Survivin expression and its potential clinical significance in gastrointestinal stromal sarcoma

This study was designed to determine the level of survivin expression and its clinical significance as a prognostic factor in gastrointestinal stromal sarcoma (GIST). Twenty patients (12 males and 8 females) ranging in age from 25 to 72, with a median age of 53 were evaluated. Failure of TKI treatment was higher in the survivin-positive group (p = 0.06). The rate of metastasis was significantly higher in the survivin positive group vs. the negative group (80% vs. 30%, p = 0.18). The median overall survival (OS) time was 114 (range 29–199) months, and the median disease-free survival (DFS) time was 88 (range 40–135) months. The median progression-free survival (PFS) time was 40 (range 24–55) months. Further, a comparison of patients with survivin positive versus negative tumors, revealed no significant difference for OS, DFS, and PFS (p = 0.45, p = 0.19, p = 0.55, respectively), number of mitoses in 50 HPF (p = 0.14), and tumor size (p = 0.94).In conclusion, survivin was highly expressed in GISTs, although we found no correlation between survivin expression and PFS, DFS and OS, survivin may be a predictive marker in GISTs for disease progression. We believe that additional studies are warranted to determine the clinical significance of survivin expression as a prognostic or predictive marker in patients with GIST.     

Prognostic importance of markers for inflammation,angiogenesis and apoptosis in high grade glial tumors during temozolomide and radiotherapy

IntroductionAngiogenesis, inflammation and apoptosis have an important place in the carcinogenesis of high-grade gliomas (HGG). We evaluated the postoperative levels and the prognostic importance of tumor necrosis factor-alpha (TNFα), interleukin 6 (IL6), endoglin (CD105), vascular endothelial growth factor (VEGF), M65 and M30 as markers of inflammation, angiogenesis and apoptosis in patients with HGG.Methods and resultsPostoperative pretreatment sera were collected from 44 newly diagnosed patients with HGG. The control group was also consisted of 44 healthy people. The median age of all patients with HGG was 59 (range: 30–80). Temozolomide concurrent with radiotherapy was given to 37 patients. Thereafter 24 patients received consolidation temozolomide monotherapy. Mean chemotherapy cycle was 4.2. Progression free survival and overall survival were 6 (95% CI; 5.16–6.83) and 16 months (95% CI; 13.07–18.93) respectively in patients treated with concurrent chemoradiotherapy and consolidation chemotherapy. Relative to the control cohort endoglin (p = 0.000) and TNFα (p = 0.000) levels were significantly lower; however VEGF (p = 0.030) levels were higher in the patient group. In contrast, there were no significant change in IL-6 levels and the plasma apoptotic markers M65 (p = 0.085) and M30 (p = 0.292). In separate log rank tests, these biological markers did not correlate with survival.Discussion and conclusionIn HGG, a significant decrease in endoglin and TNFα levels was observed, while VEGF levels were significantly increased postoperatively. However, with the power from this patient population, no correlation with survival was observed.     

Heavy menstrual bleeding in women treated with rivaroxaban and vitamin K antagonists and the risk of recurrent venous thromboembolism

Anticoagulants increase the risk of heavy menstrual bleeding (HMB). We sought to investigate the incidence, predictors and management of HMB in women on rivaroxaban compared to those on vitamin K antagonists (VKA). We addressed the issue as to whether HMB is associated with VTE recurrences. We performed a single-center prospective study in menstruating women aged 18–55 years treated with rivaroxaban or VKA ≥ 3 months since the index VTE episode. Seventy six women on rivaroxaban and 45 patients on VKA were included. Patients on rivaroxaban more commonly reported HMB compared with those on VKA (31 [41%] vs. 8 [18%], p = 0.009). Women treated with rivaroxaban more frequently needed interventions to reduce menstruation compared with those on VKA (29 [38%] vs. 6 [13%], p = 0.004). During the median follow-up time of 13 months, there were 8 (11%) recurrent VTE on rivaroxaban and 3 (7%) on VKA (p = 0.5). Rivaroxaban treatment predisposed to HMB (odds ratio [OR] 3.2, 95% [confidence interval] CI 1.4–8.2, p = 0.007) and the interruption of anticoagulant treatment for 2–3 days (OR 3.2, 95% CI 1.1–11.6, p = 0.033). HMB during the rivaroxaban treatment predisposed to recurrent VTE (OR 5.3, 95% CI 1.1–33.3, p = 0.038). In menstruating women following VTE, rivaroxaban is associated with a two-fold higher risk of HMB compared with VKA. HMB predisposes to recurrent VTE episode, most likely due to the short interruptions of anticoagulation.     

Prognostic and clinicopathological utility of PD-L2 expression in patients with digestive system cancers: A meta-analysis

ObjectiveProgrammed death ligand-2 (PD-L2) has been detected in various cancers. However, its prognostic value in digestive system cancers (DSCs) remains unclear. Accordingly, this meta-analysis investigated the prognostic and clinicopathological utility of PD-L2 in patients with DSCs.MethodsWe systematically searched PubMed, EMBASE, Web of Science, ClinicalTrials.gov., Scopus, and Cochrane Library databases for eligible studies up to April 30, 2020. The hazard ratio (HR), odds ratio (OR), and corresponding 95% confidence interval (CI) of the outcomes were calculated.ResultsTwenty two studies with 4886 patients were included in this meta-analysis. The pooled results showed that PD-L2 overexpression was significantly associated with poor overall survival (OS) (HR 1.470, 95% CI: 1.252–1.728, p < 0.001) and worse disease-free survival (DFS) (HR1.598, 95% CI: 1.398–1.826, p < 0.001). Subgroup analysis revealed that elevated PD-L2 was a significant prognostic indicator of worse OS in hepatocellular carcinoma (HR 1.703, 95% CI: 1.456–1.991, p < 0.001) and colorectal cancer (HR 3.811, 95% CI: 1.718–8.454, p = 0.001). Concerning clinicopathologic factors, PD-L2 overexpression was associated with lymphatic metastasis (OR 1.394., 95% CI: 1.101–1.764, p = 0.006), tumor metastasis (OR 1.599, 95% CI: 1.072–2.383, p = 0.021), and the histopathological stage (OR 0.704, 95% CI: 0.566–0.875, p = 0.002).ConclusionPD-L2 overexpression in DSCs after surgery might predict a poor prognosis, especially in hepatocellular carcinoma and colorectal cancer. Larger patient cohorts are needed to validate its prognostic role.     

Prevalence and predictors of high-on treatment platelet reactivity with ticagrelor in ACS patients undergoing stent implantation

BackgroundResidual high-on treatment platelet reactivity (HRPR) predicts outcomes and major cardiovascular events. Ticagrelor has provided pharmacological and clinical evidence of more predictable and more potent antiplatelet effect as compared to clopidogrel. However, so far, few data have investigated the prevalence and predictors of HRPR in unselected patients treated with ticagrelor, that is therefore the aim of the current study.Methods and resultsOur population is represented by 195 patients undergoing coronary stenting for ACS and receiving ASA and ticagrelor. Platelet function was assessed by multiplate impedance aggregometry (MEA) between 1 and 3 months after stenting. Main clinical features and biochemistry parameters were collected. HRPR for ticagrelor was defined for aggregation > 417 AUC after MEA-ADP stimulation. A total of 26 patients, (13.3%), displayed HRPR with ticagrelor. Older age (≥ 70 years, p = 0.002), hypertension (p = 0.02) previous myocardial infarction (p = 0.04), therapy with nitrates and beta-blockers (p = 0.02), diuretics (p = 0.03) and fasting glycaemia (p = 0.05) were associated to HRPR with ticagrelor. By multivariate analysis, age ≥ 70 years (OR [95%CI] = 4.6[1.55–13.8], p = 0.006), concomitant therapy with beta-blockers (OR [95%CI] = 3.2[1.06–9.6], p = 0.04) and platelets count (OR[95%CI] = 1.0007 [1–1.016], p = 0.05) were identified as independent predictors of HRPR with ticagrelor.ConclusionThe present study firstly demonstrates that the occurrence of HRPR in patients treated with ticagrelor is not so futile, as it was observed in 13% of patients treated with ticagrelor. Older age, beta-blockers administration and platelets count are independent predictors of HRPR with ticagrelor.     

Short term omega-3 polyunsaturated fatty acid supplementation induces favorable changes in right ventricle function and diastolic filling pressure in patients with chronic heart failure; A randomized clinical trial

IntroductionOmega-3 polyunsaturated fatty acids (omega 3-PUFAs) seem to favorably affect cardiac hemodynamics and may benefit the clinical course of heart failure patients. The role of omega 3-PUFAs supplementation on the left and right ventricular function of patients with chronic compensated systolic heart failure, under optimal treatment, was studied.Methods205 consecutive patients with chronic compensated heart failure, due to ischemic (IHF) or dilated cardiomyopathy (DCM)-NYHA classification I–III, under optimal medical treatment, were enrolled. Participants were 1-to-1 randomized on 1000 mg omega 3-PUFA supplementation or no supplementation, in a non-blinded fashion. Echocardiographic assessment was performed at first visit and 6 months after. Plasma BNP and serum creatinine levels were also measured.ResultsAs compared with the control group, BNP levels in omega 3-PUFA intervention group were 34.6% lower (p = 0.001); end-diastolic and end-systolic left ventricle dimensions were decreased by 2.5% (p = 0.047) and 3.7% (p = 0.01), maximum diameter of left atrium was decreased by 8.4% (p = 0.004), left atrium ejection fraction was ameliorated by 6.03% (p = 0.021) and as regards tissue Doppler parameters, TDI_Etv/Atv was decreased in omega 3-PUFA intervention group by 6.3% (p = 0.038). Moreover, improvement in diastolic indices was more prominent in subjects with DCM as compared to IHF patients.ConclusionOmega 3-PUFA supplementation was associated with improved left diastolic function and decreased BNP levels in patients with chronic heart failure. These findings suggest a beneficial role of omega 3-PUFAs on the hemodynamic course of patients with systolic heart failure.     

Sunitinib as a second-line therapy for advanced GISTs after failure of imatinib: relationship between efficacy and tumor genotype in Korean patients

Background To assess the efficacy and safety of sunitinib with regards to primary genotypes of tumor in Korean patients with advanced gastrointestinal stromal tumors (GISTs) who failed an initial therapy of imatinib. Methods Clinical data were collected from 88 consecutive patients with metastatic/unresectable GISTs treated with sunitinib at the Asan Medical Center. Results The median time-to-progression (TTP) and overall survival (OS) times were 7.1 months and 17.6 months, respectively. Of the 74 patients tested for KIT (exons 9, 11, 13, 17) and PDGFRA (exons 12 and 18), patients with KIT exon 9 mutant GIST (n = 11, 14.9%) showed numerically better clinical benefit (objective response or stable disease ≥24 weeks) rate (63.6% vs 46.8%, p = 0.504) and TTP (median 13.6 mo vs 6.9 mo, p = 0.631) than those with KIT exon 11 mutant GIST (n = 47, 63.5%). The most common grade 3/4 adverse events included neutropenia (34.1%), thrombocytopenia (33.0%) and hand-foot skin reaction (25.0%). Conclusions Sunitinib is an effective and safe second-line therapy for Korean patients with advanced GIST. The superior efficacy of sunitinib against GISTs with KIT exon 9 mutations appears to be similar in Korean patients to Western experience although statistical significance was not secured.     

Influence of the number and interval of treatment cycles on cytokine-induced killer cells and their adjuvant therapeutic effects in advanced non-small-cell lung cancer (NSCLC)

ObjectiveCytokine-induced killer (CIK) cells have important therapeutic effects in adoptive cell transfer (ACT) for the treatment of various malignancies. In this study, we focused on in vitro expansion of CIK cells and their clinical efficacy in combination with chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC).MethodsA total of 64 patients with NSCLC (enrolled from 2011 to 2012), including 32 patients who received chemotherapy alone or with sequential radiotherapy (conventional treatment, control group) and 32 patients who received conventional treatment and sequential CIK infusion (study group), were retrospectively analyzed. The time to progression (TTP), overall survival (OS) and adverse effects were analyzed and the phenotype of lymphocytes in CIK population was also determined by flow cytometry.ResultsAfter in vitro expansion, the average percentage of CIK cells was 26.35%. During the 54-month follow up, the median OS and TTP were significantly longer in the study group than in the control group (P = 0.0189 and P = 0.0129, respectively). The median OS of the ACT ≥ 4 cycles subgroup was significantly longer than that of the ACT < 4 cycles subgroup (P = 0.0316). The percentage of CIK cells in patients who received ≥ 4 cycles of ACT was higher than that in patients treated with < 4 cycles of ACT (P = 0.0376). Notably, CIK cells were difficult to expand in vitro in some patients after the first ACT cycle but became much easier as the treatment cycles increased monthly. Longer treatment interval negatively impacted the expansion of CIK cells.ConclusionsSystematic immune levels can be increasingly boosted by reinfusion of ACT. Conventional treatment plus CIK cells is an effective therapeutic strategy to prevent progression and prolong survival of patients with advanced NSCLC.     

Associations between binge drinking frequency and tobacco use among young adults

Tobacco use is greater among young adults who binge drink; yet there is limited research on tobacco use characteristics among different types of binge drinkers based on frequency. We aimed to characterize this relationship among young adults (18–25 years old) who used both substances in the past month (smoked ≥ 1 cigarette, and drank ≥ 1 alcoholic beverage) using an anonymous online survey. Participants (N = 1405, 65.0% male) were grouped based on binge drinking frequency and compared for tobacco use characteristics and demographics using bivariate analyses and multinomial logistic regression. Binge drinking frequency groups were: non-binge drinkers who consumed alcohol (0 days; 27.5%); occasional (1–3 days; 37.9%); intermediate (4–8 days; 21.9%); and frequent (9 + days; 12.7%) binge drinkers. Comparing each binge drinking group to non-binge drinkers: Both occasional and frequent binge drinkers smoked more cigarettes per day (p = 0.001; p = 0.002); frequent binge drinkers reported greater temptations to smoke in positive affective/social situations (p = 0.02); intermediate binge drinkers were less likely to have a tobacco abstinence goal (p = 0.03) but more likely to have made a serious tobacco quit attempt; all of the binge groups were more likely to be social smokers (all p < 0.01). Overall, we also found a high rate of smoking on binge drinking days. Individuals smoked cigarettes on 85.7% ± 32.9% of days they binge drank. Extent of binge drinking (not just prevalence) is an important factor influencing smoking characteristics in young adults.     

Shift from darbepoetin-α to continuous erythropoietin receptor activator decreases serum aluminium concentration in patients on hemodialysis

ObjectiveThe response of erythropoietic stimulating agents (ESA) in uremic patients may be associated with the changes of biochemical parameters, metal elements and inflammation status during the shift from one ESA to another.MethodWe compared changes in above mentioned factors after switching from darbepoetin-α (DPO) 20 μg weekly for 10 weeks to continuous erythropoietin receptor activator (CERA) 100 μg monthly for 10 weeks in uremic patients on hemodialysis. The haematocrit (Hct), metal elements and inflammation status are the primary outcome. Subjects included 54 patients without transfusion or bleeding or additional ESAs. Responders (IR, n = 36) were defined as patients with an increase in Hct after the swtich.ResultAlthough there was no significant difference in overall mean Hct after the switch (p = 0.135), there are significantly greater mean number of red blood cells (RBC) (p = 0.006), higher platelet numbers (p = 0.001), larger RBCs (p = 0.017) and higher creatinine (p = 0.04) and total cholesterol (T-CHOL) (p = 0.003) levels. Mean overall aluminium (Al) level decreased significantly (p = 0.001). C-reactive protein (CRP) also decreased (p = 0.016). The overall LDH increased (p = 0.049) and potassium decreased significantly (p = 0.036), which indicating active erythropoiesis. The calcium (Ca) level was significantly higher (p = 0.034) and phosphate was significantly lower (p = 0.028) after the shift. Although there was no significant increase in overall levels of parathyroid hormone (PTH) after the shift (p = 0.061), but the pre-shift and post-shift PTH level was significantly higher in IRs than in non-IRs (p = 0.003 and p = 0.027, respectively). IRs had a significantly lower initial T-CHOL (p = 0.03) and initial CRP (p = 0.012) than non-responders, which may be related to lower inflammation.ConclusionWe found the shift from DPO to CERA results in lower Al levels, a reduced inflammatory response, and an increase in RBC number and PTH level in uremic patients on hemodialysis.     

Platelet reactivity in patients with impaired renal function receiving dual antiplatelet therapy with clopidogrel or ticagrelor

BackgroundSuboptimal platelet inhibition still represents an important challenge, especially for patients undergoing percutaneous coronary interventions (PCI). Chronic kidney disease (CKD) is a common comorbidity of patients with coronary artery disease, and may potentially influence platelet reactivity. So far only few studies have assessed the role of CKD on response to dual antiplatelet therapy (DAPT) with conflicting results. Therefore, the aim of our study was to evaluate the impact of CKD on platelet function in patients treated with DAPT after a recent acute coronary syndrome (ACS) or PCI.MethodsPatients treated with DAPT, acetylsalicylic acid (ASA) + adenosine diphosphate antagonist (ADP-antagonist) such as clopidogrel or ticagrelor, for ACS or elective patients undergoing PCI were scheduled for platelet function assessment at 30–90 days post-discharge. Platelet function was assessed by whole blood impedance aggregometry (Multiplate®- Roche Diagnostics AG), high residual platelet reactivity (HRPR) was considered for ASPI test > 862 AU*min (for ASA) and ADP test values ≥ 417 AU*min (for ADP-antagonists). Chronic renal failure was defined as an estimated glomerular filtration rate of 60 mol/min/1.73m² or less, calculated by applying MDRD (Modification of Diet in renal Disease) formula.ResultsOur population included a total of 537 patients of which 308 (57.3%) received ASA and clopidogrel and 229 (42.6%) received ASA and ticagrelor. Patients with renal failure at baseline (101 out of 537, 18.8%) were older, with higher prevalence of hypertension, previous myocardial infarction and coronary artery bypass graft surgery. Moreover, they had a lower ejection fraction at baseline and were more often in therapy with diuretics, but less often with statins at admission. They had lower haemoglobin and higher glycated haemoglobin. HRPR was observed in 1.5% of patients treated with ASA with no difference according to renal function (p = 0.18). HRPR for ADP-antagonists was observed in 23.7% of patients, with no difference according to renal function (p = 0.50). This result was confirmed either with clopidogrel (31.9% versus 38%, p = 0.41) and ticagrelor (13.1% versus 10.8%, p = 0.99), also after correction for all baseline confounders (clopidogrel: adjusted OR[95%CI] = 1.26 [0.60–2.63], p = 0.54) (ticagrelor: adjusted OR[95%CI] = 0.95 [0.54–1.65], p = 0.84). The absence of association between renal function and platelet reactivity was confirmed at linear regression analysis both with clopidogrel (r = − 0.04, p = 0.52) and ticagrelor (r = 0.006, p = 0.92).ConclusionIn patients receiving DAPT, chronic renal failure did not influence ADP-mediated platelet reactivity, with both ticagrelor or clopidogrel. No influence of chronic renal failure was found on the effectiveness of ASA.     

Decline in platelet count and long-term post-PCI ischemic events: Implication of the intra-aortic balloon pump

AimsThrombocytopenia (TC) following a percutaneous coronary intervention (PCI) has been associated not only with hemorrhagic, but also with ischemic outcomes. The purpose of this study was to re-examine the relationship of TC with ischemic events at a 1-year follow-up, and investigate the possible associations.Methods and resultsWe studied a real-world, unselected population of ischemic patients undergoing PCI, totaling 861 patients-year, and divided into two groups: with TC (delta platelet count ≥ 25% from baseline to post-PCI during the hospital admission) and without TC. Compared with patients without TC, patients with TC had a higher and earlier incidence of both hemorrhagic and ischemic events. In them, the use of intra-aortic balloon pump (IABP) was ten-fold higher. In Kaplan–Meier curves assessing the contribution of both TC and IABP to outcome, IABP was a univariate detrimental factor additive to the role of TC. In a forced Cox model, the relative decline (delta) in platelet count (p = 0.05) and the use of IABP (p = 0.0001) were both associated with ischemic outcomes. After excluding all patients with IABP, the delta platelet count was no longer significantly associated with ischemic outcomes (p = 0.66). After excluding all patients with shock and all those who undergone thrombolysis, there was still a relationship (p = 0.0042) between the delta platelet count and ischemic events.ConclusionsIn this patient population the use of IABP, but not thrombocytopenia per se, is a possible primary cause of worse ischemic outcomes.     

Indirect comparison between pembrolizumab and nivolumab for the treatment of non-small cell lung cancer: A meta-analysis of randomized clinical trials

ObjectiveThe purpose of this study is to evaluate the efficacy and adverse effects of nivolumab and pembrolizumab for the treatment of advanced non-small-cell lung cancer (NSCLC) by meta-analysis.Materials and methodsThis meta-analysis of randomized controlled trials (RCTs) was performed after searching PubMed, EMBASE, and American Society of Clinical Oncology meeting abstracts, clinicaltrial gov, and Cochrane library databases. Two reviewers independently assessed the quality of the trials. Outcomes analysis was overall response rates (ORR), overall survival (OS), progression- free survival (PFS) and major adverse effects with odds ratio (OR) or hazard ratio (HR) and 95% confidence intervals (CI).ResultsResults reported from three RCTs involving 1,887 patients are included in this analysis. Indirect comparison between pembrolizumab and nivolumab in advanced NSCLC shows no statistically significant difference in ORR (OR: 1.14, 95% CI, 0.60–2.01), OS (HR: 0.98, 95% CI, 0.35–2.74) and PFS (HR: 1.12, 95% CI, 0.70–1.77). The incidence of grades ≥ 3 adverse effects is higher with pembrolizumab as compared with nivolumab (OR: 3.44, 95% CI, 1.87–6.32). There are no significant statistical differences between severe adverse effects, such as pneumonitis and hypothyroidism, of the two drugs.ConclusionsThis study has demonstrated that pembrolizumab and nivolumab have similar survival outcomes in patients with advanced NSCLC, but pembrolizumab has a higher incidence of grades ≥ 3 adverse effects than nivolumab.     

Immediate infusion-related adverse reactions to intravenous immunoglobulin in a prospective cohort of 1765 infusions

Intravenous immunoglobulin (IVIG) is increasingly recommended for many diseases apart from primary immunodeficiency diseases (PID). Although effective and safe, adverse reactions may occur. We conducted a 2-year prospective observational study in 117 patients with PID who received regular IVIG replacement therapy at a median dose of 600 mg/kg every 3 to 4 weeks to examine IVIG's adverse effects; 1765 infusions were performed (mean = 15/patient) in 75 males and 42 females (aged 3 months to 77 years) in 3 groups: ≤ 9 years (34.2%), 10–19 years (26.5%), and ≥ 20 years (39.3%). Fifty patients had common variable immunodeficiency (CVID), 11 had X-linked agammaglobulinemia (XLA), and 55 had other immune system disorders. The drugs administered were Octagam® (49.1%), Tegeline® (17.3%), Imunoglobulin® (18.6%), Flebogama® (12.9%), Vigam® (1.2%), and Kiovig® (0.4%). Immediate infusion-related adverse reactions occurred in the cases of 38 out 1765 infusions (2.15%, IC95% 1.53%–2.94%), which were classified as mild (81.6%), moderate (10.5%), or severe (7.9%). Time until reaction ranged from 10 to 240 min (mean = 85.7, median = 60). Reaction rates were similar across age groups. The most common reactions were malaise, headache, and abdominal pain. Reported severe events were tightness of the throat and seizure. All symptoms improved with temporary or complete IVIG interruption and symptomatic medications. Sixteen of 38 reactions to infusions occurred in the presence of an acute infection (p = 0.09). Tegeline® represented a greater reaction risk factor than Octagam® (p < 0.001). These results indicate that IVIG infusion can be considered a safe procedure. Low reaction incidence and few severe immediate infusion-related adverse reactions were observed.     

Statins in prevention of repeat revascularization after percutaneous coronary intervention—A meta-analysis of randomized clinical trials

Recent prospective cohort studies have shown that patients discharged on statins after percutaneous coronary intervention (PCI) are at lower risks of repeat revascularization and mortality when compared to those not on statins after discharge. However, few randomized clinical trials among post-PCI patients confirmed these beneficial effects. It is needed to evaluate the effects of post-procedural statin therapy on individual clinical outcomes to facilitate the further investigation on identifying the underlying mechanism(s). A meta-analysis of randomized clinical trials was conducted to examine the effects of statin therapy initiated after coronary angioplasty on repeat revascularization, all-cause mortality and myocardial infarction (MI). From relevant reports on Medline (from inception to October 2009), six randomized clinical trials comprising 2979 patients were included. Relative risks were evaluated for pooled data via random effect models. Compared with controls, post-PCI statin therapy was associated with a significantly decreased risk of repeat revascularization (risk ratio (RR) = 0.73, 95% confidence interval (CI), 0.55–0.98, p = 0.04), nonsignificantly decreased risks of all-cause mortality (RR = 0.88, 95% CI, 0.35–2.21, p = 0.79), MI (RR = 0.76, 95% CI, 0.49–1.18, p = 0.23), and target lesion or target vessel revascularization (RR = 0.58, 95% CI, 0.24–1.39, p = 0.22). In conclusion, statin therapy after PCI can reduce the risk of repeat revascularization. Further investigation is needed to identify the underlying mechanism(s).     

Increased self-efficacy to quit and perceived control over withdrawal symptoms predict smoking cessation following nicotine dependence treatment

AimTo examine changes in nicotine withdrawal, nicotine craving, self-efficacy to quit smoking, and perceived control over withdrawal symptoms as predictors of smoking cessation following behavioral counseling and nicotine replacement therapy in a sample of smokers.Design and settingThe data were ascertained from a randomized effectiveness trial comparing nicotine patch to nicotine lozenge. Predictors of smoking cessation were assessed at baseline and 5 weeks post-baseline, and 24-hour point prevalence abstinence, biochemically confirmed, was assessed at the end-of-treatment (week 15) and 6 months after a target quit date (week 27).Participants642 treatment-seeking smokers randomized to 12 weeks of nicotine patch or nicotine lozenge.FindingsParticipants who showed a greater increase in self-efficacy to quit smoking (OR = 1.09, 95% CI: 1.02–1.16, p = .01) and perceived control over withdrawal symptoms (OR = 1.02, 95% CI: 1.00–1.04, p = .05) were significantly more likely to have quit smoking at week 15. Participants who showed a greater increase in self-efficacy to quit smoking (OR = 1.04, 95% CI: 1.01–1.06, p = .01) were significantly more likely to have quit smoking at week 27. Changes in withdrawal symptoms and craving were not related to week 15 or week 27 abstinence rates.ConclusionsThe results highlight two relatively under-studied potential psychological predictors of abstinence following treatment for nicotine dependence. Behavioral counseling interventions to promote smoking cessation should help smokers develop confidence in their ability to quit smoking and increase their sense of control over withdrawal symptoms to increase their chances for cessation.     

Distinct cognitive performance and patterns of drug use among early and late onset cocaine users

IntroductionAdolescence is a crucial period for neurodevelopment, but few studies have investigated the impact of early cocaine use on cognitive performance and patterns of substance use.MethodsWe evaluated 103 cocaine dependent inpatients divided in two groups: early-onset users (EOG; n = 52), late-onset users (LOG; n = 51), and 63 healthy controls. Neuropsychological functioning was evaluated using Digits Forward (DF) and Backward (DB), Trail Making Test (TMT), Stroop Color Word Test (SCWT), Controlled Oral Word Association Test (COWAT), Wisconsin Card Sorting Test (WCST), Rey Osterrieth Complex Figure Test (ROCFT), Frontal Assessment Battery (FAB), and Iowa Gambling Test (IGT). Use of alcohol and other drugs was assessed with the Addiction Severity Index (ASI-6).ResultsAnalyses of covariance controlling for age, IQ and years of education showed that EOG presented worse performance in attention span (DF, p = 0.020), working memory (DB, p = 0.001), sustained attention (WCST, p = 0.030), declarative memory (ROCFT, p = 0.031) and general executive functioning (FAB, p = 0.003) when compared with the control group. LOG presented impairments on divided attention (TMT, p = 0.003) and general executive functioning (FAB, p = 0.001) in relation to the control group. EOG presented higher use of cannabis and alcohol than LOG (p ≤ 0.001).ConclusionEarly-onset cocaine users display more pronounced neuropsychological alterations than controls, as well as a greater frequency of polydrug consumption than LOG. The prominent cognitive deficits in EOG probably reflect the deleterious interference of cocaine use with early stages of neurodevelopment. This may be related to more severe clinical characteristics of substance disorder in this subgroup, including polysubstance abuse.     

Severity of regional myocardial dysfunction is not affected by cardiomyocyte apoptosis in non-ischemic heart failure

The role of myocardial apoptosis during the development of heart failure (HF), in the absence of coronary artery stenosis, is still debated. The aim of the study was to evaluate whether (similar to functional impairment) the activation of myocardial apoptosis follows a regional pattern in an established model of pacing-induced HF. HF was induced in adult male minipigs by rapid and sustained left ventricular (LV) epicardial pacing (n = 8; n = 5 healthy controls). Progressive regional derangement of the contractile function and perfusion was assessed by magnetic resonance imaging as LV end-systolic wall thickening (LVESWT) and relative upslope of signal intensity (LVRUSI, %) in the anterior/anterior-lateral (pacing site, PS) and infero-septal LV region (opposite site, OS). LV tissue from PS and OS was analyzed for biomarkers of cell apoptosis and injury. After 21 days of LV pacing, LVESWT was lower in the PS compared to OS (7.6 ± 3.7 vs 24.16 ± 3.6%, p < 0.05), and LV ejection fraction was 24.0 ± 3.7 (p < 0.05 vs control). The mRNA expression of caspase (Casp)-3 was significantly higher in the PS of HF hearts than in controls (1.28 ± 0.125 vs 0.82 ± 0.10), but not Casp-9. Bcl-2 and Hsp72 expression was significantly increased in PS compared to control (0.90 ± 0.60 vs 0.63 ± 0.033; 0.72 ± 0.10 vs 0.28 ± 0.098), in the presence of a TNF-α level increased by 50.7%. The regional myocardial apoptotic index, assessed by TUNEL, was unchanged in HF. In conclusion, the activators and inhibitors of cell apoptosis are equally expressed without affecting the survival of cardiomyocytes and the magnitude of regional myocardial dysfunction during development of non-ischemic HF.     

Effects of n-3 polyunsaturated fatty acids on depressive symptoms,anxiety and emotional state in patients with acute myocardial infarction

BackgroundOur aim was to assess whether an early introduced n-3 polyunsaturated fatty acids (n-3 PUFA) supplementation affects depression symptoms, anxiety and emotional state in patients with acute myocardial infarction (AMI) and no history of mental disorders.MethodsFifty two patients with AMI were enrolled into the study and randomized to the study group (group P; n = 26; standard therapy + n-3 PUFA1 g daily) or the control group (group C; n = 26; standard therapy). The following psychological tests were used at the baseline (3rd day of AMI) and after one month (30 ± 1 days): Beck Depression Inventory (BDI), State-Trait Anxiety Inventory in a specific situation (STAI-S) and as a general trait (STAI-T), Emotional State Questionnaire (ESQ).ResultsThe baseline characteristics, pharmacotherapy and BDI, STAI-S/T and ESQ were similar between both groups. The mean test scores assessed for all patients (group P and C) during the one-month observation were significantly lower for BDI (p = 0.04), STAI-T (p = 0.03), STAI-S (p = 0.01) and harm/loss emotions (p = 0.005). After adjusting for age, sex, body mass index, coronary artery disease severity, ejection fraction, serum troponin level and the baseline tests results, n-3 PUFAintervention revealed additional significant decrease in BDI (p = 0.046), STAI-S (p = 0.03) and harm/loss emotions (p = 0.04).ConclusionsOur study provides novel and preliminary observations – n-3 PUFAsupplementation reveals additional decreasing effects on depressive and anxiety symptoms in early post-MI patients.