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Background and Aim: 25-hydroxyvitamin D deficiency represents a widespread social problem but also an emerging risk factor for cardiovascular disease. Genetic variants of the Vitamin D Binding Protein (VDBP), the main transporter of vitamin D in the bloodstream, have been shown to account for a significant variability in the levels and systemic effects of vitamin D. We investigated whether the single nucleotide polymorphisms, rs7041 and rs4588, of VDBP are associated to the prevalence and extent of coronary artery disease.Methods and Results: A consecutive cohort of patients undergoing coronary angiography in a single centre were included. Significant CAD was defined as at least 1 stenosis >50%, severe CAD for as left main and/or three-vessel disease. VDBP genetic status was assessed by polymerase chain reaction and restriction fragment length polymorphism technique. We included 1080 patients, 57% carried the mutated G allele of rs7041, whereas 22% carried the A allele of rs4588. Higher levels of C- reactive protein were observed in the carriers of G allele of rs7041 (p = 0.02), whereas 25-hydroxyvitamin D levels were similar across groups. A higher prevalence of lesions in the left anterior descending artery and a longer lesion length were observed in "A" carriers for rs4588 (p = 0.04 and p = 0.03, respectively). On the contrary, a higher prevalence of bifurcation lesions and chronic occlusions was observed in G carriers (p = 0.002 and p = 0.01 respectively). Both polymorphisms of VDBP did not affect the prevalence of CAD (rs7041: 79.1% TT vs 80.3% TG vs 78.5% GG, p = 0.81; rs4588 = 80.3% CC vs 78.5% AC + AA, p = 0.49) and severe CAD, (rs7041: 31.1% TT % vs 31.3% TG vs 30.6% GG, p = 0.88; rs4588: 32.2% CC vs 29.3% AC + AA, p = 0.31). Results were confirmed at multivariate analysis, for both rs7041 and rs4588. However, when including the levels of 25-hydroxyvitamin D in the multivariate model, we observed that 25(OH)D status and not genetic variants of VDBP were significantly associated with CAD (25-hydroxyvitamin D OR [95% CI] = 0.99 [0.97-1.0], p = 0.05; rs7041 TG: OR [95% CI] = 1.26 [0.73-2.19], p = 0.41; rs7041 GG: OR [95% CI] = 1.25 [0.82-1.91], p = 0.30; rs4588 AC + AA: OR [95% CI] = 0.76 [0.51-1.13], p = 0.18).Conclusion: This study showed in a large cohort of patients undergoing coronary angiography, that the polymorphisms rs7041 and rs4588 of VDBP are not associated with the levels of 25-hydroxyvitamin D nor with the prevalence and extent of CAD. In fact, 25-hydroxyvitamin D levels but not VDBP genetic status independently predicted the occurrence of coronary lesions at angiography. [ABSTRACT FROM AUTHOR]

Background and Aims: New antithrombotic therapies have significantly improved the outcomes of patients with acute coronary syndrome (ACS), where the introduction of ticagrelor has provided the greatest mortality benefits. However, ticagrelor treatment has been associated with a potential increase in the serum uric acid (SUA) levels, which may influence endothelial dysfunction and prothrombotic status, thereby affecting the risk of acute cardiovascular events in patients requiring dual antiplatelet therapy (DAPT). The present study aimed to compare the impact of antiplatelet agents such as ticagrelor or clopidogrel on SUA levels and their effect on platelet reactivity.Methods and Results: We included patients admitted for ACS or elective percutaneous coronary intervention (PCI) and discharged with ASA (acetylsalicylic acid; 100-160 mg) and clopidogrel (75 mg) or ticagrelor (90 mg twice a day). Chemistry was assessed at admission (baseline) and after a 30-90-day period of DAPT (together with platelet reactivity). The absolute and percentage variations of SUA after DAPT introduction were considered. Multiple-electrode aggregometry was used to assess platelet function. A total of 378 patients were enrolled, with 145 treated with aspirin and clopidogrel (AC) and 233 with aspirin and ticagrelor (AT). The AC patients were older (p = 0.003) and more often showed elective PCI as an indication to DAPT (<0.001); they received chronic therapy with ARB (angiotensin II receptor blocker; p = 0.001), nitrates (p = 0.044), CCB (calcium channel blocker; p = 0.005) and diuretics (p = 0.044). The AT patients displayed a higher percentage of ACS diagnosis (p < 0.001) and received chronic therapy with ACE (angiotensin-converting enzyme) inhibitors (p = 0.001), beta blockers (p = 0.001) and statins (p = 0.013). The AC patients displayed higher platelet reactivity at COL (collagen) test, ASPI test and ADP (adenosine diphosphate) test (p = 0.03, 0.001 and <0.001, respectively) and a higher percentage of HRPR (high residual platelet reactivity) in the ADP test (p = 0.001). No difference was found in the baseline uric acid and creatinine levels between AC and AT patients. At 30-90 days, a significant absolute and percentage increase in the SUA levels was found in AT as compared to AC patients (0.204 mg/dl vs. -0.165 mg/dl, p = 0.034; 6.26% vs. -0.005%, p = 0.018, respectively). Results were not influenced by variations in renal function. At multivariate analysis, in fact, ticagrelor therapy emerged as an independent predictor of increase in the uric acid levels (odds ratio (OR; 95% confidence interval (CI)) = 2.79 (1.66-4.67), p < 0.001). However, the variation in the SUA levels did not affect platelet reactivity or HRPR in both AC and AT patients.Conclusion: An increase in the SUA levels at 30-90 days was observed in patients receiving chronic DAPT with ticagrelor, but not clopidogrel treatment. However, the changes in the SUA levels do not influence platelet aggregation. [ABSTRACT FROM AUTHOR]

Background and Aim: High residual platelet reactivity (HRPR) is still an important challenge, despite the advent of new potent ADP-antagonists. Therefore it is of extreme importance to identify factors that can influence platelet activation. Serum uric acid (SUA) has been largely addressed in the past as a possible risk factor for coronary artery disease, with a possible association with platelets hyperreactivity. So far no studies have assessed the role of serum uric acid on the response to dual antiplatelet therapy. Therefore, the aim of our study was to evaluate the impact of uric acid levels on platelet function in patients treated with dual antiplatelet therapy (DAPT) with clopidogrel or ticagrelor.Methods and Results: We scheduled for platelet function assessment at 30-90 days post-discharge patients treated with DAPT (ASA + clopidogrel or ticagrelor) for an ACS or elective percutaneous coronary intervention (PCI). Platelet function was assessed by whole blood impedance aggregometry (Multiplate(®)-Roche Diagnostics AG), HRPR was considered for ASPI test >862 AU(∗)min (for ASA) and ADP test values ≥417 AU* min (for ADP-antagonists).Results: We included a total of 493 patients (262 were on ASA and clopidogrel and 231 on ASA and ticagrelor). Patients were divided according to quartiles of serum uric acid levels measured at the time of platelet aggregation assessment (Group 1 <4.6 mg/dL, n = 114; Group 2, 4.7-5.8 mg/dL, n = 133; Group 3, 5.9-6.8 mg/dL, n = 124; Group 4, >6.9, n = 122). Patients with higher uric acid levels were older, more often smokers, with history of hypertension and previous coronary artery bypass surgery and renal failure and were more often on therapy with diuretics at admission. Patients with higher SUA had higher triglycerides and fibrinogen. Uric acid levels did not influence ASPI, COL, TRAP and ADP tests. High residual platelet reactivity (HRPR) was observed in 1.5% of patients treated with ASA, with no difference according to SUA quartiles (p = 0.60), confirmed at multivariate analysis after correction for baseline confounders (adjusted OR[95%CI] = 1.05 [0.44-2.52], p = 0.90). HRPR for ADP-antagonists was observed in 23.6% of patients, with no difference according to SUA quartiles (p = 0.47); this result was confirmed also after correction for baseline confounders (adjusted OR[95%CI] = 1.04 [0.84-1.28], p = 0.73). Moreover, no association was found between HRPR and uric acid levels both among patients treated with clopidogrel (p = 0.35) or ticagrelor (p = 0.74), that was confirmed after correction for baseline confounding factors (adjusted OR[95%CI] = 1.18 [0.90-1.55], p = 0.23) and (adjusted OR[95%CI] = 0.96 [0.63-1.47], p = 0.85). The absence of association between SUA and platelet reactivity was confirmed at linear regression analysis both with clopidogrel (r = 0.03, p = 0.55) or ticagrelor (r = -0.01, p = 0.85).Conclusion: This is the first large study showing that in patients receiving DAPT, uric acid levels do not influence response to ticagrelor and clopidogrel or the effectiveness of ASA. [ABSTRACT FROM AUTHOR]

Object. The aim of this paper is to present a clinical case in which the CAD-CAM procedure was applied for a prosthetic rehabilitation on implants. Materials. Digital CAD-CAM production by laboratory of the final restoration. Results. CAD-CAM production offers the opportunity to easily collaborate with laboratory. This prosthetic production gives better and demonstrated clinical results for the patient. Conclusion. CAD-CAM production is a very important instrument for prosthetic team. This work-flow compared with traditional methods is faster, precise and predictable. [ABSTRACT FROM AUTHOR]

Background Coronary artery disease (CAD) is the leading cause of mortality among diabetic patients, and the neutrophil-to-lymphocyte ratio (NLR) has recently emerged from among inflammatory parameters as a potential indicator of vascular complications and poorer outcome in patients with diabetes. This study aimed to evaluate: 1) the impact of diabetes on NLR; and 2) the role of NLR on the extent of CAD among diabetic patients undergoing coronary angiography. Methods Consecutive patients undergoing coronary angiography were included. Diabetic status and main chemistry parameters were assessed at the time of admission. Significant CAD was defined as at least one vessel with stenosis > 50%, while severe CAD was left main and/or three-vessel disease, as evaluated by quantitative coronary angiography (QCA). Results Diabetes was observed in 1377 of 3756 patients (36.7%); they were older, and displayed higher-risk cardiovascular profile and more complex CAD. Diabetic status was also associated with a significant increase in NLR ( P = 0.004). Among diabetics, higher NLR tertile values were related to ageing ( P < 0.001), dyslipidaemia ( P < 0.001), renal failure ( P < 0.001), body mass index ( P < 0.001), previous percutaneous coronary revascularization ( P = 0.004) and cerebrovascular events ( P = 0.003), acute presentation ( P < 0.001), treatment at admission with beta-blockers/statins/ASA (all P < 0.001), diuretics ( P = 0.01) or clopidogrel ( P = 0.04), platelet count ( P = 0.03), white blood cell count, creatinine, glycaemia and C-reactive protein ( P < 0.001), and inversely related to haemoglobin, triglyceride levels ( P < 0.001) and smoking ( P = 0.03). NLR was associated with multivessel disease ( P < 0.001), degree of stenosis ( P = 0.01), type C lesions ( P = 0.02), coronary calcifications and intracoronary thrombus ( P < 0.001), but inversely with in-stent restenosis ( P = 0.003) and TIMI flow grade ( P = 0.02). Also, NLR was directly related to CAD prevalence ( P < 0.001; adjusted OR [95% CI]: 1.62 [1.27–2.07], P < 0.001) and CAD severity ( P < 0.001; adjusted OR [95% CI]: 1.19 [1.00–1.43], P = 0.05). Conclusion NLR is increased among diabetic patients and, in such patients, is independently associated with the prevalence and severity of CAD. Further studies are now needed to confirm present results and to evaluate the underlying pathophysiological mechanisms behind our findings. [ABSTRACT FROM AUTHOR]

Background and aim There has been a surge of interest in the cardiovascular effects of vitamin D (25(OH)D), preventing the processes leading to vascular wall degeneration and coronary artery disease (CAD). Gender differences have been suggested for vitamin D status, with a higher rate of deficiency occurring especially in post-menopausal women, increasing the risk of bone fractures and osteoporosis. However, to date, few studies have evaluated the differences in 25(OH)D levels according to gender and their impact on the extent of CAD, which was therefore the aim of the present study. Methods and results In patients undergoing coronary angiography, fasting samples were collected for the assessment of 25(OH)D levels. Significant CAD was defined as at least one vessel stenosis >50%, while severe CAD was defined as left main and/or three-vessel disease. Of the 1811 patients included, 530 (29.3%) were females, who displayed older age ( p < 0.001), higher rate of renal failure ( p < 0.001), hypertension ( p = 0.05), treatment with angiotensin-receptor blockers ( p = 0.03) and diuretics ( p < 0.001), acute presentation ( p < 0.001), higher platelet count ( p < 0.001), glycosylated haemoglobin ( p = 0.02) and cholesterol ( p = 0.001), but an inverse relationship with smoking ( p < 0.001), previous cardiovascular events ( p < 0.001), treatment with statins and acetylsalicylic acid (ASA) ( p < 0.001), body mass index ( p = 0.002), haemoglobin ( p < 0.001), leucocytes ( p = 0.03) and triglycerides ( p < 0.001). Female gender was associated with lower vitamin D levels (14.5 ± 10.9 vs. 15.9 ± 9.5, p = 0.007) and independently associated with severe vitamin D deficiency (41.9% vs. 30.4%, p < 0.001; adjusted odds ratio (OR) (95% confidence interval (CI)) = 1.42 (1.08–1.87), p = 0.01). Lower tertiles of vitamin D were associated with an increased prevalence and severity of CAD in females (adjusted OR (95% CI = 1.26 (1.10–1.44), p = 0.001 for CAD; adjusted OR (95% CI) = 1.6 (1.39–1.87), p < 0.001 for severe CAD). In males, vitamin D status was independently related to the prevalence (adjusted OR (95% CI) = 1.28 (1.02–1.61), p = 0.03) of CAD, but not the extent of CAD (adjusted OR (95% CI) = 1.02 (0.86–1.2), p = 0.84). Conclusion Gender significantly affects vitamin D status. The lower 25(OH)D levels observed in females, as compared to males, play a more relevant role in conditioning the severity of CAD. [ABSTRACT FROM AUTHOR]

Background and aim Contrast Induced Nephropathy (CIN) is a common complication of procedures that require the use of contrast media, and seems to be mediated by oxidative stress and reactive oxygen species generation. Hyperuricemia is characterized by inhibited nitric oxide system and enhanced synthesis of reactive oxygen species. However, few studies have so far investigated the association between hyperuricemia and CIN that is therefore the aim of the current study among patients undergoing coronary angiography or percutaneous intervention. Methods and results We analyzed a total of 1950 patients with Creatinine clearance <90 ml/min) undergoing elective or urgent coronary angiography and/or angioplasty. Patients were divided according to tertiles of baseline uric acid (Group 1, ≤5.5 mg/dL n = 653; Group 2, 5.6–7.0 mg/dL, n = 654; Group 3, ≥7.0 mg/dL, n = 643). CIN was defined as an absolute ≥0.5 mg/dl or a relative ≥25% increase in the serum creatinine level at 24 or 48 h after the procedure. Patients with higher uric acid levels were older, previous smokers, with higher prevalence of hypertension and diabetes, but with lower family history of CAD. They had more often history of a previous CABG and baseline renal dysfunction. Patients of the third Tertile had also higher levels of white blood cells, higher triglycerides and lower HDL-cholesterol and higher percentage of dilated cardiomyopathy/valvular disease as indication for angiography and consequently a lower prevalence of PCI. Patients with higher SUA were more often on therapy with ACE inhibitors and diuretics, but less often with statins, nitrate, ASA and Clopidogrel at admission. The occurrence of CIN was observed in 251 patients (12.9%), and was significantly associated with uric acid levels (12.3% in Group 1, 10.4% in Group 2 and 16.0% in Group 3; p = 0.04). Similar results were observed when the analysis was performed according to each tertiles values in both male and female gender. The association between elevated uric acid (≥7 mg/dl) and CIN was confirmed by multivariate analysis after correction for baseline confounding (Adjusted OR [95%CI] = 1.42 [1.04–1.93], p = 0.026). Similar results were observed across major subgroups of high-risk patients, such as patients with diabetes, female gender, renal failure, hypertension, and elderly. Conclusions This is the first large study showing that among patients undergoing coronary angiography or percutaneous interventions elevated uric acid level is independently associated with an increased risk of CIN. [ABSTRACT FROM AUTHOR]

Background and aim High density lipoproteins (HDL) have been addressed as a potential strategy for cardiovascular prevention, with great controversies on pharmacological approaches for HDL-elevation. Our aim was to compare HDL-rising treatment with niacin or CETP-inhibitors with optimal medical therapy in cardiovascular outcome. Methods and results Randomized trials were searched. Primary endpoint was cardiovascular death, secondary were: non fatal myocardial infarction; coronary revascularization; cerebrovascular accidents and safety endpoints. As many as 18 randomized trials, for a total of 69,515 patients, were included. HDL-modifiers did not reduce cardiovascular mortality (2.3%vs3.4%; OR [95%CI] = 0.96 [0.87–1.05], p = 0.37, phet = 0.58), with no benefit from niacin/CETP inhibitors according to patients' risk profile (beta [95%CI] = −0.14 [−0.29 to 0.02], p = 0.09) or the amount of HDL increase (beta [95%CI] = 0.014 [−0.008 to 0.04], p = 0.21). Niacin but not CETP-I reduced myocardial infarction and coronary revascularization, but higher rate of SAE occurred with HDL-modifiers (OR [95%CI] = 1.24 [1.18–1.31], p < 0.00001, phet = 0.02), in particular new onset of diabetes with niacin and worsening of hypertension with CETP-inhibitors. Conclusions Niacin and CETP inhibitors do not influence cardiovascular mortality. Significant benefits in MI and coronary revascularization were observed with niacin, despite the higher occurrence of diabetes. [ABSTRACT FROM AUTHOR]

Nail loss might represent a new, reversible, adverse event associated with teriflunomide treatment. It shares close analogies with hair loss and thinning, known adverse events of teriflunomide. MS specialists should be aware of this possibility and evaluate treatment discontinuation. [ABSTRACT FROM AUTHOR]

Abstract: Background and aim: Pro-thrombotic status and platelet hyperreactivity still represent an important challenge for periprocedural myocardial infarction (PMI) after coronary stenting. Hyperhomocysteinemia has been suggested to increase the risk of cardiovascular events. The genetic variant of methylenetetrahydrofolate reductase (MTHFR) 677 C > T has been associated to reduced function of the enzyme, thus inducing hyperhomocysteinemia. In our study we investigated whether MTHFR 677 C > T polymorphism is associated with increased risk of periprocedural MI in patients undergoing coronary stenting. Methods and results: We included 778 patients undergoing PCI. Homocysteinemia and genetic status were assessed at admission for all patients. Myonecrosis biomarkers were dosed at intervals from 6 to 48 h, PMI was defined as CKMB increase by 3 times the ULN or 50% of pre-PCI value, periprocedural myonecrosis for troponin I increase by 3 times the ULN or by 50% of the baseline. As many as 521 patients carried the MTHFR-T allele. No difference was found for main demographical and clinical features nor for biochemistry parameters, but for higher rate of statins treatment (p = 0.03) in T-carriers. Polymorphic patients displayed significantly higher levels of homocysteine (p = 0.005), with additive effect of the mutated T-alleles. Angiographic and procedural features were similar according to genetic status. MTHFR677T was not associated with periprocedural myocardial infarction (adjusted OR = 0.97[0.67–1.4], p = 0.87) or myonecrosis (adjusted OR = 1.03[0.83–1.36], p = 0.82). Same results were found at subgroup analysis in higher-risk subsets of patients. Conclusion: Our study showed that among patients undergoing PCI, MTHFR 677 C > T polymorphism is associated to higher homocysteine levels, but does not influence the risk of periprocedural myocardial infarction. [Copyright &y& Elsevier]

Abstract: Background and aim: Clinical trials have reported lower mortality and repeated revascularization rate in diabetic patients treated with coronary artery bypass grafting (CABG) as compared to percutaneous revascularization. However, these studies were conducted in the era of bare-metal stents. Therefore, we performed a meta-analysis to compare CABG to PCI with drug-eluting stents (DES) in diabetic patients with multivessel and/or left main disease. Methods and results: The literature was scanned by formal search of electronic databases (Medline, EMBASE, and Cochrane databases), and major international scientific session abstracts from 2000 to 2013. Primary endpoint was mortality. A total of 14 (4 randomized and 10 non-randomized) trials were finally included, with a total of 7072 patients. Up to 5 years follow-up, CABG was associated with a reduction in mortality (7.3% vs 10.4%, OR[95%CI] = 0.65[0.55–0.77], p < 0.0001; phet = 0.00001), with similar results in both RCTs (OR[95%CI] = 0.64[0.50–0.82], p = 0.0005) and NRCTs (OR[95%CI] = 0.75[0.6–0.94)], p = 0.01) (p int = 0.93). A significant relationship was observed between risk profile and benefits in mortality with CABG (p < 0.001). CABG reduced target vessel revascularization (TVR; 5.2% vs 15.7%, OR[95%CI] = 0.30[0.25–0.36], p < 0.00001, p het = 0.02), with a relationship between risk profile and the benefits from CABG as compared to DES (p < 0.0001). CABG was associated with a lower rate of MACCE (14.9% vs 22.9%, OR[95%CI] = 0.59[0.51–0.67], p < 0.00001, p het<0.00001) but higher risk of CVA (3.6% vs 1.4%, OR[95%CI] = 2.34[1.63–3.35], p < 0.00001, p het = 0.71). Conclusions: The present meta-analysis demonstrates that among diabetic patients with multivessel disease and/or left main disease, CABG provides benefits in mortality and TVR, especially in high-risk patients but it is counterbalanced by a higher risk of stroke. Future trials are certainly needed in the era of new DES and improved antiplatelet therapies. [Copyright &y& Elsevier]

Abstract: Background: Hyperuricemia may be involved in the atherosclerotic process due to endothelial dysfunction and facilitation of smooth muscle cell proliferation. However, debates still exist on the independent role of hyperuricemia, due to its association with several cardiovascular risk factors, such as hypertension, hyperlipidemia, obesity and insulin resistance. Thus, the aim of the current study was to investigate in a consecutive cohort of patients undergoing coronary angiography whether hyperuricemia is associated with the extent of coronary artery disease. Methods and Results: Our population is represented by a total of 1901 consecutive patients undergoing coronary angiography between May 2007 and January 2010 at the Azienda Ospedaliera “Maggiore della Carità”, Novara, Italy. We additionally evaluated platelet aggregation by PFA-100 (Collagen/Epinefrine) and Multiplate. Quantitative coronary angiography and analysis of IMT were performed by experienced cardiologists who had no knowledge of the patients’ clinical information. Higher uric acid was associated with advanced age, larger prevalence of male gender, diabetes, renal insufficiency, hypertension, previous CABG and MI, but with a lower prevalence of family history of CAD. Patients with high uric acid were more often on calcium antagonists, ace-inhibitors, angiotensin receptor antagonists, and, as expected, on diuretics. A significant relationship was observed between uric acid and the prevalence (OR [95% CI] = 1.18 [1.04–1.32], p = 0.01) and severity of CAD (OR [95% CI] = 1.17 [1.03–1.33], p = 0.014). However, the relationship disappeared after correction for baseline confounding factors for both prevalence (OR [95% CI] = 1.06 [0.93–1.21], p = 0.35) and extent of CAD (OR [95% CI] = 1.0 [0.87–1.15], p = 0.96). No relationship was observed between acid uric and IMT (p = 0.73) analyzed in 359 consecutive patients. Finally, there was no relationship between uric acid and platelet aggregation in patients with or without aspirin therapy, as measured by PFA-100 and Multiplate. Conclusions: Our study showed that uric acid is not associated with platelet aggregation, the extent of coronary artery disease and IMT. Thus, waiting for the results of additional large studies, uric acid may not be considered as a risk factor for coronary artery disease, and its reduction by specific therapies may not be recommended to prevent coronary artery disease and atherosclerosis. [Copyright &y& Elsevier]

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The isotretinoin, a 13-cisretinoic acid, has revolutionized the management of severe treatment-resistant acne and it has been widely used for a range of dermatological conditions, in 90% of the time in young women between 13 and 45 years of age. This agent has severe teratogenic effects, as serious craniofacial, cardiovascular, thymic and central nervous system malformations. The baseline population risk of malformations is 3-5%, but it increases to almost 30% in women exposed to isotretinoin during the first trimester of pregnancy. Generally, patients in treatment with isotretinoin avoid eventual pregnancy during assumption and, after its stopping, fertility and foetal development are normal once circulating isotretinoin levels return to normal. There are no known deleterious effects on male fertility and on long term teratogenic effect of isotretinoin. In this report, we suppose the possibility to develop a foetal malformations after a long term wash out from isotretinoin therapy. A 32 year-old healthy nullipara pregnant woman, with an uneventful past gynaecological history, was admitted in Hospital, with a severe depressive syndrome in a 18 weeks malformed pregnancy for thoraco-omphalopagus conjoined twins. She only assumed isotretinoin, at dose of 1 mg/kg a day, for a severe and scarring acne for 7 months. After 3 months of pharmacological wash out, patient become pregnant and manifested this severe malformation. Woman interrupted gestation, by labour induction. [ABSTRACT FROM AUTHOR]

BackgroundPrevious reports have suggested an impact of patient's risk profile and percutaneous coronary intervention (PCI) -- related time delay on the benefits of primary angioplasty as compared with fibrinolysis. However, several factors, such as inappropriate interpretation and definition of delays, missing currently available trials, and arguable risk-benefit analysis, limit the value of these reports. Thus, the aim of the current review is to assess whether the prognostic impact of PCI-related time delay may vary according to patient's risk profile, presentation delay, and type of lytic therapy.MethodsWe obtained results from all randomized trials comparing fibrinolysis and primary angioplasty in ST-segment elevation myocardial infarction. The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL) for papers published from January 1990 to April 2007. The following key words were used: randomized trial, myocardial infarction, reperfusion, primary angioplasty, rescue angioplasty, fibrinolysis, thrombolysis, duteplase, reteplase, tenecteplase, and alteplase. Major clinical end point assessed was mortality at 30-day follow-up. The relationship between mortality benefits from primary angioplasty, patient's risk profile, and PCI-related time delay was evaluated by using a weighted least-square regression in which results from each trial were weighted by the square root of the number of patients of each trial.ResultsA total of 27 trials were finally included, with 4399 patients randomized to primary angioplasty and 4474 patients randomized to fibrinolysis. The relationship between the benefits from primary angioplasty and PCI-related time changed according to risk profile. The higher the risk profile, the larger the reduction in mortality benefits from primary angioplasty as compared with fibrinolysis per each 10 minutes of PCI-related time delay (0.75%, 0.45%, and 0%, in high-, medium-, and low-risk patients, respectively). Furthermore, the impact was observed only in trials enrolling patients within the first 6 hours from symptom onset.ConclusionsWhen primary angioplasty is selected as reperfusion strategy, all efforts should be attempted to shorten time-to-treatment, particularly in medium- or high-risk patients and in early presenters, because in these patients, a larger loss of mortality benefits as compared with fibrinolysis is observed per each 10 minutes of PCI-related time delay.© 2009 Elsevier Inc. All rights reserved. [ABSTRACT FROM AUTHOR]

Objective: C-reactive protein (CRP) is a marker of systemic inflammation. Recently, it has been shown that CRP is present in amniotic fluid and fetal urine, and that elevated levels are associated with adverse pregnancy outcome. However, the precise source of amniotic fluid CRP, its regulation, and function during pregnancy is still a matter of debate. The present in vivo and in vitro studies were designed to investigate the production of CRP in human placental tissues. Material and methods: Ten paired blood samples from peripheral maternal vein (MV), umbilical cord artery (UA) and umbilical vein (UV) were collected from women with elective caesarean sections at term. The placental protein accumulation capacity of hCG, hPL, leptin and CRP was compared with the dual in vitro perfusion method of an isolated cotyledon of human term placentae and quantified by ELISA. Values for accumulation (release) were calculated as total accumulation of maternal and fetal circuits normalized for tissue weight and duration of perfusion. For gene expression, RNA was extracted from placental tissue and reverse transcribed. RT-PCR and real-time PCR were performed using specific primers. Results: The median (range) CRP level was significantly different between UA and UV [50.1ng/ml (12.1–684.6) vs. 61ng/ml (16.9–708.1)]. The median (range) difference between UV and UA was 9.3ng/ml (2.2–31.6). A significant correlation was found between MV CRP and both UA and UV CRP levels. Median (range) MV CRP levels [2649ng/ml (260.1–8299)] were 61.2 (6.5–96.8) fold higher than in the fetus. In vitro, the total accumulation rates (mean±SD) were 31±13 (mU/g/min, hCG), 1.16±0.19 (μg/g/min, hPL), 4.71±1.91 (ng/g/min, CRP), and 259±118 (pg/g/min, leptin). mRNA for hCG, hPL and leptin was detectable using conventional RT-PCR, while CRP mRNA could only be demonstrated by applying real-time RT-PCR. In the perfused tissue the transcript levels for the four proteins were comparable to those detected in the native control tissue. Conclusions: Our results demonstrate that the human placenta produces and releases CRP mainly into the maternal circulation similarly to other analyzed placental proteins under in vitro conditions. Further studies are needed to explore the exact role of placental CRP during pregnancy. [Copyright &y& Elsevier]