Success of the Cytokine Absorption Therapies in COVID-19 Patients Diagnosed with Cytokine Release Syndrome.

OBJECTIVE: To compare the effects of cytokine absorption therapy with a resin-based cytokine absorption cartridge to tocilizumab treatment in critically ill COVID-19 patients diagnosed with cytokine release syndrome (CRS). STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: University of Health Sciences, Izmir Bozyaka Training and Research Hospital, Izmir, Turkey from April 2020 to April 2021. METHODOLOGY: Twenty-four intensive care unit (ICU) patients were included in the study. Inclusion criteria were diagnosis of severe COVID-19, diagnosis of CRS and age of older than 18 years. Exclusion criteria were pregnancy, malignancy, prior COVID-19 vaccination, procalcitonin levels higher than 2 ng/ml and life-threatening comorbidities before ICU admission. Twelve patients received tocilizumab and the other 12 patients received cytokine absorption therapy. The groups were compared for clinical outcomes and inflammatory markers (CRP, fibrinogen, ferritin, D-dimer). RESULTS: Inflammatory markers showed smilar changes with both treatments, mostly toward improvement, on the same post-treatment days. The mortality rate was 58% (seven patients) in the cytokine absorption group and 50% (six patients) in the tocilizumab group (p = 0.682). CONCLUSION: It was found that the cytokine absorption therapy reduces inflammatory mediators in intubated and critically ill Covid-19 patients similar to tocilizumab treatment, and both treatments have comparable clinical outcomes. KEY WORDS: SARS-CoV-2, Cytokine release syndrome, Chemokines, Absorption, Tocilizumab.

How did radiologists' diagnostic performance has changed in COVID-19 pneumonia: A single-centre retrospective study.

AIMS: Delay and false positivity in PCR test results have necessitated accurate chest CT reporting for the management of patients with COVID-19-suspected symptoms. Pandemic related workload and level of experience on covid-dedicated chest CT scans might have affected the diagnostic performance of on-call radiologists. The aim of this study was to reveal the interpretation errors (IEs) in chest CT reports of COVID-19-suspected patients admitted to the Emergency Room (ER). METHODS: Chest CT scans between March and June 2020 were re-evaluated and compared with the former reports and PCR test results. CT scan results were classified into four groups. Parenchymal involvement ratios, radiology departments' workload, COVID-19-related educational activities have been examined. RESULTS: Out of 5721 Chest CT scans, 783 CTs belonging to 664 patients (340 female, 324 male) were included in this study. PCR test was positive in 398; negative in 385 cases. PCR positivity was found to be highest in "normal" and "typical for covid" groups whereas lowest in "atypical for covid" and "not covid" groups. 5%-25% parenchymal involvement ratio was found in 84.2% of the cases. Regarding the number of chest CT scans performed, radiologists' workload has found to be increased six-folds. With the re-evaluation, a total of 145 IEs (18.5%) have been found. IEs were mostly precipitated in the first two months (88.3%) and mostly in the "not covid" class (60%) regardless of PCR positivity. COVID-19 and radiology entitled educational activities along with the ER admission rates within the first two months of the pandemic have seemed to be related to the decline of IEs within time. CONCLUSION: COVID-19 pandemic made a great impact on radiology departments with an inevitable burden of daily chest CT reporting. This workload and concomitant factors have effects on diagnostic challenges in COVID-19 pneumonia.

COVID-19 pneumonia in kidney transplant recipients: A promising treatment algorithm in the absence of a disease-specific drug.

There is no consensus on the management of coronavirus disease 2019 (COVID-19) and modification of immunosuppressive therapy in kidney transplant recipients (KTRs). In this study, we examined the clinical outcome of our KTRs with COVID-19 disease, who were treated with a broad-spectrum anti-inflammatory protocol. This protocol is essentially composed of intravenous immunoglobulin +/- tocilizumab in KTRs with severe COVID-19 pneumonia. Among 809 KTRs, 64 patients diagnosed with COVID-19 disease between April 2020 and February 2021, were evaluated. Twenty-nine patients with pneumonia confirmed by chest computed tomography (CCT) were hospitalized. The treatment protocol included high-dose intravenous methylprednisolone, favipiravir, enoxaparin, and empirical antibiotics. Patients with pneumonic involvement of more than 25% on CCT with or without respiratory failure were given a total of 2 g/kg intravenous immunoglobulin (IVIg) therapy. Nonresponders received tocilizumab, an interleukin-6 receptor antibody. Of the 29 patients with pneumonia, 6 were treated in other hospitals. These six patients did not receive IVIg and 5 of them deceased. In our center, IVIg treatment was applied to 15 of 23 patients. Seven of them required tocilizumab. Respiratory parameters improved significantly in all but one patient after IVIg ± tocilizumab treatment. The mortality rate was 6.6% in patients who received IVIg therapy and 35.7% in those who did not (p = 0.08). The mortality rate was higher in patients who received treatment in external centers (2.2% vs. 26.3%; p = 0.0073). The treatment of KTRs with severe COVID-19 pneumonia in organ transplant centers with significant experience yields better results. The administration of broad-spectrum anti-inflammatory treatment in this patient group was safe and provided excellent outcomes.

Evaluation of extensively drug-resistant gram-negative bacteremia among solid-organ transplant recipients: a multicenter study

Background/aim: The aim of this study is to evaluate the distribution, sources, clinical features, and mortality rates of bacteremia due to evaluation of extensively drug-resistant (XDR) gram negative among solid-organ transplant (SOT) recipients. Materials and methods: A retrospective study of SOT recipients with bacteremia due to XDR gram-negative pathogens in 11 centers between 2016 and 2018 was conducted. Patients' records were evaluated. Results: Of 171 bacteremia that occurred in 164 SOT recipients, 93 (56.7%) were liver, 46 (28%) kidney, 14 (8.5%) heart, and 11 (6.7%) lung recipients. Bacteremia episodes were recorded in the first year in 63.7% of the patients (n = 109), early-onset bacteremia was recorded in 45% (n = 77) of the episodes. In multivariate analysis, catheter-associated bacteremia was an independent risk factor for 7-day mortality (p = 0.037), and early-onset bacteremia was found as an independent risk factor for 30-day mortality (p = 0.017). Conclusion: Difficult-to-treat infections due to XDR bacteria in SOT recipients shadow the success of transplantation. Central venous catheters seem to be the main risk factor. Judicious use of medical devices is of pivotal importance.

Evaluation of a Cytomegalovirus Prophylaxis Protocol in Cytomegalovirus-IgG Positive Renal Transplant Recipients (R+).

BACKGROUND: The aim of the study was to evaluate the efficacy of a unique cytomegalovirus- (CMV) prophylaxis protocol in terms of CMV infection and disease progression in CMV IgG positive kidney transplant recipients. METHODS: Achievement of negative CMV load, using concurrent prophylactic intravenous ganciclovir therapy during induction immunosuppression, combined with a 6-month prophylactic course of acyclovir, would yield a reduced incidence of early CMV infection and disease. CMV DNA was tested for at discharge, at the third, and sixth post-op months, and at the occurrence of any event that could be associated with CMV infection. CMV DNA positive patients received ganciclovir treatment until the viral load became negative. CMV replication was monitored using a quantitative PCR method capable of detecting as few as 42.5 copies/mL. All patients were given a maintenance dose of acyclovir. RESULT: The file data of 267 patients who had undergone kidney transplantation between 2007 to 2016 were examined. Thirty-four patients were excluded from the study for various reasons, unrelated to the protocol. Of the remaining 233 patients, 42 (18%) had CMV DNA infection. Three patients had CMV disease (1.3%), 1of whom died of pneumonia. Diabetes mellitus (DM) was a risk factor for CMV DNA positivity (P < .004). CONCLUSION: The incidence of CMV infection and disease is low in renal transplant recipients whose CMV viral load is eliminated after concurrent ganciclovir administration with induction immunosuppression.

The relationship between mortality and microbiological parameters in febrile neutropenic patients with hematological malignancies.

OBJECTIVES: To determine effective risk factors on mortality in febrile neutropenic cases with hematologic malignancy. Patients with hematologic diseases are more prone to infections and those are frequent causes of mortality. METHODS: This retrospective study was performed using data of 164 febrile neutropenic cases with hematologic malignancies who were followed up in a hematology clinic of a tertiary health care center between 2011-2015. The relationship between descriptive and clinical parameters rates and rates of mortality on the 7th and the 21st days were investigated. RESULTS: Patients with absolute neutrophil count less than 100/mm3, duration of neutropenia longer than 7 days, pneumonia or gastrointestinal foci of infection, central catheterization (p=0.025), isolation of Gram (-) bacteria in culture, carbapenem resistance, septic shock, and bacterial growth during intravenous administration of antibiotic treatment were under more risk for mortality on both the 7th and the 21st days. The final multivariate logistic regression results showed that pneumonia (p less than 0.0001), septic shock (p=0.004) and isolation of Gram-negative bacteria (p=0.032) were statistically significant risk factors. CONCLUSION: Early diagnosis and appropriate treatment of serious infections, which are important causes of morbidity and mortality, are crucial in patients with febrile neutropenia. Thus, each center should closely follow up causes of infection and establish their empirical antibiotherapy protocols to accomplish better results in the management of febrile neutropenia.

A long-term multicenter study: Entecavir versus Tenofovir in treatment of nucleos(t)ide analogue-naive chronic hepatitis B patients.

BACKGROUND: Entecavir (ETV) and tenofovir disoproxil fumarat (TDF) are the two first-line therapies recommended in the treatment of chronic hepatitis B because of having potent antiviral effect and high genetic barriers against resistance. We aimed to compare efficacy of these drugs and to evaluate predictors of viral suppression. METHODS: This multicenter retrospective study was conducted in nucleos(t)ide analogue-naive chronic hepatitis B (CHB) patients from different 6 centers. RESULTS: Of the 252 patients, 166 received ETV and 86 TDF. The two groups were similar in terms of age, gender, baseline ALT levels and fibrosis scores. ETV had significantly higher baseline HBV DNA, histological activity index and lower hepatitis B early antigen (HBeAg) seropositivity. Treatment duration was longer in ETV group (P<0.001). In univariate analysis, undetectable HBV DNA and ALT normalization rates were detected significantly higher in ETV groups (P<0.001 and 0.049, respectively). There was no significant difference between groups in terms of HBeAg seroconversion, virological breakthrough, time to virological breakthrough and time to ALT normalization. Entecavir was more effective in reducing HBV DNA levels at the 3rd, 6th and 12th months of the treatment (P=0.06, 0.021 and 0.012, respectively). However, multivariate Cox regression analysis indicated that TDF therapy compared to ETV had an increased probability of achieving complete viral suppression (HR=1, 66; 95% CI 1.21-2.33; P=0.010). Hepatitis B surface antigen (HBsAg) seroconversion was occurred in only one patient in ETV group. CONCLUSION: ETV leads to an early response on HBV DNA decline in the first year of the treatment. However, TDF is more successful than entecavir in achieving virological suppression.

A persistently low HBV DNA level is a predictor of spontaneous HBsAg clearance in patients with chronic hepatitis B.

BACKGROUND/AIM: The incidence and predictors of spontaneous hepatitis B surface-antigen (HBsAg) seroclearance in patients with chronic hepatitis B virus (HBV) were evaluated. MATERIALS AND METHODS: A total of 1427 patients with chronic HBV infection, who were followed between 1994 and 2013, were investigated in this retrospective study. All data were extracted from patient files. RESULTS: Spontaneous HBsAg seroclearance occurred in 84 patients during 8798 person-years of follow-up. The patients were categorized into 3 groups at follow-up based on HBV DNA features as continuously <100 copies/mL (Group A), 0-10,000 copies/mL (Group B), and 0 to >10,000 copies/mL (Group C). Alanine aminotransferase features in the 2 groups were categorized as continuously normal (<40 U/L) and 0 to >40 U/L. Spontaneous HBsAg seroclearance was seen primarily in patients with Group A HBV DNA features, and continuously low HBV DNA values were the main predictor of HBsAg seroclearance (P < 0.001). CONCLUSION: These results suggest that a continuously low viral load is the most important factor affecting spontaneous HBsAg seroclearance.

Screening for Electrophysiological Abnormalities in Chronic Hepatitis C Infection: Peripheral Neuropathy and Optic Neuropathy.

INTRODUCTION: To investigate the existence of peripheral and optic neuropathies in asymptomatic individuals with hepatitis C infection. METHODS: Thirty consecutive patients who were followed in a hepatitis C outpatient clinic were recruited for electrophysiological evaluation together with 30 age- and gender-compatible healthy controls. All patients had a detailed neurological examination. The information regarding the disease duration and management with interferons were collected. Nerve conduction studies and visual evoked potentials (VEP) were recorded in all subjects. The results of the patient and control groups were statistically compared. RESULTS: Of the patients with hepatitis C infection, 16 were females and 14 males. The mean age was 57.5 years, and the average disease duration was 6.43 years. The P100 latencies in the patient group were within normal limits, while the amplitudes were meaningfully small by comparison with the controls. There were some abnormalities in the nerve conduction studies of 15 patients. Sensorial neuropathy was detected in two patients, sensorimotor polyneuropathy in four, carpal tunnel syndrome in seven, and carpal tunnel syndrome and sensorimotor polyneuropathy as comorbid states in another two patients. The nerve conduction studies and VEP parameters were entirely normal in the control group. CONCLUSION: Hepatitis C-related neurological abnormalities may occur both in the central and peripheral nervous system. Mononeuritis multiplex, sensorial axonal neuropathy, and multiple mononeuropathies are some of the presentations of the peripheral nervous system involvement. The mode of infection is considered to be via vasculitic mechanisms. In addition, optic neuropathy is a known complication of interferon treatment. Autoantibodies, cytokines, chemokines, and cryoglobulins are accused to play roles in the pathogenesis. In this study, we investigated the involvement of the peripheral nervous system and optic nerves in a group of patients with hepatitis C. The results were in favor of peripheral nerve injury of various types and optic neuropathy of the axonal type.

Efficacy of entecavir treatment among chronic hepatitis B nucleos(t)ide-naïve and -experienced patients.

BACKGROUND/AIM: To evaluate the efficacy of entecavir (ETV) among chronic hepatitis B (CHB) nucleos(t)ide-naive and -experienced patients in clinical practice. MATERIALS AND METHODS: In this retrospective study 85 CHB patients who had been receiving ETV and who attended our clinic since 2007 were included. Fifty patients were nucleos(t)ide analogue (NA)-naïve. Factors including sex, positive HBeAg, baseline HBV DNA level, baseline alanine aminotransferase level, and prior lamivudine (LAM) resistance were evaluated in terms of their predictive role in treatment response, which was defined as a serum HBV DNA decrease of <31.4 copies/mL. RESULTS: Resistance was detected in 18 (51.4%) of 35 lamivudine-experienced patients. Virological response (VR) was achieved in 48 (96.0%) of NA-naive patients, while 16 (45.7%) of NA-experienced patients achieved VR. LAM-resistant patients had significantly lower response rates (P < 0.001). More responders with a low initial viral load achieved VR at the end of the 12-month follow-up period compared to those with a high initial viral load (91.7% vs. 70.0%, P = 0.004). CONCLUSION: ETV has greater efficacy in NA-naïve patients and in NA-experienced patients without prior LAM resistance. The rate of VR achievement at 12 months was higher in patients who initially had a low viral load with ETV treatment.

Prognostic significance of serum galectin-3 levels in patients with hepatocellular cancer and chronic viral hepatitis.

BACKGROUND/AIM: Galectins affect diverse physiological and pathophysiological processes such as development, inflammation, and tumor growth. We aimed to compare serum galectin-3 levels in three patient groups with chronic hepatitis B and C virus (HBV, HCV), cirrhosis secondary to HBV or HCV, and hepatocellular carcinoma (HCC) secondary to HBV or HCV and evaluate the role of galectin-3 during HCC progression. PATIENTS AND METHODS: Nineteen patients with hepatocellular cancer, 22 patients with cirrhosis, and 24 patients with chronic hepatitis B and C were included in this study. Serum galectin-3 levels in different liver diseases were assessed by enzyme-linked immunosorbent assay. RESULTS: The mean galectin-3 levels were 4.61 ng/mL (±2.32) in HCC patients, 5.68 ng/mL (±2,2) in cirrhotic patients, 1.98 ng/mL (±1.50) in chronic viral hepatitis group. There were no statistical differences between HCC and cirrhotic patients (P = 0.5), but lower in chronic hepatitis group statistically compared with cirrhosis and HCC (P < 0.001, P = 0.002, respectively). In case of cirrhotic patients, galectin-3 levels were significantly higher in patients with cirrhosis secondary to HCV compared with HBV (P = 0.03). When we evaluated galectin-3 levels in HCC patients, it was found to be 3.92 ng/mL in HCC secondary to hepatitis B and 5.37 ng/mL in HCC secondary to hepatitis C. CONCLUSION: Serum galectin-3 levels in patients with chronic HBV or HCV may guide us about progression to cirrhosis or HCC and prognosis of the disease. Especially, galectin-3 levels may be more pronounced in case of HCV.

Long-term treatment of persistent disseminated Nocardia cyriacigeorgica infection.

In this paper a disseminated persistent Nocardia cyriacigeorgica infection in an immunocompetent patient is described. The patient's long-term treatment, as well as its implications for managing similar cases in the future, is emphasized. Presenting with high fever, multiple nodules, and ulcerative cutaneous lesions of body sites, the patient was treated with various antimicrobials. Under combined therapy, empyema and arthritis, leading to disseminated nocardiosis, were seen. The overall treatment course was 28 months. It can be concluded that the choice of the antibiotics and optimal duration of treatment are uncertain; therefore the treatment of nocardiosis requires expertise.

Clinical, diagnostic and therapeutic approaches to complications of brucellosis: an experience of 12 years.

OBJECTIVE: To describe the clinical presentations, laboratory findings, prevalence and pattern of complications and the response to treatment of brucellosis in a 12-year period in a Turkish research hospital. MATERIALS AND METHODS: Between 1996 and 2008, 231 patients were diagnosed with brucellosis and treated in our clinic. Medical records of 189 of the 231 patients with at least one demonstrable complication of the disease were reviewed for anamnesis, diagnosis, complications, treatment and clinical outcomes. RESULTS: The decreasing order of the complications was: hematological, 104 (55%); osteoarticular, 70 (37%); hepatobiliary, 59 (31%), and gastrointestinal, 23 (12%). The most common laboratory findings were anemia, lymphomonocytosis, elevated sedimentation rate and C-reactive protein, and elevated aminotransaminases. CONCLUSION: The hematological, osteoarticular and hepatobiliary manifestations were predominant. Bursitis, synovitis, glomerulonephritis, cutaneous lesion and deep vein thrombosis were the rare complications observed in our study. In clinical practice, brucellosis should be considered in the differential diagnosis in the presence of infrequent complications.

Rate of chronicity and time of disappearance of HBsAg following acute hepatitis B.

BACKGROUND/AIMS: Chronic hepatitis B is associated with significantly increased risk of developing cirrhosis, and hepatocellular carcinoma. It's, therefore, important to understand the incidence and risk factors associated with chronicity following acute hepatitis B. METHODOLOGY: Among 863 acute hepatitis patients admitted consecutively to the hospital, 320 with serum immunoglobulin M antibody to hepatitis B core antigen were classified as acute hepatitis B. Of these patients, serum samples were collected 3 and 6 months after clinical onset. RESULTS: Complete follow-up was achieved in 240 patients and 11 (4.6%) became chronic carriers. Only alcohol addiction other than epidemiological, clinical or biochemical parameters was found to be significantly associated with chronic evaluation. In serum samples collected from 205 of 240 patients 3 months after the onset of infection, hepatitis B surface antigen clearance was observed in 181 (88.3%). Number of patients increased to 194 (94.6%) at the end of 6 month and both of these rates were found to be highly significant. CONCLUSIONS: There is still no certain way of predicting the outcome of acute hepatitis B whether a newly infected patient will resolve the illness or not. Alcohol addiction seems to have an impact on the chronicity but additional research is needed.