Pancreatic Fat Infiltration Is Associated with a Higher Risk of Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a poor survival rate, partly due to delayed diagnosis. Identifying high-risk individuals could lead to early detection and improve survival. A number of risk factors such as alcohol consumption and metabolic syndrome are associated with fatty infiltration of the pancreas. Experimental models show that a fatty pancreas promotes tissue inflammation and fibrosis, which could promote PDAC. METHODS: We conducted a case-control study in a single-university tertiary hospital. Sixty-eight PDAC cases with recent non-contrast computed tomography (CT) and 235 controls were studied. The controls had no history of malignancy and underwent CT colonography for cancer screening in the same period. Pancreatic fat was estimated by calculating pancreatic (P) attenuation, corrected to splenic (S) attenuation, measured in three 1.0-cm2 regions of the pancreas. The P.S100 value calculated was used to estimate fatty infiltration of the pancreas (FIP), with a lower P.S100 representing a higher FIP. RESULTS: The PDAC patients had a lower BMI and a higher rate of type 2 diabetes mellitus. The P.S100 was lower in cases than in controls (86.452 vs. 92.414, p = 4.016e-06), suggesting that FIP is higher with PDAC. The risk of developing PDAC steadily increased significantly for the quartiles with a higher FIP compared to the low FIP quartile. No correlation between BMI and FIP (r = -0.1031179; 95% confidence interval [CI] -0.22267106 to 0.01949092) was found. Adjusting for confounders (age, sex, BMI, and DM), the risk of developing PDAC according to the FIP was estimated to be 3.75 (95% CI 1.9234408-7.993337; p = 0.000171). FIP was stable before and after the diagnosis of PDAC in 9 cases with prior CT scans when no pancreatic tumor was identifiable. CONCLUSION: Fatty pancreas is associated with an increased risk of pancreatic cancer. Once confirmed in larger-scale studies, these findings could help to identify at-risk individuals, particularly in high-risk groups such as chronic alcohol consumers.

Articulation of an alumina-zirconia composite ceramic against living cartilage - An in vitro wear test.

BACKGROUND: There is interest in minimally invasive solutions that reduce osteoarthritic symptoms and restore joint mobility in the early stages of cartilage degeneration. The aim of the present study was to evaluate an alumina-zirconia composite (AZC) as a counterface for articulation against live cartilage explants in comparison to the clinically relevant cobalt-chromium (CoCrMo) alloy. METHODS: A four-station bioreactor designed to articulate against living tissue in an incubator was used for testing. Twelve 32 mm AZC and twelve 32 mm CoCrMo femoral heads with equal surface roughness made up both test groups. Each head articulated against a cartilage disk harvested from stifle joints of 24-week old steers. Test samples and free-swelling control cartilage samples were cultured in Mini ITS medium. Testing was conducted 3 h daily over 10 days applying a contact load of approximately 2 MPa. PG/GAG and hydroxyproline were analyzed using biochemical assays. Additionally, chondrocyte survival and Mankin score analyses were performed on histological slides. RESULTS: Cells stayed alive during the course of the experiment, with cell survival values close to 80% at test completion in the superficial zone. There was no significant difference between AZC and free-swelling control tissue. However, cell count values were inferior for CoCrMo (p = 0.003). Tested tissue suffered mostly structural abnormalities. The PG/GAG content in medium was not different between CoCrMo and AZC (p = 0.315); however, the hydroxyproline release into medium was nearly 30% higher for CoCrMo (p = 0.024). CONCLUSION: Based on average values, AZC induces less cell and tissue damage than CoCrMo. However, only the hydroxyproline measurements reached statistical significance, partially due to substantial scatter within both groups.

Brainstem regions affecting minimum alveolar concentration and movement pattern during isoflurane anesthesia.

BACKGROUND: Spinal transection or selective delivery of volatile anesthetics to the spinal cord reduces minimum alveolar concentration (MAC), whereas precollicular decerebration does not. The authors sought to determine which brainstem regions influence anesthetic requirements and movement responses with isoflurane. METHODS: Movement (biceps femoris electromyogram) and MAC were measured in adult rats before and after decerebration at the precollicular, mid-collicular, pontine or medullary level, or decerebellation. Additional experiments assessed the effects of lidocaine inactivation of the mesencephalic locomotor region on MAC and the effects of isoflurane on nociceptive neuronal responses in this region. RESULTS: Transections placed at the level of the mid-colliculus, rostral pons, and pontomedullary junction significantly reduced MAC by approximately 10, 40, and 45%, respectively. MAC was decreased 9% after mid-medullary transections that were placed caudal to the nucleus raphe magnus but rostral to the dorsal reticular nucleus; however, only weak, single movements occurred. Caudal medullary transections at the obex decreased MAC by 60%. Bilateral inactivation of the mesencephalic locomotor region with lidocaine caused a reversible, 32% decrease in MAC and reduced the number and amplitude of movements at sub-MAC isoflurane concentrations. Neuronal responses of mesencephalic locomotor region neurons to supramaximal noxious tail clamp were reduced by 87% by 1.2 MAC isoflurane. CONCLUSIONS: The authors conclude that the mesencephalic locomotor region influences anesthetic requirements and promotes repetitive movement with sub-MAC isoflurane by facilitating ventral spinal locomotor circuits, where anesthetics seem to exert their key immobilizing effects. However, net brainstem influences on MAC seem to result from interaction among descending nociceptive and locomotor modulatory pathways.