Immunosuppressive Medication Adherence in Patients With Hepatocellular Cancer Who Have Undergo Liver Transplantation: A Case Control Study.

BACKGROUND: We aimed to compare the adherence to immunosuppressive medication use in patients who underwent liver transplantation (LT) due to hepatocellular carcinoma (HCC) and non-HCC reasons. METHODS: The study population was determined as 242 patients with HCC and 1290 patients with non-HCC who had LT performed in our institute between March 2002 and November 2021; all these patients were contacted by phone in March 2022. The sample size was calculated using the MedCalc software program, and the number of patients required in each group was determined as 111 patients. Furthermore, we used the sample.int function, a random integer generator in the R (version 4.1.2) software program. Whereas demographic and clinical parameters were determined as independent variables, the immunosuppressive medication adherence scale (IMAS) score was determined as a dependent variable. Patients were evaluated by the IMAS. This 11-item IMAS scale evaluates the lowest compliance score as 11 and the highest as 55. RESULTS: Out of a total number of 221 patients, 161 (72%) were men and 60 (27.1%) were women, with a median age of 58 years (IQR: 14); one patient in the non-HCC group was excluded due to lack of data. Among the HCC and non-HCC groups, significant differences were found in terms of the variables of age (P = .003), IMAS score (P < .001), sex (P = .001), working status (P = .004), chronic diseases (P = .008), tacrolimus alone (P < .001), tacrolimus plus everolimus (P < .001), and often medication changes (P < .001). A statistically significant correlation was found between the IMAS score and whether the patients had HCC (P < .001) and frequently changing immunosuppressive drugs (P = .023). CONCLUSION: This study showed that patients with frequent drug changes or non-HCC etiology had better adherence to immunosuppressive drug use.

Early effects of inactivated (CoronaVac) SARS-CoV-2 vaccine on retrobulbar vascular blood flow and retinal vascular density.

AIMS: We aimed to investigate the early effects of inactivated SARS-CoV-2 vaccine on retrobulbar vascular blood flow and retinal vascular density in healthy subjects. METHODS: Thirty-four eyes of 34 healthy volunteers who received the CoronaVac (Sinovac Life Sciences, China) were included in this prospective study. Resistive index (RI), pulsatility index (PI) and peak systolic velocity (PSV) of the ophthalmic artery (OA), central retinal artery (CRA), and the temporal and nasal posterior ciliary arteries (PCA) were evaluated with color Doppler ultrasonography (CDUS) before vaccination, at the 2nd and 4th weeks after vaccination. Superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel density (VD), foveal avascular zone (FAZ), and choriocapillaris blood flow (CCF) measurements were made using optical coherence tomography angiography (OCTA). RESULTS: When compared to the pre-vaccination values, there was no significant change in OA-PSV, temporal-nasal PCA-PSV, CRA-EDV, temporal-nasal PCA-EDV at 2nd and 4th weeks after vaccination. However statistically significant reductions were found in the OA-RI, OA-PI, CRA-RI, CRA-PI, temporal-nasal PCA-RI, temporal-nasal PCA-PI values, CRA-PSV at post-vaccination 2nd week (p<0.05 for all). While there was sustained reduction in OA-RI, OA-PI, CRA-PSV, and nasal PCA-RI values at 4th week after vaccination, the change in CRA-RI, CRA-PI, temporal PCA-RI, temporal-nasal PCA-PI values were not significant compared to pre-vaccination values. There was no statistically significant difference in the SCP-VD, DCP-VD, FAZ and CCF measurements. CONCLUSIONS: Our findings demonstrating that CoronaVac vaccine did not affect retinal vascular density in the early period, but it caused alterations in the retrobulbar blood flow.

Three-Country Snapshot of Ornithine Transcarbamylase Deficiency.

X-linked ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle defect. The disease severity ranges from asymptomatic carrier state to severe neonatal presentation with hyperammonaemic encephalopathy. We audited the diagnosis and management of OTCD, using an online 12-question-survey that was sent to 75 metabolic centres in Turkey, France and the UK. Thirty-nine centres responded and 495 patients were reported in total. A total of 208 French patients were reported, including 71 (34%) males, 86 (41%) symptomatic and 51 (25%) asymptomatic females. Eighty-five Turkish patients included 32 (38%) males, 39 (46%) symptomatic and 14 (16%) asymptomatic females. Out of the 202 UK patients, 66 (33%) were male, 83 (41%) asymptomatic and 53 (26%) symptomatic females. A total of 19%, 12% and 7% of the patients presented with a neonatal-onset phenotype in France, Turkey and the UK, respectively. Vomiting, altered mental status and encephalopathy were the most common initial symptoms in all three countries. While 69% in France and 79% in Turkey were receiving protein restriction, 42% were on a protein-restricted diet in the UK. A total of 76%, 47% and 33% of patients were treated with ammonia scavengers in Turkey, France and the UK, respectively. The findings of our audit emphasize the differences and similarities in manifestations and management practices in three countries.

CAMLG-CDG: a novel congenital disorder of glycosylation linked to defective membrane trafficking.

The transmembrane domain recognition complex (TRC) pathway is required for the insertion of C-terminal tail-anchored (TA) proteins into the lipid bilayer of specific intracellular organelles such as the endoplasmic reticulum (ER) membrane. In order to facilitate correct insertion, the recognition complex (consisting of BAG6, GET4 and UBL4A) must first bind to TA proteins and then to GET3 (TRC40, ASNA1), which chaperones the protein to the ER membrane. Subsequently, GET1 (WRB) and CAML form a receptor that enables integration of the TA protein within the lipid bilayer. We report an individual with the homozygous c.633 + 4A>G splice variant in CAMLG, encoding CAML. This variant leads to aberrant splicing and lack of functional protein in patient-derived fibroblasts. The patient displays a predominantly neurological phenotype with psychomotor disability, hypotonia, epilepsy and structural brain abnormalities. Biochemically, a combined O-linked and type II N-linked glycosylation defect was found. Mislocalization of syntaxin-5 in patient fibroblasts and in siCAMLG deleted Hela cells confirms this as a consistent cellular marker of TRC dysfunction. Interestingly, the level of the v-SNARE Bet1L is also drastically reduced in both of these models, indicating a fundamental role of the TRC complex in the assembly of Golgi SNARE complexes. It also points towards a possible mechanism behind the hyposialylation of N and O-glycans. This is the first reported patient with pathogenic variants in CAMLG. CAMLG-CDG is the third disorder, after GET4 and GET3 deficiencies, caused by pathogenic variants in a member of the TRC pathway, further expanding this novel group of disorders.

Theranostic potential of self-luminescent branched polyethyleneimine-coated superparamagnetic iron oxide nanoparticles.

Polyethylenimine (PEI), which is frequently used for polyplex formation and effective gene transfection, is rarely recognized as a luminescent polymer. Therefore, it is usually tagged with an organic fluorophore to be optically tracked. Recently, we developed branched PEI (bPEI) superparamagnetic iron oxide nanoparticles (SPION@bPEI) with blue luminescence 1200 times stronger than that of bPEI without a traditional fluorophore, due to partial PEI oxidation during the synthesis. Here, we demonstrate in vitro dye-free optical imaging and successful gene transfection with luminescent SPION@bPEI, which was further modified for receptor-mediated delivery of the cargo selectively to cancer cell lines overexpressing the epidermal growth factor receptor (EGFR). Pro-apoptotic polyinosinic-polycytidylic acid sodium (PIC) was delivered to HeLa cells with SPION@bPEI and caused a dramatic reduction in the cell viability at otherwise non-toxic nanoparticle concentrations, proving that bPEI coating is still an effective component for the delivery of an anionic cargo. Besides, a strong intracellular optical signal supports the optically traceable nature of these nanoparticles. SPION@bPEI nanoparticles were further conjugated with Erbitux (Erb), which is an anti-EGFR antibody for targeting EGFR-overexpressing cancer cell lines. SPION@bPEI-Erb was used for the delivery of a GFP plasmid wherein the transfection was confirmed by the luminescence of the expressed gene within the transfected cells. Poor GFP expression in MCF7, a slightly better expression in HeLa, and a significant enhancement in the transfection of HCT116 cells proved a selective uptake and hence the targeting ability of Erb-tagged nanoparticles. Altogether, this study proves luminescent, cationic, and small SPION@bPEI nanoparticles as strong candidates for imaging and gene therapy.

A mysterious case with abdominal pain and syndrome of inappropriate anti-diuretic hormone secretion.

BACKGROUND: Acute intermittent porphyria (AIP) is a rare, hereditary, metabolic disease caused by a defect in heme biosynthesis. Hormonal changes may trigger porphyria attacks. CASE: Here we present a 17 -year- old adolescent refugee mother who applied to the pediatric emergency department with the complaint of diffuse abdominal pain at puerperium. The patient was hypertensive, and had convulsions after admission. Hyponatremia (serum sodium; 121 meq/L) was detected, and syndrome of inappropriate anti-diuretic hormone secretion (SIADH) was found to be the cause of hyponatremia which responded well to fluid restriction. Infectious, autoimmune and toxicologic laboratory work-up did not reveal any specific pathologies. Despite prompt utilization of analgesic treatment, the patient continued to have unbearable abdominal pain. The preference of prone position to relieve the pain and the family history of a mother who had died with similar symptoms, led us to the diagnosis of AIP. Genetic analysis showed a heterozygous mutation in hydroxymethylbilane synthase (HMBS) gene (c160+6T > A) which confirmed our diagnosis. CONCLUSION: Acute porphyrias should be considered in differential diagnosis of abdominal pain, especially when there are accompanying symptoms like hyponatremia, seizures, mental changes and hypertension.

Treatment of breast cancer with autophagy inhibitory microRNAs carried by AGO2-conjugated nanoparticles.

Nanoparticle based gene delivery systems holds great promise. Superparamagnetic iron oxide nanoparticles (SPIONs) are being heavily investigated due to good biocompatibility and added diagnostic potential, rendering such nanoparticles theranostic. Yet, commonly used cationic coatings for efficient delivery of such anionic cargos, results in significant toxicity limiting translation of the technology to the clinic. Here, we describe a highly biocompatible, small and non-cationic SPION-based theranostic nanoparticles as novel gene therapy agents. We propose for the first-time, the usage of the microRNA machinery RISC complex component Argonaute 2 (AGO2) protein as a microRNA stabilizing agent and a delivery vehicle. In this study, AGO2 protein-conjugated, anti-HER2 antibody-linked and fluorophore-tagged SPION nanoparticles were developed (SP-AH nanoparticles) and used as a carrier for an autophagy inhibitory microRNA, MIR376B. These functionalized nanoparticles selectively delivered an effective amount of the microRNA into HER2-positive breast cancer cell lines in vitro and in a xenograft nude mice model of breast cancer in vivo, and successfully blocked autophagy. Furthermore, combination of the chemotherapy agent cisplatin with MIR376B-loaded SP-AH nanoparticles increased the efficacy of the anti-cancer treatment both in vitro in cells and in vivo in the nude mice. Therefore, we propose that AGO2 protein conjugated SPIONs are a new class of theranostic nanoparticles and can be efficiently used as innovative, non-cationic, non-toxic gene therapy tools for targeted therapy of cancer.

Real-time ultrasound elastographic evaluation of extraocular muscle involvement in Graves' ophthalmopathy.

Purpose: To evaluate the affected extraocular muscles (EOMs) of patients with Graves' ophthalmopathy (GO) using real-time ultrasound elastography (UE) and to compare these results with those of healthy subjects.Methods: This prospective, comparative case series included 70 eyes of 35 patients with moderate-to-severe GO with type 2 orbitopathy (myogenic variant) according to their computed tomography (CT) scans. Forty-six eyes of 23 healthy subjects were evaluated as the control group. The strain ratio of orbital fat to medial rectus was calculated as the ratio of the medial rectus to orbital fat tissue, and the strain ratio of orbital fat to lateral rectus was calculated as the ratio of lateral rectus to orbital fat tissue.Results: The strain ratio of orbital fat to medial rectus was 3.03 ± 1.25 (range: 1.05-5.07) in the GO group, and 0.54 ± 0.20 (range: 0.14-1.08) in the control group (p = .0001). The strain ratio of orbital fat to lateral rectus was 0.97 ± 0.29 (range: 0.56-1.55) in the GO group, and 0.63 ± 0.23 (range: 0.18-1.09) in the control group (p = .0001).Conclusion: By using real-time UE, we found the medial and the lateral recti of GO patients to be stiffer compared to those of healthy subjects.

Magnetofection of Green Fluorescent Protein Encoding DNA-Bearing Polyethyleneimine-Coated Superparamagnetic Iron Oxide Nanoparticles to Human Breast Cancer Cells.

Gene therapy is a developing method for the treatment of various diseases. For this purpose, the search for nonviral methods has recently accelerated to avoid toxic effects. A strong alternative method is magnetofection, which involves the use of superparamagnetic iron oxide nanoparticles (SPIONs) with a proper organic coating and external magnetic field to enhance the localization of SPIONs at the target site. In this study, a new magnetic actuation system consisting of four rare-earth magnets on a rotary table was designed and manufactured to obtain improved magnetofection. As a model, green fluorescent protein DNA-bearing polyethyleneimine-coated SPIONs were used. Magnetofection was tested on MCF7 cells. The system reduced the transfection time (down to 1 h) of the standard polyethyleneimine transfection protocol. As a result, we showed that the system could be effectively used for gene transfer.

Clinical and molecular characteristics and time of diagnosis of patients with classical galactosemia in an unscreened population in Turkey.

Classical galactosemia is an autosomal recessive inborn error of metabolism caused by biallelic pathogenic variants in the GALT gene. With the benefit of early diagnosis by newborn screening, the acute presentation of galactosemia can be prevented. In this study, we describe the clinical phenotypes, time of diagnosis and GALT genotypes of 76 galactosemia patients from Turkey, where the disease is not yet included in the newborn screening program. The median age at first symptom was 10 days (range 5-20), while the median age at diagnosis was 30 days (range 17-53). Nearly half of the patients (36 patients, 47.4%) were diagnosed later than age 1 month. Fifty-eight individuals were found to have 18 different pathogenic variants in their 116 mutant alleles. In our sample, Q188R variant has the highest frequency with 53%, the other half of the allele frequency of the patients showed 17 different genotypes. Despite presenting with typical clinical manifestations, classical galactosemia patients are diagnosed late in Turkey. Due to the geographical location of our country, different pathogenic GALT variants may be seen in Turkish patients. In the present study, a clear genotype-phenotype correlation could not be established in patients.

Color Doppler imaging of ocular hemodynamic changes in patients with rheumatoid arthritis unrelated to disease activity.

We aimed to investigate how orbital blood flow rates in patients with rheumatoid arthritis (RA) are affected by the active and remission phase of the disease. This prospective study included a total of 56 patients with RA (study group) and 24 control individuals (control group). All RA patients were divided into two groups, as active (Group 1) and remission (Group 2) according to the disease activity index (DAS 28) score. For each eye, retrobulbar vascular structures were evaluated [central retinal artery (CRA), posterior ciliary artery (PCA), and ophthalmic artery (OA)], respectively. The peak systolic velocity (PSV) and end-diastolic velocity (EDV) values were obtained for each artery and the vascular resistance index (RI) measurement was calculated. The median RI of the OA was 0.70 (0.57; 0.79) in the control group, 0.77 (0.55; 0.87) in group 1, and 0.73 (0.47; 0.87) in group 2. The median RI in the PCA was 0.70 (0.56; 0.82) in the control group, 0.76 (0.52; 0.88) in the group 1, and 0.74 (0.52; 0.86) in the group 2. The median RI of CRA was 0.73 (0.48; 0.81) in the control group, 0.71 (0.64; 0.81) in group 1, and 0.68 (0.61; 0.85) in group 2. The RI value was a significant difference between control and group 1 (p < 0.05). Active and remission RA patients had different effects on the flow rate of eye blood vessels.

A Very Rare Etiology of Hypotonia and Seizures: Congenital Glutamine Synthetase Deficiency.

Mutations in the human GLUL gene, which encodes the enzyme glutamine synthetase (GS), may cause congenital glutamine synthetase deficiency. The disease was first described in 2005 and only three patients have been reported to date. We report a fourth patient suffering from congenital GS deficiency who was found to have some distinctive clinical findings. The patient was a 30-month-old girl who was referred to us due to developmental delay and seizures which began at 5 months of age. She was seizure free for 5 months with valproic acid and vigabatrin. At presentation, she was found to have microcephaly and hypotonia. Her plasma glutamine concentration was near normal and she had mild hyperammonemia. Cranial magnetic resonance imaging (MRI) showed mild changes. Whole exome sequencing (WES) revealed a homozygous c.121C > T (p.R41C) (p.Arg41Cys) pathogenic variant of the GLUL gene. The diagnosis of this patient underlines the importance of careful evaluation of patients with borderline low glutamine levels. Treatment was begun with L-glutamine and nicotinamide and biochemical improvements have been observed at 6 months of follow-up. The outcome of this patient may provide important data about the effectiveness of glutamine and nicotinamide treatment in patients with congenital GS deficiency.

An assessment of ocular elasticity using real time ultrasound and ocular response analyzer in active or remission rheumatoid arthritis.

PURPOSE: To investigate the elasticity of ocular structures in patients with rheumatoid arthritis (RA) without ocular involvement. METHODS: The study included 56 RA patients (study group) and 24 healthy volunteers as the control group. The rheumatoid arthritis patients were divided into two subgroups as those in active phase (Group 1, n = 25) or in remission phase (Group 2, n = 31) according to the disease activity index (DAS 28) score. The elastography values of the ratio of orbital fat-sclera (ROF/S) were measured with real-time US elastography, and corneal mechanical values were measured with the Reichert Ocular Response Analyzer in each eye. RESULTS: The mean ROF/S value was 5.2 ± 1.8 in Group 1, 0.7 ± 0.4 Group 2, and 0.6 ± 0.1 in the control group. There was a significant difference between the Group 1 and control group with regard to ROF/S (p < 0.001), but no significant difference was determined between Group 2 and control group (p > 0.05). The mean ROF/S value was a significant difference between the Group 1 and 2 (p < 0.001). ROF/S was significantly correlated with DAS-28 and C-reactive protein (CRP) (r = 0.816, p < 0.001 and r = 0.259, p = 0.006). CONCLUSIONS: ROF/S was significantly increased in patients in the active phase of RA. Findings revealed that ocular tissue structural changes may occur in the active phase and these could be related to ocular complications as a prognostic factor.

Evaluation of Optic Nerve Head Biomechanical Properties in Pseudoexfoliation Glaucoma with Real-time Elastography.

PURPOSE: To investigate the biomechanical properties of the optic nerve head in patients with Pseudoexfoliation (PEX) glaucoma using Real-time Elastography (RTE) and to compare these results with those of Primary Open Angle Glaucoma (POAG) patients and healthy subjects. METHODS: Twenty eyes of 20 PEX glaucoma patients (PEX group), 20 eyes of 20 POAG patients (POAG group), and 20 eyes of 20 healthy subjects (control group) were enrolled in this prospective study. The strain Ratios of Orbital Fat to Optic Nerve head (ROFON) and lateral rectus muscle to optic nerve head (RLRON) were determined. Comparisons were performed using Chi-square, Kruskal Wallis, Mann-Whitney U, and One-way ANOVA tests. RESULTS: The strain ratios of orbital fat to optic nerve head were 2.34, 6.85 and 1.76 in PEX glaucoma, POAG, and control groups, respectively (p<0.001). The strain ratios of the lateral rectus muscle to the optic nerve head were 0.51, 0.82, and 0.55 in PEX glaucoma, POAG, and control groups, respectively (p=0.256). CONCLUSION: The strain ratios of orbital fat to optic nerve head were different in PEX glaucoma patients than in POAG and control groups. RTE can provide biomechanical assessment of the optic nerve head in a non-invasive, quick, easily accessible, and user-friendly manner.

Neonatal form of biotin-thiamine-responsive basal ganglia disease. Clues to diagnosis.

Degerliyurt A, Gündüz M, Ceylaner S, Ünal Ö, Ünal S. Neonatal form of biotin-thiamine-responsive basal ganglia disease. Clues to diagnosis. Turk J Pediatr 2019; 61: 261-266. Biotin-thiamine-responsive basal ganglia disease is characterized by seizures, dystonia and encephalopathy attacks, with an acute-subacute onset in childhood. It causes cerebral damage especially with caudate head and putamen involvement and may lead to severe sequelae and even death if left untreated. We report a patient with the neonatal form of biotin-thiamine-responsive basal ganglia disease who presented with encephalopathy and lactic acidosis in the neonatal period together with the diagnostic magnetic resonance imaging (MRI) clues. MRI in the neonatal period revealed bilateral involvement of the putamen, thalamus, and perirolandic cortical regions. However, MRI obtained at 32 months revealed involvement of the caudate nuclei in addition to the putamen and thalami. The neuroimaging findings of our patient and relevant literature indicate that patients with biotin-thiamine-responsive basal ganglia disease who are symptomatic in the neonatal period have putamen, thalami, and perirolandic cortical involvement. However, these patients do not have caudate involvement, unlike the patients who present in childhood.

Alpha methyl acyl CoA racemase deficiency: Diagnosis with isolated elevated liver enzymes.

Gündüz M, Ünal Ö, Küçükçongar-Yavas A, Kasapkara Ç. Alpha methyl acyl CoA racemase deficiency: Diagnosis with isolated elevated liver enzymes. Turk J Pediatr 2019; 61: 289-291. Alpha methy acyl CoA racemase (AMACR) deficiency is a rare autosomal recessive peroxisomal disorder characterized by cholestatic liver disease in the neonatal period, and variable neurologic symptoms affecting central and peripheral nervous systems in the following years. We report a Turkish patient who was diagnosed with AMACR deficiency with presentation of isolated elevated liver enzymes. The patient was referred for elevated liver enzymes when he was 10 months old. He had no cholestasis history in the neonatal period. Initially, an etiology could not be identified. Ultimately, the patient was diagnosed with AMACR deficiency with previously unreported p.Cys20Tyr (c.596G > A) homozygous pathogenic variant. At last visit, when he was 7.5 years old, his growth, development and neurologic examination were all normal. Biochemical analysis was normal except for mildly elevated AST levels. We suggest that checking VLCFA analysis may be useful in isolated elevated liver enzymes with unknown etiology.

Optic Nerve Head Elastometry in Both Eyes of Patients with Unilateral Non-arteritic Anterior Ischaemic Optic Neuropathy - May It Be a Novel Aspect of the Pathogenesis?

In this prospective study, the biomechanical properties of optic nerve head (ONH) and cornea in both eyes of patients with non-arteritic anterior ischaemic optic neuropathy and healthy control eyes were investigated. ONH elastometry was measured with real-time elastography, and corneal elastometry was measured with ocular response analyser. Elastometry of cornea and ONH was lower in both eyes of patients with unilateral non-arteritic ischaemic optic neuropathy than in healthy control eyes. The role of these biomechanical differences in the pathogenesis of non-arteritic ischaemic optic neuropathy should be investigated further.

Progressive deafness-dystonia due to SERAC1 mutations: A study of 67 cases.

OBJECTIVE: 3-Methylglutaconic aciduria, dystonia-deafness, hepatopathy, encephalopathy, Leigh-like syndrome (MEGDHEL) syndrome is caused by biallelic variants in SERAC1. METHODS: This multicenter study addressed the course of disease for each organ system. Metabolic, neuroradiological, and genetic findings are reported. RESULTS: Sixty-seven individuals (39 previously unreported) from 59 families were included (age range = 5 days-33.4 years, median age = 9 years). A total of 41 different SERAC1 variants were identified, including 20 that have not been reported before. With the exception of 2 families with a milder phenotype, all affected individuals showed a strikingly homogeneous phenotype and time course. Severe, reversible neonatal liver dysfunction and hypoglycemia were seen in >40% of all cases. Starting at a median age of 6 months, muscular hypotonia (91%) was seen, followed by progressive spasticity (82%, median onset = 15 months) and dystonia (82%, 18 months). The majority of affected individuals never learned to walk (68%). Seventy-nine percent suffered hearing loss, 58% never learned to speak, and nearly all had significant intellectual disability (88%). Magnetic resonance imaging features were accordingly homogenous, with bilateral basal ganglia involvement (98%); the characteristic "putaminal eye" was seen in 53%. The urinary marker 3-methylglutaconic aciduria was present in virtually all patients (98%). Supportive treatment focused on spasticity and drooling, and was effective in the individuals treated; hearing aids or cochlear implants did not improve communication skills. INTERPRETATION: MEGDHEL syndrome is a progressive deafness-dystonia syndrome with frequent and reversible neonatal liver involvement and a strikingly homogenous course of disease. Ann Neurol 2017;82:1004-1015.

A novel ultrasound-based technique to establish a correlation between disease activity and local carotid stiffness parameters in rheumatoid arthritis.

AIM: Cardiovascular (CV) disease is the reason for most mortality cases in RA and cannot be explained only by the presence of traditional CV risk factors. In this study, we aimed to investigate the relationship between local carotid stiffness (CS) parameters measured by a novel ultrasound method and inflammatory disease activity in rheumatoid arthritis (RA) patients. Material and methods: The study was conducted with 70 RA patients and 35 control subjects. According to their disease activity score (DAS-28), the RA patients were classified into active RA (n = 36; DAS-28 > 3.2) and inactive RA (n = 34; DAS-28 ≤ 3.2) groups. A novel non-invasive echo-tracking system was used to measure carotid intima-media thickness (C-IMT), diameter, pulsatile strain, distensibility, and carotid pulse wave velocity (PWV) on 128 sites of the common carotid artery. Erythrocytesedimentation rate (ESR) and C-reactive protein (CRP) levels were also determined. RESULTS: Carotid PWV and IMT were significantly higher in the active RA patients (8.20±1.47 m/s and 6.88±1.50 mm, respectively) compared to the inactive group (6.06±1.21 mm and 7.32±1.19 m/s, respectively) and the control subjects (0.68±0.12 mm and 6.41±0.98, respectively). In all RA patients, a statistically significant correlation was found between carotid PWV and age (r=0.435, p<0.001), ESR (r=0.257, p=0.033), and DAS-28 (r=0.314, p=0.009). According to the multivariate logistic regression analysis, age, DAS-28, and ESR were independent predictors of CS. CONCLUSION: A strong correlation was found between disease activity and local CS parameters in patients with RA. We also demonstrated that both active and inactive RA patients showed increased PWV values compared with the control subjects. This easily applicable and previously confirmed method can be used in future to assess cardiovascular risk in broad study populations from different risk groups.