SUMMARY Circadian clocks and metabolism are inextricably intertwined, where central and hepatic circadian clocks coordinate metabolic events in response to light-dark and sleep-wake cycles. We reveal an additional key element involved in maintaining host circadian rhythms, the gut microbiome. Despite persistence of light-dark signals, germ-free mice fed low or high fat diets exhibit markedly impaired central and hepatic circadian clock gene expression and do not gain weight compared to conventionally-raised counterparts. Examination of gut microbiota in conventionally-raised mice showed differential diurnal variation in microbial structure and function dependent upon dietary composition. Additionally, specific microbial metabolites induced under low or high fat feeding, particularly short chain fatty acids, but not hydrogen sulfide, directly modulate circadian clock gene expression within hepatocytes. These results underscore the ability of microbially-derived metabolites to regulate or modify central and hepatic circadian rhythm and host metabolic function, the latter following intake of a Westernized diet.

To investigate the importance of route of nutrient administration on septic complications after blunt and penetrating trauma, 98 patients with an abdominal trauma index of at least 15 were randomized to either enteral or parenteral feeding within 24 hours of injury. Septic morbidity was defined as pneumonia, intra-abdominal abscess, empyema, line sepsis, or fasciitis with wound dehiscence. Patients were fed formulas with almost identical amounts of fat, carbohydrate, and protein. Two patients died early in the study. The enteral group sustained significantly fewer pneumonias (11.8% versus total parenteral nutrition 31.%, p less than 0.02), intra-abdominal abscess (1.9% versus total parenteral nutrition 13.3%, p less than 0.04), and line sepsis (1.9% versus total parenteral nutrition 13.3%, p less than 0.04), and sustained significantly fewer infections per patient (p less than 0.03), as well as significantly fewer infections per infected patient (p less than 0.05). Although there were no differences in infection rates in patients with injury severity score less than 20 or abdominal trauma index less than or equal to 24, there were significantly fewer infections in patients with an injury severity score greater than 20 (p less than 0.002) and abdominal trauma index greater than 24 (p less than 0.005). Enteral feeding produced significantly fewer infections in the penetrating group (p less than 0.05) and barely missed the statistical significance in the blunt-injured patients (p = 0.08). In the subpopulation of patients requiring more than 20 units of blood, sustaining an abdominal trauma index greater than 40 or requiring reoperation within 72 hours, there were significantly fewer infections per patient (p = 0.03) and significantly fewer infections per infected patient (p less than 0.01). There is a significantly lower incidence of septic morbidity in patients fed enterally after blunt and penetrating trauma, with most of the significant changes occurring in the more severely injured patients. The authors recommend that the surgeon obtain enteral access at the time of initial celiotomy to assure an opportunity for enteral delivery of nutrients, particularly in the most severely injured patients.

Nonoperative management is safe for hemodynamically stable patients with blunt hepatic injury, regardless of injury severity. There are fewer abdominal complications and less transfusions when compared with a matched cohort of operated patients. Based on admission characteristics or CT scan, it is not possible to predict failures; therefore, intensive care unit monitoring is necessary.

ObjectiveTo analyze the outcome of hemodynamically stable patients with blunt hepatic injury managed nonoperatively, and to examine the impact of this approach on the outcome of all patients with blunt hepatic injury. Summary Background DataUntil recently, operative management has been the standard for liver injury. A prospective trial from the authors' institution had shown that nonoperative management could safely be applied to hemodynamically stable patients with blunt hepatic injury. The present study reviewed the authors' institutional experience with blunt hepatic trauma since that trial and compared the results with prior institutional experience. MethodsSix hundred sixty-one patients with blunt hepatic trauma during the 5-year period ending December 1998 were reviewed (NONOP2). The outcomes were compared with two previous studies from this institution: operative 1985 to 1990 (OP) and nonoperative 1993 to 1994 (NONOP1). ResultsAll 168 OP patients were managed operatively. Twenty-four (18%) of 136 NONOP1 patients and 101 (15%) of the 661 NONOP2 patients required immediate exploration for hemodynamic instability. Forty-two (7%) patients failed nonoperative management; 20 were liver-related. Liver-related failures of nonoperative management were associated with highergrade injuries and with larger amounts of hemoperitoneum on computed tomography scanning. Twenty-four-hour transfusions, abdominal infections, and hospital length of stay were all significantly lower in the NONOP1 and NONOP2 groups versus the OP cohort. The liver-related death rate was constant at 4% in the three cohorts over the three time periods. ConclusionsAlthough urgent surgery continues to be the standard for hemodynamically compromised patients with blunt hepatic trauma, there has been a paradigm shift in the management of hemodynamically stable patients. Approximately 85% of all patients with blunt hepatic trauma are stable. In this group, nonoperative management significantly improves outcomes over operative management in terms of decreased abdominal infections, decreased transfusions, and decreased lengths of hospital stay.

Changes in mucosal defense have been implicated as important factors affecting infections complications in critically ill patients. To study the effects of nutrient administration on gut-associated lymphatic tissue (GALT), ICR mice were randomized to receive chow plus intravenous saline, intravenous feeding of a total parenteral nutrition (TPN) solution, or enteral feeding of the same TPN solution. In a second series of experiments, a more complex enteral diet (Nutren) was compared with chow feeding and enteral TPN. After 5 days of feeding with experimental diets, lymphocytes were harvested from the mesenteric lymph nodes (MLNs), Peyer's patches (PPs), lamina propria (LP) cells, and intraepithelial (IE) spaces of the small intestine to determine cell yields and phenotypes. Small intestinal washings, gallbladder contents, and sera were collected and analyzed for immunoglobulin A (IgA) levels. In both series of experiments, there were no significant changes within the MLNs. There were significant decreases in total cell yields from the PPs, IE spaces, and LP in animals fed with TPN solution, either enterally or parenterally, as compared with chow-fed mice. Total T cells were decreased in both TPN-fed groups in the PPs and LP, whereas total B cells were decreased in the PP, IE, and LP populations. Total cell numbers remained normal in the Nutrenfed group, except for a decrease in LP T cells. CD4+ LP cells decreased significantly with a reduction in the CD4/CD8 ratio in mice fed TPN solution either intravenously or enterally, whereas IgA recovery from small intestinal washings was significantly decreased in the same groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Purpose. The treatment of electrolyte disorders in adult patients in the intensive care unit (ICU), including guidelines for correcting specific electrolyte disorders, is reviewed. Summary. Electrolytes are involved in many metabolic and homeostatic functions. Electrolyte disorders are common in adult patients in the ICU and have been associated with increased morbidity and mortality, as has the improper treatment of electrolyte disorders. A limited number of prospective, randomized, controlled studies have been conducted evaluating the optimal treatment of electrolyte disorders. Recommendations for treatment of electrolyte disorders in adult patients in the ICU are provided based on these studies, as well as case reports, expert opinion, and clinical experience. The etiologies of and treatments for hyponatremia hypotonic and hypernatremia (hypovolemic, isovolemic, and hypervolemic), hypokalemia and hyperkalemia, hypophosphatemia and hyperphosphatemia, hypocalcemia and hypercalcemia, and hypomagnesemia and hypermagnesemia are discussed, and equations for determining the proper dosages for adult patients in the ICU are provided. Treatment is often empirical, based on published literature, expert recommendations, and the patient's response to the initial treatment. Actual electrolyte correction requires individual adjustment based on the patient's clinical condition and response to therapy. Clinicians should be knowledgeable about electrolyte homeostasis and the underlying pathophysiology of electrolyte disorders in order to provide the optimal therapy to patients. Conclusion. Treatment of electrolyte disorders is often empirical, based on published literature, expert opinion and recommendations, and patient's response to the initial treatment. Clinicians should be knowledgeable about electrolyte homeostasis and the underlying pathophysiology of electrolyte disorders to provide optimal therapy for patients.

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Elective, non-emergent esophageal and pancreatic procedures performed in patients who could have had surgery delayed for preoperative nutrition, but did not, result in higher risk than colon surgery at any given level of serum albumin below 3.25 g/dL. Patient populations in trials should be stratified by operative site and by markers of nutritional status. Degree of hypoalbuminemia and other potential markers of nutritional status may explain many of the discrepancies between trials of nutrition support. Preexisting hypoalbuminemia in patients undergoing elective surgery remains underappreciated, unrecognized, and untreated in many hospitalized patients.