Phenotype and risk factors of venom-induced anaphylaxis: A case-control study of the European Anaphylaxis Registry

Background: Venom-induced anaphylaxis (VIA) is a common, potentially life-threatening hypersensitivity reaction associated with (1) a specific symptom profile, 2) specific cofactors, and 3) specific management. Identifying the differences in phenotypes of anaphylaxis is crucial for future management guidelines and development of a personalized medicine approach. Objective: This study aimed to evaluate the phenotype and risk factors of VIA. Methods: Using data from the European Anaphylaxis Registry (12,874 cases), we identified 3,612 patients with VIA and analyzed their cases in comparison with sex- and age-matched anaphylaxis cases triggered by other elicitors (non-VIA cases [n = 3,605]). Results: VIA more frequently involved more than 3 organ systems and was associated with cardiovascular symptoms. The absence of skin symptoms during anaphylaxis was correlated with baseline serum tryptase level and was associated with an increased risk of a severe reaction. Intramuscular or intravenous epinephrine was administered significantly less often in VIA, in particular, in patients without a history of anaphylaxis. A baseline serum tryptase level within the upper normal range (8-11.5 ng/mL) was more frequently associated with severe anaphylaxis. Conclusion: Using a large cohort of VIA cases, we have validated that patients with intermediate baseline serum tryptase levels (8-11 ng/mL) and without skin involvement have a higher risk of severe VIA. Patients receiving β-blockers or angiotensin-converting enzyme inhibitors had a higher risk of developing severe cardiovascular symptoms (including cardiac arrest) in VIA and non-VIA cases. Patients experiencing VIA received epinephrine less frequently than did cases with non-VIA

An investigation of breast cancer risk factors in Cyprus: a case control study

Background: Breast cancer is the most common form of malignancy affecting women worldwide. It is also the leading cancer in females in Cyprus, with approximately 400 new cases diagnosed annually. It is well recognized that genetic variation as well as environmental factors modulate breast cancer risk. The main aim of this study was to assess the strength of associations between recognized risk factors and breast cancer among Cypriot women. This is the first epidemiological investigation on risk factors of breast cancer among the Cypriot female population.Methods: We carried out a case-control study, involving 1,109 breast cancer patients and a group of 1,177 controls who were recruited while participating in the National screening programme for breast cancer. Information on demographic characteristics and potential risk factors were collected from both groups during a standardized interview. Logistic regression analysis was used to assess the strength of the association between each risk factor and breast cancer risk, before and after adjusting for the possible confounding effect of other factors.Results: In multivariable models, family history of breast cancer (OR 1.64, 95% CI 1.23, 2.19) was the strongest predictor of breast cancer risk in the Cypriot population. Late menarche (OR 0.64, 95% CI 0.45, 0.92 among women reaching menarche after the age of 15 vs. before the age of 12) and breastfeeding (OR 0.74, 95% CI 0.59, 0.92) exhibited a strong protective effect. In the case of breastfeeding, the observed effect appeared stronger than the effect of pregnancy alone. Surprisingly, we also observed an inverse association between hormone replacement therapy (HRT) although this may be a product of the retrospective nature of this study.Conclusion: Overall the findings of our study corroborate with the results of previous investigations on descriptive epidemiology of risk factors for breast cancer. This investigation provides important background information for designing detailed studies that aim to improve our understanding of the epidemiology of breast cancer in the Cypriot population, including the study of gene-environment interactions. Furthermore, our study provides the first scientific evidence for formulating targeted campaigns for prevention and early diagnosis of breast cancer in Cyprus

Microbubble-Based Sonothrombolysis Using a Planar Rectangular Ultrasonic Transducer

The aim of the proposed study was to evaluate in an in vitro flow model the ability of small planar rectangular (2 × 10 mm2) ultrasonic transducer to enhance thrombolysis induced by the thrombolytic agent tenecteplase (TNK-tPA). Methods To provide a more realistic clinical environment of stroke, the study was conducted under realistic flow conditions and TNK-tPA concentrations. Fully retracted porcine blood clots were used to determine the thrombolytic efficacy of ultrasound (US) waves as an adjunct to TNK-tPA or in combination with microbubbles (MBs). Two ultrasonic flat rectangular transducers were used in the experiments, operating at 3.7 and 5.2 MHz respectively. A pulsed US protocol that maintained temperature elevation at the target of 1°C was applied. Thrombolysis efficacy was measured in milligrams of mass clot removed. Results The effect of experimental parameters, such as power, frequency, and MBs administration, on thrombolysis efficacy was explored. Conclusions The results revealed that thrombolysis efficacy decreases at higher frequency, and therefore, the possibility of using lower frequency to improve efficacy should be further investigated. Additionally, study findings demonstrated that the combination of 3.7 MHz with MBs as an adjunct to TNK-tPA strongly enhanced thrombolysis efficacy, because with 30 minutes of treatment, 700 mg of clot was removed through nonthermal mechanisms. As a final point, this study has shown that MBs dose influences thrombolysis enhancement, because higher thrombolytic efficacy was observed with higher doses of MBs

The Enhancing Effect of Focused Ultrasound on TNK-Tissue Plasminogen Activator-Induced Thrombolysis Using an In Vitro Circulating Flow Model

Background The limited efficacy of thrombolytic therapy in patients with ischemic stroke has created the need to use focused ultrasound (FUS) energy as a way to enhance thrombolysis efficacy (sonothrombolysis). Using an in vitro circulating flow model, we evaluated the role of physical parameters on tenecteplase (TNK-tPA)-mediated thrombolysis. Materials and Methods Fully retracted porcine blood clots were used for the proposed experimental study. To provide a more realistic clinical environment of stroke, the study was conducted under realistic flow conditions and TNK-tPA concentrations. Two spherically FUS transducers (4-cm diameter), focusing at 10 cm and operating at .6 and 1.05 MHz, respectively, were used. Pulsed ultrasound protocols that maintained a localized temperature elevation at the focus of 1°C were applied. Thrombolysis efficacy was measured in milligram of mass clot removed. Results The effect of physical parameters such as temperature, FUS frequency, acoustic power (AP), FUS energy, and microbubble (MB) administration on thrombolysis efficacy was examined. Conclusions Study findings established that higher FUS frequencies (1 MHz) are associated with enhanced thrombolysis compared to lower FUS frequencies (.6 MHz). Furthermore, an increase in the linear relationship between AP and thrombolysis efficacy was exhibited. Also, the outcome of the study showed that the combination of 1-MHz FUS pulses with MBs strongly enhanced the enzymatic thrombolytic efficacy of TNK-tPA, because with 30 minutes of treatment, 1050 mg of clot was removed through nonthermal mechanisms. Taking into consideration that stroke is time dependent, this thrombolytic rate should be sufficient for timely recanalization of the occluded cerebral artery