Publications by authors named "Geoffrey Urbanski"

38 Publications

Achieving Expert-Level Interpretation of Serum Protein Electrophoresis through Deep Learning Driven by Human Reasoning.

Clin Chem 2021 Sep 7. Epub 2021 Sep 7.

Laboratoire de Biochimie et Biologie Moléculaire, Centre Hospitalier Universitaire d'Angers, Angers, France.

Background: Serum protein electrophoresis (SPE) is a common clinical laboratory test, mainly indicated for the diagnosis and follow-up of monoclonal gammopathies. A time-consuming and potentially subjective human expertise is required for SPE analysis to detect possible pitfalls and to provide a clinically relevant interpretation.

Methods: An expert-annotated SPE dataset of 159 969 entries was used to develop SPECTR (serum protein electrophoresis computer-assisted recognition), a deep learning-based artificial intelligence, which analyzes and interprets raw SPE curves produced by an analytical system into text comments that can be used by practitioners. It was designed following academic recommendations for SPE interpretation, using a transparent architecture avoiding the "black box" effect. SPECTR was validated on an external, independent cohort of 70 362 SPEs and challenged by a panel of 9 independent experts from other hospital centers.

Results: SPECTR was able to identify accurately both quantitative abnormalities (r ≥ 0.98 for fractions quantification) and qualitative abnormalities [receiver operating characteristic-area under curve (ROC-AUC) ≥ 0.90 for M-spikes, restricted heterogeneity of immunoglobulins, and beta-gamma bridging]. Furthermore, it showed highly accurate at both detecting (ROC-AUC ≥ 0.99) and quantifying (r = 0.99) M-spikes. It proved highly reproducible and resilient to minor variations and its agreement with human experts was higher (κ = 0.632) than experts between each other (κ = 0.624).

Conclusions: SPECTR is an algorithm based on artificial intelligence suitable to high-throughput SPEs analyses and interpretation. It aims at improving SPE reproducibility and reliability. It is freely available in open access through an online tool providing fully editable validation assistance for SPE.
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http://dx.doi.org/10.1093/clinchem/hvab133DOI Listing
September 2021

Brain abscess caused by Bartonella henselae associated with arteriovenous malformation.

Infect Dis Now 2021 Sep 30;51(6):574-576. Epub 2020 Dec 30.

Department of internal medicine, University hospital of Angers, Angers, France.

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http://dx.doi.org/10.1016/j.idnow.2020.11.012DOI Listing
September 2021

Tear metabolomics highlights new potential biomarkers for differentiating between Sjögren's syndrome and other causes of dry eye.

Ocul Surf 2021 Jul 28;22:110-116. Epub 2021 Jul 28.

Mitolab, MitoVasc Institute, CNRS, 6015, INSERM U1083, University of Angers, France; Department of Biochemistry and Molecular Biology, University Hospital, Angers, France.

Purpose: The lacrimal exocrinopathy of primary Sjögren's syndrome (pSS) is one of the main causes of severe dry eye syndrome and a burden for patients. Early recognition and treatment could prevent irreversible damage to lacrimal glands. The aim of this study was to find biomarkers in tears, using metabolomics and data mining approaches, in patients with newly-diagnosed pSS compared to other causes of dry eye syndrome.

Methods: A prospective cohort of 40 pSS and 40 non-pSS Sicca patients with dryness was explored through a standardized targeted metabolomic approach using liquid chromatography coupled with mass spectrometry. A metabolomic signature predictive of the pSS status was sought out using linear (logistic regression with elastic-net regularization) and non-linear (random forests) machine learning architectures, after splitting the studied population into training, validation and test sets.

Results: Among the 104 metabolites accurately measured in tears, we identified a discriminant signature composed of nine metabolites (two amino acids: serine, aspartate; one biogenic amine: dopamine; six lipids: Lysophosphatidylcholine C16:1, C18:1, C18:2, sphingomyelin C16:0 and C22:3, and the phoshatidylcholine diacyl PCaa C42:4), with robust performances (ROC-AUC = 0.83) for predicting the pSS status. Adjustment for age, sex and anti-SSA antibodies did not disrupt the link between the metabolomic signature and the pSS status. The non-lipidic components also remained specific for pSS regardless of the dryness severity.

Conclusion: Our results reveal a metabolomic signature for tears that distinguishes pSS from other dry eye syndromes and further highlight nine key metabolites of potential interest for early diagnosis and therapeutics of pSS.
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http://dx.doi.org/10.1016/j.jtos.2021.07.006DOI Listing
July 2021

Warning Signals of Post-Exertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Retrospective Analysis of 197 Patients.

J Clin Med 2021 Jun 7;10(11). Epub 2021 Jun 7.

Department of Internal Medicine and Clinical Immunology, Angers University Hospital, 49933 Angers, France.

Post-exertional malaise (PEM), the key feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), is characterized by baseline symptom exacerbation after exposure to a stressor, and some patients can experience new or non-typical symptoms. We hypothesized that new or non-typical symptoms occurring long enough before onset of baseline symptom exacerbation could be warning signals predicting PEM. Adult ME/CFS patients who attended the internal medicine department of Angers University Hospital (France) between October 2011 and December 2019 were included in a retrospective medical records review. Patients who experienced one or more new or non-typical symptoms before baseline symptom exacerbation were compared with the rest of the study population for PEM features, epidemiological characteristics, fatigue features, and comorbidities. New or non-typical symptoms preceded baseline symptom exacerbation in 27/197 (13.7%) patients, and the most frequent ones were mood disorders (37%). When compared to the rest of the study population, only PEM intensity was significantly lower in these patients ( = 0.004), even after adjustment for sex and age at disease onset ( = 0.007). New or non-typical symptoms preceding baseline symptom exacerbation in some ME/CFS patients could be warning signals for PEM. Their identification could help preventing PEM occurrences or reducing their intensity leading to improving disease prognosis.
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http://dx.doi.org/10.3390/jcm10112517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201170PMC
June 2021

Persistent elevation of plasma vitamin B12 is strongly associated with solid cancer.

Sci Rep 2021 Jun 25;11(1):13361. Epub 2021 Jun 25.

Department of Internal Medicine and Clinical Immunology, Angers University Hospital, Angers, France.

Elevated plasma vitamin B12 has been associated with solid cancers, based on a single B12 measurement. We evaluated the incidence of solid cancers following B12 measurement in patients with persistent elevated B12, compared to patients without elevated B12 and to patients with non-persistent elevated B12. The study population included patients with at least two plasma B12 measurements without already known elevated-B12-related causes. Patients with elevated plasma B12 (≥ 1000 ng/L) at first measurement (n = 344) were matched for age and sex with patients having 2 normal B12 measurements (< 1000 ng/L) (NN group, n = 344). The patients with elevated plasma B12 at first measurement were split into 2 groups, according to the presence (EE group, n = 144) or the absence (EN group, n = 200) of persistent elevated plasma B12 at second measurement. We compared the cancer-free survival during 60 months between the groups after adjustment for the other elevated-B12-related causes in a survival competing risk model. Compared to the NN group, a persistent elevated plasma B12 ≥ 1000 ng/mL was strongly associated with the occurrence of solid cancer (HR 5.90 [95% CI 2.79-12.45], p < 0.001), contrary to non-persistent plasma B12 elevation (p = 0.29). These results could help to select patients in whom the screening for solid cancers would be of interest.
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http://dx.doi.org/10.1038/s41598-021-92945-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233305PMC
June 2021

Splenectomy for haemophagocytic lymphohistiocytosis of unknown origin: risks and benefits in 21 patients.

Br J Haematol 2021 Aug 7;194(3):638-642. Epub 2021 May 7.

Laboratory of cellular and molecular mechanisms of hematological disorders and therapeutic implications, INSERM U1163, Imagine Institut, Sorbonne Paris University, Paris, France.

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http://dx.doi.org/10.1111/bjh.17497DOI Listing
August 2021

Severe Joint Involvement in VEXAS Syndrome: A Case Report.

Ann Intern Med 2021 07 30;174(7):1025-1027. Epub 2021 Mar 30.

Angers University Hospital, Angers, France.

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http://dx.doi.org/10.7326/L21-0023DOI Listing
July 2021

Symptomatic aortitis at giant cell arteritis diagnosis: a prognostic factor of aortic event.

Arthritis Res Ther 2021 01 7;23(1):14. Epub 2021 Jan 7.

Department of Internal Medicine, CHU Nantes, 1 place Alexis Ricordeau, 44093, Nantes, France.

Background: Giant cell arteritis (GCA) is frequently associated with aortic involvement that is likely to cause life-threatening structural complications (aneurysm, dissection). Few studies have investigated the occurrence of these complications, and no predictive factor has been identified so far. The aim of this study was to investigate factors associated with the risk of aortic complications in a cohort of GCA aortitis.

Methods: Data of all patients managed with aortitis (CT or 18 FDG PET) at the diagnosis of GCA in five hospitals from May 1998 and April 2019 were retrospectively collected. Clinical features were compared according to the presence of aortitis symptoms. The predictive factors of occurrence or aggravation of aortic structural abnormalities were investigated.

Results: One hundred and seventy-one patients with GCA aortitis were included; 55 patients (32%) had symptoms of aortitis (dorsal/lumbar/abdominal pain, aortic insufficiency) at diagnosis. The median follow-up was 38 months. Aortic complications occurred after a median time of 32 months. There were 19 new aortic aneurysms or complications of aneurysm and 5 dissections. Survival without aortic complication was significantly different between the symptomatic and non-symptomatic groups (Log rank, p = 0.0003). In multivariate analysis the presence of aortitis symptoms at diagnosis (HR 6.64 [1.95, 22.6] p = 0.002) and GCA relapse (HR 3.62 [1.2, 10.9] p = 0.02) were factors associated with the occurrence of aortic complications.

Conclusion: In this study, the presence of aortitis symptoms at the diagnosis of GCA aortitis and GCA relapse were independent predictive factors of occurrence of aortic complications during follow-up.
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http://dx.doi.org/10.1186/s13075-020-02396-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792092PMC
January 2021

Impact of aging on phenotype and prognosis in IgA vasculitis.

Rheumatology (Oxford) 2021 09;60(9):4245-4251

Université Paris Descartes.

Objectives: Immunoglobulin A vasculitis (IgAV) is a small-vessel vasculitis most frequently benign in children while more severe in adults. We aimed to study the impact of age on presentation and outcome of adult IgAV.

Methods: We conducted a nationwide retrospective study including 260 IgAV patients. Patients were divided into four quartiles according to the age at IgAV diagnosis: <36, 36 ≤ age < 52; 52 ≤ age < 63 and ≥63 years. Comparison of presentation and outcome were performed according to age of disease onset.

Results: Mean age at diagnosis was 50.1 (18) years and 63% were male. IgAV diagnosed in the lowest quartile of age was associated with more frequent joint (P < 0.0001) and gastrointestinal involvement (P = 0.001). In contrast, the oldest patients had more severe purpura with necrotic lesions (P = 0.001) and more frequent renal involvement (P < 0.0001), with more frequent haematuria, renal failure, higher urine protein excretion and more frequent tubulointerstitial lesions. Patients were treated similarly in all groups of age, and clinical response and relapse rates were similar between groups. In the 127 treated patients with follow-up data for >6 months, clinical response and relapse rates were similar between the four groups. Median follow-up was of 17.2 months (9.1-38.3 months). Renal failure at the end of follow-up was significantly more frequent in the highest quartile of age (P = 0.02), but the occurrence of end-stage renal disease was similar in all groups. Last, overall and IgAV-related deaths were associated with increase in age.

Conclusion: Aging negatively impacts the severity and outcome of IgAV in adults. Younger patients have more frequent joint and gastrointestinal involvement, while old patients display more frequent severe purpura and glomerulonephritis.
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http://dx.doi.org/10.1093/rheumatology/keaa921DOI Listing
September 2021

Association of Primary Sjögren's Syndrome and Vitamin B12 Deficiency: A Cross-Sectional Case-Control Study.

J Clin Med 2020 Dec 16;9(12). Epub 2020 Dec 16.

Department of Internal Medicine, Angers University Hospital, 4 Rue Larrey, 49000 Angers, France.

Descriptive and retrospective studies without control groups have suggested a possible association between primary Sjögren's syndrome (pSS) and vitamin B12 (B12) deficiency. This is of importance because several mucosal and neurological features are common to these two conditions and could be prevented or reversed in case of B12 deficiency. We aimed to evaluate the association between pSS and B12 deficiency. We prospectively assessed the B12 status of 490 patients hospitalized in an internal medicine department over a 15-week period. Patients with pernicious anemia were excluded. We extracted patients with pSS and paired them with controls according to age and sex, with a 1:5 ratio. Twenty-one pSS patients were paired with 105 control patients. The median age was 70 years old (51-75) and 95.2% of patients were women. The plasma B12 level was lower in pSS patients (329 (293-521) ng/L vs. 456 (341-587) ng/L, < 0.0001). B12 deficiency was associated with pSS (42.9% among pSS patients vs. 11.4% among controls), even after adjustment for other causes of B12 deficiency (OR 6.45 (95%CI: 2.08-20.0)). In conclusion, pSS appeared to be associated with B12 deficiency, even after the exclusion of pernicious anemia. This justifies screening and treating B12 deficiency in pSS patients.
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http://dx.doi.org/10.3390/jcm9124063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765802PMC
December 2020

New insights on IgA vasculitis with underlying solid tumor: a nationwide French study of 30 patients.

Clin Rheumatol 2021 May 24;40(5):1933-1940. Epub 2020 Oct 24.

Department of Internal Medicine and Clinical Immunology, CHRU Tours, Tours, France.

Objective: IgA vasculitis (IgAV) frequently occurs during or after a mucosal infection; it also rarely occurs in patients with cancer. We hypothesized that cancer could impact the baseline characteristics and/or outcome of vasculitis. We aimed to describe the presentation of IgAV in patients with cancer (IgAV ca+) compared to patients without cancer.

Methods: We conducted a nationwide retrospective study of adult patients in France who presented with both IgAV and cancer. Baseline characteristics were described and compared with those of the 260 patients included in a nationwide French IgAV study.

Results: Thirty patients were included. The mean age was 69 ± 12 years; 80% were men. Compared to patients without underlying cancer, IgAV ca+ patients were older (69 ± 12 vs. 50 ± 18 years; p < 0.0001) and they presented more frequently with necrotic purpura (53 vs. 26%; p < 0.002) and intra-alveolar hemorrhage (10 vs. 0.5%; p < 0.0001). IgAV ca+ patients frequently had elevated serum IgA levels (79 vs. 53%; p < 0.034); most (n = 22, 73%) had adenocarcinoma or urothelial carcinoma involving the large intestines (n = 6), bladder (n = 5), and lung (n = 5). Most IgAV ca+ patients had progressive cancer (n = 21); a minority had metastatic disease (n = 2) at IgAV diagnosis. After a median follow-up of 3 months, 8 deaths were observed but none was related to IgAV.

Conclusion: Compared to their noncancer counterpart, patients with IgAV related to cancer were older and more frequently presented with necrotizing purpura, intra-alveolar hemorrhage, and elevated serum IgA levels. Adult patients with IgAV and these latter characteristics should be carefully screened for cancer. Key Points • Clinical and biological characteristics of patients presenting with IgAV are distinct depending on the underlying cause of vasculitis related to cancer. • Patients with IgAV related to cancer are older, and compared to their counterparts without IgAV, they present more frequently with necrotic purpura, alveolar hemorrhage, and elevated serum IgA levels. • All adult patients with IgAV should be screened for cancer, and there should be a focus on elderly male patients presenting with necrotic purpura and/or alveolar hemorrhage.
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http://dx.doi.org/10.1007/s10067-020-05455-zDOI Listing
May 2021

Diagnosis of vitamin B12 deficiency: combined indicator of B12-status should be interpreted with caution in the case of renal impairment.

Clin Chem Lab Med 2020 Oct 19. Epub 2020 Oct 19.

Department of Internal Medicine, University Hospital, Angers, France.

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http://dx.doi.org/10.1515/cclm-2020-1245DOI Listing
October 2020

Obstetrical outcome and treatments in seronegative primary APS: data from European retrospective study.

RMD Open 2020 08;6(2)

Sorbonne Université, AP-HP, Hôpital Saint-Antoine, Service de Médecine Interne and Inflammation-Immunopathology-Biotherapy Department (DMU 3iD), Paris, France

Objective: To compare characteristics, pregnancies and treatments during pregnancies of seronegative and seropositive antiphospholipid syndrome (APS), to analyse factors associated with obstetrical outcome.

Patients And Methods: Inclusion criteria were: (1) thrombotic and/or obstetrical APS (Sydney criteria); (2) absence of conventional antiphospholipid antibodies (APL); (3) at least one persistent non-conventional APL among IgA anticardiolipin antibodies, IgA anti-B2GPI, anti-vimentin G/M, anti-annexin V G/M, anti-phosphatidylethanolamine G/M and anti-phosphatidylserine/prothrombin G/M antibodies. The exclusion criteria were: (1) systemic lupus erythematosus ( SLE) or SLE-like disease; and (2) other connective tissue disease.

Results: A total of 187 women (mean 33±5 years) with seronegative APS were included from 14 centres in Austria, Spain, Italy, Slovenia and France and compared with 285 patients with seropositive APS. Seronegative APS has more obstetrical rather than thrombotic phenotypes, with only 6% of venous thrombosis in comparison to seropositive APS. Cumulative incidence of adverse obstetrical events was similar in seronegative and seropositive APS patients, although higher rates of intrauterine deaths (15% vs 5%; p=0.03), of preeclampsia (7% vs 16%, p=0.048) and lower live birth term (36±3 vs 38±3 weeks of gestation; p=0.04) were noted in seropositive APS. The cumulative incidence of adverse obstetrical events was significantly improved in treated versus untreated seronegative APS (log rank<0.05), whereas there was no difference between patients who received aspirin or aspirin-low-molecular weighted heparin combination.

Conclusion: Several non-criteria APL can be detected in patients with clinical APS features without any conventional APL, with various rates. The detection of non-criteria APL and thus the diagnosis of seronegative APS could discuss the therapeutic management similar to seropositive APS, but well-designed controlled studies are necessary.
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http://dx.doi.org/10.1136/rmdopen-2020-001340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507995PMC
August 2020

IgA Vasculitis With Underlying Liver Cirrhosis: A French Nationwide Case Series of 20 Patients.

J Rheumatol 2021 05 15;48(5):735-740. Epub 2020 Aug 15.

A. Bigot, MD, F. Maillot, MD, A. Audemard-Verger, MD, PhD, Department of Internal Medicine and Clinical Immunology, CHRU Tours, and University of Tours, Tours;

Objective: Immunoglobulin A vasculitis (IgAV) and nephropathy (IgAN) share common immunological mechanisms. Liver cirrhosis is well known to be associated with IgAN. Here, we aimed to describe the presentation and outcome of IgAV patients with underlying cirrhosis.

Methods: We conducted a French nationwide retrospective study of adult patients presenting with both IgAV and cirrhosis. Baseline characteristics were compared to those of the 260 patients included in the French nationwide IgAV registry (IGAVAS).

Results: Twenty patients were included, and 7 (35%) were female. The mean ± SD age was 62.7 ± 11 years. At baseline, compared with IGAVAS patients, patients with underlying cirrhosis were older (62.7 ± 11 vs 50.1 ± 18, < 0.01) and displayed more constitutional symptoms (weight loss 25% vs 8%, = 0.03). Patients with underlying cirrhosis were also more likely to exhibit elevated serum IgA levels (5.6 g/L vs 3.6 g/L, = 0.02). Cirrhosis and IgAV were diagnosed simultaneously in 12 patients (60%). Cirrhosis was mainly related to alcohol intake (n = 15, 75%), followed by nonalcoholic steato-hepatitis (n = 2), chronic viral hepatitis (n = 1), hemochromatosis (n = 1), and autoimmune hepatitis (n = 1). During follow-up with a median of 17 months (IQR 12-84), 10/13 (77%) exhibited IgAV remission at Month 3. One patient presented a minor relapse. Six patients died, but no deaths were related to IgAV.

Conclusion: We report the first case series of IgAV patients with underlining cirrhosis, to our knowledge, which was mainly alcohol related. The liver disease did not seem to affect baseline vasculitis characteristics. Physicians should investigate the existence of liver cirrhosis at IgAV diagnosis, especially in the context of alcohol abuse.
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http://dx.doi.org/10.3899/jrheum.200293DOI Listing
May 2021

Diagnostic Performances of Urinary Methylmalonic Acid/Creatinine Ratio in Vitamin B12 Deficiency.

J Clin Med 2020 Jul 22;9(8). Epub 2020 Jul 22.

Department of Internal Medicine, University Hospital, 49000 Angers, France.

Sole measurement of plasma vitamin B12 is no longer enough to identify vitamin B12 (B12) deficiency. When plasma vitamin B12 is in the low-normal range, especially between 201 and 350 ng/L, B12 deficiency should be assessed by measurements of plasma homocysteine and/or plasma methylmalonic acid (MMA). However, these biomarkers also accumulate during renal impairment, leading to a decreased specificity for B12 deficiency. In such cases, urinary methylmalonic acid/creatinine ratio (uMMA/C) could be of interest, due to the stable urinary excretion of MMA. The objectives were to evaluate the influence of renal impairment on uMMA/C compared to plasma homocysteine and plasma methylmalonic acid, and to determine the diagnostic performances of uMMA/C in the diagnosis of B12 deficiency. We prospectively studied 127 patients with a plasma B12 between 201 and 350 ng/L. We noticed that uMMA/C was not dependent on renal function ( = 0.34), contrary to plasma homocysteine and plasma methylmalonic acid. uMMA/C showed a perspective diagnostic performance (AUC 0.71 [95% CI: 0.62-0.80]) and the threshold of 1.45 umol/mmol presented a high degree of specificity (87.9% [95% CI: 72.0-98.9]). In conclusion, uMMA/C is a promising biomarker to assess vitamin B12 status in doubtful cases, notably during renal impairment.
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http://dx.doi.org/10.3390/jcm9082335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466029PMC
July 2020

Parietal cell antibodies: evolution of plasma vitamin B12 during oral supplementation to differentiate true and false positives for pernicious anemia.

Pol Arch Intern Med 2020 09 4;130(9):813-815. Epub 2020 Jul 4.

Department of Internal Medicine, University Hospital, Angers, France;

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http://dx.doi.org/10.20452/pamw.15478DOI Listing
September 2020

Epidemiological and clinical factors associated with post-exertional malaise severity in patients with myalgic encephalomyelitis/chronic fatigue syndrome.

J Transl Med 2020 06 22;18(1):246. Epub 2020 Jun 22.

Department of Internal Medicine, University Hospital, 49000, Angers, France.

Background: Post-exertional malaise (PEM), the cardinal feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), occurs generally after exposure to a stressor. It is characterized by the worsening of ME/CFS symptoms and results in aggravating the course of the disease and the quality of life of patients. Due to its unpredictable onset, severity, and recovery time, identifying patients with higher risk for severe PEM would allow preventing or reducing its occurrence. We thus aimed at defining possible factors that could be associated with PEM severity.

Methods: Adult patients fulfilling ME international consensus criteria who attended the internal medicine department of University hospital Angers-France between October 2011 and December 2019 were included retrospectively. All patients were systematically hospitalized for an etiological workup and overall assessment. We reviewed their medical records for data related to the assessment: epidemiological data, fatigue features, clinical manifestations, and ME/CFS precipitants. PEM severity was appreciated by the Center for Disease Control self-reported questionnaire. The study population was classified into quartiles according to PEM severity scores. Analyses were performed with ordinal logistic regression to compare quartile groups.

Results: 197 patients were included. PEM severity was found to be positively associated with age at disease onset ≥ 32 years (OR 1.8 [95% CI 1.1-3.0] (p = 0.03)), recurrent infections during the course of the disease (OR 2.1 [95% CI 1.2-3.7] (p = 0.009)), and when ME/CFS was elicited by a gastrointestinal infectious precipitant (OR 5.7 [1.7-19.3] (p = 0.006)).

Conclusion: We identified some epidemiological and clinical features, which were positively associated with PEM severity in subsets of ME/CFS patients. This could help improving disease management and patients' quality of life.
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http://dx.doi.org/10.1186/s12967-020-02419-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309998PMC
June 2020

Differences in clinical features between small fiber and sensitive large fiber neuropathies in Sjögren's syndrome.

Eur J Intern Med 2020 09 27;79:58-62. Epub 2020 May 27.

Department of Internal Medicine, University Hospital, Angers, 49000, France. Electronic address:

Background: To distinguish large (LFN) and small fiber neuropathies (SFN) in Sjögren's syndrome (SS) requires electroneuromyography (EMG) first, but this is time-consuming and has sometimes a limited accessibility, which can lead to a diagnostic delay. We aimed to identify clinical features that could distinguish SFN from sensitive LFN in SS.

Methods: The study included patients with SS who were monitored in the internal medicine and neurology departments at Angers University Hospital between 2010 and 2016, and who were tested for suspected peripheral neuropathy. Patients with clinical motor involvement were excluded. LFN diagnosis was based on EMG. SFN diagnosis was based on intraepidermal nerve fiber density on skin biopsies in patients with no abnormality on EMG.

Results: LFN and SFN were diagnosed respectively in 22 (6.9%) and 17 (5.4%) patients among 317 patients with SS. Prevalence of anti-SSA antibodies was lower in the SFN group compared to the LFN group (p=0.002). The types of paresthesia did not differ between the 2 groups. After adjustment for age and sex, SFN was associated with dysautonomia (p=0.01, OR 8.4 [CI 95%: 1.7-42.4]) and without length-dependent topography (p=0.03, OR 0.2 [0.04-0.8] in comparison with the LFN group.

Conclusions: An association of non-length-dependent pattern and dysautonomia seems to predict the absence of LFN in SS and encourages the search for SFN. In contrary, patients with length-dependent involvement and without dysautonomia should be prioritized for EMG.
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http://dx.doi.org/10.1016/j.ejim.2020.05.004DOI Listing
September 2020

Gastrointestinal involvement in adult IgA vasculitis (Henoch-Schönlein purpura): updated picture from a French multicentre and retrospective series of 260 cases.

Rheumatology (Oxford) 2020 Oct;59(10):3050-3057

Department of Internal Medicine.

Objectives: To describe the clinical presentation, treatments and prognosis of gastrointestinal (GI) involvement in adult IgA vasculitis (IgAV).

Methods: Data from 260 adults with IgAV included in a French multicentre retrospective survey were analysed. Presentation and outcomes of patients with (GI+) and without (GI-) GI involvement were compared.

Results: One hundred and thirty-seven (53%) patients had GI involvement. Initial manifestations were abdominal pain in 99%, intestinal bleeding in 31%, diarrhoea in 26% and acute surgical abdomen in only 4%. Abdominal imaging revealed thickening of intestinal wall in 61%, and endoscopies revealed abnormalities in 87%, mostly mucosal ulcerations. GI+ vs GI- patients were younger (46 ± 18 vs 54 ± 18 years; P = 0.0004), had more constitutional symptoms (43% vs 23%; P = 0.0005) and joint involvement (72 vs 50%; P = 0.0002), and higher CRP levels (3.7 vs 1.9 mg/dl; P = 0.001). Clinical response and relapse rates were comparable between groups, and all causes mortality (2 vs 4%) and IgAV-related mortality (1% vs 2%) as well. GI-related deaths were due to intestinal perforation and mesenteric ischaemia.

Conclusion: GI involvement is frequent in adult IgAV. GI involvement is frequent in adult IgAV. Mortality is not uncommon but does not seem to be specifically related to GI. Immunosuppressants should not be preferred as first-line therapy for GI+ patients but may be required in case of acute surgical abdomen.
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http://dx.doi.org/10.1093/rheumatology/keaa104DOI Listing
October 2020

Unstimulated whole saliva flow for diagnosis of primary Sjögren's syndrome: time to revisit the threshold?

Arthritis Res Ther 2020 02 24;22(1):38. Epub 2020 Feb 24.

Department of Internal Medicine, University Hospital, 4 rue Larrey, 49000, Angers, France.

Background: Unstimulated whole saliva (UWS) flow rate is one of the ACR/EULAR 2016 criteria for primary Sjögren's syndrome (pSS). With a single threshold of ≤ 0.1 mL/min, UWS flow does not take into account the age- and sex-related physiological variations. Furthermore, it has a low sensitivity for the diagnosis of pSS (about 50%), contrary to the screening test for xerophthalmia, Schirmer's test (sensitivity of about 70%). We aimed to identify UWS thresholds allowing better performances for a screening test for pSS comparable to Schirmer's test, and considering age- and sex-related variations.

Methods: A prospective cohort of 185 patients with oral and/or ocular dryness was classified into 3 groups: men, women < 50 (< 50 years old), and women ≥ 50 (≥ 50 years old). The diagnostic performances of UWS flow rate in these groups were compared in terms of sensitivity, specificity, positive and negative predictive values, and ROC curves. The identification of thresholds that optimize diagnostic performances was carried out using Youden's index.

Results: The diagnostic performances of UWS flow rate varied according to age and sex. UWS had poor diagnostic performances whatever the threshold in the women ≥ 50 group. The threshold of 0.2 mL/min had a sensitivity of ≥ 70% and a specificity of ≥ 50% in both men and women < 50 groups. In the whole population and compared to the current cutoff, a threshold of 0.2 mL/min increased sensitivity (+ 19.8%) and positive (+ 2.3%) and negative (+ 7.0%) predictive values, with a better specificity (65.2%) than Schirmer's test.

Conclusion: For objective assessment of xerostomia, raising the threshold of the UWS flow rate to 0.2 mL/min would optimize its screening performances for pSS.
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http://dx.doi.org/10.1186/s13075-020-2132-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041275PMC
February 2020

Strength of the Association of Elevated Vitamin B12 and Solid Cancers: An Adjusted Case-Control Study.

J Clin Med 2020 Feb 9;9(2). Epub 2020 Feb 9.

Department of Internal Medicine, Angers University Hospital, 49933 Angers, France.

The association between elevated plasma vitamin B12 (B12) level and solid cancers has been documented by two national registries. However, their design did not allow for the adjustment for other conditions associated with elevated B12. The objectives of this study were to confirm this association after the adjustment for all causes of elevated B12, and to study the variations according to the increasing B12 level, the type of cancers, and the presence of metastases. We compared 785 patients with B12 ≥ 1000 ng/L with 785 controls matched for sex and age with B12 < 1000 ng/L. Analyses were adjusted for the causes of elevated B12: myeloid blood malignancies, acute or chronic liver diseases, chronic kidney failure, autoimmune or inflammatory diseases, and excessive B12 supplementation. A B12 ≥ 1000 ng/L was associated with the presence of solid cancer without metastases (OR 1.96 [95%CI: 1.18 to 3.25]) and with metastases (OR 4.21 [95%CI: 2.67 to 6.64]) after adjustment for all elevated B12-related causes. The strength of the association rose with the increasing B12 level, in particular in cases of metastases. No association between liver cancers and elevated B12 level was found after adjustment for chronic liver diseases. In conclusion, unexplained elevated B12 levels should be examined as a possible marker of solid cancer.
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http://dx.doi.org/10.3390/jcm9020474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073937PMC
February 2020

Pasteurella bacteraemia: Impact of comorbidities on outcome, based on a case series and literature review.

Int J Infect Dis 2020 Mar 8;92:89-96. Epub 2020 Jan 8.

Department of Internal Medicine, Angers University Hospital, 4, rue Larrey, 49933 Angers, France. Electronic address:

Objectives: Pasteurella bacteraemia is rare, but has been associated with a high mortality rate. The aim of this study was to estimate the impact of comorbidities on patients with Pasteurella bacteraemia.

Methods: All cases of Pasteurella bacteraemia in adults treated in our centre between January 2008 and December 2017 were included retrospectively and compared with cases identified in a systematic review of the literature via MEDLINE covering the years 1951-2017. The epidemiological, bacteriological, and clinical data were collected, as well as the instances of death after 30 days.

Results: Twenty cases of Pasteurella bacteraemia identified in our centre and 99 cases from the literature review were included. A major comorbidity was found in 80/119 (67.2%) patients. The death rate at 30 days was 31.1%. The most common comorbidities were cirrhosis, immunosuppressive therapy, and malignant diseases. Age was not associated with mortality. On multivariate analysis, the only factor associated with mortality was a major comorbidity (odds ratio 2.78, 95% confidence interval 1.01-7.70; p = 0.04).

Conclusions: This study confirms the high mortality rate and highlights the importance of the host background, independent of age, in Pasteurella bacteraemia. Clinicians should be aware of the comorbidities in cases of Pasteurella infection, due to the poor prognosis of bacteraemia.
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http://dx.doi.org/10.1016/j.ijid.2020.01.003DOI Listing
March 2020

Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with Myalgic encephalomyelitis/Chronic fatigue syndrome.

Sci Rep 2019 12 11;9(1):18817. Epub 2019 Dec 11.

Department of internal medicine, University Hospital, Angers, 49000, France.

Elevated blood lactate after moderate exercise was reported in some of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We hypothesised that blood lactate could be also elevated in resting conditions. We aimed investigating the frequency of elevated lactate at rest in ME/CFS patients, and comparing characteristics of ME/CFS patients with and without elevated lactate. Patients fulfilling international consensus criteria for ME/CFS who attended the internal medicine department of University hospital Angers-France between October 2011 and December 2017 were included retrospectively. All patients were systematically hospitalised for an aetiological workup and overall assessment. We reviewed their medical records for data related to the assessment: clinical characteristics, comorbidities, fatigue features, post-exertional malaise (PEM) severity, and results of 8 lactate measurements at rest. Patients having ≥1 lactate measurement ≥2 mmol/L defined elevated lactate group. The study included 123 patients. Elevated (n = 55; 44.7%) and normal (n = 68; 55.3%) lactate groups were comparable except for PEM, which was more severe in the elevated lactate group after adjusting for age at disease onset, sex, and comorbidities (OR 2.47, 95% CI: 1.10-5.55). ME/CFS patients with elevated blood lactate at rest may be at higher risk for more severe PEM. This finding may be of interest in ME/CFS management.
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http://dx.doi.org/10.1038/s41598-019-55473-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906377PMC
December 2019

Effectiveness and tolerance of off-label use of tocilizumab in autoimmune diseases: A Multicenter Study.

Joint Bone Spine 2020 03 12;87(2):179-180. Epub 2019 Sep 12.

Department of Internal Medicine, hôpital Joseph-Ducuing, 15, rue Varsovie, 31076 Toulouse, France; Groupe de recherche des internistes FEHAP (GRIF), Paris, France; Department of Internal Medicine, groupe hospitalier Diaconesses Croix Saint Simon, Paris, France; Department of Internal Medicine, Saint Joseph Hospital, Marseille, France; Department of Internal Medicine, hôpital européen, Marseille, France; Department of Internal Medicine, Angers University Hospital, Angers, France; Toulouse University hospital, Internal Medicine, Toulouse, France; Tarbes Hospital, Internal Medicine, Tarbes, France; Cahors Hospital, Internal Medicine, Cahors, France; Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.1016/j.jbspin.2019.08.002DOI Listing
March 2020

Juvenile temporal arteritis: A clinicopathological multicentric experience.

Autoimmun Rev 2019 May 4;18(5):476-483. Epub 2019 Mar 4.

Department of internal medicine, Hôtel-Dieu, CHU Nantes, Nantes, France. Electronic address:

Introduction: Juvenile temporal arteritis (JTA) is a recently-described and little-known inflammatory disease and its etiology is undetermined. Less than forty cases have been published. This paper is aimed at reporting the largest JTA series and to compare it to literature data to better evaluate its characteristics at diagnosis, its evolution and treatment options.

Material And Methods: We conducted a retrospective and descriptive multicentric study in France by identifying adult patients under the age of 50 which had a pathological temporal artery biopsy owing to the presence of a temporal arteritis. Patients with temporal arteritis as a manifestation of systemic vasculitis were excluded.

Results: We included 12 patients and the literature review identified 32 cases described in 27 articles, thus a total of 44 patients - 34 men and 10 women - with a median age of 30 and a maximum of 44. All patients presented either a lump in the temporal region or prominent temporal arteries, and 47.7% of patients suffered from headaches. Only 11.4% of patients presented general symptoms and 6.8% a biological inflammatory syndrome; 34.1% had peripheral blood eosinophilia; 83.7% presented a single episode and complete excision without further treatment was documented for 72.7%. Pathology analysis revealed infiltrate of inflammatory cells in the arterial wall in 97.6% of patients but also sparse giant cells for 25% and granuloma for 22.9%, perivascular extension of the inflammation for 82.6%, and presence of lymphoid follicles or germinal centres for 60%. Clinical relapses were present in 16.3% of cases.

Conclusion: JTA is a rare, localized and benign disease. The majority of cases have only one episode which is cured by local surgery.
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http://dx.doi.org/10.1016/j.autrev.2019.03.007DOI Listing
May 2019

Arthritis in primary Sjögren's syndrome: Characteristics, outcome and treatment from French multicenter retrospective study.

Autoimmun Rev 2019 Jan 5;18(1):9-14. Epub 2018 Nov 5.

Service de médecine interne, Hôpital Saint-Antoine, APHP, Paris, France; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), F-75012 Paris, France. Electronic address:

Objective: To describe the characteristics and the outcome of primary Sjögren Syndrome (pSS) associated arthritis and to compare the efficacy of different therapeutic regimen.

Methods: We conducted a retrospective study using Club Rhumatisme and Inflammation (CRI) and French Internal Medicine Society (SNFMI) networks. All patients with a diagnosis of pSS and at least one episode of clinical and/or echographic synovitis were included. Patients with synovitis (cases) were compared to pSS patients without synovitis (controls).

Results: 57 patients (93% women) were included with a median age of 54 years [45-63]. Patients with synovitis had more frequently lymph node enlargement (12.3% vs. 1.8%, p = .007) and a higher ESSDAI score (8 [6-12] vs. 2 [1-4], p < .0001). There was no difference concerning CRP levels, rheumatoid factor and cyclic citrullinated peptide (CCP)-antibodies positivity. Among 57 patients with synovitis, 101 various treatment courses have been used during the follow-up of 40 [22.5-77] months. First treatment course consisted in steroids alone (3.5%), steroids in association (79%) with hydroxychloroquine (HCQ) (49%), methotrexate (MTX) (35%), rituximab (RTX) (5.3%) or other immunosuppressive drugs (7%). HCQ, MTX, and RTX were associated with a significant reduction of tender and swollen joint count, and a significant steroids-sparing effect. No difference could be shown for the joint response between these treatment regimens.

Conclusion: pSS articular manifestations may include synovitis which could mimic rheumatoid arthritis but differ by the absence of structural damage. Even if the use of HCQ, MTX, and RTX seem to be effective for joint involvement, the best regimen remains to be determined.
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http://dx.doi.org/10.1016/j.autrev.2018.06.015DOI Listing
January 2019
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