Selective placement of autogenous arteriovenous fistulae in an over 80-year-old population.

INTRODUCTION: With improved life expectancy and quality of life, elderly patients constitute a progressively larger fraction of consumers utilising renal replacement therapy (RRT). Although substantial data exist for younger cohorts, minimal evidence exists for outcomes of arteriovenous fistula (AVF) and central catheters (CVC) placed in those patients over 80 years. We examined outcomes of primary AVF placement in this cohort to ascertain durability and benefits of AVF in the over 80-year-old population. METHODS: Retrospective analysis was undertaken of all autogenous AVFs and CVCs placed in patients aged over 80 years at Gold Coast University Hospital between March 2010 and February 2016. Prospectively collected demographic data, co-morbidities and operative factors were analysed. RESULTS: Sixty-five AVF and 12 CVC patients were identified. Mean age at intervention was 83.9 years and 76% of the patients were male. The majority of procedures were autogenous radio-cephalic AVF; median post-operative length of stay was 2 days. Cumulative AVF patient survival at 12 and 24 months was 82% and 72%, respectively. This was significantly better than survival rates of CVC patients, with 12-month survival of 45%. Primary patency at 6, 12 and 24 months was 58%, 39% and 31%. There were 113 follow-up procedures in 41 patients required to maintain patency. CONCLUSIONS: Although patency rates are inferior and re-intervention rates higher than in younger patients, AVF can be a durable option for RRT in selected elderly patients with improved mortality rates compared with CVC. Age alone should not preclude primary AVF placement.

Systemic messenger RNA as an etiological treatment for acute intermittent porphyria.

Acute intermittent porphyria (AIP) results from haploinsufficiency of porphobilinogen deaminase (PBGD), the third enzyme in the heme biosynthesis pathway. Patients with AIP have neurovisceral attacks associated with increased hepatic heme demand. Phenobarbital-challenged mice with AIP recapitulate the biochemical and clinical characteristics of patients with AIP, including hepatic overproduction of the potentially neurotoxic porphyrin precursors. Here we show that intravenous administration of human PBGD (hPBGD) mRNA (encoded by the gene HMBS) encapsulated in lipid nanoparticles induces dose-dependent protein expression in mouse hepatocytes, rapidly normalizing urine porphyrin precursor excretion in ongoing attacks. Furthermore, hPBGD mRNA protected against mitochondrial dysfunction, hypertension, pain and motor impairment. Repeat dosing in AIP mice showed sustained efficacy and therapeutic improvement without evidence of hepatotoxicity. Finally, multiple administrations to nonhuman primates confirmed safety and translatability. These data provide proof-of-concept for systemic hPBGD mRNA as a potential therapy for AIP.

Effect of osteochondral graft insertion forces on chondrocyte viability.

BACKGROUND: Because chondrocytes are responsible for articular cartilage matrix synthesis and maintenance, reduced chondrocyte viability could compromise graft survival, healing, and clinical outcome. HYPOTHESIS: Typical forces used in osteochondral grafting reduce the viability of the chondrocytes in the graft. STUDY DESIGN: Controlled laboratory study. METHODS: Osteochondral grafting was performed in 4 fresh-frozen cadaver knees (n = 16 per knee). Impact force was measured during extrusion of the donor graft from the harvester into the recipient site, seating the graft flush with the articular surface of the surrounding cartilage using a tamp, and recessing the graft surface below the recipient articular surface. The magnitudes of forces measured during cadaver surgery (200, 400, and 800 N) were reproduced using a drop-tower apparatus on 80 fresh osteochondral grafts harvested from knee blocks provided by tissue banks. Cell viability and glycosaminoglycan release in media were measured at 48 hours after injury. RESULTS: Forces were relatively low (range, 124-356 N) during graft extrusion from the harvester into the recipient defect or during flush seating (range, 191-418 N) of the graft. Attempts to recess the graft generated significantly greater force (range, 147-685; P < .01). When the donor graft length was 2 mm longer than the depth of the recipient hole, the mean impact force generated was even higher (range, 240-1114 N) than the force seen in a donor graft of equal length. No reduction in viability was seen at 200-N and 400-N impacts. However, a significant decrease in chondrocyte viability was seen in the group impacted with 800 N (only 50% of cells were viable, compared with 91% in the sham group; P < .01). Glycosaminoglycan levels in culture media did not correlate significantly with insertion force. CONCLUSION: Typical graft insertion forces did not significantly reduce chondrocyte viability. However, increased graft length relative to the depth of the recipient hole and attempts to recess the graft generated higher forces, which reduced chondrocyte viability. CLINICAL RELEVANCE: Any theoretical benefits of cancellous bone compaction that may occur in grafts that are recessed or are longer than the recipient holes must be balanced against the potential reduction in chondrocyte viability.

General Surgeons and trauma. A questionnaire survey of General Surgeons training in ATLS and involvement in the trauma team.

OBJECTIVE: To determine the level of training of General Surgeons in the UK in the Advanced Trauma Life Support (ATLS) course and their involvement with hospital trauma teams. METHODS: Postal questionnaire sent to General Surgical Consultants and Higher Surgical Trainees (HSTs). RESULTS: 58% of General Surgeons who responded had attended ATLS, but only 30% of those who had been Consultants for more than 10 years. Eighty-seven percent considered the course 'essential' or 'some value'. Sixty-one percent of hospitals represented had a trauma team. A Consultant General Surgeon was a member of the team in 50% and the General Surgical HST in 82%. CONCLUSION: ATLS has been widely accepted by General Surgical Trainees and recently appointed Consultants. The trauma team approach to resuscitation has yet to become fully established in the UK and there is limited input from Consultant General Surgeons.