Adipose tissue is inflamed in NAFLD due to obesity but not in NAFLD due to genetic variation in PNPLA3

Aims/hypothesis

The rs738409 C>G single-nucleotide polymorphism in PNPLA3 leads to a missense mutation (I148M) which increases liver fat but does not cause insulin resistance. We hypothesised that patients with non-alcoholic fatty liver disease (NAFLD) due to the PNPLA3 variant (‘PNPLA3 NAFLD’?=?PNPLA3-148MM) do not have adipose tissue (AT) inflammation in contrast with those with NAFLD due to obesity (‘obese NAFLD’).

Methods

Biopsy specimens of AT were taken, and PNPLA3 genotype and liver fat (¹H-magnetic resonance spectroscopy) were determined in 82 volunteers, who were divided into groups based on either median BMI (obese 36.2?±?0.7 kg/m²; non-obese 26.0?±?0.4 kg/m²) or PNPLA3 genotype. All groups were similar with respect to age and sex. The PNPLA3 subgroups were equally obese (PNPLA3-148MM, 31.1?±?1.3 kg/m²; PNPLA3-148II, 31.2?±?0.8 kg/m²), while the obese and non-obese subgroups had similar PNPLA3 genotype distribution. Gene expression of proinflammatory (MCP-1, CD68) and anti-inflammatory (Twist1, ADIPOQ) markers was measured using quantitative real-time RT-PCR.

Results

Liver fat was similarly increased in obese NAFLD (9.5?±?1.3% vs 5.1?±?0.9%, obese vs non-obese, p?=?0.007) and PNPLA3 NAFLD (11.4?±?1.7% vs 5.3?±?0.8%, PNPLA3-148MM vs PNPLA3-148II, p?<?0.001). Fasting serum insulin was higher in the obese than the non-obese group (76?±?6 vs 47?±?6 pmol/l, p?<?0.001), but similar in PNPLA3-148MM and PNPLA3-148II (60?±?8 vs 62?±?5 pmol/l, NS). In obese vs non-obese, MCP-1 and CD68 mRNAs were upregulated, whereas those of Twist1 and ADIPOQ were significantly downregulated. AT gene expression of MCP-1, CD68, Twist1 and ADIPOQ was similar in PNPLA3-148MM and PNPLA3-148II groups.

Conclusions/interpretation

PNPLA3 NAFLD is characterised by an increase in liver fat but no insulin resistance or AT inflammation, while obese NAFLD has all three of these features.     

Insulin-mediated suppression of lipolysis in adipose tissue and skeletal muscle of obese type 2 diabetic men and men with normal glucose tolerance

Aims/hypothesis

Impaired regulation of lipolysis and accumulation of lipid intermediates may contribute to obesity-related insulin resistance and type 2 diabetes mellitus. We investigated insulin-mediated suppression of lipolysis in abdominal subcutaneous adipose tissue (AT) and skeletal muscle (SM) of obese men with normal glucose tolerance (NGT) and obese type 2 diabetic men.

Methods

Eleven NGT men and nine long-term diagnosed type 2 diabetic men (7?±?1 years), matched for age (58?±?2 vs 62?±?2 years), BMI (31.4?±?0.6 vs 30.5?±?0.6 kg/m²) and V ? O 2 max $ \overset{\cdot }{V}{\mathrm{O}}_{2 \max } $ (28.9?±?1.5 vs 29.5?±?2.4 ml kg^?1 min^?1) participated in this study. Interstitial glycerol concentrations in AT and SM were assessed using microdialysis during a 1 h basal period and a 6 h stepwise hyperinsulinaemic–euglycaemic clamp (8, 20 and 40 mU m^?2 min^?1). AT and SM biopsies were collected to investigate underlying mechanisms.

Results

Hyperinsulinaemia suppressed interstitial SM glycerol concentrations less in men with type 2 diabetes (?7?±?6%, ?13?±?9% and ?27?±?9%) compared with men with NGT (?21?±?7%, ?38?±?8% and ?53?±?8%) (p?=?0.014). This was accompanied by increased circulating fatty acid and glycerol concentrations, a lower glucose infusion rate (21.8?±?3.1 vs 30.5?±?2.0 μmol kg body weight^?1 min^?1; p?<?0.05), higher hormone-sensitive lipase (HSL) serine 660 phosphorylation, increased saturated diacylglycerol (DAG) lipid species in the muscle membrane and increased protein kinase C (PKC) activation in type 2 diabetic men vs men with NGT. No significant differences in insulin-mediated reduction in AT interstitial glycerol were observed between groups.

Conclusions/interpretation

Our results suggest that a blunted insulin-mediated suppression of SM lipolysis may promote the accumulation of membrane saturated DAG, aggravating insulin resistance, at least partly mediated by PKC. This may represent an important mechanism involved in the progression of insulin resistance towards type 2 diabetes. Trial registration: ClinicalTrials.gov NCT01680133     

Diversion stoma after colorectal surgery: loop colostomy or ileostomy?

Background

The total rate as well as the clinical outcome of anastomotic leakage in colorectal and coloanal anastomosis necessitates a loop stoma for fecal diversion. The aim of this study was to determine the outcome of loop transverse colostomy compared to loop ileostomy as a temporary defunctioning stoma following colorectal surgery with colorectal or coloanal anastomosis.

Methods

Data of 200 patients between January 2003 and January 2009 were analyzed in this two-center study to determine the surgical outcome in patients with loop colostomy (n?=?100) in comparison to loop ileostomy (n?=?100) for fecal diversion including outcome of stoma creation and complication rates during stoma reversal.

Results

During stoma placement, dermatitis and renal insufficiency occurred significantly more often in the loop ileostomy group than in the loop transverse colostomy group (15% vs. 0%; p?p?=?0.005). During stoma reversal, wound infection occurred significantly more often in the loop transverse colostomy group than in the loop ileostomy group (27% vs. 8%; p?p?p?p?Conclusions Both methods provide a good operative outcome with low complication rates. We do recommend the loop ileostomy in all patients in which dehydration is not to be expected since wound infection rate is lower and hospital stay is shorter during stoma reversal.     

The clinical differences between dengue and scrub typhus with acute respiratory failure in southern Taiwan

Background

For both dengue and scrub typhus, acute respiratory failure (ARF) is a serious complication. The present study was carried out in order to investigate the clinical courses and outcomes of adult dengue and scrub typhus patients with ARF, and to identify the clinical differences between adult dengue and scrub typhus patients with ARF.

Methods

We conducted a retrospective study of the serologically confirmed adult dengue or scrub typhus patients admitted between 1998 and 2008 at Kaohsiung Chang Gung Memorial Hospital. A total of 980 dengue and 102 scrub typhus adult patients were included in our study.

Results

Eighteen of the 980 adult dengue patients and 8 of the 102 adult scrub typhus patients had ARF. There were significant differences that existed for eschar (P?=?0.001; dengue 0%; scrub 62.5%), cough (P?=?0.016; dengue 55.6%; scrub typhus 100%), white blood cell (WBC) count [P?=?0.026; dengue 7.40?±?5.74; scrub typhus 11.84?±?4.95 (×10³/??L)], platelet count [P?=?0.008; dengue 42.2?±?33.9; scrub typhus 104.1?±?93.3 (×10⁹/L)], prothrombin time (PT) [P?=?0.007; dengue 12.82?±?1.36; scrub typhus 10.74?±?0.98 (s)], activated partial thromboplastin time (APTT) [P?=?0.002; dengue 50.81?±?10.08; scrub typhus 37.44?±?4.06 (s)], blood urea nitrogen (BUN) [P?P?P?=?0.027; dengue 2.9?±?1.3; scrub typhus 5.4?±?2.6 (days)], and ventilator duration [P?=?0.022; dengue 9.4?±?14.0; scrub typhus 14.8?±?10.4 (days)] between both groups.

Conclusions

This study provides relatively rare data regarding the clinical differences between adult dengue and scrub typhus patients with ARF.     

Bone mineralization in children with Wilson’s disease

Background

The goal of this study was to determine bone mineralization in children with Wilson’s disease (WD).

Methods

Twenty-seven patients (16 males) and two age- and gender-matched healthy children for each patient were enrolled in the study. Bone mineral content (BMC, grams) and density (BMD, g/cm²) at lumbar 1–4 vertebrae were measured by dual-energy X-ray absorptiometry. Urinary calcium excretion was calculated in 19 patients. The effect of cirrhosis and hypercalciuria on BMC and BMD was also evaluated in WD patients.

Results

There was no statistically significant difference between patients and healthy controls regarding mean BMC (33.0?±?13.9 vs. 35.8?±?13.8 g) (p?=?0.940) and mean BMD values (0.66?±?0.16 vs. 0.71?±?0.18 g/cm²) (p?=?0.269), respectively. Nine (47.4 %) patients had hypercalciuria. Hypercalciuric patients had statistically significant lower BMC and BMD values than those without hypercalciuria. A significant difference continued to be present after age, weight, height, and pubertal stage adjustment was done, but disappeared after weight, height, follow up duration, and pubertal stage adjustment was done. The presence of cirrhosis did not affect BMC and BMD significantly in WD patients.

Conclusions

BMC and BMD in children with WD were normal. The presence of hypercalciuria but not cirrhosis may affect BMC and BMD negatively in the patients.     

Associations Between Markers of Colorectal Cancer Stem Cells and Adenomas Among Ethnic Groups

Background and Purposes

Most colorectal tumors develop from adenomatous polyps, which are detected by colonoscopy. African Americans (AAs) have higher incidence of colorectal cancer (CRC) and greater mortality from this disease than Caucasian Americans (CAs). We investigated whether differences in predisposition to CRC and its surrogate (colonic adenomas) between these ethnic groups were related to numbers of cancer stem or stem-like cells (CSCs) in colonocytes.

Methods

We analyzed colonic effluent from 11 AA and 14 CA patients who underwent scheduled colonoscopy examinations at the John D. Dingell Veterans Affairs Medical Center. We determined proportions of cells that expressed the CSC markers CD44 and CD166 by flow cytometry.

Results

The proportion of colonocytes that were CD44⁺CD166^? in effluent from patients with adenomas was significantly greater than from patients without adenomas (P?=?0.01); the proportion of CD44⁺CD166⁺ colonocytes was also greater (P?=?0.07). Effluent from AAs with adenomas had 60?% more CD44⁺166^? colonocytes than from CAs with adenomas. Using cutoff values of 8?% for AAs and 3?% for CAs, the proportion of CD44⁺166^? colonocytes that had positive predictive value for detection of adenomas was 100?% for AAs and CAs, determined by receiver operator characteristic curve analysis.

Conclusion

The proportion of CD44⁺166^? colonocytes in colonic effluent can be used to identify patients with adenoma. AAs with adenomas have a higher proportion of CD44⁺166^? colonocytes than CA. The increased proportion of CSCs in colonic tissue from AA might be associated with the increased incidence of CRC in this population.     

Differences in intraprocedural ACTs with standardized heparin dosing during catheter ablation for atrial fibrillation in patients treated with dabigatran vs. patients on uninterrupted warfarin

Purpose

Effective intraprocedural anticoagulation for catheter ablation for atrial fibrillation is critical to minimize the risk of cerebral thromboembolism. The effect of dabigatran on anticoagulation with heparin during the procedure is unknown. This study compares heparin anticoagulation in patients treated with dabigatran vs. patients on uninterrupted warfarin.

Methods

Seventy-six consecutive patients (24 dabigatran and 52 warfarin) subjected to a standard intraprocedural heparin protocol were included. Heparin administration and rapidity and degree of anticoagulation were compared between the groups.

Results

Despite greater administration of heparin (52.5?±?22.0 vs. 33.2?±?10.1?units?kg^?1?h^?1; p?<?0.001), the mean (320.3?±?19.5?s) and peak (358.8?±?28.6?s) activated clotting time (ACT) for the dabigatran group were significantly lower than for the warfarin group (mean, 362.9?±?35.9 and peak, 410.4?±?49.7; p?<?0.001). The time from initial heparin bolus to first ACT of ??300?s in the dabigatran group was more than twice that observed in the warfarin group (45.0?±?30.4 vs. 20.9?±?14.5?min; p?<?0.001). The time to first ACT of ??350?s was similarly prolonged (109.1?±?60.0 vs. 55.2?±?51.1?min; p?<?0.001) in the dabigatran group, with eight patients (33?%) failing to reach this target. Outcome differences persisted following analysis using linear models and Cox proportional hazard regression with adjustment for propensity scores.

Conclusion

A standard intraprocedural heparin protocol results in delayed and lower levels of anticoagulation as measured by the ACT for patients treated with dabigatran compared with those on uninterrupted warfarin.     

Neutrophil gelatinase-associated lipocalin (NGAL) in inflammatory bowel disease: association with pathophysiology of inflammation, established markers, and disease activity

Background

Neutrophil gelatinase-associated lipocalin (NGAL) is a multi-potent 25-kDa protein mainly secreted by neutrophils. In inflammatory bowel disease (IBD), overexpression of NGAL in colon epithelium has been previously shown. This is the first study analyzing serum and urinary NGAL levels in IBD patients, with regard to specific characteristics of patients and disease.

Methods

Serum and urinary NGAL levels were determined in 181 patients with IBD, 93 with ulcerative colitis (UC), and 88 with Crohn’s disease (CD), 82 healthy controls (HC), and 41 patients with irritable bowel syndrome (IBS).

Results

Serum NGAL levels were elevated in IBD patients (88.19?±?40.75?ng/mL) compared with either HC (60.06?±?24.18?ng/mL) or IBS patients (60.80?±?20.30?ng/mL), P?P?Conclusions Serum NGAL is elevated particularly in active IBD and correlates with established markers of inflammation and disease activity, implicating its role in the pathophysiology of IBD.     

Clinical significance of lymph vessel density in T3 colorectal carcinoma

Purpose

The purpose of the present study is to characterise the lymphatic vessel density (LVD) in the T3 colorectal carcinoma and to correlate it with N status, grading and presence of tumour budding.

Methods

A total of 56 cases of T3 colorectal carcinoma were retrieved from the pathology’s archive of Klinikum Augsburg. All slides were stained immunohistochemically with D2-40 (lymphatic endothelium) and with pancytokeratin to assess the tumour budding. Tumour budding and lymph vessel density were investigated independently by BM and CC. The highest density of lymphatic vessels was counted both in tumour centre (ILVD) and at the periphery of the tumour (PLVD) within an area of 0.24?mm².

Results

Due to the strong intra-observer (BM and CC) difference in ILVD and PLVD, all cases were re-evaluated establishing a consensus that has been used for the further analyses. There was a significant difference between PLVD and ILVD (12?±?4 versus 6?±?3; P?P?=?0.072). There was no association between tumour budding and ILVD and PLVD (P?=?0.249 and 0.38).

Conclusion

Colorectal carcinoma induces lymphangiogenesis. A higher PLVD could increase the capability of cancer cell to invade the lymphatic system. However, the obvious difficulties in immunohistochemical evaluation and the rather small differences between nodal positive and negative cases in T3 colorectal cancer seem to limit the clinical value of LVD evaluation.     

The prevention of colorectal anastomotic leakage with tissue adhesives in a contaminated environment is associated with the presence of anti-inflammatory macrophages

Background

Colorectal anastomoses created in a contaminated environment result in a high leakage rate. This study investigated whether using anastomotic sealants (TissuCol®, Histoacryl® Flex, and Duraseal®) prevents leakage in a rat peritonitis model.

Study design

Sixty-seven Wistar rats were divided into control and experimental groups (TissuCol, Histoacryl, and Duraseal groups). Peritonitis was induced 1 day before surgery with the cecal ligation puncture model. On day 0, colonic anastomosis was constructed with sutures and then sealed with no adhesive (control group) or one select adhesive (experimental groups). Bursting pressure, abscess formation, and adhesion severity were evaluated on day 3 or day 14. Hematoxylin and eosin staining and immunohistochemical staining for CD4, CD8, CD206, and iNOS were performed.

Results

On day 3, bursting pressures of the TissuCol group (120.1?±?25.3 mmHg), Histoacryl group (117.3?±?20.2 mmHg), and Duraseal group (123.6?±?35.4 mmHg) were significantly higher than the that of the control group (24.4?±?31.7 mmHg, p?iNOS+ cells (M1 macrophages), a higher M2/M1 index, and a higher CD4+/CD8+ index were seen at the anastomotic site in all experimental groups compared with the control group on day 3. On day 14, abscesses were only found in the control group. Adhesion severity in the Duraseal group was significantly lower than that in the control group (p?=?0.001).

Conclusions

Anastomotic sealing using TissuCol®, Histoacryl® Flex, or Duraseal® seems to be an effective and safe option to prevent leakage in contaminated colorectal surgery. The presence of large numbers of anti-inflammatory macrophages seems to be involved in preventing the leakage.     

Feasibility of multiple short, 40-s, intra-procedural ECG recordings to detect immediate changes in heart rate variability during catheter ablation for arrhythmias

Purpose

This study aims to evaluate a method to detect heart rate variability (HRV) changes using short ECG segments during ablation for arrhythmias.

Methods

HRV was averaged from sequentially shorter time windows from 5-min ECG recordings in 15 healthy volunteers. The 40-s window was identified as the shortest duration that yielded reproducible values in high frequency (HF) and low frequency (LF) HRV. This method was validated in patients undergoing tilt table testing to see if the expected modulation in HRV that occurs prior to syncope could be detected from multiple 40-s recordings. Lastly, this method was used to assess HRV changes in 75 patients undergoing ablation for atrial fibrillation (AF) and other arrhythmias, to see if autonomic modulation as a result of ablation could be detected. A further 14 patients had stepwise HRV measurements at different stages of the AF ablation procedure to determine whether intra-procedural HRV changes could be detected.

Results

HRV, averaged from multiple 40-s recordings, demonstrated the expected increase immediately preceding syncope compared with baseline (LF: 341?±?311?C1,536?±?1,368 ms², p?<?0.05; HF: 342?±?339?C1,628?±?1,755 ms², p?<?0.05). AF ablation, particularly following right pulmonary vein circumferential ablation, produced immediately detectable reductions in LF (153?±?251?C50?+?116 ms², p?<?0.001) and HF (86?±?195?C33?±?83 ms², p?<?0.001) without any change in RR interval (877?±?191?C843?±?220 ms, p?=?0.261). Ablation for atrial flutter did not change the mean RR interval, LF or HF HRV.

Conclusion

Averaging multiple 40-s windows give valid HF and LF HRV measurements that enable detection of intra-procedural changes. Left atrial ablation around the right-sided pulmonary veins is unique in producing reductions in HRV. This method has the potential for use as an endpoint marker for adjunctive autonomic ablation procedures.     

In patients with type 1 diabetes simultaneous pancreas and kidney transplantation preserves long-term kidney graft ultrastructure and function better than transplantation of kidney alone

Aims/hypothesis

In patients with type 1 diabetes and end-stage renal disease (ESRD) we aimed to determine whether long-term normoglycaemia, as achieved by successful simultaneous pancreas and kidney (SPK) transplantation, would preserve kidney graft structure and function better than live donor kidney (LDK) transplantation alone.

Methods

Estimated GFR (eGFR) was calculated in SPK (n?=?25) and LDK (n?=?17) recipients in a stable phase 3 months after transplantation and annually during follow-up. Kidney graft biopsies were obtained at follow-up for measurement of glomerular volume (light microscopy), glomerular basement membrane (GBM) and podocyte foot process widths and mesangial volume fraction (electron microscopy).

Results

SPK and LDK recipients were similar in age and diabetes duration at engraftment. Donor age was higher in the LDK group. Median follow-up time was 10.1 years. Mean HbA_1c levels during follow-up were 5.5?±?0.4% (37?±?5 mmol/mol) and 8.3?±?1.5% (68?±?16 mmol/mol) in the SPK and LDK group, respectively (p?p?=?0.008) and increased mesangial volume fraction (median 0.23 [range 0.13–0.59] vs 0.16 [0.10–0.41]; p?=?0.007) at follow-up. Absolute eGFR change from baseline was ?11?±?21 and ?23?±?15 ml min^?1 1.73 m^?2 (p?=?0.060), whereas eGFR slope was ?1.1 (95% CI ?1.7, ?0.5) and ?2.6 (95% CI ?3.1, ?2.1)?ml min^?1 1.73 m^?2 per year in the SPK and LDK group, respectively (p?=?0.001).

Conclusions/interpretation

In patients with type 1 diabetes and long-term normoglycaemia after successful SPK transplantation, kidney graft ultrastructure and function were better preserved compared with LDK transplantation alone.     

Simultaneous assessment of contact pressure and local electrical coupling index using robotic navigation

Purpose

Contact with cardiac tissue is a determinant of lesion efficacy during atrial fibrillation (AF) ablation. The Sensei®X Robotic Catheter System (Hansen Medical, CA) has been validated for contact force sensing. The electrical coupling index (ECI) from the EnSite Contact? system (St. Jude Medical, MN) has been validated as an indicator of tissue contact. We aimed at analyzing ECI behavior during radiofrequency (RF) pulses maintaining a stable contact through the robotic navigation contact system.

Methods

In 15 patients (age, 59?±?12) undergoing AF ablation, pulmonary vein (PV) isolation was guided by the Sensei®X System, employing the Contact? catheter.

Results

During the procedure, we assessed ECI changes associated with adequate contact based on the IntelliSense® force-sensing technology (Hansen Medical, CA. Baseline contact (27?±?8 g/cm²) ECI value was 99?±?13, whereas ECI values in a noncontact site (0 g/cm²) and in a light contact site (1–10 g/cm²) were respectively 66?±?12 and 77?±?10 (p?<?0.0001). Baseline contact ECI values were not different depending on AF presentation (paroxysmal AF, 98?±?9; persistent AF, 100?±?9) or on cardiac rhythm (sinus rhythm, 97?±?7; AF,101?±?10). In all PVs, ECI was significantly reduced during and after ablation (ECI during RF, 56?±?15; ECI after RF, 72?±?16; p?<?0.001). A mean reduction of 32.2 % during RF delivery and 25.4 % immediately after RF discontinuation compared with baseline ECI was observed.

Conclusions

Successful PV isolation is associated with a significant decrease in ECI of at least 20 %. This may be used as a surrogate marker of effective lesion in AF ablation.     

Colorectal cancer surgery remains effective with rising patient age

Background

The incidence of colorectal cancer rises disproportionally in aging persons. With a shift towards higher population age in general, an increasing number of older patients require adequate treatment. This study aims to investigate differences between young and elderly patients who undergo resection for colorectal cancer, regarding clinical characteristics, morbidity, and prognosis.

Methods

By retrospective analysis of 6 years (2007 to 2012) of a prospectively documented database, a total of 636 patients were identified who underwent oncological resection for colorectal cancer at our institution. Of this total, all 569 patients with primary colorectal adenocarcinoma were included. Four hundred ten patients were 74 years or younger and 159 were 75 years or older. The median follow-up was 22 months.

Results

Older patients had significantly more comorbidities (85 % vs. 56 %, p?<?0.001) and a higher ASA score (p?<?0.001). The mean length of stay in the hospital was longer (24 vs. 20 days, p?=?0.002), as was the length of postoperative intensive care stay (4 vs. 2 days, p?=?0.003). However, elderly patients did not have significantly higher rates of intraoperative complications or surgical morbidity. Tumor-specific 2-year survival was 83?±?4 % for the elderly and 87?±?2 % for the younger patients, which was not significantly different (p?=?0.90).

Conclusions

Long-term outcome after oncologic resection for colorectal cancer does not differ between elderly and younger patients. Age in general should not be considered as a limiting factor for colorectal cancer surgery or tumor-specific prognosis.     

Point-by-point pulmonary vein antrum isolation guided by intracardiac echocardiography and 3D mapping and duty-cycled multipolar AF ablation: effect of multipolar ablation on procedure duration and fluoroscopy time

Purpose

Pulmonary vein antrum isolation (PVAI) guided by intracardiac echocardiography and a roaming circular mapping catheter is an effective treatment modality for atrial fibrillation. Unfortunately, the complexity of this technique leads to long procedure times and high fluoroscopy exposure. Single-catheter multipolar ablation holds the promise to reduce these parameters. This study examined the effect of the conventional point-by-point PVAI with that of single-catheter multipolar ablation on the procedural characteristics and clinical outcomes of atrial fibrillation ablation.

Methods

Referred patients underwent PVAI guided by a magnetic-based 3D mapping (CARTO 3^? System; group 1) or duty-cycled multipolar AF ablation using the pulmonary vein ablation catheter (PVAC, group 2) between June 2010 and May 2011.

Results

Data were analyzed from 19 patients in group 1 and 31 patients in group 2. There was no significant difference in the length of the procedure between the two groups (135?±?26 vs 125?±?25?min, P?=?0.20). Patients who underwent ablation using PVAC spent significantly less time in the procedure room pre- and post-procedure than those who underwent conventional PVAI (205?±?38 vs 179?±?30?min, P?=?0.02) and had a significantly shorter fluoroscopy exposure (50?±?16 vs 36?±?14?min, P?=?0.003) and radiofrequency energy delivery time (54?±?26 vs 32?±?33?min, P?=?0.02). No differences in safety and efficacy were seen between the groups.

Conclusions

Single-catheter multipolar AF ablation was associated with significantly lower fluoroscopy duration, radiofrequency energy delivery time, and the time the patient spent in the procedure room before and after ablation, although measured short-term clinical outcomes were similar.     

Statin-Induced Immunomodulation Alters Peripheral Invariant Natural Killer T-cell Prevalence in Hyperlipidemic Patients

Purpose

To assess the difference in the prevalence of invariant Natural Killer T (iNKT) lymphocytes between hyperlipidemic and control individuals and to evaluate changes in iNKT cell levels after 6?months lipid lowering therapy.

Methods

A total of 77 hyperlipidemic individuals (54?±?5?years) were assigned to simvastatin 40?mg or ezetimibe 10?mg daily for 6?months. Fifty individuals with normal cholesterol levels were used as control. iNKT cells were measured by flow cytometry in peripheral blood.

Results

Patients with hypercholesterolemia had significantly lower iNKT cell levels (percentage on the lymphocyte population) compared to control group (0.16?±?0.04% vs 0.39?±?0.08%, p?=?0.03). iNKT cells significantly increased after 6?months treatment with simvastatin (from 0.15?±?0.04% to 0.28?±?0.11%, p?=?0.03) but not with ezetimibe (from 0.16?±?0.05% to 0.17?±?0.06%, p?=?0.55). Simvastatin treatment did not alter the activation status of iNKT cells as measured by HLA-DR expression. Changes of iNKT cells were independent from changes in total (r ²?=?0.009, p?=?0.76) or LDL cholesterol (r ²?=?0.008, p?=?0.78) reached by simvastatin.

Conclusions

Hyperlipidemic patients have reduced numbers of iNKT in peripheral circulation compared to individuals with normal cholesterol levels. Their number is increasing after long term administration of simvastatin 40?mg but not after ezetimibe.     

CRP evolution pattern in CPAP-treated obstructive sleep apnea patients. Does gender play a role?

Background??aim

C-reactive protein (CRP) is directly implicated in atherogenesis and associated cardiovascular morbidity in patients with obstructive sleep apnea (OSA). Effective continuous positive airway pressure (CPAP) treatment has been shown to gradually decrease CRP levels and thus consequently improve disease-related cardiovascular morbidity. However, the influence of gender on the CRP evolution pattern has never been assessed before. The aim of our study was to investigate possible gender differences in CRP evolution in OSA patients 3 and 6?months after the start of effective CPAP treatment.

Methods

The study population consisted of 436 patients (252 males/184 females) with newly diagnosed moderate to severe OSA and good CPAP compliance assessed by a thorough follow up. High-sensitivity C-reactive protein (hs-CRP) was assessed before CPAP initiation and at the third and sixth month of the follow-up period.

Results

C-reactive protein values showed a statistically significant decrease at the third and sixth month of CPAP therapy [initial values 0.79?±?0.65?mg/dL versus 0.70?±?0.52?mg/dL (p?p?p?p?>?0.05). After 6?months?? treatment, CRP decreased significantly in both genders (males from 0.74?±?0.53?mg/dL to 0.28?±?0.32?mg/dL, p?p?Conclusion Our results suggest a delay in the normalization of CRP levels in females despite effective CPAP treatment. A time period of at least 6?months appeared to be required in women in order to reduce CRP levels and consequent cardiovascular risk. In contrast, CPAP??s protective role in males is achieved at an earlier time point. Gender-related hormonal and genetic factors may influence the above CRP evolution pattern.     

Cardiac autonomic function in metabolic syndrome: a comparison of ethnic Turkish and Japanese patients

Background

Metabolic syndrome (MetS) prevalence shows some differences at various regions of the world in terms of race and ethnicity. The cardiac autonomic functions between Turkish and Japanese MetS patients with heart rate turbulence (HRT) and heart rate variability (HRV) were compared as the aim of this study.

Methods

This study consists of 149 nondiabetic subjects with MetS. All patients were further classified into subgroups based on ethnicity (76 from Turkey, 73 from Japan). Twenty-four-hour ambulatory Holter ECG recording was applied to all subjects whose HRV and HRT (total onset (TO), total slope (TS)) parameters were analyzed.

Results

The waist circumference was the only demographic parameter that was significantly different between the Turkish and Japanese patients with MetS (99.31?±?6.12 vs 91.12?±?6.89 for men and 91.48?±?7.45 vs 86.26?±?5.78 for woman; p?<?0.001 and <0.001). There was a significant difference between Turkish and Japanese patients with MetS in terms of the HRT values. (TO Turkish, 0.77?±?0.19?%; TO Japanese, 0.49?±?1.03?%, p?=?0.031; TS Turkish, 1.93?±?1.26; TS Japanese, 2.44?±?1.37, p?=?0.041, respectively). As for HRV parameters, standard deviation of all NN intervals index was only different between Turkish and Japanese patients with MetS (90.79?±?58.94, 128.18?±?105.30; p?=?0.034, respectively).

Conclusion

HRT and some HRV scores of ethnic Turkish MetS patients are worse than the scores of ethnic Japan MetS patients. We think that these differences are related to the central obesity.     

Local calprotectin production in colorectal cancer and polyps--active neutrophil recruitment in carcinogenesis

Aim

The aim of this study is to examine the expression level and localization of calprotectin in cancer tissue, tumor-adjacent mucosa, and polyps in colonic biopsies. Calprotection expression was correlated with neutrophil infiltration, markers of bacteremia, and systemic inflammation.

Materials and methods

Patients with colorectal cancer (n?=?28) and adenoma (n?=?38) were compared with healthy controls (n?=?33). Calprotectin expression levels were measured by ELISA, and its localization was visualized by immunohistochemistry and correlated with the degree of neutrophil infiltration (visualized by Esterase staining). The expression of tumor necrosis factor (TNF)-alpha, procalcitonin, endotoxemia, carcinoembryonic antigen (CEA), and C-reactive protein was also investigated.

Results

Mucosal calprotectin was expressed in significantly higher concentrations in carcinoma (94.2?±?31.2?ng/mg total protein) and adenoma (122.8?±?60.3?ng/mg total protein) in comparison with mucosal biopsies from healthy controls (20.4?±?5.4?ng/mg total protein), tumor-adjacent mucosa from patients with colorectal carcinoma (21.6?±?5.1?ng/mg total protein), and adenoma (45?±?14.6?ng/mg total protein, all p?<?0.05). Immunohistochemistry showed calprotectin reactivity mainly in granulocytes and macrophages with only singular reactive epithelial cells. Positive staining (quantified by the number of positive cells per square millimeter) was markedly increased in carcinoma tissue (85?±?21.5) and in adenoma (67.5?±?20) as compared with tumor-adjacent epithelia (18.8?±?4.3, p?=?0.0007, p?=?0.003, respectively), and there was a highly significant correlation, r?=?0.89, p?=?0.001) between calprotectin staining and neutrophil infiltration. No significant differences were found in the systemic levels of TNF-alpha, procalcitonin, and endotoxemia, whereas CEA and C-reactive protein levels were significantly higher in the cancer group (p?<?0.05).

Conclusion

Our results support the evidence that increased calprotectin expression is an early step in the neoplastic transformation during colorectal carcinogenesis. Moreover, its expression is closely related to an inflammatory response and points out a possible biological link between inflammation and neoplastic transformation in colorectal cancer.     

A multi-purpose spiral high-density mapping catheter: initial clinical experience in complex atrial arrhythmias

Purpose

There is an increasing need for catheter ablation procedures to treat complex atrial tachycardias (AT) and atrial fibrillation (AF), often requiring detailed endocardial mapping. The sequential point-to-point contact mapping of complex arrhythmias is time-consuming and may not always be feasible. We assessed the utility of a novel spiral duo-decapolar high-density (HD) mapping catheter to delineate complex arrhythmia substrates for ablation.

Methods

The patients underwent HD mapping using a spiral catheter (AFocusII) and the EnSite NavX system, during catheter ablation procedures, to treat atrial arrhythmias.

Results

In 26 patients, a total of 32 atrial arrhythmias were mapped and ablated, comprising of five focal AT, eight macroreentrant AT, 11 persistent AF and eight paroxysmal AF. The HD catheter was used to acquire endocardial surface geometries in all cases and to map the pulmonary veins in patients undergoing AF ablation. In persistent AF, HD catheter mapping permitted the creation of highly detailed complex fractionated electrogram maps (left atrium 449?±?128 points in 7.2?±?2.6 min; right atrium 411?±?113 points in 6.7?±?1.6 min). In AT, activation mapping was performed with the acquisition of 305?±?158 timing points in 7.3?±?2.6 min, guiding successful ablation in all cases. During the follow-up of 7.0?±?2.6 months, all AT patients remained free of significant arrhythmia.

Conclusions

High-density contact mapping with a novel spiral multipolar catheter allows rapid assessment of focal and macroreentrant AT, and complex fractionated electrical activity in the atria. It has further multi-functional capabilities as a pulmonary vein mapping catheter and for accurate geometry creation when used with a 3D mapping system.