Inflammatory Disease Patients Research Articles

Efficacy and Safety of Hyperbaric Oxygen Therapy for Radiation-Induced Hemorrhagic Cystitis: A Systematic Review and Meta-Analysis.

Background: Radiation-induced hemorrhagic cystitis (RHC) is a chronic inflammatory disease in patients undergoing radiation therapy that causes a cluster of symptoms which may have a latent period of months to years. The current non-invasive treatments include drug treatment and hyperbaric oxygen therapy (HBOT), which has been widely applied for RHC so far but with limited evidence. Thus, we conducted a systematic review and meta-analysis to clarify the effects and safety of HBOT for RHC. Methods: A systematic review and meta-analysis were utilized, searching in the databases of Embase, Pubmed, and Web of Science. The primary endpoint of the present study was complete remission of hematuria. The meta-analysis was conducted using a random effects model, and a pooled odds ratio with 95% CI was calculated. Results: A total of 317 studies were searched and fourteen articles with 556 patients were collected. The results showed that a total of 500 patients (89.9%) had symptom improvement, and the pooled results demonstrated that 55% of patients with HBOT had complete remission of hematuria (95% CI 51-59%). Conclusions: A significant improvement of symptoms when treated with HBOT was shown in this meta-analysis for patients with RHC.

Prevalence and coexistence of type 2 inflammatory diseases.

Type 2 inflammation has been described as a pathophysiological basis common to some diseases, such as atopic dermatitis (AD), chronic rhinosinusitis with nasal polyps, and asthma (CRSwNP). The present study used population-based prevalence in Catalonia to analyse the coexistence of type 2 inflammatory diseases in patients primarily diagnosed with the above mentioned conditions. We found a high degree of coexistence of type 2 inflammatory diseases among these patients, with the prevalence being higher in the severe forms, except for AD. For the severe forms of primary diseases, the proportion of patients with coexisting type 2 inflammatory diseases (severe or non-severe) was 16.2% for AD, 19.8% for asthma, and a striking 62.4% for CRSwNP. This patient population has the highest proportion of coexisting type 2 inflammatory diseases, both severe (48.9%) and non-severe (13.5%). Our findings have significant implications for the management of patients with AD, asthma, and CRSwNP.

Topical Use of Cannabis in Inflammatory Diseases in patients of the IPS Salud Social in Barranquilla, Colombia

To relate the topical use of cannabis as an analgesic therapeutic alternative in patients with some inflammatory diseases in Salud Social I.P.S during May to July 2023. An analytical, retrospective study was carried out. The population from which the sample was obtained corresponds to patients diagnosed with Arthrosis, Unspecified, Non-Toxic Multinodular Goiter, Epilepsy, Unspecified Type Venous Insufficiency (Chronic) (Peripheral), Unspecified Lumbago, Secondary Gonarthrosis, Rotator Cuff Syndrome, Carpal Tunnel Syndrome, in Salud Social I.P.S of Barranquilla, Atlántico. A sample of 23 patients diagnosed with these pathologies was obtained by non-probabilistic convenience sampling. All patients showed pain relief after two months of follow-up, two experienced adverse effects. Some studies suggest that cannabinoids present in cannabis, such as CBD and THC, may have analgesic and anti-inflammatory properties that could alleviate pain and inflammation associated with these conditions. This is consistent with the present study. Topical cannabis is presented as a therapeutic alternative in inflammatory diseases, however, it is important to highlight that research on the use of cannabis in these diseases is limited and more studies are needed to fully understand its effects and potential benefits.

Prevalence and Clinical Impact of Immune-Mediated Inflammatory Diseases in Patients with Inflammatory Bowel Disease: Results from a Large Retrospective Observational Study.

(1) Background: Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders involving innate and adaptive immune responses. Despite primarily affecting the gut, recent insights highlight systemic implications, expanding our understanding beyond intestinal boundaries. (2) Methods: This retrospective multicentric study explored the association of IBD and immune-mediated inflammatory diseases (IMIDs) and the impact of concurrent IMIDs on the course of IBD. Clinical data were collected from consecutive medical records of patients with IBD. For assessing the impact of concurrent IMIDs, a control group of IBD patients without associated IMIDs was considered. (3) Results: Of 6589 IBD patients, 6.8% exhibited concomitant IMIDs. Notably, 79.8% of these patients had an aggressive disease course. Psoriasis, atopic dermatitis, and type 1 diabetes mellitus prevalence were lower in the IBD population than in the general population. Conversely, multiple sclerosis, primary sclerosing cholangitis, and pyoderma gangrenosum were more prevalent in IBD patients. Among the patients with a concomitant IMID, 79.8% had an aggressive disease course vs. 8.1% in the control group (p < 0.001). (4) Conclusions: This study underscores the frequency of IMIDs in IBD patients and their association with a more aggressive disease course. The recognition of concurrent IMIDs is crucial for comprehensive patient management, influencing therapeutic decisions and potentially improving outcomes.

Causal relationship between ankylosing spondylitis and ocular inflammatory diseases: a Mendelian randomization study.

Observational studies have shown an increased risk of ocular inflammatory diseases in patients with ankylosing spondylitis (AS), but the genetically predicted association remains unclear. The aim of this study was to systematically assess the causal relationship between AS and ocular inflammatory diseases. We conducted a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between AS and several common ocular inflammatory diseases based on genome-wide association study (GWAS) data and public health data. Five methods, namely, inverse-variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode, were used. Sensitivity analysis was performed using MR-Egger intercept, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), Cochran's Q test, outlier methods, leave-one-out analysis, and funnel plots. The MR analysis showed a significantly increased risk of uveitis (ORIVW = 2.825, 95%CIIVW = 1.709-4.672, and PIVW < 0.001), iridocyclitis (ORIVW = 3.806, 95%CIIVW = 2.809-5.157, and PIVW < 0.001), scleritis (ORIVW = 1.738, 95%CIIVW = 1.190-2.539, and PIVW < 0.001), and episcleritis (ORIVW = 5.113, 95%CIIVW = 2.067-12.645, and PIVW = 0.004) associated with AS. However, no correlation was found between genetically predicted AS and keratitis (ORIVW = 1.041, 95%CIIVW = 0.886-1.222, and PIVW = 0.628) and optic neuritis (ORIVW = 0.868, 95%CIIVW = 0.441-1.709, and PIVW = 0.682). AS increases the genetically predicted risk for uveitis, iridocyclitis, scleritis, and episcleritis. No potential association of AS with keratitis and optic neuritis was found. It may provide clues for the prevention of AS complications.

Systemic inflammatory disease in patients with spontaneous coronary artery dissection

Abstract Background Spontaneous coronary artery dissection (SCAD) is an increasingly recognised cause of non-atherosclerotic myocardial infarction (MI). Systemic inflammatory diseases are commonly associated with SCAD patients, but the link between inflammatory diseases and SCAD remains unclear. Purpose To determine the prevalence of systemic inflammatory disease (SID) and elevated inflammatory markers (EIM) at SCAD presentation. To compare long-term outcomes between SCAD patients with and without SID, and with and without EIM at presentation. Methods We reviewed patients enrolled in the Canadian SCAD Study who had laboratory measurements of inflammatory markers at presentation with SCAD. We compared the baseline demographics, presence of SID, presentation characteristics, and long-term outcomes between patients with and without SID, and between patients presenting with and without EIM at time of SCAD. SID was determined using past medical history and patient self-identification. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were used as inflammatory biomarkers. Major adverse cardiovascular events (MACE) were defined as the composite of all-cause mortality, stroke or transient ischemic attack, MI, hospitalization for heart failure and unplanned revascularization. Results Of 1307 patients with SCAD, 360 had inflammatory markers measured at presentation. Of these 360 patients, 150 (43.1%) had EIM at presentation, and 13 (3.6%) reported a history of SID. Mean age was 52.9±9.8 years for patients with EIM, vs. 50.8±10.9years for patients without EIM (p=0.06). Patients with EIM had significantly higher body mass index compared to those without EIM (35.5% vs 17.6%, p=0.001). Of the patients with reported SID, there was higher prevalence of diabetes and hypertension. There was no significant difference in mean inflammatory marker levels, ESR (13.4±15.6mm/h vs 13.7±13.2mm/h, p=0.965) and CRP (15.6± 23.1mg/L vs 11.9± 26.8mg/L, p=0.644) among SID vs. no SID patients at SCAD presentation. Overall mean follow-up was 3.7±1.9 years. There was no difference in in-hospital MACE and overall MACE between patients with EIM vs. no EIM, and between SID and no SID cohorts. There were also no significant difference in angiographic findings, fibromuscular dysplasia prevalence, proportion treated conservatively vs. with revascularization in these cohorts. Conclusion There was no significant difference between presentation, laboratory values, treatment, or outcomes between SCAD patients with or without SID, and between patients who present with and without EIM. This suggests that both active inflammation and history of inflammatory diseases do not contribute to SCAD or outcomes.Table 1.SCAD cohort demographics &amp; data

Type 2 Inflammatory Diseases in Atopic Dermatitis: A Short Review

Abstract Type 2 inflammatory diseases are characterized by the dysregulation of the T helper (Th) 2 pathway, the prototype being atopic dermatitis (AD). The common inflammatory pathways, genetic risk factors, epidermal barrier dysfunction, parental atopy, and environmental factors are all associated with the codevelopment of type 2 inflammatory diseases in patients with AD. Acute skin barrier disruption leads to the production of both alarmin and dopamine, both of which promote Th2 skewing and mast cell activation, which then finally leads to inflammation, pruritus, and initiation of type 2 immune responses. Since AD is considered “starting point” for various other allergic diseases, its judicious management can help in decreasing the comorbidity posed by respiratory allergy and allergic rhinitis. This review discusses our current understanding of the type 2 inflammation in AD and highlights the nuances between the various type 2 inflammatory disorders. The article tends to focus on the fact that type 2 inflammatory diseases have a significant burden in patients with AD and it is far beyond the cutaneous manifestations and the “Atopic March.” There is an emphasis on early identification and an integrative approach in the treatment of AD in order to alleviate the overall disease morbidity. Type 2 immunity will be reviewed in the light of the prevailing as well as forthcoming targeted treatment options for AD and other related type 2 inflammatory disorders.

MBL Binding with AhR Controls Th17 Immunity in Silicosis-Associated Lung Inflammation and Fibrosis.

ObjectiveMannan-binding lectin (MBL), a soluble pattern recognition molecule of the innate immune system, is primarily synthesized in the liver and secreted into the circulation. Low serum level of MBL has been reported to be related to an increased risk of lung diseases. Herein, we aimed to investigate the function of MBL in silicosis-associated pulmonary inflammation.MethodsSerum collected from silicosis patients was tested for correlation between serum MBL levels and Th17 immunity. In vitro studies were performed to further demonstrated the effect of MBL on Th17 polarization. Silica was intratracheally injected in wild type (WT) or MBL-deficient (MBL–/–) mice to induce silicosis-associated lung inflammation and fibrosis. Th17 response was evaluated to explore the effect of MBL on silicosis in vivo.ResultsSilicosis patients with high serum MBL levels displayed ameliorative lung function. We demonstrated that serum MBL levels negatively correlated to Th17 cell frequency in silicosis patients. MBL protein markedly reduced expression of IL-17 but enhanced expression of Foxp3 in CD4+ T cells in vitro when subjected to Th17 or Treg polarizing conditions, respectively. The presence of MBL during Th17 cell polarization significantly limited aryl hydrocarbon receptor (AhR) expression and suppressed the signal transducer and activator of transcription 3 (STAT3) phosphorylation. Treatment with the AhR antagonist abolished the effect of MBL on Th17 response. Strikingly, MBL directly bound to AhR and affected its nuclear translocation. Furthermore, MBL–/– mice displayed elevated Th17 cell levels compared with WT mice in response to the silica challenge. The CD4+ T lymphocytes from silica-administrated MBL–/– mice exhibited more AhR expression than the wild-type counterparts.ConclusionOur study suggested that MBL limited the Th17 immunity via controlling the AhR/STAT3 pathway, thus providing new insight into silicosis and other inflammatory diseases in patients with MBL deficiency.

Interleukin-2 in the Complex Treatment of Surgical Patients

Immunotherapy for surgical diseases remains one of the urgent scientific and clinical issues. Immunodeficiency is manifested in patients with purulent wounds, pancreatic necrosis, osteomyelitis, oncological diseases, echinococcosis, gastroduodenal ulcers and other pathology. Drugs inducing interleukin-2 synthesis have shown high efficacy for the correction of immunodeficiency status. Clinical effects of rIL-2 are due to its ability to activate clonal proliferation of T- and B-lymphocytes, to enhance the effector potential of cytotoxic T-lymphocytes (CTL cells) and natural killer cells (NK cells), functional activity of mononuclear phagocytes and antigen-presenting cells, synthesis of specific immunoglobulins of most isotypes by plasma cells and to reduce apoptosis of mononuclears. This cytokine is a key link determining the development of cellular and humoral immunity. Interleukin-2 provides antitumor, antiviral, antibacterial and antifungal protection, being able to stimulate the processes of tissue regeneration and repair. The high clinical activity of the drug was revealed in the treatment of endotoxicosis, immunological insufficiency, inflammatory diseases in patients with surgical, oncological, traumatological, combustiological, resuscitation profiles, involving abdominal organs, pelvis and retroperitoneal space. It is rational to use recombinant interleukin-2 in case of previous inefficient conventional treatment and the process chronization. The drug has a number of positive aspects: rapid effect; reduced terms of treatment, frequency of infectious complications and sepsis; reduced mortality rate. The negative side of its administration is its high cost. Thus, immunosuppressive conditions are manifested in multiple surgical diseases. High clinical efficacy of recombinant interleukin 2, absence of complications, adverse reactions and undesirable effects, and favourable tolerability of the drug allow recommending it for wider use in surgical practice.

Prognostic impact of chronic inflammatory diseases in patients with ST-segmentelevation myocardial infarction

Chronic inflammatory diseases (CID) are common and affect 5 to 7% of the general population. In primary prevention the presence of CID increases the risk of cardiovascular disease (e.g. ST-segment elevation myocardial infarction or STEMI), but the prognosis after the occurrence of STEMI in these patients is poorly studied. The objective of our study is to determine the prognostic impact related to the presence of a MIC on mortality in patients with STEMI. Single-centre cohort including patients managed at the University Hospital of Limoges for STEMI from June 2011 to May 2019 and included in the SCALIM registry. The presence of any MIC defined the CID+ group, compared to other patients (CID-). The primary endpoint was mortality. Secondary endpoints included cardiovascular mortality, recurrent coronary events, new cardiac hospitalizations, occurrence of acute peripheral arterial events and ischemic stroke, and all of those combined. Our study included 1941 patients aged 65 ± 14 years, 75% of whom were men. The prevalence of CID in the SCALIM registry was 4.6% (including 22% rhumatoid arthritis, 19% psoriasis and 16% ankylosing spondylitis) and 40% were on corticosteroid therapy and 20% on biotherapy at STEMI. Over a mean follow-up of 3.4 ± 2.6 years after STEMI, we found no significant difference in mortality in the CID+ and CID- groups respectively (22.5% vs. 15.9% P = 0.14) or in the combined secondary endpoint (29% vs. 49% P = 0.11). Long-term corticosteroid therapy was associated with excess mortality in the CID+ group (39% vs. 12%, P < 0.01). Despite the cardiovascular excess risk described in the literature related to the presence of a MIC, we did not show mortality excess related to these conditions after a STEMI. The mortality risk excess in patients under corticosteroids suggests a multidisciplinary discussion on their management. Further analysis is needed to confirm our results.

Leptotrichia and leptothrix: linguistic incident, or difficulties of microbiological diagnostics?

In medical literature bacteria of the genera Leptotrix and Leptotrichia are often considered as identical. Actually, they are antipodes, standing very far apart from each other in evolutionary terms. The confusion arose due to morphological similarity (filamentous forms). Leptotrix is a type of iron bacteria that live in neutral and slightly acidic fresh waters with a very low concentration of organic matter. The energy metabolism of leptotrix is strictly aerobic, oxidative, and chemoorganoheterotrophic (they oxidize divalent iron ions into trivalent iron to produce energy). Its clinical role has not yet been proven. Bacteria of the genus Leptotrichia are normal inhabitants of the oral cavity, urogenital tract and intestine of humans, they are strict anaerobes (some strains are microaerophiles). They cause inflammatory diseases in patients with immunosuppression of different genesis. However, assessment of their clinical role, when they are isolated from non-sterile habitats, requires the use of a skilled ecological approach, including knowledge of the dynamics of cell numbers, the dominance of a particular species, etc. It is absolutely unacceptable to diagnose the diseases caused by leptotrichia on the base of smear microscopy results (for example, smears of discharge from urogenital tract).

A STATISTICAL ANALYSIS OF WOMEN’S REPRODUCTIVE HEALTH CHARACTERISTICS AFTER INEFFECTIVE REATTEMPTS OF USING ART

The aim: To carry out a statistical analysis of physical and reproductive health characteristics in women after ineffective reattempts of using assisted reproductive technologies and identify significant medical and social factors contributing to the development of chronic endometritis. Materials and methods: We carried out a statistical analysis involving 177 outpatient medical records: group 1 includes 127 women aged under 45 with two or more ineffective attempts of in vitro fertilization; group 2 comprised 50 healthy women without reproductive disorders. The complete physical exam included past history, clinical and gynecologic examination, lab techniques and medical imaging according to outpatient medical records obtained during the follow-up care in Isida-IVF Medical Center LLC. Chronic endometritis was recognized by means of histologic examination of endometrium, with the samples obtained by an endometrial pipelle biopsy on day 4-9 of the menstrual cycle. Results: The prevalence of pelvic inflammatory disease in patients of group 1 comprised 47.2%, endometritis - 41.7%; p1.2 <0.01. The prevalence of acute endometritis among patients of group 1 comprised 6.3%; p1.2 >0.05 and was associated with an infection after abortion. In group 1, sexually transmitted infections were reported in 67.7% of patients, p1.2> 0.05, bacterial vaginosis was registered 1.5 times more often - 28.4%; p1.2 <0.05. In group 1, single induced abortion was reported in 15.0%, while 2 times it took place in 15.7% (p1.2 <0.05). Laparoscopies were previously performed in 59.8% of women, laparotomies - in 62.2%, while in 25.4% of women these interventions were reperformed. Unilateral salpingectomy, due to ectopic pregnancy, was performed in 25.4% of women, bilateral - in 12.7%. Fallopian tube removal, due to sactosalpinx, was performed in 25.4% of women, unilateral salpingectomy took place in 3.9% of cases. The most significant risk factors of chronic endometritis in groups studied are acute postabortal endometritis, RR (relative risk) = 1.439, p = 0.029 and postoperative peritonitis provoked by the complications of appendectomy, RR = 1.430, p = 0.084. We detected none of significant effects of pelvic inflammatory disease on the development of chronic endometritis (RR = 45.132, Confidence interval (CI) (6.151-331.167), p = 0.001). The analysis of reproductive failures, as a risk factor of chronic endometritis in women of group 1, showed a significant relative risk: with the past history of premature birth, RR = 1.44, p = 0.039, in case of reattempts of induced abortions, RR = 1.5, p<0.001, Spontaneous miscarriage RR = 1.572, p = 0.001. A higher relative risk of developing chronic endometritis was observed during pregnancy - RR = 1.597, p = 0.001. Conclusions: Statistical analysis of women's reproductive health after ineffective reattempts of using ART revealed that the high rate of fetal interventions, low rate of alternative and safe abortion methods are registered in these women, as well as the nonavailability of any system of health measures after reproductive failures. A significant increase in miscarriage at early stages takes place, as well as the absence of a tendency for preterm labor to decrease in the rate. Maintaining women's reproductive health is a considerable medical and social issue, whose resolving depends on joint efforts of governmental and public entities, healthcare agencies and the population responsibility for own health. Designing and adopting the program of preconception care and planning for pregnancy in women after ineffective reattempts of using ART, with chronic endometritis as a primary disease, should be the top priority area of a health care system.

Polymyalgia rheumatica: A case series from Colombia and analysis of Latin America

ObjectivePolymyalgia rheumatica (PMR) is the most common inflammatory disease in patients over 50 years. Information about the disease in Latin America (LATAM) is scarce. We aimed to evaluate a group of Colombian patients with PMR and to conduct a systematic review of PMR in LATAM. MethodsA multicentric retrospective study was performed. Medical records of 256 PMR patients were evaluated. Patients were divided into two groups, those fulfilling the 2012 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for PMR and those who did not (i.e., clinical diagnosis). A systematic literature review and meta regression was performed comparing Colombian vs LATAM patients. ResultsFrom 256 patients, 145 (56.6%) fulfilled the 2012 EULAR/ACR criteria, and 111 (43.3%) were classified by clinical diagnosis. Inflammatory bilateral shoulder pain, pelvic girdle aching, morning stiffness >45 min, elevated erythrocyte sedimentation rate (ESR), and C-reactive protein (CPR), and Methotrexate (MTX) prescription were more common in the 2012 EULAR/ACR group. None of the included patients presented overt polyautoimmunity (PolyA), whereas up to 24% exhibited latent PolyA. In addition, these patients showed high frequency of malignancy (7.59%). In the meta regression analysis, Colombian patients exhibited lower ESR levels, and were less likely to develop giant cell arteritis (GCA) as compared to the rest of LATAM data. ConclusionPatients with PMR in LATAM exhibit similar phenotypes from other cohorts worldwide. Malignancy, GCA and latent PolyA should be considered in the routine clinical follow-up of patients with PMR.

A Gut Feeling about C9ORF72

C9ORF72 mutations are the most common genetic cause of ALS and FTD, leading to neurodegeneration via complex mechanisms. Mutations also lead to loss of C9ORF72 function and inflammatory diseases in patients and knockout mice. Burberry et al. now show that C9orf72-associated inflammation and premature death in mice are directly modified by the gut microbiome.

"Effectiveness of Jinying capsule on pelvic inflammatory disease in patients with symptom pattern of damp and heat accumulation: a double-blinded, multicenter, randomized, placebo-controlled clinical trial".

To evaluate the therapeutic effectiveness and safety of Jinying capsule on pelvic inflammatory disease (PID) in patients with symptoms identified as the pattern of damp and heat accumulation in terms of Traditional Chinese Medicine (TCM). We conducted a double-blinded, multicenter, randomized, placebo-controlled clinical trial which included 155 patients diagnosed with PID and identified as symptom pattern of damp and heat accumulation. They were randomly divided into experimental group (n = 78) and control group (n = 77) according to a random number table. The treatment lasted for a period of 28 d. The experimental group was given Jinying capsules and oral levofloxacin plus oral metronidazole for first 7 d. They continued with Jinying capsules and levofloxacin placebo and metronidazole placebo for another 7 d. For the remaining 14 d, they continued with Jinying capsules only. Whereas, the control group was treated with oral levofloxacin and metronidazole and Jinying capsule placebo for the first 14 d in the same way as the experimental group and then continued with Jinying capsule placebo only for the remaining 14 d. The clinical efficacy was assessed using McCormack scale, TCM symptom pattern scores, physicochemical indexes including white blood cell and erythrocyte sedimentation rate, C-reaction protein, smear of vaginal discharge, and pelvic ultrasound. Comparing McCormack scale between both groups after treatment, the difference in curative effect between both groups was significant (P = 0.0269). The cure rate of the experimental group and control group is 76.32% and 59.46% respectively at week 4. Comparing TCM symptom pattern scores between both groups before and after treatment, the differences in total effective rate were both significant (P < 0.05). The curative effect rate of experimental group is 2.63% and 13.70% of the control group at week 1 (P = 0.0131), and 73.33% of the experimental group and 56.94% of the control group at week 4 (P = 0.0369). No significant differences were found between the two groups on the Physicochemical indexes (all P > 0.05). No adverse events or reactions occurred in the experimental groups. Jinying capsule can reduce the dosage of antibiotics needed for PID treatment, and improve the symptoms in PID patients.

P795 Risk of incident paradoxical immune-mediated inflammatory diseases in patients with inflammatory bowel diseases treated with anti-TNF therapies: a nationwide Danish cohort study

Abstract Background Tumour necrosis factor (TNF) has a central role in the pathophysiology of immune-mediated inflammatory diseases (IMIDs) including rheumatoid arthritis, psoriasis, hidradenitis suppurativa, and inflammatory bowel diseases (IBD). However, there have been case reports of patients receiving an anti-TNF therapy for one IMID subsequently developing a second IMID. We conducted a nationwide cohort study investigating the risk of incident IMID following anti-TNF exposure in patients with IBD in Denmark. Methods We followed patients with IBD from 1 January 2005 or date of IBD diagnosis (whichever occurred last) to an outcome event including incident diagnosis of hidradenitis suppurativa, arthropathic psoriasis, other forms of psoriasis, or rheumatoid arthritis; or emigration, death or 31 December 2018 (whichever occurred first). Patients were defined as exposed after a 3-month lag period from first anti-TNF infusion throughout follow-up, analogous to an intention-to-treat design. The lag period was censored from analyses to avoid including incipient IMIDs, unlikely to be caused by newly initiated anti-TNF treatment. We excluded patients initiating anti-TNF or with an outcome diagnosis before either 1 January 2005 or IBD diagnosis. We used Cox regression models with age as the underlying timescale, and sex, type of IBD (Crohn’s disease or ulcerative colitis), and calendar period of IBD diagnosis (in 5 year groups) as strata to estimate hazard ratios for each outcome, comparing anti-TNF users and non-users. Results Incidence rates (and 95% confidence intervals [CI]) as events per 100 000 person-years among anti-TNF users and non-users were, respectively, 138 (109–173) and 25.6 (22.0–29.7) for hidradenitis suppurativa, 26.3 (15.6–44.4) and 7.81 (5.95–10.2) for arthropathic psoriasis, 1177 (1085–1277) and 204 (121–189) for other forms of psoriasis, and 152 (121–189) and 95.6 (88.5–103) for rheumatoid arthritis. Hazard ratios (and 95% C.I.) were increased for hidradenitis suppurativa 2.91 (2.15–3.94), arthropathic psoriasis 2.62 (1.40–4.93), other forms of psoriasis 4.76 (4.27–5.31), and rheumatoid arthritis 2.35 (1.83–3.01). Conclusion The results indicate that patients with IBD receiving anti-TNF have an increased risk of IMIDs. An almost 5-fold increase in the risk of psoriasis is consistent with previous reports of psoriasiform skin lesions related to anti-TNF use. However, as more severe IBD is likely to be associated with both initiating anti-TNF and the incidence of other inflammatory diseases, the results are subject to confounding by indication. Thus, these results should be considered preliminary, and we plan to further address confounding by using propensity score methods.

The role of homeostatic disorders in development of periodontal generalized inflammatory diseases in patients with β-thalassemya major

Periodontitis as a manifestation of the systemic diseases was placed in separated part in the contemporary periodontal diseases classification. It has its own specific traits caused by features of the common pathology. The way as ß-thalassemia major is impacting to periodontium could be recognized as the indirect acting out of the side of dental and occlusal anomalies or direct acting of ß-thalassemia major to the periodontium. The range of the influence on periodontium depends on the degree of intensity of the systemic diseases.

The vimentin intermediate filament network restrains regulatory T cell suppression of graft-versus-host disease.

Regulatory T cells (Tregs) are critical for maintaining immune homeostasis. However, current Treg immunotherapies do not optimally treat inflammatory diseases in patients. Understanding the cellular processes that control Treg function may allow for the augmentation of therapeutic efficacy. In contrast to activated conventional T cells, in which protein kinase C-θ (PKC-θ) localizes to the contact point between T cells and antigen-presenting cells, in human and mouse Tregs, PKC-θ localizes to the opposite end of the cell in the distal pole complex (DPC). Here, using a phosphoproteomic screen, we identified the intermediate filament vimentin as a PKC-θ phospho target and show that vimentin forms a DPC superstructure on which PKC-θ accumulates. Treatment of mouse Tregs with either a clinically relevant PKC-θ inhibitor or vimentin siRNA disrupted vimentin and enhanced Treg metabolic and suppressive activity. Moreover, vimentin-disrupted mouse Tregs were significantly better than controls at suppressing alloreactive T cell priming in graft-versus-host disease (GVHD) and GVHD lethality, using a complete MHC-mismatch mouse model of acute GVHD (C57BL/6 donor into BALB/c host). Interestingly, vimentin disruption augmented the suppressor function of PKC-θ-deficient mouse Tregs. This suggests that enhanced Treg activity after PKC-θ inhibition is secondary to effects on vimentin, not just PKC-θ kinase activity inhibition. Our data demonstrate that vimentin is a key metabolic and functional controller of Treg activity and provide proof of principle that disruption of vimentin is a feasible, translationally relevant method to enhance Treg potency.

Dashboards for Therapeutic Monoclonal Antibodies: Learning and Confirming.

Inflammatory diseases (ID) are incurable, progressive diseases. Literature evidence cites increasing incidence of these diseases worldwide. When treatments with chemical immunosuppressive agents fail, patients are often treated with monoclonal antibodies (MAbs). However, MAb failure rates are generally high, with approximately half the patients being discontinued within 4years, necessitating switching to another MAb. One potential cause of treatment failure is subtherapeutic exposure. Several studies demonstrated associations between trough MAb concentrations and clinical response, supporting the notion that improving drug exposure may result in improved outcomes. MAbs exhibit complex and highly variable pharmacokinetics in ID patients with numerous factors affecting clearance. Bayesian-guided dosing with dashboard systems is a new tool being investigated in the treatment of ID to reduce variability in exposure. Simulations suggest dashboards will be effective at maintaining patients at target troughs. However, when patients are dosed using doses or intervals outside those listed in prescribing information, there is concern that patients may have drug exposures beyond or below the ranges found to be safe and efficacious. This manuscript reviews the rationale behind dashboard development, evaluations of expected performance, and a simulated assessment of MAb exposure with dashboard-based dosing versus dosing based on the prescribing information. We introduce the concept of pharmacologic equivalence-if patients are dosed based on individual pharmacokinetics, the resulting exposure is consistent with exposures achieved using labeled dosing. We further show that dashboard-based dosing results in observed exposures that are generally contained within the range of exposures achieved with labeled dosing.

Disease activity assessment in patients with psoriatic arthritis.

Psoriatic arthritis (PsA) is an inflammatory disease in patients with a personal or family history of psoriasis. While synovitis is the major hallmark, enthesitis, dactylitis, axial inflammation, and skin and nail involvement are variable in prevalence and severity. The assessment of disease activity is important to determine the treatment target ("Treat-to-Target") as well as early response to therapy, because a prolonged ineffective medication may not only be associated with an adverse disease outcome but constitutes a waste of individual and/or societal expenses. Various measures of disease activity have been established for all manifestations individually ('uni-dimensional approach') or by combining such measures into a single umbrella score ('multi-dimensional approach'). Because pathogeneses and therapeutic responsiveness differ among individual domains, a uni-dimensional approach is preferred. The major uni-dimensional index is the Disease Activity index for PSoriatic Arthritis, which provides a continuous scale and allows calculating disease activity at any point in time, determining response to therapy and defining disease activity states, such as remission, as a treatment target. The assessment of the various domains by individual and combined indices is discussed.