Serum uric acid levels are associated with lupus nephritis in patients with normal renal function

Uric acid has been recognised as a potential marker of endothelial dysfunction and kidney disease but there are scarce data about its importance in systemic lupus erythematosus (SLE) nephritis. This study aimed to evaluate serum uric acid (UA) levels in lupus nephritis (LN), by comparing SLE patients with normal renal function, with and without nephritis. Forty-six female SLE patients were consecutively selected and divided in two groups according to renal activity at the evaluation: presence of a recently diagnosed lupus nephritis (LN+, n?=?18) and absence of lupus nephritis (LN?, n?=?28). Age-matched healthy women were selected (CONTROL, n?=?28). Patients with gout, creatinine clearance lower than 80 ml/min and use of drugs that interfere in UA were excluded. Laboratory and clinical data were analysed by appropriate tests. A multivariate analysis was performed, and a receiver operating characteristic (ROC) curve was plotted, and the area under the curve was calculated to assess the diagnostic strength of UA in LN. The mean age was similar among LN+, LN? and CONTROL groups (32.44?±?6.09 vs. 30.68?±?5.36 vs. 30.86?±?5.00 years, p?=?0.52). UA was significantly higher in LN+ compared to LN? (5.54?±?1.67 vs. 3.65?±?1.090 mg/dL, p?<?0.001) and CONTROL (5.54?±?1.67 vs. 3.92?±?0.95 mg/dL p?<?0.001). Multivariate analysis confirmed that high UA was an independent variable related to LN (p?<?0.001). The cut-off value for UA using the ROC curve was 4.47 mg/dL (AUC 0.86, p?=?0.00004, CI 95% 0.75–0.96). Lupus nephritis was associated with higher UA. Hyperuricemia as a predictor of renal damage in SLE needs to be evaluated in further studies.     

Evolution of chronic kidney disease in patients with systemic lupus erythematosus over a long-period follow-up: a single-center inception cohort study

The objective is to investigate the accrual rate and risk factors of chronic kidney disease (CKD) in an inception cohort of patients with systemic lupus erythematosus (SLE) followed at a single tertiary center. A prospectively collected database of 256 consecutive patients with SLE followed over a 25-year period was systematically interrogated for demographic, disease manifestations, co-morbidities, and outcome. Standardized SLE activity and damage scores were determined for the first and last study visits, and estimated glomerular filtration rate (eGFR; MDRD formula) was calculated at the time of diagnosis and at each year of the follow-up. CKD was defined as eGFR <60 ml/min/1.73 m². Results were analyzed with univariate and multivariate models and Kaplan-Meier curves, as appropriate. The cohort was predominantly female (90 %) and Jewish (91.1 %). Mean age at diagnosis was 38?±?15.5 years, mean SLE activity score 6.4?±?3.8, mean disease duration 8.8?±?6.6 years, and mean damage score 0.2?±?0.6. Seventy-five patients (30.8 %) were diagnosed with American College of Rheumatology (ACR)-defined lupus renal disease during the study period. There was a progressive decrease in eGFR over time. The prevalence of CKD was 46.7 % in patients with ACR-defined renal lupus disease and 16.4 % in those without. The hazards ratio for CKD was significantly higher in patients with lupus nephritis (LN) than without (p?<?0.001). Earlier CKD was positively associated with hypertension (p?=?0.01), older age at diagnosis (p?=?0.01), and LN (p?<?0.001), and negatively associated with hydroxychloroquine treatment (p?<?0.001). The prevalence of CKD increases cumulatively in patients with SLE, also in those without overt lupus renal disease. Lupus renal disease poses a significant hazard for earlier development of CKD, and hypertension is a major risk factor for patients with and without nephritis. Antimalarial treatment is associated with renal preservation only in patients with lupus nephritis.     

Persistent expression and function of P-glycoprotein on peripheral blood lymphocytes identifies corticosteroid resistance in patients with systemic lupus erythematosus

Corticosteroids (CS) are the mainstay of treatment in systemic lupus erythematosus (SLE) patients. However, some patients have poor response to CS treatment. Among the multiple mechanisms of CS resistance, overexpression of P-glycoprotein (P-gp) on peripheral blood lymphocytes (PBL) may be one of them as this result in efflux of CS from lymphocytes. Thus, we evaluated the role of P-gp protein on PBLs in patients with SLE in its response to CS therapy. SLE patients (n?=?42) (fulfilling ACR revised criteria) who were naïve to CS and immunosuppressive drugs were enrolled. Disease activity was assessed using SLE disease activity index (SLEDAI) and expression, and function of P-gp was evaluated by flow cytometry at baseline and after 3 months of therapy with CS. At 3 months, patients with SLEDAI >4 and SLEDAI ≤4 were grouped as nonresponders and responders, respectively. P-gp expression was significantly increased on PBLs of SLE patients as compared to healthy controls (p?<?0.001). P-gp expression and function correlated with SLEDAI (r?=?0.49, p?=?0.005; and r?=?0.49, p?=?0.001, respectively). P-gp expression and function were not different in responders and nonresponders at baseline. However, at 3 months of CS therapy, P-gp expression and function decreased in responders (p?<?0.001 and p?<?0.005, respectively), whereas in nonresponders, it remained unchanged. Persistent overexpression and activity of P-gp are associated with poor response to CS in CS naïve patients of SLE.     

The predictive factors of low serum 25-hydroxyvitamin D and vitamin D deficiency in patients with systemic lupus erythematosus

Vitamin D is a steroid hormone with pleiotropic effects. The association between serum 25-hydroxyvitamin D level [25(OH) D] and lupus nephritis are not clearly known. We aim to determine serum 25(OH) D levels in patients with inactive SLE, active SLE without lupus nephritis (LN) and active SLE with LN and to identify clinical predictor of vitamin D deficiency. One hundred and eight SLE patients were included. Patients were classified as Group (Gr) 1, 2 and 3 if they had SLE disease activity index (SLEDAI) <3, ≥3 but no LN and ≥3 with LN. Important baseline characteristics were collected. 25(OH) D was measured by high performance liquid chromatography (HPLC). SLEDAI in Gr1, Gr2 and Gr3 was 0.7 (0.9), 5.6 (2.3) and 9.2 (5.2), respectively. 43.5 % had vitamin D insufficiency and 29.6 % had vitamin D deficiency. Mean 25(OH) D in each groups was 28.3 (8.0), 26.7 (9.5) and 19.9 (7.6) ng/ml (p < 0.001 comparing Gr1 and 3) (p = 0.003 comparing Gr2 and 3). Vitamin D deficiency was found in 11.1, 22.2 and 55.6 % of Gr1, 2 and 3. Linear regression analysis found that 25(OH) D was significantly correlated with serum albumin (r = 0.28, p = 0.004), inversely correlated with SLEDAI (r = ?0.22, p = 0.03) and urinary protein creatinine index (UPCI) (r = ?0.28, p = 0.005), but not with sun exposure score, body mass index and estimated GFR. Only UPCI was significantly inversely correlated with 25(OH) D (p = 0.02) from multiple linear regression. LN was a significant predictor of vitamin D deficiency from multivariate logistic regression (OR 5.97; p = 0.006). Vitamin D deficiency and insufficiency was found in 93 and 86 % of LN with proteinuria ≥ and <500 mg/day. We conclude that SLE patients with LN have significantly lower vitamin D level than inactive SLE and active SLE without LN. Hence, nephritis is a significant predictor of vitamin D deficiency in SLE patients.     

Increased expression of Bruton’s tyrosine kinase in peripheral blood is associated with lupus nephritis

Systemic lupus erythematosus (SLE) is an autoimmune disease manifested by multiorgan impairment. It is reported that B cells participate in the onset of SLE. Bruton’s tyrosine kinase (Btk), as a downstream signaling molecule of B cell antigen receptor (BCR) signaling pathway, is involved in the development, activation, and survival of B cells. The aim of our study was to explore the specific role of Btk in lupus nephritis (LN). We determined the percentages of Btk+ B cells in peripheral blood mononuclear cells (PBMCs) from SLE patients by flow cytometry and analyzed the correlation between the percentage of Btk+ B cells and lupus-related clinical indexes. Immunohistochemistry was used to detect the Btk expression in kidney from LN patients and tumor surrounding tissues. Compared with controls, the frequency of Btk+ B cells in SLE patients was upregulated (p < 0.01), and it was significantly correlated with the SLE Disease Activity Index (SLEDAI) (p < 0.01), levels of plasma anti-dsDNA antibody (p < 0.05), the amount of 24-h urine protein (p < 0.05), and levels of plasma C3 (p < 0.05). The frequency of Btk+ B cells in the patients with LN was significantly higher than those without LN (p < 0.05). Although the Btk expression in glomerulus of LN patients was significantly increased compared with controls (p < 0.001), but it had no correlation with the renal pathology activity index, SLEDAI, or 24-h urine protein. In conclusion, the increased expression of Btk in peripheral blood was correlated with LN, indicating that it may be a therapeutic target for SLE.     

Hepatitis C in patients with β-thalassemia major. A single-centre experience

Chronic hepatitis C (CHC) and iron overload are the main causes of liver disease in β-thalassemia major (βTM). There is limited data regarding the course of CHC in this population. All patients (n?=?144) from the thalassemia centre of the University Hospital of Patras were evaluated (January 1981 to June 2012). Patients were classified into group A (n?=?57), which consisted of patients with CHC, who either had received antiviral treatment (n?=?49) or not (n?=?8), and group B which included 87 patients without CHC. Nineteen patients died during follow-up (median: 257.5 months (1–355)). Survival rates were 84.2 % and 88.5 % for group A and B, respectively. The causes of death were heart failure (63.2 %), accident (10.5 %), sepsis (5.3 %), liver failure (5.3 %), hepatocellular carcinoma (HCC) (5.3 %), non-Hodgkin lymphoma (5.3 %) and multiorgan failure (5.3 %). There were no differences in total survival between the two groups (p?=?0.524). In the multivariate analysis, survival was neither correlated with CHC (p?=?ns), nor with anti-HCV treatment (p?=?ns), whereas independent negative predictors were presence of heart failure (p?<?0.001), presence of malignancy other than HCC (p?=?0.001) and non-adherence to chelation treatment (p?=?0.013). Predictive factors for the development of cirrhosis were: CHC (p?<?0.001), age?>?35 years (p?=?0.007), siderosis grade 3/4 (p?=?0.029) and splenectomy (p?=?0.001); however, multivariately, only siderosis grade 3/4 was found to be significant (p?=?0.049). In this study, survival of patients with βTM was mainly associated with heart failure, presence of malignancy other than HCC and non-adherence to chelation treatment, rather than with liver disease. Multicentre studies need to be designed to define more accurately the indications of antiviral treatment in this population.     

Distinct antibody profile: a clue to primary antiphospholipid syndrome evolving into systemic lupus erythematosus?

We have performed a retrospective study to determine if patients with antiphospholipid syndrome that developed systemic lupus erythematosus (APS/SLE) had distinct clinical and/or serological features. All 80 primary APS (PAPS) patients followed up at our APS unit were included in the study and divided into two groups: 14 APS/SLE and 66 PAPS. Prior or at onset of lupus manifestations, six patients were uniformly negative for lupus and Sjögren autoantibodies, and the other eight patients had persistent positive. In the first year after diagnosis of SLE, three patients remained with negative antibodies, the other seven patients maintained the same antibodies, and four patients developed other antibodies. APS/SLE group had a significant lower mean age at PAPS diagnosis (26.0?±?8.0 vs. 34.2?±?11.9 years, p?=?0.03) and a longer disease duration (14.0?±?7.0 vs. 6.0?±?5.0 years, p?<?0.0001). The mean time for PAPS to develop SLE was 5.2?±?4.3 years. The typical clinical and laboratorial findings of APS did not discriminate both groups of patients. At lupus onset, antinuclear antibodies were more frequently observed in those who evolved to SLE (100 vs. 51.5 %, p?=?0.0005). Anti-double-stranded DNA (dsDNA), anti-ribosomal P, anti-Ro/SS-A, anti-La/SS-B, and anti-U1RNP antibodies were exclusively found in the APS/SLE patients, whereas anti-Smith (Sm) antibodies were not detected in both groups. The detection of a distinct subgroup of lupus-associated autoantibody in PAPS patients seems to be a hint to overt SLE disease, particularly in those patients with young age at diagnosis.     

Age impacts the pattern of care for elderly patients with rectal cancer

Purpose

This study analyzed the current approaches for rectal cancer treatment in elderly patients.

Methods

We retrospectively studied 240 rectal cancer patients who had undergone radiotherapy from 2000 to 2008. The ages of the patients ranged from 65 and 75 years (group A, n?=?127) and older than 75 years (group B, n?=?113). The distribution of the Charlson comorbidity index was similar between the two groups, but the ECOG performance status (PS) differed between the groups (66 % of the patients of group A were PS 0, and 40 % were PS 0 in group B (p?<?0.0001)). The tumor stages were comparable between groups.

Results

The median age of the patients was 74.3 years (range 65–90.6). Treatment was discussed during a multidisciplinary cancer team meeting before treatment for 55 % of the cases in group A and 73 % of the cases in group B (p?<?0.001), and treatment proposals were in accordance with guidelines in 96 % of the cases in group A and 76 % of the cases in group B (p?<?0.001). Group B patients received slightly less concurrent chemotherapy (35 vs. 30 % for group A; p?=?0.54), more hypofractionated radiotherapy (41 vs. 54 % for group A; p?=?0.064), less surgery (92 vs. 80 % for group A; p?=?0.014), and less adjuvant chemotherapy (34 vs. 10 % for group A; p?<?0.001). Finally, 80 % of the patients in group A and 60 % of the patients in group B received treatment in accordance with guidelines (p?=?0.007) and in the logistic regression model. Non-metastatic patients who were aged below 75 years were predicted for conformal management (HR?=?0.323; 95 % CI?=?0.152–0.684) irrespective of their performance status, comorbidity, or disease stage.

Conclusions

Treatment proposals and administered therapy differed according to age.     

The clinical course of polymyalgia rheumatica in Chinese

Polymyalgia rheumatica (PMR) is diagnosed based on clinical features that may overlap with other rheumatic conditions like rheumatoid arthritis (RA). Furthermore, a proportion of PMR patients may subsequently evolve into RA. The aim of this study was to examine the clinical characteristics of PMR patients in a Chinese cohort compared to a Caucasian series. Patients diagnosed to have PMR during 1997–2008 were reviewed for clinical features and compared to a reported Caucasian series. Rheumatoid factor (RF) and anticyclic citrullinated peptide (CCP) antibodies were determined by immunonephelometry and enzyme-linked immunosorbent assay, respectively. Forty-four patients of southern Chinese origin were diagnosed to have PMR according to specialist opinion. Seventy-five percent of patients (n?=?33) were >65 years of age at diagnosis (mean?±?standard deviation, 75.8?±?9.6 years). The commonest feature at disease onset was elevated erythrocyte sedimentation rate >40 mm/h (100% vs. 95.7%; p?=?0.17) and bilateral shoulder pain or stiffness (95.5% vs. 90.8%; p?=?0.31), comparable in frequency to the Caucasian cohort. However, Chinese patients had significantly longer duration of symptoms before diagnosis (p?<?0.001) but less bilateral upper arm tenderness (p?<?0.001) and generalized stiffness (p?=?0.01). Twelve (27.3%) patients evolved into RA after a median duration of 2 months from onset of PMR. RF and anti-CCP antibodies were positive in 66.7% and 60% of these patients compared to 9.4% and 6.2%, respectively, among those who did not evolve into RA during the period observed. Chinese patients with PMR have modestly different clinical profile compared to the Caucasian counterpart. RF and anti-CCP antibodies were more likely to be present in those who subsequently developed into RA.     

Incidence and predictors of hematological side effects in chronic HCV Egyptian patients treated with PEGylated interferon and ribavirin

Aim

The aim of this paper was to study the incidence and predictors of hematological abnormalities during treatment of chronic hepatitis C virus (HCV) patients with interferon and ribavirin.

Methods

One thousand and eighty-one chronic HCV patients who were treated with PEGylated interferon α-2a 180 μg (n?=?536) or α-2b 1.5 μg/kg (n?=?545) plus ribavirin for 48 weeks were included. Baseline demographic, laboratory, and histopathological data and, during treatment, hematological data were collected and analyzed using univariate and multivariate analyses to identify independent predictors of hematological side effects.

Results

During therapy, 168 of 1,018 (15.5 %) had moderate anemia (Hb?<10 and ≥8.5 g/dL) and 88 (8.1 %) had severe anemia (Hb?<8.5 g/dL). Two hundred and six patients (19.1 %) had moderate neutropenia (absolute neutrophil count (ANC)?<750 and ≥500/mm³); only 55 (5.1 %) had severe neutropenia (ANC?<500/mm³). Forty-three patients (4 %) had moderate (platelet <50,000 and ≥25,000/mm³) and 5 (1.4 %) had severe thrombocytopenia (platelet <25,000/mm³). Fibrosis stage, week 4 Hb level, and week 2 and 4 reduction level in Hb were independent predictors of moderate and severe anemia (p?<?0.001). Fibrosis stage and ANC at weeks 2 and 4 were predictors of neutropenia (p?<?0.001, 0.001, and 0.004, respectively). Fibrosis stage and platelet count at weeks 2 and 4 were predictors of thrombocytopenia (p?<?0.001, <0.001, and 0.005, respectively). There was no association between interferon type and anemia (p?=?0.57), neutropenia (p?=?0.6), or thrombocytopenia (p?=?0.79).

Conclusions

Fibrosis stage and week 2 and 4 hematological parameter reduction levels were independent predictors of hematological side effects, which are not related to interferon type.     

Non-physiological increase of AV conduction time in sinus disease patients programmed in AAIR-based pacing mode

Purpose

The EVOCAV_DS trial aimed to quantify the paradoxal atrioventricular (AV) conduction time lengthening in sinus node (SD) patients (pts) paced in AAIR-based pacing mode.

Methods

SD pts, implanted with dual-chamber pacemaker programmed in AAIR-based pacing mode, were randomized in two arms for a 1-month period: the low atrial pacing (LAP; basic rate at 60 bpm, dual sensor with minimal slope) and the high atrial pacing (HAP; basic rate at 70 bpm, dual sensor with optimized slope, overdrive pacing) arm. At 1 month, crossover was performed for an additional 1-month period. AV conduction time, AV block occurrence and AV conduction time adaptation during exercise were ascertained from device memories at each follow-up.

Results

Seventy-nine pts participated to the analysis (75?±?8 years; 32 male; PR?=?184?±?38 ms; bundle branch block n?=?12; AF history n?=?36; antiarrhythmic treatment n?=?53; beta-blockers n?=?27; class III/Ic n?=?18; both n?=?8). The mean AV conduction time was significantly greater during the HAP (275?±?51 ms) vs. LAP (263?±?49 ms) period (p?<?0.0001). Class III/Ic drugs were the only predictors of this abnormal behaviour. Degree II/III AV blocks occurred in 49 % of pts in the HAP vs. 19 % in the LAP period (p?<?0.0001). Fifty-two patients (66 %) presented a lengthening of AV conduction time during exercise.

Conclusion

AAIR-based pacing in SD pts may induce a significant lengthening of pts’ AV conduction time, including frequent abnormal adaptation of AV conduction time during exercise.     

Combination of Sildenafil and Bosentan for Pulmonary Hypertension in a Human Ex Vivo Model

Purpose

Both sildenafil and bosentan have been used clinically to treat pulmonary arterial hypertension. As these substances target different pathways to modulate vasoconstriction, we investigated the combined effects of both drug classes in isolated human pulmonary vessels.

Methods

Segments of pulmonary arteries (PA) and veins (PV) were harvested from 51 patients undergoing lobectomy. Contractile force was determined isometrically in an organ bath. Vessels were constricted with norepinephrine (NE) to determine effects of sildenafil. They were constricted with ET-1 to assess effects of bosentan, and with NE and ET-1 to evaluate the combination of both substances.

Results

Sildenafil (1E-5 M) significantly reduced maximum constriction by NE of both PA (13.0?±?11.1 vs. 34.9?±?7.6 % relative to KCl induced constriction; n?=?6; p?<?0.001) and PV (81.2?±?34.2 vs 121.6?±?20.8 %; n?=?6; p?<?0.01) but did not affect basal tones. Bosentan (1E-5 M) significantly reduced maximum constriction of PV (56.6?±?21.5 vs. 172.1?±?30.0 %; n?=?6; p?<?0.01) by ET-1 and led to a small but insignificant decrease of basal tone (p?=?0.07). Bosentan almost completely abolished constriction of PA (1.0?±?0.9 vs. 74.7?±?25.7 %; n?=?6; p?<?0.001) by ET-1, but did not affect basal tone. Bosentan (1E-7 M) significantly attenuated combined ET-1/NE dose–response curves in PA (93.1?±?47.4 vs. 125.3?±?41.0 %; n?=?12; p?<?0.001) whereas the effect of sildenafil (1E-5 M) was less pronounced (103.6?±?20.2 %; p?<?0.05). Simultaneous administration of both substances showed a significantly greater reduction of maximum constriction in PA compared to individual administration (64.6?±?26.3 %; p?<?0.001).

Conclusions

Sildenafil only at its highest concentration was effective in suppressing NE induced pulmonary vessel contraction. Bosentan was able to completely suppress ET-1 induced contraction of PA and strongly attenuated contraction of PV. The present data suggest a benefit of sildenafil/bosentan combination therapy as they affect different pathways and may allow lower dosages.     

Serum β2-microglobulin level is a useful indicator of disease activity and hemophagocytic syndrome complication in systemic lupus erythematosus and adult-onset Still’s disease

This study demonstrates whether serum β₂-microglobulin (β₂-MG) level can be an indicator of the status of systemic lupus erythematosus (SLE) and adult-onset Still’s disease (AOSD), and development of hemophagocytic syndrome (HPS) complication. Serum β₂-MG level was compared between the active and inactive statuses of SLE and AOSD in hospitalized patients. Active status was defined as a state for which a therapy was introduced. Serum β₂-MG level was also compared between patients with and without HPS complication. HPS was diagnosed on the basis of clinical and pathological findings. Laboratory markers of HPS including peripheral blood cell counts and levels of serum lactate dehydrogenase (LDH), serum ferritin, plasma fibrin/fibrinogen degradation product (FDP), and plasma D-dimer were examined to determine their correlations with serum β₂-MG level. Sixteen SLE and seven AOSD patients (all females, aged 39.0?±?16.4) were included. The serum β₂-MG level was high in the active status of underlying diseases and decreased significantly after the therapy (3.5?±?1.4 vs. 2.1?±?0.8 mg/L, p?<?0.001). Among patients with active status, the β₂-MG level was higher in patients with HPS (two with SLE and three with AOSD) than in patients without HPS (4.9?±?1.8 vs. 3.3?±?1.4 mg/L, p?<?0.05). Serum β₂-MG level significantly correlated with the levels of serum LDH (r _s?=?0.42, p?<?0.05), plasma FDP (r _s?=?0.58, p?<?0.05), and plasma D-dimer (r _s?=?0.77, p?<?0.01). Serum β₂-MG level would be a useful indicator of disease activity and development of HPS complication in patients with SLE and AOSD.     

Chest imaging manifestations in lupus nephritis

The purpose of this study was to analyze the association between renal histopathological features and chest computed tomography (CT) findings in lupus nephritis (LN) patients. We retrospectively reviewed the medical records and chest thin-section CT findings of 152 patients with an established diagnosis of LN based on renal biopsy and 93 systemic lupus erythematosus (SLE) patients without LN between April 2009 and March 2012. The 64-detector row CT images were retrospectively evaluated by an experienced thoracic radiologist without knowledge of the patients’ clinical information except that all patients had SLE. Lupus nephritis patients have a significantly higher incidence of lung/plural disease than those without LN (61.8 versus 44.0 %, p?<?0.05). The patients in LN group were more prone to ground glass opacity, interlobular septal thickening, reticular opacities, pleural effusions, and consolidation on CT images than in non-LN group (p?<?0.05). Class I, class III, and class IV lupus nephritis were associated with traction bronchiectasis, ground glass opacity, and pleural effusions, respectively (p?<?0.05). The presence of cord on chest CT scans was significantly associated with renal interstitial lesion and interstitial inflammation/fibrosis (p?<?0.05). Ground glass opacity and reticular opacities on chest CT scans were also related to renal hyaline thrombi (p?<?0.05). There was a significant association between pleural effusions and cellular/fibrous crescents, interstitial lesion, or interstitial inflammation/fibrosis (p?<?0.05). It was shown that hyaline thrombi in renal biopsy was an independent risk factor of the presence of ground glass opacity on CTs with logistic regression analysis (Wald?=?4.124, p?=?0.042). LN patients were more likely to suffer from lung/pleural disease. The patients with hyaline thrombi in renal biopsy were more prone to have ground glass opacity on CTs.     

In palindromic rheumatism,hand joint involvement and positive anti-CCP antibodies predict RA development after 1 year of follow-up

This study aimed to determine the frequency of rheumatoid factor (RF) and cyclic citrullinated peptide (CCP) antibodies in a cohort of patients with palindromic rheumatism (PR) and to find determinants for progression to rheumatoid arthritis (RA). All new cases of PR (n?=?90) were included prospectively and followed up for 1 year, and a comparison group of RA cases (n?=?70) was also included. At study entry in all patients in both groups, RF and anti-CCP antibodies were tested, and the findings were compared and correlated. In the PR group at presentation, RF was positive in 30 patients (33.3 %) and, in the RA group, in 45 patients (64.3 %). Anti-CCP antibodies were positive in 35 patients (38.9 %) with PR and in 58 patients (82.9 %) with RA. In the PR group, positive correlations were observed between RF and C-reactive protein (CRP) (p?=?0.036), while anti-CCP positively correlated with disease duration (p?=?0.015) and CRP (p?<?0.001). At 1-year follow-up, 25 cases (27.5 %) had progressed to RA, 3 (3.3 %) cases had developed systemic lupus, 43 cases had responded to hydroxychloroquine with complete remission, five cases had developed other rheumatic diseases, and 14 cases had progressed to undifferentiated arthritis. After regression analysis, the involvement of hand joints and positive anti-CCP were the only predictors that determined progression into RA within a year (p?<?0.001 and p?=?0.02, respectively). Early hand joint involvement and positive anti-CCP at disease onset are good predictors for progression to RA in this domain.     

Diabetic foot in patients below 40 years of age

Data on diabetic foot ulcers (DFU) in young patients are scarce. We aimed to examine the risk factors, clinical presentation, wound characteristics, and outcome of DFU among young diabetic patients and to compare them with similar age diabetics without foot ulcer and those of older age diabetics with foot ulcers. A prospective cohort of 745 patients (834 ulcers) below 40 years of age, 7620 patients (9405 ulcers) ages 40 years and above, and 992 patients below 40 years diabetics without foot ulcers in a single multidisciplinary diabetes center were studied. Registered patients with foot ulcers in Jabir Abu Eliz Diabetes Centre (JADC) in Khartoum, Sudan from March 2001 to Dec 2011 were reviewed. Below 40 years of age constituted 8.9 % (n?=?7450) of all patients with DFU. Male-to-female ratio was 1.7:1. IDDM type was prevalent in 60.9 %. Thirty-six per cent of below 40 years had peripheral neuropathy compared to 61.6 % of older group (p?<?0.0002) and 8.7 % of below 40 without DFU (p?<?0.0002). ABI <0.9 was found in 38.7 % (n?=?288) in below 40 years with ulcers compared to 41.4 % in older patients (p?=?0.8989) and 36.3 % (n?=?360) of below 40 without DFU (p?=?0.3125). HbA1c >7 % was significantly more in diabetics below 40 years with foot ulcers compared to those without foot ulcers (83.5 vs. 75.1 %) (p?=?0.0002). In below 40 years of age, 80.1 % of ulcers healed compared to 70.6 % in older age group (p?>?0.0002). Major lower extremity amputation was performed in 4.8 % in below 40 years patients compared to 7.3 % in older group (0.0105). Young diabetics with foot ulcers had significantly longer duration of the disease, more foot deformities, and callus formation and more severe neuropathy than young diabetics without ulcers but had a lesser duration of diabetes than elderly diabetics with foot ulcers. HbA1c in young diabetics with foot ulcers was significantly higher than young diabetics without ulcers, and their foot ulcers healed better and with less major lower extremity amputation than elderly patients.     

Noninvasive evaluation of gastric emptying and gastric wall thickness in SLE patients

Objective: The objective of this study is to evaluate the gastric emptying in patients with systemic lupus erythematosus (SLE) with gastrointestinal involvement using three-dimensional (3D) ultrasonography.

Methods: The gastric emptying times at 25% (T1), 50% (T2), and 75% (T3) of SLE patients with gastrointestinal involvement (n?=?40) and healthy controls (n?=?80) were evaluated and compared. In addition, the correlations among the gastric wall thickness, SLE disease activity index (SLEDAI), and upper gastrointestinal symptoms were calculated.

Results: The gastric wall thickness was correlated with the SLEDAI (r?=?0.928, p?<?0.001) and the upper gastrointestinal symptom index (r?=?0.848, p?<?0.001). The emptying times T1, T2, and T3 of the SLE patients were 17.08?±?2.65?min (mean?±?standard deviation), 39.85?±?6.54?min, and 83.58?±?7.12?min, respectively. For healthy controls, they were 19.65?±?5.39?min, 41.08?±?7.51?min, and 70.34?±?8.03?min. The T1 of the SLE patients was shorter (p?<?0.01), while the T3 was longer (p?<?0.001). Moreover, T3 in the SLE group had the best correlation with the upper gastrointestinal symptom index (r?=?0.553, p?<?0.001). T1 in the SLE group was anti-correlated with early satiety (r?=??0.366, p?<?0.05).

Conclusions: Combining the emptying times T1 and T3, as well as the gastric wall thickness, the SLEDAI and the upper gastrointestinal symptoms index can provide accurate clinical diagnosis of SLE with gastric involvement.     

Progression of carotid atherosclerosis in patients with systemic lupus erythematosus

The progression of carotid atherosclerosis in lupus patients is frequently encountered, and it is determined by both traditional and nontraditional risk factors. Of the 181 patients initially included in the study, 157 patients were reevaluated after 39(37–42)?months. The progression of atherosclerosis was defined as the increase in the intima-media thickness (IMT) >0.15 mm and/or an increase of the plaque score. The predictive factors of progression were identified using the Poisson regression model. The median of the cohort age at baseline was 38 years (range 29–46 years; 96.2% female, 75.8% nonwhite). Carotid atherosclerosis progression was observed in 43 patients (27.4%), an increased plaque score was observed in nine patients (5.7%), an increase of IMT >0.15 mm was observed in 31 (19.7%), and both issues were present in three patients (1.9%). The univariate determinants of atherosclerosis progression were age, systemic lupus erythematosus (SLE) duration, and higher serum level of triglycerides (p?<?0.05). The presence of nephrotic proteinuria (p?=?0.063), stage 3 or greater chronic kidney disease (p?=?0.091), and longer duration of prednisone use (p?=?0.056) showed a tendency towards association with progression of atherosclerosis. The independent risk factors for progression were the SLE duration (p?=?0.008, RR?=?1.06, 95% CI?=?1.03–1.10) and the presence of nephrotic proteinuria (p?=?0.022, RR?=?4.22, 95% CI?=?2.18–8.15). The progression of atherosclerosis occurred in a substantial number of young SLE patients during a short-term follow-up. The independent factors associated with this progression emphasize the importance of SLE in determining atherosclerosis in these individuals.     

St. John’s Wort in Patients Non-responders to Clopidogrel Undergoing Percutaneous Coronary Intervention: a Single-Center Randomized Open-Label Trial (St. John’s Trial)

We assessed if St. John’s Wort (SJW) improves platelet response in patients (pts) resistant to clopidogrel after percutaneous coronary intervention (PCI). Stable angina pts non-responders to 600 mg clopidogrel (P2Y12 reaction units (PRU) >240) were randomized (2:1) to SJW (n?=?15) or placebo (n?=?8). SJW (300 mg × 3/day) was administrated for 2 weeks after PCI. Platelet reactivity was assessed by VerifyNowTM before (BL), 2 (T1), and 4 weeks (T2) after PCI. PRU significantly changed during protocol in SJW (BL (316?±?60) vs. T1 (170?±?87) vs. T2 (220?±?96), p?<?0.0001) and placebo group (BL (288?±?36) vs. T1 (236?±?31) vs. T2 (236?±?62), p?=?0.046). Yet, PRU changes from BL were higher at T1 in SJW than in placebo group (Δ%, ?47?±?24 vs. ?16?±?15, p?=?0.0033), with no differences at T2 between the groups (Δ%, ?30?±?29 vs. ?17?±?24, p?=?0.30). Residual platelet reactivity improved with SJW during the first month post-PCI.     

Eating two larger meals a day (breakfast and lunch) is more effective than six smaller meals in a reduced-energy regimen for patients with type 2 diabetes: a randomised crossover study

Aims/hypothesis

The aim of the study was to compare the effect of six (A6 regimen) vs two meals a day, breakfast and lunch (B2 regimen), on body weight, hepatic fat content (HFC), insulin resistance and beta cell function.

Methods

In a randomised, open, crossover, single-centre study (conducted in Prague, Czech Republic), we assigned 54 patients with type 2 diabetes treated with oral hypoglycaemic agents, both men and women, age 30–70 years, BMI 27–50 kg/m² and HbA_1c 6–11.8% (42–105 mmol/mol), to follow two regimens of a hypoenergetic diet, A6 and B2, each for 12 weeks. Randomisation and allocation to trial groups (n?=?27 and n?=?27) were carried out by a central computer system. Individual calculations of energy requirements for both regimens were based on the formula: (resting energy expenditure?×?1.5)???2,092 kJ. The diet in both regimens had the same macronutrient and energy content. HFC was measured by proton magnetic resonance spectroscopy. Insulin sensitivity was measured by isoglycaemic–hyperinsulinaemic clamp and calculated by mathematical modelling as oral glucose insulin sensitivity (OGIS). Beta cell function was assessed during standard meal tests by C-peptide deconvolution and was quantified with a mathematical model. For statistical analysis, 2?×?2 crossover ANOVA was used.

Results

The intention-to-treat analysis included all participants (n?=?54). Body weight decreased in both regimens (p?<?0.001), more for B2 (?2.3 kg; 95% CI ?2.7, ?2.0 kg for A6 vs ?3.7 kg; 95% CI ?4.1, ?3.4 kg for B2; p?<?0.001). HFC decreased in response to both regimens (p?<?0.001), more for B2 (?0.03%; 95% CI ?0.033%, ?0.027% for A6 vs ?0.04%; 95% CI ?0.041%, ?0.035% for B2; p?=?0.009). Fasting plasma glucose and C-peptide levels decreased in both regimens (p?<?0.001), more for B2 (p?=?0.004 and p?=?0.04, respectively). Fasting plasma glucagon decreased with the B2 regimen (p?<?0.001), whereas it increased (p?=?0.04) for the A6 regimen (p?<?0.001). OGIS increased in both regimens (p?<?0.01), more for B2 (p?=?0.01). No adverse events were observed for either regimen.

Conclusions/interpretation

Eating only breakfast and lunch reduced body weight, HFC, fasting plasma glucose, C-peptide and glucagon, and increased OGIS, more than the same caloric restriction split into six meals. These results suggest that, for type 2 diabetic patients on a hypoenergetic diet, eating larger breakfasts and lunches may be more beneficial than six smaller meals during the day. Trial registration ClinicalTrials.gov number, NCT01277471, completed. Funding Grant NT/11238-4 from Ministry of Health, Prague, Czech Republic and the Agency of Charles University – GAUK No 702312.