No abstract

Puumala virus (PUUV) is considered a classic Old World etiologic agent of nephropathia epidemica (NE), or hemorrhagic fever with renal syndrome (HFRS). HFRS is considered to be distinct from hantavirus (cardio-)pulmonary syndrome (HPS or HCPS), described in the New World. Here, we report a severe case, which fulfilled most, if not all, Centers for Disease Control and Prevention (CDC) criteria for HPS, needing non-invasive ventilation and subsequent acute hemodialysis. However, the etiological agent was PUUV, as proved by serological testing, real-time polymerase chain reaction (PCR), and sequencing. Viral antigen was detected by specific anti-PUUV immunostaining, showing, for the first time, greenish intracytoplasmic inclusions in bronchoalveolar lavage (BAL) macrophages. This case definitely confirms that HPS can be encountered during PUUV infections. Interestingly, special findings could render the diagnosis easier, such as greenish homogeneous cytoplasmic inclusions, surrounded by a fine clear halo in BAL macrophages. Therefore, although the diagnosis remains difficult before the onset of renal involvement, the occurrence of severe respiratory failure mimicking community-acquired pneumonia must alert the clinician for possible HPS, especially in endemic areas.

Purpose: Patients with advanced urothelial carcinoma who fail platinum-containing chemotherapy (treatment fails) have a poor prognosis and limited treatment options. Recent approvals of immune-checkpoint inhibitors confirmed the value of immunomodulatory therapy in urothelial carcinoma. Tremelimumab is a selective human immunoglobulin G2 (IgG2) monoclonal antibody against cytotoxic T-lymphocyte-associated antigen 4 with demonstrated durable response rate in metastatic melanoma. This is the first study to report the efficacy and safety of tremelimumab in urothelial carcinoma. Patients and Methods: We report the results of the urothelial carcinoma cohort from a phase II, open-label, multicenter study of patients with advanced solid tumors (NCT02527434). Patients with locally advanced/metastatic urothelial carcinoma were treated with tremelimumab monotherapy (750 mg via intravenous infusion every 4 weeks for seven cycles, then every 12 weeks for two additional cycles) for up to 12 months or until disease progression, initiation of other anticancer therapy, unacceptable toxicity, or consent withdrawal. Results: In 32 evaluable patients with metastatic urothelial carcinoma, objective response rate was 18.8% (95% confidence interval, 7.2-36.4), including complete response (CR) in 2 (6.3%), and partial response in 4 patients (12.5%). Median duration of response has not been reached. Stable disease of 12 months was reported in 1 patient (3.1%), yielding a disease control rate at 12 months of 21.9%. Overall, tremelimumab was generally well tolerated; safety results were consistent with the known safety profile. Conclusions: Tremelimumab monotherapy demonstrated clinical activity and durable responses in patients with metastatic urothelial carcinoma. This study is the first in which CR has been observed with tremelimumab as a single agent in urothelial carcinoma.