Catastrophic Bleeding From Gastroduodenal Artery After Whipple Procedure Managed With Resuscitative Endovascular Balloon Occlusion of the Aorta.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is designed to control traumatic intra-abdominal or pelvic hemorrhage. There are few case reports of REBOA use in nontraumatic gastrointestinal (GI) hemorrhage. A 53-year-old man with pancreatic cancer status post Whipple procedure presented with GI hemorrhage from the gastroduodenal artery. Endoscopy and angioembolization were unsuccessful at stopping the hemorrhage. REBOA was used to stabilize the patient until definitive surgical control. REBOA is a potentially lifesaving measure in cases of massive abdominal or pelvic hemorrhage. REBOA can be used as an adjunct in unstable patients with GI bleeding until definitive GI, interventional radiology, or surgical control.

Evolution and Current Trends in the Management of Acute Appendicitis.

The treatment of appendicitis has evolved since the first appendectomy in the eighteenth century. It seems to have come full circle with nonoperative management in the era before frequent surgical interventions, to open surgical interventions, minimally invasive interventions, and now back to a renewed interest in nonoperative management of acute appendicitis. Scoring systems to help refine the diagnosis of acute appendicitis and advances in medical imaging have also changed the management of this condition. Scientific investigations into the effects the microbiome of the appendix plays in this disease process are also being considered.

Erratum: Asparagine bioavailability governs metastasis in a model of breast cancer.

This corrects the article DOI: 10.1038/nature25465.

Asparagine bioavailability governs metastasis in a model of breast cancer.

Using a functional model of breast cancer heterogeneity, we previously showed that clonal sub-populations proficient at generating circulating tumour cells were not all equally capable of forming metastases at secondary sites. A combination of differential expression and focused in vitro and in vivo RNA interference screens revealed candidate drivers of metastasis that discriminated metastatic clones. Among these, asparagine synthetase expression in a patient's primary tumour was most strongly correlated with later metastatic relapse. Here we show that asparagine bioavailability strongly influences metastatic potential. Limiting asparagine by knockdown of asparagine synthetase, treatment with l-asparaginase, or dietary asparagine restriction reduces metastasis without affecting growth of the primary tumour, whereas increased dietary asparagine or enforced asparagine synthetase expression promotes metastatic progression. Altering asparagine availability in vitro strongly influences invasive potential, which is correlated with an effect on proteins that promote the epithelial-to-mesenchymal transition. This provides at least one potential mechanism for how the bioavailability of a single amino acid could regulate metastatic progression.

The use of mass spectrometry to analyze dried blood spots.

Dried blood spots (DBS) typically consist in the deposition of small volumes of capillary blood onto dedicated paper cards. Comparatively to whole blood or plasma samples, their benefits rely in the fact that sample collection is easier and that logistic aspects related to sample storage and shipment can be relatively limited, respectively, without the need of a refrigerator or dry ice. Originally, this approach has been developed in the sixties to support the analysis of phenylalanine for the detection of phenylketonuria in newborns using bacterial inhibition test. In the nineties tandem mass spectrometry was established as the detection technique for phenylalanine and tyrosine. DBS became rapidly recognized for their clinical value: they were widely implemented in pediatric settings with mass spectrometric detection, and were closely associated to the debut of newborn screening (NBS) programs, as a part of public health policies. Since then, sample collection on paper cards has been explored with various analytical techniques in other areas more or less successfully regarding large-scale applications. Moreover, in the last 5 years a regain of interest for DBS was observed and originated from the bioanalytical community to support drug development (e.g., PK studies) or therapeutic drug monitoring mainly. Those recent applications were essentially driven by improved sensitivity of triple quadrupole mass spectrometers. This review presents an overall view of all instrumental and methodological developments for DBS analysis with mass spectrometric detection, with and without separation techniques. A general introduction to DBS will describe their advantages and historical aspects of their emergence. A second section will focus on blood collection, with a strong emphasis on specific parameters that can impact quantitative analysis, including chromatographic effects, hematocrit effects, blood effects, and analyte stability. A third part of the review is dedicated to sample preparation and will consider off-line and on-line extractions; in particular, instrumental designs that have been developed so far for DBS extraction will be detailed. Flow injection analysis and applications will be discussed in section IV. The application of surface analysis mass spectrometry (DESI, paper spray, DART, APTDCI, MALDI, LDTD-APCI, and ICP) to DBS is described in section V, while applications based on separation techniques (e.g., liquid or gas chromatography) are presented in section VI. To conclude this review, the current status of DBS analysis is summarized, and future perspectives are provided.

Isotope-labeled differential profiling of metabolites using N-benzoyloxysuccinimide derivatization coupled to liquid chromatography/high-resolution tandem mass spectrometry.

RATIONALE: An isotopic labeling strategy based on derivatizing amine-containing metabolites has been developed using light ((12) C6 ) and heavy ((13) C6 ) N-benzoyloxysuccinimide reagents for semi-targeted metabolomic applications. METHODS: Differentially labeled samples were combined and analyzed simultaneously by liquid chromatography/high-resolution tandem mass spectrometry (LC/HR-MS/MS) to compare relative amounts of amine-containing metabolites. The selectivity of the reaction was determined with model metabolites and was shown to also be applicable to thiol and phenol moieties. The potential for relative quantitation was evaluated in cell extracts and the method was then applied to quantify metabolic perturbations occurring in human cultured cells under normal vs. oxidative stress conditions. RESULTS: A total of 279 derivatized features were detected in HL60 cell extracts, 77 of which yielded significant concentration changes upon oxidative stress treatment. Based on accurate mass measurements and MS/MS spectral matching with reference standard solutions, 10 metabolites were clearly identified. Derivatized compounds were found to have diagnostic fragment ions from the reagent itself, as well as structurally informative ions useful for metabolite identification. CONCLUSIONS: This simple derivatization reaction can be applied to the relative quantitation of amine-, thiol- and phenol-containing compounds, with improved sensitivity and chromatographic peak shapes due to the increased hydrophobicity of polar metabolites not readily amenable to reversed-phase LC/MS analysis.

[Sample preparation and bioanalysis in mass spectrometry]. / Préparation d'échantillon et bioanalyse en spectrométrie de masse.

The quantitative analysis of compounds of clinical interest of low molecular weight (<1000 Da) in biological fluids is currently in most cases performed by liquid chromatography-mass spectrometry (LC-MS). Analysis of these compounds in biological fluids (plasma, urine, saliva, hair...) is a difficult task requiring a sample preparation. Sample preparation is a crucial part of chemical/biological analysis and in a sense is considered the bottleneck of the whole analytical process. The main objectives of sample preparation are the removal of potential interferences, analyte preconcentration, and converting (if needed) the analyte into a more suitable form for detection or separation. Without chromatographic separation, endogenous compounds, co-eluted products may affect a quantitative method in mass spectrometry performance. This work focuses on three distinct parts. First, quantitative bioanalysis will be defined, different matrices and sample preparation techniques currently used in bioanalysis by mass spectrometry of/for small molecules of clinical interest in biological fluids. In a second step the goals of sample preparation will be described. Finally, in a third step, sample preparation strategies will be made either directly ("dilute and shoot") or after precipitation.

Two hospitals with 1 trauma system: a joint approach to the care of the injured patient.

BACKGROUND: Trauma centers are closing at an alarming rate, but the need for trauma care persists. This article shows the sustainability and feasibility of a joint trauma system whereby 2 university-affiliated hospitals function as a single trauma center system in a moderate-sized city. METHODS: Since 1994, 3 days per week, trauma patients are transported by emergency medical services (EMS) to hospital A. The other 4 days they are transported to hospital B. Trauma registry data from 1994 to 2008 were analyzed. Cost data were also examined. RESULTS: The joint system admitted 28,338 trauma patients. On each center's nontrauma days, trauma team activation was required infrequently. The 2 centers share costs; they perform joint outreach, educational training, and quality control. The joint trauma system has been sustained since 1994. CONCLUSIONS: Two hospitals functioning as a single trauma center system is a viable model of care for injured patients in a moderate-sized city with mostly blunt trauma.

Venous thromboembolic disease in trauma and surveillance ultrasonography.

BACKGROUND: The literature reports a wide variation in the incidence of venous thromboembolic (VTE) disease in trauma patients. The performance of routine surveillance venous duplex ultrasound of bilateral lower extremities is controversial. Furthermore, recent examinations of the national trauma databank registry have suggested that routine duplex surveillance is associated with higher deep venous thrombosis (DVT) detection rates. MATERIALS AND METHODS: We examined the incidence and risk factors for VTE disease in 2827 trauma patients admitted over a 2-y period to a state-verified level I trauma center. Detailed chart review was carried out for patients with VTE disease. We then evaluated the effects of a routine bilateral lower extremity duplex surveillance guideline on VTE detection in the subset of injury patients admitted to the trauma service. RESULTS: We found an approximately 2% incidence of venous thromboembolic disease in a mostly blunt trauma population. Amongst patients with VTE disease, the most common risk factors were obesity and significant head injury. We then evaluated the 998 patients with injury who were admitted to the trauma service 1 y before and after surveillance guideline implementation. Despite a nearly 5-fold increase in the number of duplex scans, with a substantial increase in cost, we found no significant difference in the incidence of DVT. CONCLUSIONS: Our preliminary data argue against the use of routine duplex surveillance of lower extremities for DVT in trauma patients. A larger, prospective analysis is necessary to confirm these findings.

Use of recombinant factor VILa in Operation Iraqi Freedom and Operation Enduring Freedom: survey of Army surgeons.

Military physicians are using recombinant factor VIIa (rFVIIa) in Iraq and Afghanistan to help stop life-threatening hemorrhage in trauma patients. We constructed a questionnaire and surveyed Army general surgeons deployed to Iraq and/or Afghanistan about their predeployment experience, deployment experience, and projected postdeployment practice regarding rFVIIa usage. Most surgeons had rFVIIa available during their deployment (65%). The drug was used with varying frequency and subjective therapeutic effect. A majority of surgeons (79%) were unaware of any guideline or policy governing the use of rFVIIa. Seventy percent of respondents would use the drug in their future practice. Deployed surgeons generally have positive attitudes regarding the use of rFVIIa, but greater guidance and outcome measures are needed.

Ultra-fast quantitation of saquinavir in human plasma by matrix-assisted laser desorption/ionization and selected reaction monitoring mode detection.

We present herein an ultra-fast quantitative assay for the quantitation of saquinavir in human plasma, without prior chromatographic separation, with matrix-assisted laser desorption/ionization using the selected reaction monitoring quantitation mode (MALDI-SRM/MS). The method was found to be linear from 5 to 10,000 ng/ml using pentadeuterated saquinavir (SQV-d5) as an internal standard, and from 5 to 1000 ng/ml using reserpine as internal standard (IS). Accuracy and precision were in the range of 101-108%, 3.9-11% with SQV-d5 and in the range 93-108%, 3.5-15% with reserpine. Plasma samples (250 microl) were extracted with a mixture of ethyl acetate/hexane. MALDI spotting of the extract was automated using electrodeposition and the dried droplet method using alpha-cyano-4-hydroxycinnamic acid (CHCA) as matrix. A 96 spots MALDI plate was prepared within 20 min in a fully unattended manner. Each sample was spotted four times and quantitation was based on the average of their analyte/IS area ratio. Samples were analyzed on a triple quadrupole linear ion trap (QqQ(LIT)) equipped with a high repetition laser source (1000 Hz). The analysis time of one sample was approximately 6 s, therefore 96 samples could be analyzed in less than 10 min. With liquid-liquid extraction sample preparation no significant matrix effects were observed. Moreover, the assay showed sufficient selectivity for samples to be analyzed at the lower limit of quantification (LLOQ) in the presence of other antiretroviral drugs, without prior chromatographic steps. In parallel, to assess the selectivity of the assay with real samples, a liquid chromatography (LC)-SRM/MS method was developed and a cross validation with clinical samples was successfully performed.

Abdominal wall endometriosis: a surgeon's perspective and review of 445 cases.

BACKGROUND: Abdominal wall endometriosis (AWE) is defined as endometrial tissue superficial to the peritoneum. AWE often is misdiagnosed and referred to surgeons for treatment. We performed a systematic review of published cohorts to quantify demographics, symptoms, and outcomes of patients having AWE. METHODS: An English language PubMed search from January 1951 to August of 2006 was conducted using several search terms for endometrioma. CONCLUSIONS: Twenty-nine articles describing 455 patients were identified and met inclusion criteria. The pooled mean age was 31.4 years. Ninety-six percent presented with a mass, 87% presented with pain, and 57% presented with cyclic symptoms. AWE was associated with a caesarian scar or hysterectomy in 57% and 11% of cases, respectively. The interval from index surgery to presentation was 3.6 years. Recurrence after resection was 4.3%. The most common presentation of AWE is the development of a painful mass after uterine surgery. Surgical treatment appears to result in a cure more than 95% of the time.

Use of rFVIIa in the trauma setting--practice patterns in United States trauma centers.

Much excitement has been generated regarding the off label use of recombinant factor VIIa (rFVIIa) in the severely injured trauma patient. The purpose of our study is 3-fold: 1) describe the type of centers that use rFVIIa, 2) determine which centers use the drug more frequently, and finally 3) investigate how this drug is being administered at trauma centers. A survey was mailed or e-mailed to 435 trauma centers (Level I and II) throughout the nation. One hundred fifty-six surveys were returned. American College of Surgeons (ACS) verification and trauma Level I designation were independent predictors of rFVIIa use (odds ratio [OR] 3.74 and 5.40, P < 0.05). High users of rFVIIa were defined as those centers that had above median usage of the drug. Level I centers accounted for 67 per cent of the high users. Only the number of fellowship-trained trauma surgeons and trauma volume predicted high usage of rFVIIa (OR 1.38 and 14.09, P < 0.05). Trauma volume predicted whether or not Factor VII users implemented a protocol based approach to administration of the drug (OR 6.57, P < 0.05). Most protocols incorporated packed red blood cells (74%) before giving rFVIIa. The dose of 90 mcg/kg was exceeded in 34 per cent of centers, and 3 per cent used the 200 mcg/kg dose. High volume Level I trauma centers use rFVIIa more frequently and are more likely to use a systematic approach to its administration. However, there is no standardized approach to rFVIIa administration in United States trauma centers.

Transperineal resection of a retroperitoneal liposarcoma presenting as a perineal mass.

BACKGROUND: Liposarcomas can present as giant liposarcomas in the retroperitoneal position. CASE: A healthy woman presented with a large recurrent proboscis-type mass at the left gluteus and underwent a transperineal resection of the mass. The patient tolerated the procedure well and was discharged after a short hospitalization. CONCLUSION: Once invasion into adjacent structures has been ruled out, a transperineal resection of giant retroperitoneal liposarcomas can be performed.

Aneurisma gigante no topo da artéria basilar: relato de caso operado sob hipotermia e parada circulatória / Giant basilar artery aneurism operated on with hypothermia and circulatory arrest. Case report

Os aneurismas gigantes da artéria basilar constituem um desafio para o neurocirurgião em virtude das limitações do acesso cirúrgico e da complexidade da patologia. A história natural da doença, no entanto, justifica procedimentos mais agressivos. É relatado um caso de aneurisma gigante no topo da artéria basilar, parcialmente trombosado, operado com parada circulatória e hipotermia. São discutidos os fundamentos da técnica e a indicação.