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Hospitalized patients with cirrhosis frequently undergo multiple procedures. The risk of procedural-related bleeding remains unclear, and management is not standardized. We conducted an international, prospective, multicenter study of hospitalized patients with cirrhosis undergoing nonsurgical procedures to establish the incidence of procedural-related bleeding and to identify bleeding risk factors. Hospitalized patients were prospectively enrolled and monitored until surgery, transplantation, death, or 28 days from admission. The study enrolled 1187 patients undergoing 3006 nonsurgical procedures from 20 centers. A total of 93 procedural-related bleeding events were identified. Bleeding was reported in 6.9% of patient admissions and in 3.0% of the procedures. Major bleeding was reported in 2.3% of patient admissions and in 0.9% of the procedures. Patients with bleeding were more likely to have nonalcoholic steatohepatitis (43.9% vs 30%) and higher body mass index (BMI; 31.2 vs 29.5). Patients with bleeding had a higher Model for End-Stage Liver Disease score at admission (24.5 vs 18.5). A multivariable analysis controlling for center variation found that high-risk procedures (odds ratio [OR], 4.64; 95% confidence interval [CI], 2.44–8.84), Model for End-Stage Liver Disease score (OR, 2.37; 95% CI, 1.46–3.86), and higher BMI (OR, 1.40; 95% CI, 1.10–1.80) independently predicted bleeding. Preprocedure international normalized ratio, platelet level, and antithrombotic use were not predictive of bleeding. Bleeding prophylaxis was used more routinely in patients with bleeding (19.4% vs 7.4%). Patients with bleeding had a significantly higher 28-day risk of death (hazard ratio, 6.91; 95% CI, 4.22–11.31). Procedural-related bleeding occurs rarely in hospitalized patients with cirrhosis. Patients with elevated BMI and decompensated liver disease who undergo high-risk procedures may be at risk to bleed. Bleeding is not associated with conventional hemostasis tests, preprocedure prophylaxis, or recent antithrombotic therapy. [Display omitted] Predicting bleeding in patients with cirrhosis undergoing procedures is challenging. Bleeding caused by procedures was rare, and conventional testing did not predict bleeding. Rather, obese patients with advanced liver disease undergoing high-risk procedures were at the highest risk to bleed. [ABSTRACT FROM AUTHOR]

TTF-1 is a homeodomain transcriptional factor expressed in thyroid, lung, and parts of the brain. In vitro, TTF-1 can activate the promoter of thyroid- and pulmonary-specific genes. We postulated that TTF-1 not only is essential for the activation of tissue-specific genes, but also may directly participate in epithelial cell morphogenesis. To test this postulate, we used an antisense oligonucleotide inhibitory strategy in an in vitro model of embryonic mouse lung branching morphogenesis. This strategy suppressed TTF-1 translation and inhibited lung branching morphogenesis. The resulting abnormal phenotype was characterized by hyperplastic and unorganized proliferation of epithelial cells in the airways. The mesenchymal compartment of the lung appeared to be unaffected. These results demonstrate, for the first time, that the expression of a homeoprotein transcriptional regulator is necessary for lung epithelial morphogenesis.

Highlights: [•] We review the latest treatment algorithms for treating chronic hepatitis C infection. [•] We explain how direct-acting antivirals (DAAs) target specific aspects of the hepatitis C virus (HCV) life cycle. [•] The NS5B polymerase inhibitor, sofosbuvir, is efficacious across all HCV genotypes. [•] Combining DAAs across distinct classes without requiring interferon is the next step. [Copyright &y& Elsevier]

Abstract: Purpose: At our level 1 pediatric trauma center, 9-54 intermediate-level (“level 2”) trauma activations are received per month. Previously, the surgery team was required to respond to and assume responsibility for all patients who had “level 2” trauma activations. In 8/2011, we implemented a protocol where the emergency room (ER) physician primarily manages these patients with trauma consultation for surgical evaluation or admission. The purpose of this study was to prospectively evaluate the effects of the new protocol to ensure that patient safety and quality of care were maintained. Methods: We compared outcomes of patients treated PRE-implementation (10/2010-7/2011) and POST-implementation (9/2011-5/2012), including surgeon consultation rate, utilization of imaging and laboratory testing, ER length of stay, admission rate, and missed injuries or readmissions. Statistical analysis included chi-square and Student's t-test. Results: We identified 472 patients: 179 in the PRE and 293 in the POST period. The populations had similar baseline clinical characteristics. The surgical consultation rate in the POST period was only 42%, with no missed injuries or readmissions. The ER length of stay did not change. However, in the POST period there were significant decreases in the admission rate (73% to 44%) and the mean number of CT scans (1.4 to 1), radiographs (2.4 to 1.7), and laboratory tests (5.1 to 3.3) ordered in the emergency room (all p<0.001). Conclusion: Intermediate-level pediatric trauma patients can be efficiently and safely managed by pediatric emergency room physicians, with surgical consultation only as needed. The protocol change improved resource utilization by decreasing testing and admissions and streamlining resident utilization in an era of reduced duty hours. [Copyright &y& Elsevier]

Background: Most hospitals that perform primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) in the United States exceed the recommended door-to-balloon time. There is heightened interest in identifying and eliminating factors that introduce delay. Methods: We performed a key process analysis of our primary PCI program, assessed the relative contribution of individual time intervals on total ischemic time, and identified predictors of delay. Results: Median times and predictors of delay within each time interval were determined for the entire STEMI cohort (“real world”) and after exclusion of patients with atypical symptoms and/or presentations of STEMI that resulted in inherent delay in diagnosis and treatment (“ideal world”). Delays in therapy were symptom onset to presentation (120 minutes [interquartile range, IQR, 60-310 minutes, ideal world] and 150 minutes [IQR 60-360 minutes, real world]; predictors of delay were peripheral vascular disease, self-transportation, daytime and weekend presentation); door-to-balloon time (118.5 minutes [IQR 96-141 minutes, ideal world] and 125 minutes [IQR 100-170 minutes, real world]; predictors of delay were female sex, previous stroke, nighttime and weekend presentation, and cardiogenic shock); and symptom onset to first balloon inflation (272 minutes [IQR 187-465 minutes, ideal world] and 297 minutes [IQR 198-560 minutes, real world]; predictors of delay were peripheral vascular disease, weekend presentation, and self-transportation). Conclusions: Key process analysis of a primary PCI program identifies treatment delays unique to the hospital and the patient population it serves. [Copyright &y& Elsevier]

Cholesteryl ester transfer protein (CETP) mediates the exchange of cholesteryl ester for triglyceride between high density lipoprotein (HDL) and very low density lipoprotein. The B2 allele of the TaqIB polymorphism located in the first intron of the CETP gene occurs with an allele frequency of about 0.40 in Caucasians and is associated with decreased CETP levels and activity and with higher HDL-cholesterol (HDL-C) levels in this racial group. We hypothesized that the higher levels of HDL-C seen in African Americans compared with Caucasians could be in part explained by a higher frequency of the TaqI B2 allele. We determined the distribution of this polymorphism in a total of 395 African Americans and 362 Caucasian ascertained as two independent cohorts: one of healthy volunteers (NORM) and the other of patients undergoing cardiac catheterization (CATH). Of the 244 NORM-African Americans studied, 56% were B1B1, 37% B1B2 and 7% B2B2, compared with the 224 NORM-Caucasians of which 33% were B1B1, 45% B1B2 and 22% B2B2. In the CATH-African American group (n=151) 51% were B1B1, 41% B1B2 and 8% B2B2 compared with 35% CATH-Caucasians B1B1, 54% B1B2 and 11% B2B2. The frequency of the B2 allele in the Caucasian subjects in both cohorts was similar to that reported in the literature. The frequency of the B2 allele was significantly lower in African Americans than in Caucasians in the NORM group (0.26 vs 0.44; χ2=36.5, P<0.001) and in the CATH group (0.28 vs 0.38, χ2=4.7, P=0.01). Carriers of the B2 allele had higher HDL-C levels compared with B1B1 subjects in Caucasians (NORM: 57 vs 53 mg/dl, P=0.035; CATH: 47 vs 42 mg/dl, P=0.049) and in CATH-African Americans (48 vs 43 mg/dl, P=0.028), but not in NORM-African Americans (55 vs 54 mg/dl, P=0.494). There were no other significant associations between this polymorphism and other lipids and lipoproteins in the subjects studied. These results suggest that, in contrast to our hypothesis, the B2 allele of the TaqIB polymorphism is less frequent in African Americans compared with Caucasians and that this polymorphism is unlikely to contribute to the higher levels of HDL-C reported in the African American population. [Copyright &y& Elsevier]

In-situ remediation of groundwater uranium (U) contamination via the precipitation of uranyl phosphate (U-P) minerals is a promising, passive remedial approach for aquifers impacted by mobile hexavalent U (U(VI)). We demonstrate the efficacy of U stabilization in a contaminated aquifer using a metastable form of hydroxyapatite (mHAP) derived from fish bone. This material was reacted with depleted uranium (DU) contaminated groundwater both under ambient flow in-situ, and under pumped flow ex-situ. The U immobilized under both ambient and accelerated flow conditions was strongly bound in solid phases, with greater than 99% U removal from groundwater. Stable U uptake in excess of 50 g U/kg solid was achieved due to the precipitation of the crystalline U-P mineral chernikovite. Prior field trials yielded U immobilization by sorption alone [Fuller et al., 2003, Env. Sci. Technol . 37 , 4642.], likely due to higher pH and alkalinity groundwater conditions, which increase the solubility of U-P phases via aqueous complexation. Our study is the first to demonstrate the feasibility of U immobilization by U-P precipitation from natural groundwater. These findings suggest that in groundwaters contaminated by U(VI) with circumneutral pH and low carbonate alkalinity, fish bone-derived hydroxyapatite is an effective material for in-situ U remediation that can be readily implemented, requiring no redox manipulation. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Although cardiovascular diseases (CVD) are the leading cause of death among Americans, significant disparities persist in CVD prevalence, morbidity, and mortality based on race and ethnicity. However, few studies have examined risk factor reduction among the poor and ethnic minorities. Methods: Community-based participatory research (CBPR) study using a cluster randomized design — African-American church congregations are the units of randomization and individuals within the congregations are the units of analysis. Outcome variables include dietary change (Diet History Questionnaire), level of physical activity (7-Day Physical Activity Recall), lipoprotein levels, blood pressure, fasting glucose, and hemoglobin A1c. Results: Eighteen (18) church congregations were randomized to either a health maintenance intervention or a control condition. Complete data were obtained on 392 African-American individuals, 18 to 70years of age, predominantly employed women with more than a high school diploma. Treatment and intervention groups were similar at baseline on saturated fat intake, metabolic equivalent of tasks (METS) per day, and other risk factors for CVD. Conclusions: The GoodNEWS trial successfully recruited and evaluated CVD-related risk among African-American participants using a CBPR approach. Several logistical challenges resulted in extending the recruitment, preliminary training, and measurement periods. The challenges were overcome with the assistance of a local community consultant and a professional event planner. Our experience supports the need for incorporating non-traditional community-based staff into the design and operational plan of CBPR trials. [Copyright &y& Elsevier]

: ObjectivesThe Early Retavase-Thrombolysis In Myocardial Infarction (ER-TIMI) 19 trial tested the feasibility of prehospital initiation of the bolus fibrinolytic reteplase (rPA) and determined the time saved by prehospital rPA in the setting of contemporary emergency cardiac care.: BackgroundNewer bolus fibrinolytics have undergone only limited evaluation for prehospital administration. In addition, as door-to-drug times have decreased, the relevance of findings from prior trials of prehospital fibrinolysis has become less certain.: MethodsPatients (n = 315) with ST-elevation myocardial infarction (STEMI) were enrolled in 20 emergency medical systems in North America. The time from emergency medical service (EMS) arrival to administration of a fibrinolytic was compared between study patients receiving prehospital rPA and sequential control patients from 6 to 12 months before the study who received a fibrinolytic in the hospital.: ResultsAcute myocardial infarction was confirmed in 98%. The median time from EMS arrival to initiation of rPA was 31 min (25th to 75th percentile, 24 min to 37 min). The time from EMS arrival to in-hospital fibrinolytic for 630 control patients was 63 min (25th to 75th percentile, 48 min to 89 min), resulting in a time saved of 32 min (p < 0.0001). By 30 min after first medical contact, 49% of study patients had received the first bolus of fibrinolytic compared with only 5% of controls (p < 0.0001). In-hospital mortality was 4.7%. Intracranial hemorrhage occurred in 1.0%.: ConclusionsPrehospital administration of rPA is a feasible approach to accelerating reperfusion in patients with STEMI. Valuable time savings can be achieved in the setting of contemporary transport and door-to-drug times and may translate into an improvement in clinical outcomes. [Copyright &y& Elsevier]