Upregulation of RET induces perineurial invasion of pancreatic adenocarcinoma.

Tumor spread along nerves, a phenomenon known as perineurial invasion, is common in various cancers including pancreatic ductal adenocarcinoma (PDAC). Neural invasion is associated with poor outcome, yet its mechanism remains unclear. Using the transgenic Pdx-1-Cre/KrasG12D /p53R172H (KPC) mouse model, we investigated the mechanism of neural invasion in PDAC. To detect tissue-specific factors that influence neural invasion by cancer cells, we characterized the perineurial microenvironment using a series of bone marrow transplantation (BMT) experiments in transgenic mice expressing single mutations in the Cx3cr1, GDNF and CCR2 genes. Immunolabeling of tumors in KPC mice of different ages and analysis of human cancer specimens revealed that RET expression is upregulated during PDAC tumorigenesis. BMT experiments revealed that BM-derived macrophages expressing the RET ligand GDNF are highly abundant around nerves invaded by cancer. Inhibition of perineurial macrophage recruitment, using the CSF-1R antagonist GW2580 or BMT from CCR2-deficient donors, reduced perineurial invasion. Deletion of GDNF expression by perineurial macrophages, or inhibition of RET with shRNA or a small-molecule inhibitor, reduced perineurial invasion in KPC mice with PDAC. Taken together, our findings show that RET is upregulated during pancreas tumorigenesis and its activation induces cancer perineurial invasion. Trafficking of BM-derived macrophages to the perineurial microenvironment and secretion of GDNF are essential for pancreatic cancer neural spread.

Cold Atmospheric Plasma, Created at the Tip of an Elongated Flexible Capillary Using Low Electric Current, Can Slow the Progression of Melanoma.

INTRODUCTION: Cold Atmospheric Plasma Jet (CAPJ), with ion temperature close to room temperature, has tremendous potential in biomedical engineering, and can potentially offer a therapeutic option that allows cancer cell elimination without damaging healthy tissue. We developed a hand-held flexible device for the delivery of CAPJ to the treatment site, with a modified high-frequency pulse generator operating at a RMS voltage of <1.2 kV and gas flow in the range 0.3-3 l/min. The aims of our study were to characterize the CAPJ emitted from the device, and to evaluate its efficacy in elimination of cancer cells in-vitro and in-vivo. METHODS AND RESULTS: The power delivered by CAPJ was measured on a floating or grounded copper target. The power did not drastically change over distances of 0-14 mm, and was not dependent on the targets resistance. Temperature of CAPJ-treated target was 23°-36° C, and was dependent on the voltage applied. Spectroscopy indicated that excited OH- radicals were abundant both on dry and wet targets, placed at different distances from the plasma gun. An in-vitro cell proliferation assay demonstrated that CAPJ treatment of 60 seconds resulted in significant reduction in proliferation of all cancer cell lines tested, and that CAPJ activated medium was toxic to cancer cells. In-vivo, we treated cutaneous melanoma tumors in nude mice. Tumor volume was significantly decreased in CAPJ-treated tumors relatively to controls, and high dose per fraction was more effective than low dose per fraction treatment. Importantly, pathologic examination revealed that normal skin was not harmed by CAPJ treatment. CONCLUSION: This preliminary study demonstrates the efficacy of flexible CAPJ delivery system against melanoma progression both in-vitro and in-vivo. It is envisioned that adaptation of CAPJ technology for different kinds of neoplasms use may provide a new modality for the treatment of solid tumors.

Prognostic Performance of Current Stage III Oral Cancer Patients After Curative Intent Resection: Evidence to Support a Revision of the American Joint Committee on Cancer Staging System.

BACKGROUND: The American Joint Committee on Cancer (AJCC) stage III classification of oral cavity squamous cell carcinoma (OCSCC) represents a heterogeneous group of patients with early local disease with regional metastases (T1N1 and T2N1) and advanced local disease with or without regional metastasis (T3N0 and T3N1). OBJECTIVE: The aim of this study was to evaluate prognostic heterogeneity in the stage III category. METHODS AND PATIENTS: An international retrospective multicenter study of 1815 patients who were treated for OCSCC from 2003 to 2011. RESULTS: Kaplan-Meier survival analysis and multivariate models of stage III patients revealed better overall survival (OS; HR 2.12, 95 % CI 1.03-4.15; p = 0.01) and disease-specific survival (DSS; HR 1.7, 95 % CI 1.16-4.12; p = 0.04) rates for patients with T1-2N1/T3N0 disease than for patients with T3N1 disease. The outcomes of patients with T3N1 and stage IVa disease were similar (p = 0.89 and p = 0.78 for OS and DSS, respectively). Modifying stage classification by transferring the T3N1 category to the stage VIa group resulted in a better prognostic performance [Harrell's concordance index, C index 0.76; Akaike's Information Criterion (AIC) 4131.6] compared with the AJCC 7th edition staging system (C index 0.65; AIC 4144.9) for OS. When DSS was assessed, the suggested staging system remained the best performing model (C index 0.71; AIC 1061.3) compared with the current AJCC 7th edition staging (C index 0.64; AIC 1066.2). CONCLUSIONS: The prognosis of T3N1 and stage IVa disease are similar in OCSCC, suggesting that these categories could be combined in future revisions of the nodal staging system to enhance prognostic accuracy.

Elective neck dissection during salvage total laryngectomy--a beneficial prognostic effect in locally advanced recurrent tumours.

OBJECTIVES: Elective neck dissection during salvage laryngectomy is controversial. The goal of our study was to evaluate the effect of elective neck dissection during salvage laryngectomy in patients with locally advanced disease at recurrence. DESIGN: Multicentre, retrospective study. SETTINGS: Two tertiary medical centres. PARTICIPANTS: Eighty-seven patients treated by salvage laryngectomy. MAIN OUTCOME MEASURES: Disease-Free and Overall Survival. RESULTS: Fifty-seven patients underwent salvage total laryngectomy for locally advanced recurrent squamous cell carcinoma of the larynx, and 30 patients underwent salvage laryngectomy for limited recurrent disease. Elective lateral neck dissection was performed in 48 patients. The groups were similar in age, sex, initial TNM stage and pre-operative treatment. Survival analysis showed that both disease-free survival and overall survival were improved in patients with locally advanced disease who underwent elective neck dissection. This beneficial effect was not demonstrated in patients with limited disease at recurrence. Multivariate analysis showed that the extent of the recurrent disease as well as elective neck dissection was associated with improved disease-free survival and overall survival. CONCLUSIONS: Elective neck dissection during salvage total laryngectomy seems to improve survival in patients with advanced local disease at recurrence. The role of neck dissection in the treatment of smaller tumours awaits further studies.

Macrophages mediate gemcitabine resistance of pancreatic adenocarcinoma by upregulating cytidine deaminase.

Resistance to pharmacologic agents used in chemotherapy is common in most human carcinomas, including pancreatic ductal adenocarcinoma (PDA), which is resistant to almost all drugs, including gemcitabine, a nucleoside analog used as a first-line treatment. Poor survival rates of PDA patients have, therefore, not changed much over 4 decades. Recent data indicated that tumor-associated macrophages (TAMs), which are abundant in the microenvironment of several tumors, including PDA, secrete pro-tumorigenic factors that contribute to cancer progression and dissemination. In this study, we show for the first time that TAMs can also induce chemoresistance of PDA by reducing gemcitabine-induced apoptosis. Macrophages co-cultured with cancer cells or TAM-conditioned medium significantly reduced apoptosis and activation of the caspase-3 pathway during gemcitabine treatment. In vivo PDA models of mice, which have reduced macrophage recruitment and activation, demonstrated improved response to gemcitabine compared with controls. Similarly, inhibition of monocytes/macrophages trafficking by a CSF1-receptor antagonist GW2580 augmented the effect of gemcitabine in a transgenic mouse PDA model that was resistant to gemcitabine alone. Analysis of multiple proteins involved in gemcitabine delivery and metabolism revealed that TAMs induced upregulation of cytidine deaminase (CDA), the enzyme that metabolizes the drug following its transport into the cell. Decreasing CDA expression by PDA cells blocked the protective effect of TAMs against gemcitabine. These results provide the first evidence of a paracrine effect of TAMs, which mediates acquired resistance of cancer cells to chemotherapy. Modulation of macrophage trafficking or inhibition of CDA may offer a new strategy for augmenting the response of PDA to chemotherapy.

Lymph node density in oral cavity cancer: results of the International Consortium for Outcomes Research.

BACKGROUND: Lymph node density (LND) has previously been reported to reliably predict recurrence risk and survival in oral cavity squamous cell carcinoma (OSCC). This multicenter international study was designed to validate the concept of LND in OSCC. METHODS: The study included 4254 patients diagnosed as having OSCC. The median follow-up was 41 months. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control and distant metastasis rates were calculated using the Kaplan-Meier method. Lymph node density (number of positive lymph nodes/total number of excised lymph nodes) was subjected to multivariate analysis. RESULTS: The OS was 49% for patients with LND0.07 compared with 35% for patients with LND>0.07 (P<0.001). Similarly, the DSS was 60% for patients with LND0.07 compared with 41% for those with LND>0.07 (P<0.001). Lymph node density reliably stratified patients according to their risk of failure within the individual N subgroups (P=0.03). A modified TNM staging system based on LND ratio was consistently superior to the traditional system in estimating survival measures. CONCLUSION: This multi-institutional study validates the reliability and applicability of LND as a predictor of outcomes in OSCC. Lymph node density can potentially assist in identifying patients with poor outcomes and therefore for whom more aggressive adjuvant treatment is needed.

Distribución de las enteroparasitosis en un pueblo joven de Lambayeque / Distribution of intestinal parasites in young people of Lambayeque

Introducción: Las enteroparasitosis siguen siendo un problema de salud pública en nuestro país. Algunos parásitos requieren, para su diagnóstico, técnicas especiales. No se encuentran datos de prevalencia de Strongyloides stercolaris en Lambayeque. Objetivo: Determinar la prevalencia de infección por Strongyloides stercolaris y otras enteroparasitosis en el pueblo joven Santo Toribio de Mogrovejo de Chiclayo durante el 2011. Diseño: Estudio descriptivo, transversal; Lugar: Pueblo Joven Santo Toribio de Mogrovejo de Chiclayo. Participantes: 106 pobladores a quienes se les solicitó tres muestras de heces elegidos por muestreo aleatorio, estratificado, polietápico. Intervenciones: datos epidemiológicos y aplicación de 5 técnicas parasitológicas: Examen directo de heces, Baermann modificado en Copa por Lumbreras, Test de sedimentación espontánea, Cultivo en agar y Cultivo Dancescu. Resultados: Se visitaron 124 casas; el porcentaje de respuesta fue de 85,4%. Se entrevistaron 106 personas. El promedio de edad fue de 27,8 +/- 16,9 años; 31 hombres (29,2%) y 75 mujeres (70,8%). El 26,4% habían realizado un viaje a la Sierra y/o Selva en los últimos 5 años con una estancia mayor a un mes. El piso de tierra fue el más frecuente (55,6%); 102 personas (96,2 %) tenían desagüe; 23 pobladores (21,7 %) tuvieron al menos un parásito detectado. No se hallaron pobladores infectados con Strongyloides stercolaris. La enteroparasitosis más frecuente fue por protozoarios, con predominio de Blastocystis hominis (12,3%) y Giardia lamblia (9,4%). Conclusiones: Se halló una baja frecuencia de enteroparasitosis y ausencia de pobladores infectados con Strongyloides stercolaris. Los parásitos más frecuentes fueron Blastocystis hominis y Giardia lamblia.(AU)

Introduction: Enteroparasites are still a public health problem in our country. Some infections require specific techniques to be recognized. There are no data on the prevalence of Strongyloides stercolaris infection in Lambayeque.Objectives: To determine the prevalence of Strongyloides stercolaris infection and other enteroparasites in the pueblo joven "Santo Toribio de Mogrovejo" of Chiclayo during 2011. Design: Descriptive and cross-sectional study. Place: pueblo joven Santo Toribio de Mogrovejo of Chiclayo Participants:106 residents selected by random, stratiffied, bietapic sampling. Three samples were collected per patient;Interventions: epidemiological data and application of five parasitological techniques: Direct examination of stool, sedimentation in glass modified by Lumbreras, Spontaneous sedimentation test, Agar Culture test and Agar Dancescu Culture test. Results: 124 households were visited. The response rate was 85.7%; 106 people were interviewed. The average age was 27.8 + / - 16.9 years. There were 31 men (29.2%) and 75 women (70.8%); 26.4% of people tested, had made a trip to the mountains or jungle region during the last 5 years with a stay longer than one month. Soil was the more frequent material of the floor (55.6%); 102 people (96.2%) had drain; 23 people (21.7%) had at least one parasite detected.There were no people infected with Strongyloides stercolaris.Protozoans were the most frequent intestinal parasites found.Blastocystis hominis cysts were found in 12.3% people; Giardia lamblia in 9.4%. Conclusions: A low frequency of intestinal parasites and no cases of Strongyloides stercolaris infection were found. Blastocystis hominis was the more frequent parasite.(AU)

Are drug provocation tests still necessary to test the safety of COX-2 inhibitors in patients with cross-reactive NSAID hypersensitivity?

Background: COX-2 inhibitors are safe alternatives in patients with cross-reactive non-steroidal anti-inflammatory drug (NSAID) hypersensitivity. These drugs are recommended to these patients after negative drug provocation tests (DPTs). However, cumulative data on encouraging results about the safety of COX-2 inhibitors in the majority of these patients bring the idea as to whether a DPT is always mandatory for introducing these drugs in all patients with cross-reactive NSAID hypersensitivity. Objective: To document the safety of COX-2 inhibitors currently available and to check whether or not any factor predicts a positive response. Methods: This study included the retrospective analysis of cases with cross-reactive NSAID hypersensitivity who underwent DPTs with COX-2 inhibitors in order to find safe alternatives. DPTs were single-blinded and placebo controlled. Results: The study group consisted of 309 patients. COX-2 inhibitors were well tolerated in the majority of the patients [nimesulide: 91.9%; meloxicam: 90.2%; rofecoxib: 94.9%; and celecoxib: 94.9%)]. Twenty-five patients (30 provocations) reacted to COX-2 inhibitors. None of the factors were found be associated with positive response. Conclusion: Our results suggest to follow the traditional DPT method to introduce COX-2 inhibitors for finding safe alternatives in all patients with cross-reactive NSAID hypersensitivity before prescription as uncertainty of any predictive factor for a positive response continues. However, these tests should be performed in hospital settings in which emergency equipment and experienced personnel are available (AU)

Ketamine for palliative sedation in the emergency department.

BACKGROUND: Palliative sedation to treat severely distressing symptoms in those with a poor prognosis is well-accepted. OBJECTIVE: We discuss palliative sedation in the Emergency Department and the use of ketamine. CASE REPORT: We present the case of a patient with angioedema of the tongue and severe respiratory distress. The patient's nursing home was unable to control her symptoms and she was transferred to the Emergency Department. The patient received fentanyl 50 µg i.v. and ketamine 50 mg i.v. every 5 min until adequate palliative sedation was achieved. CONCLUSION: Ketamine can be considered for Emergency Department palliative sedation in selected patients. Identifying and caring for unmet palliative care needs is an important skill for Emergency Medicine.

A case of Evans' syndrome following influenza vaccine.

BACKGROUND: Evans' syndrome is an uncommon condition defined by the combination (either simultaneously or sequentially) of immune thrombocytopenia purpura and autoimmune hemolytic anemia with a positive direct antiglobulin test in the absence of known underlying etiology. OBJECTIVES: We present a case of Evans' syndrome following influenza vaccination. CASE REPORT: A 50-year-old man with no prior medical history developed Evans' syndrome 4 days after receiving influenza immunization. The patient improved following treatment with oral prednisone and intravenous immunoglobulin. CONCLUSION: Influenza vaccine is one of the most commonly used vaccines worldwide, with millions of people being vaccinated annually. Despite its wide use, only sparse information has been published concerning any hematological effects of this vaccine. The rarity of such effects supports the safety of using this vaccine.

Intravenous ketamine in a dissociating dose as a temporizing measure to avoid mechanical ventilation in adult patient with severe asthma exacerbation.

BACKGROUND: Patients experiencing severe asthma exacerbations occasionally deteriorate to respiratory failure requiring endotracheal intubation and mechanical ventilation. Mechanical ventilation in this setting exposes the patients to substantial iatrogenic risk and should be avoided if at all possible. OBJECTIVES: To describe the use of intravenous ketamine in acute asthma exacerbation. CASE REPORT: We present a case of severe asthma exacerbation in an adult female patient who failed to improve with standard therapies, but promptly improved with the administration of intravenous ketamine (0.75 mg/kg i.v. bolus followed by continuous drip of 0.15 mg/kg/h). SUMMARY: This case suggests that intravenous ketamine given in a dissociative dose may be an effective temporizing measure to avoid mechanical ventilation in adult patients with severe asthma exacerbations.

How (un)useful is the pelvic ring stability examination in diagnosing mechanically unstable pelvic fractures in blunt trauma patients?

OBJECTIVES: Our goal was to evaluate the utility of the pelvic ring stability examination for detection of mechanically unstable pelvic fractures in blunt trauma patients. METHODS: Retrospective chart review. RESULTS: We enrolled 1,502 consecutive blunt trauma patients and found 115 patients with pelvic fractures including 34 patients with unstable pelvic fractures (Tile classification B and C). Unstable pelvic ring on physical examination had a sensitivity and specificity of 8% (95% CI 4-14) and 99% (95% CI 99-100), respectively, for detection of any pelvic fracture and 26% (95% CI 15-43) and 99.9% (95% 99-100), respectively, for detection of mechanically unstable pelvic fractures. The sensitivity and specificity of pelvic pain or tenderness in patients with Glasgow Coma Scale >13 were 74% (95% CI 64-82) and 97% (95% CI 96-98), respectively for diagnosing any pelvic fractures, and 100% (95% CI 85-100) and 93% (95% CI 92-95), respectively for diagnosing of mechanically unstable pelvic fractures. The sensitivity and specificity of the presence of pelvic deformity were 30% (95% CI 22-39) and 98% (95% CI 98-99), respectively for detection of any pelvic fracture and 55% (95% CI 38-70) and 97% (95% CI 96-98), respectively for detection of mechanically unstable pelvic fractures. CONCLUSIONS: The presence of either pelvic deformity or unstable pelvic ring on physical examination has poor sensitivity for detection of mechanically unstable pelvic fractures in blunt trauma patients. Our study suggests that blunt trauma patients with Glasgow Coma Scale >13 and without pelvic pain or tenderness are unlikely to suffer an unstable pelvic fracture. A prospective study is needed to determine whether a set of clinical criteria can safely detect or exclude the presence of an unstable pelvic fracture.

A case of acute keratoconjunctivitis from exposure to latex of Euphorbia tirucalli (pencil cactus).

We present a case of a 40-year-old man who suffered chemical eye injury from the latex of Euphorbia tirucalli (pencil cactus), resulting in acute keratoconjunctivitis. The Euphorbia genus of plants contains numerous species widely distributed throughout all major continents, and therefore this may be a more common Emergency Department occurrence than previously thought.

Low diagnostic yield of electrocardiogram testing in younger patients with syncope.

STUDY OBJECTIVE: Routine ECG testing is recommended in the evaluation of syncope, although the value of such testing in young patients is unclear. For ECG testing, we assess the diagnostic yield (frequency that ECG identified the reason for syncope) and predictive accuracy for 14-day cardiac events after an episode of syncope as a function of age. METHODS: Adult patients with syncope or near-syncope were prospectively enrolled for 1 year at a single academic emergency department (ED). A 3-physician panel reviewed ED charts, hospital records, and telephone interview forms to identify predefined cardiac events. The primary outcome included all 14-day, predefined cardiac events including arrhythmia, myocardial ischemia, and structural heart disease. RESULTS: Of 592 eligible patients, 477 (81%) provided informed consent. Direct telephone contact or admission/outpatient records were successfully obtained for 461 (97%) patients, who comprised the analytic cohort. There were 44 (10%) patients who experienced a 14-day cardiac event. Overall diagnostic yield of ECG testing was 4% (95% confidence interval 2% to 6%). For patients younger than 40 years, ECG testing had a diagnostic yield of 0% (95% confidence interval 0% to 3%) and was associated with a 10% frequency of abnormal findings. CONCLUSION: ECG testing in patients younger than 40 years did not reveal a cardiac cause of syncope and was associated with a significant frequency of abnormal ECG findings unrelated to syncope. Although our findings should be verified in larger studies, it may be reasonable to defer ECG testing in younger patients who have a presentation consistent with a benign cause of syncope.

Lack of evidence to support routine digital rectal examination in pediatric trauma patients.

BACKGROUND: Current advanced trauma life support guidelines recommend that a digital rectal examination (DRE) should be performed as part of the initial evaluation of all trauma patients. Our primary goal was to estimate the test characteristics of the DRE in pediatric patients for the following injuries: (1) spinal cord injuries, (2) bowel injuries, (3) rectal injuries, (4) pelvic fractures, and (5) urethral disruptions. METHODS: We conducted a nonconcurrent, observational, chart review study of a consecutive series of pediatric trauma patients. We enrolled all patients younger than 18 years seen in our ED from January 2003 to February 2005, for whom the trauma team was activated and who had a documented DRE. For each patient, we reviewed all available clinical documents in a computerized medical record system to identify the DRE findings followed by review of radiological reports, operative reports, and discharge summaries to identify specific injuries. RESULTS: Two hundred thirteen patients met our selection criteria and were included in the analysis. We identified 3 patients with spinal cord injury (1% prevalence), 13 patients with bowel injury (6%), 5 patients with rectal injury (2%), 12 patients with a pelvic fracture (6%), and 1 patient with urethral disruption (0.5%). The DRE failed to diagnose (false-negative rate) 66% of spinal cord injuries, 100% of bowel injuries, 100% of rectal wall injuries, 100% of pelvic fractures, and 100% of urethral disruption injuries. CONCLUSIONS: The DRE has poor sensitivity for the diagnosis of spinal cord, bowel, rectal, bony pelvis, and urethral injuries. Our findings suggest that the DRE should not be routinely used in pediatric trauma patients.

Poor test characteristics for the digital rectal examination in trauma patients.

STUDY OBJECTIVE: Current advanced trauma life support guidelines recommend that a digital rectal examination be performed as part of the initial evaluation of all trauma patients. Our goal is to estimate the test characteristics of the digital rectal examination in trauma patients. METHODS: We conducted a retrospective medical record review study of consecutive trauma patients treated in our emergency department from January 2003 to February 2005 for whom the trauma team was activated and who had a documented digital rectal examination. RESULTS: One thousand four hundred one patients met our selection criteria and were included in the analysis. We estimated the composite sensitivity of the digital rectal examination (any abnormal finding) for detecting any of the index injuries to be 22.9% (95% confidence interval [CI] 16% to 30%) and the specificity to be 94.7% (95% CI 93% to 96%). The calculated sensitivity and specificity for the digital rectal examination were 37% (95% CI 23% to 50%) and 96% (95% CI 95% to 97%), respectively, for detection of spinal cord injury, 5.7% (95% CI 0% to 13%) and 98.9% (95% CI 98% to 99%) for detection of bowel injury, 33.3% (95% CI 0% to 87%) and 99.8% (95% CI 99% to 100%) for detection of rectal injury, 0% and 99.8% (95% CI 99% to 100%) for detection of pelvic fracture, and 20% (95% CI 0% to 55%) and 99% (95% CI 98% to 100%) for detection of urethral disruption. CONCLUSION: The digital rectal examination has poor sensitivity for the diagnosis of spinal cord, bowel, rectal, bony pelvis, and urethral injuries. Our findings suggest that the digital rectal examination should not be used as a screening tool for detecting injuries in trauma patients.

Blind urethral catheterization in trauma patients suffering from lower urinary tract injuries.

OBJECTIVES: The goals of our study were to review all cases of urethral and bladder trauma that presented to the University of California, Los Angeles (UCLA) Medical Center between January 1998 and August 2005 and determine (1) the clinical characteristics of patients with urethral and/or bladder injuries as well as the sensitivities of those clinical characteristics; (2) whether or not a blind attempt to insert a urethral catheter was performed; and (3) whether there is any evidence that a blind attempt to insert a urethral catheter worsened the initial urinary tract injury. METHODS: This is a retrospective chart review. RESULTS: The study cohort comprised 46 patients with a mean age of 30 years, including 36 men (78.2%) and 10 women (21.8%). Bladder tears were found in 33 patients, 10 patients had urethral lacerations, and 3 patients had combined bladder and urethral lacerations. The most sensitive finding for urinary bladder or urethral injury was the presence of gross hematuria in the urethral catheter (100%, 95% confidence interval [CI] 0.63-0.89). Blinded insertion of a urethral catheter was attempted in 30 (90.9%, 95% CI 0.75-0.98) patients who suffered from urinary bladder injury, 6 (50%, 95% CI 0.26-0.87) patients who suffered from urethral injury and 1 (33%, 95% CI 0.0-0.9) patient who suffered from a combined urinary bladder and urethral injuries. We did not find evidence that a blind attempt to insert a urethral catheter worsened the initial urinary injury. CONCLUSION: Gross hematuria in the urethral catheter was the most sensitive sign for the presence of a urethral or urinary bladder injury in our study cohort, and often the only sign of such an injury. We found no evidence that a blind attempt to insert a urethral catheter in patients suffering from urethral and or urinary bladder injuries worsened the initial injury. Larger studies will be needed to determine the safety of blind urethral catheterization in patients that are suspected to suffer from a lower urological trauma. It is our opinion that the current guidelines should be revised to better reflect the current knowledge, technologies, and clinical practice.

External validation of the San Francisco Syncope Rule.

STUDY OBJECTIVE: We externally validate the ability of the San Francisco Syncope Rule to accurately identify syncope patients who will experience a 7-day serious clinical event. METHODS: Patients who presented to a single academic emergency department (ED) between 8 am and 10 pm with syncope or near-syncope were prospectively enrolled. Treating physicians recorded the presence or absence of all San Francisco Syncope Rule risk factors. Patients were contacted by telephone at 14 days for a structured interview. A 3-physician panel, blinded to the San Francisco Syncope Rule score, reviewed ED medical records, hospital records, and telephone interview forms to identify predefined serious clinical events. The primary outcome was the ability of the San Francisco Syncope Rule to predict any 7-day serious clinical event. A secondary outcome was the ability of the San Francisco Syncope Rule to predict 7-day serious clinical events that were not identified during the initial ED evaluation. RESULTS: Of 592 eligible patients, 477 (81%) provided informed consent. Direct telephone contact or admission/outpatient records were successfully obtained for 463 (97%) patients. There were 56 (12%) patients who had a serious 7-day clinical event, including 16 (3%) who received a diagnosis after the initial ED evaluation. Sensitivity and specificity of the San Francisco Syncope Rule for the primary outcome were 89% (95% confidence interval [CI] 81% to 97%) and 42% (95% CI 37% to 48%), respectively, and 69% (95% CI 46% to 92%) and 42% (95% CI 37% to 48%), respectively, for the secondary outcome. Estimates of sensitivity were minimally affected by missing data and most optimistic assumptions for missing follow-up information. CONCLUSION: In this external validation cohort, the San Francisco Syncope Rule had a lower sensitivity and specificity than in previous reports.