Comparative validation of the knee inflammation MRI scoring system and the MRI osteoarthritis knee score for semi-quantitative assessment of bone marrow lesions and synovitis-effusion in osteoarthritis: an international multi-reader exercise.

Background: Bone marrow lesions (BMLs) and synovitis on magnetic resonance imaging (MRI) are associated with symptoms and predict degeneration of articular cartilage in osteoarthritis (OA). Validated methods for their semiquantitative assessment on MRI are available, but they all have similar scoring designs and questionable sensitivity to change. New scoring methods with completely different designs need to be developed and compared to existing methods. Objectives: To compare the performance of new web-based versions of the Knee Inflammation MRI Scoring System (KIMRISS) with the MRI OA Knee Score (MOAKS) for quantification of BMLs and synovitis-effusion (S-E). Design: Retrospective follow-up cohort. Methods: We designed web-based overlays outlining regions in the knee that are scored for BML in MOAKS and KIMRISS. For KIMRISS, both BML and S-E are scored on consecutive sagittal slices. The performance of these methods was compared in an international reading exercise of 8 readers evaluating 60 pairs of scans conducted 1 year apart from cases recruited to the OA Initiative (OAI) cohort. Interobserver reliability for baseline status and baseline to 1 year change in BML and S-E was assessed by intra-class correlation coefficient (ICC) and smallest detectable change (SDC). Feasibility was assessed using the System Usability Scale (SUS). Results: Mean change in BML and S-E was minimal over 1 year. Pre-specified targets for acceptable reliability (ICC ⩾ 0.80 and ⩾ 0.70 for status and change scores, respectively) were achieved more frequently for KIMRISS for both BML and synovitis. Mean (95% CI) ICC for change in BML was 0.88 (0.83-0.92) and 0.69 (0.60-0.78) for KIMRISS and MOAKS, respectively. KIMRISS mean SUS usability score was 85.7 and at the 95th centile of ranking for usability versus a score of 55.4 and 20th centile for MOAKS. Conclusion: KIMRISS had superior performance metrics to MOAKS for quantification of BML and S-E. Both methods should be further compared in trials of new therapies for OA.

The OMERACT Knee Inflammation MRI Scoring System: Validation of quantitative methodologies and tri-compartmental overlays in osteoarthritis.

OBJECTIVE: To validate a revised version of the KIMRISS method for quantification of BML and synovitis-effusion in the knee by comparison with an established method, MOAKS. METHODS: Novel calibration tools were developed for both methods. We compared reliability for status and change scores of BML and synovitis-effusion on baseline and one-year MRI scans. RESULTS: Significant increase in both BML and synovitis-effusion was evident using KIMRISS but only for synovitis-effusion using MOAKS. Pre-specified targets for acceptable reliability (≥0.80 and ≥0.70 for status and change scores, respectively) were achieved more frequently for KIMRISS for both BML and synovitis. CONCLUSION: Per OFISA criteria, KIMRISS should progress to assessment of discrimination.

Decision-Making, Ethics, and End-of-Life Care in Pediatric Extracorporeal Membrane Oxygenation: A Comprehensive Narrative Review.

OBJECTIVES: Pediatric extracorporeal membrane oxygenation is associated with significant morbidity and mortality. We sought to summarize literature on communication and decision-making, end-of-life care, and ethical issues to identify recommended approaches and highlight knowledge gaps. DATA SOURCES: PubMed, Embase, Web of Science, and Cochrane Library. STUDY SELECTION: We reviewed published articles (1972-2020) which examined three pediatric extracorporeal membrane oxygenation domains: 1) decision-making or communication between clinicians and patients/families, 2) ethical issues, or 3) end-of-life care. DATA EXTRACTION: Two reviewers independently assessed eligibility using Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. DATA SYNTHESIS: Of 2,581 publications screened, we identified one systematic review and 35 descriptive studies. No practical guides exist for communication and decision-making in pediatric extracorporeal membrane oxygenation. Conversation principles and parent/clinician perspectives are described. Ethical issues related to consent, initiation, discontinuation, resource allocation, and research. No patient-level synthesis of ethical issues or end-of-life care in pediatric extracorporeal membrane oxygenation was identified. CONCLUSIONS: Despite numerous ethical issues reported surrounding pediatric extracorporeal membrane oxygenation, we found limited patient-level research and no practical guides for communicating with families or managing extracorporeal membrane oxygenation discontinuation.

Do high doses of AT(1)-receptor blockers attenuate central sympathetic outflow in humans with chronic heart failure?

In patients with CHF (chronic heart failure) sympathetic activity increases as cardiac performance decreases and filling pressures increase. We hypothesized that in patients with mild-to-moderate CHF, higher than conventional doses of an AT1-receptor [AngII (angiotensin II) type 1 receptor] antagonist would achieve greater central AT1-receptor blockade, resulting in diminished MSNA (muscle sympathetic nerve activity) and augmented MSNA variability, two indices of central effects on sympathetic outflow. In total, 13 patients with ischaemic cardiomyopathy [NYHA (New York Heart Association) class II-III] were weaned off all pharmacological RAS (renin-angiotensin system) modifiers, and then randomized to receive a low (50 mg/day) or high (200 mg/day) dose of losartan. Central haemodynamics, MSNA and its variability, plasma catecholamines, AngI (angiotensin I) and AngII and aldosterone were assessed both before and 3 months after randomization. Neither dose altered BP (blood pressure), PCWP (pulmonary capillary wedge pressure) or CI (cardiac index) significantly. Compared with 50 mg daily, losartan 200 mg/day decreased MSNA significantly (P<0.05), by approximately 15 bursts/min, and increased MSNA variability within the 0.27-0.33 Hz high-frequency range by 0.11 units(2)/Hz (P=0.06). PNE [plasma noradrenaline (norepinephrine)] fell in parallel with changes in MSNA (r=0.62; P<0.05). These findings support the hypothesis that higher than conventional doses of lipophilic ARBs (AT1-receptor blockers) can modulate the intensity and variability of central sympathetic outflow in patients with CHF. The efficacy and safety of this conceptual change in the therapeutic approach to heart failure merits prospective testing in clinical trials.

Sleep restriction leads to increased activation of brain regions sensitive to food stimuli.

BACKGROUND: Epidemiologic evidence shows an increase in obesity concurrent with a reduction in average sleep duration among Americans. Although clinical studies propose that restricted sleep affects hormones related to appetite, neuronal activity in response to food stimuli after restricted and habitual sleep has not been investigated. OBJECTIVE: The objective of this study was to determine the effects of partial sleep restriction on neuronal activation in response to food stimuli. DESIGN: Thirty healthy, normal-weight [BMI (in kg/m²): 22-26] men and women were recruited (26 completed) to participate in a 2-phase inpatient crossover study in which they spent either 4 h/night (restricted sleep) or 9 h/night (habitual sleep) in bed. Each phase lasted 6 d, and functional magnetic resonance imaging was performed in the fasted state on day 6. RESULTS: Overall neuronal activity in response to food stimuli was greater after restricted sleep than after habitual sleep. In addition, a relative increase in brain activity in areas associated with reward, including the putamen, nucleus accumbens, thalamus, insula, and prefrontal cortex in response to food stimuli, was observed. CONCLUSION: The findings of this study link restricted sleep and susceptibility to food stimuli and are consistent with the notion that reduced sleep may lead to greater propensity to overeat.

Activity with ambulation attenuates diuretic responsiveness in chronic heart failure.

INTRODUCTION: We hypothesized that discharged heart failure (HF) patients could develop clinical congestion despite adhering to prescribed diuretics, because ambulation attenuates diuretic and natriuretic responsiveness. METHODS: We studied 9 patients aged 57 ± 13 (mean ± SD) years with New York Heart Association functional class II-III symptoms and ejection fraction <40% (28 ± 7%) and receiving furosemide (≥80 mg/d [113 ± 53 mg/d]) plus renin-angiotensin system antagonists and beta-blockade. Inulin and p-amminohippuric acid were infused to estimate glomerular filtration rate (GFR) and renal plasma flow (RPF). Furosemide was administered intravenously at 75% of the usual oral morning dose. Participants were randomized to supine (90 minutes recumbancy) or upright (90 minutes sitting and treadmill walking) posture and assumed the other position on their second day. Primary outcome variables were urine volume and sodium excretion 90 minutes after furosemide. RESULTS: On the upright, compared with the supine, day, urine volume (792 ± 484 vs 1,290 ± 503 mL; P = .02) and sodium (79 ± 55 vs 141 ± 61 mmol; P < .01) were attenuated, whereas plasma norepinephrine (4.4 ± 2.7 vs 2.3 ± 1.8 mmol/L; P = .01) and renin (327 ± 250% of supine; P < .01) were augmented. Urinary K+, mean pressure, GFR, and RPF were similar. CONCLUSIONS: Activation of the sympathetic nervous system and renin-angiotensin axis by upright ambulation may attenuate diuresis and natriuresis by increasing proximal tubular reabsorption of sodium and water.

Effect of angiotensin AT1 receptor blockade on sympathetic responses to handgrip in healthy men.

BACKGROUND: To determine whether angiotensin II (ANG II) contributes to the reflex skeletal muscle sympathoexcitation elicited by isometric and isotonic exercise, we tested the hypothesis that angiotensin AT(1) receptor blockade (ARB) would attenuate reflex sympathoneural responses to handgrip (HG) and to post-handgrip ischemia (PHGI). METHODS: Seventeen healthy men were studied before and 1 week after random double-blind crossover allocation to oral losartan (100 mg daily) and placebo. Heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) were recorded at rest, and during 2 min bouts of isotonic HG at 50% maximum voluntary contraction (MVC) and isometric HG at 30% MVC, performed randomly, each followed by 2 min of PHGI. RESULTS: At rest, losartan doubled plasma renin (P = 0.01) and ANG II (P = 0.03) concentrations, and lowered BP (P < 0.01) yet had no effect on MSNA burst frequency or incidence. HR trended higher (P = 0.060). Losartan's hypotensive effect persisted throughout each exercise bout (P < 0.045). MSNA and HR responses to isotonic exercise and postexercise ischemia were not affected by losartan. Isometric exercise and postexercise ischemia increased MSNA on both sessions (all P < 0.01). Losartan augmented the HR response (P ≤ 0.03), and after losartan MSNA burst frequency (P < 0.01) and incidence (P < 0.04) were significantly higher at all time points, but the magnitude of the MSNA response to isometric exercise and postexercise ischemia was unchanged. CONCLUSION: In healthy men, short-term ARB does not attenuate reflex sympathoneural responses to HG or PHGI.