Variation in annual volume at a university hospital does not predict mortality for pancreatic resections.

Annual volume of pancreatic resections has been shown to affect mortality rates, prompting recommendations to regionalize these procedures to high-volume hospitals. Implementation has been difficult, given the paucity of high-volume centers and the logistical hardships facing patients. Some studies have shown that low-volume hospitals achieve good outcomes as well, suggesting that other factors are involved. We sought to determine whether variations in annual volume affected patient outcomes in 511 patients who underwent pancreatic resections at the University of California, San Francisco between 1990 and 2005. We compared postoperative mortality and complication rates between low, medium, or high volume years, designated by the number of resections performed, adjusting for patient characteristics. Postoperative mortality rates did not differ between high volume years and medium/low volume years. As annual hospital volume of pancreatic resections may not predict outcome, identification of actual predictive factors may allow low-volume centers to achieve excellent outcomes

NKT Cells in Sepsis

Sepsis is currently a leading cause of death in hospital intensive care units. Previous studies suggest that the pathophysiology of sepsis involves the hyperactivation of complex proinflammatory cascades that include the activation of various immune cells and the exuberant secretion of proinflammatory cytokines by these cells. Natural killer T-cells (NKTs) are a sublineage of T cells that share characteristics of conventional T cells and NK cells and bridge innate and adaptive immunity. More recently, NKT cells have been implicated in microbial immunity, including the onset of sepsis. Moreover, apolipoprotein E (apoE), a component of triglyceride-rich lipoproteins, has been shown to be protective in endotoxemia and gram-negative infections in addition to its well-known role in lipid metabolism. Here, we will review the role of NKT cells in sepsis and septic shock, the immunoregulatory role of apoE in the host immune response to infection, and propose a mechanism for this immunoregulation

Contemporary concepts in hernia prevention: Selected proceedings from the 2017 International Symposium on Prevention of Incisional Hernias.

Incisional hernia is a frequent complication of midline laparotomy and enterostomal creation and is associated with high morbidity, decreased quality of life, and high costs. The International Symposium on Incisional Hernia Prevention was held October 19 –20, 2017, at the InterContinental Hotel in San Francisco, CA, hosted by the Department of Surgery, University of California, San Francisco. One hundred and three attendees included general and plastic surgeons from 9 countries, including principal participants for several of the seminal studies in the field. Over the course of the 2-day meeting, there were 38 oral presentations, 3 keynote lectures, and 2 panel discussions. The Symposium was a combination of new information but also a comprehensive review of the existing data so as to assess the current state of the field and to set the stage for future research. Further, the Symposium sought to increase awareness and thus emphasize the importance of preventing the formation of incisional and enterostomal hernias.pre-print443 K

NKT cells in sepsis.

Sepsis is currently a leading cause of death in hospital intensive care units. Previous studies suggest that the pathophysiology of sepsis involves the hyperactivation of complex proinflammatory cascades that include the activation of various immune cells and the exuberant secretion of proinflammatory cytokines by these cells. Natural killer T-cells (NKTs) are a sublineage of T cells that share characteristics of conventional T cells and NK cells and bridge innate and adaptive immunity. More recently, NKT cells have been implicated in microbial immunity, including the onset of sepsis. Moreover, apolipoprotein E (apoE), a component of triglyceride-rich lipoproteins, has been shown to be protective in endotoxemia and gram-negative infections in addition to its well-known role in lipid metabolism. Here, we will review the role of NKT cells in sepsis and septic shock, the immunoregulatory role of apoE in the host immune response to infection, and propose a mechanism for this immunoregulation

Lipoprotein-bound LPS induces cytokine tolerance in hepatocytes

Bacterial endotoxin (LPS) elicits dramatic responses in the host including elevated plasma lipid levels due to the increased synthesis and secretion of triglyceride (TG)-rich lipoproteins by the liver. We postulate that this cytokine-induced hyperlipoproteinemia, clinically termed the 'lipemia of sepsis', represents an innate, non-adaptive host immune response to infection. Data in support of this hypothesis include the capacity of TG-rich lipoproteins (VLDL and chylomicrons, CM) to bind and neutralize LPS. Herein, we present evidence that CM-bound LPS attenuates the hepatocellular response to pro-inflammatory cytokines. Primary rodent hepatocytes pretreated with CM-LPS complexes for 2 h demonstrated a near 70% reduction in cytokine-induced NO production as compared to non-pretreated control cells (P less than or equal to 0.04). Whereas hepatocytes were maximally tolerant to cytokine stimulation 6 h after CM-LPS pretreatment, the cells spontaneously regained cytokine responsiveness within 40 h. The induction of cytokine tolerance in hepatocytes follows the internalization of CM-LPS complexes and is a process regulated by the LDL receptor. CM-LPS complexes failed to induce cytokine tolerance in hepatocytes wherein lipoprotein receptor activity was inhibited with high dose receptor associated protein (30 mug/ml). Similarly, CM-bound LPS did not induce tolerance in hepatocytes from ldlr(-/-) mice. Thus, the biochemical or genetic inhibition of LDL receptor activity effectively prevented the CM-mediated induction of the cytokine tolerant phenotype. In conclusion, the lipemia of sepsis likely represents a mechanism by which the host combats sporadic, non-life-threatening episodes of endotoxemia. Also, it may indicate a negative regulatory mechanism for the hepatic response to sepsis, serving to effectively down-regulate the acute phase response. A better understanding of how TG-rich lipoproteins modulate the host response to LPS could yield novel biological insights with important clinical implications, including the development of lipid-based therapies for bacterial infections

Variation in annual volume at a university hospital does not predict mortality for pancreatic resections.

Annual volume of pancreatic resections has been shown to affect mortality rates, prompting recommendations to regionalize these procedures to high-volume hospitals. Implementation has been difficult, given the paucity of high-volume centers and the logistical hardships facing patients. Some studies have shown that low-volume hospitals achieve good outcomes as well, suggesting that other factors are involved. We sought to determine whether variations in annual volume affected patient outcomes in 511 patients who underwent pancreatic resections at the University of California, San Francisco between 1990 and 2005. We compared postoperative mortality and complication rates between low, medium, or high volume years, designated by the number of resections performed, adjusting for patient characteristics. Postoperative mortality rates did not differ between high volume years and medium/low volume years. As annual hospital volume of pancreatic resections may not predict outcome, identification of actual predictive factors may allow low-volume centers to achieve excellent outcomes