Serum Interferon (IFN)-Neutralizing Antibodies and Bioactivities of IFNs in Patients with Severe Type II Essential Mixed Cryoglobulinemia

The efficacy of alpha interferon (IFN-α) in the treatment of severe type II essential mixed cryoglobulinemia (EMC) has been reported previously. In some patients, the development of neutralizing antibodies to recombinant IFN-α (rIFN-α) can affect the clinical response achieved with rIFN-α; a second treatment with natural IFN-α preparations may reinduce the clinical response. In the present study the ability of leukocyte IFN (LeIFN) to restore the response was investigated from a pharmacodynamic viewpoint. Specifically, the pharmacodynamic profiles of different IFN-α preparations were studied by measuring the serum neopterin levels and the levels of expression of protein MxA mRNA in in vivo peripheral blood mononuclear cells in two patients with EMC whose resistance to rIFN-α2a treatment increased concomitantly with the development of neutralizing antibodies. These markers were measured before injection and at 24 and 48 h after a single injection of rIFN-α2a, consensus IFN [(C)IFN], or LeIFN. No increase or only a slight increase in MxA mRNA levels was detectable after administration of rIFN-α2a or (C)IFN, whereas a significant increase (≥10-fold) in MxA mRNA expression was recorded following administration of LeIFN. The neutralizing antibodies to rIFN-α2a cross-react with (C)IFN. Sera from these patients neutralized most but not all of the subtypes present in the natural IFN-α (LeIFN) mixture, and no significant increase in neopterin levels was observed after these patients were switched to LeIFN treatment. In summary, the data demonstrate that the problem of neutralizing antibodies still exists and that LeIFN may induce an increase in the level of MxA mRNA expression but not an increase in neopterin levels in patients who are resistant to treatment with rIFN-α2a or (C)IFN.     

Prognostic value of aerobic capacity and exercise oxygen pulse in postaortic dissection patients

BackgroundAlthough recommendations encourage daily moderate activities in post aortic dissection, very little data exists regarding cardiopulmonary exercise testing (CPET) to personalize those patient''s physical rehabilitation and assess their cardiovascular prognosis.DesignWe aimed at testing the prognostic insight of CPET regarding aortic and cardiovascular events by exploring a prospective cohort of patients followed‐up after acute aortic dissection.MethodsPatients referred to our department after an acute (type A or B) aortic dissection were prospectively included in a cohort between September 2012 and October 2017. CPET was performed once optimal blood pressure control was obtained. Clinical follow‐up was done after CPET for new aortic event and major cardio‐vascular events (MCE) not directly related to the aorta.ResultsAmong the 165 patients who underwent CPET, no adverse event was observed during exercise testing. Peak oxygen pulse was 1.46(1.22‐1.84) mlO2/beat, that is, 97 (83–113) % of its predicted value, suggesting cardiac exercise limitation in a population under beta blockers (92% of the population). During a follow‐up of 39(20‐51) months from CPET, 42 aortic event recurrences and 22 MCE not related to aorta occurred. Low peak oxygen pulse (<85% of predicted value) was independently predictive of aortic event recurrence, while low peak oxygen uptake (<70% of predicted value) was an independent predictor of MCE occurrence.ConclusionCPET is safe in postaortic dissection patients should be used to not only to personalize exercise rehabilitation, but also to identify those patients with the highest risk for new aortic events and MCE not directly related to aorta.     

Effect of body weight changes on 24-hour blood pressure and left ventricular mass in hypertension: a 4-year follow-up

BACKGROUND: Few data are available on the long-term effects of weight loss on 24-h blood pressure (BP) and left ventricular mass in overweight hypertensive patients. METHODS: A total of 181 never-treated overweight hypertensive subjects (body mass index, 25 to 39 kg/m(2), office BP 145/94 +/- 12/7 mm Hg) had 24-h BP monitoring and echocardiography twice, at baseline and after 3.8 +/- 2 years (minimum 1 year). None of the subjects received antihypertensive drugs during the follow-up. Main outcome measures were changes in 24-h BP and in left ventricular mass. RESULTS: Percent change in body weight had a direct relationship with 24-h BP changes (r = 0.35 and 0.31 for systolic and diastolic BP, respectively; both P <.001). The associations with office BP changes (r = 0.13, P =.10 for systolic BP; r = 0.15, P =.06 for diastolic BP) were significantly weaker (both P <.01, z test). The patients who lost weight during follow-up (n = 106) had a significantly lower increase in 24-h BP (+0.6 +/- 9/ +0.2 +/- 6 v +4.9 +/- 9/ +2.7 +/- 7 mm Hg for systolic/diastolic BP, both P <.01) and in left ventricular mass (-3 +/- 30 g v +9 +/- 32 g, P <.02) than the remaining subjects. In a multiple linear regression, a 10% weight loss independently predicted a 4.3/3.8 mm Hg decrease in 24-h systolic/diastolic BP. CONCLUSIONS: Long-term weight loss determines a sustained BP reduction during the 24 h and a decrease in left ventricular mass in overweight hypertensive subjects. The relation of weight loss with ambulatory BP changes is closer than that with office BP.     

Limitations of blood pressure target in non-dialysis chronic kidney disease: a question of method?

International guidelines recommend to reduce blood pressure (BP) levels below 130/80 mmHg in non-dialysis chronic kidney disease (CKD) patients. However, this BP target has not been validated by randomized controlled trials and is mainly driven by data obtained in observational and post-hoc analyses suggesting that it improves the renal and, to some extent, cardiovascular prognosis. The inconclusive results on the prognostic role of the BP target in patients with CKD might also relate to the limited ability of office BP readings to adequately stratify the global risk of this population. In fact, alterations of the pressure profile (such as white-coat hypertension) and nighttime hypertension are common in CKD patients. Recent studies have demonstrated that ambulatory blood pressure monitoring (ABPM) is superior to clinic BP measurements in predicting renal death and cardiovascular events. Therefore, while waiting for the results from the ongoing randomized Systolic Blood Pressure Intervention Trial (SPRINT) comparing the effect on cardiorenal prognosis of two BP target levels, the more widespread use of ABPM is desirable in CKD patients.     

Prognostic value of low and high ankle-brachial index in hospitalized medical patients

BackgroundPeripheral arterial disease (PAD) is frequently underdiagnosed in the clinical practice, leading to a lack of opportunity to detect subjects at a high risk for cardiovascular (CV) death. The ankle-brachial pressure index (ABI) represents a noninvasive, objective tool to diagnose PAD and to predict adverse outcome.MethodsABI was determined by means of Doppler velocimetry, in 707 patients, aged 50 years or older, consecutively hospitalized in an internal medicine ward, who were followed-up for at least 12 months in order to assess all-cause and CV mortality.ResultsSymptomatic PAD affected 8% of the population while the prevalence of PAD, defined as ABI < 0.90, was 29%; high ABI (> 1.40) was found in 8% of the patients. After a mean follow-up period of 1.6 years, both low and high ABI were independently associated with CV mortality with a hazard ratio of 1.99 (p = 0.016) for low and 2.13 (p = 0.04) for high ABI, compared with normal ABI (0.90–1.40). High ABI also independently predicted all-cause mortality with a hazard ratio of 1.77 (p = 0.04).DiscussionABI measurement reveals a large number of individuals with asymptomatic PAD among those hospitalized in an internal medicine department. An increased mortality was observed in patients with both low and high ABI. Hospital admission for any reason may serve as an opportunity to detect PAD and start appropriate preventive actions.