TESTING A NEW FATIGUE CHECKLIST IN SLE PATIENTS FOR EVERYDAY CLINICAL PRACTICE - AN INTERIM ANALYSIS

BackgroundFatigue is a difficult subject for both physicians and patients. It is barely addressed during consultations and can therefore burden patient-physician-relations. To improve communication regarding fatigue, we developed a checklist that includes suggestions for evaluating possible causes for fatigue. In this analysis, we describe our study population and report first results 3 and 6 months after using the checklist.ObjectivesThe aims of our study are to validate the use of our newly developed fatigue checklist and to demonstrate that addressing fatigue in daily clinical practice and offering possible interventions can improve fatigue.MethodsWe recruited n=110 SLE patients with fatigue from our university hospital-based lupus reference centre in Duesseldorf. Fatigue was measured using the FSS (Fatigue Severity Scale). Our checklist included signs of depression and anxiety using the PHQ-4 (Patient Health Questionnaire), BMI (body mass index), physical activity, anemia, hypothyroidism and vitamin D deficiency. For each applicable cause, we listed possible interventions for free selection by the treating physician, such as replacement therapy (vitamin D, vitamin B12, iron, folic acid, erythropoietin), physical activity programs and psychosomatic consultations that were discussed with the patients. We re-evaluated our patients after 3 (T1) and 6 months (T2).ResultsBaseline characteristics of patients are summarized in Table 1.Table 1.BMI=body mass index, TSH=thyroidea stimulating hormone, PHQ4=patient health questionnaire (cut-off >3 points), HAQ=health assessment questionnaire, IMET= Index for measuring restrictions on social participation (higher scores point towards more restrictions on social participation), FSS=fatigue severity scale (≥4 points equal severe fatigue)N = 110n (%)Mean (SD)Age (years)49.0 (12.34)Female sex99.0 (90.0)BMI (kg/m2)25.9 (5.55)Disease duration (years)19.1 (10.05)TSH (µIU/ml)1.5 (1.05)25-OH-Vitamin D (ng/ml)39.5 (15.35)Haemoglobin (g/dl)13.0 (1.64)Sports activities>4h/week6.0 (5.5)2-4h/week18.0 (16.4)1-2h/week16.0 (14.5)<1h/week28.0 (25.5)No sport42.0 (38.2)Depression (PHQ4 score)2.3 (1.63)Anxiety (PHQ4 score)2.0 (1.71)Functional status (HAQ score)0.8 (0.49)Participation (IMET score)2.8 (2.31)Fatigue (FSS score)5.3 (1.35)After 3 and 6 months, we re-evaluated 83 patients and saw a significant reduction in fatigue measured by the FSS score (T1: mean difference estimate 0.367 and p-value <0.001;T2: mean difference estimate 0.305;p-value <0.005).Figure 1.Comparing FSS-Scores from T0, T1 and T2[Figure omitted. See PDF]ConclusionThe preliminary analysis of our study shows for the first time that incorporation of a checklist procedure into the management of patients with fatigue may improve short-term outcome after 3 and 6 months of observation. The improvement of symptoms documented in our study occurred even though the suggested exercise program and psychosomatic counseling sessions were not available for use during the current observation period because of the COVID-19 pandemic. At present, the mechanisms behind the observed effect remain unclear. Our ongoing analysis will clarify whether an additional effect on fatigue will occur after all suggested interventions resulting from the use of the checklist have been executed. Finally, it will demonstrate whether the incorporation of our checklist into routine clinical practice is capable to reduce fatigue over a prolonged time period.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Considerations for the Management of Oncology Patients During the COVID-19 Pandemic

[...]we highlight ongoing investigational treatment approaches that are so relevant to the care of oncology patients during this extraordinary pandemic. While many therapeutic strategies are currently being evaluated as possible COVID-19 treatments, there are currently no highly effective antiviral therapies or vaccines available to combat this virus, and mortality in severe disease remains high.6 Risk factors for severe illness resulting from COVID-19 are age greater than 65 years, diabetes, chronic lung disease, and obesity,7 and cancer patients who contract COVID-19, in particular, have been shown to have worse outcomes.8 In the initial experience reported from Wuhan, China, 1% of cancer patients were noted to contract COVID-19, compared with just 0.29% incidence in the general population.8 This may be attributed to greater detection rates in more closely surveilled cancer patients, but it could also be associated with nosocomial exposures and diminished im mune defenses.8 Cancer patients were also observed to be at higher risk for the development of severe COVID-19, which may be due to generally advanced age, increased prevalence of tobacco use, and higher incidence of comorbid pulmonary disease.9 Liang et al also demonstrated that cancer patients were more likely to require intensive care or experience mortality as compared with other COVID-19 patients (39% vs 8%).9 Cancer treatment may also increase COVID-19 susceptibility. Lin et al recommend LMWH at 100 U/kg every 12 hours for at least 3 to 5 days.8 In addition, a study performed in Tongji Hospital in Wuhan reviewed 449 patients with severe COVID-19, with 94 patients receiving LMWH (40-60 mg/day) and 5 receiving unfractionated heparin (1000-15,000 U/day) for 7 days or longer;the results showed that the 28-day mortality for LMWH or unfractionated heparin users with a sepsis-induced coagulopathy score of ≥4 and D-dimers >6 times the upper limit of normal was lower than that of non-LMWH or unfractionated heparin users.14 This has led several institutions, including our own, to institute anticoagulation protocols based on various parameters such as D-dimer levels.17 Pathophysiology of COVID-19 Coronaviruses are large, single-stranded, positive-sense RNA strand that encapsulate within a membrane envelope surrounded by glycoprotein spikes, forming a crown-like appearance.18 Less-pathogenic endemic human coronaviruses such as OC43, HKU1, NL63, and 229E exist, causing seasonally, self-limited upper respiratory symptoms.19 In contrast, more severe respiratory symptoms are caused by zoonotic human coronaviruses, including severe acute respiratory distress syndrome coronavirus (SARSCoV) discovered in November 2002 in Guangdong, China;Middle Eastern respiratory syndrome-related coronavirus (MERS-CoV) identified in 2012 in Saudi Arabia;and COVID-19.18 The subfamily, Coronavirinae, is divided into 4 classes of coronaviruses: α, β, δ, and γ. ACE2 has been shown to promote anti-inflammatory and antifibrotic effects, and it protects these cells from ARDS.19 In SARS-CoV-2, ACE2 ectodomain can shed as a result of spikes from the viral glycoprotein, reducing the catalytic function of ACE2 and promoting ARDS.19 In addition, SARS-CoV-2 has been shown to reduce synthesis of interferon-α and interferon-β and to increase inflammatory cytokines and chemokines.20 In lung adenocarcinomas, ACE2 gene expression

Medication adherence evaluated through electronic monitors during the COVID19 pandemic lockdown in Switzerland

Introduction: During the lockdown enforced from March to June 2020 by authorities due to the COVID19 pandemic in Switzerland, patients included in the Interprofessional Medication Adherence Programme (IMAP) in Lausanne and Bern continued to use electronic monitors (EM), which register daily doses intake. Objective(s): The aim of this study is to use EM data to understand to what extent patients' medication implementation, described as the extent to which the patient takes the daily prescribed regimen, was impacted by the lockdown. The authors hypothesised that medication implementation might be lower during and after the lockdown compared to before. Method(s): Included participants attending the IMAP were diagnosed with diabetic kidney disease (DKD), solid cancer, HIV and miscellaneous long-term diseases. Patients' implementation was defined through a proxy: if all EM of each patient were at least opened once daily, implementation was considered optimal (= 1);and suboptimal (= 0) otherwise. 1) Implementation before (from December 2019 to March 2020), during (March to June 2020) and after (June to September 2020) the lockdown was compared. Subanalyses were also performed according to sub-groups of patients. 2) As comparison, implementation of included patients using at least one EM the year before, in 2019, during the same time frame, defined as winter, spring and summer periods, was analysed. A logistic regression model was used to estimate medication implementation according to the period, using 'before the lockdown' or 'winter' as the reference. The model was fitted using generalized estimating equation. Result(s): 1) In 2020, implementation of the 118 patients did not differ statistically before and during (OR = 0.97, CI: 0.84 - 1.15, p = 0.789), and before and after (OR = 0.91, CI: 0.79 - 1.06, p = 0.217) the lockdown. These findings remain stable even when analysing separately the implementation of patients with HIV (n = 61), DKD (n = 25) or miscellaneous long-term diseases (n = 22). Too few patients with cancer (n = 10) were included in the analysis to interpret their results. 2) In 2019, implementation of the 61/118 (51.7%) patients was statistically significantly lower during summertime compared to winter (OR = 0.73, CI: 0.59 - 0.89, p = 0.002). Conclusion(s): The authors results infirm their hypothesis as the implementation remained steady during and after the lockdown in 2020 in comparison to the period before. Still, adherence in 2020 was different compared to 2019 as the decreased implementation during summertime 2019 was not observed after the lockdown in summer 2020. Because of the COVID-19 pandemic, many patients slowed down their activities, travelled less, and may have been more cautious in managing their treatment due to the fear of developing a complication of their disease in a difficult sanitary context. Moreover, during the pandemic, continuity of care was ensured by medical teleconsultation between patients and their health care providers, mailing medications to patients' home by the pharmacy and leading interviews by phone calls for patients included in IMAP. The IMAP before, during and after the lockdown may have supported the adherence of complex patients across the pandemic in 2020. Interprofessional adherence programmes should support patients during routine-disturbance periods, such as a lockdown in a pandemic context or during summertime.

Rezidivierende Kopfschmerzattacken mit wechselnden neurologischen Symptomen und Liquorpleozytose

Bis zum Juni 2021 bestanden bei einer 17-jährigen Patientin ohne Vorerkrankungen Wohlbefinden und keinerlei Einschränkungen in der Bewältigung der schulischen Anforderungen. Nach einem unkomplizierten respiratorischen Infekt, einer ca. 1 Woche darauf erfolgten ersten COVID-19(Corona Virus Disease 2019)-Impfung (Comirnaty®) und einem Urlaub in Norditalien kam es am 12.08.2021 zu einer sich über Minuten ausbreitenden Hemiparese links, Verschwommensehen, Erbrechen und Aphasie sowie Kopfschmerzen (okzipital beginnend, dumpf-drückenden Charakters mit intermittierend kurzzeitigem Stechen frontotemporal).

An Internal Clinical Deterioration Report and Care Process: A Quality Improvement Project

During the early stages of the COVID-19 pandemic, providers initially based treatment decisions upon established guidelines for adult respiratory distress syndrome. Even though emergency intubation and mechanical ventilation were recommended for first-line treatment of critically ill patients, clinical leaders in one New Jersey hospital observed mortality rates increased sharply for patients with COVID-19 receiving mechanical ventilation, particularly among the elderly. An interprofessional team created a Deterioration Report, which aggregated key laboratory, radiologic, and other clinical biomarkers. A follow-up provider satisfaction survey indicated treatment decisions were positively influenced by the Deterioration Report, to the extent at-risk patients were identified rapidly and accurately, placed on high-flow oxygenation as first-line treatment, and successfully avoided intubation in most cases. © 2021, Anthony J. Jannetti Inc.. All rights reserved.

LONG-TERM OUTCOMES of COVID-19 VACCINATION in PATIENTS with RARE and COMPLEX CONNECTIVE TISSUE DISEASES: AN AD-INTERIM ANALYSIS of ERN-RECONNET VACCINATE STUDY

Background: Since the COVID-19 vaccination campaign was launched all over Europe, there has been general agreement on how benefts of SARS-CoV2 vaccines outweigh the risks in patients with rare connective tissue diseases (rCTDs). Yet, there is still limited evidence regarding safety and efficacy of such vaccines in these patients, especially in the long-term. For this reason, in the framework of ERN-ReCONNET, an observational long-term study (VACCINATE) was designed in order to explore the long-term outcome of COVID-19 vaccination in rCTDs patients. The consent form was developed thanks to the involvement of the ERN ReCONNET ePAG Advocates (European Patients Advocacy Group). Objectives: To evaluate the safety profile of COVID-19 vaccination in rCTDs patients and the potential impact on disease activity. Primary endpoints were the prevalence of adverse events (AEs) and of disease exacerbations post-vaccination. Secondary endpoints were the proportion of serious adverse events (SAEs) and adverse events of special interest for COVID-19 (adapted from https://bright-oncollaboration.us/wp-content/uploads/2021/01/SO2-D2.1.2-V1.2-COVID-19- AESI-update-23Dec2020-review-fnal.pdf) Methods: The frst ad-interim analysis of the VACCINATE study involved 9 ERN-ReCONNET Network centres. Patients over 18 years of age with a known rCTD and who received vaccine against COVID-19 were eligible for recruitment. Demographic data and diagnoses were collected at the time of enrolment, while the appearance of AEs and potential disease exacerbations were monitored after one week from each vaccination dose, and then after 4, 12 and 24 weeks from the second dose. A disease exacerbation was defned as at least one of the following: new manifestations attributable to disease activity, hospital-ization, increase in PGA from previous evaluation, addition of corticosteroids or immunosuppressants. Results: A cohort of 300 patients (261 females, mean age 52, range 18-85) was recruited. Systemic lupus erythematosus (44%) and systemic sclerosis (16%) were the most frequent diagnoses, followed by Sjogren's syndrome (SS,12%), idiopathic infammatory myositis (IMM,10%), undifferentiated connective tissue disease (UCTD,8%), mixed connective tissue disease (MCTD,4%), Ehlers-Dan-los's syndrome (EDS,4%), antiphospholipid syndrome (APS,2%). AEs appearing 7 days after the frst and second doses were reported in 93 (31%) and 96 (32%) patients respectively, mainly represented by fatigue, injection site reaction, headache, fever and myalgia. Otitis, urticaria, Herpes Simplex-related rash, stomatitis, migraine with aura, vertigo, tinnitus and sleepiness were reported with very low frequency. Less than 2% of patients experienced AEs within 24 weeks from the second dose. No SAEs or AEs of special interest were observed in the study period. There were 25 disease exacerbations (8%), 7 of which severe. The highest number of exacerbations was observed after 4 weeks from the second dose (12 within week 4, 6 within week 12 and 7 within week 24). Disease exacerbation was most frequent in patients with EDS (33%) and MCTD (25%). Conclusion: This preliminary analysis shows that COVID-19 vaccination is safe in rCTDs patients. AEs appear most often early after vaccination and are usually mild. Disease exacerbations are not frequent, but can be potentially severe and tend to occur most frequently within the frst month after vaccination. Exacerbations can also occur 3-6 months after vaccination, although a causal relationship with the vaccination remains to be established. Our present data underline the importance of long-term observational studies.

EVALUATION of the USE of VIDEO CONSULTATION in GERMAN RHEUMATOLOGY CARE before and during the COVID-19 PANDEMIC WAVES

Background: During the COVID-19 pandemic telemedicine tools rapidly and widely gained acceptance as indispensable management tools for the continuum of clinical care in rheumatic diseases. They have been adopted in position papers and guidelines for the management of rheumatic diseases in adult patients. Objectives: Evaluation of the use of video consultation as one form of tele-medicine before and during the COVID-19 pandemic and associated lockdowns among Rheumatology physicians in Germany. The survey results are expected to support the optimization and implementation of video consultation (VC) into routine clinical practice in rheumatology, providing long-term benefts for both parties, patients and their treating rheumatologists. Methods: Cross-sectional nationwide online survey among German rheumatolo-gists and rheumatologists in training. The survey was promoted by newsletters sent by means of mail and Twitter posts to members of the German Society for Rheumatology (n=1,650) and German Professional Society for Rheumatology (n=527). Results: Reported data refer to 205 participants. The majority of respondents was male (59%), older than 40 years (90%) and specialized in internal medicine/rheumatology (85%). They were divided into two groups: 'digital users' (38%) and 'digital non-users' (62%). Users employing telemedicine (TM) but never VC were defned as 'TM-users' (10%). Those using TM and VC were classifed as 'VC-users' (27%). 'Non-users' negated the use of VC and TM respectively. Knowledge on telemedicine was self-rated as 4 (median on a Likert Scale 1 (very high) to 6 (very low)) with a signifcant difference between user (VC-user 2.7±1.2, TM-user 3.2±1.1) and non-user (4.4±1.3). The Figure 1 shows a signifcant increase in the use of VC during the lockdown periods. Even between the lockdown phases, VC use was higher than in the pre-pandemic phase. Reasons for VC non-use in TM-user and non-user were administrative/technical efforts (21%), lack of technical equipment (15%), time constraints (12%), time required for individual VC sessions (12%), inadequate reimbursement (11%), lack of demand from patients (11%), data security concerns (9%), poor internet connection (8%), and lack of Scientific evaluation/evidence (5%). Based on the experience gained, physicians considered the following clinical situations to be particularly suitable for VC: follow-up visits (VC-user 79%, TM-user 62%, non-user 47%), emergency consultations (VC-user 20%, TM-user 33%, non-user 20%), and patients presenting for the frst time (VC-user 11%, TM-user 19%, non-user 8%). Conclusion: Despite the fact that the current pandemic situation, with social distancing and several lockdowns, provides an ideal environment for the implementation of new remote care forms such as VC, their use and acceptance remained below expectations. Given the reported decline in physician face-to-face consultations during the pandemic, these fndings are even more concerning. The identi-fed reasons for non-utilization should be addressed by policy makers, payers and medical societies to provide better foundations for future innovative care models.

ONE YEAR of DIGITAL HEALTH APPLICATIONS (DIGA) in GERMANY-RHEUMATOLOGISTS' PERSPECTIVES

Background: Based on given legislation (ŞŞ 33a and 139e SGB V, Social Code Book V) the German approach to digital health applications (Digitale Gesundheitsanwendungen, DiGA) allows reimbursed prescription of approved therapeutic software products (listed in the DIGA directory https://diga.bfarm.de/de/verzeichnis) for patients since October 6th, 2020. Objectives: To evaluate the level of knowledge on DiGA among members of the German Society for Rheumatology (DGRh) after one year of DiGA under the conditions of the COVID-19 pandemic using the DiGA Toolbox of the 'health innovation hub' (hih), a think tank and sparrings partner of the German Federal Ministry of Health. Methods: Anonymous cross-sectional online survey using LimeSurvey (https://limesurvey.org). The survey was promoted by newsletters sent out to DGRh newsletter recipients and Twitter posts. Ethical approval was obtained. Results: 75 valid participants reported that they care more than 80% of their working time for patients with rheumatic diseases. Most were working in outpatient clinics (54%) and older than 40 years of age (84%). Gender distribution was balanced (50%). 70% were aware of the possibility to prescribe DiGA. Most were informed on this for the frst time via trade press (63%), and only 8% via the professional society. 46% expect information on DiGA from professional societies and the medical chambers (36%) but rarely from the manufacturer (10%) and the responsible ministry (4%). Respondents would like to be informed about DIGA via continuing education events (face-to-face 76%, online 84%), trade press (86%), and manufacturers test accounts (64%). Only 7% have already prescribed a DiGA, 46% planned to do so, and 47% did not intend DiGA prescriptions. Relevant aspects for prescription are given in Figure 1. 86% believe that using DiGA/medical apps would at least partially be feasible and understandable to their patients. 83% thought that data collected by the patients using DiGA or other digital solutions could at least partially influence health care positively. 51% appreciated to get DiGA data directly into their patient documentation system resp. clinical electronic health record (EHR) and 29% into patients' owned EHR. Conclusion: DiGA awareness was high whereas prescription rate was low. Mostly, physician-desired aspects for DiGA prescriptions were proven efficacy and efficiency for physicians and patients, risk of adverse effects and health care costs were less important. Evaluation of patients' barriers and needs are warranted. Our results will contribute to the implementation and dissemination of DIGA.

Hypersensibilité au vaccin anti-COVID ? analyses de 1000 avis allergologiques

Déclaration de liens d’intérêts: Les auteurs n’ont pas précisé leurs éventuels liens d’intérêts.

Long-term benefit of lurbinectedin as palliative chemotherapy in progressive malignant pleural mesothelioma (MPM): final efficacy and translational data of the SAKK 17/16 study.

BACKGROUND: The SAKK 17/16 study showed promising efficacy data with lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma. Here, we evaluated long-term outcome and analyzed the impact of lurbinectedin monotherapy on the tumor microenvironment at the cellular and molecular level to predict outcomes. MATERIAL AND METHODS: Forty-two patients were treated with lurbinectedin in this single-arm study. Twenty-nine samples were available at baseline, and seven additional matched samples at day one of cycle two of treatment. Survival curves and rates between groups were compared using the log-rank test and Kaplan-Meier method. Statistical significance was set at P value <0.05. RESULTS: Updated median overall survival (OS) was slightly increased to 11.5 months [95% confidence interval (CI) 8.8-13.8 months]. Thirty-six patients (85%) had died. The OS rate at 12 and 18 months was 47% (95% CI 32.1% to 61.6%) and 31% (95% CI 17.8% to 45.0%), respectively. Median progression-free survival was 4.1 months (95% CI 2.6-5.5 months). No new safety signals were observed. Patients with lower frequencies of regulatory T cells, as well as lower tumor-associated macrophages (TAMs) at baseline, had a better OS. Comparing matched biopsies, a decrease of M2 macrophages was observed in five out of seven patients after exposure to lurbinectedin, and two out of four patients showed increased CD8+ T-cell infiltrates in tumor. DISCUSSION: Lurbinectedin continues to be active in patients with progressing malignant pleural mesothelioma. According to our very small sample size, we hypothesize that baseline TAMs and regulatory T cells are associated with survival. Lurbinectedin seems to inhibit conversion of TAMs to M2 phenotype in humans.

The added value of a European Reference Network on rare and complex connective tissue and musculoskeletal diseases: insights after the first 5 years of the ERN ReCONNET

In order to address the main challenges related to the rare diseases (RDs) the European Commission launched the European Reference Networks (ERNs), virtual networks involving healthcare providers (HCPs) across Europe. The mission of the ERNs is to tackle low prevalence and RDs that require highly specialised treatment and a concentration of knowledge and resources. In fact, ERNs offer the potential to give patients and healthcare professionals across the EU access to the best expertise and timely exchange of lifesaving knowledge, trying to make the knowledge travelling more than patients. For this reason, ERNs were established as concrete European infrastructures, and this is particularly crucial in the framework of rare and complex diseases in which no country alone has the whole knowledge and capacity to treat all types of patients. It has been five years since their kick-off launch in Vilnius in 2017. The 24 ERNs have been intensively working on different transversal areas, including patient management, education, clinical practice guidelines, patients' care pathways and many other fundamental topics. The present work is therefore aimed not only at reporting a summary of the main activities and milestones reached so far, but also at celebrating the first 5 years of the ERN on Rare and Complex Connective Tissue and Musculo-skeletal Diseases (ReCONNET), in which the members of the network built together one of the 24 infrastructures that are hopefully going to change the scenario of rare diseases across the EU.

CMR findings after COVID-19 and after COVID-19-vaccination-same but different?

Cardiac involvement has been described in varying proportions of patients recovered from COVID-19 and proposed as a potential cause of prolonged symptoms, often described as post-COVID or long COVID syndrome. Recently, cardiac complications have been reported from COVID-19 vaccines as well. We aimed to compare CMR-findings in patients with clinical cardiac symptoms after COVID-19 and after vaccination. From May 2020 to May 2021, we included 104 patients with suspected cardiac involvement after COVID-19 who received a clinically indicated cardiac magnetic resonance (CMR) examination at a high-volume center. The mean time from first positive PCR to CMR was 112 +/- 76 days. During their COVID-19 disease, 21% of patients required hospitalization, 17% supplemental oxygen and 7% mechanical ventilation. In 34 (32.7%) of patients, CMR provided a clinically relevant diagnosis: Isolated pericarditis in 10 (9.6%), %), acute myocarditis (both LLC) in 7 (6.7%), possible myocarditis (one LLC) in 5 (4.8%), ischemia in 4 (3.8%), recent infarction in 2 (1.9%), old infarction in 4 (3.8%), dilated cardiomyopathy in 3 (2.9%), hypertrophic cardiomyopathy in 2 (1.9%), aortic stenosis, pleural tumor and mitral valve prolapse each in 1 (1.0%). Between May 2021 and August 2021, we examined an additional 27 patients with suspected cardiac disease after COVID-19 vaccination. Of these, CMR provided at least one diagnosis in 22 (81.5%): Isolated pericarditis in 4 (14.8%), acute myocarditis in 9 (33.3%), possible myocarditis (acute or subsided) in 6 (22.2%), ischemia in 3 (37.5% out of 8 patients with stress test), isolated pericardial effusion (> 10 mm) and non-compaction-cardiomyopathy each in 1 (3.7%). The number of myocarditis diagnoses after COVID-19 was highly dependent on the stringency of the myocarditis criteria applied. When including only cases of matching edema and LGE and excluding findings in the right ventricular insertion site, the number of cases dropped from 7 to 2 while the number of cases after COVID-19 vaccination remained unchanged at 9. While myocarditis is an overall rare side effect after COVID-19 vaccination, it is currently the leading cause of myocarditis in our institution due to the large number of vaccinations applied over the last months. Contrary to myocarditis after vaccination, LGE and edema in myocarditis after COVID-19 often did not match or were confined to the RV-insertion site. Whether these cases truly represent myocarditis or a different pathological entity is to be determined in further studies.

Transcranial Direct Current Stimulation for the Treatment of Inattention in Adult Patients With ADHD: Results From the TUNED Trial

Background: Our main goal was to evaluate the efficacy of transcranial direct current stimulation (tDCS) for improving attention in adult patients with attention-deficit/hyperactivity disorder (ADHD) without concurrent treatment with stimulants. Methods: In this parallel, double-blind study, patients with ADHD were randomly assigned to receive active (A-tDCS) or sham tDCS (S-tDCS) using a home-based device. Treatment consisted of one daily stimulation session (30-min, 2-mA, prefrontal cortex) for 4 weeks. The primary outcome measure was a clinician-applied Adult ADHD Report Scale (AARS), inattention section (range 0-36, higher values indicating increased inattention). Analysis of the primary outcome was performed using an ANCOVA controlled for prespecified covariates (baseline AARS, sex, age, ADHD subtype). Results: From July 2019 to July 2021, a total of 147 subjects were assessed for eligibility, and 64 were randomized (mean age=38 years, 30 females). A total of 9 subjects dropped out of the study (4 due to the COVID-19 pandemic). The remaining 59 performed an average of 25 tDCS sessions. Baseline (mean±SD) AARS was 27±3.6 in S-tDCS and 27.6±4 in A-tDCS. In the intention-to-treat analysis (missing data imputed using last observation carried forward), there was a significant decrease of 3.9 (1.50 - 6.44 95% CI) points in the AARS after A-tDCS when compared to S-tDCS (p = 0.002, partial η2 = 0.15). Mild headache and moderate skin redness were more common in A-tDCS. Conclusions: A-tDCS was efficacious in improving symptoms of inattention when compared to S-tDCS and is a promising treatment for patients with ADHD who do not respond or do not tolerate stimulants. Supported By: DTL was supported by a CNPq postdoctoral fellowship (grant number 154116/2018-1), and supported by a NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation (grant number 29486). Keywords: Adult ADHD, Transcranial Direct Current Stimulation (tDCS), Inattention, Clinical Trials

Complement activation induces excessive T cell cytotoxicity in severe COVID-19

Severe COVID-19 is linked to both dysfunctional immune response and unrestrained immunopathology, and it remains unclear whether T cells contribute to disease pathology. Here, we combined single-cell transcriptomics and single-cell proteomics with mechanistic studies to assess pathogenic T cell functions and inducing signals. We identified highly activated CD16(+) T cells with increased cytotoxic functions in severe COVID-19. CD16 expression enabled immune-complex-mediated, T cell receptor-independent degranulation and cytotoxicity not found in other diseases. CD16(+) T cells from COVID-19 patients promoted microvascular endothelial cell injury and release of neutrophil and monocyte chemoattractants. CD16(+) T cell clones persisted beyond acute disease maintaining their cytotoxic phenotype. Increased generation of C3a in severe COVID-19 induced activated CD16(+) cytotoxic T cells. Proportions of activated CD16(+) T cells and plasma levels of complement proteins upstream of C3a were associated with fatal outcome of COVID-19, supporting a pathological role of exacerbated cytotoxicity and complement activation in COVID-19.

Saving Bavarian hops in a "parallel universe": lessons on the biopolitics of agricultural labor in Germany during the Corona pandemic. (Special Issue: More than disaster: creativity in growing, distributing, and accessing food during covid-19.)

When countries closed their borders to curb the spread of COVID-19 in spring 2020, seasonal migrant workers in agriculture were either unable to travel or faced unsafe conditions when performing "essential" field work. Some countries, like Germany, subsequently implemented policies to let them travel to work, and simultaneously, called on their residents to temporarily help farmers harvest crops. This paper explores the case of these temporary pandemic workers on Bavarian hops farms. Based on ethnographic research and interviews, this paper discusses the complex relationships between temporary pandemic workers, farmers, and the mostly absent seasonal workers in the exceptional moment of a global pandemic. The researchers argue that in the state of exception of the Corona pandemic in Germany, biopolitical sorting highlighted migrant workers' indispensability and disposability in a peculiar way: their short-term replaceability through recruited temporary pandemic workers formed a self-ascribed "parallel universe" or "Coronal bubble". Through new encounters (with farmers) and hands-on experiences in agricultural fields, the parallel universe often also meant uncomfortable insights into an unjust agricultural system. For those widely unexposed to agriculture, the state of exception revealed both the general and temporary biopolitics of seasonal migrant workers in agriculture and the key role they play for German agriculture as a whole.

New life after near death: Surviving critical COVID-19 infection.

Background: Few studies have explored the illness perceptions, experiences or attitudes towards the future of survivors of critical coronavirus disease 2019 (COVID-19). Through in-depth qualitative interviews, we aimed to enrich our understanding of participants' perspectives, with the hope of offering more holistic and appropriate care to future patients. Methods: Participants who had survived critical COVID-19 illness (defined as a laboratory or clinical diagnosis of COVID-19, with hypoxia requiring high-flow nasal oxygen (HFNO) or mechanical ventilation) were invited to participate. After informed consent procedures, clinic-demographic details were documented and individual interviews conducted using a topic guide, and were audio-recorded, translated, transcribed and coded into NVivo software where themes were extracted. Results: Of 21 participants (13 female, 8 male), the mean age was 51.8 years (range 34 - 68), and mean duration of COVID symptoms was 21.7 days (range 17 - 37). Eighteen participants had been on HFNO, and 5 required mechanical ventilation. The major themes were: distressing experience; faith-based beliefs sustaining them; gratitude to healthcare workers (HCWs); better understanding of COVID and how dangerous it is; optimism for the future; and a resolve to implement lifestyle changes. Conclusion: Qualitative interviews revealed our participants' experience of severe COVID-19 as a difficult and terrifying ordeal, mitigated by faith-based beliefs, and the presence and care of HCWs. These experiences were reported by the participants as life changing, and all were inspired to focus on future self-care, and invest in fulfilling relationships. These insights call for future interventions to improve patient-centred care, including follow-up debriefing sessions, and support for lifestyle changes.

Durvalumab in frail and older patients with stage iv non-small cell lung cancer: The randomized phase ii duration trial

Introduction: Checkpoint inhibitors have recently been established as first-line treatment for metastatic NSCLC. Notably, a phenomenon known as immunosenescence, i.e. the progressive remodeling of the immune system with aging, as well as the inflammatory status, may interfere with the activity of PD-1/PD-L1 inhibitors. Although frail and older patients represent a major fraction of non-small cell lung cancer (NSCLC) patients in routine clinical practice, this population is still underrepresented in most clinical trials. Thus, clinical evidence about tolerability and efficacy of these novel agents in the elder and frail population is urgently required. Methods/Design: DURATION (NCT03345810) is a prospective, open label, treatment stratified, randomized, multicenter phase II study. The protocol foresaw the enrollment of 200 patients diagnosed with stage IV NSCLC ≥70 years old and/or with Charlson-Comorbidity Index > 1 and/ or with a performance status ECOG > 1. Patients were stratified according to Cancer and Age Research Group (CARG) score in 'fit' and 'less fit'. Patients were then randomized 1:1 to receive either CT or two cycles of CT followed by two cycles of durvalumab and durvalumab maintenance. Details are shown in figure 1. The primary endpoint is the rate of treatment-related grade III/IV adverse events. Secondary endpoints are progression-free survival, response rate and overall survival and quality of life assessment. The trial is accompanied by a biomaterial repository to explore potential biomarkers. Results: The last patient was enrolled in January 2021. Forty-nine, 48, 51, and 52 patients were allocated to arm A, arm B, arm C, and arm D, respectively. Currently, 145 patients have completed the study, 13 patients are under treatment (12 in total in durvalumab-maintenance arms and 1 in the CT arm), while 42 are in follow-up. Conclusions: Inspite of the COVID-19 pandemic, the DURATION trial successfully completed the planned enrollment of 200 patients, underlying the urgent need for evidence of efficacy and tolerability of immunotherapy in the challenging population of frail and elderly patients.

Saving Bavarian Hops in a "Parallel Universe": Lessons on the Biopolitics of Agricultural Labor in Germany During the Corona Pandemic

When countries closed their borders to curb the spread of COVID-19 in spring 2020, seasonal migrant workers in agriculture were either unable to travel or faced unsafe conditions when performing "essential" field work. Some countries, like Germany, subsequently implemented policies to let them travel to work, and simultaneously, called on their residents to temporarily help farmers harvest crops. This paper explores the case of these temporary pandemic workers on Bavarian hops farms. Based on ethnographic research and interviews, this paper discusses the complex relationships between temporary pandemic workers, farmers, and the mostly absent seasonal workers in the exceptional moment of a global pandemic. We argue that in the state of exception of the Corona pandemic in Germany, biopolitical sorting highlighted migrant workers' indispensability and disposability in a peculiar way: their short-term replaceability through recruited temporary pandemic workers formed a self-ascribed "parallel universe" or "Coronal bubble". Through new encounters (with farmers) and hands-on experiences in agricultural fields, the parallel universe often also meant uncomfortable insights into an unjust agricultural system. For those widely unexposed to agriculture, the state of exception revealed both the general and temporary biopolitics of seasonal migrant workers in agriculture and the key role they play for German agriculture as a whole.