CHA2DS2-VASC Score Predicts the Risk of Stroke in Patients Hospitalized to the Internal Medicine Department Without Known Atrial Fibrillation.

BACKGROUND: The CHA2DS2-VASC score is used to assess the risk of cerebrovascular accident (CVA) in patients with atrial fibrillation (AF) or atrial flutter (AFL). OBJECTIVES: We aimed to determine whether this score can determine the risk of CVA during the first year after hospitalization, in patients without known AF/AFL. DESIGN: Single-center retrospective cohort. PATIENTS: We included all patients aged ≥ 50 who were hospitalized between January 1, 2008, and December 31, 2018, to the internal medicine departments at the Chaim Sheba Medical Center, Israel. Exclusion criteria included history or new diagnosis of CVA, TIA, and AF/AFL and use of anticoagulation at any time. MAIN MEASURES: Patients were stratified into 3 groups according to their CHA2DS2-VASC score (0-1, 2, or ≥ 3). The primary outcome was hospitalization with CVA/TIA within one year of the index hospitalization. KEY RESULTS: Of the patients, 52,206 were included in the study. CVA/TIA occurred in 0.7%, 1.3%, and 1.7% of patients with a CHA2DS2-VASC score of 0-1, 2, and ≥ 3, respectively. Compared to a CHA2DS2-VASC score of 0-1, the HR for CVA/TIA occurrence for CHA2DS2-VASC scores of 2 and ≥ 3 was 1.77 (CI 1.42, 2.22) and 2.33 (CI 1.9, 2.85), respectively (p < 0.001 for both comparisons). Each additional CHA2DS2-VASC point increased the probability for readmission with CVA/TIA within 1-year by 26% (HR 1.26, CI 1.19, 1.32, p < 0.001). Similar trends were seen in subgroup analyses by gender, age, and renal function. CONCLUSIONS: The CHA2DS2-VASC score is a predictor for CVA/TIA during the first year after hospitalization in patients without AF. High CHA2DS2-VASC scores warrant work-up for occult AF/AFL and other risk factors for CVA/TIA.

Safety of the BNT162b2 mRNA COVID-19 vaccine in patients with familial Mediterranean fever.

OBJECTIVES: Evidence suggests a possible association between the COVID-19 vaccine and autoimmune disease flares or new onset of various autoinflammatory manifestations, such as pericarditis and myocarditis. The objective of this study was to assess the safety of an mRNA-based BNT162b2 anti-COVID-19 vaccine in individuals with FMF, a prototypic autoinflammatory disease. METHODS: Patients participating in this study fulfilled the criteria for diagnosis of FMF, were older than 18 years and received at least one dose of the vaccine. Data on baseline characteristics, features of FMF, post-vaccination side effects, and disease flares were acquired using electronic medical files and telephone interviews. RESULTS: A total of 273 FMF patients were recruited for the study. >95% were vaccinated with two doses of the vaccine. The rates of local reactions following the first and second vaccine doses were 65.5% and 60%, respectively, and 26% and 50.4%, respectively, for systemic adverse events. These rates are lower than those reported for the general population from real-world and clinical trial settings. Postvaccination FMF activity remained stable in most patients. None of the patients reported an attack of pericarditis or myocarditis, considered the most serious vaccine-associated adverse events. Patients with a more active FMF disease and patients harboring the M694V mutation had a significantly higher rate of post-vaccination systemic side effects and attacks. CONCLUSION: The BNT162b2 mRNA COVID-19 vaccine is safe in patients with FMF. Our results support the administration of this vaccine to FMF patients according to guidelines applicable to the general population.

Clinical and prognostic significance of elevated ferritin levels in hospitalised adults.

PURPOSE OF THE STUDY: Elevated ferritin levels are associated with a variety of infectious, malignant and inflammatory diseases. We aimed to investigate the prognostic value of markedly elevated ferritin levels in hospitalised patients with various medical conditions. STUDY DESIGN: Retrospective analysis of patients with a ferritin level higher than 2000 ng/mL hospitalised in Sheba Medical Center between 1 January 2007 and 31 December 2015. Medical conditions of these patients were recorded. In-hospital, 30-day and 1-year mortality rates were evaluated according to ferritin ranges and clinical categories. RESULTS: The study included 722 patients (63.4% men) with a mean age of 63.9±16.7 years. The most common clinical conditions associated with markedly elevated ferritin were infectious diseases and malignancies. The highest mean ferritin levels were associated with rheumatological/inflammatory conditions (16 241.3 ng/dL), particularly in patients with macrophage activation syndrome (MAS) (96 615.5 ng/dL). In-hospital, 30-day and 1-year mortality rates were 32.3%, 46.7% and 70.8%, respectively. The highest in-hospital, 30-day and 1-year mortality rates were observed among patients with solid malignancies (40.1%, 64.7% and 90.3%, respectively), whereas the lowest rates were found among patients with rheumatological/inflammatory conditions, including MAS (21.4%, 38.1% and 45.2%, respectively). Ferritin levels were not associated with mortality. CONCLUSIONS: In hospitalised patients, ferritin levels higher than 2000 ng/mL are mainly associated with infectious and malignant diseases but do not predict mortality.

Effect of interleukin-1 inhibition in a cohort of patients with colchicine-resistant familial Mediterranean fever treated consecutively with anakinra and canakinumab.

OBJECTIVES: To evaluate the efficacy of IL-1 blockers in a cohort of patients with colchicine-resistant familial Mediterranean fever (crFMF) treated consecutively with anakinra and canakinumab. METHODS: Patients with crFMF treated with anakinra and canakinumab in any order were identified using the computerised database of Sheba Medical Centre. Background characteristics of the patients, reason for switching IL-1 inhibitor, and frequency of attacks under colchicine only, anakinra, and canakinumab were extracted from the computerised patient files. Patients were then interviewed for patient-reported outcomes. RESULTS: A total of 46 patients in our clinic were prescribed canakinumab for crFMF after previous anakinra treatment, whereas no patients who switched treatment from canakinumab to anakinra were identified. Of those, 23/46 patients (50%) discontinued anakinra due to inadequate response (11 of them with secondary failure after a good initial response). Frequency of flares was significantly decreased following switch to canakinumab from anakinra treatment (p<0.01). After the switch to canakinumab, the median duration of flares, the severity of pain during a flare, and the patient's global assessment of disease activity were all significantly decreased (p≤0.01), according to the reports from the patients. CONCLUSIONS: Canakinumab is an effective treatment for FMF after failure of anakinra due to any cause.

Anakinra for colchicine refractory familial Mediterranean fever: a cohort of 44 patients.

OBJECTIVE: FMF is an autoinflammatory disease of genetic origin. Colchicine is the mainstay of treatment for the prevention of attacks and long-term complications but 5-10% of FMF patients are resistant to colchicine therapy. The aim of our study was to investigate the real-life safety and efficacy of anakinra in a cohort of patients with colchicine-resistant FMF. METHODS: In this retrospective study, patients treated with anakinra for colchicine-resistant FMF between 2010 and 2018 were identified using the computerized database of Sheba Medical Center and enrolled in the study. Data from structured clinical files were analysed to evaluate the efficacy and safety outcomes. To assess efficacy, we used the Global Assessment Score (GAS), a measure comprised of three different domains: number of attacks per month, duration of attacks and number of sites involved in the attacks. Reported adverse events were compiled. RESULTS: A total of 44 patients (24 female) were treated with anakinra. Of these patients, 75% were homozygous for the M649V mutation. The mean duration of treatment was 18 months. The GAS decreased significantly from 6.6 (IQR 5.3-7.8) before treatment to 2 (IQR 0-4.2) while on treatment (P < 0.001). During anakinra treatment, six hospitalizations were reported (three due to related adverse effects). In addition, 11 patients suffered from injection site reactions (5 ceased treatment). Twelve patients reported mild side effects. CONCLUSION: Treatment with anakinra is beneficial for the majority of colchicine-resistant FMF patients and is relatively safe.

Incidence and risk factors of pneumothorax following pre-procedural ultrasound-guided thoracentesis.

BACKGROUND: Data regarding the incidence and risk factors of pneumothorax following pre-procedural ultrasound (US)-guided thoracentesis is scarce. We aimed to evaluate the incidence and risk factors of pneumothorax following pre-procedural US-guided thoracentesis in a tertiary medical center. METHODS: Retrospective analysis of patients who underwent pre-procedural US-guided thoracentesis in Sheba Medical Center between January 2016 and December 2018. Data collected included incidence of pneumothorax following thoracentesis, baseline clinical and demographic characteristics, and thoracentesis-associated factors. Outcomes evaluated included length of hospital stay, mortality, chest tube insertion and intensive care unit admission. RESULTS: A total of 550 patients with pleural effusions underwent pre-procedural US-guided thoracentesis. Sixty-six (12%) of them developed pneumothorax. Compared to patients who did not develop pneumothorax, those who developed pneumothorax had a higher rate of congestive heart failure (32.2% vs. 47%, P=0.026), a smaller depth of pleural fluid marking (3.4 vs. 3.2 cm, P=0.024), a larger amount of pleural fluid drained (1,093 vs. 903.5 mL, P=0.01), and were more likely to undergo bilateral procedures (7.6% vs. 2.3%, P=0.044). In the multivariate regression analysis, volume of pleural fluid drained was significantly associated with the development of pneumothorax (OR, 1.001, 95% CI, 1-1.001; P=0.042). CONCLUSIONS: The incidence of pneumothorax following pre-procedural US-guided thoracentesis was relatively high in the present study. The amount of pleural fluid drained was the main factor associated with the risk of developing pneumothorax in these cases.

Macrophage activation syndrome complicating rheumatic diseases in adults: case-based review.

Macrophage activation syndrome (MAS) is a life-threatening complication of rheumatologic diseases. Data regarding the clinical course, management and outcome of adults with MAS is limited. Therefore, we aimed to describe the clinical features, treatment and outcome of adult patients with MAS, and review the literature for previous cohorts. We retrospectively reviewed patients with MAS complicating rheumatologic diseases between the years 2007 and 2017. Through Pubmed, Medline and Scopus literature search we identified previous cases of adult patients with MAS. We identified 7 patients with MAS complicating rheumatologic diseases (5 females and 2 males). The median age of diagnosis was 32 (range 26-57) years. The median follow-up was 30 months (range 6.95-36.5) months. The underlying rheumatologic disease was adult onset Still's disease (AOSD) in 3 patients, systemic juvenile idiopathic arthritis (sJIA) in 2 patients, systemic lupus erythematosus (SLE) in 1 patient, and systemic vasculitis in 1 patient. Four patients developed MAS concurrently with the clinical development of the rheumatologic disease. All the patients were treated with systemic corticosteroids. Five patients were treated with cyclosporine A, one of which received combination therapy with anakinra, and one received tocilizumab. Two patients deceased during the hospitalization. We identified 92 patients from literature cohorts, 73 (79%) of them with AOSD. MAS developed concurrently with the underlying rheumatologic disease in 25 (27%) patients, and 30 (33%) patients deceased. Our cohort and previous cohorts demostrate that MAS often presents concurrently with the underlying rheumatologic disease and is associated with a high mortality rate. Further larger prospective studies are needed to determine the optimal management of MAS.

Type 2 myocardial infarction in general medical wards: Clinical features, treatment, and prognosis in comparison with type 1 myocardial infarction.

Type 2 myocardial infarction (MI) is defined as myocardial necrosis due to imbalance between myocardial oxygen supply and demand. The objective of this study was to assess the features, treatments, and outcomes of patients with type 2 MI in comparison with patients with type 1 MI hospitalized in general medical wards. A retrospective review was performed on patients admitted to general medicine wards diagnosed with MI in Sheba Medical Center between January 1, 2016 and December 31, 2016. Comparative analysis between patients with type 1 and type 2 MI was performed. The study included 349 patients with type 1 MI and 206 patients with type 2 MI. The main provoking factors for type 2 MI were sepsis (38.1%), anemia (29.1%), and hypoxia (23.8%). Patients with type 2 MI were older (79.1 ±â€Š11.9 vs 75.2 ±â€Š11.7, P < .001) and had a lower rate of prior MI (23.3% vs 38.1%, P < .001) and percutaneous coronary intervention (PCI) (34% vs 48.7%, P = .023) compared with patients with type 1 MI. Patients with type 2 MI were significantly less prescribed antiplatelet therapy (79.1% vs 96%, P < .001) and statins (60.7% vs 80.2%, P < .001), and were less referred to coronary angiography (10.7% vs 54.4%, P < .001). Type 2 MI was associated with a significantly higher 1-year mortality rate compared with type 1 MI (38.8% vs 26.6%, P = .004), but after accounting for age and sex differences, this association lacked statistical significance. In conclusion, type 2 MI patients were older and had similar comorbidities compared with those with type 1 MI. These patients were less prescribed medical therapy and coronary intervention, and had a higher 1-year mortality rate. Establishing a clear therapeutic approach for type 2 MI is required.

Uric acid variability at midlife as an independent predictor of coronary heart disease and all-cause mortality.

BACKGROUND: Serum uric acid (SUA) has long been associated with cardiovascular disease. Variability of serum uric acid (SUA) has seldom been examined in association with long-term morbidity and mortality. Therefore, we aimed to investigate the association between SUA variability and long-term all-cause and specific-cause mortality. METHODS: Among 10,059 men, aged 40-65, tenured civil servants and municipal employees in Israel, 8822 participants who were examined in 1963, 1965 and 1968 had assessment of diabetic and coronary morbidity status and SUA levels. We conducted analysis examining whether the standard deviations (SD) of Z-scores of SUA across study visits predicted coronary heart disease (CHD) and mortality. Hazard ratios (HR) associated with the SD of SUA-Z were calculated for stroke, CHD mortality and all-cause mortality associated with quartiles of the above variability. RESULTS: Multivariate analysis of 18-year CHD mortality yielded a significant association with the 1963-1968 SD of SUA-Z with age adjusted HR of CHD mortality of 0.97 (95% CI, 0.8-1.19), 1.05 (95% CI, 0.87-1.28) and 1.37 (95% CI, 1.15-1.65) for quartiles 2 to 4 respectively). The results of all-cause mortality similarly and strongly indicated increasing age-adjusted mortality risk with increasing SD of SUA-Z: HR = 1.08 (95% CI, 0.97-1.21), 1.15 (1.03-1.28) and 1.37 (1.23-1.51). No association was observed between the SD of SUA-Z and stroke mortality. CONCLUSION: In this cohort of tenured male workers, with diverse occupations, higher variability of SUA measurement taken over 5 years was clearly predictive of 18-year CHD and all-cause mortality, above and beyond the SUA levels proper.

Identifying Diabetes in Clinical Notes in Hebrew: A Novel Text Classification Approach Based on Word Embedding.

NimbleMiner is a word embedding-based, language-agnostic natural language processing system for clinical text classification. Previously, NimbleMiner was applied in English and this study applied NimbleMiner on a large sample of inpatient clinical notes in Hebrew to identify instances of diabetes mellitus. The study data included 521,278 clinical notes (one admission and one discharge note per patient) for 268,664 hospital admissions to medical-surgical units of a large hospital in Israel. NimbleMiner achieved overall good performance (F-score =.94) when tested on a gold standard human annotated dataset of 800 clinical notes. We found 15% more patients with diabetes mentioned in the clinical notes compared with diagnoses data. Our findings about underreporting of diabetes in the coded diagnoses data highlight the urgent need for tools and algorithms that will help busy providers identify a range of useful information, like having a diabetes.

Cytokine expression in temporal arteries: comparative analysis between patients with biopsy-positive giant cell arteritis, biopsy-negative giant cell arteritis and biopsy-negative without arteritis.

OBJECTIVES: To investigate whether expression of pro-inflammatory cytokines in the temporal artery may aid in differentiating biopsy-negative giant cell arteritis (GCA) patients from those with a negative biopsy without arteritis. METHODS: We investigated cytokine expression in temporal artery biopsy (TAB) of 54 consecutive patients: 17 with biopsy-positive GCA, 17 with biopsy-negative GCA, and 20 biopsy-negative without arteritis. We compared the expression rate of the following cytokines among these 3 groups of patients: interleukin-6 (IL-6), osteopontin (OPN), COX-2, and TNF-α. RESULTS: IL-6 was expressed in 13 (76%) patients with biopsy-positive GCA, 0 patients in biopsy-negative GCA, and 1(5%) patient with biopsy-negative without arteritis (p<0.05). OPN was expressed in 17 (100%) patients with biopsy-positive GCA, 2 (12%) patients with biopsy-negative GCA, and 0 patients with biopsy-negative without arteritis (p<0.05). Cox-2 was expressed in 16 (94%) patients with biopsy-positive GCA, 0 patients with biopsy-negative GCA, and 3 (15%) patients with biopsy-negative without arteritis (p<0.05). TNF- α was expressed in 17 (100%) patients with biopsy-positive GCA, 14 (82%) patients with biopsy-negative GCA, and 8 (40%) patients with biopsy-negative without arteritis (p<0.05). CONCLUSIONS: IL-6, COX-2 and OPN are significantly more expressed in the presence of a positive TAB compared to a negative TAB. TNF-α is significantly more expressed in GCA patients compared to non-GCA patients. Thus, TNF-α expression may suggest a diagnosis of GCA despite a negative TAB. Further larger studies are needed to confirm these findings.

Clinical significance of positive anti-neutrophil cytoplasmic antibodies without evidence of anti-neutrophil cytoplasmic antibodies-associated vasculitis.

AIM: Anti-neutrophil cytoplasmic antibodies (ANCA) have a role in the diagnostic workup of ANCA-associated vasculitis. However, the clinical significance of positive ANCA in the absence of vasculitis is yet to be determined. Therefore, we sought to investigate the clinical spectrum and rate of patients with a positive ANCA without evidence of vasculitis. METHODS: Retrospective analysis of patients positive for cytoplasmic ANCA (C-ANCA) and proteinase 3 (PR3) or P-ANCA and myeloperoxidase (MPO) between 2007 and 2016 in the Chaim Sheba Medical Center, Israel. The proportion of patients who had no evidence of vasculitis among all patients with a positive C-ANCA/PR3 or P-ANCA/MPO was calculated according to tertiles of enzyme-linked immunosorbent assay (ELISA) antibody levels. RESULTS: Among 113 patients who tested positive for C-ANCA/PR3 or P-ANCA/MPO, 68 (60.1%) had no evidence of vasculitis. ELISA antibody titers were significantly higher among patients with vasculitis than those without (6.2 vs 3.2, for C-ANCA/PR3 and 5.4 vs 2.6 for P-ANCA/MPO, P < 0.05). The proportion of patients without vasculitis among all patients with a positive C-ANCA/PR3 and among all patients with a positive P-ANCA/MPO declined in parallel to the increases in ELISA antibody level tertiles (96%, 57% and 22% in the 1st, 2nd and highest tertiles, respectively, for patients with C-ANCA/PR3 patients and 100%, 66% and 20% in the 1st, 2nd and highest tertiles, respectively, for patients with P-ANCA/MPO). CONCLUSION: A significant proportion of patients with a positive C-ANCA/PR3 or P-ANCA/MPO do not have evidence of vasculitis, particularly those with low-medium ELISA antibody titers. Using a higher threshold of ANCA titers may be required to improve specificity.

Efficacy and safety of long-term treatment with intravenous colchicine for familial Mediterranean fever (FMF) refractory to oral colchicine.

Colchicine is the mainstay of treatment for familial Mediterranean fever (FMF). Intravenous (IV) colchicine, administered over several months, has been shown to be effective for FMF patients unresponsive to oral colchicine. The objective of this study was to evaluate the efficacy and safety of long-term IV colchicine treatment in oral colchicine-resistant FMF. We analyzed data of 15 patients with frequent FMF attacks, despite a maximal tolerated dose of oral colchicine (2-3 mg/day), who were treated with weekly IV injections of 1 mg of colchicine for at least 12 months. Treatment efficacy was determined by changes in frequency, duration and severity of FMF attacks. Safety was assessed according to adverse events. The mean duration of IV colchicine treatment was 5.16 ± 2.85 years. Decreases were observed from pre-treatment period in the monthly mean rates of abdominal attacks (from 5.6 ± 3.7 to 1.9 ± 3.3, p = 0.0009), joint attacks (from 6.5 ± 5.1 to 1.6 ± 1.6, p = 0.01) and overall attacks (from 22.3 ± 16.2 to 7.4 ± 5.7, p = 0.002) as well as in the mean duration (from 3.8 ± 1.5 to 2.4 ± 1.1 days per attack, p = 0.008) and severity of attacks (from 9.9 ± 0.3 to 5.7 ± 2.6, on a scale of 0-10, p < 0.05). The rate of adverse events was low, and they were mainly gastrointestinal. No severe or serious adverse events were recorded. Long-term treatment with IV colchicine in patients unresponsive to oral colchicine therapy is effective and safe.

Familial Mediterranean fever (FMF) phenotype in patients homozygous to the MEFV M694V mutation.

The clinical presentation of familial Mediterranean fever (FMF) is remarkably variable, ranging from a quiescent to a severe and disabling disease. The M694V mutation is one of approximately 300 published genetic variations in the FMF gene. While some studies have reported a more severe phenotype for the homozygous M694V mutation, studies dedicated solely to featuring the phenotype of homozygous M694V genotype are meager. The objective of the study was to present a comprehensive characterization of the homozygous M694V mutation associated phenotype, compared to the phenotypes of other FMF genotypes. For that aim, we compared between the demographic and clinical characteristics of 57 FMF patients, homozygous for the M694V MEFV mutation, and 56 patients with other MEFV genotypes. A questionnaire, detailing demographic and clinical features was completed for each patient based on an interview, physical examination and medical file data. Compared with the control group, the double M694V MEFV mutation group comprised more patients with severe disease (89.4 vs. 32.1%, p < 0.0001) and affected with FMF-related comorbidities (29.8 vs. 12.5%, p = 0.0373). The mean frequency of attacks per year was higher for patients with the double M694V MEFV mutation, before and during colchicine treatment (23.6 ±â€¯9.3 vs.15.6 ±â€¯11.7, p = 0.0001 and 7.2 ±â€¯7.8 vs. 3.5 ±â€¯5.5, p = 0.0007, respectively); and the mean dose of colchicine used was higher (1.9 ±â€¯0.48 vs.1.48 ±â€¯0.54 mg/day, p = 0.0001). Among the genotypes tested, homozygosity to the M694V MEFV mutation was found to be associated with the most grievous phenotype in the clinical spectrum of FMF.

Hematological malignancies mimicking rheumatic syndromes: case series and review of the literature.

It is well established that some rheumatic syndromes (RS) are associated with several hematological malignancies. We aimed to describe the clinical course of patients with hematological malignancies mimicking RS. We studied a series of four patients presenting with apparent RS who were eventually diagnosed with hematological malignancies, and reviewed the relevant literature. Our series consisted of 4 patients, with a mean age of 62.8 ± 20.3 years, who presented to our rheumatology unit between December 2012 and March 2018. Two patients were initially diagnosed with polyarthritis. One of these patients was eventually diagnosed with multiple myeloma and amyloidosis and the other was diagnosed with angioimmunoblastic T-cell lymphoma. The third patient was initially diagnosed with migratory arthritis and was eventually diagnosed with acute myeloid leukemia. The fourth patient was initially diagnosed with giant cell arteritis and eventually diagnosed with anaplastic large T-cell lymphoma. All the patients displayed a very good response to corticosteroid treatment. Vigilance for occult malignancy is essential in the diagnostic workup of RS. A good response to corticosteroids may constitute a major diagnostic pitfall in patients with hematological malignancies presenting with an apparent RS. In these cases, subtle clinical and laboratory features should elicit the clinician to seek for an occult malignancy.

Negative temporal artery biopsy: predictive factors for giant cell arteritis diagnosis and alternate diagnoses of patients without arteritis.

To investigate whether among patients with a negative temporal artery biopsy (TAB) there are clinical features that may differentiate between patients with an eventual diagnosis of giant cell arteritis (GCA) and those without arteritis, and to assess the eventual diagnoses of patients without arteritis. Retrospective analysis of patients with a negative TAB performed between 1/1/2000 and 31/12/2015. Information collected included baseline clinical and laboratory data. Patients' final diagnoses were obtained from medical records. Patients eventually diagnosed with GCA were compared with those without arteritis, and predictive features for GCA diagnosis were assessed. A total of 154 patients with a negative TAB were included in the study. Among them, 31 (20%) were eventually diagnosed with GCA. The leading alternative diagnoses of patients without arteritis were self-limited disease (23%), isolated polymyalgia rheumatica (PMR) (18%), and neurological conditions (17%). In the multivariate analysis, predictors for diagnosis of GCA among patients with a negative TAB included PMR (OR = 2.86, 95% CI 1.06-7.69), platelet count (OR = 1.28, 95% CI 1.07-1.53), and ACR score > 2 (OR = 13.4, 95% CI 4.27-42.03). Among patients with a negative TAB, the best predictors for diagnosis of GCA are fulfillment of the ACR criteria, a clinical diagnosis of PMR, and high platelet levels. These features may aid in the diagnostic work-up of patients with a negative TAB.

Left Ventricular Hypertrophy Predicts Cardiovascular Events in Hypertensive Patients With Coronary Artery Calcifications.

BACKGROUND: Coronary artery calcification (CAC) is associated with increased cardiovascular (CV) risk. Left ventricular hypertrophy (LVH) is an independent risk factor for CV events. Our aim was to estimate the relative CV risk of LVH in the presence of CAC. METHODS: We included asymptomatic hypertensive patients who were enrolled in the calcification arm of the INSIGHT (International Nifedipine Study Intervention as Goal for Hypertension Therapy). Patients had baseline echocardiography and computed tomography to assess CAC. The primary end-point was the first CV event. RESULTS: Two hundred and fifty-two subjects (mean age 64.7 ± 5.5 years, 54% men) were followed for a mean of 13.3 ± 2.6 years. 72 patients (28.5%) had LVH and 159 patients (63%) had CAC. During follow up, 89 patients had a first CV event. The rate of CV events was higher in those with than in those without CAC (43.4% vs. 21.5%, P < 0.01) and in those with than in those without LVH (44% vs. 31.6%, P < 0.01). However, LVH had no effect on CV events in the absence of CAC, whereas LVH almost doubled the rate of CV events (61.4% vs. 36.5%, P < 0.01) in the presence of CAC. In comparison to patients without CAC and without LVH the hazard ratio for CV event in those with LVH was 1.46 (95% confidence interval [CI], 0.50-4.21) in those without CAC and 4.4 (95% CI, 2.02-9.56) in those with CAC. CONCLUSIONS: LVH and CAC independently predict CV events in asymptomatic hypertensive patients. However, the risk of LVH is mainly observed in those with CAC.

The prevalence and clinical effect of immunogenicity of TNF-α blockers in patients with axial spondyloarthritis.

OBJECTIVES: To evaluate the prevalence of immunogenicity of TNF-α blockers in axial spondyloarthritis (SpA) patients and to assess the effect of immunogenicity on drug levels and clinical response. METHPDS: Patients with axial SpA treated with either infliximab (INF), adalimumab (ADA) or etanercept (ETN) were recruited to our observational cross-sectional study. Demographic and clinical data were collected and disease activity scores were assessed. Drug trough levels and anti-drug antibodies were measured in serum samples and collected before the next administration. RESULTS: Thirty-nine patients with axial SpA with a mean age of 46.3±12.7 (10 women) were recruited to the study (14 receiving INF, 16 ADA and 9 ETN). Patients' mean therapy duration was 50.6 months (±46.4) and 6 (15%) of them were using MTX concomitantly with the TNF-α blockers. Anti-drug antibodies were found in 6 (15%) patients (4 with INF and 2 with ADA), all of which had undetectable drug level. No anti-drug antibodies were detected in patients treated with ETN. Immunogenicity was associated with higher BASDAI (Bath Ankylosing Spondylitis Disease Index), ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score) and ASDAS-ESR. CONCLUSIONS: Axial SpA patients failure to respond to TNF-α blockers may be at least partially related to immunogenicity. Measurement of anti-drug antibodies and drug levels in these patients may assist in determining further treatment strategies.

Toll-like receptor 2 is overexpressed in Familial Mediterranean fever patients and is inhibited by colchicine treatment.

AIM: To study the role of Toll-like receptor (TLR) 2 in Familial Mediterranean fever (FMF) inflammatory process. METHODS: TLR2 expression on monocytes of FMF attack-free patients (n = 20) and the effect of sera of FMF patients with an acute attack (n = 9) on TLR2 expression on monocytes of healthy donors were studied by flow cytometry (FACS). TLR2 expression was also studied in THP-1 cells, and TLR2 downstream signaling was studied by ELISA for the secretion of IL-1ß and pro-inflammatory cytokines or by western blotting to measure nuclear factor (NF)-κB. RESULTS: FMF attack-free patients had increased CD14 + TLR2+ cell count as compared to healthy donors. High-dose colchicine treatment (≥2 mg/d) inhibited this increased expression in FMF patients. Colchicine in vitro also inhibited TLR2 expression on THP-1 cells. Sera from FMF patients with an acute attack induced TLR2 expression by both monocytes of healthy donors and THP-1 cells as well as pro-inflammatory cytokine secretion by healthy monocytes, while colchicine inhibited this induction. Pam2CSK4 increased interleukin-1ß (IL-1ß) secretion by peripheral blood mononuclear cells (PBMCs) of healthy donors, and this activation was inhibited by colchicine. THP-1 cells presented elevated NF-κB expression when cultured with Pam2CSK4, whereas colchicine inhibited this elevation. CONCLUSIONS: TLR2 activation was upregulated in monocytes of FMF patients, and colchicine inhibited this upregulation both in -vitro and in -vivo. This indicates that elevated expression of TLR2 promotes the production of pro-inflammatory cytokines, which may contribute to uncontrolled inflammation in FMF.

Carriage of Mediterranean Fever (MEFV) Mutations in Patients with Postpericardiotomy Syndrome (PPS).

BACKGROUND: Postpericardiotomy syndrome (PPS) is characterized by pleuro-pericardial inflammation, which occurs in patients undergoing surgical procedures involving the pleura, pericardium, or both. The syndrome is considered to be immune mediated. However, its pathogenesis is not fully understood. It has previously been demonstrated that the Mediterranean Fever (MEFV) gene, which is associated with familial Mediterranean fever (FMF), has a role in the activation and expression of several inflammatory diseases. OBJECTIVES: To investigate whether carriage of the MEFV mutation may precipitate PPS or affect its phenotype. METHODS: The study population included 45 patients who underwent cardiac surgery and developed PPS. The control group was comprised of 41 patients who did not develop PPS. Clinical and demographic data was collected. The severity of PPS was evaluated. Genetic analysis to determine the carriage of one the three most common MEFV gene mutations (M694V, V726A, E148Q) was performed. The carriage rate of MEFV mutations in patients with and without PPS was compared. Association between MEFV mutation carriage and severity of PPS was evaluated. RESULTS: The rate of mutation carriage in the MEFV gene was similar in patients with and without PPS (15.6% in the study groups vs. 29.3% in the control group, P = 0.1937). The rate of mutation carriage in the MEFV gene was significantly lower among patients with severe PPS as compared to patients with mild-moderate PPS (4.8% vs. 25%, P < 0.05). CONCLUSIONS: Carriage of mutations in the MEFV gene is not associated with development of PPS; however, it may affect PPS severity.