Single versus multiple dose intravenous immunoglobulin in combination with LED phototherapy in the treatment of ABO hemolytic disease in neonates

Intravenous immunoglobulin (IVIG) has been found to decrease hemolysis in neonatal jaundice due to blood group incompatibility, but a consensus on its usage has not been reached. We conducted a study to compare single versus multiple dose of IVIG in combination with light emitting diode (LED) phototherapy in patients with neonatal jaundice secondary to ABO blood incompatibility, and compared the efficacy of these treatments with that in a group of patients who received LED phototherapy solely. Thirty-nine term neonates with ABO blood group incompatibility were enrolled in the study. Group I received one dose of IVIG (1 g/kg) and LED phototherapy, and group II two doses of IVIG (1 g/kg) and LED phototherapy, whereas group III received LED phototherapy only. In group I, exchange transfusion was performed in one patient (6%) and in group II in one patient (10%). In the control group, none of the patients required exchange transfusion. Duration of LED phototherapy was 4.3 ± 0.7 days in group I + II (IVIG group), 3.9 ± 0.6 days in group III (P = 0.06). Lowest hematocrit level in group I + II was 35.0 ± 7.8 and group III was 38.9 ± 4.2, this was statistically significant (P = 0.034). IVIG therapy, single or multiple, did not affect exchange transfusion, need of erythrocyte transfusion and hospitalization time when used in combination with LED phototherapy in the treatment of ABO hemolytic jaundice in neonates.     

IgM anti-recipient ABO antibodies predict acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation

Passenger lymphocyte syndrome (PLS) presents as transient immune hemolysis due to anti-recipient ABO antibodies produced by donor B-lymphocytes accompanying minor or bidirectional ABO incompatible allogeneic hematopoietic stem cell transplantation (HSCT). We monitored both IgM and IgG type anti-recipient ABO antibodies in 18 consecutive HSCT recipients with hematological malignancies. Five of these patients (28 %) developed transient immune hemolysis due to PLS after a median of 19 days post-HSCT. This response was associated with the detection of IgM and IgG anti-recipient ABO antibodies after a median of 16 and 22 days post-HSCT, respectively. All five patients subsequently developed acute graft-versus-host disease (GVHD) grades II–IV, and three died due to transplant-related mortality (TRM) within 1 year after HSCT, while in contrast, of the 13 patients without PLS, three (23 %) developed grades II–IV acute GVHD (p < 0.01) and the 1-year TRM was 8 % (p = 0.03). Thus, patients with PLS had a significantly lower 1-year overall survival than those without PLS (20 vs. 75 %, p = 0.03). These findings suggest that the IgM anti-recipient ABO antibody may be an early predictor of acute GVHD and poor survival after minor or bidirectional ABO incompatible HSCT.     

Higher body weight patients on clopidogrel maintenance therapy have lower active metabolite concentrations,lower levels of platelet inhibition,and higher rates of poor responders than low body weight patients

Body weight is a predictor of clopidogrel response. However, no prospective studies have compared pharmacodynamic (PD) and pharmacokinetic (PK) data based on body weight. We compared PD and PK effects of clopidogrel 75 mg in low body weight (LBW, <60 kg) and higher body weight (HBW, ≥60 kg) patients with stable coronary artery disease. LBW (n = 34, 56.4 ± 3.7 kg) and HBW (n = 38, 84.7 ± 14.9 kg) aspirin-treated patients received clopidogrel 75 mg for 10–14 days. The area under the concentration–time curve of active metabolite (Clop-AM) calculated through the last quantifiable concentration up to 4 h postdose, AUC_(0–tlast), was calculated by noncompartmental methods. Light transmission aggregometry (LTA) (maximum platelet aggregation and inhibition of platelet aggregation to 20 μM adenosine diphosphate (ADP), and residual platelet aggregation to 5 μM ADP), VerifyNow^® P2Y12 reaction units (PRU), and vasodilator-associated stimulated phosphoprotein phosphorylation platelet reactivity index (VASP–PRI) were performed. Mean AUC_(0–tlast) was lower in HBW than LBW patients: 12.8 versus 17.9 ng h/mL. HBW patients had higher platelet reactivity as measured by LTA (all p ≤ 0.01), PRU (207 ± 68 vs. 152 ± 57, p < 0.001), and VASP–PRI (56 ± 18 vs. 39 ± 17, p < 0.001). More HBW patients exhibited high on-treatment platelet reactivity (HPR) using PRU (35 vs. 9 %) and VASP–PRI (65 vs. 27 %). Body weight correlated with PRU and VASP–PRI (both p < 0.001), and inversely with log transformed AUC_(0–tlast) (p < 0.001). In conclusion, HBW patients had lower levels of Clop-AM, and higher platelet reactivity and rates of HPR than LBW subjects, contributing to their suboptimal response to clopidogrel.     

Endothelin-B receptors and ventricular arrhythmogenesis in the rat model of acute myocardial infarction

The arrhythmogenic effects of endothelin-1 (ET-1) are mediated via ETA-receptors, but the role of ETB-receptors is unclear. We examined the pathophysiologic role of ETB-receptors on ventricular tachyarrhythmias (VT/VF) during myocardial infarction (MI). MI was induced by coronary ligation in two animal groups, namely in wild-type (n = 63) and in ETB-receptor-deficient (n = 61) rats. Using a telemetry recorder, VT/VF episodes were evaluated during phase I (the 1st hour) and phase II (2–24 h) post-MI, with and without prior β-blockade. Action potential duration at 90% repolarization (APD90) was measured from monophasic epicardial recordings and indices of sympathetic activation were assessed using fast-Fourier analysis of heart rate variability. Serum epinephrine and norepinephrine were measured with radioimmunoassay. MI size was similar in the two groups. There was a marked temporal variation in VT/VF duration; during phase I, it was higher (p = 0.0087) in ETB-deficient (1,519 ± 421 s) than in wild-type (190 ± 34 s) rats, but tended (p = 0.086) to be lower in ETB-deficient (4.2 ± 2.0 s) than in wild-type (27.7 ± 8.0 s) rats during phase II. Overall, the severity of VT/VF was greater in ETB-deficient rats, evidenced by higher (p = 0.0058) mortality (72.0% vs. 32.1%). There was a temporal variation in heart rate and in the ratio of low- to high-frequency spectra, being higher (<0.001) during phase I, but lower (p < 0.05) during phase II in ETB-deficient rats. Likewise, 1 h post-MI, serum epinephrine (p = 0.025) and norepinephrine (p < 0.0001) were higher in ETB-deficient (4.20 ± 0.54, 14.24 ± 1.39 ng/ml) than in wild-type (2.30 ± 0.59, 5.26 ± 0.67 ng/ml) rats, respectively. After β-blockade, VT/VF episodes and mortality were similar in the two groups. The ETB-receptor decreases sympathetic activation and arrhythmogenesis during the early phase of MI, but these effects diminish during evolving MI.     

Analysis of early and long-term outcomes of acute type A aortic dissection according to the new international aortic arch surgery study group recommendations

To evaluate predictors of early and long-term outcomes of surgical repair of acute Type A aortic dissection. Retrospective single-centre study evaluating patients surgically treated between 1998 and 2013. Clinical follow-up was performed. Complications were classified according to the International Aortic Arch Surgery Study Group recommendations. Statistical analysis included univariate and multivariate analysis of preoperative and operative data. One hundred eighty-five patients were evaluated. The follow-up was complete for 180 patients (97 %). Mean age was 63 years, 82 % had a DeBakey type I aortic dissection, 18 % a type II. Eleven patients (6 %) died intraoperatively, 119 of the remaining (68 %) had postoperative complications. Thirty-day mortality was 21 % (38 patients). Average ICU and hospital stay were 6 and 14 days, respectively. During a mean follow-up time of 6 ± 4 years we observed 44 deaths (31 %). Twenty patients (14 %) needed late thoracic aorta reoperation. Results from the multivariate analysis are as follows. Thirty-day mortality was associated with abdominal pain at presentation (p < 0.01). The incidence of postoperative complications was related to older age at intervention (p < 0.01) and longer cross-clamp time (p < 0.01). Mortality at follow-up was significantly increased by older age at intervention (p < 0.01), with a logarithmic growth after 60 years, female sex (p < 0.01), preoperative limb ischemia (p = 0.02) and DHCA (p < 0.01). The surgical results of type A aortic dissection are affected by age at intervention with a logarithmic increase of late mortality in patients older than 60 years.     

Inflammatory activation in an unselected population of subjects with atrial fibrillation: links with structural heart disease, atrial remodeling and recent onset

Previous studies investigated circulating levels of C-reactive protein (CRP) mostly in subjects with paroxysmal atrial fibrillation (AF) and lone AF (LAF). We, therefore, aimed to investigate circulating levels of CRP in patients with new onset AF with particular regards to AF duration, even in the presence of structural heart disease (SHD). CRP levels were evaluated in 96 consecutive patients with new onset AF (50 with LAF and 46 with SHD, 41 with paroxysmal AF (PAF) (<7 days) and 55 persistent AF (>7 days). Patients with AF had higher CRP levels than controls (4.8 ± 6.99 vs. 1.59 ± 1.32 mg/L; p < 0.001). AF patients with SHD had higher CRP levels than LAF patients (7.08 ± 9.19 vs. 2.63 ± 2.47 mg/L; p < 0.01) and control subjects (vs. 1.59 ± 1.32 mg/L; p < 0.001): CRP levels in LAF patients were higher than in controls (p < 0.01). CRP levels were significantly increased in subjects with paroxysmal AF (6.67 ± 9.44 mg/L) with respect to those with persistent AF (3.54 ± 4.44 mg/L, p < 0.05) and controls (1.59 ± 1.32 mg/L, p < 0.001 vs. paroxysmal AF, p < 0.01 vs. persistent AF). Differences related to the presence of LAF and SHD remained significant even after multivariable regression analysis. CRP concentrations significantly correlated with left atrial size(r 0.23, p < 0.05). Increased CRP levels are detectable in patients with AF, proportional to atrial remodeling, recent onset of dysrhythmia and SHD.     

Efficacy of bundle ablation for cavotricuspid isthmus-dependent atrial flutter: combination of the maximum voltage-guided ablation technique and high-density electro-anatomical mapping

Introduction

Pathological studies have demonstrated that the cavotricuspid isthmus (CTI) is often composed of discrete muscle bundles, which are thought to be represented electrically as high-amplitude electrograms. Based on this observation, we visualized the bundles using an electro-anatomical mapping system (EAMS) and investigate the efficacy of bundle ablation which is an ablation method for selectively targeting high-voltage sites obtained by high-density electro-anatomical mapping along the CTI.

Methods

Sixty patients with atrial flutter were randomly assigned to cavotricuspid isthmus ablation using a conventional anatomical approach (Group 1) or bundle ablation approach (Group 2). In Group 2, CTI was mapped in detail with EAMS, and we visualized the bundles that were 1.5 mV or more on a bipolar voltage map. Radiofrequency (RF) ablation was delivered sequentially from the maximum voltage site at the shortest distance of the bundle until bidirectional block was achieved.

Results

Bidirectional block was achieved in all patients. Mean ablation times (Group 1, 1,392?±?960 s; Group 2, 638?±?342 s, p?<?0.01), the mean number of RF applications (Group 1, 31.7?±?23.6; Group 2, 13.0?±?7.0, p?<?0.01), and fluoroscopy times (Group 1, 50.4?±?28.3 min; Group 2, 42.3?±?21.3 min, p?<?0.01) were significantly shorter in Group 2 than those in Group 1.

Conclusion

Bundle ablation at CTI is highly effective for achieving a bidirectional block requiring shorter ablation times, shorter fluoroscopy times, and fewer RF applications.     

Inner lumen mapping catheter-facilitated big cryoballoon treatment for atrial fibrillation shortens procedural duration and fluoroscopic exposure with comparable mid-term efficacy

Purpose

This study aims to investigate whether the use of a novel inner lumen circular mapping catheter (IMC) can shorten the procedural duration and fluoroscopic exposure of the single transseptal big cryoballoon (CB) pulmonary vein isolation (PVI) procedures in patients with atrial fibrillation (AF).

Methods

This is a prospective non-randomized case–control study. Forty-two patients (28 men, mean age 55.7?±?12.1) with drug-refractory paroxysmal or persistent AF and underwent CB PVI procedures were divided into Group A (conventional single transseptal big CB approach, n?=?21) and Group B (IMC-facilitated approach, n?=?21). They were compared in the co-primary endpoints: (1) procedural duration and (2) fluoroscopic exposure and secondary endpoints: (1) 6-month AF-free survival and (2) number of cryo-applications.

Results

Both the procedural duration (162?±?26 vs. 215?±?25 min; p?<?0.001) and fluoroscopic exposure (44.1?±?10.4 vs. 56.8?±?11.7 min; p?=?0.001) were significantly shorter in Group B than Group A patients. With multivariate stepwise regression, only the use of IMC was an independent predictor for procedural duration (β?=??59; 95 % CI, ?84.1 to ?33.8; p?<?0.001) and fluoroscopic exposure (β?=??16.9; 95 % CI, ?28.4 to ?5.4; p?=?0.006). The number of cryo-applications was significantly fewer in Group B than Group A patients (median 8 vs. 11; p?=?0.001). There was no significant difference in the 6-month AF-free survival between the two approaches (57 % vs. 71 %; p?=?0.351).

Conclusions

Compared to conventional single transseptal big CB PVI procedures, the use of IMC may reduce procedural duration, fluoroscopic exposure and the number of cryo-applications with comparable mid-term efficacy.     

Left ventricular function in patients with coronary heart disease in the presence or absence of angina pectoris during exercise radionuclide ventriculography

This study compares left ventricular (LV) performance during exercise in patients with angiographically documented coronary artery disease (CAD) based on the presence or absence of angina pectoris during the index exercise tests. The patients were divided into 2 groups: Group I included 31 patients who had angina pectoris during the test and Group II included 43 who did not. Multivessel CAD was present in 21 patients (68%) in Group I and 26 patients (60%) in Group II (difference not significant [NS]). There were no significant differences between the 2 groups in age, sex, history of diabetes mellitus, history of myocardial infarction and in the exercise duration, work load, heart rate and systolic blood pressure. Exercise-induced ST-segment depression was present in 48% of the patients in Group I and in 40% in Group II (NS). The mean LV ejection fraction at rest was 52 ± 12% in Group I and 50 ± 17% in Group II (NS). There were significant differences in the 2 groups in the change from rest to exercise in ejection fraction (?4.5 ± 7.6% in Group I vs 1 ± 9.4% in Group II, p < 0.01), end-systolic volume (29 ± 38 ml in Group I vs 9 ± 23 ml in Group II, p < 0.005), the change in systolic blood pressure-to-end-systolic volume ratio (?0.1 ± 0.5 mm Hg/ml in Group I vs 0.3 ± 1.1 mm Hg/ml in Group II, p < 0.05), and wall motion score (?0.4 ± 0.6 in Group I vs 0.09 ± 0.7 in Group II, p < 0.05).Thus, asymptomatic myocardial ischemia may occur in patients with extensive CAD and be associated with abnormal exercise LV function; however, patients with symptomatic CAD have worse exercise LV function than those with asymptomatic CAD.     

The Impact of Mean Platelet Volume (MPV) and JAK-2 Mutation on Thrombosis in Chronic Myeloproliferative Diseases

Thrombosis and bleeding are the main complications of chronic myeloproliferative diseases. Mean platelet volume (MPV) is an important indicator of the platelet activation. The aim of the present study was to assess the interrelationships between MPV, JAK-2 gene mutation and thromboembolic events in patients with ET and PV. Patients with ET (n = 60) and PV (n = 46) were compared to the secondary erythrocytosis group (n = 19); and a control group of age and sex matched healthy volunteers (n = 52). Besides demographic, clinical and laboratory data; thrombotic and hemorrhagic events were recorded for each patient. Platelet counts, MPV and JAK2 mutations were studied; and their relation with thromboembolic events were investigated using SPSS program for statistical analysis. There was no significant difference between groups regarding age (p = 0.188). Mean platelet count was significantly higher in ET group than other groups (p < 0.0001). Mean platelet count in PV group was significantly higher than control (p < 0.0001) and secondary erythrocytosis groups (p < 0.0001). In the ET group, MPV values were significantly lower than the control group and PV group. In the ET group, those with thromboembolia had lower platelet counts. There was no relation between MPV and thromboembolic event rate in PV, ET and secondary erithrocytosis groups; while no event was recorded in the control group. There was no relation between thromboembolic event rate and JAK 2 mutation. The association of JAK-2 mutation and high MPV especially in ET and PV groups does not contribute to the thromboembolic events.     

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.     

Intermediate follow-up of pediatric heart transplant recipients with elevated pulmonary vascular resistance index

Objectives. This study examined perioperative and intermediate outcomes in pediatric cardiac transplant recipients who had elevated pulmonary vascular resistance indexes preoperatively.Background. Elevated pulmonary vascular resistance was associated with poor outcome in previous studies and constitutes a relative contraindication to transplantation. Few studies have evaluated this poor outcome risk factor in pediatric patients.Methods. To evaluate outcomes of nonneonatal transplant recipients, records were reviewed and divided into Group I (preoperative pulmonary vascular resistance index ≥6 units·m²) and Group II (pulmonary vascular resistance index <6 units·m²). Donor/recipient weight ratios, ischemic times, length of intensive care unit stay, posttransplantation infection rates, arrhythmia, response to pretransplantation vasodilator infusions and pulmonary vascular resistance indexes at the first and most recent posttransplantation biopsies were analyzed.Results. Group I (8 patients) had a mean (±SEM) pulmonary vascular resistance index of 11.5 ± 3.5 units·m²; Group II (29 patients) had a mean pulmonary vascular resistance index of 2.3 ± 0.4 units·m²(p < 0.002). Pulmonary vascular resistance index decreased from 12.3 ± 3.9 to 3.9 ± 0.9 units·m²(p < 0.05) in 7 Group I patients undergoing vasodilator infusion during pretransplantation catheterization. Thirty-six orthotopic heart transplantations were performed and one heterotopic transplantation. Donor weights exceeded recipient weights by 13% and 31% for Groups I and II, respectively (p > 0.25). Donor ischemic time was 215 min for Group I and 225 min for Group II (p > 0.75). Intensive care unit stay was 11.5 days in Group I and 15.1 days in Group II (p = 0.20). Infection rate was 38% in both groups (p > 0.80). Arrhythmias occurred in 90% of Group I and 42% of Group II (p < 0.03) patients. Pulmonary resistance index in Group I decreased from 11.5 ± 3.5 to 3.3 ± 1.2 units·m²(p < 0.03) by the first posttransplantation biopsy and have not changed subsequently. During 2.3 years (range 0.3 to 8.5) of follow-up, the mortality rate was 25% and 21% for Groups I and II, respectively (p > 0.80).Conclusions. Group I patients did not require significantly oversized donors, restricted donor locations or longer intensive care unit stays or have higher infection rates; however, arrhythmias were more frequent. Pulmonary resistance index normalized early after transplantation. Pulmonary vascular reactivity may be more important for survival than absolute resistance index.     

Pancreatic cancer causing acute pancreatitis: a comparative study with cancer patients without pancreatitis and pancreatitis patients without cancer

Background/purpose

Although pancreatic cancer produces upstream obstructive pancreatitis, acute pancreatitis is a less common manifestation of pancreatic cancer. This study aimed to clarify the subgroup of pancreatic cancer patients who present with an episode of acute pancreatitis (Group I) in comparison with a matched group of pancreatic cancer patients without pancreatitis (Group II) and another group of acute pancreatitis patients without pancreatic cancer (Group III).

Methods

This was a retrospective comparative study of 18 patients in Group I, 300 patients in Group II and 141 patients in Group III.

Results

The mean age of Group I was 63.7 years and the male to female ration was 1:0.3. Serum CA 19-9 levels were elevated in 80 %. The main pancreatic duct was incompletely obstructed in 7 patients. There were no significant differences in location of tumor, clinical stage, resection rate and survival months between Group I and II. Acute pancreatitis secondary to pancreatic cancer was more likely to be mild (94 vs. 72 %, p < 0.05) and relapsed (39 vs. 16 %, p < 0.05) compared with Group III.

Conclusions

Anatomic evaluation of the pancreas should be performed in patients with acute pancreatitis with no obvious etiology, even if the pancreatitis is mild, to search for underlying malignancy.     

Hypoxia-Inducible Factor 1-Alpha Release After Intracoronary Versus Intramyocardial Stem Cell Therapy in Myocardial Infarction

We have investigated the effect of stem cell delivery on the release of hypoxia-inducible factor 1 alpha (HIF-1α) in peripheral circulation and myocardium in experimental myocardial ischemia. Closed-chest, reperfused myocardial infarction (MI) was created in domestic pigs. Porcine mesenchymal stem cells (MSCs) were cultured and delivered (9.8?±?1.2?×?10⁶) either percutaneously NOGA-guided transendocardially (Group IM) or intracoronary (Group IC) 22?±?4 days post-MI. Pigs without MSC delivery served as sham control (Group S). Plasma HIF-1α was measured at baseline, immediately post- and at follow-up (FUP; 2 h or 24 h) post-MSC delivery by ELISA kit. Myocardial HIF-1α expression of infarcted, normal myocardium, or border zone was determined by Western blot. Plasma level of HIF-1α increased immediately post-MI (from 278?±?127 to 631?±?375 pg/ml, p?<?0.05). Cardiac delivery of MSCs elevated the plasma levels of HIF-1α significantly (p?<?0.05) in groups IC and IM immediately post-MSC delivery, and returned to baseline level at FUP, without difference between the groups IC and IM. The myocardial tissue HIF-1α expression in the infarcted area was higher in Group IM than in Group IC or S (1,963?±?586 vs. 1,307?±?392 vs. 271?±?110 activity per square millimeter, respectively, p?<?0.05), while the border zone contained similarly lower level of HIF-1α, but still significantly higher as compared with Group S. Trend towards increase in myocardial expression of HIF-1α was measured in Group IM at 24 h, in contrast to Group IC. In conclusion, both stem cell delivery modes increase the systemic and myocardial level of HIF-1α. Intramyocardial delivery of MSC seems to trigger the release of angiogenic HIF-1α more effectively than does intracoronary delivery.     

Impaired Sleep Quality in Crohn’s Disease Depends on Disease Activity

Background

Little is known concerning the relationship of disease activity and sleep disturbances in inflammatory bowel disease (IBD) and specifically in patients with Crohn’s disease.

Aim

This study examined the prevalence of poor sleep quality in patients with active and inactive Crohn’s disease compared with healthy controls.

Methods

Participants included 108 patients with Crohn’s disease attending the IBD clinic of a tertiary medical center in 2009–2010 and 36 healthy volunteers. All prospectively completed a demographic questionnaire and the Pittsburgh sleep quality index (PSQI). Patients with Crohn’s disease completed the Crohn’s disease activity index (CDAI) and were divided into two groups accordingly: inactive disease (CDAI ≤150) and active disease (CDAI >150). Data on disease duration, medications, complications, and treatment were collected from the medical files.

Results

Seventy-one patients had inactive Crohn’s disease and 37 had active disease. All three groups were similar in mean age, sex distribution, and body mass index. Mean duration of Crohn’s disease was 10.22 ± 8.6 years; 40 patients (37 %) had ileal disease, 16 (15 %) colonic disease, and 56 (50 %) ileo-colonic disease. Patients with active disease had a significantly higher mean ± SD global score on the PSQI (8.6 ± 2.4; indicating poorer sleep quality) than patients with inactive disease (4.6 ± 1.9) or control subjects (5.1 ± 1.7) (p < 0.0001 for both), with no significant difference between the inactive-disease and control groups. The correlation between the CDAI and PSQI scores was statistically significant (p < 0.001).

Conclusions

Impaired sleep quality is associated with active Crohn’s disease, but not inactive disease.     

Longitudinal Characterization of Depression and Mood States Beginning in Primary HIV Infection

Though depression is known to frequently afflict those with chronic HIV, mood during the early course of HIV is not well characterized. In a prospective study we assessed mood during primary HIV infection [primary HIV infection (PHI), <1 year duration], its association with neuropsychological performance and markers of neurological disease, and its longitudinal course including effects of antiretroviral therapy (ART). The Beck Depression Inventory (BDI) and Profile of Mood States (POMS) subscales were longitudinally administered prior to and after ART in PHI subjects. This evaluation of mood was done concurrently with blood, cerebrospinal fluid (CSF) and neuropsychological [total z and global deficit score (GDS)] evaluation at each visit. Analysis employed Spearman’s rho, logistic regression, and linear mixed models. 47.7 % of the 65 men recruited at a median 3.5 months HIV duration met BDI criteria for clinical depression at baseline, classified as ‘mild’ (n = 11), ‘moderate’ (n = 11), or ‘severe’ (n = 9). Drug, alcohol, and depression history did not associate with BDI score. Proportional somatic-performance scores were worse than cognitive-affective scores (p = .0045). Vigor subscore of POMS was reduced compared to norms and correlated with total z (r = 0.33, p = 0.013) and GDS (r = ?0.32, p = 0.016). BDI and POMS correlated with one another (r = 0.85, p < .0001), but not with CSF or plasma HIV RNA, WBC, albumin ratio or neopterin. Improvement was not observed in BDI and POMS over 330 total follow-up visits, even after initiation of ART. Depression was prevalent during PHI in our subjects, associated with abnormal somatic-performance and vigor scores. Neither neuropsychological performance nor disease biomarkers correlated with depressed mood. Mood indices did not improve over time in the presence of ART.     

Differential effects of functional autonomic blockade on the variables of sinus nodal automaticity in sick sinus syndrome

To study the pathophysiologic mechanism of sick sinus syndrome and to establish the relation of intrinsic heart rate, corrected sinus nodal recovery time and sinoatrial conduction time in this syndrome, electrophysiologic studies were conducted in 22 men (mean age 60 ± 12 years) with the clinical diagnosis of sick sinus syndrome. Measurements were determined before and after autonomic blockade with propranolol (0.2 mg/kg body weight) and atropine sulfate (0.04 mg/kg). Fifty-nine percent of patients (Group I) had an abnormal intrinsic heart rate, suggesting intrinsic abnormality of sinus nodal automaticity; 41 percent (Group II) had a normal intrinsic heart rate after autonomic blockade, suggesting disturbed autonomic regulation. One patient with an observed intrinsic heart rate higher than the upper limit of predicted intrinsic heart rate was also included in Group II. The mean corrected sinus nodal recovery time before autonomic blockade was 751 ± 502.8 ms and was abnormal (more than 450 ms) in 10 of the 13 patients in Group I and 2 of the 9 patients in Group II. After autonomic blockade this interval was 694 ± 638.7 ms and was abnormal in 12 of the 13 patients in Group I and in 2 of the 9 patients in Group II. The patients in each group could be further classified into three groups on the basis of normal or abnormal corrected sinus nodal recovery time before or after autonomic blockade. Not all patients with abnormal intrinsic heart rate (Group I) had abnormal corrected sinus nodal recovery time and vice versa. Patients in Group II were younger in age, had a lesser incidence of organic heart disease and were more severely symptomatic.Mean sinoatrial conduction time during control studies was 210.4 ±96.3 ms and decreased significantly (143.2 ± 59.6 ms, p < 0.005) after autonomic blockade. This interval was abnormal in 3 of the 13 patients in Group I and in 6 of the 9 patients in Group II during control studies; after autonomic blockade it remained abnormal in 3 patients in Group I and in 1 patient in Group II.It is concluded that determination of heart rate and corrected sinus nodal recovery time after autonomic blockade increases the sensitivity of electrophysiologic testing and offers some insight into the pathophysiology of sick sinus syndrome. Patients with sick sinus syndrome who have a normal intrinsic heart rate have a greater incidence of abnormal sinoatrial conduction time than do those with an abnormal intrinsic heart rate. Thus, abnormal sinoatrial conduction time is usually due to extrinsic autonomic influences.     

Edge dissection of calcified plaque as a possible mechanism for acute coronary syndrome

We evaluated the incidence and predictors of edge dissection of the calcified culprit plaque in patients with acute coronary syndrome (ACS) or stable angina (SA). Calcified plaque is not rare in patients with ACS, and compliance mismatch may create edge dissection of the calcified plaque to trigger ACS. However, little data are available on calcium edge dissection in relation to ACS. Pre-intervention intravascular ultrasound data were analyzed in 143 patients with ACS (n = 53) or SA (n = 90). Edge dissection of the calcified plaque was found in 14 patients (9.8 %). Patients were divided into two groups based on calcium edge dissection: group I (edge dissection, n = 14) and group II (no edge dissection, n = 129). Clinical and angiographic characteristics were largely similar between the two groups; however, ACS was more common in group I than in group II (64.3 vs. 34.1 %, respectively, p = 0.039). Intravascular ultrasound variables did not differ between the two groups except thrombus and reference measurements, with thrombus more frequently observed in group I than in group II (35.7 vs. 8.5 %, respectively, p = 0.010). Likewise, proximal and distal reference measurements were larger in group I than in group II. Multivariate analysis showed that ACS was the only independent predictor of calcium edge dissection (odds ratio 3.5, 95 % confidence interval 1.1–11.0, p = 0.034). Edge dissection of the calcified plaque was present and more common in ACS patients than in SA patients. Calcium edge dissection may play a role in the pathogenesis of ACS.     

Factor-Xa inhibitors protect against systemic oxidant damage induced by peripheral-ischemia reperfusion

Factor-Xa inhibitors are often used for prophylaxis and for the treatment of thrombotic vascular disorders. However, it is not known whether they are beneficial during the recanalization of the thrombotic vascular segment and during tissue reperfusion. Herein, we describe an animal study that was designed to investigate the possible protective effects and antioxidant properties of factor-Xa inhibitors. Forty rats were included in the study and were randomly divided into five equal groups. The first group served as a control group from which we obtained basal oxidant and antioxidant parameters. Peripheral ischemia was induced in the second group (sham group) for 6 h, and plasma levels of nitrogen oxide (NO_x), prolidase and malondialdehyde (MDA) were obtained after 30 min of reperfusion. The sham group did not receive any drugs. Oral rivaroxaban (3 mg/kg) was administrated to Group III, intraperitoneal enoxaparin sodium (250 U/kg) was administrated to Group IV, and intraperitoneal bemiparine sodium (250 U/kg) was administrated to Group V 1 week prior to the induction of peripheral ischemia (for 6 h)–reperfusion. After 30 min of reperfusion, blood samples were obtained and NO_x, prolidase and MDA levels in these groups were detected, and the rats were sacrificed. NO_x levels were statistically similar (p > 0.05) between Groups I, II, III, IV, and V (20.7 ± 10.4, 17.4 ± 9.7, 25.9 ± 24.2, 27.0 ± 11.9, 23.3 ± 17.3 μmol/L, respectively). MDA levels were significantly lower (p < 0.05) in Groups III (rivaroxaban), IV (enoxaparin sodium), and V (bemiparine sodium) (24.9 ± 11.9, 25.9 ± 4.4, 25.4 ± 10.8 μmol/L, respectively) when compared with the sham group (Group II) (75.6 ± 24.3 μmol/L). Prolidase levels were higher (p > 0.05) in the ischemia reperfusion groups (659.2 ± 130.6 in II (sham), 1,741.0 ± 1,530.6 in III (rivaroxaban), 2,453.8 ± 1,590.4 in IV (enoxaparin sodium), and 889.2 ± 574.7 U/g in V (bemiparine sodium) than in the control group (144.6 ± 131.8 U/g). Ischemia-reperfusion events may occur in prothrombotic disorders. During these events, prophylactic or therapeutic factor-Xa inhibitors can protect against thrombosis and oxidative reperfusion injury. The new oral factor-Xa inhibitor, rivaroxaban, appears to provide the same antioxidant support as injectable low molecular weight heparins (LMWHs).     

Hormonal parameters and sex hormone receptor gene polymorphisms in men with autoimmune diseases

Autoimmune diseases (ADs) are more common in women than in men. Sex hormones may play a role. Sex hormone receptors (SHR) are expressed in cells of the immune system. We investigated the possible role of hormonal parameters and of common polymorphisms of the estrogen receptor alpha (ESR1), beta (ESR2), and androgen receptor (AR) genes in the appearance of AD in men. 277 men were studied; 125 with ≥1 AD: Hashimoto’s autoimmune thyroiditis (n = 65), Graves’ disease (n = 12), SLE (n = 10), and RA (n = 38). 152 were controls. Hormonal and biochemical parameters were measured after discontinuation for ≥1 month of any corticosteroid therapy. ESR1 PvuII, ESR2 AluI, and the AR (CAG)n repeats polymorphisms were analyzed. AD patients had higher estradiol levels (31.32 ± 12.10, controls 20.37 ± 7.91 pg/ml, p < 0.001). In multivariate analysis, significant predictors for AD were estrogen and BMI. The allele frequency of ESR1 PvuII and ESR2 AluI did not differ between patients and controls (AD: 47.8 %, 37.6 %; controls 49.8 %, 39.9 %). The distribution of (CAG)n did not differ between groups. In AD group, shorter (CAG)n alleles were associated with younger age of AD onset (short: 38.52 ± 14.8, long: 47.14 ± 17.34 years, p = 0.048). Carriers of ESR1 PvuII presented less frequently ≥2 AD (carriers 6.5 %, non-carriers 25.1 %, p = 0.019); carriers of AluI had lower SHBG levels and higher ΒΜΙ compared to non-carriers (p < 0.04). Higher estradiol may play a role in AD in men. Distribution of SHR gene polymorphisms is similar between patients and controls. Shorter AR (CAG)n repeats may predispose for younger AD onset. Coexistence of ≥2 AD is less frequent in carriers of ESR1 PvuII. ESR2 AluI may adversely affect obesity parameters.