The Feline Acute Patient Physiologic and Laboratory Evaluation (Feline APPLE) Score: a severity of illness stratification system for hospitalized cats.

BACKGROUND: Scores allowing objective stratification of illness severity are available for dogs and horses, but not cats. Validated illness severity scores facilitate the risk-adjusted analysis of results in clinical research, and also have applications in triage and therapeutic protocols. OBJECTIVE: To develop and validate an accurate, user-friendly score to stratify illness severity in hospitalized cats. ANIMALS: Six hundred cats admitted consecutively to a teaching hospital intensive care unit. METHODS: This observational cohort study enrolled all cats admitted over a 32-month period. Data on interventional, physiological, and biochemical variables were collected over 24 hours after admission. Patient mortality outcome at hospital discharge was recorded. After random division, 450 cats were used for logistic regression model construction, and data from 150 cats for validation. RESULTS: Patient mortality was 25.8%. Five- and 8-variable scores were developed. The 8-variable score contained mentation score, temperature, mean arterial pressure (MAP), lactate, PCV, urea, chloride, and body cavity fluid score. Area under the receiver operator characteristic curve (AUROC) on the construction cohort was 0.91 (95% CI, 0.87-0.94), and 0.88 (95% CI, 0.84-0.96) on the validation cohort. The 5-variable score contained mentation score, temperature, MAP, lactate, and PCV. AUROC on the construction cohort was 0.83 (95% CI, 0.79-0.86), and 0.76 (95% CI, 0.72-0.84) on the validation cohort. CONCLUSIONS AND CLINICAL IMPORTANCE: Two scores are presented enabling allocation of an accurate and user-friendly illness severity measure to hospitalized cats. Scores are calculated from data obtained over the 1st 24 hours after admission, and are diagnosis-independent. The 8-variable score predicts outcome significantly better than does the 5-variable score.

The acute patient physiologic and laboratory evaluation (APPLE) score: a severity of illness stratification system for hospitalized dogs.

BACKGROUND: Objective risk stratification models are used routinely in human critical care medicine. Applications include quantitative and objective delineation of illness severity for patients enrolled in clinical research, performance benchmarking, and protocol development for triage and therapeutic management. OBJECTIVE: To develop an accurate, validated, and user-friendly model to stratify illness severity by mortality risk in hospitalized dogs. ANIMALS: Eight hundred and ten consecutive intensive care unit (ICU) admissions of dogs at a veterinary teaching hospital. METHODS: Prospective census cohort study. Data on 55 management, physiological, and biochemical variables were collected within 24 hours of admission. Data were randomly divided, with 598 patient records used for logistic regression model construction and 212 for model validation. RESULTS: Patient mortality was 18.4%. Ten-variable and 5-variable models were developed to provide both a high-performance model and model maximizing accessibility, while maintaining good performance. The 10-variable model contained creatinine, WBC count, albumin, SpO(2) , total bilirubin, mentation score, respiratory rate, age, lactate, and presence of free fluid in a body cavity. Area under the receiver operator characteristic (AUROC) on the construction data set was 0.93, and on the validation data set was 0.91. The 5-variable model contained glucose, albumin, mentation score, platelet count, and lactate. AUROC on the construction data set was 0.87, and on the validation data set was 0.85. CONCLUSIONS AND CLINICAL IMPORTANCE: Two models are presented that enable allocation of an accurate and user-friendly illness severity index for dogs admitted to an ICU. These models operate independent of primary diagnosis, and have been independently validated.

An overview of evidence from systematic reviews evaluating early enteral nutrition in critically ill patients: more convincing evidence is needed.

International quality improvement initiatives such as Fast-Hug bring a focus on improving the delivery of early enteral nutrition to critically ill patients, however surveys demonstrate current practice remains variable. One way to reduce variability in practice is to provide strong evidence to convince clinicians to change. The purpose of this overview was to identify current best evidence supporting the delivery of early enteral nutrition in critical illness. We sought high-quality evidence in the form of systematic reviews containing meta-analyses of randomised controlled trials. Two authors independently identified studies and assessed methodological quality. Data sources included Medline, EMBASE and hand-searching of guideline reference lists. The literature search identified five systematic reviews that summarised 30 clinical trials. These systematic reviews focused on acutely hospitalised patients, critical illness, burns, elective intestinal surgery and pancreatitis. Early enteral nutrition significantly reduced mortality in elective intestinal surgery patients (relative risk 0.41, 95% confidence interval 0.18 to 0.93, P = 0.03, I2 = 0.0%) and significantly reduced infectious complications in acutely ill hospitalised patients (relative risk 0.45, 95% confidence interval 0.3 to 0.66, P = 0.00006, heterogeneity P = 0.049). Four of five identified systematic reviews had key methodological quality deficiencies. The results of this overview highlight the variability in the evidence regarding the benefits of early enteral nutrition in critically ill patient populations. The inconsistent delivery to critically ill patients may be explained by the lack of convincing evidence. Better evidence may be needed to reduce the irregularity in the provision of early enteral nutrition to critically ill patients.

Illness severity scores in veterinary medicine: what can we learn?

Illness severity scores are gaining increasing popularity in veterinary medicine. This article discusses their applications in both clinical medicine and research, reviews the caveats pertaining to their use, and discusses some of the issues that arise in appropriate construction of a score. Illness severity scores can be used to decrease bias and confounding and add important contextual information to research by providing a quantitative and objective measure of patient illness. In addition, illness severity scores can be used to benchmark performance, and establish protocols for triage and therapeutic management. Many diagnosis-specific and diagnosis-independent veterinary scores have been developed in recent years. Although score use in veterinary research is increasing, the scores available are currently underutilized, particularly in the context of observational studies. Analysis of treatment effect while controlling for illness severity by an objective measure can improve the validity of the conclusions of observational studies. In randomized trials, illness severity scores can be used to demonstrate effective randomization, which is of particular utility when group sizes are small. The quality of veterinary scoring systems can be improved by prospective multicenter validation. The prevalence of euthanasia in companion animal medicine poses a unique challenge to scores based on a mortality outcome.

The investigation of bronchospasm during induction of anaesthesia.

BACKGROUND: The aim of this study was to ascertain whether anaesthetic induction-related anaphylactic bronchospasm could be distinguished from other types of bronchospasm by clinical features and response to treatment. Such features could then be used to identify a group of patients in whom skin testing is indicated. METHODS: We retrospectively studied data from 183 patients referred to an anaesthetic allergy clinic because of bronchospasm during induction. For the analysis, the patients were divided into two groups depending on whether there was evidence suggesting immunological anaphylaxis. RESULTS: When the patients in whom intradermal tests were positive were compared with those in whom intradermal tests were negative, the skin test-positive patients had significantly more severe reactions, and they were more commonly associated with other clinical signs. Mast cell tryptase (MCT) was an excellent discriminator between reactions likely to be allergic and those unlikely to be allergic. CONCLUSIONS: Anaphylactic bronchospasm related to induction of anaesthesia is more likely to be severe than bronchospasm due to non-immune causes. An allergic cause is more likely if there are associated features of anaphylaxis (skin changes, hypotension, angioedema) or elevated MCT. Patients with any of these features should undergo immuno-allergolical investigation.

Pulmonary artery catheters for adult patients in intensive care.

BACKGROUND: Pulmonary artery catheterization was adopted about 30 years ago and widely disseminated without rigorous evaluation as to whether it benefited critically ill patients. The technique is used to measure cardiac output and pressures in the pulmonary circulation to guide diagnosis and treatment. Clinicians believe these data can improve patients' outcomes, even in the absence of consensus about the specific interpretation of the data. OBJECTIVES: To assess the effect of pulmonary artery catheterization on mortality and cost of care in adult intensive care patients. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2, 2006); MEDLINE (all records to April 2006); EMBASE (all records to April 2006); CINAHL (all records to April 2006) and reference lists of articles. We contacted manufacturers and researchers in the field. SELECTION CRITERIA: We included all randomized controlled trials in adults, comparing management with and without a pulmonary artery catheter (PAC). DATA COLLECTION AND ANALYSIS: We screened the titles and abstracts of the electronic search results and obtained the full text of studies of possible relevance for independent review. We determined the final results of the literature search by consensus between the authors. We did not contact study authors for additional information. MAIN RESULTS: We identified 12 studies. Mortality was reported as hospital, 28-day, 30-day, or intensive care unit. We considered studies of high-risk surgery patients (eight studies) and general intensive care patients (four studies) separately for the meta-analysis. The pooled odds ratio for the studies of general intensive care patients was 1.05 (95% confidence interval (CI) 0.87 to 1.26) and for the studies of high-risk surgery patients 0.99 (95% CI 0.73 to 1.24). Of the eight studies of high-risk surgery patients, five evaluated the effectiveness of pre-operative optimization but there was no difference in mortality when these studies were examined separately. Pulmonary artery catheterization did not affect intensive care unit (reported by 10 studies) or hospital (reported by nine studies) length of stay. Four studies, conducted in the United States, measured costs based on hospital charges billed to patients, which on average were higher in the PAC groups. AUTHORS' CONCLUSIONS: To date, there have been two multi-centre trials of the effectiveness of PACs for managing critically ill patients admitted to intensive care, although only one was adequately powered. Efficacy studies are needed to determine optimal management protocols and patient groups who could benefit from management with a PAC.

Evidence-based veterinary medicine: what it is, what it isn't and how to do it.

EBM represents a more formal process for considering the merits of published research in the context of clinical decision making. By combining the application of formal rules of evidence in evaluating the clinical literature (critical appraisal) with the ability to conduct efficient and effective literature searches, any clinician is able to keep current on topics of interest. Learning the core skills that enable the practice of EBM is easier than expected. The EBM Working Group published a series of Users' Guides to enable clinicians to learn critical appraisal of the primary literature in a systematic fashion. The complete series of Users' Guides is available free of charge over the web (www. CCHE.net). Similarly, PubMed, which contains a number of easy to use search filters (Clinical Queries) that can identify high-quality papers published in key veterinary journals, is also available free of charge over the web (www.PubMed.org). How ever one obtains the core skills, an efficient, structured approach to the practice of EBM can actually reduce the amount of time one requires to keep current by helping the user locate and identify methodologically rigorous research. Although the entire process can be self-taught, as with any new technique, other effective ways to bring these new skills into your practice setting include attending a conference workshop or even hiring a new graduate who has already been trained in the process.

The Southwestern Ontario Joint Replacement Pilot Project: electronic point-of-care data collection. Southwestern Ontario Study Group.

OBJECTIVE: To pilot a provincial joint replacement registry using electronic point-of-care data collection. DESIGN: Data collection study. SETTING: Southwestern Ontario, which has a population base of 3.5 million people. PARTICIPANTS: Eighteen orthopedic surgeons. METHOD: Information on total hip and knee replacements was obtained by the orthopedic surgeons over a 6-month period. Information was obtained in paper form and electronically on hand-held computers. MAIN OUTCOME MEASURES: Patient demographics, waiting times from referral to operation, patient satisfaction and relevance and value of electronic records compared with paper records. MAIN RESULTS: Data were collected on 815 total hip and knee arthroplasties. A slightly greater number of hips required revision than knees. The majority of patients were in the 60 to 90-year age range. With respect to the waiting time from referral to operation 10% of patients waited less than 5 weeks, 50% waited less than 30 weeks, and 90% waited less than 59 weeks. There was a high level of patient satisfaction with the operation and with hospital care received. Most surgeons found that the gathering and use of data electronically was relevant and easy. The electronic data were more timely, accurate and complete than paper records. CONCLUSION: Electronic point-of-care data collection is appropriate, particularly in high-volume, high-cost surgical interventions such as total joint replacements.

Intracranial pressure monitoring and outcomes after traumatic brain injury.

OBJECTIVE: Uncontrolled intracranial hypertension after traumatic brain injury (TBI) contributes significantly to the death rate and to poor functional outcome. There is no evidence that intracranial pressure (ICP) monitoring alters the outcome of TBI. The objective of this study was to test the hypothesis that insertion of ICP monitors in patients who have TBI is not associated with a decrease in the death rate. DESIGN: Study of case records. METHODS: The data files from the Ontario Trauma Registry from 1989 to 1995 were examined. Included were all cases with an Injury Severity Score (ISS) greater than 12 from the 14 trauma centres in Ontario. Cases identifying a Maximum Abbreviated Injury Scale score in the head region (MAIS head) greater than 3 were selected for further analysis. Logistic regression analyses were conducted to investigate the relationship between ICP and death. RESULTS: Of 9001 registered cases of TBI, an MAIS head greater than 3 was recorded in 5507. Of these patients, 541 (66.8% male, mean age 34.1 years) had an ICP monitor inserted. Their average ISS was 33.4 and 71.7% survived. There was wide variation among the institutions in the rate of insertion of ICP monitors in these patients (ranging from 0.4% to over 20%). Univariate logistic regression indicated that increased MAIS head, ISS, penetrating trauma and the insertion of an ICP monitor were each associated with an increased death rate. However, multivariate analyses controlling for MAIS head, ISS and injury mechanism indicated that ICP monitoring was associated with significantly improved survival (p < 0.015). CONCLUSIONS: ICP monitor insertion rates vary widely in Ontario's trauma hospitals. The insertion of an ICP monitor is associated with a statistically significant decrease in death rate among patients with severe TBI. This finding strongly supports the need for a prospective randomized trial of management protocols, including ICP monitoring, in patients with severe TBI.

Metallothionein expression in renal cancer.

OBJECTIVES: To assess metallothionein (MT) expression with immunohistochemical localization in human renal cell carcinoma and to determine whether a possible relationship with the histopathologic findings, tumor grade, or pathologic tumor stage is demonstrable, because MT may have a role in carcinogenesis. METHODS: Archival pathologic specimens and medical records were reviewed for 28 patients with renal cell carcinoma. Immunohistochemical localization of MT was performed with a polyclonal-antibody-to-rat-liver MT, an anti-rabbit IgG linking antibody, and an avidin-biotin horseradish peroxidase complex. Correlation was sought between immunohistochemical data (MT staining intensity, extension, and subcellular site) and clinical data (histologic cell type, tumor grade, and pathologic stage). RESULTS: The mean patient age was 61.7 years (range 42 to 86). The predominant histologic cell type was the clear cell variant. Three, sixteen, and nine tumors were pathologically staged as 1, 2, and 3, respectively. There were 1, 13, 10, and 4 tumors with grades 1, 2, 3, and 4, respectively. Among the independent variables, greater immunoreactivity was observed in Stage 2 tumors (P = 0.028). A significant inverse relationship between tumor grade and MT staining intensity was also observed (P = 0.007). CONCLUSIONS: The inverse relationship in renal cell carcinoma between MT immunoreactivity and tumor grade may indicate a role for MT in tumor growth and dedifferentiation. Increased MT immunoreactivity in lower stage tumors may be related to rapid tumor growth during their growth cycle. Further study is required to elucidate the role of MT in renal cell carcinoma oncogenesis and its possible use as a clinical prognostic parameter.

Using the Vista 350 telephone to communicate the results of home monitoring of diabetes mellitus to a central database and to provide feedback.

PURPOSE: Self-monitoring of blood glucose has become routine practice in the management of diabetes mellitus. When all the data is complete, however, the amount of information to be taken into account when making therapeutic decisions becomes overwhelming not only for the patient but for the healthcare provider. Computers excel at processing large amounts of information quickly and impassively, which makes them potentially helpful for collating and communicating the data in a manner that facilitates decision-making by patient and healthcare provider. This should in turn improve control and help prevent acute and chronic complications. METHOD: Using the Vista 350 telephone, we have developed a system that enables patients with diabetes to record home monitoring data to a central database and receive feedback summaries. A small trial was conducted to determine if the Vista 350 telephone is an acceptable and feasible method to communicate the results of home monitoring of diabetes mellitus to a central database and receive feedback summaries. A total of 35 volunteers with insulin-requiring diabetes mellitus in the London area were randomly allocated to either use the Vista 350 phone for 6 months, or to a control group that continued to use traditional methods for recording home monitoring data. RESULTS: 33 of the 35 patients enrolled completed the trial. All 16 patients who began using the phone continued to do so for 6 months confirming the feasibility of the system. Questionnaires completed at 3 and 6 months confirmed the Vista 350 telephone system to be acceptable to the subjects. The results will enable some minor modifications to be made to the telephone system before a larger definitive trial, designed to determine the effect on diabetes control, is conducted later this year.

Osteopontin expression in a group of lymph node negative breast cancer patients.

The aim of this study was to examine the cellular distribution of osteopontin (OPN) protein [by immunohistochemical (IHC) analysis] and mRNA [by in situ hybridization (ISH)] in the primary tumors of lymph node negative (LNN) breast cancer patients and to determine whether the level of immunodetectable OPN may be associated with tumor aggressiveness. We examined OPN levels in tumors from 154 patients with LNN breast cancer who were followed for a median of 7 years (range 1.7-16.3 years). IHC staining for OPN was seen in tumor infiltrating macrophages and lymphocytes in 70% of these tumors, and in the carcinoma cells themselves in 26%. ISH was performed to determine cellular distribution of OPN mRNA expression in sections from selected tumors. OPN mRNA was detected in groups of tumor cells, individual tumor cells and tumor infiltrating macrophages and lymphocytes. Matched sections showed that some tumor cells with IHC staining for OPN protein were also positive for OPN mRNA by ISH, in contrast with previous studies which have shown OPN mRNA expression only in tumor infiltrating inflammatory cells. Our results thus indicate that OPN protein can be produced by breast cancer cells in vivo and suggest that it may also be taken up from the environment (i.e., secreted by inflammatory cells or other tumor cells). Tumor cell IHC staining intensity was then assessed using a semiquantitative scoring system. Univariate analysis showed tumor cell OPN positivity above an optimized cutpoint to be significantly associated with decreased disease-free survival (DFS) and overall survival (OS). The results of this pilot study thus suggest that the ability of breast cancer cells to either synthesize OPN or to bind and sequester OPN from the microenvironment may be associated with tumor aggressiveness and poor prognosis.

Understanding articles describing clinical prediction tools. Evidence Based Medicine in Critical Care Group.

OBJECTIVES: Clinical prediction rules and models are developed by applying statistical techniques to find combinations of predictors that categorize a heterogeneous group of patients into subgroups of risk. Our goal is to teach clinicians how to evaluate the validity, results, and applicability of articles describing clinical prediction tools. CLINICAL EXAMPLE: An article describing a rule to predict the need for intensive care unit care admission in patients presenting to the emergency room with chest pain. RECOMMENDATIONS: Valid clinical prediction tools are developed by completely following up a representative group of patients, by evaluating all potential predictors and testing the independent contribution of each predictor variable, and by ensuring that the outcomes were independent of the predictors. To evaluate the results of an article describing a clinical prediction tool, clinicians need to know what the prediction tool is, how well it categorizes patients into different levels of risk, and what the confidence intervals are around the risk estimates. Valid prediction tools are not applicable in every patient population. Before patient care application, the clinician should ensure that the tool maintains its prediction power in a new sample of patients, that the patients are similar to patients used to test the tool, and that the tool has been shown to improve clinical decision-making. CONCLUSIONS: There has been an increase in the development and validation of clinical prediction rules and models. It is important to evaluate the validity and reliability of these prediction tools before application.

Interpreting and using clinical trials.

In 1754, aboard HMS Salisbury, James Lind conducted a simple, controlled clinical trial. He took 12 patients with "pale and bloated skin, listlessness, an aversion to exercise, swollen gums, halitosis, ecchymotic mucous membranes, and limb edema" and allocated them to receive treatment with one of six different therapies. Since the patients receiving two of his six chosen interventions had such a dramatic recovery, he felt ethically obligated to end his trial and administer these treatments to all the remaining sailors. Today we fully recognize the impact that the controlled clinical trial can have on the development of new interventions. Unfortunately, very few of these interventions are likely to have as dramatic an impact on outcomes as lemons and oranges did on scurvy. Because the interventions we study tend to have relatively small treatment effects, and because the design and reporting of published RCTs has consistently been documented to be less than perfect, there is a real need for us to develop critical appraisal skills. This article is by no means the only approach to critical appraisal, but hopefully it serves as an adequate starting point for the journey.

Polymyxin-dextran antiendotoxin pretreatment in an ovine model of normotensive sepsis.

OBJECTIVE: To test the hypothesis that adult sheep pretreated with polymyxin-dextran and then made septic by cecal ligation and perforation would have fewer changes in microvascular integrity and cellular architecture in extrapulmonary organs. DESIGN: Prospective, randomized, double-blind, placebo-controlled animal study. SETTING: An animal research facility in a university-affiliated hospital. SUBJECTS: Mature, male Suffolk sheep (32 to 67 kg). INTERVENTIONS: Animals with chronic indwelling catheters were pretreated with polymyxin B-dextran (6 mg/kg) or placebo (dextran) and an intra-abdominal focus of infection was then produced by cecal ligation and perforation. Treatment (polymyxin B or placebo) was continued every 8 hrs for 48 hrs. MEASUREMENTS AND MAIN RESULTS: Forty-eight hours after randomization, the polymyxin B-dextran group manifested significantly less pyrexia (p = .04), higher mean arterial pressures (p = .02), less variable serum albumin concentrations (p = .05), and a trend toward decreased lactate concentrations (p = .10). Qualitative morphometry and semiquantitative scoring of tissue from gastrocnemius muscle demonstrated that polymyxin B-dextran-treated sheep had significantly increased total capillary (p = .04) and capillary luminal areas (p = .038) and less mitochondrial swelling and damage (p = .03) compared with the placebo sheep. CONCLUSIONS: Pretreatment of sheep in a polymicrobial, peritonitis model of sepsis with polymyxin B-dextran resulted in a significant amelioration of sepsis-induced ultrastructural damage. In placebo-treated control animals, these ultrastructural lesions were associated with a greater severity of sepsis, as measured by the presence of pyrexia, increased lactate concentrations, and less stable blood pressures. These findings justify the investigation of the effects of polymyxin B-dextran in a post onset model of sepsis.

Biologic characteristics of breast cancer detected by mammography and by palpation in a screening program: a pilot study.

OBJECTIVE: To compare the histopathologic features and expression of p53 and c-erb B2 in the tumours detected by mammography only (clinically occult tumours) and the tumours detected by a nurse examiner (clinically palpable tumours). SETTING: London branch of the Ontario Breast Screening Program, which uses both clinical breast examination and mammography as screening methods. INTERVENTIONS: Pathologic review and immunohistochemical staining of all tumours detected between 1990 and 1993. OUTCOME MEASURES: Categorization of tumours by detection method and analysis of tumour size, grade, type, lymph node status and c-erb B2 and p53 expression in each group. RESULTS: From 1990 to 1993, 131 tumours were detected in patients ranging in age from 50 to 85 years (median 63 years). Sixty-seven occult tumours and 64 palpable lesions were detected. The occult tumours were significantly smaller (1.34 cm v. 2.29 cm, p < 0.0001) than the palpable ones and included a higher proportion of special-type lesions and ductal carcinoma in situ (43.3% v. 10.9%, p < 0.0001). Occult invasive carcinomas were of lower grade than palpable carcinomas (68.4% grade 1, 21.1% grade 2, 10.5% grade 3 v. 32.8% grade 1, 36.1% grade 2, 31.1% grade 3, p < 0.0001). Fewer occult lesions showed axillary nodal metastases (19.6% v. 40.6%, p = 0.02). No statistically significant differences were found for p53 or c-erb B2 positivity between the 2 groups. CONCLUSION: Tumours detected by different screening methods in a screening program have different pathologic characteristics.

Relationship of a new histological categorization of ductal carcinoma in situ of the breast with size and the immunohistochemical expression of p53, c-erb B2, bcl-2, and ki-67.

Ductal carcinoma in situ (DCIS) represents a heterogeneous group of diseases. There is no generally accepted classification for the different cytological and architectural types of DCIS. A recent study (Scott et al, 1995) indicates that over 90% of DCIS can be easily classified into the following five categories: high grade (HG), intermediate grade (IG), low grade (LG), pure micropapillary (M), and pure apocrine (A). The aim of this study was to determine if there is a relationship between lesion size and the immunohistochemical expression of p53, c-erb B2, bcl-2, and ki67 with this reproducible categorization of DCIS. Seventy cases of DCIS diagnosed between 1984 and 1995 were obtained from the Departments of Pathology at two teaching hospitals in London, Ontario. The original sections were reviewed, classified according to Scott et al (1995), and representative sections were cut for immunohistochemical (IHC) studies. IHC stains were scored using a previously described semiquantitative scoring system (Allred et al, 1993). Size was taken from the gross measurement if the lesion was palpable or recorded as the largest dimension, as measured on the histological slide, for nonpalpable cases. Of the 70 DCIS cases, 17 (24.3%) were HG, 23 (32.9%) were IG, 21 (30%) were LG, seven (10%) were pure micropapillary cases, and two (2.9%) were pure apocrine DCIS. The mean size of the DCIS for each subcategory was statistically significantly different (P = .008). In particular, the micropapillary DCIS cases were largest (mean size, 17 mm). The mean immunohistochemical scores for c-erb B2 for each category were also statistically different (P = .007), whereas the mean scores for p53 and ki67 for each category trended toward significance (P = .073, P = .062, respectively). There were no significant differences between bcl-2 mean scores and each subcategory. Size of DCIS and c-erb B2 positivity are known to be associated with more aggressive clinical behavior and more advanced histologic features, respectively. Because this combined histological cytological classification system is predictive of size and c-erb B2 positivity, our results support the clinical relevance of this classification system.

Transfusing red blood cells stored in citrate phosphate dextrose adenine-1 for 28 days fails to improve tissue oxygenation in rats.

OBJECTIVE: To determine whether the time that red blood cells are stored in citrate phosphate dextrose adenine-1 solution before transfusion alters the ability to improve tissue oxygenation. DESIGN: Prospective, randomized, controlled study. SETTING: University research institute laboratory. SUBJECTS: Male Sprague-Dawley rats (350 to 450 g). INTERVENTIONS: Twenty-four hours after randomization to sham laparotomy (n = 21) or cecal ligation and perforation (n = 16)1 supply-dependency of systemic oxygen uptake (VO2) was induced in rats by isovolemic hemodilution. Rats were then re-randomized to receive either rat red blood cells stored in citrate phosphate dextrose adenine-1 for 3 days ("fresh" n = 17) or rat red blood cells stored in citrate phosphate dextrose adenine-1 for 28 days ("old" n = 20). MEASUREMENTS AND MAIN RESULTS: Changes in systemic VO2 were measured for 90 mins to determine the efficiacy of the treatment. Statistical analysis included a fully factorial repeated-measures, generalized linear model. No significant interaction was found between cecal ligation and perforation or sham animals and transfusion with fresh or old red blood cells. However, comparing the combined groups of animals receiving either fresh or old red blood cells, we found that after the transfusion of old red blood cells, systemic VO2 was not significantly improved (after hemodilution 1.68 +/- 0.27 mL/100 g/min, after transfusion 1.86 +/- 0.17 mL/100 g/min; p > .05). In contrast, transfusion with fresh red blood cells acutely increased systemic VO2 (after hemodilution 1.62 +/- 0.06 mL/100 g/min, after transfusion 2.10 +/- 0.09 mL/100 g/min; p = .049). CONCLUSION: Storage of rat red blood cells for 28 days in citrate phosphate dextrose adenine-1 impaired their ability to improve tissue oxygenation when transfused into either control or septic rats placed into supply dependency of systemic VO2.