The evil relationship between liver fibrosis and cardiovascular disease in metabolic dysfunction-associated fatty liver disease (MAFLD): Looking for the culprit.

Metabolic dysfunction-associated fatty liver disease (MAFLD), the hepatic component of the metabolic syndrome caused by insulin resistance, is a major public health problem, affecting about the 25 % of the general population in Western countries. Morbidity and mortality of MAFLD patients is increased primarily due to cardiovascular disease (CVD). Liver fibrosis, the byproduct of hepatic repair, is the main determinant of MAFLD progression and the strongest predictor for overall mortality. Since the mechanistic relationship between MAFLD, fibrosis, insulin resistance and the cardiometabolic risk is far to be clear, deciphering the functional link of hepatic fibrogenesis with genetic factors and hypercoagulability in MAFLD-associated CVD may hold translational potential for risk profiling and innovative therapeutic targeting.

Measurement of Electron-Neutrino Charged-Current Cross Sections on

Using an 185-kg NaI[Tl] array, COHERENT has measured the inclusive electron-neutrino charged-current cross section on ^{127}I with pion decay-at-rest neutrinos produced by the Spallation Neutron Source at Oak Ridge National Laboratory. Iodine is one the heaviest targets for which low-energy (≤50 MeV) inelastic neutrino-nucleus processes have been measured, and this is the first measurement of its inclusive cross section. After a five-year detector exposure, COHERENT reports a flux-averaged cross section for electron neutrinos of 9.2_{-1.8}^{+2.1}×10^{-40} cm^{2}. This corresponds to a value that is ∼41% lower than predicted using the MARLEY event generator with a measured Gamow-Teller strength distribution. In addition, the observed visible spectrum from charged-current scattering on ^{127}I has been measured between 10 and 55 MeV, and the exclusive zero-neutron and one-or-more-neutron emission cross sections are measured to be 5.2_{-3.1}^{+3.4}×10^{-40} and 2.2_{-0.5}^{+0.4}×10^{-40} cm^{2}, respectively.

First Probe of Sub-GeV Dark Matter beyond the Cosmological Expectation with the COHERENT CsI Detector at the SNS.

The COHERENT Collaboration searched for scalar dark matter particles produced at the Spallation Neutron Source with masses between 1 and 220 MeV/c^{2} using a CsI[Na] scintillation detector sensitive to nuclear recoils above 9 keV_{nr}. No evidence for dark matter is found and we thus place limits on allowed parameter space. With this low-threshold detector, we are sensitive to coherent elastic scattering between dark matter and nuclei. The cross section for this process is orders of magnitude higher than for other processes historically used for accelerator-based direct-detection searches so that our small, 14.6 kg detector significantly improves on past constraints. At peak sensitivity, we reject the flux consistent with the cosmologically observed dark-matter concentration for all coupling constants α_{D}<0.64, assuming a scalar dark-matter particle. We also calculate the sensitivity of future COHERENT detectors to dark-matter signals which will ambitiously test multiple dark-matter spin scenarios.

Measurement of the Coherent Elastic Neutrino-Nucleus Scattering Cross Section on CsI by COHERENT.

We measured the cross section of coherent elastic neutrino-nucleus scattering (CEvNS) using a CsI[Na] scintillating crystal in a high flux of neutrinos produced at the Spallation Neutron Source at Oak Ridge National Laboratory. New data collected before detector decommissioning have more than doubled the dataset since the first observation of CEvNS, achieved with this detector. Systematic uncertainties have also been reduced with an updated quenching model, allowing for improved precision. With these analysis improvements, the COHERENT Collaboration determined the cross section to be (165_{-25}^{+30})×10^{-40} cm^{2}, consistent with the standard model, giving the most precise measurement of CEvNS yet. The timing structure of the neutrino beam has been exploited to compare the CEvNS cross section from scattering of different neutrino flavors. This result places leading constraints on neutrino nonstandard interactions while testing lepton flavor universality and measures the weak mixing angle as sin^{2}θ_{W}=0.220_{-0.026}^{+0.028} at Q^{2}≈(50 MeV)^{2}.

CT scan structured report for the study of abdominal wall defects: a fast, easy and practical tool at the service of both surgeons and radiologist.

PURPOSE: The advantages offered by structured reporting have already been highlighted in the literature. However, there is still no evidence on the validity of this reporting method for the study of abdominal wall defects. This study aims to show the experience of the Trentino Hernia Team (THT) multidisciplinary group in the development and use of a structured CT scan report for the study of abdominal wall defects. METHODS: A regional multidisciplinary team (THT group) used a Delphi method to identify and select the most important CT scan parameters needed to describe and stage abdominal wall defects for correct preoperative planning. Based on the selected parameters, a CT scan structured report was worked out and collectively accepted. The first 20 structured reports obtained were individually tested for compilation speed and homogeneity of the data reported by five distinct radiologists. The reports were then evaluated by five different surgeons to test the simplicity of interpretation. RESULTS: We produced a model of a structured report for the study of the abdominal wall defects and tested it in our hospital network on the first 20 reports. The average completion time was 18 min (range 12-25). There was no heterogeneity among the reported data. The reports were analysed by five distinct surgeons to evaluate completeness and simplicity of interpretation. Each surgeon used a Likert scale from 0 to 5 to evaluate each report, producing average scores of 4.8 and 4.1 for completeness and comprehensibility respectively, with a mean combined total score of 8.9 out of 10. CONCLUSIONS: Our structured report represents a fundamental tool capable of providing the surgeon with all the measurements of the parameters necessary for correct preoperative planning. At the same time, it is of crucial help for the radiologists representing an easy and fast way to report all the needed parameters using the same standards.

First Measurement of Coherent Elastic Neutrino-Nucleus Scattering on Argon.

We report the first measurement of coherent elastic neutrino-nucleus scattering (CEvNS) on argon using a liquid argon detector at the Oak Ridge National Laboratory Spallation Neutron Source. Two independent analyses prefer CEvNS over the background-only null hypothesis with greater than 3σ significance. The measured cross section, averaged over the incident neutrino flux, is (2.2±0.7)×10^{-39} cm^{2}-consistent with the standard model prediction. The neutron-number dependence of this result, together with that from our previous measurement on CsI, confirms the existence of the CEvNS process and provides improved constraints on nonstandard neutrino interactions.

Prospective observational study of abdominal wall reconstruction with THT technique in primary midline defects with diastasis recti: clinical and functional outcomes in 110 consecutive patients.

INTRODUCTION: Surgical treatment of diastasis recti is still a matter of debate. Open approaches such as abdominoplasty, which offer the possibility to combine reparation of the diastasis with abdominal cosmetic surgery, are challenged by the emerging less-invasive laparoscopic or robotic techniques that offer shorter recovery for patients. However, evidence in favour of one of the two approaches concerning both short- and long-term complications and functional results is still lacking. In this paper, we analysed clinical and functional results of a new endo-laparoscopic technique for midline reconstruction (THT technique) in patients with primary abdominal wall defects associated with diastasis recti. METHODS: Prospective observational study on 110 consecutive patients was submitted to endo-laparoscopic reconstruction of the abdominal wall with linear staplers. Morbidity and relapse rates with clinical and radiological follow-up were recorded at 1, 6, 12, and 24 months after the operation. Data regarding the impact of surgery on patients' quality of life (EuraHSQol) on chronic low back pain (Oswestry Disability Index, ODI) and urinary stress incontinence (Incontinence Severity Index, ISI) were gathered. RESULTS: After a mean follow-up of 14 months, the morbidity rate was 9.1% and no recurrences were recorded. 6-month follow-up ultrasound showed a rectus muscles mean distance of 6.7 mm; EuraHSQol, ODI, and ISI scores significantly improved in 93%, 77%, and 63% of the cases, respectively. CONCLUSIONS: The THT technique proved to be a feasible, safe, and effective alternative for corrective surgery of primary midline hernias associated with diastasis recti. Short- and mid-term results are encouraging but need to be confirmed by further studies with longer follow-up. The achieved midline reconstruction offers a significant improvement of patients' perceived quality of life through reduction of abdominal wall pain, bulging, low back pain, and urinary stress incontinence.

Cosmic-ray antinuclei as messengers of new physics: status and outlook for the new decade.

The precise measurement of cosmic-ray antinuclei serves as an important means for identifying the nature of dark matter and other new astrophysical phenomena, and could be used with other cosmic-ray species to understand cosmic-ray production and propagation in the Galaxy. For instance, low-energy antideuterons would provide a "smoking gun" signature of dark matter annihilation or decay, essentially free of astrophysical background. Studies in recent years have emphasized that models for cosmic-ray antideuterons must be considered together with the abundant cosmic antiprotons and any potential observation of antihelium. Therefore, a second dedicated Antideuteron Workshop was organized at UCLA in March 2019, bringing together a community of theorists and experimentalists to review the status of current observations of cosmic-ray antinuclei, the theoretical work towards understanding these signatures, and the potential of upcoming measurements to illuminate ongoing controversies. This review aims to synthesize this recent work and present implications for the upcoming decade of antinuclei observations and searches. This includes discussion of a possible dark matter signature in the AMS-02 antiproton spectrum, the most recent limits from BESS Polar-II on the cosmic antideuteron flux, and reports of candidate antihelium events by AMS-02; recent collider and cosmic-ray measurements relevant for antinuclei production models; the state of cosmic-ray transport models in light of AMS-02 and Voyager data; and the prospects for upcoming experiments, such as GAPS. This provides a roadmap for progress on cosmic antinuclei signatures of dark matter in the coming years.

Identification and quantification of gold engineered nanomaterials and impaired fluid transfer across the rat placenta via ex vivo perfusion.

Development and implementation of products incorporating nanoparticles are occurring at a rapid pace. These particles are widely utilized in domestic, occupational, and biomedical applications. Currently, it is unclear if pregnant women will be able to take advantage of the potential biomedical nanoproducts out of concerns associated with placental transfer and fetal interactions. We recently developed an ex vivo rat placental perfusion technique to allow for the evaluation of xenobiotic transfer and placental physiological perturbations. In this study, a segment of the uterine horn and associated placenta was isolated from pregnant (gestational day 20) Sprague-Dawley rats and placed into a modified pressure myography vessel chamber. The proximal and distal ends of the maternal uterine artery and the vessels of the umbilical cord were cannulated, secured, and perfused with physiological salt solution (PSS). The proximal uterine artery and umbilical artery were pressurized at 80 mmHg and 50 mmHg, respectively, to allow countercurrent flow through the placenta. After equilibration, a single 900 µL bolus dose of 20 nm gold engineered nanoparticles (Au-ENM) was introduced into the proximal maternal artery. Distal uterine and umbilical vein effluents were collected every 10 min for 180 min to measure placental fluid dynamics. The quantification of Au-ENM transfer was conducted via inductively coupled plasma mass spectrometry (ICP-MS). Overall, we were able to measure Au-ENM within uterine and umbilical effluent with 20 min of material infusion. This novel methodology may be widely incorporated into studies of pharmacology, toxicology, and placental physiology.

Effect of Gestational Age on Maternofetal Vascular Function Following Single Maternal Engineered Nanoparticle Exposure.

Normal pregnancy outcome is accomplished, in part, by rapid and expansive physiological adaptations to the systemic circulation, the extent of which is specific to gestational day (GD) and anatomical location. Pregnancy-related hemodynamic changes in uterine placental blood flow stimulate compensatory vascular signaling and remodeling that begins early and continues throughout gestation. Exposure of the maternal environment to engineered nanomaterials (ENM) during pregnancy has been shown to impact health of the dam, fetus, and adult offspring; however, the consequences of specific temporal (gestational age) and spatial (vascular location) considerations are largely undetermined. We exposed pregnant Sprague-Dawley rats to nano-TiO2 aerosols at three critical periods of fetal development (GD 4, 12, and 17) to identify vascular perturbations associated with ENM exposure at these developmental milestones. Vascular reactivity of the maternal thoracic aorta, the uterine artery, the umbilical vein, and the fetal thoracic aorta were evaluated using wire myography on GD 20. While impairments were noted at each level of the maternofetal vascular tree and at each exposure day, our results indicate the greatest effects may be identified within the fetal vasculature (umbilical vein and fetal aorta), wherein effects of a single maternal inhalational exposure to nano-TiO2 on GD 4 modified responses to cholinergic, NO, and α-adrenergic signaling.

Observation of coherent elastic neutrino-nucleus scattering.

The coherent elastic scattering of neutrinos off nuclei has eluded detection for four decades, even though its predicted cross section is by far the largest of all low-energy neutrino couplings. This mode of interaction offers new opportunities to study neutrino properties and leads to a miniaturization of detector size, with potential technological applications. We observed this process at a 6.7σ confidence level, using a low-background, 14.6-kilogram CsI[Na] scintillator exposed to the neutrino emissions from the Spallation Neutron Source at Oak Ridge National Laboratory. Characteristic signatures in energy and time, predicted by the standard model for this process, were observed in high signal-to-background conditions. Improved constraints on nonstandard neutrino interactions with quarks are derived from this initial data set.

Pleuropulmonary involvement in patients with systemic lupus erythematosus from a Latin American inception cohort (GLADEL).

Objectives The objectives of this study were to examine the demographic and clinical features associated with the occurrence of pleuropulmonary manifestations, the predictive factors of their occurrence and their impact on mortality in systemic lupus erythematosus (SLE) patients. Materials and methods The association of pleuropulmonary manifestations with demographic and clinical features, the predictive factors of their occurrence and their impact on mortality were examined in GLADEL patients by appropriate univariable and multivariable analyses. Results At least one pleuropulmonary manifestation occurred in 421 of the 1480 SLE patients (28.4%), pleurisy being the most frequent (24.0%). Age at SLE onset ≥30 years (OR 1.42; 95% CI 1.10-1.83), the presence of lower respiratory tract infection (OR 3.19; 95% CI 2.05-4.96), non-ischemic heart disease (OR 3.17; 95% CI 2.41-4.18), ischemic heart disease (OR 3.39; 95% CI 2.08-5.54), systemic (OR 2.00; 95% CI 1.37-2.91), ocular (OR 1.58; 95% CI 1.16-2.14) and renal manifestations (OR 1.44; 95% CI 1.09-1.83) were associated with pleuropulmonary manifestations, whereas cutaneous manifestations were negatively associated (OR 0.47; 95% CI 0.29-0.76). Non-ischemic heart disease (HR 2.24; 95% CI 1.63-3.09), SDI scores ≥1 (OR 1.54; 95% CI 1.10-2.17) and anti-La antibody positivity (OR 2.51; 95% CI 1.39-4.57) independently predicted their subsequent occurrence. Cutaneous manifestations were protective of the subsequent occurrence of pleuropulmonary manifestations (HR 0.62; 95% CI 0.43-0.90). Pleuropulmonary manifestations independently contributed a decreased survival (HR: 2.79 95% CI 1.80-4.31). Conclusion Pleuropulmonary manifestations are frequent in SLE, particularly pleuritis. Older age, respiratory tract infection, cardiac, systemic and renal involvement were associated with them, whereas cutaneous manifestations were negatively associated. Cardiac compromise, SDI scores ≥1 and anti-La positivity at disease onset were predictive of their subsequent occurrence, whereas cutaneous manifestations were protective. They independently contributed to a decreased survival in these patients.

A closer look at the physical and optical properties of gold nanostars: an experimental and computational study.

A combined experimental and computational study was carried out to design a semi-empirical method to determine the volume, surface area, and extinction coefficients of gold nanostars. The values obtained were confirmed by reconstructing the nanostar 3D topography through high-tilt TEM tomography and introducing the finite elements in COMSOL Multiphysics through which we have also calculated the morphology-dependent extinction coefficient. Doing so, we have, for the first time, modeled the heat losses of a real, experimentally synthesized nanostar, and found the plasmon resonances to be in excellent agreement with those obtained experimentally. We believe that our approach could substantially improve the applicability of this remarkable nanomaterial.

Radiotherapy-induced miR-223 prevents relapse of breast cancer by targeting the EGF pathway.

In breast cancer (BC) patients, local recurrences often arise in proximity of the surgical scar, suggesting that response to surgery may have a causative role. Radiotherapy (RT) after lumpectomy significantly reduces the risk of recurrence. We investigated the direct effects of surgery and of RT delivered intraoperatively (IORT), by collecting irradiated and non-irradiated breast tissues from BC patients, after tumor removal. These breast tissue specimens have been profiled for their microRNA (miR) expression, in search of differentially expressed miR among patients treated or not with IORT. Our results demonstrate that IORT elicits effects that go beyond the direct killing of residual tumor cells. IORT altered the wound response, inducing the expression of miR-223 in the peri-tumoral breast tissue. miR-223 downregulated the local expression of epidermal growth factor (EGF), leading to decreased activation of EGF receptor (EGFR) on target cells and, eventually, dampening a positive EGF-EGFR autocrine/paracrine stimulation loop induced by the post-surgical wound-healing response. Accordingly, both RT-induced miR-223 and peri-operative inhibition of EGFR efficiently prevented BC cell growth and reduced recurrence formation in mouse models of BC. Our study uncovers unknown effects of RT delivered on a wounded tissue and prompts to the use of anti-EGFR treatments, in a peri-operative treatment schedule, aimed to timely treat BC patients and restrain recurrence formation.

Carboxy-terminated immuno-SERS tags overcome non-specific aggregation for the robust detection and localization of organic media in artworks.

Methods combining immunology and surface-enhanced Raman scattering (SERS) have been developed for the simultaneous detection, identification, and localization of proteinaceous binding media found in artworks. However, complex surface topographies and heterogeneous compositions of art samples represent significant challenges for the general optimization of this technique. In particular, aggregation of immuno-SERS nanoparticles can lead to non-specific SERS response across the sample surface, resulting in inaccurate identification of binding media or dubious localization maps. This aggregation also diminishes the sample area available for analysis, as excitation of visible nanoparticle aggregates by the Raman laser must be avoided during data collection. In the present work, we synthesize several types of immuno-SERS nanoparticles and investigate their applicability for the detection and localization of ovalbumin-rich (egg-based) binding media in art samples. Dimers of gold nanoparticles (Au NPs) connected by a Raman-active dithiolated linker are conjugated to secondary antibodies through either an amino or a carboxyl functional group (SERS tags). The SERS tags display localized surface plasmon resonance (LSPR) at 532 nm. SERS spectra are acquired at 633 nm (SERS-633) in order to maximize tuning between laser excitation and LSPR, while avoiding sample burning. In an indirect immunoassay applied to replica art samples, carboxy-terminated SERS-633 tags show strong Raman reporter signal, specificity for the target protein, robust response in the presence of various inorganic pigments, and reduced aggregation on sample surfaces compared to amino-terminated or commercial SERS tags. Scanning electron microscopy (SEM) is used to visualize Au NPs bound to egg media in situ, demonstrating that carboxy-terminated SERS-633 tags remain as discrete dimer units throughout the assay.

Multibacillary leprosy mimicking systemic lupus erythematosus: case report and literature review.

Leprosy is an infectious chronic disease with a wide range of clinical and serological manifestations. We report a case of a woman presenting with a malar rash, painless oral ulcers, photosensitivity, arthritis, positive antinuclear antibodies test and leuko-lymphopenia. Our case illustrates an unusual presentation of leprosy initially diagnosed as systemic lupus erythematosus (SLE). After the confirmation of multibacillary leprosy and multidrug therapy recommended by the World Health Organization, a good clinical response was observed. Recognition of rheumatic manifestations in leprosy is important as they may be confused with SLE. A literature review is presented to encourage clinicians to consider leprosy as a differential diagnosis. Specifically in patients with unusual rheumatic manifestations and persistent skin lesions, and when neurological symptoms are present. Leprosy has not been eradicated, so misdiagnosis can be frequent. It is necessary to increase medical practitioner awareness in order start proper treatment.

Lupus in Latin-American patients: lessons from the GLADEL cohort.

The need for comprehensive published epidemiologic and clinical data from Latin American systemic lupus erythematosus (SLE) patients motivated the late Dr Alarcón-Segovia and other Latin American professionals taking care of these patients to spearhead the creation of the G: rupo L: atino A: mericano D: e E: studio del L: upus (GLADEL) cohort in 1997. This inception cohort recruited a total of 1480 multiethnic (Mestizo, African-Latin American (ALA), Caucasian and other) SLE patients diagnosed within two years from the time of enrollment from 34 Latin American centers with expertise in the diagnosis and management of this disease. In addition to the initial 2004 description of the cohort, GLADEL has contributed to improving our knowledge about the course and outcome of lupus in patients from this part of the Americas. The major findings from this cohort are highlighted in this review. They have had important clinical implications for the adequate care of SLE patients both in Latin America and worldwide where these patients may have emigrated.

Late-onset systemic lupus erythematosus in Latin Americans: a distinct subgroup?

OBJECTIVE: To examine the characteristics of patients who developed late onset systemic lupus erythematosus (SLE) in the GLADEL (Grupo Latino Americano de Estudio del Lupus) cohort of patients with SLE. METHODS: Patients with SLE of less than two years of disease duration, seen at 34 centers of nine Latin American countries, were included. Late-onset was defined as >50 years of age at time of first SLE-related symptom. Clinical and laboratory manifestations, activity index (SLEDAI), and damage index (SLICC/ACR- DI) were ascertained at time of entry and during the course (cumulative incidence). Features were compared between the two patient groups (<50 and ≥50) using descriptive statistics and hypothesis tests. Logistic regression was performed to examine the association of late-onset lupus, adjusting for other variables. RESULTS: Of the 1480 patients included, 102 patients (6.9 %) had late-onset SLE, 87% of which were female. Patients with late-onset SLE had a shorter follow-up (3.6 vs. 4.4 years, p < 0.002) and a longer time to diagnosis (10.1 vs. 5.8 months, p < 0.001) compared to the younger onset group. Malar rash, photosensitivity, and renal involvement were less prevalent while interstitial lung disease, pleural effusions, and sicca symptoms were more frequent in the older age group (p > 0.05). In multivariable analysis, late onset was independently associated with higher odds of ocular (OR = 3.66, 95% CI = 2.15-6.23), pulmonary (OR = 2.04, 95% CI = 1.01-4.11), and cardiovascular (OR = 1.76, 95% CI = 1.04-2.98) involvement and lower odds of cutaneous involvement (OR = 0.41, 95% CI = 0.21-0.80), number of cumulative SLE criteria (OR = 0.79, 95% CI = 0.64-0.97), use of cyclophosphamide (OR = 0.47, 95% CI = 0.24-0.95), and anti-RNP antibodies (OR = 0.43, 95% CI = 0.20-0.91). A Cox regression model revealed a higher risk of dying in older onset than the younger-onset SLE (OR = 2.61, 95% CI = 1.2-5.6). CONCLUSION: Late-onset SLE in Latin Americans had a distinct disease expression compared to the younger-onset group. The disease seems to be mild with lower cumulative SLE criteria, reduced renal/mucocutaneous involvements, and less use of cyclophosphamide. Nevertheless, these patients have a higher risk of death and of ocular, pulmonary, and cardiovascular involvements.

Rituximab versus an alternative TNF inhibitor in patients with rheumatoid arthritis who failed to respond to a single previous TNF inhibitor: SWITCH-RA, a global, observational, comparative effectiveness study.

OBJECTIVES: To compare the effectiveness of rituximab versus an alternative tumour necrosis factor (TNF) inhibitor (TNFi) in patients with rheumatoid arthritis (RA) with an inadequate response to one previous TNFi. METHODS: SWITCH-RA was a prospective, global, observational, real-life study. Patients non-responsive or intolerant to a single TNFi were enrolled ≤4 weeks after starting rituximab or a second TNFi. Primary end point: change in Disease Activity Score in 28 joints excluding patient's global health component (DAS28-3)-erythrocyte sedimentation rate (ESR) over 6 months. RESULTS: 604 patients received rituximab, and 507 an alternative TNFi as second biological therapy. Reasons for discontinuing the first TNFi were inefficacy (n=827), intolerance (n=263) and other (n=21). A total of 728 patients were available for primary end point analysis (rituximab n=405; TNFi n=323). Baseline mean (SD) DAS28-3-ESR was higher in the rituximab than the TNFi group: 5.2 (1.2) vs 4.8 (1.3); p<0.0001. Least squares mean (SE) change in DAS28-3-ESR at 6 months was significantly greater in rituximab than TNFi patients: -1.5 (0.2) vs -1.1 (0.2); p=0.007. The difference remained significant among patients discontinuing the initial TNFi because of inefficacy (-1.7 vs -1.3; p=0.017) but not intolerance (-0.7 vs -0.7; p=0.894). Seropositive patients showed significantly greater improvements in DAS28-3-ESR with rituximab than with TNFi (-1.6 (0.3) vs -1.2 (0.3); p=0.011), particularly those switching because of inefficacy (-1.9 (0.3) vs -1.5 (0.4); p=0.021). The overall incidence of adverse events was similar between the rituximab and TNFi groups. CONCLUSIONS: These real-life data indicate that, after discontinuation of an initial TNFi, switching to rituximab is associated with significantly improved clinical effectiveness compared with switching to a second TNFi. This difference was particularly evident in seropositive patients and in those switched because of inefficacy.