Superoxide Dismutase 1 Regulation of CXCR4-Mediated Signaling in Prostate Cancer Cells is Dependent on Cellular Oxidative State.

BACKGROUND/AIMS: CXCL12, acting via one of its G protein-coupled receptors, CXCR4, is a chemoattractant for a broad range of cell types, including several types of cancer cells. Elevated expression of CXCR4, and its ligand CXCL12, play important roles in promoting cancer metastasis. Cancer cells have the potential for rapid and unlimited growth in an area that may have restricted blood supply, as oxidative stress is a common feature of solid tumors. Recent studies have reported that enhanced expression of cytosolic superoxide dismutase (SOD1), a critical enzyme responsible for regulation of superoxide radicals, may increase the aggressive and invasive potential of malignant cells in some cancers. METHODS: We used a variety of biochemical approaches and a prostate cancer cell line to study the effects of SOD1 on CXCR4 signaling. RESULTS: Here, we report a direct interaction between SOD1 and CXCR4. We showed that SOD1 interacts directly with the first intracellular loop (ICL1) of CXCR4 and that the CXCL12/CXCR4-mediated regulation of AKT activation, apoptosis and cell migration in prostate cancer (PCa) cells is differentially modulated under normal versus hypoxic conditions when SOD1 is present. CONCLUSIONS: This study highlights a potential new regulatory mechanism by which a sensor of the oxidative environment could directly regulate signal transduction of a receptor involved in cancer cell survival and migration.

Carbon footprint reduction associated with a surgical outreach clinic.

BACKGROUND: Healthcare systems generate substantial carbon footprints that may be targeted to decrease greenhouse gas emissions. Outreach clinics may represent tools to assist in this reduction by optimizing patient related travel. Therefore, we sought to estimate the carbon footprint savings associated with a head and neck surgery outreach clinic. METHODS: This study was a cross-sectional survey of patient travel patterns to a surgical outreach clinic compared to a regional cancer treatment centre from December 2019 to February 2020. Participants completed a self-administered survey of 12 items eliciting travel distance, vehicle details, and ability to combine medical appointments. Canadian datasets of manufacturer provided vehicular efficiency were used to estimate carbon emissions for each participant. Geographic information systems were used for analyses. RESULTS: One hundred thirteen patients were included for analysis. The majority of patients (85.8%) used their own personal vehicle to travel to the outreach clinic. The median distance to the clinic and regional centre were 29.0 km (IQR 6.0-51.9) and 327.0 km (IQR 309.0-337.0) respectively. The mean carbon emission reduction per person was therefore 117,495.4 g (SD: 29,040.0) to 143,570.9 g (SD: 40,236.0). This represents up to 2.5% of an average individual's yearly carbon footprint. Fewer than 10% of patients indicated they were able to carpool or group their appointments. CONCLUSION: Surgical outreach clinics decrease carbon footprints associated with patient travel compared to continued care at a regional centre. Further research is needed to determine possible interventions to further reduce carbon emissions associated with the surgical care of patients.

Ovarian Cancer Metastasis to the Larynx: A Case Report and Review of the Literature.

Laryngeal secondary malignancies are rare, and most spread locoregionally from hypopharyngeal or thyroid primaries. Metastasis of ovarian carcinoma to the larynx is extremely rare. A 65-year-old woman with a history of high grade serous ovarian carcinoma was undergoing carboplatin chemotherapy for recurrence. She presented with progressive dysphagia and hoarseness; a computer tomography (CT) scan demonstrated bilateral necrotic lymphadenopathy and hypopharyngeal fullness. A hypopharyngeal mass was confirmed on examination, and operative biopsy identified it as high-grade serous ovarian. To our knowledge, this report describes the second immunohistochemically proven metastatic ovarian cancer detected in the larynx in the world literature.

Idiopathic facial lipoatrophy in a healthy middle-aged woman: a case report.

BACKGROUND: Facial lipoatrophy is a rare condition described by the disappearance of facial subcutaneous fat. The etiology of lipoatrophy can be congenital, or acquired including traumatic, iatrogenic or idiopathic. Idiopathic facial lipoatrophy has only been previously identified in three case reports, among which, the patient demographics vary considerably. Two of these case reports have identified a role for autologous fat transfer as a means of treatment. This case differs from those in the literature in patient demographics and severity of the facial lipoatrophy. The aim of the current report is to present a rare case of idiopathic facial lipoatrophy, and to assess the use of autologous fat transfer as a treatment modality. CASE PRESENTATION: We present a case of a 40-year old woman from Nova Scotia, Canada who presented with asymptomatic idiopathic facial lipoatrophy. The patient was otherwise healthy, taking no medications with no trauma or surgery in the region affected. Investigations, including a full autoimmune workup, were unremarkable. The facial lipoatrophy was considerably disfiguring and was assessed as a Grade 4 on the facial lipoatrophy scale. The patient was treated over the course of 2 years with two autologous fat transfers. CONCLUSIONS: Achieving resolution of idiopathic lipoatrophy is important to patients because it can manifest in a disfiguring form and have negative effects on quality of life. The current study reports a treatment of idiopathic lipoatrophy that achieved results acceptable to the patient.

Reduction of Benzodiazepine Use in Patients Prescribed Medical Cannabis.

Background: Benzodiazepines are a class of medication with sedative properties, commonly used for anxiety and other neurological conditions. These medications are associated with several well-known adverse effects. This observational study aims to investigate the reduction of benzodiazepine use in patients using prescribed medical cannabis. Methods: A retrospective analysis was performed on a cohort of 146 medical cannabis patients (average age 47 years, 61% female, 54% reporting prior use of cannabis) who reported benzodiazepine use at initiation of cannabis therapy. These data are a part of a database gathered by a medical cannabis clinic (Canabo Medical). Descriptive statistics were used to quantify associations of the proportion of benzodiazepine use with time on medical cannabis therapy. Results: After completing an average 2-month prescription course of medical cannabis, 30.1% of patients had discontinued benzodiazepines. At a follow-up after two prescriptions, 65 total patients (44.5%) had discontinued benzodiazepines. At the final follow-up period after three medical cannabis prescription courses, 66 total patients (45.2%) had discontinued benzodiazepine use, showing a stable cessation rate over an average of 6 months. Conclusion: Within a cohort of 146 patients initiated on medical cannabis therapy, 45.2% patients successfully discontinued their pre-existing benzodiazepine therapy. This observation merits further investigation into the risks and benefits of the therapeutic use of medical cannabis and its role relating to benzodiazepine use.

Adenosine and Adenosine 5'-triphosphate Catabolism in Systemic Blood as a Potential Biomarker for Doxorubicin Cardiotoxicity in an Experimental Rat Model in vivo.

BACKGROUND: Previous studies have shown that metabolism of adenosine 5'-triphosphate (ATP) in systemic blood is a potential surrogate biomarker for cardiovascular toxicity. OBJECTIVE: To investigate the acute effect of high dose of doxorubicin (DOX) on adenosine and ATP catabolism in systemic blood in vivo. METHOD: Sprague Dawley (SD) rats were each given either 10 mg/kg of DOX (n = 8) or normal saline (1 mL/kg, n = 11) twice daily for 4 doses by subcutaneous (sc) injection. Blood samples were collected sequentially for up to 6 hours for measuring circulating concentrations of ATP, adenosine and their metabolites. Hemodynmic recording was obtained continuously after the last injection. The difference in response between groups was considered significant at p < 0.05 (t-test). RESULTS: Diastolic blood pressure (DBP) was significantly lower in the DOX treated rats than in the control before the final injection (87 ± 12 vs. 104 ± 11 mmHg, p < 0.05). Blood pressure fell gradually after the last injection and the decrease was significantly greater in the DOX treated group (p < 0.05). Plasma concentration of adenosine was significantly lower in the DOX treated group. In contrast, plasma concentrations of uric acid and hypoxanthine, as well as Red Blood Cell (RBC) concentrations of AMP, were significantly higher (p < 0.05). CONCLUSION: Acute cardiotoxicity induced by DOX may be measured by the increased breakdown of ATP to AMP in the RBC and also breakdown of adenosine to hypoxanthine and uric acid in plasma.

Polypharmacy and use of potentially inappropriate medications in long-term care facilities: does coordinated primary care make a difference?

OBJECTIVES: Polypharmacy is both common and harmful for frail residents of long-term care facilities (LTCF). We aimed to study rates of polypharmacy and potentially inappropriate medications (PIMs) before and after the implementation of a new model of coordinated primary care in LTCF, 'Care by Design (CBD)'. METHODS: This was an observational before/after study in 10 LTCFs in Halifax, NS, Canada. Chart reviews were conducted for 529 LTCF residents for whom medication use was available. Both regularly scheduled and PRN medications were included but topical, inhaled and other non-systemic agents were excluded. Polypharmacy was defined as the concomitant use of more than 10 medications. PIMs were identified using Beers Criteria. KEY FINDINGS: Mean age of LTCF residents was older pre- versus post-CBD (85.7 versus 82.1 years; P = 0.0015). The burden of polypharmacy was high, but decreased significantly from 86.8% pre-CBD to 79.5% post-CBD (P = 0.046). The mean number of medications per resident decreased from 16.7 (SD 5.6) pre- to 15.5 (SD 6.2) post-CBD (P = 0.037). Residents with dementia were taking fewer medications both overall and following the implementation of CBD (mean 15.9, SD 0.6 pre-CBD versus 14.4, SD 0.4 post-CBD; P = 0.04). PIM rates were high and showed no change with CBD (86.2% versus 81.1%, P = 0.16). CONCLUSIONS: Polypharmacy was the norm of this sample of LTCF residents. Implementation of coordinated care through the CBD model was associated with a small decrease in polypharmacy but not overall use of PIMs. Further targeted efforts are required to substantially reduce both polypharmacy and PIMs in clinical practice.