Austin L. Spitzer

Applying Ockham's Razor to Pancreatitis Prognostication: A Four-Variable Predictive Model

Objective:We sought to develop a simple yet accurate prognostic scoring system to determine the severity of acute pancreatitis at admission. Summary Background Data:Because acute pancreatitis has a variable and frequently unpredictable course, identifying individuals at greatest risk for significant, life-threatening complications and stratifying their care appropriately remain a concern. Previous prognostic scoring systems predict severity reasonably well but are limited by time constraints, are unwieldy to use, or both. Methods:Data from the international phase III trial of the platelet-activating factor receptor-antagonist Lexipafant were used to develop a 4-variable prognostic model. We then compared the models ability to predict the severity of acute pancreatitis with the Ranson, Glasgow, and APACHE II systems. Results:The model (BALI), which included BUN ≥25 mg/dL, Age ≥65 years, LDH ≥300 IU/L, and IL-6 ≥300 pg/mL, measured at admission, was similar to the Ranson, Glasgow, and APACHE II systems in its ability to identify increased mortality from acute pancreatitis. The receiver operating characteristic curve area for the BALI model was ≥0.82 ± 0.03 (mean ± SD) versus 0.75 ± 0.04 (Ranson), 0.80 ± 0.03 (Glasgow), and 0.79 ± 0.03 (APACHE II). Furthermore, at a prevalence of 15%, the positive and negative predictive values for increased mortality were similar for all systems. Conclusion:The prognostic ability of the BALI 4-variable model was similar to the Ranson, Glasgow, and APACHE II systems but is unique in its simplicity and ability to accurately predict disease severity when used at admission or anytime during the first 48 hours of hospitalization.

Pancreaticoduodenectomy: Volume is not Associated with Outcome within an Academic Health Care System

Hypothesis. Smaller and lower-volume hospitals can attain surgical outcomes similar to high-volume centers if they incorporate the expertise and health care pathways of high-volume centers. Setting. The academic tertiary care center, Moffit-Long Hospital (ML); the community-based Mount Zion Hospital (ZION); the San Francisco County General Hospital (SFGH); and the Veterans Affairs Medical Center of San Francisco (VAMC). Patients. 369 patients who underwent pancreaticoduodenectomy between October 1989 and June 2003 at the University of California, San Francisco (UCSF) affiliated hospitals. Interventions. Pancreaticoduodenectomy. Design. Retrospective chart review. To correct for the potentially confounding effect of small case volumes and event rates, data for SFGH, VAMC, and ZION was combined (Small Volume Hospital Group; SVHG) and compared against data for ML. Main Outcome Measures. Complication rates; three-year and five-year survival rates. Results. The average patient age and health, as determined by ASA score, were similar between ML and the SVHG. The postoperative complication rate did not differ significantly between ML and the SVGH (58.8% versus 63.1%). Patients that experienced a complication averaged 2.5 complications in both groups. The perioperative mortality rate was 4% for patients undergoing pancreaticoduodenectomy at either ML or the SVGH. Although the 3-year survival rate for patients with adenocarcinoma of the pancreas was nearly twice as high at ML (31.2% versus 18.3% at SVHG), there was no significant difference in the 5-year survival rates (19% at ML versus 18.3% at SVHG). Conclusions. Low-volume hospitals can achieve similar outcomes to high-volume tertiary care centers provided they import the expertise and care pathways necessary for improved results.

Contemporary standards for the diagnosis and treatment of heparin-induced thrombocytopenia (HIT)

BACKGROUND Heparin binding to platelet factor 4 (PF4) generates a new antigenic epitope. In an unpredictable fashion, as many as approximately 17% of patients treated with unfractionated heparin (UFH) and approximately 8% treated with low-molecular-weight heparin (LMWH) subsequently develop the anti-heparin-PF4 antibodies that mediate heparin-induced thrombocytopenia and thrombosis (HIT). Very few of those patients with circulating anti-heparin-PF4 antibodies, however, progress to develop clinical HIT (referred to previously as Type II HIT). Only 20% of those who harbor antibodies ( approximately 3% of those exposed to heparin) will manifest the thrombocytopenia subsequently. Even fewer patients (0.03% to 0.09% of those exposed to heparin) experience the marked platelet activation and morbid thromboses characteristic of the HIT syndrome. The pathogenesis of heparin-induced thrombocytopenia (HIT) remains elusive. The pathophysiologic understanding to date has revolved around pathogenic anti-heparin-PF4 antibodies that trigger platelet activation, release of platelet procoagulant microparticles, and resultant thrombosis. The clinical diagnosis of HIT is confusing because current assays to detect anti-heparin-PF4 antibodies do not correlate well with the disease. Currently available assays lack either adequate sensitivity and interlaboratory reproducibility (ie, functional serotonin release assays) or specificity (ie, enzyme-linked immunosorbent assays or ELISAs). CONCLUSIONS Fortunately, the treatment for HIT is not confusing. The purposes of this review are as follows: (1) to examine the relevant clinical definition of HIT, (2) to explore our current understanding as to the pathogenesis of HIT, and (3) to present an algorithm for the identification and treatment of the HIT syndrome.

Early Nonenhanced Abdominal Computed Tomography Can Predict Mortality in Severe Acute Pancreatitis

We wondered whether nonenhanced computed tomography (CT) within 48 hours of admission could identify individuals at risk for higher mortality from acute pancreatitis. Data from the international phase III study of the platelet-activating factor-inhibitor Lexipafant was used to analyze noncontrast CT versus acute pancreatitis mortality. Nonenhanced CT examinations of the abdomen from the trial were classified by disease severity (Balthazar grades A-E) and then correlated with patient survival. Among the 477 individuals who underwent CT within 48 hours of admission and 220 individuals who did so over the subsequent 6 days, higher CT grades were associated with increased mortality. Each unit increase in Balthazar grade during the initial 48 hours was associated with an estimated increase in the risk of mortality of 33%, and this trend increased to 50% if pancreatic enlargement and peripancreatic stranding (grades B and C) were combined (P < 0.05). CT grade correlated minimally with Ranson, Glasgow, or APACHE II score during the initial 48 hours; however, this correlation improved over 3–8 days. Early nonenhanced abdominal CT in patients with acute pancreatitis is a valuable prognostic indicator of mortality in acute pancreatitis, even among patients without clinical features of severe acute pancreatitis.

Chylomicrons combined with endotoxin moderate microvascular permeability

Triglyceride-rich lipoprotein-bound endotoxin (CM-LPS) inhibits the host innate immune response to sepsis by attenuating the hepatocellular response to pro-inflammatory cytokine stimulation. This ‘cytokine tolerance’ in hepatocytes is a transient, receptor-dependent process that correlates with internalization of CM-LPS via low density lipoprotein (LDL) receptors. Since endothelial cells are integral to the immune response and similarly express LDL receptors, we hypothesized that CM-LPS could be internalized and ultimately attenuate the deleterious effects of pro-inflammatory molecules like tumor necrosis factor-α (TNF-α) and platelet activating factor (PAF) on endothelial permeability. Here, we show that CM-LPS complexes induce cytokine tolerance in endothelial cells. In rats, TNF-α increased hydraulic conductivity 2.5-fold over baseline and PAF increased it 5-fold; but, pretreatment with CM-LPS or an attenuated analog (CM-LPS*) inhibited these changes. Nuclear/cytoplasmic levels of p65 were reduced after TNF-α-stimulation in endothelial cell monolayers pretreated with CM-LPS, a finding consistent with inhibition of nuclear factor (NF)-κB translocation. Also consistent with inhibition was stabilized intercellular adhesion, as illustrated with antibody to VE-cadherin using confocal microscopy. These results provide additional support for the integral role of lipoproteins in the innate immune response to infection and lend further credence to developing lipid-based therapy for Gram-negative sepsis.