Patients undergoing abdominal surgery often develop delirium, which greatly influences their postoperative course of clinical recovery and length of hospital stay (LOS).^1-3 Delirium affects 13% to 50% of patients undergoing noncardiac surgery,⁴ and the health care costs attributable to delirium are more than $164 billion per year in the United States.^5,6 Older surgical patients (≥65 years of age) have a particularly high risk for developing delirium, with detrimental effects on their recovery.⁶ Delirium has been associated with alterations in cholinergic activity, inflammatory processes induced by neural signaling, and excessive depth of anesthesia and sedation.^7,8 Delirium may also be precipitated by factors such as infection, malnutrition, electrolyte and fluid imbalances, anemia, and social isolation.^4,9,10 Nevertheless, 30% to 40% of cases of delirium are preventable¹¹; thus, implementing effective interventions to prevent incident delirium and reduce LOS is a clinical priority.

Individuals with the metabolic syndrome (MS), a clustering of risk factors (high levels of triglycerides and serum glucose, low level of high-density-lipoprotein cholesterol, high blood pressure, abdominal obesity) defined by the Third Report of the National Cholesterol Education Program Expert Panel of Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (ATPIII), are at high risk of developing coronary heart disease and type 2 diabetes mellitus and may benefit from surgically induced weight loss. Prospectively controlled clinical study. A tertiary referral center. From December 1, 1999, to March 31, 2002, 645 consecutive morbidly obese patients were enrolled in a surgically supervised weight loss program, and the efficacy of weight loss 1 year after surgery was examined. Laparoscopic weight reduction surgery. Prevalence of the MS as defined by the ATPIII (>3 of the following): waist circumference greater than 102 cm in men and 88 cm in women; serum triglyceride level of at least 150 mg/dL (1.70 mmol/L); high-density lipoprotein cholesterol level less than 40 mg/dL (1.04 mmol/L) in men and 50 mg/dL (1.30 mmol/L) in women; blood pressure of at least 130/85 mm Hg; and serum glucose level of at least 110 mg/dL (6.11 mmol/L). Of 645 individuals, 337 (52.2%) met the ATPIII definition of the MS. Individuals with the MS had significant differences in age (31.5 years vs 28.1 years), sex (127 [37.7%] of 337 men vs 81 [26.3%] of 308 women), and many metabolic abnormalities compared with patients without the MS. Laparoscopic vertical banded gastroplasty was performed in 528 patients (81.9%) and laparoscopic gastric bypass in 117 (18.1%). A significant decrease in weight was found in both groups, but individuals who underwent laparoscopic gastric bypass lost significantly more weight (mean +/- SD, 38.4 +/- 14.4 kg vs 35.1 +/- 16.8 kg) and achieved a lower body mass index (29.3 +/- 4.8 vs 32.0 +/- 5.4) than individuals who underwent laparoscopic vertical banded gastroplasty. Substantial mean weight reduction (31.9%) of patients with the MS resulted in a substantial reduction of systolic (11.0 mm Hg) and diastolic (11.4 mm Hg) blood pressure and levels of glucose (46.1 mg/dL [2.56 mmol/L]), triglycerides (196.6 mg/dL [2.22 mmol/L]), and total cholesterol (33.7 mg/dL [0.88 mmol/L]) 1 year after surgery. These improvements resulted in a 95.6% resolution of the MS 1 year after surgery. There was no difference between operations (laparoscopic vertical banded gastroplasty or laparoscopic gastric bypass) in the resolution rate of the MS 1 year after surgery (95.0% vs 98.4%, respectively). The MS is prevalent in 52.2% of morbidly obese individuals enrolling in an obesity surgery program. Significant weight reduction 1 year after surgery markedly improved all aspects of the MS and resulted in a cure rate of 95.6%. Obesity surgery performed by laparoscopic surgery is recommended for obese patients with the MS.

A recent study showed that the injection of mitochondria isolated from a nonischemic region mitigated myocardial injury. We tested the protective effects of infusing isolated mitochondria on the reperfusion injury in the liver of rats. A partial liver ischemia-reperfusion (I/R) model in male Wistar rats was used. At the 45th minute of liver ischemia, the recipient's spleen was infused with vehicle (I/R-vehicle group) or vehicle containing isolated mitochondria (7.7 × 10 ± 1.5 × 10/mL, I/R-mito group). After a 240-min reperfusion, the serum and livers were collected to assess tissue injury. Our results show that the elevation of serum alanine aminotransferase (414.3 ± 67.1 vs. 208.8 ± 30.2 U/L), the necrosis of hepatocytes on hematoxylin-eosin staining, increase in positive counts in TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining (59.5% ± 4.4% vs. 24.6% ± 9.1%), the expression of cytosolic cytochrome c, cleaved caspase 9, and 4-hydroxynonenal were all reduced in the I/R-mito group, compared with the I/R-vehicle group. The membrane potential of the isolated mitochondria measured by JC-1 fluorescence remained high, and the infused mitochondria were distributed in the liver parenchyma at 240 min after reperfusion. These results demonstrate that an intrasplenic infusion of viable mitochondria isolated from the donor before reperfusion significantly reduced I/R injury in the liver.

Background. We have reported the protective role of heme oxygenase-1 (HO-1) in the mechanism of hypoxic preconditioning. We wish to investigate the role of HO-1 in remote preconditioning (RP) against hepatic ischemia/reperfusion (I/R) injury in rats. Methods. The remote preconditioning was produced by four cycles of 10-min ischemia-reperfusion of the hind limb of rats. Partial hepatic ischemia was produced in the left lobes for 45 min followed by 240 min of reperfusion. Zinc-protoporphyrin IX (ZnPP), a specific inhibitor of HO enzymatic activity, was intra-peritoneally injected 1 hr before the ischemia-reperfusion injury in separate groups of RP rats. Serum alanine transaminase (ALT) levels, expression of hepatic HO-1 protein and mRNA, immunohistochemical staining and HO enzymatic activity were measured. Results. HO-1 was induced in the livers of rats 4 hr after the RP stimuli, and the overexpression persisted for 24 hr. Immunohistochemical staining demonstrated induction of HO-1 in the hepatocytes. The peripheral lymphocytes did not express HO-1 after RP. RP diminished the elevation of serum ALT levels 4 hr after I/R injury (283.7±167.4 U L⁻¹) when compared with controls (1297.7±729.3 U L⁻¹) and RP+ ZnPP pretreated groups (1429.9±750.9 U L⁻¹). The heme oxygenase activity in treated rats also correlated these results (286.8±34.3 pmol mg⁻¹ protein hr⁻¹ for the RP group, 156.3±27.5 pmol mg⁻¹ protein hr⁻¹ for the RP+ ZnPP pretreated group, and 170.6±19.4 pmol mg⁻¹ protein hr⁻¹ for the control group, 144.8±7.8 pmol mg⁻¹ protein hr⁻¹ for the control+ ZnPP pretreated group). Conclusion. Our results indicated that the induction of HO-1 in remote preconditioning played a protective role against hepatic I/R injury.

β4 integrin and focal adhesion kinase (FAK) are often associated with a poor prognosis in cancer patients and their signaling events have recently been linked to malignant outcomes. Here, we demonstrate, for the first time, physical and functional interactions between β4 integrin and FAK that influence breast cancer malignancy. An amino-terminal linker within FAK is essential for its binding with the cytodomain of β4 integrin. Moreover, EGFR/Src-signaling triggers the tyrosine phosphorylation of β4 integrin, which, in turn, recruits FAK to β4 integrin and leads to FAK activation and signaling. Upon disruption of the β4 integrin/FAK complex, tumorigenesis and metastasis in triple-negative breast cancer were markedly reduced. Importantly, the concomitant overexpression of β4 integrin and FAK significantly correlates with malignant potential in patients with triple-negative breast cancer. This study describes a pro-metastatic EGFR/Src-dependent β4 integrin/FAK complex that is involved in breast cancer malignancy and is a novel therapeutic target for triple-negative breast cancer.