Sirolimus-eluting versus paclitaxel-eluting stent in primary angioplasty: a pooled patient-level meta-analysis of randomized trials

Large interests have been focused on the role of drug-eluting stents in the setting of ST-segment elevation myocardial infarction (STEMI) and concerns have emerged regarding an higher risk of stent thrombosis. Aim of the current study was to perform a meta-analysis using individual patient data to evaluate the long-term safety and effectiveness of sirolimus-eluting stent (SES) as compared to paclitaxel-eluting stent (PES) in patients undergoing primary percutaneous coronary intervention (PCI) for STEMI. The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL). We examined all completed randomized trials of SES versus PES for STEMI. No language restriction was applied. Primary study endpoint was the occurrence of major adverse cardiac events (MACE). Secondary endpoints were the occurrence of death, reinfarction, stent thrombosis, target-vessel revascularization (TVR). Individual patient data were obtained from 4 out of 5 trials identified, including a total of 1,000 patients, 504 (50.4 %) randomized to SES and 496 (49.6 %) randomized to PES. At long-term follow-up (1,021 [372–1,351] days), no difference was observed between SES and PES in terms of TVR (10 vs 11.6 %, HR [95 % CI 0.73 [0.45–1.16], p = 0.18, p het = 0.92]) (primary endpoint) or death (9.4 vs 10.4 %, HR [95 % CI 0.95 [0.58–1.54], p = 0.82, p het = 0.89]), reinfarction (8.2 vs 10.4 %, HR [95 % CI 0.91 [0.53–1.57], p = 0.73, p het = 0.83]), stent thrombosis (7.4 vs 4.6 %, HR [95 % CI 1.04 [0.55–2.05], p = 0.92, p het = 0.65]), and MACE (10 vs 13.6 %, HR [95 % CI 0.86 [0.63–1.18], p = 0.36, p het = 0.84]) (secondary endpoints). The present pooled patient-level meta-analysis demonstrates that, among STEMI patients undergoing primary PCI, SES and PES are associated with a similar outcome at long-term follow-up, in terms of death, reinfarction, stent thrombosis, TVR and MACE.     

The value of plasma D-dimer level on admission in predicting no-reflow after primary percutaneous coronary intervention and long-term prognosis in patients with acute ST segment elevation myocardial infarction

D-dimer is a final product of fibrin degradation and gives an indirect estimation of the thrombotic burden. We aimed to investigate the value of plasma D-dimer levels on admission in predicting no-reflow after primary percutaneous coronary intervention (p-PCI) and long-term prognosis in patients with ST segment elevation myocardial infarction (STEMI). We retrospectively involved 569 patients treated with p-PCI for acute STEMIs. We prospectively followed up the patients for a median duration of 38 months. Angiographic no-reflow was defined as postprocedural thrombolysis in myocardial infarction (TIMI) flow grade <3 or TIMI 3 with a myocardial blush grade <2. Electrocardiographic no-reflow was defined as ST-segment resolution <70 %. The primary clinical end points were mortality and major adverse cardiovascular events (MACE). The incidences of angiographic and electrocardiographic no-reflow were 31 and 39 % respectively. At multivariable analysis, D-dimer was found to be an independent predictor of both angiographic (p < 0.001), and electrocardiographic (p < 0.001) no-reflow. Both mortality (from Q1 to Q4, 5.7, 6.4, 11.3 and 34.1 %, respectively, p < 0.001) and MACE (from Q1 to Q4, 17.9, 29.3, 36.9 and 52.2 %, respectively, p < 0.001) rates at long-term follow-up were highest in patients with admission D-dimer levels in the highest quartile (Q4), compared to the rates in other quartiles. However, Cox proportional hazard model revealed that high D-dimer on admission (Q4) was not an independent predictor of mortality or MACE. In contrast, electrocardiographic no-reflow was independently predictive of both mortality [Hazard ratio (HR) 2.88, 95 % confidence interval (CI) 1.04–8.58, p = 0.041] and MACE [HR 1.90, 95 % CI 1.32–4.71, p = 0.042]. In conclusion, plasma D-dimer level on admission independently predicts no-reflow after p-PCI. However, D-dimer has no independent prognostic value in patients with STEMI.     

Evaluating the Optimal Timing of Revascularisation in Patients with Transient ST-Segment Elevation Myocardial Infarction: Rationale and Design of the TRANSIENT Trial

Patients with chest pain and a prehospital ST-segment elevation myocardial infarction (STEMI) are preferably treated with immediate percutaneous coronary intervention (PCI). However, patients with normalization of symptoms and ST-segment elevation upon hospital arrival (transient STEMI) received inconsistent therapy due to logistic reasons and the absence of evidence or explicit guidelines. In this trial, the optimal timing of coronary angiography and subsequent revascularisation is investigated in patients presenting with transient STEMI. In this prospective, multicentre, randomized controlled clinical trial, 142 consecutive patients with initially acute chest pain and STEMI, whose symptoms and ST-segment elevation resolve upon admission, are randomized to immediate intervention or a delayed intervention. Primary outcome is infarct size measured at 4 days determined by cardiovascular magnetic resonance. Secondary outcomes are left ventricular function and volumes, myocardial salvage and microvascular injury at baseline; the change in left ventricular function, volumes and infarct size at 4 months; and major adverse cardiac events at 4 and 12 months. The TRANSIENT Trial evaluates whether a delayed invasive strategy (according to NSTEMI-guidelines) is superior to an immediate invasive strategy (according to STEMI-guidelines) in patients with a transient STEMI.     

Prognostic implications of left ventricular regional function heterogeneity assessed with two-dimensional speckle tracking in patients with ST-segment elevation myocardial infarction and depressed left ventricular ejection fraction

The aim of the current study was to evaluate the prognostic implications of myocardial tissue heterogeneity assessed with two-dimensional speckle-tracking echocardiography in patients three months after first ST-segment elevation myocardial infarction (STEMI) with left ventricular ejection fraction (LVEF) ≤35 %. For this purpose, a total of 79 patients with first STEMI and LVEF ≤35 % at three months postinfarction were evaluated. Based on left ventricular (LV) speckle-tracking longitudinal strain echocardiography, the infarct core, border zone, and remote zone at baseline and three months’ follow-up were defined. Patients were followed for the occurrence of the composite end point of appropriate implantable cardioverter-defibrillator (ICD) therapy and/or cardiac mortality. During a median follow-up of 46 months, 13 patients (17 %) reached the composite end point. At baseline, patients with and without events showed comparable values of LV longitudinal strain at the infarct, border, and remote zones. However, at three months’ follow-up, patients with events showed significantly more impaired longitudinal strain at the border zone (?6.8 ± 3.1 % vs. ?10.5 ± 4.9 %, P = 0.002), whereas LVEF was comparable (28 ± 6 % vs. 31 ± 4 %, P = 0.09). The median three-month LV longitudinal strain at the border zone was ?9.4 %. Multivariate Cox regression analysis demonstrated that three-month longitudinal strain >?9.4 % at the border zone was independently associated with the composite end point (hazard ratio 3.94, 95 % confidence interval 1.05–14.70; P = 0.04). In conclusion, regional longitudinal strain at the border zone three months post-STEMI is associated with appropriate ICD therapy and cardiac mortality.     

Time to treatment—door-to-balloon time is not everything

International guidelines for the management of patients with ST-elevation myocardial infarction (STEMI) recommend various performance measures to monitor the quality of STEMI systems of care. Door-to-balloon (D2B) time (arrival at hospital to percutaneous coronary intervention, PCI) and overall health care system delay (first medical contact to reperfusion) are acknowledged as valuable performance measures when treating patients with primary percutaneous coronary intervention (PPCI). However, there is confusion regarding the exact definition of these performance measures, and moreover system delay and PCI-related delay (the extra delay acceptable to perform PPCI instead of fibrinolysis) are often used synonymously, which add confusion when considering reperfusion strategy. The present paper calls for a consensus regarding the use and definition of objective performance measures when treating patients with STEMI, and exemplifies why it is insufficient just to focus on D2B time.     

Prognostic value of estimated glomerular filtration rate in hospitalized elderly patients

A multicenter observational study, REPOSI (REgistro POliterapie Società Italiana di Medicina Interna), was conducted to assess the prognostic value of glomerular filtration rate (eGFR) on in-hospital mortality, hospital re-admission and death within 3 months, in a sample of elderly patients (n = 1,363) admitted to 66 internal medicine and geriatric wards. Based on eGFR, calculated by the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, subjects at hospital admission were classified into three groups: group 1 with normal eGFR (≥60 ml/min/1.73 m², reference group), group 2 with moderately reduced eGFR (30–59 ml/min/1.73 m²) and group 3 with severely reduced eGFR (<30 ml/min/1.73 m²). Patients with the lowest eGFR (group 3) on admission were more likely to be older, to have a greater cognitive and functional impairment and a high rate of comorbidities. Multivariable logistic regression analysis showed that severely reduced eGFR at the time of admission was associated with in-hospital mortality (OR 3.00; 95 % CI 1.20–7.39, p = 0.0230), but not with re-hospitalization (OR 0.97; 95 % CI 0.54–1.76, p = 0.9156) or mortality at 3 months after discharge (OR 1.93; 95 % CI 0.92–4.04, p = 0.1582). On the contrary, an increased risk (OR 2.60; 95 % CI 1.13–5.98, p = 0.0813) to die within 3 months after discharge was associated with decreased eGFR measured at the time of discharge. Our study demonstrates that severely reduced eGFRs in elderly patients admitted to hospital are strong predictors of the risk of dying during hospitalization, and that this measurement at the time of discharge helps to predict early death after hospitalization.     

Osteopontin circulating levels correlate with renal involvement in systemic lupus erythematosus and are lower in ACE inhibitor-treated patients

Elevated serum levels of osteopontin have been associated with cardiovascular disease, diabetic nephropathy, and autoimmune disease activity. Aim of the study was to investigate the relationship between osteopontin serum levels and renal damage in a population of patients with systemic lupus erythematosus (SLE). Osteopontin serum levels were analyzed in 101 SLE patients and compared to those of 115 healthy controls. Associations between osteopontin levels and renal involvement, disease activity and damage index, biochemical parameters, and therapy were assessed. Overall osteopontin serum levels were higher in SLE patients (median, 17.93 ng/mL; interquartile range, 8.13–35.07 ng/mL) than in healthy controls (median, 5.62 ng/mL; interquartile range, 2.61–13.83 ng/mL). Univariate logistic analysis among cases showed that high osteopontin levels (higher vs medium–lower tertile) were associated with renal involvement (p?=?0.012), renal function (p?=?0.007), proteinuria (p?=?0.011), anemia (p?p?p?=?0.008), proteinuria (OR?=?4.56; 95 % CI, 1.15–18.04; p?=?0.027), anemia (OR?=?4.66; 95 % CI, 1.25–17.43; p?=?0.008), and use of renin–angiontensin system antagonists (OR?=?0.234; 95 % CI, 0.06–0.98; p?=?0.047). This study shows that elevated osteopontin serum levels significantly correlate with renal involvement and anemia in SLE. Moreover, it suggests that renin–angiontensin system antagonists decrease osteopontin levels—this effect is consistent with the inhibitory effect of these drugs on osteopontin renal expression, detected in animal models by other authors, and may provide a new rationale for their employment.     

Prevalence and 1-year prognosis of transient heart failure following coronary revascularization

The occurrence of heart failure during the whole pre-discharge course of coronary revascularization, as far as its influence on subsequent prognosis, is poorly understood. The present study examined the effect of transient heart failure (THF) developing in the acute and rehabilitative phase on survival after coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI). Patients in the Italian survey on cardiac rehabilitation and secondary prevention after cardiac revascularization (ICAROS) were analyzed for THF, the latter being defined either as signs and symptoms consistent with decompensation or cardiogenic shock. ICAROS was a prospective, multicenter registry of 1,262 consecutive patients discharged from 62 cardiac rehabilitation (CR) facilities, providing data on risk factors, lifestyle habits, drug treatments, and major cardiovascular events (MACE) during a 1-year follow-up. Records were linked to the official website of the Italian Association of Cardiovascular Prevention and Rehabilitation (GICR-IACPR). The overall prevalence of pre-discharge THF was 7.6 %, with 69.8 % of cases in acute wards, 22.9 % during CR, and 7.3 % in both settings. THF affected more frequently patients with chronic cardiac condition (42.7 vs. 30.6 %; p < 0.05), age ≥75 years (33.3 vs. 23.1 %; p < 0.005), COPD (19.8 vs. 12.3 %; p < 0.05), and chronic kidney disease (17.7 vs. 7 %; p < 0.001). After discharge, THF patients showed good maintenance rates of RAAS modulators (90.6 %) and beta-blockers (83.3 %), while statin therapy significantly decreased from 81.3 to 64.6 % (p < 0.05). The pursuit of secondary prevention targets, as far as self-reported drug adherence, was not different among groups. Patients with THF had increased 1-year mortality (8.3 vs. 1.6 %, p < 0.001). Moreover, THF independently predicted adverse outcome with OR for recurrent events (mainly further episodes of decompensation) of 2.4 (CI 1.4–4.3). Patients who experienced THF after coronary revascularization had increased post-discharge mortality and cardiovascular events. Hemodynamic instability, rather than recurrent myocardial ischemia, seems to be linked with worse prognosis.     

Magnetic resonance defecography versus clinical examination and fluoroscopy: a systematic review and meta-analysis

Background

Magnetic resonance defecography (MRD) allows for dynamic visualisation of the pelvic floor compartments when assessing for pelvic floor dysfunction. Additional benefits over traditional techniques are largely unknown. The aim of this study was to compare detection and miss rates of pelvic floor abnormalities with MRD versus clinical examination and traditional fluoroscopic techniques.

Methods

A systematic review and meta-analysis was conducted in accordance with recommendations from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. MEDLINE, Embase and the Cochrane Central Register of Controlled Trials were accessed. Studies were included if they reported detection rates of at least one outcome of interest with MRD versus EITHER clinical examination AND/OR fluoroscopic techniques within the same cohort of patients.

Results

Twenty-eight studies were included: 14 studies compared clinical examination to MRD, and 16 compared fluoroscopic techniques to MRD. Detection and miss rates with MRD were not significantly different from clinical examination findings for any outcome except enterocele, where MRD had a higher detection rate (37.16% with MRD vs 25.08%; OR 2.23, 95% CI 1.21–4.11, p = 0.010) and lower miss rates (1.20 vs 37.35%; OR 0.05, 95% CI 0.01–0.20, p = 0.0001) compared to clinical examination. However, compared to fluoroscopy, MRD had a lower detection rate for rectoceles (61.84 vs 73.68%; OR 0.48 95% CI 0.30–0.76, p = 0.002) rectoanal intussusception (37.91 vs 57.14%; OR 0.32, 95% CI 0.16–0.66, p = 0.002) and perineal descent (52.29 vs 74.51%; OR 0.36, 95% CI 0.17–0.74, p = 0.006). Miss rates of MRD were also higher compared to fluoroscopy for rectoceles (15.96 vs 0%; OR 15.74, 95% CI 5.34–46.40, p < 0.00001), intussusception (36.11 vs 3.70%; OR 10.52, 95% CI 3.25–34.03, p = 0.0001) and perineal descent (32.11 vs 0.92%; OR 12.30, 95% CI 3.38–44.76, p = 0.0001).

Conclusions

MRD has a role in the assessment of pelvic floor dysfunction. However, clinicians need to be mindful of the risk of underdiagnosis and consider the use of additional imaging.

     

Listeria monocytogenes meningoencephalitis in adults: analysis of factors related to unfavourable outcome

Purpose

To analyse the short-term outcome in patients with Listeria monocytogenes meningoencephalitis (LMME) to improve management and outcome.

Methods

Observational study with adult patients with LMME between 1977 and 2009 at a tertiary hospital in Barcelona, Spain. Parameters that predicted outcome were assessed with univariate and logistic regression analysis.

Results

Of 59 cases of LMME, 28 occurred in the last decade. Since 1987, a new protocol has been used and 29/45 patients (64 %) treated since then received adjuvant dexamethasone. In patients who received this treatment there was a trend towards fewer neurological sequelae (5 vs 33 %; p = 0.052). Antiseizure prophylaxis with phenytoin was administered in 13/45 (28 %) patients. Seizures occurred in 7/45 (16 %) patients, all in the group who did not receive phenytoin. Hydrocephalus presented in 8/59 (14 %). It was never present at admission and five patients needed neurosurgical procedures. Sequelae after 3 months were present in 8/45 (18 %), mostly cranial nerve palsy. Rhombencephalitis (RE) was related to the presence of neurologic sequelae (OR: 20.4, 95 % CI: 1.76–236). Overall mortality was 14/59 (24 %), 9/59 (15 %) due to neurological causes related to hydrocephalus or seizures. Mortality was defined as early in 36 % and late in 64 %. In the multivariate analysis, independent risk factors for mortality were presence of hydrocephalus (OR: 17.8, 95 % CI: 2.753–114) and inappropriate empirical antibiotic therapy (OR: 6.5, 95 % CI: 1.201–35).

Conclusions

Outcome of LMME may be improved by appropriate empirical antibiotic therapy, suspicion and careful management of hydrocephalus. Use of adjuvant dexamethasone or phenytoin in a subgroup of these patients might have a benefit.     

<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.     

Improved oncologic outcomes with image-guided intensity-modulated radiation therapy using helical tomotherapy in locally advanced hepatocellular carcinoma

Aim

To investigate whether image-guided intensity-modulated radiation therapy (IG-IMRT) improves survival in hepatocellular carcinoma (HCC) relative to 3-dimensional conformal radiotherapy (3D-CRT).

Methods

Between 2006 and 2011, 187 HCC patients treated with definitive RT were reviewed. Median age was 53(range 51–83). All patients were stage III or IV-A. Concurrent chemoradiation was received by 178 patients (95.2 %). Overall actuarial survival (OS), progression-free survival (PFS), and infield-failure-free survival (IFFS) analyses were performed by Kaplan–Meier method. A Cox proportional hazards model was used for univariate and multivariate analysis. Pearson’s chi-square test or Fisher’s exact test was used to compare patient characteristics and treatment-related toxicity between the groups.

Results

Sixty-five patients were treated with IG-IMRT and 122 patients with 3D-CRT. No significant differences were seen between the groups for all patient characteristics. IG-IMRT delivered higher doses than 3D-CRT (median biological effective dose 62.5 vs 53.1 Gy, P < 0.001). IG-IMRT showed significantly higher 3-year OS (33.4 vs 13.5 %, P < 0.001), PFS (11.1 vs 6.0 %, P = 0.004), and IFFS (46.8 vs 28.2 %, P = 0.007) than 3D-CRT. On univariate and multivariate analysis, RT modality was significant prognostic factor for OS (HR 2.18; 95 % CI 1.45–3.25; P < 0.001), PFS (HR 1.64; 95 % CI 1.17–2.29; P = 0.004). There was no significant difference between the two modalities for radiation-induced liver disease (P = 0.716).

Conclusion

Our findings suggest that IG-IMRT could be an effective treatment that provides survival benefit without increasing severe toxicity in locally advanced HCC.     

RABBIT risk score and ICU admission due to infection in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) patients are at increased risk of infection. Aim of the present study was to investigate whether RA patients admitted to an intensive care unit (ICU) due to infection have higher Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) risk scores compared to control RA patients. Seventy-four RA patients (32.4% male) admitted to an ICU due to infection (from January 2002 to December 2013) and 74 frequency-matched control RA patients (16.2% male) were included in this cross-sectional study. There was strong evidence for a higher RABBIT risk score in ICU patients (median 2.0; IQR 1.3–3.2) as compared to controls (1.3; IQR 0.8–2.0; p < 0.0001). Traditional disease-modifying anti-rheumatic drugs (DMARDs) (82.4 vs 64.9%; p = 0.015) and biological DMARDs (28.4 vs 14.9%; p = 0.012) were more frequently given to RA patients without ICU admission. Glucocorticoid users were more frequently found in the ICU group (51.4 vs 31.1%; p = 0.012). In a multivariable analysis tDMARD use was associated with lower (OR 0.38; 95% CI 0.15–0.93; p = 0.034) and glucocorticoid use with borderline higher odds of ICU admission (OR 2.05; 95% CI 0.92–4.58; p = 0.078). Chronic obstructive pulmonary disease (OR 2.89; 95% CI 1.10–7.54; p = 0.03), chronic kidney disease (OR 16.08; 95% CI 2.00–129.48; p = 0.009), and age category (OR 2.67; 95% CI 1.46–4.87; p = 0.001) were strongly associated with ICU admission. There was a strong trend towards higher odds of ICU admission with increasing RABBIT risk score. Use of tDMARDs was associated with lower odds of ICU admission. In an adjusted analysis, bDMARDs were not associated with ICU admission. COPD, CKD, and age were strong risk factors for ICU admission.     

Smoking is associated with impaired glucose regulation and a decrease in insulin sensitivity and the disposition index in first-degree relatives of type 2 diabetes subjects independently of the presence of metabolic syndrome

The aim of this study was to investigate glucose tolerance, insulin secretion and insulin resistance according to smoking habits in first-degree relatives of type 2 diabetes patients, a population at high risk for developing diabetes. One thousand three hundred (646 females and 654 males) subjects underwent an oral glucose tolerance test (OGTT) to investigate their glucose metabolism and answered questionnaires about their lifestyle habits. Smoker subjects showed significant impairment compared with non-smoker subjects in 2-h post-oral glucose tolerance test (2hOGTT, 129.3 ± 40.2 vs. 117.7 ± 37.6 mg/dl, p < 0.001), the OGTT insulin sensitivity (386.3 ± 54.9 vs. 400.5 ± 53.4 ml min^?1 m², p < 0.01) method and the insulin sensitivity and secretion index-2 (ISSI-2, 1.7 ± 0.8 vs. 2.0 ± 1.0, p < 0.005). Metabolic syndrome (MS) was higher in the smoker than in the non-smoker group (46.5 vs. 29.7 %, p < 0001), and smokers were more sedentary than non-smokers (3.94 ± 3.77 vs. 4.86 ± 4.41 h/week, p < 0.001). Smokers showed an increased risk of impaired glucose regulation (IGR: impaired glucose tolerance or diabetes mellitus) with a hazard ratio (HR) adjusted by gender, metabolic syndrome and physical activity of 1.78, 95 % CI 1.27–2.47 (p < 0.001). The association between smoking and MS conferred a risk of IGR that was five times higher (HR 5.495, 95 % CI 4.07–7.41, p < 0.001). Smoking habit was a significant explanatory variable in a multiple forward stepwise regression analysis performed using 2hOGTT and ISSI-2 as dependent variables (p < 0.0001, R = 0.313 and p < 0.0001, R = 0.347, respectively). In conclusions, our results show that tobacco smoking is tightly associated with impairments in glucose metabolism and insulin sensitivity and insulin secretion.     

A meta-analysis of the clinicopathological characteristics and survival outcomes of inflammatory bowel disease associated colorectal cancer

Purpose

The current study aims to use meta-analytical techniques to compare the clinicopathological characteristics and survival outcomes of inflammatory bowel disease (IBD) associated and sporadic colorectal carcinoma (CRC). Patients with IBD have an established increased risk of developing CRC. There is no consensus, however, on the clinicopathological characteristics and survival outcomes of IBD associated CRC when compared to sporadic CRC.

Methods

A comprehensive search for published studies comparing IBD associated and sporadic CRC was performed. Random effect methods were used to combine data. This study adhered to the recommendations of the MOOSE guidelines.

Results

Data were retrieved from 20 studies describing 571,278 patients. IBD associated CRC had an increased rate of synchronous tumors (OR 4.403, 95% CI 2.320–8.359; p < 0.001), poor differentiation (OR 1.875, 95% CI 1.425–2.466; p < 0.001), and a reduced rate of rectal cancer (OR 0.827, 95% CI 0.735–0.930; p = 0.002). IBD associated CRC however did not affect the frequency of T3/T4 tumors (OR 0.931, 95% CI 0.782–1.108; p = 0.421), lymph node positivity (OR 1.061, 95% CI 0.929–1.213; p = 0.381), metastasis at presentation (OR 0.970, 95% CI 0.776–1.211; p = 0.786), sex distribution (OR 0.978, 95% CI 0.890–1.074; p = 0.640), or 5-year overall survival (OR 1.105, 95% CI 0.414–2.949; p = 0.842).

Conclusions

In this large analysis of available data, IBD associated CRC was characterized by less rectal tumors and more synchronous and poorly differentiated tumors compared with sporadic cancers, but no discernable difference in sex distribution, stage at presentation, or survival could be identified.

     

Association of glucokinase regulatory gene polymorphisms with risk and severity of non-alcoholic fatty liver disease: an interaction study with adiponutrin gene

Background

Recent genome-wide association studies demonstrated an association between single nucleotide polymorphisms (SNPs) on the glucokinase regulatory gene (GCKR) with hepatic steatosis. This study attempted to investigate the association of GCKR rs780094 and rs1260326 with susceptibility to non-alcoholic fatty liver disease (NAFLD) and its severity.

Methods

The genotypes were assessed on 144 histologically confirmed NAFLD patients and 198 controls using a Sequenom MassARRAY platform.

Results

The GCKR rs1260326 and rs780094 allele T were associated with susceptibility to NAFLD (OR 1.49, 95 % CI 1.09–2.05, p = 0.012; and OR 1.51, 95 % CI 1.09–2.09, p = 0.013, respectively), non-alcoholic steatohepatitis (NASH) (OR 1.55, 95 % CI 1.10–2.17, p = 0.013; and OR 1.56, 95 % CI 1.10–2.20, p = 0.012, respectively) and NASH with significant fibrosis (OR 1.50, 95 % CI 1.01–2.21, p = 0.044; and OR 1.52, 95 % CI 1.03–2.26, p = 0.038, respectively). Following stratification by ethnicity, significant association was seen in Indian patients between the two SNPs and susceptibility to NAFLD (OR 2.64, 95 % CI 1.28–5.43, p = 0.009; and OR 4.35, 95 % CI 1.93–9.81, p < 0.0001, respectively). The joint effect of GCKR with adiponutrin rs738409 indicated greatly increased the risk of NAFLD (OR 4.14, 95 % CI 1.41–12.18, p = 0.010). Histological data showed significant association of GCKR rs1260326 with high steatosis grade (OR 1.76, 95 % CI 1.08–2.85, p = 0.04).

Conclusion

This study suggests that risk allele T of the GCKR rs780094 and rs1260326 is associated with predisposition to NAFLD and NASH with significant fibrosis. The GCKR and PNPLA3 genes interact to result in increased susceptibility to NAFLD.     

Evaluation of Endoscopic Transpapillary Brushing Cytology for the Diagnosis of Bile Duct Cancer Based on the Histopathologic Findings

Background and Aim

Diagnosis of the bile duct cancer still needs more accuracy. Studies on endoscopic retrograde cholangiopancreatography (ERCP)-guided brushing cytology were carried to evaluate the role of the endoscopic transpapillary brushing cytology for the diagnosis of bile duct cancer.

Patients and Method

The study involved 76 consecutive patients who underwent ERCP-guided bile duct cytology for the diagnosis of bile duct cancer from 2008 to August 2012. Three types of cytological specimens were obtained using different sampling methods, i.e., bile aspiration cytology (BAC), brush tip cytology (BTC), and post brushing bile cytology (PBC), to investigate their diagnostic abilities, and comparatively studied with each macroscopic type of the surgically resected specimens.

Results

The cancer-positive rate was 67.1 % (BAC alone: 41.9 %), and the use of BTC and PBC in addition to BAC yielded a statistically significant increase of the cancer-positive rate (p = 0.0031). In 34 resected cases, the cancer-positive rate in relation to the macroscopic type was improved by the addition of BTC and PBC to BAC alone for the papillary (87.5 vs. 40.0 %, p = 0.071) and nodular (100 vs. 70.0 %, p = 0.0603) types, but not for the flat type (62.5 vs. 57.1 %; p = 0.7651).

Conclusion

The diagnostic ability of ERCP-guided brushing cytology could be improved by the addition of PBC. However, the cancer-positive rate was the lowest for the flat type of bile duct cancer.     

Correlations Between Small Airway Function,Ventilation Distribution,and Functional Exercise Capacity in COPD Patients

Background

Interest in using the nitrogen single-breath washout (N₂SBW) test to measure ventilation inhomogeneity and small airway function in COPD patients has grown in recent years. Our aim was to assess the correlation of the measures obtained by the N₂SBW test and other pulmonary function parameters with the six-minute walk distance (6MWD), the degree of dyspnea score, and health status in COPD patients.

Methods

In this cross-sectional study, 31 patients with COPD were subjected to the N₂SBW test, spirometry, whole-body plethysmography, carbon monoxide diffusing capacity measurement, the six-minute walk test, the modified Medical Research Council (mMRC) scale, and the COPD Assessment Test (CAT).

Results

We found a strong correlation between the 6MWD and the phase III slope of the nitrogen single-breath washout (Phase III slope_N2SBW) (r = ?0.796; p = 0.0001). We found moderate correlations between the 6MWD and the residual volume (RV) (r = ?0.651; p = 0.0001) and RV/total lung capacity (RV/TLC) (r = ?0.600; p = 0.0004). We also found moderate correlations between the CAT score and Phase III slope_N2SBW (r = 0.728; p = 0.0001), RV (r = 0.646; p = 0.0001) and RV/TLC (r = 0.603; p = 0.0003). There was a significant difference between the mMRC grades for the following variables: Phase III slope_N2SBW (p = 0.0001), RV (p = 0.0001), and smoking history (p = 0.008). Multivariate analysis showed that Phase III slope_N2SBW was the only independent predictor of the 6MWD (R ²  = 0.703; p = 0.0001), CAT score (R ²  = 0.586; p = 0.0001), and mMRC scale (relative risk = 1.14; p = 0.0001).

Conclusions

In patients with COPD, our findings suggest that the ventilation inhomogeneity impacts the functional exercise capacity, the degree of dyspnea, and health status.     

Socioeconomic status and the risk for being diagnosed with spondyloarthritis and chronic pain: a nested case–control study

Socioeconomic status could potentially impact on which type of rheumatic diagnosis a patient receives. We determined whether different socioeconomic status is a risk factor for being diagnosed with spondyloarthritis (SpA) or chronic pain. In a nested case–control study, we identified two sets of adult cases diagnosed with (i) SpA (n = 1,194) and (ii) chronic pain (n = 3,730) during 2010–2012 in Skåne region, Sweden. We randomly sampled controls matched for age and sex. Level of education, marital status, and income were identified in national registers 4 years before inclusion. We also studied health-care utilization, prescribed pharmaceuticals, and work status. We used conditional logistic regressions and included socioeconomic variables and geographic area in the models. Low (odds ratio [OR] 1.69 95 % CI 1.50–1.91) or moderate education (OR 1.43 95 % CI 1.30–1.57), and low (OR 1.40 95 % CI 1.25–1.57) or moderate income (OR 1.24 95 % CI 1.10–1.38) were associated with a chronic pain diagnosis. For a SpA diagnosis, moderate income (OR 1.25 95 % CI 1.04–1.50) was the only significant factor identified. Both case groups had a larger proportion that did not work (P < 0.001), used more health care (P < 0.001), and were more frequently prescribed NSAIDs (P < 0.001) 4 years before diagnosis than controls. We confirmed that lower levels of education and income are associated with a chronic pain diagnosis. This association may reflect a true higher incidence of chronic pain and/or increased consultation propensity for such pain in people with socioeconomic status. We found no such association for SpA.