Pharmacokinetics of rivaroxaban after bariatric surgery: a case report

Rivaroxaban is a direct factor Xa inhibitor, which is rapidly absorbed in the upper gastrointestinal (GI) tract. In large trials, it has been shown to be effective and safe in VTE treatment. However, in these trials patients with morbid obesity were not reported and it is unknown if the standard dosage of 20 mg rivaroxaban is sufficient for bariatric patients, especially after bariatric surgery, which may impact the resorption of rivaroxaban. We report the case of a bariatric patient with high venous thromboembolism risk and instable INR after recent bariatric surgery, who was switched from Vitamin-K antagonists to rivaroxaban. After intake of 20 mg rivaroxaban, plasma concentration were repeatedly measured until 3 h after the second dose using a commercially available chromogenic aXa-assay. Furthermore, INR and aPTT were measured. Peak concentrations of 224.22 ng/ml were observed. After 6 h, plasma concentration decreased to 86.9 ng/ml and remained stable until 12 h (86.32 ng/ml). After 24 h, a trough level of 35.54 ng/ml was observed. The patients INR did immediately increase and remained significantly elevated throughout the day with a slow decrease. Since peak values of rivaroxaban plasma concentrations were in the expected range of published data, we conclude that resorption of rivaroxaban was immediate and not significantly impaired by bariatric surgery of the upper GI tract. Consequently, no dose adjustments seem to be necessary in this high-risk population.     

Novel adipokines vaspin and irisin as risk biomarkers for cardiovascular diseases in type 2 diabetes mellitus

Aims

Vaspin and irisin are novel cytokines proposed as potential new biomarkers of insulin resistance and endothelial dysfunction. This work is to investigate circulating levels of vaspin and irisin in patients with type 2 diabetes mellitus (T2DM) with and without cardiovascular disease (CVD) to study potential association with disease risk.

Measurement of dabigatran and rivaroxaban in primary prevention of venous thromboembolism in 106 patients, who have undergone major orthopedic surgery: an observational study

No routine coagulation laboratory test is recommended during rivaroxaban or dabigatran treatment. However measuring drug concentration and/or anticoagulant activity can be desirable in some special clinical settings, such as bleeding, thrombosis recurrence or emergency surgery. The effects of dabigatran etexilate and rivaroxaban on various coagulation assays have been previously studied in normal plasma spiked with increasing concentrations of the drug. In contrast, few data are available in routinely treated patients. In order to perform and to interpret the results of these tests, it is necessary to determine the usual responses of patient’s plasma. We have used several coagulation tests in a prospective study including 106 patients receiving thromboprophylactic treatment with dabigatran 150 or 220 mg od and rivaroxaban 10 mg od for major orthopaedic surgery. The most common tests—prothrombin time (PT) and activated partial thromboplastin time (aPTT)—give results, which vary according to the reagent used. To overcome this limitation, we advocate the use of plasma calibrators, which decreases the inter-laboratory heterogeneity of results. Anti-Xa measurement and Hemoclot, a thrombin diluted clotting assay, are specific assays which have been proposed for rivaroxaban and dabigatran respectively. These tests, conventional PT, aPTT and thrombin generation (TG) have been performed. We demonstrated that measurements of both drugs can determine reliably the drug concentration in patients’ plasmas. PT is more prolonged with rivaroxaban than with dabigatran. Interestingly, the pattern of TG was clearly different in relation to the difference in the mechanism of action of the two new anticoagulants. A significant inter-individual variability of response is detected. Rivaroxaban—mean Cmax 140 ng/mL (extremes 0–412) induces a greater increase of PT than dabigatran. aPTT is sensitive to dabigatran. Rivaroxaban concentrations were in good agreement with two other studies while unexplained lower than expected concentrations were found in dabigatran patients receiving 220 mg once a day [mean Cmax 60 ng/mL (extremes 0–320)]. An interference by pantoprazole, a drug which reduces dabigatran absorption, could explain the observed lower than expected results.     

Serum Surfactant Protein Levels in Patients Admitted to the Hospital with Acute COPD Exacerbation

Surfactant proteins (SPs) have been studied in COPD patients as biomarkers of disease severity and as predictive factors of unfavorable outcomes. The aim of this exploratory study was to evaluate serum levels of SP-A, SP-B, SP-C, and SP-D in patients with COPD both during AECOPD and in stability and to test their possible associations with disease severity and with the development of new exacerbation events. 20 consecutive COPD patients hospitalized for AECOPD were included. Serum SP levels were measured on admission, at discharge, and on stability. SP-A levels were significantly lower both on admission and at discharge in patients with early relapse compared to those with late or no relapse (29.2?±?9.1 vs. 43.9?±?16.9 ng/ml, p?=?0.037, and 24.3?±?2.8 vs. 39.3?±?14.2 ng/ml, p?=?0.011, respectively). SP-B levels were found to have a trend to be higher at discharge and significantly higher on stability in patients experiencing an early relapse compared to those with late or no relapse (52.5?±?31.6 vs. 31.4?±?32.3 ng/ml, p?=?0.052 and 64.8?±?32.6 vs. 32.8?±?25.6 ng/ml, p?=?0.024, respectively). Finally, the ROC analysis showed that serum SP-A, SP-B, and SP-C levels at discharge, seemed to be significant predictors of early relapse. Our conclusion is that serum levels of SPs might be related to disease outcomes in COPD patients.     

Safety of new oral anticoagulants for patients undergoing atrial fibrillation ablation

Background

The new oral anticoagulants (NOAC), dabigatran and rivaroxaban, have been demonstrated to be at least equivalent to warfarin for preventing cardiac thromboembolism (TE) in patients with atrial fibrillation (AF). However, there is limited data regarding use around catheter ablation (CA) procedures.

Objective

We evaluated the risk of bleeding and TE complications associated with NOAC use during AF ablation.

Methods

Consecutive patients undergoing AF ablation between January 2011 and 6 September 2013 were grouped based on peri-procedural anticoagulation regimen: (1) uninterrupted warfarin with therapeutic INR (WARF), n?=?114, (2) dabigatran, n?=?89, or (3) rivaroxaban, n?=?98. NOACs were held for 24 h (dabigatran) or 36 h (rivaroxaban) prior to the procedure. Heparin infusion was initiated 6 h post-procedure for the NOAC groups; NOACs were resumed the morning after the procedure. Antral PVI was performed with activated clotting time (ACT) maintained >300 s. TE or bleeding complications during ablation and through 30 days were compared.

Results

Three hundred and one patients underwent ablation for paroxysmal (71 %) or persistent (29 %) AF. International Normalization Ratio (INR) for the WARF group was 2.0?±?0.5. Baseline characteristics were similar among the groups. There were two TE events (asymptomatic cerebral emboli and TIA), and there were 17 bleeding events (large hematoma n?=?4; pericardial effusion n?=?6; persistent hematuria n?=?1; pseudoaneurism/AV fistula n?=?6). Of the six pericardial effusions, three required drainage. There was no significant difference in combined TE/bleeding risk among the groups (WARF vs. dabigatran vs. rivaroxaban; 6.2 % vs. 6.7 % vs. 6.0 %; p?=?0.82)

Conclusions

In this group of AF patients undergoing CA, use of peri-procedure dabigatran or rivaroxaban compared to uninterrupted warfarin did not lead to an increase in bleeding or TE complications.     

H-FABP, cardiovascular risk factors, and functional status in asymptomatic spinal cord injury patients

Background

This was a cross-sectional study in the setting of a rehabilitation hospital.

Objective

The aim of the study was to determine the serum levels of heart-type fatty acid-binding protein (H-FABP) in patients with spinal cord injury (SCI). A further goal was to examine whether there is a relationship between H-FABP levels and Functional Ambulation Classification (FAC) scale, Functional Independence Measure (FIM) score, American Spinal Injury Association (ASIA) status, and metabolic syndrome (MetS).

Methods

The study included 56 SCI patients and 37 age- and sex-matched healthy control subjects who had not been diagnosed with coronary artery disease in the past.

Results

Serum H-FABP levels were significantly higher in patients with SCI than in control subjects: paraplegia group, 18.5?±?11.4; tetraplegia group, 16.3?±?9.1; control group, 6.7?±?5.1 ng/ml (p?<?0.001). There was no difference between the other cardiac enzymes (troponin I, AST, ALT, CK, CK-MB, and LDH) among the groups. The relationship between the serum H-FABP levels and FAC status was examined. There was a negative correlation between FAC status and H-FABP levels (p?<?0.001, r?=???0.581). Patients with complete SCI were divided into two groups according to the level of the lesion: (lesion levels in C6–T6, n?=?25; lesion levels in T7–L2, n?=?11). In patients with complete motor injury, H-FABP levels were higher in subjects with injuries above T6 than in those with injuries below T6 (24.21?±?10.1 and 14.1?±?10.4, respectively; p?=?0.011). Serum levels of H-FABP were higher in SCI patients with MetS (n?=?10) than in those without MetS (n?=?46; 25.8?±?11.6 ng/ml vs. 16.42?±?10.3 ng/ml, respectively; p?=?0.014). Patients were then divided into two groups according to SCI duration: <?12 months (n?=?27) and >?12 months (n?=?29). H-FABP levels showed statistically significant differences between the two groups (14.8?±?11.7 ng/dl and 20.9?±?9.9 ng/dl, respectively; p?=?0.036).

Conclusion

H-FABP is related to MetS and FAC status in asymptomatic SCI patients.     

Rationale and design of VENTURE-AF: a randomized,open-label,active-controlled multicenter study to evaluate the safety of rivaroxaban and vitamin K antagonists in subjects undergoing catheter ablation for atrial fibrillation

Purpose

To evaluate the safety of uninterrupted rivaroxaban, a novel oral anticoagulant that directly inhibits factor Xa, and a vitamin K antagonist (VKA) in eligible adult patients with nonvalvular AF (NVAF) who are scheduled for a catheter ablation.

Methods/design

This is a prospective, randomized, open-label, active-controlled, global multicenter safety study of up to 250 randomized patients. Eligible patients with paroxysmal or persistent NVAF, a left ventricular ejection fraction >40 %, and a creatinine clearance >50 mL/min will be randomized 1:1 to rivaroxaban 20 mg orally once daily or to dose-adjusted oral VKA (recommended international normalized ratio (INR) 2.0–3.0) and stabilized on anticoagulation therapy for 1–7 days (if no intracardiac thrombus on transesophageal echocardiogram (TEE) immediately prerandomization/post-randomization or if 3 weeks of sufficient anticoagulation is documented) or for 4–5 weeks (if no TEE, no documented 3 weeks of sufficient anticoagulation, or by patient choice). During catheter ablation, heparin will be administered (ACT-targeted range?=?300–400 s) after catheter ablation, and VKA will be managed per usual care. The next dose of rivaroxaban will be provided at least 6 h after establishment of hemostasis. The primary endpoint will be the incidence of post-procedure major bleeding events observed during the first 30?±?5 days post-ablation. Secondary endpoints will include post-procedure thromboembolic events, additional bleeding, time-to-event, and medication adherence.

Relevance

This study is intended to provide information about the safety characteristics of rivaroxaban in patients with NVAF undergoing catheter ablation.     

Efficacy of a twice-daily antiretroviral regimen containing 100 mg ritonavir/400 mg indinavir in HIV-infected patients

OBJECTIVE: To evaluate the pharmacokinetics, efficacy and tolerability of a low-dose boosted indinavir (IDV)/ritonavir (RTV) regimen [100 mg RTV/400 mg IDV twice daily (bid)] in patients previously receiving a standard IDV regimen [800 mg three times a day (tid)]. METHODS: In a prospective, open-label, cross-over trial, patients with plasma HIV RNA < 200 copies/ml receiving an IDV-containing regimen (800 mg tid) were switched to an RTV/IDV (100/400 mg bid)-containing regimen. Minimal and maximal IDV plasma concentrations ( Cmin and Cmax ) were determined before the switch (day 0), at week 2 and week 4 after the switch. The CD4 cell count and plasma HIV RNA were determined at day 0, week 2 and week 4, then every 8 weeks. The primary end-point was the percentage of patients with plasma HIV RNA below 200 copies ml at week 48. RESULTS: Twenty patients were enrolled. At baseline, on IDV 800 mg tid, median IDV Cmin was 194 ng/ml and median IDV Cmax was 8449 ng/ml. On RTV/IDV (100/400 mg), median IDV Cmin increased to 536 ng/ml at week 2 and 475 ng/ml at week 4, while Cmax decreased to 2983 ng/ml at week 2 and 2997 ng/ml at week 4 ( P < 0.001). The median area under the IDV plasma concentration-time curve measured in seven patients was 25 126 ng.h/ml, and the IDV half-life (t1/2 ) was 4.4 h. All patients had plasma HIV RNA remaining < 200 copies/ml at week 48. Tolerability of RTV/IDV was excellent. CONCLUSION: RTV/IDV (100/400 mg bid) yields significantly higher IDV plasma Cmin and lower IDV Cmax values relative to the standard IDV regimen, thereby improving both tolerability and efficacy.     

Standardized use of novel oral anticoagulants plasma level thresholds in a new thrombolysis decision making protocol

Acute ischemic stroke (AIS) patients receiving non-vitamin-K antagonist oral anticoagulants (NOAC) are commonly excluded from thrombolytic therapy, as interpretation of coagulation tests remains unclear. We aimed to investigate the applicability of a novel institutional protocol for thrombolysis based on current expert recommendations and NOAC specific coagulation assessment. We included hospitalized AIS patients receiving NOAC for at least 24 h and consecutive AIS patients not receiving NOAC into a prospective study. We performed standard coagulation tests and specific tests for dabigatran, rivaroxaban and apixaban plasma levels. We studied 65 patients: mean age 72 ± 13 years, 30 (46 %) male, median NIHSS score 3 (IQR 6). Fifteen (23 %) were on NOAC treatment (5 dabigatran, 5 rivaroxaban, and 5 apixaban, respectively) and 50 (77 %) were not. In patients without NOAC, dabigatran was not detectable (0 ng/ml), and plasma levels of rivaroxaban (median: 10.0 ng/ml, IQR 7.0) and apixaban (7.2 ng/ml, IQR 6.7) were below our lower thresholds that allow thrombolysis. In patients with dabigatran pre-treatment, trough levels (58.0 ng/ml, IQR 143.0) were below our upper threshold that would allow thrombolysis in 3/5 patients. In patients receiving rivaroxaban, trough level (68.0 ng/ml, IQR 64.0) was below our predefined upper thresholds that would allow thrombolysis in 4/5 patients. In all patients on apixaban, trough level was above our predefined threshold of 40 ng/ml that precludes thrombolysis (98.2 ng/ml, IQR 84.3). Predefined thresholds of NOAC plasma levels in the decision of thrombolysis in NOAC treated AIS patients might supplement routine coagulation tests and should be validated in a larger study population.     

Vitamin A improve Th17 and Treg regulation in systemic lupus erythematosus

The aim of this study was to determine the role of vitamin A in modulating T helper 17 (Th17) and regulatory T cell (Treg) balance in systemic lupus erythematosus (SLE) patients. Sixty-two female SLE patients and sixty-two female controls were measured for vitamin A levels from serum by enzyme-linked immunosorbent assay (ELISA) and percentages of Th17 and Treg from peripheral blood mononuclear cells (PBMC) by flow cytometry. We also performed an in vitro study to evaluate the effects of retinoic acid treatment (0, 0.1, 0.2, and 0.3 μg/ml) in modulating Th17/Treg balance in CD4⁺ T cell culture from hypovitaminosis A SLE patients. Th17 and Treg percentages from cell cultures were measured by flow cytometry. Vitamin A levels in the SLE patients were lower compared to those in the healthy control (46.9?±?43.4 vs. 75.6?±?73.1 ng/ml, p?=?0.015). Vitamin A levels also had a negative correlation to Th17 percentages in the SLE patients (p?=?0.000, R?=??0.642). Th17 percentages in the hypovitaminosis A SLE patients were higher compared to those SLE patients with normal vitamin A levels (10.9?±?5.3 vs. 2.9?±?2.2 %, p?=?0.000). Treatment of 0.3 μg/ml of retinoic acid could increase Treg differentiation (33.9?±?1.6 vs. 21.8?±?1.1 %, p?=?0.000) and decrease Th17 differentiation (27.2?±?2.5 vs. 37.4?±?1.3 %, p?=?0.000). In conclusion, vitamin A has important roles in modulating Th17/Treg balance in the SLE patients shown by the significant decrease of vitamin A levels in the SLE patients which negatively correlate with Th17 population, and treatment of retinoic acid could decrease Th17 and increase Treg percentages in CD4⁺ T cells cultures.     

Increased H-FABP concentrations in nonalcoholic fatty liver disease

Aim

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder which is reported as the hepatic manifestation of metabolic syndrome with an increased risk of cardiovascular events. Patients with NAFLD are also at risk of future cardiac events independently of metabolic syndrome. The aim of this study was to examine serum concentrations of heart type fatty acid binding protein (H-FABP) in NAFLD and to investigate its correlations with metabolic parameters and subclinical atherosclerosis.

Patients and methods

A total of 34 patients with NAFLD and 35 healthy subjects were enrolled in the study. NAFLD patients had elevated liver enzymes and steatosis graded on ultrasonography. Healthy subjects had normal liver enzymes and no steatosis on ultrasonography. H-FABP levels were measured using an enzyme linked immunosorbent assay (ELISA) method and correlations with metabolic parameters and subclinical atherosclerosis were examined. Subclinical atherosclerosis was determined with carotid artery intima–media thickness (CIMT) which was measured by high resolution B mode ultrasonography.

Results

H-FABP levels were elevated in patients with NAFLD (16.3?±?4.0 ng/ml) when compared with healthy controls (13.8?±?2.1 ng/ml; p??<?0.001). NAFLD patients had significantly higher CIMT than the controls had (0.64?±?0.17 mm vs. 0.43?±?0.14 mm, p?=?0.009). The H-FABP concentrations were significantly positively correlated with body mass index (r?=?0.255, p?=?0.042), fasting blood glucose level (r?=?0.300, p?=?0.013), CIMT (r?=?0.335, p?=?0.043), and homeostasis model assessment-estimated insulin resistance (HOMA-IR; r?=?0.156, p?=?0.306). In multiple linear regression analysis, H-FABP levels were only independently associated with CIMT (p?=?0.04)

Conclusion

Serum H-FABP concentrations increase in patients with NAFLD. Our results may not only suggest that H-FABP is a marker of subclinical myocardial damage in patients with NAFLD but also of subclinical atherosclerosis, independent of metabolic syndrome and cardiac risk factors.     

The impact of obesity on balance control in community-dwelling older women

Older individuals have impaired balance control, particularly those that are frail and/or have sensory deprivations. Obese individuals show faster body sway during upright stance than normal weight individuals, suggesting that they also have difficulty controlling balance even if they do not have the same sensory issues as the older people. Therefore, the objective of this study was to examine if obesity is associated to a decreased balance control in older women. Postural sway of normal weight (n?=?15, age?=?70.8?±?5.5 years; BMI?=?22.2?±?1.9 kg/m²), overweight (n?=?15, age?=?71.7?±?4.3 years; BMI?=?27.3?±?1.3 kg/m²), and obese (n?=?15, age?=?71.1?±?4.3 years; BMI?=?33.1?±?3.4 kg/m²) women was measured with a force platform for normal quiet stance lasting for 30 s in opened and closed eyes conditions. The obese group oscillated at a faster speed than the normal weight group (vision 0.99?±?0.29 cm/s vs. 0.70?±?0.16 cm/s, p?<?0.01; no vision 1.43?±?0.50 cm/s vs. 0.87?±?0.23 cm/s, p?<?0.01). The obese group exhibited greater range in both axes without vision compared to the normal weight group (p?<?0.05). When observing sway density parameters, the obese group also spent less time in stability zones (2 mm radius area in which the center of pressure is relatively stable), and the distance between these stability zones are greater than the normal weight group in both visual conditions (p?<?0.01 and p?<?0.05, respectively). Obesity clearly affects postural control in older women. Our results suggest that obesity has a negative impact on the capacity of older woman to adequately use proprioceptive information for posture control. As postural instability or balance control deficits are identified as a risk factor for falling, our results also suggest that obesity in older women could be considered as another potential contributing factor for falling.     

Potential role of vitamin D deficiency on Fabry cardiomyopathy

Patients with Fabry disease frequently develop left ventricular (LV) hypertrophy and renal fibrosis. Due to heat intolerance and an inability to sweat, patients tend to avoid exposure to sunlight. We hypothesized that subsequent vitamin D deficiency may contribute to Fabry cardiomyopathy. This study investigated the vitamin D status and its association with LV mass and adverse clinical symptoms in patients with Fabry disease. 25-hydroxyvitamin D (25[OH]D) was measured in 111 patients who were genetically proven to have Fabry disease. LV mass and cardiomyopathy were assessed by magnetic resonance imaging and echocardiography. In cross-sectional analyses, associations with adverse clinical outcomes were determined by linear and binary logistic regression analyses, respectively, and were adjusted for age, sex, BMI and season. Patients had a mean age of 40?±?13 years (42 % males), and a mean 25(OH)D of 23.5?±?11.4 ng/ml. Those with overt vitamin D deficiency (25[OH]D?≤?15 ng/ml) had an adjusted six fold higher risk of cardiomyopathy, compared to those with sufficient 25(OH)D levels >30 ng/ml (p?=?0.04). The mean LV mass was distinctively different with 170?±?75 g in deficient, 154?±?60 g in moderately deficient and 128?±?58 g in vitamin D sufficient patients (p?=?0.01). With increasing severity of vitamin D deficiency, the median levels of proteinuria increased, as well as the prevalences of depression, edema, cornea verticillata and the need for medical pain therapy. In conclusion, vitamin D deficiency was strongly associated with cardiomyopathy and adverse clinical symptoms in patients with Fabry disease. Whether vitamin D supplementation improves complications of Fabry disease, requires a randomized controlled trial.     

Phenotypic and clinical differences between Caucasian and South Asian patients with psoriatic arthritis living in North East London

To test for demographic and clinical differences between Caucasian and South Asian patients with psoriatic arthritis (PsA) living in the same environment and for differences between sexes. The demographic characteristics of patients attending outpatient clinics were obtained using a semi-structured questionnaire. Clinical parameters included disease activity (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), erythrocyte sedimentation rate (ESR), C-reactive protein), function (Bath Ankylosing Spondylitis Functional Index (BASFI)) and visual analogue scale (VAS) scores for well-being and night pain (10 cm, where 10?=?worst possible response). The first symptom experienced at disease onset and the main symptoms during the disease course were recorded in the questionnaire. A total of 217 patents were assessed of whom 151 were Caucasians and 66 were Asians. South Asian patients were significantly younger [(mean) 45.9 years [(SD)(±11.4)] for Asians and 53.1 years (±14.2) for Caucasians (p?<?0.005)] and were diagnosed at an earlier age [40.7 years (±11.7) for Asians and 46.7 years (±15.8) for Caucasians (p?<?0.05)] compared to Caucasians patients. Asian females with PsA had worse disease in terms of activity (ESR?=?23.9 mmHg/h; BASDAI?=?6.7), function (BASFI?=?5.5), night pain (7.1 on VAS) and well-being (6.6 on VAS) compared with Asian males (13.2 mmHg/h, 5.3, 3.6, 4.1, 4.6, respectively) or Caucasian males and females (15.8 mmHg/h, 5.9, 5.3, 5.4, 5.4; 18.9 mmHg/h, 6.1, 6.1, 5.3, 5.8, respectively). There were no significant differences in symptoms at disease onset or the main symptoms during the disease course between Caucasian and Asian patients, although there was a trend towards more frequent enthesitis in Asian females during the course of disease suggested by pain with pressure compared to Asian males. South Asian patients may develop PsA earlier in life than Caucasian patients do, but their clinical characteristics are generally similar. Asian females with PsA have worse disease activity, function, night pain and well-being than Asian males and Caucasian males and females.     

Risk factors for severe bacterial infections in patients with systemic autoimmune diseases receiving rituximab

The risk of serious bacterial infectious events (SIEs) after an RTX course used in severe and refractory cases of systemic autoimmune diseases (SAID) is well known. Risk factors for SIEs merit investigation. For this case–control study, data were collected in a single centre of internal medicine and included all patients who received rituximab (RTX) for SAID between 2005 and 2011 (rheumatoid arthritis was excluded). Sixty-nine patients with SAID received a total of 87 RTX courses. Thirteen SIEs were reported in 12 patients leading to death in 5 patients. Patients with a history of SIE were significantly older (63.6?±?18.8 vs 48.8?±?16.7; p?=?0.0091), suffered most frequently of diabetes mellitus (33.3 % vs 5.3 %, p?=?0.015), had a lower CD19 count (1.0?±?1.2/mm³ vs 3.9?±?7.2/mm³) and had most frequently a prednisone dose >15 mg/day (91.7 % vs 47.7 %) at the start of the first RTX course. The SIE rate was 18.7 per 100 patient-years. At the initiation of the RTX course, risk factors for SIEs were lower IgG levels (OR?=?0.87, 95%CI?=?0.77–0.99, p?=?0.03), lower CD19 count (OR?=?0.85, 95%CI?=?0.73–1.00) and creatinine clearance?≤?45 ml/min (OR?=?7.78, 95%CI?=?1.36–44.38, p?=?0.002). Conversely history of pneumococcal vaccination significantly decreased the risk of SIEs (OR?=?0.11, 95%CI?=?0.03–0.41, p?=?0.0009). Concomitant treatment with prednisone at a dose >15 mg/day significantly increased the SIE risk (OR?=?8.07, 95%CI?=?1.94–33.59, p?=?0.0004). SIEs are frequent in SAID treated with RTX, particularly in patients receiving high-dose corticosteroids, in patients with renal insufficiency and in patients with low IgG levels or a low CD19 count.     

Relevance of vitamin D deficiency in patients with chronic autoimmune atrophic gastritis: a prospective study

Background

Chronic autoimmune atrophic gastritis (CAAG) is an autoimmune disease characterized by hypo/achlorhydria. A role of CAAG in the pathogenesis of nutritional deficiencies has been reported, therefore we hypothesized a possible association between CAAG and 25-OH-Vitamin D [25(OH)D] deficiency. Aim of the present study is to evaluate the prevalence of 25(OH)D deficiency in CAAG patients. Methods: 87 CAAG patients (71 females; mean age 63.5?±?12.8 years) followed at our Centre from January 2012 to July 2015 were consecutively evaluated. 25(OH)D, vitamin B₁₂, parathormone, and calcium were measured in all the CAAG patients. The results were compared with a control group of 1232 healthy subjects.

Results

In the CAAG group the mean 25(OH)D levels were significantly lower than in the control group (18.8 vs. 27.0 ng/ml, p?<?0.0001). 25(OH)D levels <?20 ng/ml was observed in 57 patients, while levels <?12.5 ng/ml in 27 patients. A significant correlation between vitamin B₁₂ values at diagnosis and 25(OH)D levels was observed (r_s?=?0.25, p?=?0.01). Interestingly, the CAAG patients with moderate/severe gastric atrophy had lower 25(OH)D values as compared to those with mild atrophy (11.8 vs. 20 ng/ml; p?=?0.0047). Moreover, the 25(OH)D levels were significantly lower in CAAG patients with gastric carcinoid as compared to those without gastric carcinoid (11.8 vs. 19.8 ng/ml; p?=?0,0041).

Conclusion

Data from the present study showed a significant reduction of 25(OH)D levels in CAAG patients and a possible impairment of vitamin D absorption in CAAG may be postulated. Any implication to the genesis of gastric carcinoids remains to be elucidated.

     

Comparison of initial warfarin response in obese patients versus non-obese patients

Achieving therapeutic anticoagulation with warfarin is complicated by substantial inter-patient and intra-patient variability with numerous factors known to influence dose requirements. Obesity is one factor for which there remains no study to date investigating its initial effect on warfarin response assessed by INR, stratified by BMI category in hospitalized patients. To compare initial warfarin response between obese and non-obese patients by evaluating average daily dose (ADD), time required to attain therapeutic INR, and mean discharge dose (MDD), stratified by BMI category. A retrospective review was conducted to evaluate initial warfarin response in hospitalized patients of different BMI categories initiated on warfarin with ≥4 consecutive days of therapy and managed by pharmacy dosing service. 211 patients were included (10 underweight, 45 normal weight, 48 overweight, 71 obese, 37 morbidly obese). Across BMI categories, the percentage of patients attaining therapeutic INR prior to discharge differed (p = 0.0004) with 71.1 % of normal weight therapeutic compared to 42.3 % of obese and 38 % of morbidly obese. Within BMI categories, when comparing ADD between patients therapeutic and subtherapeutic at discharge, no differences were observed, except among overweight patients (5.6 ± 0.3 vs. 7 ± 0.4 mg, p = 0.0143). Compared to normal weight, obese and morbidly obese required a significantly longer median time to achieve therapeutic INR (8 and 10 days vs. 6 days) and a higher ADD (6.6 ± 0.3 and 7.6 ± 0.5 vs. 5 ± 0.3 mg) and MDD (6.7 ± 0.5 and 6.7 ± 0.7 vs. 4.4 ± 0.5 mg). Compared to normal weight, obese and morbidly obese patients had a decreased initial response to warfarin.     

Acute and long-term effect of infliximab on humoral and echocardiographic parameters in patients with chronic inflammatory diseases

Tumor necrosis factor alpha (TNF-alpha) plays an important role in the pathogenesis of chronic inflammatory diseases, i.e., rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD), and ulcerative colitis (UC). Anti-TNF-alpha strategies are successfully used in their treatment. However, their effect on heart function is still uncertain. The objectives of the study were to examine the acute and long-term effect of infliximab on the heart morphology and function in patients with chronic inflammatory disorders. Thirty-one patients (21 men and 10 women) were included. Ten percent of them were diagnosed with RA, 22.5 % with AS, 22.5 % with CD, and 45 % with UC, respectively. N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) was measured before and immediately after infliximab administration at the beginning of the study and in the sixth and 12th months. Echocardiography was performed at baseline and in the sixth and 12th months. There was a significant increase in NT-proBNP after the first infliximab infusion (88.40?±?14.09 vs. 95.24?±?14.28 pg/ml, p?=?0.0046) and similar response was detected after each infusion in the sixth and 12th months. Plasma NT-proBNP slightly but not significantly decreased (88.40?±?14.09 vs. 81.74?±?23.14 pg/ml, p?=?0.583, and 88.40?±?14.09 vs. 56.83?±?17.77 pg/ml, p?=?0.0576, in the sixth and 12th months, respectively). There were no significant changes in echocardiographic structural and functional parameters of the left ventricle during follow-up. Plasma NT-proBNP mildly but significantly increases immediately after infliximab infusion. However, long-term infliximab administration does not deteriorate both cardiac morphology and function.     

Evaluation of serum procalcitonin and C-reactive protein levels as biomarkers of Henoch-Schönlein purpura in pediatric patients

Henoch-Schönlein purpura (HSP) is a vasculitic disorder resulting from autoinflammatory-mediated tissue injury. Procalcitonin (PCT) and C-reactive protein (CRP) are two biomarkers of the immune response that recognize bacterial infection and inflammation, respectively. This study tested whether levels of PCT and CRP were associated with selected clinical features, disease severity, and organ damage in HSP. Eighty-nine pediatric patients with HSP were analyzed for clinical manifestations and organ damage. Serum CRP, PCT, and occult blood in the urine and stool (prior to steroid therapy) were measured. Disease severity was classified according to previously established clinical classifications. Sixty patients (67.4 %) had a low clinical score (LCS) of <4 (group A) while 29 patients (32.5 %) had a high clinical score (HCS) of ≥4 (group B). When patients were then classified by the presence of gastrointestinal bleeding, 66 (74.2 %) cases lacked alimentary tract hemorrhage (group C) while 23 (25.8 %) cases presented with gastrointestinal bleeding (group D). There were no significant differences in CRP (group A: median?=?5.26, range?=?1.00–77.60 vs. group B: median?=?8.59, range?=?1.00–144.00 mg/l; u?=?1.397) or PCT levels (group A: median?=?0.05, range?=?0.05–0.24 vs. group B: median?=?0.08, range?=?0.05–1.02 ng/ml; u?=?1.709) between groups A and B. When serum PCT levels were examined in relation to gastrointestinal bleeding, the levels of serum PCT were higher in group D than group C patients (group D: median?=?0.09, range?=?0.05–1.02 vs. group C: median?=?0.05, range?=?0.05–0.32 ng/ml; u?=?2.849). It is important to note that the average PCT level was below the threshold for a systemic bacterial infection (0.5 ng/ml). We did not observe a correlation between CRP levels and the absence or presence of GI bleeding in groups C or D (group C: median?=?4.66, range?=?1.00–144.00 vs. group D: median?=?9.44, range?=?1.06–124.00 mg/l; u?=?1.783), respectively. In all patients, there was a significant correlation between the concentrations of PCT and CRP (r?=?0.721, p?=?0.002). In patients with HSP, inflammatory markers are not uniformly associated with the disease and instead, show variable association depending on the clinical severity and level of organ damage. In patients with severe HSP, elevated serum PCT was significantly associated with gastrointestinal bleeding. In contrast, CRP was not a specific predictor for different clinical classifications of HSP, despite a similar pattern of concentration changes to PCT.