Ma, Yaohua

ABSTRACT Background Sulfa antibiotic allergy labels (SALs) are encountered frequently in kidney transplant recipients (KTs). This often results in patients receiving second‐line prophylaxis for both Pneumocystis jiroveci and urinary tract infections (UTIs). The effect of SAL on outcomes including UTIs after KT is unclear. Methods In our single‐center retrospective cohort study, we investigated the effect of SALs on bacteriuria after KT. We identified patients with pre‐KT SALs from 2011 to 2022. A matched cohort was then created using KT with no pretransplant SALs. The groups were compared using proportional analysis and univariable and multivariable Cox proportional regression models. The primary outcome of interest was the proportion of individuals experiencing one or more episodes of bacteriuria within 1 year posttransplant. Secondary outcomes included bacteremic UTIs, acute kidney injury, and opportunistic infections. Results We found that the proportion of individuals experiencing bacteriuria within the first‐year posttransplant was significantly greater in the SAL group versus the control group ( n = 21, 28% vs. n = 22, 14.7%, p = 0.012). This result was also seen in univariable and multivariable survival analysis. In addition, episodes of UTI with associated bacteremia ( n = 11, 14.7% vs. n = 5, 3.3%, p = 0.002) were statistically significantly higher in the SAL group. Conclusion There was a significantly greater number of episodes of bacteriuria in the first‐year posttransplant in subjects with pretransplant SAL. Based on our findings, we suggest that all KTs with pretransplant SALs undergo evaluation and intervention prior to transplantation. image

PURPOSE Predictive biomarkers to better tailor therapy for patients with early-stage human epidermal growth factor 2 (HER2)-positive breast cancer are a priority. We hypothesized that HER2 and immune-based biomarkers would be predictive of pathologic complete response (pCR) to preoperative trastuzumab/pertuzumab (HP). MATERIALS AND METHODS Patients with stage II/III, estrogen receptor (ER)-negative, HER2-positive breast cancer received neoadjuvant HP in the TBCRC026 clinical trial. The pCR after receiving HP alone was 22% (18/83). Tumor biopsies were performed at baseline. Secondary correlative objectives were to determine the relationship between HER2-based biomarkers and immune processes with pCR. NanoString code sets BC360 and IO360 were used to compare differential gene expression in baseline tumors that underwent pCR versus no pCR. NanoString GeoMx digital spatial profiling was used to assess immune protein abundance in intraepithelial and stromal segments. Stromal tumor-infiltrating lymphocytes and Ki67 were evaluated by hematoxylin and eosin and immunohistochemistry, respectively. RESULTS Intraepithelial HER2 protein abundance was significantly associated with pCR ( P = .001). Low HER2 abundance tumors were primarily basal-like, and essentially all (19/20) failed to achieve pCR. High HER2 abundance tumors that achieved pCR (14/51) exhibited a high degree of immune cell activity, whereas high HER2 abundance tumors that failed to achieve pCR tumors (37/51) were enriched for M-phase processes and epidermal growth factor receptor signaling. Baseline Ki67 was significantly higher in nonresponders ( P = .04). CONCLUSION ER-negative, HER2-positive breast cancer has unique molecular and immunologic features that may predict pCR after neoadjuvant HP. Validation of these potential biomarkers and composite biomarker analyses may guide design of future clinical trials.