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We are doing this study to compare the early treatment (before you have cancer symptoms) of Venetoclax and Obitnutuzumab (V-O) to the usual treatment of V-O after you have cancer symptoms. This study will help doctors figure out if early treatment is better, the same, or worse than the usual approach of waiting until the patient has cancer symptoms before starting treatment.

In this study, people go through a screening period and testing to learn more about their cancer. Based on special features of the cancer, called biomarkers, they are placed into one of three groups. In each group, people are also placed by chance into one of two treatment options. In all groups, one option is to receive a medicine called durvalumab. The other option is to receive durvalumab together with another medicine. The extra medicine depends on the group and may be saruparib, ceralasertib, or monalizumab. The goal of the study is to see which treatment works best for different types of cancer based on their specific features.

In this study, people will be randomly placed into one of two groups, like flipping a coin. One group will take a new medicine called safusidenib, and the other group will take a fake pill called a placebo. They will take the pills twice a day in 28-day cycles. Doctors will check their health and the size of their brain tumor with regular MRI scans, blood tests, and check-ups. People will also answer questions about how they feel. The study will keep going until the tumor grows or there is another reason to stop.

People in this study will get two medicines through an IV: pembrolizumab (about 30 minutes) and ADU 1805 (about 1.5 hours). Treatments happen every 3 weeks and can last up to 2 years, with safety checks for about 4 more months. At first, there are extra visits, then visits every 3 weeks with an extra one every 9 weeks. Scans like CT or MRI will be done every 8 weeks to see how tumors respond. Some people will need tissue samples called biopsies before and after treatment, depending on their cancer type.

Observational study.

We are doing this study to collect data and samples to store them for future research. We hope the data and samples will lead to improved treatment of patients who are seriously ill or have been injured.

This is a biosample collection study for people in the Surgical Critical Initiative Tissue and Data Acquisition Study If you join this study, you will: - Have blood drawn (an extra 2 teaspoons) at time of your injury or surgery, on Days 1, 3 and 7 after your injury or surgery, and weekly while you are in the hospital. We may also collect fluid or tissue from your wound and pictures of it We will also collect blood near time of surgery or if you get worse. We will also ask to use data collected under TDAP for analyses.

We are doing this to see the effects of giving long-term red blood cell exchange transfusion to patients with sickle cell disease (SCD). We want to know if exchange blood transfusion may help with serious complications of SCD or reduce the chances of a new, serious problem happening.