Timothy A. Pritts

Comparison of outcomes after laparoscopic versus open appendectomy for acute appendicitis at 222 ACS NSQIP hospitals.

BACKGROUND The benefit of laparoscopic (LA) versus open (OA) appendectomy, particularly for complicated appendicitis, remains unclear. Our objectives were to assess 30-day outcomes after LA versus OA for acute appendicitis and complicated appendicitis, determine the incidence of specific outcomes after appendectomy, and examine factors influencing the utilization and duration of the operative approach with multi-institutional clinical data. METHODS Using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database (2005-2008), patients were identified who underwent emergency appendectomy for acute appendicitis at 222 participating hospitals. Regression models, which included propensity score adjustment to minimize the influence of treatment selection bias, were constructed. Models assessed the association between surgical approach (LA vs OA) and risk-adjusted overall morbidity, surgical site infection (SSI), serious morbidity, and serious morbidity/mortality, as well as individual complications in patients with acute appendicitis and complicated appendicitis. The relationships between operative approach, operative duration, and extended duration of stay with hospital academic affiliation were also examined. RESULTS Of 32,683 patients, 24,969 (76.4%) underwent LA and 7,714 (23.6%) underwent OA. Patients who underwent OA were significantly older with more comorbidities compared with those who underwent LA. Patients treated with LA were less likely to experience an overall morbidity (4.5% vs 8.8%; odds ratio [OR], 0.60; 95% confidence interval [CI], 0.54-0.68) or a SSI (3.3% vs 6.7%; OR, 0.57; 95% CI, 0.50-0.65) but not a serious morbidity (2.6% vs 4.2%; OR, 0.86; 95% CI, 0.74-1.01) or a serious morbidity/mortality (2.6% vs 4.3%; OR, 0.87; 95% CI, 0.74-1.01) compared with those who underwent OA. All patients treated with LA were significantly less likely to develop individual infectious complications except for organ space SSI. Among patients with complicated appendicitis, organ space SSI was significantly more common after laparoscopic appendectomy (6.3% vs 4.8%; OR, 1.35; 95% CI, 1.05-1.73). For all patients with acute appendicitis, those treated at academic-affiliated versus community hospitals were equally likely to undergo LA versus OA (77.0% vs 77.3%; P = .58). Operative duration at academic centers was significantly longer for both LA and OA (LA, 47 vs 38 minutes [P < .0001]; OA, 49 vs 44 minutes [P < .0001]). Median duration of stay after LA was 1 day at both academic-affiliated and community hospitals. CONCLUSION Within ACS NSQIP hospitals, LA is associated with lower overall morbidity in selected patients. However, patients with complicated appendicitis may have a greater risk of organ space SSI after LA. Academic affiliation does not seem to influence the operative approach. However, LA is associated with similar durations of stay but slightly greater operative times than OA at academic versus community hospitals.

Implementation of a Clinical Pathway Decreases Length of Stay and Cost for Bowel Resection

OBJECTIVE To examine the effect of a clinical pathway for small and large bowel resection on cost and length of hospital stay. SUMMARY BACKGROUND DATA Clinical pathways are designed to streamline patient care delivery and maximize efficiency while minimizing cost. Theoretically, they should be most effective in commonly performed procedures, in which volume and familiarity are high. METHODS A clinical pathway to assist in the management of patients undergoing bowel resection was developed by a multidisciplinary team and implemented. Data about length of stay and cost was collected for all patients undergoing bowel resection 1 year before and 1 year after pathway implementation. Three groups were compared: patients undergoing bowel resection in the year prior to pathway implementation (prepathway), patients in the year after pathway implementation but not included on the pathway (nonpathway), and patients included in the pathway (pathway). RESULTS The mean cost per hospital stay was

Mucosal and enterocyte IL-6 production during sepsis and endotoxemia--role of transcription factors and regulation by the stress response.

19,997.35 +/- 1244.61 for patients in the prepathway group,

Microparticles from Stored Red Blood Cells Activate Neutrophils and Cause Lung Injury after Hemorrhage and Resuscitation

20,835.28 +/- 2286.26 for those in the nonpathway group, and

Dantrolene reduces serum TNFα and corticosterone levels and muscle calcium, calpain gene expression, and protein breakdown in septic rats

13,908.53 +/- 1113.01 for those in the pathway group (p < 0.05 vs. other groups). Mean postoperative length of stay was 9.98 +/- 0.62 days (prepathway), 9.68 +/- 0.88 days for (nonpathway), and 7.71 +/- 0.37 days (pathway) (p < 0.05 vs. other groups). CONCLUSIONS Implementation of the pathway produced significant decreases in length of stay and cost in the pathway group as compared to the prepathway group. These results support the further development of clinical pathways for general surgical procedures.

Intestinal ischemia-reperfusion injury: reversible and irreversible damage imaged in vivo

BACKGROUND Sepsis and endotoxemia are associated with increased production of interleukin-6 (IL-6) in gut mucosa. Mucosal IL-6 may regulate enterocyte acute phase protein synthesis and intestinal IgA production. In addition, increased IL-6 has been proposed to be a mechanism of loss of mucosal integrity in critical illness. The purpose of this review is to describe current knowledge of the regulation of IL-6 production in the enterocyte/mucosa during inflammation caused by sepsis and endotoxemia. DATA SOURCES Recent publications describing the influence of sepsis, endotoxemia, and proinflammatory cytokines on mucosal/enterocyte IL-6 production. CONCLUSIONS IL-6 production is increased in gut mucosa during sepsis and endotoxemia and in cultured enterocytes after treatment with endotoxin or proinflammatory cytokines. The IL-6 gene is regulated by multiple transcription factors, including NF-kappaB, AP-1, and C/EBP. Because of the multiple important biological roles of IL-6, understanding the cellular and molecular mechanisms of mucosal/enterocyte IL-6 production as well as methods to modulate IL-6 production is of clinical importance in the setting of sepsis and other critical illness.

A murine model of mild traumatic brain injury exhibiting cognitive and motor deficits

BACKGROUND Transfusion of stored blood is associated with increased complications. Microparticles (MPs) are small vesicles released from RBCs that can induce cellular dysfunction, but the role of RBC-derived MPs in resuscitation from hemorrhagic shock is unknown. In the current study, we examined the effects of RBC-derived MPs on the host response to hemorrhage and resuscitation. STUDY DESIGN MPs were isolated from murine packed RBC units, quantified using flow cytometry, and injected into healthy mice. Separate groups of mice underwent hemorrhage and resuscitation with and without packed RBC-derived MPs. Lungs were harvested for histology and neutrophil accumulation and assessed by myeloperoxidase content. Human neutrophils were treated with human RBC-derived MPs and CD11b expression, superoxide production, and phagocytic activity were determined. RESULTS Stored murine packed RBC units contained increased numbers of RBC-derived MPs compared with fresh units. Hemorrhaged mice resuscitated with MPs demonstrated substantially increased pulmonary neutrophil accumulation and altered lung histology compared with mice resuscitated without MPs. Intravenous injection of MPs into normal mice resulted in neutrophil priming, evidenced by increased neutrophil CD11b expression. Human neutrophils treated with RBC-derived MPs demonstrated increased CD11b expression, increased superoxide production, and enhanced phagocytic ability compared with untreated neutrophils. CONCLUSIONS Stored packed RBC units contain increased numbers of RBC-derived MPs. These MPs appear to contribute to neutrophil priming and activation. The presence of MPs in stored units can be associated with adverse effects, including lung injury, after transfusion.

γδ T cells mitigate the organ injury and mortality of sepsis

The effects of dantrolene on serum TNFalpha and corticosterone levels and on muscle calcium, calpain gene expression, and protein breakdown were studied in rats with abdominal sepsis induced by cecal ligation and puncture. Treatment of rats with 10 mg/kg of dantrolene 2 h before and 8 h after induction of sepsis reduced serum TNFalpha and corticosterone, muscle calcium levels, mRNA levels for m- and mu-calpain, and the muscle specific calpain p94, as well as total and myofibrillar protein breakdown rates, determined as release of tyrosine and 3-methylhistidine, respectively, from incubated extensor digitorum longus muscles. The results support the concept that increased calcium concentrations may be an important mechanism of sepsis-induced muscle protein breakdown. The data also indicate that other mechanisms, in addition to reduced muscle calcium concentrations such as decreased levels of TNFalpha and glucocorticoids, may contribute to the anti-catabolic effects of dantrolene during sepsis. The observations are important from a clinical standpoint because they suggest that the catabolic response in skeletal muscle during sepsis may be prevented by treatment with a calcium antagonist.

Interleukin 6 mediates neuroinflammation and motor coordination deficits after mild traumatic brain injury and brief hypoxia in mice.

The early events in an intestinal ischemic episode have been difficult to evaluate. Using in vivo microscopy we have analyzed in real-time the effects of short (15 min) and long (40-50 min) ischemia with subsequent reperfusion (IR), evaluating structure, integrity, and functioning of the mouse jejunal mucosa while monitoring blood flow by confocal microscopy. IR was imposed by inflation/deflation of a vascular occluder, and blood flow was monitored and confirmed with scanning confocal imaging. After short ischemia, villus tip cells revealed a rapid increase (23%) in the intracellular NAD(P)H concentration (confocal autofluorescence microscopy), and the pH-sensitive probe BCECF showed a biphasic response of the intracellular pH (pH(i)), quickly alkalinizing from the resting value of 6.8 +/- 0.1 to 7.1 +/- 0.1 but then strongly acidifying to 6.3 +/- 0.1. Upon reperfusion, values returned toward control. In contrast, results were heterogeneous after long IR. During long ischemia, one-third of the epithelial cells remained viable with reversible changes upon reperfusion, but remaining cells lost membrane integrity (Lucifer Yellow uptake, LY) and had membrane blebs during ischemia. These effects became more pronounced as the reperfusion interval progressed when cells exhibited more severely affected NAD(P)H and pH(i) values, larger blebs, and more LY uptake and eventually were shed from the villus. Results from stereo microscopy suggest that these irreversible effects of IR may have occurred as a result of incomplete restorations of local blood flow, especially at the antimesenteric side of the intestine. We conclude that the adverse effects of short ischemia on the jejunum epithelium are fully reversible during the reperfusion interval. However, after long ischemia, reperfusion cannot restore normal structure and functioning of a majority of cells, which deteriorate further. Our results provide a basis for defining the cellular events that cause tissue to transit from reversible to irreversible damage during IR.

Resuscitation with fresh whole blood ameliorates the inflammatory response after hemorrhagic shock.

BACKGROUND Mild traumatic brain injury (TBI) is a serious public health concern affecting more than 1.7 million people in the United States annually. Mild TBI is difficult to diagnose and is clinically associated with impaired motor coordination and cognition. METHODS We subjected mice to a mild TBI (mTBI-1 or mTBI-2) induced by a weight drop model. We assessed brain injury histologically and biochemically, the latter by serum neuron-specific enolase and glial fibrillary acidic protein. Systemic and brain inflammation were measured by cytokine array. We determined blood-brain barrier integrity by cerebral vascular leakage of micromolecular and macromolecular fluorescent molecules. We evaluated mice using a rotarod device and novel object recognition to measure motor coordination and cognition, respectively. RESULTS Mice undergoing mTBI-1 or mTBI-2 had significant deficits in motor coordination and cognition for several days after injury compared with controls. Furthermore, both mTBI-1 and mTBI-2 caused micromolecular leakage in the blood-brain barrier, whereas only mTBI-2 caused macromolecular leakage. Serum neuron-specific enolase and glial fibrillary acidic protein were elevated acutely and corresponded to the degree of injury, but returned to baseline within 24 h. Serum cytokines interleukin-6 and keratinocyte-derived chemokine were significantly increased within 90 min of TBI. Interleukin-6 levels correlated with the degree of injury. CONCLUSIONS The current study provides a reproducible model of mild TBI in mice that exhibits pathologic features of mild TBI in humans. Furthermore, our data suggest that serum cytokines, such as IL-6, may be effective biomarkers for severity of head injury.