Extra-low dose combinat ion of two anticytokines reduces disease activity and cardiovascular events Immunotherapy reduces cardiovascular risk in patients with rheumatoid arthritis, according to research presented by Professor Aida Babaeva, head of the Department of Internal Medicine, Volgograd State Medical University, Volgograd, Russia. The combination of two extralow dose anticytokine drugs reduced rheumatoid arthritis disease activity and cardiovascular events.
‘Rheumatoid arthritis is an autoimmune disease in which cytokines such as tumour necrosis factor (TNF) and interferon (IFN), which normally protect the
body, attack healthy cells,’ said Professor Babaeva. ‘Patients have painful and inflamed joints. They are also at increased cardiovascular risk, particularly if their rheumatoid arthritis is not controlled.’
Professor Babaeva’s previous research showed that treatment with anticytokine drugs can decrease the activity of rheumatoid arthritis. Extra-low dose anti-TNFα reduced levels of inflammatory mediators and cytokines including C-reactive protein (CRP), rheumatoid factor, TNF, interleukin-1 (IL-1), and interleukin-6 (IL-6). The effect was more apparent and developed earlier when patients were treated with a combination of anti-TNFα and anti-IFNγ both at extra-low doses.
The current study investigated the impact of the combination of drugs on cardiovascular events. It included 68 patients who had suffered from active rheumatoid arthritis for at least five years. Patients were randomized to receive the combination of anti-TNFα and anti-IFNγ plus standard disease-modifying therapy (38 patients) or placebo plus standard therapy (30 patients). During the three year follow up period the investigators monitored rheumatoid arthritis disease activity and cardiovascular events.
Patients taking the combination of anticytokines had a lower rheumatoid arthritis disease activity score, as measured by the DAS28,2 and more dramatic decreases in IL-1, IL-6 and TNFα than the group on standard therapy alone.
The incidence of cardiovascular events (unstable angina, severe hypertensive crisis, and deterioration of chronic heart failure) was more than double in the group on conventional disease-modifying drugs alone (37percent) compared to those also taking the combination of anticytokines (13percent).
Professor Babaeva said: ‘Our findings suggest that the decreased  rheumatoid arthritis disease activity with the combination of anticytokines translates into decreased cardiovascular risk. Rheumatoid arthritis promotes the development of cardiovascular disease in a number of ways. Therefore, decreasing disease activity may also reduce cardiovascular risk by slowing down or halting these processes.’
For example, rheumatoid arthritis is associated with dysfunction of the blood  vessel lining (called endothelium), which leads to lipid accumulation in the artery wall, plaque formation and atherosclerosis. Increased disease activity is also linked with a pro-coagulant state in which patients are more prone to blood clots and thrombosis. Patients with active disease have an increase in molecules that promote inflammation, which has been associated with an increased risk of cardiovascular disease.
In patients with hypertension, target blood pressure was reached in 71percent of those taking the combination of anticytokines compared to just 32percent of patients on standard therapy alone.
Professor Babaeva said: ‘This doesn’t mean that the two drugs directly impact on blood pressure. But the combination can improve endothelial function and it could be that blood pressure is more stable when disease activity is low.’
‘We found that the combination of two anticytokines containing extra-low doses of antibodies against TNFα and IFNγ can improve the efficacy of standard rheumatoid arthritis therapy and decrease cardiovascular risk,’ said Professor Babaeva.

European Society of Cardiology http://tinyurl.com/gny3vyg

Hospitalization in an intensive care unit (ICU) can be a frightening and sometimes traumatizing experience for patients. Although engaging the patient and improving communication among the clinical team can positively impact care and the patient experience, the ICU environment can be a challenging place to engage patients. In new research, led by Brigham and Women’s Hospital, researchers tested a structured and technology-centred program that was focused on team communication and patient engagement. They found that this approach was associated with a lower rate of adverse events and improved patient satisfaction. Results of this project, named PROSPECT (Promoting Respect and Ongoing Safety through Patient Engagement Communication and Technology), have recently been published.
“Our goal was to shift our clinical thinking from ‘What is the matter?’ to discovering ‘What matters to you?’” said Patricia Dykes, PhD, RN, a senior nurse scientist in the Center for Patient Safety, Research and Practice at BWH and lead author of the paper. “If we can effectively collaborate with our patients and their care partners and engage them in their care, then we have the potential to enhance the care, improve adherence to care plans, positively impact satisfaction rates and reduce healthcare costs.”
Researchers developed an intervention to support integrated, multidisciplinary patient-centred communication characterized by shared checklists, health information, and goals of care articulated by both clinicians and patients. The aim of the intervention, which was tested in two medical ICUs at BWH and included 1,075 patients and their care partners, was to reduce adverse events defined as falls, pressure ulcers, catheter-associated urinary tract infections and ventilator-associated events. Secondarily, the team also sought to improve patient and care partners’ satisfaction rates, agreement on care plans between patient and providers, and healthcare utilization.
The specific interventions were systems-based and included a 60-min training session for all clinicians involved in the study. The training introduced a standard model for care meant to enhance clinicians’ responsiveness to the needs, concerns and expectations of the patients and their care partners as well as training on a web-based toolkit to facilitate team communication and patient engagement. The web-based toolkit included an ICU safety checklist that populated with real-time data from the patient’s electronic health record (EHR). The toolkit also included shared care planning and messaging tools accessed by clinicians through the EHR and by patients and care partners through a bedside portal on an iPad. Eighteen percent of patients and care partners used the portal to document their goals of care, their preferences, and to directly communicate.
When compared to a similar group of ICU patients, researchers found that the intervention was associated with a 29 percent reduction in adverse events. The reduction was determined by the drop in adverse events per 1,000 patient days. Patient days are the total number of days for all patients who were admitted for an episode of care, for example, 20 patients in a hospital for 1 day would represent 20 patient days. The rate fell from 59 per 1,000 patient days in the baseline period to 41.9 per 1,000 patient days in the intervention period, driven by a drop in the number of catheter-associated urinary tract infections and pressure ulcers. While researchers are unable to determine which specific component of the intervention drove this reduction, they suspect it is due largely to implementation of the electronic check list, as only a small percentage of patients or care partners participated through the portal.
“We took the paper checklist that is widely used in ICUs across the country and enhanced it with technology. This allowed more patient-specific information to be available to the multidisciplinary group of clinicians that were making daily decisions about a patient’s care while they executed the checklist,” said Dykes. “For example, if you’re deciding whether or not to remove a catheter or a central line, it is extremely helpful to know the type of catheter and when it was put in. When using a paper check list, that information is not available, but if you transition that checklist to a web-based tool that pulls data from a patient’s electronic health record, then you can make a much more informed decision.”
Researchers also found an improvement in patient satisfaction scores, which were captured through a survey of a subsample of patients and care partners. Ninety-three percent of patients in the intervention who responded to the survey assigned a top score to their overall hospital rating score compared to 71.8 percent of patients in the baseline group. Care partner satisfaction also improved, from 84.3 to 90 percent. Changes in concordance of the care plan between the care team and patients was not observed and resource utilization did not significantly change between the intervention and baseline groups.

Brigham and Women’s Hospital
www.brighamandwomens.org/about_bwh/publicaffairs/news/pressreleases/PressRelease.aspx?sub=0&PageID=2782

Having a stroke damages immune cells as well as affecting the brain, research has found. The findings help explain why patients have a greater risk of catching life-threatening infections, such as pneumonia, after having a stroke.

Therapies that boost survival of the affected immune cells or compensate for their damage could help improve the recovery of stroke patients, the researchers say.

The study found that patients have reduced levels of protective antibodies in their blood after having a stroke, which might explain why they are more susceptible to infections. Tests with mice revealed those which experienced a stroke had fewer numbers of specialised immune cells called marginal zone B cells, which produce antibodies. Affected mice were more susceptible to bacterial lung infections, the researchers found. Loss of the B cells was caused by a chemical called noradrenaline produced by nerves activated during stroke.

Researchers, led by the University of Edinburgh’s Roslin Institute, found they could protect the mice from infections using a therapy to block the effects of noradrenaline.

We now plan to build on our findings by developing and testing new treatments that can block or bypass these immune deficits with B cells a particular target.

Noradrenaline is part of the body’s fight or flight response. It helps to prepare the body for action and has a range of effects, such as raising heart rate, boosting blood supply and triggering the release of energy from stores.

Blocking noradrenaline would probably be too dangerous in stroke patients, the researchers caution.

They say development of other therapies that block or bypass the damage to the immune system could offer new approaches to help cut the risk of infection after stroke.

University of Edinburgh www.ed.ac.uk/news/2017/immune-discovery-points-to-stroke-therapy

A new study shows that a hybrid molecular imaging system unites three imaging modalities to map the composition of dangerous arterial plaques before they rupture and induce a major cardiac event.
Certain types of plaques associated with atherosclerosis are prone to instability and tend to break apart, which can lead to embolism and sudden death, if left untreated. Lesions called thin-cap fibro atheroma (TCFA) are especially prone to rupture. Stanford University researchers have developed a scanner that unites optical, radioluminescence, and photoacoustic imaging to evaluate for TCFA.
“This is the first clinical imaging system able to detect vulnerable plaque in their earliest stages,” said Raiyan T. Zaman, PhD, instructor of cardiovascular medicine at Stanford University School of Medicine in Stanford, Calif. “Our novel imaging system can detect these vulnerable plaques despite their small size, complex biochemistry and morphology. This could lead to a paradigm shift in the way coronary artery disease is diagnosed and assessed.”
Early diagnosis and treatment could save lives by preventing the progression, and subsequent rupture, of these plaques. That is precisely why researchers designed the Circumferential-Intravascular-Radioluminescence-Photoacoustic-Imaging (CIRPI) system, which allows not just high-acuity optical imaging via beta-sensitive probe, but also radioluminescent marking inside the artery to determine the extent of inflammation. Photoacoustic imaging also provides information about the often-complex biological makeup of the plaques (how much is calcified or comprised of cholesterol or triglycerides).
“This is an important and potentially life-saving tool that could one day be used by interventional cardiologists to identify the appropriate treatment plan for patients at risk of future TCFA rupture,” explained Zaman.
For this study, researchers focused on atherosclerotic samples of both human and mouse carotid arteries and performed CIRPI following injection of fluorine-18 fluorodeoxyglucose (18F-FDG). Photoacoustic lasers were used at different wavelengths to delineate plaque composition. The result was a never-before-seen 360-degree perspective of arterial plaque burden, confirmed effective by follow-up radiography, ultrasound and histology.

Society of Nuclear Medicine and Molecular Imaging www.snmmi.org/NewsPublications/NewsDetail.aspx?ItemNumber=24263