Abstract
Objectives
To investigate the performance of cranial PET/CT for the diagnosis of GCA.
Methods
All patients with a suspected diagnosis of GCA were prospectively enrolled in this study and had ...a digital PET/CT with evaluation of cranial arteries if they had not started glucocorticoids >72 h previously. The diagnosis of GCA was retained after at least 6 months of follow-up if no other diagnosis was considered by the clinician and the patient went into remission after at least 6 consecutive months of treatment. Cranial PET/CT was considered positive if at least one arterial segment showed hypermetabolism similar to or greater than liver uptake.
Results
For cranial PET/CT, sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) were 73.3%, 97.2%, 91.7% and 89.7%, respectively. For extracranial PET/CT, diagnostic performance was lower (Se = 66.7%, Sp = 80.6%, PPV = 58.8%, NPV = 85.3%). The combination of cranial and extracranial PET/CT improved overall sensitivity (Se = 80%) and NPV (NPV = 90.3%) while decreasing overall specificity (Sp = 77.8%) and PPV (PPV = 60%).
Conclusion
Cranial PET/CT can be easily combined with extracranial PET/CT with a limited increase in examination time. Combined cranial and extracranial PET/CT showed very high diagnostic accuracy for the diagnosis of GCA.
Trial registration
ClinicalTrials.gov, https://clinicaltrials.gov, NCT05246540.
Recently developed cell-based therapies have shown potential for graft-versus-host disease (GvHD) mitigation. Our team previously developed a protocol to generate human monocyte-derived suppressor ...Cells (HuMoSC), a subpopulation of CD33+ suppressor cells of monocytic origin. CD33+HuMoSC successfully reduced xenoGvHD severity in NOD/SCID/IL-2Rγc
(NSG) mice. While CD33+ HuMoSC culture supernatant inhibits T cell activation and proliferation, the recovery of CD33+ HuMoSC immunosuppressive cells and the subsequent production of their supernatant is limited. An attractive solution would be to use both the CD33+ and the large number of CD14+ cells derived from our protocol. Here, we assessed the immunoregulatory properties of the CD14+HuMoSC supernatant and demonstrated that it inhibited both CD4 and CD8 T cell proliferation and decreased CD8 cytotoxicity.
, injection of CD14+HuMoSC supernatant reduced xenoGvHD in NSG mice. Furthermore, CD14+HuMoSC supernatant maintained its immunoregulatory properties in an inflammatory environment. Proteomic and multiplex analyses revealed the presence of immunosuppressive proteins such as GPNMB, galectin-3 and IL-1R(A) Finally, CD14+HuMoSC supernatant can be produced using good manufacturing practices and be used as complement to current immunosuppressive drugs. CD14+HuMoSC supernatant is thus a promising therapy for preventing GvHD. .
Objectives An increased risk of hematological malignancies (HM) has been reported in giant cell arteritis (GCA) patients. Our study aimed to investigate the incidence and the type of HM occurring in ...GCA. Methods All patients with GCA and HM living in Côte D’Or (France) were identified by crossing data from the RHEMCO (Registre des Hémopathies Malignes de Côte d’Or) and those having a positive temporal artery biopsy between 1st January 2001 and 31 December 2018. Results Among 276 biopsy-proven GCA patients, 14 HM were identified in 12 patients (4.3%). In comparison with the general population aged over 50 years, the incidence of myeloid HM and myeloproliferative syndromes were increased in GCA patients (standardized incidence ratios = 2.71 and 5.16, respectively), with a specific increase in men with GCA (SIR = 4.82 and 9.04, respectively) but not in women. In addition, the study of standardized incidence ratios depending on the chronology between GCA and HM diagnoses suggests that there was an increased risk of developing GCA in men but not in women, after a diagnosis of myeloid HM (SIR = 9.56), especially if it was a MPS (SIR = 17.56). Conclusions Our study shows a particular epidemiology of HM in GCA patients, which is characterized by an increased incidence of myeloid HM, especially MPS, in male GCA patients. The chronology of the diagnoses of GCA and HM raises the hypothesis that clonal hematopoiesis may be implicated in some cases of GCA.
Abstract
Introduction
Extremity war-wounds present an elevated risk of infection and compromise reconstructive procedures. In a French military hospital, a multi-disciplinary meeting (MDM) was ...created to standardize the care given to soldiers with osteoarticular infection. The aim of this study was to evaluate the usefulness of MDM decisions.
Methods
An observational case study was performed including the French wounded at war treated for an osteoarticular infection between 2004 and 2016. They were separated into two groups according to their time of management: before (group A) or after (group B) the MDM creation in September 2010. Various operative and bacteriological parameters were analyzed retrospectively. A questionnaire was created to evaluate healthcare professionals’ satisfaction toward the usefulness of the MDM on their practice.
Results
During the study period, 38 patients were included: 19 in group A and 19 in group B. Initial tests found an infection with one pathogen in 15 patients, an infection with 2 pathogens in 11 patients, and an infection with 3 or more pathogens in 12 patients. Enterobacter cloacae was the most common pathogen. Pseudomonas aeruginosa and Escherichia coli were also frequent. The mean number of samples taken to conduct the bacteriological tests per operating session was significantly higher for group B than for group A. Twelve of the 14 questioned healthcare professionals believed the MDM was very useful in their patient management.
Conclusion
The MDM seems to have had a beneficial impact on orthopedic surgeon practices. A significant increase of the number of samples taken was the most obvious sign that the French recommended practices for osteoarticular infections were followed since the creation of MDM.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Vascular smooth muscle cells (VSMCs) have been shown to play a role in the pathogenesis of giant cell arteritis (GCA) through their capacity to produce chemokines recruiting T cells and monocytes in ...the arterial wall and their ability to migrate and proliferate in the neointima where they acquire a myofibroblast (MF) phenotype, leading to vascular stenosis. This study aimed to investigate if MFs could also impact T-cell polarization. Confocal microscopy was used to analyze fresh fragments of temporal artery biopsies (TABs). Healthy TAB sections were cultured to obtain MFs, which were then treated or not with interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) and analyzed by immunofluorescence and RT-PCR. After peripheral blood mononuclear cells and MFs were co-cultured for seven days, T-cell polarization was analyzed by flow cytometry. In the neointima of GCA arteries, we observed a phenotypic heterogeneity among VSMCs that was consistent with a MF phenotype (α-SMA+CD90+desmin+MYH11+) with a high level of STAT1 phosphorylation. Co-culture experiments showed that MFs sustain Th1/Tc1 and Th17/Tc17 polarizations. The increased Th1 and Tc1 polarization was further enhanced following the stimulation of MFs with IFN-γ and TNF-α, which induced STAT1 phosphorylation in MFs. These findings correlated with increases in the production of IL-1β, IL-6, IL-12 and IL-23 by MFs. Our study showed that MFs play an additional role in the pathogenesis of GCA through their ability to maintain Th17/Tc17 and Th1/Tc1 polarizations, the latter being further enhanced in case of stimulation of MF with IFN-γ and TNF-α.
Oral metronomic topotecan represents a novel approach to chemotherapy delivery which, in preclinical models, may work synergistically with pazopanib in targeting angiogenesis. A phase I and ...pharmacokinetic (PK) study of this combination was performed in children with relapsed/refractory solid tumors. Oral topotecan and pazopanib were each administered daily without interruption in 28-day cycles at five dose levels (0.12 to 0.3 mg/m2 topotecan and 125 to 160 mg/m2 pazopanib powder for oral suspension (PfOS)), with dose escalation in accordance with the rolling-six design. PK studies were performed on day 1 and at steady state. Thirty patients were enrolled, with 26 evaluable for dose-limiting toxicity (DLT), with median age 12 years (3–20). Toxicities were generally mild; the most common grade 3/4 adverse events related to protocol therapy were neutropenia (18%), thrombocytopenia (11%), lymphopenia (11%), AST elevation (11%), and lipase elevation (11%). Only two cycle 1 DLTs were observed on study, both at the 0.3/160 mg/m2 dose level comprising persistent grade 3 thrombocytopenia and grade 3 ALT elevation. No AEs experienced beyond cycle 1 required treatment discontinuation. The best response was stable disease in 10/25 patients (40%) for a median duration of 6.4 (1.7–45.1) months. The combination of oral metronomic topotecan and pazopanib is safe and tolerable in pediatric patients with solid tumors, with a recommended phase 2 dose of 0.22 mg/m2 topotecan and 160 mg/m2 pazopanib. No objective responses were observed in this heavily pre-treated patient population, although 40% did achieve stable disease for a median of 6 months. While this combination is likely of limited benefit for relapsed disease, it may play a role in the maintenance setting.
•26 technical measures are proposed to reduce agricultural GHG emissions in France.•One third of the total abatement potential is at negative cost by saving inputs.•Assuming additivity, the cumulated ...abatement would be 32.3Tg CO2e per year in 2030.
The agriculture, forestry and other land use sector are responsible for 24% (10–12Pg CO2e per year) of anthropogenic greenhouse gas (GHG) emissions worldwide, with concomitant opportunities for mitigation. A scientific panel used deliberative methods to identify ten technical measures comprising 26 sub-measures to reduce GHG emissions from agriculture in France. Their abatement potential and cost are compared. The proposed measures concern nitrogen (N) management, management practices that increase carbon stocks in soils and biomass, livestock diets, and energy production and consumption on farms. Results show that the total abatement potential can be divided into three parts. One third of the cumulated abatement potential corresponds to sub-measures that can be implemented at a negative technical cost. These sub-measures focus on increased efficiency in input use including N fertilisers, animal feed and energy. The second third are sub-measures with moderate cost (<€25 per metric Mg of avoided CO2e). These sub-measures require specific investments or changes to cropping systems, but additional costs or lower incomes are partially compensated for by a reduction in other costs or by the production of other marketable products. The remaining third are high-cost sub-measures (>€25 per metric Mg of avoided CO2e). These require investment with no direct financial return, the purchase of particular inputs, dedicated labour time or involve production losses. Assuming additivity, the cumulated abatement is 32.3Tg CO2e per year in 2030, but only 10Tg (i.e. 10% of current agricultural emissions) when calculated under current inventory rules. This study confirms that a significant abatement potential exists in the agricultural sector, with two thirds of this potential at low or even negative cost. This is likely to be an underestimated as it is based on a status quo of the current agricultural system. Results also emphasise the need to upgrade inventory rules so that efforts to reduce emissions can be accounted for.
the effect of pathological aging on explicit memory
is very well documented, but relatively few studies have addressed this issue in the musical domain. To examine learning and consolidation of ...melodies, we designed a melodic recognition task involving immediate and delayed recognition of 16 target melodies (8 familiar and 8 unfamiliar). Seventeen patients with mild to moderate Alzheimer's disease (AD) and 17 age-matched controls were tested. During the initial presentation of the targets, the participant had to decide whether or not the melody was familiar. Recognition was tested after one and three presentations of the target melodies using a yes/no recognition paradigm. Delayed recognition was tested after 24 hours to evaluate consolidation. In keeping with the findings of Bartlett, Halpern, and Dowling (1995), age-matched controls showed better recognition of familiar than unfamiliar melodies. Controls also showed improved performance with multiple presentations for both familiar and unfamiliar melodies, without forgetting after 24-hour delay. In contrast, patients with AD showed impaired learning and recognition of both unfamiliar and familiar melodies with no benefit of familiarity on recognition. Nevertheless, the familiarity decision-based ratings of patients was in keeping with controls. These findings suggest that musical recognition memory is impaired in AD, but the musical lexicon (as assessed by familiarity ratings) is preserved. These findings highlight the need to use both familiar and unfamiliar music in experimental tasks to study the different processes underlying recognition memory.
An increased risk of haematological malignancies (HM) has been reported in GCA patients. Our study aimed to investigate the incidence and the type of HM occurring in GCA.
All patients with GCA and HM ...living in Côte d'Or (France) were identified by crossing data from the RHEMCO (Registre des Hémopathies Malignes de Côte d'Or) and those having a positive temporal artery biopsy between 1 January 2001 and 31 December 2018.
Among 276 biopsy-proven GCA patients, 14 HM were identified in 12 patients (4.3%). In comparison with the general population aged >50 y, the incidence of myeloid HM and myeloproliferative syndromes were increased in GCA patients standardized incidence ratios (SIR) = 2.71 and 5.16, respectively, with a specific increase in men with GCA (SIR = 4.82 and 9.04, respectively) but not in women. In addition, the study of SIR depending on the chronology between GCA and HM diagnoses suggests that there was an increased risk of developing GCA in men but not in women, after a diagnosis of myeloid HM (SIR = 9.56), especially if it was a MPS (SIR = 17.56).
Our study shows a particular epidemiology of HM in GCA patients, which is characterized by an increased incidence of myeloid HM, especially MPS, in male GCA patients. The chronology of the diagnoses of GCA and HM raises the hypothesis that clonal hematopoiesis may be implicated in some cases of GCA.
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