The persistence of SARS-CoV-2 neutralizing antibodies after COVID-19: A one-year observation. Is a SARS-CoV-2 vaccination booster dose necessary?

Introduction: The aim of this study was to investigate the persistence of SARS-CoV-2 neutralizing antibodies (NAbs) one year after contracting COVID-19. Material and methods: The study included 38 patients - 34 men and 4 women - suffering from COVID-19 between March 15 and May 26, 2020. The median age in the group was 31 years, ranging from 22 to 67 years. The levels of neutralizing antibodies were measured at three time-points - baseline, 6 months, and 12 months. The primary endpoint was a post-infection positive result for NAbs (> 15 AU/ml; Liaison SARS-CoV-2 S1/S2 IgG quantitative test) 12 months after infection. Results: The median level of NAbs after 12 months was 26.5 AU/ml. At the end of observation (12 months), 21 of the 38 patients had a NAb level of >15 AU/ml (positive). The median antibody half-life was 5.8 months. Conclusions: A high percentage of the patients maintained positive levels of antibodies 6 and 12 months after COVID-19 infection. The dynamics of the antibody level decline suggests the need for booster vaccination at least once a year.

Multinational evaluation of clinical decision-making in the treatment and management of mild-to-moderate ulcerative colitis.

OBJECTIVES: To understand current thinking and clinical decision-making in the treatment and management of patients with mild-to-moderate ulcerative colitis (UC). METHODS: This multinational, survey-based study was conducted in 2021. Two meetings were held, involving 11 IBD specialists, that used a series of questions and discussion to identify all factors possibly related to the management of UC. The importance of identified factors was assessed using an online questionnaire covering three scenarios - active disease, remission and patient empowerment. Each factor was scored on a scale of 0 (very-unimportant) to 100 (very-important) within each scenario, by a separate group of healthcare professionals working in IBD. RESULTS: A total of 157 individual factors were identified by the 11 IBD specialists and scored in the three scenarios by 56 respondents (52; 93% specialist gastroenterologists) from Europe and North America (25; 45%), South America (19; 34%) and the Middle East, Asia and Australia (12; 21%). For all scenarios, factors related to educating patients regarding UC and its treatment and understanding of patient goals ranked highest, ahead of clinical considerations regarding disease activity and treatment history. Setting realistic short-term treatment targets was a key consideration. 5-ASA optimisation and use of faecal calprotectin monitoring were core strategies across the three scenarios tested. Support for patients during longer-term management of their disease, starting from initial flare, was an important recurring theme. CONCLUSION: The current management approach for mild-to-moderate UC was found to be guided primarily by the patient's perspectives and goals, alongside assessment of their medical and disease history.

A Prospective Questionnaire-Based Study to Evaluate Factors Affecting the Decision to Receive COVID-19 Vaccination in 267 Patients with Inflammatory Bowel Disease in Poland.

BACKGROUND The aim of the study was to assess the rate of COVID-19 vaccination and the attitudes toward receiving COVID-19 vaccination among patients with inflammatory bowel disease (IBD) in Poland. An important aim of the study was to determine why some people get vaccinated and others refuse to do so. MATERIAL AND METHODS This was a single-center, prospective survey. The study included 267 IBD patients who agreed to complete an anonymous questionnaire comprising 31 questions. RESULTS We found that 71.2% of the IBD patients had been vaccinated. The history of COVID-19 was associated with a lower vaccination rate (16.9% vs 36.8%; P=0.001), regardless of IBD severity. In the vaccinated group, there were more vaccinated people among household members (90.4% vs 43.4%; p<0.001) and friends (52.9% vs 22.4%; P<0.001). Family safety (71.1%), the desire to avoid COVID-19 (67.9%), social responsibility (60.5%), the desire to return to normal life (51.6%), and faith in vaccination as such (43.2%) were the most common reasons for vaccination. The most common cause of non-vaccination was concern about adverse effects (50.0%), including long-term adverse effects (36.8%), and about the possible exacerbation of gastroenterological disease (34.2%). CONCLUSIONS IBD patients are more likely to be vaccinated against SARS-CoV-2 than the rest of the population in Poland. Young age, low socioeconomic status, low education, and living in the countryside were factors associated with lower vaccination rates. Family and friends had the greatest influence on the decision to vaccinate, but the influence of the mass media was very small.

Deep Remission at 1 Year Prevents Progression of Early Crohn's Disease.

BACKGROUND & AIMS: We investigated the effects of inducing deep remission in patients with early Crohn's disease (CD). METHODS: We collected follow-up data from 122 patients (mean age, 31.2 ± 11.3 y) with early, moderate to severe CD (median duration, 0.2 years; interquartile range, 0.1-0.5) who participated in the Effect of Tight Control Management on CD (CALM) study, at 31 sites, representing 50% of the original CALM patient population. Fifty percent of patients (n = 61) were randomly assigned to a tight control strategy (increased therapy based on fecal level of calprotectin, serum level of C-reactive protein, and symptoms), and 50% were assigned to conventional management. We categorized patients as those who were vs were not in deep remission (CD endoscopic index of severity scores below 4, with no deep ulcerations or steroid treatment, for 8 or more weeks) at the end of the follow-up period (median, 3.02 years; range, 0.05-6.26 years). The primary outcome was a composite of major adverse outcomes that indicate CD progression during the follow-up period: new internal fistulas or abscesses, strictures, perianal fistulas or abscesses, or hospitalization or surgery for CD. Kaplan-Meier and penalized Cox regression with bootstrapping were used to compare composite rates between patients who achieved or did not achieve remission at the end of the follow-up period. RESULTS: Major adverse outcomes were reported for 34 patients (27.9%) during the follow-up period. Significantly fewer patients in deep remission at the end of the CALM study had major adverse outcomes during the follow-up period (P = .01). When we adjusted for potential confounders, deep remission (adjusted hazard ratio, 0.19; 95% confidence interval, 0.07-0.31) was significantly associated with a lower risk of major adverse outcome. CONCLUSIONS: In an analysis of follow-up data from the CALM study, we associated induction of deep remission in early, moderate to severe CD with decreased risk of disease progression over a median time of 3 years, regardless of tight control or conventional management strategy.

Pharmacokinetics and safety of fidaxomicin in patients with inflammatory bowel disease and Clostridium difficile infection: an open-label Phase IIIb/IV study (PROFILE).

Objectives: Inflammatory bowel disease (IBD) poses an increased risk for Clostridium difficile infection (CDI). Fidaxomicin has demonstrated non-inferiority to vancomycin for initial clinical cure of CDI in patients without IBD; however, lack of data has caused concerns regarding potential systemic absorption of fidaxomicin in patients with IBD. Methods: The plasma pharmacokinetics (PK) of fidaxomicin and its primary metabolite OP-1118 were evaluated in a multicentre, open-label, single-arm, Phase IIIb/IV study enrolling patients with active IBD and CDI. Patients received fidaxomicin, 200 mg twice daily for 10 days. The primary and secondary endpoints were, respectively, plasma and stool PK of fidaxomicin and OP-1118 on Days 1, 5 and 10 of treatment. Other secondary endpoints included safety of fidaxomicin treatment (assessed until Day 180). ClinicalTrials.gov identifier: NCT02437591. Results: Median Tmax of fidaxomicin and OP-1118 for the PK analysis set (PKAS; 24 patients) was 1-2 h across Days 1, 5 and 10. Cmax ranges were 1.2-154 ng/mL for fidaxomicin and 4.7-555 ng/mL for OP-1118 across Days 1, 5 and 10 (PKAS). The ranges of concentrations in stool were 17.8-2170 µg/g for fidaxomicin and 0-1940 µg/g for OP-1118. Sixty percent (15/25) of patients experienced treatment-emergent adverse events (TEAEs), none of which led to treatment discontinuation or death. Conclusions: Maximum fidaxomicin and OP-1118 plasma concentrations observed in this study population suggest no increase in absorption, compared with patients without IBD. Incidence of TEAEs was similar to previous Phase III trials, suggesting that fidaxomicin is comparatively well tolerated in patients with IBD.

Soluble urokinase-type plasminogen activator receptor (suPAR) in patients with acute pancreatitis (AP) - Progress in prediction of AP severity.

BACKGROUND: Soluble urokinase-type plasminogen activator receptor (suPAR) is a glycoprotein secreted during inflammation and infections. Moreover, increased levels of suPAR are observed after hypoxia and ischaemia. The aim of the study was to assess whether suPAR could represent a useful marker of acute pancreatitis (AP) severity. PATIENTS AND METHODS: We have observed a cohort of 126 prospectively enrolled patients. Based on the presence of persistent organ failure (more than 48 h) and local complications (diagnosis of moderate AP [MSAP]), patients were classified into three groups: mild AP (MAP), moderate and severe AP (SAP). The blood samples were taken on admission for detecting suPAR concentrations. RESULTS: AP was considered severe in 33 patients (26.2%), MSAP was found in 37 patients (29.4%), and MAP was found in 56 patients (44,4%). The AUC for SAP predicted by suPAR was 0.993. The calculated cut-off point for prognosis SAP is 4.75 ng/mL. The BISAP score of ≥3 for detection of SAP had sensitivity and specificity of 94.6% and 63.6%, respectively. The AUC for severity predicted by BISAP amounted to 0.916. Additionally, suPAR turned out to be a good predictor of fatal AP: for the cut-off point 7.05 ng/mL, the AUC was 0.917. The AUC for death prediction in AP patients based on the BISAP score ≥3 was 0.894. CONCLUSIONS: suPAR concentration is a promising new diagnostic and prognostic indicator in SAP obtainable in the early stage of disease. Larger studies are recommended to evaluate this role further.

Post-COVID-19 syndrome in everyday clinical practice: interdisciplinary expert position statement endorsed by the Polish Society of Civilization Diseases.

Post-COVID-19 syndrome, also known as long COVID-19 syndrome, is a complex set of symptoms that persist for weeks or months after recovery from an acute phase of COVID-19. These symptoms can affect various body systems, including the respiratory, nervous, cardiovascular, and digestive systems. The most common complaints are fatigue, shortness of breath, joint pain, taste and smell disorders, as well as problems with memory and concentration. Pathogenesis of post-COVID-19 syndrome is complicated and not fully understood, but it is likely related to an overactive immune system, disturbances in the intestinal microbiome, and cell and tissue damage caused by the virus. Incorporating a multidisciplinary approach to treating and rehabilitating patients and further research into this syndrome's underlying mechanisms and therapy are crucial for understanding and effectively treating this complex and multifaceted condition.

SARS-CoV-2 vaccination in inflammatory bowel disease (IBD) patients - does treatment for IBD negatively affect SARS-CoV-2 antibodies? A single-centre, prospective study.

Introduction: Inflammatory bowel disease (IBD) patients use a wide variety of immunosuppressive drugs, including biologics, but their effect on SARS-CoV-2 vaccine antibody levels remains a mystery. Aim: We analysed whether the drugs used in the treatment of IBD patients could affect the concentration of SARS-CoV-2 antibodies. Material and methods: This is a prospective, single-centre evaluation of the persistence of SARS-CoV-2 antibodies after vaccination at various time points: every 2 months throughout the 6th month after the first dose. Results: We included a total of 346 vaccinated IBD patients in the study. A negative correlation between antibody level and time from full vaccination was confirmed for the following types of therapy: infliximab (rho = -0.32, p < 0.001), adalimumab (rho = -0.35, p = 0.025), and vedolizumab (rho = -0.50, p < 0.001). In the case of other, long-term drug administration, a negative correlation between antibody level and time from full vaccination was confirmed for mesalazine (rho = -0.35, p < 0.001), budesonide (rho = -0.58, p = 0.004), systemic glucocorticoids (rho = -0.58, p < 0.001), and azathioprine (rho = -0.44, p < 0.001). Conclusions: Due to the immunosuppressive and biological treatment, IBD patients are exposed to a shorter persistence of SARS-CoV-2 antibodies and require booster doses. The role of gastroenterologists in educating patients about the need to continue SARS-CoV-2 vaccination remains crucial.

Dermal lesions associated with anti-tumor necrosis factor-α therapy in patients with inflammatory bowel disease: findings from an inflammatory bowel disease tertiary center in Poland.

INTRODUCTION: There is little data on the development of dermal lesions in patients with inflammatory bowel disease (IBD) treated with anti - tumor necrosis factor-α (anti-TNF-α), while their characteristics, clinical course, and impact on treatment are of great concern. OBJECTIVES: The aim of this study is to assess the prevalence, risk factors, and clinical sequelae of dermal lesions in IBD patients treated with anti-TNF-α antibodies. PATIENTS AND METHODS: This retrospective, single-center study evaluated 541 IBD patients treated with anti-TNF-α drugs and compared them with 688 IBD anti-TNF-α-naïve patients. RESULTS: A significant higher prevalence of dermal lesions was noted during the anti-TNF-α therapy of 30.9% patients versus 16.4% (P <0.001). Risk factors for dermal lesions were higher body mass index (BMI), Crohn's disease located in the small intestine, and longer duration of therapy. Some types of dermal lesions were associated with anti-TNF-α therapy: infusion reactions and injection site reactions, cutaneous infection, psorasiform reactions, and lupus-like symptoms. Dermal lesions (alopecia, lupus-like symptoms, melanoma, and psoriasis) occurred in 5.9% of patients who discontinued or changed anti-TNF-α therapy. CONCLUSIONS: We observed a higher prevalence of dermal lesions in patients with IBD undergoing anti-TNF-α therapy, although the development of such lesions rarely necessitated a change in or discontinuation of treatment. Patients with IBD should undergo regular dermatological follow-up, which may improve the detection of dermal lesions. Moreover, biological therapy in IBD patients requires close collaboration with an experienced dermatologist.

Assessment of the activity of the immune system in patients with inflammatory bowel diseases and asymptomatic COVID-19.

Introduction: Although the phenomenon of cytokine storm is well described in patients with severe COVID-19, little is known about the role of the immune system in asymptomatic patients, especially in the group with autoimmune diseases, such as inflammatory bowel disease (IBD). Aim: To assess the stimulation of the immune system expressed through the production of cytokines in IBD patients with asymptomatic COVID-19. Material and methods: This is a multi-centre, prospective study in which the concentration of many cytokines (IL-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL- 15, IL-17, IL-23, IFN-γ, TNF-α, TNF-ß) was assessed in patients with IBD and asymptomatic SARS-CoV-2 infection diagnosed by serological tests. Results: In the group of patients with a recent SARS-CoV-2 infection, defined as positive antibodies in the IgA + IgM class, a higher percentage of patients with the presence of interleukin (IL) 2 (IL-2) was found. No association with other cytokines or effects of IBD activity or treatment was found. However, the effect of the applied treatment on the concentration of some cytokines was found: a negative association of infliximab, vedolizumab, and prednisone with IL-2, a positive correlation of steroids, thiopurines with IL-10, and in the case of tumor necrosis factor-α (TNF-α), negative with infliximab, and positive with vedolizumab. Conclusions: The increased concentration of IL-2 may result from its regulatory role in inhibiting excessive activation of the immune system; however, considering the studies of patients with severe COVID-19, its role in the initial phase of SARS-CoV-2 infection requires further research.

The use of andexanet alpha in the Polish setting: An interdisciplinary protocol. Expert consensus statement of the Polish Cardiac Society.

Andexanet alfa (AA) is a recombinant inactive analog of human activated factor X (FXa), effectively reversing the effects of its inhibitors - rivaroxaban and apixaban, which are available in Poland. The drug was approved for clinical use registration after the publication of the results of the ANNEXA-4 trial (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXa Inhibitors 4), in which its efficacy in restoring hemostasis in life-threatening hemorrhages in patients receiving using the aforementioned anticoagulants was demonstrated. Hence, AA is now recommended for patients on apixaban or rivaroxaban therapy with massive and uncontrollable hemorrhages, including hemorrhagic strokes (HS) and gastrointestinal bleeding. Drug-specific chromogenic anti-Xa assays are generally best suited for estimating rivaroxaban and apixaban plasma levels, aside from direct assessment of their concentrations. The absence of anti-Xa activity, determined using these assays, allows us to rule out the presence of clinically relevant plasma concentrations of any FXa inhibitor. On the other hand, the dose of AA should not be modified based on the results of coagulation tests, as it depends solely on the time that elapsed since the last dose of FXa inhibitor and oon the dose and type of FXa inhibitor. AA is administered as an intravenous (i.v.) bolus, followed by an i.v. infusion of the drug. The maximum reversal of anti-Xa activity occurs within two minutes of the end of the bolus treatment, with the continuation of the continuous i.v. infusion allowing the effect to be maintained for up to two hours afterwards. Because anticoagulant activity can reappear after the infusion is completed, it is currently unclear at what point after AA administration FXa inhibitors or heparin should be re-administered. In Poland AA is starting to become available and its urgent need to administer it to patients with severe bleeding on apixaban or rivaroxaban.

Gut microbiome dynamics and predictive value in hospitalized COVID-19 patients: a comparative analysis of shallow and deep shotgun sequencing.

The COVID-19 pandemic caused by SARS-CoV-2 has led to a wide range of clinical presentations, with respiratory symptoms being common. However, emerging evidence suggests that the gastrointestinal (GI) tract is also affected, with angiotensin-converting enzyme 2, a key receptor for SARS-CoV-2, abundantly expressed in the ileum and colon. The virus has been detected in GI tissues and fecal samples, even in cases with negative results of the reverse transcription polymerase chain reaction in the respiratory tract. GI symptoms have been associated with an increased risk of ICU admission and mortality. The gut microbiome, a complex ecosystem of around 40 trillion bacteria, plays a crucial role in immunological and metabolic pathways. Dysbiosis of the gut microbiota, characterized by a loss of beneficial microbes and decreased microbial diversity, has been observed in COVID-19 patients, potentially contributing to disease severity. We conducted a comprehensive gut microbiome study in 204 hospitalized COVID-19 patients using both shallow and deep shotgun sequencing methods. We aimed to track microbiota composition changes induced by hospitalization, link these alterations to clinical procedures (antibiotics administration) and outcomes (ICU referral, survival), and assess the predictive potential of the gut microbiome for COVID-19 prognosis. Shallow shotgun sequencing was evaluated as a cost-effective diagnostic alternative for clinical settings. Our study demonstrated the diverse effects of various combinations of clinical parameters, microbiome profiles, and patient metadata on the precision of outcome prognostication in patients. It indicates that microbiological data possesses greater reliability in forecasting patient outcomes when contrasted with clinical data or metadata. Furthermore, we established that shallow shotgun sequencing presents a viable and cost-effective diagnostic alternative to deep sequencing within clinical environments.

Assessment of the effectiveness of Budesonide MMX® for active, mild-to-moderate ulcerative colitis in the Polish sub-group of the CORE Practice prospective multi-centre observational study.

Introduction: Budesonide MMX® is approved for induction of remission in mild-to-moderate active ulcerative colitis (UC) in adults in whom 5-ASA is not sufficient. There is a lack of data on its effectiveness and safety in clinical practice. Material and methods: The CORE Practice study was a multi-centre prospective, observational study of mild-to-moderate UC-patients treated with Budesonide MMX® 9 mg for up to 8 weeks (induction). Enrolled patients had previously been prescribed Budesonide MMX® 9 mg in accordance with the SmPC within a 5-day time window. The primary endpoint was the percentage of patients achieving a decrease ≥ 3 points in the UCDAI clinical sub-score at the end of the induction treatment. Other endpoints were clinical remission (decrease ≤ 1 in UCDAI clinical sub-score), resolution of symptoms, change in Short Inflammatory Bowel Disease Questionnaire (SIBD-Q) score, treatment satisfaction, and tolerability. This report presents results from the Polish study sites. Results: The data from a Polish subgroup of 181 patients with mild-to-moderate UC were analysed. Clinical improvement ≥ 3 points in the UCDAI at the end of treatment induction was achieved in 63.8% patients. Clinical remission was observed in 55.9% of patients at the end of the induction treatment. Full resolution of symptoms (rectal bleeding = 0 and stool frequency = 0) at the end of the Budesonide MMX® treatment was achieved in 52.5% of patients. Significant improvement in quality of life was seen in mean SIBD-Q total score from 40 points at baseline to 56 points at last assessment (p < 0.001). A treatment satisfaction score of more than 8 out of 10 was observed in 72.9% of patients. One patient discontinued Budesonide MMX® due to an adverse event that was related to the study drug, which counted for less than 1% of patients. Conclusions: The data from the Polish subgroup of the real-life study CORE Practice confirms the clinical efficacy of Budesonide MMX® 9 mg in the majority of patients with active mild-to-moderate UC. Budesonide MMX® was safe and well tolerated. The therapy was satisfactory for patients and showed a beneficial effect on the patients' quality of life.

Selected personality traits and emotional disorders of women diagnosed with gastrointestinal disease - a pilot study.

Introduction: There are many studies on the influence of psychological factors in the appearance of symptoms and their treatment among gastroenterological patients. It is increasingly indicated that these factors are of great importance also for the quality of life of people struggling with a chronic disease. Aim: To evaluate personality traits and emotional disorders in female patients with gastrointestinal conditions such as functional dyspepsia (FD), irritable bowel syndrome (IBS), or inflammatory bowel disease (IBD). Material and methods: The sample of 28 patients was verified in terms of the disease using the GAST questionnaire and assessed by personality questionnaires and psychological tests: the Spielberger State-Trait Anxiety Inventory (STAI), EAS Temperament Survey, Eysenck Personality Inventory (EPQ-R), Coping Inventory for Stressful Situations (CISS); Beliefs about Pain Control Questionnaire (BPCQ), General Self-efficacy Scale (GSES), and Satisfaction with Life Scale (SWLS). Results: The control group was recruited from female university students declaring full health. The conducted statistical analysis showed that there is a significant relationship between personality traits, psychological predispositions, and both the experience of illness and satisfaction with life among this specific group of patients. Conclusions: This pilot study demonstrated the need for a personalized approach to gastroenterological patients, also based on their personality characteristics. Such an approach may increase the effectiveness of therapy and bring benefits in long-term treatment.

Gastrointestinal symptoms in COVID-19.

SARS-CoV-2 infection manifests mainly by involving the respiratory system. Due to the presence of abdominal symptoms, the digestive system is clearly involved in the expression, transmission, and possible pathogenesis of COVID-19. There are many theories regarding the development of abdominal symptoms, including angiotensin 2 receptor, cytokine storm, and disturbances of the intestinal microbiome. This paper provides an overview of the most important meta-analyses and publications on gastrointestinal symptoms and the gut microbiome in COVID-19.

Awareness and Compliance with the Recommendations of Primary and Secondary Prevention of Cancer in Patients with Inflammatory Bowel Disease.

INTRODUCTION: Patients with Inflammatory Bowel Disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are at high risk of developing malignancies, so prevention and adherence to cancer screening may improve detection. The aim of this study was to assess compliance with medical recommendations, especially primary and secondary prevention of cancer. METHODS: This one-center cross-sectional study was carried out between June and December 2021 amongst patients at the Department of Internal Medicine and Gastroenterology, IBD Division, National Medical Institute of Ministry of Interior Affairs and Administrations, or the outpatient clinic. Patients with IBD were asked to complete an anonymous questionnaire, which included 42 questions concerning lifestyle, cancer risk factors, cancer history, and checkups. STATISTICAL METHODS: The results of the qualitative variables were expressed as frequencies and percentages. We used Fisher's exact test and the Chi-squared test. A value of p < 0.05 was considered significant. Statistical analyses were performed with the SPSS statistical package. RESULTS: A total of 313 patients were enrolled in the study: 145 women and 168 men. In the group, 182 had Crohn's disease (CD), 120 had ulcerative colitis (UC), and 11 with IBDU (unclassified IBD). Most participants had a disease duration of over 8 years and received biological treatment, corticoids, and/or immunosuppressive therapy. Amongst respondents, 17% (31) of patients with CD and 25.8% (31) with UC were overweight, and 10.5% (19) with CD and 15.8% (19) with UC were obese (p = 0.017). We found that 16.3% of all respondents were smokers (79.6% (144) with CD, 90.8% (109) with UC, and 72.7% (8) with IBDU; p = 0.053), and 33.9% declared that they consumed alcohol (39.4% (71) with CD, 26.9% (32) with UC, and 18.2% (2) with IBDU; p = 0.045). A total of 25.4% of patients were exposed to UV radiation, but only 18.8% used sunblock. In addition, 58.8% (67) of patients with CD and 35.8% (19) with UC receiving immunosuppressants had regular laboratory tests (p = 0.02). Furthermore, 41.4% (46) of patients with UC, 27.1% (49) of patients with CD, and 70.0% (7) of patients with IBDU declared not to perform any dermatological control (p = 0.013). A total of 77% of patients had abdominal ultrasound. Out of 52.9% of patients for whom colonoscopy was recommended, only 27.3% had it performed (16.9% (30) with CD vs. 43.1% (50) with UC p < 0.001). Most examinations were ordered by gastroenterologists. Female patients had regular breast control (CD, 78.6% (66); UC, 91.2% (52); IBDU, 50% (2); p = 0.034), and 93.8% (76) had gynecological examinations. Additionally, 80.2% of patients knew about HPV, but most declared not to be vaccinated. A total of 17.9% of patients had urological control, but most had no important pathology detected. CONCLUSIONS: According to our study, many patients are still exposed to risk factors, such as obesity, smoking, and low physical activity, that are modifiable. Laboratory tests in patients with immunosuppressive treatment should be performed regularly. Systematic control, especially dermatological checkups, should be recommended. Additionally, not only gastrologists but also other specialists and GPs should remind patients about regular checkups. Primary prevention, such as HPV vaccinations, should be recommended to all patients.

Long-lasting dyspeptic symptoms - another consequence of the COVID-19 pandemic?

Introduction: It is known that the virus SARS-CoV-2 can attack the gastrointestinal (GI) tract and induce gastroenteritis. This can trigger a wide variety of disorders of gut-brain interaction (DGBIs) or functional gastrointestinal disorders (FGIDs), including post-infectious dyspepsia, which remains underestimated. Aim: To estimate the prevalence of dyspeptic symptoms following COVID-19, immediately after discharge and 3, 6, and 9 months after hospitalization. Material and methods: A prospective, single-centre evaluation of questions regarding functional dyspepsia (FD) as assessed by the Gastroduodenal Module of ROME IV Diagnostic Questionnaire for Adult FGIDs among 320 patients who had had COVID-19. Results: The FD ROME IV criteria were met at the respective time-points by 0.0% (0), 4.8% (12), 3.2% (8), and 3.2% (8) of cases. However, the presence of GI symptoms that suggested FD but did not meet the timeframe ROME IV criteria for FD were found in 9.6% (24), 23.5% (59), 20.7% (52), and 20.7% (52) of cases, respectively. Conclusions: The presence and persistence of gastrointestinal dyspeptic symptoms following COVID-19 is a significant problem. The timeframe of the Rome IV criteria may underestimate the number of patients with persistent dyspeptic symptoms following COVID-19 disease.

Risk Factors for Osteoporosis among Patients with Inflammatory Bowel Disease-Do We Already Know Everything?

INTRODUCTION: There are many known risk factors for osteoporosis (OST) among patients with inflammatory bowel disease (IBD), one of which is physical activity. MATERIAL AND METHODS: The aim of the study is to assess the frequency and risk factors of OST among 232 patients with IBD compared to a group of 199 patients without IBD. The participants underwent dual-energy X-ray absorptiometry, laboratory tests, and completed a questionnaire about their physical activity. RESULTS: It was found that 7.3% of IBD patients suffered from OST. Male gender, ulcerative colitis, extensive inflammation in the intestine, exacerbation of disease, rare physical activity, other forms of physical activity, past fractures, lower levels of osteocalcin, and higher levels of C-terminal telopeptide of type 1 collagen were risk factors for OST. As many as 70.6% of OST patients were rarely physically active. CONCLUSIONS: OST is a common problem in IBD patients. OST risk factors differ significantly between the general population and those with IBD. Modifiable factors can be influenced by patients and by physicians. The key to OST prophylaxis may be regular physical activity, which should be recommended in clinical remission. It may also prove valuable to use markers of bone turnover in diagnostics, which may enable decisions regarding therapy.

Burnout in healthcare - the Emperor's New Clothes.

Burnout is common among physicians; it severely alters their health and has a negative impact on functioning of healthcare systems. Hypertension, increased cortisol levels, maladaptive behaviors with negative social consequences, and suboptimal quality of care have been associated with healthcare providers' burnout. As the number of patients with cancers, psychiatric and neurodegenerative disorders will rise, we need new solutions to maintain physicians' health and, therefore, quality of care. Coping strategies before the COVID-19 pandemic seem ineffective in scaling all the deficits of the global healthcare systems. Examples of new initiatives include new collaborative projects, such as COH-FIT (The Collaborative Outcomes study on Health and Functioning during Infection Times - https://www.coh-fit.com), which aims to collect global data and understand the impact of the COVID-19 pandemic on physical and mental health in order to identify various coping strategies for patients and healthcare workers during infection times, or MEMO (Minimizing Error, Maximizing Outcome), funded by the Agency of Healthcare Research and Quality (AHRQ). Others: i) Rome Foundation GastroPsych undertake efforts dedicated to the science and practice of psychogastroenterology, a burgeoning field with roots in behavioral intervention, cognitive science and experimental psychology focused on fostering the professional growth and collaboration of those engaged in medical practices, or ii) World Gastroenterology Organisation (WGO), Train The Trainers (TTT) program including a new topic of the impact of burnout on career longevity in order to foster strategies for staying healthy and increasing career satisfaction. There is a need for continuous development of digital technologies (e.g. training simulators, telemedicine, robots and artificial intelligence). Their implementation into medical practice is inevitable. Now more than ever, there is a need for a new spirit in healthcare. Together with others in the field, we believe this article is a desperate call for maximizing the use of novel technologies supported by collaborative interactions among healthcare providers and medical professionals of diverse medical fields.

Etrolizumab as induction and maintenance therapy in patients with moderately to severely active Crohn's disease (BERGAMOT): a randomised, placebo-controlled, double-blind, phase 3 trial.

BACKGROUND: Etrolizumab is a gut-targeted anti-ß7 monoclonal antibody targeting α4ß7 and αEß7 integrins. We aimed to compare the safety and efficacy of two doses of etrolizumab with placebo in patients with Crohn's disease. METHODS: BERGAMOT was a randomised, placebo-controlled, double-blind, phase 3 study done at 326 treatment centres worldwide. We included patients aged 18-80 years with moderately to severely active Crohn's disease (Crohn's Disease Activity Index [CDAI] score of 220-480, and a mean daily stool frequency score of ≥6 or a mean daily stool frequency score of >3, and a mean daily abdominal pain score of >1, as well as the presence of active inflammation on screening ileocolonoscopy) who had intolerance, inadequate response, or no response to one or more of corticosteroids, immunosuppressants, or anti-TNF therapy within the past 5 years. BERGAMOT consisted of three induction cohorts (a placebo-controlled, double-blind exploratory cohort [cohort 1]; an active treatment cohort not containing a placebo control [cohort 2]; and a placebo-controlled, double-blind pivotal cohort [cohort 3]) and one maintenance cohort. In induction cohort 3, during the 14-week induction, patients were randomly assigned (2:3:3) to receive matched placebo, 105 mg etrolizumab subcutaneously every 4 weeks (at weeks 0, 4, 8, and 12) or 210 mg etrolizumab subcutaneously (at weeks 0, 2, 4, 8, and 12), stratified by concomitant treatment with oral corticosteroids, concomitant treatment with immunosuppressants, baseline disease activity, and previous exposure to anti-TNF therapy. To preserve masking, all patients received two injections at weeks 0, 4, 8, and 12 and one injection at week 2. Week 14 etrolizumab responders from all cohorts were re-randomly assigned (1:1) to receive 105 mg etrolizumab (etrolizumab maintenance group) or placebo (placebo maintenance group) every 4 weeks for 52 weeks; patients in the induction placebo group underwent a sham re-randomisation to preserve masking. During maintenance, randomisation was stratified by CDAI remission status, concomitant treatment with oral corticosteroids, induction dose regimen, and previous exposure to anti-TNF therapy. All participants and study site personnel were masked to treatment assignment for both induction and maintenance. Co-primary induction endpoints at week 14 (placebo vs 210 mg etrolizumab) were clinical remission (mean stool frequency ≤3 and mean abdominal pain ≤1, with no worsening) and endoscopic improvement (≥50% reduction in Simple Endoscopic Score for Crohn's Disease [SES-CD]). Co-primary maintenance endpoints at week 66 (placebo vs etrolizumab) were clinical remission and endoscopic improvement. Efficacy was analysed using a modified intention-to-treat (mITT) population, defined as all randomised patients who received at least one dose of study drug (induction) and as all patients re-randomised into maintenance who received at least one dose of study drug in the maintenance phase (maintenance). Safety analyses included all patients who received at least one dose of study drug. Maintenance safety analyses include all adverse events occurring in both induction and maintenance. This trial is registered with ClinicalTrials.gov, NCT02394028, and is closed to recruitment. FINDINGS: Between March 20, 2015, and Sept 7, 2021, 385 patients (209 [54%] male and 326 [85%] white) were randomly assigned in induction cohort 3 to receive placebo (n=97), 105 mg etrolizumab (n=143), or 210 mg etrolizumab (n=145). 487 patients had a CDAI-70 response in any of the induction cohorts and were enrolled into the maintenance cohort, of whom 434 had a response to etrolizumab and were randomly assigned to placebo (n=217) or 105 mg etrolizumab (n=217). At week 14, 48 (33%) of 145 patients in the 210 mg induction etrolizumab group versus 28 (29%) of 96 patients in the placebo induction group were in clinical remission (adjusted treatment difference 3·8% [95% CI -8·3 to 15·3]; p=0·52), and 40 (27%) versus 21 (22%) showed endoscopic improvement (5·8% [-5·4 to 17·1]; p=0·32). At week 66, a significantly higher proportion of patients receiving etrolizumab than those receiving placebo had clinical remission (76 [35%] of 217 vs 52 [24%] of 217; adjusted treatment difference 11·3% [95% CI 2·7-19·7]; p=0·0088) and endoscopic improvement (51 [24%] vs 26 [12%]; 11·5% [4·1-18·8]; p=0·0026). Similar proportions of patients reported one or more adverse events during induction (95 [66%] of 143 in the 105 mg etrolizumab group, 85 [59%] of 145 in the 210 mg etrolizumab group, and 51 [53%] of 96 in the placebo group) and maintenance (189 [87%] of 217 in the etrolizumab group and 190 [88%] of 217 in the placebo group). During induction, the most common treatment-related adverse events were injection site erythema (six [4%] of 143 in the 105 mg etrolizumab group, four [3%] of 145 in the 210 mg etrolizumab group, and none of 96 in the placebo group), and arthralgia (two [1%], one [1%], and four [4%]). In the maintenance cohort, the most common treatment-related adverse events were injection site erythema (six [3%] of 217 in the etrolizumab group vs 14 [6%] of 217 in the placebo: group), arthralgia (five [2%] vs eight [4%]), and headache (five [2%] vs seven [3%]). The most common serious adverse event was exacerbation of Crohn's disease (14 [6%] of 217 patients taking placebo and four [2%] of 217 patients taking 105 mg etrolizumab in the maintenance cohort). INTERPRETATION: A significantly higher proportion of patients with moderately to severely active Crohn's disease achieved clinical remission and endoscopic improvement with etrolizumab than placebo during maintenance, but not during induction. FUNDING: F Hoffmann-La Roche.