Total Synthesis of Cyanobactin Natural Product Balgacyclamide B.

Balgacyclamide A-C are a family of cyanobactin natural products isolated from freshwater cyanobacteria Microcystis aeruginosa. These macrocyclic peptides are characterized by their oxazoline-thiazole core, their 7 or 8 stereocenters, and their antiparasitic activities. Balgacyclamide B is known for its activity towards Plasmodium falciparum chloroquine-resistant strain K1, Trypanosoma brucei rhodesiense, and Leishmania donovani. In this report, the first total synthesis of Balgacyclamide B is described in a 17-steps pathway and a 2 % overall yield. The synthetic pathway toward balgacyclamide B can be adapted for the future syntheses of balgacyclamide A and C. In addition, a brief history background of oxazolines syntheses is shown to emphasize the importance of the cyclization conditions used to interconvert or retain configuration of ß-hydroxy amides via dehydrative cyclization.

Characteristics of Dog Bites in Arkansas.

OBJECTIVE: Dog bite injuries are encountered frequently in emergency departments and can cause significant morbidity. The objective of this study was to explore the associations between the multiple variables at play during these occurrences (eg, the patient's age, the bite location, the bite severity, the dog's relationship with the patient, the breed of dog). METHODS: This two-institution study collected and analyzed dog bite data from Arkansas' only Level I trauma centers. The charts of 740 patients were included in our retrospective chart review. The chart review extracted data, including each individual patient's age, sex, dog bite location, and dog bite severity, as well as the patient's relationship to the dog and the dog's breed. To determine the relation between and among variables, contingency tables were created and analyzed to determine odds ratios (ORs) and confidence intervals (CIs). In addition, standard t tests were used in statistical comparisons of means and proportions. RESULTS: Of the 740 patient charts reviewed, 574 were for patients who presented to Arkansas Children's Hospital and 166 were for patients who presented to the University of Arkansas for Medical Sciences. Of the patients across both institutions, 267 (37.1%) required some form of repair, with 225 (30.4%) receiving closure within the emergency department and 42 (6.7%) requiring an operative intervention. Among children, those younger than age 5 years were >8 times as likely to require an operative repair (OR 8.1, 95% CI 2.77-23.58, P < 0.0001), >4 times as likely to be bitten on the head and neck (OR 4.30, 95% CI 3.00-6.16, P < 0.0001), and ≤3 times as likely to be bitten by a family dog (OR 2.97, 95% CI 2.10-4.20, P < 0.0001). Conversely, children older than age 12 years were >3 times as likely to be bitten on an extremity (OR 3.43, 95% CI 2.08-5.65, P < 0.0001). CONCLUSIONS: The results of this retrospective review are aligned mostly with the general trends found in previous national and global studies, supporting the notion that family dogs represent a more significant threat than often is realized and that, among the breeds identified, pit bulls are proportionally linked with more severe bite injuries. Our data further validate previous studies that note an increased risk of bites and bite severity in children younger than 5 years. In addition, our data show that bites to the head and neck occurred more frequently among children younger than 5 years than among older children, and that boys younger than 5 years were bitten more frequently than girls.

Platelet adenosine diphosphate inhibition in trauma patients by thromboelastography correlates with paradoxical increase in platelet dense granule content by flow cytometry.

BACKGROUND: The mechanism of platelet dysfunction in acute traumatic coagulopathy is unknown. Traumatic brain injury is hypothesized as a cause, while some investigators presume platelets become "exhausted." We hypothesized that platelet hyperstimulation and consumption resulting from trauma leads to decreased platelet function secondary to depletion of platelet granules. METHODS: Twenty-five trauma patients were divided into traumatic brain injury and no traumatic brain injury groups. Healthy volunteers served as controls. All had thromboelastography with platelet mapping and flow cytometric assays of mepacrine performed. Mepacrine uptake in unstimulated platelets was used for quantification of platelet content of dense granules. RESULTS: Twelve patients with traumatic brain injury and 13 patients without traumatic brain injury were enrolled. Twenty-one trauma patients showed adenosine diphosphate inhibition (>30%) on thromboelastography with platelet mapping compared with the healthy volunteers who served as controls (P < .01). Mepacrine assay showed a difference in mean fluorescent intensity for all trauma patients of 4,259 ± 1,341 compared with controls of 3,143 ± 709 (P = .044), correlating with greater quantities of dense granules. Neither adenosine diphosphate inhibition nor average difference in mean fluorescent intensity between traumatic brain injury and no traumatic brain injury groups were significant (P = .2). CONCLUSION: Trauma patients maintain their dense granule, contradicting the theory of platelet granule exhaustion as the etiology for platelet dysfunction in traumatic brain injury.

Failure of the Platelet Function Assay (PFA)-100 to detect antiplatelet agents.

BACKGROUND: Antiplatelet therapy is a complicating factor in patients with traumatic brain injuries (TBI), as well as those with hemorrhagic cerebrovascular accidents (CVAs). Platelet Function Assay (PFA)-100 is a coagulation device that can detect platelet dysfunction caused by aspirin and adenosine diphosphate inhibition. Our retrospective study reviewed the effectiveness of PFA-100 in detecting platelet dysfunction caused by aspirin and clopidogrel and determined its clinical importance. METHODS: All patients with PFA-100 tests from January 2013 to February 2014 were collected. Diagnoses indicative of a TBI or CVA were chosen for analysis. Patients with a normal PFA-100 indicating no platelet dysfunction but with documented aspirin and/or clopidogrel use were selected. An extensive chart review was performed to determine the relevance to their clinical care. RESULTS: A total of 475 patients were evaluated with a PFA-100 from January 2013 to February 2014. PFA-100 detected platelet dysfunction as the result of pre-injury use of antiplatelet agents in TBI and CVA patients with a sensitivity of only 48.6% and a specificity of 74.8%. Had these antiplatelet medications been known during initial workup, these patients would have had a change in management that may have impacted their outcomes. CONCLUSION: Despite its common usage, the PFA-100 is an unreliable tool to assist in the management of TBI and CVA patients. Additional investigation into alternative methods for detecting platelet dysfunction is warranted.

Trauma transfers and definitive imaging: patient benefit but at what cost?

Many patients undergo computed tomography (CT) scan before transfer to definitive care. Despite this, studies are often repeated on arrival to the trauma center. We evaluated a policy to provide formal in-house interpretation of images performed at outside hospitals. A 3-month retrospective analysis was performed. Two groups were compared. Patients in the in-house interpretation (IHI) group underwent in-house interpretation of outside images. Those images not meeting criteria were placed in the comparison group without in-house radiologic interpretation. Demographics, CT scan data, billing and productivity loss, and extrapolated cancer risk reduction were analyzed. There were no significant differences in demographic or injury data. Fewer total CT scans were performed in the IHI group (223 vs. 320, P = 0.04). The IHI group underwent fewer repeated CT scans (25 vs. 62, P = 0.02; odds ratio [OR], 0.53). Fewer patients were exposed to repeat CT scans (17 vs. 32; OR, 0.48). Total hospital billings decreased by $188,285 ($4,592/patient) in the IHI group. Uncaptured work relative value units totaled 152.19 (3.71/patient) in the IHI group. Radiation exposure decreased by 8 per cent. Use of outside hospital imaging as the definitive evaluation of injured patients is safe and results in an overall decrease in radiation exposure and healthcare cost.

Experience with prothrombin complex for the emergent reversal of anticoagulation in rural geriatric trauma patients.

BACKGROUND: Therapeutic anticoagulation in the geriatric trauma population is increasingly common. Fresh frozen plasma, while the criterion standard for correction, has limited availability and associated transfusion risks. We examined our use of prothrombin complex concentrate for immediate reversal of therapeutically anticoagulated geriatric trauma patients. METHODS: This was a 1-year, retrospective review of 25 geriatric trauma patients who received either fresh frozen plasma alone or prothrombin complex concentrate and met the inclusion criteria of age >55 years, current warfarin use, and an admission international normalized ratio of >1.5. Fifteen patients received prothrombin complex concentrate and 10 patients received fresh frozen plasma alone. We examined demographics, laboratory values, and blood product use. RESULTS: The mean ages were similar (77 vs 80 years). Patients had similar mean Injury Severity Score (19.1 vs 19.2). Survivor duration of hospital stay (7.7 vs 9.5; P = .37) and duration of stay in the intensive care unit (4.4 vs 7.1; P = .25) trended positively in the prothrombin complex concentrate group. The prothrombin complex concentrate group received fewer units of fresh frozen plasma (1.6 [range, 0-6] vs 2.7 [range, 2-4]; P = .05), with a greater decrease in international normalized ratio (51% vs 43%; P = .05). Six patients (40%) in the prothrombin complex concentrate group avoided fresh frozen plasma transfusion altogether. CONCLUSION: Prothrombin complex may be used safely and effectively to reverse emergently anticoagulation in geriatric trauma patients.