Biopharmaceutical study of nanosystems containing betulin for inhalation administration

Betulin, a triterpenoid present in birch bark, possesses a broad spectrum of biological activity. Its bioavailability is limited by low solubility in water whereas the shape and size of particles are not suited for administration via inhalation. One of the main drawbacks of inhalation preparations is low bioavailability because of the sedimentation of particles in the mouth. The present work was aimed at a biopharmaceutical study of nanosystems with betulin for administration via inhalation. Nanosystems were characterized by photon-correlation spectroscopy, differential scanning calorimetry, and x-ray powder diffraction. In addition, their dissolution profile was obtained by the Dissolution test. It is established that the obtained nanosystems with betulin exhibit high bioavailability, have optimal physicochemical properties for inhalation administration, and ensure deposition of betulin in the lower part of the respiratory tract.     

Functional and prognostic significance of the genomic amplification of frizzled 6 (FZD6) in breast cancer

Frizzled receptors mediate Wnt ligand signalling, which is crucially involved in regulating tissue development and differentiation, and is often deregulated in cancer. In this study, we found that the gene encoding the Wnt receptor frizzled 6 (FZD6) is frequently amplified in breast cancer, with an increased incidence in the triple‐negative breast cancer (TNBC) subtype. Ablation of FZD6 expression in mammary cancer cell lines: (1) inhibited motility and invasion; (2) induced a more symmetrical shape of organoid three‐dimensional cultures; and (3) inhibited bone and liver metastasis in vivo. Mechanistically, FZD6 signalling is required for the assembly of the fibronectin matrix, interfering with the organization of the actin cytoskeleton. Ectopic delivery of fibronectin in FZD6‐depleted, triple‐negative MDA‐MB‐231 cells rearranged the actin cytoskeleton and restored epidermal growth factor‐mediated invasion. In patients with localized, lymph node‐negative (early) breast cancer, positivity of tumour cells for FZD6 protein identified patients with reduced distant relapse‐free survival. Multivariate analysis indicated an independent prognostic significance of FZD6 expression in TNBC tumours, predicting distant, but not local, relapse. We conclude that the FZD6–fibronectin actin axis identified in our study could be exploited for drug development in highly metastatic forms of breast cancer, such as TNBC. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Comparative evaluation of three JAK2V617F mutation detection methods

The correlation of JAK2V617F with a proportion of chronic myeloproliferative disorders has generated numerous studies focused on the development of molecular-based assays for JAK2V617F detection. The current parallel study comparatively evaluated 3 JAK2V617F molecular detection methods. Genomic DNA from blood or bone marrow was assayed by 3 laboratories using allele-specific polymerase chain reaction (AS-PCR) or kit-based restriction fragment length polymorphism methods, which used polyacrylamide gel or capillary electrophoresis analysis. In addition, samples were sequenced in 2 of the laboratories. Results found 100% concordance among the 3 methods, with analytic sensitivities of 5% for both kit methods and 0.01% for AS-PCR. The kitbased assays detect JAK2V617F with equal sensitivity regardless of analysis method, and, despite greater sensitivity of AS-PCR, all 3 methods yielded 100% concordant results for this 36-sample set. Consistent with other reports, direct sequencing was insufficiently sensitive to serve as an initial diagnostic tool for JAK2V617F detection.     

The MHC influences NK and NKT cell functions associated with immune abnormalities and lifespan

The lifespans of H-2 congenic mice differ significantly. The B10.AKM (H-2m) strain has a median survival time (MST) of 15 months, whereas the B10.BR (H-2k) strain has an MST of 24 months. It was previously shown that B10.AKM mice at 13-15 months of age have immunological function comparable to those of B10.BR mice at 22-26 months of age. These functions include: a low proliferative response, reduced levels of intracellular calcium release [Ca2+]i, and an increase in the frequency of memory helper T-cells (CD4+ CD44hiCD45RBlo). In this report similar deficiencies were demonstrated in B10.AKM mice at 2-4 months of age and show that activated spleen NK1.1+CD4+ T (NKT) cells from young B10.AKM mice produce a significantly higher level of IL-4 but a lower level of IFN-gamma as compared to NKT cells from B10.BR mice of the same age. Also, the cytotoxic activity of natural killer (NK) cells from spleens of young (2-4 months) as well as adult (12-16 months) B10.AKM mice is significantly lower (P < 0.01) than that of NK cells from B10.BR mice. These findings suggest that the NKT activity in young B10.AKM mice is a factor for the early onset of immune dysfunction leading to a shorter lifespan.     

Intralobar pulmonary sequestration: Value of aortography and pulmonary arteriography

Twelve patients with plain roentgenographic findings of intralobar pulmonary sequenstration were evaluated with aortography and, in most instances, pulmonary arteriography. Correlative criteria from aortography and pulmonary arteriography permit a precise diagnosis to be made. Pulmonary infections must be differentiated from intralobar pulmonary sequestration because treatment for the latter should be surgical.     

Direct versus indirect transfer for traumatic brain injury to James Cook University Hospital: a retrospective study

IntroductionPatients with traumatic brain injury are referred to the neurosurgical unit at James Cook University Hospital, Middlesbrough, either from local accident and emergency departments (direct transfer from the scene) or from other hospitals (indirect transfer). This study looked at the outcome in both groups.Material and methodsThis was a retrospective observational study using trauma audit research network data for patients treated for traumatic brain injury at the neurosurgery department at the neurosurgical unit at James Cook University Hospital.ResultsA total of 356 patients with traumatic brain injury were admitted under the care of neurosurgeons; 143 (40%) of these patients had a neurosurgical procedure. Of the patients undergoing a neurological procedure, 111 patients were transferred directly while 32 were indirect transfers; 213 patients were managed conservatively. Of those managed conservatively, 165 were transferred directly while 48 were indirect transfers.We compared the length of hospital stay and Glasgow Outcome Scale score for the patients based on whether they were conservatively managed or required surgery in the direct and indirect transfer groups. The difference in the length of stay in the surgical and conservative groups following direct and indirect transfer was insignificant (p = 0.07). The time to the operation in direct and indirect transfer was also not statistically significant (p = 0.06).ConclusionPatients are as safe, if not safer, by reaching the nearest trauma unit with facilities for resuscitation and imaging.     

Correlation of MR imaging findings with intraoperative findings after cervical spine trauma

BACKGROUND AND PURPOSE: There are limited data correlating MR imaging and anatomic findings of ligamentous injury in cervical spine trauma. This study compares acute MR imaging with surgical observations of disk/ligamentous injury after blunt cervical trauma. MATERIALS AND METHODS: Consecutive patients with acute cervical spine trauma who underwent preoperative MR imaging and surgery from 1998 to 2001 were identified. MR imaging was obtained within 48 hours of injury for most patients. All scans included sagittal T1, T2 fat-saturated, and short tau inversion recovery sequences. At surgery, extent of injury at the operated level was recorded on a standardized form for either anterior or posterior structures or both depending upon the operative approach. MR examinations were separately evaluated by 2 readers blinded to the intraoperative findings. Radiologic and surgical findings were then correlated. RESULTS: Of 31 patients, an anterior surgical approach was chosen in 17 patients and a posterior approach in 13 patients. In one patient anterior and posterior approaches were utilized. Seventy-one percent of patients had spinal cord injury on MR imaging. MR imaging was highly sensitive for injury to disk (93%), posterior longitudinal ligament (93%), and interspinous soft tissues (100%), but it was less sensitive for injury to the anterior longitudinal ligament (71%) and ligamentum flavum (67%). For most ligamentous structures, there was limited agreement between specific MR imaging findings and injury at surgery. CONCLUSION: In acute cervical spine trauma, MR imaging has moderate to high sensitivity for injury to specific ligamentous structures but limited agreement between specific MR imaging findings and injury at surgery. MR imaging may overestimate the extent of disruptive injury when compared with intraoperative findings, with potential clinical consequences.     

The impact of surgeon volume on patient outcome in spine surgery: a systematic review

Purpose

Recently, strategies aimed at optimizing provider factors have been proposed, including regionalization of surgeries to higher volume centers and adoption of volume standards. With limited literature promoting the regionalization of spine surgeries, we undertook a systematic review to investigate the impact of surgeon volume on outcomes in patients undergoing spine surgery.

Methods

We performed a systematic review examining the association between surgeon volume and spine surgery outcomes. To be included in the review, the study population had to include patients undergoing a primary or revision spinal procedure. These included anterior cervical discectomy and fusion (ACDF), anterior/posterior cervical fusion, laminectomy/decompression, anterior/posterior lumbar decompression with fusion, discectomy, and spinal deformity surgery (spine arthrodesis).

Results

Studies were variable in defining surgeon volume thresholds. Higher surgeon volume was associated with a significantly lower risk of postoperative complications, a lower length of stay (LOS), lower cost of hospital stay and a lower risk of readmissions and reoperations/revisions.

Conclusions

Findings suggest a trend towards better outcomes for higher volume surgeons; however, further study needs to be carried out to define objective volume thresholds for individual spine surgeries for surgeons to use as a marker of proficiency.