Baseline [18F]FDG PET features are associated with survival and toxicity in patients treated with CAR T cells for large B cell lymphoma.

PURPOSE: Chimeric antigen receptor (CAR) T cells have established themselves as an effective treatment for refractory or relapsed large B cell lymphoma (LBCL). Recently, the sDmax, which corresponds to the distance separating the two farthest lesions standardized by the patient's body surface area, has appeared as a prognostic factor in LBCL. This study aimed to identify [18F]FDG-PET biomarkers associated with prognosis and predictive of adverse events in patients treated with CAR T cells. METHODS: Patients were retrospectively included from two different university hospitals. They were being treated with CAR T cells for LBCL and underwent [18F]FDG-PET just before CAR T cell infusion. Lesions were segmented semi-automatically with a threshold of 41% of the maximal uptake. In addition to clinico-biological features, sDmax, total metabolic tumor volume (TMTV), SUVmax, and uptake intensity of healthy lymphoid organs and liver were collected. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The occurrence of adverse events, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), was reported. RESULTS: Fifty-six patients were included. The median follow-up was 9.7 months. Multivariate analysis showed that TMTV (cut-off of 36 mL) was an independent prognostic factor for PFS (p < 0.001) and that sDmax (cut-off of 0.15 m-1) was an independent prognostic factor for OS (p = 0.008). Concerning the occurrence of adverse events, a C-reactive protein level > 35 mg/L (p = 0.006) and a liver SUVmean > 2.5 (p = 0.027) before CAR T cells were associated with grade 2 to 4 CRS and a spleen SUVmean > 1.9 with grade 2 to 4 ICANS. CONCLUSION: TMTV and sDmax had independent prognostic values, respectively, on PFS and OS. Regarding adverse events, the mean liver and spleen uptakes were associated with the occurrence of grade 2 to 4 CRS and ICANS, respectively. Integrating these biomarkers into the clinical workflow could be useful for early adaptation of patients management.

Proteic composition of corpora amylacea in the bovine mammary gland.

Histochemical studies of mammary gland sections obtained from healthy lactating Prim' Holstein cows contained numerous corpora amylacea, mainly located in active alveoli. Observations by electron microscopy revealed a cauliflower shape, with a fibrillar or multilayered organization. Mineral studies confirmed the presence of high calcium levels (12.3% of dry matter) and phosphorus (7.4%) in the corpora amylacea composition. These bodies stained positive to Von Kossa silver nitrate and to Periodic acid-Schiff. However, depending on the gland of origin, corpora amylacea stained positive or negative to Congo red. Histochemical studies seemed, therefore, insufficient to determine the presence or absence of amyloid. The amount of total protein varied by approximately 25%. Immunoblotting and analysis of the amino acid sequence of a peptidic fragment obtained from corpora amylacea gave clear evidence of the occurrence of caseins, beta-lactoglobulin and alpha-lactalbumin. However, the comparison between the amino acid composition of corpora amylacea and those of the main milk proteins indicated the presence of other proteins. Electrophoretic analysis also gave evidence of the presence of several other proteins, i.e. glycoproteins. Therefore, it is probable that corpora amylacea composition is much more complex than previously reported.

Microparticle-enhanced nephelometric immunoassay of human plasminogen.

A microparticle-enhanced nephelometric immunoassay was developed for plasminogen quantitation in human plasma. It is based on the nephelometric measurement of the light scattered by microparticle clusters formed during a sandwich reaction between plasminogen, microparticle--anti-plasminogen conjugate, and the free antibodies of anti-plasminogen rabbit antiserum. This immunoassay was sensitive (detection limit in reaction mixture, 34 micrograms/L) and could be performed in 500-fold diluted human plasma, excluding any interference or sample pretreatment. It allowed the quantitation of plasminogen on a large range of concentrations (17-550 mg/L), with a security in antigen excess reaching 1,100 mg/L, with accuracy (linear recovery in dilution-overloading assay and correlation with conventional immunonephelometry), and precision (within- and between-run coefficients of variation lower than 8%). A normal reference range from 54 to 148 mg/L (mean +/- 2 SD) was calculated from plasminogen concentration in plasma from 130 adults. Easy to perform (no washing or phase separation) and rapid (two steps of 30 minutes then 1 hour of incubation at room temperature), this microparticle-enhanced nephelometric immunoassay could be an interesting alternative method for human plasminogen quantitation.

Quantitative characterization of bovine plasminogen binding to caseins.

The binding of bovine plasminogen to whole casein, alpha s-casein, beta-casein, and kappa-casein is responsible for the progressive proteolysis of milk and dairy products. A sensitive and accurate microparticle-enhanced nephelometric immunoassay was developed to measure free plasminogen after interaction between bovine plasminogen and caseins and the quantitative parameters of plasminogen/casein binding were established. Two classes of binding sites for plasminogen were found in this study on each of the investigated caseins. Their dissociation constants (Kd) were determined by varying the plasminogen concentration at pH 6.6 and performing Scatchard analysis. The two binding sites appeared to be one of high affinity (Kd = 32 nM) and the other of lower affinity (Kd > 370 nM). The number of both binding sites per casein monomer was low (0.04 to 0.53). The great propensity of casein monomers to self-associate in homopolymers where plasminogen binding sites could be hidden and in copolymers present in bovine milk in the form of whole casein micelles accounts for calculated binding sites < 1 per monomer.

[Evaluation of pulmonary systolic arterial pressures by continuous Doppler in tricuspid regurgitation in adults. Apropos of 43 cases]. / Estimation des pressions artérielles pulmonaires systoliques par le Doppler continu en présence d'une fuite tricuspide chez l'adulte. A propos de 43 cas.

Forty-three hospital patients with tricuspid regurgitation were prospectively explored by continuous wave Doppler ultrasound to determine their pulmonary systolic arterial pressure. In the absence of pathology of the pulmonary orifice this value corresponds to the sum of the right atrioventricular systolic gradient calculated by Bernoulli's equation DP = 4V2 from the tricuspid regurgitation and the right atrial pressure evaluated by clinical examination. The values obtained are compared with the results of right heart catheterization. Our study showed good correlation (r = 0.90) with a standard error of 8.2 mmHg, the main source of effort being the clinical quantification of right atrial pressure. These results confirm that pulmonary systolic arterial pressure can reliably be measured by this method in the presence of tricuspid regurgitation. The method is of considerable interest in permanent pulmonary hypertension or in emergencies.

Side-chain interactions and conformation in alpha-helical poly(gamma-phenacyl L-glutamate). Aggregation in dilute solutions.

The behavior of alpha-helical poly(gamma-phenacyl L-glutamate) (PPLG) has been studied by hydrodynamic, optical rotation, dielectric, and nmr measurements in different solvents. Special attention has been paid to side-chain interactions which depend on the ease of solvation of the phenacyl chromophore. Thus, in hexafluoro-2-propanol the circular dichroism spectrum is very similar to that usually observed for an alpha helix, and hydrogen bonding was shown to occur between the solvent and phenacyl CO group. In other heliocogenic solvents, side chain-side chain interactions occur. In dimethylformamide and pyridine they give rise at low temperature and low concentrations to an aggregation phenomenon whose molecular mechanism implies a molecular weight dependent folding of the molecules. Models for the side-chain conformation are proposed for the polymer in the solid state on the basis of infrared dichroism.