Prospective randomized trial of metal versus resorbable plates in surgical stabilization of rib fractures.

BACKGROUND: Surgical stabilization of rib fractures has gained popularity as both metal and resorbable plates have been approved for fracture repair. Is there a difference between metal and resorbable plate rib fixation regarding rib fracture alignment, control of pain, and quality-of-life (QOL) scores (Rand SF-36 survey)? METHODS: Eligible patients (pts) included 18 years or older with one or more of the following: flail chest, one or more bicortical displaced fractures (3-10), nondisplaced fractures with failure of medical management. Patients were randomized to either metal or resorbable plate fixation. Primary outcome was fracture alignment. Secondary outcomes were pain scores, opioid use, and QOL scores. RESULTS: Thirty pts were randomized (15 metal/15 resorbable). Total ribs plated 167 (88 metal/79 resorbable). Patients with rib displacement at day of discharge (DOD) metal 0/14 (one pt died, not from plating) versus resorbable 9/15 or 60% ( p = 0.001). Ribs displaced at DOD metal 0/88 versus resorbable 22/79 or 28% ( p < 0.001), 48% in posterior location. Patients with increased rib displacement 3 months to 6 months: metal, 0/11 versus resorbable, 3/9 or 33% ( p = 0.043). Ribs with increased displacement 3 months to 6 months metal 0 of 67 versus resorbable 6 of 49 or 12.2% ( p < 0.004). Pain scores and narcotic use at postoperative Days 1, 2, 3, DOD, 2 weeks, 3 months and 6 months showed no statistically significant difference between groups. QOL scores were also similar at 3 months and 6 months. Trauma recidivism in outpatient period resulted in fracture of resorbable plates in two pts requiring a second surgery. CONCLUSION: Metal plates provided better initial alignment with no displacement over time. Clinical outcomes were similar regarding pain, narcotic use, and QOL scores. Routine use of resorbable plates for posterior rib fractures is not warranted. Lateral repairs were technically most feasible for using resorbable plates but still resulted in significant displacement. Resorbable plates may not maintain rib alignment when exposed to subsequent injury. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level II.

Manufacturing biological medicines on demand: Safety and efficacy of granulocyte colony-stimulating factor in a mouse model of total body irradiation.

Protein therapeutics, also known as biologics, are currently manufactured at centralized facilities according to rigorous protocols. The manufacturing process takes months and the delivery of the biological products needs a cold chain. This makes it less responsive to rapid changes in demand. Here, we report on technology application for on-demand biologics manufacturing (Bio-MOD) that can produce safe and effective biologics from cell-free systems at the point of care without the current challenges of long-term storage and cold-chain delivery. The objective of the current study is to establish proof-of-concept safety and efficacy of Bio-MOD-manufactured granulocyte colony-stimulating factor (G-CSF) in a mouse model of total body irradiation at a dose estimated to induce 30% lethality within the first 30 days postexposure. To illustrate on-demand Bio-MOD production feasibility, histidine-tagged G-CSF was manufactured daily under good manufacturing practice-like conditions prior to administration over a 16-day period. Bio-MOD-manufactured G-CSF improved 30-day survival when compared with saline alone (p = .073). In addition to accelerating recovery from neutropenia, the platelet and hemoglobin nadirs were significantly higher in G-CSF-treated animals compared with saline-treated animals (p < .05). The results of this study demonstrate the feasibility of consistently manufacturing safe and effective on-demand biologics suitable for real-time release.

Point-of-care production of therapeutic proteins of good-manufacturing-practice quality.

Manufacturing technologies for biologics rely on large, centralized, good-manufacturing-practice (GMP) production facilities and on a cumbersome product-distribution network. Here, we report the development of an automated and portable medicines-on-demand device that enables consistent, small-scale GMP manufacturing of therapeutic-grade biologics on a timescale of hours. The device couples the in vitro translation of target proteins from ribosomal DNA, using extracts from reconstituted lyophilized Chinese hamster ovary cells, with the continuous purification of the proteins. We used the device to reproducibly manufacture His-tagged granulocyte-colony stimulating factor, erythropoietin, glucose-binding protein and diphtheria toxoid DT5. Medicines-on-demand technology may enable the rapid manufacturing of biologics at the point of care.