Effects of alcohol septal ablation on left ventricular diastolic filling patterns in obstructive hypertrophic cardiomyopathy

Alcohol septal ablation (ASA) has been shown to improve left ventricular (LV) diastolic function in patients with obstructive hypertrophic cardiomyopathy (HCM). However, its beneficial effect on diastolic function assessed by cardiac magnetic resonance (CMR) has not been reported. We investigated the mid-term changes of diastolic function by CMR combined with echocardiography in HCM patients after ASA at a median of 14-month follow-up. CMR parameters of diastolic function including peak filling rate (PFR), and time to peak filling rate (TPFR) were evaluated in 43 patients (aged 48 ± 9 years). LV diastolic function improved significantly measured by echocardiography with the decrease in ratio of transmitral early LV filling velocity (E) to early diastolic mitral lateral annular velocity (E′) (14.20 ± 1.17 to 11.58 ± 1.16, p < 0.001) and E-wave deceleration time (194.04 ± 19.30 to 168.45 ± 12.58 ms, p < 0.001). PFR increased significantly with associated decrease in TPFR after ASA (both p < 0.001) at follow-up. Furthermore, patients with larger decrease in LVOT gradients had a greater improvement of LV diastolic function, as measured by the reduction of E/E′ (p < 0.001) and increase of PFR (p < 0.001). In conclusion, this study demonstrated that successful ASA results in both echocardiographic and CMR indices of diastolic function improvement after ASA at 14-month follow-up. ASA therapy can significantly reduce LVOT gradient and mitral regurgitation, both of which may contribute to the improvement of diastolic function.     

Autoantibodies against myelin sheath and S100β are associated with cognitive dysfunction in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) has been associated with cognitive impairment and peripheral production of autoantibodies. Autoantibodies against central nervous system (CNS) proteins and S100 calcium-binding β (S100β) were found increased in diseases characterized by cognitive impairment like Alzheimer disease and Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). The aim of this study was to investigate the plasma levels of autoantibodies against myelin basic protein (anti-MBP), myelin oligodendrocyte glycoprotein (anti-MOG) and S100β, and their relationships with cognitive performance in RA patients. Twenty patients with active rheumatoid arthritis and 19 age-, sex-, and schooling-matched healthy controls were recruited. Multiple dimensions of cognitive function were evaluated by structured clinical questionnaires. Autoantibodies and S100β levels were assessed by ELISAs. Patients had significantly higher levels of anti-MBP IgG (17.51 ± 1.36 vs. 5.24 ± 0.53 ng/mL), anti-MOG IgG (5.68 ± 1.34 vs. 0.51 ± 0.49 ng/mL), and S100β protein (2.24 ± 0.50 vs. 0.47 ± 0.06) than controls (all p < 0.0001). After adjusting for potential confounders, RA group presented worse cognitive performance involving the working memory and executive functions such as inhibition, flexibility, and mental control in parallel to higher autoantibodies and S100β levels than healthy controls (all p < 0.001). Levels of anti-MBP were negatively associated with delayed verbal recall (DVR; r = ?0.42, p = 0.005), Stroop Color-Word (r = ?0.48, p = 0.004), and N-Back Total scores (r = ?0.59, p < 0.0001) and positively with Trail Making Test B (TMB, r = 0.53, p = 0.001). Negative correlation was found between levels of anti-MOG and DVR (r = ?0.64, p < 0.0001), N-Back Total scores (r = ?0.35, p = 0.03), Stroop Color-Word (r = ?0.51, p = 0.001), and positively with TMB (r = 0.50, p = 0.003). S100β levels were associated with DVR (r = ?0.51, p = 0.002), TMB (r = 0.46, p = 0.008), Stroop Color-Word (r = ?0.67, p < 0.0001), and N-Back Total (r = ?0.52, p = 0.003). RA is associated with impaired cognitive performance associated with higher levels of CNS-related autoantibodies and S100β levels. Given the importance of myelin integrity to cognition, our data indicate that these autoantibodies may be harmful to proper cognitive function.     

Lymph node retrieval in colorectal cancer: determining factors and prognostic significance

Purpose

The study aimed to analyze clinicopathological factors that determine the extent of lymph node retrieval and to evaluate its prognostic impact in patients with colorectal cancer (CRC).

Methods

The number of retrieved lymph nodes was analyzed in 381 CRC specimens. Lymph node count was related to different clinicopathological variables by binary logistic regression. Progression-free survival (PFS) and cancer-specific survival (CSS) were determined using the Kaplan-Meier method and Cox regression models.

Results

The median number of retrieved lymph nodes was 20 (mean 21 ± 10, range 1–65) in right-sided, 13 (16 ± 10, 1–66) in left-sided, and 15 (18 ± 11, 3–64) in rectal tumors. The number of retrieved lymph nodes was independently associated with T-classification (p < 0.001), N-classification (p = 0.014), and tumor size (p = 0.005) as well as right-sided tumor location (p = 0.012). There was no association with age, sex, tumor grade, mismatch-repair status, and lymph or blood vessel invasion. The longer the surgical specimen, the higher were the numbers of retrieved and positive lymph nodes (p < 0.001, respectively). In patients with locally advanced (T3/T4) tumors (n = 283), analysis of more than 12 lymph nodes was independently associated with PFS (HR = 0.63, p = 0.025) and CSS (HR = 0.54, p = 0.004). In the subset of T3/T4 N0 patients (n = 130), analysis of more than 12 lymph nodes similarly proved to be an independent predictor of outcome (PFS, HR = 0.48, p = 0.046; OS, HR = 0.41, p = 0.026).

Conclusion

The number of retrieved lymph nodes is associated with higher tumor stage, tumor size, and right-sided location. Low lymph node count indicates adverse outcome in patients with locally advanced (T3/T4) disease.

     

Continuous Positive Airways Pressure and Uvulopalatopharyngoplasty Improves Pulmonary Hypertension in Patients with Obstructive Sleep Apnoea

Objective

Data are sparse regarding the prevalence of pulmonary hypertension (PH) in obstructive sleep apnoea (OSA) patients without COPD and clinically manifest cardiac diseases and the role of continuous positive airway pressure (CPAP) and Uvulopalatopharyngoplasty (UPPP) in normalizing this parameter.

Patients/Methods

We studied 75 consecutive OSA patients, 55 of them men, using transthoracic echocardiography. A mild PH [pulmonary artery pressure (PAPs) 38.2 ± 6.8] was found in 25 subjects (prevalence 33 %). These patients were divided into two groups: group 1A (n = 17), those treated with CPAP, and group 1B (n = 8), those who have the indication for a UPPP. We scheduled a follow-up at 3, 6 and 9 months. During follow-up, we performed echocardiography, measurement of anthropometric parameters (BMI, neck and waist–hip circumference), and of biochemical parameters (uric acid, fasting glucose, cholesterol, triglycerides) and blood pressure.

Results

Patients with PH had a higher BMI: 32 ± 6 versus 29 ± 4 (p < 0.001) and NC: 39.8 ± 4.76 versus 37.14 ± 3.49 (p = 0.003), were predominantly men (72 %) and older: 64 ± 20 versus 55 ± 16 (p = 0.025) and had a significantly higher value of uric acid: 7.91 ± 2.35 versus 6.56 ± 1.31 (p = 0.003). We found a positive correlation between PH and BMI (r = 0.456; p < 0.001) and between uric acidic and PH (r = 0.636; p < 0.001). PAPs significantly changed, from 39.8 ± 4.1 to 27.1 ± 4, to 25.2 ± 3.1 and to 22.2 ± 3 mmHg (CI 95 %; 15.09–20.11; p < 0.001) in group 1A and from 39.5 ± 5.1 to 23.4 ± 3.2, to 23.0 ± 3.1 and to 21.9 ± 2.9 mmHg (CI 95 %; 13.15–22.05; p < 0.001) in group 1B (difference between the groups p = 0.12).

Conclusions

PH was frequent in OSA patients and normalized after 6 months with both CPAP and UPPP. A similar trend was noted in diastolic blood pressure.

     

Correlations of the changes in bioptic findings with echocardiographic,clinical and laboratory parameters in patients with inflammatory cardiomyopathy

Patients with myocarditis and left ventricular (LV) dysfunction may improve after standard heart failure therapy. This improvement seems to be related to retreat of myocardial inflammation. The aim of the present study was to assess changes in clinical, echocardiographic and some laboratory parameters and to correlate them with changes in the number of inflammatory infiltrating cells in endomyocardial biopsy (EMB) samples during the 6-month follow-up, and to define predictors of LV function improvement among baseline parameters. Forty patients with biopsy-proven myocarditis and impaired LV function (LV ejection fraction—LVEF <40 %) with heart failure symptoms ≤6 months were evaluated. Myocarditis was defined as the presence of >14 mononuclear leukocytes/mm² and/or >7 T-lymphocytes/mm² in the baseline EMB. The EMB, echocardiography and clinical evaluation were repeated after 6 months of standard heart failure therapy. LVEF improved on average from 25 ± 9 to 42 ± 12 % (p < 0.001); LV end-systolic volume and LV end-diastolic volume (LVEDV) decreased from 158 ± 61 to 111 ± 58 ml and from 211 ± 69 to 178 ± 63 ml (both p < 0.001). NYHA class decreased from 2.6 ± 0.5 to 1.6 ± 0.6 (p < 0.001) and NTproBNP from 2892 ± 3227 to 851 ± 1835 µg/ml (p < 0.001). A decrease in the number of infiltrating leukocytes (CD45+/LCA+) from 23 ± 15 to 13 ± 8 cells/mm² and in the number of infiltrating T lymphocytes (CD3+) from 7 ± 5 to 4 ± 3 cells/mm² (both p < 0.001) was observed. The decline in the number of infiltrating CD45+ cells significantly correlated with the change in LVEF (R = ?0.43; p = 0.006), LVEDV (R = 0.39; p = 0.012), NYHA classification (R = 0.35; p = 0.025), and NTproBNP (R = 0.33; p = 0.045). The decrease in the number of CD3+ cells correlated with the change of systolic and diastolic diameters of the left ventricle (R = ?0.33; p = 0.038 and R = ?0.45; p = 0.003) and with the change in LVEDV (R = ?0.43; p = 0.006). Tricuspid annular plane systolic excursion (TAPSE) (OR 0.61; p = 0.005) and early transmitral diastolic flow velocity (E wave) (OR 0.89; p = 0.002) were identified as predictors of LVEF improvement. Improvements in clinical status, LV function and NTproBNP levels correlated with decrease in the number of infiltrating inflammatory cells. TAPSE and E wave velocity were significant predictors of improvement in multivariate regression. Our observations suggest that contemporary guidelines-based therapy of heart failure is an effective treatment option in patients with recent onset biopsy-proven inflammatory cardiomyopathy.     

Relationship between HRV measurements and demographic and clinical variables in a population of patients with atrial fibrillation

Little is known about the role of HRV in atrial fibrillation (AF) patients. Aim of our study was to assess the relationship between HRV measurements and demographic and clinical variables in a population of 274 AF patients. We selected all consecutive patients with persistent/permanent AF among whom had performed a Holter ECG in our Department from April 2010 to April 2015. Time-domain analysis of HRV was evaluated. Demographic and clinical variables were collected for each patient. At multivariable logistic regression, a higher pNN50 was associated with ACE inhibitors/ARBs (p = 0.016) and a lower pNN50 with obesity (p = 0.037) and higher heart rate (HR) (p < 0.0005). A higher RMSSD was associated with ACE inhibitors/ARBs (p = 0.001), digitalis (p < 0.0005) and beta-blockers (p = 0.002) and a lower RMSSD with a higher HR (p < 0.0005). A higher SDNN_i was associated with ACE inhibitors/ARBs (p < 0.0005), digitalis (p < 0.0005) and beta-blockers (p = 0.002) and a lower SDNN_i with dysthyroidism (p = 0.048) and higher HR (p < 0.0005). A higher SDANN was associated with non-dihydropyiridine calcium-channel-blockers (p = 0.002) and ACE inhibitors/ARBs (p = 0.002) and a lower SDANN with hypertension (p = 0.034), obesity (p = 0.011), stroke (p = 0.031), pneumonia (p = 0.005) and higher HR (p < 0.0005). A higher SDNN was associated with ACE inhibitors/ARBs (p < 0.0005), digitalis (p < 0.0005) and beta-blockers (p = 0.022) and a lower SDNN with obesity (p = 0.012), pneumonia (p = 0.049) and higher HR (p < 0.0005). Our study showed that, in AF patients, there is a direct relationship between some clinical variables and HRV measurements; as for patients with sinus rhythm, even in AF patients this relationship seemed to reflect the autonomic nervous system activity.     

Esophageal intraluminal baseline impedance is associated with severity of acid reflux and epithelial structural abnormalities in patients with gastroesophageal reflux disease

Background

The esophageal intraluminal baseline impedance may be used to evaluate the status of mucosa integrity. Esophageal acid exposure decreases the baseline impedance. We aimed to compare baseline impedance in patients with various reflux events and with different acid-related parameters, and investigate the relationships between epithelial histopathologic abnormalities and baseline impedance.

Methods

A total of 229 GERD patients and 34 controls underwent 24-h multichannel intraluminal impedance and pH monitoring (MII–pH monitoring), gastroendoscopy, and completed a GERD questionnaire (GerdQ). We quantified epithelial intercellular spaces (ICSs) and expression of tight junction (TJ) proteins by histologic techniques.

Results

Mean baseline values in reflux esophagitis (RE) (1752 ± 1018 Ω) and non-erosive reflux disease (NERD) (2640 ± 1143 Ω) were significantly lower than in controls (3360 ± 1258 Ω; p < 0.001 and p = 0.001, respectively). Among NERD subgroups, mean baselines in the acid reflux group (2510 ± 1239 Ω) and mixed acid/weakly acidic reflux group (2393 ± 1009 Ω) were much lower than in controls (3360 ± 1258 Ω; p = 0.020 and p < 0.001, respectively). The mean baseline in severe RE patients was significantly lower than in mild RE patients (LA-C/D vs. LA-A/B: 970 ± 505 Ω vs. 1921 ± 1024 Ω, p < 0.001). There was a significant negative correlation between baseline value and acid exposure time (AET) (r = ?0.41, p < 0.001), and a weak but significant correlation (r = ?0.20, p = 0.007) between baseline value and weakly AET. Negative correlations were observed between ICS and the baseline impedance (r = ?0.637, p < 0.001) and claudin-1 and the baseline impedance (r = ?0.648, p < 0.001).

Conclusions

Patients with dominant acid reflux events and with longer AET have low baseline impedance. Baseline values are correlated with esophageal mucosal histopathologic changes such as dilated ICS and TJ alteration.

     

Circulating Bone Marrow-Derived CD45−/CD34+/CD133+/VEGF+ Endothelial Progenitor Cells in Adults with Crohn’s Disease

Background

Circulating endothelial progenitor cells (EPCs) are bone marrow-derived stem cells able to migrate to sites of damaged endothelium and differentiate into endothelial cells. Altered EPC level and function have been described in various inflammatory diseases and have been shown to augment vasculogenesis in murine models. Previous studies of EPC in the context of Crohn’s disease (CD) have yielded conflicting results.

Aim

To determine whether the circulating levels of EPCs are changed in the context of CD.

Methods

CD patients and healthy controls were recruited. Disease activity was assessed by CDAI. Peripheral blood mononuclear cells were isolated and EPC numbers evaluated by FACS analysis using anti-CD34, anti-VEGF receptor-2, anti-CD133, and anti-CD45 markers.

Results

Eighty-three subjects, including 32 CD patients and 51 controls were recruited, including 19 (59.4 %) and 23 (45 %) males (p = 0.26), aged 34.8 ± 14.9 and 43.3 ± 18.5 years (p = 0.64), in cases and controls, respectively. Mean CDAI was 147 ± 97, disease duration was 12.7 ± 11.1 years, and 28 (87.5 %) were receiving biologics for a mean duration of 21.7 ± 16.8 months. The mean level of peripheral EPCs in CD patients was 0.050 ± 0.086 percent and 0.007 ± 0.013 % in controls (p < 0.01). There was no significant correlation between EPC levels and age (r = ?0.13, p = 0.47), CDAI (r = ?0.26, p = 0.15), disease duration (r = ?0.04, p = 0.84), or duration of treatment with biologics (r = 0.004, p = 0.99).

Conclusion

EPCs are elevated in patients with CD. Further studies are needed to examine the function of EPCs and their possible role as a marker of disease severity or therapeutic response.

     

Tumor necrosis factor-α -308 A/G gene polymorphism in children with juvenile idiopathic arthritis: relation to disease activity,damage, and functional status

The study aims to evaluate the clinical significance of serum levels of tumor necrosis factor alpha (TNF-α) and -308 A/G promoter polymorphism in juvenile idiopathic arthritis (JIA) patients and find any association to the subsets, clinical and laboratory features, disease activity, and damage as well as functional disability. Forty-eight JIA children and 30 controls were included in the present study. Juvenile arthritis disease activity score in 27 joints (JADAS-27) was calculated, juvenile arthritis damage index (JADI) was assessed, and Childhood Health Assessment Questionnaire (CHAQ) measured the functional status. Serum TNF-α was assayed by ELISA and gene (-308) promoter polymorphism was determined by polymerase chain reaction. The 48 JIA children (mean age 11.5 ± 2.8 years) were 13 systemic, 17 oligoarticular, and 18 polyarticular onset. The serum TNF-α was significantly higher in patients (90.4 ± 6.3 ng/ml) compared to control (3.5 ± 2.6 ng/ml) (p < 0.0001) with a tendency to be higher in the polyarticular subtype. All controls had TNF-α -308 GG alleles. The frequency of GG genotype tended to be higher in systemic onset compared to oligoarticular and polyarticular subtypes. The serum TNF-α significantly correlated with JADAS-27 (r = 0.32, p = 0.03) and CHAQ (r = 0.37, p = 0.01) and negatively with the presence of GG alleles (r = ?0.48, p = 0.001). The GG alleles were significantly negatively associated with C-reactive protein (r = ?0.32, p = 0.03) with a tendency to negatively correlate with JADAS-27, CHAQ, and JADI-extrarticular (r = ?0.28, p = 0.06; r = ?0.25, p = 0.09 and r = ?0.25, p = 0.09, respectively). There is evidence of a possible influence of the ?308 SNP promoter position on the production of TNF-α, the severity of JIA which may consequently influence the response to anti-TNF-α treatment.     

Bilateral internal thoracic artery grafting in octogenarians: where are the benefits?

The use of bilateral internal thoracic artery (BITA) grafting for myocardial revascularization is usually discouraged in the very elderly because of increased risk of perioperative complications. The aim of the study was to analyze early and late outcomes of BITA grafting in octogenarians. From January 1999 throughout February 2014, 236 consecutive octogenarians with multivessel coronary artery disease underwent primary isolated coronary bypass surgery at the authors’ institution. Six of these patients underwent emergency surgery and were excluded from this retrospective study; consequently, 135 BITA patients were compared with 95 single internal thoracic artery (SITA) patients according to early and late outcomes. Between BITA and SITA patients, there was no significant difference in the operative risk (EuroSCORE II: 8 ± 7.7 vs. 7.6 ± 6.1 %, p = 0.65). There was a lower aortic manipulation in BITA patients. Hospital mortality (3 vs. 4.2 %, p = 0.44) and perioperative complications were similar except that only BITA patients experienced sternal wound infection (5.2 %, p = 0.022). The mean follow-up was 4.7 ± 3.3 years. There were no differences between the two groups in overall survival (p = 0.79), freedom from cardiac and cerebrovascular deaths (p = 0.73), major adverse cardiac and cerebrovascular events (p = 0.63) and heart failure hospital readmission (p = 0.64). Predictors of decreased late survival were diabetes (p = 0.0062) and congestive heart failure (p = 0.0004). BITA grafting can be routinely used in octogenarians with atherosclerotic ascending aorta without an increase in hospital mortality or major adverse cardiac and cerebrovascular complications. However, there is an increased risk of sternal wound infection without a demonstrable long-term benefit.     

Impact of distal embolization on myocardial perfusion and survival among patients undergoing primary angioplasty with glycoprotein IIb–IIIa inhibitors: insights from the EGYPT cooperation

Even though primary angioplasty is able to obtain TIMI 3 flow in the vast majority of STEMI patients, epicardial recanalization does not guarantee optimal myocardial perfusion, that remain suboptimal in a relatively large proportion of patients. Large interest has been focused in recent years on the role of distal embolization as major determinant of impaired reperfusion. The aim of the current study was to investigate in a large cohort of STEMI undergoing primary angioplasty with Gp IIb–IIIa inhibitors the impact of distal embolization on myocardial perfusion and survival. Our population is represented by patients undergoing primary angioplasty for STEMI included in the EGYPT database. Distal embolization was defined as an abrupt ‘‘cutoff’’ in the main vessel or one of the coronary branches of the infarct-related artery, distal to the angioplasty site. Myocardial perfusion was evaluated by angiography or ST-segment resolution, whereas infarct size was estimated by using peak CK and CK-MB. Follow-up data were collected between 30 days and 1 year after primary angioplasty. Data on distal embolization were available in a total of 1182 patients (71% of total population). Distal embolization was observed in 132 patients (11.1%). Patients with distal embolization were older (P < 0.001), with larger prevalence of diabetes (P = 0.01), previous MI (P = 0.048) and advanced Killip class at presentation (P = 0.018), abciximab administration (P < 0.001), with a lower prevalence of smoking (P = 0.04). Patients with distal embolization had more often poor preprocedural recanalization (P = 0.061), less often postprocedural TIMI 3 flow (P < 0.001), postprocedural MBG 2–3 (P < 0.001), complete ST-segment resolution (P = 0.021) and larger infarct size (CK-MB: 328 ± 356 U/l vs. 259 ± 226 U/l, P = 0.012). The impact of distal embolization on myocardial perfusion was confirmed after correction for baseline confounding factors as evaluated by MBG 2–3 (adjusted OR [95% CI] = 3.14 [2.06–4.77], P < 0.0001) but not complete ST-segment resolution (adjusted OR [95% CI] = 1.23 [0.84–1.92], P = 0.26). At 208 ± 160 days follow-up, distal embolization was associated with a significantly higher mortality (9.2% vs. 2.7%, HR [95% CI] = 3.41 [1.73–6.71], P < 0.0001), that was confirmed after correction for baseline confounding factors (adjusted HR [95% CI] = 2.23 [1.1–4.7], P = 0.026). This study showed among STEMI patients treated with Gp IIb–IIIa inhibitors, that distal embolization is independently associated with impaired myocardial perfusion and survival.     

Small-fibre neuropathy in men with type 1 diabetes and erectile dysfunction: a cross-sectional study

Aims/hypothesis

The aim of this study was to identify the contribution of small- and large-fibre neuropathy to erectile dysfunction in men with type 1 diabetes mellitus.

Methods

A total of 70 participants (29 without and 41 with erectile dysfunction) with type 1 diabetes and 34 age-matched control participants underwent a comprehensive assessment of large- and small-fibre neuropathy.

Results

The prevalence of erectile dysfunction in participants with type 1 diabetes was 58.6%. After adjusting for age, participants with type 1 diabetes and erectile dysfunction had a significantly higher score on the Neuropathy Symptom Profile (mean ± SEM 5.3 ± 0.9 vs 1.8 ± 1.2, p = 0.03), a higher vibration perception threshold (18.3 ± 1.9 vs 10.7 ± 2.4 V, p = 0.02), and a lower sural nerve amplitude (5.0 ± 1.1 vs 11.7 ± 1.5 mV, p = 0.002), peroneal nerve amplitude (2.1 ± 0.4 vs 4.7 ± 0.5 mV, p < 0.001) and peroneal nerve conduction velocity (34.8 ± 1.5 vs 41.9 ± 2.0 m/s, p = 0.01) compared with those without erectile dysfunction. There was also evidence of a marked small-fibre neuropathy with an impaired cold threshold (19.7 ± 1.4°C vs 27.3 ± 1.8°C, p = 0.003), warm threshold (42.9 ± 0.8°C vs 39.0 ± 0.9°C, p = 0.005) and heart rate variability (21.5 ± 3.1 vs 30.0 ± 3.7 beats/min, p = 0.001) and reduced intraepidermal nerve fibre density (2.8 ± 0.7 vs 5.9 ± 0.7/mm, p = 0.008), corneal nerve fibre density (12.6 ± 1.5 vs 23.9 ± 2.0/mm², p < 0.001), corneal nerve branch density (12.7 ± 2.5 vs 31.6 ± 3.3/mm², p < 0.001) and corneal nerve fibre length (8.3 ± 0.7 vs 14.5 ± 1.0 mm/mm², p < 0.001) in participants with type 1 diabetes and erectile dysfunction. Erectile dysfunction correlated significantly with measures of both large- and small-fibre neuropathy.

Conclusions/interpretation

Small-fibre neuropathy is prominent in patients with type 1 diabetes, and is associated with erectile dysfunction and can be objectively quantified using corneal confocal microscopy. This may allow the identification of patients who are less likely to respond to conventional therapies such as phosphodiesterase type 5 inhibitors.

     

Subendocardial viability ratio in patients with rheumatoid arthritis: comparison with healthy controls and identification of prognostic factors

Cardiac involvement is common in rheumatoid arthritis. Subendocardial viability ratio (SEVR) is a non-invasive measure of microvascular coronary perfusion, yet it remains unclear whether it is affected in rheumatoid arthritis patients. We additionally sought predictors of SEVR in rheumatoid arthritis among a wide range of disease-related parameters, cardiac and hemodynamic factors, and markers of atherosclerosis, arteriosclerosis, and endothelial dysfunction. SEVR was estimated in rheumatoid arthritis patients and healthy controls by applanation tonometry, which was also used to evaluate arterial stiffness (pulse wave velocity and augmentation index). In the rheumatoid arthritis group, carotid intima–media thickness (cIMT) was additionally estimated by ultrasound, cardiac and hemodynamic parameters by impedance cardiography, and endothelial dysfunction by measurement of asymmetric dimethylarginine (ADMA). In a total of 122 participants, SEVR was lower among 91 patients with rheumatoid arthritis compared to 31 controls (141.4 ± 21.9 vs 153.1 ± 18.7%, p = 0.009) and remained so among 29 rheumatoid arthritis patients without hypertension, diabetes, or cardiovascular diseases, compared to the control group (139.7 ± 21.7 vs 153.1 ± 18.7%, p = 0.013). SEVR did not significantly correlate with arterial stiffness, cIMT, ADMA, or disease-related parameters. Multivariate analysis revealed gender (p = 0.007), blood pressure (p = 0.028), heart rate (p = 0.025), cholesterol levels (p = 0.008), cardiac index (p < 0.001) and left ventricular ejection time (p = 0.004) as independent predictors of SEVR among patients with rheumatoid arthritis. Patients with rheumatoid arthritis exhibit lower values of SEVR compared to healthy individuals. Cardiac and hemodynamic parameters, rather than functional indices of endothelial and macrovascular dysfunction, may be useful as predictors of myocardial perfusion in rheumatoid arthritis.     

Gender Differences in Platelet Reactivity in Patients Receiving Dual Antiplatelet Therapy

Background

Cardiovascular risk is still underestimated in women, experiencing higher mortality and worse prognosis after acute cardiovascular events. Gender differences have been reported in thrombotic and hemorrhagic risk during dual antiplatelet therapy (DAPT), thus suggesting a potential variability in platelet reactivity according to sex. The aim of the present study was to assess the role of gender on platelet function and the prevalence of high-on treatment residual platelet reactivity (HRPR) during DAPT in patients with recent acute coronary syndrome or percutaneous coronary revascularization.

Methods

Patients treated with DAPT (ASA and clopidogrel or ticagrelor) were scheduled for platelet function assessment at 30–90 days post-discharge. By whole blood impedance aggregometry, HRPR was considered for ASPI test >862 AU*min (for ASA) and ADP test values ≥417 AU*min (for ADP-antagonists).

Results

We included 541 patients on DAPT, 122 (22.6 %) of whom were females. Females were older (p < 0.001), displayed more frequently hypercholesterolemia (p = 0.003), renal failure (p = 0.04), acute presentation (p < 0.001), higher cholesterol levels and platelets count (p < 0.001). Inverse association was demonstrated with smoking (p < 0.001), previous PCI (p = 0.04) and statin use (p = 0.03), creatinine and haemoglobin (p < 0.001). Female gender did not influence mean platelet reactivity or the prevalence of HRPR for ASA (1.7 % vs 1.4 %, OR[95%CI] = 1.14[0.17–4.36], p = 0.99, adjusted OR[95%CI] = 1.54[0.20–11.6], p = 0.68) or ADP-antagonists (26.3 % vs 22.8 %, OR[95%CI] = 1.17[0.52–1.34], p = 0.45, adjusted OR[95%CI] = 1.05[0.59–1.86], p = 0.87). Results did not change when considering separately the 309 patients treated with clopidogrel (34 % vs 31.3 %, OR[95%CI] = 1.13[0.62–2.07], p = 0.76, adjusted OR[95%CI] = 1.35[0.63–2.9], p = 0.44 for females vs males), or patients (n = 232) on ticagrelor (20.4 % vs 11.1 %, OR[95%CI] = 2.27[0.99–5.17], p = 0.06 for females vs males), confirmed after correction for baseline differences (adjusted OR[95%CI] = 1.21[0.28–2.29], p = 0.68).

Conclusion

In patients receiving dual antiplatelet therapy, gender does not impact on the prevalence of high-on treatment residual platelet reactivity (HRPR) with the major antiplatelet agents ASA, clopidogrel or ticagrelor.

     

Extraperitoneal sigmoidostomy: a surgical approach with less complications and better functions for abdominoperineal resection of rectal cancer

Objective

The aim of this study is to explore the safety and function of extraperitoneal sigmoidostomy for patients with rectal cancer who underwent abdominoperineal resection.

Methods

We systematically reviewed records of patients with rectal cancer who underwent abdominoperineal resection and extraperitoneal or intraperitoneal sigmoidostomy from January 2010 to December 2014 at our department. They were grouped into the extraperitoneal (group A) and intraperitoneal sigmoidostomy (group B) groups. Clinical data were collected and statistically analyzed.

Results

A total of 231 consecutive cases were included: 108 cases in group A and 123 in group B. Patient demographics were similar in both groups. Group A was associated with less time for sigmoidostomy (19.6 ± 2.8 vs. 27.0 ± 4.5 min, p < 0.001), shorter postoperative hospitalization (6.4 ± 1.3 vs. 6.9 ± 1.6 days, p = 0.036), less incidence of stoma-related complications (p = 0.002) and less possibility of re-operation related to stomal complications (p = 0.037). Functions of stoma including stimulation of excrement, stimulating time for excrement, frequency of excrement, self-controlled ability of excrement, and regularity of excrement were all better than those in group B patients (p < 0.001, < 0.001, 0.018, 0.004, and 0.001, respectively). Patients in group A had less psychological problems including anxiety (p = 0.008), depression (p = 0.045), and impaired social interaction (p = 0.010).

Conclusions

Extraperitoneal sigmoidostomy is associated with shorter operative duration and postoperative hospitalization and has fewer complications and better outcome for abdominoperineal resection of rectal cancer, and patients also had less psychological problems.

     

Preventive effect of oral nicorandil on contrast-induced nephropathy in patients with renal insufficiency undergoing elective cardiac catheterization

This study aims to investigate the preventive effect of oral nicorandil on contrast-induced nephropathy (CIN) in patients with renal insufficiency undergoing elective cardiac catheterization. A total of 240 patients with an estimated glomerular filtration rate (eGFR) of 60 mL/min or less, who were undergoing elective cardiac catheterization, were randomly assigned to nicorandil group (n = 120, 10 mg nicorandil, three times daily from 2 days before to 3 days after procedure) or control group (n = 120, matching placebo as the same method). The primary endpoint was the incidence of CIN defined as 25 % increase in serum creatinine (SCr) from baseline or 44 μmol/L (0.5 mg/dL) increase in absolute value within 72 h after exposure to contrast medium. The secondary endpoints were: (1) the changes of SCr, Cystatin-C (Cys-C) and eGFR within 72 h; (2) major adverse events (MACE) occurring within 30 days. Baseline characteristics of the patients in the two groups were similar. The incidence of CIN was significantly lower in nicorandil group compared with control group (6.67 vs. 17.5 %, P = 0.017). Compared with the control group, nicorandil group tended to have a lower SCr and Cys-C levels as well as a higher eGFR at 48 h after the procedure (all P < 0.05). There was no difference about the incidence of MACE within 30 days between nicorandil group and control group (4.16 vs. 5.83 %, P = 0.767). Multivariate logistic analysis showed that nicorandil was an independent protective factor against CIN (OR = 0.260, 95 % CI = 0.1–0.676, P = 0.006). Therefore, we concluded that oral nicorandil was associated with a decline in the incidence of CIN in patients with renal insufficiency undergoing elective cardiac catheterization.     

Mirabegron,a Clinically Approved β3 Adrenergic Receptor Agonist,Does Not Reduce Infarct Size in a Swine Model of Reperfused Myocardial Infarction

The administration of the selective β3 adrenergic receptor (β3AR) agonist BRL-37344 protects from myocardial ischemia/reperfusion injury (IRI), although the lack of clinical approval limits its translatability. We tested the cardioprotective effect of mirabegron, the first-in-class β3AR agonist approved for human use. A dose-response study was conducted in 6 pigs to select the highest intravenous dose of mirabegron without significant detrimental hemodynamic effect. Subsequently, closed chest anterior myocardial infarction (45 min ischemia followed by reperfusion) was performed in 26 pigs which randomly received either mirabegron (10 μg/kg) or placebo 5 min before reperfusion. Day-7 cardiac magnetic resonance (CMR) showed no differences in infarct size (35.0?±?2.0% of left ventricle (LV) vs. 35.9?±?2.4% in mirabegron and placebo respectively, p?=?0.782) or LV ejection fraction (36.3?±?1.1 vs. 34.6?±?1.9%, p?=?0.430). Consistent results were obtained on day-45 CMR. In conclusion, the intravenous administration of the clinically available selective β3AR agonist mirabegron does not reduce infarct size in a swine model of IRI.     

Assessment of risk factors and left ventricular function in patients with slow coronary flow

Slow coronary flow (SCF) is characterized by delayed distal vessel opacification in the absence of significant epicardial coronary disease. Life-threatening arrhythmias and sudden cardiac death can occur; however, the pathological mechanism and influence on left ventricular function remain undetermined. We aimed to assess the risk factors and left ventricular (LV) function in SCF and evaluate the relationships between thrombolysis in myocardial infarction frame count (TFC) and the number of involved coronary arteries with LV function in patients with SCF. We included 124 patients who underwent coronary angiography because of symptoms of angina; 71 patients with angiographically proven SCF and 53 cases with normal coronary flow pattern. SCF was diagnosed as TFC >27 in at least one coronary artery. Complete blood count and biochemical parameters were compared between the two groups. Conventional echocardiography and tissue Doppler imaging were used to assess LV systolic and diastolic function. Platelet aggregation rate induced by ADP was an independent predictor of SCF and positively correlated with coronary artery mean TFC (mTFC) (r = 0.514, P < 0.001) and the number of coronary arteries with SCF (r = 0.628, P < 0.001). Early diastolic mitral inflow velocity (E) (0.66 ± 0.15 vs. 0.74 ± 0.17, P = 0.008), ratio of early to late diastolic mitral inflow velocity (E/A) (0.95 ± 0.29 vs. 1.15 ± 0.35, P = 0.002), global myocardial peak early diastolic velocity (gVe) (4.41 ± 1.25 vs. 4.96 ± 1.45, P = 0.037), and ratio of global myocardial peak early to late diastolic velocity (gVe/gVa: 1.09 ± 0.45 vs. 1.36 ± 0.58, P = 0.006) were decreased in patients with SCF compared with controls. gVe (3 vs. 0 branches, 4.08 ± 1.14 vs. 4.97 ± 1.45, respectively, P = 0.008) deteriorated significantly in patients with SCF involving three coronary arteries. mTFC negatively correlated with E and E/A (r = ?0.22, P = 0.02; r = ?0.20, P = 0.04, respectively). The number of coronary arteries with SCF negatively correlated with E, E/A, gVe and gVe/gVa (r = ?0.23, P = 0.02; r = ?0.25, P = 0.009; r = ?0.25, P = 0.008; r = ?0.21, P = 0.03, respectively). Platelet aggregation rate induced by ADP was an independent predictor of SCF and positively correlated with coronary artery TFC and the number of affected coronary arteries. Left ventricular global and regional diastolic function was impaired in SCF patients. Furthermore, the number of coronary arteries involved rather than coronary artery TFC determined the severity of left ventricular dysfunction in patients with SCF.     

Non-steroidal Anti-inflammatory Drugs may Worsen the Course of Community-Acquired Pneumonia: A Cohort Study

Purpose

Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed or used as self-medication in cases of community-acquired pneumonia (CAP). Nevertheless, the consequences of such medication on the risk of pleuroparenchymal complications are not well known. The aim was to investigate whether exposure to NSAIDs prior to hospital admission among patients suffering from CAP is associated with the development of pleural complications or a lung abscess.

Methods

All consecutive non-immunocompromised patients with CAP and admitted to a university hospital were prospectively included (2-year period). The risk of pleuropulmonary complications was analyzed according to previous exposure to NSAIDs.

Results

Of the 221 included patients, 40 (18.1%) had developed a pleuropulmonary complication. NSAIDs intake prior to admission was reported for 24 patients (10.9%) who were younger (50.6 ± 18.5 vs. 66.5 ± 16.4 years; p = 0.001), had less comorbidities (60 vs. 25.1%; p = 0.001), had a longer duration between the first symptoms of CAP and the start of an antibiotic therapy (6.1 ± 7.6 vs. 2.8 ± 3.8 days; p = 0.001), and who had a higher incidence of pleuropulmonary complications (33.3 vs. 16.2%; p = 0.048). In multivariate analyses, two factors were independently associated with the development of pleuroparenchymal complications: NSAIDs intake [Odds Ratio (OR) = 2.57 [1.02–6.64]; p = 0.049] and alcohol abuse (OR = 2.68 [1.27–5.69]; p = 0.01).

Conclusions

Our findings suggest that NSAIDs, often taken by young and healthy patients, may worsen the course of CAP with delayed therapy and a higher rate of pleuropulmonary complications.

     

<Emphasis Type="Italic">C-reactive protein</Emphasis> +1444CT (rs1130864) genetic polymorphism is associated with the susceptibility to systemic lupus erythematosus and C-reactive protein levels

The T rare allele of +1444CT (rs1130864) polymorphism of C-reactive protein (CRP) has been associated with increased CRP levels in some inflammatory conditions, but its role on systemic lupus erythematosus (SLE) susceptibility and on CRP levels in SLE patients remains uncertain. The objective of the study was to evaluate the association between the rs1130864 CRP polymorphism with SLE susceptibility, disease activity, and CRP levels in SLE Brazilian patients. The study enrolled 176 SLE patients and 137 controls. SLE disease activity was assessed using the SLE Disease Activity Index (SLEDAI). The rs1130864 CRP polymorphism was determined using polymerase chain reaction and restriction fragment length polymorphism. SLE patients presented higher body mass index (p = 0.046) and CRP levels (p = 0.017) than controls. The genotype and allele frequencies of patients differed from controls [CC vs. CT = odds ratio (OR) 1.730, 95% confidence interval (CI) 1.068–2.803, p = 0.035; CC vs. TT = OR 3.667, 95% CI 1.410–9.533, p = 0.009; C vs. T = OR 1.883, 95% CI 1.299–2.728, p = 0.001)]. Patients carrying the T allele presented higher CRP levels (p = 0.009), were more frequent Caucasians (p = 0.018), and with no use of immunosuppressive treatment (p = 0.004) than those carrying the C allele. However, the SLEDAI and anti-double-stranded DNA positivity did not differ from those carrying T vs. C allele (p = 0.595 and p = 0.243, respectively). The rs1130864 CRP polymorphism was associated with SLE susceptibility and CRP levels, but not with disease activity, suggesting that this polymorphism may play a role in the pathophysiology of SLE through increasing the CRP that, probably, plays an inflammatory role in SLE pathophysiology.