Ramucirumab in the second-line for patients with hepatocellular carcinoma and elevated alpha-fetoprotein: patient-reported outcomes across two randomised clinical trials

Background: Symptoms of advanced hepatocellular carcinoma (HCC) represent a substantial burden for the patient and are important endpoints to assess when evaluating treatment. Patient-reported outcomes were evaluated in subjects with advanced HCC and baseline alpha-fetoprotein (AFP) ≥400 ng/mL treated with second-line ramucirumab. Patients and methods: Patients with AFP≥400 ng/mL enrolled in the REACH or REACH-2 phase 3 studies were used in this analysis. Eligible patients had advanced HCC, Child-Pugh A, Eastern Cooperative Oncology Group performance status 0/1 and prior sorafenib. Patients received ramucirumab 8 mg/kg or placebo once every 2 weeks. Disease-related symptoms and health-related quality of life (HRQoL) were assessed with the Functional Assessment of Cancer Therapy Hepatobiliary Symptom Index (FHSI)-8 and EuroQoL-5-Dimensions (EQ-5D) instruments, respectively. Time to deterioration (TTD) (≥3-point decrease in FHSI-8 total score;≥0.06-point decrease in EQ-5D score, from randomisation to first date of deterioration) was determined using Kaplan-Meier estimation and the Cox proportional hazards model. Both separate and pooled analyses for REACH AFP≥400 ng/mL and REACH-2 patients were conducted. Results: In the pooled population with AFP ≥400 ng/mL (n=542; ramucirumab, n=316; placebo, n=226), median TTD in FHSI-8 total score was prolonged with ramucirumab relative to placebo (3.3 vs 1.9 months; HR 0.725; (95% CI 0.559 to 0.941); p=0.0152), including significant differences in back pain (0.668; (0.497 to 0.899); p=0.0044), weight loss (0.699; (0.505 to 0.969); p=0.0231) and pain (0.769; (0.588 to 1.005); p=0.0248) symptoms. TTD in EQ-5D score was not significantly different between ramucirumab and placebo groups (median 2.9 vs 1.9 months). Results in the individual trials were consistent with these findings. Conclusions: Ramucirumab in second-line treatment of advanced HCC demonstrates consistent benefit in the delay of deterioration in disease-related symptoms with no worsening of HRQoL. Taken with previously demonstrated ramucirumab-driven survival benefits in this setting, these data may inform patient-clinician discussions about the benefit-risk profile of this therapy

River Otter (Lontra canadensis) Killed by Wolves (Canis lupus) during Winter in Northern Minnesota

Few accounts exist of Gray Wolves (Canis lupus) killing small sympatric mammalian predators. In January 2017, we observed a River Otter (Lontra canadensis) that had been killed by wolves on the ice in Voyageurs National Park, Minnesota. This is one of only a few documented instances of wolves killing otters

The Evolution of Cloud Computing in ATLAS

The ATLAS experiment has successfully incorporated cloud computing technology and cloud resources into its primarily grid-based model of distributed computing. Cloud R&D activities continue to mature and transition into stable production systems, while ongoing evolutionary changes are still needed to adapt and refine the approaches used, in response to changes in prevailing cloud technology. In addition, completely new developments are needed to handle emerging requirements. This work will describe the overall evolution of cloud computing in ATLAS. The current status of the VM management systems used for harnessing IAAS resources will be discussed. Monitoring and accounting systems tailored for clouds are needed to complete the integration of cloud resources within ATLAS' distributed computing framework. We are developing and deploying new solutions to address the challenge of operation in a geographically distributed multi-cloud scenario, including a system for managing VM images across multiple clouds, a system for dynamic location-based discovery of caching proxy servers, and the usage of a data federation to unify the worldwide grid of storage elements into a single namespace and access point. The usage of the experiment's HLT farm for Monte Carlo production, in a specialized cloud environment, will be presented. Finally, we evaluate commercial clouds, and have conducted a study assessing cost vs. benchmark performance

Posttransfusion Sepsis Attributable to Bacterial Contamination in Platelet Collection Set Manufacturing Facility, United States.

During May 2018‒December 2022, we reviewed transfusion-transmitted sepsis cases in the United States attributable to polymicrobial contaminated apheresis platelet components, including Acinetobacter calcoaceticus‒baumannii complex or Staphylococcus saprophyticus isolated from patients and components. Transfused platelet components underwent bacterial risk control strategies (primary culture, pathogen reduction or primary culture, and secondary rapid test) before transfusion. Environmental samples were collected from a platelet collection set manufacturing facility. Seven sepsis cases from 6 platelet donations from 6 different donors were identified in patients from 6 states; 3 patients died. Cultures identified Acinetobacter calcoaceticus‒baumannii complex in 6 patients and 6 transfused platelets, S. saprophyticus in 4 patients and 4 transfused platelets. Whole-genome sequencing showed environmental isolates from the manufacturer were closely related genetically to patient and platelet isolates, indicating the manufacturer was the most probable source of recurrent polymicrobial contamination. Clinicians should maintain awareness of possible transfusion-transmitted sepsis even when using bacterial risk control strategies