Two years of the COVID-19 pandemic in the population of Czech patients with inflammatory bowel disease treated with biological therapy*experience of the tertiary IBD center.

Background: Inflammatory bowel disease (IBD) may be associated with a more severe course of infections and a different response to vaccination, especially in complicated IBD course and in association with immune-modifying IBD treatment. The aim of this study was to describe COVID-19 pandemic during years 2020 2022 in IBD patients with long-Term biological therapy. Method(s): A retrospective analysis of SARS-CoV-2 infection incidence in the population of 1,177 IBD (Crohn s disease or ulcerative colitis) patients with long-Term biological therapy (IBD cohort) was performed. The incidence rate, crude incidence rate and standardized incidence ratio of COVID-19 in the IBD cohort, the odds ratio of infection depending on the type of biologic therapy administered, the dynamics of COVID-19 incidence depending on the predominant SARS-CoV-2 variant in the population and the current vaccination coverage of the IBD cohort were calculated. Result(s): From January 2020 to April 2022, 548 confirmed cases of COVID-19 (46.6%) were reported in the IBD cohort, with 39% share of PCR positivity in vaccinated individuals and with 95% occurrence of infection in unvaccinated part of the IBD cohort. Standardized incidence rate ratio of COVID-19 was 27% higher in the IBD cohort compared to the general Czech population. The dynamics of the development of the number of positive cases of COVID-19 in the IBD cohort was identical to the situation in the entire country. A higher odds ratio of the chances of infection was demonstrated in patients treated with tumor necrosis factor inhibitors, but not in patients treated with anti-integrins or monoclonal antibodies against interleukins. In the IBD cohort, 85.2% of patients were properly vaccinated, which was significantly more than the vaccination rate of the entire Czech population. Discussion and conclusion: During the two pandemic years, the incidence of COVID-19 in patients with severe IBD and long-Term biological treatment was higher compared to the general Czech population, despite the favorable vaccination coverage of this high-risk patients group. A higher risk was associated with tumor necrosis factor inhibitor therapy.Copyright © 2023 Galen s.r.o.. All rights reserved.

Big Data in Studying Acute Pain and Regional Anesthesia.

The digital transformation of healthcare is advancing, leading to an increasing availability of clinical data for research. Perioperative big data initiatives were established to monitor treatment quality and benchmark outcomes. However, big data analyses have long exceeded the status of pure quality surveillance instruments. Large retrospective studies nowadays often represent the first approach to new questions in clinical research and pave the way for more expensive and resource intensive prospective trials. As a consequence, the utilization of big data in acute pain and regional anesthesia research has considerably increased over the last decade. Multicentric clinical registries and administrative databases (e.g., healthcare claims databases) have collected millions of cases until today, on which basis several important research questions were approached. In acute pain research, big data was used to assess postoperative pain outcomes, opioid utilization, and the efficiency of multimodal pain management strategies. In regional anesthesia, adverse events and potential benefits of regional anesthesia on postoperative morbidity and mortality were evaluated. This article provides a narrative review on the growing importance of big data for research in acute postoperative pain and regional anesthesia.

Anti-SARS-CoV-2 vaccination and antibody response in patients with inflammatory bowel disease on immune-modifying therapy. prospective single tertiary center study on 602 IBD patients

BACKGROUND AND AIM: Patients with inflammatory bowel disease (IBD) on immune-modifying treatment could be at an increased risk for severe coronavirus disease of 2019 (COVID-19), thus data on the efficacy and safety of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines are essential. We have conducted a prospective study of IBD patients vaccinated with BNT162b2, CX- 024414 and ChAdOx1 nCoV-19 vaccines. The aim was to evaluate the rate and the magnitude of seroconversion, to assess the effect of different immune-modifying treatment modalities on the magnitude of anti-SARS-CoV-2 IgG antibody levels, and to analyze the impact of anti-SARS-CoV-2 vaccination on the inflammatory biomarkers of IBD. METHODS: The study included 602 IBD patients and 168 immunocompetent health-care workers serving as controls. Serum anti-SARS-CoV-2 IgG antibodies were measured by chemiluminescent microparticle immunoassay before the vaccination, and 8 weeks after the end of vaccination. RESULTS: Of IBD patients, 82.2% were receiving biological treatment: most of them were treated TNF-alpha inhibitors (48.5%) and just under half of them with concomitant thiopurines or methotrexate, followed by vedolizumab (18.6%) and ustekinumab (15.1%). Only 8.1% of patients were on 5-aminosalicylates, and a minority (2.2%) were treatment-free. The post-vaccine seropositivity rate among IBD patients and controls was 97.8% versus 100%. Median anti-SARS-CoV-2 IgG levels were lower among IBD recipients of ChAdOx1 nCoV-19 compared to two other vaccines (p < 0.0001) and to control ChAdOx1 nCoV-19 recipients (p = 0.01). No correlation was found between serum trough levels and anti-SARS-CoV-2 IgG concentrations for any of the biological drugs used. TNFalpha inhibitors with concomitant immunosuppressive treatment but no other treatment modalities were associated with the lower post-vaccination antibody response ( p <0.0001). When evaluating the laboratory activity of IBD by C-reactive protein and fecal calprotectin levels, no significant differences were found before the vaccination and eight weeks after its completion. CONCLUSION: Our findings warrant particular attention to the anti-SARS-CoV-2 vaccination of IBD patients treated with TNFa inhibitors with concomitant immunomodulators and show priority of mRNA vaccines in this specific group of patients.

Zinc and gut microbiota in health and gastrointestinal disease under the COVID-19 suggestion.

Microelements represent an emerging resource for medicine and its preventive branch. Zinc is the second most abundant element in our organism with peculiar physiologic functions and pathophysiologic implications in systemic and gastrointestinal (GI) diseases. It interacts very often with gut microbiota (GM) and can affect natural course of GI diseases through a bidirectional relationship with intestinal bugs. We aimed to review literature data regarding zinc chemistry, role in health, and GI diseases in man with a special focus on its interaction with GM. We conducted a search on the main medical databases for original articles, reviews, meta-analyses, randomized clinical trials and case series using the following keywords and acronyms and their associations: zinc, microelements, gut microbiota, gut health, and COVID-19. Zinc has a rapid and simple metabolism and limited storage within our body. Its efficacy on immune system modulation reflects on improved response to pathogens, reduced inflammatory response, and improved atopic/allergic reactions. Zinc is also involved in cell cycle regulation (namely, apoptosis) with potential anti-cancerogenic effects. All these effects are in a "symbiotic" relationship with GM. Finally, zinc shows preliminary viral antireplicative effects. Zinc seems to gain more and more evidences on its efficacy in allergic, atopic and infectious diseases treatment, and prevention. COVID-19 can be the booster for research on future applications of zinc as perfect "postbiotic" in medicine.

Design, synthesis, and characterization of PROTACs targeting the androgen receptor in prostate and lung cancer models.

Although the androgen receptor (AR) is a validated target for the treatment of prostate cancer, resistance to antiandrogens necessitates the development of new therapeutic modalities. Exploiting the ubiquitin-proteasome system with proteolysis-targeting chimeras (PROTACs) has become a practical approach to degrade specific proteins and thus to extend the portfolio of small molecules used for the treatment of a broader spectrum of diseases. Herein, we present three subgroups of enzalutamide-based PROTACs in which only the exit vector was modified. By recruiting cereblon, we were able to demonstrate the potent degradation of AR in lung cancer cells. Furthermore, the initial evaluation enabled the design of an optimized PROTAC with a rigid linker that degraded AR with a DC50 value in the nanomolar range. These results provide novel AR-directed PROTACs and a clear rationale for further investigating AR involvement in lung cancer models.

Imaging approach to COVID-19 associated pulmonary embolism.

The novel coronavirus disease-2019 (COVID-19) illness and deaths, caused by the severe acute respiratory syndrome coronavirus-2, continue to increase. Multiple reports highlight the thromboembolic complications, such as pulmonary embolism (PE), in COVID-19. Imaging plays an essential role in the diagnosis and management of COVID-19 patients with PE. There continues to be a rapid evolution of knowledge related to COVID-19 associated PE. This review summarises the current understanding of prevalence, pathophysiology, role of diagnostic imaging modalities, and management, including catheter-directed therapy for COVID-19 associated PE. It also describes infection control considerations for the radiology department while providing care for patients with COVID-19 associated PE.

Investigating Cellular Trajectories in the Severity of COVID-19 and Their Transcriptional Programs Using Machine Learning Approaches.

Single-cell RNA sequencing of the bronchoalveolar lavage fluid (BALF) samples from COVID-19 patients has enabled us to examine gene expression changes of human tissue in response to the SARS-CoV-2 virus infection. However, the underlying mechanisms of COVID-19 pathogenesis at single-cell resolution, its transcriptional drivers, and dynamics require further investigation. In this study, we applied machine learning algorithms to infer the trajectories of cellular changes and identify their transcriptional programs. Our study generated cellular trajectories that show the COVID-19 pathogenesis of healthy-to-moderate and healthy-to-severe on macrophages and T cells, and we observed more diverse trajectories in macrophages compared to T cells. Furthermore, our deep-learning algorithm DrivAER identified several pathways (e.g., xenobiotic pathway and complement pathway) and transcription factors (e.g., MITF and GATA3) that could be potential drivers of the transcriptomic changes for COVID-19 pathogenesis and the markers of the COVID-19 severity. Moreover, macrophages-related functions corresponded more to the disease severity compared to T cells-related functions. Our findings more proficiently dissected the transcriptomic changes leading to the severity of a COVID-19 infection.

Impact of the COVID-19 pandemic on endoscopy practice in the Czech Republic - Survey research

Introduction: The SARS-CoV-2 pandemic caused significant changes in gastrointestinal endoscopy practice in the Czech Republic during March and April 2020. The Czech Society of Gastroenterology (CSG) developed statements and guidelines aimed at solving specific practical problems in this situation. On April 20, 2020, internet based survey was published (under the heading of the Czech Gastroenterology Study Group): Endoscopy in the SARS-CoV-2 pandemic. Aim and methods: Aim of the survey was to obtain basic information on the SARS-CoV-2 infection in the field of digestive endoscopy in the Czech Republic, on the feasibility of measures recommended by the CSG and on problematic areas during the first phase of the pandemic. A set of 23 questions was created, covering the period between 1.3. and 20.4.2020. The links to the survey were sent to all CSG members (875 original e-mail addresses). Results: Ninety questionnaires were evaluated. The survey involved 62 men (69%) and 28 women (31%) of whom 92% were certified gastroenterologists, 52% hospital staff and 48% physicians in private endoscopy practice. A total of 72 responses were obtained from endoscopy unit leaders. Eight respondents (9%) were in contact with an infected patient and only one endoscopist (1%) became ill during the monitored period. There were seven patients only who underwent acute endoscopy with a diagnosis of COVID-19. The endoscopic care plan for patients with COVID-19 was developed in 53% of all respondents and in 88% of units dedicated to endoscopy of at-risk patients. The CSG statements were a source of information and recommendations for a total of 63% of respondents (68% of COVID-19 dedicated endoscopy units). The majority of endoscopy units significantly reduced endoscopy activities during the monitored period (86%), mainly to acute and selected elective procedures. Complete discontinuation of practice was reported by 7% only. A significant problem was the lack of personal protective equipment (83% of units dedicated to endoscopy in COVID-19 positive patients) during the first phase of pandemic. The collection of epidemiological data (91%) and stratification of patients (77%) were generally the most frequently used measures, followed by the choice of personal protective equipment according to the degree of the risk. The possibilities of testing before digestive endoscopy (polymerase chain reaction of SARS-CoV-2 from nasopharyngeal swab) were significantly limited (not available for 57% of respondents). Conclusion: The SARS-CoV-2 pandemic represents a new experience in the field of gastrointestinal endoscopy with the need to introduce a number of epidemiological and hygienic regulations. The statements of the Czech Society of Gastroenterology represented an important source of information and recommendations in this context. The data obtained from the survey enabled a critical evaluation of the pandemic impact in the Czech Republic and thus future creation of revised and realistic measures in digestive endoscopy too.

Oncology-Inspired Treatment Options for COVID-19.

CR3022 is a human antibody that binds to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we explore the use of CR3022 as a molecularly targeted radiotherapeutic. Methods: CR3022 was labeled with 131I and purified, yielding 131I-CR3022. Using a magnetic bead assay and a recombinant SARS-CoV-2 spike protein fragment, we tested binding of 131I-CR3022 in the presence and absence of CR3022. Results: We conjugated the antibody CR3022 with a purity of more than 98% and a specific activity of more than 292 MBq/mg. Using a bead-based assay, we confirmed that binding of 131I-CR3022 is selective and is significantly reduced in the presence of unlabeled antibody (3.14% ± 0.14% specific uptake and 0.10% ± 0.01% specific uptake, respectively; P < 0.0001). Conclusion: Our results confirm the potential of CR3022 as a molecularly targeted probe for SARS-CoV-2. A labeled version of CR3022 could potentially be used for Auger radiotherapy or noninvasive imaging.