Low Urinary Free Cortisol as a Risk Factor for Patients with Variceal Bleeding.

Background and Objectives: Specificity and reliability issues of the current cortisol assessment methods lead to limitations on the accurate assessment of relative adrenal insufficiency. Although free cortisol provides a more accurate evaluation of adrenal cortisol production, the expense and time-consuming nature of these assays make them impractical for routine use. Research has, thus, focused on alternative methods, such as indirectly measuring free cortisol using Coolens' equation or directly assessing salivary cortisol concentration, which is considered a more favorable approach despite associated challenges like sampling issues and infection risks. The aim of this study was to explore correlations between 24 h urinary free cortisol (UFC), free plasma cortisol, serum total cortisol, and salivary cortisol as potential reliable indices of free cortisol in the setting of variceal bleeding. Additionally, we assessed the predictive value of UFC for 6-week mortality and 5-day treatment failure in patients with liver cirrhosis and variceal bleeding. Materials and Methods: A total of 40 outpatients with liver cirrhosis and variceal bleeding were enrolled. Free cortisol levels in serum, saliva, and urine were assessed using the electrochemiluminescence immunoassay method. For the measurement of plasma-free cortisol, a single quadrupole mass spectrometer was employed. The quantification of free cortisol was fulfilled by analyzing the signal response in the negative ESI-MS mode. Results: UFC was significantly correlated to free plasma cortisol. Negative correlations were demonstrated between UFC, the Child-Pugh (CP) score, and C reactive protein (CRP) levels. In the multivariate analysis, CP stage C was associated with 6-week mortality risk and portal vein thrombosis with 5-day treatment failure using Cox regression and binary logistic regression analyses, respectively. Patients who experienced rebleeding, infection, or death (or any combination of these events) presented with lower levels of UFC. Conclusions: This study suggests that low levels of UFC may impose a risk factor for patients with liver cirrhosis and variceal bleeding. The use of UFC as an index of adrenal cortisol production in variceal bleeding warrants further investigation.

A comparison of video laryngoscopy to direct laryngoscopy for the emergency intubation of trauma patients.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 < 0.05). In multivariate regression analysis DL was associated with higher risk of intubation failure compared to VL (OR 1.82, CI: 1.15-2.86). CONCLUSIONS: In trauma patients intubated emergently, VL had a significantly higher success rate than DL. These data suggest that, in select circumstances, VL is superior to DL for the intubation of trauma patients with difficult airways.

Diagnostic imaging for acute appendicitis: interfacility differences in practice patterns.

PURPOSE: To evaluate trends and factors associated with interfacility differences in imaging modality selection in the diagnosis and management of children with suspected acute appendicitis. METHODS: We conducted a retrospective review of diagnostic imaging selection and outcomes in patients <20 years of age who underwent appendectomy at a single Children's Hospital from June 2008 to June 2013. These results were then compared with those of referring hospitals. RESULTS: A total of 232 children underwent appendectomy during the study period. Imaging results contributed to diagnostic and management decisions in 95.3 % of cases. CT scan was utilized as first-line imaging in 50 % of cases. CTs were preferentially performed at referring institutions (78 vs. 46 %, p < 0.001). Children were five times more likely to undergo CT at referring institutions (OR = 5.5, CI 3.0-10.2). Adjusting for demographics and Alvarado score, diagnostic imaging choice was independent of patient's clinical status. CONCLUSION: This study demonstrates that initial presentation to a referring hospital independently predicts the use of CT scan for suspected acute appendicitis. Further efforts should be undertaken to develop a clinical pathway that minimizes radiation exposure in the diagnosis of acute appendicitis, with focus on access to pediatric abdominal ultrasound.

Minimally invasive repair of pectus excavatum: analyzing contemporary practice in 50 ACS NSQIP-pediatric institutions.

BACKGROUND: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.

Age, Sex and BMI Relations with Anti-SARS-CoV-2-Spike IgG Antibodies after BNT162b2 COVID-19 Vaccine in Health Care Workers in Northern Greece.

The aim of this work was to study age, sex, and BMI (Body Mass Index)-related differences in the development of anti-SARS-CoV-2-Spike IgG antibodies, after vaccination with the BNT162b2 COVID-19 vaccine, in health care workers of a General Hospital in a city in Northern Greece. Blood sampling was drawn two to four weeks following the second dose of the vaccine, and six months after the first blood sample collection. Measurement of serum IgG antibodies against the spike domain of SARS-CoV-2 was performed using the SARS-CoV-2 IgG II Quant assay. All participants had sufficient serum IgG titers in the first measurement. Women developed higher IgG titers than men. The IgG titers were inversely related to age in both sexes; there was also a small, insignificant tendency to be inversely related to BMI. Six months after the first measurement, the IgG titers decreased dramatically to values less than 5% of the initial. This decrease was observed in both men and women and was inversely related to age. Multivariate regression analysis showed that age and sex explained with statistical significance 9% of the variance in SARS-CoV-2 IgG titers in our study population; the role of BMI was limited and insignificant.

Combinations of bisphosphonates and classical anticancer drugs: a preclinical perspective.

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.

Urinary free cortisol is a reliable index of adrenal cortisol production in patients with liver cirrhosis.

BACKGROUND: 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. AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Microvascular endothelial cell responses in vitro and in vivo: modulation by zoledronic acid and paclitaxel?

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.

Parastomal gallbladder hernia in a septic patient.

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.

Novel pyrazolopyridine derivatives as potential angiogenesis inhibitors: Synthesis, biological evaluation and transcriptome-based mechanistic analysis.

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.

Abscess due to perforated appendicitis: factors associated with successful percutaneous drainage.

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.

The use of whole body computed tomography scans in pediatric trauma patients: Are there differences among adults and pediatric centers?

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≤18years) 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.

Blunt bilateral diaphragmatic rupture-A right side can be easily missed.

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.

Laparoscopic versus open appendectomy in children: the effect of surgical technique on healthcare costs.

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.

The impact of obesity on laparoscopic appendectomy: Results from the ACS National Surgical Quality Improvement Program pediatric database.

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.

Secondary overtriage in pediatric trauma: can unnecessary patient transfers be avoided?

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 15 years 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 24 hours. 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.

A contemporary series of patients undergoing open debridement for necrotizing pancreatitis.

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 < .01), preoperative intensive care unit admission (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.

Time and cost analysis of gallbladder surgery under the acute care surgery model.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%, p < 0.001). 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. CONCLUSION: 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. LEVEL OF EVIDENCE: Therapeutic study, level IV.