Dynamic mechanical loading is a strong anabolic signal in the skeleton, increasing osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) and increasing the bone-forming activity of osteoblasts, but its role in bone metastatic cancer is relatively unknown. In this study, we integrated a hydroxyapatite-containing three-dimensional (3D) scaffold platform with controlled mechanical stimulation to investigate the effects of cyclic compression on the interplay between breast cancer cells and BM-MSCs as it pertains to bone metastasis. BM-MSCs cultured within mineral-containing 3D poly(lactide-co-glycolide) (PLG) scaffolds differentiated into mature osteoblasts, and exposure to tumor-derived soluble factors promoted this process. When BM-MSCs undergoing osteogenic differentiation were exposed to conditioned media collected from mechanically loaded breast cancer cells, their gene expression of osteopontin was increased. This was further enhanced when mechanical compression was simultaneously applied to BM-MSCs, leading to more uniformly deposited osteopontin within scaffold pores. These results suggest that mechanical loading of 3D scaffold-based culture models may be utilized to evaluate the role of physiologically relevant physical cues on bone metastatic breast cancer. Furthermore, our data imply that cyclic mechanical stimuli within the bone microenvironment modulate interactions between tumor cells and BM-MSCs that are relevant to bone metastasis.
PurposeTo analyze differences in esophageal cancer survival by geographic region of the U.S. from the 1970s to the 2000s, and attribute the causes of these discrepancies.MethodsRaw data were obtained from the Surveillance Epidemiology and End Results (SEER) program of the National Cancer Institute. Patients were stratified by decade of diagnosis and by geographic region (East, Hawaii/Alaska, Midwest, Southwest, and West), containing SEER registries. The Kaplan-Meier method with the log-rank test was used to compare the overall survival (OS) among these geographic groups. A multivariate Cox Proportional Hazard analysis was conducted to evaluate the impact of the following factors on differences in survival: patient age, gender, race, tumor stage, site, histology, treatment method, and metropolitan size.ResultsA total of 87,834 patients were identified. OS has increased significantly since 1973, with five-year OS improving from 4.9% (the 1970s) to 15.3% (2000s) (P<0.001). Residence in the East was prognostic for higher OS compared to all the other regions, with a median OS of six months in the 1970s and 12 months in the 2000s (P<0.001). The multivariate analysis revealed increased age, African American race, distant disease, non-distal tumor location, squamous cell histology, and no radiation therapy were associated with worse OS. The West and East had the highest amount of cancer centers (12 and seven, respectively). And the East had the highest number of cancer centers per person (5.7E-07) while the South had the lowest (1.6E-07).ConclusionsThere are disparities in esophageal cancer survival and quality of care through different geographic regions of the U.S., which may be attributed to a combination of the unbalanced distribution of medical resources, the regional differences in cancer biology, and other lifestyle and socioeconomic factors. More research should be conducted to further characterize regional differences and guide the implementation of improvements in survival.
Background: Children undergoing cleft palate repair present challenges to postoperative management due to several factors that can complicate recovery. Utilization of multimodal analgesic protocols can improve outcomes in this population. We report experience designing and implementing an enhanced recovery after surgery (ERAS) pathway for cleft palate repair to optimize postoperative recovery. Aims:The primary aim was to implement an ERAS pathway with >70% bundle adherence to achieve a 30% reduction in postoperative opioid consumption within 12 months. Our secondary aims assessed intraoperative opioid consumption, length of stay, timeliness of oral intake, and respiratory recovery. Methods: A multidisciplinary team of perioperative providers developed an ERAS pathway for cleft palate patients. Key drivers included patient and provider education, formal pathway creation and implementation, multimodal pain therapy, and targetbased care. Interventions included maxillary nerve blockade and enhanced intra-and postoperative medication regimens. Outcomes were displayed as statistical process control charts.Results: Pathway compliance was 77.0%. Patients during the intervention period (n = 39) experienced a 49% reduction in postoperative opioid consumption (p < .0001) relative to our historical cohort (n = 63), with a mean difference of −0.33 ± 0.11 mg/kg (95% CI −0.55 to −0.12 mg/kg). Intraoperative opioid consumption was reduced by 36% (p = .002), with a mean difference of −0.27 ± 0.09 mg/kg (95% CI −0.45 to −0.09 mg/kg).Additionally, patients in the intervention group had a 45% reduction in time to first oral intake (p = .02) relative to our historical cohort, with a mean difference of −3.81 ± 1.56 h (95% CI −6.9 to −0.70). There was no difference in PACU or hospital length of stay, but there was a significant reduction in variance of all secondary outcomes. Conclusion:Opioid reduction and improved timeliness of oral intake is possible with an ERAS protocol for cleft palate repair, but our protocol did not alter PACU or hospital length of stay.
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