Intrafraction tumor motion monitoring and dose reconstruction for liver pencil beam scanning proton therapy.

BACKGROUND Pencil beam scanning (PBS) proton therapy can provide highly conformal target dose distributions and healthy tissue sparing. However, proton therapy of hepatocellular carcinoma (HCC) is prone to dosimetrical uncertainties induced by respiratory motion. This study aims to develop intra-treatment tumor motion monitoring during respiratory gated proton therapy and combine it with motion-including dose reconstruction to estimate the delivered tumor doses for individual HCC treatment fractions. METHODS Three HCC-patients were planned to receive 58 GyRBE (n=2) or 67.5 GyRBE (n=1) of exhale respiratory gated PBS proton therapy in 15 fractions. The treatment planning was based on the exhale phase of a 4-dimensional CT scan. Daily setup was based on cone-beam CT (CBCT) imaging of three implanted fiducial markers. An external marker block (RPM) on the patient's abdomen was used for exhale gating in free breathing. This study was based on 5 fractions (patient 1), 1 fraction (patient 2) and 6 fractions (patient 3) where a post-treatment control CBCT was available. After treatment, segmented 2D marker positions in the post-treatment CBCT projections provided the estimated 3D motion trajectory during the CBCT by a probability-based method. An external-internal correlation model (ECM) that estimated the tumor motion from the RPM motion was built from the synchronized RPM signal and marker motion in the CBCT. The ECM was then used to estimate intra-treatment tumor motion. Finally, the motion-including CTV dose was estimated using a dose reconstruction method that emulates tumor motion in beam's eye view as lateral spot shifts and in-depth motion as changes in the proton beam energy. The CTV homogeneity index (HI) The CTV homogeneity index (HI) was calculated as . RESULTS The tumor position during spot delivery had a root-mean-square error of 1.3 mm in left-right, 2.8 mm in cranio-caudal and 1.7 mm in anterior-posterior directions compared to the planned position. On average, the CTV HI was larger than planned by 3.7%-points (range: 1.0-6.6%-points) for individual fractions and by 0.7%-points (range: 0.3-1.1%-points) for the average dose of 5 or 6 fractions. CONCLUSIONS A method to estimate internal tumor motion and reconstruct the motion-including fraction dose for PBS proton therapy of HCC was developed and demonstrated successfully clinically

Healthcare provision for insect venom allergy patients during the COVID-19 pandemic

The population prevalence of insect venom allergy ranges between 3–5%, and it can lead to potentially life-threatening allergic reactions. Patients who have experienced a systemic allergic reaction following an insect sting should be referred to an allergy specialist for diagnosis and treatment. Due to the widespread reduction in outpatient and inpatient care capacities in recent months as a result of the COVID-19 pandemic, the various allergy specialized centers in Germany, Austria, and Switzerland have taken different measures to ensure that patients with insect venom allergy will continue to receive optimal allergy care. A recent data analysis from the various centers revealed that there has been a major reduction in newly initiated insect venom immunotherapy (a 48.5% decline from March–June 2019 compared to March–June 2020: data from various centers in Germany, Austria, and Switzerland). The present article proposes defined organizational measures (e.g., telephone and video appointments, rearranging waiting areas and implementing hygiene measures and social distancing rules at stable patient numbers) and medical measures (collaboration with practice-based physicians with regard to primary diagnostics, rapid COVID-19 testing, continuing already-initiated insect venom immunotherapy in the outpatient setting by making use of the maximal permitted injection intervals, prompt initiation of insect venom immunotherapy during the summer season, and, where necessary, using outpatient regimens particularly out of season) for the care of insect venom allergy patients during the COVID-19 pandemic

A position paper from German and Austrian Allergy Societies AeDA, DGAKI, GPA and ÖGAI

Background: For the preventive treatment of the 2019 coronavirus disease (COVID-19) an unprecedented global research effort studied the safety and efficacy of new vaccine platforms that have not been previously used in humans. Less than one year after the discovery of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral sequence, these vaccines were approved for use in the European Union (EU) as well as in numerous other countries and mass vaccination efforts began. The so far in the EU approved mRNA vaccines BNT162b2 and mRNA-1273 are based on similar lipid-based nanoparticle carrier technologies; however, the lipid components differ. Severe allergic reactions and anaphylaxis after COVID-19 vaccination are very rare adverse events but have drawn attention due to potentially lethal outcomes and have triggered a high degree of uncertainty. Methods: Current knowledge on anaphylactic reactions to vaccines and specifically the new mRNA COVID-19 vaccines was compiled using a literature search in Medline, PubMed, as well as the national and international study and guideline registries, the Cochrane Library, and the Internet, with special reference to official websites of the World Health Organization (WHO), US Centers for Disease Control and Prevention (CDC), Robert Koch Institute (RKI), and Paul Ehrlich Institute (PEI). Results: Based on the international literature and previous experience, recommendations for prophylaxis, diagnosis and therapy of these allergic reactions are given by a panel of experts. Conclusion: Allergy testing is not necessary for the vast majority of allergic patients prior to COVID-19 vaccination with currently licensed vaccines. In case of allergic/anaphylactic reactions after vaccination, allergy workup is recommended, as it is for a small potential risk population prior to the first vaccination. Evaluation and approval of diagnostic tests should be done for this purpose

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

Anaphylaxis in Elderly Patients-Data From the European Anaphylaxis Registry

Background: Elicitors and symptoms of anaphylaxis are age dependent. However, little is known about typical features of anaphylaxis in patients aged 65 years or more. Methods: The data from the Network for Online Registration of Anaphylaxis (NORA) considering patients aged ≥65 (elderly) in comparison to data from adults (18–64 years) regarding elicitors, symptoms, comorbidities, and treatment measures were analyzed. Results: We identified 1,123 elderly anaphylactic patients. Insect venoms were the most frequent elicitor in this group (p < 0.001), followed by drugs like analgesics and antibiotics. Food allergens elicited less frequently anaphylaxis (p < 0.001). Skin symptoms occurred less frequently in elderly patients (77%, p < 0.001). The clinical symptoms were more severe in the elderly (51% experiencing grade III/IV reactions), in particular when skin symptoms (p < 0.001) were absent. Most strikingly, a loss of consciousness (33%, p < 0.001) and preexisting cardiovascular comorbidity (59%, p < 0.001) were more prevalent in the elderly. Finally, adrenaline was used in 30% of the elderly (vs. 26% in the comparator group, p < 0.001) and hospitalization was more often required (60 vs. 50%, p < 0.001). Discussion and Conclusion: Anaphylaxis in the elderly is often caused by insect venoms and drugs. These patients suffer more often from cardiovascular symptoms, receive more frequently adrenaline and require more often hospitalization. The data indicate that anaphylaxis in the elderly tends to be more frequently life threatening and patients require intensified medical intervention. The data support the need to recognize anaphylaxis in this patient group, which is prone to be at a higher risk for a fatal outcome

Risk of severe allergic reactions to COVID-19 vaccines among patients with allergic skin diseases - practical recommendations. A position statement of ETFAD with external experts.

Since the introduction of active vaccination against SARS‐CoV‐2 infection, there has been a debate about the risk of developing severe allergic or anaphylactic reactions among individuals with a history of allergy. Indeed, rare cases of severe allergic reactions have been reported in the United Kingdom and North America. By February 2021 a rate of 4,5 severe allergic reactions occurred among 1 million patients vaccinated with the mRNA‐based COVID‐19 vaccines, which is higher than the generally expected rate of severe allergic reactions to vaccinations of around 1 in 1 million

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good