When clonal plasma cells grow at anatomic sites distant from the bone marrow or grows contiguous from osseous lesions that break through the cortical bone, it is referred to as extramedullary ...multiple myeloma (EMD). EMD remains challenging from a therapeutic and biological perspective. The pathogenetic mechanisms are not completely understood and it is generally associated with high-risk cytogenetics which portends poor outcomes. There is a rising incidence of EMD in the era of novel agents, likely a reflection of longer OS, with no standard treatment approach. Patients benefit from aggressive chemotherapy-based approaches, but the OS and prognosis remains poor. RT has been used for palliative care. There is a need for large prospective trials for development of treatment approaches for treatment of EMD.
A model's ability to express its own predictive uncertainty is an essential attribute for maintaining clinical user confidence as computational biomarkers are deployed into real-world medical ...settings. In the domain of cancer digital histopathology, we describe a clinically-oriented approach to uncertainty quantification for whole-slide images, estimating uncertainty using dropout and calculating thresholds on training data to establish cutoffs for low- and high-confidence predictions. We train models to identify lung adenocarcinoma vs. squamous cell carcinoma and show that high-confidence predictions outperform predictions without uncertainty, in both cross-validation and testing on two large external datasets spanning multiple institutions. Our testing strategy closely approximates real-world application, with predictions generated on unsupervised, unannotated slides using predetermined thresholds. Furthermore, we show that uncertainty thresholding remains reliable in the setting of domain shift, with accurate high-confidence predictions of adenocarcinoma vs. squamous cell carcinoma for out-of-distribution, non-lung cancer cohorts.
Silicon photonics is emerging as a competitive platform for electronic-photonic integrated circuits (EPICs) in the 2 µm wavelength band where GeSn photodetectors (PDs) have proven to be efficient ...PDs. In this paper, we present a comprehensive theoretical study of GeSn vertical
homojunction waveguide photodetectors (WGPDs) that have a strain-free and defect-free GeSn active layer for 2 µm Si-based EPICs. The use of a narrow-gap GeSn alloy as the active layer can fully cover entire the 2 µm wavelength band. The waveguide structure allows for decoupling the photon-absorbing path and the carrier collection path, thereby allowing for the simultaneous achievement of high-responsivity and high-bandwidth (BW) operation at the 2 µm wavelength band. We present the theoretical models to calculate the carrier saturation velocities, optical absorption coefficient, responsivity, 3-dB bandwidth, zero-bias resistance, and detectivity, and optimize this device structure to achieve highest performance at the 2 µm wavelength band. The results indicate that the performance of the GeSn WGPD has a strong dependence on the Sn composition and geometric parameters. The optimally designed GeSn WGPD with a 10% Sn concentration can give responsivity of 1.55 A/W, detectivity of 6.12 × 10
cmHz
W
at 2 µm wavelength, and ~97 GHz BW. Therefore, this optimally designed GeSn WGPD is a potential candidate for silicon photonic EPICs offering high-speed optical communications.
Type 2 diabetes mellitus (T2DM) is a chronic disease that is characterized by impaired glucose metabolism and insulin resistance. The objectives of the study were to evaluate the pattern of leptin ...receptor gene polymorphism Gln223Arg in T2DM and to identify its association with the serum leptin and insulin levels as well as with insulin resistance in diabetes.
In this cross-sectional study, genotyping of leptin receptor was done for Gln223Arg alleles by PCR-restriction fragment length polymorphism in 39 patients with type 2 diabetes. Serum leptin and insulin levels were assayed using enzyme linked sorbent assay in 39 cases and 45 nondiabetic controls. Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) formula. Statistical analysis was performed with Graph pad Instat version 3.
Hardy-Weinberg Equilibrium for the leptin receptor (LEPR) gene variants showed that alleles were in equilibrium. Leptin levels were insignificantly low in patients with diabetes compared to those in controls. Women in the control group showed significantly higher leptin levels (p < 0.05) compared with men. There was a significant difference in the serum insulin levels and insulin resistance (HOMA-IR) among patients with different genotypes (p = 0.04 and p = 0.0378, respectively).
Leptin receptor gene polymorphism affected glucose metabolism by altering insulin resistance and pancreatic beta cells. Thus, single-nucleotide polymorphism of LEPR may affect the pathogenesis of T2DM.
BCMA-directed CAR T-cell therapy (CAR-T) has altered the treatment landscape of relapsed/refractory (r/r) multiple myeloma, but is hampered by unique side effects that can lengthen hospital stays and ...increase morbidity. Hematological toxicity (e.g. profound and prolonged cytopenias) represents the most common grade ≥ 3 toxicity and can predispose for severe infectious complications. Here, we examined the utility of the CAR-HEMATOTOX (HT) score to predict toxicity and survival outcomes in patients receiving standard-of-care idecabtagene vicleucel and ciltacabtagene autoleucel.
Data were retrospectively collected from 113 r/r multiple myeloma patients treated between April 2021 and July 2022 across six international CAR-T centers. The HT score-composed of factors related to hematopoietic reserve and baseline inflammatory state-was determined prior to lymphodepleting chemotherapy.
At lymphodepletion, 63 patients were HT
(score 0-1) and 50 patients were HT
(score ≥ 2). Compared to their HT
counterparts, HT
patients displayed prolonged severe neutropenia (median 9 vs. 3 days, p < 0.001), an increased severe infection rate (40% vs. 5%, p < 0.001), and more severe ICANS (grade ≥ 3: 16% vs. 0%, p < 0.001). One-year non-relapse mortality was higher in the HT
group (13% vs. 2%, p = 0.019) and was predominantly attributable to fatal infections. Response rates according to IMWG criteria were higher in HT
patients (≥ VGPR: 70% vs. 44%, p = 0.01). Conversely, HT
patients exhibited inferior progression-free (median 5 vs. 15 months, p < 0.001) and overall survival (median 10.5 months vs. not reached, p < 0.001).
These data highlight the prognostic utility of the CAR-HEMATOTOX score for both toxicity and treatment response in multiple myeloma patients receiving BCMA-directed CAR-T. The score may guide toxicity management (e.g. anti-infective prophylaxis, early G-CSF, stem cell boost) and help to identify suitable CAR-T candidates.
Majority of non-Hodgkin lymphoma (NHL) patients who achieve partial response (PR) or stable disease (SD) to CAR T-cell therapy (CAR T) on day +30 progress and only 30% achieve spontaneous complete ...response (CR). This study is the first to evaluate the role of consolidative radiotherapy (cRT) for residual fluorodeoxyglucose (FDG) activity on day +30 post- CAR T in NHL. We retrospectively reviewed 61 patients with NHL who received CAR T and achieved PR or SD on day +30. Progression-free survival (PFS), overall survival (OS), and local relapse-free survival (LRFS) were assessed from CAR T infusion. cRT was defined as comprehensive - treated all FDG-avid sites - or focal. Following day +30 positron emission tomography scan, 45 patients were observed and 16 received cRT. Fifteen (33%) observed patients achieved spontaneous CR, and 27 (60%) progressed with all relapses involving initial sites of residual FDG activity. Ten (63%) cRT patients achieved CR, and four (25%) progressed with no relapses in the irradiated sites. The 2-year LRFS was 100% in the cRT sites and 31% in the observed sites (P<0.001). The 2-year PFS was 73% and 37% (P=0.025) and the 2-year OS was 78% and 43% (P=0.12) in the cRT and observation groups, respectively. Patients receiving comprehensive cRT (n=13) had superior 2- year PFS (83% vs. 37%; P=0.008) and 2-year OS (86% vs. 43%; P=0.047) compared to observed or focal cRT patients (n=48). NHL patients with residual FDG activity following CAR T are at high risk of local progression. cRT for residual FDG activity on day +30 post-CAR T appears to alter the pattern of relapse and improve LRFS and PFS.
F-18 fluorodeoxyglucose positron emission tomography computed tomography (PET/CT) is used to assess response of non-Hodgkin lymphoma (NHL) to chimeric antigen receptor T cell (CAR-T) therapy. We ...sought to describe metabolic and volumetric PET prognostic factors at one month post-CAR-T and identify which patients with partial response (PR) or stable disease (SD) are most likely to subsequently achieve complete response (CR), and which will develop progressive disease (PD) and death.
Sixty-nine patients with NHL received axicabtagene ciloleucel CAR-T therapy. One-month post-CAR-T infusion and PET/CT scans were segmented with a fixed absolute SUV maximum (SUVMax) threshold of 2.5 using a semiautomated workflow with manual modification to exclude physiologic uptake as needed. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), SUVMax, and other lesion characteristics were calculated and associated with risk of PD and death.
Patients with total MTV > 180 cc, presence of bone or parenchymal disease, SUVMax > 10, single lesion TLG > 245 g, or > 2 total lesions had increased risk of death. Patients with total MTV > 55 cc, total TLG > 250 cc, SUV Max > 10, or > 2 total lesions had increased risk of PD. For the subset of 28 patients with PR/SD, higher SUVMax was associated with increased risk of subsequent PD and death. While 86% of patients who had SUVMax ≥ 10 eventually had PD (HR 3.63, 1.13-11.66, p = 0.03), only 36% of those with SUVMax < 10 had PD.
Higher SUVMax at one month post-CAR-T is associated with higher risk of PD and death. SUVMax ≥ 10 may be useful in guiding early salvage treatment decisions in patients with SD/PR at one month.
Abstract In the present study, three varieties of kidney beans (Red Rajma (RR), Rajma Chitra (RC), and Rajma Sharmili (RS)) were physically characterized and the effect of pre-gelatinization by ...microwave and hot water on functional and pasting properties of flour were studied. A significant difference was observed in the physical properties of all the kidney beans, indicating that they can be easily characterized and identified based on physical properties. Pre-gelatinization treatment led to variation in color, functional and pasting properties of flours. Color parameters L*, b*, chroma, and hue values reduced with the treatment, whereas a* and total color difference ( $$\Delta$$ Δ E) values increased. Water absorption capacity (WAC) and oil absorption capacity (OAC) varied in the range of 1.15–1.91% and 1.25–1.75% for microwave and hot water treatment, respectively. The highest value of WAC and OAC was observed for microwave-treated RC and hot water-treated RR, respectively. WAC increases with both treatments, whereas OAC increases only with water bath cooking. Functional group analysis (FTIR) showed no major peaks shifting in water bath treatment, whereas a slight deflation of certain peaks was observed in the case of microwave treatment. Pasting curves showed a significant reduction in peak and final viscosity after pre-gelatinization treatment; however, none of the samples showed any breakdown during cooking. Graphical Abstract
PDF
