Low skeletal muscle mass and treatment outcomes among adults with haematologic malignancies: A systematic review and meta-analysis.

BACKGROUND: Low skeletal muscle mass (LSMM) and/or, function associated with an increased risk of treatment-related toxicities and inferior overall survival (OS) among adults with solid malignancies. However, the association between LSMM and treatment-related toxicities among adults with haematologic malignancies remains unclear. METHODS: Using a pre-published protocol (CRD42020197814), we searched seven bibliographic databases from inception to 08/2021 for studies reporting the impact of LSMM among adults ≥18 years with a known haematologic malignancy. The primary outcome of interest was OS, and secondary outcomes included progression free survival (PFS) and non-relapse mortality (NRM). These effect sizes were quantified in terms of hazards ratio (HR) along with 95% confidence interval (CI) and pooled across studies using a DerSimonian-Laird random-effects model. Heterogeneity was assessed using the Cochran's Q and the I2 statistic. All hypothesis testing was two-sided with an alpha of 0.05. RESULTS: Of 3791 studies screened, we identified 20 studies involving 3468 patients with a mean age of 60 years; 44% were female and the most common malignancy was diffuse large B-cell lymphoma (42%). Most studies measured muscle mass using single slice computed tomography imaging at the L3 level. The presence of LSMM was associated with worse OS (pooled HR = 1.81, 95% CI = 1.48-2.22, P < 0.001) with moderate heterogeneity (Cochran's Q, I2 = 60.4%), PFS (pooled HR = 1.61, 95% CI = 1.28-2.02, P < 0.001) with moderate heterogeneity (Cochran's Q, I2 = 66.0%). Similarly, LSMM was associated with worse NRM (HR = 1.72, 95% CI = 1.34-2.22, P < 0.001) with little evidence of heterogeneity (Cochran's Q, I2 = 0.0%). CONCLUSIONS: LSMM is associated with worse survival outcomes among adults with haematologic malignancies. Further research into understanding the underlying mechanism of this association and mitigating the negative effects of LSMM among adults with haematologic malignancies is needed.

Family Medicine Residency Virtual Adaptations for Applicants During COVID-19.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic resulted in significant changes to the US residency application process for medical school graduates. Due to the lack of in-person activities, family medicine programs have utilized various social media platforms to connect with their applicants. In this paper, we describe how family medicine residency programs have adapted for the 2021 application cycle by using social media platforms. METHODS: We evaluated all family residency programs listed on the Electronic Residency Application Service (ERAS) for the presence of departmental and residency Twitter, Instagram, and Facebook accounts. We reviewed programs' websites and social media posts for posts regarding virtual opportunities for prospective applicants. We noted family medicine virtual subinternship opportunities on the Visiting Student Application Service (VSAS). We collected data from October 17, 2020 through November 2, 2020. RESULTS: Of 675 identified family medicine residency programs, 372 (55%) had some form of social media presence. Open house opportunities were offered by 46 (6.8%) programs on Twitter, 60 (8.9%) programs on Instagram, and 64 (9.5%) programs on Facebook. One hundred ninety-five of 578 residency-specific accounts were created after March 1, 2020; Instagram accounts (103 of 195) represented most of these; five virtual subinternships were identified on VSAS. CONCLUSIONS: Family medicine residency programs have adapted to the challenges that came with the COVID-19 pandemic by increasing social media outreach, particularly through Instagram. This has allowed residency programs to virtually communicate with prospective applicants during an unprecedented application cycle.

Defining α-synuclein species responsible for Parkinson's disease phenotypes in mice.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by fibrillar neuronal inclusions composed of aggregated α-synuclein (α-syn). These inclusions are associated with behavioral and pathological PD phenotypes. One strategy for therapeutic interventions is to prevent the formation of these inclusions to halt disease progression. α-Synuclein exists in multiple structural forms, including disordered, nonamyloid oligomers, ordered amyloid oligomers, and fibrils. It is critical to understand which conformers contribute to specific PD phenotypes. Here, we utilized a mouse model to explore the pathological effects of stable ß-amyloid-sheet oligomers compared with those of fibrillar α-synuclein. We biophysically characterized these species with transmission EM, atomic-force microscopy, CD spectroscopy, FTIR spectroscopy, analytical ultracentrifugation, and thioflavin T assays. We then injected these different α-synuclein forms into the mouse striatum to determine their ability to induce PD-related phenotypes. We found that ß-sheet oligomers produce a small but significant loss of dopamine neurons in the substantia nigra pars compacta (SNc). Injection of small ß-sheet fibril fragments, however, produced the most robust phenotypes, including reduction of striatal dopamine terminals, SNc loss of dopamine neurons, and motor-behavior defects. We conclude that although the ß-sheet oligomers cause some toxicity, the potent effects of the short fibrillar fragments can be attributed to their ability to recruit monomeric α-synuclein and spread in vivo and hence contribute to the development of PD-like phenotypes. These results suggest that strategies to reduce the formation and propagation of ß-sheet fibrillar species could be an important route for therapeutic intervention in PD and related disorders.