Charité Clinical Journal Club (English) by Fred Luft - 27.03.2019

The N Engl J Med image of the week concerns an 18-year-old man who presented to the emergency department with generalized tonic–clonic seizures. On physical examination, the patient was confused. He had swelling over the right eye and tenderness in the right testis. Magnetic resonance imaging of the head showed numerous well-defined cystic lesions throughout the cerebral cortex. What is the diagnosis? You are offered: cerebral metastases, progressive multifocal leukoencephalopathy, cerebral vasculitis, neurosyphilis, and neurocystecircosis. We discuss these conditions. Renal cancer is refractory to treatment. In a single-group, phase 1b trial, avelumab (PD-L1) plus axitinib (VEGFR) resulted in objective responses in patients with advanced renal-cell carcinoma. A phase 3 trial involving previously untreated patients with advanced renal-cell carcinoma compared avelumab plus axitinib with the standard-of-care sunitinib was performed. Investigators randomly assigned patients in a 1:1 ratio to receive avelumab (10 mg per kilogram of body weight) intravenously every 2 weeks plus axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The two independent primary end points were progression-free survival and overall survival among patients with programmed death ligand 1 (PD-L1)–positive tumors. The objective response rate was 55.2% with avelumab plus axitinib and 25.5% with sunitinib; at a median follow-up for overall survival of 11.6 months and 10.7 months in the two groups. The combination of pembrolizumabn (also PD-L1) and axitinib showed antitumor activity in a phase 1b trial involving patients with previously untreated advanced renal-cell carcinoma. Whether pembrolizumab plus axitinib would result in better outcomes than sunitinib in such patients was unclear. In a very similar open-label, phase 3 trial, investigators randomly assigned 861 patients with previously untreated advanced clear-cell renal-cell carcinoma to receive pembrolizumab (200 mg) intravenously once every 3 weeks plus axitinib (5 mg) orally twice daily (432 patients) or sunitinib (50 mg) orally once daily for the first 4 weeks of each 6-week cycle (429 patients). The primary end points were overall survival and progression-free survival in the intention-to-treat population. Treatment with pembrolizumab plus axitinib resulted in a 47% lower risk of death and a 31% lower risk of disease progression or death than treatment with sunitinib. The objective response rate was 23.6 percentage points higher in the pembrolizumab–axitinib group than in the sunitinib group. Thus, outcomes for renal cancer patients could improve. The prescription use of the stimulants methylphenidate and amphetamine for the treatment of attention deficit–hyperactivity disorder (ADHD) has been increasing. Dopamine release is 4X as high with amphetamines compared to methylphenidate. Whether or not the risk of psychosis in adolescents and young adults with ADHD differs among various stimulants has not been extensively studied. Investigators used data from two commercial insurance claims databases to assess patients 13 to 25 years of age who had received a diagnosis of ADHD and who started taking methylphenidate or amphetamine between January 1, 2004, and September 30, 2015. The outcome was a new diagnosis of psychosis for which an antipsychotic medication was prescribed during the first 60 days after the date of the onset of psychosis. The risk of new-onset psychosis was approximately 1 in 660 patients who received a prescription for stimulants for ADHD, but the risk was about twice as high among patients who started amphetamine as among patients who started methylphenidate. Pulmonary embolism is one of the leading causes of maternal death in the Western world. Because of the low specificity and sensitivity of the d-dimer test, all pregnant women with suspected pulmonary embolism undergo computed tomographic (CT) pulmonary angiography or ventilation–perfusion scanning, both of which involve radiation exposure to the mother and fetus. Whether a pregnancy-adapted algorithm could be used to safely avoid diagnostic imaging in pregnant women with suspected pulmonary embolism is unknown. We learn that the YEARS algorithm fits the bill. We next encounter a woman with a homozygous deletion of the GC gene, encoding vitamin D-binding protein..