Centre Hospitalier Universitaire de Grenoble

The calcium load test (CLT) was developed by Pak et al. in 1974 to better discriminate hypercalciuria. Absorptive hypercalciuria (AH) is defined by an increase of the difference between urinary calcium/creatinine ratio (ΔUCa/Cr) of more than 0.5 mmol/mmol with a 4-hour CLT. In clinical practice and more recent studies, CLT is a 2-hour test. We hypothesized that the 4 h timepoint is more efficient in AH diagnosis.

We report a single-centre retrospective study including all patients who underwent CLT because of hypercalciuria or hyperparathyroidism. After a 3-day low-calcium diet and a 12-hour fast, 24-hour urines were collected. Blood and urinary samples were done at arrival and after 2 h and 4 h of oral ingestion of 1 g of calcium. AH was diagnosed by ΔUCa/Cr between baseline and 2 h or 4 h of more than 0.05 mmol/mmol.

We included 328 patients. Baseline UCa/Cr ratio was 0.3 ± 0.2 mmol/mmol and increased significantly after 2 h and 4 h (0.6 ± 0.3 and 0.8 ± 0.4 mmol/mmol, P < 0.001). ΔUCa/Cr was significantly different between baseline and 2 h or 4 h (0.2 ± 0.2 versus 0.5 ± 0.4, P < 0.001). AH was diagnosed in 35 (10.7%) patients after 2 h, 84 (25.6%) more were diagnosed at 4 h (P < 0.001).

The 4 h CLT improves the diagnosis of AH with more than 50% of AH diagnosed within 4 h of calcium ingestion. It seems that there are cases of AH of later diagnosis with a similar clinical and biological profile depending on enteral absorption.

Patients with atopic dermatitis (AD) may discontinue dupilumab owing to dupilumab-induced ocular adverse events (DOAEs) or dupilumab-induced facial redness (DFR).

To evaluate DOAE and DFR outcomes after switching to tralokinumab or Janus kinase inhibitor (JAKi).

This retrospective study included 106 patients discontinuing dupilumab because of DOAEs and/or DFR. The primary outcome was the proportion of patients with resolution of adverse events or improvement between dupilumab discontinuation (M0) and 3 to 6 months of tralokinumab or JAKi (M3-M6) treatment; the secondary outcome was the percentage of patients with controlled AD defined by Investigator's Global Assessment scores of 0/1 at M3 to M6.

Proportions of patients with DOAE (92% vs 72%; P = .0244) and DFR (85% vs 33%; P = .0006) resolution or improvement were higher with JAKi than with tralokinumab. Proportions of patients reaching an Investigator's Global Assessment score of 0/1 increased from M0-M3 through M6 (22% vs 42%; P = .0067) in the JAKi group and remained similar (32% vs 35%) in the tralokinumab group. However, 57% discontinued the new treatment after 8 months on average, mainly owing to lack of efficacy.

Janus kinase inhibitor appears to be more efficient than tralokinumab in managing dupilumab-induced AE; however, both strategies may fail to control AD.

Despite the use of midostaurin (MIDO) with intensive chemotherapy (ICT) as frontline treatment for Fms-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML), complete remission rates are close to 60% to 70%, and relapses occur in >40% of cases. Here, we studied the molecular mechanisms underlying refractory/relapsed (R/R) disease in patients with FLT3-mutated AML. We conducted a retrospective and multicenter study involving 150 patients with R/R AML harboring FLT3–internal tandem duplication (ITD) (n = 130) and/or FLT3–tyrosine kinase domain mutation (n = 26) at diagnosis assessed by standard methods. Patients were treated with ICT + MIDO (n = 54) or ICT alone (n = 96) according to the diagnosis date and label of MIDO. The evolution of FLT3 clones and comutations was analyzed in paired diagnosis–R/R samples by targeted high-throughput sequencing. Using a dedicated algorithm for FLT3-ITD detection, 189 FLT3-ITD microclones (allelic ratio [AR] of <0.05) and 225 macroclones (AR ≥ 0.05) were detected at both time points. At R/R disease, the rate of FLT3-ITD persistence was lower in patients treated with ICT + MIDO than in patients not receiving MIDO (68% vs 87.5%; P = .011). In patients receiving ICT + MIDO, detection of multiple FLT3-ITD clones was associated with a higher FLT3-ITD persistence rate at R/R disease (multiple clones: 88% vs single clones: 57%; P = .049). If only 24% of FLT3-ITD microclones detected at diagnosis were retained at relapse, 43% became macroclones. Together, these results identify parameters influencing the fitness of FLT3-ITD clones.