Resuscitation of fat embolism syndrome with extracorporeal membrane oxygenation

Embolization of marrow fat appears to be an inevitable consequence of long bone fractures. Pulmonary fat embolism (FE) with cardiovascular collapse is associated with a high mortality rate because of acute right ventricular failure and hypoxia. Immediate and appropriate resuscitation is required to prevent sudden death. Although extracorporeal membrane oxygenation (ECMO) has been used for a multitude of applications involving respiratory and circulatory collapse, its full potential as a standard conventional therapy has yet to be exploited. Herein, we describe the successful use of veno-venous (V-V) ECMO in a trauma patient who initially presented with fractures of the right ulna and femur. After surgery, the patient rapidly decompensated despite massive ventilatory support and was placed on ECMO. ECMO support lasted approximately 120 hours followed by an uneventful recovery and discharge 10 days later.     

New concepts in sepsis

An estimated 750,000 cases of severe sepsis occur annually in the United States, and the mortality rate is about 30%. As a condition that disproportionately affects the elderly and is related to invasive and immunosuppressive healthcare, increases in the frequency of sepsis are anticipated. The complex pathophysiology of sepsis encompasses the interplay of pro- and anti-inflammatory mediators, activated circulating and resident inflammatory cells, disrupted coagulation, endothelial activation and injury, vasodilatation and vascular hyporesponsiveness to vasoactive mediators, cardiac dysfunction, and cellular dysoxia. Current management of severe sepsis includes eradication of infection through source control and antimicrobial therapy, aggressive and targeted shock resuscitation that includes fluid administration, correction of anemia, vasopressor support, modest inotropic therapy, infusion of human recombinant activated protein C to selected patients, and compulsive supportive care to manage organ dysfunction and to avoid complications.     

Federal health information policy: a case of arrested development

Computerized patient records (CPRs) have reached a state of technical maturity that makes them an essential component of modern patient care. However, because uniform technical standards do not exist, CPRs constructed by different vendors do not convey clinical information easily from provider to provider. Moreover, unequal access to capital may mean a two-tier clinical information environment in the future. HIPAA, while important, did not anticipate the CPR revolution. New federal activism is required to assure not only interoperability of clinical data systems, but also that providers who lack capital and technical resources can make the needed digital conversion.     

Novel targets for HIV therapy

There are currently 25 drugs belonging to 6 different inhibitor classes approved for the treatment of human immunodeficiency virus (HIV) infection. However, new anti-HIV agents are still needed to confront the emergence of drug resistance and various adverse effects associated with long-term use of antiretroviral therapy. The 21st International Conference on Antiviral Research, held in April 2008 in Montreal, Canada, therefore featured a special session focused on novel targets for HIV therapy. The session included presentations by world-renowned experts in HIV virology and covered a diverse array of potential targets for the development of new classes of HIV therapies. This review contains concise summaries of discussed topics that included Vif-APOBEC3G, LEDGF/p75, TRIM 5α, virus assembly and maturation, and Vpu. The described viral and host factors represent some of the most noted examples of recent scientific breakthroughs that are opening unexplored avenues to novel anti-HIV target discovery and validation, and should feed the antiretroviral drug development pipeline in the near future.     

Fetal death certificates as a source of surveillance data for stillbirths with birth defects

OBJECTIVE: We assessed fetal death certificates (FDCs) as a source of surveillance for stillbirths with birth defects by linkage with data from the Metropolitan Atlanta Congenital Defects Program (MACDP), a population-based birth defects surveillance system. METHODS: Stillbirths with defects in MACDP were identified from 1994 through 2002 and linked to FDCs. Sensitivity of FDCs for capturing stillbirths with defects was estimated, and predictors for a case being reported were assessed. Concordance for selected variables from each data source was evaluated. RESILTS: Two hundred twenty-four of 257 stillbirths with birth defects in MACDP were linked to an FDC (linkage rate = 87.2%; 95% confidence interval [CI] 82.4, 91.0). Stillbirths of non-Hispanic black and Hispanic/other mothers were more likely to be issued an FDC (odds ratio [OR] = 5.6 [95% CI 1.9, 17.0] and 14.0 [95% CI 1.7, 114.0], respectively). Cases undergoing autopsy were more likely to be issued an FDC (OR = 3.2; 95% CI 1.1, 8.7). Performance of an amniocentesis was poorly recorded on FDCs. The sensitivity and positive predictive value of FDCs for selected classes of defects ranged from 10% to 70% and 25% to 93%, respectively. CONCLUSIONS: Compared to FDCs, MACDP's active case identification improves the ascertainment of stillbirths with birth defects and the quality of certain recorded data.     

A comparison of methods for assessing hypothalamic-pituitary-adrenal (HPA) axis activity in asthma patients treated with inhaled corticosteroids

Suppression of the hypothalamic-pituitary-adrenal (HPA) axis is an accepted indicator of potential side effects from inhaled corticosteroids. Although cortisol monitoring is frequently used to detect changes in HPA axis activity, the optimal method for identifying the subset of asthma patients on inhaled steroids who experience severe cortisol suppression of potential clinical significance has not been established. The objective of this study was to compare several methods for assessing HPA axis activity in asthma patients taking inhaled corticosteroids. After screening, 153 patients with mild to moderate asthma were randomly assigned to receive inhaled fluticasone propionate (110, 220, 330, or 440 microg bid), flunisolide (500 microg or 1000 microg bid), or one of two control regimens (prednisone or placebo) for 21 days. Salivary (8 a.m.) and urinary (24-h) cortisol determinations were compared against 22-hour area under the serum cortisol concentration-time curve (AUC0-22 h) measured at baseline and on day 21. Comparisons were also made against 8 a.m. serum cortisol. A significant positive correlation was found between AUC0-22 h of serum cortisol and 8 a.m. serum cortisol level (r = 0.5140; p = 0.0001). The AUC0-22 h of serum cortisol was weakly correlated with 24-hour urinary cortisol levels, both corrected (r = 0.4388; p = 0.0001) and uncorrected (r = 0.3511; p = 0.0001) for creatinine excretion. The 8 a.m. salivary cortisol level correlated positively with the 8 a.m. serum cortisol level (r = 0.5460; p = 0.0001). Salivary cortisol was both sensitive and specific for the detection of a 50% decline in AUC0-22 h of serum cortisol. Cortisol reductions of this magnitude have been observed following repeated use of inhaled steroids. Because it is noninvasive, salivary cortisol measurement offers distinct advantages as a screening method for detecting pronounced HPA axis suppression in asthma patients receiving corticosteroid therapy.     

Critical data‐based re‐evaluation of minocycline as a putative specific microglia inhibitor

Minocycline, a second generation broad‐spectrum antibiotic, has been frequently postulated to be a “microglia inhibitor.” A considerable number of publications have used minocycline as a tool and concluded, after achieving a pharmacological effect, that the effect must be due to “inhibition” of microglia. It is, however, unclear how this “inhibition” is achieved at the molecular and cellular levels. Here, we weigh the evidence whether minocycline is indeed a bona fide microglia inhibitor and discuss how data generated with minocycline should be interpreted. GLIA 2016;64:1788–1794     

Feasibility of transcatheter intervention for severe aortic stenosis in patients >or=90 years of age: aortic valvuloplasty revisited.

OBJECTIVES: The goals of this study were to determine the feasibility, safety, and early outcomes of balloon aortic valvuloplasty (BAV) for severe aortic stenosis in a nonagenarian population. BACKGROUND: This very elderly population is expanding rapidly, has a high incidence of aortic stenosis, and uncommonly undergoes surgical aortic valve replacement. These patients may best be treated with a transcatheter approach due to comorbidities, surgical risk, and personal preference. METHODS: We reviewed 31 consecutive patients >or=90 years of age who underwent BAV at our institution from July 2003 to August 2006 for data pertinent to patient characteristics, procedural techniques, and 30-day outcomes. RESULTS: Our patients had a mean age of 93 +/- 3.0 years (90-101). The society of thoracic surgery risk score was 18.5 (+/-10.2) and logistic Euroscore was 35.8 (+/-19.3). Twenty-five patients (81%) underwent retrograde BAV and 6 (19%) antegrade BAV. Five patients (16%) underwent combined BAV and coronary stenting. Overall mean aortic valve area increased from 0.52 cm2 (+/-0.17) to 0.92 cm2 (+/-0.22) and mean New York Heart Association (NYHA) functional class improved from 3.4 to 1.8. Intraprocedural mortality occurred in one patient (3.2%) and 30-day mortality in three patients (9.7%). CONCLUSIONS: BAV can be carried out in high risk nonagenarian patients with an acceptable complication rate, low perioperative mortality, and early improvement in NYHA functional class.     

TRIM5alpha mediates the postentry block to N-tropic murine leukemia viruses in human cells

Murine leukemia viruses (MLVs) have been classified as N-tropic (N-MLV) or B-tropic (B-MLV), depending on their ability to infect particular mouse strains. The early phase of N-MLV infection is blocked in the cells of several mammalian species, including humans. This block is mediated by a dominant host factor that targets the viral capsid soon after virus entry into the cell has been achieved. A similar block to HIV-1 in rhesus monkey cells is mediated by TRIM5alpha. Here we show that human TRIM5alpha is both necessary and sufficient for the restriction of N-MLV in human cells. Rhesus monkey TRIM5alpha, which potently blocks HIV-1 infection, exhibited only modest inhibition of N-MLV infection. B-MLV was resistant to the antiviral effects of both human and rhesus monkey TRIM5alpha; susceptibility to TRIM5alpha-mediated restriction was conferred by alteration of residue 110 of the B-MLV capsid protein to the amino acid found in the N-MLV capsid. Our results demonstrate that species-specific variation in TRIM5alpha governs its ability to block infection by diverse retroviruses.