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ABSTRACT Background Methods Results Conclusion Chimeric antigen receptor T‐cell (CAR‐T) therapy has demonstrated remarkable efficacy in relapsed or refractory large B cell lymphoma, but real‐world evidence is needed to confirm safety and efficacy when facing the unique challenges of a wide geographical catchment area.We reviewed patients treated with commercially available CAR‐T at a medium‐sized single center in Canada (The Ottawa Hospital) between December 2020 and July 2022 (Canadian implementation started in 2020).Fifty‐one patients (59% male, median age 62) traveled a median distance of 655 km (range 3–3659) for treatment. Median time from apheresis to CAR‐T infusion was 36 days (range 26–81). With a median follow‐up of 383 days (95% CI: 333–480), median progression‐free survival (PFS) and overall survival (OS) were 257 days (95% CI: 92‐NE) and 422 days (95% CI: 106‐NE), respectively. The median PFS for out‐of‐province patients was 115 days (95% CI: 91‐NE) versus 280 days for in‐province patients (95% CI: 142‐NE), p = 0.12. Multivariate analysis demonstrated that distance from treatment center (p = 0.05) and refractory disease status (p = 0.003) were independently associated with shorter PFS. The time from the last disease progression to CAR‐T referral was longer for out‐of‐province patients, but there was no difference in the time of referral to CAR‐T consult, apheresis, or CAR‐T infusion between in‐province and out‐of‐province patients.Our results confirm that despite the complexity of CAR‐T therapy administration, Ottawa can effectively provide commercial CAR‐T therapy in a timely fashion for patients from across the country. [ABSTRACT FROM AUTHOR]

Peripheral neurotoxicity is a debilitating condition that afflicts up to 90% of patients with colorectal cancer receiving oxaliplatin-containing therapy. Although emerging evidence has highlighted the importance of various solute carriers to the toxicity of anticancer drugs, the contribution of these proteins to oxaliplatin-induced peripheral neurotoxicity remains controversial. Among candidate transporters investigated in genetically engineered mouse models, we provide evidence for a critical role of the organic cation transporter 2 (OCT2) in satellite glial cells in oxaliplatin-induced neurotoxicity, and demonstrate that targeting OCT2 using genetic and pharmacological approaches ameliorates acute and chronic forms of neurotoxicity. The relevance of this transport system was verified in transporter-deficient rats as a secondary model organism, and translational significance of preventive strategies was demonstrated in preclinical models of colorectal cancer. These studies suggest that pharmacological targeting of OCT2 could be exploited to afford neuroprotection in cancer patients requiring treatment with oxaliplatin., Introduction Clinical use of the chemotherapeutic agent oxaliplatin is associated with a characteristic pattern of peripheral neurotoxicity that affects more than 90% of patients (1). The onset of neurotoxicity may [...]

Turbochargers (TCs) aid to produce smaller and more fuel-efficient passenger vehicle engines with power outputs comparable to those of large displacement engines. This paper presents further progress on the nonlinear dynamic behavior modeling of rotor-radial bearing system by including engine-induced (TC casing) excitations. The application is concerned with a semifloating bearing design commonly used in high speed turbochargers. Predictions from the model are validated against test data collected in an engine-mounted TC unit operating at a top speed of 160 krpm (engine speed = 3600 rpm). The bearing model includes noncylindrical lubricant films as in a semifloating-ring bearing with an antirotation button. The nonlinear rotor transient response model presently includes input base motions for the measured TC casing accelerations for increasing engine load conditions. Engines induce TC casing accelerations rich in multiple harmonic frequencies; amplitudes being significant at two and four times the main engine speed. Fast Fourier transfor frequency domain postprocessing of predicted nonlinear TC shaft motions reveals a subsynchronous whirl frequency content in good agreement with test data, in particular, for operation at the highest engine speeds. Predicted total shaft motion is also in good agreement with test data for all engine loads and over the operating TC shaft speed range. The comparisons validate the rotor-bearing model and will aid in reducing product development time and expenditures. [DOI: 10.1115/1.3159368]