Moderate Inflammatory Activity Research Articles

Assessment of inflammation activity in the small and large bowel using the MaRIAs index for Crohn’s disease

Aim: to evaluate diagnostic value of magnetic resonance enterocolonography (MR-enterocolonography) with the use of the segmental index MaRIAs (Simplified Magnetic Resonance Index of Activity) for inflammation activity in small and large intestine colon compared with ileocolonoscopy.Patients and Methods: the prospective cohort study included 58 patients with Crohn’s disease aged 19–45 years. All patients underwent MR-enterocolonography with intravenous contrast and ileocolonoscopy. MR-enterocolonography assessed inflammatory activity in the large and small intestine (406 segments) using the MaRIAs index (segmental). MRI data were compared with ileocolonoscopy.Results: ileocolonoscopy showed no signs of inflammatory activity in 71 (71/406, 17.5%) segments. In 168 (168/406, 41.3%) segments endoscopic signs of low or moderate inflammatory activity were detected, in 167 (167/406, 41.2%) segments inflammatory activity with the presence of ulcers were detected. MR-enterocolonography did not detect any activity in 121 (121/406, 29.8%) segments (0 points by MaRIAs index), in 285 (285/406, 70.2%) segments, the inflammation activity was revealed by MaRIAs index from 1 to 5 points. There was a moderate agreement (Cohen’s Kappa: 0.57) between the data of MR-enterocolonography and ileocolonoscopy in detection of affected segments. ROC analysis revealed that with the value of the MaRIAs index (segmental) of 1 point or more with sensitivity of 82.0% and specificity of 92.0% (AUC 0.85), it is possible to consider the presence of inflammatory activity of any severity, and with index value of 2 points or more with sensitivity of 75.0% and specificity of 91.0% (AUC 0.91) can diagnose the severe inflammation with ulcers.Conclusion: the results obtained revealed the value of MaRIAs index and the further study to evaluate the effectiveness of conservative treatment of Crohn’s disease is needed.

Smouldering Lesion in MS: Microglia, Lymphocytes and Pathobiochemical Mechanisms.

Multiple sclerosis (MS) is an immune-mediated, chronic inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS). Immune cell infiltration can lead to permanent activation of macrophages and microglia in the parenchyma, resulting in demyelination and neurodegeneration. Thus, neurodegeneration that begins with acute lymphocytic inflammation may progress to chronic inflammation. This chronic inflammation is thought to underlie the development of so-called smouldering lesions. These lesions evolve from acute inflammatory lesions and are associated with continuous low-grade demyelination and neurodegeneration over many years. Their presence is associated with poor disease prognosis and promotes the transition to progressive MS, which may later manifest clinically as progressive MS when neurodegeneration exceeds the upper limit of functional compensation. In smouldering lesions, in the presence of only moderate inflammatory activity, a toxic environment is clearly identifiable and contributes to the progressive degeneration of neurons, axons, and oligodendrocytes and, thus, to clinical disease progression. In addition to the cells of the immune system, the development of oxidative stress in MS lesions, mitochondrial damage, and hypoxia caused by the resulting energy deficit and iron accumulation are thought to play a role in this process. In addition to classical immune mediators, this chronic toxic environment contains high concentrations of oxidants and iron ions, as well as the excitatory neurotransmitter glutamate. In this review, we will discuss how these pathobiochemical markers and mechanisms, alone or in combination, lead to neuronal, axonal, and glial cell death and ultimately to the process of neuroinflammation and neurodegeneration, and then discuss the concepts and conclusions that emerge from these findings. Understanding the role of these pathobiochemical markers would be important to gain a better insight into the relationship between the clinical classification and the pathomechanism of MS.

Differential Brain Structural and Functional Patterns in Crohn's Disease Patients are Associated with Different Disease Stages.

Crohn's disease (CD) is an inflammatory, chronic disorder that alternates between a quiescent phase and inflammatory flare-ups. Research has begun to elucidate the impact of CD in modulating brain structure and function. The previous neuroimaging studies mainly involved CD patients in remission (CD-R); therefore, little is known about how inflammation influences brain-related features in different stages of the disease. We carried out a magnetic resonance imaging (MRI) study to explore whether the different levels of disease activity may differentially affect brain structure and function. Fourteen CD-R patients, 19 patients with mild to moderate inflammatory activity (CD-A), and 18 healthy controls (HCs) underwent an MRI scan including structural and functional sequences. Between-group comparisons showed morphological and functional brain differences distinctively associated with the stage of disease activity. The CD-A patients had reduced gray matter within the posterior cingulate cortex (PCC) relative to CD-R patients. Analysis on resting fMRI data showed the following patterns: (1) increased connectivity within the left fronto-parietal network (in the superior parietal lobe) in CD-R patients relative to CD-A patients; (2) decreased connectivity in the motor network (in parietal and motor areas) in the CD-A group relative to the HC group; (3) reduced connectivity in the motor network and (4) in the language network (in parietal areas and in the PCC) in CD-R patients relative to HC. The present findings represent a further step towards understanding brain morphological and functional changes in the active vs remission stages of CD patients.

S3241 A Case of Autoimmune Hepatitis in the Setting of the Janssen COVID-19 Vaccine

Introduction: Autoimmune hepatitis (AIH) is an inflammatory autoimmune condition that can result in chronic liver disease, it can be caused by the interaction of hereditary, epigenetic, immune, and environmental triggers. Vaccine related AIH is an uncommon phenomenon that has been reported in the presence of other vaccinations.. We present a unique case of AIH in the setting of the Janssen SARS-CoV-2 vaccine (JJ). Case Description/Methods: A 45-year-old female with a history ofHTN, DM, GERD, and obesity presented from her primary care physician’s office with abnormal liver chemistries in a hepatocellular pattern. Her hepatic profile showed AST 1119, ALT 988, AP 130, and total bilirubin of 1.5 (R-factor 22.8). Given the magnitude and rapidity of the elevated chemistries a broad serologic workup was initiated. She was negative for hepatitis A, B, and C, as well as HSV 1/2, EBV, CMV, HIV, VZV, and adenovirus. Her ferritin and iron studies did not suggest iron overload. Her ceruloplasmin and alpha 1 antitrypsin levels were within acceptable ranges. Her ANA was negative; her smooth muscle antibody was positive (1:320), IgG was elevated to 3,451 mg/dL. Her urine toxin screen was negative. She had chronically been on HCTZ and took occasionally seamoss supplements. She denied using tylenol or any other over the counter or herbal supplements. In the past month she had received a single dose of the Janssen SARS CoV-2 vaccination (Johnson and Johnson). Her liver chemistries prior were AST 17, ALT 14, AP 52, and total bilirubin of 0.3. She subsequently underwent a liver biopsy which showed moderate (grade 3) lobular inflammatory activity, mild (grade 2) periportal activity, and mild (stage 2) fibrosis with an abundance of plasma cells consistent with autoimmune hepatitis. Treatment was initiated with oral prednisone with a resulting improvement in her liver chemistries (Figure). Discussion: Autoimmune hepatitis in the setting of recent administration COVID 19 vaccine administration has been rarely reported. We present a unique case of COVID vaccine induced autoimmune hepatitis from a non-mRNA based vaccine. It has been suggested that possible mechanisms may include molecular mimicry or bystander activation of dormant autoreactive T-helper cells for both tissue-specific and non-tissue-specific reactions. We aim to shed light to this interesting paradigm and to spark the scientific discourse to further delineate potential mechanisms leading to this uncommon complication.Figure 1.: Liver biopsy which showed moderate (grade 3) lobular inflammatory activity, mild (grade 2) periportal activity, and mild (stage 2) fibrosis with an abundance of plasma cells consistent with autoimmune hepatitis.

Relationship of cytokine level dynamics with longterm results of early rheumatoid arthritis therapy

The aim of the work – to research the relationship between the dynamics of cytokine levels in the early period (the first 12 and 24 weeks) of pharmacotherapy for rheumatoid arthritis (RA) and long-term outcomes in patients with the disease.Material and methods. The analysis included 93 patients with early RA. The majority of patients were women (n=77), middle-aged (58 [49; 66] years), with an early stage of the disease (the duration of the disease is 7 [4–11.5] months), seropositive according to IgM rheumatoid factor and cyclic citrullinated peptide antibodies, who had high (59.7%) or moderate (38.8%) disease activity.The concentration of 27 cytokines in the blood serum was determined with the help of multiplex xMAP technology on the Bio-Plex array system analyzer (BIORAD, USA). Repeated clinical examination of patients was carried out after 6 years.Results. Patients who achieved remission/low disease activity SDAI after 6 years had a lower level of IL-6 (7.7 [7.4; 23.3]), IL-9 (13.5 [9.1; 18.9]) 12 weeks after the start of therapy; lower IL-9 level (12.6 [6.8; 16.2]) 24 weeks after the start of the treatment, compared with the group of patients with moderate and high inflammatory activity (23.5 [12.4; 69.5], 17.8 [15; 29] and 18.5 [14.2; 22.8] respectively).Findings. The assessment of the level of proinflammatory cytokines (IL-6, IL-17), immunoregulatory cytokine IL-9 allows to evaluate the activity of the disease more fully and identify a group of patients, who needs the therapy intensification.

Chronic viral HBeAg-negative hepatitis B: Epidemiological, clinical and biochemical characteristics in an outpatient descriptive cohort in Burkina Faso

IntroductionOur study aimed to describe epidemiological and diagnostic features in an outpatient's cohort with chronic HBeAg-negative hepatitis B. Patients and methodsA cross-sectional descriptive study with a retrospective data collection was implemented from January 2004 to April 2016 in the hepato-gastroenterology department of the University Teaching Hospital Yalgado Ouédraogo (CHU-YO) in Burkina Faso. ResultsOverall 325 HBeAg negative patients met the inclusion criteria. The sex ratio was 1.5 and the mean age 38.7 years. The most frequent circumstance of diagnosis was the health check-up (54.5%). The mean HBsAg concentration and viral load were 7861.6 IU/mL and 32 237.20 IU/mL, respectively. Low or moderate inflammatory activity was found in 44% and 24% of patients, respectively at the liver biopsy; 32% presented a portal fibrosis with some septa (F2). 43.9% and 41.6% had low (A1) or moderate (A2) inflammatory activity, respectively at the hepatic fibrosis blood test, while 59.1% and 20.4% had low (F1) or moderate (F2) fibrosis stage, respectively. Of the five biochemical and virological profiles among the untreated patients, the profile 1 represented 67.2% of the sample. ConclusionThe proportions of negative HBeAg in chronic hepatitis B patients are increasing in Burkina Faso. Most of the patients have a high viral load, a low to moderate inflammatory activity or fibrosis stage.

Predictors of inflammatory activity in treatment-naive hepatitis B e-antigen-negative patients with chronic hepatitis B infection.

ObjectiveLiver inflammatory activity staging is critical to guide the treatment of chronic hepatitis B virus (CHB) infection. Here, we aimed to identify practical clinical biomarkers of moderate inflammatory activity in hepatitis B e-antigen (HBeAg)-negative CHB patients.MethodsTreatment-naïve HBeAg-negative CHB patients who underwent liver biopsy at our hospital from 1 January 2013 to 31 December 2016 were enrolled. Markers of inflammatory activity were analyzed using binary logistic regression. The area under the receiver operator characteristic curve (AUROCC) was used to assess diagnostic accuracy.ResultsA total of 106 HBeAg-negative treatment-naive CHB patients were enrolled. According to their METAVIR inflammatory scores, 30.2% of patients were in stage ≥A2. Total triiodothyronine (TT3) and hepatitis B virus (HBV) DNA levels were predictors of moderate inflammatory activity (A ≥ 2). The AUROCCs of TT3 and HBV DNA levels were 0.651 and 0.797, respectively. The optimal cut-off values for TT3 and HBV DNA were 1.755 nmol/L and 4.61 log10 IU/mL, respectively.ConclusionsA sizable proportion of treatment-naive HBeAg-negative CHB patients required antiviral treatment (30.2%) after undergoing liver biopsy. TT3 and HBV DNA helps identify patients with moderate inflammatory activity (A ≥ 2), potentially reducing the need for liver biopsies and helping guide treatment of CHB patients.

EFFICACY AND SAFETY OF TOFACITINIB IN PATIENTS WITH PSORIATIC ARTHRITIS IN REAL CLINICAL PRACTICE

Objective: to evaluate the clinical efficacy and safety of the targeted synthetic disease-modifying anti-rheumatic drug (DMARD) tofacitinib (TOFA; Yakvinus®) in patients with active psoriatic arthritis (PsA) at 12 and 24 weeks after starting treatment. To define the place of TOFA in the therapy of PsA patients. Subjects and methods. Examinations were made in 41 patients (17 men and 24 women) with active PsA and an insufficient response to previous treatment with synthetic DMARDs and/or biological agents (BA). Before starting therapy, the median disease activity for psoriatic arthritis (DAPSA) and disease activity score (DAS28) were 44.2 [37.8; 55.3] and 5.5 [4.7; 6.1], respectively. TOFA tablets were prescribed at a dose of 5 mg twice daily for 24 weeks with possible dose escalation to 10 mg twice daily after 12 weeks. At the beginning of the investigation, at 12 and 24 weeks, the investigators assessed disease activity and TOFA therapy efficiency of according to DAPSA, DAS28 and minimal disease activity (MDA) criteria: tender joint count ≤1, swollen joint count ≤1, a psoriasis area severity index (PASI) ≤1 or body surface area (BSA) ≤3%, pain intensity ≤15 mm, patient global assessment ≤20 mm, Health Assessment Questionnaire (HAQ) ≤0.5, and enthesitis ≤1. They also determined the number of patients who had achieved remission (DAPSA ≤4, DAS28 score <2.6), low disease activity (DAPSA 5-14, ≤2.6, DAS28 <3.2) or MDA (5 out of the 7 criteria) during TOFA therapy at 24-week follow-up. The safety of therapy was evaluated by analyzing the drug-induced adverse events (AE): the frequency, severity and time of their occurrence were studied. Results and discussion. At 24 weeks after initiation of TOFA therapy, there was a significant decrease of median DAPSA and DAS28 values as compared to baseline, to 11 [4.3; 17.3] and 2.6 [1.7; 3.4] respectively. The median Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) also significantly decreased from 6 [4.2; 7] and 3.8 [2.8; 4.4] to 1.4 [0.6; 3.2] and 1.5 [1; 2.1] respectively. The median BSA was significantly reduced from 3 [1; 5] to 0.5 [0.1; 2]. At 24 weeks after initiation of TOFA therapy, DAPSA and DAS28 low disease activity/remission were achieved by 38.5/23.1% and 17.9/53.9% of patients, respectively. Fifteen (38.5%) patients achieved MDA. 38 (92.7%) of the 41 patients completed a full TOFA therapy cycle. Two patients dropped out of the investigation due to ineffective therapy and one due to AE (diarrhea occurring up to 10 times daily, headache, elevated blood pressure, and lacrimation). At 24 weeks, 14 (34.2%) patients reported to have AE. The most common AE noted in 7 (17.1%) patients were infections: acute respiratory viral infection (n=3), fever (n=2), and folliculitis (n=2). In addition, two patients had diarrhea and two had headache. Conclusion. TOFA is an effective drug for the treatment of PsA patients with moderate or high inflammatory activity, has a significant effect on all clinical manifestations of PsA and has a satisfactory safety profile.

The efficacy and safety of apremilast in patients with psoriatic arthritis concurrent with comorbidity in clinical practice

Objective: to evaluate the clinical efficacy and safety of the targeted synthetic disease-modifying antirheumatic drug (DMARD) apremilast (AP; Otesla®) in patients with active psoriatic arthritis (PsA) at 14 and 26 weeks after starting the treatment and to identify the place of AP in the combination therapy of patients with PsA, by taking into consideration a comorbidity.Subjects and methods. Examinations were made in 20 patients (11 women and 9 men) with active PsA who had comorbidity, lack of efficiency of or intolerance to previous therapy with synthetic DMARDs or biologic agents, and contraindications to its use. The median baseline Disease Activity in Psoriatic Arthritis (DAPSA) score was 35.6 [24.8; 55.6]; those of DAS and DAS28 were 3.8 [3.2; 5.0] and 4.4 [4.0; 5.2], respectively. AP (Otesla®) was administered in tablets with a starting dose of 10 mg/day with a daily dose escalation of 10 mg to the therapeutic dose of 60 mg/day for 26 weeks. At baseline, 14 and 26 weeks, the disease activity and efficiency of AP were evaluated using DAPSA, DAS, and DAS28, as well as minimal disease activity (MDA) criteria (tender joint count ≤1; swollen joint count ≤1; PASI ≤1 or BSA ≤3%; a patient’s assessment of pain ≤15 mm; patient’s global assessment ≤ 20 mm; Health Assessment Questionnaire (HAQ) ≤ 0.5; enthesitis ≤1). The investigators estimated the number of patients who had achieved remission (DAPSA≤4; DAS<1.6; DAS28<2.6), low activity (5≤DAPSA≤14; 1.6≤DAS<2.4; 2.6≤DAS28<3.2) or MDA (5 of the 7 criteria) during AP therapy at 26-week follow-up. The safety of therapy was evaluated, by analyzing the adverse events (AE): the frequency, severity, and time of their occurrence were studied.Results and discussion. At 26 weeks after AP therapy initiation, there was a significant decrease of all PsA activity scores as compared to the baseline ones to the following median values: DAPSA 25.9 [11.3; 35.2]; DAS 3.3 [1.8; 3.9], and DAS28 3.4 [2.3; 4.8]. The median BASDAI and ASDAS scores also significantly declined from 5.1 [2.5; 7.3] and 3.35 [2.3; 4.2] to 3.45 [2.15; 6.15] and 2.7 [1.8; 3.35], respectively. The median area of psoriatic skin lesions (body surface area (BSA)) significantly reduced from 2 [0.35; 6] to 1 [0.2; 2]. At 26 weeks after starting AP therapy, the low activity/remission according to DAPSA, DAS, and DAS28 was achieved by 20/10%, 20/15%, and 10/35% of patients, respectively. Three (15%) patients achieved MDA. Fifteen (75%) of the 20 patients completed an AP therapy course. In the period of 14 to 26 weeks, four patients dropped out of the study due to ineffective therapy and one because of a severe AE (pneumonia at 14 weeks of treatment); at 26 weeks, another patient was withdrawn due to lack of effect. At 14 weeks, ten patients had a moderate AE that did not required treatment discontinuation. The most common AE were diarrhea in 5 (25%) patients, headache in 4 (20%), nausea in 3 (15%), and insomnia in 3 (15%).Conclusion. AP is a safe and effective drug for the treatment of PsA patients with moderate and high inflammatory activity and various comorbidities that do not allow the use of conventional DMARDs.

Evaluation of lipid peroxidation processes in patients with chronic parenteral viral hepatitis and HIV co-infection depending on degree of inflammatory process activity in the liver

The aim of the study. To evaluate of parameters of lipid peroxidation - antioxidant defense changes in women of fertile age with chronic viral hepatitis (CVH) and with HIV (human immunodeficiency virus) infection, depending on the degree of inflammatory process activity in the liver. Materials and methods. 99 women of reproductive age were examined, of them 44 patients with chronic parenteral viral hepatitis, 27 patients with HIV co-infection (HIV + hepatitis B and/or C) and 28 practically healthy women (control group). Results. Patients with CVH in combination with HIV-infection with the presence of minimal and low degree of inflammatory activity in comparison with patients with CVH-monoinfection had a higher content of lipid peroxidation products (an increase in the content of diene conjugates and ketodienes and conjugated trienes), reduced values of total antioxidant activity, superoxide dismutase activity, as well as the concentration of fat-soluble vitamins α-tocopherol and retinol. In the group with CVH and HIV with moderate and high degree of activity, similar, but even more pronounced changes in the system of lipid peroxidation were observed. Conclusion. The presence of co-infection - CVH in combination with HIV infection with minimal and low, as well as moderate and high inflammatory activity, is characterized by more intensive lipid peroxidation processes and a pronounced lack of antioxidant factors than with CVH-monoinfection.

Evaluation of lipid peroxidation processes in patients with chronic parenteral viral hepatitis and HIV co-infection depending on degree of inflammatory process activity in the liver.

To evaluate of parameters of lipid peroxidation - antioxidant defense changes in women of fertile age with chronic viral hepatitis (CVH) and with HIV (human immunodeficiency virus) infection, depending on the degree of inflammatory process activity in the liver. 99 women of reproductive age were examined, of them 44 patients with chronic parenteral viral hepatitis, 27 patients with HIV co-infection (HIV + hepatitis B and/or C) and 28 practically healthy women (control group). Patients with CVH in combination with HIV-infection with the presence of minimal and low degree of inflammatory activity in comparison with patients with CVH-monoinfection had a higher content of lipid peroxidation products (an increase in the content of diene conjugates and ketodienes and conjugated trienes), reduced values of total antioxidant activity, superoxide dismutase activity, as well as the concentration of fat-soluble vitamins α-tocopherol and retinol. In the group with CVH and HIV with moderate and high degree of activity, similar, but even more pronounced changes in the system of lipid peroxidation were observed. The presence of co-infection - CVH in combination with HIV infection with minimal and low, as well as moderate and high inflammatory activity, is characterized by more intensive lipid peroxidation processes and a pronounced lack of antioxidant factors than with CVH-monoinfection.

Diagnosis of IgG4 - related ophthalmic disease in a group of patients with various lesions of the eye and orbits.

To provide demographic, clinical, laboratory, ultrasound, radiological, morphological/ immunomorphological phenotype of IgG4-related ophthalmic diseases, which allowsmaking a differential diagnosis with granulomatous, autoimmune, inflammatory, endocrine and hematologic diseases affecting the eye and orbits. From 2004 to 2016 108 (78.2%) of the 138 patients were diagnosed with non-tumoral lesions of eye and orbits. In 48 patients (35%) at admission and 5 patients in the follow were diagnosed IgG4-related ophthalmic disease. In the analysis of 82 (f-44, m-38) patients with IgG4-related disease, localization of lesions in orbit observed in 53 (f-36, m-17) and it was the most frequent involvement in patients with IgG4-related disease (64.5%). Only 7 patients had isolated IgG4-related ophthalmic disease, whereas 46 patients (87%) had involvement of 2-7 locations, as a manifestation of IgG4-related systemic disease.During the examination, the average age of patients with IgG4-related ophthalmic disease was 47.5 years (19-73 years). Median time to diagnosis was 52.8 months before 2004 and 36 months 2004-2016. We noted the predominance of females in the ratio 2: 1 inthe group of patients with IgG4-related ophthalmic disease. Edema of the eyelids, nasal congestion (55-60%), tumor-like formations of the upper eyelids and increased lacrimation prevailed at the onset of the disease, whereas such functional impairment like limited mobility and pain in eyeballs, exophthalmos, ptosis and diplopia appeared later at 15-38% with a loss visual acuity in one case. Bilateral lesion (86%), mainly affecting the lacrimal glands (93.5%), infiltration of the ex- traocular muscles (83.5%) and retrobulbar tissue with a thickening of the optic nerve in one third of patients were the main localizations IgG4-related ophthalmic disease. Clinical symptoms were accompanied by the appearance of moderate inflammatory activity (38%), in- creased levels IgG (44%), IgG4(88%) and IgE (61%). Indicators of autoimmune disorders observed in 6-22% of patients, most often in pa- tients with simultaneous involvement of the salivary glands. Significant lymphoplasmacytic infiltration (94%) with a ratio of plasma cells (IgG4/IgG) secreting IgG4> 40% (90%) with fibrosis formation (94%) and follicle formation (71%) with a moderate amount of eosinophils (34%) were the major morphological / immunomorphological manifestations of IgG4-related ophthalmic disease. Signs of vasculitis and obliterative phlebitis were found in a small amount of patients. Determination of elevated levels of IgG-4 / IgE in patients with edema, pseudotumor of the eyelid, sinusitis and increase of the palpebral lobe of the lacrimal gland suggests the presence of IgG4-related ophthalmic disease. Minimally invasive incisional biopsy of lacrimal glands and salivary glands followed by morphological / immunomorphological research is needed for the correct diagnosis. Diagnostic orbitotomy in ophthalmic hospitals in such cases is inexpedient, since it leads to the development of dry eye. Massive lymphoplasmacytic infiltration with IgG4 / IgG ratio more than 40%, advanced fibrosis in biopsiesof the orbits tissue or salivary glands when combined lesions are required for the making the diagnosis of IgG4-related ophthalmic disease.

IMMUNOGENICITY AND SAFETY OF 23-VALENT POLYSACCHARIDE PNEUMOCOCCAL VACCINE IN PATIENTS WITH RHEUMATOID ARTHRITIS: RESULTS OF A TWO-YEAR FOLLOW-UP STUDY

Objective: to investigate the immunogenicity, safety, and clinical efficacy of 23-valent polysaccharide pneumococcal vaccine in patients with rheumatoid arthritis (RA) during a two-year follow-up study.Subjects and methods. The prospective open-label comparative study enrolled 110 people, of them there were 81 (73.6%) women and 29 (26.4%) men at the age of 23 to 76 years, including 79 patients with RA, as well as 31 subjects without systemic inflammatory rheumatic diseases (RD) (a control group). The group of RA patients exhibited a predominance of middle-aged women who had > 3 years’ disease duration and a moderate inflammatory activity (the mean value of DAS28, 4.32). 52 patients received methotrexate (MTX), 14 had Leflunomide (LEF), and 13 were treated with tumor necrosis factor-α (TNF-α) inhibitors + MTX.The 23-valent polysaccharide pneumococcal vaccine Pneumo-23 (Sanofi Pasteur, France) was administered in a single dose of 0.5 ml subcutaneously during continuous MTX or LEF therapy for the underlying disease or 3–4 weeks before the use of TNF-α inhibitors. Clinical examinations of the patient and conventional clinical and laboratory studies were performed during control visits (1, 3, 12, and 24 months after vaccination). Clinical effectiveness and safety were evaluated in all the patients included in the study. The serum levels of anti-pneumococcal capsular polysaccharide antibodies (Ab) were measured in 72 patients with RA and in 30 individuals in the control group during a 12-month follow-up study, including in 25 patients with RA for a 24-month follow-up study by enzyme immunoassay using commercial VaccZymeTM Anti-PCP IgG Enzyme Immunoassay kits (The Binding Site Group Ltd, Birmingham, United Kingdom). Along with this, the post-immunization response coefficient was calculated for each patient as the ratio of postvaccination Ab levels during Visits 2, 3, 4, and 5 to the baseline Ab level.Results and discussion. No clinical and radiological symptoms of pneumonia were recorded in any case during the follow-up period. The patients with RA and the control group showed a more than double significant increase of anti-pneumococcal Ab level during 3 months following vaccination. Despite the decrease in their concentration by month 12, the latter remained at the appropriate level and significantly increased at 24-month follow-up. Vaccination was well tolerated. A favorable course of the postvaccinal period was noted in all cases. There were no adverse reactions to vaccination in 72 (65%) patients; 38 (35%) patients were noted to have pain, skin swelling and hyperemia up to 2 cm in diameter at the site of injection, as well as low-grade fever. There were no episodes of a RD exacerbation or any new autoimmune disorders during the follow-up period.Conclusion. The findings were suggestive of the sufficient immunogenicity and good tolerability of 23-valent pneumococcal vaccine in patients with RD during the two-year follow-up period.

Serum amyloid A immunohistochemical staining patterns in hepatitis.

Serum amyloid A is an acute phase reactant that is produced by hepatocytes in response to either inflammatory or neoplastic conditions. Because inflammatory adenomas produce this protein, serum amyloid A immunohistochemistry has been used in the evaluation of hepatocellular neoplasms. However, studies evaluating the expression of this protein in hepatitis are lacking. The aim of this study was to perform serum amyloid A immunostains on medical liver biopsy specimens of patients with common chronic liver diseases and correlate them with disease activity and stage. We performed serum amyloid A immunostains on 160 medical liver biopsies, including 100 cases of hepatitis C virus infection at different stages (20 cases of each) and 20 cases each of hepatitis B viral infection, steatohepatitis and autoimmune hepatitis. The extent and location of staining was recorded and correlated with grade, stage and laboratory values (transaminases, bilirubin and viral load). Data were analysed using the Cochran-Mantel-Haenszel χ2 test for trend. Serum amyloid A staining was present in 130 (81%) cases and was limited to zone 3 perivenular hepatocytes in 66 (41%). Biopsy specimens with less fibrosis and/or mild portal inflammation showed significantly more staining than those with cirrhosis (P < 0.001), or at least moderate inflammatory activity (P < 0.001). There was no significant association between lobular inflammation (P = 0.06), bilirubin levels or viral load and immunohistochemical staining for serum amyloid A. Our results show that liver biopsy specimens with mildly active chronic hepatitis, early fibrosis and normal serum transaminases show more serum amyloid A immunopositivity compared with cases with more inflammatory activity, fibrosis or transaminitis. These findings indicate that serum amyloid A is expressed primarily in the early phases of disease and might influence progression and/or response to treatment.

Lewis Score – Prognostic Value in Patients with Isolated Small Bowel Crohn’s Disease

Small bowel capsule endoscopy (SBCE) allows mapping of small bowel inflammation in Crohn's disease (CD). We aimed to assess the prognostic value of the severity of inflammatory lesions, quantified by the Lewis score (LS), in patients with isolated small bowel CD. A retrospective study was performed in which 53 patients with isolated small bowel CD were submitted to SBCE at the time of diagnosis. The Lewis score was calculated and patients had at least 12 months of follow-up after diagnosis. As adverse events we defined disease flare requiring systemic corticosteroid therapy, hospitalization and/or surgery during follow-up. We compared the incidence of adverse events in 2 patient subgroups, i.e. those with moderate or severe inflammatory activity (LS ≥790) and those with mild inflammatory activity (135 ≤ LS < 790). The LS was ≥790 in 22 patients (41.5%), while 58.5% presented with LS between 135 and 790. Patients with a higher LS were more frequently smokers (p = 0.01), males (p = 0017) and under immunosuppressive therapy (p = 0.004). In multivariate analysis, moderate to severe disease at SBCE was independently associated with corticosteroid therapy during follow-up, with a relative risk (RR) of 5 (p = 0.011; 95% confidence interval [CI] 1.5-17.8), and for hospitalization, with an RR of 13.7 (p = 0 .028; 95% CI 1.3-141.9). In patients with moderate to severe inflammatory activity there were higher prevalences of corticosteroid therapy demand and hospitalization during follow-up. Thus, stratifying the degree of small bowel inflammatory activity with SBCE and LS calculation at the time of diagnosis provided relevant prognostic value in patients with isolated small bowel CD.

Stem cell transplantation for multiple sclerosis. Hamburg experiences and state of international research

Autologous hematopoietic stem cell transplantation (aHSCT) is still not the standard treatment for highly inflammatory multiple sclerosis (MS). Even though randomized controlled trials are lacking, predictors for treatment response have been established. Since 2007, ten patients have received aHSCT in Hamburg. To present observational data from patients treated in Hamburg and a review of the literature. Descriptive statistics were used for evaluating the course of the expanded disability status scale (EDSS) as a measure for clinical outcome, magnetic resonance imaging (MRI) and neuropsychology. New gadolinium and T2-MRI uptake lesions per scan were compared. In addition, a systematic review of the currently available literature was performed. The Hamburg series can be divided in two groups, one group including four patients with chronic progressive MS with low inflammatory activity (median EDSS = 6.25, 0.5 relapses per year, no gadolinium-enhancing lesions) and the other group including six patients with mild to moderate disability, relapses and inflammatory activity (median EDSS = 4.25, 1 relapse per year, 2 gadolinium-enhancing lesions). The median follow-up was 2.4 years. While the first group did not seem to benefit from aHSCT, an improvement in five out of six patients was observed in the second group. New T2 lesions occurred within the first 6 months but gadolinium-enhancing lesions were not observed (p < 0.05). A systematic literature search identified a higher efficacy of aHSCT in younger, less disabled MS patients with inflammatory activity, similar to the findings from Hamburg. Cohort reports describe aHSCT as a safe and efficient treatment option in highly inflammatory MS. Based on these data aHSCT seems to be a reasonable option in selected patients with highly inflammatory MS but a randomized controlled trial is warranted.

Influence of NADPH oxidase on inflammatory response in primary intestinal epithelial cells in patients with ulcerative colitis

BackgroundThe aim of this study is to evaluate the role of NADPH oxidase in primary intestinal epithelial cells during the active phase of UC.MethodsThe primary human colonic epithelial cells were isolated from 19 patients with mild to moderate inflammatory activity of UC and 14 controls using chelation method. The cells were cultivated under the effect of mediators. Viability of cells was assessed by fluorescent microscopy. Production of reactive oxygen species (ROS) by the cells was measured fluorimetrically using Amplex Red. Production of TNF-α cytokine by the colonic epithelial cells was analysed by ELISA.ResultsThe results of our study showed that unstimulated cells of UC patients had a decreased viability, increased ROS production, but similar TNF-α level when compared to the controls. Stimulation with LPS increased hydrogen peroxide and TNF-α level in the UC group. Treatment of colonic epithelial cells with NADPH oxidase inhibitor increased cell viability decreased the levels of ROS and TNF-α in the LPS-treated cells isolated from UC patients.ConclusionsOur study showed that bacterial endotoxins induced NADPH oxidase activation in the colonic epithelial cells. Moreover, we revealed that treatment with NADPH oxidase inhibitors had a protective effect against pro-inflammatory action of LPS in human colonic epithelium cells during inflammation.

Efficiency of log wood combustion affects the toxicological and chemical properties of emission particles

Context: Particulate matter (PM) has been identified as a major environmental pollutant causing severe health problems. Large amounts of the harmful particulate matter (PM) are emitted from residential wood combustion, but the toxicological properties of wood combustion particles are poorly known.Objective: To investigate chemical and consequent toxicological characteristics of PM1 emitted from different phases of batch combustion in four heating appliances.Materials and methods: Mouse RAW264.7 macrophages and human BEAS-2B bronchial epithelial cells were exposed for 24 h to different doses (15–300 µg/mL) of wood combustion particles. After the exposure, cytotoxicity, genotoxicity, production of the inflammatory mediators (TNF-α and MIP-2) and effects on the cell cycle were assessed. Furthermore, the detected toxicological responses were compared with the chemical composition of PM1 samples including PAHs, metals and ions.Results: All the wood combustion samples exerted high cytotoxicity, but only moderate inflammatory activity. The particles emitted from the inefficient phase of batch combustion in the sauna stove (SS) induced the most extensive cytotoxic and genotoxic responses in mammalian cells. Polycyclic aromatic hydrocarbons (PAHs) and other organic compounds in PM1 samples might have contributed to these effects. Instead, water-soluble metals seemed to participate in the cytotoxic responses triggered by the particles from more efficient batch combustion in the masonry heaters. Overall, the toxicological responses were decreased when the combustion phase was more efficient.Conclusion: Efficiency of batch combustion plays a significant role in the harmfulness of PM even under incomplete wood combustion processes.

Clinical Picture and Liver Histology of Chronic Hepatitis C in Children

Background and Aim Chronic hepatitis C (CHC) is still a significant clinical problem because of not only a large proportion of infected individuals, but also unclear remote consequences of the disease. The aim of the study was to analyze the clinical course and the liver histology of CHC in children searching for potential influencing factors. Methods Sixty-eight children were enrolled into the study (mean, 13.34 [SD, 3.27] years). Medical records and a current clinical status of children were analyzed considering clinical symptoms, liver function tests, and qualitative and quantitative hepatitis C virus–RNA assay with genotype and liver histology. Results A parenteral route of infection concerned 98% of children; mean length of infection was 7.34 (SD, 4.03) years. Genotype 1a was found in 78% and 1b in 16.2% children. The history of malignancy was present in 74% of patients. The symptoms of liver cirrhosis with abnormal vein circulation were found in 2 children (3%). An increased alanine aminotransferase activity was detected in 62% of patients, whereas viral load less than 6 × 105 IU/mL was found in 56 children (82%). Histological evaluation of biopsy specimens showed moderate inflammatory activity (G2) and fibrosis (S2; mean, 2.0). Progression of fibrosis was proportional to the age at infection. Conclusions The clinical course of CHC is usually mild but may result in the liver cirrhosis during childhood. Transient or constant increased alanine aminotransferase activity is observed in majority of children. Inflammatory activity and fibrosis have moderate progression in children and are proportional to the age at infection.

Appraisal of anti-inflammatory and free radical scavenging activities of ethanol extract of Ilex ficoidea Hemsl and Ilex centrochinensis S.Y. Hu

This study was to appraise the anti-inflammatory and free radical scavenging activities of ethanol extracts of Ilex ficoidea Hemsl (EIFH) and Ilex centrochinensis S.Y. Hu (EICC). Anti-inflammatory activities were evaluated using xylene-induced ear edema and the cotton pellet granuloma tests. Some antioxidants produced during chronic inflammation were quantitated and the DPPH, superoxide anion and hydroxyl free radicals scavenging activities in vitro were also investigated. EICC showed a significant anti-inflammatory effect during the acute inflammation and chronic inflammation without any acute oral toxicity. However, EIFH exhibited a negligible anti-acute inflammatory and a moderate anti-chronic inflammatory activity. EICC significantly inhibited the formation of MDA and markedly raised the activities of SOD, CAT and GSH-Px. EIFH could reduce the level of MDA and elevate the activity of SOD only at the high dose. The free radical scavenging activities of EICC are higher than that of EIFH. These results suggest that EICC possesses significant anti-inflammatory and free radical scavenging activities. The anti-inflammatory mechanism is attributed, in part, to enhance the activities of antioxidant enzymes.