Background: While clindamycin-induced acute kidney injury (AKI) is uncommon, it has occurred more frequently in recent years. Summary: We investigated 24 patients diagnosed with clindamycin-induced AKI retrospectively. The dosage of clindamycin was 1.0-1.5 g/day. Fifteen patients had episodes of gross hematuria, but fever, skin rash and eosinophilia were rare. Urine analysis revealed mild proteinuria and severe tubular dysfunction. Twenty-three patients were diagnosed with AKI stage 3 upon admission. The clindamycin lymphocyte transformation assay was positive for 63.2% of the patients. Acute interstitial nephritis (AIN) and acute tubular necrosis (ATN) were proven by renal biopsy, and renal insufficiency appeared to result from tubular toxicity and drug crystals. In the majority (87.5%) of the patients, AKI was severe and required renal replacement therapy, but all of their renal function recovered significantly 2 months after discharge. Clindamycin-induced AKI is largely reversible and has episodes of gross hematuria. Renal biopsies confirmed AIN or ATN in these patients.
Background Microcalcification is one of the most reliable clinical features of the malignancy risk of breast cancer, and it is associated with enhanced tumour aggressiveness and poor prognosis. However, its underlying molecular mechanism remains unclear. Methods Clinical data were retrieved to analyse the association between calcification and bone metastasis in patients with breast cancer. Using multiple human breast cancer cell lines, the osteogenic cocktail model was established in vitro to demonstrate calcification-exacerbated metastasis. Migration and invasion characteristics were determined by wound healing and transwell migration. mRNA and protein expression were identified by quantitative PCR and western blotting. Metabolic alterations in breast cancer cells were evaluated using Seahorse Analyser. Results The osteogenic differentiation of human breast cancer cells activated the classical TGF-β/Smad signalling pathway and the non-canonical MAPK pathway, which, in turn, exacerbated the progression of epithelial–mesenchymal transition (EMT). The metabolic programme switched to enhancing mitochondrial oxidative phosphorylation (OXPHOS) upon osteogenic differentiation. Rotenone was used to inhibit the OXPHOS complex during osteogenesis to block mitochondrial function, consequently reversing the EMT phenotype. Conclusions This study provides important insights into the mechanisms involved in breast cancer bone metastasis, and outlines a possible strategy to intervene in OXPHOS for the treatment of breast tumours.
ImportanceEpithelial ovarian carcinoma is heterogeneous and classified according to the World Health Organization Tumour Classification, which is based on histologic features and molecular alterations. Preoperative prediction of the histologic subtypes could aid in clinical management and disease prognostication.ObjectiveTo assess the value of radiomics based on contrast-enhanced computed tomography (CT) in differentiating histologic subtypes of epithelial ovarian carcinoma in multicenter data sets.Design, Setting, and ParticipantsIn this diagnostic study, 665 patients with histologically confirmed epithelial ovarian carcinoma were retrospectively recruited from 4 centers (Hong Kong, Guangdong Province of China, and Seoul, South Korea) between January 1, 2012, and February 28, 2022. The patients were randomly divided into a training cohort (n = 532) and a testing cohort (n = 133) with a ratio of 8:2. This process was repeated 100 times. Tumor segmentation was manually delineated on each section of contrast-enhanced CT images to encompass the entire tumor. The Mann-Whitney U test and voted least absolute shrinkage and selection operator were performed for feature reduction and selection. Selected features were used to build the logistic regression model for differentiating high-grade serous carcinoma and non–high-grade serous carcinoma.ExposuresContrast-enhanced CT-based radiomics.Main Outcomes and MeasuresIntraobserver and interobserver reproducibility of tumor segmentation were measured by Dice similarity coefficients. The diagnostic efficiency of the model was assessed by receiver operating characteristic curve and area under the curve.ResultsIn this study, 665 female patients (mean [SD] age, 53.6 [10.9] years) with epithelial ovarian carcinoma were enrolled and analyzed. The Dice similarity coefficients of intraobserver and interobserver were all greater than 0.80. Twenty radiomic features were selected for modeling. The areas under the curve of the logistic regression model in differentiating high-grade serous carcinoma and non–high-grade serous carcinoma were 0.837 (95% CI, 0.835-0.838) for the training cohort and 0.836 (95% CI, 0.833-0.840) for the testing cohort.Conclusions and RelevanceIn this diagnostic study, radiomic features extracted from contrast-enhanced CT were useful in the classification of histologic subtypes in epithelial ovarian carcinoma. Intraobserver and interobserver reproducibility of tumor segmentation was excellent. The proposed logistic regression model offered excellent discriminative ability among histologic subtypes.
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