Elizabeth Beale

Subcutaneous Adipose Tissue Macrophage Infiltration Is Associated With Hepatic and Visceral Fat Deposition, Hyperinsulinemia, and Stimulation of NF-κB Stress Pathway

OBJECTIVE To examine in obese young adults the influence of ethnicity and subcutaneous adipose tissue (SAT) inflammation on hepatic fat fraction (HFF), visceral adipose tissue (VAT) deposition, insulin sensitivity (SI), β-cell function, and SAT gene expression. RESEARCH DESIGN AND METHODS SAT biopsies were obtained from 36 obese young adults (20 Hispanics, 16 African Americans) to measure crown-like structures (CLS), reflecting SAT inflammation. SAT, VAT, and HFF were measured by magnetic resonance imaging, and SI and β-cell function (disposition index [DI]) were measured by intravenous glucose tolerance test. SAT gene expression was assessed using Illumina microarrays. RESULTS Participants with CLS in SAT (n = 16) were similar to those without CLS in terms of ethnicity, sex, and total body fat. Individuals with CLS had greater VAT (3.7 ± 1.3 vs. 2.6 ± 1.6 L; P = 0.04), HFF (9.9 ± 7.3 vs. 5.8 ± 4.4%; P = 0.03), tumor necrosis factor-α (20.8 ± 4.8 vs. 16.2 ± 5.8 pg/mL; P = 0.01), fasting insulin (20.9 ± 10.6 vs. 9.7 ± 6.6 mU/mL; P < 0.001) and glucose (94.4 ± 9.3 vs. 86.8 ± 5.3 mg/dL; P = 0.005), and lower DI (1,559 ± 984 vs. 2,024 ± 829 ×10−4 min−1; P = 0.03). Individuals with CLS in SAT exhibited upregulation of matrix metalloproteinase-9 and monocyte antigen CD14 genes, as well as several other genes belonging to the nuclear factor-κB (NF-κB) stress pathway. CONCLUSIONS Adipose tissue inflammation was equally distributed between sexes and ethnicities. It was associated with partitioning of fat toward VAT and the liver and altered β-cell function, independent of total adiposity. Several genes belonging to the NF-κB stress pathway were upregulated, suggesting stimulation of proinflammatory mediators.

Beta-Blockers in Isolated Blunt Head Injury

BACKGROUND The purpose of this study was to evaluate the effect of beta-blockers on patients sustaining acute traumatic brain injury. Our hypothesis was that beta-blocker exposure is associated with improved survival. STUDY DESIGN The trauma registry and the surgical ICU databases of an academic Level I trauma center were used to identify all patients sustaining blunt head injury requiring ICU admission from July 1998 to December 2005. Patients sustaining major associated injuries (Abbreviated Injury Score > or = 4 in any body region other than the head) were excluded. Patient demographics, injury profile, Injury Severity Score, and beta-blocker exposure were abstracted. The primary outcomes measure evaluated was in-hospital mortality. RESULTS During the 90-month study period, 1,156 patients with isolated head injury were admitted to the ICU. Of these, 203 (18%) received beta-blockers and 953 (82%) did not. Patients receiving beta-blockers were older (50 +/- 21 years versus 38 +/- 20 years, p < 0.001), had more frequent severe (Abbreviated Injury Score > or = 4) head injury (54% versus 43%, p < 0.01), Glasgow Coma Scale < or = 8 less often (37% versus 47%, p = 0.01), more skull fractures (20% versus 12%, p < 0.01), and underwent craniectomy more frequently (23% versus 4%, p < 0.001). Stepwise logistic regression identified beta-blocker use as an independent protective factor for mortality (adjusted odds ratio: 0.54; 95% CI, 0.33 to 0.91; p = 0.01). On subgroup analysis, elderly patients (55 years or older) with severe head injury (Abbreviated Injury Score > or = 4) had a mortality of 28% on beta-blockers as compared with 60% when they did not receive them (odds ratio: 0.3; 96% CI, 0.1 to 0.6; p = 0.001). CONCLUSIONS Beta-blockade in patients with traumatic brain injury was independently associated with improved survival. Older patients with severe head injuries demonstrated the largest reduction in mortality with beta-blockade.

Thyroid Hormone Therapy for Obesity and Nonthyroidal Illnesses: A Systematic Review

CONTEXT Thyroid hormone therapy to enhance weight loss in obesity during caloric deprivation and to improve morbidity and mortality in adults with nonthyroidal illnesses remains controversial. OBJECTIVE The aim of this study was to conduct a systematic review evaluating effectiveness and risks of T(3) and/or T(4) therapy in these populations. DATA SOURCES Electronic databases and reference lists were searched. STUDY SELECTION Studies with comparable control groups comparing T(3) and/or T(4) therapy to placebo in randomized controlled trials (RCTs) or prospective observational studies were selected. DATA EXTRACTION Three reviewers performed serial abstraction. DATA SYNTHESIS During caloric deprivation of obese subjects, T(3) therapy decreased serum TSH and T(4) concentrations. Consistent effects of T(3) or T(4) on weight loss, protein breakdown, metabolic rate, and heart rate could not be established. In euthyroid cardiac patients, T(3) decreased TSH and free T(4) levels, without consistent effects of T(3) or T(4) on heart rate, cardiac output, or systemic vascular resistance. Mortality increased 3.3-fold with T(4) therapy in acute renal failure patients, whereas an effect in cardiac, critically ill, and burn patients could not be established. Equivalence testing indicated that larger RCTs are required to determine whether thyroid hormone therapy alters end-points in obesity or nonthyroidal illnesses. LIMITATIONS Numbers of usable unique studies were small, numbers of patients in each study were inadequate, end-points were variable, few RCTs were performed, and study quality of non-RCTs was poor. CONCLUSIONS Available data are inconclusive regarding effectiveness of thyroid hormone therapy in treating obesity or nonthyroidal illnesses, whereas data support that such therapy induces subclinical hyperthyroidism.

Acute Diabetes Insipidus in Severe Head Injury: A Prospective Study

BACKGROUND The incidence and risk factors for acute diabetes insipidus after severe head injury and the effect of this complication on outcomes have not been evaluated in any large prospective studies. STUDY DESIGN We conducted a prospective study of all patients admitted to the surgical ICU of a Level I trauma center with severe head injury (head Abbreviated Injury Score [AIS] >or= 3). The following potential risk factors with p < 0.2 on bivariate analysis were included in a stepwise logistic regression to identify independent risk factors for diabetes insipidus and its association with mortality: age, mechanism of injury (blunt or penetrating), blood pressure, Glasgow Coma Scale, Injury Severity Score, head and other body area AIS, skull fracture, cerebral edema and shift, intracranial hemorrhage, and pneumocephaly. RESULTS There were 436 patients (blunt injuries, 392; penetrating injuries, 44); 387 patients had isolated head injury. Diabetes insipidus occurred in 15.4% of all patients (blunt, 12.5%; penetrating, 40.9%; p < 0.0001) and in 14.7% of patients with isolated head injury (blunt, 11.8%; penetrating, 39.5%; p < 0.0001). The presence of major extracranial injuries did not influence the incidence of diabetes insipidus. Independent risk factors for diabetes insipidus in isolated head injury were Glasgow Coma Scale<or=8, cerebral edema, and head AIS>3. Diabetes insipidus was an independent risk factor for death (adjusted odds ratio, 3.96; 95% CI [1.65, 9.72]; adjusted p value = 0.002). CONCLUSIONS The incidence of acute diabetes insipidus in severe head injury is high, especially in penetrating injuries. Independent risk factors for diabetes insipidus include a Glasgow Coma Scale<or=8, cerebral edema, and head AIS>3. Acute diabetes insipidus was associated with significantly increased mortality.

Thyroid Hormone Therapy for Postoperative Nonthyroidal Illnesses: A Systematic Review and Synthesis

CONTEXT Effects of thyroid hormone therapy on postoperative morbidity and mortality in adults remain controversial. OBJECTIVE The aim was to conduct a systematic review evaluating effects and risks of postoperative T(3) therapy in adults. DATA SOURCES Electronic databases and reference lists through March 2010 were searched. STUDY SELECTION Studies with comparable control groups comparing T(3) to placebo therapy in randomized controlled trials were selected. DATA EXTRACTION Two reviewers independently screened and reviewed titles, abstracts, and articles. Data were abstracted from 14 randomized controlled trials (13 cardiac surgery and one renal transplantation). In seven studies, iv T(3) was given in high doses (0.175-0.333 μg/kg · h) for 6 to 9 h, in four studies iv T(3) was given in low doses (0.0275-0.0333 μg/kg · h for 14 to 24 h), and in three studies T(3) was given orally in variable doses and durations. DATA SYNTHESIS Both high- and low-dose iv T(3) therapy increased cardiac index after coronary artery bypass surgery. Mortality was not significantly altered by high-dose iv T(3) therapy and could not be assessed for low-dose iv or oral T(3). Effects on systemic vascular resistance, heart rate, pulmonary capillary wedge pressure, new onset atrial fibrillation, inotrope use, serum TSH and T(4) were inconclusive. LIMITATIONS Numbers of usable unique studies and group sizes were small. Duration of T(3) therapy was short, and dosages and routes of administration varied. CONCLUSIONS Short duration postoperative iv T(3) therapy increases cardiac index and does not alter mortality. Effects on other parameters are inconclusive.

Changes in Serum Cortisol with Age in Critically Ill Patients

Background: Mortality in the intensive care unit (ICU) rises with age, a high basal serum cortisol and a small response to adrenocorticotropin (ACTH) stimulation. Even slight impairment of the adrenal response during severe illness can be lethal. Objectives: To determine if age is associated with changes in basal or stimulated serum cortisol in critically ill patients. Methods: We studied 2 groups of surgical ICU patients with hypotension despite ≧6 h of catecholamine therapy. Group 1 comprised 7 patients aged <30 (mean 22.9 ± 3.7) years, and group 2 comprised 8 patients aged >60 (mean 75.8 ± 10.3) years (p < 0.001). We compared baseline serum cortisol levels and the serum cortisol response 30 and 60 min after stimulation with low-dose (1 µg) and 2 h later standard-dose (250 µg) ACTH. We also determined the incidence of adrenal insufficiency in each group using standard criteria and compared selected clinical variables. Results: There was no significant difference in the mean serum cortisol at baseline although it tended to be higher in older patients. Group 2 patients had a significantly smaller response to the low-dose test at 30 min (p = 0.002), and to the standard-dose test at both 30 (p = 0.02) and 60 min (p = 0.04). There was no significant difference in the incidence of adrenal insufficiency between the 2 groups: 1/7 or 14.3% in group 1 vs. 1/8 or 12.5% in group 2 (p = 1.0). There was no significant difference between the 2 groups in the mean acute physiology score, blood pressure, serum albumin, dopamine, or dobutamine dose (p > 0.05). Creatinine clearance was significantly lower in group 2 (p > 0.001) and endogenous ACTH significantly higher (p = 0.04). Significantly more patients in group 1 (5/7, 72%) than group 2 (1/8, 12.5%) had a diagnosis of trauma on admission (p = 0.04). Seven of the eight patients (88%) in group 2 vs. 1/7 (14%) of patients in group 1 died in the ICU, but this difference was not statistically significant (p = 0.18). Conclusion: In this small exploratory study, baseline serum cortisol tended to be higher in older patients and older patients had a significantly smaller response to ACTH stimulation on both low-dose and standard-dose tests. In view of the high death rate in the older ICU patients, the findings in this study need to be confirmed in a larger study. The mechanism and clinical significance of these findings remain to be determined but may be related to deterioration in renal function with age.

Effect of delaying same-admission cholecystectomy on outcomes in patients with diabetes

Recent studies have suggested that same‐admission delayed cholecystectomy is a safe option. Patients with diabetes have been shown to have less favourable outcomes after cholecystectomy, but the impact of timing of operation for acute cholecystitis during the same admission is unknown.

The effect of diabetes on outcomes following emergency appendectomy in patients without comorbidities: a propensity score-matched analysis of National Surgical Quality Improvement Program database

BACKGROUND The effect of diabetes and the role of laparoscopic surgery on outcomes following appendectomy for acute appendicitis are not known. METHODS National Surgical Quality Improvement Program study, including patients with acute appendicitis and no significant comorbidities (American Society of Anesthesiologists grade I or II) who underwent appendectomy. Diabetic patients were matched (1:3) with nondiabetic patients. The primary outcomes were 30-day mortality, surgical site infections (SSIs), and systemic infectious complications. RESULTS SSI was encountered more frequently in the diabetic group as compared with the nondiabetic group (6.1% vs 4.3%, P = .010). Also, the hospital length of stay was significantly longer in the diabetic group. In the diabetic group, laparoscopic appendectomy did not affect mortality, reoperation, SSI, and systemic infectious complication rates in patients with or without peritonitis (P > .05), but the hospital length of stay was significantly shorter when compared with the open procedure. CONCLUSIONS Patients with diabetes and no significant comorbidities have a higher risk of developing SSIs and longer hospital stay than patients without diabetes. Laparoscopic appendectomy had no effect on SSIs in patients with diabetes.

Early pancreatic dysfunction after resection in trauma: An 18-year report from a Level I trauma center

BACKGROUND Early pancreatic dysfunction after resection in trauma has not been well characterized. The objective of this study was to examine the incidence and clinical impact of new-onset endocrine and exocrine dysfunction after pancreatic resection for trauma. METHODS All patients sustaining a pancreatic injury from 1996 to 2013 were identified. Patients with preinjury diabetes were excluded. Survivors were divided into three groups according to the extent of anatomic resection—distal, proximal, or total pancreatectomy. Clinical demographics and outcome data were abstracted. Blood glucose levels, hemoglobin A1c, and insulin requirements were used to assess endocrine pancreatic function. Reported steatorrhea, diarrhea, or supplemental pancreatic enzyme requirements were used to assess exocrine pancreatic function. RESULTS During the study period, 331 pancreatic injuries were identified, of which 109 (33%) required resection and 84 survived to hospital discharge. Four were excluded. Of 80 cases analyzed, 73 (91%) underwent distal pancreatectomy, 7 (9%) proximal pancreatectomy, and none a total pancreatectomy. The distal resection group was predominantly male (88%), median age 24 years, and mean BMI 27 (kg/m2). Thirty-eight (52%) required insulin postoperatively, with the greatest proportion (47%) requiring insulin for ⩽1 day; no patients were discharged on insulin. The proximal resection group was predominantly male (86%), median age 31 years, and mean BMI 32 (kg/m2). Six of seven required insulin postoperatively and two of seven were insulin dependent at time of hospital discharge. For both distal and proximal resections, none had evidence of exocrine dysfunction or received pancreatic enzyme supplementation at discharge. CONCLUSION Exocrine dysfunction after distal or proximal pancreatectomy for trauma is rare. The incidence of early onset endocrine dysfunction after traumatic distal pancreatectomy is also rare; however, it can be seen after proximal resection. Level of Evidence Therapeutic study, level IV.

The effects of body mass index on complications and mortality after emergency abdominal operations: The obesity paradox

BACKGROUND Recent literature suggests that obesity is protective in critically illness. This study addresses the effect of BMI on outcomes after emergency abdominal surgery (EAS). METHODS Retrospective, ACS-NSQIP analysis. All patients that underwent EAS were included. The study population was divided into five groups based on BMI; regression models were used to evaluate the role of obesity in morbidity and mortality. RESULTS 101,078 patients underwent EAS; morbidity and mortality were 19.5% and 4.5%, respectively. Adjusted mortality was higher in underweight patients (AOR 1.92), but significantly lower in all obesity groups (AORs 0.73, 0.66, 0.70, 0.70 respectively). Underweight and class III obesity was associated with increased complications (AOR 1.47 and 1.30), while mild obesity was protective (AOR 0.92). CONCLUSIONS Underweight patients undergoing EAS have increased morbidity and mortality. Although class III obesity is associated with increased morbidity, overweight and class I obesity were protective. All grades of obesity may be protective against mortality after EAS relative to normal weight patients.