing first BSI episode was 50% after 6 days and 100% after 25 days. Of the 179 patients, 149 (83.2%) died, and a statistically significant difference (p < 0.001) was found in the survival distribution in favor of the group without BSI. CONCLUSION: BSI is a common complication in COVID-19 patients followed in the ICU, and it can lead to mortality. Failure in infection control measures, intensive immunosuppressive treatments, and invasive interventions are among the main factors leading to BSIs.

The incidence, clinical characteristics, and outcome of COVID-19 in a prospectively followed cohort of patients with Behçet's syndrome.

Initial case series of small number of patients at the beginning of the pandemic reported a rather guarded prognosis for Behçet's syndrome (BS) patients infected with SARS-CoV-2. In this prospective study, we describe the incidence, clinical characteristics, disease course, management, and outcome in a large cohort of BS patients with laboratory-confirmed infection of SARS-CoV-2. We defined a cohort of 1047 registered BS patients who were aged between 16 and 60 years and seen routinely before the pandemic at the multidisciplinary outpatient clinic. We followed prospectively this cohort from beginning of April 2020 until the end of April 2021. During 13 months of follow-up, of the 1047 (599 M/448 F) patients, 592 (56.5%) were tested for SARS-CoV-2 PCR at least once and 215 (20.5%; 95% CI 0.18-0.23) were tested positive. We observed 2 peaks which took place in December 2020 and April 2021. Of the 215 PCR positive patients, complete information was available in 214. Of these 214, 14 (6.5%) were asymptomatic for COVID-19. In the remaining, the most common symptoms were anosmia, fatigue, fever, arthralgia, and headache. A total of 40 (18.7%) had lung involvement, 25 (11.7%) were hospitalized, 1 was admitted to the intensive care unit while none died. Favipiravir was the most prescribed drug (74.3%), followed by colchicine (40.2%), and hydroxychloroquine (20.1%) in the treatment of COVID-19. After COVID-19, 5 patients (2.3%) were given supplemental O2 and 31 (14.5%) antiaggregant or anticoagulants. During COVID-19, of the 214 PCR positive patients, 116 (54.2%) decreased the dose of their immunosuppressives or stopped taking completely; 36 (16.8%) experienced a BS flare which was mostly oral ulcers (10.3%). None of the patients reported a thrombotic event. A total of 93 (43.5%) patients reported BS flares after a median 45 days of COVID-19 infection and this was found to be significantly associated with immunosuppressive drug discontinuation. Multiple regression analysis adjusted for age and gender indicated that smoking and using interferon-alpha decreased the likelihood of getting COVID-19. The incidence and severity of COVID-19 did not differ between those who were using colchicine or not. The cumulative incidence of COVID-19 in this prospectively followed cohort of BS patients was almost two folds of that estimated for the general population living in Istanbul, Turkey, however, the clinical outcome of COVID-19 was not severe and there was no mortality. The protective effect of smoking and interferon deserves further investigation. On the other hand, colchicine did not have any positive or negative effect against COVID-19. Significant number of patients flared after COVID-19, however, this was significantly associated with immunosuppressive discontinuation during the infection. Contrary to our previous observations, COVID-19 did not seem to exacerbate thrombotic events during or after the infection.

Safety of SARS-CoV-2 vaccination in patients with Behcet's syndrome and familial Mediterranean fever: a cross-sectional comparative study on the effects of M-RNA based and inactivated vaccine.

Most of the published data relate to classical forms of rheumatic diseases (RD) and information on rare inflammatory disorders such as Behçet's syndrome (BS) and familial Mediterranean fever (FMF) is limited. We studied the frequency of side effects and disease flares after COVID-19 vaccination with either Pfizer/BioNTech or Sinovac/CoronaVac in 256 patients with BS, 247 with FMF, and 601 with RD. Telephone interviews were conducted using a questionnaire survey in a cross-sectional design in patients with BS, FMF, and RD followed by a single university hospital. Study participants were vaccinated either with CoronaVac (BS:109, FMF: 90, and RD: 343,) or BioNTech (BS: 147, FMF: 157 and RD: 258). The majority have received double dose (BS: 94.9%, FMF 92.3% and RD: 86.2%). BioNTech ensured a significantly better efficacy than CoronaVac against COVID-19 in all patient groups (BS: 1.4% vs 10.1%; FMF: 3.2% vs 12.2%, RD:2.7% vs 6.4%). Those with at least one adverse event (AE) were significantly more frequent among those vaccinated with BioNTech than those with CoronaVac (BS: 86.4% vs 45%; FMF: 83.4% vs 53.3%; and RD: 83.3% vs 45.5%). The majority of AEs were mild to moderate and transient and this was true for either vaccine. There were also AEs that required medical attention in all study groups following CoronaVac (BS: 5.5%, FMF: 3.3%, and RD:2.9%) or BioNTech (BS: 5.4%, FMF: 1.9%, and RD: 4.7%). The main causes for medical assistance were disease flare and cardiovascular events. Patients with BS (16.0%) and FMF (17.4%) were found to flare significantly more frequently when compared to those with RD (6.0%) (p < 0.001). This was true for either vaccine. BS patients reported mainly skin-mucosa lesions; there were however, 11 (4.3%) who developed major organ attack such as uveitis, thrombosis or stroke. Flare in FMF patients were associated mainly with acute serositis with or without fever. Arthralgia/arthritis or inflammatory back pain were observed mainly in the RD group. Our study demonstrates that BS and FMF patients vaccinated with either CoronaVac or BioNTech demonstrated similar AE profile and frequency compared to RD patients. AEs that required physician consultation or hospitalization occurred in all study groups after either CoronaVac or BioNTech. Increased frequency of flares in BS and FMF compared to that seen in RD might reflect defects in innate immunity and deserves further investigation. Caution should be required when monitoring these patients after vaccination.

Clinical outcomes of geriatric patients with COVID-19: review of one-year data.

AIMS: In this study, we aimed to reveal mortality rates and factors affecting survival in geriatric patients infected with COVID-19. METHODS: This is a retrospective study of 873 geriatric patients with COVID-19 who were hospitalized between March 11, 2020 and March 11, 2021. Demographic, clinical, laboratory data, and treatment options were obtained from electronic medical records. Multivariate logistic regression was used to explore the risk factors for in-hospital death. RESULTS: During the specified period, 643 patients were discharged, and 230 patients died in the hospital. The mean age was 75.08 ± 7.39 years (mean ± SD) and 51.8% were males. We found that older age (≥ 85), polypharmacy, dyspnea, abnormal thorax computed tomography (CT), lower doses of anticoagulation, and high values of white blood cell, aspartate aminotransferase, C-reactive protein, lactate dehydrogenase, ferritin were associated with a significant increase in mortality (P < 0.001 for all). Although all of these values were significant in multivariate logistic regression analysis, the most important ones were dyspnea (Odds ratio (OR) 57.916, 95% confidence interval (CI) 23.439-143.104, P < 0.001), polypharmacy (OR 6.782, 95% CI 3.082-14.927, P < 0.001), and thorax CT classification (typical; OR 9.633, 95% CI 2.511-37.122, P < 0.001). CONCLUSION: Older age, polypharmacy, dyspnea, and abnormal thorax CT were the most significant mortality criteria and in addition appropriate anticoagulant use was associated with reduced mortality. Identifying the risk factors to predict mortality in older adults with COVID-19 is important to treat future cases successfully.

A pan-resistant Myroides odoratimimus catheter-related bacteremia in a COVID-19 patient and review of the literature.

Myroides spp. are opportunistic environmental Gram-negative bacteria. These affect mostly immunocompromised hosts and generally lead to soft tissue, and urinary tract infections. Bacteremia most commonly develop secondary to soft tissue or catheter related infections and may lead rarely to mortality. Myroides spp. are generally suscetible to fluoroquinolones, piperacillin/tazobactam, trimethoprim/sulfamethoxazole, carbapenems or tetracyclines however, pan-resistant isolates and multiple resistance genes have been reported in clinical isolates of Myroides spp. We report a pan-resistant Myroides odoratimimus bacteremia in a patient with severe COVID-19 ending with fatality and in this context a review of reported Myroides bacteremias are also described. In this study, a 64-year old male patient with history of coronary artery bypass was admitted to ICU with severe COVID-19 pneumonia accompanied by pneumomediastinum and pneumopericardium. Continous renal replacement therapy and extracorporeal membraneous-oxygenation were initiated due to acute renal failure and persistent hypercarbia/hypoxia, respectively. Within four weeks of hospitalization various episodes of bacteremia developed and multiple antibiotics were used. On the 5th week of follow-up, acute phase reactants increased and empirical broad spectrum antibiotics were initiated. Blood culture revealed Gram-negative rods. The patient became hypotensive and despite maximum medical care he was lost due to cardiac arrest. M. odoratimimus was identified by MALDI-TOF and the bacterium was pan-resistant. According to Center for Genomic Epidemiology results the strain was identified as M. odoratimimus PR63039 and the genome analysis revealed antibiotic resistance genes associated with resistance to beta-lactams (bla OXA-347, bla MUS-1, bla EBR-1), tetracyclines (tetX), sulfonamides (sul2), macrolides (ereD), (ermF).

Remdesivir treatment for patients with moderate to severe COVID-19.

BACKGROUND: Remdesivir, which was first developed for the treatment of Ebola disease but failed to meet expectations, has become hope in the fight against the COVID-19 pandemic. This study aimed to evaluate risk factors for mortality and prognosis of adult moderate/severe COVID-19 patients treated with remdesivir, and safety and tolerability of 5 days of remdesivir treatment. METHODS: This multicenter prospective observational study was conducted in 14 centers in Turkey. Pregnancy or breastfeeding, multiorgan failure, or usage of vasopressors for septic shock, ALT > 5 × the upper limit of the normal range, or eGRF <30 mL/min or dialysis and receiving favipiravir were the exclusion criteria of the study. RESULTS: Among 500 patients, 494 patients were included in the study. On admission, 392 (79.3%) patients had moderate and 102 (20.6%) patients had severe COVID-19. The 28-day mortality was 10.1%. The median of the scores of the seven-category ordinal scale assessed on days 0, 3, 5, 7 were 4 and 3 on day 14. When the survival status of the patients was evaluated according to the time between the remdesivir start date and the end date of the symptoms, no statistically significant difference was found between the medians of the groups (p = 0.404). In multivariable analysis, age (OR, 1.05; 95%CI, 1.02-1.08; p = 0.003), SpO2 level on admission (OR, 3.03; 95%CI, 1.35-6.81; p = 0.007), heart rate (OR, 2.48; 95%CI, 1.01-6.07; p = 0.047), follow-up site at the hospital (clinic/ICU) (OR, 26.4; 95%CI, 11.6-60.17; p < 0.001) were independently associated with increased mortality. Grade 3 adverse event (AE) was observed in 4 (0.8%) patients. None of the patients experienced grade 4 or 5 AEs. DISCUSSION: Remdesivir is a safe and well-tolerated drug and older age, low SpO2 level on admission, tachycardia, and ICU admission are independently associated with increased mortality among patients with moderate/severe COVID-19 receiving remdesivir treatment.

Colistin resistance increases 28-day mortality in bloodstream infections due to carbapenem-resistant Klebsiella pneumoniae.

Mortality due to K. pneumoniae bacteremia is on rise, particularly in regions with high rates of carbapenem and colistin resistance. We aimed to define risk factors for colistin resistance and its impact on mortality. Patients diagnosed with "carbapenem-resistant K. pneumoniae (CRKp)" bacteremia between 2014 and 2018 were divided into two groups as "colistin susceptible (ColS)" and "colistin resistant (ColR)" based on broth microdilution method. Retrospective case-control study was conducted to compare characteristics and outcomes. Multiple logistic regression model was used to define independent risk factors for acquired colistin resistance and Cox proportional hazard model for 28-day mortality. A total of 82 patients (39 ColS and 43 ColR) were included. Mean age was 61.5 years, and 50 (61%) were male. Colistin resistance was significantly increased with duration of hospital stay (p = 0.007) and prior colistin use (p = 0.007). Overall, the 28-day mortality rate was 66%. Age (p = 0.014) and colistin resistance significantly increased 28-day (p = 0.009) mortality. Microbiological response to treatment within 7 days favors survival. PFGE analysis revealed an outbreak with K. pneumoniae ST78 and ST45 clones. Patients treated with combined antimicrobials had significantly lower 28-day mortality (p = 0.045) in comparison to monotherapy. However, types of combinations did not show significant superiority on each other. Colistin resistance increases 28-day mortality in CRKp bacteremia. Although combined regimens are more effective than monotherapy, existing antibacterial combinations have no apparent superiority to each other. New treatment options are pivotal.

Change in species distribution and antifungal susceptibility of candidemias in an intensive care unit of a university hospital (10-year experience).

Candidemia is a nosocomial infection mostly found in critically ill patients. Our objectives were to evaluate the change in distribution and resistance profile of Candida spp. isolated from candidemic patients in our intensive care unit over two 5-year periods spanning 15 years and to evaluate the risk factors. Records from the microbiology laboratory were obtained, from January 2004 to December 2008 and from January 2013 to December 2017, retrospectively. Antifungal susceptibility was performed by E-test and evaluated according to EUCAST breakpoints. A total of 210 candidemia cases occurred; 238 Candida spp. were isolated in 197 patients (58.8% male; mean age, 59.2 ± 19.6 years). The most predominant risk factor was central venous catheter use. Species distribution rates were 32%, 28%, 17%, and 11% for C. albicans (n = 76), C. parapsilosis (n = 67), C. glabrata (n = 40), and C. tropicalis (n = 27), respectively. Resistance rate to anidulafungin was high in C. parapsilosis over both periods and increased to 73% in the second period. Fluconazole showed a remarkable decrease for susceptibility in C. parapsilosis (94 to 49%). The prevalence of MDR C. parapsilosis (6%/33%) and C. glabrata (0%/44%) increased in the second period. We observed a predominance of non-albicans Candida spp., with C. parapsilosis being the most frequent and C. glabrata infections presenting with the highest mortality. High level of echinocandin resistance in C. parapsilosis and increasing prevalences of MDR C. parapsilosis and C. glabrata seem emerging challenges in our institution.

An easy-to-use nomogram for predicting in-hospital mortality risk in COVID-19: a retrospective cohort study in a university hospital.

BACKGROUND: One-fifth of COVID-19 patients are seriously and critically ill cases and have a worse prognosis than non-severe cases. Although there is no specific treatment available for COVID-19, early recognition and supportive treatment may reduce the mortality. The aim of this study is to develop a functional nomogram that can be used by clinicians to estimate the risk of in-hospital mortality in patients hospitalized and treated for COVID-19 disease, and to compare the accuracy of model predictions with previous nomograms. METHODS: This retrospective study enrolled 709 patients who were over 18 years old and received inpatient treatment for COVID-19 disease. Multivariable Logistic Regression analysis was performed to assess the possible predictors of a fatal outcome. A nomogram was developed with the possible predictors and total point were calculated. RESULTS: Of the 709 patients treated for COVID-19, 75 (11%) died and 634 survived. The elder age, certain comorbidities (cancer, heart failure, chronic renal failure), dyspnea, lower levels of oxygen saturation and hematocrit, higher levels of C-reactive protein, aspartate aminotransferase and ferritin were independent risk factors for mortality. The prediction ability of total points was excellent (Area Under Curve = 0.922). CONCLUSIONS: The nomogram developed in this study can be used by clinicians as a practical and effective tool in mortality risk estimation. So that with early diagnosis and intervention mortality in COVID-19 patients may be reduced.

Tocilizumab in COVID-19: The Cerrahpasa-PREDICT score.

BACKGROUND: Cytokine release syndrome (CRS), characterized by overproduction of proinflammatory cytokines in the course of severe coronavirus disease 2019 (COVID-19), has been suggested as the major cause of mortality. Tocilizumab, a recombinant humanized monoclonal antibody against human IL-6 receptor, poses a therapeutic option for the treatment of CRS leading to severe acute respiratory syndrome in coronavirus-2 (SARS-CoV-2) infection. METHODS: We performed a single-center retrospective study to reveal the outcome of COVID-19 patients on tocilizumab and proposed "the Cerrahpasa-PREDICT score", a new clinical scoring system using clinical and laboratory parameters that would help predicting the 28-day mortality of COVID-19 patients receiving tocilizumab. RESULTS: Eighty-seven patients (median age: 59 years) were included of whom 75.8% were male. Tocilizumab use significantly improved clinical and laboratory parameters. The 28-day mortality rate on tocilizumab was 16.1%. The Cerrahpasa-PREDICT score, consisting of platelet counts, procalcitonin, D-dimer levels, SO2R and the time from symptom onset to tocilizumab administration had a positive predictive value of 94.5% and negative predictive value of 92.9% for anticipating 28-day mortality. CONCLUSIONS: Severe COVID-19 should closely be monitored for the signs of hyperinflammation. We showed that administration of tocilizumab early in the course of the disease (prior to ICU admission) resulted in a favorable outcome. Close monitoring usually aids identifying patients who would benefit from tocilizumab. In this regard, the Cerrahpasa-PREDICT score might serve as a practical tool for estimating the 28-day mortality in COVID-19 patients who received tocilizumab and would facilitate timely recognition of fatal cases to be evaluated for other therapeutic options.

Willingness to get the COVID-19 vaccine among patients with rheumatic diseases, healthcare workers and general population in Turkey: a web-based survey.

OBJECTIVES: Vaccination against COVID-19 emerges as an effective strategy for combating the pandemic. While many of our patients with rheumatic diseases (RD) wonder whether it is safe to get the vaccine, vaccine hesitancy is rising among the general population. We assessed the willingness to get vaccination and its probable predictors among patients with RD compared to healthcare workers and a sample from the general population. METHODS: We conducted a web-based questionnaire survey in a cross-sectional design in 3 groups of participants just before the mass vaccination program in Istanbul, Turkey. The questionnaire sought socio-demographic variables, COVID-19 related risk factors, willingness to get vaccination, and concerns and thoughts about vaccine. COVID-19 anxiety scale (CAS) was also evaluated. RESULTS: We studied in total 732 patients with RD (Group 1), 763 individuals representing general population (Group 2) and 320 hospital workers (Group 3). Dysfunctional anxiety related to COVID-19 was found in 4.9%, 3.8% and 4.1%, in Group 1, 2 and 3, respectively. Of the patients with RD, 29.2% were willing to be vaccinated, 19.0% were unwilling and 51.8% were undecided. These were somewhat similar among the general population (yes: 34.6%, no: 23.3% and unsure: 42.1%), with significantly less undecided individuals (p < 0.001). On the other hand, hospital workers were significantly more willing (yes: 52.5%, no: 20.9% and unsure: 26.6%) (p < 0.001). Main concerns were probable side effects, unknown scientific results and having no trust. Being male, older age, working in a hospital, not having contracted COVID-19 and high scores on CAS were found to be independently associated with willingness. CONCLUSIONS: The low rate of vaccine acceptance among patients with RD, as well as general population sampling is worrying. Healthcare policies should aim to implement communication, promote confidence and increase demand for COVID-19 vaccine.

Antibody response to inactivated COVID-19 vaccine (CoronaVac) in immune-mediated diseases: a controlled study among hospital workers and elderly.

OBJECTIVE: To assess antibody response to inactivated COVID-19 vaccine in patients with immune-mediated diseases (IMD) among hospital workers and people aged 65 and older. METHODS: In this cross-sectional study, we studied 82 hospital workers with IMD (mean age: 42.2 ± 10.0 years) and 300 (mean age: 41.7 ± 9.9 years) controls. Among + 65 aged population, we studied 22 (mean age: 71.4 ± 4.5 years) patients and 47 controls (mean age: 70.9 ± 4.8 years). All study subjects had a negative history for COVID-19. Sera were obtained after at least 21 days following the second vaccination. Anti-spike IgG antibody titers were measured quantitatively using a commercially available immunoassay method. RESULTS: Patients with IMD were significantly less likely to have detectable antibodies than healthy controls both among the hospital workers (92.7% vs 99.7%, p < 0.001) and elderly population (77.3% vs 97.9%, p = 0.011). Among patients with IMD, those using immunosuppressive or immune-modulating drugs (64/75, 85.3%) were significantly less likely to have detectable antibodies compared to those off treatment (29/29, 100%) (p = 0.029). Additionally, a negative association between age and the antibody titer categories among patients (r = - 0.352; p < 0.001) and controls (r = - 0.258; p < 0.001) were demonstrated. CONCLUSIONS: Among hospital workers, the vast majority of patients with IMD and immunocompetent controls developed a significant humoral response following the administration of the second dose of inactivated COVID-19 vaccine. This was also true for the elderly population, albeit with lower antibody titers. Immunosuppressive use, particularly rituximab significantly reduced antibody titers. Antibody titers were significantly lower among those aged ≥ 60 years both in patient and control populations. Whether these individuals should get a booster dose warrants further studies.

[Clinical Characteristics of Mild-Moderate COVID-19 Patients and Risk Factors for the Development of Pneumonia]. / Hafif-Orta Klinik Seyirli COVID-19 Hastalarinin Genel Özellikleri ve Pnömoni Gelisimi için Risk Faktörler.

Limited data exists to date on the predictors for the development of pneumonia in patients with mild and moderate coronavirus (COVID-19). In this study, it was aimed to evaluate the demographic characteristics and clinical findings of mild and moderate COVID-19 and to determine the risk factors for the development of COVID-19 pneumonia in patients admitted to the pandemic outpatient clinic of a university hospital. A total of 414 patients with laboratory confirmed COVID-19 were included. Of these, 220 (53.1%) were male, the mean age was 38.3 ± 12.7. Median duration of hospital admission from the onset of symptoms was three days (0-11). Of the confirmed COVID-19 cases, 154 (37.2%) had a history of family contact and the most common symptoms were weakness (68.4%), myalgia (61.8%), headache (56.5%), loss of smell (45.2%), loss of taste (43.2%) and anorexia (42.8%). Among females, weakness (p= 0.016), headache (p= 0.008), sore throat (p= 0.032), nausea (p= 0.003), anorexia (p= 0.045), loss of taste (p= 0.005) and loss of smell (p<0.001) were more common. Loss of taste (47.6% vs. 25%, p<0.001) and loss of smell (50% vs. 26.3%, p<0.001) were more common in patients with under the age of 50 and cough (43.4% vs. 29.3%, p= 0.003) was more common in patients with above the age of 40. Among 46 (11.1%) patients with asymptomatic COVID-19, there was no significant difference (p= 0.500) between the genders. Pneumonia was detected in 150 (43.8%) of 339 patients who underwent thorax computed tomography. In the univariate analysis; advanced age (p<0.001, odds ratio (OR)= 1.44), obesity (p<0.001 OR= 2.5), not being actively smoking (p<0.001, OR= 6.19), fever at first admission (p= 0.002, OR= 2.02), cough (p<0.001, OR= 3.26), shortness of breath (p<0.001, OR= 23.37), weakness (p= 0.042, OR= 1.63), anorexia (p= 0.009, OR= 1.79) and elevation of D-dimer (p= 0.014, OR= 1.92) were associated with the development of pneumonia. In multivariate analysis, obesity (p= 0.005, OR= 2.69), not being actively smoking (p<0.001, OR= 5.43), cough at first admission p= 0.017, OR= 2.16) and shortness of breath (p= 0.008, OR= 16.22) was determined as an independent risk factor for the development of pneumonia. CRP (p<0.001), D-dimer (p<0.001), ferritin (p<0.001) values among 108 (26.1%) patients with a body-mass index(BMI) >30 were high, and 60.9% of the patients had pneumonia (p<0.001) . CRP (p<0.001), D-dimer (p= 0.010) values were low, lymphocyte count (p= 0.001) was high among 106 (25.6%) active smokers, and 15.6% of the patients had pneumonia (p<0.001). Of the patients reported with persistent symptoms, 25.9% had loss of smell, 25% had weakness, and 23.1% had loss of taste on the seventh day; 21.1% had loss of smell, 21.1% had myalgia, and 19.7% had loss of taste on the 14th day. During their follow-up, the COVID-19 polymerase chain reaction (PCR) test was studied in 286 patients for control purposes. The median time of being negative for COVID-19 PCR test was eight days (3-56). In conclusion, symptoms may last longer than 14 days in 20- 30% of patients presenting with mild-moderate clinical findings. In addition, obesity should be considered as an important risk factor for COVID-19 pneumonia.

Ten-year follow-up of a randomized controlled clinical trial in chronic hepatitis delta.

Hepatitis delta virus (HDV) infection causes the most severe form of viral hepatitis. PEG-interferon alpha-2a (PEG-IFNα-2a) is the only effective treatment but its long-term clinical impact is unclear. The aim of this study was to investigate the long-term outcome after 48 weeks of pegylated interferon alpha-2a therapy. We performed a retrospective follow-up study of the Hep-Net-International-Delta-Hepatitis-Intervention-Study 1 (HIDIT-I trial). Patients had received 48 weeks of treatment with either PEG-IFNα-2a plus adefovir dipivoxil (ADV) (Group I), PEG-IFNα-2a alone (Group II) or adefovir dipivoxil alone (Group III). Liver-related complications were defined as liver-related death, liver transplantation, liver cancer and hepatic decompensation defined as development of Child-Pugh scores B or C or an increase in Model for End-stage Liver Disease (MELD) scores of five or more points in relation to baseline values. Patients were considered for further analysis when they were retreated with PEG-IFNα-2a. Follow-up data (at least 1 visit beyond post-treatment week 24) were available for 60 patients [Group I, (n = 19), Group II (n = 20), Group III (n = 21)]. Mean time of follow-up was 8.9 (1.6 - 13.4) years. 19 patients were retreated with IFN-based therapy: 42% (n = 8) in PEG-IFNα-2a arms and 58% (n = 11) in the adefovir only arm. Clinical complications on long-term follow-up occurred in 17 patients and were associated with nonresponse to therapy and baseline cirrhosis. The annual event-free survival rate in patients with cirrhosis vs noncirrhotic patients at year 5 and 10 was 70% vs 91% and 35% vs 76%. Long-term follow-up of a large randomized clinical trial suggests that off-treatment HDV RNA response to PEG-IFNα-2a treatment leads to improved clinical long-term outcome.

An eleven-year cohort of bloodstream infections in 552 febrile neutropenic patients: resistance profiles of Gram-negative bacteria as a predictor of mortality.

Antimicrobial stewardship is of major importance in patients with febrile neutropenia (FN). In this study, we aimed to investigate the trends in resistance and the relationship with mortality rates in patients with FN. The single-center surveillance data of inpatients with FN and diagnosed as microbiologically confirmed bloodstream infections (BSIs) between 2006 and 2016 were reviewed retrospectively. A total of 950 episodes in 552 patients with BSIs were analyzed. Of whom, 55.9% were male, the median age was 43 years, and 35.6% had acute myeloid leukemia. In total, 1016 microorganisms were isolated from blood cultures. Gram-negatives accounted for 42.4% (n = 403) of the episodes. Among Gram-negatives, Enterobacteriaceae accounted for 346 (86%) (E. coli, n = 197; 34% extended-spectrum ß-lactamases (ESBL) producers, and Klebsiella spp., n = 120; 48.3% ESBL producers). Also, 24 (20.0%) of Klebsiella spp. had carbapenemase activity. There were 6 (5.0%) colistin-resistant Klebsiella spp. Thirteen (26.5%) of Pseudomonas spp. and 17 (60.7%) of Acinetobacter spp. had carbapenemase activity. There were 2 (5.6%) colistin-resistant Acinetobacter spp. The 30-day mortality rates were 12.0%, 21.5%, 34.6%, and 29.0% in BSIs due to Gram-positive, Gram-negative bacterial, fungal, and polymicrobial etiology respectively (p = 0.001). BSIs with ESBL-producing (p = 0.001) isolates, carbapenem (p < 0.001), and colistin-resistant isolates (p < 0.001) were associated with increased mortality risk. The tremendous rise in resistance rates among Gram-negatives is dreadfully related to increasing mortality and leads to sharp shifts toward extreme restrictions of unnecessary antibiotic uses. Antimicrobial stewardship in patients with FN requires vigilance and tailoring of treatment upon local surveillance data.

Stigma in Hospital: an examination of beliefs and attitudes towards HIV/AIDS patients, Istanbul.

HIV/AIDS-related stigma remains a crucial public health problem in the world. Unfortunately, health provider staffs such as nurses and physicians are the major source of stigmatization and discrimination against peoples living with HIV (PLHIVs) including in Turkey. The aim of this study was to assess HIV-related stigma towards to PLHIV by nurses and physicians and to examine related factors. Descriptive Assessment Form and the HIV-Related Stigma Scale used for data collection. The study consisted of 405 health workers including 251 nurses and 154 physicians. Over 86% of physicians and 69.3% of nurses had no specific education about HIV. More than 11% of the nurses and 8.4% of the physicians expressed that HIV can be transmitted with handshaking or breathing in a shared environment. Fear-driven stigma was significantly different by age, education, occupation, and work experience. Over 14% of the discrimination (Adjusted R2 = .14 F(15-389) = 4.46 P = .000), and 10% of the disclosure were explained by the variables (Adjusted R2 = .10 F(15-389) = 4.29 P = .000). The discrimination dimension had a strong positive relationship with the knowledge of HIV transmission modes. In our view, if physicians and nurses receive adequate and comprehensive training on HIV including stigma, the formations of stigma may be prevented and may not develop.

Genome-wide Association Study Identifies Genetic Variants Associated With Early and Sustained Response to (Pegylated) Interferon in Chronic Hepatitis B Patients: The GIANT-B Study.

BACKGROUND: (Pegylated) Interferon ([Peg]IFN) therapy leads to response in a minority of chronic hepatitis B (CHB) patients. Host genetic determinants of response are therefore in demand. METHODS: In this genome-wide association study (GWAS), CHB patients, treated with (Peg)IFN for at least 12 weeks ± nucleos(t)ide analogues within randomized trials or as standard of care, were recruited at 21 centers from Europe, Asia, and North America. Response at 24 weeks after (Peg)IFN treatment was defined as combined hepatitis B e antigen (HBeAg) loss with hepatitis B virus (HBV) DNA <2000 IU/mL, or an HBV DNA <2000 IU/mL for HBeAg-negative patients. RESULTS: Of 1144 patients, 1058 (92%) patients were included in the GWAS analysis. In total, 282 (31%) patients achieved the response and 4% hepatitis B surface antigen (HBsAg) loss. GWAS analysis stratified by HBeAg status, adjusted for age, sex, and the 4 ancestry components identified PRELID2 rs371991 (B= -0.74, standard error [SE] = 0.16, P = 3.44 ×10-6) for HBeAg-positive patients. Importantly, PRELID2 was cross-validated for long-term response in HBeAg-negative patients. G3BP2 rs3821977 (B = 1.13, SE = 0.24, P = 2.46 × 10-6) was associated with response in HBeAg-negative patients. G3BP2 has a role in the interferon pathway and was further examined in peripheral blood mononuclear cells of healthy controls stimulated with IFNα and TLR8. After stimulation, less production of IP-10 and interleukin (IL)-10 proteins and more production of IL-8 were observed with the G3BP2 G-allele. CONCLUSIONS: Although no genome-wide significant hits were found, the current GWAS identified genetic variants associated with (Peg)IFN response in CHB. The current findings could pave the way for gene polymorphism-guided clinical counseling, both in the setting of (Peg)IFN and the natural history, and possibly for new immune-modulating therapies. CLINICAL TRIALS REGISTATION: NCT01401400.

Hepatitis B core-related antigen monitoring during peginterferon alfa treatment for HBeAg-negative chronic hepatitis B.

Serum Hepatitis B core-related antigen (HBcrAg) level moderately correlates with cccDNA. We examined whether HBcrAg can add value in monitoring the effect of peginterferon (PEG-IFN) therapy for HBeAg-negative chronic hepatitis B (CHB) infection. Thus, serum HBcrAg level was measured in 133 HBeAg-negative, mainly Caucasian CHB patients, treated with 48 weeks of PEG-IFN alfa-2a. We assessed its association with response (ALT normalization & HBV DNA < 2000 IU/mL) at week 72. HBcrAg level strongly correlated with HBV DNA level (r = 0.8, P < 0.001) and weakly with qHBsAg and ALT (both r = 0.2, P = 0.01). At week 48, mean HBcrAg decline was -3.3 log U/mL. Baseline levels were comparable for patients with and without response at week 72 (5.0 vs 4.9 log U/mL, P = 0.59). HBcrAg decline at week 72 differed between patients with and without response (-2.4 vs -1.0 log U/mL, P = 0.001), but no cut-off could be determined. The pattern of decline in responders resembled that of HBV DNA, but HBcrAg decline was weaker (HBcrAg -2.5 log U/mL; HBV DNA: -4.0 log IU/mL, P < 0.001). For early identification of nonresponse, diagnostic accuracy of HBV DNA and qHBsAg decline at week 12 (AUC 0.742, CI-95% [0.0.629-0.855], P < 0.001) did not improve by adding HBcrAg decline (AUC 0.747, CI-95% [0.629-0.855] P < 0.001), nor by replacing HBV DNA decline by HBcrAg decline (AUC 0.754, CI-95% [0.641-0.867], P < 0.001). In conclusion, in Caucasian patients with HBeAg-negative CHB, decline of HBcrAg during PEG-IFN treatment was stronger in patients with treatment response. However, HBcrAg was not superior to HBV DNA and qHBsAg in predicting response during PEG-IFN treatment.