Usefulness of the Mortality in Severe Sepsis in the Emergency Department score in an urban tertiary care hospital.

BACKGROUND: The Mortality in Severe Sepsis in the Emergency Department (MISSED) score is a newly proposed scoring system. The goal of this study is to determine if the MISSED score is generalizable to an urban tertiary care hospital. METHODS: This is a retrospective chart review conducted from July 2012 to June 2014. Inclusion criteria consisted of adult emergency department (ED) patients with severe sepsis, defined as lactate level 4mmol/L or greater. Demographics, lactate, international normalized ratio (INR), albumin, intensive care unit admission, and ED intubation were analyzed using χ(2) test, t test, and logistic regression. The MISSED score was calculated using the variables albumin 27g/L or less, INR 1.3 or greater, and age 65years or older and analyzed using the area under the curve. The primary outcome was inhospital mortality. RESULTS: A total of 182 patients met inclusion criteria, and mortality was 32%. Patients in the mortality group had older age (58.1±17.2 vs 62.7±14.7; P=.07), higher lactate (5.9±2.7 vs 7.3±3.1; P<.01), lower albumin (34.3±8.3 vs 25.6±7.1; P<.0001), higher INR (1.4±0.6 vs 2.4±1.9; P<.0001), ED intubation (21% vs 56%; P<.0001), and intensive care unit admission (41% vs 78%; P<.0001). The regression model found that albumin of 27g/L or less (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.05-3.36), INR 1.3 or greater (OR, 8.3; 95% CI, 3.35-20.51), and ED intubation (OR, 5.6; 95% CI, 2.56-12.35) predicted mortality. The area under the curve for the MISSED score was 0.78 (95% CI, 0.73-0.85). CONCLUSION: The MISSED score is useful for predicting mortality in ED patients with severe sepsis.

Pterostilbene induces mitochondrially derived apoptosis in breast cancer cells in vitro.

BACKGROUND: The ability of a breast cancer cell to evade apoptosis has a key role in tumor progression and sensitivity to treatment. High levels of Bcl-2-associated X protein (Bax) in tumor cells have been found to promote apoptosis and sensitize cells to anti-cancer therapies. Bcl-2-associated X protein redistribution to the mitochondrial membrane results in the release of proapoptotic factors including cytochrome C, second-mitochondrial-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low PI (Smac/DIABLO), and Ca(2+). We aimed to explore this pathway in cancerous breast cell lines treated with the naturally occurring antioxidant 3,5-dimethoxy-4-hydroxystilbene (pterostilbene). METHODS: We used whole cell lysates +/- Bax SiRNA from the cell lines MCF-7 and MDA-MB-231 in an enzyme-linked immunosorbent assay to quantify Bax, cytochrome C, Smac/DIABLO expression, and manganese superoxide dismutase (MnSOD) activity after treatment with pterostilbene. We quantified cell death using histone-related DNA complexes from cytosolic and mitochondrial fractions and used methylthiazol tetrazolium assay to analyze cell proliferation, in the presence of Bax-silencing or scrambled RNA. We measured changes in cytosolic calcium using the ratiometric calcium-sensitive dye fura-2-AM using an inverted ratiometric monochromator microscope. RESULTS: Treatment of MCF-7 and MDA-MB-231 (MDA) cells with pterostilbene caused concentration-dependent increases in intracellular Bax at all doses tested. RNA silencing of Bax resulted in reduced rates of apoptosis in both cells types and increased cell survival when treated with pterostilbene. We observed an increase in cytochrome C in MDA cells after treatment with pterostilbene. The MCF-7 cells showed a net increase in cytosolic cytochrome C, with a corresponding reduction in mitochondrial cytochrome C after treatment with 50 and 75 µmol/L pterostilbene. We observed this again in Smac/DIABLO expression in both cell types. In MCF-7 cells, pterostilbene treatment caused an increase in cytosolic but a decrease in mitochondrial Smac/DIABLO protein concentrations. Pterostilbene significantly increase MnSOD activity in MDA-MB-231 cells. Finally, pterostilbene resulted in significant increases in cytosolic calcium concentrations. CONCLUSIONS: The natural dietary compound pterostilbene has an anti-proliferative effect and induces apoptosis in breast cancer cells in vitro via Bax activation and overexpression, resulting in increased MnSOD, Smac/DIABLO, and cytochrome C activity and cytosolic Ca(2+) overload.

Pterostilbene and cancer: current review.

Pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene) is an antioxidant that is primarily found in blueberries. Studies suggest that pterostilbene exhibits the hallmark characteristics of an effective anticancer agent based on its antineoplastic properties in several common malignancies. In vitro models have shown that pterostilbene inhibits cancer growth through alteration of the cell cycle, induction of apoptosis, and inhibition of metastasis. In vivo, pterostilbene inhibits tumorigenesis and metastasis with negligible toxicity. Pterostilbene has also been shown to be effective as an inducer of antioxidant capacity in multiple cancer cell lines that may facilitate its function as an anticarcinogenic compound. Additionally, preliminary studies show that pterostilbene exhibits much greater bioavailability compared with other stilbene compounds; however the exact pharmacologic mechanism of pterostilbene and its effects in humans are still under investigation. In this review, we present a comprehensive summary of the antineoplastic mechanisms of pterostilbene based on the results of preclinical studies and highlight recent advances in the study of this dietary compound.

Pterostilbene ameliorates tumor necrosis factor alpha-induced pancreatitis in vitro.

BACKGROUND: We have previously demonstrated that pterostilbene, a compound in blueberries, exerts antiproliferative effects against pancreatic adenocarcinoma. However, little is known about the anti-inflammatory effects of pterostilbene in pancreatitis. Therefore, the aim of this study was to evaluate the effect of pterostilbene on inflammatory markers in an in vitro pancreatitis model. We hypothesized that pterostilbene would ameliorate the immediate inflammatory response in tumor necrosis factor alpha (TNF-α)-induced pancreatitis through downregulation of signal transducer and activator of transcription 3 (STAT3) and inhibition of TNF-α-induced secretion of lipase and proinflammatory cytokines interleukins (ILs) 1ß and 6. METHODS: AR42J acinar cells were pretreated with TNF-α to induce pancreatitis followed by 25 and 50 µM pterostilbene for 15 and 30 min. Secretion of lipase was quantified using a lipase assay and used as a marker of TNF-α-induced pancreatitis. Detection of STAT3, IL-1ß, and IL-6 was performed using enzyme-linked immunosorbent assay. Analysis of variance and Tukey post hoc analysis were used for statistical analysis. RESULTS: TNF-α increased the secretion of lipase, IL-1ß, and IL-6. Pterostilbene treatment inhibited TNF-α-induced secretion of lipase (P<0.01 and P<0.001), IL-1ß (P<0.05), and IL-6 (P<0.05 and P<0.01). Inhibition of STAT3 by pterostilbene occurred with treatment doses of 25 and 50 µM (P<0.001 and P<0.01). CONCLUSIONS: The dietary compound pterostilbene exerts an anti-inflammatory effect in pancreatitis through downregulation of STAT3 and decreased the secretion of lipase, IL-1ß, and IL-6. Pterostilbene's amelioration of pancreatitis in vitro makes it an advantageous anti-inflammatory agent. Further studies are necessary to determine pterostilbene's role as a protective or therapeutic agent in pancreatitis.

Traumatic Injuries in Sexual Assault Patients in the Emergency Department.

INTRODUCTION: The emergency department (ED) is at the forefront for treatment of sexual assault patients. Many require treatment for injuries sustained during the assault, ranging from mild to severe. Our objective in this study was to characterize types of injuries associated with sexual assault and identify associated factors. METHODS: We reviewed ED charts from an inner-city trauma center and nearby community hospital from 2019-2020 for patients age ≥13 years with a chief complaint of sexual assault. We used descriptive statistics, chi square, and logistic regression to characterize demographics and identify factors associated with trauma. RESULTS: A total of 157 patients met inclusion criteria. The mean age was 27.9 years old (range 13-79 years) and 92.4% were female. Adult patients (age >18 years) comprised 77.5% of assaults vs adolescents (age 13-18 years) at 22.3%. Most patients presented to the trauma center compared to the community hospital (69.4% vs 30.6%). The assailants were reported as 61.2% acquaintance, 22.9% stranger, and 15.9% intimate partner. A forensic rape kit was performed in 92 (58.6%) cases. The patient was intoxicated with alcohol in 39 (24.8%) cases, and 22 (14%) patients reported drug-facilitated assault where an unknown substance was given to them. Alcohol (P = 0.95) and drug-facilitated assault (P = 0.64) did not change the occurrence of injuries. Fifty-seven (36.3%) patients exhibited physical trauma on presentation. Forty-five (28.6%) patients had minor injuries of abrasions, lacerations, or contusions. Major trauma was defined as fracture, brain injury, hemorrhage, strangulation, or injury requiring surgical consultation. There were 12 patients with major trauma consisting of fracture injury or nonfatal strangulation. None of the patients required admission. Sexual assault by an intimate partner (odds ratio [OR] 2.6; 95% CI: 1.1-6.5) and being an adult patient compared to adolescent (OR 3.0; 95% CI, 1.1-7.7) was significantly associated with physical trauma. Sexual assault by an intimate partner was also associated with nonfatal strangulation (OR 4.0; 95% CI, 1.1-15.4). CONCLUSION: Physical injuries that resulted from sexual assault were mostly minor and occurred in 36% of rape victims. Intimate partner violence was found to be associated with physical trauma as well as nonfatal strangulation. Overall, this study helps us to understand key factors associated with sexual violence.

Mesenteric fibromatosis mimicking a gastrointestinal stromal tumor.

Mesenteric fibromatosis is a locally aggressive tumor of the mesentery with a high propensity for bowel involvement. Mesenteric fibromatosis often mimics gastrointestinal stromal tumors in size, location and immunohistochemical features. We report the case of a 30-year-old male who underwent resection of a mesenteric tumor, initially diagnosed as gastrointestinal stromal tumor. The tumor was categorized as high-risk and the patient was treated with chemotherapy. Two years later the patient was found to have a mass in the mesentery and restarted on chemotherapy. The tumor did not respond to medical management. The patient underwent a second en bloc resection and pathology results were conclusive for mesenteric fibromatosis. This case highlights the significance of accurately differentiating mesenteric fibromatosis from gastrointestinal stromal tumor. Making a concrete diagnosis is often difficult because both gastrointestinal stromal tumors and mesenteric fibromatosis share a number of morphological and immunohistochemical features including CKIT expression.

Sexually Transmitted Infections.

The diagnosis and treatment of sexually transmitted infections is a crucial component of providing evidence-based care in the emergency department. Understanding how to make the diagnosis and implement effective treatment is essential to maintaining and improving public health. Providers should also be adept at giving care to sexual assault survivors and seeking out the expertise of specially trained professionals within networks known as SANE, SAFE, or SART. These networks are critical to providing standardized care to sexual assault patients. Prophylaxis remains a key element for the prevention of sexually transmitted infections in all patients who are considered high risk.

Text messaging versus email for emergency medicine residents' knowledge retention: a pilot comparison in the United States.

We evaluated the effectiveness of text messaging versus email, as a delivery method to enhance knowledge retention of emergency medicine (EM) content in EM residents. We performed a multi-centered, prospective, randomized study consisting of postgraduate year (PGY) 1 to PGY 3 & 4 residents in three United States EM residency programs in 2014. Fifty eight residents were randomized into one delivery group: text message or email. Participants completed a 40 question pre- and post-intervention exam. Primary outcomes were the means of pre- and post-intervention exam score differences. Data were analyzed using descriptive statistics, paired t-test, and multiple linear regressions. No significant difference was found between the primary outcomes of the two groups (P=0.51). PGY 2 status had a significant negative effect (P=0.01) on predicted exam score difference. Neither delivery method enhanced resident knowledge retention. Further research on implementation of mobile technology in residency education is required.

A review of pterostilbene antioxidant activity and disease modification.

Pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene) is a natural dietary compound and the primary antioxidant component of blueberries. It has increased bioavailability in comparison to other stilbene compounds, which may enhance its dietary benefit and possibly contribute to a valuable clinical effect. Multiple studies have demonstrated the antioxidant activity of pterostilbene in both in vitro and in vivo models illustrating both preventative and therapeutic benefits. The antioxidant activity of pterostilbene has been implicated in anticarcinogenesis, modulation of neurological disease, anti-inflammation, attenuation of vascular disease, and amelioration of diabetes. In this review, we explore the antioxidant properties of pterostilbene and its relationship to common disease pathways and give a summary of the clinical potential of pterostilbene in the prevention and treatment of various medical conditions.

Genomic analysis of pterostilbene predicts its antiproliferative effects against pancreatic cancer in vitro and in vivo.

BACKGROUND: To investigate the inhibitory role of pterostilbene in pancreatic cancer, we conducted a genomic analysis of pterostilbene-treated pancreatic cancer cells. We also investigated the effect of pterostilbene upon the carcinogenic markers, manganese superoxide dismutase, cytochrome C, Smac/DIABLO, and STAT3 phosphorylation in vitro. The antiproliferative effects of pterostilbene were further evaluated in an in vivo model. METHODS: Pancreatic cancer cells were treated with pterostilbene and evaluated with DNA microarray analysis. Pterostilbene-treated cells were analyzed for cytochrome C, Smac/DIABLO, manganese superoxide dismutase (MnSOD)/antioxidant activity, and STAT3 phosphorylation using ELISA. Data were statistically analyzed using ANOVA. Pterostilbene was then administered to nude mice for 8 weeks, and tumor growth rates were recorded and statistically analyzed. RESULTS: Microarray analysis of pterostilbene-treated cells revealed upregulation of pro-apoptosis genes. In vitro, pterostilbene treatment altered levels of phosphorylated STAT3, MnSOD/antioxidant activity, cytochrome C, and Smac/DIABLO. In nude mice, oral pterostilbene inhibited tumor growth rates. CONCLUSION: Pterostilbene alters gene expression in pancreatic cancer and increases the antiproliferative markers cytochrome C, Smac/DIABLO, and MnSOD/antioxidant activity. It was also shown to inhibit phosphorylated STAT3, a marker of accelerated tumorigenesis, and decrease pancreatic tumor growth in vivo. Further studies are warranted to elucidate the effects of pterostilbene in humans.

The antiproliferative effects of pterostilbene on breast cancer in vitro are via inhibition of constitutive and leptin-induced Janus kinase/signal transducer and activator of transcription activation.

BACKGROUND: The hormone leptin is implicated in breast carcinogenesis in obese women. One mechanism is through its activation of Janus kinase/signal transducer and activator of transcription (JAK/STAT3) and apoptosis dysregulation. We have shown that the antioxidant pterostilbene inhibits proliferation and induces apoptosis in breast cancer. Therefore, the goal of this study was to evaluate the effect of pterostilbene on cell proliferation and JAK/STAT3 signaling in leptin-stimulated breast cancer. METHODS: Breast cancer cells were treated with leptin alone or in combination with pterostilbene. Detection of cell proliferation and JAK/STAT3 signaling were performed using enzyme-linked immunosorbent assay protocols. Statistical analysis was performed with analysis of variance and Tukey post hoc analysis. RESULTS: Pterostilbene suppresses constitutive as well as leptin-induced JAK/STAT3 activation. Pterostilbene treatment also inhibited leptin-induced cell proliferation. CONCLUSIONS: Pterostilbene has an inhibitory effect on leptin-stimulated breast cancer in vitro through reduction of cell proliferation and JAK/STAT3 signaling, a critical regulatory component of tumorigenesis in obesity-related breast cancer.

Micro-laparoscopic cholecystectomy: an alternative to single-port surgery.

INTRODUCTION: Recent advances in minimally invasive surgery aimed at diminishing incision size have led to the development of single-port surgery (SPS). SPS has an increased level of complexity and requires a higher level of surgical skill compared to traditional laparoscopy. We explored micro-laparoscopy as an alternative to routine laparoscopic cholecystectomy. METHODS: The study is a retrospective review of consecutive elective laparoscopic cholecystectomies performed by a single surgeon at a community teaching hospital over 24 months. All surgeries were performed using a 5-mm trocar for the umbilical port and 3-mm trocars for other ports in standard configuration. RESULTS: Seventy-nine cholecystectomies were performed by micro-laparoscopy during the 24-month period. Three cases required upgrade in trocar size for technical reasons, resulting in a completion rate of 96%. Intraoperative cholangiography was performed in 70 cases (89%). There were no conversions to open surgery. There were no intra- or postoperative complications, and all patients were discharged on the day of surgery. CONCLUSION: Micro-laparoscopic cholecystectomy is safe, feasible, and represents an alternative to other minimally invasive techniques. Future developments in surgical technology will allow the use of even smaller instruments, diminishing the surgical "footprint" even further and contributing to better cosmesis and decreased postoperative pain in cholecystectomy patients.