Long-Term Follow-Up of Open Gustilo-Anderson IIIB Fractures Treated With an Adjuvant Local Antibiotic Hydroxyapatite Bio-Composite.

Background Open fractures associated with significant tissue loss are complex and present challenges in management; they are associated with poor outcomes such as infection, non-union or amputation. This study aimed to evaluate outcomes of using an adjuvant local antibiotic hydroxyapatite bio-composite in the management of open Gustilo-Anderson IIIB fractures with up to eight years of follow-up. Methods This was a retrospective study. A total of 81 patients with Gustilo-Anderson IIIB fractures treated with "fix and flap" limb reconstruction with adjuvant local antibiotic therapy using a bio-composite carrier were reviewed. Results  The mean follow-up time for all the patients, at the time of data collection, was 55.8 months. Union was achieved in 96% with a limb salvage rate of 96.3% and a deep infection rate of 3.7%. Conclusion The use of local antibiotic therapy, together with a combined orthoplastic "fix and flap" approach for Gustilo-Anderson IIIB open fractures, was found to be associated with a very low rate of metalwork infection and high union and limb salvage rates. Future studies should include some functional and quality of life outcome measures to see the efficacy of this method.

Description and efficacy of a response-based "QUAD" cyclical hypofractionated palliative-intent radiation protocol in dogs with macroscopic solid tumours: 108 cases.

Palliative-intent radiation therapy can alleviate pain and clinical signs in dogs with cancer, but optimal fractionation scheme is unknown. The objective of this retrospective case series is to evaluate clinical benefit, objective response, adverse effects, and outcomes in 108 dogs with macroscopic solid tumours treated with a cyclical "QUAD" hypofractionated palliative-intent radiation therapy protocol. Median QUAD dose was 14 Gy (14-16 Gy). Median total dose was 28 Gy (14-48 Gy). Clinical benefit rate was 93%, with median onset of subjective palliation 21 days after the first QUAD, lasting a median of 134 days. Tumour volumetric objective response was assessed with CT prior to the third QUAD in 36 dogs, with stable disease in 24 dogs (67%) and partial response in 9 dogs (25%). Sinonasal and oral were the most common tumour locations in 32 and 30 dogs, respectively. Median progression-free survival was 153 days (95% CI 114-200). Median overall survival was 212 days (95% CI 152-259). Number of QUAD cycles completed, clinical benefit achieved, anti-inflammatory received, total radiation dose, time to maximum clinical benefit, and response duration were positively associated with progression-free and overall survival. Acute toxicities were observed in 15 dogs (14%) with 3 high-grade (grade 3) toxicities (3%). Low-grade (grade 1 and 2) late skin and ocular toxicities were observed in 31 dogs (29%), predominantly leukotrichia, alopecia, keratoconjunctivitis sicca, and cataracts. This report demonstrates that QUAD radiation is an alternative protocol to be considered for palliation of dogs with inoperable or advanced stage solid tumours.

Medical Marijuana Use for Cancer-Related Symptoms among Floridians: A Descriptive Study.

Background: Thirty-six states, including Florida, have legalized marijuana for medical and/or recreational use, yet how it is used and perceived by persons with cancer is not well understood. Objectives: The purpose of this study was to identify patterns of use, perceived benefits, and side effects of medical marijuana (MMJ) among cancer patients in Florida. Methods: For this descriptive, cross-sectional study, anyone residing within the state of Florida who was diagnosed or treated for a malignancy within the last five years and had used MMJ was eligible. An online survey containing questions about dosing, side effects, perceived benefits, and barriers to use was used. Descriptive statistics including frequencies, percentages, means, and standard deviations were used to analyze quantitative data. Responses to open-ended questions were coded and categorized. Results: Sleep (n = 112), pain (n = 96), and anxiety (n = 82) were the most common symptoms participants used MMJ to relieve and overall felt it was highly effective. MMJ was well tolerated with a minority (10.3%) reporting any adverse effects. Cost was the most frequent barrier reported by participants (42.8%). A variety of legal, bureaucratic, and system-related barriers were described. Conclusion: Participants perceived MMJ to be helpful in alleviating cancer symptoms. They held negative perceptions of the way MMJ is implemented and integrated into their oncology treatment plan. Enhanced communication and patient/provider education on MMJ are needed to inform patient decision making.

Relationship between histological tumor margins and magnetic resonance imaging signal intensities in brain neoplasia of dogs.

BACKGROUND: Intracranial neoplasia is relatively common in dogs and stereotactic radiotherapy, surgical debulking, or both, are the most successful treatment approaches. A key component of treatment planning involves delineating tumor margin on magnetic resonance imaging (MRI) examinations. How MRI signal intensity alterations relate to histological tumor margins is unknown. OBJECTIVES: Directly compare histological brain sections to MRI sequence images and determine which sequence alteration best correlates with tumor margins. ANIMALS: Five dogs with glioma, 4 dogs with histiocytic sarcoma, and 3 dogs with meningioma. METHODS: Retrospective cohort study. Histological brain sections were registered to in vivo MRI scan images obtained within 7 days of necropsy. Margins of signal intensity alterations (T2-weighted, fluid-attenuating inversion recovery [FLAIR], T1-weighted and contrast enhancement) were compared directly to solid tumor and surgical margins identified on histology. Jacquard similarity metrics (JSM) and cross-sectional areas were calculated. RESULTS: In glioma cases, margins drawn around T2-weighted hyperintensity were most similar to surgical margins (JSM, 0.66 ± 0.17) when compared to other sequences. In both meningioma (JSM, 0.57 ± 0.21) and histiocytic sarcoma (JSM, 0.75 ± 0.11) margins of contrast enhancement were most similar to surgical margins. CONCLUSIONS AND CLINICAL IMPORTANCE: Signal intensities correspond to tumor margins for different tumor types and facilitate surgical and radiation therapy planning using MRI images.

The effect of cannabidiol on canine neoplastic cell proliferation and mitogen-activated protein kinase activation during autophagy and apoptosis.

Low tetrahydrocannabinol Cannabis sativa products, also known as hemp products, have become widely available and their use in veterinary patients has become increasingly popular. Despite prevalence of use, the veterinary literature is lacking and evidence-based resource for cannabinoid efficacy. The most prevailing cannabinoid found in hemp is cannabidiolic acid (CBDA) and becomes cannabidiol (CBD) during heat extraction; CBD has been studied for its direct anti-neoplastic properties alone and in combination with standard cancer therapies, yielding encouraging results. The objectives of our study were to explore the anti-proliferative and cell death response associated with in vitro treatment of canine cancer cell lines with CBD alone and combination with common chemotherapeutics, as well as investigation into major proliferative pathways (eg, p38, JNK, AKT and mTOR) potentially involved in the response to treatment with CBD. CBD significantly reduced canine cancer cell proliferation far better than CBDA across five canine neoplastic cell lines when treated with concentrations ranging from 2.5 to 10 µg/mL. Combinatory treatment with CBD and vincristine reduced cell proliferation in a synergistic or additive manner at anti-proliferative concentrations with less clear results using doxorubicin in combination with CBD. The cellular signalling effects of CBD treatment, showed that autophagy supervened induction of apoptosis and may be related to prompt induction of ERK and JNK phosphorylation prior to autophagy. In conclusion, CBD is effective at hindering cell proliferation and induction of autophagy and apoptosis rapidly across neoplastic cell lines and further clinical trials are needed to understand its efficacy and interactions with traditional chemotherapy.

Response and outcome following radiation therapy of macroscopic canine plasma cell tumours.

Thirty dogs with macroscopic plasma cell tumours (PCTs) were treated with radiation therapy (RT). Twelve patients were treated with palliative-intent prescriptions (range, 4-10 Gy/fraction (median, 7 Gy/fraction) for a total dose of 20 to 35 Gy (median total dose 30 Gy). Eighteen patients received definitive-intent prescriptions (range, 3.0-4.2 Gy/fraction (median, 3 Gy/fraction) for a total dose of 42 to 54 Gy (median total dose 48 Gy). Involved sites included the oral cavity, skin, multiple myeloma (MM)-associated lytic bone lesions, bone (solitary osseous plasmacytoma; SOP), nasal cavity, larynx, retrobulbar space, lymph node and rectum. Ninety-five percent of evaluable dogs had a complete (CR; 16/22) or partial response (PR; 5/22). Patients with MM experienced significant analgesia. The median progression-free survival (PFS) was 611 days (range: 36-2001 days). Events in the non-MM cases included in-field progression (5/26, 19%) and disseminated disease (5/26, 19%). The median survival time (MST) for all dogs was 697 days (range: 71-2075 days), and when only non-MM cases were considered, MST was 771 days (range: 71-2075 days). Fourteen patients were alive without disease progression or had died of unrelated causes. Achievement of a PR was associated with an inferior PFS and MST as compared with CR. Palliative-intent RT was associated with inferior MST as compared with definitive-intent RT. RT is a useful therapeutic modality for PCTs and tumour responses are often complete and durable, with protracted survivals. The optimal radiation dose and schedule are yet to be defined.

Comparison of lateral surgical margins of up to two centimeters with margins of three centimeters for achieving tumor-free histologic margins following excision of grade I or II cutaneous mast cell tumors in dogs.

OBJECTIVE: To determine whether conservative lateral surgical margins (equal to tumor diameter for tumors < 2 cm in diameter or 2 cm for larger tumors) were noninferior to wide (3-cm) lateral surgical margins for achieving tumor-free histologic margins following excision of grade I and II cutaneous mast cell tumors (MCTs) in dogs. ANIMALS: 83 grade I and II MCTs excised with a deep surgical fascial margin and requisite lateral surgical margins from 68 dogs from 2007 to 2017. Tumors representing scar revision or local recurrence were excluded. PROCEDURES: A pathology department database was searched to identify qualifying MCTs, and medical records were cross-referenced to obtain data regarding patients and tumors. Outcome (complete vs incomplete excision as histologically determined) was compared between conservative- and wide-margin groups. A noninferiority margin of ≥ 0.9 was used for the risk ratio (probability of complete excision for the conservative- vs wide-margin group), implying that noninferiority would be established if the data indicated that the true risk of complete excision with the conservative-margin approach was at worst 90% of that for the wide-margin approach. RESULTS: The proportion of excised MCTs with tumor-free histologic margins was similar between the conservative- (43/46 [93%]) and wide- (34/37 [92%]) margin groups. There were no differences in tumor diameter or location between treatment groups. The risk ratio (1.02; 95% confidence interval, 0.89 to 1.19) met the criterion for noninferiority. CONCLUSIONS AND CLINICAL RELEVANCE: The conservative-margin approach appeared to be noninferior to the wide-margin approach for achieving tumor-free histologic margins in the dogs of this study, and its use could potentially reduce the risk of postoperative complications. (J Am Vet Med Assoc 2020;256:567-572.

Distraction osteogenesis for brachymetatarsia using initial circular fixator and early trans-fixation metatarsal K-wires-a series of three cases†.

Brachymetatarsia is a rare forefoot deformity predominantly affecting the fourth metatarsal. Current treatment include gradual lengthening by distraction osteogenesis using an external fixator or single-stage lengthening with bone grafting or a combination of the above two procedures. Our aim was to assess outcomes and complications of a novel technique for gradual metatarsal lengthening using a circular fixator. The procedure was performed on three female patients with unilateral congenital shortening of the fourth ray. All participants reported aesthetic dissatisfaction as well as pressure related complications of the deformity and opted for lengthening and distraction osteogenesis using a frame. Mean duration of the treatment was 122 days and average length gained was 12 mm. The desired metatarsal length was achieved in all three patients with no significant complications. This method of treatment of brachymetatarsia is effective and reproducible. This a promising technique, owing to its low complication rates and efficacy in lengthening.

Foreign body reaction with granuloma following Achilles tendon reconstruction with the LARS ligament.

Ligament reconstruction with the LARS ligament has been a popular choice owing to its low-complication rates compared with previously commercially available grafts. The non-active nature of the implant also meant that there were no foreign body reactions that had been described with other synthetic grafts. We describe the first reported case of a granulomatous foreign body reaction in a LARS ligament Achilles tendon graft and a technique to reconstruct the tendon following its excision.

Hypohydration impairs endurance performance: a blinded study.

The general scientific consensus is that starting exercise with hypohydration >2% body mass impairs endurance performance/capacity, but most previous studies might be confounded by a lack of subject blinding. This study examined the effect of hypohydration in a single blind manner using combined oral and intragastric rehydration to manipulate hydration status. After familiarization, seven active males (mean ± SD: age 25 ± 2 years, height 1.79 ± 0.07, body mass 78.6 ± 6.2, VO2peak 48 ± 7 mL·kg·min-1) completed two randomized trials at 34°C. Trials involved an intermittent exercise preload (8 × 15 min exercise/5 min rest), followed by a 15-min all-out performance test on a cycle ergometer. During the preload, water was ingested orally every 10 min (0.2 mL·kg body mass-1). Additional water was infused into the stomach via a gastric feeding tube to replace sweat loss (EU) or induce hypohydration of ~2.5% body mass (HYP). Blood samples were drawn and thirst sensation rated before, during, and after exercise. Body mass loss during the preload was greater (2.4 ± 0.2% vs. 0.1 ± 0.1%; P < 0.001), while work completed during the performance test was lower (152 ± 24 kJ vs. 165 ± 22 kJ; P < 0.05) during HYP At the end of the preload, heart rate, RPE, serum osmolality, and thirst were greater and plasma volume lower during HYP (P < 0.05). These results provide novel data demonstrating that exercise performance in the heat is impaired by hypohydration, even when subjects are blinded to the intervention.

The influence of an elective introductory clinical research course on pharmacy student interest in pursuing research-based careers.

OBJECTIVE: To assess the impact of an elective clinical research course on second- and third-year pharmacy students' knowledge of clinical research methods, training programs, career options, and interest in pursuing postgraduate training. DESIGN: A 2-credit hour elective course in clinical research was designed that included lectures, discussions, workshops, and in-class presentations related to study design and implementation, protocol synthesis, research evaluation, ethical and legal considerations, data analysis, and professional opportunities involving clinical research. Learner knowledge of these topics was assessed using several methods, including 3 assignments related to research protocol, ethical documentation, and presentation. ASSESSMENT: A survey instrument designed to evaluate the effect the course had on pharmacy students' knowledge of clinical research methods and interest in pursuing postgraduate training in clinical research was administered. Students who completed the elective had a greater level of familiarity with research-related topics, training options, and career opportunities (p < 0.05) and a greater interest in pursuing a career in clinical research (p < 0.05) than did students in a matched control group. CONCLUSION: Taking a 2-credit hour elective course in clinical research increased pharmacy students' interest in pursuing a career in clinical research.

Understanding the effects of surface chemistry on Q: mechanical energy dissipation in alkyl-terminated (C1-C18) micromechanical silicon resonators.

The rate of mechanical energy dissipation in 300-nm-thick, megahertz-range micromechanical silicon resonators is sensitive to single monolayer changes in surface chemistry. Resonators terminated with a single monolayer of methyl groups have significantly higher quality factors (Q's), and thus lower mechanical energy dissipation, than comparable resonators terminated with either long-chain alkyl monolayers (C2H2n+1, n = 2-18) or monolayers of hydrogen atoms. This effect cannot be attributed to mechanical energy dissipation within the alkyl monolayer, as a 9-fold increase in alkyl chain length does not lead to an observable increase in dissipation. Similarly, this effect is not correlated with the chemical structure of the silicon-monolayer interface (e.g., the density of Si-H vs Si-C bonds.) Instead, the chemical trends in resonator quality and stability are consistent with a dissipation mechanism involving the coupling of long-range strain fields to localized, electronically active defects in the monolayer coatings.