A simple clinical method for predicting the benefit of prone vs. supine positioning in reducing heart exposure during left breast radiotherapy

Background and purpose: The benefit of reduced radiation heart exposure in the prone vs. supine position individually differs. In this prospective cohort study, the goal was to develop a simple method for the operation of a validated model for the prediction of preferable treatment position during left breast radiotherapy. Material and methods: In 100 cases, a single CT slice was utilized for the collection of the needed patientspecific data (in addition to body mass index, the distance of the LAD from the chest wall and the area of the heart included in the radiation fields at the middle of the heart in the supine position). Outcome was analyzed in relation to the full CT series acquired in both positions and dosimetric data. Results: Great consistency was found between the tested and original method regarding sensitivity and specificity. The prioritization of LAD dose, and the use of heart dose and position-specific dose constraints as safety measures ensure sensitivity and specificity values of 82.8% and 87.3%, respectively. In an additional ‘‘routine clinical practice” series of 60 patients the new method seemed feasible in routine clinical practice. External testing on a 28-case series indicated similar accuracy. Conclusion: We consider this simple clinical tool appropriate for assisting individual positioning aiming at maximum heart protection during left breast irradiatio

The effect of ranibizumab and aflibercept treatment on the prevalence of outer retinal tubulation and its influence on retreatment in neovascular age-related macular degeneration

Abstract Background We aimed to analyze the differences in the prevalence of outer retinal tubulation (ORT) in neovascular age-related macular degeneration (AMD) treated with anti-vascular endothelial growth factor (anti-VEGF) agents, either aflibercept or ranibizumab. Our further aim was to examine the changes in the frequency of injections of ranibizumab before and after ORT appearance. Methods Two hundred thirty six eyes of 230 patients were included in the study (184 eyes treated with ranibizumab by pro re nata regimen (PRN), 52 eyes with aflibercept bimonthly) and followed for 6–24 months. Using optical coherence tomography (OCT), the first appearance of ORT was documented, and fixed time point evaluations were also made every six months to determine the existence of ORT. The number of injections, the presence or absence of subretinal hyperreflective material (SHRM) at treatment initiation and visual acuity were also noted. Results The survival analysis with Cox proportional hazard model showed no significant difference between the ranibizumab and aflibercept groups in relation to the development of ORT (p = 0.79, hazard ratio 0.92). In the PRN treated ranibizumab group the number of injections showed significant decrease after ORT development (p = 0.004). When SHRM was present at treatment initiation the chance of developing ORT was 2.75 and 11.14 times higher in the ranibizumab and aflibercept groups, respectively. Conclusions The prevalence of ORT increased over time independently from the chosen anti-VEGF drug. Our results suggest that upon the appearance of ORT a decrease in retreatments can be expected

Absolute beat-to-beat variability and instability parameters of ECG intervals:biomarkers for predicting ischaemia-induced ventricular fibrillation

BACKGROUND AND PURPOSE: Predicting lethal arrhythmia liability from beat-to-beat variability and instability (BVI) of the ECG intervals is a useful technique in drug assessment. Most investigators use only arrhythmia-free ECGs for this. Recently, it was shown that drug-induced torsades de pointes (TdP) liability can be predicted more accurately from BVI measured irrespective of rhythm, even during arrhythmias (absolute BVI). The present study tested the broader applicability of this assessment by examining whether absolute BVI parameters predict another potential lethal arrhythmia, ischaemia-induced ventricular fibrillation (VF). EXPERIMENTAL APPROACH: Langendorff-perfused rat hearts were subjected to regional ischaemia for 15 min. Absolute BVI parameters were derived from ECG intervals measured in 40 consecutive ventricular complexes (irrespective of rhythm) immediately preceding VF onset and compared with time-matched values in hearts not expressing VF. KEY RESULTS: Increased frequency of non-sinus beats and ‘R on T’ arrhythmic beats, shortened mean RR and electrical diastolic intervals, and increased BVI of cycle length and repolarization predicted VF occurrence. Absolute BVI parameters that quantify variability of repolarization (e.g. ‘short-term variability’ of QT interval) had the best predictive power with high sensitivity and specificity. In contrast, VF was not predicted by any BVI parameter derived from the last arrhythmia-free interlude before VF. CONCLUSIONS AND IMPLICATIONS: The novel absolute BVI parameters that predicted TdP in rabbit also predict ischaemia-induced VF in rat, indicating a diagnostic and mechanistic congruence. Repolarization inhomogeneity represents a pivotal biomarker of ischaemia-induced VF. The newly validated biomarkers could serve as surrogates for VF in pre-clinical drug investigations

Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicentre observational study in 261 hospitals in Europe

Background Little is known about the incidence of severe critical events in children undergoing general anaesthesia in Europe. We aimed to identify the incidence, nature, and outcome of severe critical events in children undergoing anaesthesia, and the associated potential risk factors. Methods The APRICOT study was a prospective observational multicentre cohort study of children from birth to 15 years of age undergoing elective or urgent anaesthesia for diagnostic or surgical procedures. Children were eligible for inclusion during a 2-week period determined prospectively by each centre. There were 261 participating centres across 33 European countries. The primary endpoint was the occurence of perioperative severe critical events requiring immediate intervention. A severe critical event was defined as the occurrence of respiratory, cardiac, allergic, or neurological complications requiring immediate intervention and that led (or could have led) to major disability or death. This study is registered with ClinicalTrials.gov, number NCT01878760. Findings Between April 1, 2014, and Jan 31, 2015, 31 127 anaesthetic procedures in 30 874 children with a mean age of 6.35 years (SD 4.50) were included. The incidence of perioperative severe critical events was 5.2% (95% CI 5.0-5.5) with an incidence of respiratory critical events of 3.1% (2.9-3.3). Cardiovascular instability occurred in 1.9% (1.7-2.1), with an immediate poor outcome in 5.4% (3.7-7.5) of these cases. The all-cause 30-day in-hospital mortality rate was 10 in 10 000. This was independent of type of anaesthesia. Age (relative risk 0.88, 95% CI 0.86-0.90; p<0.0001), medical history, and physical condition (1.60, 1.40-1.82; p<0.0001) were the major risk factors for a serious critical event. Multivariate analysis revealed evidence for the beneficial effect of years of experience of the most senior anaesthesia team member (0.99, 0.981-0.997; p<0.0048 for respiratory critical events, and 0.98, 0.97-0.99; p=0.0039 for cardiovascular critical events), rather than the type of health institution or providers. Interpretation This study highlights a relatively high rate of severe critical events during the anaesthesia management of children for surgical or diagnostic procedures in Europe, and a large variability in the practice of paediatric anaesthesia. These findings are substantial enough to warrant attention from national, regional, and specialist societies to target education of anaesthesiologists and their teams and implement strategies for quality improvement in paediatric anaesthesia