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Top publications · les plus citées

• 1

  Autologous T cell therapy for MAGE-A4(+) solid cancers in HLA-A*02(+) patients: a phase 1 trial

  Nature medicine · 2023

  📚 156 citations🎯 RCR 12.76Top 2% NIH🩺 Clinique🔓 Open Access📄 PDF gratuit ↗

  Lire l'abstract Crossref ↓

  AbstractAffinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancer/testis antigen expressed at varying levels in multiple solid tumors. We conducted a multicenter, dose-escalation, phase 1 trial in patients with relapsed/refractory metastatic solid tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head and neck cancer (NCT03132922). The primary endpoint was safety, and the secondary efficacy endpoints included overall response rate (ORR) and duration of response. All patients (N = 38, nine tumor types) experienced Grade ≥3 hematologic toxicities; 55% of patients (90% Grade ≤2) experienced cytokine release syndrome. ORR (all partial response) was 24% (9/38), 7/16 (44%) for SS and 2/22 (9%) for all other cancers. Median duration of response was 25.6 weeks (95% confidence interval (CI): 12.286, not reached) and 28.1 weeks (95% CI: 12.286, not reached) overall and for SS, respectively. Exploratory analyses showed that afami-cel infiltrates tumors, has an interferon-γ-driven mechanism of action and triggers adaptive immune responses. In addition, afami-cel has an acceptable benefit–risk profile, with early and durable responses, especially in patients with metastatic SS. Although the small trial size limits conclusions that can be drawn, the results warrant further testing in larger studies.

• 2

  Staphylococcus aureus Small-Colony Variants from Airways of Adult Cystic Fibrosis Patients as Precursors of Adaptive Antibiotic-Resistant Mutations

  Antibiotics (Basel, Switzerland) · 2023

  📚 11 citations🎯 RCR 1.72🔓 Open Access📄 PDF gratuit ↗

  Lire l'abstract Crossref ↓

  Prototypic Staphylococcus aureus and their small-colony variants (SCVs) are predominant in cystic fibrosis (CF), but the interdependence of these phenotypes is poorly understood. We characterized S. aureus isolates from adult CF patients over several years. Of 18 S. aureus-positive patients (58%), 13 (72%) were positive for SCVs. Characterization included genotyping, SCCmec types, auxotrophy, biofilm production, antibiotic susceptibilities and tolerance, and resistance acquisition rates. Whole-genome sequencing revealed that several patients were colonized with prototypical and SCV-related clones. Some clonal pairs showed acquisition of aminoglycoside resistance that was not explained by aminoglycoside-modifying enzymes, suggesting a mutation-based process. The characteristics of SCVs that could play a role in resistance acquisition were thus investigated further. For instance, SCV isolates produced more biofilm (p < 0.05) and showed a higher survival rate upon exposure to ciprofloxacin and vancomycin compared to their prototypic associated clones. SCVs also developed spontaneous rifampicin resistance mutations at a higher frequency. Accordingly, a laboratory-derived SCV (ΔhemB) acquired resistance to ciprofloxacin and gentamicin faster than its parent counterpart after serial passages in the presence of sub-inhibitory concentrations of antibiotics. These results suggest a role for SCVs in the establishment of persistent antibiotic-resistant clones in adult CF patients.

• 3

  Intrarater and interrater reliability of the first metatarsophalangeal joint dorsiflexion resistance test

  Musculoskeletal care · 2023

  📚 10 citations🎯 RCR 4.38Top 9% NIH🔓 Open Access📄 PDF gratuit ↗

  Lire l'abstract Crossref ↓

  AbstractBackgroundThe first metatarsophalangeal joint plays a fundamental role during the gait cycle. The Hubscher manoeuvre, which consists of passively dorsiflexing the first metatarsophalangeal joint of an individual in relaxed stance and observing the raising of the medial longitudinal arch, is a clinical test thought to examine the function of the first metatarsophalangeal joint. However, the hallux dorsiflexion achieved during this test is not related to hallux dorsiflexion during gait. On the other hand, unlike kinematic tests, results from kinetic tests have been shown to be strongly correlated with dynamic joint biomechanics. Thus, given the need for valid and reliable tests to evaluate the function of the first metatarsophalangeal joint, this study aimed to assess the reliability of a new kinetic test, namely, the first metatarsophalangeal joint dorsiflexion resistance test.MethodThirty young adults completed two data collection sessions 1 week apart, during which the first metatarsophalangeal joint dorsiflexion resistance test was performed. Intrarater and interrater reliability were assessed using intraclass correlation coefficients (ICC), minimal detectable difference (MDD), standard error of the mean (SEM) and limits of agreements (LoA).ResultsFor the intrarater reliability, the ICC was 0.77 (p < 0.001), the SEM was 6.5 N, the MDD was 18.1 N and the LoA were −7.9 to 26.9 N. For the interrater reliability, the ICC was 0.86 (p < 0.001), the SEM was 6.9 N, the MDD was 19.0 N and the LoA were −6.4 to 21.8 N.ConclusionThe results of this study demonstrate good intra and interrater reliability of the first metatarsophalangeal joint dorsiflexion resistance test, which provides evidence to support its use in clinical and research contexts. Further work is required to establish the test results' relationship with joint kinetics during gait and to provide normative values in individuals with and without musculoskeletal disorders as well as among different age groups and genders to optimise its utilization in clinical and research settings.

Publications scientifiques (50) — classées par pathologie

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