Background Peripheral and mucosal eosinophilia may be associated with more aggressive disease in inflammatory bowel disease (IBD) patients. Vedolizumab blocks T lymphocytes, eosinophil adhesion, and extravasation in the gastrointestinal tract. It is not known if mucosal eosinophilia is a predictor for the therapeutic efficacy of vedolizumab. Methods This was a retrospective cohort study of IBD patients with ileal or colonic biopsies who were off steroids before starting vedolizumab. Biopsies were rereviewed by pathologists, and mean eosinophil density was quantified. Patient characteristics and steroid-free clinical response 6 months after beginning vedolizumab were determined. Features were compared between nonresponders and responders, and multivariable logistic regression was performed to identify predictors of clinical response. Results Of 251 IBD patients starting vedolizumab therapy, 65 patients (48% Crohn’s disease, 52% ulcerative colitis) met inclusion criteria. All IBD patients not responding to vedolizumab were more likely to have a higher baseline mean eosinophil count (340 ± 156 vs 236 ± 124; P = 0.004), be previously exposed to an anti-TNF (96% vs 56%; P = 0.001), and be male (58% vs 28%; P = 0.02). Mean eosinophil counts were significantly increased in colonic biopsies in UC nonresponders (438 ± 149 vs 299 ± 145; P = 0.01). A similar trend was seen in CD nonresponders. On multivariable analysis, colonic eosinophil density and prior anti-TNF exposure—and the combination of both—were independent predictors of response. Conclusion In ulcerative colitis, colonic eosinophilia and prior anti-TNF exposure were independent predictors of 6-month clinical nonresponse to vedolizumab. Mucosal eosinophil density as a novel biomarker should be explored in larger patient cohorts. Aside from the previous anti-TNF exposure, eosinophil density in the colon of patients with UC is a negative predictor for a steroid-free long-term response to vedolizumab. The degree colonic eosinophilia may be a novel biomarker that should be further explored.
Objective: Breast MRI is used to screen high-risk patients and determine extent of disease in breast cancer (BC) patients. The goal of this study was to determine the pathologic correlates of breast MRI abnormalities biopsied under MRI guidance. Methods:We retrospectively identified 101 MRI-guided core needle biopsies (CNB) of the breast from 79 women over a 4-year period. MRI-detected lesions biopsied with ultrasound or stereotactic guidance were excluded. MRI studies and pathology were reviewed by breast radiologists and pathologists.Results: Of the 79 patients, 72 (91%) had a history of prior (n=13) or concurrent (n=59) BC. There were 101 MRI abnormalities: 60 (59%) with non-mass enhancement (NME) and 41 (41%) with mass enhancement. Pathology was benign in 83/101 (82%), including in the majority of NME lesions (43/60, 72%). The most common benign findings were: fibrocystic changes (FCC) (49%), sclerosing lesions (13%), and fibroadenoma (FA) (9%). There were 18 (18%) malignant diagnoses: 8 (44%) invasive lobular carcinoma (ILC), 7 (39%) ductal carcinoma in situ (DCIS), and 3 (17%) invasive ductal carcinoma (IDC). Of the 18 malignant diagnoses, 16 (89%) occurred in 14 unique patients with concurrent BC. Based on the malignant MRI-guided CNB, 6 (46%) of
Background There are no clinical trials involving patients with diffuse large B-cell lymphoma (DLBCL) in sub-Saharan Africa since antiretroviral therapy (ART) for HIV became widely available in this region. We aimed to establish the safety and efficacy of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with DLBCL in Malawi.Methods This prospective, single-arm, non-randomised phase 1/2 clinical trial was done at Kamuzu Central Hospital Cancer Clinic (Lilongwe, Malawi). Eligible patients were adults (aged 18-60 years) with newly diagnosed DLBCL, an Eastern Cooperative Oncology Group performance status of 0-2, a CD4 count of 100 cells per µL or higher (if HIVpositive), measurable disease by physical examination, an absolute neutrophil count of 1000 × 10⁹ cells per L or higher, a platelet count of 100 × 10⁹ platelets per L or higher, a serum creatinine concentration of 132•60 µmol/L or less, a total bilirubin concentration of 34•21 µmol/L or less, a negative urine pregnancy test in women of childbearing potential, and no previous cytotoxic therapy. Pregnant or breastfeeding women, and individuals with CNS involvement from DLBCL, chronic hepatitis B infection (unless they were receiving tenofovir plus lamivudine), or any other comorbidities that would compromise the protocol objectives were excluded. Eligible patients received intravenous rituximab 375 mg/m², cyclophosphamide 750 mg/m², doxorubicin 50 mg/m², and vincristine 1•4 mg/m² (maximum 2 mg/m²), and oral prednisone 100 mg or an equivalent drug every 21 days for up to six cycles. HIV-positive patients received concurrent ART. The primary outcome was the proportion of patients with National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 or 4 non-haematological toxic effects or treatment-related deaths after six cycles of treatment. Secondary efficacy outcomes included the proportion of patients with a complete response after six cycles of treatment, and progression-free survival and overall survival at 12 months and 24 months. This trial is registered with ClinicalTrials.gov, NCT02660710.
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