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Abstract The availability of a number of bDMARDs with different mechanism of action increases potential treatment pathways in psoriatic arthritis (PsA). In clinical practice, following the failure of one bDMARD, it is normal to consider which options are the best for switching strategy. In most cases this choice involves IL17i and TNFi. The main aim of this study was to compare the effectiveness of cycling (from TNFi to another TNFi) and swapping (from TNFi to IL17i or vice versa) strategies. In this monocentric retrospective observational study, all PsA patients treated with TNFi or IL17i between January 2016 and January 2022 were enrolled. The prescriptions were clustered in one cycling group (CG), and two swap groups: from TNFi to IL17i (SG1) and from IL17i to TNFi (SG2). The Kaplan–Meier method and Cox regression models were applied to compare the drug retention rates and to identify factors affecting treatment persistence. A total of 122 patients were enrolled. The CG, SG1 and SG2 2-years retention rates were 51%, 58% and 34% (p = 0.1), respectively. SG1 strategy (HR 0.53; CI 0.31–0.89; p = 0.02), age (HR 0.98; CI 0.96–0.99; p = 0.003), Disease Activity PsA (HR 1.11; CI 1.08–1.13; p

Coffee is a key agricultural product in national and international markets. Physiological parameters, such as plant growth indicators, can signal interruptions in these processes. This study aimed to characterize the temperature obtained by a thermal camera embedded in a remotely piloted aircraft (RPA) and evaluate its relationship with the water potential (WP) and stomatal conductance (gs) of an experimental coffee plantation using geostatistical techniques. The experiment was conducted at the Federal University of Lavras, Minas Gerais, Brazil. A rotary-wing RPA with an embedded thermal camera flew autonomously at a height of 10 m and speed of 10 m/s. Images were collected on 26 November 2019 (rainy season), and 11 August 2020 (dry season), between 9:30 am and 11:30 am. Data on gs and WP were collected in the field. The thermal images were processed using FLIR Tools 5.13, and temperature analysis and spatialization were undertaken using geostatistical tools and isocolor maps by Kriging interpolation in R 4.3.2 software. Field data were superimposed on final crop temperature maps using QuantumGIS version 3.10 software. The study found that with decreasing WP, stomatal closure and reduction in gs occurred, increasing the temperature due to water deficit. The temperature distribution maps identified areas of climatic variations indicating water deficit.

ABSTRACT: Allowing dairy cattle to access pasture or outdoor areas is known to be beneficial for cows' welfare and is considered important by the general public. However, in confinement-based operations with high-yielding cows, pasture access may be difficult to implement, especially for lactating animals. Providing pasture access to heifers and dry cows seems a more feasible option for most farms. The objective of this study was to investigate the effects of providing high-yielding dairy cows with free-choice pasture access during the dry period on their health, behavior, and milk production. Over the study period, a total of 78 Holstein cows were assigned to 1 of 2 treatments during the dry period (51 ± 8 d): housing with free-choice access to the pasture (PAST) or housing continuously without any access to the outdoors (CTRL). After calving, all cows from both treatments were mixed and housed continuously. To assess the effects of the treatment on cows' performance, all animals enrolled were monitored both before calving and during the first 100 d in milk of the following lactation. The behavior of all cows involved was monitored continuously during the whole observation period using collar-based sensors. All cows were inspected monthly to assess lameness, hock lesions, cleanliness, and body condition score. During the period after calving (0–100 d in milk), milk production and composition were also monitored. Results showed that free-choice pasture access affected cows' feeding behavior. Before calving, the animals in PAST spent more time feeding than in CTRL and, interestingly, this difference tended to persist for several weeks after calving. During the dry period, cows in PAST were cleaner than in CTRL but no differences in locomotion and body condition score were found between the 2 groups. Free-choice pasture access during the dry period also affected milk production during the following lactation. The cows that spent the dry period in PAST produced more milk than CTRL counterparts, particularly for the animals that calved during summer. In the current study we have found that providing free-choice pasture access during the dry period can positively affect the performance of dairy cattle and represents a desirable practice in confinement-based dairy production systems.

Objectives: The persistence in therapy of rheumatoid arthritis drugs and particularly bDMARD is a limiting factor for their long-term use. The randomized controlled trials (RCTs) may not reflect real-world contexts due to strict inclusion and exclusion criteria. Baricitinib, which targets both JAK1 and JAK2, has been used in Italy for several years. The aim of this multi-center study is to assess the real world persistence on therapy of baricitinib in RA patients and to identify predictive factors of baricitinib's survival rate. Methods: This is a retrospective, multicentric, Italian, longitudinal study. All patients were enrolled according to the following criteria: a) age ≥ 18 years old; b) diagnosed with RA according 2010 ACR/EULAR classification criteria; c) treated with baricitinib. In order to describe baricitinib clinical efficacy, the survival rate was evaluated by The Kaplan–Meier curve. Then, predictive factors of drug retention rate were assessed by performing the Cox analysis, identifying which risk factors influenced treatment persistence. Results: Overall, we included 478 patients treated with baricitinib. Among them, 380 (79.5%) were females. Baricitinib's survival rate was 94.6% at 6 months, 87.9% at 12 months, 81.7% at 24 months and 53.4% at 48 months. The Cox analysis regression showed that a higher bDMARDs/tsDMARD line of therapy seems to be a negative prognostic factor for the drug retention rate (HR 1.26 CI 95% 1.07–1.49, p = 0.006. Conclusion: Real-life study confirms baricitinib effectiveness up to 4 years, but previous treatment with bDMARDs was a negative prognostic factor for its survival rate.

Brazil stands as one of the world’s leading producers of animal protein, ranking sixth in global egg production. However, estimated growth in production demand, along with environmental impacts, represents a potential threat to the sustainability of the food system. Methods for assessing and quantifying the environmental impacts generated by Brazilian egg production remain scarce, lacking current reports on comparative effects or guiding standards. The objective of this study was to conduct a life cycle assessment from cradle to farm gate, adhering to ISO 14040 and 14044 standards, for the battery cage egg production systems and associated products in Brazil, with the aim of supporting and promoting sustainability improvements in the Brazilian egg industry. The entire life cycle modeling and process sustainability analysis were executed using the openLCA software, integrated with the Ecoinvent database. Emissions related to egg production yielded results of 65.06 kg SO2 eq., 27.74 kg N eq., 3086.71 kg CO2 eq., 75,152.66 CTUe, 2.75 × 10−5 CFC-11 eq., and 10,044.68 kg MJ eq. per ton of eggs produced. These findings can serve as comparative benchmarks for future studies and for analyzing data across different egg production systems in Brazil.

Abstract Background US Food and Drug Administration has issued Emergency Use Authorizations for hundreds of serological assays to support Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) diagnosis. The aim of this study is to evaluate, for the first time in children, the performance of three widely utilized SARS-CoV-2 serology commercial assays, Diesse Diagnostics (IgG, IgA, IgM) and Roche Diagnostics, both Roche Nucleocapsid (N) IgG and Roche Spike (S) IgG assays. Methods Sensitivity and 95% confidence intervals (CIs) were estimated for each of the three different serological tests and mixed and direct comparison were performed. Univariate and multivariate Poisson regression models were fitted to calculate incidence rate ratios and 95% CIs as estimate of the effects of age, gender, time on the serology title. A p-value

Photogrammetric data are systematically used in several segments. Products such as Digital Terrain Models (DTMs) provide detailed surface information, however the geometric reliability of these products is questionable compared to data collected by topographic survey by GNSS RTK. The present research assesses the quality of DTMs obtained using an Unmanned Aerial Vehicle (UAV) with different parameters, overlap percentages, and flight directions, comparing the results to those of the topography method Global Navigation Satellite System – Real-Time Kinematic (GNSS RTK). Were done twelve flight plans with different overlaps (90x90, 80x80, 80x60, 70x50, 70x30, and 60x40%) and directions (transverse and longitudinal to the planting line). The parameters of height (Above Ground Land- AGL) and speed were fixed at 90 m and 3 m/s respectively and a Ground Sample Distance (GSD) of 0,1 m is obtained for all flights. Overall, the flight with 70x50% overlap in the transverse direction generated the best results, with a total processing time of 12 minutes and 17 seconds (about 1.5 hours faster than 90x90%), an Root Mean Square Error (RMSE) 0.589 m, and meets the minimum overlap required by 60X30% aerophotogrammetry; furthermore, the results did not differ statistically from the high overlaps of 90x90% and 80x80%.

Coffee is a key agricultural product in national and international markets. Physiological parameters, such as plant growth indicators, can signal interruptions in these processes. This study aimed to characterize the temperature obtained by a thermal camera embedded in a remotely piloted aircraft (RPA) and evaluate its relationship with the water potential (WP) and stomatal conductance (gs) of an experimental coffee plantation using geostatistical techniques. The experiment was conducted at the Federal University of Lavras, Minas Gerais, Brazil. A rotary-wing RPA with an embedded thermal camera flew autonomously at a height of 10 m and speed of 10 m/s. Images were collected on 26 November 2019 (rainy season), and 11 August 2020 (dry season), between 9:30 am and 11:30 am. Data on gs and WP were collected in the field. The thermal images were processed using FLIR Tools 5.13, and temperature analysis and spatialization were undertaken using geostatistical tools and isocolor maps by Kriging interpolation in R 4.3.2 software. Field data were superimposed on final crop temperature maps using QuantumGIS version 3.10 software. The study found that with decreasing WP, stomatal closure and reduction in gs occurred, increasing the temperature due to water deficit. The temperature distribution maps identified areas of climatic variations indicating water deficit. [ABSTRACT FROM AUTHOR]

In recent years, unmanned aerial vehicles (UAVs) have been increasingly used to monitor and assess air quality. The interest in the application of UAVs in monitoring air pollutants and greenhouse gases is evidenced by the recent emergence of sensors with the most diverse specifications designed for UAVs or even UAVs designed with integrated sensors. The objective of this study was to conduct a comprehensive review based on bibliometrics to identify dynamics and possible trends in scientific production on UAV-based sensors to monitor air quality. A bibliometric analysis was carried out in the VOSViewer software (version 1.6.17) from the Scopus and Web of Science reference databases in the period between 2012 and 2022. The main countries, journals, scientific organizations, researchers and co-citation networks with greater relevance for the study area were highlighted. The literature, in general, has grown rapidly and has attracted enormous attention in the last 5 years, as indicated by the increase in articles after 2017. It was possible to notice the rapid development of sensors, resulting in smaller and lighter devices, with greater sensitivity and capacity for remote work. Overall, this analysis summarizes the evolution of UAV-based sensors and their applications, providing valuable information to researchers and developers of UAV-based sensors to monitor air pollutants.

ObjectivesTo investigate the inter/intra-reliability of ultrasound (US) muscle echogenicity in patients with rheumatic diseases.MethodsForty-two rheumatologists and 2 radiologists from 13 countries were asked to assess US muscle echogenicity of quadriceps muscle in 80 static images and 20 clips from 64 patients with different rheumatic diseases and 8 healthy subjects. Two visual scales were evaluated, a visual semi-quantitative scale (0–3) and a continuous quantitative measurement (“VAS echogenicity,” 0–100). The same assessment was repeated to calculate intra-observer reliability. US muscle echogenicity was also calculated by an independent research assistant using a software for the analysis of scientific images (ImageJ). Inter and intra reliabilities were assessed by means of prevalence-adjusted bias-adjusted Kappa (PABAK), intraclass correlation coefficient (ICC) and correlations through Kendall’s Tau and Pearson’s Rho coefficients.ResultsThe semi-quantitative scale showed a moderate inter-reliability [PABAK = 0.58 (0.57–0.59)] and a substantial intra-reliability [PABAK = 0.71 (0.68–0.73)]. The lowest inter and intra-reliability results were obtained for the intermediate grades (i.e., grade 1 and 2) of the semi-quantitative scale. “VAS echogenicity” showed a high reliability both in the inter-observer [ICC = 0.80 (0.75–0.85)] and intra-observer [ICC = 0.88 (0.88–0.89)] evaluations. A substantial association was found between the participants assessment of the semi-quantitative scale and “VAS echogenicity” [ICC = 0.52 (0.50–0.54)]. The correlation between these two visual scales and ImageJ analysis was high (tau = 0.76 and rho = 0.89, respectively).ConclusionThe results of this large, multicenter study highlighted the overall good inter and intra-reliability of the US assessment of muscle echogenicity in patients with different rheumatic diseases.

Aim: We developed tailored axillary surgery (TAS) to reduce the axillary tumor volume in patients with clinically node-positive breast cancer to the point where radiotherapy can control it. The aim of this study was to quantify the extent of tumor load reduction achieved by TAS. Methods: International multicenter prospective study embedded in a randomized trial. TAS is a novel pragmatic concept for axillary surgery de-escalation that combines palpation-guided removal of suspicious nodes with the sentinel procedure and, optionally, imaging-guided localization. Pre-specified study endpoints quantified surgical extent and reduction of tumor load. Results: A total of 296 patients were included at 28 sites in four European countries, 125 (42.2%) of whom underwent neoadjuvant chemotherapy (NACT) and 71 (24.0%) achieved nodal pathologic complete response. Axillary metastases were detectable only by imaging in 145 (49.0%) patients. They were palpable in 151 (51.0%) patients, of whom 63 underwent NACT and 21 had residual palpable disease after NACT. TAS removed the biopsied and clipped node in 279 (94.3%) patients. In 225 patients with nodal disease at the time of surgery, TAS removed a median of five (IQR 3–7) nodes, two (IQR 1–4) of which were positive. Of these 225 patients, 100 underwent ALND after TAS, which removed a median of 14 (IQR 10–17) additional nodes and revealed additional positive nodes in 70/100 (70%) of patients. False-negative rate of TAS in patients who underwent subsequent ALND was 2.6%. Conclusions: TAS selectively reduced the tumor load in the axilla and remained much less radical than ALND.

Background: Tofacitinib (TOFA) was the first Janus kinase inhibitor (JAKi) to be approved for the treatment of rheumatoid arthritis (RA). However, data on the retention rate of TOFA therapy are still far from definitive. Objective: The goal of this study is to add new real-world data on the TOFA retention rate in a cohort of RA patients followed for a long period of time. Methods: A multicenter retrospective study of RA subjects treated with TOFA as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was conducted in 23 Italian tertiary rheumatology centers. The study considered a treatment period of up to 48 months for all included patients. The TOFA retention rate was assessed with the Kaplan–Meier method. Hazard ratios (HRs) for TOFA discontinuation were obtained using Cox regression analysis. Results: We enrolled a total of 213 patients. Data analysis revealed that the TOFA retention rate was 86.5% (95% CI: 81.8–91.5%) at month 12, 78.8% (95% CI: 78.8–85.2%) at month 24, 63.8% (95% CI: 55.1–73.8%) at month 36, and 59.9% (95% CI: 55.1–73.8%) at month 48 after starting treatment. None of the factors analyzed, including the number of previous treatments received, disease activity or duration, presence of rheumatoid factor and/or anti-citrullinated protein antibody, and presence of comorbidities, were predictive of the TOFA retention rate. Safety data were comparable to those reported in the registration studies. Conclusions: TOFA demonstrated a long retention rate in RA in a real-world setting. This result, together with the safety data obtained, underscores that TOFA is a viable alternative for patients who have failed treatment with csDMARD and/or biologic DMARDs (bDMARDs). Further large, long-term observational studies are urgently needed to confirm these results.

Extraintestinal manifestations are the cause of morbidity and affect the quality of life of patients with inflammatory bowel diseases (IBDs). Musculoskeletal manifestations, in particular, spondyloarthritis and osteoporosis, are the most frequent extraintestinal manifestation of IBDs. The diagnosis and management of the musculoskeletal manifestation of IBDs relies on imaging. Conventional radiography, magnetic resonance imaging, computed tomography, and ultrasound can help to detect pathological signs of spondyloarthritis, both peripheral and with axial involvement. Dual-energy X-ray absorptiometry is the gold standard for identifying the presence of osteoporosis, whereas conventional radiology and computed tomography can reveal occult vertebral fractures. The aim of this narrative review is to describe the imaging of musculoskeletal manifestations of IBDs.

Ultrasound is a reliable imaging modality for diagnosing and assessing musculoskeletal disorders. Recent advancements in ultrasound technology have substantially improved image resolution, enabling the visualization of anatomic structures on a near-microscopic level. However, existing guidelines for standardized shoulder ultrasound primarily rely on earlier machine models and settings that may not harness the full potential of these high-resolution imaging capabilities. This article provides a simple and systematic guide to high-resolution sonography of the shoulder using anatomical and histological images from cadavers for comparison. International standard techniques are considered, and images were obtained using modern equipment. This two-article series systematically shows the examination and normal findings, presenting first the posterior, then frontal, then further anterior, followed by lateral and, optionally, the axillary examination. In this article, the focus is on the posterior and coronal shoulder. [ABSTRACT FROM AUTHOR]

This is the second part of a two‐part article in which we focus on the ultrasound (US) appearance of the pathological ulnar nerve (UN) and its main branches. Findings in a wide range of our pathological cases are presented with high‐resolution US images obtained with the latest‐generation US machines and transducers. [ABSTRACT FROM AUTHOR]

Growth performance and meat quality traits of 24 Massese suckling lambs reared up to 69 days of age in different farming systems were evaluated. Three groups were considered: stall (S) reared indoors and fed concentrate and hay; pasture (P) reared outdoor and fed pasture and hay; semi free-range (F) reared indoors during the night and at pasture during the day, fed concentrate, hay and herbage. The lambs remained constantly with their dams for the whole period, having thus always access to mothers’ milk. Animals weights were recorded, and, after slaughtering, carcase traits were considered. Fatty acids composition and chemical/physical parameters of milk and meat were analysed. Lambs growth was similar in the first 30 days, while afterwards differences emerged: P lambs recorded the worst values reaching slaughter weight of 14.6 kg versus 22.3 and 22.7 of the S and the F group, respectively. Carcase of P lambs resulted less fat and with a lower lean/bone ratio than the other groups (1.8, 2.1 and 2.3 for P, S and F, respectively). Fatty acids composition of ewes’ milk had effect on lambs’ meat profile, probably because they continued to suck milk until slaughter. Moreover, also farming system affected fatty acids profile of lambs’ meat: grazing animals, especially P, showed the highest PUFA and the lowest SFA percentage and P meat showed the best composition for human health. As regards physical traits, F meat was more coloured than P and S meat, while P meat was less tender than others.Highlights Two-month-old Massese lamb is a marketable product. Suckled milk affected lambs’ meat composition also at later ages. Pasture in lambs’ diet increases PUFA content in the meat.

Background: To date, only a few real-world-setting studies evaluated apremilast effectiveness in psoriatic arthritis (PsA). The aims of this retrospective observational study are to report long-term Disease Activity Index for Psoriatic Arthritis (DAPSA) response of apremilast in PsA patients and to analyze the predictors of clinical response. Methods: All PsA consecutive patients treated with apremilast in fifteen Italian rheumatological referral centers were enrolled. Anamnestic data, treatment history, and PsA disease activity (DAPSA) at baseline, 6 months, and 12 months were recorded. The Mann–Whitney test and chi-squared tests assessed the differences between independent groups, whereas the Wilcoxon matched pairs signed-rank test assessed the differences between dependent samples. Logistic regressions verified if there were factors associated with achievement of DAPSA low disease activity or remission at 6 and 12 months. Results: DAPSA low disease activity or remission rates at 6 and 12 months were observed, respectively, in 42.7% (n = 125) and 54.9% (n = 161) patients. Baseline DAPSA was inversely associated with the odds of achieving low disease activity or remission at 6 months (odds ratio (OR) 0.841, 95% confidence interval (CI) 0.804–0.879; p < 0.01) and at 12 months (OR 0.911, 95% CI 0.883–0.939; p < 0.01). Conclusions: Almost half of the PsA patients receiving apremilast achieved DAPSA low disease activity or remission at 6 and 12 months. The only factor associated with achievement of low disease activity or remission at both 6 and 12 months was baseline DAPSA.

Dyspnea is a common symptom in Systemic Sclerosis (SSc) that considerably decreases patients’ quality of life (QoL). Pulmonary Rehabilitation (PR) mitigates dyspnea impact on daily activities. The aim of this study is to evaluate the effect on respiratory disability of home-based PR in SSc patients with dyspnea. In this observational prospective monocentric study, we screened all dyspneic SSc consecutive patients attending the Rheumatological day hospital in the University hospital of Parma from January 2019 and June 2019. The aim of our study was to understand if a PR unsupervised home-based program could improve respiratory disability in this specific population. Dyspnea was evaluated with the self-administered questionnaires modified Medical Research Council (mMRC) and Saint George's Respiratory Questionnaire (SGRQ).Patients also filled in Short Form 36 (SF36) and the Modified-Health Assessment Questionnaire for SSc (HAQ-MOD). Health Professionals assessed and trained the patients and collected data before PR and at the end of the program. PR consisted in 5 weekly unsupervised sessions for 8 weeks. Wilcoxon test for paired data evaluated the changes after PR. p

Simple Summary: Promoting sustainability in food production has become essential to meet market demands, mainly due to its tendency to expand throughout the world. Life cycle assessment is a methodology recognized for providing quantitative information on the environmental impacts caused throughout the production cycle in different categories. The objective of this study was to carry out an assessment of the life cycle, from the cradle to the farm gate, following ISO 14040 and 14044 standards, for the battery cage egg production systems and associated products in Brazil. The results showed that interventions focused on feed formulation, manure management, and the welfare of laying hens play a fundamental role in promoting sustainability in battery cage egg production systems. Brazil stands as one of the world's leading producers of animal protein, ranking sixth in global egg production. However, estimated growth in production demand, along with environmental impacts, represents a potential threat to the sustainability of the food system. Methods for assessing and quantifying the environmental impacts generated by Brazilian egg production remain scarce, lacking current reports on comparative effects or guiding standards. The objective of this study was to conduct a life cycle assessment from cradle to farm gate, adhering to ISO 14040 and 14044 standards, for the battery cage egg production systems and associated products in Brazil, with the aim of supporting and promoting sustainability improvements in the Brazilian egg industry. The entire life cycle modeling and process sustainability analysis were executed using the openLCA software, integrated with the Ecoinvent database. Emissions related to egg production yielded results of 65.06 kg SO2 eq., 27.74 kg N eq., 3086.71 kg CO2 eq., 75,152.66 CTUe, 2.75 × 10−5 CFC-11 eq., and 10,044.68 kg MJ eq. per ton of eggs produced. These findings can serve as comparative benchmarks for future studies and for analyzing data across different egg production systems in Brazil. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by joint involvement, extra-articular manifestations, comorbidities, and increased mortality. In the last few decades, the management of RA has been dramatically improved by the introduction of a treat-to-target approach aiming to prevent joint damage progression. Moreover, the increasing knowledge about disease pathogenesis allowed the development of a new drug class of biologic agents targeted on immune cells and proinflammatory cytokines involved in RA network. Despite the introduction of several targeted drugs, a significant proportion of RA patients still fail to achieve the clinical target; so, more recently the focus of research has been shifted toward the inhibition of kinases involved in the transduction of the inflammatory signal into immune cells. In particular, two Janus kinase (JAK) inhibitors, baricitinib and tofacitinib, have been licensed for the treatment of RA as a consequence of a very favorable profile observed in randomized controlled trials (RCTs) conducted across different RA subpopulations. Both these new compounds are active on the majority of four JAK family members (JAK1, JAK2, JAK3, and TYK2), whereas the most recent emerging approach is directed toward the development of JAK1 selective inhibitors (upadacitinib and filgotinib) with the aim to improve the safety profile by minimizing the effects on JAK3 and, especially, JAK2. In this narrative review, we discuss the rationale for JAK inhibition in RA, with a special focus on the role of JAK1 selective blockade and a detailed description of available data from the results of clinical trials on upadacitinib and filgotinib.

Martina Biggioggero,1 Chiara Crotti,2 Andrea Becciolini,1 Ennio Giulio Favalli1 1Department of Rheumatology, Gaetano Pini Institute, Milan, Italy; 2Department of Clinical Sciences and Health Community, University of Milan, Division of Rheumatology, Gaetano Pini Institute, Milan, Italy Abstract: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by articular and systemic manifestations, such as anemia, fatigue, osteoporosis, and increased risk for cardiovascular diseases. The pathogenesis of RA is driven by a complex network of proinflammatory cytokines, with a pivotal role of IL-6 and tumor necrosis factor (TNF). The management of RA has been dramatically changed during the last years by the introduction of a treat-to-target approach aiming to achieve an acceptable disease control. Nowadays, TNF inhibitors (TNFis) are the most frequently prescribed class of biologic therapies, but the significant proportion of patients experiencing the failure of a TNFi led to the development of alternative therapeutic options targeted on different pathways. Considering the increasing number of targeted therapeutic options for RA, there is a growing interest in the identification of potential predictors of clinical response to each available mechanism of action, with the aim to drive the management of the disease toward a personalized approach according to the concept of precision medicine. Tocilizumab (TCZ) is the first humanized anti-IL-6 receptor subunit alpha (anti-IL-6R) monoclonal antibody approved for the treatment of RA refractory to methotrexate or TNFis. TCZ inhibits both the cis- and trans-signaling cascades involving the Janus kinase-signal transducer and the activator of transcription pathway, playing a crucial role in modulating not only joint inflammation but also the previously mentioned extra-articular manifestations and comorbidities of RA, such as fatigue, anemia, bone loss, depression, type 2 diabetes, and increased cardiovascular risk. In this review, moving from pathogenetic insights and evidence-based clinical data from randomized controlled trials and real-life observational studies, we will discuss the drivers for the selection of patient candidates to receive TCZ, in order to clarify the current positioning of this drug in the treatment algorithm of RA. Keywords: IL-6, profiling, clinical trials, efficacy, real-life

Chiara Crotti,1,2 Martina Biggioggero,3 Andrea Becciolini,3 Ennio Giulio Favalli3 1Department of Clinical Sciences and Health Community, University of Milan, 2Division of Rheumatology, Gaetano Pini Institute, Milan, Italy; 3Department of Rheumatology, Gaetano Pini Institute, Milan, Italy Abstract: In the last few decades, strategies for the management of rheumatoid arthritis (RA) have been increasingly oriented toward more comprehensive control of the disease, taking into account even RA extra-articular manifestations, comorbidities, and the patient’s perception about the disease. The need for improving the shared decision-making process suggested by European League Against Rheumatism recommendations is leading to an increasing interest in the role of patient-reported outcomes (PROs) beside the usual more objective criteria for defining clinical response based on disease-activity composite indices. Measurement of such PROs as pain or fatigue may be significantly influenced by mood disorders often complicating RA, the pathogenesis of which is deeply interconnected with phlogistic processes mediated by proinflammatory cytokines. IL6 is a pleiotropic mediator involved in neuroendocrine and neuropsychological processes, besides its well known effects on immune, cardiovascular, and metabolic systems. Therefore, there is a growing body of evidence about the efficacy of IL6 blockade in PRO improvement in RA patients. Sarilumab is a monoclonal antibody binding both soluble and membrane-bound IL6Rα, inhibiting the IL6-mediated signaling pathway with favorable efficacy and safety profile. This review analyzes the importance of PROs in strategies for the management of RA and the pathogenic mechanisms linking IL6 with the patient’s perception of the disease. Moreover, the main findings from sarilumab randomized controlled trials are summarized in detail, emphasizing the potential role of this IL6 blocker in the holistic treatment of RA. Keywords: rheumatoid arthritis, interleukin-6, sarilumab, patient reported outcome

Ennio Giulio Favalli,1 Andrea Becciolini,1 Martina Biggioggero,2 Ilaria Bertoldi,3 Chiara Crotti,2 Maria Gabriella Raimondo,2 Antonio Marchesoni1 1Department of Rheumatology, Gaetano Pini Institute, Milan, Italy; 2Department of Clinical Sciences and Health Community, University of Milan, Division of Rheumatology, Gaetano Pini Institute, Milan, Italy; 3Pfizer Innovative Health, I&I Medical Affairs, Rome, Italy Objective: To evaluate the pattern of prescription and maintenance over time of concomitant methotrexate (MTX), and its impact on a 2-year clinical response in a cohort of rheumatoid arthritis (RA) patients treated with a first-line tumor necrosis factor alpha inhibitor (TNFi). Patients and methods: The study population included all RA patients receiving adalimumab or etanercept a as first-line biologic drug, extracted from a local registry. Enrolled patients were stratified into 3 subgroups according to baseline concomitant MTX: no MTX, low-dose MTX (≤10 mg/wk), and high-dose MTX (≥12.5 mg/wk). The 2-year persistence of the initial MTX regimen was computed by the Kaplan–Meier method, and a Cox proportional hazard model was developed to examine potential predictors of MTX withdrawal/change of dosage. European League Against Rheumatism remission and good-to-moderate response were evaluated according to baseline MTX regimen and MTX maintenance over time. Results: A total of 330 patients (163 treated with adalimumab and 167 with etanercept) were included; 141 were prescribed TNFi without MTX and 112 received low-dose and 77 high-dose concomitant MTX. Male sex, younger age, and shorter mean disease duration were predictors of high-dose MTX use. Among MTX users (76.2% parenteral and 23.8% oral), initial MTX dose persisted over time in 79.9% at 1 year and 70.2% at 2 years. Fifty-one patients (27%) underwent MTX dose de-escalation/discontinuation because of intolerance/adverse events. The 2-year EULAR remission rate was higher in the patients receiving and maintaining high-dose MTX than in those receiving low-dose or no MTX (46.2% vs 29.5% and 23.4%, respectively; p=0.009). The same was true for good-to-moderate response rate (71.2% vs 52.6% and 50.4%, respectively; p=0.031). Conclusion: In a real-life setting, about one-third of RA patients treated with TNFis experienced dose reduction/discontinuation of concomitant MTX because of intolerance/adverse events over a 2-year follow-up period. Initial high-dose MTX and its maintenance over time are associated with better 2-year clinical response. Keywords: rheumatoid arthritis, methotrexate, biologic drugs, combination therapy, etanercept, adalimumab

Organic fertilization is a profitable option and an environmentally correct alternative. The compost barn confinement system generates an organic material that can be applied to fertilize crops used to produce food for dairy cattle. This work objective is to evaluate the use of this material as an organic fertilizer. For the tests, sunflowers were planted in 15 L pots made up of ¾ soil and ¼ sand, kept in a greenhouse and four doses of fertilizer were tested (0, 5, 25 and 125 g/pot), using organic compost generated by a compost barn with Holstein dairy cows. The tests showed positive results for plant growth and development and for grain production for all doses, with a significant difference only for the 125 g dose, which presented an average number of leaves of 15.96, stem diameter of 12.5 mm and thousand seed weight of 28.63 g. It was found that there was greater plant growth and greater grain filling with an increase in the fertilizer dose, proving the positive effects on the plant of using organic compost from a compost barn. [ABSTRACT FROM AUTHOR]

This is the first of a two‐part article in which we focus on the ultrasound (US) appearance of the normal ulnar nerve (UN) and its main branches. The detailed US anatomy of the UN course is presented with high‐resolution US images obtained with the latest‐generation US machines and transducers. [ABSTRACT FROM AUTHOR]

The dairy sector significantly contributes to global food production, however, it is closely associated with environmental concerns, specifically the emission of greenhouse gases such as methane (CH4) and carbon dioxide (CO2). The research problem focuses on the environmental impact of livestock farming, particularly in relation to the emission of greenhouse gases (GHG) such as methane (CH4) and carbon dioxide (CO2). Therefore, the objective of this paper was to assess the spatial variability of CH4 and CO2, as well as the thermal environment through the Temperature and Humidity Index (THI) and of air velocity (V, m s-1) in a Compost Bedded Pack (CBP). The experiment was carried out in October 2023, in a commercial dairy cattle facility measuring 54×22×4.5 m (length×width×height) that housed 80 lactating cows. Measurements were collected at 75 points, 0.25 m above the bedding, for one minute in each point. To characterize the distribution of gases and the thermal environment, the data were underwent geostatistical techniques and kriging maps. THI values ranged from 72.4 to 78.4, categorizing the animals into two environments within the facility, comfort and alert to thermal conditions. The maximum recorded for CO2 was 713.60 ppm in the region with a low ventilation incidence. CH4 reached a ranging from 103.38 to 196.73 ppm in areas with low ventilation and higher temperatures. The use of geostatistics enabled the characterization of spatial variability of greenhouse gases CH4 and CO2, as well as THI and V. Analyzing these variables is crucial for implementing mitigation actions and developing an increasingly sustainable production system. [ABSTRACT FROM AUTHOR]

The use of sensor technologies to monitor cows’ behavior is becoming commonplace in the context of dairy production. This study aimed at validating a commercial collar-based sensor system, the AFICollar® (Afimilk, Kibbutz Afikim, Israel), designed to monitor dairy cattle feeding and ruminating behavior. Additionally, the performances of two versions of the software for behavior classification, the current software AFIfarm® 5.4 and the updated version AFIfarm® 5.5, were compared. The study involved twenty Holstein-Friesian cows fitted with the collars. To evaluate the sensor performance under different feeding scenarios, the animals were divided into four groups and fed three different types of feed (total mixed ration, long hay, animals allowed to graze). Recordings of hourly rumination and feeding time produced by the sensor were compared with visual observation by scan sampling at 1 minute intervals using Spearman correlation, concordance correlation coefficient (CCC), Bland–Altman plots and linear mixed models for assessing the precision and accuracy of the system. The analyses confirmed that the updated software version V5.5 produced better detection performance than the current V5.4. The updated software version produced high correlations between visual observations and data recorded by the sensor for both feeding (r = 0.85, CCC = 0.86) and rumination (r = 0.83, CCC = 0.86). However, the limits of agreement for both behaviors remained quite wide (feeding: −19.60 min/h, 17.46 min/h; rumination: −15.80 min/h, 15.00 min/h). Type of feed did not produce significant effects on the agreement between visual observations and sensor recordings. Overall, the results indicate that the system can provide farmers with adequately accurate data on feeding and rumination time, and can be used to support herd management decisions. Despite all this, the precision of the system remained relatively limited, and should be improved with further developments in the classification algorithm.

Andrea Becciolini,1 Maria Gabriella Raimondo,2 Chiara Crotti,2 Elena Agape,2 Martina Biggioggero,2 Ennio Giulio Favalli1 1Department of Rheumatology, 2Department of Clinical Sciences and Health Community, University of Milan, Division of Rheumatology, Gaetano Pini Institute, Milan, Italy Abstract: The introduction of biological agents drastically changed the treatment paradigm of inflammatory arthritides, ameliorating the natural history of the diseases but concomitantly increasing the drug costs due to the manufacturing process. On this concern, biosimilar drugs may represent a valid option for reducing this elevated cost and increasing the availability of these highly effective treatments. Recently, CT-P13, the first biosimilar of infliximab, has been approved with the same indications established for the reference product (RP), and its daily use is progressively increasing. However, the experience with biosimilar drugs in the field of rheumatology is still limited, raising potential doubts and concerns on their correct management in real-life settings. Comparability analysis between CT-P13 and its RP was evaluated in equivalence randomized controlled trials (RCTs) – PLANETRA and PLANETAS – performed on patients with rheumatoid arthritis and axial spondylitis, respectively. CT-P13 and RP showed similar profile in terms of quality, biological activity, safety, immunogenicity, and efficacy. However, the interchangeability between infliximab RP and its biosimilar still represents the most challenging issue because of a lack of a long-lasting experience. To date, reassuring preliminary data on this topic were reported in open-label extensions of PLANETRA and PLANETAS RCTs and in ongoing real-life observational studies. These findings, taken all together, significantly affect the landscape of biosimilar regulatory pathways and strongly support CT-P13 introduction as a great opportunity for expanding the accessibility to these very effective and high-cost therapies. Keywords: biological therapy, biosimilars, interchangeability, TNF inhibitors, rheumatic diseases

Maria Gabriella Raimondo,1 Martina Biggioggero,1 Chiara Crotti,1 Andrea Becciolini,2 Ennio Giulio Favalli2 1Department of Clinical Sciences and Health Community, Division of Rheumatology, University of Milan, 2Department of Rheumatology, Gaetano Pini Institute, Milan, Italy Abstract: In recent years the use of biotechnological agents has drastically revolutionized the therapeutic approach and the progression of rheumatoid arthritis (RA). In particular, interleukin-6 (IL-6) has been demonstrated as a pivotal cytokine in the pathogenesis of the disease by contributing to both the innate and the adaptive immune system perturbation, and to the production of acute-phase proteins involved in the systemic expression of the disorder. The first marketed IL-6 blocker was tocilizumab, a humanized anti-IL-6 receptor (anti-IL-6R) monoclonal antibody. The successful use of tocilizumab in RA has encouraged the development of other biologic agents specifically targeting the IL-6 pathway, either directed against IL-6 cytokine (sirukumab, olokizumab, and clazakizumab) or IL-6 receptor (sarilumab). One Phase II and six Phase III randomized controlled trials demonstrated a broad efficacy of sarilumab across all RA patient subtypes, ranging from methotrexate (MTX) to tumor necrosis factor inhibitor insufficient responders. In particular, sarilumab as monotherapy demonstrated a clear head-to-head superiority over adalimumab in MTX-intolerant subjects. In addition, compared with tocilizumab, sarilumab showed a similar safety profile with significantly higher affinity and longer half-life, responsible for a reduction of the frequency of administration (every other week instead weekly). All these aspects may be important in defining the strategy for positioning sarilumab in the treatment algorithm of RA. Indeed, observational data coming from post-marketing real-life studies may provide crucial additional information for better understanding the role of sarilumab in the management of the disease. This review summarizes both the biological role of IL-6 in RA and the clinical data available on sarilumab as an alternative therapeutic option in RA patients. Keywords: rheumatoid arthritis, interleukin-6, sarilumab, monoclonal antibody, biologic drugs