A retrospective study to determine the risk of red cell alloimmunization and transfusion during pregnancy

A retrospective review of post-delivery antibody records was performed at a teaching hospital and a community hospital to determine the frequency of new red cell alloantibody production and transfusion during pregnancy. If alloantibody was undetected at delivery, it was assumed that alloimmunization had not occurred. When antibody was detected, a chart review was performed to determine if the antibody was present at the beginning of the pregnancy or was newly produced during the pregnancy. A total of 17,568 pregnancies were reviewed. Antibody was detected at delivery in 948 (5.4%) cases, of which 89.5 percent (848/948) involved passive anti-D or clinically insignificant antibodies. The remaining 100 pregnancies involved clinically significant IgG antibodies. In 58 pregnancies, the antibody was detected in the first trimester, and in 42, new antibody production occurred during the pregnancy. Thus, the prevalence of new antibody production during pregnancy was 0.24 percent (95% confidence interval [CI], 0.17-0.32). Transfusion records indicated that the prevalence of transfusions during pregnancy was 0.09 percent (95% CI, 0.04-0.14). None of the women with new alloantibody formation during their pregnancies required transfusion; hence, new alloantibody production and the need for transfusion appear to be independent events. The probability of these events occurring together was 2.1 × 10(-6), or 1 in 500,000 deliveries.     

The alloimmune response and effector mechanisms of allograft rejection

Allograft rejection is the consequence of the recipient's alloimmune response to nonself antigens expressed by donor tissues. Allospecific T lymphocytes are activated by donor peptides which are presented in the context of major histocompatibility complex molecules by either donor or recipient antigen presenting cells. Antigen presenting cells also provide essential costimulatory signals which are required for T cell proliferation and differentiation into either helper or effector lymphocytes. Effector mechanisms of allograft rejection include those mediated by cytotoxic T lymphocytes, macrophages, natural killer cells, and B lymphocytes. Importantly, alloimmune responses are controlled by regulatory molecules which include membrane receptors and cytokines. Novel insights into the interactions between antigen presenting cells and T lymphocytes, and further understanding of how alloimmune responses are regulated, will help in developing effective antirejection and tolerance-inducing strategies.     

Hyperkalemia in the Hypertensive Patient

Purpose of Review

Hyperkalemia develops in a patient with systemic arterial hypertension (HTN) if one or more risk factors are present, namely chronic kidney disease (CKD) (especially severe stage 4-5 CKD), diabetes mellitus (DM), heart failure (HF), or pharmacological therapies that interfere with potassium homeostasis, mainly through renin-angiotensin-aldosterone inhibition (RAASi). Hyperkalemia is a considerable reason of morbidity (emergency department (ED) visits and hospitalizations) and portends a higher mortality risk in patients at risk; for instance, hyperkalemia increases the risk of mortality within 1 day of a hyperkalemic event. This review aims to identify the risk factors for high-serum potassium, highlight the risk versus benefit of RAASi in certain patient populations, and outline preventive as well as therapeutic strategies for hyperkalemia.

Recent Findings

A growing body of evidence supports the safety and efficacy of cation-exchange resins, patiromer, or sodium zirconium cyclosilicate, in patients with a compelling indication for RAASi, yet in whom such therapy was complicated by hyperkalemia, allowing these patients to benefit from continued RAASi therapy.

Summary

In summary, novel cation exchange polymers present the clinician with a new and safe strategy to address hyperkalemia in patients with a compelling indication for ongoing RAASi therapy instead of withdrawal of such therapy.

     

Clinical outcomes of percutaneous interventions in saphenous vein grafts using drug-eluting stents compared to bare-metal stents: a comprehensive meta-analysisof all randomized clinical trials

Background:

Clinical outcomes of percutaneous coronary intervention (PCI) in patients with saphenous vein grafts (SVGs) remain poor despite the use of drug‐eluting stents (DES). There is a disparity in clinical outcomes in SVG PCI based on various registries, and randomized clinical data remain scant. We conducted a meta‐analysis of all existing randomized controlled trials (RCTS) comparing bare‐metal stents (BMS) and DES in SVGPCIs.

Hypothesis:

PCI in patients with SVG disease using DES may reduce need for repeat revascularization without an excess mortality when compared to BMS.

Methods:

An aggregate data meta‐analysis of clinical outcomes in RCTs comparing PCI with DES vs BMS for SVGs reporting at least 12 months of follow‐up was performed. A literature search between Janurary 1, 2003 and September 30, 2011 identified 4 RCTs (812 patients; DES = 416, BMS = 396). Summary odds ratio (OR) and 95% confidence interval (CI) were calculated using the random‐effects model. The primary endpoint was all‐cause mortality. Secondary outcomes included nonfatal myocardial infarction (MI), repeat revascularization, and major adverse cardiac events (MACE). These outcomes were assessed in a cumulative fashion at 30 days, 18 months, and 36 months.

Results:

There were no intergroup differences in baseline clinical and sociodemographic characteristics. At a median follow‐up of 25 months, patients in the DES and BMS group had similar rates of death (OR: 1.63, 95% CI: 0.45–5.92), MI (OR; 0.83, 95% CI: 0.27‐2.60), and MACE (OR: 0.58, 95% CI: 0.25–1.32). Patients treated with DES had lower rates of repeat revascularization (OR: 0.40, 95% CI: 0.22–0.75).

Conclusions:

In this comprehensive meta‐analysis of all RCTs comparing clinical outcomes of PCI using DES vs BMS in patients with SVG disease, use of DES was associated with a reduction in rate of repeat revascularization and no difference in rates of all‐cause death and MI. Clin. Cardiol. 2012 DOI: 10.1002/clc.21984 Dr. Virani is supported by a Department of Veterans Affairs Health Services Research and Development Service (HSR&D) Career Development Award (CDA‐09‐028), and has research support from Merck and National Football League Charities (all grants to the institution and not individual). The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. The authors have no other funding, financial relationships, or conflicts of interest to disclose.     

Test–retest repeatability of [18F]Flortaucipir PET in Alzheimer’s disease and cognitively normal individuals

The aim of this study was to investigate the test–retest (TRT) repeatability of various parametric quantification methods for [¹⁸F]Flortaucipir positron emission tomography (PET). We included eight subjects with dementia or mild cognitive impairment due to Alzheimer’s disease and six cognitively normal subjects. All underwent two 130-min dynamic [¹⁸F]Flortaucipir PET scans within 3 ± 1 weeks. Data were analyzed using reference region models receptor parametric mapping (RPM), simplified reference tissue method 2 (SRTM2) and reference logan (RLogan), as well as standardized uptake value ratios (SUVr, time intervals 40–60, 80–100 and 110–130 min post-injection) with cerebellar gray matter as reference region. We obtained distribution volume ratio or SUVr, first for all brain regions and then in three tau-specific regions-of-interest (ROIs). TRT repeatability (%) was defined as |retest–test|/(average (test + retest)) × 100. For all methods and across ROIs, TRT repeatability ranged from (median (IQR)) 0.84% (0.68–2.15) to 6.84% (2.99–11.50). TRT repeatability was good for all reference methods used, although semi-quantitative models (i.e. SUVr) performed marginally worse than quantitative models, for instance TRT repeatability of RPM: 1.98% (0.78–3.58) vs. SUVr_80–100: 3.05% (1.28–5.52), p < 0.001. Furthermore, for SUVr_80–100 and SUVr_110–130, with higher average SUVr, more variation was observed. In conclusion, while TRT repeatability was good for all models used, quantitative methods performed slightly better than semi-quantitative methods.