Anne L. Flamm

Steps toward mapping the human vasculature by phage display.

The molecular diversity of receptors in human blood vessels remains largely unexplored. We developed a selection method in which peptides that home to specific vascular beds are identified after administration of a peptide library. Here we report the first in vivo screening of a peptide library in a patient. We surveyed 47,160 motifs that localized to different organs. This large-scale screening indicates that the tissue distribution of circulating peptides is nonrandom. High-throughput analysis of the motifs revealed similarities to ligands for differentially expressed cell-surface proteins, and a candidate ligand–receptor pair was validated. These data represent a step toward the construction of a molecular map of human vasculature and may have broad implications for the development of targeted therapies.

Challenges in outpatient end-of-life care: Wishes to avoid resuscitation

Ms P. was a 69-year-old woman with anaplastic thyroid carcinoma and progressive compression of her airway, despite chemoradiotherapy. She had recently been admitted to the hospital for worsening respiratory distress. Her physician, after discussing her poor prognosis with her, referred her to inpatient hospice. She completed a Living Will directing comfort care only in the event of terminal or irreversible illness. Her physician wrote a do not resuscitate (DNR) order after discussing with her that she was unlikely to survive to hospital discharge if she had to be resuscitated after a cardiac arrest. Both the Living Will and DNR order were placed in her medical record. Two days later, Ms P. was discharged to an inpatient hospice. One week later, because of the scarcity of local inpatient hospice beds, Ms P. was discharged to continue hospice care at home. A few weeks later, while she was home, Ms P. became increasingly short of breath. Her family called 911. On their arrival, the emergency medical technicians (EMTs) noted that Ms P. was in respiratory distress. Shortly thereafter, she became apneic and pulseless. The EMTs intubated Ms P. and initiated chest compressions. Fifteen minutes later, Ms P. arrived in the emergency center (EC) in ventricular fibrillation. EC staff administered defibrillation and continued resuscitative efforts. Ten minutes later, the inpatient DNR order from the previous hospital admission was verified. The EC physician contacted Ms P.’s primary physician, who confirmed that the DNR order should be honored. Resuscitative efforts were discontinued, and Ms P. died. The EMTs’ chart note stated, “Family reported patient was DNR at home, but they didn’t have any paperwork.”