Age of uptake of early cancer detection facilities by low-risk and high-risk patients with familial breast and ovarian cancer.

INTRODUCTION: Some 5-10% of all cases of breast cancer and ovarian cancer have a hereditary genesis. In the setting of an interdisciplinary cancer genetics clinic, a study of the age at which patients first take advantage of early cancer detection (ECD) facilities was conducted in order to assess the influence of familial risk on health issues. METHODS: The study included 556 women who fulfilled the inclusion criteria (IC) for genetic analysis of the BRCA1 and BRCA2 genes, as well as 205 who did not meet these criteria but attended the primary consultation. RESULTS: Consulters who met the inclusion criteria took advantage of nearly all methods of ECD at an earlier time than women who did not. A comparison of consulters with or without breast cancer showed that those without breast cancer participated in all methods of ECD at an earlier time. CONCLUSION: Methods of improving and increasing participation in ECD facilities, and of encouraging women who are at risk to start on such programs at a younger age, need to be discussed. In this study, familial risk already resulted in a younger age of uptake of ECD facilities.     

Systemic oxidative stress in children with cystic fibrosis with bacterial infection including Pseudomonas Aeruginosa

IntroductionOxidative stress (OS) occurs in cystic fibrosis (CF).ObjectiveThe objective of this work is to evaluate the influence of bacterial infection on biomarkers of OS (catalase [CAT], glutathione peroxidade [GPx], reduced glutathione [GSH]), markers of oxidative damage (protein carbonyls [PC], thiobarbituric acid reactive substances [TBARS]), together with the nutritional status and lung function in children with CF.MethodsCross‐sectional study including CF group (CFG, n = 55) and control group (CG, n = 31), median age: 3.89 and 4.62 years, respectively. CFG was distributed into CFG negative bacteriology (CFGB−, n = 27) or CFG positive bacteriology (CFGB+, n = 28), and CFG negative Pseudomonas aeruginosa (CFGPa−, n = 36) or CFG positive Pseudomonas aeruginosa (CFGPa+, n = 19).ResultsCompared with CG, CFG (P = .034) and CFGB+ (P = .042) had lower body mass index‐for‐age z‐score; forced expiratory volume in the first second was lower in CFGB+ and CFGPa+ (both P < .001). After adjusting for confounders and compared with CG: CFG showed higher TBARS (P ≤ .001) and PC (P = .048), and lower CAT (P = .004) and GPx (P = .003); the increase in PC levels was observed in CFGB+ (P = .011) and CFGPa+ (P = .001) but not in CFGB− (P = .510) and CFGPa− (P = .460).ConclusionsThese results indicate a systemic OS in children with CF. The presence of bacterial infection particularly Pseudomonas aeruginosa seems to be determinant to exacerbate the oxidative damage to proteins, in which PC may be a useful biomarker of OS in CF.     

Non-arteritic anterior ischemic optic neuropathy (NA-AION) after intravitreal injection of bevacizumab (Avastin®) for treatment of angoid streaks in pseudoxanthoma elasticum

Background

To report a case of nonarteritic anterior ischemic optic neuropathy (NA-AION) following intravitreal injection of bevacizumab (Avastin®).

Methods

Interventional case report with an 18-month follow-up.

Results

A 51-year-old male with pseudoxanthoma elasticum presented with NA-AION 2 weeks after treatment with intravitreal of bevazicumab (Avastin®) for choroidal neovascularisation secondary to angioid streaks. Except from a small optic disc without cupping he did not show further risk factors.

Discussion

Risk of NA-AION should be taken into consideration when deciding for intravitreal application of drugs including anti-vascular endothelial growth factors (VEGF) agents like bevacizumab (Avastin®) in the treatment of retinal vascular diseases.

     

Human placental lactogen and unconjugated estriol concentrations in twin pregnancy: monitoring of fetal development in intrauterine growth retardation and single intrauterine fetal death

Human placental lactogen and unconjugated estriol concentrations in maternal serum were evaluated in 100 uneventful twin pregnancies, and these values were compared with those observed in 16 twin pregnancies associated with intrauterine growth retardation or single intrauterine fetal death. In pregnancies associated with intrauterine growth retardation (n = 8), human placental lactogen levels were at the lower limit of normal range for singleton pregnancies, whereas estriol levels were normal in most cases. When one of the fetuses had died before week 33 of pregnancy (n = 5), both human placental lactogen and estriol levels were low and they were almost at the levels in singleton pregnancy. When intrauterine fetal death occurred after week 36 of pregnancy (n = 3), both hormone levels remained normal until term. Thus human placental lactogen rather than estriol is a good indicator of intrauterine growth retardation in twin pregnancy. Both human placental lactogen and estriol are useful for the monitoring of the surviving fetus in the case of single intrauterine fetal death.     

Relative efficacy of lasmiditan versus rimegepant and ubrogepant as acute treatments for migraine: network meta-analysis findings

BackgroundIn the absence of head-to-head trials, comprehensive evidence comparing onset of efficacy of novel agents for acute treatment of migraine is lacking. This study aimed to explore the relative efficacy of lasmiditan (serotonin [5-hydroxytryptamine] 1F receptor agonist) versus rimegepant and ubrogepant (calcitonin gene-related peptide antagonists) for the acute oral treatment of migraine through network meta-analysis (NMA).MethodsData included in the NMA were identified through a systematic literature search (conducted April 2018, updated May/December 2020) of phase II–IV, randomised controlled trials (RCTs) in adults with chronic/episodic migraine with/without aura. Treatments included: lasmiditan 50, 100, 200 mg; rimegepant 75 mg; ubrogepant 25, 50, 100 mg. Pairwise treatment comparisons from Bayesian fixed-effect/random-effects NMA, adjusted by baseline risk where appropriate, were conducted. Comparisons were reported as odds ratios with 95% credible intervals. Early-onset efficacy endpoints included: pain freedom at 2 hours and pain relief at 1 and 2 hours. Adverse drug reaction (ADR) profiles were summarised. Heterogeneity and inconsistency in the network were explored; sensitivity analyses investigated robustness of findings.ResultsAcross 12 RCTs included in the base case, females represented >80% of included patients (mean age 37.9–45.7 years). Odds of achieving both pain freedom and pain relief at 2 hours were higher with lasmiditan 100 and 200 mg versus rimegepant 75 mg and ubrogepant 25 and 50 mg. Results for pain relief at 1 hour were consistent with those at 2 hours, but fewer comparisons were available. There were no statistically significant differences between lasmiditan 50 mg and ubrogepant or rimegepant for any outcome. Sensitivity analyses were in the same direction as base case analyses. Most commonly reported ADRs (incidence ≥2%) were: dizziness, fatigue, paraesthesia, sedation, nausea/vomiting and muscle weakness with lasmiditan; nausea with rimegepant; and nausea, somnolence and dry mouth with ubrogepant.ConclusionsThe efficacy findings of this indirect comparison indicate that lasmiditan 100 mg or 200 mg might be an appropriate acute treatment option for patients with migraine seeking a fast onset of action. Differently from rimegepant and ubrogepant, lasmiditan use is associated with mainly neurological events, which are mostly mild or moderate in severity and self-limiting.350/350 wordsSupplementary InformationThe online version contains supplementary material available at 10.1186/s10194-022-01440-w.     

Predictors associated with mortality of extracorporeal life support therapy for acute heart failure: single-center experience with 679 patients

BackgroundExtracorporeal life support (ECLS) therapy is increasingly used for cardiac and respiratory support postcardiotomy, refractory cardiogenic shock and cardiopulmonary resuscitation. This study aims to describe in-hospital mortality of patients requiring ECLS, identify independent predictors associated with mortality and analyze changes of mortality over time.MethodsThis retrospective study includes all adult ECLS cases at the University Hospital Zurich, a designated ECLS center in Switzerland, in the period 2007 to 2019.ResultsECLS therapy was required in 679 patients (median age 60 years, 27.5% female). In-hospital mortality was 55.5%. Cubic spline interpolation did not detect evidence for a change in mortality over the whole period of 13 years. In-hospital mortality significantly varied between ECLS indications: 70.7% (152/215) for postcardiotomy, 67.9% (108/159) for cardiopulmonary resuscitation, 47.0% (110/234) for refractory cardiogenic shock, and 9.9% (7/71) for lung transplantation and expansive thoracic surgery (P<0.001). Logistic regression modelling showed excellent discrimination in the receiver operating characteristic (ROC) area under the curve (AUC) of 0.89 [95% confidence interval (CI): 0.87–0.92] and identified significant mortality predictors: age, simplified acute physiology score (SAPS) II, as well as new liver failure and each allogenic blood transfusion unit given per day. ECLS after cardiopulmonary resuscitation was associated with significantly higher mortality compared to ECLS for refractory cardiogenic shock.ConclusionsIn-hospital mortality of patients treated with ECLS therapy is high. Outcomes have not changed significantly in the observed period. We identified age, SAPS II, new liver failure and each allogenic blood transfusion unit given per day as independent mortality predictors. Knowledge of predictors strongly associated with in-hospital mortality may affect future decisions about ECLS indications and the respective management to use this elaborate therapy more effectively.     

Resin infiltration of deproteinised natural occlusal subsurface lesions improves initial quality of fissure sealing

The aim of this ex vivo study was to evaluate the infiltration capability and rate of microleakage of a low-viscous resin infiltrant combined with a flowable composite resin (RI/CR) when used with deproteinised and etched occlusal subsurface lesions (International Caries Detection and Assessment System code 2). This combined treatment procedure was compared with the exclusive use of flowable composite resin (CR) for fissure sealing. Twenty premolars and 20 molars revealing non-cavitated occlusal carious lesions were randomly divided into two groups and were meticulously cleaned and deproteinised using NaOCl (2%). After etching with HCl (15%), 10 premolar and 10 molar lesions were infiltrated (Icon/DMG; rhodamine B isothiocyanate (RITC)-labelled) followed by fissure sealing (G-?nial Flo/GC; experimental group, RI/CR). In the control group (CR), the carious fissures were only sealed. Specimens were cut perpendicular to the occlusal surface and through the area of the highest demineralisation (DIAGNOdent pen, KaVo). Using confocal laser-scanning microscopy, the specimens were assessed with regard to the percentage of caries infiltration, marginal adaption and internal integrity. Within the CR group, the carious lesions were not infiltrated. Both premolar (57.9%± 23.1%) and molar lesions (35.3%± 22.1%) of the RI/CR group were uniformly infiltrated to a substantial extent, albeit with significant differences (P=0.034). Moreover, microleakage (n=1) and the occurrence of voids (n=2) were reduced in the RI/CR group compared with the CR group (5 and 17 specimens, respectively). The RI/CR approach increases the initial quality of fissure sealing and is recommended for the clinical control of occlusal caries.     

Access to genetic material: reproductive technologies and bioethical issues

New assisted reproduction technologies provide access to, and require the handling of, genetic material. Such material includes gametes or early-stage embryos. After a selective appraisal of some of the most relevant developments facilitated by the access to germ cells and embryos, this paper identifies some major ethical challenges created by the assisted reproduction technologies, with a special focus on Germany. The rapid progress in medical technology makes it difficult to prohibit or allow assisted reproduction technologies on the basis of such traditional criteria as the protection of human life, medical indications or a preference to adhere to natural processes. Instead, a more open discussion and a flexible application of ethical principles may be more helpful, such as: (i) considering DNA as a biological data file which allows potential access to a person's biography or identity; (ii) reconciling the protection of the early embryo with patients' needs; and (iii) placing both the mother and her embryo at the centre of bioethical and legal considerations, instead of exclusively relying on ethical principles and expert opinions with regard to the embryo alone. To continue the success of assisted reproduction, more attention should be given to the 'lifeworld' philosophy, as some authors have put it.