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Human-environmental interaction studies typically focus on large-scale landscape modifications of vegetation or soils and rarely address smaller-scale human alterations to site settings. This approach is based on a broad concept of environment as “set” having spatially dispersed and regionally defined attributes, as opposed to something that is mutable at the scale of individual groups of humans living at a specific location. This paper examines how two prehistoric groups, the Final Neolithic to Early Bronze Age 2 occupants on the island of Kos, Greece and the Late Formative Period occupants in the Upper Basin, northern Arizona, selected and modified habitation locations involving exposed bedrock. Although chronologically separated by thousands of years and occupying different continents, these two groups share similarities in population size, socio-political complexity, and environmental challenges. In facing these challenges, both groups apply practical, but different, approaches that utilized one of the most prevalent globally available resources -- limestone bedrock.

The measurement of total and free cortisol has been studied as a clinical index of adrenal cortisol production in patients with liver cirrhosis. Correlations between free plasma and salivary cortisol have previously been reported in stable cirrhotic patients. Urinary free cortisol constitutes an index of adrenal cortisol production; however, it has never been used in assessing adrenal function in patients with liver cirrhosis.The aim of this observational study was to determine associations between urinary free cortisol, serum total, salivary, measured and calculated plasma free cortisol levels in cirrhotics, determining which of them can be used as an indirect index of free cortisol levels. Moreover, we investigated the potential use of 24 h urinary free cortisol as a prognostic factor for mortality.Seventy-eight outpatients with liver cirrhosis were included. Serum, salivary and urinary free cortisol were measured using the electrochemiluminenscence immunoassay. Plasma free cortisol determination was conducted using a single quadrupole mass spectrometer. The quantification of free cortisol was achieved by determining the signal response on negative ESI-MS mode.Twenty-four hour urinary free cortisol levels correlated with free cortisol determined by mass spectrometer, total cortisol and calculated free cortisol levels. Patients with low levels of urinary free cortisol presented a significantly higher mortality rate compared to those with high levels. The factors associated with death risk were determined by Cox regression. In the multivariate analysis, two models were applied; in the first model, CP score, PVT and urinary free cortisol were found to be significantly related to patients' survival, whereas in the second, MELD score, ascites and urinary free cortisol were independently related to survival.This study suggests that 24 h urinary free cortisol could be considered as a potential index of adrenal cortisol production in patients with liver cirrhosis and it potentially detects patients with a high mortality risk.

The Temple of Apollo Pythios, built in the Hellenistic era (3rd&ndash, 1st century BC), is located in the ancient Acropolis of Rhodes. It was excavated during the Italian occupation and reconstructed by the Italians in the period 1937&ndash, 8. The method of the &ldquo, scenographic&rdquo, restoration was the &ldquo, mixed structure&rdquo, technique using a core of reinforced concrete in combination with new biocalcarenite stones and the integration of very few ancient architectural members. Its proximity to the sea and the corresponding salt decay phenomena, aggravated by the erroneous reconstruction methodology and materials, have further deteriorated its state of preservation. Today, the four columns, epistyle and entablature of the Italian interventions demand immediate restoration actions to ensure the monument&rsquo, s sustainability. This can only be achieved through a combined study of the performance of potential restoration materials and assessment of their compatibility with the historical materials. In the present study, the characteristics of the Temple&rsquo, s historical porous stones are presented along with the characteristics of five quarry stones, aiming to evaluate which quarry stone is the most appropriate for use in the upcoming restoration. Restoration mortars are designed and evaluated in respect to both the historical materials and the quarry stones, aiming to select the optimum restoration mortar, which can achieve the required level of performance and compatibility and ensure sustainability of the structure as a whole.

An enterocutaneous (EC) fistula is defined as an abnormal connection between the gastrointestinal (GI) tract and the skin. The majority of EC fistulas are iatrogenic due to a missed enterotomy or anastomotic leak, and are generally defined based on their etiology, location and daily output. Patients may present either with drainage of enteric contents from the surgical site/abdominal wall or with abdominal pain, ileus, fevers, malaise, and computer tomography (CT) findings consistent with an intraabdominal abscess. Regardless of etiology, initial management requires a multidisciplinary approach consisting of fluid resuscitation, characterization of EC fistula and intraabdominal collections with cross-sectional imaging, control of sepsis, nutritional support, and local wound care. Spontaneous closure occurs in about one third of patients in the first 4–6 weeks after formation. Risks factors for nonspontaneous closure include high fistula outputs, distal obstruction, ongoing infection, inflammatory bowel disease, epithelialized or short (

Crohn’s colitis affects about 15% of Crohn’s patients and is confined to any segment of the colon between the cecum and rectum. It presents with a bimodal age distribution, the first and most common between ages 15 and 30 and second between 55 and 80 years. Clinical manifestations include abdominal pain, diarrhea, weight loss, and fevers. Macroscopic features include a thickened colon wall, aphthous ulcers, cobblestone appearance of the mucosa, mesenteric fat creeping, and presence of strictures and fistulae. Microscopically they present with focal full-thickness inflammation, mucosal ulceration, and lymphocytic proliferation that can lead to granulomas. Diagnosis is established with a combination of endoscopic and radiologic findings as well as laboratory markers. Medical management consists of antibiotics, sulfa drugs, steroids, immunomodulators, or biologic therapy. Surgery is not curative and therefore should only be considered in patients who fail medical management and develop complications such as stricture, perforation or symptomatic fistulizing disease, and dysplasia or malignancy.

Phytochemical analysis of the aerial parts of Stachys candida Bory & Chaubard, growing wild in Greece led to the isolation of eleven bioactive secondary metabolites. Nine flavones, one of them methylated, one phenylethanoid glycoside and one phenolic acid were isolated from the methanol extract of this plant. The structure elucidation of the isolated compounds was achieved on the basis of NMR spectroscopy (1D and 2D spectra). The phytochemical profile was appeared to be similar with other Greek endemic Stachys species, while a strong difference was the absence of iridoids. Importantly, the chemotaxonomic significance of the isolated compounds has extensively been described.

Modified purine derivatives exemplified by pyrazolopyrimidines have emerged as highly selective inhibitors of several angiogenic receptor tyrosine kinases. Herein, we designed and synthesized a new series of substituted pyrazolopyridines and explored their ability to influence crucial pro-angiogenic attributes of endothelial cells. Four of the synthesized compounds, possessing analogous substitution pattern, were found able to inhibit at low micromolar concentrations endothelial cell proliferation, migration and differentiation, constitutively or in response to Vascular Endothelial Growth Factor (VEGF) and to attenuate VEGF-induced phosphorylation of VEGF receptor-2 and downstream kinases AKT and ERK1/2. Administration of effective compounds in mice delayed the growth of syngeneic Lewis lung carcinoma transplants and reduced tumor microvessel density, without causing toxicity. Genome-wide microarray and gene ontology analyses of treated endothelial cells revealed derivative 18c as the most efficient modulator of gene expression and "mitotic cell cycle/cell division" along with "cholesterol biosynthesis" as the most significantly altered biological processes.

Background Percutaneous drainage is the standard treatment for perforated appendicitis with abscess. We studied factors associated with complete resolution (CR) with percutaneous drainage alone. Methods Ninety-eight patients underwent percutaneous drainage for acute appendicitis complicated by abscess (October 1990 to September 2010). CR was defined as clinical recovery, resolution of the abscess on imaging, and drain removal without recurrence. Patients achieving CR were compared with patients not achieving CR. Results The rate of CR was 78.6% (n = 77). Abscess grade was the only radiological factor associated with CR ( P = .007). The CR rate was higher with transgluteal drainage (90.9% vs 79.2%) than with other anatomic approaches ( P = .018) and higher with computed tomography-guided drainage than with ultrasound-guided drainage (82.7% vs 64.3%, P = .046). Conclusion CR was more likely to be achieved in patients with lower abscess grade, computed tomography-guided drainage, and a transgluteal approach.

Introduction Whole body CT (WBCT) scan is known to be associated with significant radiation risk especially in pediatric trauma patients. The aim of this study was to assess the use WBCT scan across trauma centers for the management of pediatric trauma patients. Methods We performed a two year (2011–2012) retrospective analysis of the National Trauma Data Bank. Pediatric (age ≤ 18 years) trauma patients managed in level I or II adult or pediatric trauma centers with a head, neck, thoracic, or abdominal CT scan were included. WBCT scan was defined as CT scan of the head, neck, thorax, and abdomen. Patients were stratified into two groups: patients managed in adult centers and patients managed in designated pediatric centers. Outcome measure was use of WBCT. Multivariate logistic regression analysis was performed. Results A total of 30,667 pediatric trauma patients were included of which; 38.3% (n = 11,748) were managed in designated pediatric centers. 26.1% (n = 8013) patients received a WBCT. The use of WBCT scan was significantly higher in adult trauma centers in comparison to pediatric centers (31.4% vs. 17.6%, p = 0.001). There was no difference in mortality rate between the two groups (2.2% vs. 2.1%, p = 0.37). After adjusting for all confounding factors, pediatric patients managed in adult centers were 1.8 times more likely to receive a WBCT compared to patients managed in pediatric centers (OR [95% CI]: 1.8 [1.3–2.1], p = 0.001). Conclusions Variability exists in the use of WBCT scan across trauma centers with no difference in patient outcomes. Pediatric patients managed in adult trauma centers were more likely to be managed with WBCT, increasing their risk for radiation without a difference in outcomes. Establishing guidelines for minimizing the use of WBCT across centers is warranted.

The risks deriving from the lack of compliance with universal safety precautions (USPs) are unequivocal. However, the adoption of these prophylactic precautions by healthcare providers remains unacceptably low. We hypothesized that trauma teams are not routinely adhering to USPs and that a brief educational intervention, followed by real-time peer feedback, would substantially improve compliance rates. This before-and-after interventional study took place in the resuscitation bay of a Level I Trauma Center during trauma team activations. Six USPs were examined: hand washing (before and after patient contact), use of gloves, gowns, eye protection, and masks. Surgery and Emergency Medicine attending physicians, residents, and nurses, who had direct patient contact, were included. Following 162 baseline observations, an educational intervention in the form of brief lectures was conducted, emphasizing the danger to self from dereliction of USPs. Subsequently, 167 post-intervention observations were made after a one-month period of knowledge decay. Finally, real-time feedback was provided by trauma team leaders and study staff. Adherence to prophylactic measures was recorded again. Baseline compliance rates were dismal. Only hand washing prior to patient interaction, the use of eye protection, and the use of masks improved significantly (p

Parastomal gallbladder herniation is a rare complication of enterostomies with only 6 previously reported cases. Most cases have occurred in elderly women. Patients typically presented with acute abdominal pain and the majority was managed operatively. Here, we report the clinical course of an 88-year-old female who presented with signs of sepsis and minimal abdominal symptoms. She was subsequently found to have a parastomal gallbladder herniation and Klebsiella pneumoniae bacteremia. Given the patient's multiple comorbidities, she was managed nonoperatively with manual reduction of the parastomal hernia and antibiotics.

For a disease process that affects so many, we continue to struggle to define optimal care for patients with diverticular disease. Part of this stems from the fact that diverticular disease requires different treatment strategies across the natural history- acute, chronic and recurrent. To understand where we are currently, it is worth understanding how treatment of diverticular disease has evolved. Diverticular disease was rarely described in the literature prior to the 1900’s. In the late 1960’s and early 1970’s, Painter and Burkitt popularized the theory that diverticulosis is a disease of Western civilization based on the observation that diverticulosis was rare in rural Africa but common in economically developed countries. Previous surgical guidelines focused on early operative intervention to avoid potential complicated episodes of recurrent complicated diverticulitis (e.g., with free perforation) that might necessitate emergent surgery and stoma formation. More recent data has challenged prior concerns about decreasing effectiveness of medical management with repeat episodes and the notion that the natural history of diverticulitis is progressive. It has also permitted more accurate grading of the severity of disease and permitted less invasive management options to attempt conversion of urgent operations into the elective setting, or even avoid an operation altogether. The role of diet in preventing diverticular disease has long been debated. A high fiber diet appears to decrease the likelihood of symptomatic diverticulitis. The myth of avoid eating nuts, corn, popcorn, and seeds to prevent episodes of diverticulitis has been debunked with modern data. Overall, the recommendations for “diverticulitis diets” mirror those made for overall healthy lifestyle – high fiber, with a focus on whole grains, fruits and vegetables. Diverticulosis is one of the most common incidental findings on colonoscopy and the eighth most common outpatient diagnosis in the United States. Over 50% of people over the age of 60 and over 60% of people over age 80 have colonic diverticula. Of those with diverticulosis, the lifetime risk of developing diverticulitis is estimated at 10–25%, although more recent studies estimate a 5% rate of progression to diverticulitis. Diverticulitis accounts for an estimated 371,000 emergency department visits and 200,000 inpatient admissions per year with annual cost of 2.1–2.6 billion dollars per year in the United States. The estimated total medical expenditure (inpatient and outpatient) for diverticulosis and diverticulitis in 2015 was over 5.4 billion dollars. The incidence of diverticulitis is increasing. Besides increasing age, other risk factors for diverticular disease include use of NSAIDS, aspirin, steroids, opioids, smoking and sedentary lifestyle. Diverticula most commonly occur along the mesenteric side of the antimesenteric taeniae resulting in parallel rows. These spots are thought to be relatively weak as this is the location where vasa recta penetrate the muscle to supply the mucosa. The exact mechanism that leads to diverticulitis from diverticulosis is not definitively known. The most common presenting complaint is of left lower quadrant abdominal pain with symptoms of systemic unwellness including fever and malaise, however the presentation may vary widely. The gold standard cross-sectional imaging is multi-detector CT. It is minimally invasive and has sensitivity between 98% and specificity up to 99% for diagnosing acute diverticulitis. Uncomplicated acute diverticulitis may be safely managed as an out-patient in carefully selected patients. Hospitalization is usually necessary for patients with immunosuppression, intolerance to oral intake, signs of severe sepsis, lack of social support and increased comorbidities. The role of antibiotics has been questioned in a number of randomized controlled trials and it is likely that we will see more patients with uncomplicated disease treated with observation in the future Acute diverticulitis can be further sub classified into complicated and uncomplicated presentations. Uncomplicated diverticulitis is characterized by inflammation limited to colonic wall and surrounding tissue. The management of uncomplicated diverticulitis is changing. Use of antibiotics has been questioned as it appears that antibiotic use can be avoided in select groups of patients. Surgical intervention appears to improve patient’s quality of life. The decision to proceed with surgery is recommended in an individualized manner. Complicated diverticulitis is defined as diverticulitis associated with localized or generalized perforation, localized or distant abscess, fistula, stricture or obstruction. Abscesses can be treated with percutaneous drainage if the abscess is large enough. The optimal long-term strategy for patients who undergo successful non-operative management of their diverticular abscess remains controversial. There are clearly patients who would do well with an elective colectomy and a subset who could avoid an operation all together however, the challenge is appropriate risk-stratification and patient selection. Management of patients with perforation depends greatly on the presence of feculent or purulent peritonitis, the extent of contamination and hemodynamic status and associated comorbidities. Fistulas and strictures are almost always treated with segmental colectomy. After an episode of acute diverticulitis, routine colonoscopy has been recommended by a number of societies to exclude the presence of colorectal cancer or presence of alternative diagnosis like ischemic colitis or inflammatory bowel disease for the clinical presentation. Endoscopic evaluation of the colon is normally delayed by about 6 weeks from the acute episode to reduce the risk associated with colonoscopy. Further study has questioned the need for endoscopic evaluation for every patient with acute diverticulitis. Colonoscopy should be routinely performed after complicated diverticulitis cases, when the clinical presentation is atypical or if there are any diagnostic ambiguity, or patient has other indications for colonoscopy like rectal bleeding or is above 50 years of age without recent colonoscopy. For patients in whom elective colectomy is indicated, it is imperative to identify a wide range of modifiable patient co-morbidities. Every attempt should be made to improve a patient’s chance of successful surgery. This includes optimization of patient risk factors as well as tailoring the surgical approach and perioperative management. A positive outcome depends greatly on thoughtful attention to what makes a complicated patient “complicated”. Operative management remains complex and depends on multiple factors including patient age, comorbidities, nutritional state, severity of disease, and surgeon preference and experience. Importantly, the status of surgery, elective versus urgent or emergent operation, is pivotal in decision-making, and treatment algorithms are divergent based on the acuteness of surgery. Resection of diseased bowel to healthy proximal colon and rectal margins remains a fundamental principle of treatment although the operative approach may vary. For acute diverticulitis, a number of surgical approaches exist, including loop colostomy, sigmoidectomy with colostomy (Hartmann’s procedure) and sigmoidectomy with primary colorectal anastomosis. Overall, data suggest that primary anastomosis is preferable to a Hartman’s procedure in select patients with acute diverticulitis. Patients with hemodynamic instability, immunocompromised state, feculent peritonitis, severely edematous or ischemic bowel, or significant malnutrition are poor candidates. The decision to divert after colorectal anastomosis is at the discretion of the operating surgeon. Patient factors including severity of disease, tissue quality, and comorbidities should be considered. Technical considerations for elective cases include appropriate bowel preparation, the use of a laparoscopic approach, the decision to perform a primary anastomosis, and the selected use of ureteral stents. Management of the patient with an end colostomy after a Hartmann’s procedure for acute diverticulitis can be a challenging clinical scenario. Between 20 – 50% of patients treated with sigmoid resection and an end colostomy after an initial severe bout of diverticulitis will never be reversed to their normal anatomy. The reasons for high rates of permanent colostomies are multifactorial. The debate on the best timing for a colostomy takedown continues. Six months is generally chosen as the safest time to proceed when adhesions may be at their softest allowing for a more favorable dissection. The surgical approach will be a personal decision by the operating surgeon based on his or her experience. Colostomy takedown operations are challenging surgeries. The surgeon should anticipate and appropriately plan for a long and difficult operation. The patient should undergo a full antibiotic bowel preparation. Preoperative planning is critical; review the initial operative note and defining the anatomy prior to reversal. When a complex abdominal wall closure is necessary, consider consultation with a hernia specialist. Open surgery is the preferred surgical approach for the majority of colostomy takedown operations. Finally, consider ureteral catheters, diverting loop ileostomy, and be prepared for all anastomotic options in advance. Since its inception in the late 90’s, laparoscopic lavage has been recognized as a novel treatment modality in the management of complicated diverticulitis; specifically, Hinchey III (purulent) diverticulitis. Over the last decade, it has been the subject of several randomized controlled trials, retrospective studies, systematic reviews as well as cost-efficiency analyses. Despite being the subject of much debate and controversy, there is a clear role for laparoscopic lavage in the management of acute diverticulitis with the caveat that patient selection is key. Segmental colitis associated with diverticulitis (SCAD) is an inflammatory condition affecting the colon in segments that are also affected by diverticulosis, namely, the sigmoid colon. While SCAD is considered a separate clinical entity, it is frequently confused with diverticulitis or inflammatory bowel disease (IBD). SCAD affects approximately 1.4% of the general population and 1.15 to 11.4% of those with diverticulosis and most commonly affects those in their 6th decade of life. The exact pathogenesis of SCAD is unknown, but proposed mechanisms include mucosal redundancy and prolapse occurring in diverticular segments, fecal stasis, and localized ischemia. Most case of SCAD resolve with a high-fiber diet and antibiotics, with salicylates reserved for more severe cases. Relapse is uncommon and immunosuppression with steroids is rarely needed. A relapsing clinical course may suggest a diagnosis of IBD and treatment as such should be initiated. Surgery is extremely uncommon and reserved for severe refractory disease. While sigmoid colon involvement is considered the most common site of colonic diverticulitis in Western countries, diverticular disease can be problematic in other areas of the colon. In Asian countries, right-sided diverticulitis outnumbers the left. This difference seems to be secondary to dietary and genetic factors. Differential diagnosis might be difficult because of similarity with appendicitis. However accurate imaging studies allow a precise preoperative diagnosis and management planning. Transverse colonic diverticulitis is very rare accounting for less than 1% of colonic diverticulitis with a perforation rate that has been estimated to be even more rare. Rectal diverticula are mostly asymptomatic and diagnosed incidentally in the majority of patients and rarely require treatment. Giant colonic diverticula (GCD) is a rare presentation of diverticular disease of the colon and it is defined as an air-filled cystic diverticulum larger than 4 cm in diameter. The pathogenesis of GCD is not well defined. Overall, the management of diverticular disease depends greatly on patient, disease and surgeon factors. Only by tailoring treatment to the patient in front of us can we achieve optimal outcomes.

Blunt diaphragmatic rupture (BDR) is uncommon with a reported incidence range of 1%–2%. The true incidence is not known. Bilateral BDR is particularly rare. We presented a case of bilateral BDR and we think that the incidence is under-recognised thanks to an easily missed and difficult to diagnose right sided injury. Keywords: Blunt, Diaphragm, Bilateral, Injury

Background Reducing healthcare costs while maintaining quality of care is one of the challenges of the current healthcare system. The purpose of this study was to compare the hospital charges accrued following laparoscopic (LA) and open (OA) appendectomies in the pediatric population. Methods We retrospectively reviewed all pediatric appendectomies (n = 264) performed from 2007 to 2013 at a single academic center. Subgroup analysis on charges and costs was performed on perforated and nonperforated LA and OA. Results A total of 195 (73.9%) appendectomies were performed laparoscopically. LA in both perforated and nonperforated groups was associated with higher surgical supply, operating room, and total hospital charges compared with OA. Surgical supply costs to the facility were higher by an average of $1,000 for both nonperforated and perforated appendicitis in the LA group. Length of stay and postoperative complications were comparable within all groups. Conclusions In this study, LA is associated with significantly higher surgical costs and charges than OA without improvement in outcomes. Investigation into cost reduction strategies of laparoscopy should be a component of future clinical appendicitis research.

Chronic inflammation is associated with the development of human hepatocellular carcinoma (HCC), an essentially incurable cancer. Anti-inflammatory nutraceuticals have emerged as promising candidates against HCC, yet the mechanisms through which they influence the cell signaling machinery to impose phenotypic changes remain unresolved. Herein we implemented a systems biology approach in HCC cells, based on the integration of cytokine release and phospoproteomic data from high-throughput xMAP Luminex assays to elucidate the action mode of prominent nutraceuticals in terms of topology alterations of HCC-specific signaling networks. An optimization algorithm based on SigNetTrainer, an Integer Linear Programming formulation, was applied to construct networks linking signal transduction to cytokine secretion by combining prior knowledge of protein connectivity with proteomic data. Our analysis identified the most probable target phosphoproteins of interrogated compounds and predicted translational control as a new mechanism underlying their anticytokine action. Induced alterations corroborated with inhibition of HCC-driven angiogenesis and metastasis.

Minimally invasive repair of pectus excavatum (MIRPE) is a well-established procedure. However, morbidity rate varies widely among institutions, and the incidence of major complications remains unknown.The American College of Surgeons 2012 National Surgical Quality Improvement Program-Pediatric (NSQIP-P) participant user file was utilized to identify patients who underwent MIRPE at 50 participant institutions. Outcomes of interest were overall 30-day morbidity, hospital readmission, and reoperation.Chest wall repair designated MIRPE accounted for 0.6% (n = 264) of all surgical cases included in the NSQIP-P database in 2012. The median age at surgical repair was 15.2 years. Thoracoscopy was used in 83.7% of cases. No mediastinal injuries or perioperative blood transfusions were identified. The 30-day readmission rate was 3.8%. Three patients (1.1%) required re-operation due to the following complications: superficial site infection, bar displacement and pneumothorax. The overall morbidity was 3.8% with no incidences of mortality.This analysis of a large prospective multicenter dataset demonstrates that major complications following MIRPE are uncommon in contemporary practice. Wound infection is the most common complication and the main cause of hospital readmission. Targeted quality improvement initiative should be focused on perioperative strategy to further reduce wound occurrences and hospital readmission.

To evaluate trends and factors associated with interfacility differences in imaging modality selection in the diagnosis and management of children with suspected acute appendicitis. We conducted a retrospective review of diagnostic imaging selection and outcomes in patients

Direct laryngoscopy (DL) has long been the gold standard for tracheal intubation in emergency and trauma patients. Video laryngoscopy (VL) is increasingly used in many settings and the purpose of this study was to compare its effectiveness to direct laryngoscopy in trauma patients. Our hypothesis was that the success rate of VL would be higher than that of DL. Data were collected prospectively on all trauma patients, from January 2008 to June 2011, who were intubated emergently in an academic level I trauma center. After intubation, the physician that performed the intubation completed a structured data collection form that included demographics, complications, and the presence of difficult airway predictors. Our primary outcome measure was overall successful tracheal intubation, which was defined as successful intubation with the first device used. During the study period, 709 trauma patients were intubated by either VL or DL. VL was performed in 55 % of cases. The overall success rate of VL was 88 % compared to 83 % with DL (P = 0.05). Cervical (C-Spine) immobilization was predictive of higher initial success with VL (87 %) than with DL (80 %) (P

Background For patients with acute pancreatitis complicated by infected necrosis, minimally invasive techniques have taken hold without substantial comparison with open surgery. We present a contemporary series of open necrosectomies as a benchmark for newer techniques. Methods Using a prospective database, we retrospectively identified consecutive patients undergoing debridement for necrotizing pancreatitis (2006 to 2009). The primary endpoint was in-hospital mortality. Results Sixty-eight patients underwent debridement for pancreatic/peripancreatic necrosis. In-hospital mortality was 8.8% ( n = 6). Infection ( n = 43, 63%) and failure-to-thrive ( n = 13, 19%) comprised the most common indications for necrosectomy. The false negative rate (FNR) for infection of percutaneous aspirate was 20.0%. Older age ( P = .02), Acute Physiology and Chronic Health Evaluation II score upon admission ( P = .03) or preoperatively ( P P = .01), and postoperative organ failure ( P = .03) were associated with mortality. Conclusions Open debridement for necrotizing pancreatitis results in a low mortality, providing a useful comparator for other interventions. Given the high FNR of percutaneous aspirate, debridement should not be predicated on proven infection.

There is an ongoing debate among pediatric surgeons regarding the need or lack thereof to centralize the surgical care of children to high-volume children's centers. Risk-adjusted comparisons of hospitals performing pediatric surgery are needed.Admissions from 2006 to 2010 from two national administrative databases were analyzed. Only nontrauma pediatric patients undergoing a noncardiac surgical procedure were included. Risk-adjustment was performed with a validated International Classification of Diseases, 9th Revision code-based tool. Hospitals were grouped into metropolitan regions using the first three digits of their zip code. Poorly performing outlier hospitals were defined by an odds ratio1 and P value.05 for mortality compared with the center with the greatest pediatric operative volume in that same region.Information was obtained from 415,546 pediatric surgical admissions, and 173 hospitals in 55 regions were compared. A total of 18 poor performing hospitals (adjusted odds ratio, range 1.91-35.95) in 15 regions were identified. Mortality in poor performers ranged from 1.11% to 10.19% whereas that in the high-volume reference centers was 0.37-2.41%. A subset analysis in patients1 year of age showed 37 poor performers in 46 regions. Median number of surgical admissions was 345 (interquartile range 152-907) for nonoutlier and 240 (interquartile range 135-566) for outlier centers (P = .30).The present analysis is a novel risk-adjusted assessment of the performance of hospitals delivering pediatric surgical care. By identifying the existence of multiple poor performing outlier hospitals, this study provides valuable data for discussion as health care delivery systems continue to debate optimal resource distribution and regionalization of the surgical care of children.

Background/Aims: The cytotoxic agent paclitaxel and the anti-resorptive drug zoledronic acid are used in the early and advanced breast cancer setting, respectively. Both agents have been demonstrated to have anti-tumour and anti-endothelial actions. Combining paclitaxel with zoledronic acid induces a synergistic increase in apoptotic breast cancer cell death in vitro, suggesting an increased anti-tumour effect in vivo, but any specific effects on the normal microvasculature and potential side-effects of this combination remain to be established. Methods: The effects of zoledronic acid and paclitaxel were investigated, alone and in combination, on human microvascular endothelial cells in vitro, using functional assays including proliferation, migration, tubule formation and apoptosis. The in vivo effect of the drugs on the normal microvasculature was determined using the dorsal microcirculation chamber model. Results/Conclusion: Zoledronic acid reduced human dermal microvascular endothelial cell (HuDMEC) proliferation, caused accumulation of cells in S phase, and inhibited migration, tube formation and Rap1a prenylation. Paclitaxel significantly inhibited tube formation and proliferation, and increased endothelial necrosis; the combination induced HuDMEC apoptosis and further enhanced the inhibition of tube formation and migration. The combination caused minimal effects on the normal microvasculature in vivo, suggesting that this potential therapeutic strategy is not associated with deleterious microvascular side-effects.

Background In an era of wide regionalization of pediatric trauma systems, interhospital patient transfer is common. Decisions regarding the location of definitive trauma care depend on prehospital destination criteria (primary triage) and interfacility transfers (secondary triage). Secondary overtriage can occur in any resource-limited setting but is not well characterized in pediatric trauma. Methods The National Trauma Data Bank from 2008 to 2011 was queried to identify patients 15years or younger who were transferred to pediatric trauma centers. Secondary overtriage was defined as meeting all 4 of the following criteria: injury severity score (ISS) less than 9, no need for surgical procedure, no critical care admission, and length of stay of less than 24hours. All other transfers were deemed appropriate triage. Results Our definition of secondary overtriage was met in 32,318 patients out of 144,420 transfers (22.4%). Within this group, 37.5% were discharged directly from the emergency department of the receiving hospital without hospital admission. Appropriately triaged patients required a therapeutic procedure in 43.5% of cases. Differences in age, sex, mechanism of injury, and payer status were modest. Conclusions Secondary overtriage is prevalent in pediatric trauma systems nationwide and is not associated with any particular patient characteristics. Because clinical outcomes and healthcare spending are increasingly scrutinized, secondary overtriage may reflect unnecessary patient transfer and a source of potential cost savings. Development of better guidelines for secondary triage of pediatric trauma patients may enable timely assessment and treatment of children who require a higher level of care while also preventing inefficient use of available resources.

Angiogenesis, with a prominent role in tumor growth, is a physiological process through which new blood vessels are generated from pre-existing vasculature. The effect of angiogenesis inhibition test agents to cell differentiation can be evaluated using the matrigel differentiation assay, an environment simulating in vitro the natural angiogenic process under study. Using this assay, angiogenic activity can be evaluated by the quantification of tubules, junctions and other structures of interest in the matrigel images, i.e. microphotographs of the formed cellular networks under different fields of view. In this work, we present an image analysis workflow that uses separate channels in the RGB matrigel images, each contributing different information related to angiogenic activity (tubules, junctions) and other structures (cells, lumens). The workflow is successfully showcased on the basis of a series of matrigel images generated for the evaluation of angiogenesis inhibition compounds, and results are cross-validated with a manual expert scoring.

Background Childhood obesity is a worsening epidemic. Little is known about the impact of elevated BMI on perioperative and postoperative complications in children who undergo laparoscopic surgery. The purpose of this study was to examine the effects of obesity on surgical outcomes in children using laparoscopic appendectomy as a model for the broader field of laparoscopic surgery. Study design Using the Pediatric National Surgical Quality Improvement Program (NSQIP) data from 2012, patients aged 2–18years old with acute uncomplicated and complicated appendicitis who underwent laparoscopic appendectomy were identified. Children with a body mass index (BMI)≥95th percentile for their age and gender were considered obese. Primary outcomes, including overall morbidity and wound complications, were compared between nonobese and obese children. Multivariate regression analysis was conducted to identify the impact of obesity on outcome. Results A total of 2812 children with acute appendicitis who underwent appendectomy were included in the analysis; 22% were obese. Obese children had longer operative times but did not suffer increased postoperative complications when controlling for confounders (OR 1.3, 95% CI: 0.83–0.072 for overall complications, OR 1.3, 95% CI: 0.84–1.95 for wound complications). Conclusions Obesity is not an independent risk factor for postoperative complications following laparoscopic appendectomy. Although operative times are increased in obese children, obesity does not increase the likelihood of 30-day postoperative complications.

Helicopter Emergency Medical Services (HEMS) have been designed to provide faster access to trauma center care in cases of life-threatening injury. However, the ideal recipient population is not fully characterized, and indications for helicopter transport in pediatric trauma vary dramatically by county, state, and region. Overtriage, or unnecessary utilization, can lead to additional patient risk and expense. In this study we perform a nationwide descriptive analysis of HEMS for pediatric trauma and assess the incidence of overtriage in this group.We reviewed records from the American College of Surgeons National Trauma Data Bank (2008-11) and included patients less than 16 years of age who were transferred from the scene of injury to a trauma center via HEMS. Overtriage was defined as patients meeting all of the following criteria: Glasgow Coma Scale (GCS) equal to 15, absence of hypotension, an Injury Severity Score (ISS) less than 9, no need for procedure or critical care, and a hospital length of stay of less than 24 hours.A total of 19,725 patients were identified with a mean age of 10.5 years. The majority of injuries were blunt (95.6%) and resulted from motor vehicle crashes (48%) and falls (15%). HEMS transported patients were predominately normotensive (96%), had a GCS of 15 (67%), and presented with minor injuries (ISS9, 41%). Overall, 28 % of patients stayed in the hospital for less than 24 hours, and the incidence of overtriage was 17%.Helicopter overtriage is prevalent among pediatric trauma patients nationwide. The ideal model to predict need for HEMS must consider clinical outcomes in the context of judicious resource utilization. The development of guidelines for HEMS use in pediatric trauma could potentially limit unnecessary transfers while still identifying children who require trauma center care in a timely fashion.

Background & Aims: Endogenous heparinoids have been detected by thromboelastography and quantified by clotting based anti-Xa activity assays in patients with cirrhosis, but their presence in variceal bleeding has not been established yet.Methods: Clotting based anti-Xa activity was measured in A) 30 cirrhotics with variceal bleeding, B) 15 noncirrhotics with peptic ulcer bleeding, C) 10 cirrhotics without infection or bleeding, and D) 10 cirrhotics with hepatocellular carcinoma (HCC).Results: Anti-Xa activity was not detected in ulcer bleeders or in cirrhotics without infection or bleedingbut was present in seven (23%) variceal bleeders (median levels: 0.03 u/mL (0.01-0.07)) and was quantifiable for 3 days in six of seven patients. Four of seven variceal bleeders with anti-Xa activity present had HCC (p=0.023). Age, creatinine, platelet count and total infections the second day from admission were significantly correlated with the presence of measureable anti-Xa levels (p=0.014, 0.032, 0.004 and 0.019, respectively). In the HCC group, anti-Xa activity was present in three patients (30%) [median levels: 0.05 u/mL (0.01-0.06)].Conclusions: In this study, variceal bleeders and 30% of the patients with HCC had endogenous heparinoids that were detected by a clotting based anti-Xa activity assay, whereas there was no anti Xa activity present in patients with cirrhosis without infection, or bleeding or HCC, nor in those with ulcer bleeding. Thus, the anti-Xa activity is likely to be a response to bacterial infection and/or presence of HCC in cirrhosis.List of abbreviations: AFP, alpha-fetoprotein; aPTT, activated partial thromboplastin time; CP, Child-Pugh; FXa, activated factor X; GAGS, glycosaminoglycans; Hb, hemoglobin; HCC, hepatocellular carcinoma; HVPG, hepatic venous pressure gradient; INR, International normalized ratio; LMWHs, low molecular weight heparins; MELD, Model for End-stage Liver Disease; PPP, platelet-poor plasma; PRBC, packed red blood cells; PT, prothrombin time; SBP, sponataneous bacterial peritonitis; TEG, thromboelastography; WBC, white blood cells.

The acute care surgery (ACS) model has been shown to improve work flow efficiency and to reduce hospital stay. We hypothesized that, in patients with gallbladder (GB) disease who were admitted through our emergency department (ED) and then underwent surgery, the ACS model shortened the time to surgery, decreased the length of hospital stay, and reduced hospital costs.We retrospectively queried our GB surgery practice records for 2008 (before the establishment of the ACS model at our institution in 2009). We then performed time and cost comparison with our prospectively maintained GB surgery practice database for 2010. We excluded any inpatient GB surgeries and any GB surgeries that were performed for choledocholithiasis and acute pancreatitis.Our study was composed of 94 patients from the pre-ACS period (2008) and 234 patients from the ACS period (2010). Patients' baseline characteristics were similar between the two periods, except for a higher percentage of females in the ACS period (77% vs. 66%, p = 0.04). Approximately one third of patients from both periods had acute cholecystitis. In the ACS period, the mean time to surgery, that is, from ED arrival to operating room arrival, was shorter (20.8 [13.8] hours vs. 25.7 [16.2] hours, p = 0.007); more patients underwent surgery within 24 hours after ED arrival (75% vs. 59%, p = 0.004); and more patients underwent surgery between 12:00 midnight and 7:00 AM (25% vs. 6.4%, p0.001). As a result, hospital length of stay was 1.4 days shorter in the ACS period, with cost saving per patient of approximately $1,000.We found that implementation of ACS model led to benefits for patients who came to our ED with GB disease, including shorter time to surgery, shorter hospital stay, and decreased hospital costs. The ACS model benefits the health care system.Therapeutic study, level IV.

Health care personnel are at high risk for hepatitis B virus (HBV) transmission. The aim of the present study was to investigate hepatitis B (HB) knowledge and vaccination acceptance among health care personnel in southwestern Greece, using the Hepatitis B Vaccine Knowledge and Acceptance Questionnaire. One hundred eighty-three employees participated (71 males). Occupation (p < .001), higher education (p < .001), and vaccination (p = .007) were significantly related to HB knowledge. The rate of HBV vaccination coverage was 70.9%. Participants considering themselves at high risk for HBV infection did not report significantly increased vaccination rates. In the multivariate analysis, university personnel (p = .002), occupational category (p < .001), and HB knowledge (p = .049) were significantly associated with vaccination. In conclusion, 29% of hospital personnel were not vaccinated mainly due to negligence. Occupation, education, and knowledge about HB seem to be associated with HBV vaccination.

Pneumothoraces (PTXs) are a common entity in thoracic trauma. Micropower impulse radar (MIR) has been able to detect PTXs in surgical patients. However, this technology has not been tested previously on trauma patients. The purpose of this study was to determine the sensitivity and specificity of MIR to detect clinically significant PTXs. We hypothesized that MIR technology can effectively screen trauma patients for clinically significant PTXs.This was a prospective observational study in Level I trauma centers in Boston, Massachusetts, and Bern, Switzerland. All trauma patients undergoing a chest computed tomographic (CT) scan were eligible for the study. Consent was obtained, and readings were performed within 30 minutes before or after the CT scan. The patients had eight lung fields tested (four on each side). The qualitative and quantitative MIR results were blinded and stored on the device. We then compared the results of the MIR to the CT scan and the need for chest tube drainage. We defined PTXs as clinically significant if they required a chest tube.Seventy-five patients were enrolled, with a mean age of 46 ± 16 years. Eighty-four percent were male. The screening test took approximately 1 minute. All but two patients had blunt chest trauma. Six true-positives, 6 false-positives, 63 true-negatives, and 0 false-negatives resulted in an overall sensitivity of 100%.MIR is an easy to use handheld technology that effectively screened patients for clinically significant PTXs, with a sensitivity and negative predictive value of 100%. MIR may be used for rapid, repeatable, and ongoing surveillance of trauma patients.Diagnostic study, level III.

Intravenous contrast extravasation (IVCE) on a trauma computed tomography has been quoted as a reason for intervention (angiographic embolization or operation). The new-generation computed tomographic (CT) scanners identify IVCE with increasing frequency. We hypothesized that most IVCEs do not require an intervention.This study was a retrospective evaluation of trauma patients with IVCE on abdomen or pelvis CT scan (January 2005-December 2009). Along with demographic and hemodynamic variables, the following characteristics of IVCE were examined as potential risk factors for intervention: maximal dimension, small (≤ 1.5 cm) versus large (1.5 cm), contained versus free, and single versus multiple and location.Sixty-nine patients with 81 IVCEs were identified: 48 IVCEs occurred in intra-abdominal solid organs, 18 IVCEs in the pelvic retroperitoneal space, and 15 IVCEs in the soft tissues or other locations. Thirty patients (43.5%) were managed without an intervention, and 39 patients (56.5%) required either an immediate (30 patients) or a delayed (9 patients) intervention. Multivariate analysis identified three independent predictors of an intervention: an admission systolic blood pressure of 100 mm Hg or lower, a large ICVE, and an Abbreviated Injury Score of the abdomen of 3 or higher. If all three independent predictors were present, 100% of patients received an intervention.Nearly half of IVCEs on CT scan did not require an intervention. A hypotension at admission, a severe abdominal trauma, and a blush diameter of 1.5 cm or greater predicted the need for intervention.Therapeutic study, level IV; prognostic study, level III.

Patient Female, 60 FINAL DIAGNOSIS: Corneal ulceration Symptoms: Blurred vision Medication: Abatacept Clinical Procedure: - Specialty: Ophthalmology. Objective Management of emergency care. Background To report a case of a patient with rheumatoid arthritis (RA) and associated peripheral corneal ulceration. Case report A 60-year-old woman with RA diagnosed 15 years ago, under immunosuppressive therapy (IV abatacept 250 mg/month), demonstrated blurring of vision in her RE (right eye). Visual acuity was 6/10 in the RE and 10/10 in the LE. Slit lamp examination revealed a paracentral superior corneal melt in the RE. Anterior chamber reaction was 2+. Laboratory investigations revealed positive anti-Ro and anti-La, anti-Extractable Nuclear Antigens (anti-ENA, ELISA), while anti-Sm, anti-Rnp, anti-Jo1 and anti-Scl70 were found negative. IgG and IgA serum immunoglobulins were found elevated, but IgE and IgM were within normal levels. Further evaluation for the underlying disease revealed highly elevated rheumatoid factor and C-reactive protein. The patient, who had been receiving anti-TNF during the last 6 months, underwent treatment with topical tobramycin and lubricants and oral prednisone 60 mg/day with tapering doses, to which methotrexate p.os. 15 mg/week was added. The condition improved within a few days after the initiation of prednisone treatment. Re-epithelization occurred 1 week after the onset of the immunosuppressive treatment. Only punctate fluorescein dye uptake was detected in the margins of the lesion. Conclusions The effective control of the underlying disease and early diagnosis of the dry eye syndrome in RA patients may prevent serious corneal complications such as corneal ulceration. The initiation of treatment with steroids and immunosuppresants was found to halt the progression of keratolysis, and assisted re-epithelization.

Background Emergent cricothyroidotomy remains an uncommon, but life-saving, core procedural training requirement for emergency medicine (EM) physician training. We hypothesized that, although most cricothyroidotomies occur in the emergency department (ED), they are rarely performed by EM physicians. Methods We conducted a retrospective analysis of all emergent cricothyroidotomies performed at two large level one trauma centers over 10 years. Operators and assistants for all procedures were identified, as well as mechanism of injury and patient demographics were examined. Results Fifty-four cricothyroidotomies were performed. Patients were: mean age of 50, 80% male and 90% blunt trauma. The most common primary operator was a surgeon (n = 47, 87%), followed by an Emergency Medical Services (EMS) provider (n = 6, 11%) and a EM physician (n = 1, 2%). In all cases, except those performed by EMS, the operator or assistant was an attending surgeon. All EMS procedures resulted in serious complications compared to in-hospital procedures (p < 0.0001). Conclusions 1. Pre-hospital cricothyroidotomy results in serious complications. 2. Despite the ubiquitous presence of emergency medicine physicians in the ED, all cricothyroidotomies were performed by a surgeon, which may represent a serious emergency medicine training deficiency.

Bone metastases are frequent complications in advanced breast and prostate cancer among others, resulting in increased risk of fractures, pain, hypercalcaemia of malignancy and a reduction in patient independence and mobility. Bisphosphonates (BPs) are in wide clinical use for the treatment of cancer-induced bone disease associated with advanced cancer, due to their potent ability to reduce skeletal-related events (SREs) and improve quality of life. Despite the profound effect on bone health, the majority of clinical studies have failed to demonstrate an overall survival benefit of BP therapy. There is increasing preclinical evidence to suggest that inclusion of the most potent nitrogen-containing BPs (NBPs) in combination therapy results in increased antitumour effects and improved survival, but that the particular schedules used are of key importance to achieve optimal benefit. Recent clinical data have suggested that there may be effects of adjuvant NBP therapy on breast tumours outside the skeleton. These findings have led to renewed interest in the use of BPs in cancer therapy, in particular how they can be included as part of adjuvant protocols. Here we review the key data reported from preclinical model systems investigating the effects of combination therapy including BPs with particular emphasis on breast and prostate cancer.

Management of severe traumatic brain injury has centered on continuous intracranial pressure (ICP) monitoring with intraparenchymal ICP monitors (IPM) or extracranial ventricular drains (EVD). Our hypothesis was that neurologic outcomes are unaffected by the type of ICP monitoring device.We reviewed 377 adult patients with traumatic brain injury requiring ICP monitoring. Primary outcome was Glasgow Outcome Score (GOS) 1 month after injury. Secondary outcomes included mortality, monitoring-related complications, and length of ICU and hospital stay.There were 253 patients managed with an IPM and 124 with an EVD. There was no difference in Glasgow Outcome Score (2.7 ± 1.3 vs 2.5 ± 1.3, p = 0.45), mortality (30.9% vs 32.2%, p = 0.82), and hospital length of stay (LOS) (15.6 ± 12.4 days vs 16.4 ± 10.7 days, p = 0.57). Device-related complications (11.9% vs 31.1%, p0.001), duration of ICP monitoring (3.8 ± 2.6 days vs 7.3 ± 5.6 days, p0.001), and ICU LOS (7.6 ± 5.6 days vs 9.5 ± 6.2 days, p = 0.004) were longer in the EVD group. Age, opening ICP, and size of midline shift were independent predictors for neurologic outcomes and mortality, when type and severity of brain injury, as well as overall injury severity were controlled for. Duration of ICP monitoring and opening ICP were independent predictors for hospital LOS and the former predicted prolonged ICU stay. Device-related complications were affected by type of device.Use of EVDs in adult traumatic brain injury patients is associated with prolonged ICP monitoring, ICU LOS, and more frequent device-related complications.

Bone metastases are frequent complications in advanced breast and prostate cancer among others, resulting in increased risk of fractures, pain, hypercalcaemia of malignancy and a reduction in patient independence and mobility. Bisphosphonates (BPs) are in wide clinical use for the treatment of cancer-induced bone disease associated with advanced cancer, due to their potent ability to reduce skeletal-related events (SREs) and improve quality of life. Despite the profound effect on bone health, the majority of clinical studies have failed to demonstrate an overall survival benefit of BP therapy. There is increasing preclinical evidence to suggest that inclusion of the most potent nitrogen-containing BPs (NBPs) in combination therapy results in increased antitumour effects and improved survival, but that the particular schedules used are of key importance to achieve optimal benefit. Recent clinical data have suggested that there may be effects of adjuvant NBP therapy on breast tumours outside the skeleton. These findings have led to renewed interest in the use of BPs in cancer therapy, in particular how they can be included as part of adjuvant protocols. Here we review the key data reported from preclinical model systems investigating the effects of combination therapy including BPs with particular emphasis on breast and prostate cancer.

Background: Vascular endothelial growth factor receptors (VEGFR) are tyrosine kinases (TK) known to promote angiogenesis and cancer. Since quinazoline and pyridopyrimidine derivatives have been proved to be potent and highly selective TK inhibitors, in this work we aimed to synthesize novel substituted pyrazolopyridines and explore their capability to modulate angiogenesis and tumor growth. Materials and methods: Pyrazolopyridine derivatives were synthesized using 2-amino-5-nitro-4-picoline as starting material, which upon suitable transformations was converted to 5-chloropyrazolo[3,4-c]pyridine. A 4-methoxybenzyl group was inserted at N1 of the heterocyclic ring system followed by a subsequent addition of a 3-phenyl group in certain derivatives. A second chlorine atom was introduced at position 7 via N-oxide metathesis and then 5- and 7-chlorine atoms were successively displaced by suitable amines. Twelve derivatives were isolated pure and their structure identified using 1D and 2D NMR and mass spectrometry. Compounds were assessed for their ability to modulate basal and/or VEGF-induced endothelial cell proliferation, migration and differentiation using MTT, transwell and matrigel tube-formation assays [ 1 ], respectively. The effect of active compounds on VEGFR2 signaling was determined by immunoblotting. In vivo activity was evaluated on a syngeneic Lewis lung carcinoma (LLC) transplantation mouse model [ 2 ] Results: Amongst test compounds, four (SC1117, SC1119, SC1123, SC1124) significantly inhibited at a concentration-dependent manner (0.2–2 µM), crucial pro-angiogenic attributes of endothelial cells related to proliferation, migration and differentiation capabilities, in part by targeting pathways downstream of VEGFR2. Moreover i.p. administration of SC1117, SC1119 and SC1124 (0.05-0.2 mg/kg body weight thrice/week, for 2 weeks) significantly reduced LLC tumor volume in mice without toxicity. Conclusions: We described three novel pyrazolopyrimidine derivatives targeting VEGFR2 as potential inhibitors of angiogenesis and tumor growth.