Recent Publications by CFE Educators

It has been shown that patients with hepatocellular carcinoma (HCC) meeting the United Network for Organ Sharing T2 (Milan) criteria have an advantage in comparison with patients without HCC under the current organ allocation system for liver transplantation (LT). We hypothesized that within the T2 HCC group, there is a subgroup with a low risk of wait-list dropout that should not receive the same listing priority. This study evaluated 398 consecutive patients with T2 HCC listed for LT with a Model for End-Stage Liver Disease exception from March 2005 to January 2011 at our center. Competing risk (CR) regression was used to determine predictors of dropout. The probabilities of dropout due to tumor progression or death without LT according to the CR analysis were 9.4% at 6 months and 19.6% at 12 months. The median time from listing to LT was 8.8 months, and the median time from listing to dropout or death without LT was 7.2 months. Significant predictors of dropout or death without LT according to a multivariate CR regression included 1 tumor of 3.1 to 5 cm (versus 1 tumor of 3 cm or less), 2 or 3 tumors, a lack of a complete response to the first locoregional therapy (LRT), and a high alpha-fetoprotein (AFP) level after the first LRT. A subgroup (19.9%) that met certain criteria (1 tumor of 2 to 3 cm, a complete response after the first LRT, and an AFP level ≤ 20 ng/mL after the first LRT) had 1- and 2-year probabilities of dropout of 1.3% and 1.6%, respectively, whereas the probabilities were 21.6% and 26.5% for all other patients (P = 0.004). In conclusion, a combination of tumor characteristics and a complete response to the first LRT define a subgroup of patients with a very low risk of wait-list dropout who do not require the same listing priority. Our results may have important implications for the organ allocation policy for HCC.

Presensitization with Mtb-derived trehalose 6,6'-dimycolate (TDM; cord factor) followed by challenge with the same glycolipid species resulted in elicitation of stronger inflammatory responses than when mice were similarly challenged with M. bovis-derived TDM. Mice presensitized to the homologous Mtb-derived TDM demonstrated cachexic over a 6 day period, whereas similarly presensitized mice challenged with the M. bovis-derived TDM, or with emulsion control, did not experience weight loss. Examination of inflammatory responses demonstrated increased lung histopathology in the Mtb-derived TDM challenged group, evidenced by severe tissue disruption, cellular influx, vascular occlusion and lymphocytic cuffing, and endothelial cell damage. Histological analysis demonstrated that lung pathology in the M. bovis challenged group was strikingly similar to that of the acute model challenge. Examination of proinflammatory mediators also showed findings consistent with histological manifestation, with significantly elevated TNF-α and IL-1β, as well as IFN-γ, in the homologous TDM challenged group relative to all other groups. Overall, these findings indicate a difference in hypersensitive immune responses to TDM derived from different mycobacterial strains. Development of specific adaptive immune responses to the Mtb-derived TDM were demonstrated that had limited cross-reactivity to that of M. bovis, thus strongly suggesting the presence of hypersensitive epitopes exclusive to Mtb TDM not present on M. bovis-derived TDM.

"Changing our culture to advance patient safety" served as the theme of the 81st Annual Meeting of the American Association of Neurological Surgeons and is an issue of personal importance to the author. To improve outcomes for patients and prevent avoidable surgical errors, neurosurgeons must change the culture that currently exists in the operating room so that safety concerns are of the utmost importance and that each member of the care team has a personal sense of accountability. Doing this will involve implementing and consistently applying systems-based strategies to ensure an adequate level of safeguards; improving communication with all members of the care team and dismantling authority gradients; and maintaining a well-trained and well-rested workforce.

BACKGROUND

To determine the incidence of electrographic seizures during continuous electroencephalography (cEEG) in the medical and surgical ICU.

METHODS

We retrospectively reviewed the records of all adults who underwent cEEG in our medical and surgical ICU over a 4.5 year period. Patients with acute brain injury were excluded. Our primary outcome was cEEG documentation of an electrographic seizure, defined as a rhythmic discharge or spike and wave pattern demonstrating definite evolution and lasting at least 10 s. To assess inter-rater variability in cEEG interpretation, two electrophysiologists independently reviewed all available cEEGs of subjects with electrographic seizures documented on their clinical cEEG report and those of an equal number of randomly selected subjects from the remaining cohort.

RESULTS

Kappa analysis showed a value of 0.88, indicating excellent inter-rater agreement. Electrographic seizures were identified in 12 of 105 patients (11 %, 95 % CI 5-18 %). This rate did not change after excluding patients with a history of seizure, remote brain injury, or seizure-like events before cEEG. In an ordinal logistic regression model controlling for age, sex, and SOFA score, electrographic seizures were associated with lower odds of good outcomes on the Glasgow Outcome Scale at discharge (OR 0.3, 95 % CI 0.1-0.8).

CONCLUSION

In a tertiary care medical and surgical ICU, electrographic seizures were seen on 11 % of cEEGs ordered for the evaluation of encephalopathy, and were associated with worse functional outcomes at discharge. Our findings confirm the results of a prior study suggesting a substantial burden of electrographic seizures in critically ill encephalopathic patients.

BACKGROUND

TMPRSS2:ERG is a hormonally regulated gene fusion present in about half of prostate tumors. We investigated whether obesity, which deregulates several hormonal pathways, interacts with TMPRSS2:ERG to impact prostate cancer outcomes.

METHODS

The study included 1243 participants in the prospective Physicians' Health Study and Health Professionals Follow-Up Study diagnosed with prostate cancer between 1982 and 2005. ERG overexpression (a TMPRSS2:ERG marker) was assessed by immunohistochemistry of tumor tissue from radical prostatectomy or transurethral resection of the prostate. Body mass index (BMI) and waist circumference, measured on average 1.3 years and 5.3 years before diagnosis, respectively, were available from questionnaires. Data on BMI at baseline was also available. We used Cox regression to calculate hazard ratios and 95% confidence intervals (CIs). All statistical tests were two-sided.

RESULTS

During a mean follow-up of 12.8 years, 119 men developed lethal disease (distant metastases or prostate cancer death). Among men with ERG-positive tumors, the multivariable hazard ratio for lethal prostate cancer was 1.48 (95% CI = 0.98 to 2.23) per 5-unit increase in BMI before diagnosis, 2.51 (95% CI = 1.26 to 4.99) per 8-inch increase in waist circumference before diagnosis, and 2.22 (95% CI = 1.35 to 3.63) per 5-unit increase in BMI at baseline. The corresponding hazard ratios among men with ERG-negative tumors were 1.10 (95% CI = 0.76 to1.59; P interaction = .24), 1.14 (95% CI = 0.62 to 2.10; P interaction = .09), and 0.78 (95% CI = 0.52 to 1.19; P interaction = .001).

CONCLUSIONS

These results suggest that obesity is linked with poorer prostate cancer prognosis primarily in men with tumors harboring the gene fusion TMPRSS2:ERG.