The genetic basis of multiple system atrophy.

Multiple system atrophy (MSA) is a heterogenous, uniformly fatal neurodegenerative ɑ-synucleinopathy. Patients present with varying degrees of dysautonomia, parkinsonism, cerebellar dysfunction, and corticospinal degeneration. The underlying pathophysiology is postulated to arise from aberrant ɑ-synuclein deposition, mitochondrial dysfunction, oxidative stress and neuroinflammation. Although MSA is regarded as a primarily sporadic disease, there is a possible genetic component that is poorly understood. This review summarizes current literature on genetic risk factors and potential pathogenic genes and loci linked to both sporadic and familial MSA, and underlines the biological mechanisms that support the role of genetics in MSA. We discuss a broad range of genes that have been associated with MSA including genes related to Parkinson's disease (PD), oxidative stress, inflammation, and tandem gene repeat expansions, among several others. Furthermore, we highlight various genetic polymorphisms that modulate MSA risk, including complex gene-gene and gene-environment interactions, which influence the disease phenotype and have clinical significance in both presentation and prognosis. Deciphering the exact mechanism of how MSA can result from genetic aberrations in both experimental and clinical models will facilitate the identification of novel pathophysiologic clues, and pave the way for translational research into the development of disease-modifying therapeutic targets.

Multimodal prehabilitation before major abdominal surgery: A retrospective study.

INTRODUCTION: Prehabilitation may benefit older patients undergoing major surgeries. Currently, its efficacy has not been conclusively proven. This is a retrospective review of a multimodal prehabilitation programme. METHODS: Patients aged 65 years and above undergoing major abdominal surgery between May 2015 and December 2019 in the National University Hospital were included in our institutional programme that incorporated aspects of multimodal prehabilitation and Enhanced Recovery After Surgery concepts as 1 holistic perioperative pathway to deal with issues specific to older patients. Physical therapy, nutritional advice and psychosocial support were provided as part of prehabilitation. RESULTS: There were 335 patients in the prehabilitation cohort and 256 patients whose records were reviewed as control. No difference in postoperative length of stay (P=0.150) or major complications (P=0.690) were noted. Patients in the prehabilitation group were observed to ambulate a longer distance and participate more actively with their physiotherapists from postoperative day 1 until 4. In the subgroup of patients with cancer, more patients had undergone neoadjuvant therapy in the prehabilitation group compared to the control group (21.7% versus 12.6%, P=0.009). Prehabilitation patients were more likely to proceed to adjuvant chemotherapy (prehabilitation 87.2% vs control 65.6%, P<0.001) if it had been recommended. CONCLUSION: The current study found no differences in traditional surgical outcome measures with and without prehabilitation. An increase in patient mobility in the immediate postoperative period was noted with prehabilitation, as well as an association between prehabilitation and increased adherence to postoperative adjuvant therapy. Larger prospective studies will be needed to validate the findings of this retrospective review.