Bone lesions in systemic mastocytosis: Bone histomorphometry and histopathological mechanisms.

Osteoporosis is considered the most frequent skeletal manifestation of systemic mastocytosis (SM). We performed a retrospective analysis of sixty patients (37 males and 23 females) who underwent a bone biopsy in the assessment of SM or in the assessment of unexplained bone fragility. Thirty-three had simultaneously a bone marrow biopsy with a Jamshidi's needle; this sample was used for immunohistochemical analysis (tryptase, c-KIT. CD20, VCAM-1). Bone biopsy was realized in 42 cases in the assessment of SM to provide histologic proof of the disease and in 18 cases in the assessment of unexplained bone fragility and surprisingly revealed a SM. An increased bone turnover was observed in patients with SM with elevated eroded surfaces, osteoclast number and bone formation rate. In addition to nodules of mast cells (MC), a high number of MC was directly apposed on the trabeculae, affixed on the osteoblasts or the lining cells. The VCAM-1 adhesion protein recognizing α4ß7 and α4ß1 integrins may be a candidate to explain this particular adherence. One third of the bone marrow biopsies did not exhibit MC nodules or MC infiltration and led to a false negative diagnosis for SM. SM can be discovered in the assessment of fracture or osteoporosis. Transiliac bone biopsy allows for the diagnosis of the disease more accurately than bone marrow biopsy; it also provides a histomorphometric analysis of bone remodeling.

Local pesticide use intensity conditions landscape effects on biological pest control.

Complex landscapes including semi-natural habitats are expected to favour natural enemies thereby enhancing natural pest biocontrol in crops. However, when considering a large number of situations, the response of natural biocontrol to landscape properties is globally inconsistent, a possible explanation being that local agricultural practices counteract landscape effects. In this study, along a crossed gradient of pesticide use intensity and landscape simplification, we analysed the interactive effects of landscape characteristics and local pesticide use intensity on natural biocontrol. During 3 years, using a set of sentinel prey (weed seeds, aphids and Lepidoptera eggs), biocontrol was estimated in 80 commercial fields located in four contrasted regions in France. For all types of prey excepted weed seeds, the predation rate was influenced by interactions between landscape characteristics and local pesticide use intensity. Proportion of meadow and length of interface between woods and crops had a positive effect on biocontrol of aphids where local pesticide use intensity was low but had a negative effect elsewhere. Moreover, the landscape proportion of suitable habitats for crop pests decreased the predation of sentinel prey, irrespectively of the local pesticide use intensity for weed seeds, but only in fields with low pesticide use for Lepidoptera eggs. These results show that high local pesticide use can counteract the positive expected effects of semi-natural habitats, but also that the necessary pesticide use reduction should be associated with semi-natural habitat enhancement to guarantee an effective natural biocontrol.

Giant cell arteritis-related aortitis with positive or negative temporal artery biopsy: a French multicentre study.

Objective: To compare the clinical presentation and outcome of giant cell arteritis (GCA)-related aortitis according to the results of temporal artery biopsy (TAB).Method: Patients with GCA-related aortitis diagnosed between 2000 and 2017, who underwent TAB, were retrospectively included from a French multicentre database. They all met at least three American College of Rheumatology criteria for the diagnosis of GCA. Aortitis was defined by aortic wall thickening > 2 mm on computed tomography scan and/or an aortic aneurysm, associated with an inflammatory syndrome. Patients were divided into two groups [positive and negative TAB (TAB+, TAB-)], which were compared regarding aortic imaging characteristics and aortic events, at aortitis diagnosis and during follow-up.Results: We included 56 patients with TAB+ (70%) and 24 with TAB- (30%). At aortitis diagnosis, patients with TAB- were significantly younger than those with TAB+ (67.7 ± 9 vs 72.3 ± 7 years, p = 0.022). Initial clinical signs of GCA, inflammatory parameters, and glucocorticoid therapy were similar in both groups. Coronary artery disease and/or lower limb peripheral arterial disease was more frequent in TAB- patients (25% vs 5.3%, p = 0.018). Aortic wall thickness and type of aortic involvement were not significantly different between groups. Diffuse arterial involvement from the aortic arch was more frequent in TAB- patients (29.1 vs 8.9%, p = 0.03). There were no differences between the groups regarding overall, aneurism-free, relapse-free, and aortic event-free survival.Conclusion: Among patients with GCA-related aortitis, those with TAB- are characterized by younger age and increased frequency of diffuse arterial involvement from the aortic arch compared to those with TAB+, without significant differences in terms of prognosis.

[Chronic superficial urticaria associated with solid cancers: Case report and literature review]. / Urticaire chronique superficielle associée aux cancers solides : un cas et revue de la littérature.

BACKGROUND: Chronic urticaria is common and is generally idiopathic ("spontaneous"). Links between solid cancer and chronic urticaria have been mentioned in the literature. PATIENTS AND METHODS: We report the case of a 63-year-old man presenting with superficial chronic urticaria associated with adenocarcinoma of the ethmoid sinus. We discuss the possibility of systemic origin in light of the severity of the disease and its resistance to treatment. Only recurrent ethmoidal cancer was highlighted. Curative care resulted in complete resolution of the urticaria without relapse at 32 months of follow-up. DISCUSSION: In a literature review, we collected 17 cases of superficial chronic urticaria associated with cancer. These cases were marked by synchronous progression and by the inefficacy (86%) of anti-histamines and systemic corticosteroids. Although cases of chronic superficial urticaria associated with cancer remain rare, the condition merits discussion due to its severity and significant resistance to therapy.

Serum ferritin/C-reactive protein ratio is a simple and effective biomarker for diagnosing iron deficiency in the context of systemic inflammation.

BACKGROUND: Diagnosing iron deficiency is challenging in the presence of systemic inflammation. AIM: To investigate the relationship between plasma C-reactive protein (CRP), serum ferritin (SF) and transferrin saturation (TS), with the objective of establishing a straightforward ratio applicable in the presence of inflammatory syndrome. DESIGN: Test prospective cohort and validation retrospective cohort. METHODS: A prospective cohort of inpatients (n = 140) assessed the correlation between CRP and SF/TS levels. The diagnostic performance of a determined ratio was evaluated for identifying iron deficiency (ID) using different definitions and in the presence of inflammation and/or chronic heart and/or kidney failure. A large validation cohort (n = 795) further assessed the predictive power of this ratio. RESULTS: In a training cohort (median age 76 years [57-84]), a linear relation was observed between SF (µg/l) and CRP (mg/l), unlike with TS. The SF/CRP ratio accurately predicted ID, with receiver operating characteristic-area under the curve (ROC-AUC) values ranging from 0.85 to 0.92 for different ID definitions. A threshold of ≤6 demonstrated the highest Youden index (0.61). In the validation cohort (age 72 years [57-84]), the SF/CRP ratio exhibited an ROC-AUC of 0.88 [95% CI: 0.85-0.90], with an odds ratio of 37.9 [95% CI: 20.3-68.9] for the threshold of ≤6. CONCLUSION: In this study, we demonstrated that the SF/CRP ratio, with a threshold of ≤6, is a simple and effective biomarker for ID, even in the presence of systemic inflammation or comorbidities. This ratio could potentially replace the complex set of criteria currently recommended by learned societies.

[Messages from the estates general on French internal medicine]. / Que retenir des états généraux de la médecine interne française ?

Internal medicine is a medical specialty that is often poorly understood by the general public and sometimes misidentified. In an era of increasing subspecialization and high technicality, it is characterized by a comprehensive approach centered on clinical evaluation. Unlike what is observed in most developed countries, where systemic autoimmune diseases are managed by organ specialists based on their mode of presentation, French internists are at the forefront for diagnosing and managing these diseases. Their multidisciplinary training gives them legitimacy to justify this role. Internists also play a crucial role in the management of patients requiring unplanned hospitalizations downstream from emergency departments and in connection with primary care. Internists primarily practice in a hospital setting, with a specific position in the French healthcare system aligned with the training frameworks of all medical specialties. To better define internal medicine, its role in care activities, as well as in education and research, internists organized a General Assembly of internal medicine that took place on September 28, 2023, in Paris. Structured around think tanks focusing on care, education, and research activities, the general assembly aimed to improve visibility on internal medicine and internists. This article recounts the discussions that animated this meeting and highlights the main ideas that emerged. These general assemblies constitute a foundational step and will be followed by a Consultation Conference in order to better identify and promote internal medicine and internists, regardless of their types and places of practice.

Genome sequencing identify chromosome 9 inversions disrupting ENG in 2 unrelated HHT families.

Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease, is a dominant inherited vascular disorder. The clinical diagnosis is based on the Curaçao criteria and pathogenic variants in the ENG and ACVRL1 genes are responsible for most cases of HHT. Four families with a negative targeted gene panel and selected by a multidisciplinary team were selected and whole-genome sequencing was performed according to the recommendations of the French National Plan for Genomic Medicine. Structural variations were confirmed by standard molecular cytogenetic analysis (FISH). In two families with a definite diagnosis of HHT, we identified two different paracentric inversions of chromosome 9, both disrupting the ENG gene. These inversions are considered as pathogenic and causative for the HHT phenotype of the patients. This is the first time structural variations are reported to cause HHT. As such balanced events are often missed by exon-based sequencing (panel, exome), structural variations may be an under-recognized cause of HHT. Genome sequencing for the detection of these events could be suggested for patients with a definite diagnosis of HHT and in whom no causative pathogenic variant was identified.

Multidimensional analysis of clinical symptoms in patients with Fabry's disease.

AIM: Fabry's disease is an X-linked inherited lysosomal storage disorder caused by the deficient activity of alpha-galactosidase A. The interrelationships between clinical symptoms in Fabry patients have not yet been fully established. Using cluster and multivariate analysis, the aim of the study was to determine the relationships among clinical symptoms and organ involvement, and predictive clinical symptoms for disease severity. METHODS: Clinical data obtained from 108 French Fabry patients were retrospectively collected and analysed using multiple correspondence analysis and hierachical ascendant classification. Multivariate analysis was also performed to determine among clinical symptoms predictors for cardiac disease (HRT), renal involvement (KDN) and brain complication (STR). RESULTS: The cohort comprised 41 male patients (aged 28.9 ± 11.6 years) and 67 female patients (aged 40.4 ± 15.5 years). Three main clusters of clinical symptoms could be delineated, characterising disease progression: the first cluster grouped digestive disorders (found in 30% of the patients) and exercise intolerance (32%), the second, cluster dyshidrosis (47%), acroparesthesia (67%), angiokeratoma (44%) and cornea verticillata (54%), the third, cluster grouped KDN (30%), HRT (39%) and STR (25%) and hearing loss (44%). In univariate analysis, the patient age predicted HRT and KDN, dyshidrosis predicted HRT and STR, angiokeratoma predicted KDN and cornea verticilla and hearing loss predicted KDN, HRT and STR. In multivariate analysis, hearing loss and age were independent predictors of organ complication. CONCLUSION: Among the various interrelated clinical symptoms occurring in Fabry disease, patients with dyshidrosis and particularly hearing disorders appear to be at higher risk of organ complications.

Early-season predation on aphids by winter-active spiders in apple orchards revealed by diagnostic PCR.

Aphids are major pests in apple orchards, debilitating the crop and spreading disease. We investigated whether early-season predation by canopy spiders may be effectively controlling aphid numbers in three organic orchards. For this purpose, we monitored the aphid population dynamics from the winter eggs to colony stages and compared this to spider abundances and rates of predation on aphids detected by diagnostic polymerase chain reaction. For the latter, we applied existing general aphid primers. We found that spiders ate colony fundatrices and that aphid numbers were negatively related to spider abundance. Spiders were the main active predators within the orchards when the first colony fundatrices were present, indicating their importance in the early control of aphid populations.

Fabry disease 'The New Great Imposter': results of the French Observatoire in Internal Medicine Departments (FIMeD).

Fabry disease (FD) is an X-linked lysosomal storage disorder due to α-galactosidase A deficiency. It is associated with a broad range of clinical symptoms, resulting in frequent misdiagnosis and diagnostic delay, which may impact on patient outcomes. This retrospective observational study of 58 FD patients referred to 10 internal medicine departments in France aimed to review differential diagnoses received prior to diagnosis and examines diagnostic delay. The average age at the time of diagnosis was 27.6 years (range: 10-60) and 42.2 years (range: 9-77) among the 23 males and 35 females analyzed, respectively. Most common symptoms that led to FD diagnosis were family history of FD (12 males and 27 females), followed by pain in extremities (10 males and 5 females), and angiokeratoma (8 males and 4 females). Eighteen patients had received alternative diagnoses prior to FD diagnosis, including a female patient with four previous diagnoses. Four case reports are presented, which illustrate the diagnostic 'odyssey' and delayed diagnosis often experienced by patients. Clinicians should consider a diagnosis of FD when presented with a wide range of symptoms, thus helping to shorten the diagnostic delay and facilitating early therapy with enzyme replacement therapy to improve patient outcomes.

Genetic inferences about the population dynamics of codling moth females at a local scale.

Estimation of demographic parameters is important for understanding the functioning of natural populations and the underlying ecological and evolutionary processes that may impact their dynamics. Here, we used sibship assignment methods to shed light on the local dynamics of codling moth females in eight orchards in a 90-ha domain near Valence, France. Based on full-sib inference among 1,063 genotyped moths, we estimated (1) the effective number of females that had offspring, (2) their fertility and (3) the distribution of their oviposition sites within and among orchards. The average number of females in all the orchards increased between the first (~130) and the second (~235) annual generations. The average fertilities of the females were similar at each generation according to the host plant considered (apple, pear, or walnut), but differed between commercial (~10) and non-treated (~25) apple orchards. Females mainly clustered their eggs on contiguous trees along orchard borders, but they also occasionally dispersed their eggs among different orchards independently of the cultivated host plants or the inter-orchard distances (up to 698 m) during the second annual generation. The mean distance between two oviposition sites was 30 m. Sibship estimates of both the effective number of females and the inter-orchard migration rates (~5%) were in agreement with the observed genetic differentiation among the eight orchards (0.006 < F ( st ) < 0.013). These results confirm and extend previous field and laboratory observations in Cydia pomonella, and they demonstrate that sibship assignments based on genetic data are an interesting alternative to mark-release-recapture methods for inferring insect population dynamics.

The arthroscopic Lapidus procedure.

BACKGROUND: Hypermobility of the first metatarsocuneiform (MC) joint is one of the causes believed to contribute to symptomatic hallux valgus. An arthrodesis of the first MC joint offers definitive correction of the intermetatarsal angle. This procedure can be associated with pseudoarthrosis and shortening of the first ray. This study presents our experience and results with an arthroscopic technique for performing this arthrodesis. MATERIALS AND METHODS: Five patients with severe hallux valgus associated with hypermobility of the first MC joint were treated with this operation. RESULTS: The functional assessment scales revealed very good results. Radiographic evaluation confirmed fusion in all the patients. The hallux valgus angle improved by 25.6°, the intermetatarsal angle improved by 10.6°. The shortening of the first ray was limited to 2.7 mm. CONCLUSION: This new technique is a valid option for performing an arthrodesis of the MC joint.

[Which adjuvant measures should be associated with long-term oral corticosteroid therapy in inflammatory diseases? A summary of existing French recommendations]. / Quelles mesures adjuvantes associer à une corticothérapie orale prolongée dans le cadre des maladies inflammatoires ? Synthèse des recommandations françaises disponibles.

It is common to initiate a long-term corticosteroid therapy for inflammatory diseases. Various specialists are involved in this prescription, and associated measures to prevent side effects are not consensual, with the exception of osteoporosis. The specialty of the prescriber has indeed a significant impact on the attention paid to the adjuvant associated measures. The aim of this review was to draw a summary of the side effects of long-term corticosteroid therapy and of the existing recommendations related to associated measures to prevent them. Unfortunately, it is difficult to give clear recommendations because of the lack of evidence in some fields, especially as they should be adapted to patient's age and comorbidities. We propose a summary table of associated measures to long-term steroid therapy prescription and suggest a monitoring frequency.

[Characteristics of patients with connective tissue disease-associated pulmonary arterial hypertension treated with prostanoids: A multicenter retrospective study]. / Caractéristiques des patients traités par prostanoïdes pour une hypertension artérielle pulmonaire associée à une connectivite : étude multicentrique rétrospective.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a severe complication of connective tissue disease (CTD). Data on use of prostanoids in this particular subset of patients are lacking. We aimed to describe the characteristics of patients with PAH-CTD treated with prostanoids and the outcomes under treatment. METHODS: In this multicenter retrospective study, all patients treated with prostanoids since 2006 were included. Data on PAH and CTD were collected at the time of prostanoid introduction and under treatment. RESULTS: Twenty-one patients were included, of whom 20 (95%) had limited cutaneous systemic sclerosis. Nineteen patients were treated with oral monotherapy or combination before addition of prostanoid. Treprostinil was the most used molecule (57% of patients). At the time of prostanoid introduction, 90% of patients were considered at high risk for death. Among patients who had right heart catheterization during follow-up, there was no significant difference in haemodynamics. No extrarespiratory worsening of the CTD was reported. The 1-year survival under prostanoid was 62%. In univariate analysis, NYHA functional class was associated with survival under treatment. CONCLUSION: This study provides original data on use of prostanoids in a cohort consisting mainly of systemic sclerosis. It underlines the difficulty to achieve a standardized assessment in this subset of patients. Safety profile was comparable with data reported in idiopathic PAH.

Agroecology landscapes.

Context: Agroecology combines agronomic and ecological concepts. It relies on the enhancement of biodiversity and related ecosystem services to support agricultural production. It is dependent on biological interactions for the design and management of agricultural systems in agricultural landscapes. Objectives: We review the role of landscape ecology to understand and promote biodiversity, pest regulation and crop pollination for the designing of "agroecology landscapes". We illustrate the use of landscape ecological methods for supporting agroforestry systems as an example of agroecological development, and we propose pathways to implement agroecology at landscape scale. Methods: The state of the art of how landscape ecology contributes to agroecology development is summarized based on a literature review. Results: Agroecology requires thinking beyond the field scale to consider the positioning, quality and connectivity of fields and semi-natural habitats at larger spatial scales. The spatial and temporal organisation of semi-natural elements and the crop mosaic interact. Understanding this interaction is the pre-requisite for promoting patterns and mechanisms that foster biodiversity and ecosystem service provision. Promoting agroecological practices beyond individual farm borders can be rooted in a bottom-up approach from agroecological lighthouse farms to farm networks to amplify agroecology adoption at the landscape scale. Conclusions: Achieving agricultural landscapes composed of fields and farms following agroecological management requires understanding of biodiversity patterns, biological interactions and mechanisms that determine and boost ecosystem functioning to improve services at landscape scale, involving farmers in a bottom-up and context-specific approach.

Barriers to gene flow between emerging populations of Watermelon mosaic virus in Southeastern France.

Since 1999, "emerging" (EM) strains of Watermelon mosaic virus (WMV) have been detected in cucurbit crops of southeastern France, probably as a result of recent introductions. Population genetic approaches were used to study the structure of EM isolates in southeastern France and to identify factors involved in their spatial distribution. A population clustering method (SAMOVA) and a maximum-difference algorithm (Monmonier's algorithm) were combined to visualize and quantify barriers to gene flow between populations. Both methods yielded similar results and two main barriers were identified. A North/South oriented barrier may be related to physical obstacles to gene flow (Rhône River, presence of an area with few cucurbit crops). Although the barrier was very strong, some "crossing" events were detected. A second barrier, oriented Northwest to Southeast, was not correlated with obvious geographical features. The two methods used here are complementary and confirm the limited spread of WMV-EM isolates. This approach can be useful in epidemiology studies to characterize the structure of viral populations and identify barriers to gene flow.

Nemaline bodies as unique pathological feature in the course of treated dermatomyositis.

Dermatomyositis was diagnosed on clinical and muscle histological criteria in a 42-year-old woman. Despite treatment, the patient complained of deterioration of her muscle condition. Since her symptoms were discordant with the rest of the data, muscle biopsy was performed and disclosed rod-bearing non-atrophic fibers as the unique and predominant pathological feature. Their significance is examined in this paper.

Assessing the environmental performance for more local and more circular biowaste management options at city-region level.

Biomass, biobased materials and food waste are considered priority areas for Europe's transition towards a circular economy (CE). Waste management is a central activity for this transition and offers multiple CE implementation options which should be evaluated from environmental perspective. The purpose of this work was to analyze the environmental consequences when redirecting biowaste flows from conventional to more circular management systems and to identify the CE option with the best environmental performance. We were particularly interested in studying the combined management of green and food waste, analyzing the challenges when introducing separate collection and different treatment processes, and evaluating the substitution potential for by-products. To determine environmental impacts, we performed a life cycle assessment (LCA) based on local data. Following the purpose analyzing a change in the system, we applied a consequential LCA and compared impacts from processes that are replaced with impacts from alternative management options such as co-composting, anaerobic digestion (AD) and decentralized composting. The LCA results show clear advantages for impacts on ecosystems and resource use for the local AD system with separate combined collection. The decentralized system shows reductions in resource use, whereas the industrial co-composting system has higher or similar impacts than the baseline scenario. We conclude that local systems with combined food and green waste management can show benefits if process emissions are properly managed and if by-products are used in applications with high substitution potentials. However, a change towards a CE does not necessarily result in environmental benefits. Our research highlights the complexity of biowaste systems and proposes a novel combination of local data, databases and models to handle this issue. With this research we are further contributing to the understanding of the combined management of food and green waste, which is a relevant, but so far under-researched, management option for cities.

Cutaneous manifestations in Hymenoptera and Diptera anaphylaxis: relationship with basal serum tryptase.

OBJECTIVES: To compare the clinical presentation of systemic anaphylaxis to Hymenoptera and Diptera with regard to basal serum tryptase (BT) and to evaluate mastocytosis in patients with elevated tryptase. PATIENTS AND METHODS: The medical records of 140 patients with a history of a systemic reaction to venom were retrospectively reviewed. Symptoms and severity of anaphylaxis and BT were recorded. Most patients with elevated tryptase were screened for mastocytosis: a dermatological examination with a skin biopsy was performed in 19 cases and a bone marrow biopsy in 14 cases. RESULTS: Tryptase was elevated in 23 patients. These patients reported fewer usual skin reactions (urticaria in 26.1% of cases with raised tryptase vs. 76.1% of cases with normal tryptase), more flushing (52.2% vs. 4.3%) and frequently did not present skin reaction (26.1% vs. 9.4%). They presented a more severe reaction (mean grade of severity: 3.48 vs. 2.69). Mastocytosis was diagnosed in seven patients with elevated tryptase: indolent systemic mastocytosis in six cases and cutaneous mastocytosis without systemic involvement in one case. In five cases, mastocytosis was previously undiagnosed. Lesions of cutaneous mastocytosis, diagnosed in five patients, consisted of urticaria pigmentosa in all cases and were often inconspicuous. CONCLUSION: These results demonstrate particular clinical features of the allergic reaction in patients with elevated BT and the higher frequency of mastocytosis in this population. In patients with a severe anaphylactic reaction without urticaria, but with flushing, tryptase should be assayed and an underlying mastocytosis should be considered.

An arthroscopic technique to treat the iliotibial band syndrome.

Iliotibial band syndrome (ITBS) is an overuse injury mainly affecting runners. The initial treatment is conservative. Only, in recalcitrant cases surgery is indicated. Several open techniques have been described. The purpose of this study is to evaluate the results of a standardized arthroscopic technique for treatment of a resistant ITBS. Thirty-six athletes with a resistant ITBS were treated with a standardized arthroscopic technique, limited to the resection of lateral synovial recess. Thirty-three patients were available for follow-up (mean 2 years 4 months). Thirty-two patients (34 knees) had good or excellent results. All patients went back to sports after 3 months. In two patients a meniscal lesion was found, which required treatment. One patient with only a fair result had associated cartilage lesions of the femoral condyle. Our results show that arthroscopic treatment of resistant ITBS is a valid option with a consistently good outcome. In addition, this arthroscopic approach allows excluding or treating other intra-articular pathology.