Long-term efficacy of implantable cardiac resynchronization therapy plus defibrillator for primary prevention of sudden cardiac death in patients with mild heart failure: an updated meta-analysis

Previous studies of implantable cardiac resynchronization therapy plus defibrillator (CRT-D) therapy used for primary prevention of sudden cardiac death have suggested that CRT-D therapy is less effective in patients with mild heart failure and a wide QRS complex. However, the long-term benefits are variable. We performed a meta-analysis of randomized trials identified in systematic searches of MEDLINE, EMBASE, and the Cochrane Database. Three studies (3858 patients) with a mean follow-up of 66 months were included. Overall, CRT-D therapy was associated with significantly lower all-cause mortality than was implantable cardioverter defibrillator (ICD) therapy (OR, 0.78; 95 % CI, 0.63–0.96; P = 0.02; I ² = 19 %). However, the risk of cardiac mortality was comparable between two groups (OR, 0.74; 95 % CI, 0.53–1.01; P = 0.06). CRT-D treatment was associated with a significantly lower risk of hospitalization for heart failure (OR, 0.67; 95 % CI, 0.50–0.89; P = 0.005; I ² = 55 %). The composite outcome of all-cause mortality and hospitalization for heart failure was also markedly lower with CRT-D therapy than with ICD treatment alone (OR, 0.67; 95 % CI, 0.57–0.77; P < 0.0001; I ² = 0 %). CRT-D therapy decreased the long-term risk of mortality and heart failure events in patients with mild heart failure with a wide QRS complex. However, long-term risk of cardiac mortality was similar between two groups. More randomized studies are needed to confirm these findings, especially in patients with NYHA class I heart failure or patients without LBBB.     

Low blood pressure levels for fall injuries in older adults: the Health,Aging and Body Composition Study

Fall injuries cause morbidity and mortality in older adults. We assessed if low blood pressure (BP) is associated with fall injuries, including sensitivity analyses stratified by antihypertensive medications, in community-dwelling adults from the Health, Aging and Body Composition Study (N = 1819; age 76.6 ± 2.9 years; 53% women; 37% black). Incident fall injuries (N = 570 in 3.8 ± 2.4 years) were the first Medicare claims event from clinic visit (7/00–6/01) to 12/31/08 with an ICD-9 fall code and non-fracture injury code, or fracture code with/without a fall code. Participants without fall injuries (N = 1249) were censored over 6.9 ± 2.1 years. Cox regression models for fall injuries with clinically relevant systolic BP (SBP; ≤ 120, ≤ 130, ≤ 140, > 150 mmHg) and diastolic BP (DBP; ≤ 60, ≤ 70, ≤ 80, > 90 mmHg) were adjusted for demographics, body mass index, lifestyle factors, comorbidity, and number and type of medications. Participants with versus without fall injuries had lower DBP (70.5 ± 11.2 vs. 71.8 ± 10.7 mmHg) and used more medications (3.8 ± 2.9 vs. 3.3 ± 2.7); all P < 0.01. In adjusted Cox regression, fall injury risk was increased for DBP ≤ 60 mmHg (HR = 1.25; 95% CI 1.02–1.53) and borderline for DBP ≤ 70 mmHg (HR = 1.16; 95% CI 0.98–1.37), but was attenuated by adjustment for number of medications (HR = 1.22; 95% CI 0.99–1.49 and HR = 1.12; 95% CI 0.95–1.32, respectively). Stratifying by antihypertensive medication, DBP ≤ 60 mmHg increased fall injury risk only among those without use (HR = 1.39; 95% CI 1.02–1.90). SBP was not associated with fall injury risk. Number of medications or underlying poor health may account for associations of low DBP and fall injuries.     

Fostamatinib,an oral spleen tyrosine kinase inhibitor,in the treatment of rheumatoid arthritis: a meta-analysis of randomized controlled trials

Fostamatinib is a selective inhibitor of spleen tyrosine kinase which has a role in the pathogenesis of RA. Multiple RCTs have been performed to study the effects of fostamatinib. The objective of this study was to perform a meta-analysis to analyze the efficacy and safety of fostamatinib in the management of RA. We searched PubMed, EMBASE and Cochrane CENTRAL through 11/9/15. Random effect model was used to estimate odds ratio (OR) and 95 % confidence interval. We measured outcomes with efficacy analysis using ACR20/50/70 response criteria and safety with adverse events. Five studies were included in the meta-analysis with total of 2105 patients including 1419 in fostamatinib group and 686 in placebo. Fostamatinib was effective in achieving ACR20, ACR50 and ACR70 responses compared to placebo (48 vs. 32.8 %, OR 1.86, 95 % CI 1.32–2.62, P = 0.0004, I ² 63 %; 26.4 vs. 12.5 %, OR 2.50, 95 % CI 1.93–3.23, P < 0.00001, I ² 0 % and 12.7 vs. 4.4 %, OR 3.00, 95 % CI 1.99–4.51, P < 0.00001, I ² 0 %, respectively). Response to fostamatinib was rapid and significant effect on ACR20 response was seen by week 1 (OR 3.70, 95 % CI 2.33–5.87, P < 0.00001, I ² 42 %). Safety analysis showed an increased risk of infection (OR 1.59, 95 % CI 1.2–2.11; P = 0.001; I ² 0 %), diarrhea (OR 3.54; 95 % CI 2.43–5.16; P < 0.00001; I ² 2 %), hypertension (OR 2.55, 95 % CI 1.54–4.22, P = 0.0003; I ² 42 %) and neutropenia (OR 5.68, 95 % CI 1.97–16.42, P = 0.001, I ² 35 %) and showed a trend toward the increase in ALT ≥3 times ULN (OR 1.76, 95 % CI 0.99–3.13; P = 0.05; I ² 0 %). This meta-analysis concludes that fostamatinib has moderate effect in the treatment of RA with mostly mild-to-moderate adverse events and dose-dependent, transient neutropenia and hypertransaminasemia.     

Poor prognosis of young patients with colorectal cancer: a retrospective study

Purpose

The present study aimed to explore the survival outcomes of patients with colorectal cancer (CRC) aged 35 years and younger.

Methods

This retrospective cohort study included a total of 995 patients with CRC treated between January 2003 and September 2011. The patients were assorted into the young (aged 18–35 years) and older (aged 36–75 years) groups. The clinical characteristics and survival outcomes of the patients in the young group were compared with those of the patients in the older group for evaluation.

Results

Compared with the older group, a significantly higher number of patients in the young group had right-sided colon cancer (30.9 vs. 19.6%, P = 0.026), high histologic grade tumor (14.7 vs. 6.4%, P = 0.021), and stage III disease (50.0 vs. 35.5%, P = 0.016). In stage III disease, compared with the older group, the patients in the young group had worse survival outcome in terms of 5-year overall survival (OS, P = 0.007), cancer-specific survival (CSS, P = 0.010), and disease-free survival (DFS, P = 0.039). Multivariate analysis revealed that age ≤35 years was an independent risk factor in terms of 5-year OS (hazard ratio [HR] = 1.68; 95% confidence interval [CI]: 1.12–2.54; P = 0.012), CSS (HR = 1.74; 95% CI: 1.15–2.65; P = 0.009), and DFS (HR = 1.58; 95% CI: 1.06–2.35; P = 0.024).

Conclusions

The young patients with CRC aged 35 years and younger had worse prognosis compared with older patients, especially for stage III disease.

     

The Value of the Electrocardiogram for Evaluating Prognosis in Patients with Idiopathic Pulmonary Arterial Hypertension

Background

Association between electrocardiography (ECG) features and right ventricular anatomy and physiology has been established. This study is aimed to identify the value of 12-lead ECG in evaluating prognosis of patients with idiopathic pulmonary arterial hypertension (IPAH).

Method

194 patients with newly diagnosed IPAH were included in this study. Correlations between electrocardiography variables and hemodynamics were assessed. Univariate and multivariable cox regression analysis were performed to identify ECG variables for predicting all-cause mortality in IPAH.

Results

Partial correlation analysis showed that P wave amplitude in lead II correlated with the mean pulmonary arterial pressure (mPAP, r = 0.349, p ≤ 0.001) and cardiac index (CI, r = ?0.224, p = 0.002); R wave amplitude in V1 correlated with mPAP (r = 0.359, p ≤ 0.001); S wave amplitude in V6 correlated with mPAP (r = 0.259, p = 0.030) and CI (r = ?0.220, p = 0.003). P wave amplitude in lead II (HR 1.555, p = 0.033) and R wave amplitude in lead aVR (HR 5.058, p < 0.001) were the independent predictors of all-cause mortality. Kaplan–Meier survival curves showed patients with a p ≥ 0.25 mv in lead II, and R ≥ 0.4 mv in lead aVR had lower 3-year survival (55 vs. 91%, p < 0.001).

Conclusion

Specific lead-12 ECG features could reflect right ventricular overload hemodynamics, and are useful to evaluate prognosis of patients with IPAH.

     

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

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

Toe–brachial index as a predictor of cardiovascular disease and all-cause mortality in people with type 2 diabetes and microalbuminuria

Aims/hypothesis

The study aimed to evaluate toe–brachial index (TBI) and ankle–brachial index (ABI) as determinants of incident cardiovascular disease (CVD) and all-cause mortality in people with type 2 diabetes and microalbuminuria.

Methods

This was a prospective study including 200 participants. Unadjusted and adjusted (traditional risk factors and additional inclusion of N-terminal pro-brain natriuretic peptide [NT-proBNP] and coronary artery calcification) Cox regression models were performed. C statistics and relative integrated discrimination improvement (rIDI) evaluated risk prediction improvement.

Results

Median follow-up was 6.1 years; 40 CVD events and 26 deaths were recorded. Lower TBI was associated with increased risk of CVD (HR per 1 SD decrease: 1.55 [95% CI 1.38, 1.68]) and all-cause mortality (1.41 [1.22, 1.60]) unadjusted and after adjustment for traditional risk factors (CVD 1.50 [1.27, 1.65] and all-cause mortality 1.37 [1.01, 1.60]). Lower ABI was a determinant of CVD (1.49 [1.32, 1.61]) and all-cause mortality (1.37 [1.09, 1.57]) unadjusted and after adjustment for traditional risk factors (CVD 1.44 [1.23, 1.59] and all-cause mortality 1.39 [1.07, 1.60]). After additional adjustment for NT-proBNP and coronary artery calcification, lower TBI remained a determinant of CVD (p = 0.023). When TBI was added to traditional risk factors, the AUC increased significantly for CVD, by 0.063 (95% CI 0.012, 0.115) from 0.743 (p = 0.016), but not for all-cause mortality; adding ABI did not improve the AUC significantly. The rIDI for TBI was 46.7% (p < 0.001) for CVD and 46.0% (p = 0.002) for all-cause mortality; for ABI, the rIDI was 51.8% (p = 0.004) for CVD and 53.6% (p = 0.031) for all-cause mortality.

Conclusions/interpretation

Reduced TBI and ABI were associated with increased risk of CVD and all-cause mortality, independent of traditional risk factors in type 2 diabetes, and improved prognostic accuracy.

     

Final analysis of the randomised PEAK trial: overall survival and tumour responses during first-line treatment with mFOLFOX6 plus either panitumumab or bevacizumab in patients with metastatic colorectal carcinoma

Purpose

To report planned final overall (OS) and progression-free survival (PFS) analyses from the phase II PEAK trial (NCT00819780).

Methods

Patients with previously untreated, KRAS exon 2 wild-type (WT) metastatic colorectal cancer (mCRC) were randomised to mFOLFOX6 plus panitumumab or bevacizumab. The primary endpoint was PFS; secondary endpoints included OS, objective response rate, duration of response (DoR), time to response, resection and safety. Treatment effect by tumour RAS status was a prespecified objective. Exploratory analyses included early tumour shrinkage (ETS) and depth of response (DpR).

Results

One hundred seventy patients had RAS WT and 156 had RAS WT/BRAF WT mCRC. Median PFS was longer for panitumumab versus bevacizumab in the RAS WT (12.8 vs 10.1 months; hazard ratio (HR) = 0.68 [95% confidence intervals (CI) = 0.48–0.96]; p = 0.029) and RAS WT/BRAF WT (13.1 vs 10.1 months; HR = 0.61 [95% CI = 0.42–0.88]; p = 0.0075) populations. Median OS (68% OS events) for panitumumab versus bevacizumab was 36.9 versus 28.9 months (HR = 0.76 [95% CI = 0.53–1.11]; p = 0.15) and 41.3 versus 28.9 months (HR = 0.70 [95% CI = 0.48–1.04]; p = 0.08), in the RAS WT and RAS WT/BRAF WT populations, respectively. Median DoR (11.4 vs 9.0 months; HR = 0.59 [95% CI = 0.39–0.88]; p = 0.011) and DpR (65.0 vs 46.3%; p = 0.0018) were improved in the panitumumab group. More panitumumab patients experienced ≥30% ETS at week 8 (64 vs 45%; p = 0.052); ETS was associated with improved PFS/OS. No new safety signals occurred.

Conclusions

First-line panitumumab + mFOLFOX6 increases PFS versus bevacizumab + mFOLFOX6 in patients with RAS WT mCRC.

     

Association between high-sensitivity C-reactive protein and hyperuricemia

The aim of the study was to examine the cross-sectional association between high-sensitivity C-reactive protein (hsCRP) and hyperuricemia (HU). The hsCRP was measured by latex turbidity method. Uric acid was detected on Beckman Coulter AU 5800. HU was defined as uric acid ≥416 μmol/L for the male population and ≥360 μmol/L for the female population. A multivariable logistic analysis model was applied to test the association after adjusting for a number of potential confounding factors. A total of 1935 subjects were included in this study. According to the multivariable regression model, the relative odds of the prevalence of HU were increased by 0.56 times in the third quintile (OR 1.56, 95 % CI 1.03–2.38, P = 0.04), 0.55 times in the fourth quintile (OR 1.55, 95 % CI 1.01–2.36, P = 0.04) and 0.96 times in the fifth quintile (OR 1.96, 95 % CI 1.29–2.98, P < 0.01) of hsCRP comparing with the lowest quintile, and P for trend was smaller than 0.01. In the male population, a positive association existed in the highest quintile of hsCRP (OR 1.66, 95 % CI 1.04–2.66, P = 0.04), and P for trend was 0.07. In the female population, the multivariable-adjusted ORs (95 % CI) of HU in the fourth and fifth quintile of hsCRP were 3.02 (95 % CI 1.09–8.35, P = 0.03) and 3.66 (95 % CI 1.36–9.89, P = 0.01), respectively, and P for trend was smaller than 0.01. The findings of this cross-sectional study suggest that the hsCRP level is positively associated with the prevalence of HU. Level of evidence Cross-sectional study, Level III.     

Renal function on admission modifies prognostic impact of diuretics in acute heart failure: a propensity score matched and interaction analysis

Although intravenous diuretics have been mainstay drugs in patients with acute heart failure (AHF), they have been suggested to have some deleterious effects on prognosis. We postulated that renal function may modify their deleterious effects in AHF patients. The study population consisted of 1094 AHF patients from three hospitals. Renal dysfunction (RD) was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² on admission, and the cohort was divided into a high-dose furosemide (≥100 mg/48 h) and low-dose furosemide group according to the amount of intravenous furosemide used within 48 h from admission. In the whole cohort, in-hospital mortality rate was higher in the high-dose furosemide group than the low-dose furosemide group (12.5 vs. 6.6 %, respectively, P = 0.001). However, this difference in the in-hospital mortality rates was significant only in the RD subgroup (15.6 vs. 7.0 %, respectively, P < 0.001), and not in the non-RD subgroup (2.5 vs. 5.9 %, respectively, P = 0.384). Propensity score-matched analysis was performed to evaluate the impact of high-dose furosemide on prognosis. After propensity score matching, high-dose furosemide was not associated with in-hospital mortality (OR 1.25, 95 % CI 0.73–2.16, P = 0.408). However, there was a qualitative difference in OR for in-hospital mortality between AHF with RD (OR 1.77, 95 % CI 0.96–3.28, P = 0.068) and without RD (OR 0.23, 95 % CI 0.05–1.10, P = 0.064), and there was a significant interaction between eGFR and prognostic impact of high-dose furosemide (P for OR interaction = 0.013). An inverse relationship was observed between eGFR and OR for in-hospital death in the group treated with high-dose furosemide (decreasing OR with better eGFR). The deleterious effect of diuretics was significantly modified with renal function in AHF. This association may be one reason for poorer prognosis of AHF patients complicated with renal impairment.     

Independent risk factors for mortality in critically ill patients with candidemia on Italian Internal Medicine Wards

Candida is an increasing cause of bloodstream infection and is associated with significant morbidity and mortality. The aim of our study is to analyze risk factors for short-term mortality in patients with bloodstream Candida spp. infections admitted to Internal Medicine Wards (IMWs). This was a retrospective case–control study between January 2012 and December 2014 from four University Hospitals in Italy, where patients with candidemia dying within 30 days from diagnosis were matched to control cases with candidemia who survived in the same period of time. Two-hundred and fifty cases of candidemia were registered during the 36 months of enrollment. Among these, 112 patients died (45%) within 30 days from the first blood culture’s positivity for Candida spp. At multivariate analysis, septic shock [odds ratio (95% CI) = 2.919 (1.62–5.35), p < 0.001] and concomitant chronic kidney failure [odds ratio (95% CI) = 2.296 (1.07–5.12), p = 0.036] were independent predictors of mortality. Low-dose chronic steroid therapy was protective [odds ratio (95% CI) = 0.461 (0.25–0.83), p = 0.011).     

The JAK2 46/1 haplotype (GGCC) in myeloproliferative neoplasms and splanchnic vein thrombosis: a pooled analysis of 26 observational studies

Numbers of observational studies suggest that the JAK2 46/1 (GGCC) haplotype may increase the risk of myeloproliferative neoplasms (MPNs) and splanchnic vein thrombosis (SVT), but the results remain controversial. We aimed to examine the association between the JAK2 46/1 haplotype and risk of MPNs and SVT by conducting a meta-analysis. PubMed, EMBASE, Cochrane Library, CBM, and CNKI databases were searched to identify eligible studies without restrictions and by reviewing reference lists of obtained articles. Both fixed and random-effects models were used to calculate the summary risk estimates. We identified 26 observational studies of the JAK2 46/1 haplotype and risk of MPNs and SVT involving 8,561 cases and 7,434 participants. In the overall analysis, it was found that the JAK2 46/1 haplotype significantly elevated the risk of MPNs (rs10974944: C vs T: odds ratio (OR)?=?2.19, 95 % confidence interval (CI)?=?1.86–2.57, P?<?0.0001; CC vs TT: OR?=?4.63, 95 % CI?=?3.32–6.47, P?<?0.0001; CT vs TT: OR?=?2.49, 95 % CI?=?2.11–2.95, P?<?0.0001; (CC?+?CT) vs TT: OR?=?2.92, 95 % CI?=?2.51–3.39, P?<?0.0001; rs12343867: C vs T: OR?=?1.88, 95 % CI?=?1.59–2.22, P?<?0.0001; CC vs TT: OR?=?3.16, 95 %CI?=?2.14–4.65, P?<?0.0001; CT vs TT: OR?=?2.04, 95 % CI?=?1.51–2.74, P?<?0.0001; (CC?+?CT) vs TT: OR?=?2.25, 95 % CI?=?1.73–2.95, P?<?0.0001) and SVT (C vs T: OR?=?1.27, 95 % CI?=?1.06–1.52, P?=?0.011; CC vs TT: OR?=?2.33, 95 % CI?=?1.42–3.81, P?=?0.001; (CC?+?CT) vs TT: OR?=?1.25, 95 % CI?=?1.02–1.53, P?=?0.034). There was no evidence of a significant association between the rs12343867 and the risk of SVT in the genetic model (CT vs TT: OR?=?1.01, 95 % CI?=?0.80–1.29, P?=?0.906). This meta-analysis provides new evidence supporting the conclusion that the JAK2 46/1 haplotype enrichment is significantly associated with the development of MPNs and SVT in these patients.     

CTLA-4 +49A/G gene polymorphism and type 1 diabetes mellitus in the Chinese population: a meta-analysis of 2238 subjects

Previous studies reported that cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) +49A/G gene polymorphism is correlated with type 1 diabetes mellitus (T1DM) risk. However, their results remain disputable. This study aims to discuss the relationship between CTLA-4 +49A/G gene polymorphism and T1DM in a Chinese population. The current meta-analysis involved 2238 participants from seven individual studies. The pooled odds ratio (OR) and its corresponding 95 % confidence interval (95 % CI) were assessed by the random- or fixed-effects model. A significant relationship between CTLA-4 +49A/G gene polymorphism and T1DM was detected under allelic (OR: 1.84, 95 % CI: 1.62–2.10, P?<?0.00001), dominant (OR: 1.152, 95 % CI: 1.062–1.249, P?=?0.001), recessive (OR: 1.631, 95 % CI: 1.443–1.844, P?<?0.00001), and additive (OR: 1.292, 95 % CI: 1.224–1.363, P?<?0.00001) genetic models. A significant relationship exists between CTLA-4 +49A/G gene polymorphism and increased T1DM risk in the Chinese population. Individuals having the G allele of CTLA-4 +49A/G gene polymorphism have a higher risk for T1DM in the Chinese population.     

Open surgery (OS) versus endovascular aneurysm repair (EVAR) for hemodynamically stable and unstable ruptured abdominal aortic aneurysm (rAAA)

Endovascular aneurysm repair (EVAR) is an alternative treatment for ruptured abdominal aortic aneurysms (rAAA) in hemodynamically (hd) stable patients. Treatment for patients with hd-unstable rAAA remains controversial. The aim of this study was to compare the outcomes of EVAR and open surgery (OS) in hd-stable and hd-unstable rAAA patients using meta-analysis. The first part of this study included 48 articles that reported the treatment outcomes of rAAA managed with EVAR (n = 9610) and OS (n = 93867). The second part, which is the focus of this study, included 5 out of 48 articles, which further reported treatment results in hd-stable (n = 198) and hd-unstable (n = 185) patients. When heterogeneity among the groups was observed, a random-effects model was used to calculate the adjusted odds ratios (OR) or in cases of non-heterogeneity, a fixed-effects model analysis was employed. In the first part of this study, the in-hospital mortality rate was found to be lower in the EVAR group than in the OS group (29.9 vs 40.8 %; OR 0.59; 95 % CI 0.52–0.66; P < 0.01). In the second part of this study, 383 patients from 5 articles were included: 152 patients were treated by EVAR, and 231 were treated by OS. The total mortality was 147/383 (38.4 %), while the mortality of the EVAR group and the OS group was 25.7 % (39/152) and 46.8 % (108/231), respectively. In the hd-stable group, the in-hospital mortality after EVAR was significantly lower than that after OS [18.9 % (18/95) vs 28.2 % (29/103); OR 0.47; 95 % CI 0.22–0.97; P = 0.04]. For the hd-unstable rAAA patients, the in-hospital mortality after EVAR was significantly lower than that after OS [36.8 % (21/57) vs 61.7 % (79/128); OR 0.40; 95 % CI 0.20–0.79; P < 0.01]. This study indicated that compared with OS, EVAR in hd-unstable rAAA patients is associated with improved outcomes. Available publications are currently limited; thus, the best treatment strategy for this subgroup of patients remains unclear. Further clinical studies are needed to provide more detailed data, such as the shock index and long-term results.     

Clinical outcome of left ventricular multipoint pacing versus conventional biventricular pacing in cardiac resynchronization therapy: a systematic review and meta-analysis

Cardiac resynchronization therapy (CRT) is an effective treatment for selected patients with systolic heart failure. Unlike conventional biventricular pacing (BIP), the left ventricular multipoint pacing (MPP) can increase the number of left ventricular pacing sites via a quadripolar lead positioned in the coronary sinus. This synthetic study was conducted to integratively and quantitatively evaluate the clinical outcome of MPP in comparison with BIP. We systematically searched the databases of EMBASE, Ovid medline, and Cochrane Library through May 2018 for studies comparing the clinical outcome of MPP with BIP in the patients who accepted CRT. Hospitalization for reason of heart failure, left ventricular eject fraction (LVEF), CRT response, all-cause morbidity, and cardiovascular death rate was collected for meta-analysis. A total of 11 studies with 29,606 participants were included in this meta-analysis. Compared with BIP group, MPP decreased heart failure hospitalization (OR, 0.41; 95% CI, 0.33 to 0.50; P <?0.00001), improved LVEF (mean difference, 4.97; 95% CI, 3.11 to 6.83; P <?0.00001), increased CRT response (OR, 3.64; 95% CI, 1.68 to 7.87; P?=?0.001), and decreased all-cause morbidity (OR, 0.41; 95% CI, 0.26–0.66; P?=?0.0002) and cardiovascular death rate (OR, 0.21; 95% CI, 0.11–0.40; P <?0.00001). The published literature demonstrates that MPP was more effective than BIP in the heart failure patients who accepted cardiac resynchronization therapy.     

The Association Between Receipt of Guideline-Concordant Long-Term Opioid Therapy and All-Cause Mortality

Purpose

For patients receiving long-term opioid therapy (LtOT), the impact of guideline-concordant care on important clinical outcomes—notably mortality—is largely unknown, even among patients with a high comorbidity and mortality burden (e.g., HIV-infected patients). Our objective was to determine the association between receipt of guideline-concordant LtOT and 1-year all-cause mortality.

Methods

Among HIV-infected and uninfected patients initiating LtOT between 2000 and 2010 through the Department of Veterans Affairs, we used Cox regression with time-updated covariates and propensity-score matched analyses to examine the association between receipt of guideline-concordant care and 1-year all-cause mortality.

Results

Of 17,044 patients initiating LtOT between 2000 and 2010, 1048 patients (6%) died during 1 year of follow-up. Patients receiving psychotherapeutic co-interventions (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.51–0.75; P?<?0.001) or physical rehabilitative therapies (HR 0.81; 95% CI 0.67–0.98; P?=?0.03) had a decreased risk of all-cause mortality compared to patients not receiving these services, whereas patients prescribed benzodiazepines concurrent with opioids had a higher risk of mortality (HR 1.39; 95% CI 1.12–1.66; P?<?0.001). Among patients with a current substance use disorder (SUD), those receiving SUD treatment had a lower risk of mortality than untreated patients (HR 0.47; 95% CI 0.32–0.68; P?=?< 0.001). No association was found between all-cause mortality and primary care visits (HR 1.12; 95% CI 0.90–1.26; P?=?0.32) or urine drug testing (HR 0.96; 95% CI 0.78–1.17; P?=?0.67).

Conclusions

Providers should use caution in initiating LtOT in conjunction with benzodiazepines and untreated SUDs. Patients receiving LtOT may benefit from multi-modal treatment that addresses chronic pain and its associated comorbidities across multiple disciplines.

     

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.

     

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 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.     

Identifying Subpopulations with Distinct Response to Treatment Using Plasma Biomarkers in Acute Heart Failure: Results from the PROTECT Trial

Background

Over the last 50 years, clinical trials of novel interventions for acute heart failure (AHF) have, with few exceptions, been neutral or shown harm. We hypothesize that this might be related to a differential response to pharmacological therapy.

Methods

We studied the magnitude of treatment effect of rolofylline across clinical characteristics and plasma biomarkers in 2033 AHF patients and derived a biomarker-based responder sum score model. Treatment response was survival from all-cause mortality through day 180.

Results

In the overall study population, rolofylline had no effect on mortality (HR 1.03, 95% CI 0.82–1.28, p = 0.808). We found no treatment interaction across clinical characteristics, but we found interactions between several biomarkers and rolofylline. The biomarker-based sum score model included TNF-R1α, ST2, WAP four-disulfide core domain protein HE4 (WAP-4C), and total cholesterol, and the score ranged between 0 and 4. In patients with score 4 (those with increased TNF-R1α, ST2, WAP-4C, and low total cholesterol), treatment with rolofylline was beneficial (HR 0.61, 95% CI 0.40–0.92, p = 0.019). In patients with score 0, treatment with rolofylline was harmful (HR 5.52, 95% CI 1.68–18.13, p = 0.005; treatment by score interaction p < 0.001). Internal validation estimated similar hazard ratio estimates (0 points: HR 5.56, 95% CI 5.27–7–5.87; 1 point: HR 1.31, 95% CI 1.25–1.33; 2 points: HR 0.75, 95% CI 0.74–0.76; 3 points: HR 1.13, 95% CI 1.11–1.15; 4 points, HR 0.61, 95% CI 0.61–0.62) compared to the original data.

Conclusion

Biomarkers are superior to clinical characteristics to study treatment heterogeneity in acute heart failure.