Impact of COVID-19 in a Cohort of Patients With Inflammatory Intestinal Disease

BACKGROUND: There are few data on the outcome of COVID-19 in patients with IBD, none in the Chilean population. The aim of the study was to describe the demographic and clinical characteristics of patients with IBD who developed COVID-19, the evolution and clinical course of IBD at 1 month follow-up after SARS-CoV-2 infection. METHOD(S): This was an observational, cross-sectional, and analytical study. Patients with positive RT-PCR SARS-Cov-2 who were followed in the IBD Program of Clinica las Condes tertiary referral center (n = 1,493), were studied by spontaneous patient consultation and/or email survey. The clinical IBD data and COVID-19 related symptoms were obtained from the medical record and follow-up telephone interviews. Statistical significance was determined (Fisher's test P < 0.05). RESULT(S): From March 1 to August 31, 2020, 32 patients were reported positive RT-PCR SARSCov- 2, 18 (56%) ulcerative colitis and 14 (44%) Crohn's disease. The median age was 32 years (range 18 - 69), 56% women. Seven patients had an additional comorbidities. At the time of infection, 9 patients and their co-habitants maintained quarantine, isolation and social distancing recommendations. Only 1 patient was clinically active at the time of infection. Ten patients (31%) were on immunomodulator/biologic maintenance treatment, of which 4 were on combination therapy. Sixty percent of patients contacted the IBD clinical team when RT-PCR SARS-Cov-2 resulted positive. The most frequent COVID-19 onset symptoms were headache (66%), myalgia (63%), and fever (50%). Four patients required hospitalization (no 1 in Critical Care Unit), none of them were on immunomodulator nor biologic treatment. Two patients received Azithromycin and 1 received steroids as treatment for COVID-19. In univariate analysis, there were no significant differences in age, diagnosis or IBD treatment in patients who required hospitalization for COVID-19 infection. Seven patients discontinued their IBD treatment during the infection (6 at the direction of the IBD Program and 1 self-discontinued therapy). Two patients had a flare of their IBD during 1 month post-COVID-19 follow-up. CONCLUSION(S): In this cohort of patients, IBD medications, including immunomodulators and biologic therapy, were not associated with a greater severity of COVID-19 infection.

Sarcoidosis-Associated Immune Thrombocytopenic Purpura and Focal Segmental Glomerulosclerosis

Purpose of study A 32-years old male with known multi-system sarcoidosis in remission for 5 years off treatment presented to the emergency room with complaints of generalized weakness, hematemesis, epistaxis, and bruises. Physical examination was notable for petechiae, ecchymosis along with papules and plaques suggestive of active sarcoid skin lesions on his extremities. Laboratory workup was significant for thrombocytopenia 3000/uL, acute kidney injury with sub-nephrotic proteinuria. Peripheral blood smear did not show evidence of hemolysis and direct Coombs test was negative. Infectious workup including COVID-19, HIV, and hepatitis serologies were negative. Computed Tomography (CT) of chest, abdomen, and pelvis showed mild splenomegaly and an increased number of sub-centimeter hilar and mediastinal lymph nodes. The patient was treated with dexamethasone 40 mg daily for 4 days and intravenousimmunoglobulins (IVIG-2 gm/kg) for possible Immune Thrombocytopenic Purpura (ITP) with improvement in platelet count to 42000/uL by day 3. His workup for AKI and sub-nephrotic proteinuria was negative apart from a positive ANA (1: 160) with low complements. The anti-phospholipid antibody panel was negative. The ACE level was markedly elevated (>80U/L). The patient could not get a renal biopsy due to severe thrombocytopenia. He was discharged but was re-admitted in 15 days for severe thrombocytopenia of 1000/uL, epistaxis, and bruising. We continued high dose steroids along with IVIG 1 gm/kg for refractory ITP with minimal response and started anti-CD20 agent (Rituximab) 375 mg/m2 weekly with thrombopoietin-receptor agonist (Eltrombopag). His platelets count improved in response to treatment and subsequent renal biopsy showed focal and segmental glomerulosclerosis along with mild interstitial fibrosis, tubular atrophy thought to be from long standing sarcoidosis. There was also evidence of focal arteriosclerosis with no evidence of granulomas, immune complex, complement, or IgG4 deposition. Given skin lesions, thrombocytopenia, extensive lymphadenopathy, and renal involvement with markedly elevated ACE levels the overall picture was consistent with active multi-system sarcoidosis. His platelet count increased to 177,000/uL at the time of discharge. Currently, the patient is on slow steroid taper along with Eltrombopag 25 mg every other day without any recurrence of his symptoms so far. Methods used We described one case of sarcoidosis with hematologic and renal involvement. Summary of results Our patient developed hematologic and renal complications approximately 6 years after being diagnosed with sarcoidosis. Initially, he did not demonstrate sufficient clinical response to IVIG and high dose steroids. However, after a course of anti-CD20 agent (Rituximab) and with the addition of thrombopoietin-receptor agonist (Eltrombopag) he showed improvement of platelet count and stabilization of the renal function. Currently, the patient is receiving maintenance therapy with Prednisone 7.5 mg daily along with Eltrombopag 25 mg twice weekly with no recurrence of ITP and stable renal function. A further decision on whether the patient needs another cycle of Rituximab will be determined by the patient's clinical course. Conclusions Highly variable manifestations of Sarcoidosis can pose a significant diagnostic and therapeutic challenge as can be seen from our case. ITP is a rare hematological manifestation of sarcoidosis and addition of anti-CD20 agents should be considered in refractory cases.

Pediatric asthma control during the COVID-19 pandemic.

BACKGROUND: The lockdown imposed by the COVID-19 pandemic resulted in a completely different style of life with possible effects on the attitude toward their disease in patients with chronic lung disease, such as asthma. The aim of our study was to investigate in asthmatic children the level of asthma control and the maintenance therapy used during the lockdown. METHODS: Among asthmatic children attending our clinic, we identified those who had been prescribed the same therapy in March-April 2019 and March-April 2020. The level of asthma control (GINA-score) and the maintenance therapy used during the lockdown (March-April 2020) were compared with those of March-April 2019. We separately analyzed a small group of children with severe asthma treated with Omalizumab during the lockdown. RESULTS: We enrolled 92 asthmatic children (67 males). Compared to 2019, in 2020 a higher proportion of children modified their maintenance therapy (38% vs. 15.2%, p < .001), with a significant increase in both the proportion of children who increased (p = .033) and in that of children who decreased their therapy (p = .026). The level of control resulted as significantly higher in 2020 (March p = .023; April p = .007). Also, the 13 children treated with Omalizumab showed a good level of control in 2020. CONCLUSIONS: In asthmatic children, the COVID-19 pandemic lockdown had a significant impact on their asthma control and on their attitude toward maintenance therapy.

Dupilumab as a steroid-sparing treatment option in pediatric severe asthma and chronic rhinosinusitis with nasal polyps

Case report Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequent comorbidity in severe asthma in adults. Both diseases share key pathophysiological mechanisms that can involve type-2 inflammatory pathways. However, this is an uncommon presentation in pediatric patients. Dupilumab, a fully human monoclonal antibody against IL-4Ralpha, inhibits IL-4/ IL-13 signaling, which are key drivers of type-2 inflammation and interfere with both eosinophilic and allergic pathways. It is approved for patients >= 12-year- old with moderate to severe uncontrolled asthma, but its approval in CRSwNP is limited to adults. We report a case of a 12-year- old boy with severe uncontrolled asthma and highly symptomatic CRSwNP referred to our center in May 2021. He was sensitized to house dust mite and pollens, and a specific immunotherapy had been tried previously. He was treated with high dose inhaled corticosteroid, long-acting beta agonist, long-acting muscarinic antagonist, montelukast and daily intra-nasal corticosteroids. Furthermore, a bilateral endoscopic sinus surgery with polypectomy was performed in April 2021. Despite adherence to medication and surgical treatment, both diseases were uncontrolled with frequent exacerbations requiring unscheduled visits and multiple systemic corticosteroid courses. This led to failure to thrive and several missed school days. Oral corticosteroid (OCS) tapering was unachieved due to symptoms rebound and so maintenance therapy with prednisolone 10mg daily was attempted, with only a slight improvement. High levels of eosinophils (1010 cells/muL), FeNO (122 ppb) and IgE (2255 kU/L) were present. Treatment with subcutaneous dupilumab was started in July 2021. A clinical and analytical improvement was evident at the 3-month evaluation (Table 1). He was able to stop prednisolone, and no clinically relevant exacerbations occurred. He also was fully vaccinated and had an asymptomatic COVID-19 infection in December 2021. Patients with CRSwNP and comorbid asthma have a higher disease burden than patients with each disease alone. In this adolescent, dupilumab was effective as an add-on treatment, for both severe asthma and CRSwNP. It led to disease control, OCS withdrawal, reduced eosinophilic inflammation, improved lung function, smell recovery and absence of exacerbations during follow-up. Dupilumab, targeting the type 2 inflammatory process, may allow a better management of pediatric patients >=12 years old with severe CRSwNP and comorbid asthma. (Table Presented).

Persistent allergic respiratory symptoms induced by food allergy: Report of two cases

Case report Dust is a known mixture and carrier of multiple allergens and an epidemiologic study demonstrated the presence of peanut proteins in school cafeterias and classrooms, suggesting that schools may play an important role in exposure to environmental food allergens. While inhalation of food allergens is a known trigger of IgE-mediate acute respiratory reaction as rhinitis and wheezing, little is known about persistent allergic asthma and/or rhinitis induced by chronic inhalation of food allergens. Here we report two cases of teenagers with nuts allergy presenting with persistent respiratory symptoms when exposed to closed and dusty environments. The first case concerns a 12-year-old boy allergic to walnut and hazelnut (specific IgE > 100 and 81.70 kU/l, respectively). For some years he has had a persistent mild asthma, frequent nasal occlusion and rhinorrhea, without any allergic sensitization to aeroallergens. Symptoms occurred exclusively during school period when he required maintenance therapy with inhaled and nasal steroids. He was asymptomatic and did not need any treatment during summer. During the lockdown period due to Covid-19 pandemic, he did not attend school for several months and he was able to discontinue inhaled corticosteroid therapy without recurrence of asthma and rhinitis symptoms. Asthma recurred after he returned to school, but with only mild intermittent symptoms, probably thanks to the use of masks and the frequent airing of the classrooms. On a single occasion he experienced nasal occlusion and rhinorrhea after that a parent had eaten hazelnut cream in the same room where he was. The second case deals with a 17-year-old boy with a history of several food allergies (milk, egg, wheat, banana, nuts, hazelnuts) and mild persistent asthma in absence of sensitization to aeroallergens. He successfully underwent oral desensitization for milk, egg and wheat in previous years. Asthma symptoms improved over the years together with progressive development of oral tolerance to food allergens for which oral immunotherapy had been done. On the other hand, he referred persistence of allergic rhinitis especially during the school year and his symptoms got worse in classroom. Exhaled nitric oxide was quite increased with evidence of eosinophils in nasal smears. In-vitro and in-vivo tests only detected food allergens sensitizations, in particolar to walnuts and hazelnuts (specific IgE were 61.00 and 55.50 kU/l respectively). These two clinical cases suggest that food allergens might be causative agents of allergic persistent asthma and/or rhinitis as aeroallergens do.

A rare case of central post-stroke pain in a patient with migraine and lacunar infarcts in the medulla oblongata

Studies about headaches associated with acute ischemic stroke in patients suffering from migraine were limited, and therefore we present a clinical case of central post-stroke pain (CPSP) in a 47-year-old woman with migraine and lacunar infarcts in the medulla oblongata and also possible mechanisms of CPSP in patients with migraine. Magnetic resonance imaging of the brain revealed lacunar infarction in the medulla oblongata on the right (vertebral artery basin) and a single focus of gliosis in the parietal lobe on the right. Magnetic resonance angiography of cerebral vessels showed the fetal type of structure of both posterior cerebral arteries. This clinical case is a complex clinical situation of a combination of secondary headaches (post-stroke) in a patient with a primary headache (migraine), which was successfully treated by the combined administration of first-line drugs for the treatment of neuropathic pain in a patient with lacunar infarcts in the medulla oblongata. The treatment of CPSP is a difficult task due to the insufficiently unexplored mechanisms of development, the most effective approaches are those aimed at reducing the increased excitability of neurons.Copyright © 2023, Indian Association of Biomedical Scientists. All rights reserved.

COVID-19 in a patient with Good's syndrome and in 13 patients with common variable immunodeficiency

Antibody deficiencies constitute the majority of primary immunodeficiencies in adults. These patients have a well-established increased risk of bacterial infections but there is a lack of knowledge regarding the relative risks upon contracting COVID-19. In this monocentric study the disease course of COVID-19 in 1 patient with Good's syndrome and in 13 patients with common variable immunodeficiency (CVID) is described. The severity of disease ranged from very mild to severe. Several patients required hospitalization and immunomodulatory treatment but all survived. Although viral infections are not a typical feature of humoral immunodeficiencies we recommend that vigilance is increased in the management of patients with Good's syndrome and CVID during the COVID-19 pandemic.Copyright © 2021

Sarcomatoid urothelial carcinoma accompanied by elevated serum beta-HCG: Two case reports

Sarcomatoid urothelial carcinoma is a rare and aggressive variant. Serum beta-hCG levels are used as a tumor marker in gestational trophoblastic diseases and germ cell tumors, but may also be elevated in high-grade bladder cancers. Here, we report two urothelial carcinoma cases with sarcomatoid differentiation that relapsed early after surgery with elevated serum beta-hCG levels. The first case was a 65-year-old female and the second case was a 67-year-old man with sarcomatoid urothelial carcinoma located in the ureter and renal pelvicalyceal system, both of them relapsed with elevated beta-hCG serum level to 146.8 mIU/ mL and 242 mIU/mL, respectively. They died a few months after initial diagnosis;4.9 and 2.5 months respectively. Both sarcomatoid variant and beta-hCG expression were associated with poor prognosis and advanced stage. However, beta-hCG is not used as a tumor marker in urinary tract cancers yet, and its relationship with variant pathologies has not been clarified. We need multi-centered studies to reveal this relationship.Copyright © 2023, Derman Medical Publishing. All rights reserved.

Vedolizumab subcutaneous formulation maintenance therapy for patients with IBD: a systematic review and meta-analysis.

Background: The application of vedolizumab (VDZ) subcutaneous (SC) formulation has brought more convenience and hope to patients with moderate-to-severe inflammatory bowel diseases (IBDs) in the coronavirus disease 2019 context. Objective: This study aimed to systematically evaluate all previous studies that used VDZ SC formulation for maintenance therapy in patients with IBD. Design: Systematic review and meta-analysis. Data Sources and Methods: The search was conducted using the subject and free terms related to 'Vedolizumab', 'Subcutaneous', and 'IBD', in Embase, PubMed, Web of Science, Cochrane, and at ClinicalTrials.gov databases between 2008 and 2022. The methodological quality of randomized controlled trials (RCTs) and cohort studies was assessed using the Cochrane Handbook of Systematic Reviews and the Newcastle-Ottawa Scale, respectively. The endpoints included efficacy, safety, and immunogenicity. Results: A total of 60 studies and 2 completed clinical registry trials were retrieved, of which 3 RCTs with high methodological quality, and 3 cohort studies with large heterogeneity were included in the meta-analysis. In the RCT study design, patients with ulcerative colitis (UC) under different conditions after treated with VDZ SC were significantly distinct than those for placebo (PBO) in clinical remission, endoscopic remission, and biochemical remission. In Crohn's disease (CD), the aforementioned parameters were slightly higher than those for PBO, but there was not statistically significant in endoscopic remission and the efficacy of anti-tumor necrosis factor-naive patients. The clinical remission, endoscopic remission, and biochemical remission in patients with UC after VDZ SC treatment were similar to those after intravenous (IV) treatment. The risk ratios in patients experiencing adverse events (AEs) and serious AEs after VDZ SC and PBO treatments were 86% and 89% in UC, and 96% and 80% in CD, respectively. Compared with IV, safety was not statistically different. The risk of developing anti-VDZ antibody after VDZ SC treatment was only 20% of that after PBO in patients with UC, but it was 9.38 times in CD. Conclusion: VDZ SC treatment maintained the clinical efficacy of IV induction in patients with IBD without increasing the safety risk, and the efficacy was more pronounced in patients with UC. Immunogenicity might be a potential factor for the decrease in efficacy rate in patients with IBD. Registration: INPLASY 2022120115.

HIV treatment strategies across Central, Eastern and Southeastern Europe: New times, old problems.

INTRODUCTION: In the last decade, substantial differences in the epidemiology of, antiretroviral therapy (ART) for, cascade of care in and support to people with HIV in vulnerable populations have been observed between countries in Western Europe, Central Europe (CE) and Eastern Europe (EE). The aim of this study was to use a survey to explore whether ART availability and therapies have evolved in CE and EE according to European guidelines. METHODS: The Euroguidelines in Central and Eastern Europe (ECEE) Network Group conducted two identical multicentre cross-sectional online surveys in 2019 and 2021 concerning the availability and use of antiretroviral drugs (boosted protease inhibitors [bPIs], integrase inhibitors [INSTIs] and nucleoside reverse transcriptase inhibitors [NRTIs]), the introduction of a rapid ART start strategy and the use of two-drug regimens (2DRs) for starting or switching ART. We also investigated barriers to the implementation of these strategies in each region. RESULTS: In total, 18 centres participated in the study: four from CE, six from EE and eight from Southeastern Europe (SEE). Between those 2 years, older PIs were less frequently used and darunavir-based regimens were the main PIs (83%); bictegravir-based and tenofovir alafenamide-based regimens were introduced in CE and SEE but not in EE. The COVID-19 pandemic did not significantly interrupt delivery of ART in most centres. Two-thirds of centres adopted a rapid ART start strategy, mainly in pregnant women and to improve linkage of care in vulnerable populations. The main obstacle to rapid ART start was that national guidelines in several countries from all three regions did not support such as strategy or required laboratory tests first; an INSTI/NRTI combination was the most commonly prescribed regimen (75%) and was exclusively prescribed in SEE. 2DRs are increasingly used for starting or switching ART (58%), and an INSTI/NRTI was the preferred regimen (75%) in all regions and exclusively prescribed in SEE, whereas the use of bPIs declined. Metabolic disorders and adverse drug reactions were the main reasons for starting a 2DR; in the second survey, HIV RNA <500 000 c/ml and high cluster of differentiation (CD)-4 count emerged as additional important reasons. CONCLUSIONS: In just 2 years and in spite of the emergence of the COVID-19 pandemic, significant achievements concerning ART availability and strategies have occurred in CE, EE and SEE that facilitate the harmonization of those strategies with the European AIDS Clinical Society guidelines. Few exceptions exist, especially in EE. Continuous effort is needed to overcome various obstacles (administrative, financial, national guideline restrictions) in some countries.

Efficacy of risankizumab by baseline clinical, biochemical, and endoscopic disease severity in moderately to severely active Crohn's disease

Background: Risankizumab (RZB), a p19-anti-interleukin-23 monoclonal antibody, has demonstrated efficacy as induction and maintenance therapy in patients with moderately to severely active Crohn's disease (CD). This post hoc analysis evaluates the efficacy of induction and maintenance RZB therapy by baseline clinical, biochemical, and endoscopic disease severity. Method(s): In the ADVANCE (NCT03105128) and MOTIVATE (NCT03104413) studies, patients with moderately to severely active CD and intolerance/inadequate response to >= 1 biologic (both studies) and/or conventional therapy (ADVANCE) were randomized to receive intravenous (IV) RZB induction therapy or placebo (PBO) for 12 weeks. Patients achieving stool frequency and/or abdominal pain score clinical response to 12 weeks of induction therapy were rerandomized in the FORTIFY (NCT03105102) study to receive subcutaneous (SC) maintenance RZB (180 mg or 360 mg) or PBO (withdrawal). Clinical and endoscopic endpoints were evaluated by baseline disease characteristics (Crohn's Disease Activity Index [CDAI: <= 300, > 300], highsensitivity C-reactive protein [hs-CRP: < 10 mg/L, >= 10 mg/L], and Simple Endoscopic Score for Crohn's Disease [SES-CD: 6-15, > 15]). Induction analyses included patients who received RZB 600 mg or PBO;data from the ADVANCE and MOTIVATE studies were pooled. Nonresponder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used. Result(s): The induction analysis included 527 patients who received RZB 600 mg IV and 362 patients who received PBO. Patients treated with RZB 600 mg IV achieved significantly higher response rates vs PBO at week 12, regardless of subgroup (P < .05 for all;Figure 1). In the maintenance study, patients treated with SC RZB continued to achieve higher response rates vs the PBO (withdrawal) group at week 52 regardless of subgroup (P was not < .05 for all;Figure 2). Improvements in clinical and endoscopic outcomes were generally observed from weeks 12 to 52 with RZB treatment across all subgroups. Response rates were generally similar across subgroups in both induction and maintenance studies;endoscopic remission and ulcer-free endoscopy (resolution of ulcer) rates were numerically lower for patients with increased inflammation (hs-CRP > 10 mg/mL) and higher endoscopic activity (SES-CD > 15). Conclusion(s): RZB induction therapy resulted in higher response rates for clinical and endoscopic outcomes compared with PBO at week 12, regardless of baseline clinical, biochemical, and endoscopic disease severity. RZB also showed durable efficacy with continued RZB maintenance therapy, supporting the long-term use of RZB for patients across a range of baseline disease severity and activity.

The Problem of Comorbid Socially Significant Infections Under The Conditions of The COVID-19 Pandemic.

The aim of the study. To analyze formation features of the epidemic situation for tuberculosis (TB) in the context of the COVID-19 pandemic in order to predict the further actions of medical organizations. Materials and methods. The data for the region for the last 5 years (2017-2021) were analyzed, including 1,762 newly diagnosed cases of patients with TB and comorbidities (according to the data of the Regional Public Health Organization <<Regional Clinical Anti-Tuberculosis Dispensary>>). All cases were verified using standard diagnostic methods, including molecular genetic methods, to determine the resistance of pathogens to antibacterial drugs. Results. It was revealed that the epidemiological situation in the region was multidirectional: thus, during the COVID-19 epidemic, the most pronounced incidence decrease was observed among cases of chronic course hepatitis (by 16.4 times), while among patients with tuberculosis the incidence decreased by 2.75 times, and among patients with acute hepatitis - only by 1.5 times (P<0.05). Among the cases of comorbid infection, the most severe course was observed in patients with combined (TB + HIV) infection: there was both a more severe general condition, and the development of adverse (undesirable) reactions to anti-TB drugs, which required an extension of maintenance therapy. Conclusions. The results of the study showed that against the background of the COVID-19 pandemic in the region, there was no tendency towards a worsening of the epidemic situation, primarily for the more socially significant infection - tuberculosis. At the same time, there was an increase in the number of cases of comorbid pathology, including HIV + TB. In the treatment of patients with comorbid forms of infection, it is necessary to take into account the possibility of developing hepatotoxic reactions and, as a result, the appointment of accompanying drugs with hepatoprotective and detoxification effects in therapy.Copyright © Team of Authors, 2022.

Effect of upadacitinib on inflammatory markers and clinical outcomes in patients with Crohn's disease in the phase 3, U-EXCEL, U-EXCEED, and U-ENDURE studies

Background: Improvement in clinical outcomes and normalisation of objective markers of inflammation, high-sensitivity C-reactive protein (hs-CRP) and faecal calprotectin (FCP), are considered treatment targets per STRIDE-II guidelines.1 We evaluated the effect of the oral selective Janus kinase inhibitor upadacitinib (UPA) on changes in hs-CRP, FCP, and clinical outcomes in patients with Crohn's disease (CD). Method(s): In 2 phase 3, randomized, double-blind, placebo-controlled induction studies (U-EXCEL, NCT03345849;U-EXCEED, NCT03345836), patients with moderate-to-severe CD received 12-week treatment with UPA 45 mg (UPA45) once daily (QD) or placebo (PBO). Patients with clinical response to UPA45 were rerandomised in U-ENDURE (NCT03345823) to receive 52-week maintenance treatment with UPA 30 mg QD (UPA30), UPA 15 mg QD (UPA15), or PBO. Endpoints included marker normalisation (hs-CRP <= 5 mg/L, FCP <= 250 mug/g) in patients with elevated baseline marker levels, normal marker and clinical remission by Crohn's Disease Activity Index (CDAI < 150) or very soft/liquid stool frequency (SF)/abdominal pain score (APS) (average daily SF <= 2.8 and average daily APS <= 1, neither greater than baseline), and >= 50% reduction from baseline in marker values with a decrease of at least 100 points in CDAI from baseline. Median changes from baseline in marker levels were also evaluated. Non-responder imputation with no special data handling for missing data due to COVID-19 was used. Result(s): Of 1021 enrolled patients, 645 (63.2%) had elevated hs-CRP (> 5 mg/L) and 750 (73.5%) had elevated FCP (> 250 mug/g) levels at baseline. Significantly greater proportions of patients with elevated baseline marker levels achieved normalisation with UPA compared with PBO at week 12 (Fig 1A/B) and week 52 (Fig 2A/B;nominal P < .001 for all). Decreases in marker levels from baseline with UPA were observed as early as week 2 and were significantly greater than with PBO through week 12 (Fig 1C) and week 52 (Fig 2C;nominal P < .001 for all). Patients achieved clinical endpoints and improvements in markers at significantly higher rates with UPA45 vs PBO at week 12 (Fig 1D-F) and with UPA15 and UPA30 vs PBO at week 52 (Fig 2D-F;P < .001 for all). The safety profile of UPA in CD was previously reported and no new safety concerns were identified. Conclusion(s): Improvements in clinical endpoints and normalisation of objective markers of inflammation were achieved as early as week 2 with UPA45 induction and sustained with UPA15 and UPA30 maintenance therapy in patients with CD. Median changes in hs-CRP and FCP with UPA support continued improvement of inflammation up to week 52 .

Analysis of the impact of various risk factors on short-term and long-term outcomes in patients with COVID-19 on maintenance hemodialysis.

Patients receiving renal replacement therapy (RRT) in the form of maintenance hemodialysis (MHD) belong to a group of particularly high risk of infection and the course of COVID-19. The new coronavirus infection also has a great impact on long-term outcomes. Material(s) and Method(s): A retrospective observational study included 510 patients on MHD, hospitalized from April 1, 2020 to April 01, 2021. The outcome of hospitalization was chosen as the primary endpoint of the study: discharge or 28-day mortality. Death within 6 months after discharge and the development of complications related to COVID-19 during this period were considered as secondary endpoints. Data collection was carried out by analyzing electronic and archival medical records. Quantitative variables: age, duration of hospitalization, days in the intensive care unit, laboratory blood parameters: the level of D-Dimer, Glucose, Interleukin-6, Procalcitonin, Lymphocytes and Platelets, CRP, CPK, CPK-MB, LDH, Fibrinogen, Ferritin. Qualitative indicators: gender, ventilator, ARDS, the presence of diabetes, the presence of obesity, the presence of complications: cardiovascular, gastrointestinal, septic, macrothrombotic, stage of pneumonia. To identify statistically significant predictors of the risk of an event, the odds ratio (OR) method was used. Result(s): average age 57.8+/-14 years, men - 59.5%, average bed day 17.6+/-10.6 days. In concomitant diseases, diabetes mellitus was indicated in 24% of patients, obesity was registered in 4.3% of patients. Hospital mortality (28-day) in the total cohort of follow-up was 16.05%, in total with out-of-hospital mortality of 22%. Mortality in intensive care reached 62.7%, on ventilator more than 86%, with ARDS 94.3%. No statistical significance was revealed by gender and the presence of diabetes mellitus (DM) in concomitant diseases. When comparing short-term outcomes, the age groups over 65 differed statistically. The following laboratory blood parameters showed a significant difference (P<0.001): D-Dimer, Glucose, IL-6 lymphocytes, Leukocytes, Neutrophils, Platelets, LDH, Ferritin. The following odds ratios (OR) were obtained: ARDS (OR 143.78;95% CI 33.4-616.2;p=0.0001), on ventilator (OR 57.96;95% CI 23.1-144.5;p=0.0001), the presence of septic complications (OR 26.4;95% CI 13.8-50;p=0.0001), the course of the disease is defined as severe (OR 25;95% CI 12.9-48.2;p=0.0001), the course of the disease is defined as complicated (OR 11.6;95% CI 6.8-19.7;p=0.0001), the presence of gastrointestinal complications (OR 6.5;95% CI 2.28-18.4;p=0.0007), the presence of obesity (OR 2.57;95% CI 1.0-6.5;p=0.039). Mortality of patients receiving two main treatment regimens T-1 and T-2 did not differ (15.8% vs 15.7%). Significant differences (p=0.0001) appeared when compared with the T-0 and T-4 schemes, in which mortality was recorded at 8.8% and 85.7%, respectively. When comparing long-term outcomes, the analysis did not reveal statistical significance by gender. The statistical difference was noted by age. Among laboratory indicators, the PCT level was higher in survivors with complications. A significant difference among all survivors and deceased (P<0.001) was shown by: D-Dimer, blood glucose level, IL-6, CRP. The highest OR was calculated for the following indicators: the presence of gastrointestinal complications (OR 7.7;95% CI 1.0-57.7;p=0.03), the initial LDH blood level of 622 units /l (OR 4.7;95% CI 1.63-13.63;p=0.0086), the course of the disease defined as complicated (OR 4.05;95% 1.97-8.33;p=0.003), the course of the disease is defined as severe (OR 2.4;95% CI 1.17-5.0;p=0.03). Conclusion(s): gastrointestinal complications had the greatest impact on unfavorable short-term and long-term outcomes in patients on programmed hemodialysis. In relation to such laboratory markers as Ferritin, CRH, LDH, threshold values of a significant increase in the chances characteristic of dialysis patients were obtained. During the first year of the epidemic, therapy remained largely supportive and aimed at prevent ng complications, the main isolated treatment regimens showed no significant differences in the impact on the outcomes of COVID-19.Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.

Treatment outcome of tofacitinib dose reduction to 5 mg BID vs remaining on 10 mg BID in patients with Ulcerative Colitis who were in stable remission on 10 mg BID: Updated 30-month data from the double-blind, randomised RIVETING study

Background: Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. The long-term, Phase 3b/4 RIVETING study (NCT03281304) assessed the efficacy and safety of tofacitinib dose reduction from tofacitinib 10 mg twice daily (BID) maintenance therapy to 5 mg BID in patients (pts) in stable remission. 1 We present a final analysis of the RIVETING study after >=30 months of treatment. Method(s): RIVETING was a double-blind, randomised, parallelgroup study with a 42-month (M) duration. Eligible pts had received tofacitinib 10 mg BID for >=2 consecutive years in an open-label, long-term extension study (NCT01470612), had been in stable remission for >=6 months and corticosteroid-free for >=4 weeks prior to baseline. The primary efficacy endpoint was remission at M6 based on modified Mayo (mMayo) score (endoscopic and stool frequency subscores of <=1 and rectal bleeding subscore of 0).1 RIVETING was terminated (primary objective met) when all pts had passed M30 (or discontinued);some pts had already completed all visits up to M42. Here, we assess efficacy at M30 and safety throughout. Result(s): Overall, 140 pts were randomised (1:1) to tofacitinib 5 or 10 mg BID;50.0% and 62.9% were in remission based on mMayo score at M30 in the 5 and 10 mg BID dose groups, respectively, with consistent findings observed for other secondary efficacy endpoints (Table 1). At M30, observed differences for mMayo remission between tofacitinib 10 and 5 mg BID were generally greater in the subgroup with a baseline endoscopic subscore of 1 vs 0 and in the subgroup with vs without prior tumour necrosis factor inhibitor (TNFi) failure (Table 1). The percentage of pts who experienced loss of remission by M30, as estimated from Kaplan-Meier curves, was numerically higher in the 5 vs the 10 mg BID dose group (28.1%;95% confidence interval [CI], 17.68-39.49 vs 21.7%;95% CI, 12.21-32.95, respectively). Table 2 shows adverse events of special interest, by dose group. One death occurred due to fatal coronavirus disease 2019 pneumonia (10 mg BID). Conclusion(s): These long-term data showed that most pts in stable remission on tofacitinib 10 mg BID maintenance therapy maintained mMayo score remission through M30 after dose reduction to 5 mg BID. Dose group difference in remission at M30 was consistent with that at M6.1 Differences in remission between the tofacitinib 5 and 10 mg BID groups were greater in subgroups with an endoscopic subscore of 1 vs 0 and in subgroups with vs without prior TNFi failure. Overall, safety findings were consistent with tofacitinib's known safety profile;incidence of serious infections and herpes zoster was numerically higher in the tofacitinib 10 vs 5 mg BID group. (Table Presented).

Real-life experience of the efficacy, safety and pharmacokinetic data of switching from intravenous to subcutaneous infliximab in inactive inflammatory bowel disease patients. Results from the ENEIDA registry

Background: Recently, a subcutaneous formulation of biosimilar infliximab (CT-P13) (SC-IFX) has been approved for inflammatory bowel disease (IBD). The aims of this study were to evaluate efficacy, safety, pharmacokinetics and patient experience following a switching to SC-IFX in patients who are in clinical remission on IV-IFX maintenance treatment. Method(s): Multicentre, descriptive, and observational study including Crohn's disease (CD) and ulcerative colitis (UC) patients who were going to be changed from IV-IFX to SC-IFX on the ENEIDA registry (a large, prospectively maintained database of the Spanish Working Group in IBD-GETECCU). All patients were on clinical and biological remission at least 24 weeks before changing. Demographic and disease data, clinical activity (Harvey-Bradshaw index for CD and mayo index for UC), analytical data (C reactive protein (CRP) and fecal calprotectin (FC), as well as trough levels were collected at baseline, at 12 and 24 weeks. Result(s): One hundred and fifty-five patients were included: 54 UC (35%) and 91 (65%) CD;44% women and 56% men;age 45.5 years (32-55). IV-IFX was mainly administered due to active disease (72%) and perianal disease (7%) and during 32 months [range 14-56]. Preswitch, 78 (50.3%) were on 8-weekly dosing of IV-IFX, 77 (49.7%) were with intensification dose and the half (50.3%) were on concomitant immunomodulatory therapy. SC-IFX was mainly switching by COVID-19 pandemic (60%), to increase through levels (15%) or patient request (25%). The majority of patients (140, 90%) remained with standard dose, 8 (5%) required dose intensification (120 mg weekly in 4 and 240 mg every 2 weeks in 4) and 7 (4.5%) had successful de-escalation (120 mg every 3 weeks in 4 and 120 mg every 4 weeks in 3). Clinical indices, CRP levels and FC remained unchanged (Figure). Median SC-IFX levels significantly increased from baseline of 4.5 mug/ dl [range 2.6-9.2] to 14 mug/dl [range 9.5-16.2] at week 12 and 13.2 mug/ dl [range 10.4-19.7] at week 24. No factors (immunossupresor, body mass index, disease location) were associated with the increase of IFX trough levels. During 24 weeks of follow-up, 16 of the 78 patients (20.5%) stopped immunosuppressant treatment. The adverse events were recorded in 9 patients (5.8%), 4 (2.6%) were hospitalized and 4 (2.6%) had surgery (one of them for perianal disease). Nine patients (5.8%) stopped SC-IFX (1 primary failure, 2 loss of response, 4 adverse events, 1 voluntarily, and 1 surgery). Conclusion(s): The switch from IV to SC IFX maintains clinical remission safely in IBD patients, offers higher drug levels and a good patient acceptance. However, the significance of higher drug levels with SC-IFX requires further exploration.

CASE REPORT: A RARE CASE OF ALVEOLAR HEMORRHAGE AFTER COVID-19 VACCINATION IN A PATIENT WITH RENAL-LIMITED ANTINEUTROPHIL CYTOPLASMIC ANTIBODYASSOCIATED VASCULITIS

The coronavirus disease 2019 (COVID-19) vaccination campaign has progressed worldwide. Rare but severe adverse events of COVID-19 vaccination such as anaphylaxis and myocarditis have begun to be noticed. Of note, several cases of new-onset antineutrophil cytoplasmic antibody-associated vasculitis (AAV) after COVID-19 mRNA vaccination have been reported. In contrast, relapse of AAV in remission has not been recognized enough as an adverse outcome of COVID-19 vaccination. We report, to the best of our knowledge, a first case of renal-limited AAV in remission using every 6-month rituximab administration that relapsed with pulmonary hemorrhage, but not glomerulonephritis, following the first dose of the COVID-19 vaccine. Notably, the patient received the COVID-19 vaccine more than 6 months after the last dose of rituximab according to the recommendations. Ironically, his CD19 positive B cell counts were found to be increased after admission, indicating that our case might have been prone to relapse after COVID-19 vaccination. Although our case cannot establish causality between AAV relapse and COVID-19 mRNA vaccination, a clinical vigilance for relapse of AAV especially in patients undergoing rituximab maintenance therapy following COVID-19 vaccination should be maintained. Furthermore, the elapsed time between rituximab administration and COVID-19 mRNA vaccination should be carefully adjusted based on AAV disease-activity (Nishioka et al. Front Med 2022. in press).

The Problem of Comorbid Socially Significant Infections Under The Conditions of The COVID-19 Pandemic

The aim of the study. To analyze formation features of the epidemic situation for tuberculosis (TB) in the context of the COVID-19 pandemic in order to predict the further actions of medical organizations. Materials and methods. The data for the region for the last 5 years (2017-2021) were analyzed, including 1,762 newly diagnosed cases of patients with TB and comorbidities (according to the data of the Regional Public Health Organization «Regional Clinical Anti-Tuberculosis Dispensary»). All cases were verified using standard diagnostic methods, including molecular genetic methods, to determine the resistance of pathogens to antibacterial drugs. Results. It was revealed that the epidemiological situation in the region was multidirectional: thus, during the COVID-19 epidemic, the most pronounced incidence decrease was observed among cases of chronic course hepatitis (by 16.4 times), while among patients with tuberculosis the incidence decreased by 2.75 times, and among patients with acute hepatitis - only by 1.5 times (P<0.05). Among the cases of comorbid infection, the most severe course was observed in patients with combined (TB + HIV) infection: there was both a more severe general condition, and the development of adverse (undesirable) reactions to anti-TB drugs, which required an extension of maintenance therapy. Conclusions. The results of the study showed that against the background of the COVID-19 pandemic in the region, there was no tendency towards a worsening of the epidemic situation, primarily for the more socially significant infection - tuberculosis. At the same time, there was an increase in the number of cases of comorbid pathology, including HIV + TB. In the treatment of patients with comorbid forms of infection, it is necessary to take into account the possibility of developing hepatotoxic reactions and, as a result, the appointment of accompanying drugs with hepatoprotective and detoxification effects in therapy.

Acne exacerbation: the role of exposome factors and current trends in maintenance therapy

At the present stage, acne is considered as a multifactorial dermatosis, in the formation of which a significant role is played by genetically determined hyperandrogenism and impaired secretion of the sebaceous glands, as well as changes in the skin microbiome. It is known that the risk of occurrence and severity of the disease are significantly influenced by various environmental components, which are commonly called exposure factors. This article provides an analysis of studies on the influence of the most common exposure factors on the pathogenesis and clinical course of acne: diet, skin care, stress, novel coronavirus infection (COVID-19), environmental pollution and climatic conditions. It has been shown that these factors affect the main components of the skin barrier, affect the microbiota and immune reactivity, which subsequently leads to the activation of the leading pathological mechanisms of acne formation. Considering the variety of factors that provoke the disease, emphasis is placed on the need for proper skin care and pathogenetically substantiated therapy in a maintenance regimen with the appointment of topical retinoids and azelaic acid. Due to anti-inflammatory and comedonolytic effects, as well as inhibition of the growth of Cutibacterium acne, these active ingredients provide a complex effect on the main pathogenetic links of the disease. The article presents our own clinical observations of patients with acne, who underwent complex therapy and prevention of exacerbations with the use of Adaklin and Azix-Derm. It was noted that these drugs are effective both in the complex treatment and in the prevention of exacerbations in patients with mild to moderate acne, while the therapy is well tolerated by patients the resulting adverse events are reversible, easily corrected with moisturizing agents and do not require discontinuation of drugs. © 2022, Remedium Group Ltd. All rights reserved.