•Malnutrition and severe malnutrition affect, respectively, more than half and one quarter of systemic sclerosis patients.•Malnutrition and the malnutrition universal screening tool score were ...strongly associated with specific systemic sclerosis cardiac involvement in multivariate analysis.•Severe malnutrition was strongly correlated with interincisal distance <35 mm and chronic intestinal pseudoobstruction in multivariate analysis.•This cohort of 120 patients is of interest in orphan diseases, such as scleroderma, and raises concerns about the risks of malnutrition in this peculiar condition. Our work may help clinicians better assess malnutrition, and it is the first study to evaluate the recent French criteria established for this disease alongside the other usual criteria.
Systemic sclerosis (SSc) can cause malnutrition due to frequent gastrointestinal involvement. However, prevalence of malnutrition in SSc is poorly known. The aim of this study was to evaluate the prevalence of malnutrition in SSc and its potential associations with disease features in patients from a tertiary referral center.
All patients meeting American College of Rheumatology/European Alliance of Associations for Rheumatology criteria for SSc followed between January 1, 1985, and January 1, 2019, at the Department of Internal Medicine, Saint Eloi University Hospital, were included. Malnutrition was assessed using the 2020 French recommendations for SSc and the malnutrition universal screening tool score. Severe malnutrition was defined via the French Haute Autorité de Santé (National Health Authority) 2007 criteria.
A total of 120 patients were included, with mean age 64 (± 15) y and a female-to-male sex ratio of 5:1. According to 2020 French recommendations, 71 patients (59.2%) were malnourished and 30 (25%) had at least one criterion of severe malnutrition. With the malnutrition universal screening tool score, 41.7%, 20%, and 38.3%, respectively, had low, medium, and high risk of malnutrition. Multivariate analysis revealed the following results: 1) malnutrition was associated with cardiac involvement (P < 0.01); 2) a high malnutrition universal screening tool score was also associated with specific cardiac involvement (P < 0.01); and 3) severe malnutrition was strongly correlated with interincisal distance <35 mm (P = 0.02).
Malnutrition affects more than half of SSc patients and is associated with specific cardiac involvement. Interincisal distance <35 mm could be a red flag for severe malnutrition in SSc.
Abstract Objectives This study aimed to estimate the prevalence of ANCA-associated vasculitis (AAV). That is, granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic ...granulomatosis with polyangiitis (EGPA), in Southern France in 2018, and evaluate differences among Europeans and non-Europeans. Methods This population-based, cross-sectional study used four sources (hospitals, community-based physicians, laboratories, National Health Insurance) to identify adults ≥15 years diagnosed with GPA, MPA or EGPA, living in Hérault and Gard in 2018. Cases were defined using the ACR/EULAR classification criteria, and if necessary, the European Medicines Agency algorithm. Prevalence estimates were standardised to the world population and capture-recapture analysis was used to assess the comprehensiveness of the estimation. The influence of geographical origin was evaluated. Results A total of 202 patients were selected, with 86 cases of GPA (42.6%), 85 cases of MPA (42.1%) and 31 cases of EGPA (15.3%). The standardised prevalence estimates per million inhabitants for 2018 were: 103 (95%CI 84–125) for AAV, 48 (95%CI 35–64) for GPA, 39 (95%CI 28–53) for MPA and 16 (95%CI 9–26) for EGPA, 36 (95%CI 25–50) for anti-PR3 positive AAV, 46 (95%CI 34–61) for anti-MPO positive AAV, and 16 (95%CI 9–26) for ANCA-negative AAV. The global estimation of comprehensiveness by capture-recapture analysis was 80.5%. The number of AAV cases was higher for non-European residents (P = 0.001), particularly for MPA (P < 0.0001). Conclusion We provide a new estimate of AAV prevalence in France and show a higher prevalence of MPA in non-European patients.
Flare of Antiphospholipid Syndrome in the Course of COVID-19 Maria, Alexandre Thibault Jacques; Diaz-Cau, Isabelle; Benejean, Jean-Marc ...
TH open : companion journal to thrombosis and haemostasis,
07/2020, Letnik:
4, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Abstract
We report the case of a 48-year-old man followed since 2013 for primary antiphospholipid syndrome (APLS) revealed by venous thromboembolism in the presence of antiphospholipid antibodies ...(APL-Abs, anticardiolipin and anti-β-2-glycoprotein-1), who decompensated in the course of coronavirus disease (COVID-19). Despite efficient anticoagulation, he suffered bilateral adrenal glands hemorrhage and limb arterial ischemia. The tropism of severe acute respiratory syndrome coronavirus-2 for endothelium can lead to microangiopathy and increased risk for thrombosis. If APL-Abs positivity can be an epiphenomenon under inflammatory and prothrombotic conditions, COVID-19 was herein responsible for disseminated thrombosis and a threat of catastrophic APLS, despite efficient anticoagulation.
Mastocytosis is characterized by clonal mast cell proliferation with accumulation within various organs and uncontrolled activation with excessive mast cell mediator release. Ocular manifestations ...have rarely been published. We describe a 63-year-old man with bilateral exophthalmos that led to the diagnosis of systemic mastocytosis.
A patient presented with bilateral eyelid edema with exophthalmos associated with binocular diplopia. Ophthalmologic examination showed bilateral axial, symmetrical, and painless exophthalmos with eyelid edema, and limitation in elevation of the right eye. Visual acuity was normal. Orbital magnetic resonance imaging showed increased volume of both the superior and medial recti muscles and right inferior oblique muscle, and histopathological examination of orbital fat and muscle biopsies revealed an infiltration by mast cells. Serum tryptase was elevated. The patient also complained of a long history of pruritis and diffuse skin erythema that could be elicited with just mild pressure (Darier's sign). A bone marrow biopsy confirmed the infiltration of abnormal mast cells with a D816V mutation in the KIT gene. Treatment with cladribine was initiated and resulted in resolution of both ocular and systemic signs and symptoms that persisted without relapse 18 months after discontinuation. Ocular mastocytosis is a rare condition, which was previously reported to involve the conjunctiva, cornea, uvea, eyelid, orbit, and choroid. Cases of ocular mastocytosis can be classified into two main groups: mast cells tumors (mastocytomas) and ocular manifestations associated with systemic mastocytosis. Histological examination of ocular samples is rarely performed, and there are no standard criteria for the diagnosis of ocular mastocytosis. Our case emphasizes cladribine could represent an alternative treatment.
Our case is the first published case of exophthalmos and eyelid edema associated with systemic mastocytosis confirmed by pathologic examination of periocular biopsies that was treated effectively with cladribine.
Midostaurin in Advanced Systemic Mastocytosis Chandesris, Marie-Olivia; Damaj, Gandhi; Canioni, Danielle ...
The New England journal of medicine,
06/2016, Letnik:
374, Številka:
26
Journal Article
Recenzirano
Odprti dostop
To the Editor:
Advanced systemic mastocytosis
1
carries a poor prognosis.
2
Midostaurin, an inhibitor of tyrosine kinases, targets KIT mutants associated with mastocytosis.
3
The French National ...Reference Center for Mastocytosis (CEREMAST) conducted a prospective survey of patients with mastocytosis who were treated with midostaurin under a transitory-use authorization program. All the patients provided written informed consent.
From August 2012 through April 2015, a total of 28 patients with mastocytosis (including 4 with aggressive disease, 18 with associated hematologic non–mast-cell disease, 3 with mast-cell leukemia, 1 with mast-cell sarcoma, and 2 with progressive smoldering disease) received midostaurin at a dose of 100 . . .
Biotherapies targeting TNFα were proven to be effective in the most severe cases of Crohn's Disease, a chronic granulomatous inflammatory bowel disease that can involve any portion of the digestive ...tract. The tolerance of anti-TNFα therapy is usually good, although several infectious complications have been reported with these drugs.
We report a case of a Crohn's disease patient who developed pulmonary cryptococcosis following chicken manure exposition while he received adalimumab and azathioprine.
A 54-year-old man, with history of severe Crohn's disease and ankylosing spondylitis, was admitted for diarrhea and abdominal pain under azathioprine treatment. In December 2010, he was treated with oral prednisone (1mg/kg/day), but Crohn's disease relapsed when prednisone dose was lower than 30mg/a day. The patient was then treated with adalimumab, but six weeks later he developed severe pulmonary cryptococcosis. The patient experienced a good outcome under antifungal therapy. We retrospectively found a high exposure to chicken manure in the last weeks.
Cryptococcosis is an opportunistic infection that can occur under anti-TNFα therapy. The environmental exposure to Cryptococcus spp. (in particular in chicken manure) is a source of contamination. Avoiding exposition to bird manure should be a recommendation for patients who are living in rural areas.
Background
Advanced Systemic Mastocytosis (adSM) still have very poor prognosis. No standard of care is yet available. Midostaurin (PKC412) is a powerful TKI inhibit of VEGFR, FLT3 and most ...importantly the mutated CKITD816V and D816Y. Preliminarily results from an international phase II trial (Gotlib et al., Blood 2012) reported interesting results in this subgroup of patients. We report herein on the French experience of the compassionate use of PKC412 for the treatment of adSM and compare their outcome to matched adSM historical control patients (pts) who did not receive PKC412 (control group).
Methods
Over a period of 12 months (from August 2012, date of PKC412 Temporary Approval for Use in France), 22 pts received PKC412 and could be analysed. PKC412 100 mg twice daily was administered orally as continuous 28-day cycles until progression or unacceptable toxicity. Pts were evaluated according to the response criteria used in the recent phase 2 trial on midostaurin (Gotlib et al.). The overall survival (OS) of these 22 patients was compared to the OS of 42 age and WHO subcategories matched control adSM patients who were treated before PKC412 era.
Results
2 female and 20 male pts with a median age of 65 years 35-84 received midostaurin. Overall, 21 pts (95%) with adSM (5 ASM; 2 MCL; 1 MCS; 12 ASM-AHNMD; 1 SSM-AHNMD,1) and 1 pt progressive SSM. Median number of C-Findings was 3 (0-4). Hepato- and/or splenomegaly were present in 20 (91%) and 21 (95%) pts. Median tryptase level was 204 ng/l (85-2000). Median haemoglobin level, platelet and PMN counts were respectively 10.1g/dl (6.8-13.9), 117G/L (22-289) and 2.8G/L (0.3-17). Twenty (91%) pts had cKIT D816V mutation, 2 pts had cKITWT. ASXL1 and TET2 were mutated in 3/7 and 2/7 tested, respectively. Steroids, 2-chlorodeoxyadenosine and Interferon were administered in 9, 4 and 2 pts prior to midostaurin.
After a median exposure time of 6.9 1.6-27.5 months, the overall response rate (ORR) was 77.2% including, major responses (n=13; 59%) (incomplete major in 8 pts, pure clinical in 5); partial response (n=5, 23%) (good partial in 3, minor partial in 2). Three patients were rapidly progressive (<2 months) and considered refractory to PKC412 (1 MCL, 1 MCS, 1 ASM-AHNMD). Death occurred in 4 pts (refractoriness 2 pts, AHNMD progression 2 pts). After a median follow-up of 7.4 months from PKC412 start, median OS was 24.4 months 12.6-34.2. Patients with ASM seemed to better benefit from PKC412, however, no significant difference was found between the ASM and SM-AHNMD, probably due to the low patient’s number.
The control group consisted in 42 pts with a median age of 65.5 years 23-84. There were 17 ASM-AHNMD, 21 ISM-AHNMD, 2 SSM-AHNMD, 1 CM-AHNMD and 1 MCL patients. Median tryptase level was 107ng/l 19-501. Median haemoglobin level, platelet and PMN counts were respectively 12.1g/dl 8-15, 200G/L 10-1036 and 4.6G/L 0.5-24.3. Thirty-three (79%) pts had cKIT D816V mutation, 7 pts were cKITWT. ASXL1 and TET2 were mutated in 6/29 (21%) and 7/29 (24%) of pts tested, respectively. Steroids, 2-CdA, interferon, imatinib, thalidomide have been used in 19, 21, 6, 4, and 6 pts respectively.
Survival distributions were estimated using the adjusted Kaplan-Meier method from the date of diagnosis to the last follow-up for the PKC412 treated and the control groups. Median survival time for PKC412 treated patients was significantly longer than control patients (p=0.04).
Conclusion
PKC412 is active in advanced SM. Despite the absence of complete remission, PKC412 gives survival advantage for patients with adSM over pts who did not receive the drug.
No relevant conflicts of interest to declare.
The specific role of the striatum, especially its dorsolateral (DLS) and dorsomedial (DMS) parts, in male copulatory behavior is still debated. In order to clarify their contribution to male sexual ...behavior, we specifically ablated the major striatal neuronal subpopulations, direct and indirect medium spiny neurons (dMSNs and iMSNs) in DMS or DLS, and dMSNs, iMSNs and cholinergic interneurons in nucleus accumbens (NAc),
The main results of this study can be summarized as follows:
In DMS, dMSN ablation causes a reduction in the percent of mice that mount a receptive female, and a complex alteration in the parameters of the copulatory performance, that is largely opposite to the alterations induced by iMSN ablation.
In DLS, dMSN ablation causes a widespread alteration in the copulatory behavior parameters, that tends to disappear at repetition of the test; iMSN ablation induces minor copulatory behavior alterations that are complementary to those observed after dMSN ablation.
In NAc, dMSN ablation causes a marked reduction in the percent of mice that mount a receptive female and a disruption of copulatory behavior, while iMSN ablation induces minor copulatory behavior alterations that are opposite to those observed with dMSN ablation, and cholinergic neuron ablation induces a selective decrease in mount latency.
Overall, present data point to a complex region and cell-specific contribution to copulatory behavior of the different neuronal subpopulations of both dorsal and ventral striatum, with a prominent role of the dMSNs of the different subregions.
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