Trauma bypass performed by vascular surgeons demonstrate excellent long-term outcomes and limb preservation.

OBJECTIVE: Long-term outcomes in civilian trauma patients requiring upper or lower extremity revascularization is poorly studied secondary to limitations of certain large databases and the nature of the patients in this specific vascular subset. This study reports on the experience and outcomes of a Level 1 trauma center that serves both an urban and a large rural population over a 20-year period to identify bypass outcomes and surveillance protocols. METHODS: Database of a single vascular group at an academic center was queried for trauma patients requiring upper or lower extremity revascularization between January 1, 2002, and June 30, 2022. Patient demographics, indications, operative details, operative mortality, 30-day nonoperative morbidity, revisions, subsequent major amputations, and follow-up data were analyzed. RESULTS: A total of 223 revascularizations were performed, 161 (72%) lower and 62 (28%) upper extremities. One hundred sixty-seven patients (74.9%) were male, with a mean age of 39 years (range, 3-89 years). Comorbidities included hypertension (n = 34; 15.3%), diabetes (n = 6; 2.7%), and tobacco use (n = 40; 17.9%). Mean follow-up time was 23 months (range, 1-234 months), with 90 patients (40.4%) lost to follow-up. Mechanisms included blunt trauma (n = 106; 47.5%), penetrating trauma (n = 83; 37.2%), and operative trauma (n = 34; 15.3%). Bypass conduit was reversed vein (n= 171; 76.7%), prosthetic (n = 34; 15.2%), and orthograde vein (n = 11; 4.9%). Bypass inflow artery was superficial femoral (n = 66; 41.0%), above-knee popliteal (n = 28; 17.4%), and common femoral (n = 20; 12.4%) in the lower extremity, and brachial (n = 41; 66.1%), axillary (n = 10; 16.1%), and radial (n = 6; 9.7%) in the upper extremity. Lower extremity outflow artery was posterior tibial (n = 47; 29.2%), below-knee popliteal (n = 41; 25.5%), superficial femoral (n = 16; 9.9%), dorsalis pedis (n = 10; 6.2%), common femoral (n = 9; 5.6%), and above-knee popliteal (n = 10; 6.2%). Upper extremity outflow artery was brachial (n = 34; 54.8%), radial (n = 13; 21.0%), and ulnar (n = 13; 21.0%). Total operative mortality was nine patients (4.0%), all involving lower extremity revascularization. Thirty-day non-fatal complications included immediate bypass occlusion (n = 11; 4.9%), wound infection (n = 8; 3.6%), graft infection (n = 4; 1.8%), and lymphocele/seroma (n = 7; 3.1%). All major amputations (n = 13; 5.8%) were early and in the lower extremity bypass group. Late revisions in the lower and upper extremity groups were 14 (8.7%) and four (6.4%), respectively. CONCLUSIONS: Revascularization for extremity trauma can be performed with excellent limb salvage rates and has demonstrated long-term durability with low limb loss and bypass revision rates. The poor compliance with long-term surveillance is concerning and may require adjustment in patient retention protocols; however, emergent returns for bypass failure are extremely low in our experience.

Personalized medicine in CF: from modulator development to therapy for cystic fibrosis patients with rare CFTR mutations.

Cystic fibrosis (CF) is the most common life-shortening genetic disease affecting ~1 in 3,500 of the Caucasian population. CF is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. To date, more than 2,000 CFTR mutations have been identified, which produce a wide range of phenotypes. The CFTR protein, a chloride channel, is normally expressed on epithelial cells lining the lung, gut, and exocrine glands. Mutations in CFTR have led to pleiotropic effects in CF patients and have resulted in early morbidity and mortality. Research has focused on identifying small molecules, or modulators, that can restore CFTR function. In recent years, two modulators, ivacaftor (Kalydeco) and lumacaftor/ivacaftor (Orkambi), have been approved by the U.S. Food and Drug Administration to treat CF patients with certain CFTR mutations. The development of these modulators has served as proof-of-concept that targeting CFTR by modulators is a viable therapeutic option. Efforts to discover new modulators that could deliver a wider and greater clinical benefit are still ongoing. However, traditional randomized controlled trials (RCTs) require large numbers of patients and become impracticable to test the modulators' efficacy in CF patients with CFTR mutations at frequencies much lower than 1%, suggesting the need for personalized medicine in these CF patients.