ALBERT

Description: This paper presents the findings of a study into how different inlet designs for stormwater culverts increase the discharge rate. The objective of the study was to develop improved inlet designs that could be retro-fitted to existing stormwater culvert structures in order to increase discharge capacity and allow for changing rainfall patterns and severe weather events that are expected as a consequence of climate change. Three different chamfer angles and a rounded corner were simulated with the software ANSYS Fluent, each of the shapes tested in five different sizes. Rounded and 45 ∘ chamfers at the inlet edge performed best, significantly increasing the flow rate, though the size of the configurations was a critical factor. Inlet angles of 30 ∘ and 60 ∘ caused greater turbulence in the simulations than did 45 ∘ and the rounded corner. The best performing shape of the inlet, the rounded corner, was tested in an experimental flume. The flume flow experiment showed that the optimal inlet configuration, a rounded inlet (radius = 1/5 culvert width) improved the flow rate by up to 20% under submerged inlet control conditions.

Description: Abstract 3168 Background: Peripheral neuropathy (PN) is the dose-limiting toxicity of bortezomib in MM patients, affecting 〉30% patients, including painful PN. Treatment is mostly supportive with narcotics, antidepressants, and anticonvulsants. Acupuncture has been reported to be effective in treating neuropathic pain in diabetic and cancer patients. Methods: We initiated a pilot study to assess the feasibility, safety and efficacy of acupuncture in reducing the severity of BIPN in MM patients. Patients had acupuncture twice weekly for 2 weeks, weekly for 4 weeks, and then biweekly for 4 weeks. All patients continued their prescribed PN medications. Clinical Total Neuropathy Score (TNSc), Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) questionnaire and Neuropathy Pain Scale (NPS) were used to assess patients at study entry and week 1, 2, 3, 4, 5, 6, 8, 10 during and after 4 weeks of completion of therapy. Serum was obtained from the patients at baseline, right after first acupuncture and before acupuncture session on week 2, 4, 8, and at follow up visit on week 14. Serum samples were used to measure cytokines concentrations. Before and after acupuncture treatments, a complete neurological examination was performed. Nerve conduction studies at baseline and end of study were conducted. Treatment included insertion of disposable sterile acupuncture needles, which retained for 25 minutes, at the following points: bilateral ear points: shen men, point zero, two auricular points where electro-dermal signal was detected, and bilateral body acupuncture points: LI4, SJ5, LI11, ST40, and Ba Feng in upper and lower extremities. Results: From May 17, 2011 to February 28, 2012, 27 MM patients were enrolled in the study. Thirteen patients were women; median age was 63 years (range: 49–77); nine were black, one Asian, 17 Caucasian, and eight had diabetes. All patients had grade 2–4 sensorimotor PN: grade 2 (n=12), grade 3 (n=14), and grade 4 (n=1); 8 had painful PN. All patients had persistant PN despite discontinuation of bortezomib for a median of 19 months (range: 1–83). Eight patients were enrolled within 6 months of stopping bortezomib, all of them had grade 3–4 painful PN. Median time from diagnosis of MM to study entry was 30 months (range: 5–178). Nineteen patients were in remission and eight had progressive disease. MM therapy at study entry and through the follow up period included: revlimid (n=12), carflizomib (n=2). Therapy of PN included narcotics (n=13), gabapentin (12), amitriptyline (n=3), pregabalin (n=2), and duloxetine (n=2). Two patients withdrew after first acupuncture treatment. Twenty-five patients were evaluable for response after completion of 3 weeks (n=2), 6 weeks (n=2), 9 weeks (n=1) and 10 weeks of acupuncture (n=20). There were no adverse events associated with the acupuncture treatment. All but five patients maintained the same dose of pain medications throughout the study. Fourteen patients (56%) reported improved daily functions (e.g. walking and coordination). Ten patients (40%) reported 〉 50% decrease in average NPS during treatment (week 1–10). Seven patients reported 50% reduction in FACT/GOG-Ntx total scores. The decrease in NPS and FACT/GOG-Ntx, was statistically significant between baseline assessments through week 14; p-values are 0.001 and 10% increase in motor nerve amplitude but there was no correlation observed between symptoms/function improvements and nerve conduction studies. At week 8, one of the measured cytokines: Brain-Derived Neurotrophic Factor (BDNF) significantly increased from baseline (p=0.043). This increase was no longer significant at week 14 follow up. Conclusions: Acupuncture is safe and effective in treating persistent moderate to severe BIPN, with improvements of patient reported outcomes, pain and function. The increased BDNF during acupuncture treatment suggests that acupuncture may work through promoting survival and growth of neurons, a lengthy process that may explain the lag of significant objective clinical improvement in the short follow up of our patients. The mechanism of acupuncture working through BDNF to treat PN warrants further evaluation. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction : With increased use of CAR-T for relapsed/refractory (R/R) large B-cell lymphoma (LBCL), CAR-T related complications including cytokine release syndrome (CRS) and ICANS pose a significant clinical challenge. While CAR-T mediated inflammation leading to endothelial activation and blood-brain barrier disruption may play a key role in ICANS, the exact mechanism remains unclear. Prognostic or predictive biomarkers for ICANS are not well established. Recent reports (Karschnia et al, Blood 2019) suggested an association between ICANS and inferior overall survival (OS). To better understand ICANS, we herein report a single-center analysis of LBCL patients treated with CD19-directed CAR-T, exploring the associated clinical features, predictive biomarkers, and its prognostic significance. Methods: Patients (pts) with R/R LBCL treated with axicabtagene ciloleucel (Axi-cel) between 4/2018-5/2019 were identified. Data regarding patient and disease characteristics, treatment course, and clinical outcomes was collected (Table 1). Laboratory variables were collected at time of mononuclear cell harvest, day of initiation of lymphodepletive therapy, and day of CAR-T infusion (D0). CRS and ICANS were graded per the Lee and CTCAE v4.03 criteria, respectively. Time to progression (TTP) and OS were estimated by the Kaplan-Meier method and groups compared with the logrank test. Cox Proportional Hazard Model was applied for prognostic modeling. Binary logistic regression was used for multivariable analysis of patient characteristics at D0 associated with ICANS. Results: Forty-five pts with R/R LBCL (35 DLBCL, 7 TFL, 3 PMBCL) treated with Axi-cel were identified (Table 1). Twenty-five pts developed ICANS: n=7 with Grade (Gr) I-II, n=18 with Gr III-IV. Most common initial ICANS symptoms were dysgraphia, confusion, and somnolence; median time to ICANS was 5 days (range 3-11 days). Acute abnormalities were seen on brain MRI in 7 (28%) ICANS pts; EEG done in 10 ICANS pts showed diffuse slowing in all pts and focal slowing in 3 pts. All ICANS pts had preceding CRS, treated with tocilizumab (n=25, median 2.5 doses) and siltuximab (n=2). Twenty-three (92%) pts with ICANS required steroid therapy, with a median total dose equivalent to 221 mg of dexamethasone for a median duration of 12.5 days. Two pts exhibited protracted neurotoxicity manifested by short-term memory loss and profound weakness with immobility. Twenty-two (49%, 95% CI 34-64%) pts achieved CR, 16 PR, and 5 PD. At time of analysis, n=18 had disease relapse/progression and n=35 were alive. Censoring pts that progressed, the median observation time for TTP was 9.3 months. Censoring pts who died, the median observation time for OS was 7.9 months. At 9 months OS (±1 SE) was 76.1%±7.4%, and 56.0%±8.0% were progression-free. Logistic regression showed increasing fibrinogen level at D0 was associated with increasing risk of ICANS (p=0.003) and specifically, Gr III-IV ICANS [p