ALBERT

Description: Introduction Diffuse large B cell lymphoma (DLBCL) and osteoporotic fracture are commoner in older patients (pts). Steroids and chemotherapy are recognised as a risk factor (RF) for fragility-related fracture and its associated morbidity. A small randomised trial (RCT) (Westin 2013) showed bisphosphonates stabilize bone mineral density (including all ages / histologies) in NHL pts. Despite this, there is a lack of data defining the specific incidence and fracture risk in older DLBCL pts post R-CHOP. We aimed to better define this risk in this specific cohort. Methods Data on consecutive DLBCL pts ≥70 years (y) treated with R-CHOP were retrospectively collected across 7 UK centres (2009-2019). Follow up was censored in 07/2019. All pts had untreated, de novo DLBCL or untreated transformed (to DLBCL) indolent B cell NHL. PTLD, HIV and pre-treated NHL pts were excluded. All pts received 1-9 cycles of full or attenuated R-CHOP with curative intent. Pts were excluded if they had progressive disease (PD) or died 〈 6 months (m) of cycle 1 R-CHOP (RCHOP1). A detailed anonymised database included ECOG performance status (PS), body mass index (BMI), history of osteoporosis / osteopenia, documented steroid pre-phase, vitamin D supplementation, calcium and alkaline phosphatase levels, and sites of bone DLBCL involvement. Fractures at diagnosis (DLBCL-related/unrelated) and pre diagnosis were collected. Fractures (including bone site) occurring during 18m from RCHOP1 were identified from radiology records. Pts were followed for a minimum of 6m and censored at 18m from RCHOP1, or at their last follow up if 〈 18m or at PD or death if between 6-18m. Baseline pt characteristics were descriptive. Survival analyses were performed using Kaplan Meier methods and Cox regression with comparisons between categories using the log-rank test. Time to event analyses were measured from RCHOP1 until fracture event. Primary end point was 18m cumulative fracture incidence censoring pts at death or relapse. Univariable and multivariable analyses (UVA; MVA) of potential influencing RFs for fracture was assessed by Cox regression (Final stepwise model; p=0.1 for inclusion). Results Of 589 pts identified, 92 pts had PD or died prior to 6m and were excluded. 20 pts were excluded due to short follow up. Across 477 pts, the median age was 77 (range 70-93) y. 66% had an ECOG PS 0-1. The median cycles given was 6 (range 1-9). 27.3% received pre-phase steroids. The median BMI was 25.5 (range 14.2-48.1). 8.1% had a fracture prior to DLBCL, and 9.1% had a history of osteopenia or osteoporosis. 5.7% were current smokers, 3% had rheumatoid arthritis, 13.5% had type (T) 2 diabetes (DM), and 4.5% had a history of excess alcohol. At baseline, 25.2% had PET or CT-assessed cortical bone involvement. Overall, there were 52 fractures, including 50 within 18m follow up. Cumulative fracture incidence was 6.3% (95% confidence interval (CI) 4.4 - 8.9) at 6m, 9.5% (95% CI 7.1 - 12.6) at 12m and 11.5% (95% CI 8.8 - 14.9) at 18m (Fig A). 6 pts had multiple fracture sites (2; n=5, 3; n=1). 32 (62%) had vertebral fracture(s). Thoracic (34% 20/59) and lumbar vertebral (27% 16/59) were dominant sites (Fig C). 7/52 fractures were at the site of DLBCL involvement, 17/52 were at a different site from initial bone DLBCL involvement, 27/52 were in pts without bone involvement and 1/52 was unknown. Univariable RFs included female sex (hazard ratio (HR) 1.89 (95% CI 1.05 - 3.28)), known osteopenia or osteoporosis (HR 2.64 (95% CI 1.32 - 5.29)), DLBCL-related fracture at diagnosis (HR 4.05 (95% CI 2.07 - 7.92) (Fig B). Initial bone involvement was only associated with an increased risk in pts with a DLBCL-related baseline fracture (95% CI HR 4.56 (2.27 - 9.17)) (Table 1). MVA showed that DLBCL-related baseline fracture (HR 4.32 (1.97 - 9.47)) was the only significant independent RF for fracture with low BMI (p=0.051) and smoking history (p=0.052) of borderline significance (Table 2). Conclusions This is the largest series to date to show there is a clinically relevant fracture risk in older DLBCL pts specifically receiving R-CHOP in early follow up. Our data have limitations inherent to a retrospective study including the potential for unknown confounders, missing data, and medical record misinterpretation. Prospective data is required to validate RFs identified which could enable targeting a high-risk population. An RCT is needed to determine the value of prophylactic intervention(s) in high risk pts. Figure Disclosures Gibb: Takeda: Research Funding. Collins:Gilead: Consultancy, Honoraria. Eyre:Janssen: Honoraria; Abbvie: Honoraria; Gilead: Consultancy, Honoraria, Other: commercial research support; Roche: Honoraria.

Description: We investigated total electron content (TEC) at Ilorin (8.50∘ N 4.65∘ E, dip lat. 2.95) for the year 2010, a year of low solar activity in 2010 with Rz=15.8. The investigation involved the use of TEC derived from GPS, estimated TEC from digisonde portable sounder data (DPS), and the International Reference Ionosphere (IRI) and NeQuick 2 (NeQ) models. During the sunrise period, we found that the rate of increase in DPS TEC, IRI TEC, and NeQ TEC was higher compared with GPS TEC. One reason for this can be attributed to an overestimation of plasmaspheric electron content (PEC) contribution in modeled TEC and DPS TEC. A correction factor around the sunrise, where our finding showed a significant percentage deviation between the modeled TEC and GPS TEC, will correct the differences. Our finding revealed that during the daytime when PEC contribution is known to be absent or insignificant, GPS TEC and DPS TEC in April, September, and December predict TEC very well. The lowest discrepancies were observed in May, June, and July (June solstice) between the observed values and all the model values at all hours. There is an overestimation in DPS TEC that could be due to extrapolation error while integrating from the peak electron density of F2 (NmF2) to around ∼1000 km in the Ne profile. The underestimation observed in NeQ TEC must have come from the inadequate representation of contribution from PEC on the topside of the NeQ model profile, whereas the exaggeration of PEC contribution in IRI TEC amounts to overestimation in GPS TEC. The excess bite-out observed in DPS TEC and modeled TEC indicates over-prediction of the fountain effect in these models. Therefore, the daytime bite-out observed in these models requires a modifier that could moderate the perceived fountain effect morphology in the models accordingly. The daytime DPS TEC performs better than the daytime IRI TEC and NeQ TEC in all the months. However, the dusk period requires attention due to the highest percentage deviation recorded, especially for the models, in March, November, and December. Seasonally, we found that all the TECs maximize and minimize during the March equinox and June solstice, respectively. Therefore, GPS TEC and modeled TEC reveal the semiannual variations in TEC.

Description: Rate of change of TEC (ROT) and its index (ROTI) are considered a good proxy to characterize the occurrence of ionospheric plasma irregularities like those observed after sunset at low latitudes. SBASs (satellite-based augmentation systems) are civil aviation systems that provide wide-area or regional improvement to single-frequency satellite navigation using GNSS (Global Navigation Satellite System) constellations. Plasma irregularities in the path of the GNSS signal after sunset cause severe phase fluctuations and loss of locks of the signals in GNSS receiver at low-latitude regions. ROTI is used in this paper to characterize plasma density ionospheric irregularities in central–western Africa under nominal and disturbed conditions and identified some days of irregularity inhibition. A specific low-latitude algorithm is used to emulate potential possible SBAS message using real GNSS data in the western African low-latitude region. The performance of a possible SBAS operation in the region under different ionospheric conditions is analysed. These conditions include effects of geomagnetic disturbed periods when SBAS performance appears to be enhanced due to ionospheric irregularity inhibition. The results of this paper could contribute to a feasibility assessment of a European Geostationary Navigation Overlay System-based SBAS in the sub-Saharan African region.

Description: We investigated total electron content (TEC) at Ilorin (8.50°N 4.65°E, dip lat. 2.95) during a low solar activity 2010. The investigation involved the use of GPS derived TEC, TEC estimated from digisonde portable sounder data (DPS-TEC), the International Reference Ionosphere model (IRI-TEC) and NeQuick 2 model (NeQ-TEC). The five most quietest days of the months obtained from the international quiet days (IQD) from the website http://www.ga.gov.au/oracle/geomag/iqd_form.jsp were used for the investigation. During the sunrise period, we found that the rate of increases in DPS-TEC, IRI-TEC and NeQ-TEC were higher with respect to GPS-TEC. One reason for this can be alluded to an overestimation of plasmaspheric electron content (PEC) contribution in modeled TEC and DPS-TEC. A correction factor around the sunrise where a significant percentage difference of overestimations between the modeled TEC and GPS-TEC was obtained will correct the differences. Our finding revealed that during the daytime when PEC contribution is known to be absent or insignificant, GPS-TEC and DPS-TEC in April, September and December predicts TEC very well. The lowest discrepancies were observed in May, June and July (June solstice) between the observed and all the model values in all hours. There is an overestimation in DPS-TEC that could be due to extrapolation error while integrating from the peak electron density of F2 (NmF2) to around ~1000km in the Ne profile. The underestimation observed in NeQ-TEC must have come from the inadequate representation of contribution from PEC on the topside of NeQ model profile whereas the exaggeration of PEC contribution in IRI-TEC amount to overestimations of GPS-TEC. The excess bite-out observed in DPS-TEC and NeQ-TEC show the indication of overprediction of fountain effect in these models. Therefore, the daytime bite-out observed in these two models require a modifier that could moderate the perceived fountain effect morphology in the models accordingly. Seasonally, we found that all the TECs maximize and minimize during the March equinox and June solstice, respectively. Therefore, GPS-, DPS-, IRI- and NeQ-TEC reveal the semi-annual variations in TEC as reported in all regions. The daytime DPS-TEC performs better than the daytime IRI-TEC and NeQ-TEC in all the months, however, the dusk period requires attention due to highest percentage difference recorded especially for DPS-TEC and the models in March, and November and December for DPS-TEC.

Description: Introduction: Interim PET identifies patients with early stage classical HL (cHL) suitable for risk-adapted treatment escalation or de-escalation, but relapse-free survival remains inferior for patients with a negative interim PET who omit radiotherapy. Genetic risk predictors have demonstrated potential to enhance the negative predictive value of interim PET. In the BioPET study reported here, we evaluated the association between a priori selected candidate genes with interim PET and cHL-specific event free survival (cHL-EFS) for patients enrolled on the UK NCRI RAPID trial (NCT00943423). Methods: Patients with stage 1A or 2A cHL treated with 3 cycles of ABVD followed by interim PET assessment using a 5-point scale, full clinical data and available diagnostic biopsy material were included. Patients with a score of 1-2 (PET 'negative') were randomised (1:1) to involved field radiotherapy (IFRT) or no further treatment (NFT); those with a score of 3-5 (PET 'positive') received a further cycle of ABVD plus IFRT. Pre-treatment diagnostic FFPE material was obtained for 227 patients (21 with cHL events). Tissue homogenates were prepared and analysed using Quantigene 2.0 (QG_2.0) Plex for expression of 57 candidate genes known to be associated with treatment response and survival in cHL. QG_2.0 data were generated for experimental samples (n=227), RNA controls (n=15) and FFPE controls (n=12). Data were capped at both upper and lower limits of detection. Four housekeeper genes with the lowest variance (GUSB, TBP, HMBS, ABL1) were used for normalisation using the geometric mean. Candidate genes were ranked according to variability of expression. The association between gene expression, PET outcomes and cHL-EFS (disease progression or death) in the three treatment groups was evaluated in a series of regression analyses (Cox and binary logistic), both in univariable and multivariable settings using stepwise procedures, taking baseline EORTC and GHSG risk stratification into account. Analyses were run on the full dataset as there were insufficient cases for a training:validation split. Results: In total, cHL events were observed in 10/121 (8.3%) PET score 1, 4/53 (7.5%) PET score 2, 2/33 (6.1%) PET score 3, 1/10 (10.0%) PET score 4 and 4/10 (40.0%) PET score 5 respectively. Several genes were found to be associated with PET response after ABVD, and two genes remained in the multivariable model: PRF1 increased the risk of PET score 3-5 (OR=1.49, 95% CI: 1.05-2.13, p=0.03); BCL2L1 decreased risk (OR=0.65, 95% CI: 0.44-0.96, p=0.03). BCL2L1 was also strongly associated with a lower PET score (OR=0.62, 95% CI: 0.46-0.83, p

Description: Moyamoya disease, well described in literature, is a chronic cerebrovascular occlusive disorder. It is characterized by progressive stenosis/occlusion of the terminal portions of the internal carotid arteries (ICA) and the proximal portions of the middle cerebral arteries (MCA). Less frequently described is Moyamoya syndrome, the name given to radiographic findings consistent with Moyamoya disease, but with an identifiable cause. The diseases associated with Moyamoya Syndrome include Sickle Cell Disease (SCD), Thalassemias, and Down's Syndrome to name a few. Common complications of Moyamoya include both ischemic and hemorrhagic strokes. Upon literature review, Moyamoya syndrome caused by SCD is not well described. When it is, the discussion is centered around the pediatric patient population and surgical management. Our case report describes a 22-year-old African American female with SCD who initially presented with Acute Chest Syndrome. Her hospital course was complicated by development of overt debilitating neurologic deficits. Subsequently, she was found to have Moyamoya Syndrome on neuroimaging. She was successfully treated with medical management without any surgical intervention. This case highlights the necessity of thorough examination, differential diagnosis, imaging findings, and consideration of predisposing syndromes in the work-up for Moyamoya syndrome; especially individuals with Sickle Cell Disease. Disclosures No relevant conflicts of interest to declare.