Hemodynamic impact of percutaneous left atrial appendage closure in patients with paroxysmal atrial fibrillation

Purpose

Percutaneous left atrial appendage (LAA) closure has become a valid alternative to anticoagulation therapy for the prevention of thromboembolic events in patients with atrial fibrillation (AF). However, scarce data exist on the impact of LAA closure on left atrial and ventricular function. We sought to assess the acute hemodynamic changes associated with percutaneous LAA closure in patients with paroxysmal AF.

Methods

The study population consisted of 31 patients (mean age 73?±?10 years; 49% women) with paroxysmal AF who underwent successful percutaneous LAA closure. All patients were in sinus rhythm and underwent 2D transthoracic echocardiography at baseline and the day after the procedure. A subset of 14 patients underwent preprocedural cardiac computed tomography (CT) with 3D LA and LAA reconstruction.

Results

Left ventricular systolic function parameters and LA volumetric indexes remained unchanged after the procedure. No significant changes in left ventricular stroke volume (72.4?±?16.0 vs. 73.3?±?15.7 mL, p?=?0.55) or LA stroke volume (total 15.6?±?4.2 vs. 14.6?±?4.2 mL, p?=?0.21; passive 9.0?±?2.8 vs. 8.3?±?2.6 mL, p?=?0.31; active 10.3?±?5.6 vs. 10.0?±?6.4 mL, p?=?0.72) occurred following LAA closure. Mean ratio of LAA to LA volume by 3D CT was 10.2?±?2.3%. No correlation was found between LAA/LA ratio and changes in LA stroke volume (r?=?0.35, p?=?0.22) or left ventricular stroke volume (r?=?0.28, p?=?0.33).

Conclusions

The LAA accounts for about 10% of the total LA volume, but percutaneous LAA closure did not translate into any significant changes in LA and left ventricular function.

     

Effect of vitamin D level on the immunogenicity to hepatitis B vaccination in dialysis patients

We undertook this study to assess the response of hepatitis B vaccination in dialysis patients and the effect of vitamin D level on the immunogenicity to hepatitis B vaccination. It was an observational study, which included 60 patients of end-stage renal disease on maintenance dialysis. Patients with anti-HBs antibody positive at baseline were excluded. All received intramuscular recombinant hepatitis B vaccination at 0, 1, 2, and 6 months 20 μg on each deltoid muscle bilateral. Anti-HBs antibody titers were measured at 4 and 7 months of vaccination and the titer ≥10 mIU/mL was considered as “positive”. Vitamin D levels were measured at baseline before starting the vaccination. The mean vitamin D level was 15.0?±?7.8 ng/mL. The vitamin D level <10 and <20 were 23.3% and 83.3 %, respectively. The patients on hemodialysis had relatively higher vitamin D level than on peritoneal dialysis patients, i.e. 16.3?±?8.5 and 11.5?±?3.1 ng/mL, respectively (p?=?0.03). Overall, 38 patients responded to the immunization (63.3 %) and 11 patients were non-responders (36.7 %) at 4 months. Difference of vitamin D level in responder (16.6?±?9.1 ng/mL) and non-responder (12.4?±?4.1 ng/mL) was not significant (p?=?0.16). At 7 months (1 month after completion of vaccination) 61.9 % were responders and 38.1 % were non-responders. The vitamin D level in responders and non-responders were statistically not significant (p?=?0.11). In responder, titer ≥100 mIU/mL was seen in 30 % at 4 months and in 42.9 % at 7 months (p?=?0.05). In the good and weak responders at 7 months, vitamin D levels were 21.5?±?10.8 and 10.1?±?3.7 ng/mL, respectively (p?=?0.37). The association of vitamin D level and anti-HBs antibody titer were not significant (r?=?0.03 and 95 % CI was ?0.43 to 0.48, p?=?0.89) in those who responded. Most patients on dialysis were vitamin D deficient. Vitamin D levels did not differ between responding and non-responding dialysis patients.     

Arterial stiffness is associated with left ventricular dysfunction in patients with rheumatoid arthritis

Arterial stiffness (AS) has a detrimental effect on cardiovascular system particularly on left ventricle (LV). The aim of the study was to evaluate the impact of AS on LV functions in patients with rheumatoid arthritis (RA). Forty patients with RA and 25 age-sex matched control subjects (mean age 48.5?±?6.3 vs. 45.1?±?6.9 years, respectively, p?=?0.06) were enrolled in study. AS was assessed by carotid-femoral pulse wave velocity (CF-PWV) and heart rate corrected augmentation index (AIx@75) measured by applanation tonometry (SphygmoCor). LV function was evaluated using tissue Doppler-derived myocardial performance index (MPI) from lateral mitral annulus. CF-PWV (28.3?±?10.3 vs. 21.8?±?9.3 m/s, p?=?0.03), AIx@75 (10.2?±?2.3 vs. 9.2?±?1, %, p?=?0.01) and MPI (0.46?±?0.12 vs. 0.36?±?0.1, p?<?0.001) were significantly higher in patients with RA than in controls. LV MPI was found to be significantly positive correlated with CF-PWV, AIx@75, and ESR (r?=?0.360, p?=?0.005; r?=?0.334, p?=?0.009; r?=?0.293, p?=?0.023, respectively). Arterial stiffness parameters including CF-PWV and AIx@75 are associated with subclinical left ventricular dysfunction in patients with RA.     

Serum hepcidin levels,iron status,and HFE gene alterations during the first year of life in healthy Spanish infants

The aims of this study were to describe hepcidin levels and to assess their associations with iron status and the main variants in the HFE gene in healthy and full-term newborns during the first year of life, as a longitudinal study conducted on 140 infants. Anthropometric and biochemical parameters, hepcidin, hemoglobin (Hb), serum ferritin (SF), transferrin saturation (TS), mean corpuscular volume (MCV), and C-reactive protein (CRP), were assessed in 6- and 12-month-olds. Infants were genotyped for the three main HFE variants: C282Y, H63D, and S65C. Hepcidin levels increased from 6 to 12 months of age (43.7?±?1.5 to 52.0?±?1.5 ng/mL; p?<?0.001), showing higher levels in infants with better iron status compared to those with iron deficiency (ID) (44.8?±?1.5 vs 37.9?±?1.3 ng/mL, p?<?0.018, and 54.3?±?1.5 vs 44.0?±?1.4 ng/mL, p?<?0.038, in 6- and 12-month-olds, respectively). In multivariate linear regression models, iron status was found to be associated with hepcidin levels in infants with wild-type HFE gene (p?=?0.046 and p?=?0.048 in 6- and 12-month-olds, respectively). However, this association was not found in HFE-alteration-carrying infants. Hepcidin levels increased in healthy infants during the first year of life and were positively associated with iron levels only in infants with wild-type HFE gene, a situation that requires further investigation.     

Value of whole-body contrast-enhanced magnetic resonance angiography with vessel wall imaging in quantitative assessment of disease activity and follow-up examination in Takayasu’s arteritis

The aim of this study is to determine the value of whole-body contrast-enhanced magnetic resonance angiography(CE-MRI) with vessel wall imaging in quantitative assessments of Takayasu’s arteritis (TA) disease activity and follow-up examinations. Whole-body CE-MRI with vessel wall imaging (dark blood sequences) was performed in 52 TA patients and repeated in 15 patients after 6 months. Images were analyzed using quantitative scores. The distribution of Lupi-Herrera types (type III, 48.1 %; I, 40.4 %; II, 9.6 %; IV, 1.9 %) did not differ between active and inactive TA. Active vessel inflammation was found in seven patients diagnosed with inactive disease as Kerr scores and mainly involved the aortic arch, abdominal aorta, and ascending aorta. Quantitative MR scores were significantly higher in active TA (luminal stenosis 16.7?±?5.3 vs. 4.2?±?3.7, p?<?0.01; wall thickening 7.2?±?3.4 vs. 2.9?±?2.3, p?=?0.02; wall enhancement 8.7?±?4.1 vs. 3.6?±?2.4, p?=?0.04) and positively correlated with Kerr scores, ITAS 2010, erythrocyte-sedimentation rate (ESR), and C-reactive protein (CRP) and pentraxin-3 (PTX-3) levels. At 6 months, the clinical symptoms, CRP level, and ESR improved significantly (p?<?0.05) and wall enhancement decreased (6.7?±?3.1 vs. 4.1?±?2.1; p?=?0.04), but the luminal stenosis (10.2?±?4.3 vs. 8.8?±?5.2; p?=?0.12) and wall thickening (6.3?±?3.8 vs. 5.8?±?4.2; p?=?0.27) remained unchanged. Whole-body CE-MRI with vessel wall imaging detected luminal changes and vessel wall inflammation in TA. Our MR scoring system enabled quantitative assessment of TA activity.     

Side-to-end vs. straight stapled colorectal anastomosis after low anterior resection: results of randomized clinical trial

Aim

The aim of this study is to compare surgical, functional, physiologic outcomes and QOL after low anterior resection (LAR) with andside-to-end or straight colorectal anastomosis.

Method

Between 2012 and 2015, 86 patients with mid and low rectal tumors were enrolled into randomized trial. Wexner score, number of defecations, use of antidiarrheal medicine or laxatives, enemas, pads, episodes of nocturnal incontinence, and urgency were recorded. The Fecal Incontinence Quality of Life (FIQL) scale was used for assessment of QOL. Anal manometry and volumetric examination were performed.

Results

Six patients were excluded from the study. There was no mortality. The morbidity rate was 6 (14.6 %) for side-to-end vs. 8 (20.0 %) for straight anastomosis (p?=?0.57). The median Wexner score was 5 vs. 6 (p?=?0.033), 4 vs. 5 (p?=?0.006), and 2 vs. 3 (p?=?0.1) at 1, 3, and 6 months after stoma reversal, respectively. Side-to-end anastomosis resulted in a fewer mean numbers of bowel movements per day at the same check points of follow-up: 5.8?±?0.14 vs. 6.4?±?0.15 (p?=?0.006), 3.7?±?0.1 vs. 4.2?±?0.1 (p?=?0.003), and 2.5?±?0.1 vs. 3.0?±?0.10 (p?=?0.0002), correspondingly. Maximal tolerated volume was higher for side-to-end anastomosis at 3 and 6 months of follow-up: 152.0 vs. 137.8 cm³ (p?=?0.002) and 180.5 vs. 167.0 cm³ (p?=?0.006), respectively. Better FIQL score was found at 1 and 3 months in the side-to-end group.

Conclusion

Better functional outcomes and QOL were observed in a short period after stoma closure, but at 6 months of follow-up, the only benefit of side-to-end anastomosis was a lower number of bowel movements.

     

Type 1 diabetic patients with peripheral neuropathy have pan-enteric prolongation of gastrointestinal transit times and an altered caecal pH profile

Aims/hypothesis

We hypothesised that type 1 diabetic patients with established diabetic sensorimotor polyneuropathy (DSPN) would have segmental and/or pan-enteric dysmotility in comparison to healthy age-matched controls. We aimed to investigate the co-relationships between gastrointestinal function, degree of DSPN and clinical symptoms.

Methods

An observational comparison was made between 48 patients with DSPN (39 men, mean age 50 years, range 29–71 years), representing the baseline data of an ongoing clinical trial (representing a secondary analysis of baseline data collected from an ongoing double-blind randomised controlled trial investigating the neuroprotective effects of liraglutide) and 41 healthy participants (16 men, mean age 49 years, range 30–78) who underwent a standardised wireless motility capsule test to assess gastrointestinal transit. In patients, vibration thresholds, the Michigan Neuropathy Screening Instrument and Patient Assessment of Upper Gastrointestinal Symptom questionnaires were recorded.

Results

Compared with healthy controls, patients showed prolonged gastric emptying (299?±?289 vs 179?±?49 min; p?=?0.01), small bowel transit (289?±?107 vs 224?±?63 min; p?=?0.001), colonic transit (2140, interquartile range [IQR] 1149–2799 min vs 1087, IQR 882–1650 min; p?=?0.0001) and whole-gut transit time (2721, IQR 1196–3541 min vs 1475 (IQR 1278–2214) min; p?<?0.0001). Patients also showed an increased fall in pH across the ileocaecal junction (?1.8?±?0.4 vs ?1.3?±?0.4 pH; p?<?0.0001), which was associated with prolonged colonic transit (r?=?0.3, p?=?0.001). Multivariable regression, controlling for sex, disease duration and glycaemic control, demonstrated an association between whole-gut transit time and total GCSI (p?=?0.02).

Conclusions/interpretation

Pan-enteric prolongation of gastrointestinal transit times and a more acidic caecal pH, which may represent heightened caecal fermentation, are present in patients with type 1 diabetes. The potential implication of delayed gastrointestinal transit on the bioavailability of nutrition and on pharmacotherapeutic and glycaemic control warrants further investigation.

Trial registration

EUDRA CT: 2013-004375-12

     

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.     

<Emphasis Type="Italic">Vegf-A</Emphasis> mRNA transfection as a novel approach to improve mouse and human islet graft revascularisation

Aims/hypothesis

The initial avascular period following islet transplantation seriously compromises graft function and survival. Enhancing graft revascularisation to improve engraftment has been attempted through virus-based delivery of angiogenic triggers, but risks associated with viral vectors have hampered clinical translation. In vitro transcribed mRNA transfection circumvents these risks and may be used for improving islet engraftment.

Methods

Mouse and human pancreatic islet cells were transfected with mRNA encoding the angiogenic growth factor vascular endothelial growth factor A (VEGF-A) before transplantation under the kidney capsule in mice.

Results

At day 7 post transplantation, revascularisation of grafts transfected with Vegf-A (also known as Vegfa) mRNA was significantly higher compared with non-transfected or Gfp mRNA-transfected controls in mouse islet grafts (2.11- and 1.87-fold, respectively) (vessel area/graft area, mean?±?SEM: 0.118?±?0.01 [n?=?3] in Vegf-A mRNA transfected group (VEGF) vs 0.056?±?0.01 [n?=?3] in no RNA [p?<?0.05] vs 0.063?±?0.02 [n?=?4] in Gfp mRNA transfected group (GFP) [p?<?0.05]); EndoC-bH3 grafts (2.85- and 2.48-fold. respectively) (0.085?±?0.02 [n?=?4] in VEGF vs 0.030?±?0.004 [n?=?4] in no RNA [p?<?0.05] vs 0.034?±?0.01 [n?=?5] in GFP [p?<?0.05]); and human islet grafts (3.17- and 3.80-fold, respectively) (0.048?±?0.013 [n?=?3] in VEGF vs 0.015?±?0.0051 [n?=?4] in no RNA [p?<?0.01] vs 0.013?±?0.0046 [n?=?4] in GFP [p?<?0.01]). At day 30 post transplantation, human islet grafts maintained a vascularisation benefit (1.70- and 1.82-fold, respectively) (0.049?±?0.0042 [n?=?8] in VEGF vs 0.029?±?0.0052 [n?=?5] in no RNA [p?<?0.05] vs 0.027?±?0.0056 [n?=?4] in GFP [p?<?0.05]) and a higher beta cell volume (1.64- and 2.26-fold, respectively) (0.0292?±?0.0032 μl [n?=?7] in VEGF vs 0.0178?±?0.0021 μl [n?=?5] in no RNA [p?<?0.01] vs 0.0129?±?0.0012 μl [n?=?4] in GFP [p?<?0.001]).

Conclusions/interpretation

Vegf-A mRNA transfection before transplantation provides a promising and safe strategy to improve engraftment of islets and other cell-based implants.

     

Early deficits in insulin secretion,beta cell mass and islet blood perfusion precede onset of autoimmune type 1 diabetes in BioBreeding rats

Aims/hypothesis

Genetic studies show coupling of genes affecting beta cell function to type 1 diabetes, but hitherto no studies on whether beta cell dysfunction could precede insulitis and clinical onset of type 1 diabetes are available.

Methods

We used 40-day-old BioBreeding (BB) DRLyp/Lyp rats (a model of spontaneous autoimmune type 1 diabetes) and diabetes-resistant DRLyp/+ and DR+/+ littermates (controls) to investigate beta cell function in vivo, and insulin and glucagon secretion in vitro. Beta cell mass was assessed by optical projection tomography (OPT) and morphometry. Additionally, measurements of intra-islet blood flow were performed using microsphere injections. We also assessed immune cell infiltration, cytokine expression in islets (by immunohistochemistry and qPCR), as well as islet Glut2 expression and ATP/ADP ratio to determine effects on glucose uptake and metabolism in beta cells.

Results

DRLyp/Lyp rats were normoglycaemic and without traces of immune cell infiltrates. However, IVGTTs revealed a significant decrease in the acute insulin response to glucose compared with control rats (1685.3?±?121.3 vs 633.3?±?148.7; p?<?0.0001). In agreement, insulin secretion was severely perturbed in isolated islets, and both first- and second-phase insulin release were lowered compared with control rats, while glucagon secretion was similar in both groups. Interestingly, after 5–7 days of culture of islets from DRLyp/Lyp rats in normal media, glucose-stimulated insulin secretion (GSIS) was improved; although, a significant decrease in GSIS was still evident compared with islets from control rats at this time (7393.9?±?1593.7 vs 4416.8?±?1230.5 pg islet^?1 h^?1; p?<?0.0001). Compared with controls, OPT of whole pancreas from DRLyp/Lyp rats revealed significant reductions in medium (4.1?×?10⁹?±?9.5?×?10⁷ vs 3.8?×?10⁹?±?5.8?×?10⁷ μm³; p?=?0.044) and small sized islets (1.6?×?10⁹?±?5.1?×?10⁷ vs 1.4?×?10⁹?±?4.5?×?10⁷ μm³; p?=?0.035). Finally, we found lower intra-islet blood perfusion in vivo (113.1?±?16.8 vs 76.9?±?11.8 μl min^?1 [g pancreas]^?1; p?=?0.023) and alterations in the beta cell ATP/ADP ratio in DRLyp/Lyp rats vs control rats.

Conclusions/interpretation

The present study identifies a deterioration of beta cell function and mass, and intra-islet blood flow that precedes insulitis and diabetes development in animals prone to autoimmune type 1 diabetes. These underlying changes in islet function may be previously unrecognised factors of importance in type 1 diabetes development.

     

Electrophysiologic features of protected channels in late postinfarction patients with and without spontaneous ventricular tachycardia

Purpose

Protected channels of surviving myocytes in late postinfarction ventricular scar predispose to ventricular tachycardia (VT). However, only a few patients develop VT spontaneously. We studied differences in electric remodeling and protected channels in late postinfarction patients with and without spontaneous VT.

Methods

Patients with ischemic cardiomyopathy (ICM) with recurrent sustained monomorphic VT (n?=?22) were compared with stable ICM patients without spontaneous VT (control group; n?=?5). Left ventricular mapping was performed with a 20-pole catheter. Detailed pace mapping was used to identify channels of protected conduction, and confirmed, when feasible, by entrainment. Anatomical and electrophysiological properties of VT channels and non-VT channels in VT patients and channels in controls were evaluated.

Results

Seventy-three (median 3) VTs were inducible in VT patients compared to two (median 0) in controls. The VT channels in VT patients (n?=?57, 3?±?1 per patient) were lengthier (mean?±?SEM 53?±?5 vs. 33?±?4 vs. 24?±?8 mm), had longer S-QRS (73?±?4 vs. 63?±?3 vs. 44?±?8 ms), longer conduction time (103?±?13 vs. 33?±?4 vs. 24?±?8 ms), and slower conduction velocity (CV) (0.85?±?0.21 vs. 1.39?±?0.20 vs. 1.31?±?0.41 m/s) than non-VT channels in VT patients (n?=?183, 8?±?6 per patient) (p?≤?0.01) and channels in controls (n?=?46, 9?±?8 per patient) (p?≤?0.01). Additionally, non-VT channels in VT patients had longer S-QRS (p?=?0.02); however, they were similar in length, conduction time, and CV compared to channels in controls.

Conclusions

Channels supporting VT are lengthier, with longer conduction times and slower CV compared to channels in patients without spontaneous VT. These observations may explain why some ICM patients have spontaneous VT and others do not.

     

Effects of <Emphasis Type="Italic">S</Emphasis>-Nitrosoglutathione on Electrophysiological Manifestations of Mechanoelectric Feedback

Electromechanical coupling studies have described the intervention of nitric oxide and S-nitrosylation processes in Ca²⁺ release induced by stretch, with heterogeneous findings. On the other hand, ion channel function activated by stretch is influenced by nitric oxide, and concentration-dependent biphasic effects upon several cellular functions have been described. The present study uses isolated and perfused rabbit hearts to investigate the changes in mechanoelectric feedback produced by two different concentrations of the nitric oxide carrier S-nitrosoglutathione. Epicardial multielectrodes were used to record myocardial activation at baseline and during and after left ventricular free wall stretch using an intraventricular device. Three experimental series were studied: (a) control (n?=?10); (b) S-nitrosoglutathione 10 µM (n?=?11); and (c) S-nitrosoglutathione 50 µM (n?=?11). The changes in ventricular fibrillation (VF) pattern induced by stretch were analyzed and compared. S-nitrosoglutathione 10 µM did not modify VF at baseline, but attenuated acceleration of the arrhythmia (15.6?±?1.7 vs. 21.3?±?3.8 Hz; p?<?0.0001) and reduction of percentile 5 of the activation intervals (42?±?3 vs. 38?±?4 ms; p?<?0.05) induced by stretch. In contrast, at baseline using the 50 µM concentration, percentile 5 was shortened (38?±?6 vs. 52?±?10 ms; p?<?0.005) and the complexity index increased (1.77?±?0.18 vs. 1.27?±?0.13; p?<?0.0001). The greatest complexity indices (1.84?±?0.17; p?<?0.05) were obtained during stretch in this series. S-nitrosoglutathione 10 µM attenuates the effects of mechanoelectric feedback, while at a concentration of 50 µM the drug alters the baseline VF pattern and accentuates the increase in complexity of the arrhythmia induced by myocardial stretch.     

Antioxidant enzyme activities,lipid peroxidation,and total antioxidant status in children with Henoch–Schönlein purpura

The aim of this study was to assess the role of oxidative stress in the pathogenesis of Henoch–Schönlein purpura (HSP) vasculitis. The activities of catalase (CAT), arylesterase (ARYL), and paraoxonase (PON) as antioxidant enzymes and serum malondialdehyde (MDA) level as an indicator of lipid peroxidation, together with total antioxidant status (TAS), were measured in 29 children with HSP (mean age 9.3?±?2.7 years), both at the onset of the disease and at the remission period and in matched controls. Active-stage HSP had significantly higher MDA level (15.5?±?7.3 vs 7.8?±?3.9 nmol/l, respectively, P?P?P?=?0.042), ARYL (158?±?39 vs 212?±?52 U/l, P?P?=?0.002) activities compared with the control subjects. Although CAT (P?>?0.05) and PON (P?>?0.05) activities were found to be similar between active and remission stages of HSP, the active stage of the disease had significantly lower ARYL (P?=?0.011) and TAS (P?=?0.006) and higher MDA (P?r?=?0.433, P?=?0.019) and between CAT and C-reactive protein (r?=?0.386, P?=?0.035) in the active stage of HSP. No significant differences were detected in oxidant/antioxidant parameters between patients with or without renal, gastrointestinal, or joint involvement (P?>?0.05). Increased oxidative stress and lipid peroxidation may play important roles in the pathogenesis of HSP vasculitis. Antioxidant therapeutic interventions in long-lasting vasculitis and risk of atherosclerosis secondary to increased oxidant stress remain to be investigated.     

Metabolic syndrome in Sjögren’s syndrome patients: a relevant concern for clinical monitoring

Metabolic syndrome (MetS) has been described in autoimmune diseases. However, there are scarce data about MetS and adipocytokine profile in primary Sjögren’s syndrome (pSS). Seventy-one female pSS patients (American-European Consensus Group Criteria, 2002) aged 18–65 years and 71 age-, race-matched control women were enrolled in this case–control study. Clinical data were collected by a standardized protocol. Blood levels of glucose, cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglycerides, interleukin-1beta (IL-1beta)/IL-6, B-cell activating factor (BAFF), insulin, and leptin/adiponectin/visfatin/resistin were determined. Patients and controls were comparable regarding body mass index (BMI), smoking, sedentariness, and menopause (p?>?0.05). MetS (39.4 vs. 16.9 %, p?=?0.005), hypertension (p?=?0.004), and dyslipidemia (p?=?0.002) were more frequent in patients than controls. IL-1beta, IL-6, BAFF, resistin, and adiponectin levels were higher in patients than controls (p?<?0.05). pSS patients with MetS (n?=?28) had higher BMI, waist circumference, cholesterol, LDL-C, triglycerides, insulin, leptin and HOMA-IR values, and greater hypertension and diabetes rates than pSS patients without MetS (n?=?43) (p?<?0.05). Current and/or previous prednisone use (75.0 vs. 62.8 %, p?=?0.313), current (3.0?±?4.5 vs. 1.6?±?3.2 mg/day, p?=?0.299), and cumulative prednisone doses (p?=?0.495) were similar in both groups. Otherwise, IL-1beta level was higher in MetS patients than in non-MetS patients (p?=?0.012), and this finding was confirmed (p?=?0.048) by multivariate analysis with adjustments for age, ethnicity, prednisone use, current and cumulative prednisone doses, and duration of use. We identified high MetS frequency and abnormal adipocytokine profile in pSS. The association of MetS with elevated IL-1beta level suggests that inflammation plays an important role in its pathogenesis.     

Cutaneous vasculitis in systemic lupus erythematosus: association with anti-ribosomal P protein antibody and Raynaud phenomenon

Ninety-one consecutive systemic lupus erythematosus (SLE) patients (American College of Rheumatology criteria) with a history of cutaneous vasculitis were compared to 163 SLE controls without this clinical manifestation from July to December 2007 in order to determine the possible clinical and serological association of this manifestation. Data were obtained in an ongoing electronic database protocol and autoantibodies to anti-double-stranded DNA, anti-Sm, anti-RNP, anti-Ro/SS-A, anti-La/SS-B, and anticardiolipin and ribosomal P protein antibody (anti-P) were detected by standard techniques. Exclusion criteria were the presence of anti-phospholipid syndrome or antibodies, Sjögren syndrome, and a history of thrombosis. The mean age (38.5?±?11.5 vs. 37.8?±?11.6 years, p?=?0.635), disease duration (12.5?±?7.8 vs. 11.8?±?7.9 years, p?=?0.501), and frequency of white race (71.4% vs. 70.5%, p?=?0.872) and female sex (96.8% vs. 93.7%, p?=?0.272) were comparable in both groups. The vasculitis group had a higher frequency of malar rash (97.9% vs. 87.4%, p?=?0.004), photosensitivity (91.4% vs. 81.6%, p?=?0.030), and Raynaud phenomenon (RP; 27.7% vs. 7.5%, p?p?相似文献   

Cardiovascular autonomic dysfunction in patients with idiopathic diabetes insipidus

Introduction

Central diabetes insipidus (DI) is a rare disease characterized by the excretion of excessive volumes of dilute urine due to reduced levels of the antidiuretic hormone arginine vasopressin (AVP), caused by an acquired or genetic defect in the neurohypophysis. The aim of this study was to identify any autonomic dysfunction (AD) in patients with DI as a possible cofactor responsible for their reportedly higher mortality.

Methods

The study involved 12 patients (6 females) with central idiopathic DI and a well-controlled electrolyte balance, and 12 controls matched for age, sex and cardiovascular risk factors, who were assessed using the tilt, lying-to-standing, hand grip, deep breath, Valsalva maneuver and Stroop tests.

Results

The tilt test showed a significantly more pronounced decrease in both systolic (??20.67?±?18 vs. ??1.92?±?6.99 mmHg, p?=?0.0009) and diastolic blood pressure (??10.5?±?14.29 vs. ??1.5?±?5 mmHg, p?=?0.012) in patients than in controls. Three patients with DI had to suspend the test due to the onset of syncope. The lying-to-standing test also revealed a marked reduction in blood pressure in patients with DI (1.05?±?0.13 vs. 1.53?±?0.14, p?=?0.0001). Similar results emerged for the Valsalva maneuver (Valsalva ratio, 1.24?±?0.19 vs. 1.79?±?0.11, p?<?0.0001) and deep breath test (1.08?±?0.11 vs. 1.33?±?0.08, p?<?0.0001).

Conclusions

All the principal autonomic tests performed in the study were concordant in indicating that patients with central DI have an impaired autonomic nervous system function despite a normal hydroelectrolytic balance under desmopressin therapy. This impairment may reflect damage to the autonomic system per se and/or the absence of any vasoactive effect of AVP on vascular smooth muscle. In our opinion, patients with central DI should be educated on how to prevent orthostatic hypotension, and pharmacological treatment should be considered for patients with a more marked impairment.

     

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.     

Long-term quality of life after conservative treatment versus surgery for different stages of acute sigmoid diverticulitis

Purpose

It is controversial whether patients fare better with conservative or surgical treatment in certain stages of acute diverticulitis (AD), in particular when phlegmonous inflammation or covered micro- or macro-perforation are present. The aim of this study was to determine long-term quality of life (QoL) for AD patients who received either surgery or conservative treatment in different stages.

Methods

We included patients treated for AD at the University Hospital Grosshadern, Munich, Germany, between January 1, 2000, and December 31, 2010. Patients were classified by the Hansen and Stock (HS) classification, the modified Hinchey classification, and the German classification of diverticular disease (CDD). Pre-therapeutic staging was based on multidetector computed tomography. Long-term QoL was assessed by the Cleveland Global Quality of Life (CGQL) questionnaire, the Short Form 36 (SF-36), and the Gastrointestinal Quality of Life Index (GIQLI). Data are mean?±?SEM.

Results

Patients with phlegmonous AD (HS type 2a, Hinchey Ia and CDD 1b, respectively) had a better long-term QoL on the GIQLI when they were operated (78.5?±?2.5 vs. 70.7?±?2.1; p?<?0.05). Patients with micro-abscess (CDD 2a) had a better long-term QoL on the GIQLI, CGQL, and the “Role Physical” scale of the SF-36 when they were not operated (GIQLI 86.9?±?2.1 vs. 76.8?±?1.0; p?=?0.10; CGQL 82.8?±?5.1 vs. 65.3?±?11.0; p?=?0.08; SF-36/Role Physical 100?±?0.0 vs. 41.7?±?13.9; p?<?0.001). Patients with macro-abscess (CDD 2b) had a better long-term QoL when they were operated (GIQLI 89.3?±?1.4 vs. 69.5?±?4.5; p?<?0.01; CGQL 80.3?±?7.6 vs. 60.5?±?5.8; p?<?0.05; SF-36/Role Physical 95.8?±?4.2 vs. 47.9?±?13.6; p?<?0.001).

Conclusion

Considering long-term QoL, phlegmonous AD (HS type 2a, Hinchey Ia and CDD 1b, respectively) should be treated conservatively. In patients with covered perforation, abscess size should guide the decision on whether to perform surgery later on or not. In the light of long-term quality of life, patients fare better after elective sigmoid colectomy when abscess size exceeds 1 cm.

     

Cross-sectional prevalence of pancreatic cystic lesions in patients with acromegaly,a single-center experience

Purpose

Acromegaly is a disease associated with an increased risk for several kinds of neoplasms including colon and thyroid cancer. Although the association between acromegaly and pancreatic neoplasms has not been elucidated, it has recently been reported that GNAS gene mutations were found in 58% of intraductal papillary mucinous neoplasms (IPMNs), which are representative pancreatic cystic lesions, suggesting a link between IPMNs and acromegaly. To assess the prevalence of pancreatic cystic lesions in patients with acromegaly, we performed a retrospective cross-sectional single institute study.

Methods

Thirty consecutive acromegalic patients (20 females and 10 males; mean age, 60.9?±?11.9 years) who underwent abdominal contrast-enhanced computed tomography or magnetic resonance imaging between 2007 and 2015 at Kobe University Hospital were recruited. We also analyzed the relationship between presence of pancreatic cystic lesions and somatic GNAS mutations in pituitary tumors.

Results

Seventeen of 30 (56.7%) patients studied had pancreatic cystic lesions. Nine of 17 patients (52.9%) were diagnosed with IPMNs based on imaging findings. These results suggest that the prevalence of IPMNs may be higher in acromegalic patients in acromegalic patients than historically observed in control patients (up to 13.5%). In patients with pancreatic cystic lesions, the mean patient age was higher and the duration of disease was longer than in those without pancreatic cystic lesions (67.0?±?2.3 vs. 53.0?±?2.7 years, p?<?0.001, 15.5?±?2.4 vs. 7.3?±?2.8 years, p?=?0.04). There were no differences in serum growth hormone levels or insulin-like growth factor standard deviation scores between these two groups (21.3?±?6.4 vs. 23.0?±?7.4 ng/ml, p?=?0.86, 6.6?±?0.5 vs. 8.0?±?0.6, p?=?0.70). Neither the presence of somatic GNAS mutation in a pituitary tumor nor low signal intensity of the tumor in T2 weighted magnetic resonance imaging was associated with the presence of pancreatic cystic lesions.

Conclusions

These data demonstrate that old or long-suffering patients with acromegaly have a higher prevalence of pancreatic cystic lesions. Moreover, the prevalence of pancreatic cystic lesions may be increased in acromegalic patients.