Childhood-Onset Progressive Dystonia With Mitochondrial DNA G14459A Mutation

This article reports the case of an 11-year-old boy with progressive dystonia caused by the homoplasmic G14459A mitochondrial DNA mutation. The patient presented with focal dystonia in the right upper limb at 3 years of age, which progressed over 4 years to exhibit dystonia in both the upper and lower limbs. At 7 years of age, high signal intensity lesions in the bilateral striata and the midbrain were observed on fluid-attenuated inversion recovery images. It was observed on diffusion-weighted images that with time, these high signal intensity lesions migrated from the putamen to the caudate nuclei, which closely correlated with disease progression. Because his symptoms and abnormal magnetic resonance imaging findings progressed despite treatment with coenzyme Q10 and l -carnitine, at 7 years of age he was then started on sodium succinate, hoping to improve his complex I deficiency. After treatment, progression of MRI abnormalities appeared to have been suppressed for 4 years, although no improvement was observed in dystonia

Pembrolizumab Plus Amrubicin in Patients With Relapsed SCLC: Multi-Institutional, Single-Arm Phase 2 Study

Introduction: In patients with relapsed SCLC, amrubicin (AMR) is the current standard treatment in Japan. Nevertheless, its efficacy is not satisfactory and prognosis is poor. Preclinical study suggested that anthracycline agent might induce immunogenic cell death and work synergistically with immune checkpoint inhibitors. Methods: Patients with relapsed SCLC who relapsed after completion of platinum-containing regimen were registered. Patients were treated with pembrolizumab (200 mg, flat dose on d 1, every 3 wk for 2 y) plus AMR (40 mg/m2 on d 1–3, every 3 wk until progression). Primary end point was overall response rate (ORR). Secondary end points consisted of progression-free survival (PFS), overall survival, and safety. On the basis of the hypothesis that this treatment will improve ORR from 20% to 40% (0.1 of one-sided α and power of 0.8), 25 patients are required (trial identifier: NCT03253068). Results: Between November 2017 and October 2019, a total of 25 patients were enrolled. Most participants (88%) relapsed within 90 days after platinum-containing therapy and all patients were immune checkpoint inhibitor-naive. ORR, the primary end point, was 52.0% (95% confidence interval [CI]: 31.3%–72.2%). Median PFS was 4.0 months (95% CI: 2.8–7.0 mo), and PFS rate at 1 year was 14.4%. Median overall survival was 10.6 months (95% CI: 7.3–21.3 mo). Common adverse events greater than or equal to grade 3 were neutropenia (64%), leukopenia (40%), and febrile neutropenia (16%). No treatment-related deaths occurred. Conclusions: Among patients with relapsed SCLC, pembrolizumab plus AMR was effective and tolerable