Circulating Bacterial-Derived DNA Fragment Level Is a Strong Predictor of Cardiovascular Disease in Peritoneal Dialysis Patients

BackgroundCirculating bacterial DNA fragment is related to systemic inflammatory state in peritoneal dialysis (PD) patients. We hypothesize that plasma bacterial DNA level predicts cardiovascular events in new PD patients.MethodsWe measured plasma bacterial DNA level in 191 new PD patients, who were then followed for at least a year for the development of cardiovascular event, hospitalization, and patient survival.ResultsThe average age was 59.3 ± 11.8 years; plasma bacterial DNA level 34.9 ± 1.5 cycles; average follow up 23.2 ± 9.7 months. At 24 months, the event-free survival was 86.1%, 69.8%, 55.4% and 30.8% for plasma bacterial DNA level quartiles I, II, III and IV, respectively (p < 0.0001). After adjusting for confounders, plasma bacterial DNA level, baseline residual renal function and malnutrition-inflammation score were independent predictors of composite cardiovascular end-point; each doubling in plasma bacterial DNA level confers a 26.9% (95% confidence interval, 13.0 – 42.5%) excess in risk. Plasma bacterial DNA also correlated with the number of hospital admission (r = -0.379, p < 0.0001) and duration of hospitalization for cardiovascular reasons (r = -0.386, p < 0.0001). Plasma bacterial DNA level did not correlate with baseline arterial pulse wave velocity (PWV), but with the change in carotid-radial PWV in one year (r = -0.238, p = 0.005).ConclusionsCirculating bacterial DNA fragment level is a strong predictor of cardiovascular event, need of hospitalization, as well as the progressive change in arterial stiffness in new PD patients.     

Utility of Corrected QT Interval in Orthostatic Intolerance

We performed this study to determine whether electrocardiographic corrected QT (QTc) interval predicts alterations in sympathovagal balance during orthostatic intolerance (OI). We reviewed 1,368 patients presenting with symptoms suggestive of OI who underwent electrocardiography and composite autonomic function tests (AFTs). Patients with a positive response to the head-up tilt test were classified into orthostatic hypotension (OH), neurocardiogenic syncope (NCS), or postural orthostatic tachycardia syndrome (POTS) groups. A total of 275 patients (159 OH, 54 NCS, and 62 POTS) were included in the final analysis. Between-group comparisons of OI symptom grade, QTc interval, QTc dispersion, and each AFT measure were performed. QTc interval and dispersion were correlated with AFT measures. OH Patients had the most severe OI symptom grade and NCS patients the mildest. Patients with OH showed the longest QTc interval (448.8±33.6 msec), QTc dispersion (59.5±30.3 msec) and the lowest values in heart rate response to deep breathing (HRDB) (10.3±6.0 beats/min) and Valsalva ratio (1.3±0.2). Patients with POTS showed the shortest QTc interval (421.7±28.6 msec), the highest HRDB values (24.5±9.2 beats/min), Valsalva ratio (1.8±0.3), and proximal and distal leg sweat volumes in the quantitative sudomotor axon reflex test. QTc interval correlated negatively with HRDB (r = −0.443, p<0.001) and Valsalva ratio (r = −0.425, p<0.001). We found negative correlations between QTc interval and AFT values representing cardiovagal function in patients with OI. Our findings suggest that prolonged QTc interval may be considered to be a biomarker for detecting alterations in sympathovagal balance, especially cardiovagal dysfunction in OH.     

Longitudinal analysis of peripheral blood T cell receptor diversity in patients with systemic lupus erythematosus by next-generation sequencing

IntroductionT cells play an important role in the pathogenesis of systemic lupus erythematosus (SLE). Clonal expansion of T cells correlating with disease activity has been observed in peripheral blood (PB) of SLE subjects. Recently, next-generation sequencing (NGS) of the T cell receptor (TCR) β loci has emerged as a sensitive way to measure the T cell repertoire. In this study, we utilized NGS to assess whether changes in T cell repertoire diversity in PB of SLE patients correlate with or predict changes in disease activity.MethodsTotal RNA was isolated from the PB of 11 SLE patients. Each subject had three samples, collected at periods of clinical quiescence and at a flare. Twelve age-matched healthy controls (HC) were used for reference. NGS was used to profile the complementarity-determining region 3 (CDR3) of the rearranged TCR β loci.ResultsRelative to the HC, SLE patients (at quiescence) demonstrated a 2.2-fold reduction in repertoire diversity in a given PB volume (P <0.0002), a more uneven distribution of the repertoire (Gini coefficient, HC vs SLE, P = 0.015), and a trend toward increased percentage of expanded clones in the repertoire (clone size >1.0 %, HC vs SLE, P = 0.078). No significant correlation between the overall repertoire diversity and clinical disease activity was observed for most SLE patients with only two of eleven SLE patients showing a decreasing trend in repertoire diversity approaching the flare time point. We did not observe any overlap of CDR3 amino acid sequences or a preferential Vβ or Jβ gene usage among the top 100 expanded clones from all SLE patients. In both HC and SLE, the majority of the expanded clones were remarkably stable over time (HC = 5.5 ±0.5 months, SLE = 7.2 ±2.4 months).ConclusionsA significant decrease in T cell repertoire diversity was observed in PB of SLE patients compared to HC. However, in most SLE patients, repertoire diversity did not change significantly with increases in disease activity to a flare. Thus, without a priori knowledge of disease-specific clones, monitoring TCR repertoire in PB from SLE patients is not likely to be useful to predict changes in disease activity.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0655-9) contains supplementary material, which is available to authorized users.     

Increased carotid artery intima-media thickness and myeloperoxidase level in children with newly diagnosed juvenile idiopathic arthritis

IntroductionJuvenile idiopathic arthritis (JIA) is a frequent childhood rheumatic disease characterized by chronic inflammation. The latter has been related to impairment of arterial functional-structural properties, atherogenesis and later cardiovascular events. The objective of this study was to examine intima-media thickness (IMT) and the parameters of arterial stiffness in children with JIA at diagnosis and their correlation with JIA subtype and markers of inflammation and atherosclerosis.MethodsThirty-nine newly diagnosed patients with JIA (26 girls; mean age, 13.2 ± 2.6 years) and 27 healthy controls (9 girls; mean age, 13.6 ± 3.4 years) were included in the study. Twelve patients had oligoarthritis, fifteen had extended oligoarthritis and twelve had rheumatoid factor–negative polyarthritis. IMT of the common carotid artery was determined by ultrasonography, carotid-femoral pulse wave velocity (cfPWV) and augmentation index adjusted to a heart rate of 75 beats/min (AIx@75) were determined by applanation tonometry. The serum levels of atherosclerosis-related biomarkers, such as asymmetric dimethylarginine (ADMA), myeloperoxidase (MPO) and adiponectin, were measured by enzyme-linked immunosorbent assay.ResultsMean IMT (0.46 ± 0.04 vs. 0.42 ± 0.04 mm; p = 0.0003) and MPO concentration (115.2 [95 % confidence interval {95 % CI}, 97.4–136.3] vs. 57.6 [95 % CI, 47.1–70.3] ng/ml; p < 0.0001) were higher in the patients with JIA than in the control subjects. The cfPWV, AIx@75 and serum ADMA and adiponectin levels did not significantly differ between the groups and JIA subtypes. Serum adiponectin level correlated negatively with AIx@75 in patients with JIA (r = −0.38; p < 0.05).ConclusionsPatients with JIA have increased mean IMT and elevated MPO levels at early stages of the disease. AIx@75 was inversely independently associated with adiponectin level in the patients, suggesting that lower adiponectin levels might influence arterial subclinical stiffening in patients with newly diagnosed JIA.     

Antipsychotic Dose Mediates the Association between Polypharmacy and Corrected QT Interval

Antipsychotic (AP) drugs have the potential to cause prolongation of the QT interval corrected for heart rate (QTc). As this risk is dose-dependent, it may be associated with the number of AP drugs concurrently prescribed, which is known to be associated with increased cumulative equivalent AP dosage. This study analysed whether AP dose mediates the relationship between polypharmacy and QTc interval. We used data from a cross-sectional survey that investigated the prevalence of QTc lengthening among people with psychiatric illnesses in Italy. AP polypharmacy was tested for evidence of association with AP dose and QTc interval using the Baron and Kenny mediational model. A total of 725 patients were included in this analysis. Of these, 186 (26%) were treated with two or more AP drugs (AP polypharmacy). The mean cumulative AP dose was significantly higher in those receiving AP polypharmacy (prescribed daily dose/defined daily dose = 2.93, standard deviation 1.31) than monotherapy (prescribed daily dose/defined daily dose = 0.82, standard deviation 0.77) (z = −12.62, p < 0.001). Similarly, the mean QTc interval was significantly longer in those receiving AP polypharmacy (mean = 420.86 milliseconds, standard deviation 27.16) than monotherapy (mean = 413.42 milliseconds, standard deviation 31.54) (z = −2.70, p = 0.006). The Baron and Kenny mediational analysis showed that, after adjustment for confounding variables, AP dose mediates the association between polypharmacy and QTc interval. The present study found that AP polypharmacy is associated with QTc interval, and this effect is mediated by AP dose. Given the high prevalence of AP polypharmacy in real-world clinical practice, clinicians should consider not only the myriad risk factors for QTc prolongation in their patients, but also that adding a second AP drug may further increase risk as compared with monotherapy.     

Chinese Systemic Lupus Erythematosus Treatment and Research Group Registry VI: Effect of Cigarette Smoking on the Clinical Phenotype of Chinese Patients with Systemic Lupus Erythematosus

Objectives

Our study aimed to investigate the effect of cigarette smoking on the clinical phenotype of patients registered in the Chinese Systemic Lupus Erythematosus (SLE) Treatment and Research (CSTAR) group registry database, the first online registry of Chinese patients with SLE.

Methods

A prospective cross-sectional study of Chinese SLE patients was conducted using the CSTAR. Our case-control analysis was performed on age- and gender-matched subjects to explore the potential effect of cigarette smoking on the clinical manifestation of SLE.

Results

Smokers comprised 8.9% (65/730) of patients, and the ratio of females/males was 19/46. Thirty-nine patients were current smokers, and 26 were ex-smokers. Data showed significant differences between smokers and nonsmokers in the following areas: nephropathy (58.5% vs. 39.2%; p = 0.003), microscopic hematuria (30.8% vs. 19.1%; p = 0.025), proteinuria (53.8% vs. 34.4%; p = 0.002), and SLE Disease Activity Index(DAI) scores (12.38±8.95 vs. 9.83±6.81; p = 0.028). After adjusting for age and gender, significant differences between smokers and nonsmokers were found with photosensitivity (35.9% vs. 18%; p = 0.006), nephropathy (59.4% vs. 39.8%; p = 0.011), and proteinuria (54.7% vs. 35.2%). Although smokers tended to have greater disease severity compared with nonsmokers (SLEDAI scores: 12.58±8.89 vs.10.5±7.09), the difference was not significant (p = 0.081).

Conclusions

Cigarette smoking triggers the development and exacerbation of SLE, especially with respect to renal involvement. Chinese smokers with SLE should be advised to discontinue cigarette use.     

Assessment of Femoral Version Should be Assessed Independently of Conventional Measures in Patellofemoral Instability

BackgroundThe purpose of the present study is to determine the association between femoral version and traditional pathologic bony factors commonly used to measure and define patellofemoral alignment.MethodsWe performed a retrospective review of patients treated for patellofemoral instability (PFI) at a single institution. Patients included underwent magnetic resonance imaging (MRI) of the lower extremity using a rotational protocol prior to medial patellofemoral ligament reconstruction with or without tibial tubercle osteotomy. Those with a history of ipsilateral lower extremity surgery were excluded. Two independent reviewers measured femoral version, tibial tubercle-trochlear groove (TT-TG) distance, tibial tubercle-posterior cruciate ligament (TT-PCL) distance, and tibial torsion (TT). Pearson correlation coefficients were used to describe the relationships between all radiographic measures.ResultsA total of 51 knees (43 patients) were included. The average age and body mass index were 23.7 ± 9.33 years and 29.23 ± 8.04 kg/ m2, respectively. The mean femoral version was 15.61 ± 11.57°. The degree of femoral version did not significantly correlate with TT-TG (r=0.103, p=0.474), TT-PCL (-0.086, p=0.550), or TT (r=0.111, p=0.438). Increased TT-TG distance was strongly associated with increased TT-PCL (r=0.470, p=0.001). In females, increased femoral version significantly correlated with increased TT (r=0.381, p=0.029).ConclusionNeither increased nor decreased amounts of femoral anteversion significantly correlated with TT-TG, TT-PCL, or TT. Therefore, assessment of femoral version should be measured independently of conventional measures when considering osteotomies to correct PFI.Level of Evidence: IV     

The importance of antioxidant status in gastric intestinal metaplasia

BackgroundOxidative stress status in different cancer types was investigated before, but not studied in gastric intestinal metaplasia to the best of our knowledge. Purpose of this study is to examine whether there is a difference between oxidative stress status in patients with intestinal metaplasia (IM) compared to individuals without IM, we compared the serum levels of disulfide (SS), total thiol (TT) and native thiol (NT).MethodsThis was a prospective, non-randomized casecontrol study including 67 patients with histopathologically confirmed IM and 60 individuals demographically matched in terms of age, gender, BMI, smoking status, and chronic diseases as control group.ResultsThe mean NT, TT and NT to TT (NT/TT) ratios were statistically significantly higher in IM group compared to controls ((351.71 ± 81.9 mol/L vs. 271.82 ± 54.13 mol/L, p=0.000), (391.5 ± 92.69 mol/L vs. 308.59 ± 55.53 mol/L, p=0.000) and (0.89 ± 0.6 vs. 0.87 ± 0.29, p=0.022), respectively). The mean SS to TT (SS/TT) ratio was significantly lower in IM group than control group (0.050 ± 0.31 vs. 0.060 ± 0.014, P=0.022). Median SS and mean SS/NT ratio was similar in both groups (16.3 (3.3-78) vs. 18.3 (10-32.7), p=0.271 and 0.055 ± 0.041 vs. 0.070 ± 0.019, p=0.068, respectively). In ROC analysis, cut off value of SS/NT for IM was found 0.062, in regression analysis, SS/NT <0.062 was found as an independently prognostic marker for IM (OR, 2.38; 95%CI: 1.168-4.865, P=0.017).ConclusionsSS/NT ratio lower than 0.062 was found as an independently prognostic marker for IM. This ratio could help to distinguish which patients should be followed closely for gastric cancer.     

Intestinal Lesions Are Associated with Altered Intestinal Microbiome and Are More Frequent in Children and Young Adults with Cystic Fibrosis and Cirrhosis

Methods11 subjects with CFCIR (6 M, 12.8 yrs ± 3.8) and 19 matched with CFnoLIV (10 M, 12.6 yrs ± 3.4) underwent small bowel capsule endoscopy, intestinal permeability testing by urinary lactulose: mannitol excretion ratio, fecal calprotectin determination and fecal microbiome characterization.ResultsCFCIR and CFnoLIV did not differ in key demographics or CF complications. CFCIR had higher GGT (59±51 U/L vs 17±4 p = 0.02) and lower platelet count (187±126 vs 283±60 p = 0.04) and weight (-0.86 ± 1.0 vs 0.30 ± 0.9 p = 0.002) z scores. CFCIR had more severe intestinal mucosal lesions on capsule endoscopy (score ≥4, 4/11 vs 0/19 p = 0.01). Fecal calprotectin was similar between CFCIR and CFnoLIV (166 μg/g ±175 vs 136 ± 193 p = 0.58, nl <120). Lactulose:mannitol ratio was elevated in 27/28 subjects and was slightly lower in CFCIR vs CFnoLIV (0.08±0.02 vs 0.11±0.05, p = 0.04, nl ≤0.03). Small bowel transit time was longer in CFCIR vs CFnoLIV (195±42 min vs 167±68 p<0.001, nl 274 ± 41). Bacteroides were decreased in relative abundance in CFCIR and were associated with lower capsule endoscopy score whereas Clostridium were more abundant in CFCIR and associated with higher capsule endoscopy score.ConclusionsCFCIR is associated with increased intestinal mucosal lesions, slower small bowel transit time and alterations in fecal microbiome. Abnormal intestinal permeability and elevated fecal calprotectin are common in all CF subjects. Disturbances in intestinal function in CF combined with changes in the microbiome may contribute to the development of hepatic fibrosis and intestinal lesions.     

Twelve Weeks of Sprint Interval Training Improves Indices of Cardiometabolic Health Similar to Traditional Endurance Training despite a Five-Fold Lower Exercise Volume and Time Commitment

AimsWe investigated whether sprint interval training (SIT) was a time-efficient exercise strategy to improve insulin sensitivity and other indices of cardiometabolic health to the same extent as traditional moderate-intensity continuous training (MICT). SIT involved 1 minute of intense exercise within a 10-minute time commitment, whereas MICT involved 50 minutes of continuous exercise per session.MethodsSedentary men (27±8y; BMI = 26±6kg/m²) performed three weekly sessions of SIT (n = 9) or MICT (n = 10) for 12 weeks or served as non-training controls (n = 6). SIT involved 3x20-second ‘all-out’ cycle sprints (~500W) interspersed with 2 minutes of cycling at 50W, whereas MICT involved 45 minutes of continuous cycling at ~70% maximal heart rate (~110W). Both protocols involved a 2-minute warm-up and 3-minute cool-down at 50W.ResultsPeak oxygen uptake increased after training by 19% in both groups (SIT: 32±7 to 38±8; MICT: 34±6 to 40±8ml/kg/min; p<0.001 for both). Insulin sensitivity index (CS_I), determined by intravenous glucose tolerance tests performed before and 72 hours after training, increased similarly after SIT (4.9±2.5 to 7.5±4.7, p = 0.002) and MICT (5.0±3.3 to 6.7±5.0 x 10⁻⁴ min^-1 [μU/mL]^-1, p = 0.013) (p<0.05). Skeletal muscle mitochondrial content also increased similarly after SIT and MICT, as primarily reflected by the maximal activity of citrate synthase (CS; P<0.001). The corresponding changes in the control group were small for VO₂peak (p = 0.99), CS_I (p = 0.63) and CS (p = 0.97).ConclusionsTwelve weeks of brief intense interval exercise improved indices of cardiometabolic health to the same extent as traditional endurance training in sedentary men, despite a five-fold lower exercise volume and time commitment.     

Greater subchondral vBMD at the tibia is observed between 1 and 5 years of anterior cruciate ligament injury

Objectives:This study aimed to determine if differences exist in tibial subchondral bone and muscle imbalances between individuals with and without an Anterior Cruciate Ligament (ACL) repair within the past 1 to 5 years (median 3 years).Methods:Fifteen individuals (ages 18-23 years) that had a unilateral ACL repair with no contralateral knee injuries and 15 age- and sex-matched controls (no prior knee injuries) were recruited to participate. Subchondral bone was measured using peripheral quantitative computed tomography (pQCT) distal to the tibial plateau. Muscle force, power, and force efficiency were measured using single leg jumps performed on a force platform.Results:Within subject analysis showed a greater subchondral vBMD in the injured versus uninjured legs of cases (278±11 mg/cm³ and 258±6 mg/cm³, respectively, mean±SD, p=0.01). Subchondral vBMD was greater on the injured leg of cases than controls (267±8 mg/cm³ and 237±8 mg/cm³, respectively, marginal mean±SE, p=0.01). No differences were observed between cases and controls for muscle force, power, or force efficiency.Conclusions:Greater subchondral bone mineral density was observed in participants between 1- and 5-years post-op. Given the results of this study and the known long-term effects of ACL injuries, future research must continue to focus on the prevention of these injuries.     

Dynamics of G6PD activity in patients receiving weekly primaquine for therapy of Plasmodium vivax malaria

BackgroundAcute Plasmodium vivax malaria is associated with haemolysis, bone marrow suppression, reticulocytopenia, and post-treatment reticulocytosis leading to haemoglobin recovery. Little is known how malaria affects glucose-6-phosphate dehydrogenase (G6PD) activity and whether changes in activity when patients present may lead qualitative tests, like the fluorescent spot test (FST), to misdiagnose G6PD deficient (G6PDd) patients as G6PD normal (G6PDn). Giving primaquine or tafenoquine to such patients could result in severe haemolysis.MethodsWe investigated the G6PD genotype, G6PD enzyme activity over time and the baseline FST phenotype in Cambodians with acute P. vivax malaria treated with 3-day dihydroartemisinin piperaquine and weekly primaquine, 0·75 mg/kg x8 doses.ResultsOf 75 recruited patients (males 63), aged 5–63 years (median 24), 15 were G6PDd males (14 Viangchan, 1 Canton), 3 were G6PD Viangchan heterozygous females, and 57 were G6PDn; 6 patients had α/β-thalassaemia and 26 had HbE.Median (range) Day0 G6PD activities were 0·85 U/g Hb (0·10–1·36) and 11·4 U/g Hb (6·67–16·78) in G6PDd and G6PDn patients, respectively, rising significantly to 1·45 (0·36–5·54, p<0.01) and 12·0 (8·1–17·4, p = 0.04) U/g Hb on Day7, then falling to ~Day0 values by Day56. Day0 G6PD activity did not correlate (p = 0.28) with the Day0 reticulocyte counts but both correlated over time. The FST diagnosed correctly 17/18 G6PDd patients, misclassifying one heterozygous female as G6PDn.ConclusionsIn Cambodia, acute P. vivax malaria did not elevate G6PD activities in our small sample of G6PDd patients to levels that would result in a false normal qualitative test. Low G6PDd enzyme activity at disease presentation increases upon parasite clearance, parallel to reticulocytosis. More work is needed in G6PDd heterozygous females to ascertain the effect of P. vivax on their G6PD activities.Trial registrationThe trial was registered (ACTRN12613000003774) with the Australia New Zealand Clinical trials (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363399&isReview=true).     

Time-Staged Gamma Knife Stereotactic Radiosurgery for Large Cerebral Arteriovenous Malformations: A Preliminary Report

ObjectiveWe retrospectively analyzed our experience with time-staged gamma knife stereotactic radiosurgery (GKS) in treating large arteriovenous malformation(AVM)s;≥ 10 cm³).MethodsForty-five patients who underwent time-staged GKS (2-stage, n = 37;3-stage,n = 8) between March 1998 and December 2011 were included. The mean volume treated was 20.42±6.29 cm³ (range, 10.20–38.50 cm³). Obliteration rates of AVMs and the associated complications after GKS were evaluated.ResultsMean AVM volume (and median marginal dose) at each GKS session in the 37 patients who underwent 2-stage GKS was 19.67±6.08 cm³ (13 Gy) at session 1 and 6.97±6.92 cm³ (17 Gy) at session 2. The median interval period was 39 months. After follow-up period of 37 months, the complete obliteration rate was 64.9%. The mean AVM volume (and median marginal dose) at each GKS session in the 8 patients who underwent 3-stage GKS was 23.90±6.50 cm³ (12.25 Gy), 19.43±7.46 cm³ (13.5 Gy), 7.48±6.86 cm³ (15.5 Gy) at session 1, 2, and 3, respectively. The median interval duration between each GKS session was 37.5 and 38 months, respectively. After a median follow-up period of 47.5 months, 5 patients (62.5%) achieved complete obliteration. Postradiosurgical hemorrhage developed in 5 patients (11.1%) including one case of major bleeding and 4 cases of minor bleeding. No patient suffered from clinically symptomatic radiation necrosis following radiation.ConclusionTime-staged GKS could be an effective and safe treatment option in the management of large AVMs.     

Influence of hyperbaric oxygen therapy on bone metabolism in patients with neoplasm

BackgroundHyperbaric oxygen therapy (HBOT) is useful in the treatment of complications due to radiotherapy in patients with neoplasm. Its effects on bone metabolism are unclear. In our study, we analyzed the effects of HBOT on bone remodeling in oncological patients with radiotherapy.Materials and methodsProspective clinical study in 23 patients with neoplasms undergoing treatment with HBOT due to complications of radiotherapy (hemorrhagic cystitis, proctitis or radionecrosis) and 25 patients with chronic anal fissure. The average number of HBOT sessions was 20 ± 5 (100% oxygen, 2.3 atmospheres and 90 min per day). Serum levels of aminoterminal propeptide of type I collagen (P1NP), C terminal telopeptide of type I collagen (CTX), alkaline phosphatase (AP), 25hydroxyvitamin D (25-OHD), parathyroid hormone (PTH), were measured at 3 time points: T0 (before beginning HBOT), T1 (at the end of HBOT) and T2 (6 months after HBOT).ResultsAt baseline, the patients with neoplasm have higher bone turnover than those with anal fissure. These differences were 41% in CTX (0.238 ± 0.202 ng/mL in neoplasm and 0.141 ± 0.116 ng/mL in fissure; p = 0.04), 30% for PTH (46 ± 36 pg/mL in neoplasm and 32 ± 17 pg/mL in fissure; p = 0.04) and 15% for alkaline phosphatase (80 ± 24 U/L in neoplasm and 68 ± 16 U/L in fissure; p = 0.04). In the group with neoplasm, the values of P1NP decreased 6% after HBOT (T0: 49 ± 31 ng/mL, T2: 46 ± 12 ng/mL; p = 0.03). Also, there were non-significant decreases in PTH (−34%) and CTX (−30%).ConclusionsPatients with neoplasm and complications with radiotherapy have an increase in bone remodeling that may be diminished after HBOT.     

Intracameral Interleukin 1β, 6, 8, 10, 12p,Tumor Necrosis Factor α and Vascular Endothelial Growth Factor and Axial Length in Patients with Cataract

ObjectiveTo assess associations between the aqueous humour concentration of interleukin IL-1β, IL-6, IL-8, IL-10 and IL-12p, tumor necrosis factor α (TNF-α) and vascular endothelial growth factor (VEGF) and axial length in eyes with cataract.MethodsThe hospital-based investigation included patients who underwent cataract surgery between March 2014 and April 2014. Using aqueous humour collected at the start of cataract surgery, the interleukins IL-1β, IL-6, IL-8, IL-10 and IL-12p, TNF-α and VEGF were examined using a cytometric bead array. Axial length was determined by partial coherence laser interferometry (IOL Master).ResultsThe study included 33 patients with cataract (33 eyes) with a mean age of 69.2±10.8 years (range:50–87 years) and a mean axial length of 24.7±1.9 mm (range:22.6–31.5 mm). Lower aqueous concentration of VEGF was significantly associated with longer axial length (VEGF concentration (pg/mL) = -5.12 x Axial Length (mm) + 163; correlation coefficient r = -0.41; P<0.001) and more myopic refractive error (VEGF concentration (pg/mL) = 1.27xspherical equivalent (diopters)+44.8; r = 0.383; P = 0.002). The aqueous concentrations of all other substances were not significantly (all P>0.10) associated with axial length or refractive error.ConclusionsHigher intravitreal concentrations of VEGF were measured in eyes with a longer axial length, while the intraocular concentrations of IL-1β, IL-6, IL-8, IL-10, IL-12p and TNF-α were not correlated with axial length. The lower concentration of VEGF in axially elongated eyes may be one of the reasons for the lower prevalence of age-related macular degeneration and diabetic retinopathy in myopic eyes.     

Thiol/disulfide homeostasis impaired in patients with primary Sjögren's syndrome

BackgroundPrimary Sjögren''s syndrome (pSS) is a disease associated with the overexpression of proinflammatory cytokines, and oxidative stress is one of the factors responsible for its etiopathogenesis. This study aimed to investigate the thiol/disulphide homeostasis in pSS patients.MethodsThe study included 68 pSS patients and 69 healthy controls. Thiol/disulphide homeostasis (total thiol, native thiol, and disulphide levels) was measured using the automatic spectrophotometric method developed by Erel and Neselioglu, and the results of the 2 groups were compared.ResultsThe gender and age distributions of the pSS and control groups were similar (P = 0.988 and P = 0.065). Total thiol and native thiol levels were lower in the pSS group than in the control group (470.08 ± 33.65 µmol/L vs. 528.21 ± 44.99 µmol/L, P < 0.001, and 439.14 ± 30.67 µmol/L vs. 497.56 ± 46.70 µmol/L, P < 0.001, respectively). There were no differences in disulphide levels between groups [17.00 (range 0.70-217.0) µmol/L vs. 14.95 (range 2.10-40.10) µmol/L, P = 0.195].ConclusionsIt was concluded that the thiol/disulphide balance shifted towards disulphide in patients with pSS.     

Long QT Interval in Turner Syndrome – A High Prevalence of LQTS Gene Mutations

Objectives

QT-interval prolongation of unknown aetiology is common in Turner syndrome. This study set out to explore the presence of known long QT mutations in Turner syndrome and to examine the corrected QT-interval (QTc) over time and relate the findings to the Turner syndrome phenotype.

Methods

Adult women with Turner syndrome (n = 88) were examined thrice and 68 age-matched healthy controls were examined once. QTc was measured by one blinded reader (intra-reader variability: 0.7%), and adjusted for influence of heart rate by Bazett’s (bQTc) and Hodges’s formula (hQTc). The prevalence of mutations in genes related to Long QT syndrome was determined in women with Turner syndrome and a QTc >432.0 milliseconds (ms). Echocardiographic assessment of aortic valve morphology, 24-hour blood pressures and blood samples were done.

Results

The mean hQTc in women with Turner syndrome (414.0±25.5 ms) compared to controls (390.4±17.8 ms) was prolonged (p<0.001) and did not change over time (416.9±22.6 vs. 415.6±25.5 ms; p = 0.4). 45,X karyotype was associated with increased hQTc prolongation compared to other Turner syndrome karyotypes (418.2±24.8 vs. 407.6±25.5 ms; p = 0.055). In women with Turner syndrome and a bQTc >432 ms, 7 had mutations in major Long QT syndrome genes (SCN5A and KCNH2) and one in a minor Long QT syndrome gene (KCNE2).

Conclusion

There is a high prevalence of mutations in the major LQTS genes in women with TS and prolonged QTc. It remains to be settled, whether these findings are related to the unexplained excess mortality in Turner women.

Clinical Trial Registration

{"type":"clinical-trial","attrs":{"text":"NCT00624949","term_id":"NCT00624949"}}NCT00624949. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol/sid/S0001FLI/selectaction/View/ts/3/uid/U000099E.     

Association between Obstructive Sleep Apnea and Community-Acquired Pneumonia

BackgroundWe hypothesized that obstructive sleep apnea (OSA) can predispose individuals to lower airway infections and community-acquired pneumonia (CAP) due to upper airway microaspiration. This study evaluated the association between OSA and CAP.MethodsWe performed a case-control study that included 82 patients with CAP and 41 patients with other infections (control group). The controls were matched according to age, sex and body mass index (BMI). A respiratory polygraph (RP) was performed upon admission for patients in both groups. The severity of pneumonia was assessed according to the Pneumonia Severity Index (PSI). The associations between CAP and the Epworth Sleepiness Scale (ESS), OSA, OSA severity and other sleep-related variables were evaluated using logistic regression models. The associations between OSA, OSA severity with CAP severity were evaluated with linear regression models and non-parametric tests.FindingsNo significant differences were found between CAP and control patients regarding anthropometric variables, toxic habits and risk factors for CAP. Patients with OSA, defined as individuals with an Apnea-Hypopnea Index (AHI) ≥10, showed an increased risk of CAP (OR = 2·86, 95%CI 1·29–6·44, p = 0·01). Patients with severe OSA (AHI≥30) also had a higher risk of CAP (OR = 3·18, 95%CI 1·11–11·56, p = 0·047). In addition, OSA severity, defined according to the AHI quartile, was also significantly associated with CAP (p = 0·007). Furthermore, OSA was significantly associated with CAP severity (p = 0·0002), and OSA severity was also associated with CAP severity (p = 0·0006).ConclusionsOSA and OSA severity are associated with CAP when compared to patients admitted to the hospital for non-respiratory infections. In addition, OSA and OSA severity are associated with CAP severity. These results support the potential role of OSA in the pathogenesis of CAP and could have clinical implications. This link between OSA and infection risk should be explored to investigate the relationships among gastroesophageal reflux, silent aspiration, laryngeal sensory dysfunction and CAP.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01071421","term_id":"NCT01071421"}}NCT01071421     

Coronary Stent Artifact Reduction with an Edge-Enhancing Reconstruction Kernel – A Prospective Cross-Sectional Study with 256-Slice CT

PurposeMetallic artifacts can result in an artificial thickening of the coronary stent wall which can significantly impair computed tomography (CT) imaging in patients with coronary stents. The objective of this study is to assess in vivo visualization of coronary stent wall and lumen with an edge-enhancing CT reconstruction kernel, as compared to a standard kernel.MethodsThis is a prospective cross-sectional study involving the assessment of 71 coronary stents (24 patients), with blinded observers. After 256-slice CT angiography, image reconstruction was done with medium-smooth and edge-enhancing kernels. Stent wall thickness was measured with both orthogonal and circumference methods, averaging thickness from diameter and circumference measurements, respectively. Image quality was assessed quantitatively using objective parameters (noise, signal to noise (SNR) and contrast to noise (CNR) ratios), as well as visually using a 5-point Likert scale.ResultsStent wall thickness was decreased with the edge-enhancing kernel in comparison to the standard kernel, either with the orthogonal (0.97 ± 0.02 versus 1.09 ± 0.03 mm, respectively; p<0.001) or the circumference method (1.13 ± 0.02 versus 1.21 ± 0.02 mm, respectively; p = 0.001). The edge-enhancing kernel generated less overestimation from nominal thickness compared to the standard kernel, both with the orthogonal (0.89 ± 0.19 versus 1.00 ± 0.26 mm, respectively; p<0.001) and the circumference (1.06 ± 0.26 versus 1.13 ± 0.31 mm, respectively; p = 0.005) methods. The edge-enhancing kernel was associated with lower SNR and CNR, as well as higher background noise (all p < 0.001), in comparison to the medium-smooth kernel. Stent visual scores were higher with the edge-enhancing kernel (p<0.001).ConclusionIn vivo 256-slice CT assessment of coronary stents shows that the edge-enhancing CT reconstruction kernel generates thinner stent walls, less overestimation from nominal thickness, and better image quality scores than the standard kernel.     

Association of Right Ventricular Pressure and Volume Overload with Non-Ischemic Septal Fibrosis on Cardiac Magnetic Resonance

Background

Non-ischemic fibrosis (NIF) on cardiac magnetic resonance (CMR) has been linked to poor prognosis, but its association with adverse right ventricular (RV) remodeling is unknown. This study examined a broad cohort of patients with RV dysfunction, so as to identify relationships between NIF and RV remodeling indices, including RV pressure load, volume and wall stress.

Methods and Results

The population comprised patients with RV dysfunction (EF<50%) undergoing CMR and transthoracic echo within a 14 day (5±3) interval. Cardiac structure, function, and NIF were assessed on CMR. Pulmonary artery systolic pressure (PASP) was measured on echo. 118 patients with RV dysfunction were studied, among whom 47% had NIF. Patients with NIF had lower RVEF (34±10 vs. 39±9%; p = 0.01) but similar LVEF (40±21 vs. 39±18%; p = 0.7) and LV volumes (p = NS). RV wall stress was higher with NIF (17±7 vs. 12±6 kPa; p<0.001) corresponding to increased RV end-systolic volume (143±79 vs. 110±36 ml; p = 0.006), myocardial mass (60±21 vs. 53±17 gm; p = 0.04), and PASP (52±18 vs. 41±18 mmHg; p = 0.001). NIF was associated with increased wall stress among subgroups with isolated RV (p = 0.005) and both RV and LV dysfunction (p = 0.003). In multivariable analysis, NIF was independently associated with RV volume (OR = 1.17 per 10 ml, [CI 1.04–1.32]; p = 0.01) and PASP (OR = 1.43 per 10 mmHg, [1.14–1.81]; p = 0.002) but not RV mass (OR = 0.91 per 10 gm, [0.69–1.20]; p = 0.5) [model χ² = 21; p<0.001]. NIF prevalence was higher in relation to PA pressure and RV dilation and was > 6-fold more common in the highest, vs. the lowest, common tertile of PASP and RV size (p<0.001).

Conclusion

Among wall stress components, NIF was independently associated with RV chamber dilation and afterload, supporting the concept that NIF is linked to adverse RV chamber remodeling.