Radiomic mapping model for prediction of Ki-67 expression in adrenocortical carcinoma.

AIM: To determine the value of contrast-enhanced computed tomography (CT)-derived radiomic features in the preoperative prediction of Ki-67 expression in adrenocortical carcinoma (ACC) and to detect significant associations between radiomic features and Ki-67 expression in ACC. MATERIALS AND METHODS: For this retrospective analysis, patients with histopathologically proven ACC were reviewed. Radiomic features were extracted for all patients from the preoperative contrast-enhanced abdominal CT images. Statistical analysis identified the radiomic features predicting the Ki-67 index in ACC and analysed the correlation with the Ki-67 index. RESULTS: Fifty-three cases of ACC that met eligibility criteria were identified and analysed. Of the radiomic features analysed, 10 showed statistically significant differences between the high and low Ki-67 expression subgroups. Multivariate linear regression analysis yielded a predictive model showing a significant association between radiomic signature and Ki-67 expression status in ACC (R2=0.67, adjusted R2=0.462, p=0.002). Further analysis of the independent predictors showed statistically significant correlation between Ki-67 expression and shape flatness, elongation, and grey-level long run emphasis (p=0.002, 0.01, and 0.04, respectively). The area under the curve for identification of high Ki-67 expression status was 0.78 for shape flatness and 0.7 for shape elongation. CONCLUSION: Radiomic features derived from preoperative contrast-enhanced CT images show encouraging results in the prediction of the Ki-67 index in patients with ACC. Morphological features, such as shape flatness and elongation, were superior to other radiomic features in the detection of high Ki-67 expression.

Low CHD5 expression activates the DNA damage response and predicts poor outcome in patients undergoing adjuvant therapy for resected pancreatic cancer.

The DNA damage response (DDR) promotes genome integrity and serves as a cancer barrier in precancerous lesions but paradoxically may promote cancer survival. Genes that activate the DDR when dysregulated could function as useful biomarkers for outcome in cancer patients. Using a siRNA screen in human pancreatic cancer cells, we identified the CHD5 tumor suppressor as a gene, which, when silenced, activates the DDR. We evaluated the relationship of CHD5 expression with DDR activation in human pancreatic cancer cells and the association of CHD5 expression in 80 patients with resected pancreatic adenocarcinoma (PAC) by immunohistochemical analysis with clinical outcome. CHD5 depletion and low CHD5 expression in human pancreatic cancer cells lead to increased H2AX-Ser139 and CHK2-Thr68 phosphorylation and accumulation into nuclear foci. On Kaplan-Meier log-rank survival analysis, patients with low CHD5 expression had a median recurrence-free survival (RFS) of 5.3 vs 15.4 months for patients with high CHD5 expression (P=0.03). In 59 patients receiving adjuvant chemotherapy, low CHD5 expression was associated with decreased RFS (4.5 vs 16.3 months; P=0.001) and overall survival (OS) (7.2 vs 21.6 months; P=0.003). On multivariate Cox regression analysis, low CHD5 expression remained associated with worse OS (HR: 3.187 (95% CI: 1.49-6.81); P=0.003) in patients undergoing adjuvant chemotherapy. Thus, low CHD5 expression activates the DDR and predicts for worse OS in patients with resected PAC receiving adjuvant chemotherapy. Our findings support a model in which dysregulated expression of tumor suppressor genes that induce DDR activation can be utilized as biomarkers for poor outcome.

Evaluation of ibuprofen for pressure ulcer prevention: application of a rat pressure ulcer model.

This blinded study describes the effect of ibuprofen (IBU) on experimental pressure ulcers (PU) induced in the fuzzy rat model. Ibuprofen's fibrinolytic activity has been found effective in preserving dermal vasculature in rats following burn injury. Experimental pressure ulcers were generated on the hips of fuzzy rats with the aid of computer control, using five daily, 6-hour pressure sessions. In the first study, 17 rats received intraperitoneal (I.P.) injection of IBU or saline control after each pressure session. In the second study, 44 rats received IBU or control, before, during, and after application of pressure by I.P. or intramuscular (I.M.) injections. Quantitation of histology is based on five prominent lesions, including: ulceration, infarction, panniculus carnosus necrosis, fat atrophy, and deep muscle necrosis. The following hypothesis was tested: Reperfusion injury and vascular occlusion in pressure ulcers may be similar to that which occurs in burns and, therefore, is responsive to IBU intervention. The results indicate that IBU does not have significant effects on the development of pressure ulcers. The mechanisms of IBU action in other organ and tissue systems are discussed in relation to the effect of IBU on the pressure ulcer model.

An animal model and computer-controlled surface pressure delivery system for the production of pressure ulcers.

Pressure ulcers continue to be a major health care problem. This paper describes an animal model and surface pressure delivery system for the production of experimentally derived pressure ulcers. A method for inducing dermal pressure lesions on the fuzzy rat was developed using a computer-controlled displacement column which produced a constant tissue interface pressure. The pressure column consists of a force transducer located between two 0.5-in (1.27-cm) diameter metal cylinders. The desired cutaneous pressure is maintained by a computer-controlled miniature stepper motor which displaces the column with the aid of interactive software. The force transducer signal is converted from analog to digital form, amplified, and recorded. Blood perfusion is monitored using a laser Doppler flowmeter (located in the tip of the column) during the application of pressure. The application of 145 mmHg pressure for 5 consecutive 6-hr sessions resulted in a greater than 90% incidence of pressure ulcers. The implications of our model and contributions of earlier animal models are discussed. This model provides a tightly controlled and measured environment making possible the scientific study of ulcer development and the evaluation of potential preventative or curative compounds.

Patterns of knee arthrosis and patellar subluxation.

This study was based on the unexpected observation of lateral patellofemoral subluxation in the varus osteoarthritic knee. Standardized radiographs of 109 knees (65 patients with osteoarthritis) were selected randomly from the authors' database and retrospectively reviewed. Hip-knee-ankle alignment data were correlated with patellofemoral subluxation and tilt, as well as with radiographic patellofemoral grades for arthrosis. The amount and site of patellofemoral arthrosis were correlated with patellar position and limb alignment. Patellae that were located centrally in the trochlear groove had the lowest radiographic score for arthrosis. Subluxation of the patella, either medially or laterally, was correlated with increased radiographic scores. Limb alignment was not correlated with the radiographic score. A significant percentage of varus knees (28%) had unexpected lateral subluxation of the patella. This observation has not been reported previously. It may have an impact on surgical decision-making for total knee arthroplasty and osteotomy.

Histopathology of pressure ulcers as a result of sequential computer-controlled pressure sessions in a fuzzy rat model.

This study describes the sequential histopathological changes that occur in the development of pressure ulcers experimentally induced in the fuzzy rat model. Computer-controlled pressure was applied for six hours at a maximum of five sessions, to skin over the greater trochanter of anesthetized rats. Lesions were similar, but more pronounced after the third, fourth, and fifth sessions as compared to the first or second sessions. Lesions developed first in the muscle rather than the dermis or epidermis. The lesion most often associated with pressure was necrosis of the panniculus carnosus muscle, often accompanied by damage to underlying adipose tissue. Recurrent pressure results in increasingly severe damage to the vascular system and parenchyma, consistent with an ischemia/reperfusion insult initiated through a free radical mechanism.

Underutilization of physician assistants in physical medicine and rehabilitation.

This study was undertaken to determine the utilization of physician assistants (PAs) in physical medicine and rehabilitation (PM&R). Survey questionnaires were sent to members of the American Academy of Physical Medicine and Rehabilitation, members of the American Academy of Physician Assistants, and administrators of free-standing rehabilitation facilities. One hundred thirty-seven of 1,082 physiatrists (13% of those responding) reported PAs employed in their practice settings, 83 of 549 PAs (15% of those responding) identified PM&R as their specialty, and 17 of 65 hospital administrators, (27% of those responding) reported PAs working at their facility. Seventy-nine percent (713 of 903) of physicians and 77% (50 of 65) of administrators were unaware that PA services provided in inpatient settings are reimbursed by Medicare. Eighty-four percent (108 of 129) of physiatrists employing PAs indicated that they would continue to do so even if the supply of physiatrists were adequate. PA responsibilities were concentrated in inpatient clinical areas. It is concluded that PAs are an underutilized source of health care for rehabilitation patients. Increased professional visibility and formal specialty training are recommended to enhance their contribution to the field.