The optimal use of colon capsule endoscopes in clinical practice.

Colon capsule endoscopy (CCE) has been available for nearly two decades but has grappled with being an equal diagnostic alternative to optical colonoscopy (OC). Due to the COVID-19 pandemic, CCE has gained more foothold in clinical practice. In this cutting-edge review, we aim to present the existing knowledge on the pros and cons of CCE and discuss whether the modality is ready for a larger roll-out in clinical settings. We have included clinical trials and reviews with the most significant impact on the current position of CCE in clinical practice and discuss the challenges that persist and how they could be addressed to make CCE a more sustainable imaging modality with an adenoma detection rate equal to OC and a low re-investigation rate by a proper preselection of suitable populations. CCE is embedded with a very low risk of severe complications and can be performed in the patient's home as a pain-free procedure. The diagnostic accuracy is found to be equal to OC. However, a significant drawback is low completion rates eliciting a high re-investigation rate. Furthermore, the bowel preparation before CCE is extensive due to the high demand for clean mucosa. CCE is currently not suitable for large-scale implementation in clinical practice mainly due to high re-investigation rates. By a better preselection before CCE and the implantation of artificial intelligence for picture and video analysis, CCE could be the alternative to OC needed to move away from in-hospital services and relieve long-waiting lists for OC.

Cellular and Humoral SARS-CoV-2 Vaccination Responses in 192 Adult Recipients of Allogeneic Hematopoietic Cell Transplantation.

To determine factors influencing the vaccination response against SARS-CoV-2 is of importance in recipients of allogeneic hematopoietic cell transplantation (allo-HCT) as they display an increased mortality after SARS-CoV-2 infection, an increased risk of extended viral persistence and reduced vaccination response. Real-life data on anti-SARS-CoV-2-S1-IgG titers (n = 192) and IFN-γ release (n = 110) of allo-HCT recipients were obtained using commercially available, validated assays after vaccination with either mRNA (Comirnaty™, Pfizer-BioNTech™, NY, US and Mainz, Germany or Spikevax™, Moderna™, Cambridge, Massachusetts, US) or vector-based vaccines (Vaxzevria™,AstraZeneca™, Cambridge, UK or Janssen COVID-19 vaccine™Johnson/Johnson, New Brunswick, New Jersey, US), or after a heterologous protocol (vector/mRNA). Humoral response (78% response rate) was influenced by age, time after transplantation, the usage of antithymocyte globulin (ATG) and ongoing immunosuppression, specifically corticosteroids. High counts of B cells during the vaccination period correlated with a humoral response. Only half (55%) of participants showed a cellular vaccination response. It depended on age, time after transplantation, ongoing immunosuppression with ciclosporin A, chronic graft-versus-host disease (cGvHD) and vaccination type, with vector-based protocols favoring a response. Cellular response failure correlated with a higher CD8+ count and activated/HLA-DR+ T cells one year after transplantation. Our data provide the basis to assess both humoral and cellular responses after SARS-CoV2 vaccination in daily practice, thereby opening up the possibility to identify patients at risk.

Physical activity and the development of general mental health problems or attention-deficit hyperactivity disorder (ADHD) symptoms in children and adolescents: A cross-lagged panel analysis of long-term follow-up epidemiological data.

Studies have shown that physical activity (PA) can provide a helpful, low-risk, and cost-effective intervention for children and adolescents suffering from mental health problems. This longitudinal study aimed to assess whether PA prevents the development of mental health problems, such as attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. Data were analyzed from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) collected from more than 15.000 children and adolescents at three different time points over a period of more than 10 years. Parents scored the PA of the study participants on three frequency levels according to WHO recommendations, and mental health problems were assessed by means of the Strengths and Difficulties Questionnaire (SDQ). The total problem score (SDQ-Total) and the hyperactivity/inattention symptoms sub-scale (SDQ-H/I) were used in an autoregressive cross-lagged model to examine their relationship with PA. The results showed that PA of boys and girls at preschool age was inversely associated with the occurrence of mental health problems and, in particular, ADHD symptoms about 6 years later. Higher levels of PA were associated with better general mental health and fewer ADHD symptoms at the next time point (Wave 1). These effects were not observed from preadolescence (Wave 1) to adolescence (Wave 2), neither for girls nor for boys. These findings indicate that medium-to-high PA may be a supportive factor for good mental health in children in preschool and elementary school. Future studies will have to show whether PA may be a helpful add-on for interventional programs for improving general mental health and alleviating ADHD symptoms among children and adolescents.

Covid-19 Econometric Impacts- Immediate Shocks, Resilient Performance and Confounding Management Choices

This paper examines the earliest evidence of the Covid-19 pandemic's impact on corporate results. We study the cross-sectional dispersion of corporate revenue and other performance impacts attributed to the pandemic as of the first quarter of 2020. The early business reports on this were mostly accessible through the business press or piecemeal corporate announcements. Market sentiment emerged that associated the spate of individual corporate news items with market-wide steep price declines. The Dow Jones' Index spiked downward, for example, and this was likened to a harbinger of a pandemic-induced crash. The sample is a random selection of public American SEC registrants. Our data is drawn from financial statements they filed with the SEC a short time after those early, informal reports. We examine the notion that the pandemic's immediate impact on revenue across the market in that first quarter of 2020 was pervasive and uniform. The research tracks revenue through to earnings and return on equity (ROE). We test the hypothesis that revenue changes are systematically correlated with a similar change in ROE. We also test the hypothesis that management acted to offset the reporting impacts of the pandemic at this early stage of it. We demonstrate greater cross-sectional diversity in the pandemic's impacts than reported. We demonstrate that revenue changes do not map into similarly systematic earnings and ROE changes. We continue our research into how the pandemic impacts corporate performance beyond these first financials.

Students in Dormitories Were Not Major Drivers of the Pandemic during Winter Term 2020/2021: A Cohort Study with RT-PCR and Antibody Surveillance in a German University City

The role of educational facilities, including schools and universities, in the SARS-CoV-2 pandemic is heavily debated. Specifically, the risk of infection in student dormitories has not been studied. This cohort study monitored students living in dormitories in Bochum, Germany, throughout the winter term of 2020/2021. Over the course of four months, participants were tested repeatedly for SARS-CoV-2 infections using RT-PCR from gargle samples and serological testing. An online questionnaire identified individual risk factors. A total of 810 (46.5% female) students participated. Of these, 590 (72.8%) students participated in the final visit. The cross-sectional antibody prevalence was n = 23 (2.8%) in November 2020 and n = 29 (4.9%) in February 2021. Of 2513 gargle samples analyzed, 19 (0.8%) tested positive for SARS-CoV-2, corresponding to 14 (2.4%) infections detected within the study period. Gargle samples available of cases with confirmed present infection were always positive. The person-time incidence rate was 112.7 (95% CI: 54.11–207.2) per 100,000 person weeks. The standardized incidence ratio was 0.9 (95% CI 0.51–1.46, p = 0.69). In conclusion, students living in student dormitories do not appear to be major drivers of SARS-CoV-2 infections. RT-PCR from gargle samples is a patient-friendly and scalable surveillance tool for detection of SARS-CoV-2 infections.

SARS-CoV-2-mediated dysregulation of metabolism and autophagy uncovers host-targeting antivirals.

Viruses manipulate cellular metabolism and macromolecule recycling processes like autophagy. Dysregulated metabolism might lead to excessive inflammatory and autoimmune responses as observed in severe and long COVID-19 patients. Here we show that SARS-CoV-2 modulates cellular metabolism and reduces autophagy. Accordingly, compound-driven induction of autophagy limits SARS-CoV-2 propagation. In detail, SARS-CoV-2-infected cells show accumulation of key metabolites, activation of autophagy inhibitors (AKT1, SKP2) and reduction of proteins responsible for autophagy initiation (AMPK, TSC2, ULK1), membrane nucleation, and phagophore formation (BECN1, VPS34, ATG14), as well as autophagosome-lysosome fusion (BECN1, ATG14 oligomers). Consequently, phagophore-incorporated autophagy markers LC3B-II and P62 accumulate, which we confirm in a hamster model and lung samples of COVID-19 patients. Single-nucleus and single-cell sequencing of patient-derived lung and mucosal samples show differential transcriptional regulation of autophagy and immune genes depending on cell type, disease duration, and SARS-CoV-2 replication levels. Targeting of autophagic pathways by exogenous administration of the polyamines spermidine and spermine, the selective AKT1 inhibitor MK-2206, and the BECN1-stabilizing anthelmintic drug niclosamide inhibit SARS-CoV-2 propagation in vitro with IC50 values of 136.7, 7.67, 0.11, and 0.13 µM, respectively. Autophagy-inducing compounds reduce SARS-CoV-2 propagation in primary human lung cells and intestinal organoids emphasizing their potential as treatment options against COVID-19.

Increased Incidence of Perforated Appendicitis in Children During COVID-19 Pandemic in a Bavarian Multi-Center Study.

Introduction: Since early 2020 the COVID-19 pandemic and statutory preventive reorganization of treatment capacities with cancellation of elective surgery as well as curfew regulations led to vastly decreased utilization of primary health care. Materials and Methods: To assess whether there are negative effects on pediatric acute care in Bavaria during the spring 2020 lockdown a state-wide retrospective multi-center study was performed to analyze the rate of perforated appendicitis during lockdown. Children who have been operated on during the corresponding period in 2018/19 served as control group. Results: Overall, 514 patients (292 boys, 222 girls) were included (2020: 176 patients; 2019: 181 patients; 2018: 157 patients). Median age was 11.2 years. Four hundred thirty-nine patients (85.4%) underwent laparoscopic surgery, 69 (13.4%) open surgery and 1.2% underwent conversion from laparoscopic to open surgery. In 2020 a perforation rate of 27.8% (49/176 patients) was found, in 2018-2019 perforation rate was 20.7% (70/338 patients, p = 0.0359, Cochran-Mantel-Haenszel-Test). Subgroup analysis showed that in younger patients (≤ 11.2 years), in 2020 perforation rate was significantly higher with 37.6% (32/85 patients), while 22.2% (39/176) in 2018/2019 (p = 0.014, Fisher's exact test).In boys perforation rate was significantly higher in 2020 with 35.0% (35/100 patients) compared to 21.4% in 2018-2019 (p = 0.0165, Fisher's exact test). Conclusion: During the period of curfew regulations in Bavaria the rate of perforated appendicitis in childhood increased significantly, especially in younger children and boys. Potentially this has to be attributed to delayed presentation to pediatric surgery care. Because of potential long-term sequelae of perforated appendicitis these adverse effects during curfew have to be taken into account for future political decision making to ensure reasonable patient care and avoid collateral damage in near-future or on-going pandemic situations.

[Impact of the COVID-19 pandemic on appendicitis in COVID-19 negative children]. / Auswirkung der COVID-19-Pandemie auf die Appendizitis bei COVID-19-negativen Kindern.

The global COVID-19 pandemic and the subsequent lockdown in Germany had an impact on all areas of social life. In a single-center study, we were able to demonstrate a statistically more frequent occurrence of perforated appendicitis in COVID-19 negative children for the first 6 months of the COVID-19 pandemic (39.5% vs. 20.6%; p = 0.0652). Possible causes for this trend are discussed.

Potential impact of physical distancing on physical and mental health: a rapid narrative umbrella review of meta-analyses on the link between social connection and health.

BACKGROUND: The imperative for physical distancing (mostly referred to as social distancing) during COVID-19 pandemic may deteriorate physical and mental health. We aimed at summarising the strength of evidence in the published literature on the association of physical and mental health with social connection via social isolation, living alone and loneliness. METHODS: We conducted a systematic search in April 2020 to identify meta-analyses using the Medline, PsycINFO and Web of Science databases. The search strategy included terms of social isolation, loneliness, living alone and meta-analysis. Eligible meta-analyses needed to report any sort of association between an indicator of social connection and any physical or mental health outcome. The findings were summarised in a narrative synthesis. RESULTS: Twenty-five meta-analyses met our criteria, of which 10 focused on physical health and 15 on mental health outcomes. The results suggest that lack of social connection is associated with chronic physical symptoms, frailty, coronary heart disease, malnutrition, hospital readmission, reduced vaccine uptake, early mortality, depression, social anxiety, psychosis, cognitive impairment in later life and suicidal ideation. CONCLUSIONS: The existing evidence clearly indicates that social connection is associated with a range of poor physical and mental health outcomes. A potential negative impact on these outcomes needs to be considered in future decisions on physical distancing measures.

Transcriptomic profiling of SARS-CoV-2 infected human cell lines identifies HSP90 as target for COVID-19 therapy.

Detailed knowledge of the molecular biology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is crucial for understanding of viral replication, host responses, and disease progression. Here, we report gene expression profiles of three SARS-CoV- and SARS-CoV-2-infected human cell lines. SARS-CoV-2 elicited an approximately two-fold higher stimulation of the innate immune response compared to SARS-CoV in the human epithelial cell line Calu-3, including induction of miRNA-155. Single-cell RNA sequencing of infected cells showed that genes induced by virus infections were broadly upregulated, whereas interferon beta/lambda genes, a pro-inflammatory cytokines such as IL-6, were expressed only in small subsets of infected cells. Temporal analysis suggested that transcriptional activities of interferon regulatory factors precede those of nuclear factor κB. Lastly, we identified heat shock protein 90 (HSP90) as a protein relevant for the infection. Inhibition of the HSP90 activity resulted in a reduction of viral replication and pro-inflammatory cytokine expression in primary human airway epithelial cells.

Impact of COVID-19 outbreak on regional STEMI care in Germany.

AIMS: To assess the impact of the lockdown due to coronavirus disease 2019 (COVID-19) on key quality indicators for the treatment of ST-segment elevation myocardial infarction (STEMI) patients. METHODS: Data were obtained from 41 hospitals participating in the prospective Feedback Intervention and Treatment Times in ST-Elevation Myocardial Infarction (FITT-STEMI) study, including 15,800 patients treated for acute STEMI from January 2017 to the end of March 2020. RESULTS: There was a 12.6% decrease in the total number of STEMI patients treated at the peak of the pandemic in March 2020 as compared to the mean number treated in the March months of the preceding years. This was accompanied by a significant difference among the modes of admission to hospitals (p = 0.017) with a particular decline in intra-hospital infarctions and transfer patients from other hospitals, while the proportion of patients transported by emergency medical service (EMS) remained stable. In EMS-transported patients, predefined quality indicators, such as percentages of pre-hospital ECGs (both 97%, 95% CI = - 2.2-2.7, p = 0.846), direct transports from the scene to the catheterization laboratory bypassing the emergency department (68% vs. 66%, 95% CI = - 4.9-7.9, p = 0.641), and contact-to-balloon-times of less than or equal to 90 min (58.3% vs. 57.8%, 95%CI = - 6.2-7.2, p = 0.879) were not significantly altered during the COVID-19 crisis, as was in-hospital mortality (9.2% vs. 8.5%, 95% CI = - 3.2-4.5, p = 0.739). CONCLUSIONS: Clinically important indicators for STEMI management were unaffected at the peak of COVID-19, suggesting that the pre-existing logistic structure in the regional STEMI networks preserved high-quality standards even when challenged by a threatening pandemic. CLINICAL TRIAL REGISTRATION: NCT00794001.