Subclinical atherosclerosis profiles in rheumatoid arthritis and primary Sjögren's syndrome: the impact of BAFF genetic variations.

OBJECTIVES: RA and primary SS carry increased atherosclerotic risk, while B-cell activating factor holds a vital role in disease pathogenesis and atherosclerosis. We aimed to compare subclinical atherosclerosis profiles between the two clinical entities and define whether BAFF genetic variants alter atherosclerotic risk. METHODS: DNA from 166 RA, 148 primary SS patients and 200 healthy controls of similar age and sex distribution was subjected to PCR-based assay for the detection of five single nucleotide polymorphisms of the BAFF gene (rs1224141, rs12583006, rs9514828, rs1041569 and rs9514827). Genotype and haplotype frequencies were determined by SNPStats software and statistical analysis was performed by SPSS and Graphpad Software. Subclinical atherosclerosis was defined by the presence of carotid/femoral plaque formation and arterial wall thickening. RESULTS: Atherosclerotic plaque formation was more frequently detected in the RA vs primary SS group (80.7% vs 62.2%, P-value <0.001), along with higher rates of family CVD history, current steroid dose and serum inflammatory markers. The TT genotype of the rs1224141 variant was more prevalent in RA but not primary SS patients with plaque and arterial wall thickening vs their counterparts without. Regarding the rs1014569 variant, among RA patients the TT genotype increased the risk for plaque formation while in primary SS patients the AT genotype conferred increased risk. Haplotype GTTTT was protective in the RA cohort, while TATTT and TTCTT haplotypes increased susceptibility for arterial wall thickening in the primary SS cohort. CONCLUSIONS: Increased inflammatory burden, higher steroid doses and distinct BAFF gene variations imply chronic inflammation and B-cell hyperactivity as key contributors for the augmented atherosclerotic risk among autoimmune patients.

Atherosclerosis in SLE: a potential role for serum parathormone levels.

OBJECTIVE: A link between bone metabolism and cardiovascular (CV) disease has been suggested mainly in the general population. In the current study we explored whether altered bone metabolism influence CV risk in patients with SLE. METHODS: In 138 consecutive patients with SLE, atherosclerosis was assessed by the presence of plaque and/or arterial wall thickening in carotid/femoral arteries by ultrasound. Bone mineral density (BMD) levels and hip/spinal cord fractures together with classical CV disease and osteoporosis risk factors including serum 25(OH) vitamin D3 and parathormone (PTH) levels were recorded in all patients. Serum osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-Β ligand were quantitated by commercial ELISA. Statistical analysis included both univariate and multivariate models. RESULTS: Abnormal PTH serum concentrations (>65 pg/mL)-but not 25(OH) vitamin D3 serum levels-were identified as a risk factor for both plaque formation and arterial wall thickening in patients with SLE (ORs (95% CIs): 8.2 (1.8 to 37.4) and 3.9 (1.3 to 11.8), respectively). This association remained significant following adjustment for vitamin D3 levels and classical CV risk factors. Moreover, an independent association between osteoporosis with plaque formation and arterial wall thickening was detected following adjustment for total steroid dose, premature menopause and disease duration (ORs (95% CIs): 5.3 (1.1 to 26.2) and 3.5 (1.1 to 11.4), respectively). An inverse correlation between femoral neck BMD values and intima-medial thickness scores was also observed (r: -0.42, p=0.008). CONCLUSIONS: These findings further strengthen the concept of shared pathophysiological mechanisms between atherogenesis and altered bone metabolism in autoimmune populations, revealing heightened PTH levels as a potential marker for atherosclerosis among patients with SLE.

Anxiety and Extraversion in Lupus-Related Atherosclerosis.

Objectives: Patients with systemic lupus erythematosus (SLE) are characterized by increased cardiovascular disease (CVD) risk as well as heightened rates of psychological distress. Since a link between psychological issues and CV morbidity has been previously suggested, the influence of psychological burden on subclinical atherosclerosis in SLE patients was investigated. Methods: 71 SLE patients were assessed for the presence of subclinical atherosclerosis-defined either as carotid and/or femoral plaque formation or arterial wall thickening [Intima Media Thickness (IMT) levels > 0.90 mm by Doppler ultrasound]; personality traits, anxiety and depression, sleeping habits and fatigue levels were also evaluated by specific questionnaires including Eysenck Personality Questionnaire Scale, State-Trait Anxiety Inventory (STAI), Zung Depression Scale, Athens Insomnia Scale and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Disease related clinical and laboratory features and traditional risk factors for atherosclerosis were documented. Univariate and multivariate analysis were performed. Results: SLE patients with arterial wall thickening displayed higher STAI anxiety scores (either as a current state or as a personality trait) compared to those without (49.8 ± 5.6 vs. 46.9 ± 5.4, p-value: 0.03 and 49.2 ± 4.4 vs. 45.7 ± 6.8, p-value: 0.009, respectively). In a multivariate model, trait anxiety and extraversion personality scores were found to be independently associated with arterial wall thickening and plaque formation, respectively [OR95%(CI):1.2(1.0-1.5) and 0.7(0.6-1.0), respectively], following adjustment for potential confounders. No other associations were detected. Conclusions: Anxiety and extraversion personality traits have been independently associated with subclinical atherosclerosis in lupus patients, implying psychoneuroimmunological interactions as contributors in SLE related atherosclerosis.

B-cell activating factor and related genetic variants in lupus related atherosclerosis.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease with an increased atherosclerotic risk compared to healthy population, partially explained by traditional cardiovascular (CV) risk factors. Recent data suggest B-cell activating factor (BAFF) as an important contributor in the pathogenesis of both SLE and atherosclerosis. The aim of the current study is to explore whether serum BAFF levels along with variants of the BAFF gene increase lupus related atherosclerotic risk. PATIENTS-METHODS: 250 SLE patients underwent assessment of plaque formation and/or intimal media thickness (IMT) measurements in carotid and femoral arteries by ultrasound. Disease related features and CV traditional risk factors were also assessed. Serum BAFF levels were determined by commercially available ELISA and five single nucleotide polymorphisms (SNPs) of the BAFF gene (rs1224141, rs12583006, rs9514828, rs1041569 and the rs9514827) were evaluated by PCR-based assays in all patients and 200 healthy controls (HC) of similar age and sex distribution. SLE patients were further divided in high and low BAFF groups on the basis of the upper quartile level of the distribution (1358 pg/ml). Genotype and haplotype frequencies in SLE patients and HC were determined by SNPStats and SHEsis software. RESULTS: High-BAFF SLE group displayed increased rates of both plaque formation and arterial wall thickening (defined as IMT>0.90 mm) compared to patients with low BAFF levels (58.1% vs 43.6%, p:0.048 and 38.6% vs 23.2%, p-value: 0.024, respectively). The association remained significant after disease related features were taken into account (ORs [95%CI]: 2.2 [1.0-5.1] and 2.5 [1.1-5.5] for plaque formation and arterial wall thickening, respectively). Moreover, the presence of the AA genotype of the rs12583006 BAFF gene variant increased susceptibility for both lupus and lupus related plaque formation (ORs [95%CI]: 2.8 [1.1-7.1], and 4.4 [1.3-15.4] in the codominant model, respectively). Finally, the haplotype TTTAT was found to be protective for plaque formation among SLE patients (OR 0.3 [0.1-0.9]. No associations between BAFF gene variants with arterial wall thickening were detected. CONCLUSIONS: High BAFF serum levels in the upper 4th quartile as well as BAFF genetic variants seem to increase susceptibility for both lupus and lupus related subclinical atherosclerosis implying B-cell hyperactivity as a potential contributor in the pronounced lupus related atherosclerotic risk.

Contrast-enhanced ultrasound examination of the gallbladder and bile ducts: A pictorial essay.

The gallbladder and bile ducts are usually assessed initially with conventional gray-scale ultrasound (US). Contrast enhanced US (CEUS) is used when a diagnosis cannot be reached with conventional US. CEUS is easy to learn and perform. US contrast agents can be safely administered in patients with renal function impairment. In this pictorial essay the physics, examination technique and indications of CEUS for examining the gallbladder and bile ducts are reviewed. Gallbladder indications include elucidating normal variants, differentiating sludge from neoplastic lesions, benign and malignant pathology, infection, wall rupture and hemobilia. In the biliary tree CEUS is used for studying benign and malignant tumors, including metastases and cholangiocarcinoma, as well as intrabiliary injection.

Successful endovascular treatment of transplant intrarenal artery stenosis in renal transplant recipients: Two case reports.

Transplant renal artery stenosis (TRAS) is a relatively rare complication after renal transplantation. The site of the surgical anastomosis is most commonly involved, but sites both proximal and distal to the anastomosis may occur, as well. Angioplasty is the gold standard for the treatment of the stenosis, especially for intrarenal lesions. We report two cases of intrarenal TRAS and successful management with angioplasty without stent placement. Both patients were male, 44 and 55 years old respectively, and they presented with elevated blood pressure or serum creatinine within three months after transplantation. Subsequently, they have undergone angioplasty balloon dilatation with normalization of blood pressure and serum creatinine returning to baseline level. Percutaneous transluminal balloon renal angioplasty is a safe and effective method for the treatment of the intrarenal TRAS.

Subclinical atherosclerosis and impaired bone health in patients with primary Sjogren's syndrome: prevalence, clinical and laboratory associations.

INTRODUCTION: To determine the prevalence and clinical/laboratory associations of subclinical atherosclerosis and impaired bone health in primary Sjogren's syndrome (SS). METHODS: 64 consecutive patients with primary SS, 77 with rheumatoid arthritis (RA) and 60 healthy controls (HC) οf similar age and sex distribution were enrolled. Demographics, clinical/laboratory features, classical risk factors for atherosclerosis and osteoporosis (OP) were recorded. Intima-medial thickness scores (IMT) and carotid/femoral (C/F) plaque formation, as well as bone mineral density (BMD) and fractures were evaluated. Determinants of IMT/BMD levels and the presence of plaque were assessed by univariate and multivariate models. Serum levels of the Wnt signaling mediators Dickkopf-related protein 1(DKK1) and sclerostin were determined in primary SS patients and HC. RESULTS: Increased arterial wall thickening (IMT > 0.90 mm) and impaired bone health (defined as OP or osteopenia), were detected in approximately two-thirds of primary SS and RA patients, with a mean IMT value being significantly increased compared to HC. The presence of primary SS emerged as an independent risk factor for arterial wall thickening when traditional risk factors for cardiovascular disease (CVD) including age, sex, hypertension, smoking (pack/years), LDL and HDL levels were taken into account in a multivariate model [adjusted OR 95% (CI): 2.8 (1.04-7.54)]. In primary SS, age was revealed as independent predictor of increased IMT scores; age and lymphopenia as well as increased urine pH as independent determinants of C/F plaque formation and OP/osteopenia, respectively. An independent association of OP/osteopenia with plaque formation was observed when independent predictors for both variables were considered, with low DKK1 levels being associated with both plaque formation and lower BMD levels. CONCLUSIONS: Comorbidities such as subclinical atherosclerosis and impaired bone health occur frequently in primary SS, in association with disease related features and traditional risk factors. Wnt signaling mediators are potentially involved in the pathogenesis of both entities.

Contrast enhanced ultrasound of the kidneys: what is it capable of?

One of the many imaging uses of contrast enhanced ultrasound (CEUS) is studying a wide variety of kidney pathology, due to its ability to detect microvascular blood flow in real time without affecting renal function. CEUS enables dynamic assessment and quantification of microvascularisation up to capillary perfusion. The objective of this paper is to briefly refresh basic knowledge of ultrasound (US) contrast agents' physical properties, to study technical details of CEUS scanning in the kidneys, and to review the commonest renal indications for CEUS, with imaging examples in comparison to baseline unenhanced US and computed tomography when performed. Safety matters and limitations of CEUS of the kidneys are also discussed.

Ultrasonographic features of kidney transplants and their complications: an imaging review.

Renal transplantation is the treatment of choice for managing patients with end-stage kidney disease. Being submitted to a very serious surgical procedure, renal transplant recipients can only benefit from follow-up imaging and monitoring strategies. Ultrasound is considered as the principal imaging test in the evaluation of renal transplants. It is an easily applied bedside examination that can detect possible complications and guide further imaging or intervention. In this imaging review, we present essential information regarding the sonographic features of healthy renal transplants, detailing the surgical technique and how it affects the sonoanatomy. We focus on various complications that occur following renal transplantation and their sonographic features by reviewing pertinent literature sources and our own extensive imaging archives.

Contrast-enhanced ultrasound performed under urgent conditions. Indications, review of the technique, clinical examples and limitations.

Contrast-enhanced ultrasound (CEUS) is an imaging technique with various indications, most of which refer to scheduled examinations. However, CEUS can also be performed under urgent conditions for the investigation of many different clinical questions. This article reviews basic physics of ultrasound contrast agents and examines the commonest urgent clinical applications of CEUS. These include, among others, abdominal solid organ trauma and infarcts, scrotal and penile pathology and blood vessel imaging. Patients can be examined with a very short time delay at their bedside, without exposure to ionising radiation or risk of anaphylactic reaction and renal failure, while contraindications are minimal. CEUS technique is described for various urgent indications and imaging examples from our department's experience are presented. Safety matters and limitations of CEUS are also mentioned. Teaching Points • Contrast-enhanced ultrasound (CEUS) can be performed urgently for various clinical applications. • Abdominal indications include solid organ trauma and infarcts. • CEUS in abdominal organ trauma correlates well with CT and can replace it for patient follow-up. • CEUS images testicular torsion, infection and infarction, as well as testicular and penile trauma. • Blood vessels can be assessed with CEUS for obstruction, aneurysm, thrombosis and dissection.

Imaging features of a huge spermatic cord leiomyosarcoma: Review of the literature.

Spermatic cord leiomyosarcomas (LMSs) are rare tumors which may cause significant morbidity and mortality if inadequately diagnosed or treated. We report a case of a paratesticular LMS in a 60-year-old man who presented with a right scrotal mass. The patient was evaluated by scrotal ultrasound and computed tomography of the abdomen and pelvis (including scans of the scrotum), which revealed a large extratesticular mass. The lesion proved to be malignant and the patient underwent radical orchiectomy with high cord ligation. To improve the assignment of this lesion, we further analyze the imaging features of LMS and correlate them with pathologic findings.

Emergency ultrasound of the scrotum: a review of the commonest pathologic conditions.

Ultrasound is the first imaging modality to be performed in emergency conditions of the scrotum. The commonest pathologic entities are divided into the 4 following groups: torsion, trauma, infection, and tumors. Sonographic examination should be performed as soon as possible to ensure fast diagnosis and treatment. Less acute conditions can also be noted while scanning on an emergency basis, such as anatomic variants, hydrocele, oscheocele, clinically evident varicocele, calcifications, etc. Although not threatening for scrotal integrity, they should be assessed during an emergency examination or later on. In this article, complex scrotal anatomy is reviewed and the basic examination technique is described. The commonest emergency conditions are analyzed, along with their pathophysiological basis. Nonemergent entities are also briefly mentioned. Ultrasound images of the commonest emergency conditions are demonstrated.