Increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with increased cardiovascular morbidity/mortality and an incompletely understood pathophysiology. In animal studies, central and blood-borne inflammatory cytokines that can be elevated in RA evoke pathogenic increases in sympathetic activity and reductions in baroreflex sensitivity (BRS). We hypothesised that muscle sympathetic nerve activity (MSNA) was increased and BRS decreased in RA. MSNA, blood pressure and heart rate (HR) were recorded in age- and sex-matched RA-normotensive (n = 13), RA-hypertensive patients (RA-HTN; n = 17), normotensive (NC; n = 17) and hypertensive controls (HTN; n = 16). BRS was determined using the modified Oxford technique. Inflammation and pain were determined using serum high sensitivity C-reactive protein (hs-CRP) and a visual analogue scale (VAS), respectively. MSNA was elevated similarly in RA, RA-HTN and HTN patients (32 ± 9, 35 ± 14, 37 ± 8 bursts/min) compared to NC (22 ± 9 bursts/min; P = 0.004). Sympathetic BRS was similar between groups (P = 0.927), while cardiac BRS (cBRS) was reduced in RA, RA-HTN and HTN patients (5[3-8], 4[2-7], 6[4-9] ms/mmHg) compared to NC (11[8-15] ms/mmHg; P = 0.002). HR was independently associated with hs-CRP. Increased MSNA and reduced cBRS were associated with hs-CRP although confounded in multivariable analysis. VAS was independently associated with MSNA burst frequency, cBRS and HR. We provide the first evidence for heightened sympathetic outflow and reduced cBRS in RA that can be independent of hypertension. In RA patients, reported pain was positively correlated with MSNA and negatively correlated with cBRS. Future studies should assess whether therapies to ameliorate pain and inflammation in RA restores autonomic balance and reduces cardiovascular events. This article is protected by copyright. All rights reserved.</p

Determination of putative virulence factors among clinical isolates of enterococci isolated from a military hospital in the eastern province of Saudi Arabia

Background: The pathogenic potential of enterococci to produce life-threatening infections is well-documented. The scientific community has, of late, evinced a renewed interest in the putative virulence factors of enterococci. Objective of the study was to determine the putative virulence factors of clinically isolated Enterococcus species from a military hospital and to describe the association between virulence factors and vancomycin susceptibility.Methods: A total of 245 enterococci were isolated from clinical samples collected from KFMMC, a leading military hospital in the eastern province of Saudi Arabia. Following species identification and antimicrobial susceptibility testing using the Vitek 2 system; the isolates were tested for the production of caseinase, gelatinase, biofilm, and presence of haemolysin.Results: Among the enterococcal isolates, 36.7% produced caseinase, 38% produced gelatinase, 24.1% exhibited biofilm formation, and 30.6% were positive for haemolytic activity. A significant association between vancomycin susceptibility patterns and the virulence factors, gelatinase and haemolytic activity, were noted. No significant associations were observed between vancomycin susceptibility patterns and the presence of caseinase or the formation of biofilms.Conclusions: Virulence factors are invariably produced by several clinical isolates of enterococci in our hospital, and some virulence factors are associated with vancomycin susceptibility

Low-Volume High-Intensity Interval Training in a Gym Setting Improves Cardio-Metabolic and Psychological Health.

BACKGROUND: Within a controlled laboratory environment, high-intensity interval training (HIT) elicits similar cardiovascular and metabolic benefits as traditional moderate-intensity continuous training (MICT). It is currently unclear how HIT can be applied effectively in a real-world environment. PURPOSE: To investigate the hypothesis that 10 weeks of HIT, performed in an instructor-led, group-based gym setting, elicits improvements in aerobic capacity (VO2max), cardio-metabolic risk and psychological health which are comparable to MICT. METHODS: Ninety physically inactive volunteers (42±11 y, 27.7±4.8 kg.m-2) were randomly assigned to HIT or MICT group exercise classes. HIT consisted of repeated sprints (15-60 seconds, >90% HRmax) interspersed with periods of recovery cycling (≤25 min.session-1, 3 sessions.week-1). MICT participants performed continuous cycling (~70% HRmax, 30-45 min.session-1, 5 sessions.week-1). VO2max, markers of cardio-metabolic risk, and psychological health were assessed pre and post-intervention. RESULTS: Mean weekly training time was 55±10 (HIT) and 128±44 min (MICT) (p<0.05), with greater adherence to HIT (83±14% vs. 61±15% prescribed sessions attended, respectively; p<0.05). HIT improved VO2max, insulin sensitivity, reduced abdominal fat mass, and induced favourable changes in blood lipids (p<0.05). HIT also induced beneficial effects on health perceptions, positive and negative affect, and subjective vitality (p<0.05). No difference between HIT and MICT was seen for any of these variables. CONCLUSIONS: HIT performed in a real-world gym setting improves cardio-metabolic risk factors and psychological health in physically inactive adults. With a reduced time commitment and greater adherence than MICT, HIT offers a viable and effective exercise strategy to target the growing incidence of metabolic disease and psychological ill-being associated with physical inactivity

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Association Between Corrected QT Interval and Inflammatory Cytokines in Rheumatoid Arthritis

Objective.Corrected QT (QTc) interval predicts all-cause and cardiovascular mortality and may contribute to the increased mortality risk in rheumatoid arthritis (RA). Animal experiments have shown that proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin 1 (IL-1)] can prolong cardiomyocyte action potential. We sought to determine whether elevations in circulating inflammatory cytokines were independently associated with QTc prolongation in patients with RA.Methods.One hundred twelve patients [median age 62 (interquartile range 17) yrs; 80 women (71%)] from a well-characterized RA cohort underwent baseline 12-lead electrocardiograms for QT interval measurement and contemporary blood sampling to assess concentrations of inflammatory markers including C-reactive protein (CRP), TNF-α, and interleukins (IL-1α, IL-1β, IL-6, IL-10). QTc was calculated using the Bazett (QTBAZ= QT ÷ √RR) and Framingham Heart Study (QTFHS= QT + 0.154 × [1 – RR]) heart rate correction formulas.Results.Inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-10) were positively correlated with QTBAZ(Spearman rank correlation coefficient rho = 0.199, 0.210, 0.222, 0.333; all p &lt; 0.05). In multivariable regression analysis, these associations were all confounded by age except IL-10, where higher tertile groups were independently and positively associated with QTBAZ(β = 0.202, p = 0.023) and QTFHS(β = 0.223, p = 0.009) when compared to the lower tertile. CRP (per unit increase) was independently associated with QTBAZ(β = 0.278, p = 0.001), but not QTFHS.Conclusion.To our knowledge, ours is the first study demonstrating a contemporary link between inflammatory cytokines and QT interval in humans. Our results suggest that a lower inflammatory burden may protect against QTc prolongation in patients with RA. However, further studies are required to confirm the effects of pro- and antiinflammatory cytokines on QTc interval.</jats:sec

Muscle metaboreflex and autonomic regulation of heart rate in humans

We elucidated the autonomic mechanisms whereby heart rate (HR) is regulated by the muscle metaboreflex. Eight male participants (22 ± 3 years) performed three exercise protocols: (1) enhanced metaboreflex activation with partial flow restriction (bi-lateral thigh cuff inflation) during leg cycling exercise, (2) isolated muscle metaboreflex activation (post-exercise ischaemia; PEI) following leg cycling exercise, (3) isometric handgrip followed by PEI. Trials were undertaken under control (no drug), β(1)-adrenergic blockade (metoprolol) and parasympathetic blockade (glycopyrrolate) conditions. HR increased with partial flow restriction during leg cycling in the control condition (Δ11 ± 2 beats min(−1); P < 0.05). The magnitude of this increase in HR was similar with parasympathetic blockade (Δ11 ± 2 beats min(−1)), but attenuated with β-adrenergic blockade (Δ4 ± 1 beats min(−1); P < 0.05 vs. control and parasympathetic blockade). During PEI following leg cycling exercise, HR remained similarly elevated above rest under all conditions (Δ11 ± 2, Δ13 ± 3 and Δ9 ± 4 beats min(−1), for control, β-adrenergic and parasympathetic blockade; P > 0.05 between conditions). During PEI following handgrip, HR was similarly elevated from rest under control and parasympathetic blockade (Δ4 ± 1 vs. Δ4 ± 2 beats min(−1); P > 0.05 between conditions) conditions, but attenuated with β-adrenergic blockade (Δ0.2 ± 1 beats min(−1); P > 0.05 vs. rest). Thus muscle metaboreflex activation-mediated increases in HR are principally attributable to increased cardiac sympathetic activity, and only following exercise with a large muscle mass (PEI following leg cycling) is there a contribution from the partial withdrawal of cardiac parasympathetic tone