Publications by authors named "A Cevik Tufan"

257 Publications

Activation Syndrome in a Patient With Attention-Deficit/Hyperactivity Disorder Treated With Atomoxetine: A Case Report.

Clin Neuropharmacol 2021 Mar 4. Epub 2021 Mar 4.

Department of Child and Adolescent Psychiatry, Ankara Training and Research Hospital, Ankara Department of Child and Adolescent Psychiatry, Uskudar University Faculty of Medicine, Istanbul Department of Child and Adolescent Psychiatry, Abant Izzet Baysal University Faculty of Medicine, Bolu, Turkey.

Abstract: "Activation syndrome" represents a cluster of symptoms of excessive emotional arousal or behavioral activation, which emerges after the first few weeks of antidepressant treatment or a dose increase and resolves with dose reduction or cessation of treatment. It was reported after treatment with selective serotonin reuptake inhibitor and serotonin-norepinephrine reuptake inhibitor group of agents, but no case of activation syndrome has been reported with the norepinephrine reuptake inhibitor group. Atomoxetine is a norepinephrine reuptake inhibitor and nonstimulant and is used to manage symptoms of attention-deficit/hyperactivity disorder (ADHD). Atomoxetine-related symptoms of mania and hypomania were reported in literature previously. Here, we report a case of activation syndrome arising after atomoxetine (ATX) dose titration in a prepubertal male child with ADHD. Differentiation of activation symptoms from mania/hypomania symptoms after treatment with ATX may be important for the clinicians to manage the adverse effects and understand the risk factors behind activation syndrome with use of ATX in children and adolescents diagnosed with ADHD.
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http://dx.doi.org/10.1097/WNF.0000000000000447DOI Listing
March 2021

Traumatic experiences of conditional refugee children and adolescents and predictors of post-traumatic stress disorder: data from Turkey.

Nord J Psychiatry 2021 Feb 16:1-7. Epub 2021 Feb 16.

Department of Child and Adolescent Psychiatry, Child and Adolescent Psychiatrist, Abant İzzet Baysal Universtiy, Bolu, Turkey.

Aim: We aimed to determine traumatic events, mental health problems and predictors of PTSD in a sample of conditional refugee children.

Methods: The sociodemographic features, chief complaints, traumatic experiences and psychiatric diagnoses according to DSM-5 were evaluated retrospectively.

Results: 20.7% ( = 70) of children experienced the armed conflict or exposed to firefights at their country of origin. Most common diagnoses were anxiety disorders ( = 82, 24.3%), major depressive disorder ( = 52, 15.4%) and PTSD ( = 43, 12.7%). Age, number of traumatic experiences, explosion and sexual violence are the most important predictors for PTSD.

Conclusions: Our results suggest that the number of traumas exposed as well as their nature predicted PTSD diagnosis. Refugee children have increased risk for psychiatric problems after migration and resettlement underlining the importance of an adequate follow-up for mental health and ensuring social support networks.
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http://dx.doi.org/10.1080/08039488.2021.1880634DOI Listing
February 2021

Work productivity impairment in patients with familial Mediterranean fever and effects of interleukin-1 antagonists.

Clin Rheumatol 2021 Feb 1. Epub 2021 Feb 1.

Division of Rheumatology, Department of Internal Medicine, Gazi University Faculty of Medicine, 06100, Ankara, Turkey.

Introduction: Familial Mediterranean fever (FMF) is characterized by recurrent attacks of fever, serositis, and arthritis. Some patients suffer from associated inflammatory conditions and damage related to FMF that may potentially impair work productivity which have not been studied to date.

Methods: Consecutive FMF patients who were attending a tertiary referral center and age-and sex-matched healthy subjects enrolled into the study. Disease activity was assessed with autoinflammatory disease activity index (AIDAI) and patient global assessment. Damage was evaluated using Autoinflammatory Disease Damage Index (ADDI). Quality of life (QoL) and work productivity were determined with 36-Item Short Form Health Survey (SF-36) and Work Productivity and Activity Impairment Specific Health Problem v2.0 (WPAI:SHP), respectively.

Results: There were 111 FMF patients, 60 female (54%), mean age 32.7±8.7 years. There were significant impairments in all domains of the SF-36 QoL in FMF patients. Of the 111 patients enrolled, 65 (58.6%) were employed in a paid work. Mean% ±SD impairment in work productivity both assessed as absenteeism (9.3±23.2% vs. 0.7±2.6, p=0.013) and presenteeism (35.2±32.6% vs. 9.6±14.7, p<0.001) were significantly higher in FMF patients compared to healthy subjects. Impairment in work productivity was correlated with the number of attacks, disease activity, colchicine resistance, and disease-associated damage. Impairment was most significant in colchicine-resistant FMF patients but lower in those on interleukin (IL)-1 antagonist treatments.

Conclusions: FMF causes significant work impairment and reduced QoL which is associated with disease activity and damage. The use of IL-1 antagonists may help to improve work productivity and QoL in FMF patients with frequent attacks. Key points • Work productivity is impaired in patients with FMF. • Disease activity was an independent predictor for impaired work productivity. • IL-1 antagonists may improve work productivity and quality of life in FMF patients with frequent attacks.
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http://dx.doi.org/10.1007/s10067-021-05617-7DOI Listing
February 2021

Muscle strength cutoff values calculated from the young reference population to evaluate sarcopenia in Turkish population.

Aging Clin Exp Res 2021 Jan 27. Epub 2021 Jan 27.

Division of Geriatrics, University of Ramon Y Cajal, Madrid, Spain.

Sarcopenia is defined as a progressive and generalized skeletal muscle disorder that is associated with an increased likelihood of adverse outcomes, including mobility problems and mortality. To reach a global consensus for its standard definition and diagnosis, more recently, a revised EWGSOP consensus (EWGSOP2) has been published. In EWGSOP2 definition, sarcopenia has been regarded as skeletal muscle failure and low muscle strength has been put forward as its key defining characteristics. EWGSOP2 suggested the use of handgrip strength cutoff values calculated by mean minus 2.5 standard deviations of the young healthy population. In this report, following EWGSOP2's suggestion, we aimed to outline the handgrip strength cutoffs derived from a young Turkish reference population, and compare them with the other population-specific reports.
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http://dx.doi.org/10.1007/s40520-021-01785-3DOI Listing
January 2021

Association of Disease Characteristics with the Temporal Sequence of Skin and Musculoskeletal Disease Onset in Psoriatic Arthritis.

Br J Dermatol 2021 Jan 22. Epub 2021 Jan 22.

Hacettepe University, Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Ankara, Turkey.

The temporal relationship between the onset of skin psoriasis (Pso) and psoriatic arthritis (PsA) is a long and well-known feature of psoriatic disease. Psoriatic skin lesions emerge years before the development of musculoskeletal manifestations in nearly 75% of PsA patients. While skin and joint manifestations develop within one year in 15-20% of the patients, joint manifestations precede the skin involvement by a year or more in about 10% of the patients (1).
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http://dx.doi.org/10.1111/bjd.19826DOI Listing
January 2021

The assessment of serum ACE activity in COVID-19 and its association with clinical features and severity of the disease.

Scand J Clin Lab Invest 2021 Jan 21:1-6. Epub 2021 Jan 21.

Faculty of Medicine, Rheumatology Department, Gazi University Hospital, Ankara, Turkey.

Angiotensin-converting enzyme (ACE)/Angiotensin (Ang) II pathway has crucial regulatory effects on circulatory hemostasis and immune responses. This pathway has a major role in the development of acute lung injury and acute respiratory distress syndrome (ARDS), which is a devastating complication of SARS-CoV-2 infection. The aim of this study is to investigate the serum ACE activity and its correlation with clinical features and the disease severity in patients with COVID-19. Patients with confirmed COVID-19 by detecting SARS-CoV-2 nucleic acid RT-PCR were included in the study. Demographic data, clinical features, laboratory and radiologic investigations were recorded. Patients were classified by disease severity; asymptomatic, mild, and severe pneumonia. The serum ACE activity was evaluated with an autoanalyzer based on a spectrophotometric method. Fifty-five patients (50.9% female) and 18 healthy subjects (33.3 % female) were enrolled in the study. The median age of patients was 40 years, ranging from 22 to 81 years. Eighteen healthy subjects were served as the control group. The baseline characteristics were comparable between groups. The median serum ACE activity of patients and controls (38.00 [IQR 21] U/L and 32.00 [IQR 24] U/L, respectively) and of between patients grouped by disease severity (38.5 [IQR 19], 36 [IQR 25], and 38 [IQR 22] U/L, asymptomatic, mild and severe pneumonia group, respectively) were similar. There was no correlation between the serum ACE activity and conventional inflammatory markers. In this study, we did not find an association between serum ACE activity and COVID-19 and serum ACE activity on admission did not reflect disease severity.
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http://dx.doi.org/10.1080/00365513.2021.1871641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832453PMC
January 2021

APPENDECTOMY HISTORY IS ASSOCIATED WITH SEVERE DISEASE AND COLCHICINE RESISTANCE IN ADULT FAMILIAL MEDITERRANEAN FEVER PATIENTS.

Turk J Med Sci 2021 Jan 18. Epub 2021 Jan 18.

Background/objective: Peritonitis attacks of Familial Mediterranean Fever (FMF) usually requires emergency medical admissions and it?s hard to distinguish a typical abdominal attack from surgical causes of acute abdomen. Therefore, history of abdominal surgery, particularly appendectomy, is very common in patients with FMF. However, history of appendectomy might also give some clues about the disease in the course of FMF in adulthood. This study was to determine whether the history of appendectomy help to anticipate disease course of FMF in adulthood.

Methods: All patients recruited from FMF in Central Anatolia (FiCA) cohort, comprising 971 adult subjects. All patients fulfilled the Tel Hashomer criteria. Demographic data, FMF disease characteristics, co-morbid conditions, past medical history, surgical history and disease complications were meticulously questioned and laboratory features and genotype data (if available) were recruited from patient files.

Results: Appendectomy history was evident in 240 (24.7%) subjects. Disease onset was earlier and peritonitis is strikingly more prevalent (97.1% vs 89.6%, p<0.001) in appendectomy patients. These patients had reported almost two fold more frequent attacks in the last year compared to appendix intact patients (median 3.5 vs 2 attacks, p=0.001) without a difference in frequency of musculoskeletal and skin attacks. Severe disease was more common (10% vs 5.9%, p=0.038) due to involvement of more disease sites throughout life and more frequent attacks. Appendectomy patients had used higher daily doses of colchicine to control disease (1.43±0.6 mg vs 1.27±0.52 mg, p=0.002) but colchicine resistance was also more common in these patients, 15% vs 6.7% respectively, p<0.001.

Conclusions: Appendectomy history is common in FMF patients and associated with frequent serositis attacks in adulthood. These patients require higher colchicine doses with a lower rate of response and more need for Interleukin-1 antagonist therapies.
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http://dx.doi.org/10.3906/sag-2011-74DOI Listing
January 2021

High Depression Symptoms and Burnout Levels Among Parents of Children with Autism Spectrum Disorders: A Multi-Center, Cross-Sectional, Case-Control Study.

J Autism Dev Disord 2021 Jan 18. Epub 2021 Jan 18.

Department of Medical Genetics, Başkent University, Adana Dr. Turgut Noyan Medical and Research Center, Adana, Turkey.

The diagnosis of autism spectrum disorder (ASD) in a child affects family processes, increases parenting stress and marital conflicts, and may lead to parental psychopathology. It may also affect the prognosis for their children. The aim of this study is to determine depression and burnout levels as well as their predictors among parents of children with ASD compared with those of healthy children. We also sought to evaluate rate of complementary and alternative medicine (CAM) interventions among parents and explore the associations of this phenomenon in an exploratory fashion. 145 children with ASD and 127 control children were enrolled along with their mothers and fathers. Beck Depression Inventory and Maslach Burnout Inventory were used to evaluate parents' depression symptoms and burnout levels. Symptoms of children with ASDs were evaluated according to the Childhood Autism Rating Scale by the clinicians. Family, child and CAM variables were screened by means of a sociodemographic data form. Descriptive, bivariate and correlation analyses were used in statistical evaluations. Predictors of burnout were evaluated with multiple regression analysis. Burnout and depression levels among parents of children with ASD were significantly elevated compared to controls. Burnout levels of mothers were significantly elevated compared to fathers while depression scores of fathers were significantly elevated compared to mothers. Maternal burnout was significantly predicted by presence of functional speech in child while paternal burnout was significantly predicted by paternal vocation. Maternal depression was associated with paternal depression, lack of speech in child and attendance of child to special education services. Paternal depression was associated with autistic symptom severity and maternal depression. More than half the parents sought CAM interventions. Education level did not affect search for CAM interventions while both maternal and paternal psychopathology and presence of epilepsy among children increased use of CAM methods. Psychological support should be provided to both mothers and fathers of a child receiving a diagnosis of ASD. Addressing parents' burnout and stress levels and facilitating their negotiation of knowledge on etiology and treatments for ASD may be beneficial for the family unit as a whole.
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http://dx.doi.org/10.1007/s10803-021-04874-4DOI Listing
January 2021

Transcriptional repression of NFKBIA triggers constitutive IKK- and proteasome-independent p65/RelA activation in senescence.

EMBO J 2021 Jan 18:e104296. Epub 2021 Jan 18.

Signal Transduction in Tumor Cells, Max Delbrück Center for Molecular Medicine, Berlin, Germany.

The IκB kinase (IKK)-NF-κB pathway is activated as part of the DNA damage response and controls both inflammation and resistance to apoptosis. How these distinct functions are achieved remained unknown. We demonstrate here that DNA double-strand breaks elicit two subsequent phases of NF-κB activation in vivo and in vitro, which are mechanistically and functionally distinct. RNA-sequencing reveals that the first-phase controls anti-apoptotic gene expression, while the second drives expression of senescence-associated secretory phenotype (SASP) genes. The rapidly activated first phase is driven by the ATM-PARP1-TRAF6-IKK cascade, which triggers proteasomal destruction of inhibitory IκBα, and is terminated through IκBα re-expression from the NFKBIA gene. The second phase, which is activated days later in senescent cells, is on the other hand independent of IKK and the proteasome. An altered phosphorylation status of NF-κB family member p65/RelA, in part mediated by GSK3β, results in transcriptional silencing of NFKBIA and IKK-independent, constitutive activation of NF-κB in senescence. Collectively, our study reveals a novel physiological mechanism of NF-κB activation with important implications for genotoxic cancer treatment.
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http://dx.doi.org/10.15252/embj.2019104296DOI Listing
January 2021

Drug holidays may not affect processing speed while they may reduce beneficial effects on resistance to interference among children with treated with methylphenidate: a single-center, prospective study.

Nord J Psychiatry 2020 Dec 25:1-7. Epub 2020 Dec 25.

Department of Child and Adolescent Psychiatry, Dokuz Eylul University Medical Faculty, Izmir, Turkey.

Objective: This study aimed to investigate the effects of drug holidays during summer vacations among children with attention deficit/hyperactivity disorder (ADHD) who were treated with methylphenidate in terms of ADHD symptoms and executive functions.

Methods: The study was a prospective cohort study that includes pre-treatment, post-treatment and post-drug holiday evaluations. ADHD symptom severity was evaluated with the Clinical Global Impression Scale (CGI), the Conners' Parental Rating Scale-Short Form (CPRS) and the Conners' Teacher Rating Scale- Short Form (CTRS). The Stroop Color Word Test- TBAG Form (SCWT) was used to evaluate executive functions. Fifty-one patients participated in the study according to the inclusion and exclusion criteria. Methylphenidate (MPH) was started at 0.5 mg/kg/day and titrated weekly to a maximum of 1.2 mg/kg/day. During the follow-up period, 22 (43.0%) of the patients stopped treatment.

Results: Completion times for all SCWT subtests were significantly reduced after treatment ( < 0.001,  = 0.002,  < 0.001,  = 0.002,  < 0.001; respectively). Mean number of corrections in SCWT-3 and mean number of errors as well as corrections in SCWT-5 significantly reduced after treatment ( = 0.047,  = 0.005,  = 0.007; respectively). Mean number of corrections in SCWT-3 and mean number of errors in SCWT-5 increased significantly after drug holiday compared to post-treatment ( = 0.032 and  = 0.037; respectively).

Conclusion: Our results suggest that psychomotor speed and resistance to interference improved in children with ADHD receiving methylphenidate treatment. Drug holidays did not affect psychomotor speed while beneficial effects on resistance to interference were reduced with drug holidays.
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http://dx.doi.org/10.1080/08039488.2020.1855242DOI Listing
December 2020

Serum defensin levels in patients with systemic sclerosis.

Adv Rheumatol 2020 12 22;60(1):54. Epub 2020 Dec 22.

Department of Internal Medicine, Division of Rheumatology, Gazi University Faculty of Medicine, Ankara, Turkey.

Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of skin and lung as well as involvement of kidney, gastrointestinal system and heart. Aetiology and exact mechanism of disease is poorly understood. The association between antimicrobial peptides (AMPs) and other diseases such as idiopathic pulmonary fibrosis, diffuse panbronchiolitis, pulmoner alveolar proteinosis and psoriasis have been reported. A small number of studies have examined the role of AMPs on autoimmune diseases which has not been studied in scleroderma yet. We aimed to investigate AMP serum levels and their association with disease characteristics of SSc.

Methods: Forty-two patients (40 female, mean age 42 years) and 38 healthy subjects (32 female, mean age 38 years) were enrolled. For SSc patients, the following data were recorded: disease subset (limited/diffuse), autoantibodies (antinuclear, anti-centromere (ACA), and anti-SCL-70), blood tests, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), modified Rodnan skin score, presence and history of digital ulcers, kidney, gastrointestinal disease and lung involvement assessed by computed tomography and pulmonary function tests. Association between serum AMPs and disease characteristics were analysed.

Results: Twenty-nine of the patients had diffuse (69%) and 13 of the patients had limited (31%) systemic sclerosis. Average disease duration was 5.5 years. Pulmonary involvement was detected in 20 patients (47.6%). Serum concentration of alpha defensin was higher than healthy subjects (563 ± 415 vs 377 ± 269 ng/mL, p = 0.02). However, no difference was observed for beta-1 and beta-2 defensins in SSc patients and healthy controls. In sub-group analysis patients with interstitial lung disease had higher levels of alpha defensin than those without lung involvement (684 ± 473 vs 430 ± 299 ng/ml, p = 0.04). There was also correlation between alfa defensin serum concentrations and CRP (r = 0.34).

Conclusions: Alpha defensin levels are increased in scleroderma patients and correlated with lung involvement indicating a role in the pathogenesis of disease.

Trial Registration: This study is not a clinical trial study.
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http://dx.doi.org/10.1186/s42358-020-00156-2DOI Listing
December 2020

COVID 19 SCIENTIFIC PUBLICATIONS FROM TURKEY.

Turk J Med Sci 2020 Dec 11. Epub 2020 Dec 11.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak poses a major global threat to the public health Worldwide. The infectious disease caused by the virus that affected the entire world was named as the Coronavirus disease-2019 (COVID-19). The knowledge regarding the wide clinico-biological aspects of the COVID-19 continues to evolve very rapidly, given the growing data from all over the World. During this complicated process, healthcare professionals have benefited from each other?s experiences in combatting against the COVID-19 syndrome. COVID-19 related studies have been performed by a wide variety of research groups in Turkey as well as the rest of the World. The aim of this paper is to outline Turkish COVID-19 research indexed in LitCovid system. LitCovid is a curated literature hub for tracking up-to-date scientific data about the SARS-CoV-2. COVID-19?s first case was detected in Turkey, on March 11th, 2020. Six months after the first case was observed, the total number of COVID-19 patients was reported to be as 286.455, and the total number of deaths due to SARS-CoV-2 was 6895. The genetic sequence of the novel coronavirus showed significant identity to SARS-CoV and MERS-CoV. Numerous drugs including lopinavir/ritonavir, favipiravir, neuraminidase inhibitors, remdesivir, umifenovir, azithromycin and chloroquine have been suggested for the management of COVID-19 although the exact treatment yet to be determined.
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http://dx.doi.org/10.3906/sag-2010-261DOI Listing
December 2020

Compliance of Familial Mediterranean Fever Patients With Regular Follow-up Visits and Associated Factors.

J Clin Rheumatol 2020 Dec 8. Epub 2020 Dec 8.

From the Division of Rheumatology, Department of Internal Medicine.

Background: Follow-up is crucial to detect asymptomatic complications of familial Mediterranean fever (FMF). The current European League Against Rheumatism recommendations state that patients with FMF should be evaluated at least every 6 months to monitor attacks, acute phase response, and proteinuria.

Objectives: This study aimed to assess compliance of FMF patients with regular follow-up visits and the associated factors.

Methods: Adult patients with a diagnosis of FMF who had their initial visit at least over 1 year ago were included. Demographic and socioeconomic data, family history, and comorbid diseases were obtained from medical records. The International Severity Score for FMF and the Autoinflammatory Disease Damage Index scores were calculated. We defined patients as "compliant with follow-up visits" both if they had at least 2 visits during the previous year and a compatible physician's assessment. The characteristics of the compliant and noncompliant patients were compared, and multivariable logistic regression analysis was used to determine the factors influencing visit compliance.

Results: Four hundred seventy-four patients with FMF were included. Two hundred thirty (48.5%) were compliant, and 244 (51.5%) were noncompliant with follow-up visits. A family history of FMF in parents, the absence of a family history of FMF in siblings, treatment with biologic agents, concomitant medication use, multisite involvement during FMF attacks, and treatment satisfaction were independent predictors of visit compliance.

Conclusions: Only half of the patients with FMF were compliant with follow-up visits. Better strategies should be implemented to increase the compliance of FMF patients. Identifying independent predictors would help to build one.
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http://dx.doi.org/10.1097/RHU.0000000000001632DOI Listing
December 2020

Association of Core Muscle Endurance Times With Balance, Fatigue, Physical Activity Level, and Kyphosis Angle in Patients With Ankylosing Spondylitis.

J Clin Rheumatol 2020 Nov 24. Epub 2020 Nov 24.

From the Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences.

Background/objective: Core muscle endurance (CME), which is the ability of sustaining the activity of trunk muscles, has been shown to be lower in patients with ankylosing spondylitis (AS). The aim was to investigate the possible relationship between CME times and balance, fatigue, physical activity (PA) level, and thoracic kyphosis angle.

Methods: Fifty-one patients with AS with a mean age of 41.0 years (interquartile range, 25/75 years; 29.0/51.0 years) were included in the study. Core muscle endurance times were assessed by using trunk extension, trunk flexion, and side bridge tests. Overall stability index, anteroposterior stability index, mediolateral stability index, and limits of stability were evaluated with the Biodex Balance System. Fatigue and PA levels were surveyed using Fatigue Severity Scale and International Physical Activity Questionnaire, respectively. Thoracic kyphosis angle was measured by using a digital inclinometer. Additionally, CME times were compared for "high-fatigue" versus "low-fatigue" and as "low PA" versus "moderate/high PA" groups. Spearman correlation coefficients and Mann-Whitney U test were used for statistical analysis.

Results: Significant correlations were detected between overall stability index, anteroposterior stability index, Fatigue Severity Scale, International Physical Activity Questionnaire, and all CME tests (p < 0.05) and between mediolateral stability index and side bridge test (p < 0.05). Limits of stability correlated only with side bridge test (p < 0.05). Core muscle endurance significantly differed between high-fatigue and low-fatigue groups (p < 0.05), except trunk flexor test (p > 0.05). No significant differences were observed between low PA and moderate/high PA groups (p > 0.05), except side bridge test (p < 0.05).

Conclusions: Core muscle endurance times seem to be related to PA level, fatigue, and balance but not with thoracic kyphosis angle. Assessing CME in patients with AS might help in planning individualized exercise programs.
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http://dx.doi.org/10.1097/RHU.0000000000001641DOI Listing
November 2020

Mesenchymal stem Cells as a Treatment Strategy for Coronavirus Disease 2019 (COVID-19): Need for Authority Regulations and Clinical Guidelines.

Curr Stem Cell Res Ther 2020 Nov 24. Epub 2020 Nov 24.

Department of Histology and Embryology, School of Medicine, Ankara Yıldırım Beyazıt University, Ankara,. Turkey.

The cause of coronavirus disease 2019 (COVID-19) known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, formerly designated 2019-nCoV) was first discovered in December 2019 in Wuhan, China. It then spread rapidly worldwide. Investigation for discovery of drugs to cure this disease continues. The currently accepted treatments are supportive but there is no specific disease curing intervention found yet. Since mid-February, therapies involving mesenchymal stem/stromal cells (MSCs) have been proposed for the treatment of patients with COVID-19. In light of these recent developments this review will focus on: i) the mechanism of SARS-CoV-2 action and the subsequent pathology in COVID-19, ii) the proposed mechanism(s) of outcome-improving action of MSCs or MSC-derived extracellular vesicles in COVID-19 pneumonia, iii) registered MSC-based clinical trials and interventions for the treatment of COVID-19, iv) published case studies/series/trials reporting the use of MSC-based treatments in COVID-19 cases, and finally v) the need for authority regulations and clinical guidelines for MSC-based treatment strategies for COVID-19.
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http://dx.doi.org/10.2174/1574888X16999201124224816DOI Listing
November 2020

E-mentoring program organized by the Turkish Association for Child and Adolescent Psychiatry during the COVID-19 pandemic.

Eur Child Adolesc Psychiatry 2021 01;30(1):173-175

Child and Adolescent Psychiatry Department, Medical Faculty, Fırat University, Elazıg, Turkey.

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http://dx.doi.org/10.1007/s00787-020-01671-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681764PMC
January 2021

Hypercalcemia in a Patient With Granulomatosis With Polyangiitis.

Am J Kidney Dis 2020 11;76(5):A18-A20

Nephrology, Gazi University, Ankara, Turkey.

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http://dx.doi.org/10.1053/j.ajkd.2020.05.029DOI Listing
November 2020

Prognostic value of interleukin-18 and its association with other inflammatory markers and disease severity in COVID-19.

Cytokine 2021 01 29;137:155302. Epub 2020 Sep 29.

Gazi University, Faculty of Medicine, Hospital Rheumatology Department, Ankara, Turkey.

Background: The effectual immune response is crucial to defeat viral infections. However, exuberant immune response with features of macrophage activation syndrome (MAS) lead detrimental consequences in COVID-19 patients. Interleukin (IL)-18 is one of the leading cytokines in MAS which has not been studied in COVID-19.

Objective: To investigate the association of IL-18 with the other inflammatory markers and disease severity in COVID-19 for predicting disease prognosis.

Methods: Patients with COVID-19 who had confirmed diagnosis with SARS-CoV-2 nucleic acid RT-PCR were enrolled into the study. Data on demographic and clinical characteristics, and laboratory values of CRP, ferritin, d-dimer and procalcitonin were measured on admission. Patients were followed up prospectively with a standardized approach until hospital discharge or death. Individuals were classified as asymptomatic, mild and severe pneumonia according to their clinical, laboratory and radiological characteristics. Worse outcome was defined as requirement of intensive care unit (ICU) admission or death. Blood samples were collected at enrollment and serum levels of IL-6 and IL-18 were determined by ELISA. Association between IL-18 and other inflammatory markers and prognosis were analyzed.

Results: There were 58 COVID-19 patients (50% male) with a median age of 43 (min 22-max 81) years. Twenty age and sex matched healthy subjects were served as control group. The study population was divided into three groups according to disease severity: asymptomatic (n = 20), mild pneumonia group (n = 27) and a severe group (n = 11). During follow up nine (15.5%) patients required ICU admission and three of them were died eventually. Serum IL-18 were correlated with other inflammatory markers and biochemical markers of organ injury; creatinine, liver enzymes and troponin. Serum IL-18 levels were remarkably higher in COVID-19 patients compared to healthy subjects with being highest in severe pneumonia group (p < 0.001). IL-18 serum concentrations were almost four-fold higher in patients with worse outcome compared to good outcome (p < 0.001). Serum IL-18 above the cut off value of 576 pg/mL on admission was associated with 11.7 fold increased risk of ICU admission.

Conclusions: The serum concentrations of IL-18 correlate with other inflammatory markers and reflect disease severity. Results of the present study shed light on role of IL-18 on COVID-19 pathogenesis and might provide an evidence for the clinical trials on IL-18 antagonists for the treatment of severe COVID-19 patients.
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http://dx.doi.org/10.1016/j.cyto.2020.155302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522034PMC
January 2021

Familial Mediterranean fever, from pathogenesis to treatment: a contemporary review

Turk J Med Sci 2020 11 3;50(SI-2):1591-1610. Epub 2020 Nov 3.

National Amyloidosis Centre, Royal Free London NHS Foundation Trust and University College London, London, UK

Familial Mediterranean fever (FMF) (OMIM #249100) is the most common hereditary autoinflammatory disease in the world. FMF is caused by gain of function mutations of MEFV gene which encodes an immune regulatory protein, pyrin. Over the last few years, we have witnessed several new developments in the pathogenesis, genetic testing, diagnosis, comorbidities, disease related damage and treatment approaches to FMF. Elucidation of some of the pathogenic mechanisms has led to the discovery of pathways involved in inflammatory, metabolic, cardiovascular and degenerative diseases. The use of next generation sequencing in FMF has revealed many new gene variants whose clinical significance may be clarified by developing functional assays and biomarkers. Clinically, although FMF is considered an episodic disease characterized by brief attacks, recent systematic studies have defined several associated chronic inflammatory conditions. Colchicine is the mainstay of FMF treatment, and interleukin (IL)-1 antagonists are the treatment of choice in refractory or intolerant cases. Experience of IL-1 antagonists, anakinra and canakinumab, is now available in thousands of colchicine resistant or intolerant FMF patients. In this contemporary review, we surveyed current FMF knowledge in the light of these recent advances.
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http://dx.doi.org/10.3906/sag-2008-11DOI Listing
November 2020

Predictors of persistent inflammation in familial Mediterranean fever and association with damage.

Rheumatology (Oxford) 2021 Jan;60(1):333-339

Department of Internal Medicine, Division of Rheumatology, Faculty of Medicine, Gazi University, Ankara.

Objective: Persistent inflammation is an insidious and less studied feature of FMF. We investigated clinical determinants of persistent inflammation and its associations with individual damage items.

Methods: This is a cross-sectional analysis of 917 FMF patients, who fulfilled the Tel Hashomer criteria and had at least 6 months' follow-up. Patients were stratified based on whether they had persistent inflammation. We used logistic regression analysis to investigate independent predictors of persistent inflammation and the associated individual damage items.

Results: One hundred and forty-two (15%) patients had persistent inflammation. Active FMF (54%) was the most prominent reason for the persistent inflammation. Spondylarthritis (16%), other inflammatory arthritis (8%) and IBD (2%) were other frequent reasons. Male gender, history of exertional leg pain, inflammatory comorbidities, M694V homozygosity, colchicine resistance, lower education levels and musculoskeletal attack dominance were found to be the independent predictors of persistent inflammation. Earlier disease onset led to a tendency towards persistent inflammation. Patients with persistent inflammation were more likely to suffer damage. There is an increased risk of developing proteinuria, amyloidosis and renal insufficiency.

Conclusion: We identified, for the first time, the predictors of persistent inflammation in adult FMF patients and related individual damage items of the Autoinflammatory Disease Damage Index. Persistent inflammation is insidious and one of the chief causes of damage; therefore, especially patients with these predictors should be followed up more closely. If detected, underlying inflammatory comorbidities should be assessed meticulously as early detection and proper treatment strategies may favourably impact the natural history of the disease.
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http://dx.doi.org/10.1093/rheumatology/keaa378DOI Listing
January 2021

Anakinra for the Treatment of COVID-19-Associated Pericarditis: A Case Report.

Cardiovasc Drugs Ther 2020 12 30;34(6):883-885. Epub 2020 Jul 30.

Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.

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http://dx.doi.org/10.1007/s10557-020-07044-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391046PMC
December 2020

Use of prognostic nutritional index in the evaluation of disease activity in patients with Behçet's disease.

Eur J Rheumatol 2020 Jul 21;7(3):99-104. Epub 2020 Jul 21.

Division of Rheumatology, Department of Internal Medicine, Gazi University School of Medicine, Ankara, Turkey.

Objective: Behçet's disease (BD) is a chronic, multisystem disorder that can cause severe morbidity and mortality. Monitoring tools that measure disease activity are required for effective management of BD. We aimed to investigate the association of prognostic nutritional index (PNI) with disease activity in BD.

Methods: In this cross-sectional study, we enrolled 88 adult patients with BD and 51 healthy controls. The patients were divided into patients with active and inactive BD according to their disease activities. PNI was calculated using the following formula: 10×serum albumin (g/dL)+0.005×peripheral lymphocyte count (per mm3). To evaluate BD activity, the Behçet Disease Current Activity Form was used. The relations of BD activity with PNI, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, erythrocyte sedimentation rate, and C-reactive protein were investigated. A receiver operator characteristic curve analysis was used to define the optimum cutoff value of PNI for active BD.

Results: A total of 48 patients were classified as having active BD and 40 as having inactive BD. Patients with active BD had lower mean PNI than patients with inactive BD and healthy controls (51.8±4.2, 57.4±2.9, and 56.6±3.6, respectively; p<0.001). In multivariate analysis, PNI was the only independent predictor of BD activity (odds ratio, -0.687; 95% confidence interval 0.548-0.861; p=0.001). The optimum cutoff of PNI for active BD was 55.35 with 79.2% sensitivity and 77.75% specificity.

Conclusion: PNI was significantly associated with BD activity. PNI may be a useful tool for the assessment of disease activity in BD.
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http://dx.doi.org/10.5152/eurjrheum.2020.20010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431357PMC
July 2020

Disease characteristics of psoriatic arthritis patients may differ according to age at psoriasis onset: cross-sectional data from the Psoriatic Arthritis-International Database.

Clin Exp Rheumatol 2020 Jun 30. Epub 2020 Jun 30.

Division of Rheumatology, Department of Internal Medicine, Hacettepe University, Ankara, Turkey.

Objectives: To explore the impact of early versus late-onset psoriasis (PsO) on the disease characteristics of psoriatic arthritis (PsA) in a large-multicentre cohort.

Methods: The data from a multicentre psoriatic arthritis database was analysed. Patients were grouped according to age at psoriasis onset (early onset; <40 years of age, late-onset; >40 years of age) and disease characteristics of the groups were compared by adjusting for BMI and PsA duration, where necessary.

Results: At the time of analyses, 1634 patients were recruited [62.8% females; early onset 1108 (67.8%); late-onset, 526 (32.2%)]. The late-onset group was more over-weight [66.8% vs. 86.8%, p<0.001; adjusted for age - aOR 1.55 (1.11-2.20; 95% CI)]. The early onset group had more scalp psoriasis at onset (56.7% vs. 43.0%, p<0.001), whereas extremity lesions were more common in the late-onset group (63.8% vs. 74.2%, p<0.001). Axial disease in males and psoriatic disease family history in females were significantly higher in the early onset group [38.0% vs. 25.4%; p=0.005; adjusted for PsA duration - aOR 1.76 (1.19-2.62; 95% CI) / 39.5% vs. 30.1%; p=0.003; OR 1.51 (1.15-1.99; 95% CI), respectively]. Psoriatic disease activity parameters, patient-physician reported outcomes and HAQ-DI scores were similar in both groups.

Conclusions: Clinical features of PsA may be affected by the age at onset of PsO. Different genetic backgrounds in early and late-onset PsO may be driving the differences in psoriasis and PsA phenotypes.
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June 2020

A single-nucleotide polymorphism (rs8176070) of lncRNA PART1 may reflect the risk for knee osteoarthritis.

Eur J Rheumatol 2020 Apr 1;7(2):88-89. Epub 2020 Apr 1.

Department of Histology and Embryology, Ankara Yıldırım Beyazıt University School of Medicine, Ankara, Turkey.

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http://dx.doi.org/10.5152/eurjrheum.2020.19210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343226PMC
April 2020

The Role of Endogenous Eicosapentaenoic Acid and Docosahexaenoic Acid-Derived Resolvins in Systemic Sclerosis.

Front Immunol 2020 19;11:1249. Epub 2020 Jun 19.

Department of Experimental and Clinical Medicine, University of Florence and Department of Geriatric Medicine, Division of Rheumatology AOUC, Florence, Italy.

Resolvins, the member of specialized pro-resolving mediators, are produced from omega-3 polyunsaturated fatty acids as a response to an acute inflammatory process in that termination and resolution of inflammation. In the acute inflammation, these lipid mediators limit polymorphonuclear cells infiltration, proinflammatory cytokine production; promote efferocytosis, and regulate several cell types being important roles in innate and adaptive immunity. Any dysregulation or defect of the resolution phase result in prolonged, persistent inflammation and eventually fibrosis. Resolvins are implicated in the development of various chronic autoimmune diseases. Systemic sclerosis (SSc) is a very complicated, chronic autoimmune disorder proceeding with vasculopathy, inflammation, and fibrosis. Dysregulation of innate and adaptive immunity is another important contributing factor in the pathogenesis of SSc. In this review, we will focus on the different roles of this new family of lipid mediators, characterized by the ability to prevent the spread of inflammation and its chronicity in various ways and how they can control the development of fibrotic diseases like SSc.
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http://dx.doi.org/10.3389/fimmu.2020.01249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318896PMC
June 2020

Takayasu arteritis in a patient diagnosed with acute rheumatic fever presenting with carditis: Is it a coincidental association or an aetiological relationship?

J Paediatr Child Health 2020 Jul 4. Epub 2020 Jul 4.

Faculty of Medicine, Department of Pediatric Cardiology, Eskisehir Osmangazi University, Eskisehir, Turkey.

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http://dx.doi.org/10.1111/jpc.14992DOI Listing
July 2020

The prevalence and risk factors for urinary incontinence among inpatients, a multicenter study from Turkey.

Arch Gerontol Geriatr 2020 Sep - Oct;90:104122. Epub 2020 Jun 5.

Division of Geriatrics, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Objective: To determine the prevalence and the factors associated with urinary incontinence (UI) among inpatients in Turkey.

Method: The population of this study comprised of patients screened by the "National Prevalence Measurement of Quality of Care (LPZ)" study in 2017 and 2018. Age, gender, comorbidities, length of hospital stay, sedative medications, SARC-F score, anthropometric measurements, and care parameters such as malnutrition, falls, UI-fecal incontinence (FI), restraints, and care dependency score (CDS) were noted. The LPZ questionnaire was performed by trained researchers, and multiple logistic regression analysis was performed to determine the factors associated with UI.

Results: The prevalence of UI was 29.4 % among 1176 inpatients, and 41.6 % in patients ≥65 years. Urinary incontinence was associated with older age (OR, 1.966, 95 % CI 1.330-2.905), female sex (OR, 2.055, 95 % CI 1.393-3.030), CDS (OR, 3.236, 95 % CI 2.080-5.035), the number of comorbidities (OR, 1.312, 95 % CI 1.106-1.556), end-of life management (OR, 3.156, 95 % CI 1.412-7.052), sedative medications (OR, 1.981, 95 % CI 1.230-3.191), and FI (OR, 12.533, 95 % CI 4.892-32.112) in all adults, where CDS (OR, 2.589, 95% CI 1.458-4.599), end-of life management (OR, 2.851, 95 % CI 1.095-7.424), sedative medications (OR, 2.529, 95 % CI 1.406-4.548), and FI (OR, 13.138, 95 % CI 4.352-39.661) were associated with UI among geriatric patients.

Conclusions: The factors associated with UI in geriatric and all adult inpatients are CDS, sedative medications, end-of life management, and FI plus older age, female sex, and comorbidities for the latter. The factors associated with UI vary in different age groups.
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http://dx.doi.org/10.1016/j.archger.2020.104122DOI Listing
December 2020