Nutritional Assessment in Patients after Gastric Electrical Stimulation (GES).

BACKGROUND: Gastric electrical stimulation (GES) is used for patients with drug-refractory gastroparesis (Gp) symptoms. Approximately two-thirds of patients with Gp symptoms are either overweight or obese. We aimed to assess symptoms and nutritional status pre-GES and post-GES placement in a large sample of drug-refractory Gp patients. METHODS: We conducted a chart review of 282 patients with drug-refractory Gp who received temporary followed by permanent GES at an academic medical center. Gastrointestinal symptoms were collected by a traditional standardized PRO (0-4, 0 being asymptomatic and 4 being worst symptoms), baseline nutritional status by BMI plus subjective global assessment (SGA score A, B, C, for mild, moderate, and severe nutritional deficits), ability to tolerate diet, enteral tube access, and parenteral therapy were assessed at baseline and after permanent GES placement. RESULTS: Comparing baseline with permanent, GES was found to significantly improve upper GI symptoms in all quartiles. Of the 282 patients with baseline body mass index (BMI) information, 112 (40%) patients were severely malnourished at baseline, of which 36 (32%) patients' nutritional status improved after GES. Among all patients, 76 (68%) patients' nutritional status remained unchanged. Many patients with high BMI were malnourished by SGA. CONCLUSION: We conclude that symptomatic patients of different BMIs showed improvement in their GI symptoms irrespective of baseline nutritional status. Severely malnourished patients were found to have an improvement in their nutritional status after GES therapy. We conclude that BMI, even if high, is not by itself a contraindication for GES therapy for symptomatic patients.

Baseline Characteristics and Predictive Factors of Intravenous Immunoglobulin Response in Drug and Device Refractory Gastroparesis Symptoms.

INTRODUCTION: Intravenous immunoglobulin (IVIG) has been shown in a small pilot series to be helpful for some patients with gastroparesis that is refractory to drugs, devices, and surgical therapies. Many but not all patients have serologic neuromuscular markers. We hypothesize that those patients with serologic markers and/or longer duration of therapy would have better responses to IVIG. MATERIALS AND METHODS: We studied 47 patients with a diagnosis of gastroparesis and gastroparesis-like syndrome that had all failed previous therapies including available and investigational drugs, devices, and/or pyloric therapies. Patients had a standardized 12-week course of IVIG, dosed as 400 mg/kg per week intravenously. Symptom assessment was done with Food and Drug Administration (FDA) compliant traditional patient-reported outcomes. Success to IVIG was defined as 20% or greater reduction in average symptom scores from baseline to the latest evaluation. RESULTS: Fourteen patients (30%) had a response, and 33 (70%) had no response per our definition. Patients responding had a higher glutamic acid decarboxylase 65 positivity (64% vs. 30%, P =0.049, missing=3) and longer duration of therapy (>12 wk/continuous: 86% vs. 48%, P =0.09). CONCLUSIONS: In this moderately sized open-label series of refractory patients with gastroparesis symptoms treated with IVIG, 30% of patients responded. While serologic markers and extended therapies show a trend to greater response, neither was statistically significant, except for glutamic acid decarboxylase 65 which showed a higher positivity rate in responders. We conclude that a clinical trial of IVIG may be warranted in severely refractory patients with gastroparesis symptoms.

Low-Resolution Electrogastrogram at Baseline and Response to Temporary Gastric Electrical Stimulation-A Comparison of Cutaneous With Mucosal Recordings.

INTRODUCTION: Gastric electrical stimulation (GES) is a widely accepted therapy for gastroparesis symptoms, but how a brief cutaneous electrogastrogram (EGG) can be used in conjunction with GES has not been well defined. We evaluated the clinical importance of EGG, its correlation with mucosal electrograms (mEGs), gastric emptying tests (GETs), and gastrointestinal symptoms before and after temporary GES (tGES). MATERIALS AND METHODS: We studied 1345 patients; 991 had complete data. EGG measurements like frequency and amplitude were recorded at baseline and five days post-tGES using short recording periods. A total of 266 participants having additional cutaneous propagation values were separately analyzed. Patients underwent solid GET before and after tGES and self-reported symptoms using standardized traditional patient-reported outcomes (TradPRO) scores. Pearson correlations were assessed at baseline, post-stimulation, and their changes over the follow-up period. RESULTS: EGG measures correlated with symptoms and GET results. Patients with abnormal baseline cutaneous frequency had higher baseline total symptom scores (p < 0.003). Post-tGES, one-hour gastric emptying was significantly changed (p < 0.0001) and was mainly observed with abnormal baseline cutaneous frequencies (p < 0.0001). Cutaneous frequency significantly increased after tGES (p < 0.0001), correlating positively with TradPRO scores and one-hour gastric emptying. Mucosal and cutaneous measures correlated pre- and post-treatment. Of the 266 patients, 153 changed propagation states between baseline and temporary; changing states from lower at baseline to higher at temporary was more likely than vice versa. Short EGG recording times can demonstrate changes after the bioelectric therapy of GES. CONCLUSION: EGG is valuable in the diagnosis of delayed gastric emptying and comparable with mEG. It is less invasive and can identify patients who may require GES. Frequency, amplitude, their ratio (frequency-amplitude ratio), and propagation appear to be reliable measures of EGG. EGG provides cost-effective measurement of electrophysiological properties and significantly correlates with important clinical measures. Shorter EGG recording times may be adequate to see changes from bioelectric therapies. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03876288.

Circulating MicroRNAs, Polychlorinated Biphenyls, and Environmental Liver Disease in the Anniston Community Health Survey.

BACKGROUND: Polychlorinated biphenyl (PCB) exposures have been associated with liver injury in human cohorts, and steatohepatitis with liver necrosis in model systems. MicroRNAs (miRs) maintain cellular homeostasis and may regulate the response to environmental stress. OBJECTIVES: We tested the hypothesis that specific miRs are associated with liver disease and PCB exposures in a residential cohort. METHODS: Sixty-eight targeted hepatotoxicity miRs were measured in archived serum from 734 PCB-exposed participants in the cross-sectional Anniston Community Health Survey. Necrotic and other liver disease categories were defined by serum keratin 18 (K18) biomarkers. Associations were determined between exposure biomarkers (35 ortho-substituted PCB congeners) and disease biomarkers (highly expressed miRs or previously measured cytokines), and Ingenuity Pathway Analysis was performed. RESULTS: The necrotic liver disease category was associated with four up-regulated miRs (miR-99a-5p, miR-122-5p, miR-192-5p, and miR-320a) and five down-regulated miRs (let-7d-5p, miR-17-5p, miR-24-3p, miR-197-3p, and miR-221-3p). Twenty-two miRs were associated with the other liver disease category or with K18 measurements. Eleven miRs were associated with 24 PCBs, most commonly congeners with anti-estrogenic activities. Most of the exposure-associated miRs were associated with at least one serum hepatocyte death, pro-inflammatory cytokine or insulin resistance bioarker, or with both. Within each biomarker category, associations were strongest for the liver-specific miR-122-5p. Pathways of liver toxicity that were identified included inflammation/hepatitis, hyperplasia/hyperproliferation, cirrhosis, and hepatocellular carcinoma. Tumor protein p53 and tumor necrosis factor α were well integrated within the top identified networks. DISCUSSION: These results support the human hepatotoxicity of environmental PCB exposures while elucidating potential modes of PCB action. The MiR-derived liquid liver biopsy represents a promising new technique for environmental hepatology cohort studies. https://doi.org/10.1289/EHP9467.

Baseline predictive factors for foregut and hindgut response to long-term gastric electrical stimulation using augmented energy.

INTRODUCTION: Gastric electrical stimulation (GES) has been recommended for drug refractory patients with gastroparesis, but no clear baseline predictors of symptom response exist. We hypothesized that long-term predictors to GES for foregut and hindgut symptoms exist, particularly when using augmented energies. PATIENTS: We evaluated 307 patients at baseline, 1 week post temporary GES, and one year after permanent GES. Baseline measures included upper and lower symptoms by patient-reported outcomes (PRO), solid and liquid gastric emptying (GET), cutaneous, mucosal, and serosal electrophysiology (EGG, m/s EG), BMI, and response to temporary stimulation. METHODS: Foregut and hindgut PRO symptoms were analyzed for 12-month patient outcomes. All patients utilized a standardized energy algorithm with the majority of patients receiving medium energy at 12 months. Patients were categorized based on change in average GI symptom scores at the time of permanent GES compared to baseline using a 10% decrease over time as the cutoff between improvers versus non-improvers. RESULTS: By permanent GES implant, average foregut and hindgut GI symptom scores reduced 42% in improved patients (n = 199) and increased 27% in non-improved patients (n = 108). Low BMI, baseline infrequent urination score, mucosal EG ratio, and proximal mucosal EG low-resolution amplitude remained significant factors for improvement status. CONCLUSIONS: GES, for patients responding positively, improved both upper/foregut and lower/hindgut symptoms with most patients utilizing higher than nominal energies. Low baseline BMI and the presence of infrequent urination along with baseline gastric electrophysiology may help identify those patients with the best response to GES/bio-electric neuromodulation.

Inflammatory Markers and Mortality in Diabetic Versus Idiopathic Gastroparesis.

INTRODUCTION: Markers of systemic inflammation have been shown to be elevated in patients with gastroparesis (Gp). We hypothesized the presence of elevated markers of inflammation and/or coagulation can predict death in gastroparesis. METHODS: Retrospective evaluation of 396 patients with symptoms of gastroparesis with baseline measures of inflammation and coagulation, using a database of patients from 2001 through 2011 followed for an additional 5 plus years. Patients were divided into two groups; diabetic (DM; n=137) and non-diabetic (non-DM; n=259). Inflammation, evaluated by C-reactive protein (CRP), and coagulation by fibrinogen by factor VIII assays, was compared to patient mortality, reported as death during the follow-up period. RESULTS: Six DM and 13 non-DM patients died during the study period. DM patients had higher fibrinogen, CRP, and factor VIII levels of 454.0±135.2, 4.0±6.3, and 168±63.5, versus non-DM whose levels were 410.4±127.9, 2.6±4.9, 140.4±127.9, p=0.03, 0.001, and <0.001 respectively. Hypercoagulability risk differed by DM status (37% Vs. 29%, p=0.08). Compared to living non-DM, deceased non-DM/idiopathic patients had lower factor VIII (142.3±51.2 vs 117.7±40.3, p=0.07). The majority of deceased non-DM patients had abnormal fibrinogen (62%) but CRP and factor VIII were normal (80% and 85% respectively). CONCLUSIONS: In this sample of 396 patients with symptoms of gastroparesis, systemic inflammation and coagulopathy appear related to diabetes mellitus. Patients who died had markers of inflammation and coagulation that differed from those still alive. Further analysis may suggest a link between inflammation, hypercoagulability, and the mechanism for mortality in gastroparesis or as a marker of disease severity.

Pathophysiology of Gastroparesis Syndromes Includes Anatomic and Physiologic Abnormalities.

BACKGROUND: Factors underlying gastroparesis are not well defined. AIMS: We hypothesized that multiple systems may be involved in patients with gastroparesis symptoms and performed a comparative physiologic study. METHODS: We studied 43 consecutive eligible patients with gastroparetic symptoms categorized by GI symptoms, metabolic status, illness quantification, and gastric physiology. Patients were evaluated by two methods in each of five core areas: inflammatory, autonomic, enteric, electrophysiologic, and hormonal with abnormalities examined by correlations. RESULTS: Patients had similar GI symptoms regardless of baseline gastric emptying or diabetic/idiopathic status, and all patients demonstrated abnormalities in each of the 5 areas studied. Nearly all patients presented with elevated markers of serum TNFα (88%) and serum IL-6 (91%); elevated cutaneous electrogastrogram frequency (95%); and interstitial cells of Cajal count abnormalities (inner: 97%, outer: 100%). Measures of inflammation correlated with a number of autonomic, enteric anatomy, electrophysiologic and hormonal abnormalities. CONCLUSIONS: We conclude that patients with the symptoms of gastroparesis have multiple abnormalities, when studied by traditional, as well as newer, diagnostic assessments. Inflammation appears to be a fundamental abnormality that affects other organ systems in symptomatic patients. Future work on gastroparetic syndromes and their treatment may benefit from a focus on the diffuse nature of their illness, diverse pathophysiologic mechanisms involved, especially the possible causes of underlying inflammation and disordered hormonal status. TRAIL REGISTRY: This study is registered with Clinicaltrials.gov under study # NCT03178370 https://clinicaltrials.gov/ct2/show/NCT03178370 .

Gastric Electrical Stimulation Has an Effect on Gastric Interstitial cells of Cajal (ICC) That is Associated With Mast Cells.

Introduction Gastric electrical stimulation (GES) is an emerging therapy for gastric motility disorders, showing improvement of gastroparesis related symptoms in previous studies. Interstitial cells of Cajal (ICC) and mast cells have been shown to have a relevant role in gastroparesis pathogenesis. However, the exact effects of GES in those cells is relatively unknown. Methods Full thickness biopsies (FTBx) of 20 patients with refractory gastroparesis were obtained at the time of GES placement and repeated when the device was exchanged (mean of 22.5 months between biopsies). A patient-reported outcomes survey was obtained during each office visit during this period. All biopsies were stained with cluster of differentiation 117 (CD117), S100, and mast cell tryptase antibodies and were analyzed. Results Half of the patients had a significant increase of ICC during the repeated biopsy compared with baseline (p=0.01) and the other half had significant decrease in ICC levels (p=0.006) but there was no noticeable difference in mast cells counts at baseline between groups. Mast cells analysis was performed in two different groups depending on ICC change from the baseline biopsy (CD117 increase vs CD117 decrease). There was only a significant increase of mast cells count within the CD117 worsened ICC group (p=0.007). Conclusion No significant increase in the number of mast cells count seen in patients who received a GES may indicate an improvement in overall inflammation in patients with refractory gastroparesis after GES placement.

Effects of Gastric Neuromodulation on Crohn's Disease in Patients With Coexisting Symptoms of Gastroparesis.

INTRODUCTION: Crohn's Disease (CD) results from chronic inflammation of the gastrointestinal (GI) tract involving TNF-α release. Gastrointestinal electrical stimulation (GES), a form of neuromodulation used to treat upper GI motility symptoms (UGI Sx), exerts an anti-inflammatory effect via TNF-α suppression. We hypothesized patients with CD symptoms in patients with gastroparesis (GP) may respond to GES. METHODS: We retrospectively examined 284 patients with symptomatic gastroparesis (Gp Sx), who underwent GES placement. Patients with Gp Sx were evaluated by validated GI Sx patient reported outcome. Scores were obtained at baseline, after temporary GES placement and after permanent GES placement. Eleven patients from this cohort with coexisting CD were analyzed for improvements in their CD symptomatology using the Harvey Bradshaw Index (HBI). HBI scores were compared from before GES to after two sequential applications of electrical stimulation (temporary then permanent). A 3-point decrease in HBI indicated a clinical response and an HBI <5 indicated clinical remission after GES. An unadjusted repeated measures model was used in the analysis with statistical significance set at p ≤ 0.05. RESULTS: Our cohort prevalence of CD was 3.9% (2 M & 9 F, mean age 49.8 yrs.). Within both the Gp + CD & Gp subgroups, UGI Sx substantially improved after temporary and permanent GES. Furthermore, 55% of the GP + CD subgroup demonstrated a clinical response by HBI, while one patient achieved clinical remission (p < 0.01). CD medications were reviewed before and after GES placement, and any interval changes are unlikely to explain the improved HBI scores. DISCUSSION: We conclude that both UGI and CD symptoms in GP + CD patients responded well to GES. The interaction of Gp and CD and the effects of neuromodulation on CD symptoms warrant additional investigation.

Lung Cancer Screening Registry Reveals Low-dose CT Screening Remains Heavily Underutilized.

BACKGROUND: Since 2013, the United States Preventive Services Task Force has recommended annual screening for lung cancer in high-risk patients with low-dose computed tomography (LDCT). Current literature has provided estimates of the lung cancer screening rate and only prior to appropriate insurance coverage for LDCTs. The aim of this study was to use newly established registry data to assess the lung cancer screening rate across the United States. MATERIALS AND METHODS: Using data from the Lung Cancer Screening Registry provided by the American College of Radiology in 2016, we collected the total number of LDCT screens performed from all 1962 accredited radiographic screening sites. The 2015 National Health Interview Survey was used to estimate screening eligible smokers per United States Preventive Services Task Force criteria. These data were compared to calculate screening rate. RESULTS: In 2016, 2.0% of 7.6 million eligible smokers were screened. Rates varied by region from 1.1% in the West to 3.9% in the Northeast. The South consisted of 40.4% of eligible smokers and the most accredited screening sites (37%); however, their screening rate was among the lowest (1.7%) in the nation. Smoking cessation counseling was offered to 84% of screened current smokers prior to receiving LDCTs. CONCLUSIONS: Lung cancer screening remains heavily underutilized despite guideline recommendation since 2013, insurance coverage, and its potential to prevent thousands of lung cancer deaths annually.

NSCLC patient "migration" for treatment: A retrospective analysis of patient characteristics, travel patterns, and survival differences.

PURPOSE: Every year a significant population exists of those diagnosed with nonsmall cell lung cancer (NSCLC) who do not receive initial treatment upon diagnosis and then "migrate" to additional hospital before ultimately getting treatment. Migration to different hospitals may play a role in the decision to treat or not-to-treat, and we aimed to evaluate the potential factors that lead to treatment. METHODS: A retrospective review of 6212 patients with NSCLC from 29 Kentucky hospital registries from 2012 to 2014 was performed. Variables collected included hospital accreditation status, age at diagnosis, stage, overall survival (OS), and insurance status. Hospital records were matched to Kentucky Cancer Registry records to determine the number of hospitals visited for treatment. RESULTS: Most patients were treated at their initial hospital (73%). Of the remaining patients, 36% migrated to a different hospital where most received treatment (93%). Migrating to another hospital was associated with Stage I-III disease, younger age (66.4 vs 72.2 years), and longer OS (561 vs 157 days). Notably, migration was also associated with private insurance status and missing treatment modalities at the initial hospital. Treatment after migrating was associated with Stage I-II disease, younger age (65.8 vs 72.8 years), and longer OS (595 vs 153 days). After adjusting for confounders, treated migrating patients lived longer than initially treated patients (591 vs 505 days), especially among those with stage III (563 vs 495 days) and IV (379 vs 300 days) disease. CONCLUSION: This analysis demonstrates a survival benefit for initially untreated patients with advanced disease who migrate to another hospital for treatment. Migration was associated with having private insurance, thus making it noteworthy of the relationship between NSCLC survival benefit and insurance status.

Performance of community-based lung cancer screening program in a Histoplasma endemic region.

OBJECTIVES: Lung cancer screening with low dose computed-tomography (LDCT) is currently recommended for high-risk populations based on mortality benefit shown in the National Lung Screening Trial (NLST). This study evaluated performance of a community-based lung cancer screening program in a Histoplasma endemic region. MATERIALS AND METHODS: Demographic and clinical information was collected through retrospective review of patients in the Lung Cancer Screening program of a Kentucky (Histoplasma endemic region) health system from 2016 and 2017. A positive LDCT screen is defined as Lung-RADS version 1.0 assessment categories 3 or 4. Patients characteristics, initial screening results and follow up were analyzed and compared to NLST results. RESULTS: A total of 4500 LDCT screens were performed in 2016 (39%) and 2017 (61%) with 43% adherence rate to repeat annual screen in 2017. Mean age of patients was 64 years, with majority being females (54%) and current smokers (69%) with average 52-pack year smoking history. The rate of positive LDCT was 13.3% (600) varying based on baseline (14.6%) and annual (9.5%) screen. A total of 70 lung cancers were diagnosed among all positive LDCT screens (11.7%) with a false positive rate of 12%. CONCLUSIONS: Baseline positive screens in our study are similar to NLST data with Lung-RADS criteria implementation (14.6% vs 13.6%, p = 0.15) despite being a Histoplasma endemic region. Our study shows a successful performance of a community-based lung cancer screening program in a Histoplasma endemic region.

Timing of treatment in small-cell lung cancer.

Small-cell lung cancer (SCLC) is an aggressive disease with poor survival and rapid doubling time. Current practice is to treat SCLC as soon as possible but evidence on appropriate timing of treatment from diagnosis (TTD) is lacking. This is a retrospective analysis of SCLC patients from the 2012 to 2015 Kentucky Cancer Registry. Data collected included age at diagnosis, stage, gender, race, insurance and treatment. Factors and survival associated with TTD were identified with logistic regression analyses and Cox proportional hazards models. Among the 2992 SCLC patients, 2371 (79%) of SCLC patients were treated with one or more treatment modalities. Among treated patients, 93% received chemotherapy ± radiation with the mean TTD of 18 days. Most patients (80%) have TTD of ≤ 4 weeks with 33% treated within 1 week, 20% 1-2 weeks, and 27% 2-4 weeks from diagnosis. Delay in treatment (TTD > 4 weeks) was less in stage III and IV disease (odds ratio: 0.33 and 0.27 respectively, p < 0.01) but not significantly associated with age, race, gender, and insurance. One and two-year survival of patients with TTD ≤ 4 weeks was significantly worse when compared to > 4 weeks (hazard ratio = 1.43, 95% CI 1.2-1.6, p < 0.01; HR = 1.45, 95% CI 1.3-1.6, p < 0.01 respectively). These results show a trend toward better survival with late treatment of SCLC. Therefore, a general urgency to treat SCLC needs to be re-evaluated with consideration of patients needing more optimization before treatment. Further studies are needed to better clarify the appropriate timing of treatment from diagnosis in SCLC and who will benefit from early versus late treatment.

Gastroparesis syndromes: Response to electrical stimulation.

BACKGROUND AND AIMS: Factors underlying gastroparesis are not well defined, nor is the mechanism of action of gastric electrical stimulation (GES). We hypothesized that GES acts via several mechanisms related to underlying disordered pathophysiology. METHODS: We studied 43 consecutive eligible patients with gastroparetic symptoms, previously evaluated by two methods in each of five core areas: inflammatory, autonomic, enteric, electrophysiologic, and hormonal; and also categorized by GI symptoms, metabolic status, illness quantification, and gastric physiology. We then studied 41 patients who underwent temporary GES for 5-7 days. Thirty-six of those patients were implanted and 30 were followed up at 6 months after permanent GES. RESULTS: In previous but separately reported work, patients had similar GI symptoms regardless of baseline gastric emptying or diabetic/idiopathic status and all patients demonstrated abnormalities in each of the five areas studied. After GES, patients showed early and late effects of electrical stimulation with changes noted in multiple areas, categorized by improvement status. CONCLUSION: Patients with symptoms of gastroparesis have multiple abnormalities, including systemic inflammation and disordered hormonal status. GES affects many of these abnormalities. We conclude electrical stimulation improves symptoms and physiology with (a) an early and sustained anti-emetic effect; (b) an early and durable gastric prokinetic effect in delayed emptying patients; (c) an early anti-arrhythmic effect that continues over time; (d) a late autonomic effect; (e) a late hormonal effect; (f) an early anti-inflammatory effect that persists; and (g) an early and sustained improvement in health-related quality of life. This study is registered with Clinicaltrials.gov under study # NCT03178370 (https://clinicaltrials.gov/ct2/show/NCT03178370).

Implications of Statin Use on Vasopressor Therapy in the Setting of Septic Shock.

Background: Pleiotropic anti-inflammatory and immunomodulatory effects of statins have been associated with improved outcomes in the critically ill population. Objective: To evaluate the implications of prior statin use on the duration of vasopressor therapy in the setting of septic shock. Methods: This was a retrospective, multicenter study of adult patients who were diagnosed with septic shock. Patients were included if they were treated with any vasopressor for greater than 6 hours from the time of admission. The primary outcome was to compare the duration of vasopressor therapy in patients with septic shock with and without previous statin exposure. Results: A total of 88 statin-exposed cases and 205 unexposed controls were included in the analysis. Despite 92% of statin-exposed patients being reinitiated on therapy within 24 hours, the duration of vasopressors did not differ between groups (44 hours, statin group vs 53 hours, control group, P = .51). There were also no mortality differences between the statin group and the controls (40% vs 47%, P = .27). Conclusions: Long-term statin exposure does not impact the duration of vasopressor therapy in septic shock. The lack of differences in clinical outcomes supports the concept that sepsis involves pro- and anti-inflammatory pathways as well as other nonimmunologic pathways. Results lend further credence to the recent conceptualization of sepsis, with complications leading to organ dysfunction caused not primarily due to inflammatory responses but by a dysregulated response to infection.

Liver Disease in a Residential Cohort With Elevated Polychlorinated Biphenyl Exposures.

Endocrine and metabolism disrupting chemicals (EDCs/MDCs) have been associated with environmental liver diseases including toxicant-associated steatohepatitis (TASH). TASH has previously been characterized by hepatocellular necrosis, disrupted intermediary metabolism, and liver inflammation. Polychlorinated biphenyls (PCBs) are environmental EDCs/MDCs associated with the genesis and progression of steatohepatitis in animal models and human liver injury in epidemiology studies. The cross-sectional Anniston Community Health Survey (ACHS) investigates ortho-substituted PCB exposures and health effects near a former PCB manufacturing complex. The rates of obesity, diabetes, and dyslipidemia were previously determined to be high in ACHS. In this study, 738 ACHS participants were categorized by liver disease status using the serum cytokeratin 18 biomarker. Associations between PCB exposures and mechanistic biomarkers of intermediary metabolism, inflammation, and hepatocyte death were determined. The liver disease prevalence was high (60.2%), and 80.7% of these individuals were categorized as having TASH. Sex and race/ethnicity differences were noted. TASH was associated with increased exposures to specific PCB congeners, insulin resistance, dyslipidemia, proinflammatory cytokines, and liver necrosis. These findings are consistent with PCB-related steatohepatitis. ΣPCBs was inversely associated with insulin resistance/production, leptin, and hepatocyte apoptosis, while other adipocytokines were increased. This is possibly the largest environmental liver disease study applying mechanistic biomarkers ever performed and the most comprehensive analysis of PCBs and adipocytokines. It provides insight into the mechanisms of PCB-related endocrine and metabolic disruption in liver disease and diabetes. In the future, associations between additional exposures and liver disease biomarkers will be evaluated in the ACHS and follow-up ACHS-II studies.

Serotonin-Modulating Antidepressants and Risk of Bleeding after Trauma.

Serotonin-modulating antidepressants have been associated with increased risk of gastrointestinal bleeding and increased blood loss during elective surgery. This study sought to investigate the effect of preinjury selective-serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) use on transfusion requirements after trauma, and to evaluate whether resumption of SSRI/SNRI after trauma may worsen bleeding risk. This was a retrospective matched-cohort study evaluating patients with solid organ injury. Preinjury SSRI/SNRI users were matched to non-SSRI/SNRI users based on age, preinjury aspirin use, Injury Severity Score, and abdominal Abbreviated Injury Severity Score. The primary endpoint was transfusion requirement during hospitalization. The absolute need for transfusion was higher in SSRI/SNRI users throughout hospitalization (50.9% vs 37.3%, P = 0.02). After logistic multivariate analysis, SSRI/SNRI users were more likely to require transfusion at 24 hours (odds ratio (95% confidence interval): 2.73 (1.41, 5.29), P = 0.003), but this difference did not persist for overall hospitalization (odds ratio (95% confidence interval): 1.32 (0.74, 2.36), P = 0.35). Fewer patients restarted on SSRI/SNRI therapy within 72 hours required packed red blood cell transfusion compared with those who were restarted later or not at all (43.2% vs 60.3%; P = 0.04). Preinjury use of serotonin-modulating antidepressants led to an increased requirement of blood transfusions after solid organ injury. Although clinicians should weigh bleeding risk before reinitiation of SSRI/SNRI, the results of this study indicate that reasonable efforts to restart these medications after stabilization do not result in further risk for transfusion.

Surgical Wound Classification and Surgical Site Infections in the Orthopaedic Patient.

INTRODUCTION: The Centers for Disease Control and Prevention created a surgical wound classification system (SWC: I, clean; II, clean/contaminated; III, contaminated; and IV, dirty) to preemptively identify patients at risk of surgical site infection (SSI). The validity of this system is yet to be demonstrated in orthopaedic surgery. We hypothesize a poor association between the SWC and the rate of subsequent SSI in orthopaedic trauma cases. METHODS: Nine hundred fifty-six orthopaedic cases were reviewed. Wounds were risk stratified intraoperatively using the SWC grades (I-IV). SSI was diagnosed clinically or with objective markers. The SWC was compared with SSI rates using a Fisher exact test. Significance was set at P < 0.05. RESULTS: Four hundred patients met the selection criteria. The rate of infection was not significantly different across the SWC grades (P = 0.270). There was a significantly higher risk of SSI among patients with diabetes (P = 0.028). CONCLUSIONS: The Centers for Disease Control and Prevention SWC showed poor utility in predicting and risk stratifying postoperative SSIs in orthopaedic surgical cases.