Rosemarie Metzger

Obesity and Site-Specific Nosocomial Infection Risk in the Intensive Care Unit

BACKGROUND Obese patients are at higher than normal risk for postoperative infections such as pneumonia and surgical site infections, but the relation between obesity and infections acquired in the intensive care unit (ICU) is unclear. Our objective was to describe the relation between body mass index (BMI) and site-specific ICU-acquired infection risk in adults. METHODS Secondary analysis of a large, dual-institutional, prospective observational study of critically ill and injured surgical patients remaining in the ICU for at least 48 h. Patients were classified into BMI groups according to the National Heart, Lung and Blood Institute guidelines: <or= 18.5 kg/m(2) (underweight), 18.5-24.9 kg/m(2) (normal), 25-29.9 kg/m(2) (overweight), 30.0-39.9 kg/m(2) (obese), and >or= 40.0 kg/m(2) (severely obese). The primary outcomes were the number and site of ICU-acquired U.S. Centers for Disease Control and Prevention-defined infections. Multivariable logistic and Poisson regression were used to determine age-, sex-, and severity-adjusted odds ratios (ORs) and incidence rate ratios associated with differences in BMI. RESULTS A total of 2,037 patients had 1,436 infection episodes involving 1,538 sites in a median ICU length of stay of 9 days. After adjusting for age, sex, and illness severity, severe obesity was an independent risk factor for catheter-related (OR 2.2; 95% confidence interval [CI] 1.5, 3.4) and other blood stream infections (OR 3.2; 95% CI 1.9, 5.3). Cultured organisms did not differ by BMI group. CONCLUSION Obesity is an independent risk factor for ICU-acquired catheter and blood stream infections. This observation may be explained by the relative difficulty in obtaining venous access in these patients and the reluctance of providers to discontinue established venous catheters in the setting of infection signs or symptoms.

Aggressive versus conservative initiation of antimicrobial treatment in critically ill surgical patients with suspected intensive-care-unit-acquired infection: a quasi-experimental, before and after observational cohort study

BACKGROUND Antimicrobial treatment in critically ill patients can either be started as soon as infection is suspected or after objective data confirm an infection. We postulated that delaying antimicrobial treatment of patients with suspected infections in the surgical intensive care unit (SICU) until objective evidence of infection had been obtained would not worsen patient mortality. METHODS We did a 2-year, quasi-experimental, before and after observational cohort study of patients aged 18 years or older who were admitted to the SICU of the University of Virginia (Charlottesville, VA, USA). From Sept 1, 2008, to Aug 31, 2009, aggressive treatment was used: patients suspected of having an infection on the basis of clinical grounds had blood cultures sent and antimicrobial treatment started. From Sept 1, 2009, to Aug 31, 2010, a conservative strategy was used, with antimicrobial treatment started only after objective findings confirmed an infection. Our primary outcome was in-hospital mortality. Analyses were by intention to treat. FINDINGS Admissions to the SICU for the first and second years were 762 and 721, respectively, with 101 patients with SICU-acquired infections during the aggressive year and 100 patients during the conservative year. Compared with the aggressive approach, the conservative approach was associated with lower all-cause mortality (13/100 [13%] vs 27/101 [27%]; p=0·015), more initially appropriate therapy (158/214 [74%] vs 144/231 [62%]; p=0·0095), and a shorter mean duration of therapy (12·5 days [SD 10·7] vs 17·7 [28·1]; p=0·0080). After adjusting for age, sex, trauma involvement, acute physiology and chronic health evaluation (APACHE) II score, and site of infection, the odds ratio for the risk of mortality in the aggressive therapy group compared with the conservative therapy group was 2·5 (95% CI 1·5-4·0). INTERPRETATION Waiting for objective data to diagnose infection before treatment with antimicrobial drugs for suspected SICU-acquired infections does not worsen mortality and might be associated with better outcomes and use of antimicrobial drugs. FUNDING National Institutes of Health.

Hypocaloric compared with eucaloric nutritional support and its effect on infection rates in a surgical intensive care unit: a randomized controlled trial

BACKGROUND Proper caloric intake goals in critically ill surgical patients are unclear. It is possible that overnutrition can lead to hyperglycemia and an increased risk of infection. OBJECTIVE This study was conducted to determine whether surgical infection outcomes in the intensive care unit (ICU) could be improved with the use of hypocaloric nutritional support. DESIGN Eighty-three critically ill patients were randomly allocated to receive either the standard calculated daily caloric requirement of 25-30 kcal · kg(-1) · d(-1) (eucaloric) or 50% of that value (hypocaloric) via enteral tube feeds or parenteral nutrition, with an equal protein allocation in each group (1.5 g · kg(-1) · d(-1)). RESULTS There were 82 infections in the hypocaloric group and 66 in the eucaloric group, with no significant difference in the mean (± SE) number of infections per patient (2.0 ± 0.6 and 1.6 ± 0.2, respectively; P = 0.50), percentage of patients acquiring infection [70.7% (29 of 41) and 76.2% (32 of 42), respectively; P = 0.57], mean ICU length of stay (16.7 ± 2.7 and 13.5 ± 1.1 d, respectively; P = 0.28), mean hospital length of stay (35.2 ± 4.9 and 31.0 ± 2.5 d, respectively; P = 0.45), mean 0600 glucose concentration (132 ± 2.9 and 135 ± 3.1 mg/dL, respectively; P = 0.63), or number of mortalities [3 (7.3%) and 4 (9.5%), respectively; P = 0.72]. Further analyses revealed no differences when analyzed by sex, admission diagnosis, site of infection, or causative organism. CONCLUSIONS Among critically ill surgical patients, caloric provision across a wide acceptable range does not appear to be associated with major outcomes, including infectious complications. The optimum target for caloric provision remains elusive.

High Levels of Endogenous Estrogens are Associated With Death in the Critically Injured Adult

BACKGROUND Sex hormones exhibit predictable changes in their physiologic patterns during critical illness. Endogenous estrogens are elevated in both genders as a result of the peripheral conversion of androgens to estrogens by the aromatase enzyme. Elevated endogenous estrogens have been associated with death in medical and mixed surgical intensive care unit (ICU) patients. Our objective was to determine the relationship between endogenous estrogens and outcomes in critically injured patients. METHODS A prospective cohort of injured patients remaining in the ICU for at least 48 hours at two trauma centers was enrolled. Sex hormones (estradiol, progesterone, testosterone, prolactin, and dehydroepiandrosterone-sulfate) were assayed and mortality was assessed. A logistic regression model was used to determine the association between estradiol and death. The area under the receiver operating characteristic (AUROC) curve was used to estimate the accuracy of estradiol in predicting death. RESULTS Nine hundred ninety-one patients were enrolled with a 13.4% mortality rate. Despite no detectable difference in mortality among genders, estradiol was significantly elevated in nonsurvivors (16 pg/mL vs. 35 pg/mL, p < 0.001). Estradiol was a marker for injury severity with the most severely injured patients exhibiting the highest levels. The ability of estradiol to predict death (AUROC = 0.65) was comparable with Trauma and Injury Severity Score (AUROC = 0.65) and superior to Injury Severity Score (AUROC = 0.54) in this cohort. CONCLUSIONS Serum estradiol is a marker of injury severity and a predictor of death in the critically injured patient, regardless of gender. Whether or not estradiol plays a causal role in outcomes is unclear, but estrogen modulation represents a potential therapy for improving outcomes in critically ill trauma patients.

Should patients with Cowden syndrome undergo prophylactic thyroidectomy

BACKGROUND Cowden syndrome (CS) is dominantly inherited and predisposes patients to tumors in multiple organs. We characterized CS-associated malignant and benign thyroid disease. METHODS Of data from 3,477 prospectively recruited CS patients with known genetic analysis, we analyzed 225 PTEN mutation+ patients whose treatment occurred at our center (n = 25) or other hospitals nationwide (n = 200). RESULTS A total of 32 of 225 PTEN mutation+ patients (14%) had thyroid cancer: 52% papillary, 28% follicular-variant papillary, 14% follicular, and 6% anaplastic. Median age at diagnosis was 35 years compared with 49 years for Surveillance Epidemiology and End Results population data. Initial thyroid ultrasonography in 16 of 25 patients revealed thyroiditis/goiters in all >13 years age, leading to FNA in 7 (64%), thyroidectomy in 3 (27%), and new cancer diagnosis in 2 (18%). Three with severe autism required intraoperative sedation for ultrasonography. A total of 9 of 25 patients were monitored after multiple partial thyroidectomies for goiters by age 42 (n = 5), thyroiditis, or cancer detected by age 36 (n = 3). CONCLUSION PTEN mutation+ patients with CS have an enormous prevalence of thyroid disease. Earlier screening may be advisable because thyroiditis and nodules are seen by the time patients reach adolescence, and cancer diagnosis occurs on average 14 years earlier than expected. Furthermore, the risks observed may justify prophylactic total thyroidectomy in select, if not all, patients, particularly those with developmental disorders.

Diagnosis-Dependent Relationships between Cytokine Levels and Survival in Patients Admitted for Surgical Critical Care

BACKGROUND Death after trauma, infection, or other critical illness has been attributed to unbalanced inflammation, in which dysregulation of cytokines leads to multiple organ dysfunction and death. We hypothesized that admission cytokine profiles associated with death would differ based on admitting diagnosis. STUDY DESIGN This 5-year study included patients admitted for trauma or surgical intensive care for more than 48 hours at 2 academic, tertiary care hospitals between October 2001 and May 2006. Cytokine analysis for interleukin (IL)-1, -2, -4, -6, -8, -10, -12, interferon-gamma, and tumor necrosis factor (TNF)-alpha was performed using ELISA on specimens drawn within 72 hours of admission. Mann-Whitney U test was used to compare median admission cytokine levels between alive and deceased patients. Relative risks and odds of death associated with admission cytokines were generated using univariate analysis and multivariate logistic regression models, respectively. RESULTS There were 1,655 patients who had complete cytokine data: 290 infected, nontrauma; 343 noninfected, nontrauma; and 1,022 trauma. Among infected patients, nonsurvivors had higher median admission levels of IL-2, -8, -10, and granulocyte macrophage-colony stimulating factor; noninfected, nontrauma patients had higher IL-6, -8, and IL-10; and nonsurviving trauma patients had higher IL-4, -6, -8, and TNF-alpha. IL-4 was the most significant predictor of death and carried the highest relative risk of dying in trauma patients, and IL-8 in nontrauma, noninfected patients. In infected patients, no cytokine independently predicted death. CONCLUSIONS Cytokine profiles of certain disease states may identify persons at risk of dying and allow for selective targeting of multiple cytokines to prevent organ dysfunction and death.

Identification of risk factors for the development of clostridium difficile-associated diarrhea following treatment of polymicrobial surgical infections

Objective:To identify risk factors for Clostridium difficile-associated diarrhea (CDAD) in surgical patients following treatment of polymicrobial infections. Summary Background Data:Infections among surgical patients are frequently anaerobic or mixed aerobic-anaerobic infections and are therefore subject to polymicrobial antibiotic coverage, including metronidazole. While multiple antibiotics are known to contribute to the development of CDAD, the role of preventive antibiotics is unproven. Methods:An 11-year dataset of consecutive infections treated in surgical patients at a single hospital was reviewed. All intra-abdominal, surgical site, or skin/skin structure infections were identified. Each infection was evaluated for antibiotic coverage and subsequent CDAD. Antibiotic usage was assessed using &khgr;2 analysis. A multiple logistic regression was used to identify independent predictors of CDAD. Results:A total of 4178 intra-abdominal, surgical site, or skin/skin structure infections were identified. Of these infections, 98 were followed by CDAD. Only carbapenem use affected the incidence of CDAD: 3.5% of infections treated with a carbapenem were followed by CDAD, whereas only 2.1% of infections treated without carbapenems were followed by CDAD (P = 0.04). Metronidazole had no association with future CDAD. Only age and Acute Physiology and Chronic Health Evaluation II (APACHE II) score were independently associated with CDAD by multiple logistic regression analysis. Conclusions:Older patients with a high severity of illness are at greatest risk for developing CDAD following treatment of polymicrobial infections. No specific antibiotic class, including fluoroquinolones, is associated with an increased incidence of CDAD in this population. Although use of metronidazole in the treatment of polymicrobial infections is appropriate for anaerobic coverage, it does not reduce the risk of future CDAD.

Characteristics of Benign and Malignant Thyroid Disease in Familial Adenomatous Polyposis Patients and Recommendations for Disease Surveillance

BACKGROUND Familial adenomatous polyposis (FAP) is a hereditary colon cancer syndrome that involves multiple extracolonic organs, including the thyroid. Several studies have estimated the rate of thyroid cancer in FAP to occur at five times the rate of the general population, but no current consensus defines screening for thyroid cancer in this cohort. This study seeks to define the features of benign and malignant thyroid disease in FAP patients, to compare thyroid cancer cases found through screening with those found incidentally, and to propose disease surveillance recommendations. METHODS Prospective screening for early thyroid cancer detection with thyroid ultrasound (US) was performed on FAP patients at the time of annual colonoscopy since November 2008. Clinical and US data were reviewed to characterize the observed thyroid nodules. Nonscreening-detected cases (NSD) were found through review of the colon cancer registry database. RESULTS Eighteen NSD were found, compared with 15 screening-detected (SD) cases, out of 205 total patients screened (Mage=42 years; 55% female). The mean tumor size was larger in the NSD group than the SD group (p=0.04), and they tended to demonstrate more positive lymph nodes and more complications than the SD group. In the screened cohort, at least one thyroid nodule was detected in 106 (51.7%) patients, with 90% of these seen on initial exam. A total of 40/106 (37.7%) patients required fine-needle aspiration biopsy of a dominant nodule (Msize=14 mm), and 28/40 (70%) of these were performed at the first US visit. Suspicious US features were present in 16/40 (40%) patients, including five sub-centimeter nodules. Cytology and/or nodule US was abnormal in 15/205 screened patients, leading to surgery and revealing 14 papillary and one medullary thyroid cancer. CONCLUSIONS Given the age and sex distribution of the screened cohort, this study reveals a higher-than-expected prevalence of both benign and malignant thyroid disease in the FAP population. Additionally, SD cases seemed to consist of smaller-sized cancers that required less radical therapy compared to NSD cases. Since it was found that the initial US in the screening program accounted for the majority of detected nodules (90%) and biopsies (70%), baseline and subsequent thyroid US surveillance is recommended in all FAP patients.

Sex- and Diagnosis-dependent Differences in Mortality and Admission Cytokine Levels Among Patients Admitted for Intensive Care*

Objectives:To investigate the role of sex on cytokine expression and mortality in critically ill patients. Design:A cohort of patients admitted to were enrolled and followed over a 5-year period. Setting:Two university-affiliated hospital surgical and trauma ICUs. Patients:Patients 18 years old and older admitted for at least 48 hours to the surgical or trauma ICU. Interventions:Observation only. Measurements and Main Results:Major outcomes included admission cytokine levels, prevalence of ICU-acquired infection, and mortality during hospitalization conditioned on trauma status and sex. The final cohort included 2,291 patients (1,407 trauma and 884 nontrauma). The prevalence of ICU-acquired infection was similar for men (46.5%) and women (44.5%). All-cause in-hospital mortality was 12.7% for trauma male patient and 9.1% for trauma female patient (p = 0.065) and 22.9% for nontrauma male patients and 20.6% for nontrauma female patients (p = 0.40). Among trauma patients, logistic regression analysis identified female sex as protective for all-cause mortality (odds ratio, 0.57). Among trauma patients, men had significantly higher admission serum levels of interleukin-2, interleukin-12, interferon-&ggr;, and tumor necrosis factor-&agr;, and among nontrauma patients, men had higher admission levels of interleukin-8 and tumor necrosis factor-&agr;. Conclusions:The relationship between sex and outcomes in critically ill patients is complex and depends on underlying illness. Women appear to be better adapted to survive traumatic events, while sex may be less important in other forms of critical illness. The mechanisms accounting for this gender dimorphism may, in part, involve differential cytokine responses to injury, with men expressing a more robust proinflammatory profile.

Inherited cancer syndromes and the thyroid: an update.

Purpose of review Knowledge related to hereditary thyroid cancer syndromes has expanded enormously. This review identifies contributions that have changed approaches to diagnosis and broadened treatment options for patients with hereditary medullary and nonmedullary thyroid cancers related to multiple endocrine neoplasia type 2 (MEN2), Cowden syndrome, and familial adenomatous polyposis (FAP). Recent findings A new risk-stratification scheme based on type of RET gene mutation informs the age at which prophylactic thyroidectomy and diagnostic screening for MEN-associated endocrine diseases should occur. Two new US Food and Drug Administration-approved targeted medical therapies are now available for medullary thyroid cancer. There is better understanding of more aggressive clinical features and increased lifetime cancer risks for patients with well differentiated thyroid cancers as part of families with and without Cowden syndrome or FAP. This has led to a clearer appreciation for the role and timing of thyroid ultrasound screening in these populations. It has also informed the appropriate extent of thyroid surgery and the circumstances in which prophylactic thyroidectomy is reasonable to consider as part of hereditary syndromes other than MEN2. Summary Recognition and early diagnosis of these syndromes allows for comprehensive medical care and may improve thyroid cancer-related outcomes. Ultrasound-based screening programs to detect thyroid disease are advised for patients and family members with hereditary cancer syndromes.