Management of Patients With Sepsis in Canadian Community Emergency Departments: A Retrospective Multicenter Observational Study.

BACKGROUND: Sepsis is a life-threatening syndrome and a leading cause of morbidity and mortality representing significant financial burden on the health-care system. Early identification and intervention is crucial to maximizing positive outcomes. We studied a quality improvement initiative with the aim of reviewing the initial management of patients with sepsis in Canadian community emergency departments, to identify areas for improving the delivery of sepsis care. We present a retrospective, multicenter, observational study during 2011 to 2015 in the community setting. METHODS: We collected data on baseline characteristics, clinical management metrics (triage-to-physician-assessment time, triage-to-lactate-drawn time, triage-to-antibiotic time, and volume of fluids administered within the first 6 hours of triage), and outcomes (intensive care unit [ICU] admission, in-hospital mortality) from a regional database. RESULTS: A total of 2056 patients were analyzed. The median triage-to-physician-assessment time was 50 minutes (interquartile range [IQR]: 25-104), triage-to-lactate-drawn time was 50 minutes (IQR: 63-94), and triage-to-antibiotics time was 129 minutes (IQR: 70-221). The median total amount of fluid administered within 6 hours of triage was 2.0 L (IQR: 1.5-3.0). The ICU admission rate was 36% and in-hospital mortality was 25%. We also observed a higher ICU admission rate (51% vs 24%) and in-hospital mortality (44% vs 14%) in those with higher lactate concentration (≥4 vs ≤2 mmol/L), independent of other sepsis-related parameters. CONCLUSION: Time-to-physician-assessment, time-to-lactate-drawn, time-to-antibiotics, and fluid resuscitation in community emergency departments could be improved. Future quality improvement interventions are required to optimize management of patients with sepsis. Elevated lactate concentration was also independently associated with ICU admission rate and in-hospital mortality rate.

The benefits of photodynamic therapy on vertebral bone are maintained and enhanced by combination treatment with bisphosphonates and radiation therapy.

Photodynamic therapy (PDT) has been shown to ablate tumors within vertebral bone and yield short-term improvements in vertebral architecture and biomechanical strength, in particular when combined with bisphosphonate (BP) treatment. Longer-term outcomes of PDT combined with current treatments for skeletal metastases are essential to understand its therapeutic potential. The objective of this study is to evaluate the response of vertebrae to PDT after a longer (6-week) time period, alone and combined with previous BP or radiation treatment (RT). Sixty-three female rnu/rnu rats were randomized to six treatment groups: untreated control, BP-only, RT-only, PDT-only, combined BP + PDT and combined RT + PDT. L2 vertebrae were structurally analyzed through µCT-based analysis, axial compressive load-to-failure testing and histological analysis of morphology, osteoid formation and osteoclast activity. Combined BP + PDT treatment yielded the largest improvements in bone architecture with combined RT + PDT treatment yielding similar findings, but of a lesser magnitude. Mechanically, ultimate force and stress were correlated to stereological parameters that demonstrated a positive structural effect from combinatory treatment. Increased osteoid formation was observed in both combination therapies without any significant differences in osteoclast activity. Overall, multimodality treatment demonstrated a sustained positive effect on vertebral structural integrity, motivating PDT as a minimally-invasive adjuvant treatment for spinal metastases.

Beyond radiation therapy: photodynamic therapy maintains structural integrity of irradiated healthy and metastatically involved vertebrae in a pre-clinical in vivo model.

Spinal metastasis commonly occurs in advanced breast cancer. Treatment is often multimodal including radiation therapy (RT), bisphosphonates (BPs), and surgery, yet alternative minimally invasive local treatments are needed. Photodynamic therapy (PDT) has been shown to ablate tumor cells and enhance bone formation secondary to metastatic breast cancer, demonstrating potential as a treatment for spinal metastasis. Combined with previous BP treatment, bone formation was further enhanced by PDT. This study aimed to determine the effects of PDT in combination with previous RT on healthy and metastatically involved vertebrae. Forty-six athymic rats underwent RT (4 Gy on day-7), twenty-three of them were inoculated with MT-1 human breast cancer cells on day 0. Thirteen healthy and ten metastatically involved rats underwent PDT treatment on day 14. All rats were sacrificed on day 21. L2 vertebrae were analyzed using µCT imaging, mechanical testing, and histological methods. In healthy vertebrae, while modest increases in trabecular structure were found in RT + PDT compared to RT only, mechanical stability was negatively affected. The 4 Gy RT dose was found to ablate all tumor cells and prevent further vertebral metastasis. As such, in metastatically involved rats, no differences in stereological or mechanical properties were detected. RT + PDT and RT-only treatment resulted in greatly improved vertebral structural and mechanical properties versus untreated or PDT-only treatment in metastatically involved rats, due to early tumor destruction in RT-treated groups. Increased amounts of woven bone and osteoid volume were found in PDT-treated vertebrae. Further investigation is needed to understand if structural improvements seen in RT + PDT treatment can translate into longer-term improvements in strength to support the potential of PDT as a viable adjuvant treatment for spinal metastasis postradiation.