Concomitant Valvular Procedures During LVAD Implantation and Outcomes: An Analysis of the MOMENTUM 3 Trial Portfolio

Purpose: Correction of valvular pathology is often undertaken in patients undergoing LVAD implantation but impact on outcomes is uncertain. We compared clinical outcomes with HeartMate 3 (HM3) LVAD implantation in those with concurrent valve procedures (VP) to those with an isolated LVAD implant within the MOMENTUM3 trial portfolio, including the Pivotal Trial (n=515, NCT02224755) and Continued Access Protocol/ CAP (n=1685, NCT02892955). Methods: The study included 2200 HM3 implanted patients. Among 820 concurrent procedures (including VP, CABG, RVAD, LAA closure), 466 (21.8%) were VPs (HM3+VP), including 81 aortic, 61 mitral, 163 tricuspid, and 85 patients with multiple VPs. Short and Long-term outcomes including peri-operative complications and healthcare resource use, major adverse events and survival were analyzed. Results: Patients undergoing HM3+VP were older (63[54-70] vs. 62[52-68] yrs), with a sicker INTERMACS profile (1-2:41% vs.31%) and higher central venous pressure (11[8-16] vs. 9[6-14] mmHg) compared to HM3 alone (all p\u3c0.05). The cardiopulmonary bypass time (124[97-158] vs.76[59-96] mins); ICU (8.5 [5-16] vs. 7 [5-13]) and hospital length of stay (20 [15-30] vs. 18 [14-24] days) were longer in HM3+VP (all p\u3c0.0001). A significantly higher incidence of stroke (4.9% vs. 2.4%), bleeding (33.9% vs. 23.8%) and right heart failure (41.5% vs. 29.6%) was noted in HM3+VP for 0-30 days post-implant (all p\u3c0.01), but 30-day survival was similar between groups (96.7% vs. 96.1%). There was no difference in 2-year survival in HM3+VP vs HM3 alone patients (HR[95%CI]:0.93 [0.71-1.21];p=0.60). Analysis of individual VPs showed no significant differences in survival compared to HM3 alone (Figure). Conclusion: Concurrent VPs are commonly performed during LVAD implantation, are associated with increased morbidity during the index hospitalization, but short and long-term survival are not impacted adversely when compared with those that undergo an isolated LVAD procedure

Endovascular or open repair strategy for ruptured abdominal aortic aneurysm: 30 day outcomes from IMPROVE randomised trial.

OBJECTIVE: To assess whether a strategy of endovascular repair (if aortic morphology is suitable, open repair if not) versus open repair reduces early mortality for patients with suspected ruptured abdominal aortic aneurysm. DESIGN: Randomised controlled trial. SETTING: 30 vascular centres (29 UK, 1 Canadian), 2009-13. PARTICIPANTS: 613 eligible patients (480 men) with a clinical diagnosis of ruptured aneurysm. INTERVENTIONS: 316 patients were randomised to the endovascular strategy (275 confirmed ruptures, 174 anatomically suitable for endovascular repair) and 297 to open repair (261 confirmed ruptures). MAIN OUTCOME MEASURES: 30 day mortality, with 24 hour and in-hospital mortality, costs, and time and place of discharge as secondary outcomes. RESULTS: 30 day mortality was 35.4% (112/316) in the endovascular strategy group and 37.4% (111/297) in the open repair group: odds ratio 0.92 (95% confidence interval 0.66 to 1.28; P=0.62); odds ratio after adjustment for age, sex, and Hardman index 0.94 (0.67 to 1.33). Women may benefit more than men (interaction test P=0.02) from the endovascular strategy: odds ratio 0.44 (0.22 to 0.91) versus 1.18 (0.80 to 1.75). 30 day mortality for patients with confirmed rupture was 36.4% (100/275) in the endovascular strategy group and 40.6% (106/261) in the open repair group (P=0.31). More patients in the endovascular strategy than in the open repair group were discharged directly to home (189/201 (94%) v 141/183 (77%); P<0.001). Average 30 day costs were similar between the randomised groups, with an incremental cost saving for the endovascular strategy versus open repair of £1186 (€1420; $1939) (95% confidence interval -£625 to £2997). CONCLUSIONS: A strategy of endovascular repair was not associated with significant reduction in either 30 day mortality or cost. Longer term cost effectiveness evaluations are needed to assess the full effects of the endovascular strategy in both men and women. TRIAL REGISTRATION: Current Controlled Trials ISRCTN48334791

Activating killer-cell immunoglobulin-like receptor haplotype influences clinical outcome following HLA-matched sibling haematopoietic stem cell transplantation

Natural killer cells are thought to influence the outcome of hematopoietic stem cell transplant (HSCT), impacting on relapse, overall survival, graft versus host disease and the control of infection, in part through the complex interplay between the large and genetically diverse killer immunoglobulin-like receptor (KIR) family and their ligands. This study examined the relationship between KIR gene content and clinical outcomes including the control of opportunistic infections such as cytomegalovirus in the setting of human leucocyte antigen (HLA)-matched sibling HSCT in an Australian cohort. The presence of the KIR B haplotype which contain more activating receptors in the donor, in particular centromeric B haplotype genes (Cen-B), was associated with improved overall survival of patients with acute myeloid leukemia (AML) undergoing sibling HSCT and receiving myeloablative conditioning. Donor Cen-B haplotype was also associated with reduced acute graft versus host disease grades II-IV whereas donor telomeric-B haplotype was associated with decreased incidence of CMV reactivation. In contrast, we were not able to demonstrate a reduced rate of relapse when the donor had KIR Cen-B, however relapse with a donor Cen-A haplotype was a competing risk factor to poor overall survival. Here we show that the presence of donor activating KIR led to improved outcome for the patient, potentially through reduced relapse rates and decreased incidence of acute GvHD translating to improved overall survival. This article is protected by copyright. All rights reserved

Potential severe asthma hidden in UK primary care

Funding: ISAR is conducted by Observational & Pragmatic Research Institution (OPRI), and co-funded by OPC Global and AstraZeneca. This research study was co-funded by AstraZeneca and Optimum Patient Care Global Limited, including access to the Optimum Patient Care Research Database (OPCRD).Peer reviewedPublisher PD

Cardiovascular actions of the hypotensive agent, N, N-diallylmelamine (U-7720)

Diallylmelamine is an effective hypotensive agent in hypertensive dogs and rats, having a duration of action exceeding twenty-four hours from a single oral dose. It has limited efficacy in normotensive rats. Hypotensive activity of gradual onset is preceded by a latent period of up to two hours and becomes maximal six hours or more after dosing. This agent does not depress cardiac output or sympathetic vasoconstrictor activity. It is suggested that its hypotensive activity results from a direct effect upon vascular smooth muscle.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46303/1/210_2004_Article_BF00245728.pd

Demographic change and conflict in Northern Ireland: reconciling qualitative and quantitative evidence

Recent large-N quantitative studies have failed to uncover a link between demographic change and conflict. This seems to refute quite powerful qualitative evidence from small-scale case studies that such a relationship exists. This article attempts to reconcile the conflicting evidence by revealing how population change—in this case a major decline in the size of the Protestant majority—matters for violent conflict, but not in a direct way. In addition, relationships differ by level of geography. In the case of Northern Ireland, no significant quantitative association exists between ethnic change and violence. This holds across both geographic units and years. However, there is a significant association between ethnic demography and Protestant mobilization into the Orange Order across counties. This in turn is related to Protestant resistance to reforms aimed at extending civil rights to the Catholic population during the Stormont period. This stance was a major factor in generating Catholic support for IRA violence. Moreover, in specific locations, a direct link between Protestant population decline relative to Catholics and loyalist violence against Catholics is evident. Hence demography matters, but in conjunction with other factors, and several steps upstream from the outbreak of violence

Polymorphisms in immunoregulatory genes and the risk of histologic chorioamnionitis in Caucasoid women: a case control study

BACKGROUND: Chorioamnionitis is a common underlying cause of preterm birth (PTB). It is hypothesised that polymorphisms in immunoregulatory genes influence the host response to infection and subsequent preterm birth. The relationship between histologic chorioamnionitis and 22 single nucleotide polymorphisms in 11 immunoregulatory genes was examined in a case-control study. METHODS: Placentas of 181 Caucasoid women with spontaneous PTB prior to 35 weeks were examined for histologic chorioamnionitis. Polymorphisms in genes IL1A, IL1B, IL1RN, IL1R1, tumour necrosis factor (TNF), IL4, IL6, IL10, transforming growth factor beta-1 (TGFB1), Fas (TNFRSF6), and mannose-binding lectin (MBL2) were genotyped by polymerase chain reaction and sequence specific primers. Multivariable logistic regression including demographic and genetic variables and Kaplan-Meier survival analyses of genotype frequencies and pregnancy outcome were performed. RESULTS: Sixty-nine (34%) women had histologic evidence of acute chorioamnionitis. Carriage of the IL10-1082A/-819T/592A (ATA) haplotype [Multivariable Odds ratio (MOR) 1.9, P = 0.05] and MBL2 codon 54Asp allele (MOR 2.0, P = 0.04), were positively associated with chorioamnionitis, while the TNFRSF6-1377A/-670G (AG) haplotype (MOR 0.4, P = 0.03) and homozygosity for TGFB1-800G/509T (GT) haplotype (MOR 0.2, P = 0.04) were negatively associated. CONCLUSION: These findings demonstrate that polymorphisms in immunoregulatory genes IL10, MBL2, TNFRSF6 and TGFB1 may influence susceptibility to chorioamnionitis