Prolonged Opioid Use Is Associated With Poor Pain Alleviation After Orthopaedic Surgery.

INTRODUCTION: Severe pain after orthopaedic surgery is common and often results in chronic postsurgical pain and chronic opioid use (COU). Poor pain alleviation (PPA) after surgery is a well-described modifiable risk factor of COU. Although PPA's role in inducing COU is recognized in other areas, it is not well defined in orthopaedic surgery. The aim of this study was to evaluate the influence of PPA on COU in the population who underwent orthopaedic surgery. METHODS: Medical records from a large academic medical center from 2015 to 2018 were available for analysis. Patients undergoing nononcologic surgical procedures by the orthopaedic surgery service that also required at least 24 hours of hospital stay for pain control were included in the study. Surgery type, body location, basic demographics, preoperative opioid use, comorbidities, medications administered in the hospital, opioid prescription after discharge, and length of stay were recorded. COU was defined as a continued opioid prescription at ≥ 3 months, ≥ 6 months, or ≥ 9 months after surgery. PPA was defined as having a recorded pain score of eight or more, between 4 and 12 hours apart, three times during the hospital stay. RESULTS: A total of 7,001 patients were identified. The overall rate of COU was 25.3% at 3 months after surgery. Charlson Comorbidity Index > 0 and PPA were statistically significant predictors of opioid use at all time points. Preoperative opioid naivety was associated with decreased COU. The type and location of surgical procedures were not associated with COU, after controlling for baseline variables. CONCLUSION: Our findings demonstrated an overall high rate of COU. The known risk factors of COU were evident in our study population, particularly the modifiable risk factor of acute postsurgical PPA. Better management of postsurgical pain in orthopaedic patients may lead to a decrease in the rates of COU in this group.

Final results regarding the addition of dendritic cell vaccines to neoadjuvant chemotherapy in early HER2-negative breast cancer patients: clinical and translational analysis.

BACKGROUND: Primary breast cancer (BC) has shown a higher immune infiltration than the metastatic disease, justifying the optimal scenario for immunotherapy. Recently, neoadjuvant chemotherapy (NAC) combined with immune checkpoint inhibitors has demonstrated a gain in pathological complete responses (tpCR) in patients with BC. The aim of our study is to evaluate the safety, feasibility, and efficacy of the addition of dendritic cell vaccines (DCV) to NAC in HER2-negative BC patients. METHODS: Thirty-nine patients with early BC received DCV together with NAC conforming the vaccinated group (VG) and compared with 44 patients as the control group (CG). All patients received anthracyclines and taxanes-based NAC (ddECx4→Dx4) followed by surgery ± radiotherapy ± hormonotherapy. RESULTS: The tpCR rate was 28.9% in the VG and 9.09% in the CG (p = 0.03). Pathological CR in the triple negative (TN) BC were 50.0% versus 30.7% (p = 0.25), 16.6% versus 0% in luminal B (p = 0.15), and none among luminal A patients in VG versus CG, respectively. Impact of DCV was significantly higher in the programmed cell death ligand 1 (PD-L1) negative population (p < 0.001). PD-L1 expression was increased in patients with residual disease in the VG as compared with the CG (p < 0.01). No grade ⩾3 vaccine-related adverse events occurred. With a median follow-up of 8 years, no changes were seen in event-free survival or overall survival. Phenotypic changes post DCV in peripheral blood were observed in myeloid-derived suppressor cells (MDSC), NK, and T cells. Increase in blood cell proliferation and interferon (IFN)-γ production was detected in 69% and 74% in the VG, respectively. Humoral response was also found. Clonality changes in TCR-ß repertoire were detected in 67% of the patients with a drop in diversity index after treatment. CONCLUSION: The combination of DCV plus NAC is safe and increases tpCR, with a significant benefit among PD-L1-negative tumors. DCV modify tumor milieu and perform cellular and humoral responses in peripheral blood with no impact in outcome. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT01431196. EudraCT 2009-017402-36.