Development of Opioid Use Disorder After Breast Reconstruction: Effects of Nicotine Exposure.

INTRODUCTION: After undergoing breast reconstructive surgery, patients are typically prescribed opioids. Smoking tobacco increases rate of opioid metabolism and is associated with development of opioid use disorder (OUD). The aim of this study was to determine whether patients who smoke have an increased risk of OUD after breast reconstructive surgery. Given that OUD is a known risk factor for injection drug use and intravenous drug use increases risk of acquiring blood-borne diseases including human immunodeficiency virus (HIV) and hepatitis, the secondary aim was to determine if these patients are also at increased risk of acquiring these communicable diseases associated with OUD. METHODS: A retrospective analysis was conducted using TriNetX, a multi-institutional deidentified database. Individuals included underwent a breast reconstructive surgery and received postoperative opioid treatment. The exposed group included patients who smoke. The control group did not smoke. Risk of developing OUD, hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV from 12 to 36 months after surgery was compared between groups. Patients with preexisting OUD or associated diseases were excluded. Cohorts were matched to control for confounding factors including age, sex, race, mental health history, and concomitant substance use. RESULTS: There were 8648 patients included in the analysis. After matching, 4324 patients comprised the exposure group, and 4324 patients remained in the control group. Preoperative smoking was significantly associated with increased risk of OUD at 12, 24, and 36 months after breast reconstruction (36 months: odds ratio [OR], 2.722; confidence interval [CI], 2.268-6.375). Smoking was also associated with increased risk of HIV and HCV at all time points after surgery (36 months HIV: OR, 2.614; CI, 1.977-3.458; 36 months HCV: OR, 3.718; CI, 2.268-6.375) and increased risk of HBV beginning at 24 months after surgery (36 months HBV: OR, 2.722; CI, 1.502-4.935). CONCLUSIONS: Individuals who smoke have an increased risk of developing OUD, HIV, HCV, and HBV after breast reconstructive surgery. This risk persists for at least 3 years after surgery. Additional research and clinical interventions focusing on early identification of OUD, prevention efforts, and harm reduction strategies for patients who smoke or have nicotine dependence undergoing breast reconstruction are warranted.

The MHC Class II Antigen-Processing and Presentation Pathway Is Dysregulated in Type 1 Diabetes.

Peptide loading of MHC class II (MHCII) molecules is facilitated by HLA-DM (DM), which catalyzes CLIP release, stabilizes empty MHCII, and edits the MHCII-bound peptide repertoire. HLA-DO (DO) binds to DM and modulates its activity, resulting in an altered set of peptides presented at the cell surface. MHCII-peptide presentation in individuals with type 1 diabetes (T1D) is abnormal, leading to a breakdown in tolerance; however, no direct measurement of the MHCII pathway activity in T1D patients has been performed. In this study, we measured MHCII Ag-processing pathway activity in humans by determining MHCII, MHCII-CLIP, DM, and DO levels by flow cytometry for peripheral blood B cells, dendritic cells, and monocytes from 99 T1D patients and 97 controls. Results showed that MHCII levels were similar for all three APC subsets. In contrast, MHCII-CLIP levels, independent of sex, age at blood draw, disease duration, and diagnosis age, were significantly increased for all three APCs, with B cells showing the largest increase (3.4-fold). DM and DO levels, which usually directly correlate with MHCII-CLIP levels, were unexpectedly identical in T1D patients and controls. Gene expression profiling on PBMC RNA showed that DMB mRNA was significantly elevated in T1D patients with residual C-peptide. This resulted in higher levels of DM protein in B cells and dendritic cells. DO levels were also increased, suggesting that the MHCII pathway maybe differentially regulated in individuals with residual C-peptide. Collectively, these studies show a dysregulation of the MHCII Ag-processing pathway in patients with T1D.

Reconstructive complications and early toxicity in breast cancer patients treated with proton-based postmastectomy radiation therapy.

Background: Postmastectomy radiation therapy (PMRT) decreases the risk of locoregional recurrence and increases overall survival rates in patients with high-risk node positive breast cancer. While the number of breast cancer patients treated with proton-based PMRT has increased in recent years, there is limited data on the use of proton therapy in the postmastectomy with reconstruction setting. In this study, we compared acute toxicities and reconstructive complications in patients treated with proton-based and photon-based PMRT. Methods: A retrospective review of our institutional database was performed to identify breast cancer patients treated with mastectomy with implant or autologous reconstruction followed by PMRT from 2015 to 2020. Baseline clinical, disease, and treatment related factors were compared between the photon-based and proton-based PMRT groups. Early toxicity outcomes and reconstructive complications following PMRT were graded by the treating physician. Results: A total of 11 patients treated with proton-based PMRT and 26 patients treated with photon-based PMRT were included with a median follow-up of 7.4 months (range, 0.7-33 months). Six patients (55%) in the proton group had a history of breast cancer (3 ipsilateral and 3 contralateral) and received previous RT 38 months ago (median, range 7-85). There was no significant difference in mean PMRT (p = 0.064) and boost dose (p = 0.608) between the two groups. Grade 2 skin toxicity was the most common acute toxicity in both groups (55% and 73% in the proton and photon group, respectively) (p = 0.077). Three patients (27%) in the proton group developed grade 3 skin toxicity. No Grade 4 acute toxicity was reported in either group. Reconstructive complications occurred in 4 patients (36%) in the proton group and 8 patients (31%) in photon group (p = 0.946). Conclusions: Acute skin toxicity remains the most frequent adverse event in both proton- and photon-based PMRT. In our study, reconstructive complications were not significantly higher in patients treated with proton- versus photon-based PMRT. Longer follow-up is warranted to assess late toxicities.