El cociente de flujo cuantitativo en pacientes con estenosis aórtica grave y lesiones coronarias intermedias / Quantitative flow ratio for evaluation of borderline coronary lesions in patients with severe aortic stenosis

Introducción y objetivo: El cociente de flujo cuantitativo (quantitative flow ratio [QFR]) es un método novedoso y no invasivo para evaluar la fisiología coronaria. Sin embargo, los datos sobre QFR en pacientes con estenosis aórtica (EA) y enfermedad coronaria son escasos. Por lo tanto, se evaluó el rendimiento diagnóstico del QFR contra la relación del cociente de presión coronaria en reposo distal/aórtica (Pd/Pa), la reserva fraccional de flujo (FFR) y el índice diastólico instantáneo sin ondas (iFR), así como índices angiográficos. Métodos: Se incluyó un total de 221 pacientes con EA con 416 vasos en los que se midieron los valores de FFR/iFR. Resultados: El porcentaje medio de estenosis del diámetro (%DS) fue 58,6±13,4% y las medias de Pd/Pa, FFR, iFR y QFR, 0,95±0,03, 0,85±0,07, 0,90±0,04 y 0,84±0,07 respectivamente. Se observó una FFR ≤ 0,80 en el 26,0% de los vasos evaluados, iFR ≤ 0,89 en el 33,2% y QFR ≤ 0,80 en el 31,7%. El QFR tuvo mejor correlación con la FFR (coeficiente de correlación intraclase [ICC]=0,96; intervalo de confianza del 95% [IC95%], 0,95-0,96) que con el iFR (ICC=0,79; IC95%, 0,75-0,82) y la Pd/Pa (ICC=0.52; IC95%, 0,44-0,58). Además, el QFR mostró una mejor precisión diagnóstica (el 98,6 frente al 94,2%; p <0,001) y la función discriminatoria (área bajo la curva, 0,996 frente a 0,988; p <0,001) al utilizar como referencia el iFR en lugar de la FFR. Conclusiones: En pacientes con EA, el QFR muestra una buena correlación con la FFR y el iFR. Sin embargo, esta podría ser aún mejor utilizando el iFR como referencia, presumiblemente debido a la naturaleza compleja de la fisiología coronaria en la evaluación de la enfermedad coronaria de pacientes con EA grave (AU)

Introduction and objectives: Quantitative flow ratio (QFR) is a novel noninvasive method for evaluating coronary physiology. However, data on the QFR in patients with aortic stenosis (AS) and coronary artery disease are scarce. Thus, we compared the diagnostic performance of the QFR with that of the resting distal to aortic coronary pressure (Pd/Pa) ratio, fractional flow reserve (FFR), and instantaneous wave-free ratio (iFR), as well as angiographic indices.Methods: A total of 221 AS patients with 416 vessels undergoing FFR/iFR measurements were enrolled in the study. Results: The mean percent diameter stenosis (%DS) was 58.6%±13.4% and the mean Pd/Pa ratio, FFR, iFR, and QFR were 0.95±0.03, 0.85±0.07, 0.90±0.04, and 0.84±0.07, respectively. A FFR ≤ 0.80 was noted in 26.0% of interrogated vessels, as well as an iFR ≤ 0.89 in 33.2% and QFR ≤ 0.80 in 31.7%. The QFR had better agreement with FFR (intraclass correlation coefficient [ICC], 0.96; 95% confidence interval [95%CI], 0.95-0.96) than with the iFR (ICC, 0.79; 95%CI, 0.75-0.82) and Pd/Pa ratio (ICC, 0.52; 95%CI, 0.44-0.58). In addition, the QFR showed better diagnostic accuracy (98.6% vs 94.2%; P <.001) and discriminant function (area under the curve=0.996 vs 0.988; P <.001) when the iFR was used as the reference instead of FFR. Conclusions: In patients with AS, the QFR has good agreement with both FFR and iFR. However, the agreement appears to be even better when the iFR is used as the reference, presumably due to the complex nature of the coronary physiology in the assessment of coronary artery disease in patients with severe AS U(AU)

Remote Design of a Smartphone and Wearable Detected Atrial Arrhythmia in Older Adults Case Finding Study: Smart in OAC - AFNET 9.

Introduction: Screening for atrial fibrillation and timely initiation of oral anticoagulation, rhythm management, and treatment of concomitant cardiovascular conditions can improve outcomes in high-risk populations. Whether wearables can facilitate screening in older adults is not known. Methods and Analyses: The multicenter, international, investigator-initiated, single-arm case-finding Smartphone and wearable detected atrial arrhythmia in older adults case finding study (Smart in OAC - AFNET 9) evaluates the diagnostic yield of a validated, cloud-based analysis algorithm detecting atrial arrhythmias via a signal acquired by a smartphone-coupled wristband monitoring system in older adults. Unselected participants aged ≥65 years without known atrial fibrillation and not receiving oral anticoagulation are enrolled in three European countries. Participants undergo continuous pulse monitoring using a wristband with a photo plethysmography (PPG) sensor and a telecare analytic service. Participants with PPG-detected atrial arrhythmias will be offered ECG loop monitoring. The study has a virtual design with digital consent and teleconsultations, whilst including hybrid solutions. Primary outcome is the proportion of older adults with newly detected atrial arrhythmias (NCT04579159). Discussion: Smart in OAC - AFNET 9 will provide information on wearable-based screening for PPG-detected atrial arrhythmias in Europe and provide an estimate of the prevalence of atrial arrhythmias in an unselected population of older adults.

Comparación de seguridad y efectividad entre los accesos radiales derecho e izquierdo en la intervención coronaria percutánea / Comparison of safety and effectiveness between the right and left radial artery approach in percutaneous coronary intervention

Introducción y objetivos: Existen pocos estudios que comparen los accesos por la radial izquierda (ARI) y por la radial derecha en intervenciones coronarias percutáneas (ICP) en población general y practicadas por cirujanos con diferentes grados de experiencia en intervencionismo. El objetivo de nuestro estudio es comparar la seguridad y el beneficio clínico con cada acceso en pacientes no seleccionados con síndrome coronario agudo (SCA) y angina estable (AE). Métodos: Para evitar los posibles sesgos de un estudio no aleatorizado, se usó la puntuación de propensión para comparar ambos accesos radiales. Se recogieron datos de 18.716 pares con AE y 46.241 con SCA sometidos a ICP con implante de stent entre 2014 y 2017, en 151 centros terciarios con cardiología intervencionista en Polonia (registro nacional de Polonia [ORPKI]). Resultados: No se encontraron diferencias en cuanto a mortalidad y complicaciones periprocedimiento en AE. El ARI se asoció con mayores dosis de radiación independientemente de la presentación clínica (AE, 1.067,0±947,10 frente a 1.007,4±983,5 mGy; p=0,001; SCA, 1.212,7±1.005,5 frente a 1.053,5±1.029,7 mGy; p=0,001). En los pacientes con SCA, el ARI se asoció con mayor cantidad de contraste (174,2±75,4 frente a 167,2±72,1ml; p=0,001). Además, en los pacientes con SCA y ARI, las complicaciones periprocedimiento como disección coronaria (el 0,16 frente al 0,09%; p=0,008), fenómeno de no reflow (el 0,65 frente al 0,49%; p=0,005) y hemorragia en el sitio de punción (el 0,09 frente al 0,05%; p=0,04) resultaron más frecuentes. No hubo diferencias en la mortalidad entre los 2 grupos (p=0,90). Conclusiones: Los resultados que se presentan podrían estar en relación con una menor experiencia en el ARI. Ambos accesos son seguros en los pacientes con AE, pero el ARI se asoció con una mayor frecuencia de complicaciones periprocedimiento de ICP en el SCA (AU)

Introduction and objectives: There is a paucity of data comparing the left radial approach (LRA) and right radial approach (RRA) for percutaneous coronary intervention (PCI) in all-comers populations and performed by operators with different experience levels. Thus, we sought to compare the safety and clinical outcomes of the RRA and LRA during PCI in “real-world” patients with either stable angina or acute coronary syndrome (ACS). Methods: To overcome the possible impact of the nonrandomized design, a propensity score was calculated to compare the 2 radial approaches. The study group comprised 18 716 matched pairs with stable angina and 46 241 with ACS treated with PCI and stent implantation between 2014 and 2017 in 151 tertiary invasive cardiology centers in Poland (the ORPKI Polish National Registry). Results: The rates of death and periprocedural complications were similar for the RRA and LRA in stable angina patients. A higher radiation dose was observed with PCI via the LRA in both clinical presentations (stable angina: 1067.0±947.1 mGy vs 1007.4±983.5 mGy, P=.001; ACS: 1212.7±1005.5 mGy vs 1053.5±1029.7 mGy, P=.001). More contrast was used in LRA procedures but only in ACS patients (174.2±75.4mL vs 167.2±72.1mL, P=.001). Furthermore, periprocedural complications such as coronary artery dissection (0.16% vs 0.09%, P=.008), no-reflow phenomenon (0.65% vs 0.49%, P=.005), and puncture site bleeding (0.09% vs 0.05%, P=.04) were more frequently observed with the LRA in ACS patients. There was no difference in mortality between the 2 groups (P=.90). Conclusions: Our finding of poorer outcomes with the LRA may be related to lower operator experience with this approach. While both the LRA and RRA are safe in the setting of stable angina, the LRA was associated with a higher rate of periprocedural complications during PCI in ACS patients (AU)

Smartphone and wearable detected atrial arrhythmias in Older Adults: Results of a fully digital European Case finding study.

Aims: Simplified detection of atrial arrhythmias via consumer-electronics would enable earlier therapy in at-risk populations. Whether this is feasible and effective in older populations is not known. Methods and results: The fully remote, investigator-initiated Smartphone and wearable detected atrial arrhythmia in Older Adults Case finding study (Smart in OAC-AFNET 9) digitally enrolled participants ≥65 years without known atrial fibrillation, not receiving oral anticoagulation in Germany, Poland, and Spain for 8 weeks. Participants were invited by media communications and direct contacts. Study procedures adhered to European data protection. Consenting participants received a wristband with a photoplethysmography sensor to be coupled to their smartphone. The primary outcome was the detection of atrial arrhythmias lasting 6 min or longer in the first 4 weeks of monitoring. Eight hundred and eighty-two older persons (age 71 ± 5 years, range 65-90, 500 (57%) women, 414 (47%) hypertension, and 97 (11%) diabetes) recorded signals. Most participants (72%) responded to adverts or word of mouth, leaflets (11%) or general practitioners (9%). Participation was completely remote in 469/882 persons (53%). During the first 4 weeks, participants transmitted PPG signals for 533/696 h (77% of the maximum possible time). Atrial arrhythmias were detected in 44 participants (5%) within 28 days, and in 53 (6%) within 8 weeks. Detection was highest in the first monitoring week [incidence rates: 1st week: 3.4% (95% confidence interval 2.4-4.9); 2nd-4th week: 0.55% (0.33-0.93)]. Conclusion: Remote, digitally supported consumer-electronics-based screening is feasible in older European adults and identifies atrial arrhythmias in 5% of participants within 4 weeks of monitoring (NCT04579159).

Decreased sensitivity to paroxetine-induced inhibition of peripheral blood mononuclear cell growth in depressed and antidepressant treatment-resistant patients.

Major depression disorder (MDD) is the most widespread mental disorder. Selective serotonin reuptake inhibitors (SSRIs) are used as first-line MDD treatment but are effective in <70% of patients. Thus, biomarkers for the early identification of treatment-resistant (TR) MDD patients are needed for prioritizing them for alternative therapeutics. SSRI-induced inhibition of the growth of peripheral blood mononuclear cells (PBMCs) is mediated via their target, the serotonin transporter (SERT). Here, we examined whether antidepressant drug-induced inhibition of the growth of PBMCs differed between MDD patients and healthy controls. PBMCs from well-characterized 33 treatment-sensitive (TS) and 33 TR MDD patients, and 24 healthy volunteers were studied. Dose-dependent inhibition of PBMCs growth was observed for both the non-SSRI antidepressant mirtazapine and the SSRI antidepressant paroxetine. Significantly lower sensitivities to 20 µm paroxetine were observed in MDD compared with control PBMCs prior to treatment onset (13% and 46%, respectively; P<0.05). Following antidepressant drug treatment for 4 or 7 weeks, the ex vivo paroxetine sensitivity increased to control levels in PBMCs from TS but not from TR MDD patients. This suggests that the low ex vivo paroxetine sensitivity phenotype reflects a state marker of depression. A significantly lower expression of integrin beta-3 (ITGB3), a co-factor of the SERT, was observed in the PBMCs of MDD patients prior to treatment onset compared with healthy controls, and may explain their lower paroxetine sensitivity. Further studies with larger cohorts are required for clarifying the potential of reduced PBMCs paroxetine sensitivity and lower ITGB3 expression as MDD biomarkers.

Long-term mortality and follow-up after carotid artery stenting.

BACKGROUND: Carotid artery stenting (CAS) is an alternative to carotid endarterectomy for the prevention of stroke and transient ischemic attack (TIA). The high long-term mortality among patients who underwent CAS seems to be related to the high comorbidity burden, including coronary and peripheral artery disease. However, limited data on very long-term mortality (over four years) and predictors of death are available. AIM: We sought to investigate the very long-term survival after CAS and the impact of comorbidities on mortality at follow-up. METHODS: Data of 194 symptomatic and asymptomatic patients who underwent CAS with cerebral protection systems from December 2002 to March 2014 were analyzed. All cause mortality during long-term follow-up was assessed. Univariate and multivariate Cox regression analysis was used to find independent predictors of death. RESULTS: The median age of patients was 66 [interquartile range (IQR): 60-73] years and 78.9 % of patients were male. The median follow-up was 7.6 (IQR: 4.4-10.2) years. The all-cause mortality rate after 30 days, one year, four years, and at maximum follow-up was 0 %, 5.1 %, 17.5 % and 31.4 %, respectively. Out of 61 deaths, 37 (60 %) were cardio-cerebral vascular related deaths, 15 (25 %) non-cardiovascular deaths, and 9 (15 %) due to unknown reasons. Among cardio-cerebral vascular deaths, there were 12 fatal strokes, 18 fatal myocardial infarctions and seven other cardiac related deaths. Non-cardiac deaths were due mainly to cancer (9/15). Age and diabetes mellitus were independent predictors of all-cause death during long-term follow-up. CONCLUSIONS: The mortality rate during short and long-term follow-up after CAS was lower than reported in the literature. Age and diabetes mellitus were independent predictors of all-cause death. Further research is needed to confirm the potential association between those risk factors and decreased survival. Hippokratia 2016, 20(3): 204-208.

Relationships between obesity, bipolar spectrum features, and personality traits: a case-control study.

OBJECTIVE: Recently there has been widening stream of research on the relationships between obesity and mental disorders. Patients with obesity seem to be prone to developing bipolar spectrum disorders and they present with specific personality traits. The aim of this study was to analyze the associations between obesity, bipolarity features, and personality traits. PATIENTS AND METHODS: A nested case-control study was performed. Patients with obesity constituted the sample of cases (N = 90), and healthy individuals were ascribed to the control group (N = 70). The lifetime presence of bipolarity features was analyzed with the Mood Disorder Questionnaire (MDQ), while personality traits were assessed with the NEO-Five Factor Inventory (NEO-FFI). RESULTS: Bipolarity features were more prevalent in the patients with obesity, as compared to healthy individuals. Patients with obesity had both higher mean value of MDQ score (p = 0.01) and a higher proportion of subjects with MDQ score ≥ 7 points (p = 0.012) as well as lower score on the NEO-FFI openness to experience (p > 0.001), compared to control subjects. Using multivariate model, in patients with obesity, a significant positive correlation between bipolarity and neuroticism, and negative with agreeableness and conscientiousness was established. Such relationship was not observed in control subjects. CONCLUSIONS: In the population of patients with obesity, there is a specific combination between bipolarity and personality traits (high-trait neuroticism, low-trait conscientiousness, and low-trait agreeableness). This may have some consequences for both pharmacological and psychological management of such patients.

Mesh-covered embolic protection stent implantation in ST-segment-elevation myocardial infarction: final 1-year clinical and angiographic results from the MGUARD for acute ST elevation reperfusion trial

The MGuard, a bare metal stent covered with a polymer mesh, was designed to reduce distal embolization during percutaneous coronary intervention in ST-segment-elevation myocardial infarction. In the MGUARD for Acute ST Elevation Reperfusion trial, the primary end point of complete ST-segment resolution was significantly improved with the MGuard compared with control. We evaluated 1-year clinical and angiographic results.METHODS AND RESULTS:Patients with ST-segment-elevation myocardial infarction ≤12 hours undergoing primary percutaneous coronary intervention of a single de novo native lesion were randomized to the MGuard versus any commercially available metallic stent (39.8% drug-eluting). Clinical follow-up was performed through 1 year, and angiography at 13 months was planned in 50 MGuard patients. There was no difference in major adverse cardiac events (1.8% versus 2.3%; P=0.75) at 30 days between the groups. Major adverse cardiac events at 1 year were higher with the MGuard, driven by greater ischemia-driven target lesion revascularization (8.6% versus 0.9%; P=0.0003). Conversely, mortality tended to be lower with the MGuard at 30 days (0% versus 1.9%; P=0.04) and at 1 year (1.0% versus 3.3%; P=0.09). Late lumen loss at 13 months in the MGuard was 0.99±0.80 mm, and binary restenosis was 31.6%.CONCLUSIONS:In patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, a trend toward reduced 1-year mortality was present in patients treated with the MGuard stent. Target lesion revascularization and major adverse cardiac events rates during follow-up were higher in the MGuard group than in the control stent group, and angiographic late loss of the MGuard was consistent with that expected from bare metal stents.

[Optical coherence tomography of coronary arteries--a novel intravascular imaging modality]. / Optische Kohärenztomographie der Koronararterien.

Optical coherence tomography (OCT) is the latest intravascular imaging modality for the investigation of coronary arteries. It can be used in patients with stable coronary artery disease as well as in patients with acute coronary syndrome. Its almost microscope-like resolution of 10-20 µm (10-times greater than intravascular ultrasound) gives us the most detailed insight into the coronary artery wall in vivo so far.Optical coherence tomography can be used for accurate qualitative and quantitative assessment of stenoses in stable coronary artery disease and accurate guidance of percutaneous coronary interventions as well as accurate postprocedural control. In patients with acute coronary syndrome it can be used for the detection of culprit of the culprit lesion (vulnerable plaque) which allows the operator to cover not only angiographically tightest stenosis (angiographic culprit lesion, caused in most cases by thrombus only) but most importantly the vulnerable plaque, which led to the acute event, as well. Furthermore, optical coherence tomography allows accurate assessment of thrombotic burden, stent apposition/malapposition, edge dissections and tissue prolaps or thrombus protrusions throught stent struts, etc.

Advantages of MGuard coronary stent system.

Effectiveness of percutaneous coronary intervention (PCI) within thrombus containing lesions (ST-segment elevation myocardial infarction setting, degenerated saphenous venous grafts) is limited by the risk of occurrence of distal embolization and no-reflow phenomenon. Several pharmacological agents, as well as mechanical devices (i.e. manual aspiration catheters/mechanical thrombectomy, proximal and distal protection devices) were introduced, in the last years, to reduce the risk of angiographic complications during percutaneous coronary intervention and to improve myocardial reperfusion. Recently, the MGuard stent (Inspire MD, Tel Aviv, Israel), a bare-metal stent covered by micron level mesh, which allows to prevent distal embolization by blocking the atherothrombi prolapse through the stent struts during deployment has been introduced. This article discusses the data concerning safety and efficacy of mesh covered stent implantation in a ST-segment elevation myocardial infarction setting, as well as during percutaneous coronary intervention in saphenous venous grafts.

Use of the Hypomania Checklist-32 and the Mood Disorder Questionnaire for detecting bipolarity in 1051 patients with major depressive disorder.

PURPOSE: To use the hypomania checklist (HCL-32) and the mood disorder questionnaire (MDQ), for detecting bipolarity in depressed patients. PATIENTS: One thousand and fifty-one patients fulfilling ICD-10 criteria for unipolar major depressive episode, single or recurrent, were studied. Patients were assessed using a structured demographic and clinical data interview, and by the Polish versions of the HCL-32 and MDQ questionnaires. RESULTS: Hypomanic symptoms exceeding cut-off criteria for bipolarity by HCL-32 were found in 37.5% of patients and, by MDQ, in 20% of patients. Patients with HCL-32 (+) or MDQ (+) differed significantly from patients with HCl-32 (-) and MDQ (-) respectively, by being less frequently married, having more family history of depression, bipolar disorder, alcoholism and suicide, earlier onset of illness, and more depressive episodes and psychiatric hospitalizations. The percentage of patients resistant to treatment with antidepressant drugs was significantly higher in HCL-32 (+) vs. HCL-32 (-) and in MDQ (+) vs. MDQ (-): 43.9% vs. 30.0%, and 26.4% vs. 12.4%, respectively. CONCLUSIONS: The results confirm a substantial percentage of bipolarity in major depressive disorder. Such patients have a number of clinical characteristics pointing on a more severe form of the illness and their depression is more resistant to treatment with antidepressants.

Early glycoprotein IIb-IIIa inhibitors in primary angioplasty-abciximab long-term results (EGYPT-ALT) cooperation: individual patient's data meta-analysis.

BACKGROUND: Even although time to treatment has been shown to be a determinant of mortality in primary angioplasty, the potential benefits are still unclear from early pharmacological reperfusion by glycoprotein (Gp) IIb-IIIa inhibitors. Therefore, the aim of this meta-analysis was to combine individual data from all randomized trials conducted on upstream as compared with late peri-procedural abciximab administration in primary angioplasty. METHODS: The literature was scanned using formal searches of electronic databases (MEDLINE and EMBASE) from January 1990 to December 2010. All randomized trials on upstream abciximab administration in primary angioplasty were examined. No language restrictions were enforced. RESULTS: We included a total of seven randomized trials enrolling 722 patients, who were randomized to early (n = 357, 49.4%) or late (n = 365, 50.6%) peri-procedural abciximab administration. No difference in baseline characteristics was observed between the two groups. Follow-up data were collected at a median (25th-75th percentiles) of 1095 days (720-1967). Early abciximab was associated with a significant reduction in mortality (primary endpoint) [20% vs. 24.6%; hazard ratio (HR) 95% confidence interval (CI) = 0.65 (0.42-0.98) P = 0.02, P(het) = 0.6]. Furthermore, early abciximab administration was associated with a significant improvement in pre-procedural thrombolysis in myocardial infarction (TIMI) 3 flow (21.6% vs. 10.1%, P < 0.0001), post-procedural TIMI 3 flow (90% vs. 84.8%, P = 0.04), an improvement in myocardial perfusion as evaluated by post-procedural myocardial blush grade (MBG) 3 (52.0% vs. 43.2%, P = 0.03) and ST-segment resolution (58.4% vs. 43.5%, P < 0.0001) and significantly less distal embolization (10.1% vs. 16.2%, P = 0.02). No difference was observed in terms of major bleeding complications between early and late abciximab administration (3.3% vs. 2.3%, P = 0.4). CONCLUSIONS: This meta-analysis shows that early upstream administration of abciximab in patients undergoing primary angioplasty for ST-segment elevation myocardial infarction (STEMI) is associated with significant benefits in terms of pre-procedural epicardial re-canalization and ST-segment resolution, which translates in to significant mortality benefits at long-term follow-up.

From bouncy legs to poisoned arrows: elastic movements in invertebrates.

Elastic mechanisms in the invertebrates are fantastically diverse, yet much of this diversity can be captured by examining just a few fundamental physical principles. Our goals for this commentary are threefold. First, we aim to synthesize and simplify the fundamental principles underlying elastic mechanisms and show how different configurations of basic building blocks can be used for different functions. Second, we compare single rapid movements and rhythmic movements across six invertebrate examples - ranging from poisonous cnidarians to high-jumping froghoppers - and identify remarkable functional properties arising from their underlying elastic systems. Finally, we look to the future of this field and find two prime areas for exciting new discoveries - the evolutionary dynamics of elastic mechanisms and biomimicry of invertebrate elastic materials and mechanics.

Early glycoprotein IIb-IIIa inhibitors in primary angioplasty (EGYPT) cooperation: an individual patient data meta-analysis.

BACKGROUND: Even though time-to-treatment has been shown to be a determinant of mortality in primary angioplasty, the potential benefits from early pharmacological reperfusion by glycoprotein (Gp) IIb-IIIa inhibitors are still unclear. The aim of this meta-analysis was to combine individual data from all randomised trials conducted on facilitated primary angioplasty by the use of early Gp IIb-IIIa inhibitors. METHODS AND RESULTS: The literature was scanned by formal searches of electronic databases (MEDLINE, EMBASE) from January 1990 to October 2007. All randomised trials on facilitation by the early administration of Gp IIb-IIIa inhibitors in ST-segment elevation myocardial infarction (STEMI) were examined. No language restrictions were enforced. Individual patient data were obtained from 11 out of 13 trials, including 1662 patients (840 patients (50.5%) randomly assigned to early and 822 patients (49.5%) to late Gp IIb-IIIa inhibitor administration). Preprocedural Thrombolysis in Myocardial Infarction Study (TIMI) grade 3 flow was more frequent with early Gp IIb-IIIa inhibitors. Postprocedural TIMI 3 flow and myocardial blush grade 3 were higher with early Gp IIb-IIIa inhibitors but did not reach statistical significance except for abciximab, whereas the rate of complete ST-segment resolution was significantly higher with early Gp IIb-IIIa inhibitors. Mortality was not significantly different between groups, although early abciximab demonstrated improved survival compared with late administration, even after adjustment for clinical and angiographic confounding factors. CONCLUSIONS: This meta-analysis shows that pharmacological facilitation with the early administration of Gp IIb-IIIa inhibitors in patients undergoing primary angioplasty for STEMI is associated with significant benefits in terms of preprocedural epicardial recanalisation and ST-segment resolution, which translated into non-significant mortality benefits except for abciximab.

Dynamics of geckos running vertically.

Geckos with adhesive toe pads rapidly climb even smooth vertical surfaces. We challenged geckos (Hemidactylus garnotii) to climb up a smooth vertical track that contained a force platform. Geckos climbed vertically at up to 77 cm s(-1) with a stride frequency of 15 Hz using a trotting gait. During each step, whole body fore-aft, lateral and normal forces all decreased to zero when the animal attached or detached its toe pads. Peak fore-aft force was twice body weight at mid-step. Geckos climbed at a constant average velocity without generating decelerating forces on their center of mass in the direction of motion. Although mass-specific mechanical power to climb was ten times the value expected for level running, the total mechanical energy of climbing was only 5-11% greater than the potential energy change. Fore- and hindlegs both pulled toward the midline, possibly loading the attachment mechanisms. Attachment and detachment of feet occupied 13% and 37% of stance time, respectively. As climbing speed increased, the absolute time required to attach and detach did not decrease, suggesting that the period of fore-aft force production might be constrained. During ascent, the forelegs pulled toward, while hindlegs pushed away from the vertical surface, generating a net pitching moment toward the surface to counterbalance pitch-back away from the surface. Differential leg function appears essential for effective vertical as well as horizontal locomotion.

Impurity profiling/comparative analyses of samples of 1-phenyl-2-propanone.

1-Phenyl-2-propanone (P-2-P), also known as benzyl methyl ketone (BMK), is the main precursor used in amphetamine synthesis. In recent years, the number of seizures of P-2-P from both licit and illicit drug manufacture has increased. The present article comprises a discussion of some of the largest seizures of P-2-P diverted from regular production to the illicit market. It also presents the methods used in clandestine laboratories to synthesize P-2-P and a forensic approach to identify and differentiate between these methods. To that end, and to facilitate the monitoring of the P-2-P market, a method of P-2-P impurity profiling was designed for comparative purposes and for the identification of the synthesis route. P-2-P samples were analysed by means of gas chromatography/mass spectrometry (GC/MS). Out of 36 identified impurities, 14 were selected as markers for sample comparison. On the basis of the GC peak areas of those 14 markers, a cluster analysis was carried out, resulting in three clusters, each corresponding to a given P-2-P synthesis route. The results of P-2-P impurity profiling are stored in both a forensic database and a police database. The forensic database comprises chemical data, such as those on P-2-P purity, additives and specific impurities, as well as information on seized P-2-P samples having a similar impurity profile. Data stored in the police database, which is linked with the forensic database by case identification number, cover the circumstances of seizures and personal details of offenders. The databases enable the full use of forensic data in intelligence work and police investigative activities.

Comparison of dual-chamber pacing with nonsurgical septal reduction effect in patients with hypertrophic obstructive cardiomyopathy.

OBJECTIVES: The aim of the study was to compare the influence of dual-chamber pacing vs. nonsurgical septal reduction on hemodynamic and morphological parameters in patients with obstructive form of hypertrophic cardiomyopathy. METHODS: Nineteen patients with dual-chamber pacing (group I) and 9 patients who underwent nonsurgical septal reduction (group II) were studied at baseline and after a 6-month follow-up. The changes of left ventricular outflow tract gradient and posterior wall thickness (as an index of left ventricular hypertrophy regression) were compared. RESULTS: The baseline left ventricular outflow tract gradient was comparable between group I and group II (77+/-25 vs. 82+/-25 mm Hg, p>0.05). At 6-month follow-up, the left ventricular outflow tract gradient was reduced to a similar level in both groups (28+/-19 vs. 25+/-12 mm Hg, p>0.05). At baseline, posterior wall hypertrophy was comparable between groups (12.9+/-1.7 vs. 13.6+/-2.2 mm, p>0.05). During follow-up, the posterior wall thickness was unchanged in the pacing group (12.9+/-1.7 vs. 12.6+/-1.6 mm, p>0.05), whereas nonsurgical septal reduction induced regression of left ventricular hypertrophy in myocardial region remote from the infarcted septal segment (13.6+/-2.2 vs. 10.5+/-2.3 mm, p<0.003). CONCLUSION: Despite comparable reduction of instantaneous left ventricular outflow tract gradient, the nonsurgical septal reduction decreased posterior wall thickness, whereas pacing did not reduce left ventricular hypertrophy. Thus, regression of left ventricular hypertrophy that appeared solely after nonsurgical septal reduction may reflect the more permanent reduction of left ventricular pressure overload. Thus, not only hemodynamic but also morphological benefit from nonsurgical septal reduction seems to indicate the superiority of this method over dual-chamber pacing.

A genome screen of systemic lupus erythematosus using affected-relative-pair linkage analysis with covariates demonstrates genetic heterogeneity.

Systemic lupus erythematosus (SLE) appears to be the consequence of complex genetics and of only partly understood environmental contributions. Previous work by ourselves and by others has established genetic effects on 1q, 2q, 4p, 6p, and 16p using SLE as the phenotype. However, individual SLE affecteds are extraordinarily different from one another by clinical and laboratory measures. This variation may have a genetic basis; if so, it is advantageous to incorporate measures of between-family clinical variability as covariates in a genetic linkage analysis of affected relative pairs (ARPs) to allow for locus heterogeneity. This approach was applied to genome scan marker data from 160 pedigrees multiplex for SLE and containing 202 ARPs. Because the number of potential covariates was large, we used both ad hoc methods and formal principal components analysis to construct four composite covariates using the SLE classification criteria plus age of onset, ethnicity, and sex. Linkage analysis without covariates has detected evidence for linkage at 1q22-24, 2q37, 4p16, 12p12-11, and 17p13. Linkage analysis with these covariates uncovered linkage at 13p11, 17q11-25, and 20q12 and greatly improved evidence for linkage at 1q22-24, 2q37, 12p12-11, and 17p13. Follow-up analysis identified the original variables contributing to locus heterogeneity in each of these locations. In conclusion, allowing for locus heterogeneity through the incorporation of covariates in linkage analysis is a useful way to dissect the genetic contributions to SLE and uncover new genetic effects.

[Personality patterns in coronary artery disease]. / Cechy osobowosci a chrooba niedokrwienna serca.

Relation of personality patterns and type A behaviour to the risk and prognosis of coronary artery disease was described. The particular interest of researchers was directed toward hostility, which correlated with the course of coronary artery disease. Finally, therapeutical implications, deriving from the holistic approach to cardiological patients, were proposed.