Major adverse cardiovascular events in non-valvular atrial fibrillation with chronic obstructive pulmonary disease: the ARAPACIS study

Chronic obstructive pulmonary disease (COPD) increases the risk of mortality in non-valvular atrial fibrillation (NVAF) patients. Data on the relationship of COPD to major cardiovascular events (MACE) in AF have not been defined. The aim of the study is to assess the predictive value of COPD on incident MACE in NVAF patients over a 3-year follow-up. In the Atrial Fibrillation Registry for Ankle-Brachial Index Prevalence Assessment-Collaborative Italian Study (ARAPACIS) cohort, we evaluate the impact of COPD on the following clinical endpoints: MACE (including vascular death, fatal/non-fatal MI and stroke/TIA), cardiovascular (CV) death and all-cause mortality. Among 2027 NVAF patients, patients with COPD (9%) are more commonly male, elderly and at higher thromboembolic risk. During a median 36.0 months follow-up, 186 patients experienced MACE: vascular death (n?=?72), MI (n?=?57), stroke/TIA (n?=?57). All major outcomes (including stroke/TIA, MI, vascular death, and all-cause death) are centrally adjudicated. Kaplan–Meier curves show that NVAF patients with COPD are at higher risk for MACE (p?<?0.001), CV death (p?<?0.001) and all-cause death (p?<?0.001). On Cox proportional hazard analysis, COPD is an independent predictor of MACE (Hazard ratio [HR] 1.77, 95% Confidence Intervals [CI] 1.20–2.61; p?=?0.004), CV death (HR 2.73, 95% CI 1.76–4.23; p?<?0.0001) and all-cause death (HR 2.16, 95% CI 1.48–3.16; p?<?0.0001). COPD is an independent predictor of MACE, CV death and all-cause death during a long-term follow-up of NVAF patients.     

Incremental prognostic value of the SYNTAX score to late gadolinium-enhanced magnetic resonance images for patients with stable coronary artery disease

The prognostic significance of the SYNTAX (Synergy between PCI with Taxus and cardiac surgery) score has recently been demonstrated in patients with stable multivessel or left main coronary artery disease (CAD). The present study determines whether adding the SYNTAX score to Framingham risk score (FRS), left ventricular ejection fraction (LVEF) and presence of myocardial infarction (MI) by late gadolinium enhancement (LGE) magnetic resonance imaging can improve the risk stratification in patients with stable CAD. We calculated the SYNTAX score in 161 patients with stable CAD (mean age: 66 ± 10 years old). During a mean follow-up of 2.3 years, 56 (35 %) of 161 patients developed cardiovascular events defined as cardiovascular death, non-fatal MI, cerebral infarction, unstable angina pectoris, hospitalization due to heart failure and revascularization. Multivariate Cox regression analysis selected triglycerides [hazard ratio (HR): 1.005 (95 % confidence interval (CI): 1.001–1.008), p < 0.008], presence of LGE [HR: 6.329 (95 % CI: 2.662–15.05), p < 0.001] and the SYNTAX score [HR: 1.085 (95 % CI: 1.044–1.127), p < 0.001] as risk factors for future cardiovascular events. Adding the SYNTAX score to FRS, EF and LGE significantly improved the net reclassification index (NRI) [40.4 % (95 % CI: 18.1–54.8 %), p < 0.05] with an increase in C-statistics of 0.089 (from 0.707 to 0.796). An increase in C-statistics and significant improvement of NRI showed that adding the SYNTAX score to the FRS, LVEF and LGE incrementally improved risk stratification in patient with stable CAD.     

Association between self-reported snoring and arterial stiffness: data from the Brisighella Heart Study

The correlation of both obstructive sleep apnoea syndrome (OSAS) and snoring with cardiovascular risk is well known, but its investigation is complex and not suitable for studying large cohorts of subjects. Thus, we prospectively evaluated 1476 non-pharmacologically treated subjects selected from the last survey of the Brisighella Heart Study. Snoring and sleep apnoea were investigated asking the subjects if they were aware of snoring during the night, and if this was associated with episodes of apnoea. A full set of clinical and laboratory parameters were evaluated, while augmentation index (AIx), and pulse wave velocity (PWV) were recorded with the Vicorder^® apparatus. A logistic regression analysis identifies as main independent predictors of AIx age (OR 1.058, 95 % CI 1.043–1.065, p < 0.001), Body Mass Index (OR 1.046, 95 % CI 1.014–1.079, p = 0.005), and apolipoprotein B (OR 1.014, 95 % CI 1.004–1.023, p = 0.001). The main independent predictors of PWV are snoring (OR 1.215, 95 % CI 1.083–1.390, p < 0.001), and snoring with apnoea (OR 1.351, 95 % CI 1.135–1.598, p = 0.014), age (OR 1.078, 95 % CI 1.052–1.089, p < 0.001), serum uric acid [SUA] (OR 1.093, 95 % CI 1.026–1.151, p < 0.001) and mean arterial pressure (OR 1.042, 95 % CI 1.024–1.056, p < 0.001). In conclusion, in our cohort of overall healthy subjects, self-reported snoring and sleep apnoea are independently associated with a higher PVW, and AIx is statistically significantly higher in snorers with or without sleep apnoea than in non-snorers. Body Mass Index and apolipoprotein B are associated with AIx, while SUA and mean arterial pressure are related to PWV.     

Paced QRS duration and myocardial scar amount: predictors of long-term outcome of right ventricular apical pacing

Long-term right ventricular apical pacing (RVAP) is reportedly associated with heart failure (HF) development. However, the predictors of pacing-induced HF (PHF) remained unclear. We retrospectively enrolled 234 patients without structural heart disease who underwent a permanent pacemaker implantation with RVAP between 1982 and 2004. RVAP-induced HF was defined as left ventricular ejection fraction decrease >5 % with HF symptom without other HF development etiology. The QRS duration of a paced beat (pQRSd) and myocardial scar score were analyzed from each patient’s 12-lead ECG. During a mean 15.6 years (range 3.3–30.0 years), 48 patients (20.5 %) patients developed RVAP-induced HF. The PHF group patients had a longer pQRSd (192.4 ± 13.5 vs. 175.7 ± 14.7 ms in non-PHF patients, p < 0.001) and a higher myocardial scar score (5.2 ± 1.9 vs. 2.7 ± 1.9, respectively p < 0.001). In multivariate Cox regression analysis, old age at implantation [Hazard ratio (HR) 1.62, 95 % confidential interval (CI) 1.22–2.16, p = 0.001], a longer pQRSd (HR 1.54, 95 % CI 1.15–2.05, p = 0.003), a higher myocardial scar score (HR 1.23, 95 % CI 1.03–1.49, p = 0.037), and a higher percentage of ventricular pacing (HR 1.31, 95 % CI 1.01–1.49, p = 0.010) were independent predictors of PHF. Based on the results of the receiver-operating characteristic (ROC) curve, the pQRSd cutoff was 185 ms (AUC 0.79, sensitivity 66.7 %, specificity 76.3 %) and myocardial scar score cutoff value was 4 (AUC 0.81, sensitivity 81.3 %, specificity 66.1 %). The pQRSd was positively correlated with scar score (r = 0.70, p < 0.001). pQRSd ≥185 ms and/or myocardial scar score ≥4 might be independent long-term prognostic markers of PHF.     

Polymorphisms within the neuronal cadherin (<Emphasis Type="Italic">CDH2</Emphasis>) gene are associated with obsessive-compulsive disorder (OCD) in a South African cohort

OCD is characterised by recurrent obsessions and compulsions that result in severe distress and increased risk for comorbidity. Recently published findings have indicated that the neuronal cadherin gene (CDH2) plays a role in the development of canine OCD, and led us to investigate the human ortholog, CDH2, in a human OCD cohort. Seven CDH2 polymorphisms were selected and genotyped in a South African Caucasian cohort of 234 OCD patients and 180 healthy controls using TaqMan assays. Polymorphisms were analysed in a single-locus and haplotypic context. Of the seven polymorphisms, two reached statistical significance for OCD under additive and codominant models of inheritance (rs1120154 and rs12605662). CDH2 SNP, rs1120154, C-allele carriers were found to be significantly associated with lower risk to develop OCD compared to TT-homozygotes (OR = 0.49; 95 % CI: 0.32–0.75; p < 0.001), and rs12605662 G-allele carriers were significantly associated with reduced risk OCD compared to TT-homozygotes (OR = 0.46; 95 % CI: 0.30–0.71; p < 0.001), Furthermore, a single haplotype was found to infer an increased risk for OCD diagnosis (*rs8087457-rs1148374: A-T). Polymorphisms within the CDH2 gene are associated with susceptibility to OCD in a South African cohort.     

Clinical effectiveness of the systematic use of the GRACE scoring system (in addition to clinical assessment) for ischaemic outcomes and bleeding complications in the management of NSTEMI compared with clinical assessment alone: a prospective study

We assessed the interest of systematically using the GRACE scoring system (in addition to clinical assessment) for in-hospital outcomes and bleeding complications in the management of NSTEMI compared with clinical assessments alone. Multicentre, randomized study that included 572 consecutive NSTEMI patients, randomized 1:1, into group A: clinical stratification alone and group B: clinical+ GRACE score stratification. Main outcome measures: in-hospital outcomes and bleeding complications. There was no significant difference between the two groups for baseline data or for in-hospital MACE. In multivariate analysis, only a GRACE >140 (OR: 3.5, 95 % CI: 1.8–6.6, p < 0.001) and PCI (OR: 0.55, 95 % CI: 0.3–1.0; p = 0.05) were independent predictors of in-hospital MACE. The sub-analysis of group B showed that 56 patients (20 %) were given a compliance score of 0, showing that diagnostic angiography was performed later than as recommended by the guidelines. Interestingly, 91 % had a GRACE score >140, and these patients were significantly older, and were more likely to have a history of diabetes, stroke and renal failure, together with symptoms of heart failure. After multivariate analysis, the independent predictors of a lack of compliance with guideline delays were a GRACE score >140 (OR: 9.2; CI: 4.2–20.3, p < 0.001) and secondary referral from a non-PCI cardiology department (OR: 2.7; CI: 1.4–5.2, p = 0.003). In a real-world setting of patients admitted with NSTEMI, the systematic use of the GRACE scoring system at admission in the PCI centre does not improve in-hospital outcomes and bleeding complications.     

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.     

Elevated partial antiphospholipid score is a strong risk factor for thrombosis in patients with systemic lupus erythematosus: a validation study

This study aims to identify risk factors for thrombosis in patients with systemic lupus erythematosus (SLE) and to validate the efficacy of the partial antiphospholipid (aPL) score for thrombosis prediction and diagnosis of antiphospholipid syndrome (APS). This study included 325 SLE patients, 188 of whom completed a follow-up of 31.01 months (range 23–48 months). Partial aPL score was calculated by adding up the individual scores for activated partial thromboplastin time (APTT), lupus anticoagulant, IgG/IgM anticardiolipin antibodies (aCL), and IgG/IgM anti-β2-glycoprotein I (anti-β2GPI). A simplified aPL score was developed using only APTT, IgG/IgM aCL, and IgG/IgM anti-β2GPI. Partial aPL scores were significantly higher in SLE patients with thrombosis (p?<?0.0001). A history of thrombosis (p?<?0.0001), a partial aPL score >10 (p?<?0.0001), and immunosuppressant use (p?=?0.012) were independent risk factors for thrombosis. For patients with a history of thrombosis, partial aPL score was the strongest risk factor for recurrent thrombosis (p?<?0.0001, odds ratio?=?30.34 (95 % CI 7.70–118.81)). For APS diagnosis, the area under the receiver-operating characteristic curve (AUC) was 0.809 (95 % CI 0.73–0.89) using the partial aPL score. Similarly, the simplified aPL score was significantly associated with thrombosis (p?<?0.0001) and was acceptable for APS diagnosis (AUC 0.797, 95 % CI 0.72–0.88). An elevated partial aPL score is a strong risk factor for thrombosis in SLE patients and is a useful tool to predict recurrent thrombosis. Partial aPL score and simplified aPL score, although comprising fewer items than the original aPL score, also represent valuable quantitative indices for APS diagnosis.     

Relationship between epicardial adipose tissue volume and atrial fibrillation

Background

Several studies have suggested that epicardial adipose tissue (EAT) volume may be associated with the risk of atrial fibrillation (AF). However, these studies have reported conflicting results. We therefore aimed to investigate the relationship between EAT volume and AF.

Methods

We systematically retrieved the relevant studies reporting on the relationship between EAT volume and AF using the Cochrane Library, PubMed, Medline, EBSCO, and Embase databases. Data were extracted from applicable articles, and mean differences were pooled using the RevMan 5.3 software.

Results

Ten case-control studies were identified. With regard to the relationship between EAT volume and AF, both total-EAT volume (24.23 ml, 95?% CI: 19.40–29.06, p?<?0.00001) and EAT volume surrounding the left atrium (LA-EAT; 16.35 ml, 95?%CI: 12.73–19.98, p?<?0.00001) were significantly increased in patients with AF. With regard to the relationship between the different types of AF and EAT volume, there was a significant difference in the total-EAT volume subgroup (19.38 ml, 95?% CI: 11.45–27.31, p?<?0.0001) and in the LA-EAT volume subgroup (17.91 ml, 95?% CI: 15.13–20.69, p?<?0.00001) between patients with persistent AF (PeAF) and paroxysmal AF (PAF). However, there was no significant difference between the total-EAT and LA-EAT volume subgroups (χ ² ?=?0.12, p?=?0.70).

Conclusion

EAT volume may be associated with an increased risk of AF. Additionally, the EAT volume in patients with PeAF was larger than that in PAF patients, independent of the location of EAT.

     

Lipid peroxidation as risk factor for endothelial dysfunction in antiphospholipid syndrome patients

The aim of this study was to evaluate oxidative stress markers and it relations to endothelial damage as risk factor for thrombosis in patients with primary (PAPS) and secondary (SAPS) antiphospholipid syndrome (APS) in correlation to traditional risk factors. Flow-mediated (FMD) and nitroglycerine (NMD)-induced dilation of the brachial artery were studied in 140 APS patients (90 PAPS, 50 SAPS) and 40 controls matched by age, sex, and conventional risk factors for atherosclerosis. Markers of oxidative stress, lipid hydroperoxydes (LOOH), advanced oxidation protein products (AOPP), total sulfhydryl groups (tSHG), and paraoxonase 1 activity (PON1) were determined by spectrophotometric method. Oxidative stress dominates in APS patients. LOOH and AOPP correlate to lipid fractions (p < 0.05), unlike PON1, tSHG that correlated to antiphospholipid antibody positivity (p < 0.05). FMD was lower in APS patients comparing to controls (p < 0.001). Cholesterol is independent variable for FMD impairment in control group (p = 0.011); LOOH in PAPS (p = 0.004); LOOH, aCL, and triglycerides in SAPS patients (p = 0.009, p = 0.049, and p = 0.012, respectively). Combined predictive of aCL and LOOH is better for FMD impairment than LOOH alone in both PAPS and SAPS patients (AUC 0.727, p = 0.001, 95 % CI 0.616–0.837 and AUC 0.824, p?0.001, 95 % CI 0.690–0.957, respectively). Lipid peroxidation is independent predictor for endothelial dysfunction in APS patients. We demonstrated synergistic effect of aCL and LOOH as risk for endothelial impairment in both PAPS and SAPS patients.     

Diabetes was the only comorbid condition associated with mortality of invasive pneumococcal infection in ICU patients: a multicenter observational study from the Outcomerea research group

Purposes

Streptococcus pneumoniae is a leading pathogen of severe community, hospital or nursing facility infections. We sought to describe characteristics of invasive pneumococcal infection (IPI) and pneumonia (due to the high mortality of intensive care-associated pneumonia) and to report outcomes according to various types of comorbidity.

Methods

Multicenter observational cohort study on the prospective Outcomerea database, including adult patients, with a hospital stay?<?48 h before ICU admission and a documented IPI within the first 72 h of ICU admission. Comorbid conditions were defined according to the Knaus and Charlson classification.

Results

Of the 20,235 patients, 5310 (26.4%) had an invasive infection, including 560/5,310 (10.6%) who had an IPI. The ICU 28-day mortality was 109/560 (19.8%). Four factors were independently associated with mortality: SOFA day 1–2: [hazard ratio (HR) 1.21; 95% confidence interval (95% CI) 1.15–1.27, p?<?0.001]; maximum lactate level day 1–2: (HR 1.07, 95% CI 1.02–1.12, p?=?0.006); diabetes mellitus: (HR 1.91, 95% CI 1.23–3.03, p?=?0.006) and appropriate antibiotics (HR 0.28, 95% CI 0.15–0.50, p?<?0.001). Comparable results were obtained when other comorbid conditions were forced into the model. Diabetes impact was more pronounced in case of micro- or macro-angiopathy (HR 4.17, 95%CI 1.68–10.54, p?=?0.003), in patients?≥?65 years old (HR 2.59, 95% CI 1.56–4.28, <?0.001) and in those with body mass index (BMI)?<?25 kg/m² (HR 2.11, 95% CI 1.10–4.06, p?=?0.025).

Conclusions

Diabetes mellitus was the only comorbid condition which independently influenced mortality in patients with IPI. Its impact was more pronounced in patients with complications, aged?≥?65 years and with BMI?<?25 kg/m².

     

Relationship between abdominal aortic and coronary artery calcification as detected by computed tomography in chronic kidney disease patients

The purpose of this study was to investigate the relationship between abdominal aortic calcification (AAC) and coronary artery calcification (CAC) in chronic kidney disease (CKD) patients. We evaluated 126 asymptomatic CKD patients (mean estimated glomerular filtration rate: 36.1 ± 14.1 mL/min/1.73 m², mean age 70.3 ± 10.1 years). A non-contrast computed tomography scan was used to determine the abdominal aortic calcification index (ACI) and CAC score, and this relationship was investigated. Among the subjects, AAC was present in 109 patients (86.5 %) as defined by ACI >0 and median ACI was 11.7 %. ACI increased in accordance with advances in CAC score grades (3.0, 5.2, 17.2, and 32.8 % for CAC score 0, 1–100, 101–400, and 401 or more, respectively, p < 0.001). Even after multivariate adjustment, ACI was independently associated with severe CAC score as defined by CAC score >400 [odds ratio 1.08, 95 % confidence interval (CI) 1.04–1.12, p < 0.001]. Receiver-operating curve analysis showed that the ACI optimal cut-off value predicting severe CAC score was 16.5 % (area under the curve = 0.79, 95 % CI 0.69–0.90, p < 0.001). The C statics for predicting CAC score was significantly increased by adding ACI values to the model including other risk factors (0.853 versus 0.737, p = 0.023). In conclusion, the ACI value of 16.5 % allows us to predict the presence of severe CAC in CKD patients, and that the addition of ACI to the model with traditional risk factors significantly improves the predictive ability of severe CAC score. These data reinforce the utility of ACI as a screening tool in clinical practice.     

Effect of colchicine in prevention of pericardial effusion and atrial fibrillation: a meta-analysis

Randomized, controlled trials (RCTs) have assessed the effect of colchicine therapy in prevention of pericardial effusion (PE) and atrial fibrillation (AF). However, the effects are still inconclusive. PubMed, Cochrane Library, Google Scholar, and EMBASE database were searched. Primary outcome was the risk of PE and AF. Ten RCTs with 1981 patients and a mean follow-up of 12.6 months were included. Colchicine therapy was not associated with a significantly lower risk of post-operative PE (RR, 0.89; 95 % CI 0.70–1.13; p = 0.33, I ² = 72.8 %) and AF (RR, 0.77; 95 % CI 0.52–1.13; p = 0.18, I ² = 47.3 %). However, rates of pericarditis recurrence, symptoms persistence, and pericarditis-related hospitalization were significantly decreased with colchicine treatment. In addition, cardiac tamponade occurrence was similar between groups, and adverse events were significantly higher in the colchicine group. Colchicine may not significantly decrease the post-operative risk of PE and AF. However, only limited studies about patients undergoing cardiac surgery provide data about PE and AF.     

Occupational and environmental scleroderma. Systematic review and meta-analysis

The etiology of systemic sclerosis (SSc) remains unknown; however, several occupational and environmental factors have been implicated. Our objective was to perform a meta-analysis of all studies published on SSc associated with occupational and environmental exposure. The review was undertaken by means of MEDLINE and SCOPUS from 1960 to 2014 and using the terms: “systemic,” “scleroderma,” or “systemic sclerosis/chemically induced” [MesH]. The Newcastle-Ottawa Scale was used for the qualifying assessment. The inverse variance-weighted method was performed. The meta-analysis of silica exposure included 15 case-control studies [overall OR 2.81 (95%CI 1.86–4.23; p < 0.001)] and 4 cohort studies [overall RR 17.52 (95%CI 5.98–51.37; p < 0.001)]; the meta-analysis of solvents exposure included 13 case-control studies (overall OR 2.00 [95%CI 1.32–3.02; p = 0.001); the meta-analysis of breast implants exposure included 4 case-control studies (overall OR 1.68 (95%CI 1.65–1.71; p < 0.001)) and 6 cohort studies (overall RR 2.13 (95%CI 0.86–5.27; p = 0.10)); the meta-analysis of epoxy resins exposure included 4 case-control studies (overall OR 2.97 (95%CI 2.31–3.83; p < 0.001)), the meta-analysis of pesticides exposure included 3 case-control studies (overall OR 1.02 (95%CI 0.78–1.32; p = 0.90)) and, finally, the meta-analysis of welding fumes exposure included 4 studies (overall OR 1.29 (95%CI 0.44–3.74; p = 0.64)). Not enough studies citing risks related to hair dyes have been published to perform an accurate meta-analysis. Silica and solvents were the two most likely substances related to the pathogenesis of SSc. While silica is involved in particular jobs, solvents are widespread and more people are at risk of having incidental contact with them.     

Effect of diet-induced weight loss on lipoprotein(a) levels in obese individuals with and without type 2 diabetes

Aims/hypothesis

Elevated levels of lipoprotein(a) [Lp(a)] are an independent risk factor for cardiovascular disease (CVD), particularly in individuals with type 2 diabetes. Although weight loss improves conventional risk factors for CVD in type 2 diabetes, the effects on Lp(a) are unknown and may influence the long-term outcome of CVD after diet-induced weight loss. The aim of this clinical study was to determine the effect of diet-induced weight loss on Lp(a) levels in obese individuals with type 2 diabetes.

Methods

Plasma Lp(a) levels were determined by immunoturbidimetry in plasma obtained before and after 3–4 months of an energy-restricted diet in four independent study cohorts. The primary cohort consisted of 131 predominantly obese patients with type 2 diabetes (cohort 1), all participants of the Prevention Of Weight Regain in diabetes type 2 (POWER) trial. The secondary cohorts consisted of 30 obese patients with type 2 diabetes (cohort 2), 37 obese individuals without type 2 diabetes (cohort 3) and 26 obese individuals without type 2 diabetes who underwent bariatric surgery (cohort 4).

Results

In the primary cohort, the energy-restricted diet resulted in a weight loss of 9.9% (95% CI 8.9, 10.8) and improved conventional CVD risk factors such as LDL-cholesterol levels. Lp(a) levels increased by 14.8 nmol/l (95% CI 10.2, 20.6). In univariate analysis, the change in Lp(a) correlated with baseline Lp(a) levels (r = 0.38, p < 0.001) and change in LDL-cholesterol (r = 0.19, p = 0.033). In cohorts 2 and 3, the weight loss of 8.5% (95% CI 6.5, 10.6) and 6.5% (95% CI 5.7, 7.2) was accompanied by a median increase in Lp(a) of 13.5 nmol/l (95% CI 2.3, 30.0) and 11.9 nmol/l (95% CI 5.7, 19.0), respectively (all p < 0.05). When cohorts 1–3 were combined, the diet-induced increase in Lp(a) correlated with weight loss (r = 0.178, p = 0.012). In cohort 4, no significant change in Lp(a) was found (?7.0 nmol/l; 95% CI -18.8, 5.3) despite considerable weight loss (14.0%; 95% CI 12.2, 15.7).

Conclusions/interpretation

Diet-induced weight loss was accompanied by an increase in Lp(a) levels in obese individuals with and without type 2 diabetes while conventional CVD risk factors for CVD improved. This increase in Lp(a) levels may potentially antagonise the beneficial cardiometabolic effects of diet-induced weight reduction.

     

Alcohol intake and the risk of osteonecrosis of the femoral head in Japanese populations: a dose-response meta-analysis of case-control studies

Studies examining the association between alcohol intake and the risk of osteonecrosis of the femoral head (ONFH) have inconsistent results. The purpose of this study was to examine and summarize the evidence regarding the association between alcohol intake and ONFH based on results from case-control studies. This analysis included five case-control studies reporting data from 1251 individuals. Alcohol intake habits (never, former, or current), average drinking consumption (g/week), and cumulative drinking consumption (drink-years) were extracted. The risk of ONFH was evaluated, and a two-stage dose-response meta-analysis was performed using restricted cubic splines with four knots at fixed percentiles of 5, 35, 65, and 95% of the distribution. Former alcohol intake increased the risk of ONFH with a marginal significance (odds ratio [OR], 2.62; p = 0.055). Current alcohol intake was associated with an increased risk of ONFH (OR, 3.63; p < 0.001 in occasional drinkers, OR, 5.90; p < 0.001 in daily drinkers). The dose-response meta-analysis revealed that the risk of ONFH increased by 35.3% for every 100 g/week (95% confidence interval [CI], 1.24–1.47; p < 0.001) and by 44.1% for every 500 g drink-years (95% CI, 1.295–1.601; p < 0.001). Current intake and the dose of alcohol were positively associated with an increased risk of ONFH in a non-linear pattern.     

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.

     

Tailored therapy for different presentations of chronic pain after stapled hemorrhoidopexy

Background

As stapled hemorrhoidopexy (SH) becomes more widely used, we see more patients with chronic postoperative anal pain after this surgery. Its presentation is variable and difficult to treat. The aim of our study was to investigate the impact of chronic anal pain after SH and whether tailored therapy was likely to achieve a favorable outcome.

Methods

We retrospectively analyzed 31 consecutive patients with chronic anal pain who had undergone SH in other hospitals and were referred to our institutions. Depending on the type of pain, unrelated (at rest) or related to defecation, two groups of patients were identified. Moreover, the mean distance of the staple line from the anal verge was calculated in both groups. Treatments included: topical nifedipine, local anesthetic and steroid infiltration, removal of retained staples, anal dilation, and scar excision with mucosal suturing. A visual analog scale (VAS) was used to compare pain at baseline, postoperatively, and in the follow-up. This mean difference of the VAS score between stages was always used as the main outcome measure, depending on the type of presentation, type of pain, and type of treatment. Treatment response was defined as a 50 % decrease of VAS from baseline.

Results

There were 22 males and 9 females. The overall median age was 43 years (range 21–62 years). On digital examination and proctoscopy, 15 (48 %) patients had inflammatory changes, 19 (61 %) patients had staple retention, 8 (26 %) patients had anorectal stenosis, and 30 (97 %) patients had scar tissue. All patients had one or more of the following treatments listed from the least to most invasive: topical nifedipine in 12 (39 %) patients, anal dilation in 6 (19 %) patients, anesthetic and steroid infiltration in 18 (58 %) patients, removal of staples in 10 (32 %) patients, and scar excision in 18 (58 %) patients. The mean VAS score at baseline was 6.100, ± 1.953 SD, which dropped significantly after treatment to 1.733, ± 1.658 SD (p < 0.001) and remained low at follow-up (1.741 ± SD 1.251; p < 0.743). In patients with pain at rest (n = 20, 65 %), the symptoms improved in 19 (95 %) patients, while the VAS score decreased from 5.552 ± 2.115 SD to 1.457 ± 1.440 SD (95 % CI 3.217–4.964; p < 0.001). In patients with post-evacuation pain (n = 11, 35 %), the symptoms improved in 11 (100 %) patients, while the VAS score decreased from 6.429 ± 1.835 SD to 1.891 ± 1.792 SD (95 % CI 3.784–5.269; p < 0.001). Rating of response based on presentation was 90.0 % (0.9/10) after treatment of staple retention, which led to a significant decrease in the mean VAS score from 6.304 ± 1.845 SD to 1.782 ± 1.731 SD (95 % CI 3.859–5.185; p < 0.001). Anal stenosis was successfully treated in 100.0 % (n = 8/8) of cases with the mean VAS score dropping from 6.500 ± 1.309 SD to 2.125 ± 1.808 SD (95 % CI 2.831–5.919; p < 0.001). Anal inflammation improved in 60.0 % (n = 9/15) of patients and the mean VAS score dropped from 6.006 ± 2.138 SD to 1.542 ± 1.457 SD (95 % CI 3.217–4.964; p < 0.001). The response after scar tissue treatment was 94 % (n = 17/18) of patients with a mean VAS decreasing from 6.117 ± 2.006 SD to 1.712 ± 1.697 SD (95 % CI 3.812–4.974; p < 0.001). Success for topical nifedipine was between 13 and 25 % of patients depending on the clinical presentation. Anal dilation was successful in 75 % of patients, while Anesthetic and steroid infiltration in 23–54 % of patients depending on the clinical presentation. Staple removal was successful in 77 % of patients, and scar excision with mucosal suturing in 94 % of patients.

Conclusions

Our retrospective study suggests that most patients with chronic anal pain after SH may be cured with treatment by applying a stepwise approach from the least to the most invasive treatment.

     

Early Trends in Bronchoscopic Lung Volume Reduction: A Systematic Review and Meta-analysis of Efficacy Parameters

Introduction

The goal of our systematic review and meta-analysis is to examine the therapeutic effectiveness of bronchoscopic lung volume reduction (BLVR), and to compare it with medical management and lung volume reduction surgery.

Methods

Variables of interest were absolute change in FEV1, 6MWT, and SGRQ. Meta-analysis was performed for the BLVR modalities with ≥3 trials. Of the 18 shortlisted publications, only valves (four trials; n = 159) and coils (six trials; n = 194) qualified for meta-analysis. To avoid redundant reporting for valves, only the data for intact fissure subjects were analyzed. Outcome data are presented as the mean difference from baseline with 95% confidence interval at 6-months follow-up.

Results

For BLVR using valves, the pooled mean difference (PMD) for FEV1 was 0.146 L (95% CI 0.111–0.181; p < 0.001), 6MWT was 45.225 meters (95% CI 26.954–63.495; p < 0.001), and SGRQ was ?8.825 points (95% CI ?14.824 to ?2.825; p = 0.004). All the PMDs were statistically significant and higher than their respective minimal clinically important difference (MCID). For BLVR using coils, the PMD for FEV1 was 0.080 L (95% CI 0.057–0.104; p < 0.001), 6MWT was 45.320 meters (95% CI 28.040–62.600; p < 0.001), and SGRQ was ?10.570 points (95% CI ?13.299 to ?7.841; p < 0.001). All three variables showed statistically significant PMDs but that for FEV1 was smaller than the MCID. Data from BLVR modalities with <3 major publications are reviewed in the discussion section.

Conclusions

BLVR offers early promise in the palliation of advanced emphysema. Better characterization of patients to identify phenotypes that will derive sustained benefit is needed.

     

Surgical Resection for Pulmonary Carcinoid: Long-Term Results of Multicentric Study—The Importance of Pathological N Status,More Than We Thought

Background

Histological subdivision into typical (TC) and atypical (AC) is crucial for treatment and prognosis of lung carcinoids but can be also very challenging, even for experts. In this study, we aimed to strengthen or reduce the prognostic value of several pathological, clinical, or per-operative factors some of which are still controversial.

Methods

We retrospectively reviewed clinical records related to 195 patients affected by TC (159) or AC (36) surgically treated between 2000 and 2014, in three different centers. Survival and subtypes comparison analyses were performed to identify potential prognostic factors.

Results

TCs showed a lower rate of nodal involvement than ACs (N0 = 94.9%; N1 = 1.9%; N2 = 3.2% in typical and N0 = 63.8%; N1 = 16.6%; N2 = 19.4% in atypical carcinoids, respectively, p < 0.0001). Long-term oncological results of resected carcinoids were significantly better in TCs than ACs with higher 5- and 10-year overall survival rates (97.2 and 88.2% vs. 77.9 and 68.2%, respectively; p = 0.001) and disease-free survival rates (98.2 and 90.3% in typical and 80.8 and 70.7% atypical carcinoids, respectively; p = 0.001). Risk factors analysis revealed that AC subtype [HR 4.33 (95% CI 1.72–8.03), p = 0.002], pathological nodal involvement [HR 3.05 (95% CI 1.77–5.26), p < 0.0001], and higher SUV_max [HR 4.33 (95% CI 1.03–7.18), p = 0.002] were independently and pejoratively associated with overall survival. Factors associated with a higher risk of recurrence were AC subtype [HR 6.13 (95% CI 1.13–18.86), p = 0.002]; nodal involvement [HR 5.48 (95% CI 2.85–10.51), p < 0.0001]; higher Ki67 expression level [HR 1.09 (95% CI 1.01–1.20), p = 0.047]; and SUV_max [HR 1.83 (95% CI 1.04–3.23), p = 0.035].

Conclusion

Surgery for lung carcinoids allows satisfactory oncological results which mainly depend on carcinoid subtype dichotomy, pathological nodal status, and SUV_max.