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

Patients with a combination of left ventricular dysfunction and low aortic valve gradient, or reduced force of blood flow through the aortic valve, have higher mortality rates and a greater risk of recurrent heart failure after transcatheter aortic valve replacement (TAVR), with low aortic valve gradient the driving force behind their poor outcomes.
Patients with this profile, however, should still be considered for TAVR, especially since research on similar patients who had surgical valve replacement found that they could withstand the procedure, Suzanne J. Baron, M.D., M.Sc., the study’s lead author, said.
Low aortic valve gradient is a result of aortic stenosis, a narrowing of the opening of the aortic valve. This condition results in restricted blood flow from the left ventricle to the aorta. Stenosis can also lead to impaired left ventricular ejection fraction, meaning that the heart pumps an inadequate amount of blood with each beat.
To treat aortic stenosis, physicians typically replace the aortic valve, either through open heart surgery or through TAVR. During TAVR, a new valve is delivered to the heart through arteries in the leg or chest. For patients at high risk of surgical complications, TAVR has been shown to be at least as effective as open heart surgery.
Previous studies of valve replacement through surgery have shown that patients with impaired left ventricular ejection fraction and low aortic valve gradient do not do as well as those with better cardiac function and blood flow. In this study, researchers set out to determine the roles that left ventricular dysfunction and low aortic valve gradient play in rates of death and recurrent heart failure following this less invasive procedure.
Since left ventricular dysfunction and low aortic valve gradient are oft en seen together, researchers aimed to determine which of these factors was the driving force behind the poor clinical outcomes. Aft er adjusting for several clinical factors, including age, sex, previous cardiovascular bypass grafting, and previous angioplasty, only the presence of a low aortic valve gradient was associated with higher mortality rates and recurrent heart failure. The effect of left ventricular ejection fraction was no longer significant.
Baron, a cardiologist at Saint Luke’s Mid America Heart Institute, University of Missouri-Kansas City, in Kansas City, Missouri, said the finding that left ventricular dysfunction was not independently associated with long-term mortality after adjusting for clinical factors "provides important reassurance regarding the benefits of TAVR, even in patients with severe left ventricular dysfunction." The study results also suggest that patients with a low aortic valve gradient may be a subset of aortic stenosis patients who have less long-term benefit from this procedure, although the majority of these patients who were still alive one year after the procedure had improved quality of life. Baron concludes that "neither severe left ventricular dysfunction nor low aortic valve gradient alone or in combination provide sufficient prognostic discrimination to preclude treatment with TAVR in the absence of other adverse prognostic factors."

The American College of Cardiology http://tinyurl.com/zw28rc4

Early bicycle exercise during their stay in a hospital intensive care unit (ICU) may help some patients recover more quickly.
Researchers at McMaster University and St. Joseph’s Healthcare Hamilton have demonstrated that physiotherapists can safely start in-bed cycling sessions with critically ill, mechanically ventilated patients early on in their ICU stay.
‘People may think that ICU patients are too sick for physical activity, but we know that if patients start in-bed cycling two weeks into their ICU stay, they will walk farther at hospital discharge,’ says the study’s lead author Michelle Kho, an assistant professor with the School of Rehabilitation Science at McMaster University and physiotherapist at St. Joseph’s Healthcare Hamilton.
‘Our TryCYCLE study builds on this previous work and finds it is safe and feasible to systematically start in-bed cycling within the first four days of mechanical ventilation and continue throughout a patient’s ICU stay.’
Patients who survive their ICU stay are at high risk for muscle weakness and disability, and muscle atrophy and weakness starts within days of a patient’s admission to the ICU. Cycling targets the legs, especially the hip flexors, which are most vulnerable to these effects during bed rest.
By strengthening their muscles and overall health, patients may go home sooner, stronger and happier. This not only benefits the patient, but could alleviate the high cost of critical care for the healthcare system. TryCYCLE is the first of a series of studies that will determine the effects of early in-bed cycling with critically ill patients.
Over a year, Kho and her team conducted a study of 33 patients in the ICU at St. Joseph’s Healthcare Hamilton. The special in-bed cycling equipment was provided by the St. Joseph’s Healthcare Foundation.
Patients were 18 years of age or older, receiving mechanical ventilation, and walking independently prior to admission to the ICU. The treatment in the ICU was 30 minutes of supine cycling using a motorized stationary bicycle affixed to the bed, six days a week.
The researchers found that early cycling within the first four days of mechanical ventilation among patients with stable blood flow is safe and feasible. Patients started cycling within the first three days of ICU admission and cycled about 9 km on average during their ICU stay.

McMaster University http://tinyurl.com/h7bqgbv

New research from Karolinska Institutet refutes the findings of a previous study indicating a possible higher risk of death after sex-discordant blood transfusions for cardiac surgery.

In a study researchers from Karolinska Institutet and Lund University examined how sex-discordant blood transfusions (i.e. blood from a woman to a man or vice versa) affected survival following cardiac surgery. The study was conducted on data from the SWEDEHEART registry and the SCANDAT2 database on almost 50,000 patients who underwent cardiac surgery from 1997 to 2012 in Sweden.
This study was done after a previous Swedish study from earlier in the year indicated a possible increased risk of death after cardiac surgery from sex-discordant blood transfusions.

‘The consequences of the findings from this first study, if proved true, would have been immense and necessitated radical changes to how blood transfusions are managed around the world,’ says Martin Holzmann from Karolinska Institutet.

In the new study, however, the team found no association between sex-discordant blood transfusions and post-cardiac surgery survival.

Martin Holzmann, lead author of the new study continues:
‘Our results clearly show that there is no real connection between sex-discordant blood transfusions and the risk of death.’
The reason for the difference between the studies is that the new one fully compensated for the fact that more transfusions increase the risk of death and of a mismatch between the sex of the donor and the patient. The researchers conclude from their results that current gender-blind blood transfusion procedures are safe and do not need changing.

Karolinska Institute ki.se/en/news/no-association-between-sex-discordant-blood-transfusions-and-risk-of-death

A new study from Karolinska Institutet shows that short-course preoperative radiotherapy combined with delayed surgery reduces the adverse side-effects of rectal cancer surgery without compromising its efficacy.

Rectal cancer affects some 2,000 men and women in Sweden every year. Preoperative radiotherapy was gradually introduced in the early 1990s, with a consequent improvement in prognosis for people with rectal cancer and reduction in the risk of local recurrence.

‘Back then we showed that preoperative radiotherapy reduces the risk of local recurrence by over 50 per cent for patients with rectal cancer,’ says principal investigator Anna Martling, senior consultant surgeon and professor at Karolinska Institutet’s Department of Molecular Medicine and Surgery. ‘Thanks to our results, radiotherapy is recommended to many rectal cancer patients.’
However, radiotherapy can cause adverse reactions and the optimal radiotherapeutic method and the interval between it and the ensuing surgery have been mooted.

The study is based on the claim that the adverse effects of rectal cancer treatment can be reduced by administering more but lower doses of radiation for a longer time, or by increasing the interval between radiotherapy and surgery. These hypotheses have now been tested in a study in which rectal cancer patients were randomly assigned to three different treatment arms:

• Standard therapy, i.e. short-course (5×5 Gy) radiotherapy with direct surgery within a week.
• Delayed surgery with short-course (5×5 Gy) radiotherapy followed by surgery after 4-8 weeks.
• Delayed surgery with long-course (25×2 Gy) radiotherapy followed by surgery after 4-8 weeks.

The results of the study show that patients with delayed surgery develop fewer complications with equally good oncological outcomes. It also showed that there is no difference between long-course and short-course radiotherapy other than that the former considerably lengthens the time for treatment.
Improved therapeutic strategies
‘The results of the study will give rise to improved therapeutic strategies, fewer complications with a sustained low incidence of local recurrence, and better survival rates for rectal cancer patients,’ says Professor Martling. ‘The results can now be immediately put to clinical use to the considerable benefit of the patients.’

Karolinska Institute ki.se/en/news/new-method-reduces-adverse-effects-of-rectal-cancer-treatment