-
EClinicalMedicine Aug 2023Failure of gastrointestinal acute graft--host disease (GI-aGvHD) to respond to steroid therapy is associated with limited further therapeutic options. We aimed to assess...
BACKGROUND
Failure of gastrointestinal acute graft--host disease (GI-aGvHD) to respond to steroid therapy is associated with limited further therapeutic options. We aimed to assess the safety and efficacy of the first-in-human use of the pooled allogeneic faecal microbiota, MaaT013, for the treatment of steroid-refractory GI-aGvHD.
METHODS
This prospective, international, single-arm, phase 2a study reports clinical outcomes from a 24-patient cohort with grade III-IV, steroid refractory GI-aGvHD treated with the pooled allogeneic faecal microbiota MaaT013. MaaT013 involved pooling faecal matter from 3 to 8 screened donors then transplanting the pooled batches into patients to treat GI-aGVHD. The 24 patients were treated in the HERACLES study (Aug 2018 to Nov 2020) at 26 sites in Europe and an additional 52 patients were treated in a compassionate use/expanded access program (EAP) in France (July 2018 to April 2021). The primary endpoint was GI response at day 28, defined as the proportion of patients with GI-aGvHD who had a complete response (CR) or very good partial response (VGPR). GvHD grading and staging were assessed according to the revised Glucksberg criteria. Adverse events and severe adverse events were monitored for 6 months and 12 months, respectively. The HERACLES study was registered with ClinicalTrials.gov (NCT03359980).
FINDINGS
Compared with single donors, MaaT013 is characterised by higher microbial richness and reduced variability across batches. At day 28 (D28), the GI-overall response rate (ORR) was 38% in the prospective population, including 5 complete responses (CR), 2 very good partial responses (VGPR) and 2 partial responses (PR). In the EAP, the GI-ORR was 58% (17 CR, 9 VGPR and 4 PR). The 12-month overall survival (OS) was 25% in the prospective study and 38% in the EAP. Regarding safety, five infectious complications, including 3 sepsis, could not be excluded from being related to the study procedure in HERACLES. Shotgun sequencing analyses of the identified strains suggest that none were found in MaaT013. In the EAP, 18 pharmacovigilance cases were reported among 52 treated patients, including 11 bacteraemia/sepsis. In HERACLES, we observed in stools from responding patients at D28 a higher microbiota richness and increased levels of beneficial bacteria, in particular butyrate producers, along with increased levels of short-chain fatty acid and bile acids. In contrast, stools from non-responding (NR) patients displayed increased levels of pathogenic pro-inflammatory bacteria along with increased systemic inflammatory parameters.
INTERPRETATION
Overall, MaaT013 was safe in this population of highly immunocompromised patients and was associated with responses in some patients with GI-aGvHD and deserves further investigation.
FUNDING
MaaT Pharma.
PubMed: 37654670
DOI: 10.1016/j.eclinm.2023.102111 -
ACS Omega Dec 2023Natural and fragrant compounds, essential oils (EOs) extracted from plants through hydrodistillation, are gaining popularity as eco-friendly and sustainable agents to...
Natural and fragrant compounds, essential oils (EOs) extracted from plants through hydrodistillation, are gaining popularity as eco-friendly and sustainable agents to protect metals and alloys from corrosion in acidic environments. This research focused on extracting and characterizing an EO obtained from the (CC) plant native to India. The study aimed to evaluate the inhibitory properties of this EO on mild steel in a 0.5 M HCl solution at different concentrations. Various analytical techniques, including potentiodynamic polarization curves, electrochemical impedance spectroscopy, optical microscopy, infrared spectroscopy, and proton magnetic resonance, were employed to assess the effectiveness of this EO extract. Our findings indicate that the L (CCL) extract effectively reduces the corrosion of mild steel in hydrochloric acid with an inhibition efficiency ranging from 79.69 to 98.76%. The optimal inhibition concentration was 2 g/L of EO, and surface analysis confirmed the formation of a protective layer. Furthermore, our results suggest that the inhibitor binds to the metal surface through a charge-transfer process, creating a protective film. Finally, we utilized theoretical calculations and molecular dynamics simulations to elucidate the inhibition mechanism on both a global and local scale.
PubMed: 38107914
DOI: 10.1021/acsomega.3c06548 -
Haematologica Mar 2024Not available.
Bendamustine and rituximab as first-line treatment for symptomatic splenic marginal zone lymphoma: long-term outcome and impact of early unmeasurable minimal residual disease attainment from the BRISMA/IELSG36 phase II study.
Not available.
PubMed: 38497158
DOI: 10.3324/haematol.2023.284109 -
Haematologica Feb 2024The IELSG38 trial was conducted to investigate the effects of subcutaneous (SC) rituximab on the complete remission (CR) rate and the benefits of SC maintenance in...
The IELSG38 trial was conducted to investigate the effects of subcutaneous (SC) rituximab on the complete remission (CR) rate and the benefits of SC maintenance in patients with extranodal marginal zone lymphoma (MZL) who received frontline treatment with chlorambucil plus rituximab. Study treatment comprised an induction phase with chlorambucil 6 mg/m2/day orally on weeks 1-6, 9-10, 13-14, 17-18, and 21-22, and rituximab 375 mg/m2 intravenously on day 1 of weeks 1-4, and 1400 mg SC on weeks 9, 13, 17, and 21. Then, a maintenance phase followed with rituximab administered at 1400 mg SC every two months for two years. Of the 112 patients enrolled, 109 were evaluated for efficacy. The CR rates increased from 52% at the end of the induction phase to 70% upon completion of the maintenance phase. With a median follow-up of 5.8 years, the 5-year event-free, progression-free, and overall survival rates were 87% (95% CI, 78-92), 84% (95% CI, 75-89), and 93% (95% CI, 86-96), respectively. The most common grade ≥3 toxicities were neutropenia (33%) and lymphocytopenia (16%). Six patients experienced treatment-related serious adverse events, including fever of unknown origin, sepsis, pneumonia, respiratory failure, severe cerebellar ataxia, and fatal acute myeloid leukemia. The trial showed that subcutaneous rituximab did not improve the complete remission rate at the conclusion of the induction phase, which was the main endpoint. Nevertheless, SC maintenance might have facilitated long-term disease control, potentially contributing to enhanced event-free and progression-free survival.
PubMed: 38385243
DOI: 10.3324/haematol.2023.283918 -
EJNMMI Physics Sep 2023The aim of this study was to investigate the quantification performance of a 360° CZT camera for Lu-based treatment monitoring.
BACKGROUND
The aim of this study was to investigate the quantification performance of a 360° CZT camera for Lu-based treatment monitoring.
METHODS
Three phantoms with known Lu activity concentrations were acquired: (1) a uniform cylindrical phantom for calibration, (2) a NEMA IEC body phantom for analysis of different-sized spheres to optimise quantification parameters and (3) a phantom containing two large vials simulating organs at risk for tests. Four sets of reconstruction parameters were tested: (1) Scatter, (2) Scatter and Point Spread Function Recovery (PSFR), (3) PSFR only and (4) Penalised likelihood option and Scatter, varying the number of updates (iterations × subsets) with CT-based attenuation correction only. For each, activity concentration (ARC) and contrast recovery coefficients (CRC) were estimated as well as root mean square. Visualisation and quantification parameters were applied to reconstructed patient image data.
RESULTS
Optimised quantification parameters were determined to be: CT-based attenuation correction, scatter correction, 12 iterations, 8 subsets and no filter. ARC, CRC and RMS results were dependant on the methodology used for calculations. Two different reconstruction parameters were recommended for visualisation and for quantification. 3D whole-body SPECT images were acquired and reconstructed for Lu-PSMA patients in 2-3 times faster than the time taken for a conventional gamma camera.
CONCLUSION
Quantification of whole-body 3D images of patients treated with Lu-PSMA is feasible and an optimised set of parameters has been determined. This camera greatly reduces procedure time for whole-body SPECT.
PubMed: 37736779
DOI: 10.1186/s40658-023-00576-1 -
Applied Radiation and Isotopes :... Nov 2023In the Triple to Double Coincidence Ratio method in Liquid Scintillation Counting, the detection efficiency is calculated from the value of a free parameter describing...
In the Triple to Double Coincidence Ratio method in Liquid Scintillation Counting, the detection efficiency is calculated from the value of a free parameter describing the intrinsic light yield of the counting system. This model is generally based on a Poisson distribution of the number of photoelectrons detected and the detection efficiency is obtained from the complement of the non-detection efficiency. In the classical free parameter model, the mean of the Poisson distribution, m, is a constant but some variability of this mean could be expected from optical effects due to internal reflections inside the LS source or from non-homogeneity of the detection efficiency of the photomultiplier tubes. Then, m becomes a random variable and the distribution of the photoelectrons becomes a compound Poisson distribution, with a random variable as mean value. This paper explores the implications of the variance of m, which were, to our knowledge, never considered previously in the uncertainty budget of TDCR measurements.
PubMed: 37657226
DOI: 10.1016/j.apradiso.2023.110992 -
Thoracic Cancer Aug 2023Endobronchial ultrasound-guided (EBUS) transbronchial needle aspiration (TBNA) has significantly improved the diagnostic workup for intrathoracic lymphadenopathies. More...
Assessment of endobronchial ultrasound-guided bronchoscopy (EBUS) intranodal forceps biopsy added to EBUS 19-gauge transbronchial needle aspiration: A blinded pathology panel analysis.
BACKGROUND
Endobronchial ultrasound-guided (EBUS) transbronchial needle aspiration (TBNA) has significantly improved the diagnostic workup for intrathoracic lymphadenopathies. More recently, EBUS intranodal forceps biopsy (IFB) has been developed in an attempt to maximize diagnostic yield by providing additional tissue. In this study, we aimed to assess the improvement of diagnostic yield with EBUS-TBNA combined with EBUS-IFB, compared to EBUS-TBNA alone.
METHODS
Consecutive patients who had 19-G EBUS-TBNA and EBUS-IFB from August 30, 2018, to September 28, 2021, were included. Four senior pathologists retrospectively analyzed, independently and blindly, first, only the EBUS-TBNA samples (cell block), then, at least 1 month later, both samples from EBUS-TBNA and from EBUS-IFB together.
RESULTS
Fifty patients were included in the study and 52 lymph nodes were analyzed. Diagnostic yield was 77% (40/52) for EBUS-TBNA alone and 94% (49/52) when combined with EBUS-IFB (p = 0.023). Malignancy was diagnosed with EBUS-TBNA combined with EBUS-IFB in 25/26 cases (96%), versus 22/26 (85%) with EBUS-TBNA alone (p = 0.35); and 4/5 (80%) versus 2/5 (40%) for lymphoma specifically. Kappa interobserver agreement was 0.92 for EBUS-IFB and 0.87 for EBUS-TBNA alone. Nonmalignant condition was diagnosed with EBUS-TBNA combined with EBUS-IFB in 24/26 cases (92%), versus 18/26 (69%) for EBUS-TBNA alone (p = 0.07).
CONCLUSION
The use of EBUS-IFB combined with 19-G EBUS-TBNA improves the mediastinal lymph node diagnostic yield However the benefit appears to be mainly restricted to nonmalignant histology.
Topics: Humans; Bronchoscopy; Retrospective Studies; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Lymph Nodes; Neoplasms; Mediastinum
PubMed: 37340870
DOI: 10.1111/1759-7714.15000 -
ESMO Open May 2024Breast cancer (BC) is the second most common cancer that metastasizes to the brain. Particularly up to half of patients with human epidermal growth factor receptor 2...
BACKGROUND
Breast cancer (BC) is the second most common cancer that metastasizes to the brain. Particularly up to half of patients with human epidermal growth factor receptor 2 (HER2)-positive (HER2+) metastatic breast cancer (mBC) may develop brain metastases over the course of the disease. Nevertheless, little is known about the prevalence and the outcome of brain and leptomeningeal metastases (BLMM) in HER2-low BC. We compared the cumulative incidence of BLMM and associated outcomes among patients with HER2-low, HER2-negative (HER2-) and HER2+ mBC.
PATIENTS AND METHODS
This cohort study was conducted from the Epidemiological Strategy and Medical Economics (ESME) mBC database and included patients treated for mBC between 2012 and 2020 across 18 French comprehensive cancer centers and with known HER2 and hormone receptor (HR) status. The cumulative incidence of BLMM after metastatic diagnosis was estimated using a competing risk methodology with death defined as a competing event.
RESULTS
19 585 patients were included with 6118 (31.2%), 9943 (50.8%) and 3524 (18.0%) being HER2-low, HER2- and HER2+ mBC, respectively. After a median follow-up of 48.6 months [95% confidence interval (CI) 47.7-49.3 months], BLMM were reported in 4727 patients: 1192 (25.2%) were diagnosed with BLMM at first metastatic diagnosis and 3535 (74.8%) after metastatic diagnosis. Multivariable analysis adjusted for age, histological grade, metastases-free interval and HR status showed that the risk of BLMM at metastatic diagnosis was similar in patients with HER2- compared to HER2-low mBC [odds ratio (OR) (95% CI) 1.00 (0.86-1.17)] and higher in those with HER2+ compared to HER2-low [OR (95% CI) 2.23 (1.87-2.66)]. Similar results were found after metastatic diagnosis; the risk of BLMM was similar in HER2- compared to HER2-low [subdistribution hazard ratio (sHR) (95% CI) 1.07 (0.98-1.16)] and higher in the HER2+ group [sHR (95% CI) 1.56 (1.41-1.73)].
CONCLUSIONS
The prevalence and evolution of BLMM in HER2-low mBC are similar to those in patients with HER2- tumors. In contrast to patients with HER2+ mBC, the prognosis of BLMM remains dismal in this population.
Topics: Humans; Breast Neoplasms; Female; Middle Aged; France; Brain Neoplasms; Incidence; Receptor, ErbB-2; Meningeal Neoplasms; Aged; Cohort Studies; Adult
PubMed: 38703431
DOI: 10.1016/j.esmoop.2024.103447 -
Polymers Feb 2024Antioxidants are essential to the polymer industry. The addition of antioxidants delays oxidation and material degradation during their processing and usage. Sustainable...
Antioxidants are essential to the polymer industry. The addition of antioxidants delays oxidation and material degradation during their processing and usage. Sustainable phenolic acids such as 4-hydroxybenzoic acid or 3,4-dihydroxybenzoic acid were selected. They were chemically modified by esterification to obtain various durable molecules, which were tested and then compared to resveratrol, a biobased antioxidant, and Irganox 1076, a well-known and very efficient fossil-based antioxidant. Different sensitive matrices were used, such as a thermoplastic polyolefin (a blend of PP and PE) and a purposely synthesized thermoplastic polyurethane. Several formulations were then produced, with the different antioxidants in varying amounts. The potential of these different systems was analyzed using various techniques and processes. In addition to antioxidant efficiency, other parameters were also evaluated, such as the evolution of the sample color. Finally, an accelerated aging protocol was set up to evaluate variations in polymer properties and estimate the evolution of the potential of different antioxidants tested over time and with aging. In conclusion, these environmentally friendly antioxidants make it possible to obtain high-performance materials with an efficiency comparable to that of the conventional ones, with variations according to the type of matrix considered.
PubMed: 38337302
DOI: 10.3390/polym16030413 -
Molecules (Basel, Switzerland) Oct 2023, a therapeutic plant mentioned in the ancient Algerian pharmacopeia, specifically two species belonging to the family, . and . , were investigated in this study for...
, a therapeutic plant mentioned in the ancient Algerian pharmacopeia, specifically two species belonging to the family, . and . , were investigated in this study for their antibacterial, antioxidant, and anti-inflammatory properties. The study used aqueous extracts (AE) obtained from these plants, and the extraction yields were found to be different. The in vitro antibacterial activity was evaluated using a disc diffusion assay against three typical bacterial strains. The results showed that the two extracts were effective against all three strains. Both extracts displayed significant antioxidant activity compared to BHT. The anti-inflammatory impact was evaluated using a protein (BSA) inhibition denaturation test. The . extract was found to inhibit inflammation by 85% at a concentration of 250 µg/mL, significantly higher than the Aspirin. All phytoconstituents present good pharmacokinetic characteristics without toxicity except very slight toxicity of terpineol and cineol and a maximum binding energy of -7.53 kcal/mol for its anti-TyrRS activity in silico. The study suggests that the extracts and their primary phytochemicals could enhance the efficacy of antibiotics, antioxidants, and non-steroidal anti-inflammatory drugs (NSAIDs). As pharmaceutical engineering experts, we believe this research contributes to developing natural-based drugs with potential therapeutic benefits.
Topics: Antioxidants; Plant Extracts; Anti-Bacterial Agents; Anti-Inflammatory Agents; Phytochemicals
PubMed: 37894631
DOI: 10.3390/molecules28207153