Acıbadem Üniversitesi Açık Erişim Sistemi
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The association of antiviral drugs with COVID-19 morbidity: The retrospective analysis of a nationwide COVID-19 cohort
Background and objectivesAlthough several repurposed antiviral drugs have been used for the treatment of COVID-19, only a few such as remdesivir and molnupiravir have shown promising effects. The objectives of our study were to investigate the association of repurposed antiviral drugs with COVID-19 morbidity. MethodsPatients admitted to 26 different hospitals located in 16 different provinces between March 11-July 18, 2020, were enrolled. Case definition was based on WHO criteria. Patients were managed according to the guidelines by Scientific Board of Ministry of Health of Turkey. Primary outcomes were length of hospitalization, intensive care unit (ICU) requirement, and intubation. ResultsWe retrospectively evaluated 1,472 COVID-19 adult patients57.1\% were men (mean age = 51.9 +/- 17.7years). A total of 210 (14.3\%) had severe pneumonia, 115 (7.8\%) were admitted to ICUs, and 69 (4.7\%) were intubated during hospitalization. The median (interquartile range) of duration of hospitalization, including ICU admission, was 7 (5-12) days. Favipiravir (n = 328), lopinavir/ritonavir (n = 55), and oseltamivir (n = 761) were administered as antiviral agents, and hydroxychloroquine (HCQ, n = 1,382) and azithromycin (n = 738) were used for their immunomodulatory activity. Lopinavir/ritonavir (beta {[}95\% CI]: 4.71 {[}2.31-7.11]p = 0.001), favipiravir (beta {[}95\% CI]: 3.55 {[}2.56-4.55]p = 0.001) and HCQ (beta {[}95\% CI]: 0.84 {[}0.02-1.67]p = 0.046) were associated with increased risk of lengthy hospital stays. Furthermore, favipiravir was associated with increased risks of ICU admission (OR {[}95\% CI]: 3.02 {[}1.70-5.35]p = 0.001) and invasive mechanical ventilation requirement (OR {[}95\% CI]: 2.94 {[}1.28-6.75]p = 0.011). ConclusionOur findings demonstrated that antiviral drugs including lopinavir, ritonavir, and favipiravir were associated with negative clinical outcomes such as increased risks for lengthy hospital stay, ICU admission, and invasive mechanical ventilation requirement. Therefore, repurposing such agents without proven clinical evidence might not be the best approach for COVID-19 treatment.AUG 31
SARS-CoV-2 vaccination and risk of severe COVID-19 outcomes in patients with autoimmune hepatitis
Background: Data regarding outcome of Coronavirus disease 2019 (COVID-19) in vaccinated patients with autoimmune hepatitis (AIH) are lacking. We evaluated the outcome of COVID-19 in AIH patients who received at least one dose of Pfizer- BioNTech (BNT162b2), Moderna (mRNA-1273) or AstraZeneca (ChAdOx1-S) vaccine. Patients and methods: We performed a retrospective study on AIH patients with COVID-19. The outcomes of AIH patients who had acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection after at least one dose of COVID-19 vaccine were compared to unvaccinated patients with AIH. COVID-19 outcome was classified according to clinical state during the disease course as: (i) no hospitalization, (ii) hospitalization without oxygen supplementation, (iii) hospitalization with oxygen supplementation by nasal cannula or mask, (iv) intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v) ICU admission with invasive mechanical ventilation or (vi) death, and data was analyzed using ordinal logistic regression. Results: We included 413 (258 unvaccinated and 155 vaccinated) patients (81\%, female) with a median age of 52 (range: 17-85) years at COVID-19 diagnosis. The rates of hospitalization were (36.4\% vs. 14.2\%), need for any supplemental oxygen (29.5\% vs. 9\%) and mortality (7\% vs. 0.6\%) in unvaccinated and vaccinated AIH patients with COVID-19. Having received at least one dose of SARS-CoV-2 vaccine was associated with a significantly lower risk of worse COVID-19 severity, after adjusting for age, sex, comorbidities and presence of cirrhosis (adjusted odds ratio {[}aOR] 0.18, 95\% confidence interval {[}CI], 0.10-0.31). Overall, vaccination against SARSCoV-2 was associated with a significantly lower risk of mortality from COVID-19 (aOR 0.20, 95\% CI 0.11-0.35). Conclusions: SARS-CoV-2 vaccination significantly reduced the risk of COVID-19 severity and mortality in patients with AIH.OCT13
Polymeric Approach to Adjuvant System in Antibody Production against Leishmaniasis Based on Hybridoma Technology
Background: Leishmaniasis is a zoonotic disease, which is one of the serious public health problems in the world. Nowadays, antibody production using hybridoma technology may be a correct approach in terms of sensitivity in the diagnosis of diseases such as leishmaniasis. The aim of this study was investigation of the effectiveness of different adjuvants on polyclonal antibody production against L. tropica based on hybridoma technique.Methods: Accordingly, Freund's adjuvant (1956, M. tuberculosis), as a classic adjuvant in studies, was used comparatively with the non-toxic polymeric based Polyoxidonium adjuvant. All animal immunization procedures were conducted at Bezm-i Alem University Experimental Animal Research Center. The adjuvant response was tested both in the serum sample and in the antibodies produced by the hybridomas. The antibody titers were determined with ELISA.Results: Freund's and Polyoxidonium (PO) group blood titer's increased approximately 5.5 fold compared to control after the 6(th) and 8(th) immunization. Hybridomas produced from mice immunized with PO adjuvant induced only antigen-specific antibody response and did not develop an immune response against the adjuvant.Conclusion: Adjuvant selection is very important in terms of the specificity of antibody responses of cells produced in hybridoma technology. Therefore, PO is recommended as a new adjuvant system in this study.4OCT-DEC506-5161
The Effect of Discharging Patients with Low Hemoglobin Levels on Hospital Readmission and Quality of Life after Adult Spinal Deformity Surgery
Study design: Retrospective cohort. Purpose: This study aims to evaluate the impact of anemia on functional outcomes, health-related quality of life (HRQoL), and early hospital readmission (EHR) rates after adult spinal deformity (ASD) surgery at the time of discharge from the hospital. Overview of literature: Concerns with risks of transfusion, insufficient evidence for its benefits, and the possibility of associated adverse outcomes have led to restrictive transfusion practices. Therefore, patients are discharged according to patient blood management programs that are implemented in hospitals nationwide to reduce unnecessary blood transfusions. However, not many comprehensive kinds of studies exist on the effect of postoperative anemia on functional life and complications. Methods: Anemia severity was defined following the 2011 World Health Organization guidelines. All patients had HRQoL tests as well as complete blood counts pre- and postoperatively. EHR is the admission within 30 days of discharge and was used as the dependent parameter. Results: This study comprised 225 surgically treated ASD patients with a median age of 62.0 years, predominantly women (80\%). Of the 225 patients, 82, 137, and six had mild, moderate, and severe anemia at the time of discharge, respectively. Seventeen of the patients (mild {[}11, 64.7\%]moderate {[}5, 29.4\%]severe {[}1, 5.9\%]) were readmitted within 30 days. The mean hemoglobin values were higher in readmitted patients (p=0.071). Infection was the leading cause of readmission (n=12), but a low hemoglobin level was not observed in any of these patients at the time of discharge. Except for Scoliosis Research Society-22 questionnaire, HRQoL improvements did not reach statistical significance in early readmitted patients in the first year after surgery. Conclusions: The results of this study demonstrated that the occurrence and the severity of postoperative anemia are not associated with EHR in surgically treated patients with ASD. The findings of the current research suggested that clinical awareness of the parameters other than postoperative anemia may be crucial. Thus, improvements in HRQoL scores were poor in early readmitted patients 1 year after surgery.2APR261-2691
Safety, efficacy, and pharmacokinetics of gremubamab (MEDI3902), an anti-Pseudomonas aeruginosa bispecific human monoclonal antibody, in P. aeruginosa-colonised, mechanically ventilated intensive care unit patients: a randomised controlled trial
Background: Ventilator-associated pneumonia caused by Pseudomonas aeruginosa (PA) in hospitalised patients is associated with high mortality. The effectiveness of the bivalent, bispecific mAb MEDI3902 (gremubamab) in preventing PA nosocomial pneumonia was assessed in PA-colonised mechanically ventilated subjects. Methods: EVADE (NCT02696902) was a phase 2, randomised, parallel-group, double-blind, placebo-controlled study in Europe,Turkey, Israel, and the USA. Subjects >= 18 years old, mechanically ventilated, tracheally colonised with PA, and without new-onset pneumonia, were randomised (1:1:1) to MEDI3902 500, 1500 mg (single intravenous dose),or placebo. The primary efficacy endpoint was the incidence of nosocomial PA pneumonia through 21 days post-dose in MEDI3902 1500 mg versus placebo, determined by an independent adjudication committee. Results: Even if the initial sample size was not reached because of low recruitment, 188 subjects were randomised (MEDI3902 500/1500 mg: n =16/87placebo: n = 85) between 13 April 2016 and 17 October 2019. Out of these, 184 were dosed (MEDI3902 500/1500 mg: n =16/85placebo: n = 83), comprising the modified intent-to-treat set. Enrolment in the 500 mg arm was discontinued due to pharmacokinetic data demonstrating low MEDI3902 serum concentrations. Subsequently, enrolled subjects were randomised (1:1) to MEDI3902 1500 mg or placebo. PA pneumonia was confirmed in 22.4\% (n =19/85) of MEDI3902 1500 mg recipients and in 18.1\% (n = 15/83) of placebo recipients (relative risk reduction {[}RRR]: - 23.7\%80\% confidence interval {[}CI] - 83.8\%, 16.8\%p =0.49). At 21 days post-1500 mg dose, the mean (standard deviation) serum MEDI3902 concentration was 9.46 (7.91) mu g/mL, with 80.6\% (n =58/72) subjects achieving concentrations >1.7 mu g/mL, a level associated with improved outcome in animal models. Treatment-emergent adverse event incidence was similar between groups. Conclusions: The bivalent, bispecific monoclonal antibody MEDI3902 (gremubamab) did not reduce PA nosocomial pneumonia incidence in PA-colonised mechanically ventilated subjects.1NOV 152
Multi-Institutional Outcomes of Stereotactic Magnetic Resonance Image Guided Adaptive Radiation Therapy With a Median Biologically Effective Dose of 100 Gy(10) for Non-bone Oligometastases
Purpose: Randomized data show a survival benefit of stereotactic ablative body radiation therapy in selected patients with oligometastases (OM). Stereotactic magnetic resonance guided adaptive radiation therapy (SMART) may facilitate the delivery of ablative dose for OM lesions, especially those adjacent to historically dose-limiting organs at risk, where conventional approaches preclude ablative dosing. Methods and Materials: The RS Search Registry was queried for OM patients (1-5 metastatic lesions) treated with SMART. Freedom from local progression (FFLP), freedom from distant progression (FFDP), progression-free survival (PFS), and overall survival (LS) were estimated using the Kaplan-Meier method. FFLP was evaluated using RECIST 1.1 criteria. Toxicity was evaluated using Common Terminology Criteria for Adverse Events version 4 criteria. Results: Ninety-six patients with 108 OM lesions were treated on a 0.35 T MR Linac at 2 institutions between 2018 and 2020. SMART was delivered to mostly abdominal or pelvic lymph nodes (48.1\%), lung (18.5\%), liver and intrahepatic bile ducts (16.7\%), and adrenal gland (11.1\%). The median prescribed radiation therapy dose was 48.5 Gy (range, 30-60 Gy) in 5 fractions (range, 3-15). The median biologically effective dose corrected using an alpha/beta value of 10 was 100 Gy10 (range, 48-180). No acute or late grade 3+ toxicities were observed with median 10 months (range, 3-25) follow-up. Estimated 1-year FFLP, FFDP, PFS, and OS were 92.3\%, 41.1\%, 39.3\%, and 89.6\%, respectively. Median FFDP and PFS were 8.9 months (95\% confidence interval, 5.2-12.6 months) and 7.6 months (95\% confidence interval, 4.5-10.6 months), respectively. Conclusions: To our knowledge, this represents the largest analysis of SMART using ablative dosing for non-bone OM. A median prescribed biologically effective dose of 100 Gy10 resulted in excellent early FFLP and no significant toxicity, likely facilitated by continuous intrafraction MR visualization, breath hold delivery, and online adaptive replanning. Additional prospective evaluation of dose-escalated SMART for OM is warranted. (C) 2022 The Author(s). Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.6NOV-DEC
Anti-Inflammatory Effects of Melatonin in Rats with Induced Type 2 Diabetes Mellitus
Introduction: Insulin resistance is associated with a pro-inflammatory state increasing the risk for complications in patients with type 2 diabetes mellitus (T2DM). In addition to its chronobiotic effects, the pineal hormone melatonin is known to exert anti-inflammatory and antioxidant effects. Melatonin was also suggested to affect insulin secretion. The aim of this study was therefore to investigate the effect of melatonin on inflammation in diabetic rats and to study the possible involvement of the melatonin receptor, MT2. Materials and Methods: Male Sprague Dawley rats were randomly divided into four experimental groups (n = 10 per group): (1) control, (2) streptozotocin/nicotinamide induced diabetes type 2 (T2DM), (3) T2DM treated with melatonin (500 mu g/kg/day), and (4) T2DM treated with melatonin (500 mu g/kg/day for 6 weeks) and the selective MT2 receptor antagonist luzindole (0.25 g/kg/day for 6 weeks). Blood samples were taken for biochemical parameters and various tissue samples (liver, adipose tissue, brain) were removed for immunohistochemistry (IHC), Western blot (WB), and Q-PCR analyses, respectively. Results: Melatonin significantly reduced increased blood levels of liver transaminases (AST, ALT), blood urea nitrogen (BUN), triglyceride, very low-density lipoprotein (VLDL), and cholesterol in diabetic rats with luzindole treatment partly reversing this effect regarding the lipids. Furthermore, the liver and adipose tissues of T2DM rats treated with melatonin showed lower expression of the inflammatory markers IL-1 beta, IL-6, TNF-alpha, and NF-kappa B as compared to the T2DM group without melatonin. The results also showed that the MT2 receptor is at least partly involved in the protective effects of melatonin. Conclusions: Our results suggest that melatonin exerts relevant anti-inflammatory effects on various tissues in type 2 diabetic rats.4APR1
A New Risk-Scoring System for Colorectal Cancer and Polyp Screening by Turkish Colorectal Cancer and Polyp Study Group
Background: Colorectal cancer is one of the most commonly diagnosed types of cancer worldwide. An early diagnosis and detection of colon cancer and polyp can reduce mortality and morbidity from colorectal cancer. Even though there are a variety of options in screening tests, the question remains on which test is the most effective for the early detection of colorectal cancer. In this prospective study, we aimed to develop a simple, useful, effective, and reliable scoring system to detect colon polyp and colorectal cancer. Methods: We enrolled 6508 subjects over the age of 18 from 16 centers, with colonoscopy screening. The age, smoking status, alcohol consumption, body mass index polyp incidence, polyp size, number and localization, and pathologic findings were recorded. Results: The age, male gender, obesity, smoking, and family history were found as independent risk factors for adenomatous polyp. We have developed a new scoring system which can be used for these factors. With a score of 4 or above, we found the following: sensitivity 81\%, specificity 40\%, positive predictive value 25.68\%, and negative predictive value 89.84\%, for adenomatous polyp detectionand sensitivity 96\%, specificity 39\%, positive predictive value 3.35\%, negative predictive value 99.29\%, for colorectal cancer detection. Conclusion: Even though the first colorectal cancer screening worldwide is generally performed for individuals over 50 years of age, we recommend that screening for colorectal cancer might begin for those under 50 years of age as well. Individuals with a score >= 4 must be included in the screening tests for colorectal cancer.4APR286-2933
MYOTONOMETRIC EVALUATION OF LATENT MYOFASCIAL TRIGGER POINTS AND TAUT BAND IN ELITE ATHLETES
Introduction: Our aim was to identify the mechanical properties of the latent myofascial trigger points (MTrPs), the taut band and the non-taut band (surrounding muscle) within the gastrocnemius muscle using the myotonometric evaluation method. Material and Methods: Thirty-one asymptomatic elite rugby players (23.0 +/- 4.16 y, 97.5 +/- 22.1 kg, 183.5 +/- 7.6 cm) with a latent MTrP in lateral gastrocnemius muscle included in this study. Muscle stiffness, decrement and muscle tone of latent MTrPs, taut band and the non-taut band were measured using a myotonometer (MyotonPRO, Myoton AS, Tallinn, Estonia). One-way ANOVA was conducted to determine the differences between the three measurement points. After pairwise comparisons, Cohen's d effect sizes were calculated to determine the magnitude of differences between the measurement points. Results: Although the stiffness of the latent MTrPs was lower than its taut band, one-way ANOVA revealed that there was no difference between the latent MTrPs vs the taut band and the non-taut band for frequency, stiffness and decrement parameters (p>0.05). However, there was a difference between the taut band non-taut band for muscle tone (P= 0.016), for stiffness (P=0.035) and for decrement (P=0.012) and effect sizes were as d=0.64, d=0.69 and d=0.62 for stiffness, muscle tone and decrement respectively. Conclusion: The MTrPs and the taut bands showed an increase in muscle stiffness and muscle tone compared to the surrounding muscle. The taut band can be easily identified from the surrounding muscle using the myotonometer. Therefore, myotonometric measurement is a potentially valuable method for the identification of the taut band in elite athletes.274-80