Gustilo type IIIC open tibia fractures with vascular repair: minimum 2-year follow-up

Purpose

Salvage or amputation for grade 3C open fracture of tibia is not well responded question universally because of surgical innovations, cultural believes, difficulties in estimate the outcome, coasts, and different results in the literature. The aim of this study was to evaluate the surgical outcomes of Gustilo grade 3C open tibia fractures with at least two years follow-up in non-military adults.

Methods

Twenty-two non-military patients with a mean age of 31.1 were operated with grade 3c open fractures at tibia level in last 10 years in our clinic. We evaluated them retrospectively and asked about their daily life, pain, and if present, about the wish for secondary amputation. We also asked if they would prefer a first day amputation rather than their present status.

Results

Mean operation time after the injury was 13 h. Seven patients had nerve injury. Mean operation number was 3.5. Eight patients (%36) (all due to circulatory problem) had to have amputation. All patients treated with temporary unilateral external fixation than converted to circular external fixators when soft tissue healing was completed. Two patients were reoperated because of deformity. Four patients needed revision surgery because of non-union. At long term follow, we had osteomyelitis in one patient.

Conclusions

Scoring systems and the ischemic time are not the only predictors of amputation. The decision of the treatment mode should be made by the patient and the care team after discussing the options and outcomes rather than relying on a scoring system.

     

Preclinical evaluation of the penciclovir analog 9-(4-[(18)F]fluoro-3-hydroxymethylbutyl)guanine for in vivo measurement of suicide gene expression with PET.

The gene for herpes simplex virus thymidine kinase (HSV-tk) is widely used as a suicide gene in experimental gene therapy of cancer. 9-(4-Fluoro-3-hydroxymethylbutyl)guanine (FHBG) is an antiviral nucleoside analog that is rapidly phosphorylated by viral thymidine kinase but is a poor substrate for mammalian thymidine kinase. Recently, FHBG labeled in the 4-fluoro position with (18)F has shown promise relative to other similar compounds for imaging in vivo expression of HSV-tk using PET. In this study, we evaluated the uptake of [(18)F]FHBG in vitro and in vivo using transduced and wild-type human colon cancer cells (HT-29). We also imaged [(18)F]FHBG and measured the radioactivity concentrations of circulating [(18)F]FHBG and its metabolites in monkeys. METHODS: Sterile, pyrogen-free [(18)F]FHBG was produced routinely in good yields. Cells were transduced with the retroviral vector G1Tk1SvNa containing HSV-tk gene. In vitro uptake studies were performed by incubating cells with [(18)F]FHBG at 37 degrees C for 1 and 5 h. Biodistribution studies were performed at 2 and 5 h after injection in nude mice bearing tumors grown from wild-type or transduced cells. Sequential, whole-body PET scans of cynomolgus monkeys were obtained over a period of >2 h after intravenous injection of [(18)F]FHBG. Arterial plasma samples obtained from monkeys 15-120 min after intravenous injection were subjected to acid extraction, and the acid-soluble fractions were analyzed by high-performance liquid chromatography. RESULTS: In vitro studies showed 31 and 71 (P < 0.001) times higher uptake of the probe at 1 and 5 h, respectively, in transduced cells compared with nontransduced cells. In vivo studies in mice showed that tumor uptake of the radiotracer was 4-fold (P < 0.05) and 13-fold (P < 0.001) higher at 2 and 5 h, respectively, in tumors grown from transduced cells compared with control cells. Transduced tumor-to-normal tissue ratios ranged from 2 to 25 at 2 h and from 2 to 22 at 5 h. Recirculating labeled metabolites had only a minor effect on the biodistribution of radiolabel from [(18)F]FHBG in monkeys. CONCLUSION: These results indicate that [(18)F]FHBG may yield high-contrast PET images of HSV-tk expression in tumors and, therefore, it is a very promising radiotracer for monitoring of gene therapy of cancer with PET.     

Relaxing music reduces blood pressure and heart rate among pre‐hypertensive young adults: A randomized control trial

Prevalence of pre‐hypertension is higher among young adults and may increase the risk for hypertension and cardiovascular morbidity. Music therapy has been investigated to reduce the blood pressure in the hypertensive population; however, its efficacy on blood pressure in pre‐hypertensive young adults is not known. Thirty pre‐hypertensive (systolic blood pressure [SBP] = 120‐139 mmHg and diastolic blood pressure [DBP] = 80‐89 mmHg) young adults were recruited and randomly assigned into two groups. Music group (N = 15) received music therapy by passive listening to music for 30 minutes/day, 5 days/week for 4 weeks, along with Dietary Approaches to Stop Hypertension (DASH) eating plan (a diet rich in fruits and vegetables, low‐fat dairy or unsaturated fat) and limit the daily sodium intake less than 100 mmol/day. The control group (N = 15) practiced only DASH eating plan and sodium restriction. The SBP, DBP, and heart rate (HR) were measured before and after 4 weeks of intervention. There was a significant reduction in SBP (8.73 mmHg, p < .001) and HR (6.42 beats/minute, p = .002); however, the reduction in DBP (1.44 mmHg, p = .101) was not statistically significant in the music group. Control group did not exhibit any significant reduction in SBP (0.21 mmHg, p < .836), DBP (0.81 mmHg, p < .395) and HR (0.09 beats/minute, p < .935). In conclusion, music therapy reduced significantly SBP and HR suggesting that it could be a promising tool to prevent the progression of pre‐hypertension toward hypertension among young adults.     

Molecular imaging of active mutant L858R EGF receptor (EGFR) kinase-expressing nonsmall cell lung carcinomas using PET/CT

The importance of the EGF receptor (EGFR) signaling pathway in the development and progression of nonsmall cell lung carcinomas (NSCLC) is widely recognized. Gene sequencing studies revealed that a majority of tumors responding to EGFR kinase inhibitors harbor activating mutations in the EGFR kinase domain. This underscores the need for novel biomarkers and diagnostic imaging approaches to identify patients who may benefit from particular therapeutic agents and approaches with improved efficacy and safety profiles. To this goal, we developed 4-[(3-iodophenyl)amino]-7-{2-[2-{2-(2-[2-{2-([(18)F]fluoroethoxy)-ethoxy}-ethoxy]-ethoxy)-ethoxy}-ethoxy]-quinazoline-6-yl-acrylamide ([(18)F]F-PEG6-IPQA), a radiotracer with increased selectivity and irreversible binding to the active mutant L858R EGFR kinase. We show that PET with [(18)F]F-PEG6-IPQA in tumor-bearing mice discriminates H3255 NSCLC xenografts expressing L858R mutant EGFR from H441 and PC14 xenografts expressing EGFR or H1975 xenografts with L858R/T790M dual mutation in EGFR kinase domain, which confers resistance to EGFR inhibitors (i.e., gefitinib). The T790M mutation precludes the [(18)F]F-PEG6-IPQA from irreversible binding to EGFR. These results suggest that PET with [(18)F]F-PEG6-IPQA could be used for the selection of NSCLC patients for individualized therapy with small molecular inhibitors of EGFR kinase that are currently used in the clinic and have a similar structure (i.e., iressa, gefitinib, and erlotinib).     

A Prospective Study of Arsenic Exposure,Arsenic Methylation Capacity,and Risk of Cardiovascular Disease in Bangladesh

Background: Few prospective studies have evaluated the influence of arsenic methylation capacity on cardiovascular disease (CVD) risk.Objective: We evaluated the association of arsenic exposure from drinking water and arsenic methylation capacity with CVD risk.Method: We conducted a case–cohort study of 369 incident fatal and nonfatal cases of CVD, including 211 cases of heart disease and 148 cases of stroke, and a subcohort of 1,109 subjects randomly selected from the 11,224 participants in the Health Effects of Arsenic Longitudinal Study (HEALS).Results: The adjusted hazard ratios (aHRs) for all CVD, heart disease, and stroke in association with a 1-SD increase in baseline well-water arsenic (112 µg/L) were 1.15 (95% CI: 1.01, 1.30), 1.20 (95% CI: 1.04, 1.38), and 1.08 (95% CI: 0.90, 1.30), respectively. aHRs for the second and third tertiles of percentage urinary monomethylarsonic acid (MMA%) relative to the lowest tertile, respectively, were 1.27 (95% CI: 0.85, 1.90) and 1.55 (95% CI: 1.08, 2.23) for all CVD, and 1.65 (95% CI: 1.05, 2.60) and 1.61 (95% CI: 1.04, 2.49) for heart disease specifically. The highest versus lowest ratio of urinary dimethylarsinic acid (DMA) to MMA was associated with a significantly decreased risk of CVD (aHR = 0.54; 95% CI: 0.34, 0.85) and heart disease (aHR = 0.54; 95% CI: 0.33, 0.88). There was no significant association between arsenic metabolite indices and stroke risk. The effects of incomplete arsenic methylation capacity—indicated by higher urinary MMA% or lower urinary DMA%—with higher levels of well-water arsenic on heart disease risk were additive. There was some evidence of a synergy of incomplete methylation capacity with older age and cigarette smoking.Conclusions: Arsenic exposure from drinking water and the incomplete methylation capacity of arsenic were adversely associated with heart disease risk.     

Automated Analysis of Retinal Vascular Tortuosity on Color Retinal Images

Recent advances in medical imaging modality have enabled us to identify new features in retinal vasculature. One of the features is retinal vascular tortuosity which has been shown to become a predictive factor for cardiovascular diseases and diabetes. The changes in retinal vascular tortuosity might be a sign of severity or improvement of the disease. In this paper, we propose a new method for measuring retinal vascular tortuosity. We adopt a new technique to analyze tortuosity that consider vessel-segment’s width simultaneously. Our proposed method measures vessel-segment’s tortuosity on its edge. A qualitative assessment shows that the method is appropriate for measuring the tortuosity of the vessels in different widths and directions in the image. Finally, a comparison distinguishing tortuous vs. non tortuous vessels demonstrates that the proposed approach may be suitable for predicting or earlier diagnosis of diabetes or cardiovascular diseases.     

The Genetic Architecture of Arsenic Metabolism Efficiency:A SNP-Based Heritability Study of Bangladeshi Adults

Background

Consumption of arsenic-contaminated drinking water adversely affects health. There is interindividual variation in arsenic metabolism efficiency, partially due to genetic variation in the arsenic methyltransferase (AS3MT) gene region.

Objectives

The goal of this study was to assess the overall contribution of genetic factors to variation in arsenic metabolism efficiency, as measured by the relative concentration of dimethylarsinic acid (DMA%) in urine.

Methods

Using data on genome-wide single nucleotide polymorphisms (SNPs) and urinary DMA% for 2,053 arsenic-exposed Bangladeshi individuals, we employed various SNP-based approaches for heritability estimation and polygenic modeling.

Results

Using data on all participants, the percent variance explained (PVE) for DMA% by all measured and imputed SNPs was 16% (p = 0.08), which was reduced to 5% (p = 0.34) after adjusting for AS3MT SNPs. Using information on close relatives only, the PVE was 63% (p = 0.0002), but decreased to 41% (p = 0.01) after adjusting for AS3MT SNPs. Regional heritability analysis confirmed 10q24.32 (AS3MT) as a major arsenic metabolism locus (PVE = 7%, p = 4.4 × 10^–10), but revealed no additional regions. We observed a moderate association between a polygenic score reflecting elevated DMA% (composed of thousands of non-AS3MT SNPs) and reduced skin lesion risk in an independent sample (p < 0.05). We observed no associations for SNPs reported in prior candidate gene studies of arsenic metabolism.

Conclusions

Our results suggest that there are common variants outside of the AS3MT region that influence arsenic metabolism in Bangladeshi individuals, but the effects of these variants are very weak compared with variants near AS3MT. The high heritability estimates observed using family-based heritability approaches suggest substantial effects for rare variants and/or unmeasured environmental factors.

Citation

Gao J, Tong L, Argos M, Scannell Bryan M, Ahmed A, Rakibuz-Zaman M, Kibriya MG, Jasmine F, Slavkovich V, Graziano JH, Ahsan H, Pierce BL. 2015. The genetic architecture of arsenic metabolism efficiency: a SNP-based heritability study of Bangladeshi adults. Environ Health Perspect 123:985–992; http://dx.doi.org/10.1289/ehp.1408909     

Association between arsenic exposure from drinking water and hematuria: Results from the Health Effects of Arsenic Longitudinal Study

Arsenic (As) exposure has been associated with both urologic malignancy and renal dysfunction; however, its association with hematuria is unknown. We evaluated the association between drinking water As exposure and hematuria in 7843 men enrolled in the Health Effects of Arsenic Longitudinal Study (HEALS). Cross-sectional analysis of baseline data was conducted with As exposure assessed in both well water and urinary As measurements, while hematuria was measured using urine dipstick. Prospective analyses with Cox proportional regression models were based on urinary As and dipstick measurements obtained biannually since baseline up to six years. At baseline, urinary As was significantly related to prevalence of hematuria (P-trend < 0.01), with increasing quintiles of exposure corresponding with respective prevalence odds ratios of 1.00 (reference), 1.29 (95% CI: 1.04–1.59), 1.41 (95% CI: 1.15–1.74), 1.46 (95% CI: 1.19–1.79), and 1.56 (95% CI: 1.27–1.91). Compared to those with relatively little absolute urinary As change during follow-up (− 10.40 to 41.17 μg/l), hazard ratios for hematuria were 0.99 (95% CI: 0.80–1.22) and 0.80 (95% CI: 0.65–0.99) for those whose urinary As decreased by > 47.49 μg/l and 10.87 to 47.49 μg/l since last visit, respectively, and 1.17 (95% CI: 0.94–1.45) and 1.36 (95% CI: 1.10–1.66) for those with between-visit increases of 10.40 to 41.17 μg/l and > 41.17 μg/l, respectively. These data indicate a positive association of As exposure with both prevalence and incidence of dipstick hematuria. This exposure effect appears modifiable by relatively short-term changes in drinking water As.