Racial Disparities in Treatment and Outcomes of Pediatric Hepatoblastoma.

Pediatric Hepatoblastoma is a rare malignancy of the liver. This study used the National Cancer Database (NCDB) to identify 1068 patients diagnosed with hepatoblastoma from 2004 to 2020. χ 2 and Analysis of Variance testing, as well as Kaplan-Meier, Cox Regression, and multinomial logistic regression models were used. Data was analyzed using SPSS version 27, and statistical significance was set at α=0.05. Our results found Black patients experienced a significantly lower median survival rate compared with White patients, a difference which persisted after controlling for covariates. Black patients were also less likely to receive surgery and chemotherapy and more likely to be from low-income households than White patients. White patients had a significantly shorter inpatient hospital stay compared to Black patients and were more likely to receive treatment at more than 1 CoC accredited facility. There was no significant difference in grade, size of tumor, metastasis, or time of diagnosis to surgery. This study showed Black patients experienced inferior overall survival when diagnosed and treated for hepatoblastoma compared to White patients.

Enterohemorrhagic Escherichia coli: trigger for small vessel vasculitis.

We describe the case of a 19-year-old woman who presented with abdominal pain, vomiting, and a palpable purpuric rash. The patient subsequently developed dysentery and was found to have an infection from Shiga toxin-producing Escherichia coli. The patient also met diagnostic criteria for IgA vasculitis (also known as Henoch Schönlein purpura) but had negative immunofluorescence biopsies of the rash. The patient was treated with steroids and achieved recovery. To our knowledge, this is the first documented case of IgA vasculitis in the setting of an enterohemorrhagic E. coli infection. This case highlights an atypical presentation of IgA vasculitis and the need to include small vessel vasculitis as a differential diagnosis when treating patients of all ages.

A systematic review and meta-analysis on utilizing anti-CD19 chimeric antigen receptor T-cell therapy as a second-line treatment for relapsed and refractory diffuse large B-cell lymphoma.

Introduction: Inconsistent results observed in recent phase III trials assessing chimeric antigenic receptor T (CAR-T) cell therapy as a second-line treatment compared to standard of care (SOC) in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) prompted a meta-analysis to assess the effectiveness of CAR-T cell therapy in this setting. Methods: Random-effects meta-analysis was conducted to pool effect estimates for comparison between CAR-T cell therapy and SOC. Mixed treatment comparisons were made using a frequentist network meta-analysis approach. Results: Meta-analysis of three trials with 865 patients showed significant improvement in event-free survival (EFS: HR: 0.51; 95% CI: 0.27-0.97; I2: 92%), progression-free survival (PFS: HR: 0.47; 95% CI: 0.37-0.60; I2: 0%) with CAR-T cell therapy compared to SOC. Although there was a signal of potential overall survival (OS) improvement with CAR-T cell therapy, the difference was not statistically significant between the two groups (HR 0.76; 95% CI: 0.56 to 1.03; I2: 29%). Mixed treatment comparisons showed significant EFS benefit with liso-cel (HR: 0.37; 95% CI: 0.22-0.61) and axi-cel (HR: 0.42; 95% CI: 0.29-0.61) compared to tisa-cel. Discussion: CAR-T cell therapy, as a second-line treatment, appears to be effective in achieving higher response rates and delaying the disease progression compared to SOC in R/R DLBCL.

BRAF inhibition protects against hearing loss in mice.

Hearing loss caused by noise, aging, antibiotics, and chemotherapy affects 10% of the world population, yet there are no Food and Drug Administration (FDA)-approved drugs to prevent it. Here, we screened 162 small-molecule kinase-specific inhibitors for reduction of cisplatin toxicity in an inner ear cell line and identified dabrafenib (TAFINLAR), a BRAF kinase inhibitor FDA-approved for cancer treatment. Dabrafenib and six additional kinase inhibitors in the BRAF/MEK/ERK cellular pathway mitigated cisplatin-induced hair cell death in the cell line and mouse cochlear explants. In adult mice, oral delivery of dabrafenib repressed ERK phosphorylation in cochlear cells, and protected from cisplatin- and noise-induced hearing loss. Full protection was achieved in mice with co-treatment with oral AZD5438, a CDK2 kinase inhibitor. Our study explores a previously unidentified cellular pathway and molecular target BRAF kinase for otoprotection and may advance dabrafenib into clinics to benefit patients with cisplatin- and noise-induced ototoxicity.

Safety and pharmacokinetics of bivatuzumab mertansine in patients with CD44v6-positive metastatic breast cancer: final results of a phase I study.

The purpose of this study was to investigate the safety, pharmacokinetics and preliminary efficacy of bivatuzumab mertansine in patients with CD44v6-positive metastatic breast cancer. Anthracycline and taxane-pretreated patients with metastatic breast cancer that expressed CD44v6 received one single infusion of bivatuzumab mertansine and were observed for 21 days within one treatment course. Starting dose was 25 mg/m, while dose was escalated by increments of 25 mg/m. Patients who experienced a disease stabilization were eligible for further courses with bivatuzumab mertansine. Blood serum samples were taken throughout the treatment period for pharmacokinetic analysis. Twenty-four patients were treated at eight different dose levels (25-200 mg/m), seven of these patients received more than one course of bivatuzumab mertansine. Two dose-limiting toxicities occurred: one patient treated with 125 mg/m developed transient National Cancer Institute Common Toxicity Criteria grade 4 elevation of liver enzymes; another patient treated at 175 mg/m experienced National Cancer Institute Common Toxicity Criteria grade 3 vomiting. She died from renal failure, which might have been caused by deterioration of pre-existing renal insufficiency. The most common toxicities were transient and mild skin disorders in 75% of patients. As a consequence of one fatal toxic epidermal necrolysis that occurred in a study running in parallel, the clinical trials programme of bivatuzumab mertansine was discontinued. None of the patients developed antibodies against bivatuzumab mertansine. No objective responses were observed. Disease stabilization was achieved in 50% of patients independently of dose level. In conclusion, bivatuzumab mertansine targets CD44v6 and appears to stabilize heavily pretreated metastatic breast cancer that expresses CD44v6. The maximum tolerated dose could not be determined in this trial as the sponsor discontinued the clinical development of bivatuzumab mertansine.