Tumor endothelial marker 8 (TEM8) expression in tumor and endothelial cells

Bibliography: p. 91-109Tumor endothelial marker 8 (TEM8) is highly expressed in tumor vasculature, but not in other endothelial cells including those involved in normal physiological angiogenesis such as wound healing and corpus luteum formation. It has not been reported whether this is due to some intrinsic characteristic of the tumor endothelium or secondary to tumor microenvironmental factors. Screening of TEM8 levels in various cancer and endothelial cell lines used in this project revealed variable transcript level. Changes in level of expression of TEM8 transcripts in human umbilical vein endothelial cells (HUVECs) were examined under the influence of such microenvironmental factors as hypoxia and vascular endothelial growth factor (VEGF), the most potent pro-angiogenic agent. While hypoxia dramatically increased the levels of TEM8 in HUVECs, VEGF seemed to do so only moderately. TEM8 mRNA levels were elevated in HUVECs co­cultured with some breast cancer cell lines including, Hs578T, MDA MB 468, MDA MB 453s, MDA MB 231 and MDA MB 436. Contrary to that however, HUVECs co-cultured with the breast cancer cell lines, SKBR3, MCF-7 and BT-474 had no significant changes in TEM8 transcription. Induction of TEM8 was due to direct cell-cell contact rather than to secretion of soluble factors by the tumor cells. Interestingly, the TEM8 inducing breast cancer cell lines have a more aggressive phenotype than the non-inducing group. TEM8 may therefore be a marker of aggressiveness in breast cancer. Overexpression of TEM8 in HUVECs led to more rapid endothelial cell growth and, in contrast down-regulating the gene by AdshRNA resulted in reduced cell growth. Together, these data suggest that endothelial cell expression of TEM8 is a function of the tumor microenvironment. Its up­regulation in tumor-associated endothelial cells encourages their growth

Spondylodiscitis caused by Prevotella intermedia: A case report and literature review

Background: Spondylodiscitis is commonly caused by Staphylococcus aureus. Anaerobic organisms are the causative agents in only 3–4% of cases. Diagnosis of anaerobic spondylodiscitis can be challenging due to their low virulence nature. Case description: We describe a rare case of spondylodiscitis caused by Prevotella intermedia managed with antibiotics and spinal instrumentation and highlight the challenges in diagnosis in such cases. Conclusion: Low virulent anaerobic spondylodiscitis can be difficult to diagnose. A high degree of suspicion is necessary and multiple attempts at pathogen identification, including possible open surgical biopsy may be required for diagnosis. A good prognosis is possible in appropriately managed cases. Keywords: Spondylodiscitis, Prevotella intermedia, Low virulent spinal infection, Instrumented fusio

Closed reduction of traumatic atlantoaxial rotatory subluxation with type II odontoid fracture

Background: Traumatic atlantoaxial rotatory subluxation (TAARS) in adults is rare. We present an uncommon case of traumatic atlantoaxial rotatory subluxation with an associated type II odontoid fracture in a neurologically-intact patient and describe a novel technique used for a successful closed reduction. Case description: A 20-year-old female presented with a decreased level of consciousness after being involved in a motor vehicle accident at highway speeds. A computed tomography (CT) demonstrated atlantoaxial rotatory subluxation and a type II odontoid fracture. CT angiography showed a left V3 vertebral dissection. She was neurologically intact on examination. A halo ring was applied and the patient successfully underwent closed reduction using traction and a novel transoral reduction technique described below. After closed reduction, a C1–C2 posterior instrumented fusion was performed. At 12-weeks follow-up, the patient was asymptomatic, neurologically intact with optimally-maintained cervical spine alignment. Conclusion: Prompt manual closed reduction can safely be achieved in adults using this novel transoral reduction technique, which we describe for the first time in this report

Closed reduction of traumatic atlantoaxial rotatory subluxation with type II odontoid fracture

Background: Traumatic atlantoaxial rotatory subluxation (TAARS) in adults is rare. We present an uncommon case of traumatic atlantoaxial rotatory subluxation with an associated type II odontoid fracture in a neurologically intact patient and describe a novel technique used for a successful closed reduction. Case description: A 20-year-old female presented with a decreased level of consciousness after being involved in a motor vehicle accident at highway speeds. A computed tomography (CT) demonstrated atlantoaxial rotatory subluxation and a type II odontoid fracture. CT angiography showed a left V3 vertebral dissection. She was neurologically intact on examination. A halo ring was applied and the patient successfully underwent closed reduction using traction and a novel transoral reduction technique described below.After closed reduction, a C1–C2 posterior instrumented fusion was performed. At 12-weeks follow-up, the patient was asymptomatic, neurologically intact with optimally maintained cervical spine alignment. Conclusion: Prompt manual closed reduction can safely be achieved in adults using this novel transoral reduction technique, which we describe for the first time in this report. Keywords: Case report, Traumatic atlantoaxial rotatory subluxation, Closed reduction, Type II odontoid fractur

Adaptation of the Wound Healing Questionnaire universal-reporter outcome measure for use in global surgery trials (TALON-1 study): mixed-methods study and Rasch analysis

BackgroundThe Bluebelle Wound Healing Questionnaire (WHQ) is a universal-reporter outcome measure developed in the UK for remote detection of surgical-site infection after abdominal surgery. This study aimed to explore cross-cultural equivalence, acceptability, and content validity of the WHQ for use across low- and middle-income countries, and to make recommendations for its adaptation.MethodsThis was a mixed-methods study within a trial (SWAT) embedded in an international randomized trial, conducted according to best practice guidelines, and co-produced with community and patient partners (TALON-1). Structured interviews and focus groups were used to gather data regarding cross-cultural, cross-contextual equivalence of the individual items and scale, and conduct a translatability assessment. Translation was completed into five languages in accordance with Mapi recommendations. Next, data from a prospective cohort (SWAT) were interpreted using Rasch analysis to explore scaling and measurement properties of the WHQ. Finally, qualitative and quantitative data were triangulated using a modified, exploratory, instrumental design model.ResultsIn the qualitative phase, 10 structured interviews and six focus groups took place with a total of 47 investigators across six countries. Themes related to comprehension, response mapping, retrieval, and judgement were identified with rich cross-cultural insights. In the quantitative phase, an exploratory Rasch model was fitted to data from 537 patients (369 excluding extremes). Owing to the number of extreme (floor) values, the overall level of power was low. The single WHQ scale satisfied tests of unidimensionality, indicating validity of the ordinal total WHQ score. There was significant overall model misfit of five items (5, 9, 14, 15, 16) and local dependency in 11 item pairs. The person separation index was estimated as 0.48 suggesting weak discrimination between classes, whereas Cronbach's α was high at 0.86. Triangulation of qualitative data with the Rasch analysis supported recommendations for cross-cultural adaptation of the WHQ items 1 (redness), 3 (clear fluid), 7 (deep wound opening), 10 (pain), 11 (fever), 15 (antibiotics), 16 (debridement), 18 (drainage), and 19 (reoperation). Changes to three item response categories (1, not at all; 2, a little; 3, a lot) were adopted for symptom items 1 to 10, and two categories (0, no; 1, yes) for item 11 (fever).ConclusionThis study made recommendations for cross-cultural adaptation of the WHQ for use in global surgical research and practice, using co-produced mixed-methods data from three continents. Translations are now available for implementation into remote wound assessment pathways