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Objective: To evaluate if type 2 diabetes is an independent risk predictor for severe osteoarthritis (OA).Research Design and Methods: Population-based cohort study with an age- and sex-stratified random sample of 927 men and women aged 40-80 years and followed over 20 years (1990-2010).Results: Rates of arthroplasty (95% CI) were 17.7 (9.4-30.2) per 1,000 person-years in patients with type 2 diabetes and 5.3 (4.1-6.6) per 1,000 person-years in those without (P < 0.001). Type 2 diabetes emerged as an independent risk predictor for arthroplasty: hazard ratios (95% CI), 3.8 (2.1-6.8) (P < 0.001) in an unadjusted analysis and 2.1 (1.1-3.8) (P = 0.023) after adjustment for age, BMI, and other risk factors for OA. The probability of arthroplasty increased with disease duration of type 2 diabetes and applied to men and women, as well as subgroups according to age and BMI. Our findings were corroborated in cross-sectional evaluation by more severe clinical symptoms of OA and structural joint changes in subjects with type 2 diabetes compared with those without type 2 diabetes.Conclusions: Type 2 diabetes predicts the development of severe OA independent of age and BMI. Our findings strengthen the concept of a strong metabolic component in the pathogenesis of OA. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study combined ultrasonography of the Achilles tendon enthesis at different stages of spondylarthritis (SpA) with microanatomic studies of normal cadaveric entheses, with the aim of exploring the relationship between bone erosion and new bone formation in enthesitis. METHODS: Thirty-seven patients with SpA and Achilles tendon enthesitis (20 with early SpA and 17 with chronic SpA) and 10 normal control subjects underwent ultrasound scanning. The presence of bone erosion and spur formation was recorded at 3 sites: the proximal and distal halves of the enthesis and the adjacent calcaneal superior tuberosity. Parallel histologic analysis was performed on cadaveric Achilles tendon entheses to determine whether regional variations in bone density and trabecular architecture in relation to fibrocartilage distribution are related to disease patterns. RESULTS: Bone erosion in patients with early SpA occurred at either the proximal insertion or the superior tuberosity (11 of 20 patients; P < 0.001 versus distal enthesis). Very small spurs, which were present almost exclusively at the distal enthesis, were evident in patients with early SpA and in normal control subjects. However, large spurs were evident distally only in patients with chronic SpA (9 of 17 patients, compared with none of 20 patients with early SpA; P < 0.0001). Histologic studies showed that aged normal individuals had small spurs at the corresponding location. The bone-to-marrow ratio was also significantly lower in the regions prone to erosions (P < 0.05). CONCLUSION: Bone erosion in association with Achilles tendon enthesitis in SpA is anatomically uncoupled from bone formation-the 2 processes are topographically and temporally distinct. We thus conclude that disease patterns in SpA are related to normal enthesis structure and biomechanics. [ABSTRACT FROM AUTHOR]

Abstract The impact of increased national wealth, as measured by Gross Domestic Product (GDP), on public health is widely understood, however an equally important but less well-acclaimed relationship exists between improvements in health and the growth of an economy. Communicable diseases such as HIV, TB, Malaria and the Neglected Tropical Diseases (NTDs) are impacting many of the world's poorest and most vulnerable populations, and depressing economic development. Sickness and disease has decreased the size and capabilities of the workforce through impeding access to education and suppressing foreign direct investment (FDI). There is clear evidence that by investing in health improvements a significant increase in GDP per capita can be attained in four ways: Firstly, healthier populations are more economically productive; secondly, proactive healthcare leads to decrease in many of the additive healthcare costs associated with lack of care (treating opportunistic infections in the case of HIV for example); thirdly, improved health represents a real economic and developmental outcome in-and-of itself and finally, healthcare spending capitalises on the Keynesian 'economic multiplier' effect. Continued under-investment in health and health systems represent an important threat to our future global prosperity. This editorial calls for a recognition of health as a major engine of economic growth and for commensurate investment in public health, particularly in poor countries.

Abstract In December 2008, the US Commission on the Prevention of Weapons of Mass Destruction Proliferation and Terrorism, released a report, World At Risk. The Report points to the fact that, not only is the use of a weapon of mass destruction in a terrorist attack before the end of 2013, more likely than not, but also to the fact that terrorists are more likely to be able to obtain and use biological weapons than nuclear. This paper examines the recommendations of the report in the context of the historic and geopolitical changes, in particular globalization. The authors highlight the "dual-use" dilemma, as described in the report, as the paradoxical use of technology developed for the benefit of mankind being used for sinister purposes. The mitigation of such a threat lies in broad stakeholder involvement and cooperation, including non-state actors, governments and the bio-tech industry itself. The importance of vigilance measures within the life science community is emphasized and, the authors propose, could include a web-based didactic course in bioterrorism and weapons of mass destruction identification. The site could outline safety protocols, have detailed disaster management tutorials, and could be specifically tailored for different subsets of industry and health professionals. The paper concludes with an endorsement of a multi-pronged approach including strong international guidelines and intelligence cooperation and preparatory measures such as the wide-spread use of detection systems as well as diagnostic decision support systems for bioterrorism detection at the local level.

Rationale: Interstitial lung disease (ILD) in systemic sclerosis (SSc) is a common complication that has a varied progression rate and prognosis. Different progression definitions are available, including minimal clinically important worsening of FVC, EUSTAR (European Scleroderma Trials and Research Group) progression, OMERACT (Outcome Measures in Rheumatology Clinical Trials) progression, and Erice ILD working group progression. Pulmonary function and symptom changes may act as specific confounding factors when applying these definitions in SSc. Objectives: To assess the concordance and prognostic value of four different definitions in patients with SSc-ILD overall and in specific clinical groups. Methods: Progression status in consecutive patients with SSc-ILD was assessed over 24 months, and 60-month disease-related mortality risk was compared between progressors and nonprogressors using four definitions. Measurements and Main Results: Among 245 patients, 26 SSc-related deaths were reported. Mortality was linked to progression for minimal clinically important worsening of FVC (hazard ratio [HR], 2.27; 95% confidence interval [CI], 1.03-4.97), OMERACT (HR, 2.90; 95% CI, 1.28-6.57), and Erice definitions (HR, 2.69; 95% CI, 1.23-5.89). The association between progression and mortality was poor in patients with disease duration ≥3 years, mild functional impairment, and pulmonary artery systolic pressure ≥40 mm Hg. Erice criteria appeared superior in patients with duration ≥3 years, limited cutaneous variant, and pulmonary artery systolic pressure <40 mm Hg. OMERACT criteria performed better in diffuse cutaneous variant patients with severe functional impairment. Conclusions: The four evaluated definitions of progression in SSc-ILD are not interchangeable, resulting in up to one-third of cases being classified differently on the basis of adopted criteria and presenting different prognostic values, particularly within specific clinical groups.

Current rheumatoid arthritis (RA) treatments do not restore immune tolerance. Investigating dendritic cell (DC) populations in human synovial tissue (ST) may reveal pathways to reinstate tolerance in RA. Using single-cell and spatial transcriptomics of ST biopsies, as well as co-culture systems, we identified condition- and niche-specific DC clusters with distinct functions. Healthy tissue contained tolerogenic AXL + DC2s in the lining niche. In active RA, the hyperplasic lining niche was populated with inflammatory DC3s that activated CCL5-positive effector memory T cells, promoting synovitis. Lymphoid niches that emerged in the sublining layer were enriched with CCR7 + DC2s, which interacted with naive T cells, potentially driving the local expansion of new effector T cells. Remission saw the resolution of these pathogenic niches but lacked recovery of tolerogenic DC2s and exhibited activation of blood precursors of ST-DC3 clusters prior to flare-ups. Targeting pathogenic DC3s or restoring tolerogenic DC2s may help restore immune homeostasis in RA joints., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: The central biochemical cause of gout is hyperuricemia (elevated serum urate levels). Ultrasound features of monosodium urate (MSU) crystal deposition are common in people with asymptomatic hyperuricemia. However, it is unclear whether this is a precondition for the development of gout. This study aims to determine whether ultrasound imaging evidence of MSU crystal deposition predicts development of symptomatic gout over 5 years, in people who already have an increased risk of gout due to elevated serum urate concentrations (≥8 mg/dL)., Methods and Analysis: This is a prospective, international, multicentre study. The study population comprises over 250 participants with asymptomatic hyperuricemia (serum urate ≥8.0 mg/dL). After the baseline assessments, participants are followed for 5 years or until the development of gout, defined by the 2015 American College of Rheumatology/European Alliance of Associations for Rheumatology gout classification criteria. Baseline assessments include anthropomorphic measures, laboratory tests, questionnaires, blood and urine specimen collection, plain radiographs of the feet and standardised ultrasound scans of the lower limbs, scored according to the Outcomes in Rheumatology (OMERACT) gout ultrasound scoring system. The primary outcomes are the development of gout and time course for development of gout in people with and without ultrasound evidence of MSU crystal deposition. Exploratory analyses will examine clinical, genetic and biological factors associated with development of MSU crystal deposition and gout., Ethics and Dissemination: This study protocol was approved by the New Zealand Ministry of Health Southern Health and Disability Ethics Committee (MEC/05/10/130/AM16) on 18 December 2018. The findings from this study will be published in peer-reviewed journals and will be presented at national and international conferences., Trial Registration Number: ACTRN12619000915156., Competing Interests: Competing interests: ND has received consulting fees, speaker fees or grants from AstraZeneca, Novartis, Horizon, Selecta, Arthrosi, JW Pharmaceutical Corporation, PK Med, LG Chem, JPI, PTC Therapeutics, Protalix, Unlocked Labs, Hikma, Dexcel Pharma, Shanton Pharma, Sobi, Avalo outside the submitted work. MA reports a research grant from Grunenthal and meeting attendance support from Olatec outside the submitted work. LT has received consulting or speaker fees from Janssen, Pfizer, Novartis, UCB, and GE Healthcare outside the submitted work. TN has received consulting fees from Sobi, Horizon/Amgen outside the submitted work. EN has received speaker fees or other support from STADA, Sandoz, Egis Pharmaceuticals and AbbVie outside the submitted work. HBH has received consulting fees from AbbVie, Lilly, Novartis, and UCB outside the submitted work. M-AD’A has received consulting fees, speaker fees or grants from AbbVie, Novartis, UCB, Janssen, Galapagos, Pfizer, Amgen, AstraZeneca, GSK outside the submitted work. The other authors report no conflicts., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Advanced combination treatment (ACT), defined as a combination of at least 2 biologic agents, a biologic agent and an oral small molecule, 2 oral small molecules drug with different mechanisms of action is a proposed strategy to improve outcomes in patients with immune-mediated inflammatory disease (IMID). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing ACT with monotherapy in patients with select IMIDs., Methods: Through a systematic literature search, we identified 10 RCTs (n = 1154) comparing ACT with single agent therapy (monotherapy). The primary outcome was induction of clinical remission. Secondary outcomes were adverse events, serious adverse events, infections, and serious infections. We performed random-effects meta-analysis and used GRADE to appraise certainty of evidence., Results: Eight out of 10 trials investigated an anti-TNF-α drug (e.g., etanercept, infliximab, golimumab, certolizumab) combined with another biologic (e.g anti-IL-23, anti-integrin, anti-IL-1) or an oral small molecule. There was no significant difference in the likelihood of achieving clinical remission with ACT vs. monotherapy in patients with rheumatoid arthritis (n = 7 RCTs) (RR, 1.75 [95 % CI 0.60-5.13]; moderate heterogeneity (I 2  = 33 %)] and systemic lupus erythematosus (n = 1) (RR, 1.20 [0.53-2.72]) (GRADE; low certainty evidence). Patients with rheumatoid arthritis in the ACT arm were more likely to experience adverse events (RR, 1.07 [1.01-1.12]) compared to monotherapy. ACT led to higher rates of induction of clinical remission in patients with IBD (n = 2 RCTs) (RR, 1.68 [1.15-2.46]) with minimal heterogeneity (I 2  = 15 %) (GRADE; low certainty evidence), and no differences in the likelihood of adverse events (RR 0.92 [0.80-1.05]). There were no differences in the risk of infections or serious infections in patients treated with ACT or monotherapy with rheumatological disease or IBD., Conclusions: ACT did not offer clinical benefit in patients with rheumatological IMIDs and resulted in higher rate adverse events in rheumatoid arthritis. ACT may offer clinical benefit without a clear safety signal in patients with IBD, but further trials are warranted. The variability in ACT regimens across studies limits the generalizability of these findings., Competing Interests: Declaration of competing interest VS: No relevant disclosures. YY: No relevant disclosures. SS: has received research grants from Pfizer. CM: has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, BioJAMP, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Takeda, Pendopharm, Pfizer, Roche, Sanofi; speaker's fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, Takeda, Pendopharm, and Pfizer; royalties from Springer Publishing; research support from Ferring, Takeda, Pfizer. OMN: has received speaker fees from Janssen, AbbVie, Eli Lilly, Pfizer, Ferring, Alfa Sigma. GF: has received consultancy fees from Takeda, Abbvie, Janssen, Pfizer, Celltrion, Sandoz, Amgen, Ferring, Gilead, Galapagos, BMS. MLAF: has received speaker or advisory board fees from Janssen, Eli Lilly, Abbvie, Asofarma. LB: No relevant disclosure. M-AD: speaker or consultant fees from Novartis, BMS, Janssen, Pfizer, Amgen, Galapagos, AbbVie, UCB, and Eli Lilly. PC reports research grants from UCB, MSD and Pfizer; speaker fees or consultant fees from Pfizer, MSD, Novartis, Bristol Myers Squibb, AbbVie, UCB, Eli Lilly, Gilead and Celgene Corporation. JP: Funding for research: Abbvie, BMS, Eli Lilly & Company, Merck, Roche, Seattle Genetics; UCB consulting relationships: AbbVie, Actelion, Amgen, Bayer, BMS, Eicos Sciences, Eli Lilly & Company, Emerald, Gilead, Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB; Speakers Bureau: UCB. LPB: has received consulting fee from AbbVie, Adacyte, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HAC-Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Nordic Pharma, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Sanofi, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax. Received grants from Takeda, Fresenius Kabi, Cell Trion. Speaker fee from Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena, Lilly, Gilead, Viatris, Medac. SD: has received consulting fees from AbbVie, Alimentiv Inc., Allergan, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals Inc, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenixa, UCB Inc, and Vifor; and lecture fees from AbbVie, Amgen, Ferring Pharmaceuticals Inc, Gilead, Janssen, Mylan, Pfizer, and Takeda. VJ has received consulting/advisory board fees from AbbVie, Alimentiv Inc (formerly Robarts Clinical Trials), Arena pharmaceuticals, Asieris, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genetech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Reistone Biopharma, Roche, Sandoz, Takeda, Topivert; speaker's fees from, Abbvie, Ferring, Galapagos, Janssen Pfizer Shire, Takeda., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To evaluate prevalence of ultrasonographic remission (USR) and concordance with clinical remission in "drug-free" or "on-treatment" patients with early rheumatoid arthritis (RA)., Methods: We carried out a cross-sectional study including consecutive early RA patients in SDAI remission ≥6 months in the period 06/2022 to 02/2023. CDAI, DAS28, DAS44 and Boolean remission were also evaluated. Patients underwent B-mode and Power Doppler (PD) assessments of 42 joints and 20 tendons. Synovitis, tenosynovitis and PD were graded semi-quantitatively (0-3) using standardised scores. Four definitions of USR were examined: USR1: absence of synovial hypertrophy (SH) and PD; USR2: SH≤1 and PD=0; USR3: SH≤1 and PD≤1; USR4: PD negative., Results: Eighty patients were enrolled, of whom 12 drug-free. Overall remission rates were 100.0%, 83.7%, 91.2%, 96.2% and 80.0% for SDAI, CDIA, DAS28, DAS44 and ACR/EULAR Boolean criteria, respectively. 100% of drug-free patients were in remission according to all indices. The rate of USR in drug-free versus on-treatment remission was 58.3%, 66.7%, 66.7%, 83.3% versus 70.6%, 85.3%, 88.2%, 91.2% for USR1, USR2, USR3 and USR4, respectively., Conclusions: While clinical remission seems more frequent in drug-free patients, USR is more often observed on-treatment.

Objectives: Digital annular pulleys (DAPs) are important anatomical structures for finger function. The anatomy, histology and imaging assessment of DAPs, particularly at the level of their entheses, are still not clearly defined. The advent of high-frequency US transducers opened new perspectives in evaluating submillimetre-scale structures, such as pulleys, paving the way for their global assessment. The study aimed to characterize DAPs from an anatomical, histological and US perspective, focusing on the detection and complete description of pulley entheses., Methods: US assessment and gross anatomy dissection were conducted on 20 cadaveric hands to study DAP thickness and structure, including enthesis identification. The results of the US and anatomical measurements were correlated. DAP entheses identified by US were characterized via histological analysis. DAPs in 20 healthy controls (HCs) were detected and measured by US. The A1, A2 and A4 DAP entheses were assessed using a new dynamic manoeuvre to better evaluate those structures., Results: A total of 1200 DAPs (400 cadaveric, 800 HCs) were analysed. The cadaveric study demonstrated strong correlation between anatomical and US measurement of DAPs (r = 0.96). At the histological level, DAP entheses at the volar plate, sesamoid bones or phalangeal ridges contained fibrous and fibrocartilaginous tissue. US assessment of A1, A2 and A4 DAPs in HCs allowed the identification of 718/720 (99.73%) entheses., Conclusion: US is an effective tool to detect and study DAPs. DAP entheses reveal both fibrous and fibrocartilaginous characteristics. A newly described manoeuvre to optimize DAP enthesis visualization enhances their detection by US., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: SpA and PsA represent two frequent inflammatory rheumatic disorders characterized by an increased burden on quality of life due to the association of several comorbidities, especially cardiovascular disease (CVD). The estimated prevalence of CVD ranges from 12 to 19% and differs between the two diseases, however, the incidence of CVD is not completely known. We aimed to systematically review the literature and perform a meta-analysis of controlled observational studies to assess the incidence rate of CVD over time in SpA and PsA., Methods: We performed a systematic literature review (SLR) of longitudinal studies with a study period of at least 5 years, including SpA/PsA patients and general population. The main outcome was the occurrence of CVD, including ischaemic heart disease, stroke and death from CV causes. We then performed a random-effects model for meta-analysis., Results: The SLR included 34 articles, mainly focused on the association between SpA/PsA and CVD. Twenty-four articles were then selected for the meta-analysis. The overall incidence of CVD was increased in PsA [hazard ratio (HR) 1.28 (95% CI 1.15, 1.43)] and in SpA [HR 1.45 (95% CI 1.22, 1.72)] compared with the general population, with consistency across the different types of CVDs. Interestingly the incidence tended to decrease over time in PsA but not in SpA., Conclusion: The SLR and meta-analysis confirmed the increased incidence of CVD in both SpA and PsA patients compared with the general population, although the increase seems to be less prominent in PsA than in SpA. Future studies are needed to confirm our findings., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Mycophenolate mofetil (MMF) is a mainstay for the treatment of systemic sclerosis (SSc). The occurrence and implications of MMF-related adverse events on drug retention rates in real life remain poorly defined. We aimed to determine the MMF retention rate and to investigate the causes and patterns of discontinuation, adverse events (AEs) and treatment options used after discontinuation., Methods: SSc patients who started MMF treatment underwent a retrospective longitudinal assessment for up to 5 years. We documented the incidence, predictors, and impacts of MMF treatment on gastrointestinal intolerance, infections, laboratory abnormalities, and cancer. Rescue strategies implemented after MMF discontinuation were recorded., Results: The 5-year MMF retention rate of 554 patients stood at 70.7% and 19.6% of them stopped MMF due to AEs. One out of every four patients experienced a dose reduction or discontinuation of MMF due to AEs, with gastrointestinal intolerance being the predominant cause. The 5-year cumulative incidence rates for gastrointestinal intolerance, cancer, severe infections, and laboratory toxicity leading to MMF discontinuation were 6.4%, 4.1%, 3.1%, and 2.1%, respectively. Lower respiratory tract was the most affected, with bacteria being the predominant causative agent. Intestinal and pulmonary circulation involvement were tied to elevated AE rates and MMF discontinuation. The most common approaches post-MMF cessation were "watch and wait" and switch to rituximab., Conclusions: MMF use in SSc appears to be limited by the occurrence of AEs, both in terms of persistence and dosing of the drug. Rescue options after MMF discontinuation are limited and many patients remain without immunosuppressant., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Animals' ability to orient and navigate relies on selecting an appropriate motor response based on the perception and integration of the environmental information. This is the case, for instance, of the optokinetic response (OKR) in Drosophila melanogaster, where optic flow visual stimulation modulates head movements. Despite a large body of literature on the OKR, there is still a limited understanding, in flies, of the impact on OKR of concomitant, and potentially conflicting, inputs. To evaluate the impact of this multimodal integration, we combined in D. melanogaster, while flying in a tethered condition, the optic flow stimulation leading to OKR with the simultaneous presentation of olfactory cues, based on repellent or masking compounds typically used against noxious insect species. First, this approach allowed us to directly quantify the effect of several substances and of their concentration on the dynamics of the flies' OKR in response to moving gratings by evaluating the number of saccades and the velocity of the slow phase. Subsequently, this analysis was capable of easily revealing the actual effect, i.e. masking vs. repellent, of the compound tested. In conclusion, we show that D. melanogaster, a cost-affordable species, represents a viable option for studying the effects of several compounds on the navigational abilities of insects., (© 2024. The Author(s).)

Detecting lung diseases in medical images can be quite challenging for radiologists. In some cases, even experienced experts may struggle with accurately diagnosing chest diseases, leading to potential inaccuracies due to complex or unseen biomarkers. This review paper delves into various datasets and machine learning techniques employed in recent research for lung disease classification, focusing on pneumonia analysis using chest X-ray images. We explore conventional machine learning methods, pretrained deep learning models, customized convolutional neural networks (CNNs), and ensemble methods. A comprehensive comparison of different classification approaches is presented, encompassing data acquisition, preprocessing, feature extraction, and classification using machine vision, machine and deep learning, and explainable-AI (XAI). Our analysis highlights the superior performance of transfer learning-based methods using CNNs and ensemble models/features for lung disease classification. In addition, our comprehensive review offers insights for researchers in other medical domains too who utilize radiological images. By providing a thorough overview of various techniques, our work enables the establishment of effective strategies and identification of suitable methods for a wide range of challenges. Currently, beyond traditional evaluation metrics, researchers emphasize the importance of XAI techniques in machine and deep learning models and their applications in classification tasks. This incorporation helps in gaining a deeper understanding of their decision-making processes, leading to improved trust, transparency, and overall clinical decision-making. Our comprehensive review serves as a valuable resource for researchers and practitioners seeking not only to advance the field of lung disease detection using machine learning and XAI but also from other diverse domains., Competing Interests: SAS and AD were employed by GPI SpA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Shah, Shah, Khan, Imran, Shah, Mehmood, Qureshi, Raza, Di Terlizzi, Cavaglià and Deriu.)

Objectives: CD19-targeting chimeric antigen receptor (CAR) T-cell therapy can induce long-term drug-free remission in patients with autoimmune diseases (AIDs). The efficacy of CD19-CAR T-cell therapy is presumably based on deep tissue depletion of B cells; however, such effect has not been proven in humans in vivo., Methods: Sequential ultrasound-guided inguinal lymph node biopsies were performed at baseline and after CD19-CAR T-cell therapy in patients with AIDs. Results were compared with lymph node biopsies from rituximab (RTX)-treated AID patients with absence of peripheral B cells. Conventional and immunohistochemistry staining were performed on lymph node tissue to assess architecture as well the number of B cells, follicular dendritic cells (FDCs), plasma cells, T cells and macrophages., Results: Sequential lymph node biopsies were analysed from five patients with AID before and after CD19-CAR T-cell therapy and from five patients with AID after RTX treatment. In addition, non-lymphoid organ biopsies (colon, kidney and gallbladder) from three additional patients with AID after CD19-CAR T-cell therapy were analysed. CD19 + and CD20 + B cells were completely depleted in the lymph nodes after CD19-CAR T-cell therapy, but not after RTX treatment. Plasma cells, T cells and macrophages in the lymph nodes remained unchanged. Follicular structures were disrupted and FDCs were depleted in the lymph nodes after CD19-CAR T-cell therapy, but not after RTX. Non-lymphoid organs were completely depleted of B cells., Discussion: This study demonstrates complete B-cell depletion in secondary lymphoid tissues of patients with AIDs following CD19-CAR T-cell therapy combined with standard lymphodepleting therapy., Competing Interests: Competing interests: GS has received speaker honoraria from BMS, Cabaletta, Janssen, Kyverna, Miltenyi and Novartis. AM has received speaker honoraria and consulting fees from BMS/Celgene, Kite/Gilead, Novartis, BioNTech, Miltenyi Biomedicine, Century Therapeutics. MADA has received grants or contracts from Amgen, Abbvie, UCB, Pfizer, J&J and Galapagos and speaker honoraria and consulting fees from Abbvie, Amgen, Novartis, BMS, UCB, J&J, Biogen, MSD, Lilly and Galapagos. FM has received speaker honoraria and consulting fees from AstraZeneca, Kite/Gilead, Novartis, Sobi, BMS, Miltenyi, Janssen, BNT., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Endovascular aneurysm repair (EVAR) has become the preferred approach over open repair for abdominal aortic aneurysms (AAAs) due to its minimally invasive nature. The common femoral artery (CFA) is the main access vessel for EVAR, with both surgical exposure and percutaneous access being utilized. However, in emergent cases, percutaneous access can be challenging and may result in complications such as bleeding or dissection thrombosis, leading to the need for surgical conversion. This study aimed to share experiences in implementing a decision-making algorithm to reduce surgical conversions due to percutaneous access failures. A total of 74 aortic patients treated with EVAR in emergency settings were included in this retrospective study. This study focused on various outcomes such as perioperative mortality, morbidity, procedure time, surgical exposure time, and surgical conversion rate. After the implementation of the decision-making algorithm, decreases in surgical conversions and operating time were observed. Percutaneous access was found to be more challenging in cases with specific anatomical characteristics of the CFA, such as severe atherosclerosis or smaller vessel diameter. This study highlighted the importance of carefully assessing patient anatomical features and utilizing a decision-making algorithm to optimize outcomes in EVAR procedures. Further research is needed to continue improving practices for managing aortic aneurysms and reducing complications in femoral artery access approaches.

Objective: Pharyngeal surgery is a treatment option for patients with obstructive sleep apnea (OSA) unable to tolerate positive pressure therapy. This study aims to determine the association between palate shape as described by Woodson and pharyngeal surgical outcomes., Study Design: Exploratory analysis of retrospective cohort., Setting: Multicenter., Methods: Three blinded reviewers assessed palate shape using drug-induced sleep endoscopy (DISE) videos from a previously-assembled cohort of adults undergoing pharyngeal surgery. Palate shape scores were examined for association with surgical outcomes with univariate and multivariate analyses. Multivariate analyses included adjustment for consensus DISE findings determined previously., Results: Two hundred nine study subjects were included from 13 centers. Age was 53.7 ± 11.5 years, body mass index (BMI) was 30.3 ± 5.0 kg/m 2 , and 21% were female. In isolated soft palate surgery, greater GenuAP narrowing was associated with lesser odds of surgical response, whereas greater GenuLW narrowing was associated with greater odds of surgical response. These findings largely persisted after adjustment for key DISE findings, age, gender, OSA severity, BMI, and tonsil size. Other palate-shape findings were not clearly associated with surgical outcomes, although some palate-shape findings demonstrated trends toward an association with outcomes (P < .10)., Conclusion: Greater GenuAP narrowing and GenuLW narrowing were associated with lesser and greater, respectively, odds of surgical response after isolated soft palate surgery. Palate shape and other palate shape level scores were not clearly associated with surgical outcomes. Larger studies may determine more precisely the association between palate shape and pharyngeal surgery outcomes., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Chimeric antigen receptor (CAR) T cells are highly effective at targeting and eliminating cells of the B cell lineage. CAR T cell therapy has become a standard-of-care treatment for patients with relapsed or refractory B cell malignancies. In addition, the administration of genetically modified T cells with the capacity to deplete B cells and/or plasma cells has tremendous therapeutic potential in autoimmune diseases. In the past few years, CD19-based and B cell maturation antigen (BCMA)-based CAR T cell therapies have been applied to various B cell-mediated autoimmune diseases including systemic lupus erythematosus, idiopathic inflammatory myopathy, systemic sclerosis, neuromyelitis optica spectrum disorder, myasthenia gravis and multiple sclerosis. The scientific rationale behind this approach is that deep depletion of B cells, including autoreactive B cell clones, could restore normal immune function, referred to as an immune reset. In this Review, we discuss important aspects of CAR T cell therapy in autoimmune disease, including considerations relating to patient selection, safety, efficacy and medical management. These considerations are based on the early experiences of CAR T cell therapy in autoimmune diseases, and as the field of CAR T cell therapy in autoimmune diseases continues to rapidly evolve, these issues will remain subject to ongoing refinement and adaptation., (© 2024. Springer Nature Limited.)

Objective: To summarise current data regarding the use of imaging in crystal-induced arthropathies (CiAs) informing a European Alliance of Associations for Rheumatology task force., Methods: We performed four systematic searches in Embase, Medline and Central on imaging for diagnosis, monitoring, prediction of disease severity/treatment response, guiding procedures and patient education in gout, calcium pyrophosphate dihydrate deposition (CPPD) and basic calcium phosphate deposition (BCPD). Records were screened, manuscripts reviewed and data of the included studies extracted. The risk of bias was assessed by validated instruments., Results: For gout, 88 studies were included. Diagnostic studies reported good to excellent sensitivity and specificity of dual-energy CT (DECT) and ultrasound (US), high specificity and lower sensitivity for conventional radiographs (CR) and CT. Longitudinal studies demonstrated sensitivity to change with regard to crystal deposition by US and DECT and inflammation by US and structural progression by CR and CT. For CPPD, 50 studies were included. Diagnostic studies on CR and US showed high specificity and variable sensitivity. There was a single study on monitoring, while nine assessed the prediction in CPPD. For BCPD, 56 studies were included. There were two diagnostic studies, while monitoring by CR and US was assessed in 43 studies, showing a reduction in crystal deposition. A total of 12 studies with inconsistent results assessed the prediction of treatment response. The search on patient education retrieved two studies, suggesting a potential role of DECT., Conclusion: This SLR confirmed a relevant and increasing role of imaging in the field of CiAs., Competing Interests: Competing interests: VN-C: consulting fees: ABBvie, Galapagos, Lilly, Novartis, Lilly, Pfizer, UCB; honoraria: Abbvie, Fresenius, Lilly, Novartis, Pfizer, UCB; ASAS. MAD’A: consulting fees: Novartis, BMS, Janssen, Amgen, Boehringer Ingelheim, AbbVie, Astra-Zeneca, Pfizer, UCB, Eli Lilly; honoraria: Novartis, BMS, Janssen, Amgen, Boehringer Ingelheim, AbbVie, Astra-Zeneca, Pfizer, UCB, Eli Lilly. The other authors have no competing interests to declare., (© European Alliance of Associations for Rheumatology, EULAR 2024. Re-use permitted under CC BY-NC-ND. No commercial re-use. No derivatives. See rights and permissions. Published by BMJ on behalf of EULAR.)

Electronic Health Records (EHRs) contain a wealth of unstructured patient data, making it challenging for physicians to do informed decisions. In this paper, we introduce a Natural Language Processing (NLP) approach for the extraction of therapies, diagnosis, and symptoms from ambulatory EHRs of patients with chronic Lupus disease. We aim to demonstrate the effort of a comprehensive pipeline where a rule-based system is combined with text segmentation, transformer-based topic analysis and clinical ontology, in order to enhance text preprocessing and automate rules' identification. Our approach is applied on a sub-cohort of 56 patients, with a total of 750 EHRs written in Italian language, achieving an Accuracy and an F-score over 97% and 90% respectively, in the three extracted domains. This work has the potential to be integrated with EHR systems to automate information extraction, minimizing the human intervention, and providing personalized digital solutions in the chronic Lupus disease domain.

Objectives: Recently, the HAND osteoarthritis (OA) ULTRASOUND (US) Examination (HOUSE) inflammatory and structural damage scores were developed by the OMERACT US working group. However, the thumb base was not or only partly included. This systematic review examines US scoring methods and scanning techniques assessing thumb base OA, alongside existing evidence on validity, reliability, and responsiveness., Methods: A comprehensive search strategy in three different databases identified 30 eligible studies., Results: In general, studies predominantly focused on US assessment of the carpometacarpal (CMC) 1 joint, with fewer investigating the scaphotrapeziotrapezoid (STT) joint. Most studies utilized a semiquantitative scale for scoring structural and inflammatory features, aligning with the HOUSE scoring system. Validity was supported by a limited number of studies, with one demonstrating a positive association between US structural damage and radiographic damage, and another showing a similar association with function. Associations between US inflammatory features and pain were observed, albeit with some variability. Reliability was from moderate to good for the CMC1 joint but limited for STT joint. Responsiveness varied across studies. The methodological quality of included studies varied, indicating areas for future research improvement., Conclusion: While promising, additional research is necessary to validate the HOUSE scoring system and improve its clinical utility for thumb base OA assessment. Future research should concentrate on optimal scanning positions and on the reliability and responsiveness of the HOUSE scoring system., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)