[Head-to-head studies on psoriasis and psoriatic arthritis]. / Head-to-Head-Studien bei Psoriasis und Psoriasisarthritis.

Given the ever-increasing number of approved therapies for the treatment of psoriasis (PsO) and psoriatic arthritis (PsA), head-to-head (H2H) comparative studies are essential. These are aimed primarily at a comparative analysis of treatment effectiveness. In both PsO and PsA, biological disease-modifying antirheumatic drugs (bDMARD) have been shown to be superior to conventional therapies in H2H studies. In PsO interleukin 17 (IL-17) and IL-23 inhibitors proved superiority compared to tumor necrosis factor (TNF) inhibitors (etanercept and adalimumab) in several studies. Ustekinumab was more effective than etanercept, but less effective than IL-17 and IL-23 inhibitors. Only a few H2H studies have been published on the treatment of PsA. In the Spirit H2H study ixekizumab was superior to adalimumab using a combined endpoint of arthritis and psoriasis response (ACR-50 and PASI-100). When looking at arthritic symptoms only (ACR-20), secukinumab was not significantly superior to adalimumab in the EXCEED study but was superior in terms of the effect on skin involvement (PASI90). Other H2H studies focused on the treatment of enthesitis (ECLIPSA study), the efficacy of Janus kinase (JAK) inhibition (SELECT-PSA-1) or the additional administration of methotrexate to bDMARD treatment (MUST study). The H2H data have been incorporated into the treatment guidelines and have led to IL-17 and IL-23 inhibition being preferred over TNF inhibition in cases of relevant skin involvement in PsA.

Anatomical pattern of entheseal and synovial fibroblast activation in patients with psoriasis and its risk of developing psoriatic arthritis.

OBJECTIVES: To assess the presence and anatomical distribution of activated fibroblasts in the joints and entheses of patients with psoriasis with arthralgia and to test how fibroblast activation visualised by 68gallium-labelled fibroblast activation protein inhibitor-04 (68Ga-FAPI-04)-positron emission tomography (PET)/CT correlates with clinical tenderness, musculoskeletal ultrasound findings and progression to psoriatic arthritis (PsA). METHODS: We conducted a prospective cohort study in patients with psoriasis and arthralgia who underwent clinical and ultrasound evaluation and whole-body PET/CT imaging with 68Ga-FAPI-04. 68Ga-FAPI-04 uptake at synovial and entheseal sites was assessed by maximal standardised uptake values (SUVmax) and PET/CT Joint Index (JI); logistic regression models were used to investigate its correlation with clinical and ultrasound findings. Survival analyses were performed on patients with at least 6 months of follow-up. RESULTS: 36 patients with psoriasis were enrolled. 68Ga-FAPI-04 uptake was found in 318 (7.9%) joints and 369 (7.3%) entheses in 29 (80.6%) participants, with a mean SUVmax (SD) of 3.2 (1.8) for joints and 2.9 (1.6) for entheses. Large joints and the lower limbs were predominantly affected. A significant positive relationship was found between 68Ga-FAPI-04-PET/CT signal intensity and the 68 tender joint count (SUVmax: p<0.001; PET/CT-JI: p<0.001) and tender entheses count (SUVmax: p<0.001; PET/CT-JI: p=0.002). No correlations were found with ultrasound findings (SUVmax: p=0.969; PET/CT-JI: p=0.720). Patients with relevant synovio-entheseal 68Ga-FAPI-04 uptake showed a statistically significant higher risk of developing PsA (p=0.02), independent of ultrasound findings. CONCLUSIONS: Patients with psoriasis presenting with arthralgia show localised signs of resident tissue activation in joints and entheses, which are associated with higher risk of developing PsA.

Deep learning-based classification of erosion, synovitis and osteitis in hand MRI of patients with inflammatory arthritis.

OBJECTIVES: To train, test and validate the performance of a convolutional neural network (CNN)-based approach for the automated assessment of bone erosions, osteitis and synovitis in hand MRI of patients with inflammatory arthritis. METHODS: Hand MRIs (coronal T1-weighted, T2-weighted fat-suppressed, T1-weighted fat-suppressed contrast-enhanced) of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients from the rheumatology department of the Erlangen University Hospital were assessed by two expert rheumatologists using the Outcome Measures in Rheumatology-validated RA MRI Scoring System and PsA MRI Scoring System scores and were used to train, validate and test CNNs to automatically score erosions, osteitis and synovitis. Scoring performance was compared with human annotations in terms of macro-area under the receiver operating characteristic curve (AUC) and balanced accuracy using fivefold cross-validation. Validation was performed on an independent dataset of MRIs from a second patient cohort. RESULTS: In total, 211 MRIs from 112 patients (14 906 region of interests (ROIs)) were included for training/internal validation using cross-validation and 220 MRIs from 75 patients (11 040 ROIs) for external validation of the networks. The networks achieved high mean (SD) macro-AUC of 92%±1% for erosions, 91%±2% for osteitis and 85%±2% for synovitis. Compared with human annotation, CNNs achieved a high mean Spearman correlation for erosions (90±2%), osteitis (78±8%) and synovitis (69±7%), which remained consistent in the validation dataset. CONCLUSIONS: We developed a CNN-based automated scoring system that allowed a rapid grading of erosions, osteitis and synovitis with good diagnostic accuracy and using less MRI sequences compared with conventional scoring. This CNN-based approach may help develop standardised cost-efficient and time-efficient assessments of hand MRIs for patients with arthritis.

Unveiling Metabolic Similarities of Entheses in Patients with Psoriasis and Psoriatic Arthritis Using Noninvasive In Vivo Molecular Imaging: Results From a Cross-sectional Exploratory Study.

OBJECTIVE: We assessed and compared molecular tissue changes at the entheses in patients with psoriasis (PsO) and psoriatic arthritis (PsA) and in healthy controls (HCs) in vivo using multispectral optoacoustic tomography (MSOT) and described their relationship with clinical and ultrasound findings of enthesitis. METHODS: A cross-sectional study (MSOT and Arthrosonography in PsA) in biologic disease-modifying antirheumatic drug-naïve patients with PsA and PsO and HCs was performed. Participants underwent clinical, ultrasonographic, and MSOT examination of six entheses (lateral humeral epicondyle, distal patellar tendon attachment, and Achilles tendon attachment). MSOT-measured hemoglobin (Hb), oxygen saturation (SO2), collagen, and lipid levels were quantified, and mean differences between groups were calculated using linear mixed effects models. MSOT-measured analytes were compared between entheses with and without clinical and ultrasound anomalies. RESULTS: Ninety participants were included (30 PsO, 30 PsA, and 30 HCs), 540 entheses were clinically assessed, and 540 ultrasound and 830 MSOT scans were obtained. Patients with PsA and PsO showed increased oxygenated Hb (PsA: P = 0.003; PsO: P = 0.054) and SO2 (PsA: P < 0.001; PsO: P = 0.001) levels and decreased collagen signals (PsA: P < 0.001; PsO: P < 0.001) compared with HCs, with more pronounced changes in PsA. Significantly lower collagen levels (P = 0.01) and increased lipids (P = 0.03) were recorded in tender entheses compared with nontender ones. Erosions and enthesophytes on ultrasound were associated with significant differences in SO2 (P = 0.014) and lipid signals (P = 0.020), respectively. CONCLUSION: Patients with PsA and PsO exhibit an analogous metabolic pattern at the entheses that is exacerbated in the presence of inflammation. These findings support the notion of a psoriatic disease spectrum characterized by common immunometabolic tissue changes.

Metabolic rewiring promotes anti-inflammatory effects of glucocorticoids.

Glucocorticoids represent the mainstay of therapy for a broad spectrum of immune-mediated inflammatory diseases. However, the molecular mechanisms underlying their anti-inflammatory mode of action have remained incompletely understood1. Here we show that the anti-inflammatory properties of glucocorticoids involve reprogramming of the mitochondrial metabolism of macrophages, resulting in increased and sustained production of the anti-inflammatory metabolite itaconate and consequent inhibition of the inflammatory response. The glucocorticoid receptor interacts with parts of the pyruvate dehydrogenase complex whereby glucocorticoids provoke an increase in activity and enable an accelerated and paradoxical flux of the tricarboxylic acid (TCA) cycle in otherwise pro-inflammatory macrophages. This glucocorticoid-mediated rewiring of mitochondrial metabolism potentiates TCA-cycle-dependent production of itaconate throughout the inflammatory response, thereby interfering with the production of pro-inflammatory cytokines. By contrast, artificial blocking of the TCA cycle or genetic deficiency in aconitate decarboxylase 1, the rate-limiting enzyme of itaconate synthesis, interferes with the anti-inflammatory effects of glucocorticoids and, accordingly, abrogates their beneficial effects during a diverse range of preclinical models of immune-mediated inflammatory diseases. Our findings provide important insights into the anti-inflammatory properties of glucocorticoids and have substantial implications for the design of new classes of anti-inflammatory drugs.

Risk of developing psoriatic arthritis in psoriasis cohorts with arthralgia: exploring the subclinical psoriatic arthritis stage.

OBJECTIVE: Subjects with subclinical psoriatic arthritis (PsA), defined as the presence of arthralgia in psoriasis (PsO), are at higher risk of PsA but scant real-world data exist. Our aims were to (1) estimate the probability of PsA development in subclinical PsA, (2) characterise subclinical PsA symptoms and (3) determine the clinical patterns at PsA diagnosis. METHODS: Patients with PsO, mainly subclinical PsA, were evaluated longitudinally in two European cohorts. The key outcome was new-onset PsA. Musculoskeletal symptoms including inflammatory and non-inflammatory symptoms before PsA diagnosis were collected. Occurrence of PsA was analysed with survival analysis and cumulative incidence functions (CIFs). RESULTS: 384 patients with PsO were included with a mean follow-up of 33.0 (±20.9) months. 311 of 384 (80.9%) had subclinical PsA with a PsA incidence rate of 7.7 per 100 patient-years. Subclinical PsA displayed a higher risk of PsA development compared with PsO (HR=11.7 (95% CI 1.57 to 86.7), p=0.016). The probability of new-onset PsA estimated by the CIF was 9.4% (95% CI 4.7% to 10.6%) at month 12 and 22.7% (95% CI 17.2% to 28.6%) at month 36. 58.9% of cases reported inflammatory symptoms in the months immediately prior to PsA diagnosis but prior non-inflammatory symptoms were evident in 83.9% prior to PsA diagnosis. Peripheral joint swelling was the predominant PsA presentation pattern (82.1%). CONCLUSIONS: The probability of PsA development among subclinical PsA was relatively high, emphasising the importance of emergent musculoskeletal symptoms when aiming for PsA prevention. Joint swelling was the dominant feature in new-onset PsA, likely reflecting clinical confidence in recognising joint swelling.

Metabolic and molecular imaging in inflammatory arthritis.

It is known that metabolic shifts and tissue remodelling precede the development of visible inflammation and structural organ damage in inflammatory rheumatic diseases such as the inflammatory arthritides. As such, visualising and measuring metabolic tissue activity could be useful to identify biomarkers of disease activity already in a very early phase. Recent advances in imaging have led to the development of so-called 'metabolic imaging' tools that can detect these changes in metabolism in an increasingly accurate manner and non-invasively.Nuclear imaging techniques such as 18F-D-glucose and fibroblast activation protein inhibitor-labelled positron emission tomography are increasingly used and have yielded impressing results in the visualisation (including whole-body staging) of inflammatory changes in both early and established arthritis. Furthermore, optical imaging-based bedside techniques such as multispectral optoacoustic tomography and fluorescence optical imaging are advancing our understanding of arthritis by identifying intra-articular metabolic changes that correlate with the onset of inflammation with high precision and without the need of ionising radiation.Metabolic imaging holds great potential for improving the management of patients with inflammatory arthritis by contributing to early disease interception and improving diagnostic accuracy, thereby paving the way for a more personalised approach to therapy strategies including preventive strategies. In this narrative review, we discuss state-of-the-art metabolic imaging methods used in the assessment of arthritis and inflammation, and we advocate for more extensive research endeavours to elucidate their full field of application in rheumatology.

Tobacco use in Haiti: findings from demographic and health survey.

INTRODUCTION: Although tobacco has harmful effects on the physical and mental health of individuals, its use remains significant, according to the World Health Organization. To understand this phenomenon, studies have been carried out in many countries around the world, while in Haiti where more than 5,000 people die each year due to tobacco use, little is known about the use of this substance. The aim of this study was to examine the prevalence and the factors associated with tobacco use in Haiti. METHODS: We used data from the 2016/17 Haitian Demographic Health Survey. Both descriptive and multivariate analyses were conducted using STATA 16.0 software to assess the prevalence and identify factors associated with tobacco use. Results were reported as adjusted odds ratios with 95% confidence intervals. Statistical significance was declared at p < 0.05. RESULTS: The prevalence of tobacco use was estimated at 9.8% (95% CI: 9.2-10.4) among men and 1.7% (95% CI: 1.5-1.9) among women. Although the prevalence of tobacco use was low among young people, it increased with age. Respondents aged 35 and above, with no formal education, non-Christians, divorced/separated/widowed, from poorest households, rural areas, "Aire Métropolitaine de Port-au-Prince" region, with high media exposure had a higher likelihood of tobacco use. CONCLUSION: The low prevalence of tobacco use among Haitian women and youth represents a public policy opportunity to prevent these vulnerable groups from starting smoking. Adult male smokers should also be targeted by appropriate policy to reduce the different health burdens associated with tobacco, both for the smokers and other people they may expose to passive smoking. Government and health sector stakeholders, along with community leaders, should create and enforce awareness strategies and rules to control advertisements that encourage irresponsible and health-risky consumption behaviors.

Bacterias similares a Helicobacter pylori, en aguas de acueductos del estado Táchira y su probable asociación con patología gástrica / Similar bacteria to Helicobacter pylori, in water supplies of Táchira state and its possible association with gastric pathology

Introducción: Helicobacter pylori es uno de los agentes asociado al cáncer gástrico y posee una alta prevalencia en los países en vías de desarrollo. Sus rutas de transmisión no han sido totalmente establecidas; sin embargo, en algunos estudios se ha detectado su ADN en muestras de aguas residuales, subterráneas y superficiales. El objetivo de este trabajo fue detectar el ADN del género Helicobacter en muestras provenientes de acueductos rurales del municipio San Cristóbal y el Acueducto Regional del Táchira (ART). Materiales y métodos: Se recolectaron 500 ml de seis acueductos rurales y el ART. Se determinó la presencia de ADN del género Helicobacter a través de PCR y PCR semianidada con la posterior secuenciación de los productos de reacción. Resultados y discusión: El género Helicobacter no fue detectado mediante PCR, pero se observó la banda esperada en tres muestras mediante una PCR semianidada. La secuenciación de dos amplicones mostraron una similitud del 99% con Ralstonia pickettii, indicando que Helicobacter no fue detectada en los acueductos muestreados. Conclusiones: La secuenciación de los amplicones para el género Helicobacter, mostraron que se trata de R. pickettii un patógeno oportunista, con características similares a H. pylori.

Background: Helicobacter pylori is one of the agents associated with gastric cancer and has high prevalence in developing countries. Its routes of transmission have not been fully established, however, some studies have detected H. pylori DNA in wastewater, groundwater and surface water. The aim of our study was detect H. pylori DNA in water samples from rural water supplies of San Cristóbal and the Tachira’s Regional Water Supply (TRWS). Materials and methods: Water (500 ml) of six rural water supplies and the TRWS were collected. T DNA of Helicobacter genus was detected by Polimerase Chain Reaction (PCR) and seminested PCR and the PCR amplicons were sequenced. Results: Helicobacter genus PCR results were negative but the seminested PCR were positive in three samples. However the two amplicons sequenced showed a 99% similitud with Ralstonia pickettii. Conclusions: Helicobacter amplicon sequenced, showed a high similarity with R. pickettii, an oportunist pathogen, with similar characteristics to H. pylori.

Determinación de la factibilidad técnica y seguridad de un abordaje endoscópico transgástrico a la cavidad peritoneal en un modelo porcino / Determination of the technical feasibility and safety of transgastric peritoneal approach in a pig model

La viabilidad de un abordaje transgástrico para realizar peritoneoscopia y biopsia hepática ha sido demostrada en estudios previos en animales. Objetivo. Nuestro objetivo fue determinar la viabilidad y seguridad de un abordaje transgástrico peritoneal en una experiencia local. Resultados. El abordaje transgástrico con modelo similar a PEG (gastrostomía endoscópica percutánea) se realizó en 3 cerdos de la especie suis scrofa domesticus; el tiempo promedio del procedimiento fue de 102 minutos, no hubo complicaciones relacionadas con el acceso, y la necropsia no evidenció ningún daño de órganos adyacentes al estómago, aunque el cierre de la pared gástrica no fue exitoso en 2 cerdos. Conclusiones. Este estudio reporta la experiencia local con un abordaje transgástrico peroral a la cavidad peritoneal, técnicamente viable. El abordaje similar a PEG es simple y seguro, el cierre de la pared gástrica requiere destreza y mejor tecnología

Background. The feasibility of peroral transgastric peritoneoscopy and liver biopsy has been demonstrated in prior animal studies.Objective. Our purpose was to determine the feasibility and safety of transgastric peritoneal approach in local experience. Designs. Animal experimental feasibility study. Results. The peritoneal transgastric approach with PEG- like model was used in 3 pigs suis scrofa domesticus specie. The average procedure was 102 minutes, it did no have complications related to the access, and the necropsy did not reveal any damage to organs adjacent to the stomach. Nevertheless the gastric wall close was not successful in 2 pigs. Conclusions. This study report the local experience with peroral transgastric approach to peritoneal cavity, it’s technically feasible, a PEG- like transgastric model is simple and safe, the close of gastric wall requires skill and best technology.