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Overall Survival After Allogeneic Transplantation in Advanced Cutaneous T-Cell Lymphomas (CUTALLO): A Propensity Score–Matched Controlled Prospective Study
No full textInternational audienceCutaneous T-cell lymphomas (CTCLs) are rare, usually refractory, and sometimes fatal diseases. Patients presenting with advanced-stage CTCL usually exhibit poor long-term survival outcomes. Only very few treatments have improved progression-free survival (PFS) in advanced CTCL, and no treatment has increased overall survival (OS). In 2023, the results of the CUTALLO trial supported the hypothesis that hematopoietic stem-cell transplantation (HSCT) was associated with significantly longer PFS as compared with standard-of-care treatment among advanced-stage patients although HSCT did not significantly affect OS. We provide herein the final OS data pertaining to the same patient population after a longer median follow-up of 38.9 months. Of the 99 patients included in the analysis, 55 (56%) were assigned to the HSCT group, whereas 44 (44%) were allocated to the non-HSCT group. The updated survival analysis reported that 16 of 55 patients (29%) in the HSCT group and 22 of 44 patients (50%) in the non-HSCT group died. The median OS was not reached in the HSCT group and 51.5 months (95% CI, 26.9 to 51.5) in the non-HSCT group (hazard ratio, 0.40 [95% CI, 0.20 to 0.80]). Compared with the standard of care for advanced CTCL, after extended follow-up, allogeneic HSCT was associated with significantly longer OS. ClinicalTrials.gov NCT02520908
About two French cases of disseminated Cryptococcus neoformans infection associated with COVID-19
No full textInternational audienceSARS-CoV-2 infection is an acute respiratory distress syndrome associated with immune dysfunction, causing coronavirus disease 2019 (COVID-19) disease. The use of immunosuppressive drugs in its treatment increases the risk of opportunistic infections. In particular, opportunistic fungal infections have been described in initially non-immunocompromised patients with severe COVID-19 disease. Among them, rare cases of cryptococcosis have been described. Here we present the first two French cases of non-HIV non-transplant patients who developed disseminated Cryptococcus neoformans fungal infection in the setting of severe COVID-19 disease. Blood cultures appear to be an interesting diagnostic tool for post-COVID-19 cryptococcosis, which is an often fatal complication
Simultaneous Detection of Sarcocystis hominis , S. heydorni , and S. sigmoideus in Human Intestinal Sarcocystosis, France, 2021–2024
No full textEditorial MaterialInternational audienceTo elucidate the epidemiology of Sarcocystis spp. parasites in human intestinal infections, we used high- throughput sequencing to investigate human intestinal sarcocystosis cases identified by microscopy in France during 2021-2024. Our results indicate that humans are a definitive host of S. sigmoideus parasites and that occurrence of multiple species in 1 patient is common
Efficient enrichment of plasma-derived extracellular vesicles from small volumes of bovine blood
No full textInternational audienceThere is a growing interest in small extracellular vesicles (sEVs). These nanoparticles, which range in diameter from 30 to 150 nm, are secreted by cells into their surrounding environment and transfer biological content to distant cells. However, the lack of consensus on sEV isolation, from bovine plasma limits their study. This work aimed to develop an optimized method to enrich sEVs from 4 mL of bovine blood plasma. To increase the yield of sEVs while reducing contamination from other particles and free proteins, sEVs were isolated from 38 bovine plasma samples of crossbred heifers using sequential centrifugation and filtration with size-exclusion chromatography. In accordance with the Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines, the sEV preparations were characterized in terms of size, particles concentration, morphology, and sEV markers. To accurately estimate particle size and distribution, we used a combination of three methods. This approach confirmed that 76% of the particles fell within the expected range of 30-150 nm for sEVs. The preparations were pure, with an average particle-to-protein ratio of 2.4 × 108 particles/µg of protein. This is comparable to or exceeds recent observations in bovine and other mammalian species when blood plasma and serum are used. Moreover, albumin, accounted for only 1.8–6.5% of the final protein abundance, indicating a 90–98% depletion relatively to raw plasma. Microscopy confirmed the presence of cup-shaped particles characteristic of sEVs. Proteomic characterization identified 417 proteins (FDR 1%, ≥ 2 peptides), corresponding to 372 unique homologous human gene names, including the cytosolic (HSPA8, SDCBP, ACT, TUB, GAPDH) and membrane (CD9, CD81) markers of sEVs. Of these proteins, 347 (93%) are referenced in Vesiclepedia, an international database of sEV proteome, suggesting a strong enrichment of sEVs during the purification process. This finding is supported by the identification of 172 significantly enriched Gene Ontology terms related to sEV annotation (P < 0.01, Fisher’s one-tailed test with Benjamin–Hochberg correction) such as GO:0005615 (extracellular space) and GO:1903561 (extracellular vesicle). According to the MISEV guidelines and proteomic requirements, the proposed optimized sEV enrichment protocol is suitable for 4 mL of plasma. These results pave the way for future research into the role of sEVs in relation to animal health and performance
Short-term effects of high-protein, lower-carbohydrate ultra-processed foods on human energy balance
No full textInternational audienceProtein-enriched ultra-processed foods (UPFs) are generally perceived as a healthy and favourable dietary choice for weight management. However, compared with low-processed foods, the consumption of UPFs has been demonstrated to result in overfeeding and gains in body weight and fat mass. Here we investigate the short-term effects of protein-enriched UPFs on energy intake and energy balance in a single-blind crossover trial involving 21 healthy young adults, who were randomly assigned to 2 UPF diets for 54 hours in a whole-room calorimeter. Participants received either a high-protein (30%) and lower-carbohydrate (29%) diet (HPLC-UPF) or a normal-protein (13%) and normal-carbohydrate (46%) diet (NPNC-UPF). Meals were equally palatable, matched for calories, fat and fibre, and consumed ad libitum. As primary outcomes, compared with NPNC-UPF consumption, the HPLC-UPF diet resulted in a higher energy expenditure (128 ± 98 kcal d −1 ) and lower energy intake (−196 ± 396 kcal d −1 ), leading to a less-positive energy balance (18% versus 32%) with gains in protein and carbohydrate balance only. Postprandial ghrelin levels were lower, whereas glucagon and peptide YY levels were higher with HPLC-UPF compared with NPNC-UPF (secondary outcomes). Despite a reduction in energy intake and increased energy expenditure, the short-term consumption of protein-enriched UPFs did not prevent overeating but did favourably affect energy partitioning. ClinicalTrials.gov registration: NCT05337007
Amélioration des pratiques de recueil des données médicales dans un service hospitalo-universitaire d’Orthopédie dento-faciale
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P-gp quantification for cell resistance studies in leukemia cells using the innovative LightSpot-FL-1 fluorescent conjugate.
No full textInternational audienceMultidrug resistance proteins contribute to chemotherapy resistance in various cancers. Among them, the P-glycoprotein (P-gp) has been the most investigated. These works aim to evaluate the efficacy of the new fluorescent tracer LightSpot-FL-1 for quantifying P-gp in CCRF-CEM and KG-1a acute leukemia cell lines, as well as in blood samples from healthy donors and leukemic patients. First, The P-gp quantity in CCRF-CEM and KG-1a cells measured by LightSpot-FL-1, was 7052 ± 2789 FU and 27,666 ± 6706 FU, respectively. Then, cells exposure to 10 µM daunorubicin (DNR) for 3 h reduced P-gp expression by 54% in CCRF-CEM cells and by 62% in KG-1a cells. Moreover, this decrease preceded a dose-dependent reduction in cell viability detected after 24 h of exposure to 10 µM DNR, with 46.6% and 72.2% viable cells for CCRF-CEM and KG-1a, respectively. These findings suggest that P-gp downregulation could serve as a potential biomarker of treatment efficacy. Additionally, LightSpot-FL-1 analysis of six acute myeloid leukemia patient blood samples allowed the identification of 14 distinct blast subpopulations, revealing substantial inter- and intra-individual heterogeneity in P-gp expression. Thus, these findings underscore the potential of LightSpot-FL-1 as a valuable tool for re-evaluating the clinical relevance of P-gp in tumor resistance diagnosis
Clinical and Pathological Features Associated with Chromophobe Renal Cell Carcinoma Recurrence: Analysis from a Nationwide Cohort
No full textInternational audienceBackground and objective: Chromophobe renal cell carcinoma (chRCC) is a rare renal malignancy with a generally favourable prognosis. However, a subset of patients experiences recurrence, which remains poorly characterised. This study aims to identify the clinicopathological factors associated with recurrence in chRCC, describe the timing and anatomical patterns of recurrence, and develop a predictive model to guide surveillance strategies.Methods: We conducted a multicentre retrospective cohort study using data from the French UroCCR database, including patients treated surgically for nonmetastatic chRCC between 2010 and 2024. Clinicopathological features, recurrence-free survival (RFS), cancer-specific survival, and overall survival were analysed. Kaplan-Meier survival curves and multivariable Cox proportional-hazard models were used to assess prognostic factors.Key findings and limitations: Among the included 683 patients, 43 (6.3%) developed recurrence, with median RFS of 142 mo (95% confidence interval [CI] 121-not reached). Local recurrence was observed in 30 patients, while 18 developed distant metastases, predominantly in the retroperitoneal lymph nodes and lungs. Male sex (hazard ratio [HR] 3.1, 95% CI 1.27-7.54, p = 0.01), locally advanced disease (HR 1.94, 95% CI 1.02-3.84, p = 0.05), positive surgical margins (HR 3.03, 95% CI 1.4-6.56, p = 0.005), and lymphovascular invasion (HR 2.08, 95% CI 1.01-4.38, p = 0.05) were independently associated with recurrence. Limitations include the absence of a central pathological review and of standardised recurrence management strategies across centres.Conclusions and clinical implications: This study provides novel insights into the recurrence patterns of chRCC, highlighting the key prognostic factors. The proposed predictive model was designed to aid clinicians in identifying high-risk patients, optimising follow-up intensity, and guiding therapeutic decisions.Patient summary: We studied a rare kidney cancer type, called chromophobe renal cell carcinoma (chRCC), to understand why some patients experience recurrence. We found that being male, having advanced disease, or some aggressive pathological characteristics increased the risk of cancer coming back. Our results suggest that doctors should monitor certain patients more closely after surgery. This research may help improve long-term follow-up and treatment plans for patients with chRCC. While certain factors are associated with a higher risk of recurrence, it is important to note that chromophobe renal cell carcinoma generally has a favourable prognosis, and the absolute risk of recurrence remains low for most patients
Targeting Melanin Heterogeneity in Metastatic Melanoma: A Dual-Tumour Mouse Melanoma Model.
No full textInternational audienceABSTRACT The combination of melanin‐targeted radionuclide therapy (TRT) and immunotherapy offers potential in overcoming melanoma resistance to conventional therapies. Studying the potential abscopal effect induced by TRT is essential to evaluate such combination. We develop here a preclinical murine model comprising a target (pigmented) and non‐target (non‐pigmented) tumour to study the abscopal effect induced by melanin‐TRT in melanoma. Murine melanoma cell lines were tested: two pigmented (B16‐F10 and B16‐OVA) and one non‐pigmented (B16‐G4F), inoculated in C57BL/6 mice to assess pigmentation levels and immune infiltration. Heterogeneous tumour growth and repigmentation of the B16‐G4F tumour led us to develop a non‐pigmented cell line (B16‐OVAmTYR−/−) by tyrosinase invalidation using CRISPR/Cas9. A dual‐tumour model comprising the B16‐OVA tumour and the B16‐OVAmTYR tumour was evaluated in terms of tumour growth, pigmentation, and immune infiltrate. The B16‐OVA model displayed homogeneous tumour growth, pigmentation and high immune infiltrate (CD8+ T cells p < 0.001; CD4+ T cells p < 0.05, regulatory T cells p < 0.001). The new B16‐OVAmTYR−/− cell line ensured a consistent genetic background for comparative studies. The B16‐OVAmTYR−/− maintained a non‐pigmented phenotype without repigmentation (no melanin expression) and demonstrated similar tumour growth characteristics to its pigmented counterpart (DT = 2.4 ± 0.5 days). Establishing a dual‐tumour model using both B16‐OVA and B16‐OVAmTYR−/− cell lines enabled concurrent study of pigmented and non‐pigmented tumours in a single host, closely mirroring clinical scenarios of metastatic melanoma. We have successfully developed a new dual‐tumour pigmented and non‐pigmented mouse melanoma model mimicking clinical observations to study the abscopal effect in metastatic melanoma
