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Objective The objective of this study was to determine the feasibility of low-load resistance training with blood flow restriction (BFR) for people with advanced disability due to multiple sclerosis (MS). Methods In this prospective cohort study, 14 participants with MS (Expanded Disability Status Scale [EDSS] score = 6.0 to 7.0; mean age = 55.4 [SD = 6.2] years; 71% women) were asked to perform 3 lower extremity resistance exercises (leg press, calf press, and hip abduction) bilaterally twice weekly for 8 weeks using BFR. Feasibility criteria were as follows: enrollment of 20 participants, ≥80% retention and adherence, ≥90% satisfaction, and no serious adverse events related to the intervention. Other outcomes included knee extensor, ankle plantar flexor, and hip abductor muscle strength, 30-Second Sit-to-Stand Test, Berg Balance Scale, Timed 25-Foot Walk Test, 12-Item MS Walking Scale, Modified Fatigue Impact Scale, Patient-Specific Functional Scale, and daily step count. Results Sixteen participants consented, and 14 completed the intervention, with 93% adherence overall. All participants were satisfied with the intervention. A minor hip muscle strain was the only intervention-related adverse event. There were muscle strength improvements on the more-involved (16%–28%) and less-involved (12%–19%) sides. There were also changes in the 30-Second Sit-to-Stand Test (1.9 repetitions; 95% CI = 1.0 to 2.8), Berg Balance Scale (5.3 points; 95% CI = 3.2 to 7.4), Timed 25-Foot Walk Test (−3.3 seconds; 95% CI = −7.9 to 1.3), Modified Fatigue Impact Scale (−8.8 points; 95% CI = −16.5 to −1.1), 12-Item MS Walking Scale (−3.6 points; 95% CI = −11.5 to 4.4), Patient-Specific Functional Scale (2.9 points; 95% CI = 1.9 to 3.8), and daily step count (333 steps; 95% CI = −191 to 857). Conclusion Low-load resistance training using BFR in people with MS and EDSS scores of 6.0 to 7.0 appears feasible, and subsequent investigation into its efficacy is warranted. Impact Although efficacy data are needed, combining BFR with low-load resistance training may be a viable alternative for people who have MS and who do not tolerate conventional moderate- to high-intensity training because of more severe symptoms, such as fatigue and weakness. Lay Summary Low-load strength training with BFR was feasible in people who have advanced disability due to MS. Using BFR may provide an alternative for people with MS who do not tolerate higher intensity training due to more severe symptoms, such as fatigue and weakness. [ABSTRACT FROM AUTHOR]

Objective To assess the efficacy and safety of abatacept (ABA) in monotherapy (ABAMONO) vs combined ABA [ABA plus MTX (ABAMTX) or ABA plus non-MTX conventional synthetic DMARDs (csDMARDs) (ABANON-MTX)] in RA patients with interstitial lung disease (ILD) (RA-ILD). Methods This was a restrospective multicentre study of RA-ILD Caucasian patients treated with ABA. We analysed in the three groups (ABAMONO, ABAMTX, ABANON-MTX) the following outcome variables: (i) dyspnoea; (ii) forced vital capacity (FVC) and diffusion capacity of the lung for the carbon monoxide (DLCO); (iii) chest high-resolution CT (HRCT); (iv) DAS28-ESR; (v) CS-sparing effect; and (vi) ABA retention and side-effects. Differences between basal and final follow-up were evaluated. Multivariable linear regression was used to assess the differences between the three groups. Results We studied 263 RA-ILD patients (mean ± s. d. age 64.6 ± 10 years) [ABAMONO (n  = 111), ABAMTX (n  = 46) and ABANON-MTX (n  = 106)]. At baseline, ABAMONO patients were older (67 ± 10 years) and took higher prednisone dose [10 (interquartile range 5–15) mg/day]. At that time, there were no statistically significant differences in sex, seropositivity, ILD patterns, FVC and DLCO, or disease duration. Following treatment, in all groups, most patients experienced stabilization or improvement in FVC, DLCO, dyspnoea and chest HRCT as well as improvement in DAS28-ESR. A statistically significant difference between basal and final follow-up was only found in CS-sparing effect in the group on combined ABA (ABAMTX or ABANON-MTX). However, in the multivariable analysis, there were no differences in any outcome variables between the three groups. Conclusion In Caucasian individuals with RA-ILD, ABA in monotherapy or combined with MTX or with other conventional-DMARDs seems to be equally effective and safe. However, a CS-sparing effect is only observed with combined ABA. [ABSTRACT FROM AUTHOR]

Sepsis, among other pathologies, is an endotoxin tolerance (ET)-related disease. On admission, we classified 48 patients with sepsis into 3 subgroups according to the ex vivo response to lipopolysaccharide. This response correlates with the Acute Physiology and Chronic Health Evaluation (APACHE) II score and the ET degree. Moreover, the ET-related classification determines the outcome of these patients. Programmed cell death-ligand 1 (PD-L1) expression on septic monocytes is also linked with ET status. In addition to the regulation of cytokine production, one of the hallmarks of ET that significantly affects patients with sepsis is T-cell proliferation impairment or a poor switch to the adaptive response. PD-L1/programmed cell death-1 (PD-1) blocking and knockdown assays on tolerant monocytes from both patients with sepsis and the in vitro model reverted the impaired adaptive response. Mechanistically, the transcription factor hypoxia-inducible factor-1α (HIF1α) has been translocated into the nucleus and drives PD-L1 expression during ET in human monocytes. This fact, together with patient classification according to the ex vivo lipopolysaccharide response, opens an interesting field of study and potential personalized clinical applications, not only for sepsis but also for all ET-associated pathologies. [ABSTRACT FROM AUTHOR]