Melanoma risk alleles are associated with downregulation of the MTAP gene and hypermethylation of a CpG island upstream of the gene in dermal fibroblasts

Several association studies and GWAS on melanoma skin cancer risk have reported statistically significant signals on 9p21.3 region, where MTAP gene maps. None of the associated SNPs identified in these studies lie in the coding region of the gene and the causative relation of risk alleles with melanoma predisposition has not been elucidated. MTAP has a tumor suppressor activity and epigenetic silencing has been described in melanoma cell lines. In the present study, we show that melanoma risk alleles correlate with a MTAP allele‐specific hyper‐methylation and down‐regulation of gene expression.     

Cost-effectiveness of defibrillation by emergency medical technicians

Effective emergency systems using emergency medical technicians (EMTs) trained to defibrillate or paramedics can save more lives from out-of-hospital cardiac arrest due to ventricular fibrillation than can emergency systems staffed with basic EMTs who cannot defibrillate. This article focuses on the cost-effectiveness of systems staffed with each type of EMT. Data were collected from all 50 states and from the District of Columbia to determine the number of hours and estimated cost of initial training for the three types of EMTs in the United States in 1986. The median initial training hours for basic EMTs, EMTs trained in defibrillation, and paramedics were 110, 129, and 700, respectively. Median costs for initial training at each EMT level were +123, +150, and +1580/student. According to published survival data for emergency medical systems staffed with EMTs at each level, the total initial training personnel and equipment cost per life saved from ventricular fibrillation was +7687, +2126, and +2289 for systems staffed by the respective EMTs. The initial cost per life saved from ventricular fibrillation is more than three times greater in systems staffed by basic EMTs than in systems staffed by EMTs trained in defibrillation or paramedics. From a medical and a cost-effective standpoint, all communities served by basic EMTs should consider upgrading them to at least the defibrillation-trained EMT level.     

Effect of infusion and withdrawl of glucose and insulin on gas exchange in injured ventilated patients

To evaluate the effect induced on gas exchange and on urea excretion by glucose and insulin infusion in injured patients. The magnitude and time necessary for the full development of the metabolic effect were investigated. Six injured patients were investigated. During the first 24 hours, the fasting period, patients received 1 mg/kg^*min of glucose; during the second 24 hours, the treatment period, infusion was increased to about the 95% of the energy production rate; during the last 8 hours, (stop period) the infusion rate was again set to 1 mg/kg^*min. Gas exchange was determined in two consecutive 12-hour series, for 30 minutes every hour, either during a stabilized treatment or after its variation. Urea excretion was determinated on 4-hour samples. With respect to the fasting period, during the last 4 hours of the treatment period, the energy production rate did not vary; urea excretion (−25%) and oxygen consumption (−9%) decreased significantly. Carbon dioxide production (+16%), total respiratory quotient, and minute ventilation (+5%) increased significantly. Carbon dioxide production varied linearly with time (glucose infusion ⁺1.74 mL/min^*m2^*h, P <.05; glucose withdrawal −1.89 mL/min^*m2^*h, P < .01). Minute ventilation decreased only during the withdrawal period by 65 mL/ min^*m2^*h (P < .05). The infusion of glucose and insulin, in an amount slightly lower than the metabolic expenditure, leads to a consistently reduced amino acid catabolism and to a decreased oxygen consumption, without affecting energy requirements. Although it leads to an increase of carbon dioxide production, the measured change is so small and slow that it is not harmful unless there is severe respiratory insufficiency.     

Risk Factors for Survival after Lung Metastasectomy in Colorectal Cancer Patients: A Systematic Review and Meta-Analysis

Background

Resection of lung metastases (LM) from colorectal cancer (CRC) is increasingly performed with a curative intent. It is currently not possible to identify those CRC patients who may benefit the most from this surgical strategy. The aim of this study was to perform a systematic review of risk factors for survival after lung metastasectomy for CRC.

Methods

We performed a meta-analysis of series published between 2000 and 2011, which focused on surgical management of LM from CRC and included more than 40 patients each. Pooled hazard ratios (HR) were calculated by using random effects model for parameters considered as potential prognostic factors.

Results

Twenty-five studies including a total of 2925 patients were considered in this analysis. Four parameters were associated with poor survival: (1) a short disease-free interval between primary tumor resection and development of LM (HR 1.59, 95 % confidence interval [CI] 1.27–1.98); (2) multiple LM (HR 2.04, 95 % CI 1.72–2.41); (3) positive hilar and/or mediastinal lymph nodes (HR 1.65, 95 % CI 1.35–2.02); and (4) elevated prethoracotomy carcinoembryonic antigen (HR 1.91, 95 % CI 1.57–2.32). By comparison, a history of resected liver metastases (HR 1.22, 95 % CI 0.91–1.64) did not achieve statistical significance.

Conclusions

Clinical variables associated with prolonged survival after surgery for LM in CRC patients include prolonged disease-free interval between primary tumor and metastatic spread, normal prethoracotomy carcinoembryonic antigen, absence of thoracic node involvement, and a single pulmonary lesion.     

Percutaneous Excisional Biopsy of Palpable Breast Masses under Ultrasound Visualization

Abstract:   A palpable breast mass is a common reason for surgical consultation. Our goal was to determine whether ultrasound-guided vacuum-assisted core biopsy (US-VACB) is safe and effective in completely removing presumed benign palpable breast masses. We conducted a cohort study of 201 consecutive patients with presumed benign palpable masses who underwent removal with US-VACB. The main outcome measured was the successful removal of palpable masses. Palpable masses were successfully removed with US-VACB in 99% of cases; 2% were cancer and 7.5% were atypical ductal hyperplasia or phyllodes tumor. Two clinical recurrences representing a seroma were seen on follow-up. US-VACB is safe and effective in the initial diagnosis and management of presumed benign palpable breast masses. It provides the benefits of percutaneous biopsy and the palpable abnormality no longer remains.      

Duplication of the hepatopancreatic bud presenting as pyloric stenosis

Duplication of systemic organs is not a frequent finding. We report the occurrence of duplication of the hepatopancreatic bud with presence of mature hepatic and pancreatic tissue in a nine-day-old girl who presented with intestinal obstruction mimicking infantile hypertrophic pyloric stenosis.     

Human ventral parietal cortex plays a functional role on visuospatial attention and primary consciousness. A repetitive transcranial magnetic stimulation study

In this paper, we used repetitive transcranial magnetic stimulation (rTMS) in 18 normal subjects to investigate whether the ventral posterior parietal cortex (PPC) plays a causal role on visuospatial attention and primary consciousness and whether these 2 functions are linearly correlated with each other. Two distinct experimental conditions involved a similar visual stimuli recognition paradigm. In "Consciousness" experiment, number of consciously perceived visual stimuli was lower by about 10% after rTMS (300 ms, 20 Hz, motor threshold intensity) on left or right PPC than after sham (pseudo) rTMS. In "Attentional" Posner's experiment, these stimuli were always consciously perceived. Compared with sham condition, parietal rTMS slowed of about 25 ms reaction time to go stimuli, thus disclosing effects on endogenous covert spatial attention. No linear correlation was observed between the rTMS-induced impairment on attention and conscious perception. Results suggest that PPC plays a slight but significant causal role in both visuospatial attention and primary consciousness. Furthermore, these high-level cognitive functions, as modulated by parietal rTMS, do not seem to share either linear or simple relationships.