Post-operative outcomes in older patients: a single-centre observational study.

BACKGROUND: Improved life-expectancies have seen increased rates of older patients undergoing surgery worldwide. These patients are at increased risk of post-operative complications. Australian evidence is limited regarding the association between age and post-operative outcomes, especially rapid response calls (RRCs) as indicators of adverse outcomes. The aim was to compare the post-operative outcomes of older patients (≥80 years) to younger patients. Specifically, 30-day in-hospital mortality; unplanned intensive care unit (ICU) admission; and RRC activation within 72 h post-operatively. METHODS: Single-centre retrospective observational study conducted over 12 months in a metropolitan Australian hospital. All adult patients (≥16 years) undergoing surgical procedures were included, excluding cardiac and obstetric/gynaecological surgeries. Patient co-morbidities were quantified using Charlson co-morbidity index (CCI) and American Society of Anesthesiologists physical status classification. RESULTS: Seven thousand four hundred and seventy-nine patients met inclusion criteria, 14.5% (n = 1086) aged ≥80 years. Most procedures (65%) were elective; and general surgical procedures were most common (24.2%). Compared to younger patients, older patients had significantly higher 30-day mortality (2.3% versus 0.2%; P < 0.001), increased post-operative RRC rates (7.3% versus 1.2%; P < 0.001), and unplanned ICU admissions (3.2% versus 1.6%; P < 0.001). Increasing age was associated with increased risk of post-operative RRC, unplanned ICU admission, and in-hospital mortality (all P < 0.01), with associations remaining significant after controlling for surgery type and CCI. CONCLUSION: Older patients are at increased risk of adverse post-operative outcomes, including post-operative RRC, unplanned ICU admission, and mortality, especially if they underwent emergency procedures. This has implications for preoperative risk stratification and post-operative management. Incidence of post-operative RRCs may be an important indicator of post-operative care.

A preclinical assessment of neural stem cells as delivery vehicles for anti-amyloid therapeutics.

Transplantation of neural stems cells (NSCs) could be a useful means to deliver biologic therapeutics for late-stage Alzheimer's disease (AD). In this study, we conducted a small preclinical investigation of whether NSCs could be modified to express metalloproteinase 9 (MMP9), a secreted protease reported to degrade aggregated Aß peptides that are the major constituents of the senile plaques. Our findings illuminated three issues with using NSCs as delivery vehicles for this particular application. First, transplanted NSCs generally failed to migrate to amyloid plaques, instead tending to colonize white matter tracts. Second, the final destination of these cells was highly influenced by how they were delivered. We found that our injection methods led to cells largely distributing to white matter tracts, which are anisotropic conduits for fluids that facilitate rapid distribution within the CNS. Third, with regard to MMP9 as a therapeutic to remove senile plaques, we observed high concentrations of endogenous metalloproteinases around amyloid plaques in the mouse models used for these preclinical tests with no evidence that the NSC-delivered enzymes elevated these activities or had any impact. Interestingly, MMP9-expressing NSCs formed substantially larger grafts. Overall, we observed long-term survival of NSCs in the brains of mice with high amyloid burden. Therefore, we conclude that such cells may have potential in therapeutic applications in AD but improved targeting of these cells to disease-specific lesions may be required to enhance efficacy.