Tumor necrosis factor alpha-induced protein 3 (TNFAIP3) is a multifunctional ubiquitin binding and editing enzyme that regulates inflammation. Genetic studies have implicated polymorphisms within the TNFAIP3 locus to the development of numerous immune-related diseases. This study evaluated the frequencies of single-nucleotide polymorphism (SNPs) within the exonic regions of the TNFAIP3 gene and an associated point mutation from the Illumina array among a predominantly Hispanic cohort.

Genomic DNA was obtained from 721 participants and sequencing of all TNFAIP3 exons and an intergenic point mutation (rs6920220) was performed. In-vitro functional assessment was performed by transfecting mutated TNFAIP3 constructs into TNFAIP3 knockout cells containing the NF-kB luciferase reporter and stimulating with TNFα. Comparative statistics were performed with Student’s t-test for continuous variables and chi-squared test for categorical variables.

Sequencing revealed two missense SNPs, rs146534657:A>G and rs2230926:T>G, both within exon 3 of TNFAIP3, which encodes the protein’s deubiquitinating enzymatic domain. Frequencies of all three point mutations differed significantly across racial groups (χ2-test, P = 0.014 to P < 0.001). Compared to Caucasians, rs146534657:A>G was overrepresented among Hispanics (odds ratio (OR) [95% CI] 4.05 [1.24−13.18]), and rs2230926:T>G was more prevalent among African-Americans (OR [95% CI] 3.65 [1.58−8.43]). In-vitro assays confirm rs146534657:A>G and rs2230926:T>G decrease the ability of TNFAIP3 to abrogate NF-κB activation by 2-fold (P < 0.01) and 1.7-fold (P < 0.01), respectively.

This study reports the frequency of rs146534657:A>G among Hispanics and is the first to evaluate its potential physiologic impact, establishing a basis for future research as a potential biomarker among this population.

This study aimed to review available disaster training options for health care providers, and to provide specific recommendations for developing and delivering a disaster-response-training program for non-disaster-trained emergency physicians, residents, and trainees prior to acute deployment.

A comprehensive review of the peer-reviewed and grey literature of the existing training options for health care providers was conducted to provide specific recommendations.

A comprehensive search of the Pubmed, Embase, Web of Science, Scopus, and Cochrane databases was performed to identify publications related to courses for disaster preparedness and response training for health care professionals. This search revealed 7,681 unique titles, of which 53 articles were included in the full review. A total of 384 courses were found through the grey literature search, and many of these were available online for no charge and could be completed in less than six hours. The majority of courses focused on management and disaster planning; few focused on clinical care and acute response.

There is need for a course that is targeted toward emergency physicians and trainees without formal disaster training. This course should be available online and should utilize a mix of educational modalities, including lectures, scenarios, and virtual simulations. An ideal course should focus on disaster preparedness, and the clinical and non-clinical aspects of response, with a focus on an all-hazards approach, including both terrorism-related and environmental disasters.

HansotiB, KelloggDS, AberleSJ, BroccoliMC, FedenJ, FrenchA, LittleCM, MooreB, SabatoJJr., SheetsT, WeinbergR, ElmesP, KangC. Preparing Emergency Physicians for Acute Disaster Response: A Review of Current Training Opportunities in the US. Prehosp Disaster Med. 2016;31(6):643–647.

Hospitalizations for acute bacterial skin and skin structure infection (ABSSSI) are common. Optimizing antibiotic use for ABSSSIs requires an understanding of current management. The objective of this study was to evaluate antibiotic prescribing practices and factors affecting prescribing in a diverse group of hospitals

Multicenter, retrospective cohort study.

Seven community and academic hospitals.

Children and adults hospitalized between June 2010 and May 2012 for cellulitis, wound infection, or cutaneous abscess were eligible. The primary endpoint was a composite of 2 prescribing practices representing potentially avoidable antibiotic exposure: (1) use of antibiotics with a broad spectrum of activity against gram-negative bacteria or (2) treatment duration greater than 10 days.

A total of 533 cases were included: 320 with nonpurulent cellulitis, 44 with wound infection or purulent cellulitis, and 169 with abscess. Of 492 cases with complete prescribing data, the primary endpoint occurred in 394 (80%) cases and varied significantly across hospitals (64%–97%; P < .001). By logistic regression, independent predictors of the primary endpoint included wound infection or purulent cellulitis (odds ratio [OR], 5.12 [95% confidence interval (CI)], 1.46–17.88), head or neck involvement (OR, 2.83 [95% CI, 1.17–6.82]), adult cases (OR, 2.20 [95% CI, 1.18–4.11]), and admission to a community hospital (OR, 1.90 [95% CI, 1.05–3.44]).

Among patients hospitalized for ABSSSI, use of antibiotics with broad gram-negative activity or treatment courses longer than 10 days were common. There may be substantial opportunity to reduce antibiotic exposure through shorter courses of therapy targeting gram-positive bacteria.

Infect Control Hosp Epidemiol 2014;35(10):1241–1250

To define the utility of transesophageal echocardiography in predicting the likelihood of a successful procedure and residual shunting in patients undergoing transcatheter closure of defects within the oval fossa using the CardioSEAL® device.

Transesophageal echocardiography is used to monitor transcatheter closure of interatrial defects within the the oval fossa, but predictors of successful closure and residual shunting have yet to be determined.

We reviewed transesophageal echocardiograms obtained from 26 consecutive patients undergoing attempted transcatheter closure of interatrial defects within the oval fossa between January, 1997 and May, 1998. Assessment of the atrial septum, the septal defect, and the rims of the oval fossa bordering the defect was performed in 3 planes: longitudinal, 4- chamber, and basal short-axis.

Closure proved successful in 24 patients (92%). The defect was significantly larger, and the anterosuperior rim of the defect smaller, in the 2 patients in whom occlusion was not successful. Residual shunting 24 hrs after closure was detected in 14 patients. Significant predictors of leakage included smaller posterior and superior rims, a larger shunt prior to closure, and herniation of a one left atrial arm of the device into the right atrium. In all cases, the sites of leakage were the superior rim of the defect at the superior cavo-atrial junction, and the anterosuperior rim behind the aortic root. Herniation of a left atrial arm into the right atrium was seen in 7 patients (29%). In all, it was the anterosuperior arm which herniated Doppler color flow was suboptimal in detecting residual leaks, and was enhanced substantially with the use of contrast echocardiography.

Transesophageal echocardiography allows excellent assessment of the oval fossa and deficiencies of its floor in all of their dimensions. It is an important tool for guiding the deployment of the occlusion device in patients undergoing attempted transcatheter closure of defects within the fossa. Contrast echocardiography should be used for optimal detection of residual shunting.

First, to examine the morphology of heart specimens with defects of the oval fossa so as to define the factors that facilitate appropriate selection of the size of devices used for inteventional closure. Second, to examine the relationship between morphology and transthoracic and transesophageal echocardiography.

The success of transcatheter closure is influenced by the variable morphology of deficiencies with the oval fossa, and of the relationship of the fossa itself to adjacent structures. More appropriate selection could reduce the incidence of failures.

From over 100 specimens in the cardiac registry at the University of California, San Francisco, we judged 16 hearts with atrial septal defects within the oval fossa, either in isolation or associated with other cardiac malformation, to be suitable for this study. We measured the dimensions of the defect and the surrounding rims of the fossa. All values were normalized to the diameter of the aortic root.

A fenestrated defect was present in 9 specimens (56%). The shape defect itself was oval in all specimens, with a ratio of major to minor axes of 1.70 ± 0.63– The major axis took one of three main directions with respect to the vertical plane: in 11 specimens (69%) it was at horizontal; in 3 (19%) it was at oblique at an angle of 45 degrees; and in 2 (12%) it was vertical. Discordance was noted in some hearts between the major axis of the defect and that of the oval fossa. Structures closest to the rim of the fossa were the aortic mound, the coronary sinus, and the hinge point of the aortic leaflet of the mitral valve.

Extrapolating from these specimens permitted identification of the major and minor axes of the atrial septal defect by transthoracic and transesophageal echocardiography. Our study has identified landmarks and dimensions that may be employed to improve effectiveness of selection of patients for transcatheter closure of defects within the oval fossa.