Value of rare diseases reference centers: impact on diagnosis and access to specialized care in fibrous dysplasia of bone.

INTRODUCTION: Reference Centers and Rare Disease Health Networks aim to improve the management of patients with rare diseases. The French reference center for Fibrous Dysplasia was certified in 2006. OBJECTIVE: The objective of our study was to assess the effectiveness of our reference center since its constitution. METHODS: In a retrospective cohort study, we compared the activity of our center, including the time elapsed between access to the center and the diagnostic delay of patients with Fibrous Dysplasia between two periods, 1994-2006 (before certification) and 2007-2019 (after certification). Data were extracted from patients' records (Easily®). Wilcoxon and Fisher tests were performed, using R®. RESULTS: Our cohort included 527 patients with Fibrous Dysplasia/Mc Cune Albright syndrome. The activity of the Fibrous Dysplasia center increased from 139 patients in the first period (1994-2006) to an additional 388 patients for the second period (2007-2019). Mean time elapsed to diagnosis of Fibrous Dysplasia was 1.5 years before 2007 and 1.9 years after 2007 (p = 0.12). Diagnosis was made before referral in over 80% of patients. There was a non-significant decrease in the number of patients with delayed diagnosis: 37 patients (44%) in the first period had a diagnostic delay and 94 patients (33%) in the second period (p = 0.07). Patients were referred to our center on average 6.8 years (before 2007) and 7.9 years (after 2007) after their diagnosis (p = 0.77). CONCLUSION: Healthcare organization with reference centers significantly impacted the management of patients with Fibrous Dysplasia/Mc Cune Albright syndrome, with a substantial increase in the activity of our center, that roughly tripled since certification. This healthcare organization was also associated with a trend toward decreasing diagnostic delay. However, diagnostic delay affected more than a third of patients and the time to access to the center remained extended (≈7-8 years after diagnosis). The current challenge lies in informing primary care providers and patients about education to rare diseases and existence of reference centers for earlier and more effective specialized management.

The future of intensive care: the study of the microcirculation will help to guide our therapies.

The goal of hemodynamic resuscitation is to optimize the microcirculation of organs to meet their oxygen and metabolic needs. Clinicians are currently blind to what is happening in the microcirculation of organs, which prevents them from achieving an additional degree of individualization of the hemodynamic resuscitation at tissue level. Indeed, clinicians never know whether optimization of the microcirculation and tissue oxygenation is actually achieved after macrovascular hemodynamic optimization. The challenge for the future is to have noninvasive, easy-to-use equipment that allows reliable assessment and immediate quantitative analysis of the microcirculation at the bedside. There are different methods for assessing the microcirculation at the bedside; all have strengths and challenges. The use of automated analysis and the future possibility of introducing artificial intelligence into analysis software could eliminate observer bias and provide guidance on microvascular-targeted treatment options. In addition, to gain caregiver confidence and support for the need to monitor the microcirculation, it is necessary to demonstrate that incorporating microcirculation analysis into the reasoning guiding hemodynamic resuscitation prevents organ dysfunction and improves the outcome of critically ill patients.

Elevated plasma Galectin-3 is associated with major adverse kidney events and death after ICU admission.

BACKGROUND: Galectin-3 (Gal-3) is a proinflammatory and profibrotic protein especially overexpressed after Acute Kidney Injury (AKI). The early renal prognostic value of Gal-3 after AKI in critically ill patients remains unexplored. The objective was to evaluate the prognostic value of plasma level of Gal-3 for Major Adverse Kidney Events (MAKE) and mortality 30 days after ICU admission across AKI stages. METHODS: This is an ancillary study of a prospective, observational, multicenter cohort (FROG-ICU). AKI was defined using KDIGO definition. RESULTS: Two thousand and seventy-six patients had a Gal-3 plasma level measurement at ICU admission. Seven hundred and twenty-three (34.8%) were females and the median age was 63 [51, 74] years. Eight hundred and seven (38.9%) patients developed MAKE, 774 (37.3%) had AKI and mortality rate at 30 days was 22.4% (N = 465). Patients who developed MAKE had higher Gal-3 level at admission compared to patients without (30.2 [20.8, 49.2] ng/ml versus 16.9 [12.7, 24.3] ng/ml, p < 0.001, respectively. The area under the receiver operating characteristic curve of Gal-3 to predict MAKE was 0.76 CI95% [0.74-0.78], p < 0.001. Gal-3 was associated with MAKE (OR 1.80 CI95% [1.68-1.93], p < 0.001, non-adjusted and OR 1.37 CI95% [1.27-1.49], p < 0.001, adjusted). The use of Gal-3 improved prediction performance of prediction model including SAPSII, Screatadm, pNGAL with a NRI of 0.27 CI95%(0.16-0.38), p < 0.001. Median Gal-3 was higher in non-survivors than in survivors at 30 days (29.2 [20.2, 49.2] ng/ml versus 18.8 [13.3, 29.2] ng/ml, p < 0.001, respectively). CONCLUSION: Plasma levels of Gal-3 were strongly associated with renal function, with an increased risk of MAKE and death after ICU admission. Trial registration ClinicalTrials.gov NCT01367093. Registered on 6 June 2011.

[Pre-malignant and malignant diseases of the esophagus, a centralized and multidisciplinary approach]. / Prise en charge des cancers et affections pré-malignes de l'oesophage Approche centralisée et multidisciplinaire au centre de référence de chirurgie complexe du CHU de Liège.

Esophageal cancer is the 19th most common cancer in the European Union. Its prognosis remains poor with a 5-year survival rate estimated between 15 % and 25 %. Accurate diagnosis and pre-therapeutic assessment are essential and should allow a rapid start of therapy. Current treatment is based on multimodal management of which surgery remains the cornerstone. Since 2019, Belgium has started an agreement to centralize esophageal surgery in order to improve surgical outcomes. One year after implementation of centralization, our centre shows a low rate of severe complications (Clavien-Dindo classification IIIb-V) of 20 % and a 0 % mortality rate at 30 and 90 postoperative days. Our patients have benefited from a full minimally invasive or hybrid surgical procedure, contributing to those positive results. In the future, all our efforts must be done to improve collaboration between hospitals in order to provide best medical and surgical treatments.

Le cancer de l'oesophage est le 19ème cancer le plus fréquent dans l'Union Européenne. Son pronostic reste sombre avec un taux de survie à 5 ans estimé entre 15 % et 25 %. La précocité du diagnostic et la qualité du bilan pré-thérapeutique sont essentielles et doivent permettre d'initier un traitement rapide. Le traitement repose sur une prise en charge multidisciplinaire et multimodale dont la chirurgie reste la pierre angulaire. En Belgique, le taux de mortalité à 30 et 90 jours post-opératoires étaient de 4,1 % et 9,5 %, respectivement, pour la période allant de 2008 à 2016. Dans une perspective d'amélioration de cette prise en charge, depuis 2019, la Belgique a concentré la chirurgie de l'oesophage dans 10 centres de référence, incluant le CHU de Liège. Un an après centralisation, notre centre présente un taux de complications sévères selon Clavien-Dindo (IIIb-V) de 20 % et des taux de mortalité à 30 et 90 jours de 0 %. Le bilan d'évaluation initial de chaque patient est discuté en concertation multidisciplinaire. Une prise en charge nutritionnelle est discutée avant l'instauration du traitement. Tous nos patients bénéficient d'une approche systématique totalement mini-invasive ou hybride, participant à l'amélioration des résultats sur la morbidité et la mortalité. Une collaboration croissante avec nos hôpitaux partenaires permet d'harmoniser les mises au point et les plans de traitement oncologiques pour le bénéfice des patients.

[Multimodal evaluation of the ocular surface using a the new Lacrydiag device]. / Place du NIBUT automatisé dans l'évaluation multimodale de la surface oculaire dans le syndrome sec avec le Lacrydiag.

INTRODUCTION: Dry eye disease is a very frequent condition with a significant impact on patients' quality of life. The most common clinical sign is fluorescein break up time (BUT). Recently, non-invasive measurement of BUT (NIBUT) by Placido disc analysis has been proposed to replace FBUT. We performed an automated NIBUT analysis using Lacrydiag and compared the values obtained with other typical dry eye criteria. METHODS AND MATERIALS: A retrospective study was carried out in the Bicêtre ophthalmology department from July 1 through October 30. Dry eye patients over 18 years of age with Oxford scores>1 and OSDI scores>22 were included. They underwent slit lamp examination to determine fluorescein BUT, Oxford and Arita MGD scores. On the same day, they were tested with the Lacrydiag to assess NIBUT, tear lake height and meibography. OSDI and Schirmer's testing were performed on the date of examination. In this study, only patients' right eyes were included. The correlation between NIBUT and OSDI, Schirmer's testing and tear lake height was analyzed by Pearson's test. The correlation between NIBUT and fluorescein BUT was analysed by both Pearson and Bland-Altman statistical tests. RESULTS: Thirty right eyes (21 women, 9 men) were included. The mean age was 62.3 years (SD 16.0), mean OSDI 49.4 (SD=20.1), mean Oxford score 3.33 (SD 2.1), mean NIBUT 6.91sec (SD 3.4), and mean FBUT 3.6sec (SD 1.8). The NIBUT and FBUT were significantly correlated (R=0.139; P=0.042), with an even more significant concordance (r=0.55; P=0.001) on Bland-Altman graphic analysis, but the mean NIBUT was 2.7 seconds higher than the FBUT (P=0.001 on Bland-Altman analysis). In addition, NIBUT was correlated with the Oxford score (R=0.156; P=0.031), but not with Schirmer I score (R=0.120; P=0.061), OSDI score (R=0.018; P=0.48), tear lake height (R=0.04; P=0.148), or Arita meibomian gland dysfunction score (R=0; P=0.933). CONCLUSION: NIBUT is a possible alternative to FBUT for the measurement of tear film stability, with the advantage of lack of dependence on the amount of fluorescein instilled. In addition, modern imaging methods allow for automated, and thus reproducible, measurement. However, its role in the diagnostic tool kit remains to be precisely defined, especially given its weak correlation with other markers of dry eye and its significant difference from FBUT. The definitive diagnosis of dry eye thus remains based on the combined analysis of signs and symptoms.

[Micropulsed diode laser transscleral cyclophotocoagulation: An effective technique whose role remains to be defined]. / Cycloaffaiblisement au laser diode micropulsé : une technique efficace, mais dont la stratégie reste à définir.

Micropulse Transscleral Cyclophotocoagulation (MP-TSCP) is a recently developed cyclodestructive procedure less aggressive than conventional TSCP. In this study, we aimed to evaluate the safety and efficacy of MP-TSCP in a real-life setting. MATERIAL AND METHODS: We retrospectively included all MP-TSCP cases performed in the Bicêtre Hospital Ophthalmology department between January 2017 and September 2019. Intraocular pressure (IOP) and hypotensive medications were recorded preoperatively, at month 1, 3, 6 and at the conclusion of follow-up, as well as postoperative adverse events. Success was defined as an IOP between 6 and 21mmHg with a decrease of at least one medication or an IOP reduction>20%. RESULTS: Thirty eyes (28 patients) were included. Preoperative IOP was 27.2±10.6mmHg, with 3.5±0.6 hypotensive medications, the mean deviation on the Humphrey 24-2 visual field was -21.9±6.9dB, and 43% of eyes had a past history of filtering surgery. The mean follow-up was 13.5±8.1 months. Eleven patients (37%) had to be retreated with MP-TSCP during follow-up. At 3 and 6 months and at the conclusion of follow-up, the IOP was 18.3±7.3mmHg (-33%; P<0.0001), 22.5±11.8mmHg, (-17%; P=0.052), 22.7±12.0mmHg (-16,5%; P<0.050), respectively. The success rates were 57%, 50% et 53% at 3 months, 6 months and at the conclusion of follow-up, respectively. Severe adverse events included 3 cases of corneal ulcers and 2 cases of severe but transient ocular hypotony without visual impairment. CONCLUSION: MP-TSCP is an effective procedure for severe and/or refractory glaucoma, but retreatments are required in more than one-third of cases. Further studies are warranted to define factors predictive of success and indications for retreatment.

GNAS mutated thyroid carcinoma in a patient with Mc Cune Albright syndrome.

Mc Cune-Albright syndrome (MAS) is a rare disorder defined by the triad of polyostotic fibrous dysplasia, "café au lait" skin hyperpigmentation and hyperfunctioning endocrinopathies, such as precocious puberty. MAS is caused by an activating post zygotic somatic mutation of GNAS gene, coding for the alpha-subunit of the stimulatory G protein (Gsalpha). In endocrine tissues, this mutation results in overproduction of hormones and endocrine cell hyperfunction and proliferation. Whereas the association of hyperthyroidism and thyroid adenomas is well known in MAS, the relation with thyroid carcinoma has rarely been observed. We report the occurrence of a thyroid carcinoma in an 18-years old woman with MAS, revealed by subclinical hyperthyroidism detected during her systematic annual follow-up. Ultrasound and thyroid scintigraphy revealed the presence of a nodule in the right lobe. Pathology on hemithyroidectomy revealed an unexpected thyroid follicular carcinoma. Neoplastic thyroid cells harbored the GNAS R201C activating mutation. This observation suggests that MAS may predispose patients to thyroid carcinomas and supports the importance of thyroid assessment by physical examination, hormonal blood test and ultrasound, in the follow-up of patients with MAS. Because ultrasound diagnostic is challenging in MAS, needle puncture of palpable nodules should be advised.

Utility of anaerobic bottles for the diagnosis of bloodstream infections.

BACKGROUND: Obligate anaerobes usually account for less than 10% of bacteria recovered from blood cultures (BC). The relevance of routine use of the anaerobic bottle is under debate. The aim of this study was to evaluate the utility of anaerobic bottles for the diagnosis of bloodstream infections (BSI). METHODS: We conducted a 6-month, retrospective, monocentric study in a tertiary hospital. All positive BC were grouped into a single episode of bacteremia when drawn within 7 consecutive days. Bacteremia were classified into contaminants and BSI. Charts of patients with BSI due to obligate anaerobes were studied. RESULTS: A total of 19,739 blood cultures were collected, 2341 of which (11.9%) were positive. Anaerobic bottles were positive in 1528 (65.3%) of all positive BC but were positive alone (aerobic bottles negative) in 369 (15.8%). Overall 1081 episodes of bacteremia were identified, of which 209 (19.3%) had positive anaerobic bottles alone. The majority 126/209 (60.3%) were contaminants and 83 (39.7%) were BSI. BSI due to facultative anaerobes, obligate aerobes and obligate anaerobes were identified in 67 (80.7%), 3 (3.6%) and 13 (15.7%) of these 83 episodes, respectively. BSI due to obligate anaerobic bacteria were reported in 9 patients with gastro-intestinal disease, in 3 with febrile neutropenia and in 1 burned patient. CONCLUSIONS: Anaerobic bottles contributed to the diagnosis of a significant number of episodes of bacteremia. Isolated bacteria were mostly contaminants and non-obligate anaerobic pathogens. Rare BSI due to obligate anaerobes were reported mainly in patients with gastro-intestinal disorders and during febrile neutropenia.

Report of the first AKI Round Table meeting: an initiative of the ESICM AKI Section.

PURPOSE: Critical Care Nephrology is an emerging sub-specialty of Critical Care. Despite increasing awareness about the serious impact of acute kidney injury (AKI) and renal replacement therapy (RRT), important knowledge gaps persist. This report represents a summary of a 1-day meeting of the AKI section of the European Society of Intensive Care Medicine (ESICM) identifying priorities for future AKI research. METHODS: International Members of the AKI section of the ESICM were selected and allocated to one of three subgroups: "AKI diagnosis and evaluation", "Medical management of AKI" and "Renal Replacement Therapy for AKI." Using a modified Delphi methodology, each group identified knowledge gaps and developed potential proposals for future collaborative research. RESULTS: The following key research projects were developed: Systematic reviews: (a) epidemiology of AKI with stratification by patient cohorts and diagnostic criteria; (b) role of higher blood pressure targets in patients with hypertension admitted to the Intensive Care Unit, and (c) specific clearance characteristics of different modalities of continuous renal replacement therapy (CRRT). Observational studies: (a) epidemiology of critically ill patients according to AKI duration, and (b) current clinical practice of CRRT. Intervention studies:( a) Comparison of different blood pressure targets in critically ill patients with hypertension, and (b) comparison of clearance of solutes with various molecular weights between different CRRT modalities. CONCLUSION: Consensus was reached on a future research agenda for the AKI section of the ESICM.

[A systemic disease mimicking a rheumatoid arthritis]. / Une maladie systémique mimant une polyarthrite rhumatoïde.

INTRODUCTION: Rare systemic diseases such as amyloidosis can mimic inflammatory rheumatic diseases. Because of their poor prognosis, physicians should rule them out at the onset of inflammatory rheumatism. We report a case of AL amyloidosis misdiagnosed as rheumatoid arthritis. CASE REPORT: A 71-year-old woman was referred for seronegative rheumatoid arthritis, resistant to three biologic therapies. She had an IgA lambda monoclonal gammopathy of undetermined significance (MGUS). The patient subsequently developed glomerular proteinuria. Abdominal fat and accessory salivary glands biopsies revealed amyloid light-chain (AL) amyloidosis. Treatment with bortezomib-cyclophosphamide-dexamethasone, led to complete hematologic, renal and rheumatologic remission. Ten months after treatment interruption, the patient had an articular and hematologic relapse. CONCLUSION: Amyloid light-chain amyloidosis arthropathy is probably underdiagnosed. A review of amyloid arthropathy associated with multiple myeloma found that 33% of patients had been misdiagnosed with rheumatoid arthritis.

[Punctal and canalicular plugs: Indications, efficacy and safety (French translation of the article)]. / Les bouchons lacrymaux : indications, efficacité et tolérance.

Lacrimal occlusion with punctal or canalicular plugs have been used to treat dry eye disease for more than 40 years. Indeed, punctal plugs constitute a safe and effective tool to retain the natural tear film and prolong the effect of tear substitutes. A wide variety of plugs is available, differing in their design, location (punctal versus canalicular) and their resorbability. There indications have increasingly broadened, and they are now one of the treatment options for numerous ocular surface diseases. Current research focuses on using punctal plugs for extended delivery of drugs to the ocular surface. This review addresses physiology of lacrimal drainage, available models of punctal plugs, their indications, practical details of prescribing and placing punctal and canalicular plugs, and possible complications.

Punctal and canalicular plugs: Indications, efficacy and safety.

Lacrimal occlusion with punctal or canalicular plugs have been used to treat dry eye disease for more than 40 years. Indeed, punctal plugs constitute a safe and effective tool to retain the natural tear film and prolong the effect of tear substitutes. A wide variety of plugs is available, differing in their design, location (punctal versus canalicular) and their resorbability. There indications have increasingly broadened, and they are now one of the treatment options for numerous ocular surface diseases. Current research focuses on using punctal plugs for extended delivery of drugs to the ocular surface. This review addresses physiology of lacrimal drainage, available models of punctal plugs, their indications, practical details of prescribing and placing punctal and canalicular plugs, and possible complications.

Greenland records of aerosol source and atmospheric lifetime changes from the Eemian to the Holocene.

The Northern Hemisphere experienced dramatic changes during the last glacial, featuring vast ice sheets and abrupt climate events, while high northern latitudes during the last interglacial (Eemian) were warmer than today. Here we use high-resolution aerosol records from the Greenland NEEM ice core to reconstruct the environmental alterations in aerosol source regions accompanying these changes. Separating source and transport effects, we find strongly reduced terrestrial biogenic emissions during glacial times reflecting net loss of vegetated area in North America. Rapid climate changes during the glacial have little effect on terrestrial biogenic aerosol emissions. A strong increase in terrestrial dust emissions during the coldest intervals indicates higher aridity and dust storm activity in East Asian deserts. Glacial sea salt aerosol emissions in the North Atlantic region increase only moderately (50%), likely due to sea ice expansion. Lower aerosol concentrations in Eemian ice compared to the Holocene are mainly due to shortened atmospheric residence time, while emissions changed little.

[Ocular surface aging: Pathophysiology and consequences for management]. / Vieillissement de la surface oculaire : physiopathologie et conséquences pratiques pour la prise en charge.

All the components of the ocular surface and the lacrimal system are affected by aging. Aging induces lacrimal gland fibrosis, Meibomian gland dysfunction, loss of corneal sensitivity, decreased corneal cell density, impairment of immune defences, increased local inflammation associated with hormonal changes, conjunctivochalasis, lid abnormalities, etc. Furthermore, homeostasis of the ocular surface may be altered by various age-related systemic comorbidities and iatrogenic interventions. Altogether, aging is considered the most predominant risk factor for dry eye disease. The increasing knowledge of the pathophysiology of aging of the ocular surface allows for refinement of the management of ocular surface disease in the elderly.

Measurement of full-thickness macular hole size using en face optical coherence tomography.

PurposeTo assess the feasibility and interest of measuring macular hole (MH) size using en face optical coherence tomography (OCT) compared with manual diameter measurements on B-scans.MethodsAmong our previously published series of 100 patients operated for primary MH, patients whose images were acquired with Cirrus 5000 HD-OCT (Carl Zeiss Meditec) with a quality signal strength >5/10 were included. Three segmentations (internal limiting membrane, horizontal, and retinal pigment epithelium (RPE)) were compared for obtaining the most appropriate en face image. MH surface areas were measured using ImageJ software. Mean diameters calculated from surface areas (diameter=2 × âˆš(surface area/π)) were compared with those measured on B-scans.ResultsNineteen patients were included with a mean age of 72±8 years (56-86) and a female predominance (3/16). The mean absolute difference between horizontal and vertical diameters measured on B-scans was of 54±47 µm (0-180) without reaching significance (P=0.874). RPE segmentation provided the best en face image and was feasible without and with adjustment, respectively, in 79% and 100% (cases with vitreomacular traction) of cases. No significant difference in mean diameters was observed between those calculated from en face images (435±143 µm (195-693)) and those measured on horizontal B-scans (426±139 µm (214-705), P=0.482).ConclusionMeasuring MH size on en face OCT images is feasible, reliable, and eliminates the potential bias related to manual measurements on B-scans. Its integration into OCT devices would offer an automated and easy-to-use option for clinical practice.

Cholangiopathy in critically ill patients surviving beyond the intensive care period: a multicentre survey in liver units.

BACKGROUND: The outcome of cholangiopathy developing in intensive care unit (ICU) is not known in patients surviving their ICU stay. AIM: To perform a survey in liver units, in order to clarify the course of cholangiopathy after surviving ICU stay. METHODS: The files of the liver units affiliated to the French network for vascular liver disease were screened for cases of ICU cholangiopathy developing in patients with normal liver function tests on ICU admission, and no prior history of liver disease. RESULTS: Between 2005 and 2015, 16 cases were retrieved. Extensive burns were the cause for admission to ICU in 11 patients. Serum alkaline phosphatase levels increased from day 11 (2-46) to a peak of 15 (4-32) × ULN on day 81 (12-511). Magnetic resonance cholangiography showed irregularities or frank stenosis of the intrahepatic ducts, and proximal extrahepatic ducts contrasting with a normal aspect of the distal common bile duct. Follow-up duration was 20.6 (4.7-71.8) months. Three patients were lost to follow-up; 2 patients died from liver failure and no patient was transplanted. One patient had worsening strictures of the intrahepatic bile ducts with jaundice. Nine patients had persistent but minor strictures of the intrahepatic bile ducts on MR cholangiography, and persistent cholestasis without jaundice. One patient had normal liver function tests. CONCLUSIONS: In patients surviving their ICU stay, ICU cholangiopathy is not uniformly fatal in the short term or clinically symptomatic in the medium term. Preservation of the distal common bile duct appears to be a finding differentiating ICU cholangiopathy from other diffuse cholangiopathies.

Incidence, risk factors, and outcome of multidrug-resistant Acinetobacter baumannii acquisition during an outbreak in a burns unit.

BACKGROUND: Multidrug-resistant Acinetobacter baumannii (MR-AB) can cause outbreaks in a burns unit. AIM: To study the incidence, risk factors and outcome of MR-AB colonization during an outbreak. METHODS: A prospective study was conducted from April to November 2014 in a burns unit in Paris. Weekly surveillance cultures of patients and their environment were performed. MR-AB acquisition, discharge, or death without MR-AB colonization were considered as competing events. To identify risk factors for colonization, baseline characteristics and time-dependent variables were investigated in univariate and multivariate analyses using Cox models. MR-AB strains were genotypically compared using multi-locus sequence typing. FINDINGS: Eighty-six patients were admitted in the burns unit during the study period. Among 77 patients without MR-AB colonization at admission, 25 (32%) acquired MR-AB with a cumulative incidence of 30% at 28 days (95% CI: 20-40). Median time to MR-AB acquisition was 13 days (range: 5-34). In multivariate analysis, risk factors for MR-AB acquisition were ≥2 skin graft procedures performed [hazard ratio (HR): 2.97; 95% confidence interval (CI): 1.10-8.00; P = 0.032] and antibiotic therapy during hospitalization (HR: 4.42; 95% CI: 1.19-16.4; P = 0.026). A major sequence type of MR-AB (ST2) was found in 94% and 92% of patients and environmental strains, respectively, with all strains harbouring the blaOXA-23 gene. MR-AB colonization increased length of hospitalization (HR: 0.32; 95% CI: 0.17-0.58; P = 0.0002) by a median of 12 days. CONCLUSION: A high incidence of MR-AB acquisition was seen during this outbreak with most strains from patients and their environment belonging to single sequence type. MR-AB colonization was associated with more skin graft procedures, antibiotic use, and prolonged hospitalization.

Cessation of oral anticoagulants in antiphospholipid syndrome.

Objective To study the outcome of patients with antiphospholipid syndrome (APS) after oral anticoagulant treatment cessation. Methods We performed a retrospective study of patients with APS experiencing cessation of oral anticoagulant and enrolled in a French multicentre observational cohort between January 2014 and January 2016. The main outcome was the occurrence of recurrent thrombotic event after oral anticoagulation cessation. Results Forty four APS patients interrupted oral anticoagulation. The median age was 43 (27-56) years. The median duration of anticoagulation was 21 (9-118) months. Main causes of oral anticoagulant treatment cessation were switch from vitamin K antagonists to aspirin in 15 patients, prolonged disappearance of antiphospholipid antibodies in ten, bleeding complications in nine and a poor therapeutic adherence in six. Eleven (25%) patients developed a recurrent thrombotic event after oral anticoagulation cessation, including three catastrophic APS and one death due to lower limb ischemia. Antihypertensive treatment required at time of oral anticoagulants cessation seems to be an important factor associated with recurrent thrombosis after oral anticoagulant cessation (15.2% in patients with no relapse versus 45.5% in patients with recurrent thrombosis, p = 0.038). Oral anticoagulant treatment was re-started in 18 (40.9%) patients. Conclusion The risk of a new thrombotic event in APS patients who stopped their anticoagulation is high, even in those who showed a long lasting disappearance of antiphospholipid antibodies. Except for the presence of treated hypertension, this study did not find a particular clinical or biological phenotype for APS patients who relapsed after anticoagulation cessation. Any stopping of anticoagulant in such patients should be done with caution.