Randomized placebo controlled trial evaluating the safety and efficacy of single low dose intracoronary insulin like growth factor following percutaneous coronary intervention in acute myocardial infarction (RESUS-AMI)

Background: Residual and significant post-infarction left ventricular (LV) dysfunction, despite technically successful percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI), remains an important clinical issue. In preclinical models low dose insulin-like growth factor 1 (IGF1) has potent cytoprotective and positive cardiac remodelling effects. We studied the safety and efficacy of immediate post PCI low dose intracoronary IGF1 infusion in STEMI patients. Methods: Using a double-blind, placebo controlled, multi-dose study design, we randomized 47 STEMI patients with significantly reduced (≤ 40%) LV ejection fraction (LVEF) after successful PCI to single intracoronary infusion of placebo (n=15), 1.5ng IGF1 (n=16) or 15ng IGF1 (n=16). All received optimal medical therapy. Safety endpoints were freedom from hypoglycaemia, hypotension or significant arrhythmias within 1 hour of therapy. The primary efficacy endpoint was LVEF and secondary endpoints were LV volumes, mass, stroke volume, and infarct size at 2 months follow up, all assessed by MRI. Treatment effects were estimated by analysis of covariance adjusted for baseline (24hrs) outcome. Results: No significant differences in safety endpoints occurred between treatment groups out to 30 days (chi squared test, p-value = 0.77).There were no statistically significant differences in baseline (24 hrs post STEMI) clinical characteristics or LVEF among groups. LVEF at 2 months, compared to baseline, increased in all groups with no statistically significant differences related to treatment assignment. However, compared with placebo or 1.5ng IGF1, treatment with 15ng IGF1 was associated with a significant improvement in indexed LV end-diastolic volume (p=0.018), LV mass (p=0.004) and stroke volume (p=0.016). Late gadolinium enhancement (±SD) at 2 months was lower in 15ng IGF1 (34.5±29.6g) compared to placebo (49.1±19.3g) or 1.5ng IGF1 (47.4±22.4g) treated patients, though the result was not statistically significant (p = 0.095). Conclusion: In this pilot trial, low dose IGF1, given after optimal mechanical reperfusion in STEMI, is safe but does not improve LVEF. However, there is a signal for a dose dependent benefit on post MI remodeling that may warrant further study. Despite timely reperfusion by primary PCI (PPCI) a significant cohort of patients develop adverse left ventricular remodelling with clinical sequelae such as arrhythmia and heart failure[1].Therapeutic approaches to avert such remodeling, including a variety of cell therapy and ischemia- reperfusion-injury mitigation trials have achieved modest success 2.;3. Thus, there remains a significant opportunity for novel therapies in this field

Direct-to-implant Breast Reconstruction with Autoderm

Background:. Traditional transverse mastectomies yield suboptimal results in women with higher body mass index, wide breast footprint, and ptotic breasts. An option for this patient population is a reduction-pattern style mastectomy, and recruiting an inferiorly based dermal flap using the lower mastectomy flap. This is analogous to a vascularized dermal matrix supporting the lower pole of the implant, termed “Autoderm” breast reconstruction. This allows for aesthetically appealing skin reduction mastectomies with the added safety of a vascularized dermal flap to facilitate an immediate direct-to-implant breast reconstruction. This study assesses patient satisfaction using the validated BRECON-31 questionnaire to enhance shared-decision making with women contemplating breast reconstruction. Methods:. A 2-year retrospective review of women who underwent Autoderm direct-to-implant breast reconstruction comparing patients who underwent unilateral and bilateral reconstruction in terms of characteristics, complications, and BRECON-31 scoring. Results:. Overall patient scores were high (81.6 of 100). In particular, women scored very high on self-image (85.0), arm concerns (86.4), intimacy (87.4), satisfaction (88.3), and expectations subscales (85.5). Women choosing bilateral reconstruction outperformed unilateral reconstruction in every subgroup, but only attained statistical significance in the “self-consciousness” subgroup. Compared with a historical cohort of a mix of implant reconstruction types, Autoderm patients showed improved satisfaction (88.3 versus 82.5; P = 0.07) and breast appearance (73.9 versus 66.8; P = 0.06), approaching significance. Safety was demonstrated by low major complications (4.7%) and low implant loss rates (2.3%). Conclusions:. Autoderm breast reconstruction is a safe option in women with large, ptotic breasts, with patients reporting high satisfaction using a validated instrument