Faculty Bibliography

Dectin-1 is a C-type lectin receptor critical in anti-fungal immunity, but Dectin-1 has not been linked to regulation of sterile inflammation or oncogenesis. We found that Dectin-1 expression is upregulated in hepatic fibrosis and liver cancer. However, Dectin-1 deletion exacerbates liver fibro-inflammatory disease and accelerates hepatocarcinogenesis. Mechanistically, we found that Dectin-1 protects against chronic liver disease by suppressing TLR4 signaling in hepatic inflammatory and stellate cells. Accordingly, Dectin-1(-/-) mice exhibited augmented cytokine production and reduced survival in lipopolysaccharide (LPS)-mediated sepsis, whereas Dectin-1 activation was protective. We showed that Dectin-1 inhibits TLR4 signaling by mitigating TLR4 and CD14 expression, which are regulated by Dectin-1-dependent macrophage colony stimulating factor (M-CSF) expression. Our study suggests that Dectin-1 is an attractive target for experimental therapeutics in hepatic fibrosis and neoplastic transformation. More broadly, our work deciphers critical cross-talk between pattern recognition receptors and implicates a role for Dectin-1 in suppression of sterile inflammation, inflammation-induced oncogenesis, and LPS-mediated sepsis.

BACKGROUND: New York City (NYC) has made significant roadway infrastructure improvements, initiated a bicycle share program, and enacted Vision Zero, an action plan to reduce traffic deaths and serious injuries. The objective of this study was to examine whether bicycle helmets offer a protective advantage against traumatic brain injury (TBI) within a contemporary dense urban setting with a commitment to road safety. METHODS: A prospective observational study of injured bicyclists presenting to a Level I trauma centre was performed. All bicyclists arriving within 24h of injury were included. Data were collected between February, 2012 and August, 2014 and included demographics, imaging studies (e.g. computed tomography (CT)), injury patterns, and outcomes including Glasgow Coma Scale (GCS) and Injury Severity Score. RESULTS: Of 699 patients, 273 (39.1%) were wearing helmets at the time of injury. Helmeted bicyclists were more likely to have a GCS of 15 (96.3% [95% Confidence Interval (CI), 93.3-98.2] vs. 87.6 [95% CI, 84.1-90.6]) at presentation. Helmeted bicyclists underwent fewer head CTs (40.3% [95% CI, 34.4-46.4] vs. 52.8% [95% CI, 48.0-57.6]) and were less likely to sustain intracranial injury (6.3% [95% CI, 2.6-12.5] vs. 19.7% [14.7-25.6]), including skull fracture (0.9% [95% CI, 0.0-4.9] vs. 15.3% [95% CI, 10.8-20.7]) and subdural hematoma (0.0% [95% CI, 0.0-3.2] vs. 8.1% [95% CI, 4.9-12.5]). Helmeted bicyclists were significantly less likely to sustain significant TBI, i.e. Head AIS >/=3 (2.6% [95% CI: 0.7-4.5] vs.10.6% [7.6-12.5]). Four patients underwent craniotomy while three died; all were un-helmeted. A multivariable logistic regression model showed that helmeted bicyclists were 72% less likely to sustain TBI compared with un-helmeted bicyclists (Adjusted Odds Ratio 0.28, 95% CI 0.12-0.61). CONCLUSIONS: Despite substantial road safety measures in NYC, the protective impact of simple bicycle helmets in the event of a crash remains significant. A re-assessment of helmet laws for urban bicyclists is advisable to most effectively translate Vision Zero from a political action plan to public safety reality.

Introduction: To provide longer-term follow-up of a previously published pilot randomized trial comparing bariatric surgery vs. intensive medical weight management (MWM) in patients with type 2 diabetes (T2DM) and BMI 30-35. Additionally, to assess whether the soluble form of RAGE (receptor for advanced glycation end-products) is an adequate diabetes biomarker that may help determine which patient population would benefit most from surgery. Methods: Originally, 57 patients with T2DM and BMI 30-35 were randomized to surgery (bypass, sleeve or band, based on patient preference; n=29) vs. MWM (n=28). The 6 month results showed that surgery was significantly effective (previously published data). We performed an updated review of this patient cohort to evaluate weight loss and diabetes remission at 2 years. A repeated measures linear model was created to compare the change in HbA1C and BMI between the two groups. The outcomes were also compared to baseline sRAGE status using a repeated measures linear model. Patients who ultimately crossed over from MWM to surgery group (after the initial study) were included. Results: At baseline, mean BMI was 32.6 and mean HbA1c was 7.8. At 2 years the following was noted: The surgery group continued to have significantly higher diabetes remission (50% vs. 0%), lower BMI (28.5 vs. 30.9; p<0.0001) and lower HbA1c (7.0 vs. 7.9; p=0.019) than the MWM group. In the surgical group, those with a higher baseline sRAGE had a lower post-op BMI (p=0.037). Conclusion: At 2 years, bariatric surgery was very effective in patients with T2DM and BMI 30-35. Higher baseline sRAGE predicted success with surgery. However, larger studies will be required to confirm the accuracy of these observations

Introduction: Laparoscopic sleeve gastrectomy (LSG) is currently the most common bariatric surgical procedure in the US. It is considered technically simpler to perform than the gastric bypass and is more effective than the gastric band. It is an ideal procedure to implement in an urban safety-net hospital with limited resources. There is also debate regarding "Center of Excellence (COE)" accreditation and potential decreased access to bariatric surgery for under-represented minorities. Methods: A retrospective chart review of the first 1000 LSG at our institution was performed. Our institution is a public hospital that primarily serves under-represented minorities. Patient demographics and surgical outcomes were collected. A repeated measures model was used to create a % excess weight loss (%EWL) model. Outcomes were also compared before vs. after COE accreditation. Results: The cohort was predominantly Hispanic and non-Hispanic African American (96%). The vast majority (>75%) were insured publicly or were uninsured (15%). Mean age and BMI were 39 years and 45 kg/m2, respectively. There was an eleven-fold increase in surgical volume after COE accreditation. 1 year %EWL was 64%. 30-day readmission and reoperation was 1.5% and 0.4%, respectively. Leak rate was 1.2%. There were no mortalities. Conclusions: The COE model facilitated safe expansion of LSG at an urban safety-net institution

Objectives: Over the last decade there has been a sharp increase in the use of laparoscopic sleeve gastrectomy (LSG) relative to Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric band (LAGB). We sought to further examine national trends in bariatric surgery and determine whether the changes in bariatric procedure use over time, particularly the growth in LSG, were uniformly represented among clinical subgroups in the US. Methods: Patients with a body mass index (BMI) >35kg/m² who underwent bariatric surgery from 2005-2012 in the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database were identified. Procedure use, year of surgery, and patient population were evaluated. Logistic regression was used to analyze yearly trends in LSG versus RYGB use among clinically relevant subgroups. Results: We identified 100,304 patients who underwent bariatric procedures between 2005 and 2012 in the NSQIP database. Laparoscopic RYGB was the most common bariatric surgery type performed each year, but had a decreasing trend (75% of cases in 2005 vs. 53.2% in 2012) [Figure 1]. From 2010 to 2012, LSG increased substantially from 9.5% to 34.4% of bariatric procedures performed per year, while LAGB decreased from 28.8% to 9.7%. Over this period, minority patients represented an increasing proportion of those who underwent LSG compared to Caucasian patients. The proportion of LSG patients who were elderly (>65 years), superobese (BMI >50kg/m²), diabetic, high-risk, and ASA class 4-5 also rose, but to a significantly lesser degree than patients <65 years, BMI <50kg/m², non-diabetics, low-risk patients, and ASA class 1-3, respectively [Table 1]. In multiple logistic regression, factors independently associated with having LSG over RYGB in 2012 were age <65 (OR=1.58, 95% CI=[1.32-1.89], p<0.0001]), minority race (OR=1.30, 95% CI=[1.21-1.40], p<0.0001]), non-diabetic (OR=1.51, 95% CI=[1.39-1.63], p<0.0001), low-risk (OR=1.38, 95% CI=[1.27-1.50], p<0.0001]), ASA class 1-3 (OR=1.25, 95% CI= [1.01-1.55], p<0.0037), and BMI <50kg/m2 (OR=1.25, 95% CI=[1.16-1.35], p<0.0001]). Conclusions: LSG use has grown substantially over the last decade, but to a greater extent among certain patient subgroups. Although LSG was developed as the first stage of a two-stage biliopancreatic diversion-duodenal switch for high-risk patients, LSG is being performed on patients who are younger with less risk, whereas RYGB is targeted to those with more severe cases of obesity, surgical risk, and diabetes. Further studies will be necessary to clarify whether this approach reflects surgical preference or has been influenced by patient preferences

BACKGROUND: The objective of this study was to characterize variations in packed red blood cell (PRBC) transfusion practices in critically ill patients and to identify which factors influence such practices. We hypothesized that significant variation in transfusion triggers exists among acute care surgeons. METHODS: A survey of PRBC transfusion practices was administered to the American Association for the Surgery of Trauma members. The scenarios examined hemoglobin thresholds for which participants would transfuse PRBCs. RESULTS: A hemoglobin threshold of less than or equal to 7 g/dL was adopted by 45% of respondents in gastrointestinal bleeding, 75% in penetrating trauma, 66% in sepsis, and 62% in blunt trauma. Acute care surgeons modified their transfusion trigger significantly in the majority of the modifications of these scenarios, often inappropriately so. CONCLUSIONS: This study documents continued evidence-practice gaps and wide variations in the PRBC transfusion practices of acute care surgeons. Numerous clinical factors altered such patterns despite a lack of supporting evidence (for or against).

Necroptosis is a recently described Caspase 8-independent method of cell death that denotes organized cellular necrosis. The roles of RIP1 and RIP3 in mediating hepatocyte death from acute liver injury are incompletely defined. Effects of necroptosis blockade were studied by separately targeting RIP1 and RIP3 in diverse murine models of acute liver injury. Blockade of necroptosis had disparate effects on disease outcome depending on the precise etiology of liver injury and component of the necrosome targeted. In ConA-induced autoimmune hepatitis, RIP3 deletion was protective, whereas RIP1 inhibition exacerbated disease, accelerated animal death, and was associated with increased hepatocyte apoptosis. Conversely, in acetaminophen-mediated liver injury, blockade of either RIP1 or RIP3 was protective and was associated with lower NLRP3 inflammasome activation. Our work highlights the fact that diverse modes of acute liver injury have differing requirements for RIP1 and RIP3; moreover, within a single injury model, RIP1 and RIP3 blockade can have diametrically opposite effects on tissue damage, suggesting that interference with distinct components of the necrosome must be considered separately.

PURPOSE: The aim of this study was to determine the diagnostic accuracy of positron emission tomography (PET) in cancer patients undergoing adrenalectomy for presumed metastatic disease, utilizing the gold standard of histopathology. METHODS: We retrospectively reviewed all adrenalectomies for metastatic disease performed at our institution over the last 12 years. Preoperative PET scans were compared with final pathology reports. Statistical analyses were performed with Fisher's exact test for categorical variables and Student's t test for continuous variables. RESULTS: Forty-nine adrenalectomies were performed for metastatic disease. Thirty had preoperative PET imaging and were included in this analysis. Mean age was 65.5 +/- 13.6 years (29-91) and 54 % were male. Mean size was 3.8 cm (0.4-7.1). Primary tumor distribution was 61 % (n = 17) pulmonary; 11 % (n = 3) breast; 7 % (n = 2) gastric; 7 % (n = 2) renal; and 4 % (n = 1) each of brain, lymphoma, melanoma, and uterine. Mean standardized uptake value (SUV) was 11 +/- 7.3 (3.2-30.0). Final pathology revealed that 80 % (25/30) were positive for metastatic disease and 20 % (5/30) were negative. The positive predictive value of PET in correctly identifying adrenal metastatic disease was 83 % (24 true-positive cases and 5 false-positive cases); there was one false-negative PET. False-positive PET results were not correlated with sex (p = 0.35), age (p = 0.24), or maximum SUV units (p = 0.26). CONCLUSIONS: The 20 % false-positive rate for PET-positive adrenalectomies performed for metastatic disease should warrant its inclusion in preoperative counseling to the patient and interaction with the treating oncologist.

Bellevue Hospital's prison ward cares for male prisoners requiring medical attention that exceeds the capabilities of New York City Department of Correction (NYC-DOC) infirmaries. This study evaluated the injury patterns that occur in this patient population. Data were collected on consecutive prisoners transferred from NYC-DOC for traumatic injuries from June 1, 2003, to June 1, 2006, and analyzed by retrospective chart review. Overall, 251 patients were evaluated for traumatic injuries. Injury mechanisms were violent (75.7%), nonviolent (23.5%), and self-inflicted (0.8%). Of the 241 (96%) patients admitted, 213 (84.9%) required operative intervention. The most common injuries were mandible fractures (46.5%) and facial fractures (14.9%).