Management of bone metastasis with zoledronic acid: A systematic review and Bayesian network meta-analysis.

Background: While considered the mainstay of treatment for specific bone metastases, ZA is used predominantly to treat osteolytic lesions. The purpose of this network meta-analysis is to compare ZA to other treatment options in its ability to improve specific clinical outcomes in patients with bone metastases secondary to any primary tumor. Methods: PubMed, Embase and Web of Science were systematically searched from inception to May 5th, 2022. Keywords used were solid tumor, lung neoplasm, kidney neoplasm, breast neoplasm, prostate neoplasm, ZA and bone metastasis. Every randomized controlled trial and non-randomized quasi-experimental study of systemic ZA administration for patients with bone metastases and any comparator were included. A Bayesian network meta-analysis was done on the primary outcomes including number of SREs, time to developing a first on-study SRE, overall survival, and disease progression-free survival. Secondary outcome was pain at 3, 6 and 12 months after treatment. Results: Our search yielded 3861 titles with 27 meeting inclusion criteria. For the number of SRE, ZA in combination with chemotherapy or hormone therapy was statistically superior to placebo (OR 0.079; 95 % CrI: 0.022-0.27). For the time to the first on study SRE, the relative effectiveness of ZA 4 mg was statistically superior to placebo (HR 0.58; 95 % CrI:0.48-0.77). At 3 and 6 months, ZA 4 mg was significantly superior to placebo for reducing pain with a SMD of -0.85 (95 % CrI:-1.6, -0.0025) and -2.6 (95 % CrI:-4.7, -0.52) respectively. Conclusions: This systematic review shows the benefits of ZA in decreasing the incidence of SREs, increasing the time to the first on-study SRE, and reducing the pain level at 3 and 6 months.

Locoregional Recurrence of Esophageal Cancer Treated with Curative Intent Local Salvage Therapy: A Single Center Experience.

PURPOSE: Locoregional recurrence of esophageal carcinoma after neoadjuvant therapy and en bloc esophagectomy, although uncommon, is challenging to manage. Currently, there are no standard treatment approaches prompting many health care providers to adopt a palliative approach. We describe our experience and outcomes of treating this specific group of patients with a focus on salvage curative intent local therapy. METHODS: All patients undergoing en bloc esophagectomy following neoadjuvant therapy between 2007 and 2017 at the McGill University Health Centre, a tertiary referral center for esophageal cancer, were identified. Patient follow-up included a structured surveillance protocol with serial endoscopic and cross-sectional imaging studies. Local recurrence was defined as histologically confirmed recurrences at the anastomosis. Regional recurrence was defined as radiological evidence of celiac, mediastinal, or para-esophageal/conduit lymphadenopathy. Demographic, pathologic, therapeutic variables were extracted as well as disease free and overall survival. RESULTS: Of 755 patients identified, locoregional recurrences occurred in 27 patients (3.6%) of whom 18 were included in the analysis. The median disease-free survival post index operation was 15 months (IQR 10-23). The sites of recurrence were local (6/18, 33.3%); regional (8/18, 44.4%); and locoregional (4, 22.2%). Chemoradiation was the most common modality used to treat recurrence (10/18, 55.6%) whilst 4 (22.2%) underwent surgery. Following treatment for locoregional recurrence, 1-year overall survival was 61.1% and at 5 years was 22.2%. CONCLUSION: Consolidative salvage local therapy for locoregional recurrence after en bloc esophagectomy is feasible and can entail prolonged survival in a subset of patients.

Drone versus ground delivery of simulated blood products to an urban trauma center: The Montreal Medi-Drone pilot study.

BACKGROUND: Timely and safe distribution of quality blood products is a major challenge faced by blood banks around the world. Our primary objective was to determine if simulated blood product delivery to an urban trauma center would be more rapidly achieved by unmanned aerial vehicle (UAV) than by ground transportation. A secondary objective was to determine the feasibility of maintaining simulated blood product temperatures within a targeted range. METHODS: In this prospective pilot study, we used two distinct methods to compare UAV flight duration and ground transport times. Simulated blood products included packed red blood cells, platelet concentrate, and fresh frozen plasma. For each blood product type, three UAV flights were conducted. Temperature was monitored during transport using a probe coupled to a data logger inside each simulated blood product unit. RESULTS: All flights were conducted successfully without any adverse events or safety concerns reported. The heaviest payload transported was 6.4 kg, and the drone speed throughout all nine flights was 10 m/s. The mean UAV transportation time was significantly faster than ground delivery (17:06 ± 00:04 minutes vs. 28:54 ± 01:12 minutes, p < 0.0001). The mean ± SD initial temperature for packed red blood cells was 4.4°C ± 0.1°C with a maximum 5% mean temperature variability from departure to landing. For platelet concentrates, the mean ± SD initial temperature was 21.6°C ± 0.5°C, and the maximum variability observed was 0.3%. The mean ± SD initial fresh frozen plasma temperature was -19°C ± 2°C, and the greatest temperature variability was from -17°C ± 2°C to -16°C ± 2°C. CONCLUSIONS: Unmanned aerial vehicle transportation of simulated blood products was significantly faster than ground delivery. Simulated blood product temperatures remained within their respective acceptable ranges throughout transport. Further studies assessing UAV transport of real blood products in populated areas are warranted. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

Automated External Defibrillator Geolocalization with a Mobile Application, Verbal Assistance or No Assistance: A Pilot Randomized Simulation (AED G-MAP).

OBJECTIVE: Shockable rythms are common among victims of witnessed public out-of-hospital cardiac arrest (OHCA), but bystander defibrillation with a public automated external defibrillator (PAED) is rare. Instructions from the emergency medical dispatcher and mobile applications were developed to expedite the localization of PAEDs, but their effectiveness has not been compared. METHODS: Participants were enrolled in a three-armed randomized simulation where they witnessed a simulated OHCA on a university campus, were instructed to locate a PAED and provide defibrillation. Participants were stratified and randomized to: (1) no assistance in finding the PAED, (2) assistance from a geolocalization mobile application (AED-Quebec), or (3) verbal assistance. Data collectors tracked each participant's time elapsed and distance traveled to shock. RESULTS: Of the 52 volunteers participating in the study (46% male, mean age 37), 17 were randomized to the no assistance group, 18 to the mobile application group and 17 to the verbal group. Median (IQR) time to shock was, respectively, 10:00 min (7:49-10:00), 9:44 (6:30-10:00), and 5:23 (4:11-9:08), with statistically significant differences between the verbal group and the other groups (p ≤ 0.01). The success rate for defibrillation in <10 minutes was 35%, 56% and 76%. Multivariate regression of all participants pooled showed that knowledge of campus geography was the strongest predictor of shock in <10 minutes (aOR =14.3, 95% CI 1.85-99.9). Among participants without prior geographical knowledge, verbal assistance provided a trend towards decreased time to shock, but the differences over no assistance (7:28 vs. 10:00, p = 0.10) and over the mobile app (7:28 vs. 10:00, p = 0.11) were not statistically significant. CONCLUSION: In a simulated environment, verbally providing OHCA bystanders with the nearest PAED's location appeared to be effective in reducing the time to defibrillation in comparison to no assistance and to an AED geolocalizing mobile app, but further research is required to confirm this hypothesis, ascertain the external validity of these results, and evaluate the real-life implications of these strategies.